Announcement PDF Patrys Limited Appendix 4E Preliminary final report 1. Company details Name of entity: ABN: Reporting period: Previous period: Patrys Limited 97 123 055 363 For the year ended 30 June 2024 For the year ended 30 June 2023 2. Results for announcement to the market $ Loss from ordinary activities after tax attributable to the Owners of Patrys Limited down 49.9% to (3,539,150) Loss for the year attributable to the Owners of Patrys Limited 49.9% to (3,539,150) down Dividends There were no dividends paid, recommended or declared during the current financial year. Comments The loss for the Group after providing for income tax amounted to $3,539,150 (30 June 2023: $7,061,624). During the year, the Group had total other income of $1,394,163 (2023: $2,851,908), consisting of the R&D tax incentive of $1,285,038 (2023: $2,775,033) and interest income of $109,125 (2023: $76,875). The Group's research and development expenditure during the financial year was $3,071,793 (2023: $7,524,812). This includes direct research and development activities associated with pre-clinical and manufacturing work, as well as wages, salaries and other overheads associated with research and development. The Group had cash at bank at 30 June 2024 amounting to $2,240,661 (30 June 2023: $3,045,516). Excluding prepaid expenses, the working capital position at 30 June 2024 was $2,893,697 (30 June 2023: $6,200,682). 3. Net tangible assets Reporting period Cents Net tangible assets per ordinary security 4. Control gained over entities Not applicable. 5. Loss of control over entities Not applicable. 6. Dividends Current Year There were no dividends paid, recommended or declared during the current financial year. 0.15 Previous period Cents 0.31 Patrys Limited Appendix 4E Preliminary final report Previous Year There were no dividends paid, recommended or declared during the previous financial year. 7. Dividend reinvestment plans Not applicable. 8. Details of associates and joint venture entities Not applicable. 9. Foreign entities Details of origin of accounting standards used in compiling the report: Not applicable. 10. Audit qualification or review Details of audit/review dispute or qualification (if any): The financial statements have been audited and an unqualified opinion has been issued. 11. Attachments Details of attachments (if any): The Annual Report of Patrys Limited for the year ended 30 June 2024 is attached. 12. Signed Signed ___________________________ Date: 23 August 2024 ANNUAL REPORT FY2024 Developing novel antibodies, for life Contents From the Chair 5 Our People 6 Patrys Snapshot 8 ASX News, Media Headlines 9 IP Update 10 NETosis 12 Manufacturing Antibodies 14 Directors’ Report 18 Auditor’s Independence Declaration 34 Statement of Profit or Loss and Other Comprehensive Income 35 Statement of Financial Position 36 Statement of Changes in Equity 37 Statement of Cash Flows 38 Notes to the Financial Statements 39 Directors’ Declaration 60 Independent Auditor’s Report to the Members of Patrys Limited 61 Shareholder Information 64 Corporate Directory 68 Corporate and Social Responsibility 69 3 4 From the Chairman As I reflect on the past year, it is clear that Patrys’ journey, like so many others in the global biotechnology industry, continues to be one of careful navigation through both challenges and potential opportunities. The past year has presented challenges with the manufacturing of PAT-DX1. After a manufacturing delay in early CY 2023 we engaged independent experts to oversee the process at our Contract Development and Manufacturing Organisation (CDMO). They worked closely with our CDMO, ensuring rigorous standards and objectivity in our manufacturing processes, and helped us to address and mitigate risks. A new batch of PAT-DX1 was produced at the start of CY 2024 using our production process, and we are currently waiting on the results of the specification testing which is required in order for the drug product to be released for possible use in clinical trials. We remain committed to being guided by both scientific and commercial inputs, and always use the information and data from our studies as the fundamental basis that underpins our research and development decisions. Our collaborations have yielded compelling data over the past year, opening potentially promising avenues beyond cancer, particularly in the inflammation space. We are carefully evaluating these recent discoveries, to determine their significance as they potentially broaden our therapeutic reach and impact. The biotechnology sector demands patience, perseverance, and an unwavering commitment to scientific excellence. While we have faced our share of challenges in dealing with a novel asset, we have also uncovered new possibilities that fuel our optimism for the future. Our team’s dedication to innovation and problem-solving continues to motivate us. We are focused on applying our learnings, prudently advancing our