Corporate News

Notice of Annual General Meeting

In addition, Polarean confirms that the Annual Report and Accounts for the year ended 31 December 2022, the Notice of the Annual General Meeting ("AGM") and a Form of Proxy are now available on the Company's website (http://www.polarean-ir.com/content/investors/annual-reports.asp) and will be posted to shareholders shortly.

The AGM will be held at 2500 Meridian Parkway, Suite 175, Durham, NC 27713, USA at 2 p.m. BST / 9 a.m. EST on 28 June 2023.

Highlights

• United States Food and Drug Administration (“FDA”) approval received for the Company’s drug device combination product, XENOVIEW (xenon Xe 129 hyperpolarised), a hyperpolarised contrast agent indicated for use with magnetic resonance imaging (“MRI”) for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older
• Simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA; XENOVIEW VDP is image processing software that analyses a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualisation and evaluation of lung ventilation and the Polarean XENOVIEW 3.0T Chest Coil
• Research system placements at McMaster University in Ontario, Canada and Cincinnati Children’s Hospital Medical Center (“CCHMC”)
• Appointment of Frank Schulkes, Dan Brague and Marcella Ruddy, MD to the Board as independent Non-Executive Directors
• Appointment of Ken West as Non-Executive Chairman, following the retirement of Jonathan Allis
• Research collaboration with Oxford University Hospitals NHS Trust for long-COVID
• Net cash of US$16.4 million as of 31 December 2022

Post-period end

• First order for a XENOVIEW gas blend cylinder for the production of XENOVIEW received from CCHMC, representing key milestone and execution of commercial plan
• First clinical scan utilising XENOVIEW technology in the United States conducted at CCHMC, marking key milestone for imaging of lung ventilation
• Selected as one of the featured companies as a poster presenter at the American Thoracic Society’s (“ATS”) 2023 Respiratory Innovation Summit

Richard Hullihen, CEO of Polarean, said: "We ended the year with a tremendous positive in receiving our FDA approval for XENOVIEW. This was a long road culminating with the decision we were looking for, and an extraordinary amount of work went into this process from the entire team. We have now begun to roll out XENOVIEW for clinical use and expect to see further hospitals adopt doing clinical XENOVIEW scans in the coming months. We also continue to explore potential future applications for our technology and remain positive for the year ahead. Separately, we have been shortlisted for Breakthrough of the Year and Best Technology at the 2023 European Mediscience Awards, which celebrates private and listed healthcare, biotech and life sciences companies; we are delighted by this validation of our technology and our achievement in securing FDA approval, and are excited to see the outcome.

“On behalf of the Board and the whole Polarean team, I would like to extend my thanks to our shareholders for all their support and we look forward to further updating the market in due course.” 

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014.

Inquiries: 

About Polarean (www.polarean.com)

The Company and its wholly owned subsidiary, Polarean, Inc. (together the "Group") are revenue-generating, medical imaging technology companies operating in the high-resolution medical imaging space. Polarean aspires to revolutionise pulmonary medicine by bringing the power and safety of MRI to the respiratory healthcare community in need of new solutions to evaluate lung ventilation, diagnose disease, characterise disease progression, and monitor response to treatment. By researching, developing, and commercialising novel imaging solutions with a non-invasive and radiation-free functional imaging platform. Polarean’s vision is to help address the global unmet medical needs of more than 500 million patients worldwide suffering with chronic respiratory disease. Polarean is a leader in the field of hyperpolarisation science and has successfully developed the first and only hyperpolarised MRI contrast agent to be approved in the United States. On Dec. 23, 2022, the FDA granted approval for Polarean’s first drug device combination product, XENOVIEW^TM (Xenon Xe¹²⁹ hyperpolarised). Xe¹²⁹ MRI is also currently being studied for visualisation and quantification of gas exchange regionally in the smallest airways of the lungs, across the alveolar tissue membrane, and into the pulmonary bloodstream for future clinical indications.

XENOVIEW IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Risk of Decreased Image Quality from Supplemental Oxygen: Supplemental oxygen administered simultaneously with XENOVIEW^TM inhalation can cause degradation of image quality. For patients on supplemental oxygen, withhold oxygen inhalation for two breaths prior to XENOVIEW^TM inhalation, and resume oxygen inhalation immediately following the imaging breath hold.

Risk of Transient Hypoxia: Inhalation of an anoxic gas such as XENOVIEW^TM may cause transient hypoxemia in susceptible patients. Monitor all patients for oxygen desaturation and symptoms of hypoxemia and treat as clinically indicated.

Adverse Reactions

Adverse Reactions in Adult Patients: The adverse reactions (> one patient) in efficacy trials were oropharyngeal pain, headache, and dizziness.  Adverse Reactions in Pediatric and Adolescent Patients: In published literature in pediatric patients aged 6 to 18, transient adverse reactions were reported: blood oxygen desaturation, heart rate elevation, numbness, tingling, dizziness, and euphoria. In at least one published study of pediatric patients aged 6 to 18 years, transient decrease in SpO2% and transient increase in heart rate was reported following hyperpolarized xenon Xe 129 administration. XENOVIEW^TM is not approved for use in pediatric patients less than 12 years of age.

Please see full prescribing information at www.xenoview.net

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Chairman’s Statement

I am pleased to be able to write this letter with the very important milestone of United States Food & Drug Administration (“FDA”) approval of the Company’s drug device combination product, XENOVIEW, having been accomplished. The broad label of “evaluation of lung ventilation in adults and pediatric patients aged 12 years and older” allows the company to execute its commercial strategy of selling its polarizer and approved gas for clinical scans of patients suffering from a number of lung diseases where the accurate measurement of lung ventilation provides the physician with actionable diagnostic information. In addition, researchers using Polarean’s technology continue to conduct clinical research that supports the broad future potential applications of our technology in areas of gas exchange and cardiopulmonary diagnostics. We are excited to bring Polarean’s technology to clinical medicine, with the potential to be an important part of pulmonary and cardiopulmonary diagnostics, monitoring of severity of disease and patient response to treatments.

During 2022, we strengthened our Board with the addition of three independent Non-Executive Board members who bring extensive industry and medical experience to the Board to assist the company’s successful transition into the commercialization stage. Frank Schulkes brings substantial financing experience in the medical imaging industry and Dan Brague brings experience successfully commercializing diagnostic imaging products. In addition, Dr. Marcella Ruddy brings important pulmonary medical expertise, both in clinical practice and in pharmaceutical development. With these additions to our Board, we believe that we have a world-class Board that can lead the company to successful commercialization of Xenoview.

Having achieved FDA approval, our efforts are now focused on gaining commercial traction and engaging with potential corporate partners to further accelerate our commercial success. Once we have achieved some of these near-term milestones, we will explore the options for additional financing to more aggressively pursue the development of the next indications and advance the continued development of our polarizer system and software. The Company is exploring a broad range of options for future financing, including equity raises and corporate partnering.

On behalf of the Board, I want to thank our employees, stakeholders and shareholders and assure them that we are committed to making Xenoview a commercial and financial success.

Kenneth West

Non-Executive Chairman
25 May 2023

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Chief Executive Officer’s Statement

2022 – Year of Obtaining FDA Approval

We spent much of 2022 working on obtaining FDA approval of our New Drug Application (“NDA”) for XENOVIEW and were please received our approval on 23 December 2022. After receiving a Complete Response Letter (“CRL”) from the FDA in October 2021, we spend the subsequent six months addressing the issues raised in the CRL. On 30 March 2022, the Company refiled the NDA with the FDA. The resubmission addressed the items identified in the CRL. On 22 September the Company announced that the FDA had requested additional information related to the cGMP (Current Good Manufacturing Practice) pre-approval inspection at the partner’s production facility. The Company and its partner addressed the FDA’s request and the Company received FDA approval on 23 December 2022. We were very pleased to receive the broad label of evaluation of lung function in adults and pediatric patients twelve and older. In addition, the FDA indicated that they would allow us to submit a non-clinical plan to obtain approval in pediatric patients six and older. The FDA has granted New Chemical Entity (“NCE”) designation for Xenoview. NCE designation provides the important first mover protection envisioned under the Hatch Waxman legislation.

Commercialization

With FDA approval, the Company is focused on successful commercialization of XENOVIEW for the evaluation of lung function. The Company has an enthusiastic base of US institutions who have been using our technology for research purposes for years. We are leveraging this knowledge and enthusiasm by converting its US research sites to FDA approved configuration and clinical use, which will allow these sites to purchase Xenoview and perform clinical scans. In parallel, we are pursuing various reimbursement codes that could enable the hospitals to be reimbursed for Xenoview, the polarization process, the MRI procedure and the analysis of the pulmonary function imaging. If obtained, we believe that this reimbursement would enable a very compelling return on investment for hospitals to purchase our polarizer systems. We are aggressively pursuing our early commercialization targets of the sale of 15 to 20 polariser systems and 75 to 100 cylinders of Xenoview by the end of 2024.

We are focusing initially on addressing the high end of the US academic and teaching hospital market segment, which comprises approximately the top 1000 institutions nationally having coincident multiple Centres of Excellence in Pulmonary Medicine and Radiology. We believe our strategy of selling the capital equipment and the Xenoview drug on a per cylinder basis could provide a capital equipment and recurring drug sales model that supports rapidly growing revenue.

Financials

Sales for 2022 were below our original expectations, as we did not receive FDA approval in October 2022 as anticipated in the plan. We adjusted our spending plans commensurate with the delayed approval, which allowed us to finish 2022 with a higher than anticipated cash balance of US$16.4 million. We continued to sell our polariser systems into the research market and completed two installations during 2022. The current cash balance is expected to fund the company into late Q2-2024.

Corporate Partnering

We continue to believe that corporate partnering could be an important part of the Company’s business plan. We see the opportunity to help the pharmaceutical industry reduce by significant amounts the size, time required to conduct and costs of their pulmonary drug clinical trials by providing quantitative, reproducible image-based data. We also see the opportunity to partner with MRI manufacturers to open up the MRI applications space to include pulmonary diagnostics, driving the demand for more MRI systems. In addition, we will explore the opportunity to partner with pulmonary disease organizations and foundations to incorporate the use of Xenoview in the diagnosis and treatment of disease.

Future Indications

Researchers are currently conducting clinical trials and pharmaceutical company sponsored investigations in multiple areas of pulmonary disease using our technology. These studies are highlighting the exciting opportunities in the areas of long COVID and cardiopulmonary vascular disease. We believe that these areas could greatly expand the total addressable markets and use of the Company’s technology in the future.

2023 and Beyond

As discussed above, we are focused on achieving early commercial traction with our broad lung function evaluation label granted by the FDA in late 2022. In parallel, we are exploring a variety of partnering opportunities. Once we have achieved some of these near-term milestones, we will explore the appropriate timing and structure to finance the continued commercial efforts, clinical trials to seek approval for the high-value gas exchange and pulmonary vascular disease indications and continue to improve our polariser system and imaging software.

This important milestone of FDA approval would not have been possible without the dedicated team of employees, consultants and advisers working to bring our much needed technology to clinicians, their patients and the institutions enabling their care. I thank everyone for their hard work in accomplishing this significant achievement.

Richard Hullihen

Chief Executive Officer
25 May 2023

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Strategic Report

1. Introduction 

The Group comprises medical drug-device combination companies operating in the high-resolution medical imaging market. The Group develops equipment that enables existing MRI systems to achieve an improved level of pulmonary functional imaging and specialises in the use of polarised xenon gas (129Xe ) as an imaging agent to visualise ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of oxygen to diffuse through the alveolar membrane into the pulmonary vasculature) regionally down to the smallest airways of the lungs, the tissue barrier between the lung and the bloodstream and in the pulmonary vasculature; and now also microvascular haemodynamics within the lung, a novel diagnostic approach. The Group will also register and sell the high-performance MRI radiofrequency (RF) coils which are a required component for imaging 129Xe in the MRI system. Providing access to these coils facilitates the adoption of the Xenon technology by providing application-specific RF coils which optimise the imaging of 129Xe in MRI equipment.

The Group was formed on 31 May 2017 when the Company acquired Polarean, Inc (the “Subsidiary”). The Subsidiary was formed as a result of two mergers: the first between Polarean Merger-Sub Inc. and m2m, a company that the Subsidiary had developed a relationship with during the course of previous research and commercialisation programmes in the US and the second between m2m and the Subsidiary. m2m was previously a portfolio company of Amphion Innovations plc (“Amphion”), a developer of medical, life science, and technology businesses, which is itself currently listed on AIM.

2. Investment Case

Pulmonary disease currently affects hundreds of millions of people globally, including approximately 174 million people who suffer from Chronic Obstructive Pulmonary Disease (“COPD”), which is responsible for approximately 6% of such deaths globally each year. In the US more than 30 million people suffer from a chronic lung disease such as COPD, which includes emphysema, chronic bronchitis and asthma. In addition to its significant human toll, pulmonary disease also represents an economic burden in excess of US$150 billion annually in the US alone.

Every type of pulmonary disease involves some combination of ventilation and/or gas exchange impairment, yet the successful and cost-effective treatment of lung disease is hampered by sub-optimal methods for quantifying pulmonary ventilation and gas exchange. Current diagnostic techniques are either imprecise (such as spirometry) and/or expose the patient to potentially dangerous radiation (such as x-rays, CT scans and nuclear scintigraphy). While spirometry has benefits as a screening tool, none of these current methods can visualise ventilation or gas exchange regionally in the smallest airways, where lung disease typically begins and where improvements from new pharmaceutical therapies can first be detected.

As such, the Group operates in an area of significant unmet medical need and is pursuing approval by the US Food & Drug Administration (“FDA”) for the Group’s drug-device combination product using hyperpolarised xenon-129 gas to enhance MRI in pulmonary medicine. The Company submitted a new drug application (“NDA”) to the FDA on 5 October 2020 after the successful completion of the FDA Phase III clinical trials in the US for the Group’s technology. The 80-patient equivalence clinical trials were conducted at Duke University Medical Center, the University of Virginia and The University of Cincinnati - three leading US research hospitals. Enrolment of the clinical trials was completed in November 2019. In January 2020, the Company announced that both clinical trials met their primary endpoints, within the prospectively defined equivalence margin (+/-14.7%) when compared to the FDA-approved reference standard, 133Xenon scintigraphy imaging. On 5 October 2021, the Company received a Complete Response Letter (“CRL”) from the FDA requesting that the Company to address approvability issues identified by the FDA ahead of NDA resubmission. On 30 March 2022, the Company filed the resubmission of the NDA with the FDA. On 20 April 2022, the Company announced that the FDA had accepted the resubmission of the NDA and established a user fee goal date of 30 September 2022. On 30 September 2022, the Company announced that the FDA had granted the Company a 90 day extension to the NDA review timeline. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with magnetic resonance imaging ("MRI") for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. On 28 December 2022, the Company also announced that, simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA that will further support a successful launch of the technology into the clinical marketplace: XENOVIEW VDP software and the XENOVIEW 3.0T Chest Coil. XENOVIEW VDP is image processing software that analyzes a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualization and evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. This image analysis platform quantifies normalized xenon intensity of a ventilated space using a pulmonary hyperpolarised 129-Xe ventilation MR image and accompanying proton chest MR image. The software will be used by clinicians to assist in the interpretation and numerical classification of hyperpolarized 129-Xe ventilation MR images. The Polarean XENOVIEW 3.0T Chest Coil is a flexible, single channel, transmit-receive (T/R) RF coil tuned to 129Xe frequency on a 3.0T MRI magnetic field of a compatible MRI scanner. The Polarean XENOVIEW 3.0T Chest Coil is indicated to be used in conjunction with compatible 3.0T MRI scanners and approved xenon Xe 129 hyperpolarised for oral inhalation for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. The Chest Coil is intended to be worn by a patient who inhales hyperpolarised 129Xe gas (XENOVIEW) to obtain an MR image of the regional distribution of hyperpolarised 129Xe in the lungs.

The Group’s technology overcomes important limitations of current lung diagnostic methods, providing the ability to visualise, quantify and monitor both the structure and function of the smallest airways and alveolar spaces with enhanced sensitivity and without harmful radiation. This provides a unique, valuable and more precise tool to help diagnose disease earlier, identify the type of intervention likely to benefit a patient, monitor the efficacy of treatment and facilitate developing new therapies for pulmonary diseases.

3. Group Structure and History

The Company was incorporated in England and Wales on 24 October 2016 with company registration number 10442853. The Company’s registered office is 27-28 Eastcastle Street, London, W1W 8DH.

On 31 May 2017, m2m, a company formed in the US State of Delaware on 18 February 1999, was merged into the Company.

On 29 March 2018, the Company’s shares were admitted to trading on the AIM market of the London Stock Exchange.

4. Information on Polarean, m2m and Strategy of Group

4.1 Polarean, Inc. – Background

The Subsidiary was co-founded by Dr Bastiaan Driehuys, a current Director of the Company, and John Sudol, a former director of the Subsidiary, in 2011. Prior to co-founding the Subsidiary, Dr Driehuys was a member of a research team at Princeton University in the early 1990s which was amongst the first research teams to focus on hyperpolarised gas MRI technology; in particular isotopically enriched helium (3He). The team developed and held key patents relating to the technology. The technology was acquired in 1999 by Amersham, Inc. (“Amersham”), with the goal of commercialising hyperpolarised helium products to be marketed and distributed alongside Amersham’s full line of contrast agent products. Dr Driehuys led the development efforts for Amersham, which continued the development of these hyperpolarised helium products throughout the early 2000s until GE Healthcare (“GE”) acquired Amersham in 2004.

GE continued the research and development of hyperpolarised gas MRI after the acquisition of Amersham, focusing on 129Xe as a more effective substitute for 3 He in visualising ventilation. GE also began to explore ways in which 129Xe could be used to image gas exchange within the lung in addition to ventilation. These work programmes culminated in the conduct of a Phase I/II clinical trial at Duke University in 2008-2009. GE also filed Investigational New Drug Applications (‘INDs”) with the FDA for both 3He and 129Xe. By 2010, after an investment of approximately US$40 million in the technology and with the regulatory path for hyperpolarised gas remaining unclear, GE decided to out-license the hyperpolarised gas technology and the related patent families that it had developed and/or maintained to the Subsidiary, due to the scale at the time and the early-stage nature of the technology’s development.

In December 2011, the Subsidiary negotiated the acquisition of all of GE’s assets related to the hyperpolarised MRI project, including an inventory of polarisers and parts and the licenses (or outright ownership) of the related patent families.

Following the acquisition of GE’s hyperpolarisation assets, the Subsidiary focused on three key objectives:

• building and selling polarisers to research users to generate operating revenue and to disseminate the technology to academic research institutions that generate clinical data in order to build additional interest in the technology;
• further developing the xenon hyperpolarisation technology in order to meet clinical use specification requirements; and
• liaising with the FDA in order to clarify the FDA regulatory path under which the product could achieve clearance to market for clinical use.

In July 2012, the US Congress passed the FDA Safety and Innovation Act and the Medical Gas Act, which clarified and simplified the path under which hyperpolarised gas MRI technology could be approved for clinical use by the FDA.

As a result of discussions between the Group and the FDA, the Directors believed that a clearer path towards regulatory approval existed. As such, following listing our shares on the AIM market the Group began conducting the clinical studies required for FDA approval to market. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

Between January 2012 and May 2017, the Subsidiary generated over US$3.7 million of revenue from selling polarisers to customers in Canada, Germany, the UK and the US for research use, relating to both clinical (human) and pre-clinical (animal) applications. In addition, the Subsidiary received additional funding of approximately US$2.5 million from Nukem and other Series A investors. Prior to the m2m merger, the Subsidiary was also successful in receiving grant funding, including a US$3 million grant awarded in April 2017 by the US National Heart, Lung and Blood Institute (NHLBI) following a competitive application process (for which the research will be conducted with its clinical collaborator, the Cincinnati Children’s Hospital) and a US$250,000 small business research loan from the North Carolina Biotech Center in March 2017, which was also awarded following a competitive application process.

4.2 The Group’s Technology and Products

The Subsidiary’s lead product has been designated as a drug-device combination by the FDA. The Subsidiary’s product enables the visualisation of hyperpolarised ¹²⁹Xe (“HPX”) through MRI technology to help diagnose lung disease earlier, identify the type of intervention likely to benefit a patient and to monitor the efficacy of treatment. As a result of the FDA’s drug-device designation, the Subsidiary’s products will be approved and sold only for use with each other. The products are currently being used at a number of research sites on a pre-FDA clearance basis to facilitate the research and evaluation of lung function, to assist in making improved disease progression assessment and to clearly visualise the effectiveness of several therapeutics which are under development. The Group currently generates revenue from the sale of products within its ¹²⁹Xe gas hyperpolarisation platform.

Implementing the Group’s technology in a clinical setting is straightforward: prior to the MRI scan a patient breathes in a small amount of inert HPX to provide an extremely strong MRI signal. This transforms the MRI from a technology that is not applicable to the lungs into one that is able to provide multiple images of the lung structure and function in one 10-20 second breath-hold. HPX MRI overcomes the limitations of traditional pulmonary function testing as HPX MRI:

• is more accurate and reproducible than spirometry and other traditional pulmonary function tests, enabling the detection and mapping of small and localised changes in lung ventilation and gas exchange over time;
• provides regional information about lung disease without exposure to ionising radiation or radioactivity; and
• assesses ventilation and gas exchange in the smallest airways, where disease often begins.

The Group’s technology works in conjunction with traditional MRI, transforming it into a powerful diagnostic modality for the lung. The Group’s approach is to take ¹²⁹Xe, an inert gas, and hyperpolarise the nucleus to create an MRI signal which is approximately 100,000 times stronger than a conventional MRI signal. When the MRI scan is undertaken, the HPX resonates at different frequencies: (i) in the bronchioles and alveoli of the lung; (ii) in the barrier tissue of the lung; and (iii) when dissolved in arterial blood in the pulmonary vasculature, thus providing information on ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of air to diffuse through the alveolar membrane into the pulmonary vasculature). As all pulmonary diseases result from impairments to the free flow of air through bronchioles, or from abnormal gas exchange between the lung alveoli and the pulmonary vasculature, the images that result from HPX MRI scans which have been executed using the Group’s technology can aid diagnosis, by enhancing the physician’s ability to clearly identify issues with ventilation and gas exchange on a regional basis, down to the smallest of airways. Hyperpolarisation of the ¹²⁹Xe is accomplished by placing a non-radioactive isotope of Xenon (¹²⁹Xe) into a beam of circularly polarised laser light in the presence of very small concentration of the alkali metal Rubidium, which acts as a physical catalyst in the hyperpolarisation process. The result is ¹²⁹Xe whose nuclear magnetic spin is highly aligned but not chemically or biologically different than unpolarised ¹²⁹Xe, an inert gas. This hyperpolarised state persists for around 2 hours allowing ample time to administer the HPX to the patient.

The Group’s products include:

• the ¹²⁹Xe gas, blended and made under GMP at high purity, to be polarised within the polariser;
• the polariser itself, of which the latest model, the Polarean 9820 Xenon Hyperpolariser, has been designed to deliver up to 3 litres of HPX per hour (approximately 5-10 doses) of which each dose is to be used within 30 minutes of its production in order to retain sufficient polarisation to create a strong image;
• the dose delivery inhalation bag, made of HPX-compatible impermeable plastic materials and a mouthpiece for ease of inhalation; and
• the Polarean 2881 Polarisation Measurement Station, which provides a calibrated measurement of the polarisation of hyperpolarised gas within the dose delivery inhalation bag.

The Group currently designs and builds the polariser equipment at a contract manufacturer and has relationships with GMP gas producers to supply the Group with high purity ¹²⁹Xe according to the Group’s specifications.

In order to take advantage of the Group’s current products, an MRI machine is required to be outfitted with hardware and software capable of operating at ¹²⁹Xe frequency to detect the HPX signal. In addition, the patient will need to wear a ¹²⁹Xe RF chest coil to allow for detecting the HPX MR signal in the lungs. Approximately 35,000 MRI machines are currently in use worldwide and technically many of these can be easily adapted to be used with ¹²⁹Xe frequency. The Group’s products can be placed near the MRI scanner for ease of radiology workflow and, following the m2m merger, the Group has continued to explore ways to further integrate the Group’s existing technology with the coils which had previously been the focus of m2m.

4.3 Location

The Group is based at the Meridian Corporate Center, located in the Research Triangle Park area of North Carolina, which provides a favourable location at which to further develop the core technology and product range. The Group’s facilities consist of more than 6,900 square feet of combined offices, laboratory space, inventory warehouse and assembly and testing areas. The Group benefits from facilities that were originally purpose-built by GE for the design and manufacture of hyperpolarisation equipment and components, pursuant to FDA-mandated guidelines.

Within these facilities are a dedicated research and development laboratory equipped with 3-phase power, central compressed air, specialty gas handling and distribution and separate heating, ventilation and air conditioning. The laboratory area also includes optical cell production equipment capable of simultaneous processing of four optical cells for Xenon applications. The laboratory is designed for safe operation of class 4 lasers and is equipped with laser power and spectral testing apparatus.

The Group also maintains a dedicated polariser test bed that is used for product development and a dedicated Nuclear Magnetic Resonance (“NMR”) system capable of delivering available electromagnetic field strength, utilised for calibrating absolute polarisation measurements of hyperpolarised gas samples.

