Ethics Approval for Cynata's Clinical Trial in DFU

Cynata Therapeutics Limited Level 3, 62 Lygon Street, Carlton, Victoria 3053, Australia PO Box 7165, Hawthorn North, Victoria 3122 T: + 613 9824 5254 F: + 613 9822 7735 E: [email protected] ABN - 98 104 037 372 ASX ANNOUNCEMENT 30 June 2021 Ethics Approval for Cynata’s Clinical Trial in Diabetic Foot Ulcers Key highlights • Ethics approval received for clinical trial in patients with diabetic foot ulcers • First clinical trial to utilise the wound dressing technology recently licensed from TekCyte • Patient recruitment expected to commence in 2H CY21 Melbourne, Australia; 30 June 2021 : Cynata Therapeutics Limited (ASX: “ CYP”, “Cynata”, or the “Company”), a clinical- stage biotechnology company specialising in cell therapeutics, is pleased to announce that it has received approval by the Central Adelaide Local Health Network Human Research Ethics Committee to commence a clinical trial of Cynata’s Cymerus™ mesenchymal stem cell (MSC) product in patients with diabetic foot ulcers. The trial, entitled “A Randomised, Controlled, Phase 1 Study to Investigate Safety, Tolerability and Efficacy of CYP-006TK in Adults with Diabetic Foot Ulcers ”, aims to recruit 30 participants, who will be randomly assigned to receive either CYP-006TK or standard care treatment. This will be the first clinical trial to utilise CYP-006TK, a polymer-coated silicon dressing (seeded with Cymerus MSCs) that Cynata has licensed from TekCyte Pty Ltd (TekCyte) . As announced on 28 June 2021, Cynata has engaged leading clinical research organisation, Datapharm Australia, to assist in the conduct and management of the trial. The investigational treatment period is 4 weeks, and each patient will be evaluated for a total of 24 weeks. The primary endpoint of the trial is safety, while secondary efficacy endpoints include the following outcome measures after 12 and 24 weeks: • Percentage ulcer area change • Days to complete ulcer healing • Days to 50% ulcer healing • Percentage change in ulcer volume • Ulcer pain The trial will take place at Royal Adelaide Hospital and The Queen Elizabeth Hospital in Adelaide, under the leadership of Professor Robert Fitridge, who is Professor of Vascular Surgery at the University of Adelaide, Head of Vascular Surgery at The Queen Elizabeth Hospital, and Consultant Vascular Surgeon with the Central Adelaide Local Health Network. Patient recruitment is expected to commence in the second half of this year, subject to the completion of customary regulatory and administrative approvals, as well as other trial start up activities, which are currently underway. A corporate presentation on the DFU clinical trial is attached to this announcement. Dr Kilian Kelly, Cynata’s Chief Operating Officer, said: “Diabetic foot ulcers can severely impact quality of life, and often result in hospitalisation, amputation and even death. Existing treatment options often fail to heal diabetic ulcers in a timely manner, if at all, so new and more effective treatments are urgently needed. The estimated market value for diabetic foot ulcer treatments is already approaching US$10b, 1 and that figure is likely to grow significantly in the future, in 1 Transparency Market Research, 2020 (Reflects global DFU treatment market by 2027). Cynata Therapeutics Limited Level 3, 62 Lygon Street, Carlton, Victoria 3053, Australia PO Box 7165, Hawthorn North, Victoria 3122 T: + 613 9824 5254 F: + 613 9822 7735 E: [email protected] ABN - 98 104 037 372 tandem with the growth in the incidence of diabetes worldwide. We are on target to commence the trial this year and look forward to working with Professor Fitridge and his team on this important study.” -ENDS- Authorised for release by Dr Ross Macdonald, Managing Director & CEO CONTACTS: Dr Ross Macdonald, CEO, Cynata Therapeutics, +61 (0)412 119343, [email protected] Claire LaCagnina, U.S. Media Contact, +1 315.765.1462, [email protected] About Cynata Therapeutics (ASX: CYP) Cynata Therapeutics Limited (ASX: CYP) is an Australian clinical -stage stem cell and regenerative medicine company focused on the development of therapies based on Cymerus™, a proprietary therapeutic stem cell platform technology. Cymerus™ overcomes the challenges of other production methods by using induced pluripotent stem cells (iPSCs) and a precursor cell known as mesenchymoangioblast (MCA) to achieve economic manufacture of cell therapy products, including mesenchymal stem cells (MSCs), at commercial scale without the limitation of multiple donors. Cynata’s lead product candidate CYP -001 met all clinical endpoints and demonstrated positive safety and efficacy data for the treatment of steroid-resistant acute graft-versus-host disease (GvHD) in a Phase 1 trial. Clinical trials of Cymerus MSC products in osteoarthritis (Phase 3) and in patients with respiratory failure are currently ongoing. Planning is also underway for further clinical trials of Cymerus MSC products in GvHD (through licensee Fujifilm), diabetic foot ulcers , critical limb ischemia, idiopathic pulmonary fibrosis, and renal transplantation. In addition, Cynata has demonstrated utility of its Cymerus MSC technology in preclinical models of numerous diseases, including the clinical targets mentioned above, as well as asthma, heart attack, sepsis, acute respiratory distress syndrome (ARDS) and cytokine release syndrome. A Next Generation Stem Cell Therapeutics Company 30 June 2021 Overview of Diabetic Foot Ulcers Opportunity Ethics approval for a Phase 1 clinical trial Preclinical studies supporting further development Trial funding secured TekCyte license agreement secured Completion of trial: report top-line data and results 2 Key milestones achieved towards DFU clinical trial Cynata is progressing toward a fully funded Diabetic Foot Ulcers (DFU) clinical trial1 1. Trial to be fully funded from available cash reserves. 