Announcement PDF ASX Announcement Race investor briefing and updated presentation § Updated investor presentation available which covers recent progress and coming milestones § Investor briefing to be held online on 13 May at 10:30am AEST 5 May 2021 – Race Oncology Limited (ASX: RAC) (Race) is pleased to release an updated investor presentation and invite investors to join a special online investor briefing. Updated presentation The attached updated presentation includes: - An update on the Company's Three Pillar strategy and recent related highlights - Updates to the Board and extended team slides - Additional information on the FTO pathway (Pillar 1) for Bisantrene, including relevant comparators - Coming milestones and the expected activity timeline for Bisantrene's continued development Investor briefing invitation Investors are invited to attend a special briefing session where Managing Director and CEO, Phillip Lynch and CSO and Executive Director, Dr Daniel Tillett will discuss progress on the Company’s Three Pillar strategy, as well as the recently announced capital raise and Bonus Options Issue. Details as follows: When Thursday 13 May from 10:30am AEST Register https://us02web.zoom.us/webinar/register/WN_04Io2ZClRrSvGsfoZGlW2Q Q+A Investors will be invited to ask questions during the session. -ENDS- Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com About Race Oncology (ASX: RAC) Race Oncology is an ASX listed precision oncology company with a Phase II/III cancer drug called Bisantrene. Bisantrene is a potent inhibitor of the Fat mass and obesity associated (FTO) protein. Over-expression of FTO has been shown to be the genetic driver of a diverse range of cancers. Race is exploring the use of Bisantrene as a new therapy for melanoma and clear cell renal cell carcinoma, which are both frequent FTO over-expressing cancers. The Company also has compelling clinical data for the use of Bisantrene as a chemotherapeutic agent with reduced cardiotoxicity in Acute Myeloid Leukaemia (AML), breast and ovarian cancers and is investigating its use in these areas. Race is pursuing outsized commercial returns for shareholders via its ‘Three Pillar’ strategy for the clinical development of Bisantrene. See more at www.raceoncology.com. Release authorised by: Media contact: Phil Lynch, CEO/MD on behalf Jane Lowe of the Race Board of Directors +61 411 117 774 phillip.lynch@raceoncology.com jane.lowe@irdepartment.com.au Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com Investor Update 30 April 2021 PRECISION ONCOLOGY 2 corporate snapshot ISSUED CAPITAL Shares 141.1m Options 20.9m Shareholders (30 April 2021) 9133 MARKET CAPITALISATION Share price (30 April 2021) $3.07 Market value (30 April 2021) $433m Cash (31 March 2021) $6.47m Enterprise value $426.5m SIGNIFICANT SHAREHOLDERS Daniel Tillett (Director & CSO) 9.6% Bill Garner (Founder) 7.4% Merchant Opportunities Fund 6.0% 3 2020-2021 A pivotal period for bisantrene May 2020 Race starts preclinical breast cancer study for Bisantrene June 2020 Bisantrene highlighted as potent inhibitor of FTO in Cancer Cell – COH / Prof Chen June 2020 Impressive 40% response in Phase II AML trial Sept 2020 CCSA appointed clinical + FDA regulatory strategic advisors July 2020 Race secures 4th US patent for Bisantrene Nov 2020 Bisantrene data published in the European Journal of Haematology Nov 2020 Bisantrene data to be presented at ASH 2020 Nov 2020 Breast cancer clinical trial program initiated Nov 2020 Impressive preclinical Bisantrene breast cancer results March 2021 Multiple