4.4 The Regulatory Environment

Prior to the receipt of any approvals for clinical use, the Group sold its polarisers and disposables for research use only to academic medical centres with their research being subject to oversight by their respective institutional review boards and conducted under IND from the FDA or equivalent regulatory body.

On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

4.5 The Group’s Customers

The Group’s existing customer base already comprises some of the world’s luminary medical imaging research institutions. Indeed, there are numerous research institutions worldwide utilising the Group’s system and products, including Cincinnati Children’s Hospital, the University of Virginia, University of Wisconsin – Madison, Duke University, University of Kansas, the University of Iowa and the University of Texas MD Anderson Cancer Center in the US, Robarts Research Institute and Hospital for Sick Children (SickKids) in Canada, the University of Oxford and the University of Nottingham in the UK and the Fraunhofer Institute for Toxicology and Experimental Medicine in Germany.

4.6 The Group’s Suppliers

The Group has entered into Master Service Agreements with two CROs in relation to the Phase III trial. Pharma Start LLC, doing business as Firma Clinical Research, managed the trials and oversaw the recruitment of patients for the trial. In addition, Icon Clinical Research Limited assisted with the medical imaging aspects of the trial.

The Group has a long-standing relationship with its strategic investor Nukem Isotopes GmbH (“Nukem”), a leading global supplier of ¹²⁹Xe, the isotope of xenon which is provided to the various gas blenders that in turn supply gas to the Group. It has a supply agreement with Nukem for ¹²⁹Xe.

In June 2020 the Group signed an agreement with Linde Gas North America LLC (“Linde”), in relation to the supply of the Group’s drug product, a ¹²⁹Xenon gas blend. This agreement contains provision for the supply of bulk ¹²⁹Xe to be manufactured into the Active Pharmaceutical Product (API), ¹²⁹Xe, and for the blending, packaging, and distribution of its drug product under GMP. On 28 December 2022, the Group signed an amended agreement with Linde, which modified some commercial terms and limited the agreement to the blending packaging and distribution of it drug product under GMP.

The Group has an arrangement with the Blur Product Development (“Blur”) to build its polariser systems in Blur’s GMP facilities.

4.7 Current Trading and Prospects

Trading of the Group since the Company’s IPO continues to be in line with the Directors’ expectations. The potential of the Group’s technology enables the Directors to view the future with confidence as the Company focuses on commercialisation of XENOVIEW.

4.8 Growth Strategy

With the recent FDA approval, the Group is adopting a traditional market entry strategy of building market awareness for its technology through key opinion leaders and a direct sales force to reach the key decision makers within its initial target market of large academic medical centres. In implementing this strategy, the Group benefits from approximately 1,000 journal articles on the use of hyperpolarised gas MRI that are currently published in peer-reviewed journals. Over time, as more research centres purchase the Group’s equipment and begin clinical studies, an increasing number of peer reviewed scientific articles are likely to be published, further enhancing the Group’s credibility and raising awareness of the Group’s technology. The Directors believe that the market for polarisers will grow as the technology gains wider acceptance as a tool for studying lung disease and for monitoring the effectiveness of therapeutics. The Group also intends to continue patenting and in-licensing hyperpolarised gas technology IP to protect its current position.

The Group’s initial sales targets will be the radiology and pulmonary medicine departments of top academic hospital organisations in the US, who are opinion leaders in the use of new diagnostic technologies and their application in a clinical setting.

The Group is expanding its sales and marketing teams. Because of the specialty nature of the Group’s products in the pulmonary specialist market, which is concentrated in approximately 1,000 medical centres, the Directors believe that a small specialty sales force can be deployed effectively at reasonable cost.

The Group may also choose to partner with companies that offer complementary products.

Furthermore, the Directors believe that the Group’s products will benefit a number of clinical applications. While the Group’s HPX MRI technology provides more specific information than currently available from existing lung diagnostic procedures (especially spirometry), the Group will focus its use on specific clinical conditions where the high accuracy of HPX MRI and greater cost are justified. The Directors do not believe that HPX MRI will replace low-cost spirometry as a general screening tool but believe that it should add value in more demanding clinical applications where HPX MRI addresses unmet diagnostic needs. These applications could include, but are not limited to, the following:

• the monitoring of COPD therapy, especially for the most severe cases;
• the management of cystic fibrosis;
• determining the optimal use of biologic therapy in chronic asthma;
• a more efficient diagnosis of dyspnoea and the chronic cough;
• providing guidance for radiation therapy planning of lung cancer treatment;
• providing guidance for interventional pulmonology procedures including ablation and the placement of valves and stents;
• surgical procedure planning for lung transplant and volume reduction surgery;
• diagnosis of ILD and monitoring of ILD therapy;
• diagnosis of pulmonary vascular disease (PVD) including pulmonary arterial hypertension (PAH) and monitoring of therapy; and
• diagnosis and monitoring of long COVID patients.

The Directors have begun to develop relationships with a range of strategic partners and will evaluate opportunities which will enable the Group to address its target markets globally, either alone or in collaboration with a partner. 

5. Intellectual Property (“IP”)

The Group’s technology has been developed in four areas: (i) hyperpolarising gas; (ii) assuring the quality of the hyperpolarised gas; (iii) using the polarised gas in MRI applications; and (iv) developing and producing specialised RF coils to improve signal-to-noise ratios (“SNR”). GE had put a comprehensive patent policy in place to protect its technology from potential competitors. The Group is now the sole owner of this IP portfolio, which is based on 10 patent families, and when combined with the 7 patents that were previously owned by m2m, that were transferred to the Group following the m2m Merger, the Group’s portfolio covers four broad types of patents:

• imaging methods – these cover the imaging of a subject, or patient, who has inhaled a hyperpolarised noble gas and the functionality of the gas as a contrast agent. Newly licensed technology from Duke University extends the protection over these patents through to the early 2030s;
• hyperpolarisation methods – these are polarimetry patents covering the methods by which noble gases are polarised and the methods by which the resulting polarised gas is isolated and delivered to patients. The latest of these patents expire in the early 2020s;
• hyperpolarisation equipment – these patents cover the multiple preferred mechanical design and automation elements of hyperpolarised equipment; and
• RF coil patents – these patents cover the use of cryogenics to improve RF coils SNR and image quality and may play an important part in the next generation of applications such as neurological, cardiac and oncology imaging.

Polarean is committed to proactively developing further IP, both internally and through licensing arrangements with third parties, as part of the Group’s overall growth strategy. The third parties are likely to include the Group’s key collaborative academic sites, such as Duke University, that are seeking to develop emerging applications and technologies. Because of the Group’s extensive patent portfolio and leading market position, the Directors believe the Group is an attractive licensing partner for academic research institutions that are interested in out-licensing such IP. One such patent application (US15/120013), which is currently pending, relates to improving the overall efficiency of the hyperpolarisation process. This patent has also been exclusively licensed to the Group by Duke University. The Directors believe that this patent, now having been prosecuted successfully to issuance in a number of geographic jurisdictions worldwide, would enable the Group to protect methods for increasing the level of hyperpolarisation significantly, which could improve the competitive economics of the Group’s products.

6. Principal Risks and Uncertainties  

The principal risks and uncertainties facing the Group are detailed below:

Early stage of operations

The Group’s operations are at an early stage of development and there can be no guarantee that the Group will be able to, or that it will be commercially advantageous for the Group to, develop its proprietary technology. Further, the Group currently has no positive operating cash flow and its ultimate success will depend on the Directors’ ability to implement the Group’s strategy, generate cash flow and access capital markets.

Principal mitigation

The Group has successfully advanced the ¹²⁹Xe technology for several years, including selling polarisers for the research market. The Group has been able to access capital required to continue to advance the technology.

Regulatory approvals and compliance

The Group will need to obtain various regulatory approvals (including FDA and European Medicines Agency (“EMA”) approvals) and otherwise comply with extensive regulations regarding safety, quality and efficacy standards in order to market its future products. These regulations, including the time required for regulatory review, vary from country to country and can be lengthy, expensive and uncertain.

Principal mitigation

The Group utilises external specialists in regulatory affairs who consult with other experts to ensure that internal control processes and clinical trial designs meet current regulatory requirements. The Group also engages directly with regulatory authorities when appropriate.

Future funding requirements

The Group will need to raise additional funding or enter into a strategic partnership with industry partners to undertake work beyond that being funded by the £27 million (before expenses) 2021 fundraising. There is no certainty that this will be possible at all or on acceptable terms.

Principal mitigation

The Group successfully engaged with investors to generate significant cash resources to date, including the 2021 financing that raised £27 million, before expenses. The Group’s management team expects that continued access to capital markets, or other access to capital, will be required to support the Group through regulatory approval and initial commercialisation efforts in the US. See Going Concern discussion below.

Dependence on key personnel

The success of the Group, in common with other businesses of a similar size, will be highly dependent on the expertise and experience of the Directors and key employees. However, the retention of such key personnel cannot be guaranteed. Should key personnel leave the Group’s business, prospects, financial condition or results of operations may be materially adversely affected.

Principal mitigation

The Group’s recruitment processes are designed to identify and attract the best candidates for specific roles. The Group aims to provide competitive rewards and incentives to staff and directors.

Intellectual property and proprietary technology

No assurance can be given that any current or future patent applications will result in granted patents, that the scope of any patent protection will exclude competitors or provide competitive advantages to the Group, that any of the Group’s patents will be held valid if challenged or that third parties will not claim rights in or ownership of the patents and other proprietary rights held by the Group.

Principal mitigation

The Group has a long-standing track record of IP generation and successful applications and has a long-standing relationship with our patent attorney who has a deep understanding of our technology. The Group actively manages its IP, engaging with specialists to apply for and defend IP rights in appropriate territories.

Technology and products

The Group is a developer and service provider for noble gas ¹²⁹Xe devices and ancillary instruments with a special focus on pulmonary imaging. The development and commercialisation of its proprietary technology and future products, which are in early stages of development, will require multiple series of clinical trials and there is a risk that safety and efficacy issues may arise when the products are tested. There is also a risk that there will be delays to the development of the products or that unforeseen technical problems arise as the Group’s technology becomes increasingly automated. These risks are common to all new medical products and there is also a risk that the clinical trials may not be successful.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as safety, manufacturing and software development.

Research and development risk

The Group will be operating in the life sciences and medical device development sector and will look to exploit opportunities within that sector. The Group will therefore be involved in complex scientific research and industry experience indicates that there may be a very high incidence of delay or failure to produce results. The Group may not be able to develop new products or to identify specific market needs that can be addressed by technology solutions developed by the Group.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as conducting clinical trials and regulatory affairs.

Competition

The Group notes that several start-ups operating in the CT software space have begun efforts to commercialise products which represent to characterise lung ventilation. These technologies use ionising radiation, whereas the Group’s technology does not. In addition, these technologies are unable to further assess gas exchange, red blood cell transport, nor microvascular haemodynamics.

Principal mitigation

The Group believes that these emerging technologies validate the unmet need for the use of imaging in assessing pulmonary function. However, their use of ionising radiation, combined with their inability to assess comprehensive pulmonary function will render their utility limited and the Directors see no effect on the current market expectations of Polarean.

Reliance on third parties

The business model for the Group anticipates that it will have limited internal resources over the next few years and that it will use third party providers wherever possible to conduct the research, development, registration, manufacture, marketing and sales of its proposed products. The commercial success of the Group’s products will depend upon the performance of these third parties.

Principal mitigation

The Group seeks experts in the areas where it utilises outsourcing. Wherever possible, the Group seeks to have duplicate suppliers to lessen the reliance on a particular vendor.

Manufacturing

There can be no assurance that the Group’s proposed products will be capable of being manufactured in commercial quantities, in compliance with regulatory requirements and at an acceptable cost. The Group outsources the manufacture of the raw materials and finished products required in connection with the research, development and commercial manufacture of its proposed products and, as such, is wholly dependent upon third parties for the provision of adequate facilities and raw material supplies. ¹²⁹Xe, the specific isotope of xenon which is the active ingredient in the Group’s drug-device product, is available from a limited number of suppliers and there can be no assurance that adequate supplies of this material at acceptable cost can be obtained. In addition, where the Group is dependent upon third parties for manufacture, its ability to procure the manufacture of the drug-device in a manner which complies with regulatory requirements may be constrained, and its ability to develop and deliver such products on a timely and competitive basis may be adversely affected.

Principal mitigation

The Group has designed the manufacturing process to be scalable and has internal experts who train the outside vendors. The Group has established relationships with two ¹²⁹Xe suppliers to mitigate the risk that ¹²⁹Xe supply will be a limitation to the development and commercialisation of its products. In addition, the Group has established a relationship with a GMP outside polariser manufacturer.

Product development timelines

Product development timelines are at risk of delay, particularly since it is not always possible to predict what the FDA will require for approval of future NDA’s. There is a risk therefore that product development could take longer than presently expected by the Directors. If such delays occur the Group may require further working capital. The Directors shall seek to minimise the risk of delays by careful management of projects.

Principal mitigation

The Group utilises consultants who are experts in preparing and filing future NDAs in the US.

General legal and regulatory issues

The Group’s operations are subject to laws, regulatory restrictions and certain governmental directives, recommendations and guidelines relating to, amongst other things, occupational safety, laboratory practice, the use and handling of hazardous materials, prevention of illness and injury, environmental protection and animal and human testing. There can be no assurance that future legislation will not impose further government regulation, which may adversely affect the business or financial condition of the Group.

Principal mitigation

The Group consults experts for advice in areas such as occupational safety, laboratory practice and human testing.

Healthcare pricing environment

In common with other healthcare products companies, the ability of the Group and any of its licensees or collaborators to market its products successfully depends in part on the extent to which reimbursement for the cost of such products and related treatment will be available from government health administration authorities, private health coverage insurers and other organisations.

Principal mitigation

The Group is consulting with several experts in the field of reimbursement for healthcare products in the US to determine the best strategy for accessing adequate reimbursement for its products.

7. Section 172 statement

As required by section 172 of the Companies Act 2006 (the “Act”), a director of a company must act in the way he or she considers, in good faith, would likely promote the success of the company for the benefit of the shareholders. In doing so, the director must have regard, amongst other matters, to the following issues:

• the likely consequences of any decisions in the long term;
• the interests of the company’s employees;
• the need to foster the company’s business relationships with suppliers/customers and others;
• the impact of the company’s operations on the community and environment;
• the company’s reputation for high standards of business conduct; and
• the need to act fairly between members of the company.

The information required by section 172 of the Act is included in the full Annual Report.

Kenneth West
Non-Executive Chairman

25 May 2023

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Consolidated Statement of Comprehensive Income

The results reflected above relate to continuing activities.

There are no items of Other Comprehensive Income (“OCI”) for the year other than the loss above and therefore no separate statement of other comprehensive income has been presented.

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Consolidated Statement of Financial Position

These Financial Statements were approved and authorised for issue by the Board of Directors on 25 May 2023 and were signed on its behalf by:

Kenneth West
Non-Executive Chairman

Company number: 10442853

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Consolidated Statement of Changes in Equity

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Consolidated Statement of Cash Flows

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Notes on Financial Statements

The notes are available in the printable PDF of the results.  To download it, please click here

Notice of Annual General Meeting

In addition, Polarean confirms that the Annual Report and Accounts for the year ended 31 December 2022, the Notice of the Annual General Meeting ("AGM") and a Form of Proxy are now available on the Company's website (http://www.polarean-ir.com/content/investors/annual-reports.asp) and will be posted to shareholders shortly.

The AGM will be held at 2500 Meridian Parkway, Suite 175, Durham, NC 27713, USA at 2 p.m. BST / 9 a.m. EST on 28 June 2023.

Highlights

• United States Food and Drug Administration (“FDA”) approval received for the Company’s drug device combination product, XENOVIEW (xenon Xe 129 hyperpolarised), a hyperpolarised contrast agent indicated for use with magnetic resonance imaging (“MRI”) for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older
• Simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA; XENOVIEW VDP is image processing software that analyses a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualisation and evaluation of lung ventilation and the Polarean XENOVIEW 3.0T Chest Coil
• Research system placements at McMaster University in Ontario, Canada and Cincinnati Children’s Hospital Medical Center (“CCHMC”)
• Appointment of Frank Schulkes, Dan Brague and Marcella Ruddy, MD to the Board as independent Non-Executive Directors
• Appointment of Ken West as Non-Executive Chairman, following the retirement of Jonathan Allis
• Research collaboration with Oxford University Hospitals NHS Trust for long-COVID
• Net cash of US$16.4 million as of 31 December 2022

Post-period end

• First order for a XENOVIEW gas blend cylinder for the production of XENOVIEW received from CCHMC, representing key milestone and execution of commercial plan
• First clinical scan utilising XENOVIEW technology in the United States conducted at CCHMC, marking key milestone for imaging of lung ventilation
• Selected as one of the featured companies as a poster presenter at the American Thoracic Society’s (“ATS”) 2023 Respiratory Innovation Summit

Richard Hullihen, CEO of Polarean, said: "We ended the year with a tremendous positive in receiving our FDA approval for XENOVIEW. This was a long road culminating with the decision we were looking for, and an extraordinary amount of work went into this process from the entire team. We have now begun to roll out XENOVIEW for clinical use and expect to see further hospitals adopt doing clinical XENOVIEW scans in the coming months. We also continue to explore potential future applications for our technology and remain positive for the year ahead. Separately, we have been shortlisted for Breakthrough of the Year and Best Technology at the 2023 European Mediscience Awards, which celebrates private and listed healthcare, biotech and life sciences companies; we are delighted by this validation of our technology and our achievement in securing FDA approval, and are excited to see the outcome.

“On behalf of the Board and the whole Polarean team, I would like to extend my thanks to our shareholders for all their support and we look forward to further updating the market in due course.” 

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014.

Inquiries: 

About Polarean (www.polarean.com)

The Company and its wholly owned subsidiary, Polarean, Inc. (together the "Group") are revenue-generating, medical imaging technology companies operating in the high-resolution medical imaging space. Polarean aspires to revolutionise pulmonary medicine by bringing the power and safety of MRI to the respiratory healthcare community in need of new solutions to evaluate lung ventilation, diagnose disease, characterise disease progression, and monitor response to treatment. By researching, developing, and commercialising novel imaging solutions with a non-invasive and radiation-free functional imaging platform. Polarean’s vision is to help address the global unmet medical needs of more than 500 million patients worldwide suffering with chronic respiratory disease. Polarean is a leader in the field of hyperpolarisation science and has successfully developed the first and only hyperpolarised MRI contrast agent to be approved in the United States. On Dec. 23, 2022, the FDA granted approval for Polarean’s first drug device combination product, XENOVIEW^TM (Xenon Xe¹²⁹ hyperpolarised). Xe¹²⁹ MRI is also currently being studied for visualisation and quantification of gas exchange regionally in the smallest airways of the lungs, across the alveolar tissue membrane, and into the pulmonary bloodstream for future clinical indications.

XENOVIEW IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Risk of Decreased Image Quality from Supplemental Oxygen: Supplemental oxygen administered simultaneously with XENOVIEW^TM inhalation can cause degradation of image quality. For patients on supplemental oxygen, withhold oxygen inhalation for two breaths prior to XENOVIEW^TM inhalation, and resume oxygen inhalation immediately following the imaging breath hold.

Risk of Transient Hypoxia: Inhalation of an anoxic gas such as XENOVIEW^TM may cause transient hypoxemia in susceptible patients. Monitor all patients for oxygen desaturation and symptoms of hypoxemia and treat as clinically indicated.

Adverse Reactions

Adverse Reactions in Adult Patients: The adverse reactions (> one patient) in efficacy trials were oropharyngeal pain, headache, and dizziness.  Adverse Reactions in Pediatric and Adolescent Patients: In published literature in pediatric patients aged 6 to 18, transient adverse reactions were reported: blood oxygen desaturation, heart rate elevation, numbness, tingling, dizziness, and euphoria. In at least one published study of pediatric patients aged 6 to 18 years, transient decrease in SpO2% and transient increase in heart rate was reported following hyperpolarized xenon Xe 129 administration. XENOVIEW^TM is not approved for use in pediatric patients less than 12 years of age.

Please see full prescribing information at www.xenoview.net

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Chairman’s Statement

I am pleased to be able to write this letter with the very important milestone of United States Food & Drug Administration (“FDA”) approval of the Company’s drug device combination product, XENOVIEW, having been accomplished. The broad label of “evaluation of lung ventilation in adults and pediatric patients aged 12 years and older” allows the company to execute its commercial strategy of selling its polarizer and approved gas for clinical scans of patients suffering from a number of lung diseases where the accurate measurement of lung ventilation provides the physician with actionable diagnostic information. In addition, researchers using Polarean’s technology continue to conduct clinical research that supports the broad future potential applications of our technology in areas of gas exchange and cardiopulmonary diagnostics. We are excited to bring Polarean’s technology to clinical medicine, with the potential to be an important part of pulmonary and cardiopulmonary diagnostics, monitoring of severity of disease and patient response to treatments.

During 2022, we strengthened our Board with the addition of three independent Non-Executive Board members who bring extensive industry and medical experience to the Board to assist the company’s successful transition into the commercialization stage. Frank Schulkes brings substantial financing experience in the medical imaging industry and Dan Brague brings experience successfully commercializing diagnostic imaging products. In addition, Dr. Marcella Ruddy brings important pulmonary medical expertise, both in clinical practice and in pharmaceutical development. With these additions to our Board, we believe that we have a world-class Board that can lead the company to successful commercialization of Xenoview.

Having achieved FDA approval, our efforts are now focused on gaining commercial traction and engaging with potential corporate partners to further accelerate our commercial success. Once we have achieved some of these near-term milestones, we will explore the options for additional financing to more aggressively pursue the development of the next indications and advance the continued development of our polarizer system and software. The Company is exploring a broad range of options for future financing, including equity raises and corporate partnering.

On behalf of the Board, I want to thank our employees, stakeholders and shareholders and assure them that we are committed to making Xenoview a commercial and financial success.

Kenneth West

Non-Executive Chairman
25 May 2023

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Chief Executive Officer’s Statement

2022 – Year of Obtaining FDA Approval

We spent much of 2022 working on obtaining FDA approval of our New Drug Application (“NDA”) for XENOVIEW and were please received our approval on 23 December 2022. After receiving a Complete Response Letter (“CRL”) from the FDA in October 2021, we spend the subsequent six months addressing the issues raised in the CRL. On 30 March 2022, the Company refiled the NDA with the FDA. The resubmission addressed the items identified in the CRL. On 22 September the Company announced that the FDA had requested additional information related to the cGMP (Current Good Manufacturing Practice) pre-approval inspection at the partner’s production facility. The Company and its partner addressed the FDA’s request and the Company received FDA approval on 23 December 2022. We were very pleased to receive the broad label of evaluation of lung function in adults and pediatric patients twelve and older. In addition, the FDA indicated that they would allow us to submit a non-clinical plan to obtain approval in pediatric patients six and older. The FDA has granted New Chemical Entity (“NCE”) designation for Xenoview. NCE designation provides the important first mover protection envisioned under the Hatch Waxman legislation.

Commercialization

With FDA approval, the Company is focused on successful commercialization of XENOVIEW for the evaluation of lung function. The Company has an enthusiastic base of US institutions who have been using our technology for research purposes for years. We are leveraging this knowledge and enthusiasm by converting its US research sites to FDA approved configuration and clinical use, which will allow these sites to purchase Xenoview and perform clinical scans. In parallel, we are pursuing various reimbursement codes that could enable the hospitals to be reimbursed for Xenoview, the polarization process, the MRI procedure and the analysis of the pulmonary function imaging. If obtained, we believe that this reimbursement would enable a very compelling return on investment for hospitals to purchase our polarizer systems. We are aggressively pursuing our early commercialization targets of the sale of 15 to 20 polariser systems and 75 to 100 cylinders of Xenoview by the end of 2024.

We are focusing initially on addressing the high end of the US academic and teaching hospital market segment, which comprises approximately the top 1000 institutions nationally having coincident multiple Centres of Excellence in Pulmonary Medicine and Radiology. We believe our strategy of selling the capital equipment and the Xenoview drug on a per cylinder basis could provide a capital equipment and recurring drug sales model that supports rapidly growing revenue.

Financials

Sales for 2022 were below our original expectations, as we did not receive FDA approval in October 2022 as anticipated in the plan. We adjusted our spending plans commensurate with the delayed approval, which allowed us to finish 2022 with a higher than anticipated cash balance of US$16.4 million. We continued to sell our polariser systems into the research market and completed two installations during 2022. The current cash balance is expected to fund the company into late Q2-2024.

Corporate Partnering

We continue to believe that corporate partnering could be an important part of the Company’s business plan. We see the opportunity to help the pharmaceutical industry reduce by significant amounts the size, time required to conduct and costs of their pulmonary drug clinical trials by providing quantitative, reproducible image-based data. We also see the opportunity to partner with MRI manufacturers to open up the MRI applications space to include pulmonary diagnostics, driving the demand for more MRI systems. In addition, we will explore the opportunity to partner with pulmonary disease organizations and foundations to incorporate the use of Xenoview in the diagnosis and treatment of disease.

