INNOVATIVE BIOTECHNOLOGY LEADER DEVELOPING TRANSFORMATIVE NEW DRUGS

Nyrada Inc.  (NYR.ASX)

Nyrada Inc (ASX:NYR) specialises in the discovery and development of small molecule drugs to address unmet medical needs in treatment areas with enormous commercial potential. Nyrada’s cardiovascular program aims to deliver a cholesterol-lowering drug to help people achieve a safe cholesterol level and reduce the risk of cardiovascular disease (stroke and heart attack). The neuroprotection program aims to deliver the first treatment to prevent brain damage that can occur following a stroke, or from head trauma sustained in motor vehicle accidents, falls, and contact sports concussions. Both drugs have the potential to generate significant global sales if human trials deliver similar results to those which have been achieved in animals.

Current Drug Development Programs

Cardiovascular: Development of a PCSK9i inhibitor which lowers LDL cholesterol levels, a major contributor to coronary heart disease and stroke. The new drug would provide an alternative or an addition for patients who respond poorly to or are unable to take statin drugs. The PCSK9i inhibitor, called NYX-PCSK9i, is a small molecule drug that would be taken orally, once daily.

 

Neuroprotection: Development of the first-ever drug treatment to reduce brain damage following a stroke or after sustaining a traumatic brain injury (TBI) in a motor vehicle or other accident, during contact sports, or from bullet/shrapnel wounds and blast injuries sustained by military personnel during active service. The aim is to improve patient survivability, reduce the level of disability, and shorten recovery time.

key investment insights

Clear Business Strategy

Nyrada is focused on drug discovery developing innovative new treatments for which there is a large unmet clinical need and substantial market potential. The company aims to develop best-in-class drugs in the two areas where it is focused: cardiovascular disease (lowering cholesterol) and neuroprotection (reducing brain injury).

Successful Management

The Nyrada Board and management team include leading figures in biotech, both here in Australia and the US, who have a proven track record of success in commercialising innovative technology.

Nyrada’s CEO, James Bonnar, a chemist by training, brings 25 years of broad professional experience in the biotechnology industry. He has worked in preclinical drug development, product manufacturing, regulatory affairs, and clinical-stage drug research, most recently for Neuren overseeing the development of treatments for traumatic brain injury and neurodevelopmental disorders.

The Nyrada Board is a diverse mix of successful international entrepreneurs and dealmakers with proven track records in the pharmaceutical industry. Christopher Cox was the Chief Commercial Officer for The Medicines Company which developed the cholesterol-lowering drug  Inclisiran®, a program that was acquired by Novartis in late 2019 for US$9.7B. At the time it was the largest ever acquisition deal for a company with a single drug in development. Chris is a firm believer in Nyrada’s approach of focusing on the small molecule inhibitor to lower cholesterol and considers an oral PCSK9 medication to be the holy grail in cholesterol management. Chris has extensive industry contacts and this is an obvious benefit for Nyrada. Marcus Frampton is the Chief Financial Officer for the largest sovereign wealth fund in the US, The Alaska Permanent Fund, and has a proven record in identifying and backing successful biotech companies. Companies they have supported include Codiak BioSciences which is developing new medicines using exosomes and Juno Pharmaceuticals, an Australian company focused on the supply of off-patent drugs to hospitals. Dr. Rüdiger Weseloh works in commercial development for Merck KGA in Germany so he has a lot of experience negotiating and securing deals with pharmaceutical companies. Dr. Ian Dixon is the founder and CEO of Exopharm has a track record of success when it comes to developing new technologies such as LEAP as well as licensing external technology. Ian has been successful in translating technology challenges into valuable businesses and is very knowledgeable and experienced when it comes to intellectual property protection. Ian is the co-developer of Nyrada’s PCSK9i inhibitor.

Nyrada’s Scientific Advisory Board comprises some of the world’s most respected scientific thought leaders from Australia, The USA, France, and Japan. The Chair of the board, Prof. Gary Housley, is the Chair in Physiology at the University of New South Wales Sydney (UNSW) and is a founding director of the Translational Neuroscience Facility and has over 30 years of experience. Prof. David Burke, currently a Professor of Neurology at RPA and the Sydney Medical School and was President of the Australian & New Zealand Association of Neurologists from 2005-2007. Prof. Gilles Lambert, Prof. Junichi Nabekura, and Dr. Jim Palmer bring expertise in cardiovascular, neuroscience, and drug discovery programs, respectively.

