NYRADA INC.  (NYR.ASX)

Introduction. Nyrada Inc. (ASX:NYR) is an Australian biotechnology company leading the development of small-molecule therapies targeting critical unmet medical needs in neuroprotection and cardioprotection. Its lead candidate, NYR-BI03, is a first-in-class Transient Receptor Potential Canonical (TRPC) ion channel blocker designed to mitigate secondary brain and heart damage following traumatic brain injury (TBI), stroke, and myocardial ischemia-reperfusion injury.

Breakthrough Preclinical Success. NYR-BI03 has delivered remarkable preclinical results. It has demonstrated a 42% reduction in brain injury post-stroke in a preclinical model and an 86% reduction in cardiac tissue damage following myocardial ischemia-reperfusion injury. Nyrada has completed regulatory submission for its Phase 1a first-in-human clinical trials. The anticipated results for Phase 1a are expected in Q3CY2025, paving the way for Phase 1b trials and an Investigational New Drug (IND) submission to the U.S. FDA.

Market-First Opportunity. Despite a total addressable market projected to reach USD$41.8 billion by 2032, there are currently no FDA-approved treatments for secondary brain or cardiac injury. Nyrada is well-positioned to fill this critical treatment void, providing a substantial first-mover advantage in a field with minimal competition.

A Promising Biotech Company Underappreciated by the Market. With near-term clinical milestones approaching that are expected to drive a revaluation of its stock Nyrada offers significant upside potential from current levels. The company’s current market valuation of $16m appears notably discounted compared to peers, suggesting room for substantial value appreciation as clinical milestones are achieved.

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TRAUMATIC BRAIN INJURY EXPLAINED

Overview

Traumatic Brain Injury (TBI) is caused by external forces that disrupt brain function, resulting from incidents like falls, accidents, or violence. Its severity ranges from mild concussions to severe injuries, with outcomes varying based on the injury’s extent.

Pathophysiology

TBI’s primary injury occurs on impact, leading to damage like contusions and lacerations. However, long-term issues stem from secondary injuries, including:

• Neuroinflammation: Brain swelling and inflammation worsen damage.
• Excitotoxicity: Excess neurotransmitters cause neuron death.
• Oxidative Stress: Reactive oxygen species damage brain cells.
• BBB Disruption: The blood-brain barrier is compromised, worsening inflammation.
• Ischemia and Hypoxia: Reduced blood flow accelerates cell death.

Epidemiology

TBI is a major cause of death and disability, with over 2.8 million cases annually in the U.S. alone. The global economic burden exceeds $75 billion yearly.

Unmet Medical Need

Treatment for TBI is largely supportive, with no FDA-approved drugs targeting its underlying causes. This highlights the need for innovative therapies that can address neuroprotection and improve patient outcomes.

STROKES EXPLAINED

Overview

Stroke occurs when blood flow to the brain is disrupted, causing brain cells to die and leading to neurological impairments. It has two main types: ischemic stroke, caused by a blood vessel blockage, and hemorrhagic stroke, caused by bleeding in the brain. A transient ischemic attack (TIA), or “mini-stroke,” is a temporary reduction in blood flow that resolves without permanent damage but signals the risk of future strokes.

Pathophysiology

• Ischemic Stroke: Caused by a blood clot or debris blocking blood flow, leading to cell death through mechanisms like energy failure, excitotoxicity, and inflammation.
• Hemorrhagic Stroke: Results from bleeding into the brain, increasing pressure and damaging tissue.

Secondary brain injury processes, like neuroinflammation and oxidative stress, further exacerbate damage after the initial stroke.

Epidemiology

Stroke is a leading cause of death and disability, affecting 15 million people globally each year, with 5 million fatalities and 5 million disabled. In the U.S., nearly 800,000 strokes occur annually, with costs exceeding USD$50 billion.

Unmet Medical Need

While treatments for acute stroke exist, such as thrombolytics and thrombectomy, these are time-sensitive and benefit only some patients. No approved therapies target secondary brain injury, which continues to harm brain tissue after the acute phase. Developing treatments to address inflammation, oxidative stress, and neuroprotection offers a critical opportunity to improve stroke recovery.

