Annual General Meeting Presentation

Cynata Therapeutics Limited (ASX: CYP) – AGM Presentation 15 November 2018 A Next Generation Stem Cell Therapeutics Company www.cynata.com Important Information 2 This presentation has been prepared by Cynata Therapeutics Limited. (“Cynata” or the “Company”) based on information availabl e to it as at the date of this presentation. The information in this presentation is provided in summary form and does not contain all information necessary to make an investment decision. This presentation does not constitute an offer, invitation, solicitation or recommendation with respect to the purchase or sa le of any security in Cynata, nor does it constitute financial product advice or take into account any individual’s investment objectives, taxation situation, financial situation or needs. An investor must not act on the basis of any matter contained in this presentation but must make its own assessment of Cynata Therapeutics and conduct its own investigations. Before making an investment decision, investors should consider the appropriateness of the information having regard to their own objectives, financial situation and needs, and seek legal, taxation and financial advice appropriate to their jurisdiction and circumstances. Cynata Therapeu tics is not licensed to provide financial product advice in respect of its securities or any other financial products. Cooling off rights do not apply to the acquisition of Cynata Therapeutics securities. Although reasonable care has been taken to ensure that the facts stated in this presentation are accurate and that the opinio ns expressed are fair and reasonable, no representation or warranty, express or implied, is made as to the fairness, accuracy, completeness or correctn ess of the information, opinions and conclusions contained in this presentation. To the maximum extent permitted by law, none of Cynata Therapeutics, its officers , directors, employees and agents, nor any other person, accepts any responsibility and liability for the content of this presentation including, without limitation, any liability arising from fault or negligence, for any loss arising from the use of or reliance on any of the information contained in this presentation or othe rwise arising in connection with it. The information presented in this presentation is subject to change without notice and Cynata Therapeutics does not have any res ponsibility or obligation to inform you of any matter arising or coming to their notice, after the date of this presentation, which may affect any matter referred to in this presentation. The distribution of this presentation may be restricted by law and you should observe any such restrictions. Forward looking statements This presentation contains certain forward looking statements that are based on the Company’s management’s beliefs, assumptio ns and expectations and on information currently available to management. Such forward looking statements involve known and unknown risks, uncertainties , and other factors which may cause the actual results or performance of Cynata to be materially different from the results or performance expressed or imp lied by such forward looking statements. Such forward looking statements are based on numerous assumptions regarding the Company’s present and future bus iness strategies and the political and economic environment in which Cynata will operate in the future, which are subject to change without notice. Pa st performance is not necessarily a guide to future performance and no representation or warranty is made as to the likelihood of achievement or reasonableness o f any forward looking statements or other forecast. To the full extent permitted by law, Cynata and its directors, officers, employees, advisers, agents and inte rmediaries disclaim any obligation or undertaking to release any updates or revisions to information to reflect any change in any of the information contained in t his presentation (including, but not limited to, any assumptions or expectations set out in the presentation). www.cynata.com Agenda 3 2018 Highlights and strategy1 Graft vs. Host Disease (GvHD) update2 Critical Limb Ischemia (CLI) approach3 Outlook and next steps5 Appendix – corporate overview6 Pre-clinical programme overview4 (1) 2018 Highlights and strategy1 www.cynata.com 5 Meaningful impact on patient’s lives Completed GvHD trial Selected next clinical trial candidate Deepened relationship with Fujifilm Advanced pre-clinical programme Secured cornerstone investment • Completed data collection for Phase 1 trial in GvHD • Formal study report being finalised • Outstanding efficacy results • No safety concerns • International media attention Phase II trial expected to start in 2019 • Critical Limb Ischaemia (CLI): major clinical challenge and unmet need • Severely impaired blood flow in the arteries: typically legs • Trial design, scope, cost and schedule being developed CLI Phase II trial expected to start in 2019 • Commenced planning for Phase II trial in GvHD with Fujifilm • Conducted joint session with Japanese regulator (PMDA) and