Improving Lives, Offering Hope Nyrada Inc (ASX:NYR) ABRN 625 401 818 Annual report For the year ended 30 June 2024
NYRADA INC (ASX:NYR) 2 “Our lead brain injury program candidate, NYR-BI03, is targeting a very large and growing market. There are no current FDAapproved therapies for TBI which is experienced by over 70 million people worldwide each year. The estimated annual healthcare cost of non-fatal TBIs is over US$40 billion in the US alone.”
ANNUAL REPORT FY2024 3 Contents Nyrada overview 4 Corporate directory 5 Chair’s letter 6 CEO report 9 Directors’ report 13 Auditor’s independence declaration 35 Independent Auditor’s Report 36 Consolidated statement of profit or loss and other comprehensive income 41 Consolidated statement of financial position 42 Consolidated statement of changes in equity 43 Consolidated statement of cash flows 44 Notes to the consolidated financial statements 45 Consolidated entity disclosure statement 60 Directors’ declaration 61 Shareholder information 62
NYRADA INC (ASX:NYR) 4 Nyrada Overview Our vision To become a high growth pharmaceutical discovery and development company specialising in early-stage drug development of novel treatments. Our strategy To develop treatments for diseases where there is an unmet clinical need, or where current treatments are suboptimal, and to monetise the value of these treatments through advancing highly optimised drug candidates towards out-licensing. Lead program NYR-BI03, is a Transient Receptor Potential Cation (TRPC) ion channel blocker. It is a novel mechanism of action designed to act as a neuroprotective treatment for stroke and traumatic brain injury (TBI) sufferers.
ANNUAL REPORT FY2024 5 Corporate Directory Board of Directors John Moore (Non-Executive Chair) Rüdiger Weseloh (Non-Executive Director) Marcus Frampton (Non-Executive Director) Christopher Cox (Non-Executive Director) Ian Dixon (Non-Executive Director) Gisela Mautner (Non-Executive Director) Company secretary David Franks Registered office in Australia and principal place of business Suite 2, Level 3 828 Pacific Highway Gordon, NSW 2072 Australia Tel: +61 2 9498 3390 Registered office in place of incorporation 1209 Orange Street Wilmington, Delaware 19801 United States of America Share/CDI registry Automic Pty Ltd Level 5, 126 Phillip Street Sydney, NSW 2000 Australia Auditor William Buck Audit (Vic) Pty Ltd Level 20, 181 William Street Melbourne, VIC 3000 Australia Stock exchange listing Nyrada Inc. instruments registered for trade on the Australian Securities Exchange are CHESS Depositary Interests (CDIs). One CDI is equivalent to one Share, being Class A Common Stock. ASX code NYR Website www.nyrada.com
NYRADA INC (ASX:NYR) 6 Chair’s Letter Dear Fellow Stockholders, On behalf of the Nyrada Board of Directors, it gives me great pleasure to present our Annual Report for the 2024 Financial Year. I am delighted to share details of our Company’s progress. A New Era of Disease Targeting, Drug Discovery and Development Nyrada is dedicated to drug discovery and development, both of which are essential components of modern medicine and play a critical role in improving global health outcomes. The process of drug discovery involves identifying potential therapeutic compounds that can target specific diseases or conditions, followed by a rigorous development phase to refine these compounds into safe and effective drugs. This pathway is crucial for addressing unmet medical needs and providing new treatment options for diseases that currently lack effective therapies. It is fundamental to advancing our understanding of disease mechanisms, leading to the development of targeted therapies that offer more precise and effective treatments with fewer side effects. Over the past three decades, a deeper understanding of disease mechanisms has emerged. With this understanding, there have been corresponding advances in molecular biology to treat these disease pathways. For example, dramatically improved patient outcomes have resulted from drugs like Keytruda® and Opdivo®, which act as PD-1 inhibitors, and from Ozempic® and Mounjaro®, which are GLP-1 receptor agonists. Identifying drugs that effectively act on target pathways has led to near-miraculous health benefits for patients and significant wealth creation for investors. Nyrada’s Transient Receptor Potential Cation Channel Innovation Nyrada is the first company that we are aware of that is using a Transient Receptor Potential Cation (TRPC) channel-blocking therapy to target secondary brain injury. Nyrada is developing a small molecule drug that leverages new biomedical discoveries through pioneering TRPC channel-blocking therapies. Our lead drug, NYR-BI03, acts as a neuroprotective agent for traumatic brain injury (TBI) and stroke by seeking to block TRPC channels 3, 6, and 7. Immediately following the primary brain injury, these channels allow toxic levels of calcium to enter neurons, a process referred to as “excitotoxicity”, leading to cell death and secondary brain injury that adversely affects outcomes for the patient. “Notably, TRPC channel-blocking therapy is not limited to neurological conditions. Other researchers have published promising data related to other therapeutic areas where TRPC channels play an important role, including cardio and pulmonary diseases, autoimmune disorders, and cancer”
ANNUAL REPORT FY2024 7 Nyrada’s TRPC channel-blocking technology originated from the work of UNSW Sydney Prof. Gary Housley (Chair of Nyrada’s scientific advisory board) and Dr. Jasneet Parmar (Nyrada’s neuroscientist). Over the past ten years, Prof. Housley and Dr. Parmar have diligently developed key insights into TRPC channel inhibitors and their neurological implications. Their work included significant research on TRPC channels using mouse knockout models, focusing on how TRPC channels 3, 6, and 7 play a critical role in calcium dysregulation in neurons and glial cells. Prof. Housley’s and Dr. Parmar’s research has shown that blocking these channels can mitigate excitotoxicity and reduce brain injury expansion, signalling their potential as therapeutic targets for neuroprotection. Notably, TRPC channel-blocking therapy is not limited to neurological conditions. Other researchers have published promising data related to other therapeutic areas where TRPC channels play an important role, including