Demonstrated Safety & Efficacy in DFU Clinical Trial

Cynata Therapeutics Limited ABN – 98 104 037 372 Level 3, 100 Cubitt Street Cremorne VIC 3121 Australia T: +613 7067 6940 E: [email protected] www.cynata.com ASX ANNOUNCEMENT 5 December 2024 CYP-006TK Demonstrates Safety and Efficacy in DFU Clinical Trial Melbourne, Australia; 5 December 2024: Cynata Therapeutics Limited (ASX: “CYP”, “Cynata”, or the “Company”), a clinical-stage biotechnology company specialising in cell therapeutics, has successfully completed its Phase 1 clinical trial of CYP-006TK in diabetic foot ulcers (DFU). Key Highlights • The trial met its primary objective , with CYP -006TK found to be safe and well-tolerated – no participants withdrew from the trial due to adverse events, and no suspected serious adverse reactions were reported. • Importantly, the trial also generated positive efficacy data, indicating improved wound healing for CYP-006TK compared to the standard of care control group. • The mean1 change from baseline in wound surface area was: o After 12 weeks , a decrease (improvement) of 181 mm2 in the CYP -006TK group, and an increase (deterioration) of 355 mm2 in the standard of care control group. o After 24 weeks (end of study), a decrease (improvement) of 261 mm2 in the CYP -006TK group, and an increase (deterioration) of 62 mm2 in the standard of care control group. • The mean change from baseline in wound surface area expressed as a percentage was: o After 12 weeks, a decrease (improvement) of 64.6% in the CYP-006TK group compared to a decrease of 22.0% in the standard of care control group. o After 24 weeks, a decrease (improvement) of 83.6% in the CYP-006TK group compared to a decrease of 47.8% in the standard of care control group.2 • The study also indicates that larger wounds in particular healed to a greater extent in the CYP-006TK group compared to the standard of care control group. Dr Jolanta Airey MD, Cynata’s Chief Medical Officer said: “Diabetic foot ulcers represent a substantial unmet medical need ; they are a very prevalent and challenging complication of diabetes worldwide due to high morbidity, high risks of lower extremity amputation and associated mortality. Patients have a high rate of recurrent hospitali sations with consequent cost to the healthcare system. There is a desperate need for more effective interventions to improve wound healing and thus reduce the risk of severe infection and amputation. The results from this clinical trial of Cynata’s topical MSC product are very promising. I f subsequent trials confirm similar effects, then we might be on the path to a therapy that promotes successful wound healing in this challenging condition. We look forward to working with Cynata to continue development of this innovative product.” Dr Kilian Kelly, Cynata’s Chief Executive Officer and Managing Director, said: “We are very pleased and encouraged by these results. First and foremost, the trial achieved its primary objective of safety. Furthermore, whilst the trial was not powered to show statistically significant efficacy, we believe there is a clear signal indicating improved wound healing compared to standard of care treatments in this trial. We will now turn our attention to the next steps for this exciting program, including our strategy for further clinical development, engagement with regulatory agencies (including the FDA) Cynata Therapeutics Limited ABN – 98 104 037 372 Level 3, 100 Cubitt Street Cremorne VIC 3121 Australia T: +613 7067 6940 E: [email protected] www.cynata.com and engagement with potential commercial partners. Finally, today’s results further exemplify the commercial attractiveness of the broader Cymerus™ platform, with the Company now having two distinct product candidates that have generated positive clinical data – CYP006-TK in DFU, and CYP-001 in graft versus host disease, which also previously demonstrated very encouraging safety and efficacy data. 3,4 The Company eagerly awaits further results from three more clinical trials over the next ~18 months which could also further add to the commercial attractiveness of the Cymerus™ platform.” About the Clinical Trial CYP-006TK is Cynata’s Cymerus™ iPSC5-derived MSC6 topical wound dressing product candidate, which comprises MSCs seeded onto a novel silicone dressing. Due to reduced blood flow, patients with diabetes are at risk of developing non-healing wounds on the feet/lower limbs, which are also known as DFU. In addition to causing severe pain and discomfort, DFU pose a significant risk of infection, and if treatment is unsuccessful, amputation may be necessary – an outcome that occurs in ~20% of patients who develop DFU. 7 An estimated 38 million Americans have diabetes,8 up to 34% of whom will develop DFU. 9 The