Nyrada : Quarterly Activities Report & Appendix 4C

For personal use only

21 January 2022

Sydney, Australia

Nyrada Quarterly Activities Report & Appendix 4C

Highlights:

• Cholesterol-LoweringProgram:
• • Charles River Laboratories appointed to conduct safety pharmacology and toxicology studies in Nyrada's cholesterol-lowering drug in the US in 1H CY2022
  • Australian world-class clinical research centre will conduct Phase I first-in-human clinical trial, set to commence in 2H CY2022
  • Phase I dose escalation study will evaluate the safety, tolerability and efficacy of Nyrada's cholesterol-lowering drug candidate
  • PCT patent application filed in Dec 2021 for new generation cholesterol-lowering compounds, expanding protection of Nyrada's PCSK9 inhibitor technology
• Brain Injury Program:
• • Nyrada's brain injury drug candidate to be tested in preclinical model of stroke in Q1
    CY2022
  • Pilot Traumatic Brain Injury (TBI) preclinical study under Nyrada-UNSW Sydney- WRAIR collaboration progressing well to optimise efficacy study design
  • Phase I study to commence in 2H CY2022, evaluating safety and tolerability of
    Nyrada's drug in two indications, TBI and stroke
• Robust cash position of A$11.1 million: R&D tax incentive rebate of A$1.3 million received in January 2022

Nyrada Inc (ASX: NYR), a preclinical stage, drug development company specialising in novel small molecule drugs to treat cardiovascular and neurological diseases is pleased to provide its Quarterly Activities Report and Appendix 4C for the period ending 31 December 2021, and a summary of progress for its Cholesterol-Lowering and Brain Injury Programs.

Commenting on the quarter, Nyrada CEO, James Bonnar said: "Our drug development programs made good progress at the end of 2021, and we are excited to be advancing to the next stage as Nyrada beings to transition to a clinical drug development company in 2022.

"The Phase I clinical trial for the Cholesterol-Lowering Program will be the first time our drug candidate is evaluated in humans, representing a significant milestone for Nyrada. Furthermore, the Phase I clinical trial for the Brain Injury Program will support the

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

ARBN 625 401 818

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development of Nyrada's drug in both TBI and stroke indications, significantly expanding the commercial opportunities available to the Company. The team and I look forward to keeping investors informed of our progress in what we expect will be an active and exciting year for Nyrada," Mr Bonnar added.

Preclinical Program Update

Cholesterol-Lowering Program - PCSK9 inhibitor

Preclinical Studies

Nyrada has appointed Charles River Laboratories, Inc. ("Charles River") to conduct the Company's preclinical studies in the US in the first half of this year, ahead of a Phase I cholesterol-lowering trial in Australia. Charles River has supported the development of more than 80% of the drugs approved by the US Food & Drug Administration in the past three years.

The required preclinical studies will be used to evaluate the safety and tolerability of Nyrada's drug in research models. This is a necessary part of the drug development process given Nyrada's candidate has not been tested in humans. Data from these studies will determine the safe starting dose for the Phase I first-in-human study.

Phase I Study

The Phase I study will be a first-in-human,double-blind, randomised, dose escalation design evaluating the safety, tolerability, and pharmacokinetics of Nyrada's leading drug candidate in approximately 56 healthy volunteers aged 18 to 50 years. The Company will also evaluate efficacy by measuring changes in LDL or "bad" cholesterol levels in the blood.

Nyrada's drug candidate will be administered to participants as a once daily oral dose over the 14-day treatment period, to assess safety, tolerability, and efficacy. In the trial, participants will be split into 7 groups of 8, with each person in groups 1-5 receiving a single dose of Nyrada's drug candidate or placebo, whilst healthy volunteers in groups 6 and 7 will receive a dose of Nyrada's drug candidate or placebo over 14 days. Pathology samples and data will be collected at selected time points over the trial period for all groups.

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

Patent Cooperation Treaty (PCT) Application

Nyrada's medicinal chemistry program continued to generate further promising PCSK9 inhibitor analogues, which enabled the Company to file a PCT application for new generation PCSK9 inhibitor compounds in December 2021. A PCT application makes it possible to seek protection for an invention simultaneously in a large number of countries by filing a single "international"

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

ARBN 625 401 818

For personal use only

patent application, instead of filing several separate national or regional applications. This application builds on the patent granted by the US Patent and Trademark Office, as announced on 30 July 2021, and the corresponding European Patent which is in the final stages of examination.

Brain Injury Program

Preclinical TBI Efficacy Study Progress

In the lead-up to the efficacy study with Nyrada's brain injury drug candidate, a pilot study is being conducted to optimise the design of the efficacy study. A key focus of this pilot study is to refine the location and extent of injury in each model and select optimal timepoints to assess a therapeutic effect of Nyrada's drug in preventing secondary brain injury.