Future Indications

Researchers are currently conducting clinical trials and pharmaceutical company sponsored investigations in multiple areas of pulmonary disease using our technology. These studies are highlighting the exciting opportunities in the areas of long COVID and cardiopulmonary vascular disease. We believe that these areas could greatly expand the total addressable markets and use of the Company’s technology in the future.

2023 and Beyond

As discussed above, we are focused on achieving early commercial traction with our broad lung function evaluation label granted by the FDA in late 2022. In parallel, we are exploring a variety of partnering opportunities. Once we have achieved some of these near-term milestones, we will explore the appropriate timing and structure to finance the continued commercial efforts, clinical trials to seek approval for the high-value gas exchange and pulmonary vascular disease indications and continue to improve our polariser system and imaging software.

This important milestone of FDA approval would not have been possible without the dedicated team of employees, consultants and advisers working to bring our much needed technology to clinicians, their patients and the institutions enabling their care. I thank everyone for their hard work in accomplishing this significant achievement.

Richard Hullihen

Chief Executive Officer
25 May 2023

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Strategic Report

1. Introduction 

The Group comprises medical drug-device combination companies operating in the high-resolution medical imaging market. The Group develops equipment that enables existing MRI systems to achieve an improved level of pulmonary functional imaging and specialises in the use of polarised xenon gas (129Xe ) as an imaging agent to visualise ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of oxygen to diffuse through the alveolar membrane into the pulmonary vasculature) regionally down to the smallest airways of the lungs, the tissue barrier between the lung and the bloodstream and in the pulmonary vasculature; and now also microvascular haemodynamics within the lung, a novel diagnostic approach. The Group will also register and sell the high-performance MRI radiofrequency (RF) coils which are a required component for imaging 129Xe in the MRI system. Providing access to these coils facilitates the adoption of the Xenon technology by providing application-specific RF coils which optimise the imaging of 129Xe in MRI equipment.

The Group was formed on 31 May 2017 when the Company acquired Polarean, Inc (the “Subsidiary”). The Subsidiary was formed as a result of two mergers: the first between Polarean Merger-Sub Inc. and m2m, a company that the Subsidiary had developed a relationship with during the course of previous research and commercialisation programmes in the US and the second between m2m and the Subsidiary. m2m was previously a portfolio company of Amphion Innovations plc (“Amphion”), a developer of medical, life science, and technology businesses, which is itself currently listed on AIM.

2. Investment Case

Pulmonary disease currently affects hundreds of millions of people globally, including approximately 174 million people who suffer from Chronic Obstructive Pulmonary Disease (“COPD”), which is responsible for approximately 6% of such deaths globally each year. In the US more than 30 million people suffer from a chronic lung disease such as COPD, which includes emphysema, chronic bronchitis and asthma. In addition to its significant human toll, pulmonary disease also represents an economic burden in excess of US$150 billion annually in the US alone.

Every type of pulmonary disease involves some combination of ventilation and/or gas exchange impairment, yet the successful and cost-effective treatment of lung disease is hampered by sub-optimal methods for quantifying pulmonary ventilation and gas exchange. Current diagnostic techniques are either imprecise (such as spirometry) and/or expose the patient to potentially dangerous radiation (such as x-rays, CT scans and nuclear scintigraphy). While spirometry has benefits as a screening tool, none of these current methods can visualise ventilation or gas exchange regionally in the smallest airways, where lung disease typically begins and where improvements from new pharmaceutical therapies can first be detected.

As such, the Group operates in an area of significant unmet medical need and is pursuing approval by the US Food & Drug Administration (“FDA”) for the Group’s drug-device combination product using hyperpolarised xenon-129 gas to enhance MRI in pulmonary medicine. The Company submitted a new drug application (“NDA”) to the FDA on 5 October 2020 after the successful completion of the FDA Phase III clinical trials in the US for the Group’s technology. The 80-patient equivalence clinical trials were conducted at Duke University Medical Center, the University of Virginia and The University of Cincinnati - three leading US research hospitals. Enrolment of the clinical trials was completed in November 2019. In January 2020, the Company announced that both clinical trials met their primary endpoints, within the prospectively defined equivalence margin (+/-14.7%) when compared to the FDA-approved reference standard, 133Xenon scintigraphy imaging. On 5 October 2021, the Company received a Complete Response Letter (“CRL”) from the FDA requesting that the Company to address approvability issues identified by the FDA ahead of NDA resubmission. On 30 March 2022, the Company filed the resubmission of the NDA with the FDA. On 20 April 2022, the Company announced that the FDA had accepted the resubmission of the NDA and established a user fee goal date of 30 September 2022. On 30 September 2022, the Company announced that the FDA had granted the Company a 90 day extension to the NDA review timeline. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with magnetic resonance imaging ("MRI") for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. On 28 December 2022, the Company also announced that, simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA that will further support a successful launch of the technology into the clinical marketplace: XENOVIEW VDP software and the XENOVIEW 3.0T Chest Coil. XENOVIEW VDP is image processing software that analyzes a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualization and evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. This image analysis platform quantifies normalized xenon intensity of a ventilated space using a pulmonary hyperpolarised 129-Xe ventilation MR image and accompanying proton chest MR image. The software will be used by clinicians to assist in the interpretation and numerical classification of hyperpolarized 129-Xe ventilation MR images. The Polarean XENOVIEW 3.0T Chest Coil is a flexible, single channel, transmit-receive (T/R) RF coil tuned to 129Xe frequency on a 3.0T MRI magnetic field of a compatible MRI scanner. The Polarean XENOVIEW 3.0T Chest Coil is indicated to be used in conjunction with compatible 3.0T MRI scanners and approved xenon Xe 129 hyperpolarised for oral inhalation for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. The Chest Coil is intended to be worn by a patient who inhales hyperpolarised 129Xe gas (XENOVIEW) to obtain an MR image of the regional distribution of hyperpolarised 129Xe in the lungs.

The Group’s technology overcomes important limitations of current lung diagnostic methods, providing the ability to visualise, quantify and monitor both the structure and function of the smallest airways and alveolar spaces with enhanced sensitivity and without harmful radiation. This provides a unique, valuable and more precise tool to help diagnose disease earlier, identify the type of intervention likely to benefit a patient, monitor the efficacy of treatment and facilitate developing new therapies for pulmonary diseases.

3. Group Structure and History

The Company was incorporated in England and Wales on 24 October 2016 with company registration number 10442853. The Company’s registered office is 27-28 Eastcastle Street, London, W1W 8DH.

On 31 May 2017, m2m, a company formed in the US State of Delaware on 18 February 1999, was merged into the Company.

On 29 March 2018, the Company’s shares were admitted to trading on the AIM market of the London Stock Exchange.

4. Information on Polarean, m2m and Strategy of Group

4.1 Polarean, Inc. – Background

The Subsidiary was co-founded by Dr Bastiaan Driehuys, a current Director of the Company, and John Sudol, a former director of the Subsidiary, in 2011. Prior to co-founding the Subsidiary, Dr Driehuys was a member of a research team at Princeton University in the early 1990s which was amongst the first research teams to focus on hyperpolarised gas MRI technology; in particular isotopically enriched helium (3He). The team developed and held key patents relating to the technology. The technology was acquired in 1999 by Amersham, Inc. (“Amersham”), with the goal of commercialising hyperpolarised helium products to be marketed and distributed alongside Amersham’s full line of contrast agent products. Dr Driehuys led the development efforts for Amersham, which continued the development of these hyperpolarised helium products throughout the early 2000s until GE Healthcare (“GE”) acquired Amersham in 2004.

GE continued the research and development of hyperpolarised gas MRI after the acquisition of Amersham, focusing on 129Xe as a more effective substitute for 3 He in visualising ventilation. GE also began to explore ways in which 129Xe could be used to image gas exchange within the lung in addition to ventilation. These work programmes culminated in the conduct of a Phase I/II clinical trial at Duke University in 2008-2009. GE also filed Investigational New Drug Applications (‘INDs”) with the FDA for both 3He and 129Xe. By 2010, after an investment of approximately US$40 million in the technology and with the regulatory path for hyperpolarised gas remaining unclear, GE decided to out-license the hyperpolarised gas technology and the related patent families that it had developed and/or maintained to the Subsidiary, due to the scale at the time and the early-stage nature of the technology’s development.

In December 2011, the Subsidiary negotiated the acquisition of all of GE’s assets related to the hyperpolarised MRI project, including an inventory of polarisers and parts and the licenses (or outright ownership) of the related patent families.

Following the acquisition of GE’s hyperpolarisation assets, the Subsidiary focused on three key objectives:

• building and selling polarisers to research users to generate operating revenue and to disseminate the technology to academic research institutions that generate clinical data in order to build additional interest in the technology;
• further developing the xenon hyperpolarisation technology in order to meet clinical use specification requirements; and
• liaising with the FDA in order to clarify the FDA regulatory path under which the product could achieve clearance to market for clinical use.

In July 2012, the US Congress passed the FDA Safety and Innovation Act and the Medical Gas Act, which clarified and simplified the path under which hyperpolarised gas MRI technology could be approved for clinical use by the FDA.

As a result of discussions between the Group and the FDA, the Directors believed that a clearer path towards regulatory approval existed. As such, following listing our shares on the AIM market the Group began conducting the clinical studies required for FDA approval to market. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

Between January 2012 and May 2017, the Subsidiary generated over US$3.7 million of revenue from selling polarisers to customers in Canada, Germany, the UK and the US for research use, relating to both clinical (human) and pre-clinical (animal) applications. In addition, the Subsidiary received additional funding of approximately US$2.5 million from Nukem and other Series A investors. Prior to the m2m merger, the Subsidiary was also successful in receiving grant funding, including a US$3 million grant awarded in April 2017 by the US National Heart, Lung and Blood Institute (NHLBI) following a competitive application process (for which the research will be conducted with its clinical collaborator, the Cincinnati Children’s Hospital) and a US$250,000 small business research loan from the North Carolina Biotech Center in March 2017, which was also awarded following a competitive application process.

4.2 The Group’s Technology and Products

The Subsidiary’s lead product has been designated as a drug-device combination by the FDA. The Subsidiary’s product enables the visualisation of hyperpolarised ¹²⁹Xe (“HPX”) through MRI technology to help diagnose lung disease earlier, identify the type of intervention likely to benefit a patient and to monitor the efficacy of treatment. As a result of the FDA’s drug-device designation, the Subsidiary’s products will be approved and sold only for use with each other. The products are currently being used at a number of research sites on a pre-FDA clearance basis to facilitate the research and evaluation of lung function, to assist in making improved disease progression assessment and to clearly visualise the effectiveness of several therapeutics which are under development. The Group currently generates revenue from the sale of products within its ¹²⁹Xe gas hyperpolarisation platform.

Implementing the Group’s technology in a clinical setting is straightforward: prior to the MRI scan a patient breathes in a small amount of inert HPX to provide an extremely strong MRI signal. This transforms the MRI from a technology that is not applicable to the lungs into one that is able to provide multiple images of the lung structure and function in one 10-20 second breath-hold. HPX MRI overcomes the limitations of traditional pulmonary function testing as HPX MRI:

• is more accurate and reproducible than spirometry and other traditional pulmonary function tests, enabling the detection and mapping of small and localised changes in lung ventilation and gas exchange over time;
• provides regional information about lung disease without exposure to ionising radiation or radioactivity; and
• assesses ventilation and gas exchange in the smallest airways, where disease often begins.

The Group’s technology works in conjunction with traditional MRI, transforming it into a powerful diagnostic modality for the lung. The Group’s approach is to take ¹²⁹Xe, an inert gas, and hyperpolarise the nucleus to create an MRI signal which is approximately 100,000 times stronger than a conventional MRI signal. When the MRI scan is undertaken, the HPX resonates at different frequencies: (i) in the bronchioles and alveoli of the lung; (ii) in the barrier tissue of the lung; and (iii) when dissolved in arterial blood in the pulmonary vasculature, thus providing information on ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of air to diffuse through the alveolar membrane into the pulmonary vasculature). As all pulmonary diseases result from impairments to the free flow of air through bronchioles, or from abnormal gas exchange between the lung alveoli and the pulmonary vasculature, the images that result from HPX MRI scans which have been executed using the Group’s technology can aid diagnosis, by enhancing the physician’s ability to clearly identify issues with ventilation and gas exchange on a regional basis, down to the smallest of airways. Hyperpolarisation of the ¹²⁹Xe is accomplished by placing a non-radioactive isotope of Xenon (¹²⁹Xe) into a beam of circularly polarised laser light in the presence of very small concentration of the alkali metal Rubidium, which acts as a physical catalyst in the hyperpolarisation process. The result is ¹²⁹Xe whose nuclear magnetic spin is highly aligned but not chemically or biologically different than unpolarised ¹²⁹Xe, an inert gas. This hyperpolarised state persists for around 2 hours allowing ample time to administer the HPX to the patient.

The Group’s products include:

• the ¹²⁹Xe gas, blended and made under GMP at high purity, to be polarised within the polariser;
• the polariser itself, of which the latest model, the Polarean 9820 Xenon Hyperpolariser, has been designed to deliver up to 3 litres of HPX per hour (approximately 5-10 doses) of which each dose is to be used within 30 minutes of its production in order to retain sufficient polarisation to create a strong image;
• the dose delivery inhalation bag, made of HPX-compatible impermeable plastic materials and a mouthpiece for ease of inhalation; and
• the Polarean 2881 Polarisation Measurement Station, which provides a calibrated measurement of the polarisation of hyperpolarised gas within the dose delivery inhalation bag.

The Group currently designs and builds the polariser equipment at a contract manufacturer and has relationships with GMP gas producers to supply the Group with high purity ¹²⁹Xe according to the Group’s specifications.

In order to take advantage of the Group’s current products, an MRI machine is required to be outfitted with hardware and software capable of operating at ¹²⁹Xe frequency to detect the HPX signal. In addition, the patient will need to wear a ¹²⁹Xe RF chest coil to allow for detecting the HPX MR signal in the lungs. Approximately 35,000 MRI machines are currently in use worldwide and technically many of these can be easily adapted to be used with ¹²⁹Xe frequency. The Group’s products can be placed near the MRI scanner for ease of radiology workflow and, following the m2m merger, the Group has continued to explore ways to further integrate the Group’s existing technology with the coils which had previously been the focus of m2m.

4.3 Location

The Group is based at the Meridian Corporate Center, located in the Research Triangle Park area of North Carolina, which provides a favourable location at which to further develop the core technology and product range. The Group’s facilities consist of more than 6,900 square feet of combined offices, laboratory space, inventory warehouse and assembly and testing areas. The Group benefits from facilities that were originally purpose-built by GE for the design and manufacture of hyperpolarisation equipment and components, pursuant to FDA-mandated guidelines.

Within these facilities are a dedicated research and development laboratory equipped with 3-phase power, central compressed air, specialty gas handling and distribution and separate heating, ventilation and air conditioning. The laboratory area also includes optical cell production equipment capable of simultaneous processing of four optical cells for Xenon applications. The laboratory is designed for safe operation of class 4 lasers and is equipped with laser power and spectral testing apparatus.

The Group also maintains a dedicated polariser test bed that is used for product development and a dedicated Nuclear Magnetic Resonance (“NMR”) system capable of delivering available electromagnetic field strength, utilised for calibrating absolute polarisation measurements of hyperpolarised gas samples.

4.4 The Regulatory Environment

Prior to the receipt of any approvals for clinical use, the Group sold its polarisers and disposables for research use only to academic medical centres with their research being subject to oversight by their respective institutional review boards and conducted under IND from the FDA or equivalent regulatory body.

On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

4.5 The Group’s Customers

The Group’s existing customer base already comprises some of the world’s luminary medical imaging research institutions. Indeed, there are numerous research institutions worldwide utilising the Group’s system and products, including Cincinnati Children’s Hospital, the University of Virginia, University of Wisconsin – Madison, Duke University, University of Kansas, the University of Iowa and the University of Texas MD Anderson Cancer Center in the US, Robarts Research Institute and Hospital for Sick Children (SickKids) in Canada, the University of Oxford and the University of Nottingham in the UK and the Fraunhofer Institute for Toxicology and Experimental Medicine in Germany.

4.6 The Group’s Suppliers

The Group has entered into Master Service Agreements with two CROs in relation to the Phase III trial. Pharma Start LLC, doing business as Firma Clinical Research, managed the trials and oversaw the recruitment of patients for the trial. In addition, Icon Clinical Research Limited assisted with the medical imaging aspects of the trial.

The Group has a long-standing relationship with its strategic investor Nukem Isotopes GmbH (“Nukem”), a leading global supplier of ¹²⁹Xe, the isotope of xenon which is provided to the various gas blenders that in turn supply gas to the Group. It has a supply agreement with Nukem for ¹²⁹Xe.

In June 2020 the Group signed an agreement with Linde Gas North America LLC (“Linde”), in relation to the supply of the Group’s drug product, a ¹²⁹Xenon gas blend. This agreement contains provision for the supply of bulk ¹²⁹Xe to be manufactured into the Active Pharmaceutical Product (API), ¹²⁹Xe, and for the blending, packaging, and distribution of its drug product under GMP. On 28 December 2022, the Group signed an amended agreement with Linde, which modified some commercial terms and limited the agreement to the blending packaging and distribution of it drug product under GMP.

The Group has an arrangement with the Blur Product Development (“Blur”) to build its polariser systems in Blur’s GMP facilities.

4.7 Current Trading and Prospects

Trading of the Group since the Company’s IPO continues to be in line with the Directors’ expectations. The potential of the Group’s technology enables the Directors to view the future with confidence as the Company focuses on commercialisation of XENOVIEW.

4.8 Growth Strategy

With the recent FDA approval, the Group is adopting a traditional market entry strategy of building market awareness for its technology through key opinion leaders and a direct sales force to reach the key decision makers within its initial target market of large academic medical centres. In implementing this strategy, the Group benefits from approximately 1,000 journal articles on the use of hyperpolarised gas MRI that are currently published in peer-reviewed journals. Over time, as more research centres purchase the Group’s equipment and begin clinical studies, an increasing number of peer reviewed scientific articles are likely to be published, further enhancing the Group’s credibility and raising awareness of the Group’s technology. The Directors believe that the market for polarisers will grow as the technology gains wider acceptance as a tool for studying lung disease and for monitoring the effectiveness of therapeutics. The Group also intends to continue patenting and in-licensing hyperpolarised gas technology IP to protect its current position.

The Group’s initial sales targets will be the radiology and pulmonary medicine departments of top academic hospital organisations in the US, who are opinion leaders in the use of new diagnostic technologies and their application in a clinical setting.

The Group is expanding its sales and marketing teams. Because of the specialty nature of the Group’s products in the pulmonary specialist market, which is concentrated in approximately 1,000 medical centres, the Directors believe that a small specialty sales force can be deployed effectively at reasonable cost.

The Group may also choose to partner with companies that offer complementary products.

Furthermore, the Directors believe that the Group’s products will benefit a number of clinical applications. While the Group’s HPX MRI technology provides more specific information than currently available from existing lung diagnostic procedures (especially spirometry), the Group will focus its use on specific clinical conditions where the high accuracy of HPX MRI and greater cost are justified. The Directors do not believe that HPX MRI will replace low-cost spirometry as a general screening tool but believe that it should add value in more demanding clinical applications where HPX MRI addresses unmet diagnostic needs. These applications could include, but are not limited to, the following:

• the monitoring of COPD therapy, especially for the most severe cases;
• the management of cystic fibrosis;
• determining the optimal use of biologic therapy in chronic asthma;
• a more efficient diagnosis of dyspnoea and the chronic cough;
• providing guidance for radiation therapy planning of lung cancer treatment;
• providing guidance for interventional pulmonology procedures including ablation and the placement of valves and stents;
• surgical procedure planning for lung transplant and volume reduction surgery;
• diagnosis of ILD and monitoring of ILD therapy;
• diagnosis of pulmonary vascular disease (PVD) including pulmonary arterial hypertension (PAH) and monitoring of therapy; and
• diagnosis and monitoring of long COVID patients.

The Directors have begun to develop relationships with a range of strategic partners and will evaluate opportunities which will enable the Group to address its target markets globally, either alone or in collaboration with a partner. 

5. Intellectual Property (“IP”)

The Group’s technology has been developed in four areas: (i) hyperpolarising gas; (ii) assuring the quality of the hyperpolarised gas; (iii) using the polarised gas in MRI applications; and (iv) developing and producing specialised RF coils to improve signal-to-noise ratios (“SNR”). GE had put a comprehensive patent policy in place to protect its technology from potential competitors. The Group is now the sole owner of this IP portfolio, which is based on 10 patent families, and when combined with the 7 patents that were previously owned by m2m, that were transferred to the Group following the m2m Merger, the Group’s portfolio covers four broad types of patents:

• imaging methods – these cover the imaging of a subject, or patient, who has inhaled a hyperpolarised noble gas and the functionality of the gas as a contrast agent. Newly licensed technology from Duke University extends the protection over these patents through to the early 2030s;
• hyperpolarisation methods – these are polarimetry patents covering the methods by which noble gases are polarised and the methods by which the resulting polarised gas is isolated and delivered to patients. The latest of these patents expire in the early 2020s;
• hyperpolarisation equipment – these patents cover the multiple preferred mechanical design and automation elements of hyperpolarised equipment; and
• RF coil patents – these patents cover the use of cryogenics to improve RF coils SNR and image quality and may play an important part in the next generation of applications such as neurological, cardiac and oncology imaging.

Polarean is committed to proactively developing further IP, both internally and through licensing arrangements with third parties, as part of the Group’s overall growth strategy. The third parties are likely to include the Group’s key collaborative academic sites, such as Duke University, that are seeking to develop emerging applications and technologies. Because of the Group’s extensive patent portfolio and leading market position, the Directors believe the Group is an attractive licensing partner for academic research institutions that are interested in out-licensing such IP. One such patent application (US15/120013), which is currently pending, relates to improving the overall efficiency of the hyperpolarisation process. This patent has also been exclusively licensed to the Group by Duke University. The Directors believe that this patent, now having been prosecuted successfully to issuance in a number of geographic jurisdictions worldwide, would enable the Group to protect methods for increasing the level of hyperpolarisation significantly, which could improve the competitive economics of the Group’s products.

6. Principal Risks and Uncertainties  

The principal risks and uncertainties facing the Group are detailed below:

Early stage of operations

The Group’s operations are at an early stage of development and there can be no guarantee that the Group will be able to, or that it will be commercially advantageous for the Group to, develop its proprietary technology. Further, the Group currently has no positive operating cash flow and its ultimate success will depend on the Directors’ ability to implement the Group’s strategy, generate cash flow and access capital markets.

Principal mitigation

The Group has successfully advanced the ¹²⁹Xe technology for several years, including selling polarisers for the research market. The Group has been able to access capital required to continue to advance the technology.

Regulatory approvals and compliance

The Group will need to obtain various regulatory approvals (including FDA and European Medicines Agency (“EMA”) approvals) and otherwise comply with extensive regulations regarding safety, quality and efficacy standards in order to market its future products. These regulations, including the time required for regulatory review, vary from country to country and can be lengthy, expensive and uncertain.

Principal mitigation

The Group utilises external specialists in regulatory affairs who consult with other experts to ensure that internal control processes and clinical trial designs meet current regulatory requirements. The Group also engages directly with regulatory authorities when appropriate.

Future funding requirements

The Group will need to raise additional funding or enter into a strategic partnership with industry partners to undertake work beyond that being funded by the £27 million (before expenses) 2021 fundraising. There is no certainty that this will be possible at all or on acceptable terms.

Principal mitigation

The Group successfully engaged with investors to generate significant cash resources to date, including the 2021 financing that raised £27 million, before expenses. The Group’s management team expects that continued access to capital markets, or other access to capital, will be required to support the Group through regulatory approval and initial commercialisation efforts in the US. See Going Concern discussion below.

Dependence on key personnel

The success of the Group, in common with other businesses of a similar size, will be highly dependent on the expertise and experience of the Directors and key employees. However, the retention of such key personnel cannot be guaranteed. Should key personnel leave the Group’s business, prospects, financial condition or results of operations may be materially adversely affected.

Principal mitigation

The Group’s recruitment processes are designed to identify and attract the best candidates for specific roles. The Group aims to provide competitive rewards and incentives to staff and directors.

Intellectual property and proprietary technology

No assurance can be given that any current or future patent applications will result in granted patents, that the scope of any patent protection will exclude competitors or provide competitive advantages to the Group, that any of the Group’s patents will be held valid if challenged or that third parties will not claim rights in or ownership of the patents and other proprietary rights held by the Group.

Principal mitigation

The Group has a long-standing track record of IP generation and successful applications and has a long-standing relationship with our patent attorney who has a deep understanding of our technology. The Group actively manages its IP, engaging with specialists to apply for and defend IP rights in appropriate territories.

Technology and products

The Group is a developer and service provider for noble gas ¹²⁹Xe devices and ancillary instruments with a special focus on pulmonary imaging. The development and commercialisation of its proprietary technology and future products, which are in early stages of development, will require multiple series of clinical trials and there is a risk that safety and efficacy issues may arise when the products are tested. There is also a risk that there will be delays to the development of the products or that unforeseen technical problems arise as the Group’s technology becomes increasingly automated. These risks are common to all new medical products and there is also a risk that the clinical trials may not be successful.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as safety, manufacturing and software development.