pre-clinical FTO-directed programs initiated Feb 2021 Impressive preclinical Bisantrene ovarian cancer results April 2021 Appointment of Prof Chen of COH to SAB March 2021 Final breast cancer preclinical results demonstrating activity is treatment resistant cancer cells 4 Three heroes 1 The drug 2 The team 3 The three pillars strategy 5 1. The drug. bisantrene Bisantrene is an anti-cancer agent developed in the 1980s by Lederle Laboratories It was tested in >40 human trials; showed excellent activity in leukemia, breast and ovarian cancer and was approved in France for Acute Myeloid Leukemia (AML) Since acquiring Bisantrene, Race has Successfully manufactured the GMP drug Built a strong patent position Received US Orphan Drug designation (7 years exclusivity) Secured Rare Paediatric Disease designation and Priority Review Voucher designation • Positive single agent R/R AML trial in Israel with a 40% response rate – July 2020 • Released pre-clinical breast cancer data providing evidence to advance into human clinical trials as a potentially safer breast cancer treatment option 6 2. The team Seasoned board and executive, key opinion leaders BOARD Dr John Cullity, Non-Executive Chairman Mr Phil Lynch, CEO and Managing Director Dr Daniel Tillett, CSO and Executive Director Mary Harney Non-Executive Director MANAGEMENT Mr Phil Lynch, CEO and Managing Director Dr Daniel Tillett, PhD CSO and Executive Director Dr David Fuller Chief Medical Officer (commencing 1 July 2021) Dr Marinella Messina, PhD Clinical Program Director 7 2. The team. extended race team Clinical Advisors Business Advisors & Consultants Accountants Contracts Lawyer IP Manager Onyx Corporate Pty Ltd Elevate Legal Roberts Foster LLP Patent Lawyers Ditthavong & Steiner P.C. Patent Lawyers Griffith Hack R&D Tax Lawyers MJ Associates Investor and Public Relations IR Department Clinical Advisory Board Prof. Borje Andersson, MD, PhD, MD Andersson Cancer Centre, USA Clinical Manufacturing Drug Product IrySys LLC Clinical Advisory Board Jaap-Jan Boelens, MD, PhD, Memorial Sloane Kettering, Cancer Centre, USA Clinical Manufacturing Drug Substance GVK Bio Clinical Advisory Board Didier Blaise, MD, Institut Paoli Calmettes, France Clinical Advisory Board Anoop Enjeti, MBBS MD, PhD Calvary Mater Hospital Newcastle Scientific Advisors DelBioPharma LLC Collaborator Prof Jianjun Chen, PhD, Beckham Institute, City of Hope Regulatory Affairs CCS Associates Collaborator Quality Assurance Dianna Goldman Consulting Inc. Nikki Verrills, PhD, University of Newcastle Collaborators Prof Xu Dong Zhang PhD, A/Prof Lei Jin PhD, University of Newcastle Hunter Medical Research Institute Collaborators Clinical Manufacturing Manager Calvary Mater Newcastle Hospital Industry Partners and Scientific Collaborators A/Prof. Aaron Sverdlov, MBBS, FRCAP, PhD and A/Prof Doan Ngo PhD, University of Newcastle Clinical Manufacturing Packaging PCI Pharma Clinical Research Organisation George Clinical Clinical Research Organisation Parexel Clinical Research Organisation Datapharm Australia Pty Ltd Clinical Research Organisation Novatrials Ltd Clinical Research Organisation Agilex BioLabs Pty Ltd Clinical Research Organisation Cyprotex Discovery Limited 8 3. the three pillar strategy GOAL Plan and progress clinical programs which prove efficacy and utility in targeted indications for Bisantrene, so that its potential is realised through sale to a scaled pharma Pillar 1 FTO STRATEGIES Melanoma Clear Cell Renal Cell Carcinoma Pre Clinical ENABLERS Pillar 2 Pillar 3 Breast Cancer AML Extramedullary