cardio and pulmonary diseases, autoimmune disorders, and cancer. Nyrada’s Novel Neuroprotection Drug As part of Nyrada’s development process, our scientific team developed a broad portfolio of drug candidates that proved effective in animal models. Ultimately, NYR-BI03 was selected as our lead candidate due to its safety profile and fit for our clinical path forward in neurological applications. In February 2024, the Company reported the results from a preclinical stroke study that showed NYR-BI03 provided a statistically significant level of neuroprotection, rescuing 42% of brain injury in the penumbra region in treated animals. This was a significant result that paved the way for the Company to commence safety and tolerability studies on the path to a firstin-human Phase I clinical trial for NYR-BI03. We are very excited about these safety and tolerability studies because if we can prove NYR-BI03 is safe in humans, we then progress to Phase II studies and test for efficacy, with the potential to expand our pipeline to other TRPCrelated diseases where there is unmet or underserved clinical need. Targeting Large Unserved Market NYR-BI03 is targeting a very large and growing market in both TBI and stroke. There are no current FDA-approved therapies for TBI, which is experienced by over 70 million1 people worldwide each year. The estimated annual healthcare cost of non-fatal TBIs is over US$40 billion2 in the US alone. Approximately 15 million3 people globally suffer strokes, of whom 5 million are left permanently disabled. A recent inflection has been the massive investment in the US in clinical trial infrastructure to support the assessment of drugs like ours. The Track TBI Network is a research initiative focused on improving the understanding, diagnosis, and treatment of TBI. It spans 18 Level 1 Trauma Centres across the US and seeks to facilitate the conduct of TBI clinical trials. 1. https://pubmed.ncbi.nlm.nih.gov/33947273/ 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026675/ 3. https://www.emro.who.int/health-topics/stroke-cerebrovascular-accident/index.html
NYRADA INC (ASX:NYR) 8 Looking Forward and Conclusion We remain well-placed to achieve our goals. Nyrada's operating environment continues to be one of the best places in the world for cost-effective drug development. Australia boasts a strong and stable legal environment, produces gifted and talented scientists from a world-class university system, and benefits from a supportive governmental research and development rebate scheme. We are also excited to be collaborating with the largest potential customer in the world, the US military, in developing our drug therapy. Collectively, we strive to continue to deliver significant progress. I take this opportunity to thank my fellow Non-Executive Directors for their diligence and focus, our CEO James Bonnar for his leadership of the Company, and the Nyrada team for their efforts and insights. To my fellow stockholders, I thank you again for your ongoing support and your confidence in our efforts to reach our goals. As we move forward, we remain dedicated to delivering on our commitments. We eagerly anticipate sharing more updates and successes with you in the coming months. Together, we can turn opportunities into reality, discovery into therapies, and innovation into shareholder value. Warm regards, John Moore Non-Executive Chair “There are no current FDA-approved therapies for TBI, which is experienced by over 70 million people worldwide each year. The estimated annual healthcare cost of non-fatal TBIs is over US$40 billion in the US alone.”
ANNUAL REPORT FY2024 9 CEO Report Dear Fellow Stockholders, It is my pleasure again to provide you with this update on Nyrada’s results and operations for the 2024 financial year. On behalf of the Board, I wish to thank you all for your ongoing support. Nyrada is a biotechnology company that specialises in developing novel therapeutic drugs for diseases where there is a significant unmet clinical need or where current treatments are inadequate. The Company’s main focus this year has been on our Brain Injury Program, where we are seeking to advance our first-in-class drug, NYR-BI03, into a human volunteer Phase I clinical trial. We expect this Phase I trial to commence before the conclusion of this calendar year. Brain Injury Program Novel Mechanism of Action Nyrada’s lead Brain Injury Program candidate, NYR-BI03, is a Transient Receptor Potential Cation (TRPC) ion channel blocker. It is a novel mechanism of action designed to act as a neuroprotective treatment for stroke and traumatic brain injury (TBI) sufferers. TRPC channels are a group of ion channels located in the cellular membranes of human cells, involved in various physiological processes that influence cell function. They play an important role in various diseases, including neurological disorders, where they impact neuronal health and function mainly through their role in regulating calcium and sodium ion flow into neurons. Blocking TRPC channels can reduce calcium overload in neurons, which is a common feature of neuronal injury in stroke and TBI. By preventing excessive calcium influx, TRPC blockers can protect neurons from cell death and reduce the extent of brain damage. NYR-BI03 is specifically designed to block TRPC 3/6/7 channels which play crucial roles in calcium signalling and are involved in a wide range of physiological and pathological processes. In February 2024, Nyrada completed a preclinical stroke study to assess the efficacy of NYR-BI03. The study produced a strong signal of neuroprotective efficacy and was well tolerated. MRI brain imaging showed statistically significant neuroprotection (p-value 0.021) was achieved when animals received the NYR-BI03 treatment. On average, NYR-BI03 therapy rescued 42% of the brain injury in the penumbra region seen in animals receiving vehicle. All animals in the study survived the (induced) ischemic brain injury and drug treatment with no drug-related adverse effects reported. This built upon NYRBI03’s good safety profile for continuous intravenous delivery in the sub-acute brain injury treatment interval. “NYR-BI03 is specifically designed to block TRPC 3/6/7 channels which play crucial roles in calcium signalling and are involved in a wide range of physiological and pathological processes.”