assets, and thoroughly evaluating the data emerging from our research and collaborations. Importantly too, we are committed to responsible stewardship of our resources and to protecting the investment of our loyal shareholders, as we navigate the complex landscape of drug development. I want to express my sincere gratitude to our employees, partners, and shareholders for their continued support and belief in our mission. Together, we are navigating the complex landscape of biotechnology, turning challenges into opportunities, and striving to make a meaningful difference for patients. Thank you for your ongoing trust and investment in our Company. Sincerely, Charmaine Gittleson Dr Charmaine Gittleson Patrys Chairman 5 Our People Patrys’ team comprises specialists in research, development, and innovation who are working together to progress our deoxymab technology and develop new approaches to tackling hard-to-treat diseases. Board of Directors Charmaine Gittleson Chairman of the Board of Directors, BSc.MBBCh, GAICD Dr. Gittleson is the former Chief Medical Officer of CSL Limited with more than 20 years of experience in pharmaceutical development. Her expertise spans many aspects of the pharmaceutical industry, from drug development and clinical research through to strategic planning and executive management. She has successfully worked with regulators in key markets such as the US, EU, Asia Pacific, Japan and South America to register new products that address unmet medical needs. Dr. Gittleson is the Chair of Percheron Therapeutics Limited (ASX:PER) and a board member of George Medicines Pty Ltd. James Campbell Managing Director & Chief Executive Officer, BSc (Hons), PhD, MBA, GAICD Dr. Campbell has more than 20 years of international biotechnology research, management and leadership experience and has been involved in the creation and/or transformation of multiple successful Australian and international biotechnology companies. Dr Campbell chairs the board of Australia’s peak industry body for biotechnology, AusBiotech, and is a Non executive director of Prescient Therapeutics Limited (ASX:PTX). Michael Stork Non-Executive Director, BBA Mr. Stork is the Managing Director of Stork Holdings Ltd, an Investment Holding company active in the Canadian technology startup sector. Mr. Stork previously served on the Board of Governors of the University of Waterloo and has served on the boards of a number of leading Canadian technology startup companies. Pamela M. Klein Non-Executive Director, BSc, MD Dr. Pamela M. Klein completed her medical training at Stritch School of Medicine, Loyola University in Chicago, followed by internal medicine training at Cedars-Sinai, Los Angeles, prior to spending seven years working at the U.S. National Cancer Institute. Dr. Klein currently serves as an advisor to a range of different biotech and investment companies, with roles on Scientific Advisory Boards and Corporate Boards as well as broader advisory roles. 6 Management Our Management Team brings a cross-section of experience and expertise in clinical and commercial development. Valentina Dubljevic Vice President, Research & Development, MBB, BSc, GAICD Ms. Dubljevic is responsible for the pre‑clinical and clinical development of Patrys’ products. Ms. Dubljevic brings more than 20 years of scientific and commercial experience in the areas of antibody therapeutics, vaccine development and diagnostics. Rebecca Tunstall Vice President, Corporate Development, PhD, GAICD Dr. Tunstall has an impressive track record in clinical development and stakeholder engagement in clinical research and development. She holds strong relationships with industry, government, regulators and research partners, both in Australia, and internationally. Stefan Ross Company Secretary, BBus (Accounting) Stefan Ross has over 10 years of experience in accounting and secretarial services for ASX Listed companies. His extensive experience includes ASX compliance, corporate governance control and implementation, statutory financial reporting, shareholder meeting requirements, capital raising management, preparation of prospectus’, and board and secretarial support. Mr Ross has a Bachelor of Business, majoring in Accounting. Scientific Advisory Board Our scientific advisors are globally sought-after specialists in their fields. Peter Ordentlich, BSc, PhD Dr. Peter Ordentlich completed a PhD in Immunology at the University of Pennsylvania and a Post‑Doc at the Salk Institute for Biological Studies. He worked at X‑Ceptor Therapeutics, which was acquired by Exelixis in 2004, then in 2005 co‑founded Syndax Pharmaceuticals, a NASDAQ‑listed, clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies with three clinical stage assets. Allen Ebens, BSc, PhD Dr. Allen Ebens completed a PhD at UCLA and Post‑doctoral training at UCSF. Over 20 years his distinguished career has seen significant contributions to the scientific literature as well as advancement of multiple discovery projects to clinical development at companies including Exelixis, Genentech and Juno Therapeutics. 