Research and development risk

The Group will be operating in the life sciences and medical device development sector and will look to exploit opportunities within that sector. The Group will therefore be involved in complex scientific research and industry experience indicates that there may be a very high incidence of delay or failure to produce results. The Group may not be able to develop new products or to identify specific market needs that can be addressed by technology solutions developed by the Group.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as conducting clinical trials and regulatory affairs.

Competition

The Group notes that several start-ups operating in the CT software space have begun efforts to commercialise products which represent to characterise lung ventilation. These technologies use ionising radiation, whereas the Group’s technology does not. In addition, these technologies are unable to further assess gas exchange, red blood cell transport, nor microvascular haemodynamics.

Principal mitigation

The Group believes that these emerging technologies validate the unmet need for the use of imaging in assessing pulmonary function. However, their use of ionising radiation, combined with their inability to assess comprehensive pulmonary function will render their utility limited and the Directors see no effect on the current market expectations of Polarean.

Reliance on third parties

The business model for the Group anticipates that it will have limited internal resources over the next few years and that it will use third party providers wherever possible to conduct the research, development, registration, manufacture, marketing and sales of its proposed products. The commercial success of the Group’s products will depend upon the performance of these third parties.

Principal mitigation

The Group seeks experts in the areas where it utilises outsourcing. Wherever possible, the Group seeks to have duplicate suppliers to lessen the reliance on a particular vendor.

Manufacturing

There can be no assurance that the Group’s proposed products will be capable of being manufactured in commercial quantities, in compliance with regulatory requirements and at an acceptable cost. The Group outsources the manufacture of the raw materials and finished products required in connection with the research, development and commercial manufacture of its proposed products and, as such, is wholly dependent upon third parties for the provision of adequate facilities and raw material supplies. ¹²⁹Xe, the specific isotope of xenon which is the active ingredient in the Group’s drug-device product, is available from a limited number of suppliers and there can be no assurance that adequate supplies of this material at acceptable cost can be obtained. In addition, where the Group is dependent upon third parties for manufacture, its ability to procure the manufacture of the drug-device in a manner which complies with regulatory requirements may be constrained, and its ability to develop and deliver such products on a timely and competitive basis may be adversely affected.

Principal mitigation

The Group has designed the manufacturing process to be scalable and has internal experts who train the outside vendors. The Group has established relationships with two ¹²⁹Xe suppliers to mitigate the risk that ¹²⁹Xe supply will be a limitation to the development and commercialisation of its products. In addition, the Group has established a relationship with a GMP outside polariser manufacturer.

Product development timelines

Product development timelines are at risk of delay, particularly since it is not always possible to predict what the FDA will require for approval of future NDA’s. There is a risk therefore that product development could take longer than presently expected by the Directors. If such delays occur the Group may require further working capital. The Directors shall seek to minimise the risk of delays by careful management of projects.

Principal mitigation

The Group utilises consultants who are experts in preparing and filing future NDAs in the US.

General legal and regulatory issues

The Group’s operations are subject to laws, regulatory restrictions and certain governmental directives, recommendations and guidelines relating to, amongst other things, occupational safety, laboratory practice, the use and handling of hazardous materials, prevention of illness and injury, environmental protection and animal and human testing. There can be no assurance that future legislation will not impose further government regulation, which may adversely affect the business or financial condition of the Group.

Principal mitigation

The Group consults experts for advice in areas such as occupational safety, laboratory practice and human testing.

Healthcare pricing environment

In common with other healthcare products companies, the ability of the Group and any of its licensees or collaborators to market its products successfully depends in part on the extent to which reimbursement for the cost of such products and related treatment will be available from government health administration authorities, private health coverage insurers and other organisations.

Principal mitigation

The Group is consulting with several experts in the field of reimbursement for healthcare products in the US to determine the best strategy for accessing adequate reimbursement for its products.

7. Section 172 statement

As required by section 172 of the Companies Act 2006 (the “Act”), a director of a company must act in the way he or she considers, in good faith, would likely promote the success of the company for the benefit of the shareholders. In doing so, the director must have regard, amongst other matters, to the following issues:

• the likely consequences of any decisions in the long term;
• the interests of the company’s employees;
• the need to foster the company’s business relationships with suppliers/customers and others;
• the impact of the company’s operations on the community and environment;
• the company’s reputation for high standards of business conduct; and
• the need to act fairly between members of the company.

The information required by section 172 of the Act is included in the full Annual Report.

Kenneth West
Non-Executive Chairman

25 May 2023

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Consolidated Statement of Comprehensive Income

The results reflected above relate to continuing activities.

There are no items of Other Comprehensive Income (“OCI”) for the year other than the loss above and therefore no separate statement of other comprehensive income has been presented.

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Consolidated Statement of Financial Position

These Financial Statements were approved and authorised for issue by the Board of Directors on 25 May 2023 and were signed on its behalf by:

Kenneth West
Non-Executive Chairman

Company number: 10442853

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Consolidated Statement of Changes in Equity

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Consolidated Statement of Cash Flows

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Notes on Financial Statements

The notes are available in the printable PDF of the results.  To download it, please click here

Notice of Annual General Meeting

In addition, Polarean confirms that the Annual Report and Accounts for the year ended 31 December 2022, the Notice of the Annual General Meeting ("AGM") and a Form of Proxy are now available on the Company's website (http://www.polarean-ir.com/content/investors/annual-reports.asp) and will be posted to shareholders shortly.

The AGM will be held at 2500 Meridian Parkway, Suite 175, Durham, NC 27713, USA at 2 p.m. BST / 9 a.m. EST on 28 June 2023.

Highlights

• United States Food and Drug Administration (“FDA”) approval received for the Company’s drug device combination product, XENOVIEW (xenon Xe 129 hyperpolarised), a hyperpolarised contrast agent indicated for use with magnetic resonance imaging (“MRI”) for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older
• Simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA; XENOVIEW VDP is image processing software that analyses a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualisation and evaluation of lung ventilation and the Polarean XENOVIEW 3.0T Chest Coil
• Research system placements at McMaster University in Ontario, Canada and Cincinnati Children’s Hospital Medical Center (“CCHMC”)
• Appointment of Frank Schulkes, Dan Brague and Marcella Ruddy, MD to the Board as independent Non-Executive Directors
• Appointment of Ken West as Non-Executive Chairman, following the retirement of Jonathan Allis
• Research collaboration with Oxford University Hospitals NHS Trust for long-COVID
• Net cash of US$16.4 million as of 31 December 2022

Post-period end

• First order for a XENOVIEW gas blend cylinder for the production of XENOVIEW received from CCHMC, representing key milestone and execution of commercial plan
• First clinical scan utilising XENOVIEW technology in the United States conducted at CCHMC, marking key milestone for imaging of lung ventilation
• Selected as one of the featured companies as a poster presenter at the American Thoracic Society’s (“ATS”) 2023 Respiratory Innovation Summit

Richard Hullihen, CEO of Polarean, said: "We ended the year with a tremendous positive in receiving our FDA approval for XENOVIEW. This was a long road culminating with the decision we were looking for, and an extraordinary amount of work went into this process from the entire team. We have now begun to roll out XENOVIEW for clinical use and expect to see further hospitals adopt doing clinical XENOVIEW scans in the coming months. We also continue to explore potential future applications for our technology and remain positive for the year ahead. Separately, we have been shortlisted for Breakthrough of the Year and Best Technology at the 2023 European Mediscience Awards, which celebrates private and listed healthcare, biotech and life sciences companies; we are delighted by this validation of our technology and our achievement in securing FDA approval, and are excited to see the outcome.

“On behalf of the Board and the whole Polarean team, I would like to extend my thanks to our shareholders for all their support and we look forward to further updating the market in due course.” 

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014.

Inquiries: 

About Polarean (www.polarean.com)

The Company and its wholly owned subsidiary, Polarean, Inc. (together the "Group") are revenue-generating, medical imaging technology companies operating in the high-resolution medical imaging space. Polarean aspires to revolutionise pulmonary medicine by bringing the power and safety of MRI to the respiratory healthcare community in need of new solutions to evaluate lung ventilation, diagnose disease, characterise disease progression, and monitor response to treatment. By researching, developing, and commercialising novel imaging solutions with a non-invasive and radiation-free functional imaging platform. Polarean’s vision is to help address the global unmet medical needs of more than 500 million patients worldwide suffering with chronic respiratory disease. Polarean is a leader in the field of hyperpolarisation science and has successfully developed the first and only hyperpolarised MRI contrast agent to be approved in the United States. On Dec. 23, 2022, the FDA granted approval for Polarean’s first drug device combination product, XENOVIEW^TM (Xenon Xe¹²⁹ hyperpolarised). Xe¹²⁹ MRI is also currently being studied for visualisation and quantification of gas exchange regionally in the smallest airways of the lungs, across the alveolar tissue membrane, and into the pulmonary bloodstream for future clinical indications.

XENOVIEW IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Risk of Decreased Image Quality from Supplemental Oxygen: Supplemental oxygen administered simultaneously with XENOVIEW^TM inhalation can cause degradation of image quality. For patients on supplemental oxygen, withhold oxygen inhalation for two breaths prior to XENOVIEW^TM inhalation, and resume oxygen inhalation immediately following the imaging breath hold.

Risk of Transient Hypoxia: Inhalation of an anoxic gas such as XENOVIEW^TM may cause transient hypoxemia in susceptible patients. Monitor all patients for oxygen desaturation and symptoms of hypoxemia and treat as clinically indicated.

Adverse Reactions

Adverse Reactions in Adult Patients: The adverse reactions (> one patient) in efficacy trials were oropharyngeal pain, headache, and dizziness.  Adverse Reactions in Pediatric and Adolescent Patients: In published literature in pediatric patients aged 6 to 18, transient adverse reactions were reported: blood oxygen desaturation, heart rate elevation, numbness, tingling, dizziness, and euphoria. In at least one published study of pediatric patients aged 6 to 18 years, transient decrease in SpO2% and transient increase in heart rate was reported following hyperpolarized xenon Xe 129 administration. XENOVIEW^TM is not approved for use in pediatric patients less than 12 years of age.

Please see full prescribing information at www.xenoview.net

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Chairman’s Statement

I am pleased to be able to write this letter with the very important milestone of United States Food & Drug Administration (“FDA”) approval of the Company’s drug device combination product, XENOVIEW, having been accomplished. The broad label of “evaluation of lung ventilation in adults and pediatric patients aged 12 years and older” allows the company to execute its commercial strategy of selling its polarizer and approved gas for clinical scans of patients suffering from a number of lung diseases where the accurate measurement of lung ventilation provides the physician with actionable diagnostic information. In addition, researchers using Polarean’s technology continue to conduct clinical research that supports the broad future potential applications of our technology in areas of gas exchange and cardiopulmonary diagnostics. We are excited to bring Polarean’s technology to clinical medicine, with the potential to be an important part of pulmonary and cardiopulmonary diagnostics, monitoring of severity of disease and patient response to treatments.

During 2022, we strengthened our Board with the addition of three independent Non-Executive Board members who bring extensive industry and medical experience to the Board to assist the company’s successful transition into the commercialization stage. Frank Schulkes brings substantial financing experience in the medical imaging industry and Dan Brague brings experience successfully commercializing diagnostic imaging products. In addition, Dr. Marcella Ruddy brings important pulmonary medical expertise, both in clinical practice and in pharmaceutical development. With these additions to our Board, we believe that we have a world-class Board that can lead the company to successful commercialization of Xenoview.

Having achieved FDA approval, our efforts are now focused on gaining commercial traction and engaging with potential corporate partners to further accelerate our commercial success. Once we have achieved some of these near-term milestones, we will explore the options for additional financing to more aggressively pursue the development of the next indications and advance the continued development of our polarizer system and software. The Company is exploring a broad range of options for future financing, including equity raises and corporate partnering.

On behalf of the Board, I want to thank our employees, stakeholders and shareholders and assure them that we are committed to making Xenoview a commercial and financial success.

Kenneth West

Non-Executive Chairman
25 May 2023

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Chief Executive Officer’s Statement

2022 – Year of Obtaining FDA Approval

We spent much of 2022 working on obtaining FDA approval of our New Drug Application (“NDA”) for XENOVIEW and were please received our approval on 23 December 2022. After receiving a Complete Response Letter (“CRL”) from the FDA in October 2021, we spend the subsequent six months addressing the issues raised in the CRL. On 30 March 2022, the Company refiled the NDA with the FDA. The resubmission addressed the items identified in the CRL. On 22 September the Company announced that the FDA had requested additional information related to the cGMP (Current Good Manufacturing Practice) pre-approval inspection at the partner’s production facility. The Company and its partner addressed the FDA’s request and the Company received FDA approval on 23 December 2022. We were very pleased to receive the broad label of evaluation of lung function in adults and pediatric patients twelve and older. In addition, the FDA indicated that they would allow us to submit a non-clinical plan to obtain approval in pediatric patients six and older. The FDA has granted New Chemical Entity (“NCE”) designation for Xenoview. NCE designation provides the important first mover protection envisioned under the Hatch Waxman legislation.

Commercialization

With FDA approval, the Company is focused on successful commercialization of XENOVIEW for the evaluation of lung function. The Company has an enthusiastic base of US institutions who have been using our technology for research purposes for years. We are leveraging this knowledge and enthusiasm by converting its US research sites to FDA approved configuration and clinical use, which will allow these sites to purchase Xenoview and perform clinical scans. In parallel, we are pursuing various reimbursement codes that could enable the hospitals to be reimbursed for Xenoview, the polarization process, the MRI procedure and the analysis of the pulmonary function imaging. If obtained, we believe that this reimbursement would enable a very compelling return on investment for hospitals to purchase our polarizer systems. We are aggressively pursuing our early commercialization targets of the sale of 15 to 20 polariser systems and 75 to 100 cylinders of Xenoview by the end of 2024.

We are focusing initially on addressing the high end of the US academic and teaching hospital market segment, which comprises approximately the top 1000 institutions nationally having coincident multiple Centres of Excellence in Pulmonary Medicine and Radiology. We believe our strategy of selling the capital equipment and the Xenoview drug on a per cylinder basis could provide a capital equipment and recurring drug sales model that supports rapidly growing revenue.

Financials

Sales for 2022 were below our original expectations, as we did not receive FDA approval in October 2022 as anticipated in the plan. We adjusted our spending plans commensurate with the delayed approval, which allowed us to finish 2022 with a higher than anticipated cash balance of US$16.4 million. We continued to sell our polariser systems into the research market and completed two installations during 2022. The current cash balance is expected to fund the company into late Q2-2024.

Corporate Partnering

We continue to believe that corporate partnering could be an important part of the Company’s business plan. We see the opportunity to help the pharmaceutical industry reduce by significant amounts the size, time required to conduct and costs of their pulmonary drug clinical trials by providing quantitative, reproducible image-based data. We also see the opportunity to partner with MRI manufacturers to open up the MRI applications space to include pulmonary diagnostics, driving the demand for more MRI systems. In addition, we will explore the opportunity to partner with pulmonary disease organizations and foundations to incorporate the use of Xenoview in the diagnosis and treatment of disease.

Future Indications

Researchers are currently conducting clinical trials and pharmaceutical company sponsored investigations in multiple areas of pulmonary disease using our technology. These studies are highlighting the exciting opportunities in the areas of long COVID and cardiopulmonary vascular disease. We believe that these areas could greatly expand the total addressable markets and use of the Company’s technology in the future.

2023 and Beyond

As discussed above, we are focused on achieving early commercial traction with our broad lung function evaluation label granted by the FDA in late 2022. In parallel, we are exploring a variety of partnering opportunities. Once we have achieved some of these near-term milestones, we will explore the appropriate timing and structure to finance the continued commercial efforts, clinical trials to seek approval for the high-value gas exchange and pulmonary vascular disease indications and continue to improve our polariser system and imaging software.

This important milestone of FDA approval would not have been possible without the dedicated team of employees, consultants and advisers working to bring our much needed technology to clinicians, their patients and the institutions enabling their care. I thank everyone for their hard work in accomplishing this significant achievement.

Richard Hullihen

Chief Executive Officer
25 May 2023

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Strategic Report

1. Introduction 

The Group comprises medical drug-device combination companies operating in the high-resolution medical imaging market. The Group develops equipment that enables existing MRI systems to achieve an improved level of pulmonary functional imaging and specialises in the use of polarised xenon gas (129Xe ) as an imaging agent to visualise ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of oxygen to diffuse through the alveolar membrane into the pulmonary vasculature) regionally down to the smallest airways of the lungs, the tissue barrier between the lung and the bloodstream and in the pulmonary vasculature; and now also microvascular haemodynamics within the lung, a novel diagnostic approach. The Group will also register and sell the high-performance MRI radiofrequency (RF) coils which are a required component for imaging 129Xe in the MRI system. Providing access to these coils facilitates the adoption of the Xenon technology by providing application-specific RF coils which optimise the imaging of 129Xe in MRI equipment.

The Group was formed on 31 May 2017 when the Company acquired Polarean, Inc (the “Subsidiary”). The Subsidiary was formed as a result of two mergers: the first between Polarean Merger-Sub Inc. and m2m, a company that the Subsidiary had developed a relationship with during the course of previous research and commercialisation programmes in the US and the second between m2m and the Subsidiary. m2m was previously a portfolio company of Amphion Innovations plc (“Amphion”), a developer of medical, life science, and technology businesses, which is itself currently listed on AIM.

2. Investment Case

Pulmonary disease currently affects hundreds of millions of people globally, including approximately 174 million people who suffer from Chronic Obstructive Pulmonary Disease (“COPD”), which is responsible for approximately 6% of such deaths globally each year. In the US more than 30 million people suffer from a chronic lung disease such as COPD, which includes emphysema, chronic bronchitis and asthma. In addition to its significant human toll, pulmonary disease also represents an economic burden in excess of US$150 billion annually in the US alone.

Every type of pulmonary disease involves some combination of ventilation and/or gas exchange impairment, yet the successful and cost-effective treatment of lung disease is hampered by sub-optimal methods for quantifying pulmonary ventilation and gas exchange. Current diagnostic techniques are either imprecise (such as spirometry) and/or expose the patient to potentially dangerous radiation (such as x-rays, CT scans and nuclear scintigraphy). While spirometry has benefits as a screening tool, none of these current methods can visualise ventilation or gas exchange regionally in the smallest airways, where lung disease typically begins and where improvements from new pharmaceutical therapies can first be detected.

As such, the Group operates in an area of significant unmet medical need and is pursuing approval by the US Food & Drug Administration (“FDA”) for the Group’s drug-device combination product using hyperpolarised xenon-129 gas to enhance MRI in pulmonary medicine. The Company submitted a new drug application (“NDA”) to the FDA on 5 October 2020 after the successful completion of the FDA Phase III clinical trials in the US for the Group’s technology. The 80-patient equivalence clinical trials were conducted at Duke University Medical Center, the University of Virginia and The University of Cincinnati - three leading US research hospitals. Enrolment of the clinical trials was completed in November 2019. In January 2020, the Company announced that both clinical trials met their primary endpoints, within the prospectively defined equivalence margin (+/-14.7%) when compared to the FDA-approved reference standard, 133Xenon scintigraphy imaging. On 5 October 2021, the Company received a Complete Response Letter (“CRL”) from the FDA requesting that the Company to address approvability issues identified by the FDA ahead of NDA resubmission. On 30 March 2022, the Company filed the resubmission of the NDA with the FDA. On 20 April 2022, the Company announced that the FDA had accepted the resubmission of the NDA and established a user fee goal date of 30 September 2022. On 30 September 2022, the Company announced that the FDA had granted the Company a 90 day extension to the NDA review timeline. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with magnetic resonance imaging ("MRI") for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. On 28 December 2022, the Company also announced that, simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA that will further support a successful launch of the technology into the clinical marketplace: XENOVIEW VDP software and the XENOVIEW 3.0T Chest Coil. XENOVIEW VDP is image processing software that analyzes a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualization and evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. This image analysis platform quantifies normalized xenon intensity of a ventilated space using a pulmonary hyperpolarised 129-Xe ventilation MR image and accompanying proton chest MR image. The software will be used by clinicians to assist in the interpretation and numerical classification of hyperpolarized 129-Xe ventilation MR images. The Polarean XENOVIEW 3.0T Chest Coil is a flexible, single channel, transmit-receive (T/R) RF coil tuned to 129Xe frequency on a 3.0T MRI magnetic field of a compatible MRI scanner. The Polarean XENOVIEW 3.0T Chest Coil is indicated to be used in conjunction with compatible 3.0T MRI scanners and approved xenon Xe 129 hyperpolarised for oral inhalation for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. The Chest Coil is intended to be worn by a patient who inhales hyperpolarised 129Xe gas (XENOVIEW) to obtain an MR image of the regional distribution of hyperpolarised 129Xe in the lungs.

The Group’s technology overcomes important limitations of current lung diagnostic methods, providing the ability to visualise, quantify and monitor both the structure and function of the smallest airways and alveolar spaces with enhanced sensitivity and without harmful radiation. This provides a unique, valuable and more precise tool to help diagnose disease earlier, identify the type of intervention likely to benefit a patient, monitor the efficacy of treatment and facilitate developing new therapies for pulmonary diseases.

3. Group Structure and History

The Company was incorporated in England and Wales on 24 October 2016 with company registration number 10442853. The Company’s registered office is 27-28 Eastcastle Street, London, W1W 8DH.

On 31 May 2017, m2m, a company formed in the US State of Delaware on 18 February 1999, was merged into the Company.

On 29 March 2018, the Company’s shares were admitted to trading on the AIM market of the London Stock Exchange.

4. Information on Polarean, m2m and Strategy of Group

4.1 Polarean, Inc. – Background

The Subsidiary was co-founded by Dr Bastiaan Driehuys, a current Director of the Company, and John Sudol, a former director of the Subsidiary, in 2011. Prior to co-founding the Subsidiary, Dr Driehuys was a member of a research team at Princeton University in the early 1990s which was amongst the first research teams to focus on hyperpolarised gas MRI technology; in particular isotopically enriched helium (3He). The team developed and held key patents relating to the technology. The technology was acquired in 1999 by Amersham, Inc. (“Amersham”), with the goal of commercialising hyperpolarised helium products to be marketed and distributed alongside Amersham’s full line of contrast agent products. Dr Driehuys led the development efforts for Amersham, which continued the development of these hyperpolarised helium products throughout the early 2000s until GE Healthcare (“GE”) acquired Amersham in 2004.

GE continued the research and development of hyperpolarised gas MRI after the acquisition of Amersham, focusing on 129Xe as a more effective substitute for 3 He in visualising ventilation. GE also began to explore ways in which 129Xe could be used to image gas exchange within the lung in addition to ventilation. These work programmes culminated in the conduct of a Phase I/II clinical trial at Duke University in 2008-2009. GE also filed Investigational New Drug Applications (‘INDs”) with the FDA for both 3He and 129Xe. By 2010, after an investment of approximately US$40 million in the technology and with the regulatory path for hyperpolarised gas remaining unclear, GE decided to out-license the hyperpolarised gas technology and the related patent families that it had developed and/or maintained to the Subsidiary, due to the scale at the time and the early-stage nature of the technology’s development.

In December 2011, the Subsidiary negotiated the acquisition of all of GE’s assets related to the hyperpolarised MRI project, including an inventory of polarisers and parts and the licenses (or outright ownership) of the related patent families.

Following the acquisition of GE’s hyperpolarisation assets, the Subsidiary focused on three key objectives:

• building and selling polarisers to research users to generate operating revenue and to disseminate the technology to academic research institutions that generate clinical data in order to build additional interest in the technology;
• further developing the xenon hyperpolarisation technology in order to meet clinical use specification requirements; and
• liaising with the FDA in order to clarify the FDA regulatory path under which the product could achieve clearance to market for clinical use.

In July 2012, the US Congress passed the FDA Safety and Innovation Act and the Medical Gas Act, which clarified and simplified the path under which hyperpolarised gas MRI technology could be approved for clinical use by the FDA.

As a result of discussions between the Group and the FDA, the Directors believed that a clearer path towards regulatory approval existed. As such, following listing our shares on the AIM market the Group began conducting the clinical studies required for FDA approval to market. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

Between January 2012 and May 2017, the Subsidiary generated over US$3.7 million of revenue from selling polarisers to customers in Canada, Germany, the UK and the US for research use, relating to both clinical (human) and pre-clinical (animal) applications. In addition, the Subsidiary received additional funding of approximately US$2.5 million from Nukem and other Series A investors. Prior to the m2m merger, the Subsidiary was also successful in receiving grant funding, including a US$3 million grant awarded in April 2017 by the US National Heart, Lung and Blood Institute (NHLBI) following a competitive application process (for which the research will be conducted with its clinical collaborator, the Cincinnati Children’s Hospital) and a US$250,000 small business research loan from the North Carolina Biotech Center in March 2017, which was also awarded following a competitive application process.

4.2 The Group’s Technology and Products

The Subsidiary’s lead product has been designated as a drug-device combination by the FDA. The Subsidiary’s product enables the visualisation of hyperpolarised ¹²⁹Xe (“HPX”) through MRI technology to help diagnose lung disease earlier, identify the type of intervention likely to benefit a patient and to monitor the efficacy of treatment. As a result of the FDA’s drug-device designation, the Subsidiary’s products will be approved and sold only for use with each other. The products are currently being used at a number of research sites on a pre-FDA clearance basis to facilitate the research and evaluation of lung function, to assist in making improved disease progression assessment and to clearly visualise the effectiveness of several therapeutics which are under development. The Group currently generates revenue from the sale of products within its ¹²⁹Xe gas hyperpolarisation platform.