Move to human proof of concept clinical trials Anthracycline replacement R/R Adult & Paediatric MRD Ovarian Pre Clinical & Clinical I Collaborators I Regulatory I CMC I IP I Commercial I Board 9 FTO Central ROLE In Cancer ● Scientific discoveries over the last decade have identified dysregulation (loss of control) of RNA methylation as a key driver of cancer development1 ● Changes in m6A RNA methylation control the expression of key genes in cancer development and growth2 ● Fatso/ Fat mass- and obesity-associated Protein (FTO) is an m6A RNA demethylase1 ● Increases in the expression of FTO drives cancer development and metastasis ● Reduction of FTO activity kills or slows the growth of a wide range of cancers including leukaemia, breast, lung, ovarian, gastric, brain, melanoma, pancreatic, etc – difficult to find a cancer where FTO is not an important driver ● One of the hottest areas of cancer research 1. Deng, X., Su, R., Stanford, S., & Chen, J. (2018). Critical Enzymatic Functions of FTO in Obesity and Cancer. Frontiers in Endocrinology, 9, 724–7 2. Huang, H., Weng, H., & Chen, J. (2020). m6A Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer. Cancer Cell, 37(3), 270–28 10 FTO Inhibitor Comparative Overview Drug IC50 (nM) Potency1 Clinical Data Indications Bisantrene (CS1) 142.6 1 Yes (Phase 3) AML, Breast, Pancreatic, GBM, Skin cancers Leukopenia and myelosuppression at high doses doi.org/10.1016/j.ccell.2020.04.017 doi.org/10.1016/j.molcel.2020.12.026 doi.org/10.1038/s41467-021-22469-6 Dac51 400 3 No Colon and melanoma Preclinical. No safety or tolerability data from human clinical trials doi.org/10.1016/j.cmet.2021.04.001 Saikosaponin D 460 3 No AML Preclinical. No safety or tolerability data from human clinical trials doi.org/10.7150/thno.55574 Brequinar (CS2) 712.8 5 Yes (Phase 2) AML Failed anticancer agent. Failed transplant organ rejection drug. Very immunosuppressive. Variable plasma concentrations Compound 2 1460 10 No Dopamine Neurons IC50 value in µM range. Preclinical. No safety or tolerability data from human clinical trials doi.org/10.1101/2021.02.23.432419 FB23-2 2600 18 No AML IC50 value in µM range. Preclinical. No safety or tolerability data from human clinical trials doi.org/10.1016/j.ccell.2019.03.006 FTO-04 3400 24 No GBM Stem cells IC50 value in µM range. Preclinical. No safety or tolerability data from human clinical trials doi.org/10.1021/acschembio.0c00841 Entacapone 3500 25 Yes (Approved) Metabolic cells IC50 value in µM range. doi.org/10.1126/scitranslmed.aau7116 MA/MA2 7000 49 Yes (Approved) - IC50 value in µM range. doi.org/10.1093/nar/gku1276 MO-I-500 8700 61 No TNBC IC50 value in µM range. Preclinical. No safety or tolerability data from human clinical trials doi.org/10.1371/journal.pone.0159072 1. Relative to Bisantrene. Compounds with IC50 > 1000nM are unlikely to be useful drugs in the clinic. Efficacy & Known Side Effects References doi.org/10.1016/j.ccell.2020.04.017 11 FTO inhibitors Drug synergies Drug Value1 (USD) Indications Anti PD-1/ Immune Checkpoint Inhibitors $20.4 B (2018) $77.4 B (2026) Melanoma, colon cancer, AML TKIs $19.1 B (2027) Leukemia Alkylating Agents (Cisplatin) $1.8 B (2026) Cervical cancer PARP Inhibitors $0.8 B (2018) $8.8 B (2027) Ovarian cancer FTO inhibition decreases FZD10 mRNA stability and sensitizes the cell to PARP inhibitor Hypomethylating Agents $1.7 B (2020) $2.4 B (2022) AML Bisantrene shown to synergize with HMAs in inhibiting AML progression in immunecompetent BMT recipient mice, and combinations showed much improved therapeutic