7 Patrys Snapshot Patrys’ Deoxymabs: A novel therapeutic antibody platform Patrys has developed a new type of antibody - deoxymabs - which are attracted to cancer cells that do not have traditional cell surface markers of disease. Instead, they bind to fragments of DNA that are released from cells when they die - the rate of cell death is much higher in cancer cells than in healthy cells, meaning that deoxymabs can be used to target cancer cells regardless of their location or type. In animal experiments, Patrys has successfully demonstrated that deoxymabs are able to seek out and kill cancer cells in a variety of tissues anywhere in the body and can cross the blood brain barrier. This suggests that deoxymabs have the potential to be a versatile treatment for cancers, including brain cancers. Recent studies into the mechanism of action of deoxymabs have shown that they inhibit the formation of neutrophil extracellular traps (NETs), a process that underpins a range of inflammatory conditions. Patrys’ collaborators have expanded these studies and shown that unlike other agents that reduce NETosis, deoxymabs do not reduce neutrophil function – a particular advantage in fighting inflammatory diseases. These discoveries in inflammatory diseases have the potential to complement our existing development programs and provide increased flexibility for deoxymabs’ potential to address diseases with significant unmet medical needs. Unique attributes of Patrys’ deoxymabs Patrys’ deoxymab antibodies exhibit several distinctive properties ideal for human therapeutic applications: • They target DNA: Deoxymabs are anti-DNA antibodies and as such have the ability to target various DNA processes inside cells (cancer cells as well as others, including neutrophils) such as DNA repair and NETosis. • They cross the blood-brain barrier: The blood-brain barrier (BBB) presents a significant challenge in treating primary and secondary brain cancers as it limits the passage of drugs and antibodies into the brain. Deoxymabs possess the ability to cross the BBB and reach neural tissues, opening new avenues for treating brain diseases. • They inhibit NETosis: Excessive immune cell web formation (NETosis) contributes to the pathogenesis of cancer and many infectious, inflammatory, and autoimmune diseases. Deoxymabs significantly reduce NET formation in human neutrophils and reduce symptoms in an animal model of Anti‑Neutrophil Cytoplasmic Antibody (ANCA) associated Vasculitis (AAV). Notably, deoxymabs do not impair neutrophil activity which is important in preserving overall function of the immune system. Patrys’ commitment to advancing these innovative antibody-based approaches brings hope for more effective and targeted therapies, potentially transforming the landscape of cancer treatment and NETosis-driven inflammatory diseases. 8 ASX News, Media Headlines Milestones: FY24 During FY24, Patrys announced several clinical and commercial milestones. Ms Suzy Jones retires as Director after twelve years in the role Data from preclinical studies with PAT-DX1 and PAT-DX3 presented at US brain Sep 2023 Oct 2023 cancer conference Receives $2.7 million rebate under Federal Government’s R&D Tax Incentive Scheme Secures manufacturing slot with Contract Manufacturing & Development Organisation to commence GMP production of PAT-DX1 in Q1 CY2024 Preclinical data showing potential to use deoxymabs to treat certain autoimmune disease presented at international vasculitis conference Further positive data from preclinical studies using deoxymabs in animal models of vasculitis Nov 2023 Dec 2023 Mar 2024 Apr 2024 9 IP Update Intellectual Property Portfolio Patrys has an extensive global intellectual property (IP) portfolio with protection potentially extending through to at least 2044 in all major markets. This IP position is expected to provide the Company with substantial commercial advantages as it develops its product candidates for major markets including the United States, Europe, Japan and China. Deoxymab technology and product candidates The patents that Patrys has obtained, and continues to apply for, cover deoxymab antibodies PAT-DX1 and PAT-DX3 composition of matter, combination approaches, method of treatment and product candidates derived from these technologies. Among the indication-specific issued or pending patents covering product candidates derived from our deoxymab portfolio the company has patents covering the use of deoxymabs in a range of cancers and inflammatory diseases. There are now 12 granted patents covering the unconjugated form of deoxymab 3E10 (and derivatives thereof). These patents have been granted in the USA, throughout Europe and in both Japan and China. In addition, there are five patents covering nanoparticle conjugation that have been granted in various countries. In