joint media briefings Fujifilm’s actions indicate their support • Completed first in-human trial of CymerusTM MSCs, treating 15 patients with acute graft-versus- host disease who had failed all other approved treatment options and had a bleak outlook Improved health outcomes for patients facing extremely grim prognosis • Clear supporting data for efficacy of Cymerus MSCs in multiple indications • Broadened patent portfolio • Enables multiple commercial discussions Multiple irons in the fire • Fidelity International acquired ~9.5m shares through a combination of on market buying and a share placement of $5,2m at $1.275 • Cash balance of $10.9m at 30 Sept 18 Strong cash runway Significant progress in 2018 www.cynata.com Investment Summary: a Phase II-ready biotech with a highly scalable, proprietary platform for producing commercial quantities of allogeneic MSCs 6 Scalable, globally applicable technology  Cymerus platform enables production of high quality Mesenchymal Stem Cells at scale  Fully patented process overcomes multiple issues with today’s on-market solutions Excellent results from Phase I trial in GvHD  All trial endpoints achieved: no adverse safety events, highly encouraging efficacy  GvHD programme well positioned to progress to Phase II  Safety data enables Cynata to move directly to Phase II in other indications Clear pipeline of high- potential target areas  Cardiovascular disease identified as priority indication area for expanded trial pipeline  Planning for Phase II programme in Critical Limb Ischemia (CLI) underway  Compelling pre-clinical data in multiple other high-value target areas Well-funded to progress clinical programme  Cash balance of $10.9m as at 30 September 18, reinforced by $5.2m placement of shares to leading institutional investor Fidelity International on 30-May-18;  Fidelity: #1 shareholder (~10%) Attractive partnering business model  Fujifilm hold licence option for GvHD – will pay all costs of all further development and commercialisation plus $60m in milestone payments plus royalties if exercised  Licence agreements and strategic partners for other indications being explored Valuable and active market  Estimated $1.7bn revenue opportunity for MSC products in GvHD and CLI alone  Over 850 clinical trials investigating the efficacy of MSCs across numerous indications  Multiple pharma companies active in stem cell M&A www.cynata.com Licence available Cynata’s goal is to develop a new generation of highly potent allogeneic MSC cell therapeutics in areas of high unmet clinical need 7 GvHD Fujifilm licence option Critical Limb Ischemia Licence available Licence available A ‘hub and spoke’ business model Intention to license Cymerus technology across a range of target areas to maximise value Phase I completed, Phase II planning underway Phase II planning underway Preclinical data Potential future target areas Following successful GvHD trial, a new indication will progress direct to Phase II www.cynata.com The MSC Ecosystem • Executive Summary Contract Manufacturers (CMOs) Pharma Companies Other MSC Companies Contract Manufacturers (CMOs) • Manufacture on behalf of clients – they do not have their own specific MSC manufacturing IP • Not competitors of Cynata – companies like Cynata are potential clients Pharma companies • Typically seeking to build an MSC program • Often seeking to in-licence innovative therapies that can be manufactured at scale • Have resources and expertise to successfully commercialise new products • Ideal partners for Cynata Other MSC companies • Typically small biotechs – limited resources • Entirely dependent on perceived value of their existing MSC technology • Unlikely to be suitable partners for Cynata 7 www.cynata.com  Cynata has identified a number of additional indications that it may choose to progress to pre- clinical testing or directly to Phase II in the future  Significant volume of ongoing clinical research into MSC therapies (850+ clinical trials to date)  Cynata will continue to develop its portfolio of target areas in pre-clinical trials with the intention of progressing selected indications directly to Phase II  Direct path to market in Japan following Phase II  Fujifilm holds a licence option for development and commercialisation of Cynata’s MSCs for GvHD  Identified as high priority target area for Phase II trials  Cynata engaging with potential partners: intention to license Cynata’s MSCs for CLI New enhanced pipeline and clear pathway to commercialisation Strong clinical pipeline and program supports Cynata’s commercial objectives 9 GvHD Critical Limb Ischemia 7+ indications Other high priority indications 1. Fujifilm’s estimate of the peak annual global sales opportunity 2. ClearView’s estimate of the peak annual global sales opportunity Successful safety results from GvHD trial enables future indications to bypass Phase I Pre-clinical trials Potential target areas Phase II US$300m1 US$1.4bn2 Phase I www.cynata.com Cynata is executing on a clear scientific and commercial vision and continually assesses pathways to maximise shareholder value 10 Multiple options to create