SCALABLE BUSINESS MODEL

Nyrada’s development of medicines focused on reducing cardiovascular disease, which is one of the most common causes of death, and providing neuroprotective treatments for people who have suffered head injuries, have the potential to be widely used pharmaceutical drugs globally, assuming trials are successful in humans. Concerning cardiovascular treatments, a new alternative to statin drugs, which is taken orally as a small pill, provides one of the largest drug opportunities in the world. Lipitor®, which is owned by Pfizer, is the best-selling drug of all time having generated more than US$160B in sales since its launch in 1997. Although now off-patent, it still generates annual sales of around US$2B for Pfizer. Concerning the neuroprotection program, Nyrada has an opportunity to offer a treatment for brain injury that prevents secondary brain damage and its devastating and life-long effects. With a market that currently accounts for US$100 billion in direct and indirect costs, the level of interest in the development of a treatment for brain injury will be very high across the entire medical industry. There is also likely to be a significant level of interest from professional and amateur sports organisations and the military, as demonstrated by the company’s collaboration with the Walter Reed Army Institute of Research (WRAIR) and the UNSW. WRAIR, the medical research arm of the US Dept of Defense reports that traumatic brain injuries are common in the military with 1 in 25 soldiers suffering a TBI during active service.

High Barriers to Entry

Nyrada has a strong intellectual property protection strategy with Patent Cooperation Treaty (PCT) and provisional patents filed for both its cholesterol-lowering and brain injury drugs. These are composition of matter patents that provide the highest level of protection and essentially mean that Nyrada owns the small molecule. A US patent for the cholesterol-lowering PCSK9i inhibitor has been granted. There is a also second patent which is in the provisional stage. In terms of the brain injury drug, the company has a provisional patent. The patents are recent and therefore provide up to 20 years of protection, which can be extended in certain circumstances.

Significant Investment Upside

If either of Nyrada’s two drug development programs are successful, there is potential for significant share price upside. Both drugs target large-scale health issues worldwide. Nyrada’s development of a cost-competitive oral pill to lower cholesterol could potentially generate massive revenue and profits globally once launched. The development of a first-in-class neuroprotectant drug with an ability to reduce the damage inflicted by excitotoxicity also has significant global revenue and profit potential. Successful phase one trial results are likely to provide a value inflection point for the company lead by interest from large global pharmaceutical companies seeking to license the PCSK9i inhibitor or the neuroprotective drug. Any deal is likely to include substantial up-front payments as well as significant ongoing royalties.

Nyrada Drug Development Projects

Cardiovascular

Currently, cardiovascular disease is the largest cause of death globally. In 2019, it was estimated that over 18.7 million people died from cardiovascular disease, roughly a third of all deaths globally. In the US there are more than 600,000 deaths annually. One of the major causes of the disease is a buildup of LDL cholesterol in arteries which can cause heart attack and stroke.

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The Importance of LDL Cholesterol to Health and the Role of PCSK9

When the body has too much LDL (bad) cholesterol, it can accumulate on artery walls, restricting blood flow which can lead to heart attack and stroke. LDL cholesterol is cleared from circulation by binding to LDL receptors (LDLR) on the surface of liver cells. PCSK9 is a naturally produced protein found in the blood that plays a counter role in regulating LDL cholesterol levels. It does this by degrading the LDLR, lowering the number of receptors available to remove LDL cholesterol. This leads to increased LDL levels in the bloodstream which can lead to a buildup of plaque in arteries and blood vessels, increasing the risk of cardiovascular disease. The inhibition of PCSK9 causes an increase in LDLR on the surface of cells improving the body’s ability to clear LDL cholesterol from the bloodstream.

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Current Treatment for High Cholesterol

Statin drugs are among the most prescribed drugs in the world with a total market estimated to be $US19B in 2018. However, in about 70 percent of patients who take them, there is a sub-optimal effect where they are not able to reach target cholesterol levels that puts them at low risk of developing cardiovascular disease. In 2015 a new class of drugs called PCSK9 inhibitors entered the market. These drugs work by binding to a protein in the bloodstream called PCSK9.  PCSK9 is important because it plays a key role in the destruction of receptors in the liver which take cholesterol out of the bloodstream. They work very effectively, particularly in combination with a statin, however, they are expensive (around US$ 6,000 per year) and must be injected every two to four weeks for life and this has led to poor patient uptake. Furthermore, multiple surveys have reported that patients prefer an oral tablet taken daily. Nyrada is developing a small molecule PCSK9i inhibitor as a single pill to treat people with high levels of cholesterol. Nyrada’s differs from current PCSK9 inhibitors because, being a small molecule drug, means that it can be taken orally. Further, it can be combined with a statin as a single pill treatment to lower cholesterol. Nyrada firmly believes that there is a big market for small molecule PCSK9 inhibitors.