efficacy than either treatment alone Radiotherapy $7.2 B (2021) $11.7 B (2028) Cervical cancer FTO induces radio resistance in cervical squamous carcinoma by demethylation of βcatenin mRNA, which stabilizes its expression. Proton Pump Inhibitors $2.7 B (2020) $3.5 B (2026) Gastric cancer FTO inhibition induced by omeprazole improved the antitumor efficiency of chemotherapeutic drugs on GC cells Androgen Receptor Antagonists $13 B (2018) Prostate cancer METTL3 knockdown rendered the cells resistant to androgen receptor antagonists. Mechanism References FTO up regulation increases melanoma growth & decreases anti-PD-1 response. FTO doi.org/10.1038/s41467-019-10669-0 inhibition sensitized melanoma to anti-PD-1 treatment in mice. FTO up regulation increases doi.org/10.1016/j.bbrc.2020.06.153 doi.org/10.1016/j.ccell.2020.04.017 PD-L1 in colon cancer and AML. FTO inhibition decreases PD-L1 in colon cancer and AML. TKI resistance is linked to FTO up regulation in leukemia. FTO inhibition increases TKI sensitivity in leukemia cells. doi.org/10.1038/s41422-018-0097-4 doi.org/10.1158/1541-7786.MCR-20-0541 FTO demethylates β-catenin mRNA and stabilizes the β-catenin in cervical squamous cell carcinoma, thereby inducing chemo-radio therapy resistance. doi.org/10.1074/jbc.RA119.011009 doi.org/10.1158/0008-5472.CAN-18-3592 doi.org/10.1016/j.ccell.2020.04.017 doi.org/10.1002/mc.22782 doi.org/10.1042/BSR20200842 doi.org/10.1101/2021.01.12.426354 1. In house research performed by Race Oncology based on publically available information. All values are approximate and only illustrative of market size. 12 PILLAR 1 – FTO & Melanoma opportunity ● One of the most dangerous cancers: 7000 deaths (USA), 1500 (Aust)1 ● Major improvements in treatment (BRAF/MEK inhibitors, immune checkpoint), but the 5-year survival rate for advanced melanoma is still as low as ~25%1 ● Major problem - treatment resistance ● FTO ● FTO was found to be overexpressed in ~50% of all metastatic melanomas2 ● FTO overexpression causes treatment resistance to PD-1 (immune checkpoint) inhibitors2 ● Down-regulation of FTO has been shown to overcome PD-1 resistance2 1. www.cancer.net/cancer-types/melanoma/statistics 2. Yang, S., Wei, J., Cui, Y.-H., Park, G., Shah, P., Deng, Y., et al. (2019). m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nature Communications, 10(1), 1131–14. 13 PILLAR 1 – FTO & Clear Cell Renal cell carcinoma ● 10th most common cancer; often only diagnosed after metastasis1 ● New treatments. TKI, checkpoint inhibitors1 ● 5-year survival rate still very low (~12%)1 ● 90% of ccRCC are caused by mutations in the von Hippel-Lindau (VHL) tumour suppressor gene2 ● FTO ● FTO was found to be synthetically lethal in cells with inactive VHL3 ● Inhibition of FTO was found to kill VHL(-) ccRCC cancers3 1. www.cancer.net/cancer-types/kidney-cancer/introduction | 2. Young, A. C., Craven, R. A., Cohen, D., Taylor, C., Booth, C., Harnden, P., et al. (2009). Analysis of VHL Gene Alterations and their Relationship to Clinical Parameters in Sporadic Conventional Renal Cell Carcinoma. Clinical Cancer Research, 15(24), 7582–7592. | 3. Xiao, Y., Thakkar, K. N., Zhao, H., Broughton, J., Li, Y., Seoane, J. A., et al. (2020). The m6A RNA demethylase FTO is a HIF-independent synthetic lethal partner with the VHL tumor suppressor. Proceedings of the National Academy of Sciences, 117(35), 21441–21449. 