NYRADA INC (ASX:NYR) 10 Good Laboratory Practice Safety Studies In March 2024, Nyrada commenced Good Laboratory Practice (GLP) safety studies for NYR-BI03. GLP studies are a regulatory precursor to a first-in-human clinical trial with their purpose being to ensure safety before testing in humans. Following the conclusion of the 2024 financial year, two of the requisite GLP studies were completed: • AMES (Bacterial Reverse Mutation) evaluated the mutagenicity and predicted the genetic risks and potential carcinogenic effects of NYR-BI03. • hERG (Human Ether-a-go-go-related Gene) evaluated the cardiovascular safety of NYR-BI03. NYR-BI03 demonstrated requisite safety in these two (in vitro) studies. The remaining GLP safety studies are on track to be reported in the fourth quarter of the 2024 calendar year. Walter Reed Army Institute of Research Study Nyrada’s collaborative TBI study with the Walter Reed Army Institute of Research (WRAIR) commenced early in the fourth quarter of the 2024 financial year. This study assesses the efficacy of NYR-BI03 in a rodent model of penetrating TBI, which seeks to mimic the serious head injuries suffered by military service members. The degree to which NYR-BI03 provides neuroprotection following a penetrating TBI will be assessed and measured. The study has progressed through the controlled injury phase with all MRI images and associated analysis to be conducted at UNSW Sydney. The MRI imaging is underway and statistical analysis to follow, with study results now expected to be available in 1QCY2025. Phase I Clinical Trial Subject to the successful completion of GLP studies, Nyrada remains on track to commence its first-in-human Phase I clinical trial for NYR-BI03 late in this calendar year. This study will assess the safety and tolerability of the drug in healthy human volunteers and will seek to confirm the safe dose range to take forward into subsequent clinical trials. The design and budget for this Phase I trial is subject to final GLP study results and is thus still being finalised. However, design and cost will be moderated by the study’s conduct in Australia and with healthy human volunteers. Rebion Strategic Partnership In late June 2024, Nyrada signed a Strategic Partnership Agreement (SPA) with Boston-based medical device development company Rebion. Rebion uses Neural Performance Scanning technology to identify and monitor functional impairments in the brain stemming from disease or injury. Through this SPA, Nyrada and Rebion intend to collaborate to advance therapies and outcomes for TBI sufferers. This includes joint research, conference presentations, and applications for non-dilutive funding grants. A mid-term goal of the SPA is to conduct a joint study assessing the efficacy of Nyrada’s brain injury therapy with Rebion’s brain injury detection and monitoring capabilities; potentially as part of Nyrada’s Phase II trial of NYR-BI03. “Nyrada’s collaborative TBI study with the Walter Reed Army Institute of Research commenced early in the fourth quarter of the 2024 financial year… with results now expected to be available in 1QCY2025.”
ANNUAL REPORT FY2024 11 Other Programs The vast majority of Nyrada’s resources are focused on the advancement of the Brain Injury Program including progressing NYR-BI03 into a Phase I clinical trial. However, in the background and at low cost, Nyrada continues to explore other opportunities. This includes options for the Cholesterol Lowering Program. Nyrada maintains the view that a small molecule oral PCSK9 inhibitor is the optimal treatment for hypercholesterolemia, for which there is a significant growing addressable market driven by demographic, lifestyle, and dietary changes. Corporate Activities In March 2024, following the reporting of its Brain Injury Program preclinical stroke study, the Company raised $1.75 million (before costs) of new equity capital. An additional $0.21 million (before costs) was raised in June 2024 from Board members acquiring stock on the same terms as that for other shareholders ($0.075 per CDI). Nyrada concluded the financial year with AU$4.8 million in cash. Nyrada continues to be disciplined in its capital allocation decisions including maintaining a lean operating model with the vast proportion of resources allocated towards research and development. Conclusion I would like to take this opportunity to extend my appreciation to the Nyrada Board for their ongoing expertise, support, and guidance. Their advice has been instrumental as we work together to execute our strategy, build a great company, improve human outcomes, and create value for our shareholders. I also want to acknowledge the vital role of our Scientific Advisory Board, chaired by Scientia Professor Gary Housley. Their advice and counsel are invaluable. Additionally, I extend my gratitude to the Nyrada team for their diligence and tireless efforts. As we enter the 2025 financial year the team is working hard ahead of our lead Brain Injury Program Candidate, NYR-BI03, entering the clinic. Coupled with the results of our preclinical TBI efficacy study being undertaken with WRAIR, we believe this will open a panoply of opportunities for the company. I am excited for the future of Nyrada and look forward to updating you on our progress at the upcoming Annual General Meeting. James Bonnar Chief Executive Officer
NYRADA INC (ASX:NYR) 12 “Subject to the successful completion of GLP studies, Nyrada remains on track to commence its first-in-human Phase I clinical trial for NYR-BI03 late in this calendar year.”
