Announcement PDF Updated Bisantrene Phase II Data Presentation June 2020 Trial highlights | Chair Clinical Advisory Board, Professor Borje Andersson June 2020 About Bisantrene Bisantrene is a cancer chemotherapy that was previously approved for AML in France 1988 and then shelved. Race Oncology is returning this drug back into clinical development Bisantrene (Xantrene®) is an anthracene with anthracycline-like activity and was shown in earlier clinical trials to be an effective salvage therapy in R/R AML with little or no discernible cardiotoxicity Since then, Race: • Has successfully manufactured Bisantrene • Built a strong patent position (3 granted US patents) • US Orphan Drug designation (7 years exclusivity) • Secured a Rare Paediatric Disease designation with the potential to receive a Priority Review Voucher (PRV) Bisantrene remains an excellent cancer drug with great potential in modern cancer treatment for AML and other cancers Current AML Treatment General overview Complete AML Intensive Chemotherapy (Induction and consolidation) Response (CR) Stem Cell Transplant (HSCT) This trial Salvage chemotherapy Bisantrene IV 250mg/m2 x 7 days Cure This trial Relapsed and/or Refractory AML Management of R/R AML represents a significant therapeutic challenge with no established standard of care Phase II Bisantrene monotherapy in relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) Bisantrene is active, safe and effective in Adult R/R AML after multiple prior therapies Bisantrene 7 day (single IV course) treatment 10 patients enrolled 10 Evaluated for safety and efficacy ORR = 40% (4/10 patients * 4 Responses reported (1 CR + 3 PR) Favourable safety and tolerability *4/4 responses in high-risk extramedullary disease Study design - Phase II open-label single arm single center study (NCT03820908) - Site: Chaim Sheba Medical Center, Tel Aviv, Israel - Principal investigator. Professor Arnon Nagler Study design Criteria Inclusion Criteria Exclusion Criteria Patients with Relapsed/Refractory AML Active pulmonary disease, diffusing capacity for carbon monoxide(DCFO) < 30% Aged 18 years or older Symptomatic heart failure (NYHA Grade 2 or higher) Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 Bilirubin =/≥ 3.0 mg/dl Adequate cardiac function; left ventricular ejection fraction (LVEF) ≥ 40% Transaminase levels more than three times the upper limit of normal (ULN) Adequate birth control in potentially fertile patients Creatinine =/≥ 2.0 mg/dl Active central nervous system (CNS) disease# Active Grade III-IV graft-versus-host disease (GVHD) after previous allogeneic stem cell transplant. # Two CNS patients enrolled with a waiver approved by local IRB; NYHA - New York Heart Association [NYHA] Class III to IV Study design Treatments and assessments Treatment Bisantrene 250mg/m2 over 2-hour, one infusion daily for 7 days, one course only. Patients achieving CR may receive one 3-day consolidation course with the same daily dose and schedule. Salvage therapy - predominantly as 4th line therapy Trial Endpoints Primary  1. Overall survival [Time Frame: 24 months] Overall survival will be calculated from the day of bisantrene administration until death or last follow-up. 2. Leukemia-free survival [Time Frame: 24 months] Leukemia-free survival will be calculated from the day of bisantrene administration until relapse, death of any cause, or last follow-up. Secondary  1. To determine the safety and toxicity of bisantrene in relapsed (Rel)/refractory (Ref) AML including post allogeneic stem cell transplantation (alloSCT) 2. To determine achievement of cytogenetic or molecular remission (if relevant). 3. To evaluate the Relapse rate. 4. To determine Leukemia Free Survival (LFS). 5. To determine Overall Survival (OS). 6. To evaluate the number of hospitalization days including days of antibiotic therapy 7. To determine the Incidence of infection episodes (bacterial and fungal). 