Implementing the Group’s technology in a clinical setting is straightforward: prior to the MRI scan a patient breathes in a small amount of inert HPX to provide an extremely strong MRI signal. This transforms the MRI from a technology that is not applicable to the lungs into one that is able to provide multiple images of the lung structure and function in one 10-20 second breath-hold. HPX MRI overcomes the limitations of traditional pulmonary function testing as HPX MRI:

• is more accurate and reproducible than spirometry and other traditional pulmonary function tests, enabling the detection and mapping of small and localised changes in lung ventilation and gas exchange over time;
• provides regional information about lung disease without exposure to ionising radiation or radioactivity; and
• assesses ventilation and gas exchange in the smallest airways, where disease often begins.

The Group’s technology works in conjunction with traditional MRI, transforming it into a powerful diagnostic modality for the lung. The Group’s approach is to take ¹²⁹Xe, an inert gas, and hyperpolarise the nucleus to create an MRI signal which is approximately 100,000 times stronger than a conventional MRI signal. When the MRI scan is undertaken, the HPX resonates at different frequencies: (i) in the bronchioles and alveoli of the lung; (ii) in the barrier tissue of the lung; and (iii) when dissolved in arterial blood in the pulmonary vasculature, thus providing information on ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of air to diffuse through the alveolar membrane into the pulmonary vasculature). As all pulmonary diseases result from impairments to the free flow of air through bronchioles, or from abnormal gas exchange between the lung alveoli and the pulmonary vasculature, the images that result from HPX MRI scans which have been executed using the Group’s technology can aid diagnosis, by enhancing the physician’s ability to clearly identify issues with ventilation and gas exchange on a regional basis, down to the smallest of airways. Hyperpolarisation of the ¹²⁹Xe is accomplished by placing a non-radioactive isotope of Xenon (¹²⁹Xe) into a beam of circularly polarised laser light in the presence of very small concentration of the alkali metal Rubidium, which acts as a physical catalyst in the hyperpolarisation process. The result is ¹²⁹Xe whose nuclear magnetic spin is highly aligned but not chemically or biologically different than unpolarised ¹²⁹Xe, an inert gas. This hyperpolarised state persists for around 2 hours allowing ample time to administer the HPX to the patient.

The Group’s products include:

• the ¹²⁹Xe gas, blended and made under GMP at high purity, to be polarised within the polariser;
• the polariser itself, of which the latest model, the Polarean 9820 Xenon Hyperpolariser, has been designed to deliver up to 3 litres of HPX per hour (approximately 5-10 doses) of which each dose is to be used within 30 minutes of its production in order to retain sufficient polarisation to create a strong image;
• the dose delivery inhalation bag, made of HPX-compatible impermeable plastic materials and a mouthpiece for ease of inhalation; and
• the Polarean 2881 Polarisation Measurement Station, which provides a calibrated measurement of the polarisation of hyperpolarised gas within the dose delivery inhalation bag.

The Group currently designs and builds the polariser equipment at a contract manufacturer and has relationships with GMP gas producers to supply the Group with high purity ¹²⁹Xe according to the Group’s specifications.

In order to take advantage of the Group’s current products, an MRI machine is required to be outfitted with hardware and software capable of operating at ¹²⁹Xe frequency to detect the HPX signal. In addition, the patient will need to wear a ¹²⁹Xe RF chest coil to allow for detecting the HPX MR signal in the lungs. Approximately 35,000 MRI machines are currently in use worldwide and technically many of these can be easily adapted to be used with ¹²⁹Xe frequency. The Group’s products can be placed near the MRI scanner for ease of radiology workflow and, following the m2m merger, the Group has continued to explore ways to further integrate the Group’s existing technology with the coils which had previously been the focus of m2m.

4.3 Location

The Group is based at the Meridian Corporate Center, located in the Research Triangle Park area of North Carolina, which provides a favourable location at which to further develop the core technology and product range. The Group’s facilities consist of more than 6,900 square feet of combined offices, laboratory space, inventory warehouse and assembly and testing areas. The Group benefits from facilities that were originally purpose-built by GE for the design and manufacture of hyperpolarisation equipment and components, pursuant to FDA-mandated guidelines.

Within these facilities are a dedicated research and development laboratory equipped with 3-phase power, central compressed air, specialty gas handling and distribution and separate heating, ventilation and air conditioning. The laboratory area also includes optical cell production equipment capable of simultaneous processing of four optical cells for Xenon applications. The laboratory is designed for safe operation of class 4 lasers and is equipped with laser power and spectral testing apparatus.

The Group also maintains a dedicated polariser test bed that is used for product development and a dedicated Nuclear Magnetic Resonance (“NMR”) system capable of delivering available electromagnetic field strength, utilised for calibrating absolute polarisation measurements of hyperpolarised gas samples.

4.4 The Regulatory Environment

Prior to the receipt of any approvals for clinical use, the Group sold its polarisers and disposables for research use only to academic medical centres with their research being subject to oversight by their respective institutional review boards and conducted under IND from the FDA or equivalent regulatory body.

On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

4.5 The Group’s Customers

The Group’s existing customer base already comprises some of the world’s luminary medical imaging research institutions. Indeed, there are numerous research institutions worldwide utilising the Group’s system and products, including Cincinnati Children’s Hospital, the University of Virginia, University of Wisconsin – Madison, Duke University, University of Kansas, the University of Iowa and the University of Texas MD Anderson Cancer Center in the US, Robarts Research Institute and Hospital for Sick Children (SickKids) in Canada, the University of Oxford and the University of Nottingham in the UK and the Fraunhofer Institute for Toxicology and Experimental Medicine in Germany.

4.6 The Group’s Suppliers

The Group has entered into Master Service Agreements with two CROs in relation to the Phase III trial. Pharma Start LLC, doing business as Firma Clinical Research, managed the trials and oversaw the recruitment of patients for the trial. In addition, Icon Clinical Research Limited assisted with the medical imaging aspects of the trial.

The Group has a long-standing relationship with its strategic investor Nukem Isotopes GmbH (“Nukem”), a leading global supplier of ¹²⁹Xe, the isotope of xenon which is provided to the various gas blenders that in turn supply gas to the Group. It has a supply agreement with Nukem for ¹²⁹Xe.

In June 2020 the Group signed an agreement with Linde Gas North America LLC (“Linde”), in relation to the supply of the Group’s drug product, a ¹²⁹Xenon gas blend. This agreement contains provision for the supply of bulk ¹²⁹Xe to be manufactured into the Active Pharmaceutical Product (API), ¹²⁹Xe, and for the blending, packaging, and distribution of its drug product under GMP. On 28 December 2022, the Group signed an amended agreement with Linde, which modified some commercial terms and limited the agreement to the blending packaging and distribution of it drug product under GMP.

The Group has an arrangement with the Blur Product Development (“Blur”) to build its polariser systems in Blur’s GMP facilities.

4.7 Current Trading and Prospects

Trading of the Group since the Company’s IPO continues to be in line with the Directors’ expectations. The potential of the Group’s technology enables the Directors to view the future with confidence as the Company focuses on commercialisation of XENOVIEW.

4.8 Growth Strategy

With the recent FDA approval, the Group is adopting a traditional market entry strategy of building market awareness for its technology through key opinion leaders and a direct sales force to reach the key decision makers within its initial target market of large academic medical centres. In implementing this strategy, the Group benefits from approximately 1,000 journal articles on the use of hyperpolarised gas MRI that are currently published in peer-reviewed journals. Over time, as more research centres purchase the Group’s equipment and begin clinical studies, an increasing number of peer reviewed scientific articles are likely to be published, further enhancing the Group’s credibility and raising awareness of the Group’s technology. The Directors believe that the market for polarisers will grow as the technology gains wider acceptance as a tool for studying lung disease and for monitoring the effectiveness of therapeutics. The Group also intends to continue patenting and in-licensing hyperpolarised gas technology IP to protect its current position.

The Group’s initial sales targets will be the radiology and pulmonary medicine departments of top academic hospital organisations in the US, who are opinion leaders in the use of new diagnostic technologies and their application in a clinical setting.

The Group is expanding its sales and marketing teams. Because of the specialty nature of the Group’s products in the pulmonary specialist market, which is concentrated in approximately 1,000 medical centres, the Directors believe that a small specialty sales force can be deployed effectively at reasonable cost.

The Group may also choose to partner with companies that offer complementary products.

Furthermore, the Directors believe that the Group’s products will benefit a number of clinical applications. While the Group’s HPX MRI technology provides more specific information than currently available from existing lung diagnostic procedures (especially spirometry), the Group will focus its use on specific clinical conditions where the high accuracy of HPX MRI and greater cost are justified. The Directors do not believe that HPX MRI will replace low-cost spirometry as a general screening tool but believe that it should add value in more demanding clinical applications where HPX MRI addresses unmet diagnostic needs. These applications could include, but are not limited to, the following:

• the monitoring of COPD therapy, especially for the most severe cases;
• the management of cystic fibrosis;
• determining the optimal use of biologic therapy in chronic asthma;
• a more efficient diagnosis of dyspnoea and the chronic cough;
• providing guidance for radiation therapy planning of lung cancer treatment;
• providing guidance for interventional pulmonology procedures including ablation and the placement of valves and stents;
• surgical procedure planning for lung transplant and volume reduction surgery;
• diagnosis of ILD and monitoring of ILD therapy;
• diagnosis of pulmonary vascular disease (PVD) including pulmonary arterial hypertension (PAH) and monitoring of therapy; and
• diagnosis and monitoring of long COVID patients.

The Directors have begun to develop relationships with a range of strategic partners and will evaluate opportunities which will enable the Group to address its target markets globally, either alone or in collaboration with a partner. 

5. Intellectual Property (“IP”)

The Group’s technology has been developed in four areas: (i) hyperpolarising gas; (ii) assuring the quality of the hyperpolarised gas; (iii) using the polarised gas in MRI applications; and (iv) developing and producing specialised RF coils to improve signal-to-noise ratios (“SNR”). GE had put a comprehensive patent policy in place to protect its technology from potential competitors. The Group is now the sole owner of this IP portfolio, which is based on 10 patent families, and when combined with the 7 patents that were previously owned by m2m, that were transferred to the Group following the m2m Merger, the Group’s portfolio covers four broad types of patents:

• imaging methods – these cover the imaging of a subject, or patient, who has inhaled a hyperpolarised noble gas and the functionality of the gas as a contrast agent. Newly licensed technology from Duke University extends the protection over these patents through to the early 2030s;
• hyperpolarisation methods – these are polarimetry patents covering the methods by which noble gases are polarised and the methods by which the resulting polarised gas is isolated and delivered to patients. The latest of these patents expire in the early 2020s;
• hyperpolarisation equipment – these patents cover the multiple preferred mechanical design and automation elements of hyperpolarised equipment; and
• RF coil patents – these patents cover the use of cryogenics to improve RF coils SNR and image quality and may play an important part in the next generation of applications such as neurological, cardiac and oncology imaging.

Polarean is committed to proactively developing further IP, both internally and through licensing arrangements with third parties, as part of the Group’s overall growth strategy. The third parties are likely to include the Group’s key collaborative academic sites, such as Duke University, that are seeking to develop emerging applications and technologies. Because of the Group’s extensive patent portfolio and leading market position, the Directors believe the Group is an attractive licensing partner for academic research institutions that are interested in out-licensing such IP. One such patent application (US15/120013), which is currently pending, relates to improving the overall efficiency of the hyperpolarisation process. This patent has also been exclusively licensed to the Group by Duke University. The Directors believe that this patent, now having been prosecuted successfully to issuance in a number of geographic jurisdictions worldwide, would enable the Group to protect methods for increasing the level of hyperpolarisation significantly, which could improve the competitive economics of the Group’s products.

6. Principal Risks and Uncertainties  

The principal risks and uncertainties facing the Group are detailed below:

Early stage of operations

The Group’s operations are at an early stage of development and there can be no guarantee that the Group will be able to, or that it will be commercially advantageous for the Group to, develop its proprietary technology. Further, the Group currently has no positive operating cash flow and its ultimate success will depend on the Directors’ ability to implement the Group’s strategy, generate cash flow and access capital markets.

Principal mitigation

The Group has successfully advanced the ¹²⁹Xe technology for several years, including selling polarisers for the research market. The Group has been able to access capital required to continue to advance the technology.

Regulatory approvals and compliance

The Group will need to obtain various regulatory approvals (including FDA and European Medicines Agency (“EMA”) approvals) and otherwise comply with extensive regulations regarding safety, quality and efficacy standards in order to market its future products. These regulations, including the time required for regulatory review, vary from country to country and can be lengthy, expensive and uncertain.

Principal mitigation

The Group utilises external specialists in regulatory affairs who consult with other experts to ensure that internal control processes and clinical trial designs meet current regulatory requirements. The Group also engages directly with regulatory authorities when appropriate.

Future funding requirements

The Group will need to raise additional funding or enter into a strategic partnership with industry partners to undertake work beyond that being funded by the £27 million (before expenses) 2021 fundraising. There is no certainty that this will be possible at all or on acceptable terms.

Principal mitigation

The Group successfully engaged with investors to generate significant cash resources to date, including the 2021 financing that raised £27 million, before expenses. The Group’s management team expects that continued access to capital markets, or other access to capital, will be required to support the Group through regulatory approval and initial commercialisation efforts in the US. See Going Concern discussion below.

Dependence on key personnel

The success of the Group, in common with other businesses of a similar size, will be highly dependent on the expertise and experience of the Directors and key employees. However, the retention of such key personnel cannot be guaranteed. Should key personnel leave the Group’s business, prospects, financial condition or results of operations may be materially adversely affected.

Principal mitigation

The Group’s recruitment processes are designed to identify and attract the best candidates for specific roles. The Group aims to provide competitive rewards and incentives to staff and directors.

Intellectual property and proprietary technology

No assurance can be given that any current or future patent applications will result in granted patents, that the scope of any patent protection will exclude competitors or provide competitive advantages to the Group, that any of the Group’s patents will be held valid if challenged or that third parties will not claim rights in or ownership of the patents and other proprietary rights held by the Group.

Principal mitigation

The Group has a long-standing track record of IP generation and successful applications and has a long-standing relationship with our patent attorney who has a deep understanding of our technology. The Group actively manages its IP, engaging with specialists to apply for and defend IP rights in appropriate territories.

Technology and products

The Group is a developer and service provider for noble gas ¹²⁹Xe devices and ancillary instruments with a special focus on pulmonary imaging. The development and commercialisation of its proprietary technology and future products, which are in early stages of development, will require multiple series of clinical trials and there is a risk that safety and efficacy issues may arise when the products are tested. There is also a risk that there will be delays to the development of the products or that unforeseen technical problems arise as the Group’s technology becomes increasingly automated. These risks are common to all new medical products and there is also a risk that the clinical trials may not be successful.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as safety, manufacturing and software development.

Research and development risk

The Group will be operating in the life sciences and medical device development sector and will look to exploit opportunities within that sector. The Group will therefore be involved in complex scientific research and industry experience indicates that there may be a very high incidence of delay or failure to produce results. The Group may not be able to develop new products or to identify specific market needs that can be addressed by technology solutions developed by the Group.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as conducting clinical trials and regulatory affairs.

Competition

The Group notes that several start-ups operating in the CT software space have begun efforts to commercialise products which represent to characterise lung ventilation. These technologies use ionising radiation, whereas the Group’s technology does not. In addition, these technologies are unable to further assess gas exchange, red blood cell transport, nor microvascular haemodynamics.

Principal mitigation

The Group believes that these emerging technologies validate the unmet need for the use of imaging in assessing pulmonary function. However, their use of ionising radiation, combined with their inability to assess comprehensive pulmonary function will render their utility limited and the Directors see no effect on the current market expectations of Polarean.

Reliance on third parties

The business model for the Group anticipates that it will have limited internal resources over the next few years and that it will use third party providers wherever possible to conduct the research, development, registration, manufacture, marketing and sales of its proposed products. The commercial success of the Group’s products will depend upon the performance of these third parties.

Principal mitigation

The Group seeks experts in the areas where it utilises outsourcing. Wherever possible, the Group seeks to have duplicate suppliers to lessen the reliance on a particular vendor.

Manufacturing

There can be no assurance that the Group’s proposed products will be capable of being manufactured in commercial quantities, in compliance with regulatory requirements and at an acceptable cost. The Group outsources the manufacture of the raw materials and finished products required in connection with the research, development and commercial manufacture of its proposed products and, as such, is wholly dependent upon third parties for the provision of adequate facilities and raw material supplies. ¹²⁹Xe, the specific isotope of xenon which is the active ingredient in the Group’s drug-device product, is available from a limited number of suppliers and there can be no assurance that adequate supplies of this material at acceptable cost can be obtained. In addition, where the Group is dependent upon third parties for manufacture, its ability to procure the manufacture of the drug-device in a manner which complies with regulatory requirements may be constrained, and its ability to develop and deliver such products on a timely and competitive basis may be adversely affected.

Principal mitigation

The Group has designed the manufacturing process to be scalable and has internal experts who train the outside vendors. The Group has established relationships with two ¹²⁹Xe suppliers to mitigate the risk that ¹²⁹Xe supply will be a limitation to the development and commercialisation of its products. In addition, the Group has established a relationship with a GMP outside polariser manufacturer.

Product development timelines

Product development timelines are at risk of delay, particularly since it is not always possible to predict what the FDA will require for approval of future NDA’s. There is a risk therefore that product development could take longer than presently expected by the Directors. If such delays occur the Group may require further working capital. The Directors shall seek to minimise the risk of delays by careful management of projects.

Principal mitigation

The Group utilises consultants who are experts in preparing and filing future NDAs in the US.

General legal and regulatory issues

The Group’s operations are subject to laws, regulatory restrictions and certain governmental directives, recommendations and guidelines relating to, amongst other things, occupational safety, laboratory practice, the use and handling of hazardous materials, prevention of illness and injury, environmental protection and animal and human testing. There can be no assurance that future legislation will not impose further government regulation, which may adversely affect the business or financial condition of the Group.

Principal mitigation

The Group consults experts for advice in areas such as occupational safety, laboratory practice and human testing.

Healthcare pricing environment

In common with other healthcare products companies, the ability of the Group and any of its licensees or collaborators to market its products successfully depends in part on the extent to which reimbursement for the cost of such products and related treatment will be available from government health administration authorities, private health coverage insurers and other organisations.

Principal mitigation

The Group is consulting with several experts in the field of reimbursement for healthcare products in the US to determine the best strategy for accessing adequate reimbursement for its products.

7. Section 172 statement

As required by section 172 of the Companies Act 2006 (the “Act”), a director of a company must act in the way he or she considers, in good faith, would likely promote the success of the company for the benefit of the shareholders. In doing so, the director must have regard, amongst other matters, to the following issues:

• the likely consequences of any decisions in the long term;
• the interests of the company’s employees;
• the need to foster the company’s business relationships with suppliers/customers and others;
• the impact of the company’s operations on the community and environment;
• the company’s reputation for high standards of business conduct; and
• the need to act fairly between members of the company.

The information required by section 172 of the Act is included in the full Annual Report.

Kenneth West
Non-Executive Chairman

25 May 2023

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Consolidated Statement of Comprehensive Income

The results reflected above relate to continuing activities.

There are no items of Other Comprehensive Income (“OCI”) for the year other than the loss above and therefore no separate statement of other comprehensive income has been presented.

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Consolidated Statement of Financial Position

These Financial Statements were approved and authorised for issue by the Board of Directors on 25 May 2023 and were signed on its behalf by:

Kenneth West
Non-Executive Chairman

Company number: 10442853

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Consolidated Statement of Changes in Equity

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Consolidated Statement of Cash Flows

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Notes on Financial Statements

The notes are available in the printable PDF of the results.  To download it, please click here

2020

Notice of Annual General Meeting

In addition, Polarean confirms that the Annual Report and Accounts for the year ended 31 December 2022, the Notice of the Annual General Meeting ("AGM") and a Form of Proxy are now available on the Company's website (http://www.polarean-ir.com/content/investors/annual-reports.asp) and will be posted to shareholders shortly.

The AGM will be held at 2500 Meridian Parkway, Suite 175, Durham, NC 27713, USA at 2 p.m. BST / 9 a.m. EST on 28 June 2023.

Highlights

• United States Food and Drug Administration (“FDA”) approval received for the Company’s drug device combination product, XENOVIEW (xenon Xe 129 hyperpolarised), a hyperpolarised contrast agent indicated for use with magnetic resonance imaging (“MRI”) for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older
• Simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA; XENOVIEW VDP is image processing software that analyses a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualisation and evaluation of lung ventilation and the Polarean XENOVIEW 3.0T Chest Coil
• Research system placements at McMaster University in Ontario, Canada and Cincinnati Children’s Hospital Medical Center (“CCHMC”)
• Appointment of Frank Schulkes, Dan Brague and Marcella Ruddy, MD to the Board as independent Non-Executive Directors
• Appointment of Ken West as Non-Executive Chairman, following the retirement of Jonathan Allis
• Research collaboration with Oxford University Hospitals NHS Trust for long-COVID
• Net cash of US$16.4 million as of 31 December 2022

Post-period end

• First order for a XENOVIEW gas blend cylinder for the production of XENOVIEW received from CCHMC, representing key milestone and execution of commercial plan
• First clinical scan utilising XENOVIEW technology in the United States conducted at CCHMC, marking key milestone for imaging of lung ventilation
• Selected as one of the featured companies as a poster presenter at the American Thoracic Society’s (“ATS”) 2023 Respiratory Innovation Summit

Richard Hullihen, CEO of Polarean, said: "We ended the year with a tremendous positive in receiving our FDA approval for XENOVIEW. This was a long road culminating with the decision we were looking for, and an extraordinary amount of work went into this process from the entire team. We have now begun to roll out XENOVIEW for clinical use and expect to see further hospitals adopt doing clinical XENOVIEW scans in the coming months. We also continue to explore potential future applications for our technology and remain positive for the year ahead. Separately, we have been shortlisted for Breakthrough of the Year and Best Technology at the 2023 European Mediscience Awards, which celebrates private and listed healthcare, biotech and life sciences companies; we are delighted by this validation of our technology and our achievement in securing FDA approval, and are excited to see the outcome.

“On behalf of the Board and the whole Polarean team, I would like to extend my thanks to our shareholders for all their support and we look forward to further updating the market in due course.” 

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014.

Inquiries: 

About Polarean (www.polarean.com)

The Company and its wholly owned subsidiary, Polarean, Inc. (together the "Group") are revenue-generating, medical imaging technology companies operating in the high-resolution medical imaging space. Polarean aspires to revolutionise pulmonary medicine by bringing the power and safety of MRI to the respiratory healthcare community in need of new solutions to evaluate lung ventilation, diagnose disease, characterise disease progression, and monitor response to treatment. By researching, developing, and commercialising novel imaging solutions with a non-invasive and radiation-free functional imaging platform. Polarean’s vision is to help address the global unmet medical needs of more than 500 million patients worldwide suffering with chronic respiratory disease. Polarean is a leader in the field of hyperpolarisation science and has successfully developed the first and only hyperpolarised MRI contrast agent to be approved in the United States. On Dec. 23, 2022, the FDA granted approval for Polarean’s first drug device combination product, XENOVIEW^TM (Xenon Xe¹²⁹ hyperpolarised). Xe¹²⁹ MRI is also currently being studied for visualisation and quantification of gas exchange regionally in the smallest airways of the lungs, across the alveolar tissue membrane, and into the pulmonary bloodstream for future clinical indications.

XENOVIEW IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Risk of Decreased Image Quality from Supplemental Oxygen: Supplemental oxygen administered simultaneously with XENOVIEW^TM inhalation can cause degradation of image quality. For patients on supplemental oxygen, withhold oxygen inhalation for two breaths prior to XENOVIEW^TM inhalation, and resume oxygen inhalation immediately following the imaging breath hold.

Risk of Transient Hypoxia: Inhalation of an anoxic gas such as XENOVIEW^TM may cause transient hypoxemia in susceptible patients. Monitor all patients for oxygen desaturation and symptoms of hypoxemia and treat as clinically indicated.

Adverse Reactions

Adverse Reactions in Adult Patients: The adverse reactions (> one patient) in efficacy trials were oropharyngeal pain, headache, and dizziness.  Adverse Reactions in Pediatric and Adolescent Patients: In published literature in pediatric patients aged 6 to 18, transient adverse reactions were reported: blood oxygen desaturation, heart rate elevation, numbness, tingling, dizziness, and euphoria. In at least one published study of pediatric patients aged 6 to 18 years, transient decrease in SpO2% and transient increase in heart rate was reported following hyperpolarized xenon Xe 129 administration. XENOVIEW^TM is not approved for use in pediatric patients less than 12 years of age.