annual costs to US public and private payers to treat DFU are estimated to be US$9-13 billion per year.10 In this Phase 1 trial, which took place at a number of clinical centres around Australia, a total of 30 patients with DFU were randomised to receive either: (i) CYP 006TK treatment for four weeks, followed by standard of care treatment for the rest of the study; or (ii) standard of care treatment throughout the study. Follow-up visits in this trial continue d until 24 weeks after the initiation of study treatment. At each follow-up visit, three -dimensional images of the study ulcer we re taken using specialised camera equipment. Images were then analysed by a technician independent of the clinical centre and blind to treatment allocation. This facilitate d calculation of the wound surface area, and consequently the change in size of the wound over time. Results of the Clinical Trial The primary objective of the trial was t o assess the safety and tolerability of CYP -006TK. There were no suspected serious adverse reactions 11 reported, and no participants withdrew from the trial due to adverse events. The only adverse events considered to be at least possibly related to CYP -006TK treatment were non- serious, mild to moderate local administration site reactions, which occurred in seven participants. Change in wound surface area from baseline was assessed using the mixed-effects model for repeated measures, which is a standard statistical approach used to assess this type of outcome measure. The mean change from baseline in wound surface area expressed in terms of mm2 was: • After 12 weeks, a decrease (improvement) of 181 mm2 in the CYP-006TK group, and an increase (deterioration) of 355 mm2 in the standard of care control group. • A fter 24 weeks (end of study), a decrease (improvement) of 261 mm2 in the CYP -006TK group, and an increase (deterioration) of 62 mm2 in the standard of care control group. The mean change from baseline in wound surface area expressed as a percentage was: • After 12 weeks, a decrease (improvement) of 64.6% in the CYP -006TK group compared to a decrease of 22.0% in the standard of care control group. Cynata Therapeutics Limited ABN – 98 104 037 372 Level 3, 100 Cubitt Street Cremorne VIC 3121 Australia T: +613 7067 6940 E: [email protected] www.cynata.com • After 24 weeks, a decrease (improvement) of 83.6% in the CYP -006TK group compared to a decrease of 47.8% in the standard of care control group.2 Analysis of Larger Wounds (wounds measuring >200 mm2) The Company also conducted an analysis that segmented participants by wound size at baseline . This analysis indicates that CYP-006TK had a particularly pronounced benefit in larger wounds. A total of eleven participants had wounds measuring <200 mm2 at baseline (six in the CYP-006TK group; five in the control group). If wounds <200 mm2 are excluded, and the remaining larger wounds (>200 mm2) are analysed separately,12 there are even greater differences in outcomes between groups: • The mean change from baseline in wound surface area for larger wounds was: o After 12 weeks , a decrease (improvement) of 262 mm2 in the CYP -006TK group, and an increase (deterioration) of 540 mm2 in the standard of care control group. o After 24 weeks (end of study), a decrease (improvement) of 354 mm2 in the CYP -006TK group, and an increase of 135 mm2 in the standard of care control group. • The mean change from baseline in wound surface area for larger wounds, expressed as a percentage was: o After 12 weeks, a decrease (improvement) of 68.4% in the CYP-006TK group compared to an increase of 3.9% in the standard of care control group. o After 24 weeks, a decrease (improvement) of 84.2% in the CYP-006TK group compared to a decrease of 32.2% in the standard of care control group. 2 This indicates that the potential wound healing benefit of CYP-006TK is even greater in larger wounds. This is especially encouraging as patients with larger wounds are more likely to experience an amputation.13 Conclusion The trial met its primary objective of demonstrating safety and tolerability of CYP-006TK in participants with DFU. Importantly, the trial also generated positive efficacy data, indicating improved wound healing in the CYP-006TK group compared to the standard of care control group. It is also encouraging that this study indicates that larger wounds healed to a greater extent in the CYP -006TK group compared to the standard of care control group. Continued Trading Halt The Company will remain in trading halt pending an announcement of a potential capital raising, which is expected no later than opening of trading on Friday, 6 December 2024. The Company is not aware of any reason why the halt should not continue, nor any other information necessary to