ANNUAL REPORT FY2024 13 Directors’ Report The Directors present their report, together with the financial statements, on the Consolidated Entity (referred to hereafter as the 'Consolidated Entity') consisting of Nyrada Inc. (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 Nyrada Inc. during the whole of the financial year and up to the date of this report, unless otherwise stated: John Moore Non-Executive Chair Rüdiger Weseloh Non-Executive Director Marcus Frampton Non-Executive Director Christopher Cox Non-Executive Director Ian Dixon Non-Executive Director Gisela Mautner Non-Executive Director John Moore Non-Executive Chair, joined the Board in June 2019 John Moore is an experienced executive with a diverse background in leadership roles across various industries. He currently serves on the boards of two private companies and three public companies. Recently, John became a Director of Phase Holographic, a company specializing in live cell imaging systems for life science researchers. Phase Holographic's stock is traded on the Swedish Spotlight market and will soon be listed on the OTCQB market in the USA. John will transition from his role as Chairman of Cormetech to being a shareholder and Director. He remains the Chairman of Scientific Industries (SCNDOTCQB), a producer of laboratory instruments for the life sciences industry, and Trialogics, a clinical trial informatics business. John's prior experience includes serving as CEO of Acorn Energy from 2006 to 2015. During his tenure, the CoaLogix business was acquired for US$11 million and later sold for US$101 million. Additionally, the Comverge business was listed in the US before being sold to Constellation Energy. In 2002, John was a Partner and CEO of Edson Moore Healthcare Ventures, where he oversaw the acquisition of a portfolio of sixteen drug delivery investments from Elan Pharmaceuticals for US$148 million. John is a graduate of Rutgers University, US, and brings a wealth of experience and strategic insight to his current roles. Interest in shares and options 1,691,756 shares 2,400,000 unlisted options Special responsibilities Chair of the Board. Member of Audit & Risk Committee Member of Remuneration & Nomination Committee Directorship held in other listed entities (last 3 years) N/A Qualifications John graduated from Rutgers University with a Bachelor of Arts degree in History.
NYRADA INC (ASX:NYR) 14 Christopher Cox Non-Executive Director, joined the Board in November 2019 Christopher Cox is a Co-Founder and has been a Managing Partner of Population Health Partners since April 2020. Additionally, Chris is a retired Partner of Cadwalader, Wickersham & Taft LLP (New York) a position he held from January 2012. He remains a Senior Attorney of the firm. Previously the Chairman of Cadwalader’s Corporate Department and a member of its Management Committee, Chris advised clients on a wide array of corporate and financial matters, including mergers and acquisitions and restructurings, spin-offs, joint ventures, IP monetisation’s and other complex financing transactions. From February 2016 to March 2019, Chris was seconded to The Medicines Company, a global biopharmaceutical company, where he served as Executive Vice President and Chief Corporate Development Officer and was responsible for business development and strategy. Before January 2012, Chris was a partner at Cahill Gordon & Reindel LLP in New York. Chris also serves as the Chief Executive Officer of Symphony Capital Holdings, LLC, a private investment holding company with interests in biotechnology, network security and entertainment. Interest in shares and options 1,425,000 shares 1,200,000 unlisted options Special responsibilities Chair of Remuneration & Nomination Committee Directorship held in other listed entities (last 3 years) N/A Marcus Frampton Non-Executive Director, joined the Board in June 2019 Marcus Frampton currently serves as the Chief Investment Officer of the Alaska Permanent Fund Corporation (APFC), the US$80 billion sovereign wealth fund for the State of Alaska. Marcus manages the investment team at APFC and leads all investment decisions related to APFC’s investment portfolio within the guidelines established by APFC’s Board of Trustees. Before joining the APFC in 2012, Marcus held positions ranging from Investment Banking Analyst & Associate at Lehman Brothers (2002-2005), to private equity investing at PCG Capital Partners (20052010), and acted as an executive of a private equity-backed portfolio company at LPL Financial (2010-2012). Interest in shares and options 1,178,408 shares 1,200,000 unlisted options Special responsibilities Chair of Audit & Risk Committee Directorship held in other listed entities (last 3 years) N/A Qualifications Marcus graduated from UCLA with a Bachelor’s degree in Business-Economics and a Minor in Accounting.
ANNUAL REPORT FY2024 15 Rüdiger Weseloh Ph.D. Non-Executive Director, joined the Board in June 2019 Rüdiger Weseloh is an Executive Director of Business Development at EMD Serono, Inc, Rockland, MA, USA., where over a period of 18 years he has led more than 80 transactions for the health care division of its parent company Merck KGaA, Darmstadt, Germany. Completed deals across the drug development value chain were in the fields of Oncology, Rheumatology, Neurodegenerative diseases, and Fertility. Before joining Merck KGaA, Rüdiger spent 5 years as a Biotech/Pharma Equity Analyst, at Gontard & Metallbank AG, Frankfurt, and Sal. Oppenheim, Cologne/Frankfurt, as well as 3 years as a Postdoc at the Max-Planck-Institute for Experimental Medicine in Goettingen. Rüdiger also served 5 years on the Supervisory Board of Cytotools AG, Freiburg, Germany. Interest in shares and options 366,666 shares 1,200,000 unlisted options Special responsibilities N/A Directorship held in other listed entities (last 3 years) N/A Qualifications Rüdiger has a university diploma in Biochemistry from the University of Hannover and a PhD in Molecular Neurobiology, obtained at the Center for Molecular Neurobiology in Hamburg. Ian Dixon Ph.D. Non-Executive Director, joined the Board in September 2020. Dr Dixon has a PhD in biomedical engineering from Monash University, an MBA from Swinburne University and professional engineering qualifications. Dr Dixon brings to the Board an extensive technical and entrepreneurial background in founding, building and running technology-based companies, in recognising the potential commercial value of early-stage drug development, and in understanding the challenges involved in drug development. In 2011, Dr Dixon co-founded Cynata Inc, now a subsidiary of ASX-listed Cynata Therapeutics Ltd (ASX:CYP), a company progressing the commercialisation what has become the Cymerus stem cell therapy to treat various medical conditions including osteoarthritis, ARDS and critical limb ischemia. Also a founder and prior managing director of genetic medicines company Exopharm Ltd (ASX:EX1) in 2013. Interest in shares and options 10,380,699 shares 5,999,400 Performance Shares 1,800,000 unlisted options Special responsibilities Member of Audit & Risk Committee Member of Remuneration & Nomination Committee Directorship held in other listed entities (last 3 years) Exopharm Limited (ASX:EX1) - resigned on 1 May 2024; Medigard Limited (ASX:MGZ) – resigned on 16 April 2021; and Noxopharm Limited (ASX:NOX) - resigned on 31 August 2020 Qualifications PhD in biomedical engineering, MBA and a Bachelor of Engineering
