Nyrada : Quarterly Activities Report and Appendix 4C

For personal use only

26 July 2022

Sydney, Australia

Nyrada Quarterly Activities Report & Appendix 4C

Highlights:

• Cholesterol-LoweringProgram:
• • Nyrada's PCSK9 inhibitor shown to block the early stages of atherosclerosis in a novel human tissue-engineered blood vessel model of atherosclerosis
  • Preclinical safety and toxicology studies expected to commence Q3 CY2022
  • COVID-relatedlockdowns in Shanghai delay drug manufacture, Phase I first-in- human study expected to commence 1H CY2023
  • European Patent Office grants patent for novel compounds inhibiting PCSK9
• Brain Injury Program:
• • Biological target revealed as versatile TRPC ion channels
  • NYR-BI02is a potent TRPC ion channel blocker, limiting excitotoxicity with potential to pursue multiple additional indications
  • Preclinical stroke model study results anticipated during Q3 CY2022
  • Preclinical safety and toxicology studies expected to commence Q3 CY2022
  • Phase I first-in-human study on track to commence in 2H CY2022
• Strong financial position with cash balance of $10.8M
• • Sufficient funding for Phase I studies in both lead programs

Nyrada Inc (ASX: NYR), a preclinical stage, drug development company specialising in novel small molecule drugs to treat cardiovascular and neurological diseases today provides its Quarterly Activities Report and Appendix 4C for the period ending 30 June 2022, and a summary of progress for its Cholesterol-Lowering and Brain Injury Programs.

Commenting on the quarter, Nyrada CEO, James Bonnar said: "I am pleased with the progress in advancing both our programs during the quarter, notwithstanding the challenges presented by the ongoing COVID-19pandemic. Now that Shanghai has reopened, the team and I look forward to completing the scale-updrug manufacture process, ahead of the required preclinical and Phase I studies.

"We have already shown in preclinical studies that our PCSK9 inhibitor family of compounds are able to significantly lower LDL-cholesterol levels. Their ability to also stop the early stages of

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atherosclerosis in a novel human-tissue engineered blood vessel model of the disease, developed by researchers at Duke University, is an exciting development in understanding broader applications for PCSK9 inhibitors, particularly as atherosclerotic plaque build-up is a major cause of cardiovascular disease.

"Additionally, we are pleased with initial study results announced last month indicating that our Brain Injury Program drug candidate, NYR-BI02, is a potent blocker for three of the TRPC channels and offers significant potential to treat multiple additional diseases involving TRPC ion channels. We are focused on finalising drug synthesis in order to test the efficacy of the molecule in a TBI model as well as in a model of ischemic stroke.

"In the coming months we will be reporting on the results of the preclinical stroke model study for the Brain Injury Program and providing updates on the progress of the preclinical safety and toxicology studies for the Cholesterol-Lowering Program," Mr Bonnar added.

Preclinical Program Update

Cholesterol-Lowering Program - PCSK9 inhibitor

Evaluation of Nyrada's PCSK9 Inhibitors in a Novel Model of Atherosclerosis

Results from a study run by researchers at Duke University Pratt School of Engineering (Duke), using select candidates from Nyrada's PCSK9 inhibitor family of compounds was presented at the North American Vascular Biology Organisation (NAVBO) 2022 Vasculata conference in North Carolina on 19 July 2022.

The study aimed to determine if PCSK9 inhibitors attenuate inflammation in vascular cells in the early phases of atherosclerosis. In a human tissue-engineered blood vessel model of atherosclerosis, developed in the lab of Professor George Truskey, Nyrada's PCSK9 inhibitor blocked the early stages of atherosclerotic plaque progression, including preventing monocyte adhesion and suppression of inflammatory cytokines, both of which are key mediators of the disease process.

It is the first time the model has been used to characterise the role of PCSK9 in the early phases of atherosclerosis and the potential for small molecule inhibitors of PCSK9 to block this process. The researchers at Duke intend to publish the findings of this study in a peer-reviewed paper.

Preclinical Studies

During the quarter, the scale-up manufacture of Nyrada's lead cholesterol-lowering drug candidate for the program's preclinical studies was delayed due to the extended COVID-related lockdown in Shanghai, China. Employees of the Shanghai-based contract manufacturing

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Nyrada Inc. Level 3, 828 Pacific Highway, Gordon NSW 2072

ARBN 625 401 818

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organisation (CMO) engaged by Nyrada were unable to access laboratory worksites while the lockdown remained in place.

The required preclinical safety and toxicology studies are expected to commence in Q3 CY2022. Substantial efforts were made by the CMO to minimise the impact of the COVID- related lockdowns on drug manufacturing timelines, including the deployment of additional personnel and resources to recover lost time. As the delay impacted the availability of preclinical study slots at Charles River Laboratories, Inc., these studies will now be run at Inotiv, a US based contract research organisation (CRO).

Phase I Study

As a result of scale-up drug manufacturing delays caused by COVID-related lockdowns in Shanghai, the Phase I first-in-human study for Nyrada's Cholesterol-Lowering Program is expected to commence during the first half of CY2023.

The primary objective of the Phase I study is to evaluate Nyrada's drug candidate for safety and tolerability. 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.

Intellectual Property

The European Patent Office has formally granted the composition of matter patent for the Company's novel compounds inhibiting PCSK9, providing protection for Nyrada's intellectual property relating to its PCSK9 inhibitor technology until 16 March 2038. Nyrada now has patent protection for the compounds in both the US and European Union.