inform the market about the trading halt. -ENDS- Authorised for release by Dr Kilian Kelly, CEO & Managing Director CONTACTS: Dr Kilian Kelly, CEO & MD, Cynata Therapeutics, +61 (03) 7067 6940, [email protected] Lauren Nowak, Media Contact, +61 (0)400 434 299, [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 mesenchymoangioblas t (MCA) to achieve economic manufacture of cell therapy products, including mesenchymal stem cells (MSCs), at commercial scale without the limitation of multiple donors. Cynata Therapeutics Limited ABN – 98 104 037 372 Level 3, 100 Cubitt Street Cremorne VIC 3121 Australia T: +613 7067 6940 E: [email protected] www.cynata.com Cynata has demonstrated positive safety and efficacy data for its Cymerus™ product candidates CYP-001 and CYP-006TK, in Phase 1 clinical trials in steroid -resistant acute graft versus host disease (GvHD) , and diabetic foot ulcers (DFU) , respectively. Further clinical trials are now ongoing: a Phase 2 trial of CYP-001 in GvHD under a cleared US FDA IND; a Phase 1/2 trial of CYP-001 in patients undergoing kidney transplant; and a Phase 3 trial of CYP -004 in osteoarthritis. In addition, Cynata has demonstrated utility of its Cymerus™ technology in preclinical models of numerous other diseases, including critical limb ischaemia, idiopathic pulmonary fibrosis, asthma, heart attack, sepsis, acute respiratory distress syndrome (ARDS) and cytokine release syndrome. Cynata Therapeutics encourages all current investors to go paperless by registering their details with the designated registr y service provider, Automic Group. 1 Mean calculated using the mixed-effects model for repeated measures; differences were not statistically significant, as expected given that the study was not powered to show efficacy. 2 For clarity, the Company confirms that the change from baseline in the control group at both 12 and 24 weeks was an increase when calculated as mean change in mm2, but a decrease when calculated as a percentage. While this may seem like a discrepancy, it is correct – it is a consequence of wound size at baseline varying between patients. For example, if there were two wounds, one measuring 100 mm2, and the second measuring 1,000 mm2 at baseline, and: - The surface area of the first wound reduced from 100 mm2 to 0 mm2 (i.e. reduction of 100 mm2 or 100%) - The surface area of the second wound increased from 1,000 mm2 to 1,500 mm2 (i.e. increase of 500 mm2 or 50%). - In this example the mean change from baseline in wound surface area is an increase of 200 mm2 (-100mm2 + 500mm2 / 2) but the mean percentage change from baseline is a decrease of 25% (-100% + 50% / 2). This demonstrates that when smaller wounds improve but larger wounds deteriorate, there can be an overall reduction in mean wound surface area when expressed as a percentage, despite the mean wound surface area increasing when expressed in mm2. 3 Bloor AJC, et al. Nat Med. 2020;26:1720–1725. 4 Kelly K, et al. Nat Med. 2024;30(6):1556-1558. 5 iPSC = induced pluripotent stem cell. 6 MSC = mesenchymal stem (or stromal) cell. 7 McDermott et al. Diabetes Care. 46:209–221 (2023). 8 American Diabetes Association: https://diabetes.org/about-diabetes/statistics/about-diabetes 9 McDermott et al. Diabetes Care. 46:209–221 (2023). 10 Raghav et al. Ther Adv Endocrinol Metab. 9(1) 29-31 (2018). 11 A suspected adverse reaction is when a causal relationship between the investigational product and an adverse event is at least a reasonable possibility. 12 Post-hoc analysis. 13 Pickwell K, et al. Diabetes Care. 2015;38(5):852-7. Clinical Trial Results: Phase 1 Trial of CYP-006TK in Diabetic Foot Ulcers A Clinical Stage Company Pioneering the Next Generation of Cellular Therapies 5 December 2024 Summary information This Presentation contains summary information about Cynata Therapeutics Limited and its subsidiaries (CYP, or Cynata) which is current as at 5 December 2024. This Presentation should be read in conjunction with CYP’s other 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 financial information that has been disclosed to the ASX. 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 ‘forward looking 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. 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. 2 Important information 1. Global Graft versus Host Disease Market 2019-2029 (Reflects forecast market in 2026); 2. Zion Market Research, 2019 (represents global treatment market in 2025); 3. Persistence Market Research 2018 research report: “Osteoarthritis Treatment Market: Global Industry Analysis (2012-2016) and Forecast (2017-2025) (Reflect OA market by 2025); 4. Organ Transplant Immunosuppressant Drugs Market in 2026, Grand View Research, Inc.,2019 USYD = University of Sydney; NHMRC = National Health and Medical Research Council; LUMC = Leiden University Medical Center * Timing of events is approximate, based on the Company’s information as at the date of this presentation, and subject to change. Timing refers to calendar years. 