total, Patrys and Yale have filed numerous patent applications across 12 different patent families in major jurisdictions which provides the Company with a significant patent estate covering the use of its unique deoxymab platform for the treatment of cancer and inflammatory diseases. The Company now has a significant patent estate covering the use of its deoxymab antibodies. Patrys continues to focus on maintaining patent protection in major jurisdictions where future regulatory approvals and product sales are targeted. In addition, in many major jurisdictions the Company may be able to extend the commercial exclusivity period for its product candidates, which include, but are not limited to, the exclusive right to reference its data, orphan drug exclusivity and patent term extensions. Active intellectual property strategy in place to protect key assets Deoxymab patent portfolio 12Deoxymab patent portfolio 1813 3211 126 1 Active patent families Granted patents Patent families Patent applications pending Granted patents 1 International PCT Active patent application pending applications IPIP protection protectiongranted granted 10 1 US provisional application filed “ Our team is working with utmost discipline to realise the potential applications of our technology - and to meet the necessary checkpoints for a sustainable and scaleable clinical offering in market.” - Patrys CEO & MD, Dr James Campbell 11 NETosis Deoxymabs: Targeting NETosis to combat cancer and inflammation Neutrophils, are the most common white blood cell in the body’s immune system, and play a crucial role in defending against infections. NETosis involves neutrophils releasing web-like structures called neutrophil extracellular traps (NETs) to capture pathogens. While this mechanism is essential for fighting infections, an imbalance in NETosis, either through excessive release or impaired clearance of NETs, can lead to detrimental proinflammatory effects. These effects can contribute to the development and progression of various inflammatory diseases and metastatic cancers. Patrys’ research into the role of NETosis in metastatic cancer led to the unexpected discovery that deoxymabs inhibit NETosis and stop the release of NETs in human neutrophils. This finding identified deoxymabs possible therapeutics for a broad range of inflammatory diseases in addition to their potential as therapeutics to treat metastatic cancer. Patrys’ initial preclinical research has focused on ANCA-associated vasculitis (AAV), a severe inflammatory condition where NETs are released to fight inflammation and drive autoimmunity. In AAV, the body’s immune system mistakenly attacks small blood vessels, leading to inflammation that can damage vital organs, especially the kidneys and respiratory system. Current treatments for AAV rely heavily on broad-acting immunosuppressants and steroids, leaving patients vulnerable to infections and other serious side effects. As such, there is a real need for therapies that can effectively modify the course of the disease, restoring a more balanced immune response without compromising the patient’s overall immune defences. Patrys has shown deoxymabs inhibit human neutrophil NETosis, without affecting neutrophil viability, cytotoxicity, apoptosis, or host defense functions like phagocytosis. Deoxymabs also appear to reduce inflammation, autoimmunity, and kidney injury in an animal model of AAV. The preservation of immune function is a key differentiator of currently available treatments. Given the promising findings regarding the ability of deoxymabs to regulate NETosis, Patrys intends to expand its focus to include NETosis driven inflammatory diseases and potentially other renal disorders while continuing to investigate the role of deoxymabs in cancer, and in particular metastatic disease. In animal studies, deoxymabs ameliorate kidney injury. NETosis is emerging as a target in a number of renal diseases including lupus nephritis, diabetic nephropathy, acute tubular necrosis, anti-glomerular basement membrane disease, and anti-neutrophil cytoplasmic antibodymediated renal vasculitis. The opportunity to leverage the wealth of knowledge that Patrys has developed over recent years into an additional indication strengthens Patrys’ portfolio of activities and has the potential to expand the market opportunity beyond oncology to inflammatory diseases, particularly in nephrology. The team’s expertise in NETosis research is applicable to both cancer and inflammation. The Company intends to bolster its capabilities through additional new partnerships and securing input from key opinion leaders to support this expansion. 