NEUROPROTECTION PROGRAM

Program Overview – A Novel Mechanism of Action

Nyrada’s lead candidate for its Brain Injury Program, NYR-BI03, is a Transient Receptor Potential Canonical (TRPC) ion channel blocker with a novel mechanism of action designed to provide neuroprotection for stroke and traumatic brain injury (TBI) patients.

TRPC channels, located in cell membranes, regulate calcium and sodium ion flow, influencing neuronal excitability, neurotransmitter release, and gene expression. Overactivation of these channels during neuronal injury leads to calcium overload, a key factor in cell death and brain damage. By blocking TRPC channels, NYR-BI03 aims to prevent excessive calcium influx, protecting neurons and mitigating the severity of brain injury in stroke and TBI.

Preclinical Stroke Study

On 24 March 2024, Nyrada commenced a preclinical study on NYR-BI03, to assess its effectiveness in preventing secondary brain injury after a stroke. The company announced in October 2024 that the study demonstrated significant neuroprotection, with NYR-BI03 reducing brain injury in the penumbra region by an average of 42% (p = 0.0213). This first-in-class therapy targets TRPC ion channels, which are over-activated during brain trauma, leading to calcium overload and cell death.

The study, conducted in collaboration with UNSW Sydney, used a photothrombotic stroke model in test animals. Treatment with NYR-BI03 began 30 minutes post-injury and continued via intravenous infusion for 72 hours. MRI analysis confirmed the drug’s efficacy, with no adverse effects observed. Currently, no FDA-approved treatments exist for secondary brain injury, highlighting NYR-BI03’s promising potential.

Good Laboratory Practice (GLP) Studies

Following the promising preclinical stroke study results reported in February 2024, NYR commenced Good Laboratory Practice (GLP) studies in late March 2024 to assess the safety and tolerability of NYR-BIO3. GLP studies typically involve two animal species to ensure reliable and consistent data. Nyrada selected rats and dogs to compare safety profiles, enhancing confidence in human applicability. Testing across species also identifies potential species-specific reactions, offering a more comprehensive view of the drug’s effects. A total of 8 studies were conducted.

Following the conclusion of GLP safety studies of NYR-BIO3, on 31 December 2024, NYR announced the submission of its Phase 1a first-in-healthy human volunteer clinical trial regulatory package for review by the Human Research Ethics Committee (HREC). NYR expects the HREC review to be concluded in February 2025.

Phase 1 Clinical Trial

The study’s objective is to assess the safety, tolerability, and pharmacokinetics of NYR-BIO3. The indicative design of the study indicates that the trial will be a randomised, placebo-controlled study with five (5) cohorts of eight (8) healthy human volunteers receiving single ascending doses. The study will comprise both male and female healthy volunteers between 18 and 50 years of age. The study duration is expected to vary between 1-4 days.

Scientia Clinical Research will be the Phase Ia trial site and Southern Star Research will provide Contract Research Organisation services to support the Phase Ia trial. This study design is subject to HREC approval. Following HREC approval, which is expected to be received in January 2025, healthy human volunteer recruitment is expected to be completed by July 2025. The company plans to coordinate cohort trials with the aim of reporting the final Phase 1a results in Q3CY2025.

Phase 1b Trial and Investigational New Drug Application

Following the completion of its Phase Ia trial, Nyrada plans to promptly initiate a Phase Ib trial to evaluate the safety of NYR-BI03 through multiple ascending doses over a longer duration, addressing the need for assessments of up to 72 hours in humans.

Upon successful Phase I trials, Nyrada aims to begin Phase II trials targeting stroke and ischemia-reperfusion injury in Australia, and traumatic brain injury in the US. To support this progression, Nyrada will prepare an Investigational New Drug (IND) application for submission to the US Food and Drug Administration (FDA). FDA approval will pave the way for human studies of NYR-BI03 in the US.