3 Target indications Indication Market opportunityTrial phase Phase 2 ongoing Phase 1/2 ongoing Kidney Transplantation (managed and funded by LUMC) Phase 1 complete Diabetic Foot Ulcers (DFU) Acute Graft vs Host Disease (aGvHD) FDA Orphan Designation US$5.9bn4 US$600m1 US$11.6bn3 US$9.6bn2 Phase 3 ongoing (enrolment complete) Osteoarthritis (OA) (managed by USYD, funded by NHMRC) Cynata Funded & Managed Upcoming catalysts* Enrolment completion – H1 2025 Results – H2 2025 Results (Cohort 1) – H1 2025 Results released Dec 2024 Results – H1 2026 Partner Funded & Managed Note: Cynata retains commercial rights for both of the partner funded & managed programs 1. This is a non-exhaustive subset of key MSC properties 4 Why MSCs? Mesenchymal Stem Cells Key Unique Properties¹ Unlike many other cell therapies where patients have to be matched to donors, MSCs can be used without matching donors to recipients Anti-Inflammatory Immunomodulatory Tissue Repair & Regeneration Inflammation and inappropriate immune responses contribute to many diseases/medical disorders, and often lead to tissue damage. Consequently, the anti-inflammatory and immunomodulatory properties of MSCs, as well their ability to promote tissue repair and regeneration, can play an important role in treating many diseases. 1 2 3 Importance: Standard Process¹ New donors must be identified on regular basis; donors must consent to surgical extraction MSCs must be isolated from mixture of cells from each donation – producing only small number of MSCs per donation Extensive culture expansion required (growing cells) – large number of MSCs required Different batches of MSCs come from different donors Major Challenges Different donors = Variable starting material = Inconsistent product Small number of MSCs retrieved per donation = Extensive MSC culture expansion required Extensive MSC culture expansion = Functional changes = Loss of potency MSCs from different donors are administered to different patients = Inconsistent results Conventional MSC manufacturing process 5 Many donors Donor 1 Donor 2 Donor 3 Donor 4 Donor x Patients This is a representative, high-level summary of a typical process to produce donor-derived MSCs. Some manufacturing processes may differ. Each donor provides cells Isolation of MSCs from each donation Culture expansion of MSCs from each donation Cymerus Process Blood donation from a single donor was used to produce a high- quality iPSC1 bank Cells from same iPSC bank are used to make every batch of Cymerus MSCs iPSCs are culture expanded, then turned into MSCs using patented Cymerus process All batches of Cymerus MSCs come from the same donor Major Benefits iPSCs have effectively limitless expansion capacity = Scalability Starting material for all batches is the same = Consistent MSC product Minimal MSC culture expansion required = MSCs retain potency All patients receive MSCs from the same donor = Avoids variability The solution: the Cymerus process 6 One donor One donor Patients 1. iPSCs are induced pluripotent stem cells (iPSCs). Mature adult cells reprogrammed to become pluripotent, which means they have effectively limitless proliferation capacity and potential to differentiate into any adult cell type (including MSCs). iPSCs are the ideal starting material for commercial production of cellular products. iPSC bank Vial of iPSCs from bank iPSC expansion and differentiation Formation of MSCs CYP-006TK for Diabetic Foot Ulcers 8 Diabetic foot ulcers (DFU) • Open sore or wound that develops in patients with diabetes • Very difficult to heal, which can lead to serious complications such as serious infection • 20% of patients who develop DFU will require an amputation1 • Multi-disciplinary team can be required to treat: GP, endocrinologist, podiatrist, wound care nurse, vascular surgeon and infectious disease specialist • Cost to treat DFU in the US can exceed US$60,000 per patient (depending on severity)2 • Annual costs to US public and private payers estimated to be US$9 – 13 billion per year2 Diabetes is the fastest growing public health concern worldwide4 ~38 million Americans have diabetes5 Up to 34% of those with diabetes will develop a foot ulcer1 20% of patients with DFU will require amputation of the foot or limb1 150,000+ amputations per year in the US due to DFU6 Estimated costs to US public and private payers US$9–13 billion per year2 1. McDermott et al. Diabetes Care. 46:209–221 (2023). 2. Raghav et al. Ther Adv Endocrinol Metab. 9(1) 29-31 (2018). 