2. Commencement of trial is subject to completion of customary regulatory and administrative approvals, as well as other trial start up activities – which are currently underway Trial commences2 (expected to commence 2H FY21) Large unmet medical need Successful preclinical results Leverages TekCyte’s technology Ethics approval received 3 DFU is an attractive indication to target DFU is a serious complication of diabetes, and has a global treatment market of ~$US10B1 Positive data demonstrating the efficacy of Cymerus MSCs in a preclinical model of DFU2 First clinical trial to utilise TekCyte’s leading wound dressing technology Recruitment expected to commence in 2H CY21 (with trial start up activities currently underway) This trial will be fully funded by Cynata’s current cash reserves Head start in development Clear safety results in Phase 1 GvHD trial and efficacy in a preclinical wound model provide a sound foundation 1. Estimated DFU market (Source: Transparency Market Research, 2020 (Reflects global DFU treatment market by 2027)) 2. Trial conducted independently by the Cooperative Research Centre for Cell Therapy Manufacturing (CTM-CRC). Results of preclinical model of Diabetic Wounds announced in May 2018. . Diabetic Foot Ulcers 1. Diabetics Australia (estimated ~415m adults with diabetes in 2015) ; Mutluoglu M, Uzun G, Turhan V, Gorenek L, Ay H, Lipsky BA. How reliable are cultures of specimens from superficial swabs compared with those of deep tissue in patients with diabetic foot ulcers? J Diabetes Complications. 2012 May-Jun;26(3):225-9 2. Van Netten JJ et al. Australian diabetes-related foot disease strategy 2028-2022: The first step towards ending avoidable amputations within a generation. Diabetic Foot Australia, 2017 3. Estimated DFU market (Source: Transparency Market Research, 2020 (Reflects global DFU treatment market by 2027)). DFU is among the most common and serious complications of patients who have diabetes 4 DFU is a serious disease and presents an unmet medical need Market opportunity Next steps • DFU are sores on the feet of patients with diabetes (also known as diabetic wounds) • >400m diabetics globally, with diabetic wounds estimated to occur in ~15-25% of patients sometime during their lifetime1 • In Australia alone diabetic foot disease is estimated to result in2: o >27,000 hospitalisations annually o ~4,400 amputations annually o ~1,700 deaths annually • The global DFU treatment market is estimated to be ~US$10 billion3  Central Adelaide Local Health Network Human Research Ethics Committee (HREC) approval  Complete customary regulatory and administrative approvals, and trial start up activities  Commence recruitment of patients: expected in 2H CY21 1. Conducted by other parties 5 DFU | Phase 1 clinical trial design Recruitment is expected to commence in 2H CY21 Study design • Patients will be randomly assigned to receive CYP-006TK (polymer-coated silicon dressing seeded with Cymerus MSCs) or standard care of treatment • Treatment period will be 4 weeks • Each patient is evaluated over a total of 24 weeks • Cynata has engaged Datapharm Australia to assist in the conduct and management of the trial Endpoints • Primary endpoint will be safety • Secondary endpoints will be efficacy endpoints consistent with previous pivotal trials1 including; ‒ Percentage ulcer area change ‒ Days to complete ulcer healing ‒ Days to 50% ulcer healing ‒ Percentage change in ulcer volume ‒ Ulcer pain Target population • 30 adult patients with Diabetic Foot Ulcers Preclinical trial results Primary outcome was speed of wound healing (measured as extent of skin restoration after three days)  Cynata’sCymerus MSCs achieved 86% restoration2  Significantly faster wound healing that bone marrow-derived MSCs (which only achieved 51% restoration)  Significantly faster wound healing than dressings without MSCs (which only achieved 48% restoration) Preclinical trial design • Positive efficacy data of Cymerus MSCs in a preclinical model of DFU1 • The preclinical trial was designed to compare MSCs and cells from various sources 1. Trial conducted independently by the Cooperative Research Centre for Cell Therapy Manufacturing (CTM-CRC). Results of preclinical model of Diabetic Wounds announced in May 2018. 2. Measure of re-epithelialisation after three days Cynata’sCymerus MSCs demonstrated promising efficacy results in a preclinical model of DFU 6 Cymerus MSCs present a potential treatment for DFU Cynata plans to undertake a clinical trial in DFU based on the solid preclinical foundation and utilise TekCyte’stechnology This is the first clinical trial to utilise TekCyte’snovel wound dressing technology 7 Cynata has partnered with TekCyte to optimise chance of success 1. Refer to announcement on 3 June 2021 “Cynata signs License Agreement with TekCyte” 2. Source: https://tekcyte.com/functionalised-coatings/ TekCyte will manufacture and supply the active dressing to be utilised in Cynata’splanned DFU clinical trial TekCyte has developed proprietary surface modification technologies to product polymer-coated dressings for the delivery of MSCs to wounds. Cynata has secured a worldwide exclusive licence agreement with TekCyte Pty Ltd1 – with the option to purchase the relevant technology outright. The coating process provides key benefits in the delivery of MSCs2:  Simple to apply  Easily scalable  Low capital costs  Rapid translation from lab to the clinic  Reproducible performance Summary information This Presentation contains summary information about Cynata Therapeutics Limited and its subsidiaries (CYP) which is current at 30 June 2021. This Presentation should be read in conjunction with CYP’sother