Walter Reed Traumatic Brain Injury (TBI) Study

In parallel with the progress towards Phase Ia clinical trials for NYR-BIO3, NYR commenced a collaborative traumatic brain injury (TBI) study with the Walter Reed Army Institute of Research (WRAIR) which began in early 4QFY2024. The study evaluates the neuroprotective efficacy of NYR-BI03 using WRAIR’s proprietary rodent model, designed to replicate severe head injuries experienced by military personnel. The MRI analysis for this study will be conducted at UNSW Sydney, utilising their state-of-the-art small animal imaging facility. The results from the study are anticipated in early 3QFY2025.

Neuroprotection Market Landscape Presents Significant First-Mover Advantage

The neuroprotection market remains largely underdeveloped, with no existing FDA-approved treatments for mitigating brain damage following TBI or stroke. Despite the significant unmet medical need, only a handful of companies are actively pursuing neuroprotective therapies, reinforcing NYR’s strong positioning in this emerging market.

One such competitor is Argenica Therapeutics Limited (AGN:ASX), an Australian biotechnology company focused on reducing brain tissue death after stroke and other neurological injuries. Its lead candidate, ARG-007, a peptide-based therapy for acute ischemic stroke, is currently in Phase 2 clinical trials.

Similarly, Astrocyte Pharmaceuticals, a U.S.-based biotech, is developing small-molecule neuroprotective therapies for TBI, stroke, concussions, and neurodegenerative diseases. Its lead candidate, AST-004, is in Phase 1 human safety trials. Another player in the space is Cellvation Inc, a clinical-stage biopharmaceutical company developing CEVA-102, a cellular therapy targeting neuroinflammation associated with TBI. CEVA-102 remains in preclinical development.

The limited number of competitors highlights the significant white-space opportunity in neuroprotection, where NYR is well-positioned to become a first mover. With few companies actively developing treatments and no approved standard of care, NYR’s innovative approach has the potential to establish a dominant foothold in this market.

CARDIOPROTECTION PROGRAM

Preclinical Coronary Heart Disease Study

On 1 October 2024, NYR announced positive preclinical results for NYR-BI03 in coronary heart disease. The preclinical rat study showed NYR-BI03 provided significant cardioprotection, reducing cardiac tissue damage by 86% (p < 0.001, n=8) following myocardial ischemic-reperfusion injury – a major cause of heart damage after blood flow restoration.

The study demonstrated NYR-BI03’s strong efficacy in limiting cardiovascular damage following acute myocardial ischemic-reperfusion injury. NYR-BIO3 notably outperformed Captopril, an established FDA-approved ACE inhibitor traditionally used in managing post-ischemic events and used in the study as a positive control. By surpassing the performance of the current standard treatment, NYR-BI03 showcases promising potential as a novel therapeutic intervention for patients experiencing acute myocardial ischemic reperfusion injury.

These preclinical results validate the drug candidate’s robust protective mechanisms and signal potentially significant therapeutic and commercial opportunities for NYR in the cardiovascular treatment landscape.

Supplementary Cardioprotection Preclinical Studies

Following on from the preclinical coronary heart disease study, NYR announced the results from supplementary preclinical studies on 23 October 2024. The studies, which utilised echocardiography assessment, confirmed that NYR-BI03 prevents loss of function resulting from myocardial ischemia-reperfusion (IR) injury following myocardial infarction (heart attack) in rats. In these supplementary studies, NYR-BI03 delivered a substantial 43% increase in left ventricular ejection fraction (p < 0.0001), a key indicator of heart pumping ability, significantly improving overall cardiac function.

Currently, no FDA-approved therapies specifically target ischemia-reperfusion injury. The results further validate NYR-BI03’s effectiveness in addressing ischemia-reperfusion injury related to heart attacks, enhancing the company’s potential to fill this critical treatment gap.

Rat Heart Sample Images

The images below depict sections of rat heart tissue from four groups: normal, damaged from ischemia-reperfusion, NYR-BI03 treated, and Captopril treated (current standard therapy) for visual comparison. Red-stained areas represent metabolically active tissue, while grey-stained areas indicate dead tissue. These images clearly demonstrate that damaged heart tissue treated with NYR-BI03 showed significantly better outcomes compared to both the control and Captopril-treated groups.