3. Hicks et al. J Vasc Surg. 67:1455-62 (2018). WIfI = Wound, Ischemia, and foot Infection3 4. Hossain et al. Health Sci Rep. 7(3):e2004 (2024). 5. American Diabetes Association: https://diabetes.org/about-diabetes/statistics/about-diabetes 6. American Diabetes Association: https://diabetes.org/advocacy/amputation-prevention-alliance 9 Diabetic foot ulcer examples 10 MSCs in DFU • Primary outcome measured was extent of wound surface re-epithelialisation (healing) after 3 days • Cynata’s Cymerus MSCs resulted in significantly greater re-epithelialisation (86%) compared to bone marrow MSCs (51%) • Cynata’s Cymerus MSCs are the only MSCs capable of being produced consistently at scale Key findings 86% 51% 68% 80% 91% 0 10 20 30 40 50 60 70 80 90 100Percentage re-epithelialisation (%) Silicone patch seeded with MSCs from various sources in preclinical model of diabetic wounds Cymerus MSCs Bone marrow derived MSCs Dental pulp derived MSCs Gingival fibroblast derived MSCs Bone chip derived MSCs Major Challenges with manufacturing these MSCs consistently at scale MSCs have demonstrated strong success in pre-clinical DFU models 11 Cynata’s MSC product for DFU • Cynata has developed a proprietary wound dressing using MSCs (“CYP-006TK”) • CYP-006TK utilises a proprietary surface-coating, optimised for the delivery of MSCs directly to the wound Cymerus MSCs Plasma polymer treated surface Wound dressing Apply active wound dressing 12 DFU | Phase 1 clinical trial Indication Non-healing diabetic foot ulcers (DFU) Product CYP-006TK (Novel silicone dressing seeded with Cymerus iPSC-derived MSCs) Study Design • Randomised controlled trial in ~30 adults • Patients randomised to receive either standard of care (SOC) or CYP-006TK for 4 weeks, followed by SOC • Primary objective is safety; efficacy measures include wound healing, pain and quality of life Study Conduct • Clinical sites in Australia (Adelaide and Perth) • Patient enrolment complete (April 2024) • All patient visits complete (September 2024) Results • Final results released in December 2024 For further information: https://clinicaltrials.gov/study/NCT05165628 DFU | Phase 1 clinical trial – key results 13 Primary Objective CYP-006TK successfully achieves its primary objective: – safe and well-tolerated (primary objective) – no participants withdrew from the trial due to adverse events – no suspected serious adverse reactions were reported Time CYP-006TK Standard of Care Mean change in wound surface area from baseline (mm²)* 12 weeks Decreased by 181 mm2 Increased by 355 mm2 24 weeks Decreased by 261 mm2 Increased by 62 mm2 Mean change in wound surface area from baseline (%) 12 weeks Decreased by 64.6% Decreased by 22.0% 24 weeks Decreased by 83.6% Decreased By 47.8% *A decrease in the size of a wound demonstrates that the wound is healing (i.e. there is an improvement to the wound). An increase in the size of a wound would demonstrate that the wound is not healing (i.e. wound is getting worse). N=15 N=15 Mean change in wound surface area (mm²) 14 12 Weeks 24 Weeks Reduction in wound size (Improvement) Increase in wound size (Deterioration) A mean reduction in wound surface area (improvement) at both 12 & 24 weeks A mean increase in wound surface area (deterioration) at both 12 & 24 weeks CYP-006TK Standard of Care Mean change in wound surface area (%) 15 12 Weeks 24 Weeks • Markedly greater mean reduction (improvement) by percentage than in the standard of care control group, at both 12 & 24 weeks • Large percentage reduction in ulcer surface area from baseline in CYP-006TK group is consistent with change in mm2 Increase in ulcer surface area from baseline in mm2 combined with a reduction in percentage terms indicates that larger wounds were less likely to heal CYP-006TK Standard of Care Answer: The fact that mean wound surface area in mm2 in the standard of care control group increased (worsened), while the change in percentage terms decreased (improved), indicates that larger wounds healed to a lesser extent than smaller wounds in that group. For example, if there were two wounds, one measuring 100 mm2, and one measuring 1,000 mm2 at baseline, and: • The surface area of Wound 1 reduced from 100 mm2 to 0 mm2 (i.e. reduction of 100 mm2 or 100%) • The surface area of Wound 2 increased from 1,000 mm2 to 1,500 mm2 (i.e. increase of 500 mm2 or 50%) • In this example the mean change from baseline in wound surface area is an increase of 200 mm2, but the mean percentage change from baseline is a decrease of 25% This demonstrates that when smaller wounds improve but larger wounds deteriorate, there can be an overall reduction in mean wound surface area when expressed as a percentage, despite the mean wound surface area increasing when expressed in mm2 16 Question: How can the wound surface area in the