Brain samples from the Controlled Cortical Impact (CCI) and Penetrating Ballistic Brain Injury (PBBI) models have been collected from the Walter Reed Army Institute of Research (WRAIR) and are currently undergoing assessment at the Translational Neuroscience Facility of UNSW, utilising their sophisticated MRI technology (T2-weighted and Fractional Anisotropy MRI) to establish the nature and extent of injury. This reflects brain imaging technology used in hospital emergency rooms.

The data from the pilot study will allow Nyrada to ascertain the number of animals that will be required to provide a meaningful assessment of the therapeutic effect of the Company's drug.

Testing Nyrada's Brain Injury Drug Candidate in Stroke

The efficacy of Nyrada's brain injury drug candidate will be evaluated in a well-established preclinical model of stroke during the first quarter of this year. The model is called the Photothrombotic Model of Ischemia, where localised clot formation is achieved in a specific brain region, leading to a stroke. This model was previously used by Nyrada to test the efficacy of its first-generation molecule, which showed a promising efficacy signal.

This work in stroke is outside of the studies being undertaken as part of Nyrada's collaboration with WRAIR and UNSW. WRAIR's focus remains solely on developing a drug to mitigate the impact of TBI on military service members.

A key advantage of the drug that Nyrada is developing is it can be administered to stroke and TBI patients in the same manner, by way of intravenous dosing over a 3-day period, which is matched to patient emergency hospital admission.

Phase I Study

Nyrada expects to commence a Phase I first-in-human study for its Brain Injury Program in the second half of CY2022. The Phase I study will be run in Australia and will evaluate the safety and tolerability of the Company's brain injury drug candidate.

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

ARBN 625 401 818

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Nyrada will provide an update on the preclinical studies with WRAIR and UNSW, as well selection of the contract research organisation and study design for the Phase I study in the first half of this year.

Corporate and Financial Summary

Cash Flow & Cash Position

Total cash operating outflows for the December 2021 quarter were approximately A$1.3 million (A$1.2 million in the prior quarter). The Company anticipates cash outflows in future quarters will increase as both Programs progress towards Phase I clinical trials.

Nyrada's cash position was A$11.1 million as at 31 December 2021. Subsequent to the end of the quarter, the Company received a FY2021 R&D tax incentive refund of $1.3 million, further boosting available capital resources. 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$162,000 and included Director fees.

A summary of the operating cashflows for the twelve months ending 31 December 2021, compared with the proposed use of funds in Year 2 of Nyrada's Prospectus dated 26 November

2019 and Supplementary Prospectus dated 9 December 2019 is outlined below:

	Year 2	12-month period
	12-month period	ending 31 Dec 2021
	Per Prospectus (A$)	(A$)
Research & Development (R&D) - Salaries	1,500,000	928,000
R&D - Brain Injury program	1,000,000	910,000
R&D - Cholesterol-Lowering program	700,000	1,550,000
Other R&D	500,000	13,000
Repayment of part of the Noxopharm Loan	-	342,000
Working Capital	700,000	1,809,000
Government grants and tax incentives	-	(976,000)
Total	4,400,000	4,576,000

During the twelve-month period ending 31 December 2021, overall R&D spend remains broadly in line with the estimated use of funds as set out in the Prospectus and Supplementary Prospectus.

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

ARBN 625 401 818

For personal use only

The estimated R&D Tax incentive inflows for FY19, FY20 and FY21 were not included in the use of funds statement and are partially funding the working capital requirements along with the Company's R&D programs.

Nyrada believes the working capital outflows are consistent with the requirements for an ASX listed biotech company of its size. As a result of last year's capital raise, the Company has sufficient cash reserves to complete Phase I studies in both its Brain Injury and Cholesterol- Lowering programs.

-ENDS-

About Nyrada Inc

Nyrada is a preclinical stage, drug discovery and development company, specialising in novel small molecule drugs to treat cardiovascular and neurological diseases. The Company has two main programs, each targeting market sectors of significant size and considerable unmet clinical need. These are a cholesterol-lowering drug and a drug to treat brain injury, specifically traumatic brain injury and stroke. Nyrada Inc. ARBN 625 401 818 is a company incorporated in the state of Delaware, US, and the liability of its stockholders is limited.

www.nyrada.com

Authorised by Mr. John Moore, Non-Executive Chairman, on behalf of the Board.

Investor & Corporate Enquiries:	Company Secretary:
Laura Vize	David Franks
Investor Relations Manager	T: 02 8072 1400
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Catherine Strong
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Nyrada Inc. Level 3, 828 Pacific Highway, Gordon NSW 2072

ARBN 625 401 818