shareholder value Fujifilm holds a licence option for development and commercialisation of Cynata’s MSCs for GvHD Exercise of Fujifilm option (US$3m) • Fujifilm can exercise up to 90 days after submission of Phase 1 trial CSR. • On exercise Cynata receive upfront US$3m milestone payment • Fujifilm responsible for all further development activities and costs Build value in platform independently (e.g. continue running clinical trials) License / partner with big Pharma to develop specific target areas (e.g. Fujifilm’s existing option for GvHD) Strategic exit/merger (e.g. Strategic acquirer) Phase 2 and beyond (potential US$30m+ p.a.) • Fujifilm to pay Cynata on attaining agreed milestones ($60m+) and double-digit royalties on product sales • Fujifilm’s projections for the GvHD market suggest >US$30m per year in royalties for Cynata if Fujifilm forecast sales attained www.cynata.com Cynata is currently commercialising its Cymerus platform 11 • Cynata is commercialising a platform technology with multiple potential commercial avenues; its business model is to secure licensees to progress clinical trials and commercialise its MSC technology in a range of indications • The company is in active, confidential discussions regarding licence transactions with multiple potential partners in multiple indications; discussions ongoing with Celularity pursuant to the announced MoU • The company is currently negotiating non-binding, confidential term sheets with multiple parties; however, there can be no assurances that any of these deals will come to fruition • All license discussions are confidential and inherently commercially sensitive • The market will be informed via an ASX announcement as soon as any material commercial agreement has been concluded • The Board and Management are pleased with commercial progress in 2018 and are committed to this business model Graft vs Host Disease (GvHD) Study update and next steps 12 2 www.cynata.com Clinical Protocol: CYP-GvHD-P1-01 Primary Evaluation Period Cohort A n = 8 1 x 106 cells/kg on Day 0 and Day 7 (max 1 x 108 cells) Cohort B n = 8 (7 treated)* 2 x 106 cells/kg on Day 0 and Day 7 (max 2 x 108 cells) DSMB Review Visit 1 2 3 4 5 6 7 8 Days after first dose 0 3 7 14 21 28 60 100 Overview of clinical trial protocol Population: ~16 Adults with steroid-resistant acute GvHD * The clinical investigator determined that one patient was no longer a suitable candidate for treatment, due to a medical complication that occurred shortly after enrolment (but prior to treatment with CYP-001). 13 www.cynata.com Summary of Key Results 1. One patient in cohort A died of pneumonia (unrelated to treatment) and one patient in cohort B withdrew from the trial on Day 22 to commence palliative care. 14 Endpoint Cohort A (28 days) Cohort B (28 days) Pooled (28 days) Cohort A (100 days) Cohort B (100 days) Pooled (100 days) Safety No safety issues / treatment relate adverse events observed Complete Response 13% 57% 40% 50% 57% 53% Overall Response 75% 86% 80% 100% 86% 93% Overall Survival1 88% ≥86% ≥87% 88% ≥86% ≥87%  All endpoints achieved Excellent results in Phase 1 GvHD clinical trial, a clear validation of Cynata’s MSCs and the Cymerus platform www.cynata.com GvHD Response – By Subject Note: Complete response (CR) = absence of GvHD. Partial response (PR) = improvement by at least 1 grade 15 Substantial improvement in GvHD grades observed with the majority of patients reporting a Complete Response 0 1 2 3 4GvHD grade Patient # A1 A2 A3 A4 A5 A6 A7 A8 Grade change -1 -2 -1 -3 -1 -2 -3 -3 Best response P C P C P P C C Legend GvHD grade: As at day 0 GvHD grade: Best response Complete response Partial response Stable diseaseC P S B1 B2 B3 B4 B5 B6 B7 -2 -3 -3 -2 0 -2 -1 P C C C S C P Note: Complete response (CR) = absence of GvHD. Partial response (PR) = improvement by at least 1 grade www.cynata.com Overall response rate of 93% A meaningful impact on patients’ lives Significance of Findings Key implications of clinical trial results Number of patients Response rates Endpoints • Response rates were higher than what we expect would be required in Phase 3, to support marketing approval • Endpoints in this trial were the same as those required in a Phase 3 trial (in contrast to early phase trials for some other conditions) • Although the Phase 1 trial involved just 15 treated subjects, even late stage trials in this condition do not necessarily involve large numbers • For comparison, recently completed Phase 3 trials in Japan and US have involved just 25 and 55 patients, respectively Patients with steroid-resistant acute GvHD typically face a dire prognosis, with extremely high mortality rates For further details of the implications of Cynata’s clinical trial, please refer to a video interview with Cynata’s VP of Product Development, Dr Kilian Kelly (available here: https://www.cynata.com/news/gvhd-trial-results-and-implications) 16 www.cynata.com Competitive Position Key advantages of the CymerusTM process SCALABILITY & CONSISTENCY FEWER CELLS PER PATIENT  Consistent product quality – single donor overcomes regulatory concerns  Lower