Limited Competition in the Cardioprotection Market

Our analysis identified only one notable competitor to NYR in the cardioprotection market: Infensa Bioscience, an Australian biotechnology company. Infensa is developing a novel class of inhibitors derived from spider venom, designed to protect the heart and brain following stroke and myocardial infarction. These inhibitors function by blocking acid-sensing ion channel 1a (ASIC1a), a key driver of acid-induced cell death in both cardiac and neural tissues. Currently, Infensa remains in the preclinical stage of development.

The scarcity of competitors in the cardioprotection space underscores both the novelty and potential value of NYR’s lead candidate, NYR-BIO3. With few alternative treatment options in development, NYR is well-positioned to capitalise on this emerging market and establish a competitive advantage in addressing a critical unmet medical need.

MARKET OVERVIEW

Stroke Market

Each year, 15 million people worldwide experience a stroke, with 5 million losing their lives and another 5 million left permanently disabled, creating significant challenges for families and communities[1]. Despite the apparent need for effective treatments, there is only one approved drug class for stroke suitable for <15% of patients which is tissue plasminogen activator (tPA). Driven by innovation in treatment options, the global stroke treatment market is expected to grow at a 7.5% CAGR to US$58.09 billion in 2031 from US$32.57 billion in 2023[2].

Traumatic Brain Injury Market

There are an estimated ~5.5 million people suffering severe TBI annually with ~55 million living with the effects of medically treated TBI[3]. It is clear that effective treatment can significantly enhance patient outcomes and lower the substantial costs linked to the long-term care of brain injury survivors. However, there is currently no FDA-approved treatment available on the market. Continued advancements in surgical procedures and available treatments are expected to drive the growth of the global TBI treatment market from US$3.46 billion in 20222 to US$5.53 billion in 2030[4].

Myocardial Infarction Market

Globally, 15-20 million people suffer myocardial infarction annually, with a 15% mortality rate within 30 days[5]. Among survivors, 20-30%—particularly those experiencing cardiac arrest—develop acquired brain injury due to oxygen deprivation during arrest and reperfusion injury post-resuscitation. This leads to cognitive, neurological, or motor impairments, creating a significant unmet need. The market for myocardial infarction therapies, projected to reach US$3.7 billion by 2032, offers substantial growth potential. NYR-BI03, targeting brain injury post-myocardial infarction, represents a transformative opportunity to address this gap, improve patient outcomes, and reduce long-term disability burdens.

[1] World Health Organisation – Stroke, Cerebrovascular accident

[2] Data Bridge Market Research – Global Stroke Market Size, Share, and Trends Analysis Report

[3] National Academies of Sciences, Engineering and Medicine – Traumatic Brain Injury

[4] Global Traumatic Brain Injuries Treatment Market – Industry Trends and Forecast to 2030

[5] Spherical Insights – Global Myocardial Infarction Market Size To Grow USD 3.7 Billion By 2032

KEY PEOPLE

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  John Moore

  Non Executive Chairman

  John Moore is an experienced executive with a diverse background in leadership roles across various industries. 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$11m and later sold for US$101m. Additionally, the Comverge business was listed in the US before being sold to Constellation Energy. Prior to Acorn Energy, John was a Partner and CEO of Edson Moore Healthcare Ventures, where he oversaw the acquisition of sixteen drug delivery investments from Elan Pharmaceuticals for US$148m. John holds a Bachelor of Arts from Rutgers University in the US.

• 

  James Bonnar

  CEO
  
  

  James brings over 20 years of global experience in the Life Sciences industry, including pre-clinical research, operations management, CMC (Chemistry, Manufacturing and Controls), Regulatory Affairs, and Quality Assurance. Before joining Nyrada, James was at Neuren for eleven years across various roles including as the Director – Clinical Operations where he oversaw clinical development for drugs in the areas of TBI and neurodevelopmental disorders. Prior to that, he worked in diabetes research, GMP manufacturing, and drug formulation development.