Please see full prescribing information at www.xenoview.net

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Chairman’s Statement

I am pleased to be able to write this letter with the very important milestone of United States Food & Drug Administration (“FDA”) approval of the Company’s drug device combination product, XENOVIEW, having been accomplished. The broad label of “evaluation of lung ventilation in adults and pediatric patients aged 12 years and older” allows the company to execute its commercial strategy of selling its polarizer and approved gas for clinical scans of patients suffering from a number of lung diseases where the accurate measurement of lung ventilation provides the physician with actionable diagnostic information. In addition, researchers using Polarean’s technology continue to conduct clinical research that supports the broad future potential applications of our technology in areas of gas exchange and cardiopulmonary diagnostics. We are excited to bring Polarean’s technology to clinical medicine, with the potential to be an important part of pulmonary and cardiopulmonary diagnostics, monitoring of severity of disease and patient response to treatments.

During 2022, we strengthened our Board with the addition of three independent Non-Executive Board members who bring extensive industry and medical experience to the Board to assist the company’s successful transition into the commercialization stage. Frank Schulkes brings substantial financing experience in the medical imaging industry and Dan Brague brings experience successfully commercializing diagnostic imaging products. In addition, Dr. Marcella Ruddy brings important pulmonary medical expertise, both in clinical practice and in pharmaceutical development. With these additions to our Board, we believe that we have a world-class Board that can lead the company to successful commercialization of Xenoview.

Having achieved FDA approval, our efforts are now focused on gaining commercial traction and engaging with potential corporate partners to further accelerate our commercial success. Once we have achieved some of these near-term milestones, we will explore the options for additional financing to more aggressively pursue the development of the next indications and advance the continued development of our polarizer system and software. The Company is exploring a broad range of options for future financing, including equity raises and corporate partnering.

On behalf of the Board, I want to thank our employees, stakeholders and shareholders and assure them that we are committed to making Xenoview a commercial and financial success.

Kenneth West

Non-Executive Chairman
25 May 2023

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Chief Executive Officer’s Statement

2022 – Year of Obtaining FDA Approval

We spent much of 2022 working on obtaining FDA approval of our New Drug Application (“NDA”) for XENOVIEW and were please received our approval on 23 December 2022. After receiving a Complete Response Letter (“CRL”) from the FDA in October 2021, we spend the subsequent six months addressing the issues raised in the CRL. On 30 March 2022, the Company refiled the NDA with the FDA. The resubmission addressed the items identified in the CRL. On 22 September the Company announced that the FDA had requested additional information related to the cGMP (Current Good Manufacturing Practice) pre-approval inspection at the partner’s production facility. The Company and its partner addressed the FDA’s request and the Company received FDA approval on 23 December 2022. We were very pleased to receive the broad label of evaluation of lung function in adults and pediatric patients twelve and older. In addition, the FDA indicated that they would allow us to submit a non-clinical plan to obtain approval in pediatric patients six and older. The FDA has granted New Chemical Entity (“NCE”) designation for Xenoview. NCE designation provides the important first mover protection envisioned under the Hatch Waxman legislation.

Commercialization

With FDA approval, the Company is focused on successful commercialization of XENOVIEW for the evaluation of lung function. The Company has an enthusiastic base of US institutions who have been using our technology for research purposes for years. We are leveraging this knowledge and enthusiasm by converting its US research sites to FDA approved configuration and clinical use, which will allow these sites to purchase Xenoview and perform clinical scans. In parallel, we are pursuing various reimbursement codes that could enable the hospitals to be reimbursed for Xenoview, the polarization process, the MRI procedure and the analysis of the pulmonary function imaging. If obtained, we believe that this reimbursement would enable a very compelling return on investment for hospitals to purchase our polarizer systems. We are aggressively pursuing our early commercialization targets of the sale of 15 to 20 polariser systems and 75 to 100 cylinders of Xenoview by the end of 2024.

We are focusing initially on addressing the high end of the US academic and teaching hospital market segment, which comprises approximately the top 1000 institutions nationally having coincident multiple Centres of Excellence in Pulmonary Medicine and Radiology. We believe our strategy of selling the capital equipment and the Xenoview drug on a per cylinder basis could provide a capital equipment and recurring drug sales model that supports rapidly growing revenue.

Financials

Sales for 2022 were below our original expectations, as we did not receive FDA approval in October 2022 as anticipated in the plan. We adjusted our spending plans commensurate with the delayed approval, which allowed us to finish 2022 with a higher than anticipated cash balance of US$16.4 million. We continued to sell our polariser systems into the research market and completed two installations during 2022. The current cash balance is expected to fund the company into late Q2-2024.

Corporate Partnering

We continue to believe that corporate partnering could be an important part of the Company’s business plan. We see the opportunity to help the pharmaceutical industry reduce by significant amounts the size, time required to conduct and costs of their pulmonary drug clinical trials by providing quantitative, reproducible image-based data. We also see the opportunity to partner with MRI manufacturers to open up the MRI applications space to include pulmonary diagnostics, driving the demand for more MRI systems. In addition, we will explore the opportunity to partner with pulmonary disease organizations and foundations to incorporate the use of Xenoview in the diagnosis and treatment of disease.

Future Indications

Researchers are currently conducting clinical trials and pharmaceutical company sponsored investigations in multiple areas of pulmonary disease using our technology. These studies are highlighting the exciting opportunities in the areas of long COVID and cardiopulmonary vascular disease. We believe that these areas could greatly expand the total addressable markets and use of the Company’s technology in the future.

2023 and Beyond

As discussed above, we are focused on achieving early commercial traction with our broad lung function evaluation label granted by the FDA in late 2022. In parallel, we are exploring a variety of partnering opportunities. Once we have achieved some of these near-term milestones, we will explore the appropriate timing and structure to finance the continued commercial efforts, clinical trials to seek approval for the high-value gas exchange and pulmonary vascular disease indications and continue to improve our polariser system and imaging software.

This important milestone of FDA approval would not have been possible without the dedicated team of employees, consultants and advisers working to bring our much needed technology to clinicians, their patients and the institutions enabling their care. I thank everyone for their hard work in accomplishing this significant achievement.

Richard Hullihen

Chief Executive Officer
25 May 2023

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Strategic Report

1. Introduction 

The Group comprises medical drug-device combination companies operating in the high-resolution medical imaging market. The Group develops equipment that enables existing MRI systems to achieve an improved level of pulmonary functional imaging and specialises in the use of polarised xenon gas (129Xe ) as an imaging agent to visualise ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of oxygen to diffuse through the alveolar membrane into the pulmonary vasculature) regionally down to the smallest airways of the lungs, the tissue barrier between the lung and the bloodstream and in the pulmonary vasculature; and now also microvascular haemodynamics within the lung, a novel diagnostic approach. The Group will also register and sell the high-performance MRI radiofrequency (RF) coils which are a required component for imaging 129Xe in the MRI system. Providing access to these coils facilitates the adoption of the Xenon technology by providing application-specific RF coils which optimise the imaging of 129Xe in MRI equipment.

The Group was formed on 31 May 2017 when the Company acquired Polarean, Inc (the “Subsidiary”). The Subsidiary was formed as a result of two mergers: the first between Polarean Merger-Sub Inc. and m2m, a company that the Subsidiary had developed a relationship with during the course of previous research and commercialisation programmes in the US and the second between m2m and the Subsidiary. m2m was previously a portfolio company of Amphion Innovations plc (“Amphion”), a developer of medical, life science, and technology businesses, which is itself currently listed on AIM.

2. Investment Case

Pulmonary disease currently affects hundreds of millions of people globally, including approximately 174 million people who suffer from Chronic Obstructive Pulmonary Disease (“COPD”), which is responsible for approximately 6% of such deaths globally each year. In the US more than 30 million people suffer from a chronic lung disease such as COPD, which includes emphysema, chronic bronchitis and asthma. In addition to its significant human toll, pulmonary disease also represents an economic burden in excess of US$150 billion annually in the US alone.

Every type of pulmonary disease involves some combination of ventilation and/or gas exchange impairment, yet the successful and cost-effective treatment of lung disease is hampered by sub-optimal methods for quantifying pulmonary ventilation and gas exchange. Current diagnostic techniques are either imprecise (such as spirometry) and/or expose the patient to potentially dangerous radiation (such as x-rays, CT scans and nuclear scintigraphy). While spirometry has benefits as a screening tool, none of these current methods can visualise ventilation or gas exchange regionally in the smallest airways, where lung disease typically begins and where improvements from new pharmaceutical therapies can first be detected.

As such, the Group operates in an area of significant unmet medical need and is pursuing approval by the US Food & Drug Administration (“FDA”) for the Group’s drug-device combination product using hyperpolarised xenon-129 gas to enhance MRI in pulmonary medicine. The Company submitted a new drug application (“NDA”) to the FDA on 5 October 2020 after the successful completion of the FDA Phase III clinical trials in the US for the Group’s technology. The 80-patient equivalence clinical trials were conducted at Duke University Medical Center, the University of Virginia and The University of Cincinnati - three leading US research hospitals. Enrolment of the clinical trials was completed in November 2019. In January 2020, the Company announced that both clinical trials met their primary endpoints, within the prospectively defined equivalence margin (+/-14.7%) when compared to the FDA-approved reference standard, 133Xenon scintigraphy imaging. On 5 October 2021, the Company received a Complete Response Letter (“CRL”) from the FDA requesting that the Company to address approvability issues identified by the FDA ahead of NDA resubmission. On 30 March 2022, the Company filed the resubmission of the NDA with the FDA. On 20 April 2022, the Company announced that the FDA had accepted the resubmission of the NDA and established a user fee goal date of 30 September 2022. On 30 September 2022, the Company announced that the FDA had granted the Company a 90 day extension to the NDA review timeline. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with magnetic resonance imaging ("MRI") for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. On 28 December 2022, the Company also announced that, simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA that will further support a successful launch of the technology into the clinical marketplace: XENOVIEW VDP software and the XENOVIEW 3.0T Chest Coil. XENOVIEW VDP is image processing software that analyzes a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualization and evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. This image analysis platform quantifies normalized xenon intensity of a ventilated space using a pulmonary hyperpolarised 129-Xe ventilation MR image and accompanying proton chest MR image. The software will be used by clinicians to assist in the interpretation and numerical classification of hyperpolarized 129-Xe ventilation MR images. The Polarean XENOVIEW 3.0T Chest Coil is a flexible, single channel, transmit-receive (T/R) RF coil tuned to 129Xe frequency on a 3.0T MRI magnetic field of a compatible MRI scanner. The Polarean XENOVIEW 3.0T Chest Coil is indicated to be used in conjunction with compatible 3.0T MRI scanners and approved xenon Xe 129 hyperpolarised for oral inhalation for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. The Chest Coil is intended to be worn by a patient who inhales hyperpolarised 129Xe gas (XENOVIEW) to obtain an MR image of the regional distribution of hyperpolarised 129Xe in the lungs.

The Group’s technology overcomes important limitations of current lung diagnostic methods, providing the ability to visualise, quantify and monitor both the structure and function of the smallest airways and alveolar spaces with enhanced sensitivity and without harmful radiation. This provides a unique, valuable and more precise tool to help diagnose disease earlier, identify the type of intervention likely to benefit a patient, monitor the efficacy of treatment and facilitate developing new therapies for pulmonary diseases.

3. Group Structure and History

The Company was incorporated in England and Wales on 24 October 2016 with company registration number 10442853. The Company’s registered office is 27-28 Eastcastle Street, London, W1W 8DH.

On 31 May 2017, m2m, a company formed in the US State of Delaware on 18 February 1999, was merged into the Company.

On 29 March 2018, the Company’s shares were admitted to trading on the AIM market of the London Stock Exchange.

4. Information on Polarean, m2m and Strategy of Group

4.1 Polarean, Inc. – Background

The Subsidiary was co-founded by Dr Bastiaan Driehuys, a current Director of the Company, and John Sudol, a former director of the Subsidiary, in 2011. Prior to co-founding the Subsidiary, Dr Driehuys was a member of a research team at Princeton University in the early 1990s which was amongst the first research teams to focus on hyperpolarised gas MRI technology; in particular isotopically enriched helium (3He). The team developed and held key patents relating to the technology. The technology was acquired in 1999 by Amersham, Inc. (“Amersham”), with the goal of commercialising hyperpolarised helium products to be marketed and distributed alongside Amersham’s full line of contrast agent products. Dr Driehuys led the development efforts for Amersham, which continued the development of these hyperpolarised helium products throughout the early 2000s until GE Healthcare (“GE”) acquired Amersham in 2004.

GE continued the research and development of hyperpolarised gas MRI after the acquisition of Amersham, focusing on 129Xe as a more effective substitute for 3 He in visualising ventilation. GE also began to explore ways in which 129Xe could be used to image gas exchange within the lung in addition to ventilation. These work programmes culminated in the conduct of a Phase I/II clinical trial at Duke University in 2008-2009. GE also filed Investigational New Drug Applications (‘INDs”) with the FDA for both 3He and 129Xe. By 2010, after an investment of approximately US$40 million in the technology and with the regulatory path for hyperpolarised gas remaining unclear, GE decided to out-license the hyperpolarised gas technology and the related patent families that it had developed and/or maintained to the Subsidiary, due to the scale at the time and the early-stage nature of the technology’s development.

In December 2011, the Subsidiary negotiated the acquisition of all of GE’s assets related to the hyperpolarised MRI project, including an inventory of polarisers and parts and the licenses (or outright ownership) of the related patent families.

Following the acquisition of GE’s hyperpolarisation assets, the Subsidiary focused on three key objectives:

• building and selling polarisers to research users to generate operating revenue and to disseminate the technology to academic research institutions that generate clinical data in order to build additional interest in the technology;
• further developing the xenon hyperpolarisation technology in order to meet clinical use specification requirements; and
• liaising with the FDA in order to clarify the FDA regulatory path under which the product could achieve clearance to market for clinical use.

In July 2012, the US Congress passed the FDA Safety and Innovation Act and the Medical Gas Act, which clarified and simplified the path under which hyperpolarised gas MRI technology could be approved for clinical use by the FDA.

As a result of discussions between the Group and the FDA, the Directors believed that a clearer path towards regulatory approval existed. As such, following listing our shares on the AIM market the Group began conducting the clinical studies required for FDA approval to market. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

Between January 2012 and May 2017, the Subsidiary generated over US$3.7 million of revenue from selling polarisers to customers in Canada, Germany, the UK and the US for research use, relating to both clinical (human) and pre-clinical (animal) applications. In addition, the Subsidiary received additional funding of approximately US$2.5 million from Nukem and other Series A investors. Prior to the m2m merger, the Subsidiary was also successful in receiving grant funding, including a US$3 million grant awarded in April 2017 by the US National Heart, Lung and Blood Institute (NHLBI) following a competitive application process (for which the research will be conducted with its clinical collaborator, the Cincinnati Children’s Hospital) and a US$250,000 small business research loan from the North Carolina Biotech Center in March 2017, which was also awarded following a competitive application process.

4.2 The Group’s Technology and Products

The Subsidiary’s lead product has been designated as a drug-device combination by the FDA. The Subsidiary’s product enables the visualisation of hyperpolarised ¹²⁹Xe (“HPX”) through MRI technology to help diagnose lung disease earlier, identify the type of intervention likely to benefit a patient and to monitor the efficacy of treatment. As a result of the FDA’s drug-device designation, the Subsidiary’s products will be approved and sold only for use with each other. The products are currently being used at a number of research sites on a pre-FDA clearance basis to facilitate the research and evaluation of lung function, to assist in making improved disease progression assessment and to clearly visualise the effectiveness of several therapeutics which are under development. The Group currently generates revenue from the sale of products within its ¹²⁹Xe gas hyperpolarisation platform.

Implementing the Group’s technology in a clinical setting is straightforward: prior to the MRI scan a patient breathes in a small amount of inert HPX to provide an extremely strong MRI signal. This transforms the MRI from a technology that is not applicable to the lungs into one that is able to provide multiple images of the lung structure and function in one 10-20 second breath-hold. HPX MRI overcomes the limitations of traditional pulmonary function testing as HPX MRI:

• is more accurate and reproducible than spirometry and other traditional pulmonary function tests, enabling the detection and mapping of small and localised changes in lung ventilation and gas exchange over time;
• provides regional information about lung disease without exposure to ionising radiation or radioactivity; and
• assesses ventilation and gas exchange in the smallest airways, where disease often begins.

The Group’s technology works in conjunction with traditional MRI, transforming it into a powerful diagnostic modality for the lung. The Group’s approach is to take ¹²⁹Xe, an inert gas, and hyperpolarise the nucleus to create an MRI signal which is approximately 100,000 times stronger than a conventional MRI signal. When the MRI scan is undertaken, the HPX resonates at different frequencies: (i) in the bronchioles and alveoli of the lung; (ii) in the barrier tissue of the lung; and (iii) when dissolved in arterial blood in the pulmonary vasculature, thus providing information on ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of air to diffuse through the alveolar membrane into the pulmonary vasculature). As all pulmonary diseases result from impairments to the free flow of air through bronchioles, or from abnormal gas exchange between the lung alveoli and the pulmonary vasculature, the images that result from HPX MRI scans which have been executed using the Group’s technology can aid diagnosis, by enhancing the physician’s ability to clearly identify issues with ventilation and gas exchange on a regional basis, down to the smallest of airways. Hyperpolarisation of the ¹²⁹Xe is accomplished by placing a non-radioactive isotope of Xenon (¹²⁹Xe) into a beam of circularly polarised laser light in the presence of very small concentration of the alkali metal Rubidium, which acts as a physical catalyst in the hyperpolarisation process. The result is ¹²⁹Xe whose nuclear magnetic spin is highly aligned but not chemically or biologically different than unpolarised ¹²⁹Xe, an inert gas. This hyperpolarised state persists for around 2 hours allowing ample time to administer the HPX to the patient.

The Group’s products include:

• the ¹²⁹Xe gas, blended and made under GMP at high purity, to be polarised within the polariser;
• the polariser itself, of which the latest model, the Polarean 9820 Xenon Hyperpolariser, has been designed to deliver up to 3 litres of HPX per hour (approximately 5-10 doses) of which each dose is to be used within 30 minutes of its production in order to retain sufficient polarisation to create a strong image;
• the dose delivery inhalation bag, made of HPX-compatible impermeable plastic materials and a mouthpiece for ease of inhalation; and
• the Polarean 2881 Polarisation Measurement Station, which provides a calibrated measurement of the polarisation of hyperpolarised gas within the dose delivery inhalation bag.

The Group currently designs and builds the polariser equipment at a contract manufacturer and has relationships with GMP gas producers to supply the Group with high purity ¹²⁹Xe according to the Group’s specifications.

In order to take advantage of the Group’s current products, an MRI machine is required to be outfitted with hardware and software capable of operating at ¹²⁹Xe frequency to detect the HPX signal. In addition, the patient will need to wear a ¹²⁹Xe RF chest coil to allow for detecting the HPX MR signal in the lungs. Approximately 35,000 MRI machines are currently in use worldwide and technically many of these can be easily adapted to be used with ¹²⁹Xe frequency. The Group’s products can be placed near the MRI scanner for ease of radiology workflow and, following the m2m merger, the Group has continued to explore ways to further integrate the Group’s existing technology with the coils which had previously been the focus of m2m.

4.3 Location

The Group is based at the Meridian Corporate Center, located in the Research Triangle Park area of North Carolina, which provides a favourable location at which to further develop the core technology and product range. The Group’s facilities consist of more than 6,900 square feet of combined offices, laboratory space, inventory warehouse and assembly and testing areas. The Group benefits from facilities that were originally purpose-built by GE for the design and manufacture of hyperpolarisation equipment and components, pursuant to FDA-mandated guidelines.

Within these facilities are a dedicated research and development laboratory equipped with 3-phase power, central compressed air, specialty gas handling and distribution and separate heating, ventilation and air conditioning. The laboratory area also includes optical cell production equipment capable of simultaneous processing of four optical cells for Xenon applications. The laboratory is designed for safe operation of class 4 lasers and is equipped with laser power and spectral testing apparatus.

The Group also maintains a dedicated polariser test bed that is used for product development and a dedicated Nuclear Magnetic Resonance (“NMR”) system capable of delivering available electromagnetic field strength, utilised for calibrating absolute polarisation measurements of hyperpolarised gas samples.

4.4 The Regulatory Environment

Prior to the receipt of any approvals for clinical use, the Group sold its polarisers and disposables for research use only to academic medical centres with their research being subject to oversight by their respective institutional review boards and conducted under IND from the FDA or equivalent regulatory body.

On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

4.5 The Group’s Customers

The Group’s existing customer base already comprises some of the world’s luminary medical imaging research institutions. Indeed, there are numerous research institutions worldwide utilising the Group’s system and products, including Cincinnati Children’s Hospital, the University of Virginia, University of Wisconsin – Madison, Duke University, University of Kansas, the University of Iowa and the University of Texas MD Anderson Cancer Center in the US, Robarts Research Institute and Hospital for Sick Children (SickKids) in Canada, the University of Oxford and the University of Nottingham in the UK and the Fraunhofer Institute for Toxicology and Experimental Medicine in Germany.

4.6 The Group’s Suppliers

The Group has entered into Master Service Agreements with two CROs in relation to the Phase III trial. Pharma Start LLC, doing business as Firma Clinical Research, managed the trials and oversaw the recruitment of patients for the trial. In addition, Icon Clinical Research Limited assisted with the medical imaging aspects of the trial.

The Group has a long-standing relationship with its strategic investor Nukem Isotopes GmbH (“Nukem”), a leading global supplier of ¹²⁹Xe, the isotope of xenon which is provided to the various gas blenders that in turn supply gas to the Group. It has a supply agreement with Nukem for ¹²⁹Xe.

In June 2020 the Group signed an agreement with Linde Gas North America LLC (“Linde”), in relation to the supply of the Group’s drug product, a ¹²⁹Xenon gas blend. This agreement contains provision for the supply of bulk ¹²⁹Xe to be manufactured into the Active Pharmaceutical Product (API), ¹²⁹Xe, and for the blending, packaging, and distribution of its drug product under GMP. On 28 December 2022, the Group signed an amended agreement with Linde, which modified some commercial terms and limited the agreement to the blending packaging and distribution of it drug product under GMP.

The Group has an arrangement with the Blur Product Development (“Blur”) to build its polariser systems in Blur’s GMP facilities.

4.7 Current Trading and Prospects

Trading of the Group since the Company’s IPO continues to be in line with the Directors’ expectations. The potential of the Group’s technology enables the Directors to view the future with confidence as the Company focuses on commercialisation of XENOVIEW.

4.8 Growth Strategy

With the recent FDA approval, the Group is adopting a traditional market entry strategy of building market awareness for its technology through key opinion leaders and a direct sales force to reach the key decision makers within its initial target market of large academic medical centres. In implementing this strategy, the Group benefits from approximately 1,000 journal articles on the use of hyperpolarised gas MRI that are currently published in peer-reviewed journals. Over time, as more research centres purchase the Group’s equipment and begin clinical studies, an increasing number of peer reviewed scientific articles are likely to be published, further enhancing the Group’s credibility and raising awareness of the Group’s technology. The Directors believe that the market for polarisers will grow as the technology gains wider acceptance as a tool for studying lung disease and for monitoring the effectiveness of therapeutics. The Group also intends to continue patenting and in-licensing hyperpolarised gas technology IP to protect its current position.

The Group’s initial sales targets will be the radiology and pulmonary medicine departments of top academic hospital organisations in the US, who are opinion leaders in the use of new diagnostic technologies and their application in a clinical setting.

The Group is expanding its sales and marketing teams. Because of the specialty nature of the Group’s products in the pulmonary specialist market, which is concentrated in approximately 1,000 medical centres, the Directors believe that a small specialty sales force can be deployed effectively at reasonable cost.

The Group may also choose to partner with companies that offer complementary products.

Furthermore, the Directors believe that the Group’s products will benefit a number of clinical applications. While the Group’s HPX MRI technology provides more specific information than currently available from existing lung diagnostic procedures (especially spirometry), the Group will focus its use on specific clinical conditions where the high accuracy of HPX MRI and greater cost are justified. The Directors do not believe that HPX MRI will replace low-cost spirometry as a general screening tool but believe that it should add value in more demanding clinical applications where HPX MRI addresses unmet diagnostic needs. These applications could include, but are not limited to, the following:

• the monitoring of COPD therapy, especially for the most severe cases;
• the management of cystic fibrosis;
• determining the optimal use of biologic therapy in chronic asthma;
• a more efficient diagnosis of dyspnoea and the chronic cough;
• providing guidance for radiation therapy planning of lung cancer treatment;
• providing guidance for interventional pulmonology procedures including ablation and the placement of valves and stents;
• surgical procedure planning for lung transplant and volume reduction surgery;
• diagnosis of ILD and monitoring of ILD therapy;
• diagnosis of pulmonary vascular disease (PVD) including pulmonary arterial hypertension (PAH) and monitoring of therapy; and
• diagnosis and monitoring of long COVID patients.

The Directors have begun to develop relationships with a range of strategic partners and will evaluate opportunities which will enable the Group to address its target markets globally, either alone or in collaboration with a partner. 