periodic and continuous disclosure information lodged with the Australian Securities Exchange (ASX), which are available at www.asx.com.au. Not an offer This Presentation is not a prospectus, product disclosure statement or other offering document under Australian law (and will not be lodged with the ASIC) or any other law. This Presentation is for information purposes only and is not an invitation or offer of securities for subscription, purchase or sale in any jurisdiction. The release, publication or distribution of this Presentation (including an electronic copy) outside Australia may be restricted by law. If you come into possession of this Presentation, you should observe such restrictions. Any non-compliance with these restrictions may contravene applicable securities laws. Not investment advice This Presentation does not constitute investment or financial product advice (nor tax, accounting or legal advice) or any recommendation by CYP or its advisers to acquire CYP securities. This Presentation has been prepared without taking account of any person’s individual investment objectives, financial situation or particular needs. Before making an investment decision, prospective investors should consider the appropriateness of the information having regard to their own investment objectives, financial situation and needs and seek legal, accounting and taxation advice appropriate to their jurisdiction. CYP is not licensed to provide financial product advice in respect of CYP securities. Investment risk and past performance An investment in CYP securities is subject to known and unknown risks, some of which are beyond the control of CYP and its directors. CYP does not guarantee any particular rate of return or performance of CYP. Past performance cannot be relied upon as an indicator of (and provides no guidance as to) future CYP performance including future share price performance. Financial data All financial information in this Presentation is in Australian currency (A$) unless otherwise stated. This Presentation contains historical financial information based on the Company’sresults for the half year to December 2020. This information is disclosed in the 4D report lodged with ASX on 26 February 2021. Any discrepancies between totals and sums of components in tables and figures in this Presentation are due to rounding. Forward-looking statements This Presentation contains certain ‘forwardlooking statements’,which can generally be identified by the use of forward looking words such as ‘expect’,‘anticipate’,‘likely’,‘intend’,‘should’,‘could’,‘may’,‘predict’,‘plan’, ‘propose’,‘will’,‘believe’,‘forecast’,‘estimate’,‘target’,‘outlook’,‘guidance’,‘potential’and other similar expressions. The forward looking statements contained in this Presentation are not guarantees or predictions of future performance and involve known and unknown risks and uncertainties and other factors, many of which are beyond the control of CYP, its directors and management, and may involve significant elements of subjective judgment and assumptions as to future events which may or may not be correct. There can be no assurance that actual outcomes will not differ materially from these forward looking statements. A number of important factors could cause actual results or performance to differ materially from the forward looking statements. No representation or warranty, express or implied, is made as to the accuracy, likelihood of achievement or reasonableness of any forecasts, prospects, returns or statements in relation to future matters contained in this Presentation. The forward looking statements are based on information available to CYP as at the date of this Presentation. Except as required by law or regulation (including the ASX Listing Rules), CYP and its directors, officers, employees, advisers, agents and intermediaries undertake no obligation to provide any additional or updated information whether as a result of new information, future events or results or otherwise. You are strongly cautioned not to place undue reliance on forward-looking statements, particularly in light of the current economic climate and the significant volatility, uncertainty and disruption caused by the outbreak of COVID-19. Industry and Market data Certain market and industry data used in connection with this Presentation may have been obtained from research, surveys or studies conducted by third parties, including industry or general publications. Neither CYP nor its representatives have independently verified any such market or industry data provided by third parties or industry or general publications. Disclaimer To the maximum extent permitted by law, CYP and its advisers, affiliates, related bodies corporate, directors, officers, partners, employees and agents (Related Persons) exclude and disclaim all liability, including without limitation for negligence, for any expenses, losses, damages or costs arising from this Presentation or reliance on anything contained in or omitted from it. To the maximum extent permitted by law, CYP and its Related Persons make no representation or warranty, express or implied, as to the currency, accuracy, reliability or completeness of information in this Presentation and disclaim any obligation or undertaking to release any update or revision to the information in this Presentation to reflect any change in expectations or assumptions. Statements made in this Presentation are made only as at the date of this Presentation. The information in this Presentation remains subject to change without notice. 8 Important Information Cynata Therapeutics Limited Level 3 62 Lygon Street Carlton Victoria 3053 Australia Contact details: [email protected] www.cynata.com

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