NYRADA INC (ASX:NYR) 16 Gisela Mautner MD-PhD, MPH, MBA, GAICD Non-executive Director, joined the Board 1 August 2022 Gisela is an international business leader with significant experience developing and launching new pharmaceutical products and delivering successful corporate strategies in highly competitive global markets. She is currently the CEO and Managing Director of Noxopharm Ltd (ASX:NOX). Gisela has held senior positions with Amgen, Bayer, Siemens Medical Solutions and Merck/MSD generating successful commercial and scientific outcomes. She has strong global pharmaceutical industry networks and served as President, VicePresident and Treasurer of the Australian Pharmaceutical Physicians Association (APPA; now MAPA) for many years with serving until recently as Past-President. She is also the Australian delegate for the International Federation of Associations of Pharmaceutical Physicians (IFAPP), which connects the pharmaceutical industry globally. Gisela holds various Board roles, as Executive Director of Noxopharm, and Nonexecutive Director of Nyrada Inc. and a not-for-profit sports organization. Recently, she was appointed as Chair of the Biotechnology Committee of BIO NSW, a Notfor-Profit body to promote Life Sciences across NSW and to serve on a Policy Taskforce of AusBiotech Ltd. Interest in shares and options 1,800,000 unlisted options Special responsibilities N/A Directorship held in other listed entities (last 3 years) Noxopharm Limited (ASX:NOX) - current Qualifications Gisela holds an MD from the Technical University of Munich, a PhD from the Ludwig Maximilian University, an MPH from Harvard University and an MBA from Northwestern University Chicago. She is also a Graduate of the Australian Institute of Company Directors (GAICD). Company Secretary - David Franks David is a Chartered Accountant, Fellow of the Financial Services Institute of Australia, Fellow of the Governance Institute of Australia, Justice of the Peace, Registered Tax Agent and holds a Bachelor of Economics (Finance and Accounting) from Macquarie University. With over 25 years in finance and governance (including company secretarial and corporate finance), David has been CFO, company secretary and director for numerous ASX listed and unlisted public and private companies, in a range of industries covering energy retailing, software as a service, transport, financial services, oil and gas / mineral exploration, technology, automotive, software development, wholesale distributions, retail, biotechnology and healthcare. He has acted in these capacities for Top 200 to small-cap companies listed on ASX, including for companies with OTC listings. David is also the Company Secretary of Noxopharm Limited. David was also a Non-Executive Director of Jcurve Solutions Limited (ASX:JCS) from 2014 to 2021 and a Director, Principal and shareholder of Automic Group Pty Ltd, a service provider to the Company. Principal activities Nyrada is a drug discovery and development company specializing in novel small molecule drugs to treat neurological and cardiovascular diseases. The Company has two main programs, each targeting market sectors of significant size and considerable unmet clinical need. These are a drug to treat brain injury, specifically traumatic brain injury and stroke, and a cholesterol lowering drug. Nyrada is a Company incorporated in the state of Delaware, US and is listed on the Australian Securities Exchange (ASX: NYR).
ANNUAL REPORT FY2024 17 Significant changes in the state of affairs There were no significant changes in the state of affairs of the Consolidated Entity during the financial year. Financial results The loss for the Consolidated Entity after providing for income tax amounted to $1,391,309 (30 June 2023: $7,781,692). The year ended 30 June 2024 operating results included the following: • Research and Development Tax Incentive refund of $994,600 relating to the accrued FY2024 refund (2023: $1,309,407 relating to the accrued FY2023 refund). • Research and development costs of $2,030,502 (FY2023: $6,411,264); • Corporate and administration expenses of $577,842 (FY2023: $641,117); • Share based payment expense of $358,074 (FY2023: $541,214); • Professional services expense of $477,948 (FY2023: $409,523); and • Employee benefits expense of $1,127,500 (FY2023: $1,100,136) The cash position as at 30 June 2024 was $4,769,374 (30 June 2023: $3,708,761). Review of operations During the financial year ending 30 June 2024, Nyrada made significant progress in advancing its Brain Injury Program. The Company’s brain injury candidate is a Transient Receptor Potential Canonical (TRPC) channelblocking neuroprotectant drug designed to reduce the impact of secondary brain injury in patients following a stroke or traumatic brain injury. Work was also completed on the Company’s Cholesterol Lowering Program which is an oral Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitor drug aimed at managing high blood LDL-cholesterol levels. Brain Injury Program Novel Mechanism of Action Nyrada’s lead Brain Injury Program candidate, NYR-BI03, is a TRPC ion channel blocker. It is a novel mechanism of action designed to act as a neuroprotective treatment for stroke and traumatic brain injury (TBI) patients. TRPC channels are a group of ion channels located in the cellular membranes of human cells and are involved in various physiological processes that influence cell function. TRPC channels play roles in sensing environmental changes, cell signalling, and maintaining cellular homeostasis. TRPC channels play an important role in various diseases, including neurological disorders, where they impact neuronal health and function mainly through their role in regulating calcium and sodium ion flow into neurons. These channels are activated by various stimuli, including mechanical stress, receptor activation, and changes in intracellular calcium levels. TRPC channels can influence neuronal excitability, neurotransmitter release, and gene expression, all of which are crucial for normal brain function. Blocking TRPC channels can reduce calcium overload in neurons, which is a common feature of neuronal injury in stroke and TBI. By preventing excessive calcium influx, TRPC blockers can protect neurons from cell death and reduce the extent of brain damage.