NYX-PCSK9i Results from a Specialised Transgenic Mouse Model Encouraging

Results from a second preclinical trial in a specialised transgenic mouse model, known to be highly predictive of human outcomes, have shown encouraging efficacy levels. When given as a monotherapy, NYX-PCSK9i reduced cholesterol levels by almost half (46%), which was an equivalent reduction to the injectable PSK9 monoclonal antibody Praluent® (alirocumab, Sanofi / Regeneron) in a comparable study. When given in combination with the statin Lipitor®, NYX-PCSK9i reduced total cholesterol by two-thirds (65%). This compares to the reduction achieved using Lipitor® alone of 27% (see figure 1 and table 1 below). In the study, a dose of 50mg/kg was administered with no adverse side effects identified. The drug was well-tolerated with no significant changes in food intake, body weight, or liver function identified.

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Importantly, when the study ended at day 35, the cholesterol levels were still trending lower both as a monotherapy and in combination with the statin Lipitor. Nyrada will now move its drug candidate to safety and pharmacology and toxicology, in preparation for a Phase I first-in-human study set to commence in mid-2022.

Neuroprotection

Nyrada’s is developing a new and novel drug that reduces the long-term disability associated with stroke or traumatic brain injury (TBI) by limiting the number of brain cells that die post-injury. Currently, no treatments exist for TBI therefore the global market potential for a new drug that reduces the damage to the brain following a stroke or injury is very large.

Currently, approximately 15 million people suffer stroke worldwide each year. Of those, approximately one-third will die shortly after suffering a stroke, one-third will recover with little or no permanent disability, and one-third will be permanently disabled requiring long-term support and assistance. The neuroprotection drug development program aims to improve patient outcomes and increase the likelihood of recovery, shorten rehabilitation times and reduce the economic burden to the health system.

In the US, a stroke occurs every 40 seconds and a TBI every 15 seconds. The combined economic burden for stroke and TBI in the US amounts to more than US$100 billion in direct and indirect costs.

Concussion or mild TBI in contact sports accounts for 80% of all TBI cases and is a major cause of cognitive impairment and long-term physical illness. Repeated concussions lead to chronic traumatic encephalopathy (CTE) and brain degeneration caused by repeated head traumas. The incidence of concussion can range from 14.8-28.3 per 1000 player match hours. The economic burden of costs for rehabilitation and ongoing care for people who have suffered a TBI is very high.

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Nyrada hopes to reduce long-term disabilities that occur in people who have had a stroke or traumatic brain injury by limiting the extent of brain cell loss post-injury. The program aims to increase the chances of recovery by reducing secondary brain damage and rehabilitation times and the burden on healthcare systems as a result.

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The drug would be taken over 3-4 days beginning a soon as possible after a brain injury to disrupt and reduce excitotoxicity, which is largely responsible for secondary brain damage to the brain. Excitotoxicity is a common occurrence after stroke or traumatic brain injury. Chemicals are released from dead and dying brain cells, which have been impacted by the original injury. The chemicals affect healthy brain cells that cover a larger area than the core injury causing the death of brain cells. Long-term disabilities result from an almost doubling in size of the original injury.

Secondary brain injury can more than double the total area of brain injury following a stroke or TBI and there is currently no treatment to stop cell death. Nyrada has developed a novel family of molecules, which can stop the excitotoxicity process.

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In a laboratory study, Nyrada’s drug candidates showed the ability to cross the blood-brain-barrier and achieve concentrations anticipated to be therapeutic.

Collaboration Agreement with the Walter Reed Army Institute of Research & UNSW

In February 2021 a two-year Collaboration Agreement with the specialist TBI research team at Walter Reed Army Institute of Research (WRAIR) & UNSW Sydney was successfully negotiated. This will enable Nyrada to examine the ability of its lead neuroprotection compound to minimise the process responsible for secondary damage to the brain amongst military personnel who suffer a TBI during their active service careers. The agreement aligns Nyrada with WRAIR’s mission to develop ground-breaking treatments to mitigate the impacts of traumatic brain injury which occurs in 1 in 25 service members. The agreement may also provide Nyrada with access to non-dilutive funding to further develop its neuroprotection program.