5. Intellectual Property (“IP”)

The Group’s technology has been developed in four areas: (i) hyperpolarising gas; (ii) assuring the quality of the hyperpolarised gas; (iii) using the polarised gas in MRI applications; and (iv) developing and producing specialised RF coils to improve signal-to-noise ratios (“SNR”). GE had put a comprehensive patent policy in place to protect its technology from potential competitors. The Group is now the sole owner of this IP portfolio, which is based on 10 patent families, and when combined with the 7 patents that were previously owned by m2m, that were transferred to the Group following the m2m Merger, the Group’s portfolio covers four broad types of patents:

• imaging methods – these cover the imaging of a subject, or patient, who has inhaled a hyperpolarised noble gas and the functionality of the gas as a contrast agent. Newly licensed technology from Duke University extends the protection over these patents through to the early 2030s;
• hyperpolarisation methods – these are polarimetry patents covering the methods by which noble gases are polarised and the methods by which the resulting polarised gas is isolated and delivered to patients. The latest of these patents expire in the early 2020s;
• hyperpolarisation equipment – these patents cover the multiple preferred mechanical design and automation elements of hyperpolarised equipment; and
• RF coil patents – these patents cover the use of cryogenics to improve RF coils SNR and image quality and may play an important part in the next generation of applications such as neurological, cardiac and oncology imaging.

Polarean is committed to proactively developing further IP, both internally and through licensing arrangements with third parties, as part of the Group’s overall growth strategy. The third parties are likely to include the Group’s key collaborative academic sites, such as Duke University, that are seeking to develop emerging applications and technologies. Because of the Group’s extensive patent portfolio and leading market position, the Directors believe the Group is an attractive licensing partner for academic research institutions that are interested in out-licensing such IP. One such patent application (US15/120013), which is currently pending, relates to improving the overall efficiency of the hyperpolarisation process. This patent has also been exclusively licensed to the Group by Duke University. The Directors believe that this patent, now having been prosecuted successfully to issuance in a number of geographic jurisdictions worldwide, would enable the Group to protect methods for increasing the level of hyperpolarisation significantly, which could improve the competitive economics of the Group’s products.

6. Principal Risks and Uncertainties  

The principal risks and uncertainties facing the Group are detailed below:

Early stage of operations

The Group’s operations are at an early stage of development and there can be no guarantee that the Group will be able to, or that it will be commercially advantageous for the Group to, develop its proprietary technology. Further, the Group currently has no positive operating cash flow and its ultimate success will depend on the Directors’ ability to implement the Group’s strategy, generate cash flow and access capital markets.

Principal mitigation

The Group has successfully advanced the ¹²⁹Xe technology for several years, including selling polarisers for the research market. The Group has been able to access capital required to continue to advance the technology.

Regulatory approvals and compliance

The Group will need to obtain various regulatory approvals (including FDA and European Medicines Agency (“EMA”) approvals) and otherwise comply with extensive regulations regarding safety, quality and efficacy standards in order to market its future products. These regulations, including the time required for regulatory review, vary from country to country and can be lengthy, expensive and uncertain.

Principal mitigation

The Group utilises external specialists in regulatory affairs who consult with other experts to ensure that internal control processes and clinical trial designs meet current regulatory requirements. The Group also engages directly with regulatory authorities when appropriate.

Future funding requirements

The Group will need to raise additional funding or enter into a strategic partnership with industry partners to undertake work beyond that being funded by the £27 million (before expenses) 2021 fundraising. There is no certainty that this will be possible at all or on acceptable terms.

Principal mitigation

The Group successfully engaged with investors to generate significant cash resources to date, including the 2021 financing that raised £27 million, before expenses. The Group’s management team expects that continued access to capital markets, or other access to capital, will be required to support the Group through regulatory approval and initial commercialisation efforts in the US. See Going Concern discussion below.

Dependence on key personnel

The success of the Group, in common with other businesses of a similar size, will be highly dependent on the expertise and experience of the Directors and key employees. However, the retention of such key personnel cannot be guaranteed. Should key personnel leave the Group’s business, prospects, financial condition or results of operations may be materially adversely affected.

Principal mitigation

The Group’s recruitment processes are designed to identify and attract the best candidates for specific roles. The Group aims to provide competitive rewards and incentives to staff and directors.

Intellectual property and proprietary technology

No assurance can be given that any current or future patent applications will result in granted patents, that the scope of any patent protection will exclude competitors or provide competitive advantages to the Group, that any of the Group’s patents will be held valid if challenged or that third parties will not claim rights in or ownership of the patents and other proprietary rights held by the Group.

Principal mitigation

The Group has a long-standing track record of IP generation and successful applications and has a long-standing relationship with our patent attorney who has a deep understanding of our technology. The Group actively manages its IP, engaging with specialists to apply for and defend IP rights in appropriate territories.

Technology and products

The Group is a developer and service provider for noble gas ¹²⁹Xe devices and ancillary instruments with a special focus on pulmonary imaging. The development and commercialisation of its proprietary technology and future products, which are in early stages of development, will require multiple series of clinical trials and there is a risk that safety and efficacy issues may arise when the products are tested. There is also a risk that there will be delays to the development of the products or that unforeseen technical problems arise as the Group’s technology becomes increasingly automated. These risks are common to all new medical products and there is also a risk that the clinical trials may not be successful.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as safety, manufacturing and software development.

Research and development risk

The Group will be operating in the life sciences and medical device development sector and will look to exploit opportunities within that sector. The Group will therefore be involved in complex scientific research and industry experience indicates that there may be a very high incidence of delay or failure to produce results. The Group may not be able to develop new products or to identify specific market needs that can be addressed by technology solutions developed by the Group.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as conducting clinical trials and regulatory affairs.

Competition

The Group notes that several start-ups operating in the CT software space have begun efforts to commercialise products which represent to characterise lung ventilation. These technologies use ionising radiation, whereas the Group’s technology does not. In addition, these technologies are unable to further assess gas exchange, red blood cell transport, nor microvascular haemodynamics.

Principal mitigation

The Group believes that these emerging technologies validate the unmet need for the use of imaging in assessing pulmonary function. However, their use of ionising radiation, combined with their inability to assess comprehensive pulmonary function will render their utility limited and the Directors see no effect on the current market expectations of Polarean.

Reliance on third parties

The business model for the Group anticipates that it will have limited internal resources over the next few years and that it will use third party providers wherever possible to conduct the research, development, registration, manufacture, marketing and sales of its proposed products. The commercial success of the Group’s products will depend upon the performance of these third parties.

Principal mitigation

The Group seeks experts in the areas where it utilises outsourcing. Wherever possible, the Group seeks to have duplicate suppliers to lessen the reliance on a particular vendor.

Manufacturing

There can be no assurance that the Group’s proposed products will be capable of being manufactured in commercial quantities, in compliance with regulatory requirements and at an acceptable cost. The Group outsources the manufacture of the raw materials and finished products required in connection with the research, development and commercial manufacture of its proposed products and, as such, is wholly dependent upon third parties for the provision of adequate facilities and raw material supplies. ¹²⁹Xe, the specific isotope of xenon which is the active ingredient in the Group’s drug-device product, is available from a limited number of suppliers and there can be no assurance that adequate supplies of this material at acceptable cost can be obtained. In addition, where the Group is dependent upon third parties for manufacture, its ability to procure the manufacture of the drug-device in a manner which complies with regulatory requirements may be constrained, and its ability to develop and deliver such products on a timely and competitive basis may be adversely affected.

Principal mitigation

The Group has designed the manufacturing process to be scalable and has internal experts who train the outside vendors. The Group has established relationships with two ¹²⁹Xe suppliers to mitigate the risk that ¹²⁹Xe supply will be a limitation to the development and commercialisation of its products. In addition, the Group has established a relationship with a GMP outside polariser manufacturer.

Product development timelines

Product development timelines are at risk of delay, particularly since it is not always possible to predict what the FDA will require for approval of future NDA’s. There is a risk therefore that product development could take longer than presently expected by the Directors. If such delays occur the Group may require further working capital. The Directors shall seek to minimise the risk of delays by careful management of projects.

Principal mitigation

The Group utilises consultants who are experts in preparing and filing future NDAs in the US.

General legal and regulatory issues

The Group’s operations are subject to laws, regulatory restrictions and certain governmental directives, recommendations and guidelines relating to, amongst other things, occupational safety, laboratory practice, the use and handling of hazardous materials, prevention of illness and injury, environmental protection and animal and human testing. There can be no assurance that future legislation will not impose further government regulation, which may adversely affect the business or financial condition of the Group.

Principal mitigation

The Group consults experts for advice in areas such as occupational safety, laboratory practice and human testing.

Healthcare pricing environment

In common with other healthcare products companies, the ability of the Group and any of its licensees or collaborators to market its products successfully depends in part on the extent to which reimbursement for the cost of such products and related treatment will be available from government health administration authorities, private health coverage insurers and other organisations.

Principal mitigation

The Group is consulting with several experts in the field of reimbursement for healthcare products in the US to determine the best strategy for accessing adequate reimbursement for its products.

7. Section 172 statement

As required by section 172 of the Companies Act 2006 (the “Act”), a director of a company must act in the way he or she considers, in good faith, would likely promote the success of the company for the benefit of the shareholders. In doing so, the director must have regard, amongst other matters, to the following issues:

• the likely consequences of any decisions in the long term;
• the interests of the company’s employees;
• the need to foster the company’s business relationships with suppliers/customers and others;
• the impact of the company’s operations on the community and environment;
• the company’s reputation for high standards of business conduct; and
• the need to act fairly between members of the company.

The information required by section 172 of the Act is included in the full Annual Report.

Kenneth West
Non-Executive Chairman

25 May 2023

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Consolidated Statement of Comprehensive Income

The results reflected above relate to continuing activities.

There are no items of Other Comprehensive Income (“OCI”) for the year other than the loss above and therefore no separate statement of other comprehensive income has been presented.

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Consolidated Statement of Financial Position

These Financial Statements were approved and authorised for issue by the Board of Directors on 25 May 2023 and were signed on its behalf by:

Kenneth West
Non-Executive Chairman

Company number: 10442853

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Consolidated Statement of Changes in Equity

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Consolidated Statement of Cash Flows

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Notes on Financial Statements

The notes are available in the printable PDF of the results.  To download it, please click here

Notice of Annual General Meeting

In addition, Polarean confirms that the Annual Report and Accounts for the year ended 31 December 2022, the Notice of the Annual General Meeting ("AGM") and a Form of Proxy are now available on the Company's website (http://www.polarean-ir.com/content/investors/annual-reports.asp) and will be posted to shareholders shortly.

The AGM will be held at 2500 Meridian Parkway, Suite 175, Durham, NC 27713, USA at 2 p.m. BST / 9 a.m. EST on 28 June 2023.

Highlights

• United States Food and Drug Administration (“FDA”) approval received for the Company’s drug device combination product, XENOVIEW (xenon Xe 129 hyperpolarised), a hyperpolarised contrast agent indicated for use with magnetic resonance imaging (“MRI”) for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older
• Simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA; XENOVIEW VDP is image processing software that analyses a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualisation and evaluation of lung ventilation and the Polarean XENOVIEW 3.0T Chest Coil
• Research system placements at McMaster University in Ontario, Canada and Cincinnati Children’s Hospital Medical Center (“CCHMC”)
• Appointment of Frank Schulkes, Dan Brague and Marcella Ruddy, MD to the Board as independent Non-Executive Directors
• Appointment of Ken West as Non-Executive Chairman, following the retirement of Jonathan Allis
• Research collaboration with Oxford University Hospitals NHS Trust for long-COVID
• Net cash of US$16.4 million as of 31 December 2022

Post-period end

• First order for a XENOVIEW gas blend cylinder for the production of XENOVIEW received from CCHMC, representing key milestone and execution of commercial plan
• First clinical scan utilising XENOVIEW technology in the United States conducted at CCHMC, marking key milestone for imaging of lung ventilation
• Selected as one of the featured companies as a poster presenter at the American Thoracic Society’s (“ATS”) 2023 Respiratory Innovation Summit

Richard Hullihen, CEO of Polarean, said: "We ended the year with a tremendous positive in receiving our FDA approval for XENOVIEW. This was a long road culminating with the decision we were looking for, and an extraordinary amount of work went into this process from the entire team. We have now begun to roll out XENOVIEW for clinical use and expect to see further hospitals adopt doing clinical XENOVIEW scans in the coming months. We also continue to explore potential future applications for our technology and remain positive for the year ahead. Separately, we have been shortlisted for Breakthrough of the Year and Best Technology at the 2023 European Mediscience Awards, which celebrates private and listed healthcare, biotech and life sciences companies; we are delighted by this validation of our technology and our achievement in securing FDA approval, and are excited to see the outcome.

“On behalf of the Board and the whole Polarean team, I would like to extend my thanks to our shareholders for all their support and we look forward to further updating the market in due course.” 

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014.

Inquiries: 

About Polarean (www.polarean.com)

The Company and its wholly owned subsidiary, Polarean, Inc. (together the "Group") are revenue-generating, medical imaging technology companies operating in the high-resolution medical imaging space. Polarean aspires to revolutionise pulmonary medicine by bringing the power and safety of MRI to the respiratory healthcare community in need of new solutions to evaluate lung ventilation, diagnose disease, characterise disease progression, and monitor response to treatment. By researching, developing, and commercialising novel imaging solutions with a non-invasive and radiation-free functional imaging platform. Polarean’s vision is to help address the global unmet medical needs of more than 500 million patients worldwide suffering with chronic respiratory disease. Polarean is a leader in the field of hyperpolarisation science and has successfully developed the first and only hyperpolarised MRI contrast agent to be approved in the United States. On Dec. 23, 2022, the FDA granted approval for Polarean’s first drug device combination product, XENOVIEW^TM (Xenon Xe¹²⁹ hyperpolarised). Xe¹²⁹ MRI is also currently being studied for visualisation and quantification of gas exchange regionally in the smallest airways of the lungs, across the alveolar tissue membrane, and into the pulmonary bloodstream for future clinical indications.

XENOVIEW IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Risk of Decreased Image Quality from Supplemental Oxygen: Supplemental oxygen administered simultaneously with XENOVIEW^TM inhalation can cause degradation of image quality. For patients on supplemental oxygen, withhold oxygen inhalation for two breaths prior to XENOVIEW^TM inhalation, and resume oxygen inhalation immediately following the imaging breath hold.

Risk of Transient Hypoxia: Inhalation of an anoxic gas such as XENOVIEW^TM may cause transient hypoxemia in susceptible patients. Monitor all patients for oxygen desaturation and symptoms of hypoxemia and treat as clinically indicated.

Adverse Reactions

Adverse Reactions in Adult Patients: The adverse reactions (> one patient) in efficacy trials were oropharyngeal pain, headache, and dizziness.  Adverse Reactions in Pediatric and Adolescent Patients: In published literature in pediatric patients aged 6 to 18, transient adverse reactions were reported: blood oxygen desaturation, heart rate elevation, numbness, tingling, dizziness, and euphoria. In at least one published study of pediatric patients aged 6 to 18 years, transient decrease in SpO2% and transient increase in heart rate was reported following hyperpolarized xenon Xe 129 administration. XENOVIEW^TM is not approved for use in pediatric patients less than 12 years of age.

Please see full prescribing information at www.xenoview.net

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Chairman’s Statement

I am pleased to be able to write this letter with the very important milestone of United States Food & Drug Administration (“FDA”) approval of the Company’s drug device combination product, XENOVIEW, having been accomplished. The broad label of “evaluation of lung ventilation in adults and pediatric patients aged 12 years and older” allows the company to execute its commercial strategy of selling its polarizer and approved gas for clinical scans of patients suffering from a number of lung diseases where the accurate measurement of lung ventilation provides the physician with actionable diagnostic information. In addition, researchers using Polarean’s technology continue to conduct clinical research that supports the broad future potential applications of our technology in areas of gas exchange and cardiopulmonary diagnostics. We are excited to bring Polarean’s technology to clinical medicine, with the potential to be an important part of pulmonary and cardiopulmonary diagnostics, monitoring of severity of disease and patient response to treatments.

During 2022, we strengthened our Board with the addition of three independent Non-Executive Board members who bring extensive industry and medical experience to the Board to assist the company’s successful transition into the commercialization stage. Frank Schulkes brings substantial financing experience in the medical imaging industry and Dan Brague brings experience successfully commercializing diagnostic imaging products. In addition, Dr. Marcella Ruddy brings important pulmonary medical expertise, both in clinical practice and in pharmaceutical development. With these additions to our Board, we believe that we have a world-class Board that can lead the company to successful commercialization of Xenoview.

Having achieved FDA approval, our efforts are now focused on gaining commercial traction and engaging with potential corporate partners to further accelerate our commercial success. Once we have achieved some of these near-term milestones, we will explore the options for additional financing to more aggressively pursue the development of the next indications and advance the continued development of our polarizer system and software. The Company is exploring a broad range of options for future financing, including equity raises and corporate partnering.

On behalf of the Board, I want to thank our employees, stakeholders and shareholders and assure them that we are committed to making Xenoview a commercial and financial success.

Kenneth West

Non-Executive Chairman
25 May 2023

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Chief Executive Officer’s Statement

2022 – Year of Obtaining FDA Approval

We spent much of 2022 working on obtaining FDA approval of our New Drug Application (“NDA”) for XENOVIEW and were please received our approval on 23 December 2022. After receiving a Complete Response Letter (“CRL”) from the FDA in October 2021, we spend the subsequent six months addressing the issues raised in the CRL. On 30 March 2022, the Company refiled the NDA with the FDA. The resubmission addressed the items identified in the CRL. On 22 September the Company announced that the FDA had requested additional information related to the cGMP (Current Good Manufacturing Practice) pre-approval inspection at the partner’s production facility. The Company and its partner addressed the FDA’s request and the Company received FDA approval on 23 December 2022. We were very pleased to receive the broad label of evaluation of lung function in adults and pediatric patients twelve and older. In addition, the FDA indicated that they would allow us to submit a non-clinical plan to obtain approval in pediatric patients six and older. The FDA has granted New Chemical Entity (“NCE”) designation for Xenoview. NCE designation provides the important first mover protection envisioned under the Hatch Waxman legislation.

Commercialization

With FDA approval, the Company is focused on successful commercialization of XENOVIEW for the evaluation of lung function. The Company has an enthusiastic base of US institutions who have been using our technology for research purposes for years. We are leveraging this knowledge and enthusiasm by converting its US research sites to FDA approved configuration and clinical use, which will allow these sites to purchase Xenoview and perform clinical scans. In parallel, we are pursuing various reimbursement codes that could enable the hospitals to be reimbursed for Xenoview, the polarization process, the MRI procedure and the analysis of the pulmonary function imaging. If obtained, we believe that this reimbursement would enable a very compelling return on investment for hospitals to purchase our polarizer systems. We are aggressively pursuing our early commercialization targets of the sale of 15 to 20 polariser systems and 75 to 100 cylinders of Xenoview by the end of 2024.

We are focusing initially on addressing the high end of the US academic and teaching hospital market segment, which comprises approximately the top 1000 institutions nationally having coincident multiple Centres of Excellence in Pulmonary Medicine and Radiology. We believe our strategy of selling the capital equipment and the Xenoview drug on a per cylinder basis could provide a capital equipment and recurring drug sales model that supports rapidly growing revenue.

Financials

Sales for 2022 were below our original expectations, as we did not receive FDA approval in October 2022 as anticipated in the plan. We adjusted our spending plans commensurate with the delayed approval, which allowed us to finish 2022 with a higher than anticipated cash balance of US$16.4 million. We continued to sell our polariser systems into the research market and completed two installations during 2022. The current cash balance is expected to fund the company into late Q2-2024.

Corporate Partnering

We continue to believe that corporate partnering could be an important part of the Company’s business plan. We see the opportunity to help the pharmaceutical industry reduce by significant amounts the size, time required to conduct and costs of their pulmonary drug clinical trials by providing quantitative, reproducible image-based data. We also see the opportunity to partner with MRI manufacturers to open up the MRI applications space to include pulmonary diagnostics, driving the demand for more MRI systems. In addition, we will explore the opportunity to partner with pulmonary disease organizations and foundations to incorporate the use of Xenoview in the diagnosis and treatment of disease.

Future Indications

Researchers are currently conducting clinical trials and pharmaceutical company sponsored investigations in multiple areas of pulmonary disease using our technology. These studies are highlighting the exciting opportunities in the areas of long COVID and cardiopulmonary vascular disease. We believe that these areas could greatly expand the total addressable markets and use of the Company’s technology in the future.

2023 and Beyond

As discussed above, we are focused on achieving early commercial traction with our broad lung function evaluation label granted by the FDA in late 2022. In parallel, we are exploring a variety of partnering opportunities. Once we have achieved some of these near-term milestones, we will explore the appropriate timing and structure to finance the continued commercial efforts, clinical trials to seek approval for the high-value gas exchange and pulmonary vascular disease indications and continue to improve our polariser system and imaging software.

This important milestone of FDA approval would not have been possible without the dedicated team of employees, consultants and advisers working to bring our much needed technology to clinicians, their patients and the institutions enabling their care. I thank everyone for their hard work in accomplishing this significant achievement.

Richard Hullihen

Chief Executive Officer
25 May 2023

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Strategic Report

1. Introduction 

The Group comprises medical drug-device combination companies operating in the high-resolution medical imaging market. The Group develops equipment that enables existing MRI systems to achieve an improved level of pulmonary functional imaging and specialises in the use of polarised xenon gas (129Xe ) as an imaging agent to visualise ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of oxygen to diffuse through the alveolar membrane into the pulmonary vasculature) regionally down to the smallest airways of the lungs, the tissue barrier between the lung and the bloodstream and in the pulmonary vasculature; and now also microvascular haemodynamics within the lung, a novel diagnostic approach. The Group will also register and sell the high-performance MRI radiofrequency (RF) coils which are a required component for imaging 129Xe in the MRI system. Providing access to these coils facilitates the adoption of the Xenon technology by providing application-specific RF coils which optimise the imaging of 129Xe in MRI equipment.

The Group was formed on 31 May 2017 when the Company acquired Polarean, Inc (the “Subsidiary”). The Subsidiary was formed as a result of two mergers: the first between Polarean Merger-Sub Inc. and m2m, a company that the Subsidiary had developed a relationship with during the course of previous research and commercialisation programmes in the US and the second between m2m and the Subsidiary. m2m was previously a portfolio company of Amphion Innovations plc (“Amphion”), a developer of medical, life science, and technology businesses, which is itself currently listed on AIM.

2. Investment Case

Pulmonary disease currently affects hundreds of millions of people globally, including approximately 174 million people who suffer from Chronic Obstructive Pulmonary Disease (“COPD”), which is responsible for approximately 6% of such deaths globally each year. In the US more than 30 million people suffer from a chronic lung disease such as COPD, which includes emphysema, chronic bronchitis and asthma. In addition to its significant human toll, pulmonary disease also represents an economic burden in excess of US$150 billion annually in the US alone.

Every type of pulmonary disease involves some combination of ventilation and/or gas exchange impairment, yet the successful and cost-effective treatment of lung disease is hampered by sub-optimal methods for quantifying pulmonary ventilation and gas exchange. Current diagnostic techniques are either imprecise (such as spirometry) and/or expose the patient to potentially dangerous radiation (such as x-rays, CT scans and nuclear scintigraphy). While spirometry has benefits as a screening tool, none of these current methods can visualise ventilation or gas exchange regionally in the smallest airways, where lung disease typically begins and where improvements from new pharmaceutical therapies can first be detected.

As such, the Group operates in an area of significant unmet medical need and is pursuing approval by the US Food & Drug Administration (“FDA”) for the Group’s drug-device combination product using hyperpolarised xenon-129 gas to enhance MRI in pulmonary medicine. The Company submitted a new drug application (“NDA”) to the FDA on 5 October 2020 after the successful completion of the FDA Phase III clinical trials in the US for the Group’s technology. The 80-patient equivalence clinical trials were conducted at Duke University Medical Center, the University of Virginia and The University of Cincinnati - three leading US research hospitals. Enrolment of the clinical trials was completed in November 2019. In January 2020, the Company announced that both clinical trials met their primary endpoints, within the prospectively defined equivalence margin (+/-14.7%) when compared to the FDA-approved reference standard, 133Xenon scintigraphy imaging. On 5 October 2021, the Company received a Complete Response Letter (“CRL”) from the FDA requesting that the Company to address approvability issues identified by the FDA ahead of NDA resubmission. On 30 March 2022, the Company filed the resubmission of the NDA with the FDA. On 20 April 2022, the Company announced that the FDA had accepted the resubmission of the NDA and established a user fee goal date of 30 September 2022. On 30 September 2022, the Company announced that the FDA had granted the Company a 90 day extension to the NDA review timeline. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with magnetic resonance imaging ("MRI") for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. On 28 December 2022, the Company also announced that, simultaneously with the approval of the XENOVIEW NDA, two 510(k) devices were cleared by the FDA that will further support a successful launch of the technology into the clinical marketplace: XENOVIEW VDP software and the XENOVIEW 3.0T Chest Coil. XENOVIEW VDP is image processing software that analyzes a pulmonary hyperpolarised 129-Xe MR image and a proton chest MR image to provide visualization and evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. This image analysis platform quantifies normalized xenon intensity of a ventilated space using a pulmonary hyperpolarised 129-Xe ventilation MR image and accompanying proton chest MR image. The software will be used by clinicians to assist in the interpretation and numerical classification of hyperpolarized 129-Xe ventilation MR images. The Polarean XENOVIEW 3.0T Chest Coil is a flexible, single channel, transmit-receive (T/R) RF coil tuned to 129Xe frequency on a 3.0T MRI magnetic field of a compatible MRI scanner. The Polarean XENOVIEW 3.0T Chest Coil is indicated to be used in conjunction with compatible 3.0T MRI scanners and approved xenon Xe 129 hyperpolarised for oral inhalation for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older. The Chest Coil is intended to be worn by a patient who inhales hyperpolarised 129Xe gas (XENOVIEW) to obtain an MR image of the regional distribution of hyperpolarised 129Xe in the lungs.