cost of goods on a per cell basis compared to conventional MSC products  2 infusions per patient with CYP (compared to 8-12 for bone-marrow derived products)  Greater convenience for patients and hospitals  Lower costs incurred by healthcare system Results to date suggest that CYP-001 may be superior to other treatments for steroid-resistant acute GvHD For more information on the Cymerus platform visit Cynata’s website 17 www.cynata.com • Preparation of a Clinical Study Report (CSR) • Preparation of the CSR is a complex and time consuming process • CSR production now at an advanced stage – expect to complete ahead of industry-standard timelines • Submission to Fujifilm per terms of the license option agreement – 90 day decision period • Further meeting planned with PMDA (Japanese regulatory authority) early in 2019 • Initial highly successful meeting took place in August 2018 • Expect to commence Phase 2 clinical trials during 2019 • Trials planned to occur in Japan and rest of world (including Australia, Europe and USA) GvHD – Next Steps Rigorous on-site review and verification of all data Database locked and transferred to statisticians, who prepare tables, figures and listings (TFLs) Report text then written on basis of TFLs Quality control checks and publishing Review by key stakeholders 18 Critical Limb Ischemia (CLI) Overview of Cynata‘s approach 3 www.cynata.com Critical Limb Ischemia • Executive Summary1. ClearView’s estimate of the peak annual sales opportunity in the USA ABOUT CLI RATIONALE FOR PURSUING CLI • Critical Limb Ischemia (CLI) is an advanced stage of peripheral artery disease (PAD) – caused by a narrowing of the arteries in the limbs • Severely impaired blood flow causes pain, ulceration and gangrene • Often results in amputation and ~25% of CLI patients who are unable to undergo vascular surgery die within a year of diagnosis • MSCs may offer an effective treatment option for CLI, to restore blood flow and reduce inflammation • Improvements in amputation-free survival shown in clinical trials with MSCs • Cymerus MSCs have demonstrated compelling efficacy in a preclinical study • Development timeline is relatively rapid, involving relatively small trials • Peak net commercial opportunity in US is estimated to be $700-900m p.a.1 Cynata has prioritised Critical Limb Ischemia as its next indication to take to clinical trials 20 www.cynata.com 21 Scientific support and industry enthusiasm are high for MSCs in CLI Source: Compagna. Stem Cells Int. 2015; 2015: 931420; Dash. Rejuvenation Res. 2009 Oct;12(5):359; Lasala. Angiology. 2010 Aug;61(6):551; UptoDate; clinicaltrials.gov; KOL Interviews; ClearView Analysis 1 Ulcer healing and pain are less common, but are utilized in Stempeutics’ ongoing trial as the sole primary endpoints. AFS: Amputation-free Survival. ABI: Ankle- brachial index. RV: revascularization. Physician Perspective • Endpoints in CLI are considered to be relatively straightforward “Recruitment is not going to be a barrier, especially if targeting patients known to be ineligible for revascularization.” • Pivotal trials may last 1-2 years and require 50-100 revascularisation-ineligible patients • Endpoints include AFS and ABI, as well as ulcer healing and pain1 (6 – 12 mo.) “CLI trials are relatively straight forward, with easy-to-assess endpoints like ulcer healing. I think MSC’s would show benefit in a well-powered trial.” • Experts believed localised delivery of MSCs had the potential to improve CLI • Stempeutics, Pluristem, and Rexgenero are sponsoring ongoing MSC CLI trials “There has been a lot of interest in the field as well as industry regarding MSCs to address CLI. It makes a lot of sense.” • Small clinical MSC studies have shown amputation free survival (AFS) and ankle brachial index (ABI) endpoint benefit “If MSCs successfully dampen immune response and promote blood vessel growth, they could prevent the need for amputation.” Probability of Success Ease of Clinical Development Field Enthusiasm Mechanistic Rationale / Supporting Data Scientific RationaleClinical Feasibility www.cynata.com Critical Limb Ischemia clinical study follows excellent results from an earlier pre-clinical study 22 Results published in a peer reviewed journal Mice dosed with Cymerus MSCs experienced significantly improved outcomes when compared with control group Cytotherapy is a peer-reviewed medical journal covering the areas of cell biology and immunology, including cytokines, cytotherapy, and molecular therapy DAY TREATED CONTROL Loss of leg Animals treated with Cymerus MSCs experienced improved blood flow (p<0.006) and faster blood flow recovery (p<0.001) when compared to the control group treated with saline www.cynata.com Update on CLI clinical trial plans • Executive Summary Cymerus MSC product for CLI will be known as CYP-002 Draft clinical trial protocol synopsis is now in place o Randomised, double-blind, Phase 2 study in adults with CLI Current working assumptions:* o Primary endpoint will be Amputation Free Survival after 6 months o 3 groups: (i) low dose CYP-002; (ii) high dose CYP-002; (iii) placebo o Approximately 