12 Image Credit: Dr Kim O’Sullivan, Centre for Inflammatory Diseases, Monash University. Preclinical data shared at international meetings Dr Kim O’Sullivan from Monash University presented preclinical data on the use of both PAT-DX1 and PAT-DX3 in an animal model of the autoimmune disease anti-neutrophil cytoplasmic antibody (ANCA) vasculitis during the plenary session of the 21st International Vasculitis Workshop in Barcelona in April 2024 and at the annual meeting of the American Association of Immunologists in Chicago in May 2024. Highlights of the presentations were; • PAT-DX1 inhibits the formation of neutrophil extracellular traps from human blood neutrophils in vitro; • Both PAT-DX1 and PAT-DX3 decreased NET formation and inflammation; • Both PAT-DX1 and PAT-DX3 reduced kidney injury and resultant protein in the urine 13 Manufacturing Antibodies Antibody Manufacturing: A Complex Challenge The manufacture of antibodies is essential for developing life-saving therapies but can also present complex and multifaceted challenges. The process spans multiple intricate stages, with each stage demanding meticulous attention to detail and adherence to stringent quality control measures to ensure the safety and reproducibility of the final product. What is involved in manufacturing antibodies? • Clone Selection Commercial production of monoclonal antibodies typically begins with the identification and optimisation of the coding DNA sequence and the construction and identification of a stable high-producing clonal cell line. Once a clone is available, an antibody production platform can be used to make large quantities of antibodies. Patrys has developed a stable cell clone for each of PAT-DX1 and PAT-DX3. The choice of production system is important to ensure the clone produces correctly folded proteins that maintain the molecule’s biological activity; stability; and increase the half-life, while reducing immunogenicity. Mammalian cells, like the CHO cell line, have become the predominant method for industrial biopharmaceutical production, largely because of their ability to produce consistent and reproducible quantities of antibodies. • Upstream Development After generating a stable cell clone, the next step involves upstream development processes to grow the cells. These include cell culture process, scale up and production. Disposable bioreactors are often used for small scale production due to easy adaptation to process validation and flexibility. The process parameters including feeding strategies, and the ongoing improvement of environmental parameters, are optimised to ensure reproducible results. Close monitoring is necessary to ensure high productivity and yields to make the monoclonal antibody production more economical. • Downstream Process Development Once the cells have produced the antibodies, they need to be extracted and purified from the culture medium. A series of different purification techniques, such as chromatography and filtration, may be employed to obtain highly purified and potent antibodies. • Formulation development Patient safety is paramount in drug development. Formulation development ensures that the antibody is stable and in an acceptable format for administration to patients. With certain indications, biologics may need to be administered at high doses, requiring an increase in drug substance and drug product protein concentrations. With this increase, formulation development is central to identifying critical physico-chemical liabilities, or negative characteristics, that may hinder the performance of the antibody. • Quality analysis and product characterisation This is the final step in the process. To get an antibody into the clinic—and ultimately, the treatment approved— requires robust, efficient and reproducible manufacturing process of the investigational product in an appropriate formulation and at sufficient quantity for trials. 14 Quality analysis - a critical requirement The quality analysis stage of manufacturing is critical to ensure that the final product is safe for use in patients, and possesses the desired therapeutic properties. During quality analysis, the antibodies are subjected to rigorous testing to assess their purity, potency, and consistency. Product characterisation involves evaluating various aspects of the antibodies, such as their structure, biological activity, and stability. This information is critical for understanding how the antibodies will behave in different conditions and helps determine the appropriate storage and handling conditions. These comprehensive quality control measures are essential for gaining regulatory approval and ensuring the safety and effectiveness of the manufactured monoclonal antibodies. The path forward for Patrys Patrys has generated two different forms of deoxymabs; a dimer (two units) of primarily the binding region called PATDX1, and a full-length IgG antibody called PAT-DX3. PAT-DX1 and PAT-DX3 share the same active binding regions and have the same mechanism of action. In CY 2024 PAT-DX1 was successfully manufactured and we await the results of the specification testing which must be successfully completed for the drug material to be released for possible use in clinical trials. In parallel, Patrys has been advancing the development of PAT-DX3 as a second asset and has already completed the early stages of development for this asset (clone selection, generation of MCBs and development of upstream and downstream processes and formulation). The past year has confirmed that PAT-DX1 is a challenging antibody to work with, and this is the counter-point to its unique qualities. Patrys believes that deoxymabs have significant potential for treating a variety of hard-to-reach and treat cancers, irrespective of their location, as well as various inflammatory diseases. 