• 

  Benny Evison

  Chief Scientific Officer

  Benny brings to Nyrada expertise in advancing drug compounds from the discovery phase into clinical trials in humans. After earning a Bachelor of Medical Science with Honours and a PhD from La Trobe University, his doctoral research identified a novel mechanism of action for Pixantrone, a drug used to treat non-Hodgkin’s lymphoma. Seeking international experience, Benny became a postdoctoral fellow at St. Jude Children’s Research Hospital in Memphis, where his work on DNA repair-targeting drugs enhanced chemotherapy effectiveness. Inspired by his time with critically ill children, he returned to Australia as one of Nyrada’s founding scientists, driving impactful research and development.

• 

  Christopher Cox

  Non Executive Director

  Christopher Cox is a Co-Founder and Managing Partner of Population Health Partners since April 2020. He is also a Senior Attorney and retired Partner at Cadwalader, Wickersham & Taft LLP, where he led the Corporate Department and served on the Management Committee. With expertise in mergers and acquisitions, restructurings, spin-offs, and complex financing, Chris was seconded from 2016 to 2019 to The Medicines Company as Executive Vice President and Chief Corporate Development Officer, overseeing business development and strategy.

  Earlier in his career, he was a partner at Cahill Gordon & Reindel LLP. Currently, Chris is the CEO of Symphony Capital Holdings, LLC, a private investment firm with interests in biotechnology, network security, and entertainment.

• 

  Dr. Rüdiger Weseloh

  Non-Executive Director

  Rüdiger Weseloh is an Executive Director of Business Development at EMD Serono, Inc. in Rockland, MA, USA. Over his 18-year tenure, he has led more than 80 transactions for the healthcare division of its parent company, Merck KGaA, Darmstadt, Germany. His deal-making expertise spans the entire drug development value chain, with a focus on oncology, rheumatology, neurodegenerative diseases, and fertility. Prior to joining Merck KGaA, Rüdiger spent five years as a Biotech and Pharma Equity Analyst at Gontard & Metallbank AG in Frankfurt and Sal. Oppenheim in Cologne/Frankfurt. Earlier in his career, he conducted three years of postdoctoral research at the Max Planck Institute for Experimental Medicine in Göttingen. Additionally, he served for five years on the Supervisory Board of Cytotools AG in Freiburg, Germany.

• 

  Marcus Frampton

  Non Executive Director

  Marcus Frampton is the Chief Investment Officer of the Alaska Permanent Fund Corporation (APFC), an $80 billion sovereign wealth fund for the State of Alaska. In this role, he oversees APFC’s investment team and leads all portfolio investment decisions within the strategic framework set by the Board of Trustees.

  Frampton joined APFC in 2012, bringing a diverse background in investment banking, private equity, and asset management. He began his career as an Investment Banking Analyst and Associate at Lehman Brothers (2002–2005) before transitioning to private equity investing at PCG Capital Partners (2005–2010). He later served as an executive at LPL Financial, a private equity-backed portfolio company, from 2010 to 2012.

• 

  Dr Gisela Mautner

  Non- Executive Director

  Gisela Mauntner is a seasoned international business leader with extensive experience in pharmaceutical product development, corporate strategy, and commercial execution in competitive global markets. She currently serves as CEO and Managing Director of Noxopharm Ltd (ASX:NOX).

  Throughout her career, Gisela has held senior roles at Amgen, Bayer, Siemens Medical Solutions, and Merck/MSD, driving both commercial and scientific success. She has a strong global network in the pharmaceutical industry and has held key leadership positions within the Australian Pharmaceutical Physicians Association (APPA, now MAPA), including President, Vice President, and Treasurer. She also represents Australia in the International Federation of Associations of Pharmaceutical Physicians (IFAPP).

• 

  Ian Dixon

  Non Executive Director

  Dr. Ian Dixon has a Ph.D. in biomedical engineering from Monash University, an MBA from Swinburne University, and professional engineering qualifications. Ian has over 20 years of experience as a biotechnology entrepreneur within Australia. As a co-founder of Nyrada, he has co-invented the technology that is behind the Cholesterol Lowering Program, giving him the most insightful understanding of PCSK9 inhibitors.

  Ian has had great success in translating technology challenges into valuable businesses and respected intellectual property.