The Group’s technology overcomes important limitations of current lung diagnostic methods, providing the ability to visualise, quantify and monitor both the structure and function of the smallest airways and alveolar spaces with enhanced sensitivity and without harmful radiation. This provides a unique, valuable and more precise tool to help diagnose disease earlier, identify the type of intervention likely to benefit a patient, monitor the efficacy of treatment and facilitate developing new therapies for pulmonary diseases.

3. Group Structure and History

The Company was incorporated in England and Wales on 24 October 2016 with company registration number 10442853. The Company’s registered office is 27-28 Eastcastle Street, London, W1W 8DH.

On 31 May 2017, m2m, a company formed in the US State of Delaware on 18 February 1999, was merged into the Company.

On 29 March 2018, the Company’s shares were admitted to trading on the AIM market of the London Stock Exchange.

4. Information on Polarean, m2m and Strategy of Group

4.1 Polarean, Inc. – Background

The Subsidiary was co-founded by Dr Bastiaan Driehuys, a current Director of the Company, and John Sudol, a former director of the Subsidiary, in 2011. Prior to co-founding the Subsidiary, Dr Driehuys was a member of a research team at Princeton University in the early 1990s which was amongst the first research teams to focus on hyperpolarised gas MRI technology; in particular isotopically enriched helium (3He). The team developed and held key patents relating to the technology. The technology was acquired in 1999 by Amersham, Inc. (“Amersham”), with the goal of commercialising hyperpolarised helium products to be marketed and distributed alongside Amersham’s full line of contrast agent products. Dr Driehuys led the development efforts for Amersham, which continued the development of these hyperpolarised helium products throughout the early 2000s until GE Healthcare (“GE”) acquired Amersham in 2004.

GE continued the research and development of hyperpolarised gas MRI after the acquisition of Amersham, focusing on 129Xe as a more effective substitute for 3 He in visualising ventilation. GE also began to explore ways in which 129Xe could be used to image gas exchange within the lung in addition to ventilation. These work programmes culminated in the conduct of a Phase I/II clinical trial at Duke University in 2008-2009. GE also filed Investigational New Drug Applications (‘INDs”) with the FDA for both 3He and 129Xe. By 2010, after an investment of approximately US$40 million in the technology and with the regulatory path for hyperpolarised gas remaining unclear, GE decided to out-license the hyperpolarised gas technology and the related patent families that it had developed and/or maintained to the Subsidiary, due to the scale at the time and the early-stage nature of the technology’s development.

In December 2011, the Subsidiary negotiated the acquisition of all of GE’s assets related to the hyperpolarised MRI project, including an inventory of polarisers and parts and the licenses (or outright ownership) of the related patent families.

Following the acquisition of GE’s hyperpolarisation assets, the Subsidiary focused on three key objectives:

• building and selling polarisers to research users to generate operating revenue and to disseminate the technology to academic research institutions that generate clinical data in order to build additional interest in the technology;
• further developing the xenon hyperpolarisation technology in order to meet clinical use specification requirements; and
• liaising with the FDA in order to clarify the FDA regulatory path under which the product could achieve clearance to market for clinical use.

In July 2012, the US Congress passed the FDA Safety and Innovation Act and the Medical Gas Act, which clarified and simplified the path under which hyperpolarised gas MRI technology could be approved for clinical use by the FDA.

As a result of discussions between the Group and the FDA, the Directors believed that a clearer path towards regulatory approval existed. As such, following listing our shares on the AIM market the Group began conducting the clinical studies required for FDA approval to market. On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

Between January 2012 and May 2017, the Subsidiary generated over US$3.7 million of revenue from selling polarisers to customers in Canada, Germany, the UK and the US for research use, relating to both clinical (human) and pre-clinical (animal) applications. In addition, the Subsidiary received additional funding of approximately US$2.5 million from Nukem and other Series A investors. Prior to the m2m merger, the Subsidiary was also successful in receiving grant funding, including a US$3 million grant awarded in April 2017 by the US National Heart, Lung and Blood Institute (NHLBI) following a competitive application process (for which the research will be conducted with its clinical collaborator, the Cincinnati Children’s Hospital) and a US$250,000 small business research loan from the North Carolina Biotech Center in March 2017, which was also awarded following a competitive application process.

4.2 The Group’s Technology and Products

The Subsidiary’s lead product has been designated as a drug-device combination by the FDA. The Subsidiary’s product enables the visualisation of hyperpolarised ¹²⁹Xe (“HPX”) through MRI technology to help diagnose lung disease earlier, identify the type of intervention likely to benefit a patient and to monitor the efficacy of treatment. As a result of the FDA’s drug-device designation, the Subsidiary’s products will be approved and sold only for use with each other. The products are currently being used at a number of research sites on a pre-FDA clearance basis to facilitate the research and evaluation of lung function, to assist in making improved disease progression assessment and to clearly visualise the effectiveness of several therapeutics which are under development. The Group currently generates revenue from the sale of products within its ¹²⁹Xe gas hyperpolarisation platform.

Implementing the Group’s technology in a clinical setting is straightforward: prior to the MRI scan a patient breathes in a small amount of inert HPX to provide an extremely strong MRI signal. This transforms the MRI from a technology that is not applicable to the lungs into one that is able to provide multiple images of the lung structure and function in one 10-20 second breath-hold. HPX MRI overcomes the limitations of traditional pulmonary function testing as HPX MRI:

• is more accurate and reproducible than spirometry and other traditional pulmonary function tests, enabling the detection and mapping of small and localised changes in lung ventilation and gas exchange over time;
• provides regional information about lung disease without exposure to ionising radiation or radioactivity; and
• assesses ventilation and gas exchange in the smallest airways, where disease often begins.

The Group’s technology works in conjunction with traditional MRI, transforming it into a powerful diagnostic modality for the lung. The Group’s approach is to take ¹²⁹Xe, an inert gas, and hyperpolarise the nucleus to create an MRI signal which is approximately 100,000 times stronger than a conventional MRI signal. When the MRI scan is undertaken, the HPX resonates at different frequencies: (i) in the bronchioles and alveoli of the lung; (ii) in the barrier tissue of the lung; and (iii) when dissolved in arterial blood in the pulmonary vasculature, thus providing information on ventilation (the ability of air to reach the alveoli) and gas exchange (the ability of air to diffuse through the alveolar membrane into the pulmonary vasculature). As all pulmonary diseases result from impairments to the free flow of air through bronchioles, or from abnormal gas exchange between the lung alveoli and the pulmonary vasculature, the images that result from HPX MRI scans which have been executed using the Group’s technology can aid diagnosis, by enhancing the physician’s ability to clearly identify issues with ventilation and gas exchange on a regional basis, down to the smallest of airways. Hyperpolarisation of the ¹²⁹Xe is accomplished by placing a non-radioactive isotope of Xenon (¹²⁹Xe) into a beam of circularly polarised laser light in the presence of very small concentration of the alkali metal Rubidium, which acts as a physical catalyst in the hyperpolarisation process. The result is ¹²⁹Xe whose nuclear magnetic spin is highly aligned but not chemically or biologically different than unpolarised ¹²⁹Xe, an inert gas. This hyperpolarised state persists for around 2 hours allowing ample time to administer the HPX to the patient.

The Group’s products include:

• the ¹²⁹Xe gas, blended and made under GMP at high purity, to be polarised within the polariser;
• the polariser itself, of which the latest model, the Polarean 9820 Xenon Hyperpolariser, has been designed to deliver up to 3 litres of HPX per hour (approximately 5-10 doses) of which each dose is to be used within 30 minutes of its production in order to retain sufficient polarisation to create a strong image;
• the dose delivery inhalation bag, made of HPX-compatible impermeable plastic materials and a mouthpiece for ease of inhalation; and
• the Polarean 2881 Polarisation Measurement Station, which provides a calibrated measurement of the polarisation of hyperpolarised gas within the dose delivery inhalation bag.

The Group currently designs and builds the polariser equipment at a contract manufacturer and has relationships with GMP gas producers to supply the Group with high purity ¹²⁹Xe according to the Group’s specifications.

In order to take advantage of the Group’s current products, an MRI machine is required to be outfitted with hardware and software capable of operating at ¹²⁹Xe frequency to detect the HPX signal. In addition, the patient will need to wear a ¹²⁹Xe RF chest coil to allow for detecting the HPX MR signal in the lungs. Approximately 35,000 MRI machines are currently in use worldwide and technically many of these can be easily adapted to be used with ¹²⁹Xe frequency. The Group’s products can be placed near the MRI scanner for ease of radiology workflow and, following the m2m merger, the Group has continued to explore ways to further integrate the Group’s existing technology with the coils which had previously been the focus of m2m.

4.3 Location

The Group is based at the Meridian Corporate Center, located in the Research Triangle Park area of North Carolina, which provides a favourable location at which to further develop the core technology and product range. The Group’s facilities consist of more than 6,900 square feet of combined offices, laboratory space, inventory warehouse and assembly and testing areas. The Group benefits from facilities that were originally purpose-built by GE for the design and manufacture of hyperpolarisation equipment and components, pursuant to FDA-mandated guidelines.

Within these facilities are a dedicated research and development laboratory equipped with 3-phase power, central compressed air, specialty gas handling and distribution and separate heating, ventilation and air conditioning. The laboratory area also includes optical cell production equipment capable of simultaneous processing of four optical cells for Xenon applications. The laboratory is designed for safe operation of class 4 lasers and is equipped with laser power and spectral testing apparatus.

The Group also maintains a dedicated polariser test bed that is used for product development and a dedicated Nuclear Magnetic Resonance (“NMR”) system capable of delivering available electromagnetic field strength, utilised for calibrating absolute polarisation measurements of hyperpolarised gas samples.

4.4 The Regulatory Environment

Prior to the receipt of any approvals for clinical use, the Group sold its polarisers and disposables for research use only to academic medical centres with their research being subject to oversight by their respective institutional review boards and conducted under IND from the FDA or equivalent regulatory body.

On 28 December 2022, the Company announced that the FDA had granted approval for its drug device combination product, XENOVIEW. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarised contrast agent indicated for use with MRI for evaluation of lung ventilation in adults and pediatric patients aged 12 years and older.

4.5 The Group’s Customers

The Group’s existing customer base already comprises some of the world’s luminary medical imaging research institutions. Indeed, there are numerous research institutions worldwide utilising the Group’s system and products, including Cincinnati Children’s Hospital, the University of Virginia, University of Wisconsin – Madison, Duke University, University of Kansas, the University of Iowa and the University of Texas MD Anderson Cancer Center in the US, Robarts Research Institute and Hospital for Sick Children (SickKids) in Canada, the University of Oxford and the University of Nottingham in the UK and the Fraunhofer Institute for Toxicology and Experimental Medicine in Germany.

4.6 The Group’s Suppliers

The Group has entered into Master Service Agreements with two CROs in relation to the Phase III trial. Pharma Start LLC, doing business as Firma Clinical Research, managed the trials and oversaw the recruitment of patients for the trial. In addition, Icon Clinical Research Limited assisted with the medical imaging aspects of the trial.

The Group has a long-standing relationship with its strategic investor Nukem Isotopes GmbH (“Nukem”), a leading global supplier of ¹²⁹Xe, the isotope of xenon which is provided to the various gas blenders that in turn supply gas to the Group. It has a supply agreement with Nukem for ¹²⁹Xe.

In June 2020 the Group signed an agreement with Linde Gas North America LLC (“Linde”), in relation to the supply of the Group’s drug product, a ¹²⁹Xenon gas blend. This agreement contains provision for the supply of bulk ¹²⁹Xe to be manufactured into the Active Pharmaceutical Product (API), ¹²⁹Xe, and for the blending, packaging, and distribution of its drug product under GMP. On 28 December 2022, the Group signed an amended agreement with Linde, which modified some commercial terms and limited the agreement to the blending packaging and distribution of it drug product under GMP.

The Group has an arrangement with the Blur Product Development (“Blur”) to build its polariser systems in Blur’s GMP facilities.

4.7 Current Trading and Prospects

Trading of the Group since the Company’s IPO continues to be in line with the Directors’ expectations. The potential of the Group’s technology enables the Directors to view the future with confidence as the Company focuses on commercialisation of XENOVIEW.

4.8 Growth Strategy

With the recent FDA approval, the Group is adopting a traditional market entry strategy of building market awareness for its technology through key opinion leaders and a direct sales force to reach the key decision makers within its initial target market of large academic medical centres. In implementing this strategy, the Group benefits from approximately 1,000 journal articles on the use of hyperpolarised gas MRI that are currently published in peer-reviewed journals. Over time, as more research centres purchase the Group’s equipment and begin clinical studies, an increasing number of peer reviewed scientific articles are likely to be published, further enhancing the Group’s credibility and raising awareness of the Group’s technology. The Directors believe that the market for polarisers will grow as the technology gains wider acceptance as a tool for studying lung disease and for monitoring the effectiveness of therapeutics. The Group also intends to continue patenting and in-licensing hyperpolarised gas technology IP to protect its current position.

The Group’s initial sales targets will be the radiology and pulmonary medicine departments of top academic hospital organisations in the US, who are opinion leaders in the use of new diagnostic technologies and their application in a clinical setting.

The Group is expanding its sales and marketing teams. Because of the specialty nature of the Group’s products in the pulmonary specialist market, which is concentrated in approximately 1,000 medical centres, the Directors believe that a small specialty sales force can be deployed effectively at reasonable cost.

The Group may also choose to partner with companies that offer complementary products.

Furthermore, the Directors believe that the Group’s products will benefit a number of clinical applications. While the Group’s HPX MRI technology provides more specific information than currently available from existing lung diagnostic procedures (especially spirometry), the Group will focus its use on specific clinical conditions where the high accuracy of HPX MRI and greater cost are justified. The Directors do not believe that HPX MRI will replace low-cost spirometry as a general screening tool but believe that it should add value in more demanding clinical applications where HPX MRI addresses unmet diagnostic needs. These applications could include, but are not limited to, the following:

• the monitoring of COPD therapy, especially for the most severe cases;
• the management of cystic fibrosis;
• determining the optimal use of biologic therapy in chronic asthma;
• a more efficient diagnosis of dyspnoea and the chronic cough;
• providing guidance for radiation therapy planning of lung cancer treatment;
• providing guidance for interventional pulmonology procedures including ablation and the placement of valves and stents;
• surgical procedure planning for lung transplant and volume reduction surgery;
• diagnosis of ILD and monitoring of ILD therapy;
• diagnosis of pulmonary vascular disease (PVD) including pulmonary arterial hypertension (PAH) and monitoring of therapy; and
• diagnosis and monitoring of long COVID patients.

The Directors have begun to develop relationships with a range of strategic partners and will evaluate opportunities which will enable the Group to address its target markets globally, either alone or in collaboration with a partner. 

5. Intellectual Property (“IP”)

The Group’s technology has been developed in four areas: (i) hyperpolarising gas; (ii) assuring the quality of the hyperpolarised gas; (iii) using the polarised gas in MRI applications; and (iv) developing and producing specialised RF coils to improve signal-to-noise ratios (“SNR”). GE had put a comprehensive patent policy in place to protect its technology from potential competitors. The Group is now the sole owner of this IP portfolio, which is based on 10 patent families, and when combined with the 7 patents that were previously owned by m2m, that were transferred to the Group following the m2m Merger, the Group’s portfolio covers four broad types of patents:

• imaging methods – these cover the imaging of a subject, or patient, who has inhaled a hyperpolarised noble gas and the functionality of the gas as a contrast agent. Newly licensed technology from Duke University extends the protection over these patents through to the early 2030s;
• hyperpolarisation methods – these are polarimetry patents covering the methods by which noble gases are polarised and the methods by which the resulting polarised gas is isolated and delivered to patients. The latest of these patents expire in the early 2020s;
• hyperpolarisation equipment – these patents cover the multiple preferred mechanical design and automation elements of hyperpolarised equipment; and
• RF coil patents – these patents cover the use of cryogenics to improve RF coils SNR and image quality and may play an important part in the next generation of applications such as neurological, cardiac and oncology imaging.

Polarean is committed to proactively developing further IP, both internally and through licensing arrangements with third parties, as part of the Group’s overall growth strategy. The third parties are likely to include the Group’s key collaborative academic sites, such as Duke University, that are seeking to develop emerging applications and technologies. Because of the Group’s extensive patent portfolio and leading market position, the Directors believe the Group is an attractive licensing partner for academic research institutions that are interested in out-licensing such IP. One such patent application (US15/120013), which is currently pending, relates to improving the overall efficiency of the hyperpolarisation process. This patent has also been exclusively licensed to the Group by Duke University. The Directors believe that this patent, now having been prosecuted successfully to issuance in a number of geographic jurisdictions worldwide, would enable the Group to protect methods for increasing the level of hyperpolarisation significantly, which could improve the competitive economics of the Group’s products.

6. Principal Risks and Uncertainties  

The principal risks and uncertainties facing the Group are detailed below:

Early stage of operations

The Group’s operations are at an early stage of development and there can be no guarantee that the Group will be able to, or that it will be commercially advantageous for the Group to, develop its proprietary technology. Further, the Group currently has no positive operating cash flow and its ultimate success will depend on the Directors’ ability to implement the Group’s strategy, generate cash flow and access capital markets.

Principal mitigation

The Group has successfully advanced the ¹²⁹Xe technology for several years, including selling polarisers for the research market. The Group has been able to access capital required to continue to advance the technology.

Regulatory approvals and compliance

The Group will need to obtain various regulatory approvals (including FDA and European Medicines Agency (“EMA”) approvals) and otherwise comply with extensive regulations regarding safety, quality and efficacy standards in order to market its future products. These regulations, including the time required for regulatory review, vary from country to country and can be lengthy, expensive and uncertain.

Principal mitigation

The Group utilises external specialists in regulatory affairs who consult with other experts to ensure that internal control processes and clinical trial designs meet current regulatory requirements. The Group also engages directly with regulatory authorities when appropriate.

Future funding requirements

The Group will need to raise additional funding or enter into a strategic partnership with industry partners to undertake work beyond that being funded by the £27 million (before expenses) 2021 fundraising. There is no certainty that this will be possible at all or on acceptable terms.

Principal mitigation

The Group successfully engaged with investors to generate significant cash resources to date, including the 2021 financing that raised £27 million, before expenses. The Group’s management team expects that continued access to capital markets, or other access to capital, will be required to support the Group through regulatory approval and initial commercialisation efforts in the US. See Going Concern discussion below.

Dependence on key personnel

The success of the Group, in common with other businesses of a similar size, will be highly dependent on the expertise and experience of the Directors and key employees. However, the retention of such key personnel cannot be guaranteed. Should key personnel leave the Group’s business, prospects, financial condition or results of operations may be materially adversely affected.

Principal mitigation

The Group’s recruitment processes are designed to identify and attract the best candidates for specific roles. The Group aims to provide competitive rewards and incentives to staff and directors.

Intellectual property and proprietary technology

No assurance can be given that any current or future patent applications will result in granted patents, that the scope of any patent protection will exclude competitors or provide competitive advantages to the Group, that any of the Group’s patents will be held valid if challenged or that third parties will not claim rights in or ownership of the patents and other proprietary rights held by the Group.

Principal mitigation

The Group has a long-standing track record of IP generation and successful applications and has a long-standing relationship with our patent attorney who has a deep understanding of our technology. The Group actively manages its IP, engaging with specialists to apply for and defend IP rights in appropriate territories.

Technology and products

The Group is a developer and service provider for noble gas ¹²⁹Xe devices and ancillary instruments with a special focus on pulmonary imaging. The development and commercialisation of its proprietary technology and future products, which are in early stages of development, will require multiple series of clinical trials and there is a risk that safety and efficacy issues may arise when the products are tested. There is also a risk that there will be delays to the development of the products or that unforeseen technical problems arise as the Group’s technology becomes increasingly automated. These risks are common to all new medical products and there is also a risk that the clinical trials may not be successful.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as safety, manufacturing and software development.

Research and development risk

The Group will be operating in the life sciences and medical device development sector and will look to exploit opportunities within that sector. The Group will therefore be involved in complex scientific research and industry experience indicates that there may be a very high incidence of delay or failure to produce results. The Group may not be able to develop new products or to identify specific market needs that can be addressed by technology solutions developed by the Group.

Principal mitigation

The Group has a depth of knowledge and experience in the area of medical devices development for the high-resolution medical imaging market. The Group also utilises external experts to supplement their knowledge in critical areas such as conducting clinical trials and regulatory affairs.

Competition

The Group notes that several start-ups operating in the CT software space have begun efforts to commercialise products which represent to characterise lung ventilation. These technologies use ionising radiation, whereas the Group’s technology does not. In addition, these technologies are unable to further assess gas exchange, red blood cell transport, nor microvascular haemodynamics.

Principal mitigation

The Group believes that these emerging technologies validate the unmet need for the use of imaging in assessing pulmonary function. However, their use of ionising radiation, combined with their inability to assess comprehensive pulmonary function will render their utility limited and the Directors see no effect on the current market expectations of Polarean.

Reliance on third parties

The business model for the Group anticipates that it will have limited internal resources over the next few years and that it will use third party providers wherever possible to conduct the research, development, registration, manufacture, marketing and sales of its proposed products. The commercial success of the Group’s products will depend upon the performance of these third parties.

Principal mitigation

The Group seeks experts in the areas where it utilises outsourcing. Wherever possible, the Group seeks to have duplicate suppliers to lessen the reliance on a particular vendor.

Manufacturing

There can be no assurance that the Group’s proposed products will be capable of being manufactured in commercial quantities, in compliance with regulatory requirements and at an acceptable cost. The Group outsources the manufacture of the raw materials and finished products required in connection with the research, development and commercial manufacture of its proposed products and, as such, is wholly dependent upon third parties for the provision of adequate facilities and raw material supplies. ¹²⁹Xe, the specific isotope of xenon which is the active ingredient in the Group’s drug-device product, is available from a limited number of suppliers and there can be no assurance that adequate supplies of this material at acceptable cost can be obtained. In addition, where the Group is dependent upon third parties for manufacture, its ability to procure the manufacture of the drug-device in a manner which complies with regulatory requirements may be constrained, and its ability to develop and deliver such products on a timely and competitive basis may be adversely affected.

Principal mitigation

The Group has designed the manufacturing process to be scalable and has internal experts who train the outside vendors. The Group has established relationships with two ¹²⁹Xe suppliers to mitigate the risk that ¹²⁹Xe supply will be a limitation to the development and commercialisation of its products. In addition, the Group has established a relationship with a GMP outside polariser manufacturer.

Product development timelines

Product development timelines are at risk of delay, particularly since it is not always possible to predict what the FDA will require for approval of future NDA’s. There is a risk therefore that product development could take longer than presently expected by the Directors. If such delays occur the Group may require further working capital. The Directors shall seek to minimise the risk of delays by careful management of projects.

Principal mitigation

The Group utilises consultants who are experts in preparing and filing future NDAs in the US.

General legal and regulatory issues

The Group’s operations are subject to laws, regulatory restrictions and certain governmental directives, recommendations and guidelines relating to, amongst other things, occupational safety, laboratory practice, the use and handling of hazardous materials, prevention of illness and injury, environmental protection and animal and human testing. There can be no assurance that future legislation will not impose further government regulation, which may adversely affect the business or financial condition of the Group.

Principal mitigation

The Group consults experts for advice in areas such as occupational safety, laboratory practice and human testing.

Healthcare pricing environment

In common with other healthcare products companies, the ability of the Group and any of its licensees or collaborators to market its products successfully depends in part on the extent to which reimbursement for the cost of such products and related treatment will be available from government health administration authorities, private health coverage insurers and other organisations.

Principal mitigation

The Group is consulting with several experts in the field of reimbursement for healthcare products in the US to determine the best strategy for accessing adequate reimbursement for its products.

7. Section 172 statement

As required by section 172 of the Companies Act 2006 (the “Act”), a director of a company must act in the way he or she considers, in good faith, would likely promote the success of the company for the benefit of the shareholders. In doing so, the director must have regard, amongst other matters, to the following issues:

• the likely consequences of any decisions in the long term;
• the interests of the company’s employees;
• the need to foster the company’s business relationships with suppliers/customers and others;
• the impact of the company’s operations on the community and environment;
• the company’s reputation for high standards of business conduct; and
• the need to act fairly between members of the company.

The information required by section 172 of the Act is included in the full Annual Report.

Kenneth West
Non-Executive Chairman

25 May 2023

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Consolidated Statement of Comprehensive Income

The results reflected above relate to continuing activities.

There are no items of Other Comprehensive Income (“OCI”) for the year other than the loss above and therefore no separate statement of other comprehensive income has been presented.

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Consolidated Statement of Financial Position

These Financial Statements were approved and authorised for issue by the Board of Directors on 25 May 2023 and were signed on its behalf by:

Kenneth West
Non-Executive Chairman

Company number: 10442853

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Consolidated Statement of Changes in Equity