Drug Discovery

In addition to Nyrada’s lead Cardiovascular and Neuroprotection drug development programs, the Company is investigating drugs to treat pain associated with peripheral nerve damage (Inflammation/Pain) and autoimmune diseases such as psoriasis (Autoimmune).

The Inflammation/Pain and Autoimmune programs are part of a larger pipeline of potential drug candidates that Nyrada continues to evaluate and develop while focusing on the progression of its two lead drug development programs.

Further information concerning Nyrada’s drug development program can be obtained from following the links in the pictures below.

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key people

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John Moore – Non Executive Chairman

John has extensive industry expertise having been involved in multi-million dollar acquisitions. In 2002, Edson Moore Healthcare Ventures acquired sixteen interests in biotech corporations from Elan Pharmaceuticals, to which he was a co-founder for a sum of $148 million. John was CEO of Acorn Energy from 2006 to 2015, in which CoaLogix sold for $101 million after it was acquired for $11 million. He is currently active on 10 company boards and has been the head of 12 different companies in his career. He was educated at Rutgers State University in New Jersey.

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Christopher Cox – Non Executive Director

Chris has significant industry experience in mergers and acquisitions and corporate governance. He has received many industry awards such as one from The American Lawyer as one of the “Dealmakers of the Year” for his role in the Irish drug maker Elan Corporation sale to Perrigo Company. He was also named an M&A Atlas Top 50 Global M&A Lawyer for 2014.

He is currently CEO of Symphony Capital Holdings, LLC, a company involved in biotechnology, network security, and entertainment. Chris brings expertise in communication, corporate advisory, and restructurings with experience across foreign and domestic transactions.

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Peter Marks – Non Executive Director

Peter has over 30 years of experience across corporate advisory, investment banking, and director/advisory roles. His director-level experience has been with financial firms such as KPMG, ASX, and Merrill Lynch. Peter has been responsible for multiple listed and unlisted companies with advice on company structure, valuations, strategy, and international opportunities.

Peter currently holds directorship with several companies and specifically in the biotechnology sector. He holds an MBA from the University of Edinburgh, Scotland and a Bachelor of Economics, and a Bachelor of Laws from Monash University, Australia.

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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.

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Marcus Frampton – Non Executive Director

Marcus currently holds the position of Chief Investment Officer of the Alaska Permanent Fund Corporation. He has held roles at Lehman Brothers in an investment banking capacity, and private equity with PCG Capital Partners.

Marcus is an avid follower and investor in micro-caps with personal publications covering micro-caps with a private monthly periodical covering this sector in the market. He holds a Bachelor’s degree in Economics from the University of California, Los Angeles.

He currently is a shareholder of Scientific Industries, Inc., and holds a position as a director on the board.

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Dr. Rüdiger  Weseloh, Non-Executive Director

Rüdiger has over 14 years of experience in the pharmaceutical industry, overseeing drug development and manufacturing across Oncology, Rheumatology, Neurodegenerative diseases, and Fertility. Ruediger in his time with Merck KGaA has been the lead on over 50 transactions for the pharmaceutical division. Before this he was a Biotech Pharma Equity Analyst, giving him a breadth of experience.

He has a diploma in Biochemistry from the University of Hannover and a Ph.D. in Molecular Neurobiology, obtained at the Center for Molecular Neurobiology in Hamburg.

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James Bonnar – CEO

James has 25 years of experience in the global life sciences industry before joining Nyrada in February 2018. He has held various director-level roles across a range of functions, most recently at Neuren Pharmaceuticals where he worked for 11 years overseeing the development of a drug to treat traumatic brain injury and neurodevelopmental disorders. Before this, he held various senior roles at several pharmaceutical and healthcare product companies in New Zealand, China, and the UK. He brings an extensive scientific focus to the company and has experience in leading teams from discovery and early-stage development and through clinical development.

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Benny Evison – Chief Scientific Officer

Benny joined Noxopharm as a Director of Preclinical (Non-oncology) and subsequently joined NYR when it was formed. He has held a great passion for science from his early years and obtained a Bachelor of Medical Science with Honors as well as a Ph.D. from La Trobe University.

After a career move to Memphis, Tennessee in the USA, he developed a strong inkling to conduct and develop meaningful scientific research following on from his postdoctoral fellowship at St Jude Children’s Research Hospital. At the hospital, he worked to develop drugs specifically involving DNA repair to improve the activity of existing chemotherapies.

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