14 PILLAR 2 - Breast cancer Phase 1/2 proof-of-concept (POC) trial in advanced metastatic breast cancer patients Preclinical data suggests Bisantrene is able to kill breast cancer cells resistant to current standard of care drugs1 Aim to demonstrate activity of Bisantrene in this patient population Phase 2b trial in anthracycline naïve metastatic metastatic breast cancer patients Feasibility study underway with the aim of demonstrating cardio safety and efficacy in a patient population not exposed to anthracyclines Preclinical Molecular Study Aims to explore the mechanism of action that causes Bisantrene’s low cardiotoxicity Focused on FTO and related pathways 15 PILLAR 3 - ExtraMedullary AML ● Why extramedullary (EM) AML? ● Recent Israel results - 4/4 responders had EM AML ● Unmet clinical need - no clinical trials and EM AML patients excluded ● EM AML patients have a worse outcome than non-EM AML patients ● PET has shown EM AML is much more common than previously thought (~20%)1 ● Small number of patients needed for pivotal trial (50-75) ● Potential for expansion into paediatric AML; pathway to PRV ● FDA 505(b)(2) pathway to approval 1Stölzel, F., Lüer, T., Löck, S., Parmentier, S., Kuithan, F., Kramer, M., et al. (2020). The prevalence of extramedullary acute myeloid leukemia detected by 18FDG-PET/CT: final results from the prospective PETAML trial. Haematologica, 105(6), 1552–1558. http:// doi.org/10.3324/haematol.2019.223032 16 Rapid Progress Announced Activities in CY 2021 ● Positive breast and ovarian cancer preclinical results ● Four preclinical programs launched in collaboration with the University of Newcastle to explore: ● Use of Bisantrene in combination with standard of care drugs for the treatment of melanoma ● Use of Bisantrene as a treatment for clear cell renal cell carcinoma ● Use of Bisantrene in a mouse model of extramedullary AML ● The molecular mechanism of action of Bisantrenes low cardiotoxicity ● Appointment of Professor Chen of the City of Hope Hospital to Race’s scientific advisory board 17 Next Steps 2021/2022 2021 ● Phase 2 extramedullary AML clinical trial (Australia) ● Phase 2 R/R AML combination clinical trial (Israel) ● Phase 2 clinical trial in late stage metastatic breast cancer (Australia) ● Phase 1 dose escalation trial to determine the optimal Bisantrene dosing for targeting FTO overexpressing cancers ● Preclinical FTO-directed lung cancer program ● Initiation of EU and USA activities to support extramedullary AML clinical trials ● Scaled manufacturing of Bisantrene to support Phase 2/3 trials 2022 ● Reporting on preclinical programs ● Phase 2 FTO-directed clinical trial of Bisantrene in melanoma ● Phase 2 FTO-directed clinical trial of Bisantrene in ccRCC ● Phase 2b breast cancer trial in anthracycline naïve patients (subject to feasibility) 18 Activity TimeLine 2021 2022 2023 Preclinical melanoma All open label studies with continuous data readouts and news flows Preclinical kidney cancer (ccRCC) Preclinical EMD AML Preclinical heart safety Phase 2 Clinical Trial. Combination r/r AML Preclinical lung cancer safety Phase 1. FTO dose escalation Phase 2. Late metastatic breast cancer Phase 2. Extramedullary AML Phase 2. FTO melanoma Phase 2. FTO ccRCC concluding comments STRATEGY – capitalises on FTO opportunity while protecting legacy chemotherapy credentials RISK REWARD – multi leg strategy reduces executional risk and maximises potential for outsized returns TEAM – is focused on shareholder return, via sale / license to pharma partner CLINICAL PROGRESS – will be gated and plans advanced appropriately 20 Contact us raceoncology.com Phil Lynch, CEO/MD phillip.lynch@raceoncology.com Dr Daniel Tillett, CSO/ED daniel.tillett@raceoncology.com