30 patients per group * Subject to change based on input from external experts CRO selection process now ongoing o Once CRO is engaged, further input on protocol design will be sought from relevant key opinion leaders and decision will be taken on where trial will be conducted Expect trial to commence during 2019 23 Pre-Clinical Pipeline Overview of Cynata‘s activities 4 www.cynata.com Purpose of the pre-clinical program • Executive Summary The successful outcomes from these studies, combined with the clinical data in GvHD have facilitated a number of ongoing commercial discussions in these and other clinical indications Validate Cymerus technology Demonstrate potential of MSCs • Cynata has sought to collaborate with leading academic institutions and experts in various therapeutic areas to validate the potential clinical utility of the Cymerus technology • MSCs have already shown promising therapeutic potential in a wide range of pre-clinical models (as well as in human patients) Pre-clinical studies are intended to provide a rational basis for investigating the potential safety and efficacy of an experimental drug in a particular disease indication(s) Cost-effective • An important element has been to leverage expenditure as much as possible through grants and joint projects 25 www.cynata.com Disease target area Partner Pre-clinical trials started Proof of concept completed Key highlights *Global market opportunit y ARDS  Study to commence to evaluate effectiveness of Cymerus MSCs in sheep with ARDS in association with the Prince Charles Hospital in Brisbane. US$2.5bn by 20182 Heart attack   Pre-clinical trials suggest Cymerus MSCs may have the potential to restore cardiac function and reduce scar size after a heart attack US$18.2bn by 20193 Brain Cancer / Glioblastoma   Research collaboration in genetically modified MSCs in cancer: involves modifying stem cells to target cancer US$3.3bn by 20244 Diabetic Wounds   Independent study by CRC for Cell Therapy Manufacturing received positive data which demonstrates the efficacy of Cymerus MSCs in a preclinical model of diabetic wounds US$4.9bn by 20245 Coronary Artery Disease  Research collaboration for the development of MSC therapies to treat coronary artery disease US$22.5bn by 20216 Asthma   Cymerus MSCs demonstrated significant beneficial effects on three key components of asthma: airway hyper-responsiveness, inflammation and airway remodelling US$25.6bn by 20241 Cytokine Release Syndrome   Pre-clinical model demonstrating Cymerus MSCs significantly ameliorate the effects of Cytokine Release Syndrome, a potentially severe and life-threatening adverse reaction to cancer immunotherapy US$4.5bn by 2022 (CAR-T)7 Sepsis  Development partnership with RCSI (Royal College of Surgeons in Ireland), one of the foremost health sciences research institutions in Europe, to investigate the utility of Cymerus MSCs in sepsis, the leading cause of death in ICU’s US$5.9bn by 2026 8 Pre-clinical study programme - overview 26 Successful outcomes open many other disease targets potentially benefiting from MSCs Notes *Reflects total global market opportunity for the relevant therapeutic category 1. Grand View Research, 2016); 2. Vasomune Therapeutics company announcement, 2018 3. GBI Research, 2013; 4. Global Data, 2016; 5. Transparency Market Research, 2018;6. Smithers Apex, 2015 ; 7. Evaluate Pharma, 2017 www.cynata.com Programme overview Pre-clinical programme—Acute Respiratory Distress Syndrome (ARDS) 27 Current status Summary of progress  To investigate Cymerus MSCs as a treatment for ARDS in an animal model (sheep) with ARDS supported by ECMO, and to evaluate the effects on lung mechanics, blood flow, inflammation and lung injury, as well as safety  Programme commenced mid 2017 and is proceeding well  Project on track. Results expected Q4 2018. Next steps  Determine most suitable commercial path following release of results Existing treatment options/products  ARDS is an inflammatory process leading to build-up of fluid in the lungs and respiratory failure. Commonly occurs in previously healthy individuals, and it accounts for approximately 10% of all ICU admissions. There is no specific treatment; instead patients are managed with mechanical pulmonary support (ECMO) Study partner ~US$2.5bn by 20181Global market opportunity 1. Vasomune Therapeutics company announcement, 2018 www.cynata.com Programme overview Pre-clinical programme—Heart attack 28 Current status Summary of progress  The study aimed to determine the ability of Cymerus MSCs to repair the heart functionally and structurally after a heart attack in an animal model  Study was completed successfully in July 2018  Cymerus MSC treatment improved recovery of cardiac function post heart attack compared to either placebo or bone marrow-derived MSCs (BM-MSCs)  Cymerus MSC treatment also reduced left ventricular end-systolic diameter (LVESD) compared to either placebo or BM-MSCs. LVESD reduction is associated with lower risk of further cardiac events  Programme completed Next steps  Expressions of interest being sought from potential partner companies 1. GBI Research, 2013 Existing treatment options/products  A heart attack is life-threatening event that occurs when a blood vessel supplying the heart itself is suddenly blocked completely, threatening to damage the heart muscle and its functions. Early treatment with clot dissolving medicines, but otherwise few medical interventions available Study partner ~US$18.2bn by 20191Global market opportunity www.cynata.com Programme overview Pre-clinical programme—Brain Cancer / Glioblastoma 29 Current status Summary of progress  Production and testing in an animal model of Cynata MSCs genetically engineered to produce compounds that have anticancer effects: a type of “Trojan horse”.  