15 16 Financials 17 Patrys Limited Directors' report 30 June 2024 The Directors present their report, together with the financial statements, on the consolidated entity (referred to hereafter as the 'Group') consisting of Patrys Limited (referred to hereafter as the 'Company' or 'parent entity') and the entities it controlled at the end of, or during, the year ended 30 June 2024. Directors The following persons were Directors of Patrys Limited during the whole of the financial year and up to the date of this report, unless otherwise stated: Dr. Charmaine Gittleson (Non-Executive Chair) Mr. Michael Stork (Non-Executive Director and Deputy Chair) Dr. James Campbell (Managing Director & CEO) Dr. Pamela M. Klein (Non-Executive Director) Ms. Suzy Jones (Non-Executive Director - retired on 15 September 2023) Principal activities Patrys is leveraging its proprietary deoxymab antibody technology platform to develop new therapies for the treatment of cancer and other diseases. Unlike most other antibodies, Patrys’ deoxymabs are able to cross the blood-brain barrier, enter cells and the cell nucleus, and block the process of NETosis. Patrys is using these properties to develop new therapies that incorporate deoxymabs as a single agent, as part of a combination therapy, and for the targeted delivery of therapeutic agents to cancer cells. Through the 2023/24 financial year Patrys was focused on advancing its lead agent PAT-DX1 towards a first in human clinical study. As has been previously noted there have been challenges in the past associated with the up-scaled manufacturing of PAT-DX1. After a detailed review by external experts Patrys engaged its Contract Development Manufacturing Organization (CDMO) to manufacture a batch of PAT-DX1 for the first in human clinical study during the 2023/24 financial year. A batch of PAT-DX1 was successfully produced at the start of CY2024 (January 2024-December 2024) and we currently await the results from the specification testing which is required in order for the drug product to be released for possible use in human subjects. For several years and in parallel, Patrys has been advancing the development of PAT-DX3 as an additional deoxymab asset which is based on an antibody structure that is more commonly used for antibody therapeutics. Patrys has completed the early stages of development for PAT-DX3 including clone selection, generation of Master Cell Bank (MCB) and development of upstream and downstream processes and formulation. The past year has further highlighted that PAT-DX1 is a challenging antibody to work with, and this is the counter-point to its unique qualities. Patrys believes that deoxymabs have significant potential as therapeutics for a variety of hard-to-treat cancers, irrespective of their location, as well as for various inflammatory diseases. Patrys has an exclusive, worldwide licence to the deoxymab technology for cancer applications from Yale University, and is using this to develop and commercialise a portfolio of anti-cancer and diagnostic agents that include: anti-DNA antibodies, antibody fragments, variants and conjugates. Patrys and Yale University also have filed intellectual property pertaining to the use of deoxymabs in a range of non-cancer indications, and Patrys holds the exclusive commercial rights for these opportunities. Dividends There were no dividends paid, recommended or declared during the current or previous financial year. Review of operations R&D progress In October 2023 Patrys announced data from preclinical studies using PAT-DX1 and PAT-DX3 in animal models of high grade glioma was presented at the American Association for Cancer research (AACR) Special Conference on Brain Cancer. The data was presented by Prof Terrence Johns from the Telethon Kids Cancer Centre and described research confirming the single agent activity of both PAT-DX1 and PAT-DX3 in animal models of high-grade glioma, as well as significant survival benefits from combining PAT-DX1 with a therapeutic dose of radiation. On 13 December 2023, the Company confirmed that, following a comprehensive internal investigation and audit by both Patrys’ CDMO and independent, external evaluator, the unexpected manufacturing issue with PAT-DX1 which occurred in Q1 of CY2023 was neither predictable nor preventable. Patrys secured a manufacturing slot with its CDMO for a GMP (Good Manufa