Brain Injury Program

Target Revealed

During the quarter, Nyrada revealed the biological target of its Brain Injury Program as a class of proteins known as the "Canonical" Transient Receptor Potential, or TRPC ion channels.

These channels are present on the surface of brain cells and allow calcium to enter the cell. While calcium is critical to cell survival, excess calcium triggers cell death pathways. Following an injury in the brain, the mechanisms that keep the calcium levels in-check fail as they rely on energy, which quickly depletes. After a brain injury such as a stroke, accident impact or concussion, the TRPC channels are constantly activated, allowing sustained calcium entry into the cells leading to cell death.

Nyrada's brain injury drug candidate NYR-BI02 is a potent blocker of three subtypes of the channel - TRPC3, TRPC6 and TRPC7, which are present in high levels in brain tissue. By targeting these channels, Nyrada's brain injury drug candidate is able to interrupt the sustained entry of

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Nyrada Inc. Level 3, 828 Pacific Highway, Gordon NSW 2072

ARBN 625 401 818

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calcium into the cells and thereby reduce secondary brain injury. Presently, there are no FDA- approved small molecule blockers of TRPC 3, 6, 7 ion channels. NYR-BI02 is also able to cross the blood-brain-barrier, indicating it can reach therapeutic levels in the injured brain.

As part of its active intellectual property protection program, Nyrada has filed a provisional patent covering a library of molecules, including NYR-BI02, that block these channels. It is anticipated that the patent will have coverage firstly in Australia, followed by Europe and US.

Preclinical Studies

Stroke Model Study

The COVID-related lockdowns in Shanghai delayed the start of the preclinical stroke model study. With the re-opening of Shanghai, it is anticipated the results of the preclinical stroke model study will be available in Q3 CY2022.

Safety Toxicology and Pharmacology Studies

The required preclinical studies will be used to evaluate the safety and tolerability of Nyrada's lead brain injury drug candidate in research models. Data from these studies will determine the safe starting dose for the Phase I first-in-human study. The Company is in discussions with a number of CROs regarding the design and timing of these studies and a further update will be provided once these details are finalised. These studies are anticipated to begin in Q3 CY2022.

TBI Efficacy Study Progress

Nyrada will initially test the efficacy of its NYR-BI02 molecule as a TRPC 3, 6 and 7 channel blockers in a model of traumatic brain injury via its existing collaboration with the Walter Reed Army Institute of Research (WRAIR). With the initial pilot work at WRAIR and UNSW Sydney now complete, the study design for the efficacy study has been finalised.

The efficacy study will employ the penetrating ballistic brain injury (PBBI) model which has been developed by the WRAIR team to emulate penetrating head wounds on the battlefield. The study will involve dosing animals with a vehicle or NYR-BI02 in a blinded fashion and assessing the injury volume using a specialised MRI technique at UNSW Sydney.

The study will include assessment of blood biomarkers including GFAP and NF-L. MRI and blood biomarker assessments are commonly used in the clinical setting for diagnosis and prognosis purposes in TBI and stroke patients. The efficacy study will also incorporate assessment techniques commonly used in animal brain injury models.

The complex nature of this study requires WRAIR to contribute considerable resources to enable its completion. Like many large research organisations globally, the ongoing COVID-19 pandemic has had an impact on some project timelines. The progression of this study is largely

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Nyrada Inc. Level 3, 828 Pacific Highway, Gordon NSW 2072

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driven by availability of the necessary resources at WRAIR and is currently expected to start in the new year.

Delays to the start of the TBI efficacy study will not impact the commencement of the Phase I first-in-human study. These studies can be run in parallel.

Phase I Study

Pending scale-up manufacturing of the drug, completion of the FDA mandated preclinical safety and toxicity studies and ethics committee approval of the trial protocol, recruitment, and dosing of the first participant is expected to commence in 2H CY2022.

The Phase I study will be run in Australia and will evaluate the safety and tolerability of the Company's preferred brain injury drug candidate, NYR-BI02.

The trial participants will be split into 5 groups of 8, with 6 receiving the drug and 2 receiving a placebo. Cohorts 1 and 2 will be given a bolus single ascending dose, while cohorts 3, 4 and 5 will be given bolus and continuous infusion in ascending doses for 72 hours via intravenous infusion.

Blood samples will be drawn several times throughout the study period and analysed for drug levels. Participants will be monitored for clinical signs throughout the study duration.

Corporate and Financial Summary

Cash Flow & Cash Position

Total cash operating outflows for the June 2022 quarter were approximately A$781,000 (A$1.0 million in the prior quarter). The Company anticipates cash outflows in future quarters will increase as both Programs progress toward Phase I clinical trials.

Nyrada has a robust cash position of A$10.8 million as at 30 June 2022 (A$11.3 million as at 31 March 2022), providing the Company with sufficient cash reserves to complete Phase I studies for both its Brain Injury and Cholesterol-Lowering programs.

In accordance with Listing Rule 4.7C, payments made to related parties and their associates included in item 6.1 of the Appendix 4C was approximately A$139,000 and included Director fees.

-ENDS-

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Nyrada Inc. Level 3, 828 Pacific Highway, Gordon NSW 2072

ARBN 625 401 818