Programme completed in October 2018  Genetically engineered Cymerus MSCs were successfully produced to express diagnostic and therapeutic anti-cancer agents  Engineered Cymerus MSCs reduced the viability of both human glioblastoma cells and human melanoma cells, and slowed tumour progression in mice  Further engineered MSC pipeline developments in planning stage Next steps  Determine most suitable commercial path following further pre-clinical studies 1. Global Data, 2016 Existing treatment options/products  Glioblastoma is a type of brain cancer and is the most common type of malignant brain tumor in adults. Current treatment consists of surgery, radiotherapy, and chemotherapy. Notoriously difficult to treat Study partner ~US$3.3bn by 20241Global market opportunity www.cynata.com Programme overview Pre-clinical programme—Diabetic wounds 30 Current status Summary of progress  Evaluation of cells from five different sources: Cymerus MSCs, bone marrow-derived MSCs, and MSCs derived from dental pulp, bone chips and gingival fibroblasts in a preclinical model of diabetic wounds (also known as diabetic ulcers), in conjunction with an active wound care dressing  Findings announced May 2018  Cymerus MSCs resulted in significantly faster wound healing than bone marrow-derived MSCs  Ongoing discussions with study partner (CRC-CTM) to commence a clinical trial Next steps  Grant funding for a clinical trial being explored with CRC-CTM and their collaborators 1. Transparency Market Research, 2018 Existing treatment options/products  Diabetic wounds are prevalent among the 400m+ diabetics globally and a significant opportunity exists to improve existing treatments and meet a growing unmet medical need Study partner ~US$4.9bn by 20241Global market opportunity www.cynata.com Programme overview Pre-clinical programme—Coronary Artery Disease 31 Current status Summary of progress  Evaluation of methods to activate Cymerus MSCs to stimulate new blood vessel formation (angiogenesis) and improve blood supply to the heart in patients with CAD.  Programme commenced mid 2018 and is proceeding well  Programme on track. Results expected Q2 2019. Next steps  Determine most suitable commercial path following release of results 1. Smithers Apex, 2015 Existing treatment options/products  CAD involves a narrowing of the coronary arteries due to a build-up of fatty deposits (plaque), also known as atherosclerosis, which reduces blood flow to the heart and the major cause of heart attack. Few medications treat CAD once it has developed Study partner ~US$22.5bn by 20211Global market opportunity www.cynata.com Programme overview Pre-clinical programme—Asthma 32 Current status Summary of progress  To test the effectiveness of Cymerus MSCs in an animal model of asthma, compared with effectiveness of bone marrow derived MSCs, and corticosteroids (+/- Cymerus MSCs)  Treatment with Cymerus MSCs caused significantly greater reduction of airway hyperresponsiveness, airway remodelling and fibrosis compared to corticosteroid treatment  Combination therapy involving Cymerus MSCs and corticosteroids resulted in a pronounced synergistic effect, producing marked anti-inflammatory effects in addition to the benefits seen with Cymerus MSC treatment alone  Data published in prestigious medical journal, Federation of American Societies for Experimental Biology  Final phase of study wrapping up: histology analysis; route of administration  Final results expected late 2018 Next steps  In active discussions with potential partners to support progress to a clinical trial 1. Grand View Research, 2016: total asthma market. Difficult-to-treat subset is a proportion of this Existing treatment options/products  Chronic asthma is managed by steroid-type drugs (e.g. “puffers”). Severe, persistent, high-risk or difficult-to-control asthma is much more challenging to treat: this is the target patient population Study partner ~US$25.6bn by 20241Global market opportunity www.cynata.com Programme overview Pre-clinical programme—Cytokine Release Syndrome 33 Current status Summary of progress  Evaluate the effectiveness in a preclinical model of Cymerus MSCs to ameliorate the effects of CRS  Programme completed in September 2018  Cymerus MSC shown to be effective in protecting against CRS in mouse models  Programme completed Next steps  Expressions of interest being sought from potential partner companies active in immunotherapy product development 