ANNUAL REPORT FY22 9 Cholesterol-Lowering Program The World Health Organization (WHO) estimates that by 2030, 1 in 6 people will be aged 60 years or over, accounting for ~1.4 billion people globally.4 High cholesterol, specifically LDL or “bad” cholesterol, is a known significant risk factor for developing cardiovascular disease and is most prevalent between the ages of 55-64 in Australia, and 40-59 in the US.5 A large US study6 estimated that more than 62 million Americans have risk factors associated with cardiovascular disease, and are therefore eligible for cholesterol-lowering treatment. From this population, approximately 27 million take a statin drug, the current first line treatment for high LDL-cholesterol. Of those taking a statin, more than 18 million, or close to 70% are unable to achieve their safe target cholesterol level. As the world’s population continues to age, patient need for new, more effective, and convenient cholesterol-lowering drugs will only increase. We have shown through preclinical studies that Nyrada’s small molecule PCSK9 inhibitor is able to significantly lower LDL-cholesterol levels, while also increasing the number of LDL receptors which are responsible for removing cholesterol from the bloodstream. The drug Nyrada is developing is intended to be taken as a once-per-day pill, alone or in combination with a statin, overcoming the inconvenience of expensive injectable PCSK9 inhibitors. Small molecule drugs also have a lower manufacturing cost than biologics, which includes PCSK9 inhibitors. The program is entering an exciting period as safety, pharmacology, and toxicology studies get underway in the second half of this year, ahead of a Phase I first-in-human study expected to commence in the first half of next year, to be run in Australia. The primary objective of the Phase I study is to evaluate Nyrada’s drug candidate for safety and tolerability. However, a secondary endpoint will assess blood cholesterol levels in cohorts treated for 14 days with Nyrada’s drug candidate as a preliminary indication of the drug’s efficacy in humans. I am delighted that Nyrada’s intellectual property portfolio also continues to grow with the granting of patents for our PCSK9 inhibitor compounds in the US and Europe, providing composition of matter protection through to 2038. Brain Injury Program Nyrada’s Brain Injury Program made significant progress during the year. We revealed the biological target for the program as a class of proteins known as the “Canonical” Transient Receptor Potential, or TRPC ion channels. After a brain injury, these channels remain “open”, allowing calcium to accumulate in neuronal cells to toxic levels, leading to cell death.7 Nyrada’s brain injury drug candidate, NYR-BI02, is a potent blocker of three subtypes of the TRPC channel – TRPC 3/6/7, which are widely expressed in the brain. By targeting these channels, our brain injury drug candidate can inhibit the entry of calcium into cells and thereby reduce secondary brain injury. NYR-BI02 also readily crosses the intact blood-brain-barrier, indicating it can reach therapeutic levels in an injured brain. There is still no FDA-approved drug to treat TBI and only limited treatment options for stroke. To the Company’s knowledge, there is also no other small molecule brain injury drug in development that targets TRPC ion channels. A recent report8 estimated that annually, ~55.9 million people globally experience a mild TBI, with 5.48 million experiencing a severe TBI. More than 55 million people, or 0.7% of the world’s population are thought to be living with the effects of medically treated TBI. In the US, 4.8 million people are evaluated in emergency departments for TBI each year, with TBI being diagnosed in approximately 2% of total emergency department visits, hospitalisations, and deaths.9 This is not just a civilian issue, with 1 in 5 US military service members reporting experiencing a TBI during active duty. With the incidence of TBI increasing globally, this remains a large market with a significant unmet clinical need. Through our relationships with the world-class leading research teams at the Walter Reed Army Institute of Research (WRAIR) and UNSW Sydney (UNSW), Nyrada is in a unique position to develop the first drug to treat both TBI and stroke, with the potential to make a tangible difference in the quality of life of people affected by these injuries.