standard of care control group increase (i.e. deteriorate), but at the same time reduce (improve) when expressed as a percentage? Baseline End of Study Reduction (mm2) Reduction (%) Wound 1 100 0 100 100% Wound 2 1,000 1,500 -500 -50% Mean Reduction -200 mm2 +25% Segmenting the data – larger wounds¹ 17 Time CYP-006TK Standard of Care Mean change in wound surface area from baseline (mm²)* 12 weeks Decreased by 262 mm2 Increased by 540 mm2 24 weeks Decreased by 354 mm2 Increased by 135 mm2 Mean change in wound surface area from baseline (%) 12 weeks Decreased by 68.6% Increased by 3.9% 24 weeks Decreased by 84.2% Decreased by 32.2% A total of eleven participants had wounds measuring <200 mm² at baseline (six in the CYP-006TK group; five in the control group). If smaller wounds <200 mm² are excluded and the remaining larger wounds (>200 mm²) are analysed separately, there are even greater differences in outcomes between groups: 1. Post-hoc analysis. N=9 N=10 • A mean reduction in wound surface area (improvement) at both 12 & 24 weeks • Substantial improvement in large wounds is especially encouraging as larger DFU are more likely to lead to an amputation¹ Larger wounds measuring >200 mm² 18 12 Weeks 24 Weeks Reduction in wound size (Improvement) Increase in wound size (Deterioration) • A mean increase in wound surface area (deterioration) at both 12 & 24 weeks • Extent of mean increase (deterioration) is greater than when all wounds are included CYP-006TK Standard of Care Mean change in wound surface area (mm²) 1. Pickwell K, et al. Diabetes Care. 2015;38(5):852-7. Mean reduction (improvement) by percentage was similar in larger wounds compared to in all wounds: • 12 weeks: 68.4% (large wounds); 64.6% (all) • 24 weeks: 84.2% (large wounds); 83.6% (all) Indicates benefit of CYP-006TK in wounds of all sizes Larger wounds measuring >200 mm² 19 12 Weeks 24 Weeks Mean change by percentage was markedly worse in larger wounds than in all wounds. • 12 weeks: increase of 3.9% (large wounds); reduction of 22% (all) • 24 weeks: reduction of 32.2% (large wounds); 47.8% (all) CYP-006TK Standard of Care Mean change in wound surface area (%) Outlook and commercial potential Proprietary Platform Technology • Ability to produce MSCs consistently and at scale allows for MSCs to be used in multiple indications = Platform Technology appeal Platform Technology • Platform Technology allows CYP to target multiple multi-billion dollar indications Multiple Multi-Billion Dollar Indications • Four clinical indications currently targeted have total combined market opportunities of ~US$27.7 billion • All indications capable of being out-licensed / partnered Commercial interest • In 2019 (post Phase I results in GvHD), the Company received a non-binding indicative offer to acquire all shares in Cynata for $2 per share (The parties subsequently withdrew from discussions as a result of being unable to reach agreement on satisfactory terms) • Cynata anticipates significant commercial interest following any positive read-outs • Three further read-outs expected by H1 CY2026 Seeking Partnership Opportunities • Following the successful DFU results, Cynata will now continue discussions with potential commercial partners and engage with regulatory agencies (including FDA) as part of its strategy for further clinical development 21 Commercial Attractiveness JP Morgan BioWeek/Biotech Showcase San Francisco, January 2025 Company presentation and partnering meetings Advanced Therapies Congress London, March 2025 Company presentation and partnering meetings BIO International Boston, June 2025 Partnering meetings BIO Japan, RM Japan Yokohama, October 2025 Partnering meetings • Upcoming catalysts will accelerate and broaden partnering discussions • We attend leading conferences in our sector, to tell our story and open new discussions • Following on from multiple events earlier this year, selected key events going forward include: • We will also attend further key events in the sector (ARM, ISCT, ISSCR) and in the regions 22 Industry connections 23 Upcoming catalysts* DFU results announced Dec 2024; results from THREE further trials expected by 1H 2026 * Timing of events is approximate, and subject to changebased on the Company’s information as at the date of this presentation, Results Results Start of enrolment Q1 2025 Q2 2025 Q3 2025 Q4 2025 Q1 2026 Q2 2026 Phase 1/2 kidney transplant Phase 3 osteo- arthritis Phase 2 aGvHD Phase 1 DFU Results announced – Dec 2024 Enrolment complete Results Results Results (Cohort 1) Contact Us Cynata Therapeutics Limited Level 3, 100 Cubitt Street Cremorne Victoria 3121 Australia [email protected] www.cynata.com cynatatherapeutics @cynatastemcells cynata-therapeutics

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