NYRADA INC (ASX:NYR) 18 Source: Parmar et. al. 2023 Translational Stroke Research Nyrada’s NYR-BI03 is specifically designed to block TRPC 3/6/7 channels which play crucial roles in calcium signalling and are involved in a wide range of physiological and pathological processes. Dr. Parmar also presented on Nyrada’s brain injury program at the US Military Health System Research Symposium in mid-August 2023. • TRPC3 channels play a role in various physiological functions, including vascular smooth muscle contraction, neuronal growth, and immune responses. • TRPC6 channels are essential for the regulation of vascular tone, kidney function, and various cellular processes. • TRPC7 are known to participate in calcium entry and signalling pathways. Preclinical Stroke Study During the financial year, Nyrada conducted a preclinical study to evaluate the efficacy of its lead Brain Injury Program candidate NYR-BI03 in preventing secondary brain injury following a stroke. The study reported a significant neuroprotective signal, providing strong evidence of potential efficacy. NYR-BI03 is a first-in-class therapy with a novel mechanism of action designed to selectively block TRPC ion channels, which are over-activated during brain trauma, causing calcium overload and brain cell death. Currently, there are no FDA-approved drugs for the treatment of secondary brain injury. In collaboration with UNSW Sydney, the study induced a focal ischemic stroke using a photothrombotic model in test animals. 16 test animals were treated with either NYR-BI03 or a vehicle 30 minutes post-injury, with treatment administered for 72 hours via continuous intravenous infusion. Magnetic Resonance Imaging (MRI) was used to quantify the resulting brain injury in both drug-treated and vehicle-treated animals, focusing on the penumbra region, which NYR-BI03 targets. MRI results showed a statistically significant neuroprotection (p-value 0.0213), with NYR-BI03 therapy rescuing an average of 42% of brain injury in the penumbra region. All animals survived the brain injury and treatment without any drug-related adverse effects.
ANNUAL REPORT FY2024 19 Preclinical Traumatic Brain Injury Study Later in the financial year, Nyrada commenced a collaborative TBI study with its collaborative partners, the Walter Reed Army Institute of Research (WRAIR) and UNSW. This study evaluates the efficacy of NYR-BI03 in a rodent model of penetrating TBI, a proprietary model of WRAIR that simulates serious head injuries sustained by military service members. The study assesses the neuroprotective effects of NYR-BI03 following a penetrating TBI. Preclinical Safety Study Nyrada began Good Laboratory Practice (GLP) studies to assess the safety of NYR-BI03 in two animal species. Successful completion of these GLP studies is required before initiating a first-in-human Phase I clinical trial, scheduled for the quarter ending December 2024. In July 2024, Nyrada reported on the first tranche of GLP studies, demonstrating NYR-BI03's safety in two in vitro tests: • AMES (Bacterial Reverse Mutation) Test: Evaluated the mutagenicity and predicted genetic risks and potential carcinogenic effects of NYR-BI03. • hERG (Human Ether-a-go-go-related Gene) Test: Assessed the cardiovascular safety of NYR-BI03. The remaining GLP studies are ongoing and expected to be concluded soon, with results analysed and reported early in the quarter ending December 2024. Upon satisfactory completion of all GLP studies, Nyrada will submit a Human Research Ethics Application, aiming to commence the Phase I clinical trial in December 2024. Rebion Strategic Partnership In June, Nyrada was pleased to sign a Strategic Partnership Agreement with Boston-based medical device company Rebion, which uses Neural Performance Scanning technology to identify and monitor functional impairments in the brain stemming from disease or injury. This partnership focuses on advancing therapies and outcomes for TBI sufferers, including joint research, conference presentations, and applications for nondilutive funding grants. Cholesterol Lowering Program Early on in the 2024 financial year, Nyrada decided to not advance its cholesterol-lowering PCSK9 inhibitor drug NYX-1492 into clinical development following GLP study results. Low-cost background work continued throughout the year to explore development options for an effective and commercially viable PCSK9 inhibitor. These low-cost background works are ongoing. Nyrada continues to believe an oral small molecule PCSK9 inhibitor is an optimal approach for managing hypercholesterolemia, recognising its significant market potential. Financial summary Throughout the year, Nyrada maintained lean corporate operations, prioritising capital allocation towards research and development activities. Over 46% of net operating cash flow outflows were devoted to R&D. During the year, Nyrada raised a total of $1,965,000 equity capital (before costs), including $1,755,000 from new and existing professional and sophisticated investors, and $210,000 from board directors. In FY2024 the Company received a R&D tax incentive refund greater than the amount accrued by $2,232,325 for the period ending 30 June 2023, resulting in an increase in revenue. Consistent with prior years, the Company intends to lodge a claim under the Commonwealth Government’s Research and Development Tax Incentive scheme for research conducted in the 2024 financial year. It is estimated that Nyrada is eligible for a refund of $994,600, though the exact amount is uncertain. Any benefit received is expected in early the quarter ending December 2024.