1. Evaluate Pharma, 2017 Existing treatment options/products  Immunotherapies e.g. CAR-T cells are very promising cancer treatments, however their use is often associated with potentially fatal adverse effects, most notably the cytokine release syndrome (CRS). The management of CRS is a challenging clinical problem and no one modality has been shown to be particularly effective Study partner ~US$4.5bn by 2022 (CAR-T)1Global market opportunity www.cynata.com Programme overview Pre-clinical programme—Sepsis 34 Current status Summary of progress  Evaluate the effectiveness of Cymerus MSCs to treat sepsis  Programme costs highly leveraged through RCSI Strategic Industry Partnership Seed Fund  Programme commenced in July 2018 and is proceeding well  Programme on track. Results expected Q1 2020. Next steps  Determine most suitable commercial path following release of results 1. GlobalData, 2017 Existing treatment options/products  Sepsis is the most common cause of death in Intensive Care Units despite management with antibiotics and supportive therapy. New therapies are urgently needed to address the huge unmet clinical need associated with sepsis. Study partner ~US$5.9b by 2026 1Global market opportunity Outlook and Next Steps5 www.cynata.com Key focus areas for next 12 months 36  Commence Phase II GvHD trial, with or without Fujifilm (noting that, while Fujifilm has not yet not exercised its license option, it has, in association with Cynata, commenced preparations for clinical trials and product manufacture)  Commence Phase II trial in Critical Limb Ischemia  Advance commercial discussions for multiple indications & geographies  Continue to selectively progress the highest potential target areas from our pre- clinical programme Cynata has had a strong 12 months, with excellent operational and commercial progress. A chart of Cynata’s share price performance appears on slide 40. The Cynata team, management and Board are excited about the next 12 months, with significant operational and commercial milestones expected. www.cynata.com Key upcoming milestones 37 GvHD Critical Limb Ischemia (CLI) All other pre-clinical Commercial H1 CY2018 H2 CY2018 H1 CY2019 H2 CY2019 Today Completed Fujifilm licence option expires If Fujifilm do not exercise their option, Cynata intends to progress to Phase 2 independently or with an alternative partner Phase I clinical trials Cynata board and management seek and assess partnering and licensing opportunities on an ongoing basis and will announce material developments as they arise Detailed trial plan announced Detailed trial plan to determine timeline Recruitment commences Ongoing pre-clinical programme includes studies focused on Asthma, ARDS, Heart Attack, Coronary Artery Disease, Brain Cancer / Glioblastoma, Diabetic Wounds, Sepsis, CRS Appendix Corporate Overview 6 www.cynata.com Investment Highlights 39  Scalable, world-first technology: Cymerus platform overcomes inherent challenges of other production methods and enables mass-production of therapeutic MSCs  Phase II ready: Excellent Phase I results provide validation of Cynata’s Cymerus platform; Cynata well positioned to progress to Phase II in GvHD and other indications  Cardiovascular disease identified as priority indication area for clinical programme: Planning for Phase II in Critical Limb Ischemia has commenced; trial expected to begin in 2019  Attractive licensing-driven business model: Fujifilm licence option for GvHD potentially worth over US$60m, plus royalties  Valuable market opportunity: Estimated US$1.7bn revenue opportunity for MSC products for GvHD and CLI alone  Well-funded to progress clinical programme: Cash balance of $10.9m1 Investor Presentation August 20181. Cash balance at 30 September 2018 www.cynata.com Company profile Cynata Therapeutics is an Australian stock exchange listed clinical-stage biotechnology company developing disruptive regenerative medicines. Share price performance (last 12 months, A$) Corporate overview 40 Top shareholders Shareholder Fidelity International 9.4% Fujifilm Corporation 8.0% Board and Management 6.1% Board and Management (fully diluted)2 8.6% Share price (31-Oct-18) A$1.06 52 week low / high A$0.56 / A$1.58 Shares on issue1 100.8m Market capitalisation A$107m Cash (as at 30-Sep-18) A$10.9m Debt (as at 30-Sep-18) - Enterprise value A$96m Financial information Source: IRESS Notes: 1. Excludes 6.0m unquoted options with exercise prices ranging from $0.53 to $1.50 and expiry dates between 22-Feb-2019 and 4-Aug-2020 (1m subject to vesting conditions) 2. Represents shareholding if all options held by the Board and Management (total of 2.7m) are exercised - 0.40 0.80 1.20 1.60 Oct-17 Jan-18 Apr-18 Jul-18 Oct-18 CYP S&P/ASX 200 Health Care Index (rebased) +66% +22% www.cynata.com Cynata has the only platform in the world to produce commercial quantities of Mesenchymal Stem Cells from a single source: iPSCs 41 Today’s on-market MSC manufacturing solution has a number of shortcomings Patented Cymerus Platform overcomes shortcomings REGULATORY ISSUES REDUCED EFFICACY Sourcing cells from multiple donors leads to variability in the sourced cells, which is a major regulatory hurdle Massive cell expansion is required to create enough cells for therapeutic use, which may result in reduced efficacy  CONSISTENT PRODUCT QUALITY Single donor overcomes regulatory concerns  MAINTAINED PRODUCT EFFICACY Cymerus overcomes need for excessive expansion For more information on the Cymerus platform visit Cynata’s website Surgery required to source MSCs from bone marrow Multiple donors Complex surgery Cell expansion www.cynata.com MSCs are a highly potent form of stem cell attracting significant clinical interest – and in need of a scalable commercial solution 421. Clinicaltrials.gov (as at June 2018) Global commercial potential, with multiple target areas potentially benefiting from MSC treatment Number of MSC clinical trials (cumulative) Mesenchymal Stem Cells (MSCs) are believed to play a vital role in repair and regeneration  Modulator of the immune system  Secrete bioactive molecules and have immunosuppressive and immunoregulatory properties Over 850 clinical trials investigating the efficacy of MSCs in treating diseases have been initiated1  MSCs were approved for use as a therapeutic treatment in Japan in September 2015 and Europe in March 2018 Heart attack Brain cancer / Glioblastoma GvHD Crohn’s disease Acute respiratory distress syndrome Osteoarthritis Diabetes complications Diabetic foot ulcers Fistula Critical limb ischemia Asthma 0 250 500 750 1000 www.cynata.com Cell therapy is an active market attracting big pharma M&A interest 43 USD 379M USD 307M USD 628M Acquired by Acquired by Acquired by March 2015 • Enables Fujifilm to combine technologies with Cellular Dynamics to develop new iPSC based cell therapies • Founder of Cellular Dynamics also founded Cynata February 2016 • Enables Astellas to establish a leading position in cell therapy • Ocata CEO prior to acquisition was Paul Wotton, current Chairman of Cynata 1. Transaction pending completion following acceptance of bid by TiGenix shareholders January 20181 • Extends existing partnership between Takeda and TiGenix to develop and commercialize Cx601 (darvadstrocel) • TiGenix was the first company to receive approval for an MSC therapy in Europe www.cynata.com Globally experienced board and management team 44 Dr Paul Wotton Chairman Dr Ross Macdonald Managing Director Chief Executive Officer Dr Stewart Washer Non-Executive Director Dr John Chiplin Non-Executive Director Mr Peter Webse Non-Executive Director Company Secretary Dr Kilian Kelly Vice President, Product Development Former CEO of Ocata Therapeutics (NASDAQ: OCAT) managing it through a take-over by Astellas Pharma, in a US$379m transaction Previous executive roles with Antares Pharma Inc. (NASDAQ: ATRS), Topigen Pharmaceuticals and SkyePharma Founding CEO, Sigilon Therapeutics; member of the boards of Vericel Corporation and Veloxis; past Chairman of the Emerging Companies Advisory Board of BIOTEC Canada 30 years’ experience and a track record of success in pharmaceutical and biotechnology businesses Previous senior management positions with Hatchtech, Sinclair Pharmaceuticals, Connetics Corporation (Palo Alto, CA), and Stiefel Laboratories, the largest independent dermatology company in the world and acquired by GSK in 2009 for £2.25b 20+ years of CEO and Board experience in medical technology, biotech and agrifood companies Chairman of Orthocell Ltd and Minomic International Previously CEO roles with Calzada (ASX:CZD), Phylogica (ASX:PYC) and Celentis and managed the commercialisation of intellectual property from AgResearch in New Zealand with 650 Scientists and $130m revenues Significant international experience in the life science and technology industries Recent transactions include US stem cell company Medistem (acquired by Intrexon), Arana (acquired by Cephalon), and Domantis (acquired by GSK) Was head of the $300M ITI Life Sciences investment fund in the UK and his own investment vehicle, Newstar Ventures +25 years’ company secretarial experience Managing Director of Platinum Corporate Secretariat Pty Ltd, a company specialising in providing company secretarial, corporate governance and corporate advisory services 15 years’ experience in pharmaceutical/ biotechnology research and development, in both commercial and academic settings Previous appointments include Senior Director, Drug Development at Biota Pharmaceuticals (NASDAQ: BOTA), Vice President, Regulatory and Clinical at Mesoblast Limited (ASX:MSB) Expertise running and monetising Ocata Therapeutics, acquired by Astellas Track record of success in pharmaceutical and biotechnology businesses Deep experience growing companies as CEO and on the Board Overseen and managed a broad range of life sciences transactions 25+ years company secretarial and management experience Academic and commercial excellence, extensive relevant management experience Thank you for your attention Cynata Therapeutics Limited Level 3 62 Lygon Street Carlton Victoria 3053 Australia Contact details: [email protected] +61 (0) 412 119343 www.cynata.com

The release as fetched from its publisher. cynata.com ↗