NYRADA INC (ASX:NYR) 20 Financial position 2024 $ 2023 $ Cash and cash equivalents 4,769,374 3,708,761 Net assets / total equity 5,051,630 4,258,438 Contributed equity 26,841,743 25,320,332 Accumulated losses (27,190,133) (27,216,732) The Directors believe the Consolidated Entity is in a strong and stable financial position to expand its current operations. Liquidity and capital resources Nyrada ended the financial year with cash of $4,769,374 and anticipates receiving an Research and Development tax incentive refund of $994,600 for FY2024 following 30 June 2024, thus further boosting capital resources. Matters subsequent to the end of the financial year No matter or circumstance has arisen since 30 June 2024 that has significantly affected, or may significantly affect the Consolidated Entity's operations, the results of those operations, or the Consolidated Entity's state of affairs in future financial years. Future developments, prospects, and business strategies Disclosure of information regarding likely developments in the operations of the Company in future financial years and the expected results of those operations is likely to result in unreasonable prejudice to the Company. Information on future developments, prospects, and business strategies have only been referred to in the Chair’s Letter and CEO Report. For further information on the Company’s business strategies and material risks, refer also to the Prospectus which is available on the Company website or ASX Announcements. Environmental regulation The Consolidated Entity is not subject to any significant environmental regulation under Australian Commonwealth or State law. Directors’ shareholdings In this section, reference is made to Share ownership. The instruments registered for trade on the Australian Securities Exchange are CHESS Depositary Interests (CDIs). One CDI is equivalent to one Share, being Class A Common Stock. The following table sets out each director’s relevant interest in shares, debentures, and rights or options in shares or Directors of the Company or a related body corporate as at the date of this report: Share Number Options Number Performance Shares John Moore 1,691,756 2,400,000 - Rüdiger Weseloh 366,666 1,200,000 - Marcus Frampton 1,178,408 1,200,000 - Christopher Cox 1,425,000 1,200,000 - Ian Dixon 10,380,699 1,800,000 5,999,400 Gisela Mautner - 1,800,000 -
ANNUAL REPORT FY2024 21 Unissued Common Stock Details of unissued Common Stock, interests under option, and performance shares as at the date of this report are as follows: 1 Performance shares convert when specified milestones are achieved, these milestones are outlined in note 9 of the financial statements. 2 The exercise price is the higher of • 100% of the Fair Market Value (as defined in the Company’s Stock Incentive Plan) of the Shares on the date that Option is granted; and • an amount equal to 110% of the volume-weighted average price of the CDIs for the period of 10 trading days immediately prior to the date on which that Option vests. 3 The exercise price is the higher of • 100% of the Fair Market Value (as defined in the Company’s Stock Incentive Plan) of the Shares on the date that Option is granted; and • an amount equal to 120% of the volume-weighted average price of the CDIs for the period of 10 trading days immediately prior to the date on which that Option vests. The holders of these options and performance shares do not have the right to participate in any share issue or interest issue of the Company or of any other body corporate or registered scheme. Dividends There were no dividends paid, recommended, or declared during the current or previous financial year. Type of Security Number Exercise price Expiry date Performance shares 18,000,000 N/A1 25/11/2024 Unlisted options 4,000,000 0.22 16/01/2025 Unlisted options 4,000,000 TBC2 5 years from the vesting date Unlisted options 5,000,000 TBC2 5 years from the vesting date Unlisted options 5,000,000 TBC2 5 years from the vesting date Unlisted options 3,600,000 TBC3 25/11/2024 Unlisted options 3,600,000 TBC3 25/11/2025 Unlisted options 900,000 TBC3 3 years from the vesting date Unlisted options 4,000,000 0.40 29/06/2026 Unlisted options 2,000,000 0.60 29/06/2026 Unlisted options 2,000,000 0.90 29/06/2026 Unlisted options 1,200,000 TBC3 3 years from the vesting date Unlisted options 600,000 TBC3 18/01/2025 Unlisted options 600,000 TBC3 18/01/2026 Unlisted options 600,000 TBC3 18/01/2027 Unlisted options 5,000,000 0.14 30/06/2027
NYRADA INC (ASX:NYR) 22 Indemnity and insurance of officers As permitted under Delaware law, Nyrada indemnifies its Directors and certain officers and is permitted to indemnify employees for certain events or occurrences that happen by reason of their relationship with, or position held at, Nyrada. The Company’s Certificate of Incorporation and Bylaws provide for the indemnification of its Directors, officers, employees and other agents to the maximum extent permitted by the Delaware General Corporation Law. Nyrada has entered into indemnification agreements with its Directors and certain officers to this effect, including the advancement of expenses incurred in legal proceedings to which the Director or officer was, or is threatened to be made, a party by reason of the fact that such Director or officer is or was a Director, officer, employee or agent of Nyrada, provided that such a Director or officer acted in good faith and in a manner that the Director or officer reasonably believed to be in, or not opposed to, the Company’s best interests. At present, there is no pending litigation or proceedings involving a Director or officer for which indemnification is sought, nor is the Company aware of any threatened litigation that may result in claims for indemnification. Nyrada maintains insurance policies that indemnify the Company’s Directors and officers against various liabilities that might be incurred by any Director or officer in his or her capacity as such. The premium paid has not been disclosed as it is subject to confidentiality provisions under the insurance policy. Indemnity and insurance of auditor The Company has not, during or since the end of the financial year, indemnified or agreed to indemnify the auditor of the Company or any related entity against a liability incurred by the auditor. During the financial year, the Company has not paid a premium in respect of a contract to insure the auditor of the Company or any related entity. Meetings of Directors The following table sets out the number of directors’ meetings (including meetings of committees of Directors) held during the financial year and the number of meetings attended by each director (while they were a Director or committee member). Proceedings on behalf of the Company No person has applied to the Court under section 237 of the Corporations Act 2001 for leave to bring proceedings on behalf of the Company, or to intervene in any proceedings to which the Company is a party for the purpose of taking responsibility on behalf of the Company for all or part of those proceedings. Board of Directors Audit & Risk Committee Remuneration & Nomination Committee Attended Held Attended Held Attended Held John Moore 6 6 2 2 1 1 Rüdiger Weseloh 6 6 - - - - Marcus Frampton 6 6 2 2 - - Christopher Cox 3 6 - - - 1 Ian Dixon 6 6 2 2 1 1 Gisela Mautner 6 6 - - - -
ANNUAL REPORT FY2024 23 Non-audit services There were no non-audit services provided during the financial year by the auditor. In the event non-audit services are provided by the auditor, the Board has established procedures to ensure the provision of non-audit services is compatible with the general standard of independence for auditors. These include: • all non-audit services are reviewed and approved to ensure they do not impact the integrity and objectivity of the auditor; and • non-audit services do not undermine the general principles relating to auditor independence as set out in APES 110 ‘Code of Ethics for Professional Accountants (including Independence Standards)’ issued by the Accounting Professional & Ethical Standards Board, including reviewing or auditing the auditor’s own work, acting in a management or decision-making capacity for the Company, acting as an advocate for the Company or jointly sharing economic risks and rewards. Auditor's independence declaration A copy of the auditor's independence declaration as required under section 307C of the Corporations Act 2001 is set out immediately after this Directors' report. Presentation Currency The functional and presentation currency of the Company is Australian Dollars (AUD). The financial report is presented in AUD with all references to dollars, cents, or $’s in these financial statements presented in AUD currency, unless otherwise stated. Jurisdiction of Incorporation Nyrada is a company incorporated in the State of Delaware in the United States and registered in Australia as a foreign company. As a foreign company registered in Australia, Nyrada is subject to different reporting and regulatory regimes than Australian public companies. Corporate Governance Statement The Company's corporate governance statement is located at the Company's website: https://www.nyrada.com/site/About-Us/corporate-governance Business Risks (a) Uncertainty of clinical development There are numerous regulatory requirements to address before a drug candidate can progress into human studies, including review by a Human Research Ethics Committees (HREC). Further, there is no certainty that any of the drug candidates will receive that permission. The Group’s ability to commercialise Its intellectual property is reliant on clinical data. Drug development is a highly risky business with a high failure rate. Only less than 10% of drugs that enter Phase 1 achieve marketing approval by the US Food and Drug Administration (FDA). There are numerous reasons for this, mainly relating to low therapeutic benefit or unacceptable toxicity, with the drug’s preclinical data failing to predict those adverse outcomes. While the Group will conduct its clinical programs and eventual drug submissions on the advice of consultants experienced in clinical trial design and regulatory affairs, there is no certainty that the trial design will provide appropriate data or that the data will meet the regulator’s benchmark. This may require the Group to conduct further clinical studies, resulting in significant additional cost and delay. Once a drug enters the clinic, a final drug development path typically takes 8-10 years, depending on the indication and regulatory pathway.
NYRADA INC (ASX:NYR) 24 Any such clinical study would most likely commence in a small number of human volunteers and be a pharmacokinetic/acute safety study using very low dosages of drug. The risk associated with a first-inhuman study lies in the drug having an inappropriate pharmacokinetic profile such as being extensively metabolised and therefore inactivated or being eliminated from the body too quickly to provide a therapeutic benefit. Beyond conducting preclinical animal studies, there is no reliable way of predicting such adverse outcomes prior to testing in humans. (b) Commercialisation The Group’s current business strategy is early-stage drug development, which may include a trade sale or out-license of its drug candidates to a third party with greater resources and expertise to undertake latestage drug development, regulatory approvals, and sales and marketing. There is no certainty that any of the drug candidate will be of interest to such a third party or, if a drug candidate is of interest to such a third party, that terms can be negotiated that are commercially acceptable to the Group or will adequately realise the value of the drug candidate. (c) Additional capital requirements R&D activities require a high level of funding over a protracted period of time. However, additional development costs may arise during this period and the Company may require additional funding to meet its stated objectives or may decide to accelerate or diversify its activities within the same area The Company’s requirement for additional capital may be substantial and will depend on many factors, some of which are beyond the Company’s control, including: (1) slower than anticipated research progress; (2) the requirement to undertake additional research; (3) competing technological and market developments; (4) the cost of protecting the Company’s intellectual property. The Company will constantly evaluate data arising from its R&D activities that may indicate new uses for its products and allow the Company to file patents, thereby providing potential new development and partnering opportunities. Accordingly, the Company may alter its funding strategies to take advantage of such new opportunities if and when they present themselves. There is no assurance that the funding required by the Company from time to time to meet its business requirements and objectives will be available to it, on favourable terms or at all. To the extent available, any additional equity financing may dilute the holdings of existing shareholders and any debt financing may involve restrictions on the Company’s financing and operating activities. If the Company is unsuccessful in obtaining funds when required, it may be necessary for it to reduce the scope of its operations. (d) Intellectual property rights Obtaining, securing and maintaining the Group’s intellectual property rights is an integral part of securing potential value arising from conduct of the Group’s business. If patents are not granted, or if granted only for limited claims, the Group’s intellectual property may not be adequately protected and may be able to be copied or reproduced by third parties. The Group may not be able to achieve its objectives, to commercialise its products or to generate revenue or other returns. The Group has been granted patents in the US and Europe in relation to its Cholesterol Lowering Program and also has a provisional patent application under examination. The Company’s brain injury drug candidate will be the subject of a provisional patent application in due course. The patent position of biotechnology and pharmaceutical companies can be highly uncertain and frequently involves complex legal and factual questions. Accordingly, there can be no guarantee that the provisional patent applications will be successful and lead to granted patents or all of the claims in any application will be granted. Furthermore, should such applications be granted, there is no guarantee competitors will not develop technology to avoid those patents, or that third parties will not seek to claim an interest in the intellectual property with a view to seeking a commercial benefit from the Group. The Group has engaged patent attorneys to advise on its intellectual property strategy as it seeks to broaden the
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