8. To describe the Safety and toxicity of bisantrene treatment. Patients will be evaluated for toxicity according to CTC and infectious complications. Study design Assessments ? Safety • • • • Vital signs & physical Clinical lab tests and bone marrow examination ECG Adverse Events per CTCAE v5.0 Evaluable patients: all that received one course of bisantrene (n=10) $ Response • • Blast cells in bone marrow and in blood According to 2003 International Working Group (IWG) standardized response criteria for AML Evaluable patients: all completed bisantrene treatment (n=10) Disease mutations • Next generation sequencing (NGS) studies on patient bone marrow samples pre-treatment Evaluable patients: all that provided a sample (n=7) Patient Demographics Characteristic N=10 Median age Characteristic N=10 MRC Cytogenetic risk Years (range) 43 (22-80) Favourable Intermediate Advanced Gender Male Female 6 4 ELN 2017 risk category ECOG performance status at screening 0 1 9 (90%) 1 (10%) Disease diagnosis Antecedent myeloid disorder 3 (30%) Extramedullary disease Prior system therapy regimens (lines) 1 2 >3 4 (40%) Prior allogenic transplant 7 (70%) 1 (10%) 3 (30%) 6 (60%) 0 7 (70%) 3 (30%) Favourable Intermediate Advanced 2 (20%) 5 (50%) 3 (30%) NPM1wt NPM1mut 8 (80%) 2 (20%) FLT3wt FLT3-ITD 6 (60%) 4 (40%) NPMI status FLT3-ITD status “Hard to treat” disease setting Safety All-cause adverse events Anemia Grade 1-2 Grade 3 1 (10%) 1 (10%) Neutropenia Thrombocytopenia Grade 4 2 (20%) 2 (20%) 4 (40%) 2 (20%) Grade 5 Adverse events attributed to bisantrene Grade 1-2 Grade 3 1 (10%) 1 (10%) Fever 6 (60%) 6 (60%) Headache 1 (10%) 1 (10%) Chills 1 (10%) 1 (10%) Dyspnea 1 (10%) 1 (10%) Myocardial infarction Mucositis 1 (10%) Acute kidney injury 1 (10%) Sepsis 2 (20%) Blood bilirubin increased 1 (10%) 1 (10%) 4 (40%) 2 (20%) 1 (10%) 1 (10%) Hypernatremia 1 (10%) 2 (20%) 4 (40%) 2 (20%) 1 (10%) 1 (10%) 4 (40%) 2 (20%) 1 (10%) 2 (20%) Most frequently reported serious adverse events: • thrombocytopaenia (low blood platelets) • mucositis (mouth ulcers) Both of these are expected side effects with chemotherapeutics of this kind. 2 (20%) 1 (10%) 1 (10%) Ejection fraction decreased Cardiac arrest # 1 (10%) Atrial fibrillation 1 (10%) 1 (10%) 1 (10%) 1 (10%) Abdominal pain 1 (10%) 1 (10%) Diarrhea 1 (10%) 1 (10%) Vomiting 1 (10%) 1 (10%) Rash 1 (10%) 1 (10%) Upper gastrointestinal bleeding 2 (20%) 1 (10%) 1 (10%) 2 (20%) Confusion Grade 4 1 (10%) 1 (10%) # Deemed due to pre-transplant chemotherapy conditioning regimen Outcomes - Of the 10 patients, one patient (10%) achieved a complete remission and three patients achieved a partial remission → Overall Response Rate of 40% - All 4 responders had high-risk extramedullary disease: • Patient with leukaemia cutis (skin) achieved CR and was bridged to allogeneic stem cell transplantation • Patient with breast chloromas achieved high reduction in sites of disease deemed as partial response based on serial PET-scans. • Two patients with CNS disease achieved transient clearance of peripheral blood blasts with one resulting in partial remission of ocular disease involvement and the other had a partial response of CNS (leptomeningeal) disease Conclusion Established safety and tolerability of current Bisantrene formulation Confirmed previously recorded anti-leukeamic activity The Dose and Schedule (250mg/m2 once daily for 7 days) maintains effectiveness in R/R AML Bisantrene is safe and its efficacy confirmed in the dose and schedule used. Positioned to be investigated with complementary anti-leukemic therapy to re-enter the modern AML therapy landscape. So where, henceforth ……….. 6/19/2020 B.S. Andersson Other Activities | CSO Daniel Tillett June 2020 The MRD opportunity 2-year survival and residual disease status at transplant 100 Up to 80% of AML patients who are fit enough for induction chemotherapy (3+7) with enter remission (CR) and may then be candidates for a human stem cell transplant (HSCT) ● MRD(+) patients (those with MRD) have less than 25% two- year survival time ● MRD(-) patients have a 80% survival post transplant = potential cure! As yet, there are no approved treatments that can change MRD status from (+) to (-) for AML ● Bisantrene is potentially the answer 80 % 2 year survival Whether the transplant results in long term survival depends largely on the patient’s MRD (Measurable Residual Disease) status at the time of transplant 90 70 60 50 40 30 20 1 0 0 MRD(+) MRD(-) Bisantrene in AML treatment for MRD Bisantrene could transform cure rates by changing MRD status MRD(+) Fit patients Newly Diagnosed AML Unfit patients 3+7 Induction Chemotherapy Complete Response (CR) MRD(-) Bisantrene MRD(-) Stem Cell Transplant (HSCT) Nonresponders Various salvage combination +/or targeted therapies Relapsed +/or Refractory AML Cure 1 Phase II MRD trial Phase II study of Bisantrene treatment after (7+3) induction chemotherapy to change MRD status Aim to run trial in USA and/or Israel in partnership with a leading US cancer center Eligibility Transplant eligible MRD(+) patients in CR after induction chemotherapy – potential for paediatric study too Study Design Open label 7-day Bisantrene 250mg/m2/day treatment in 28 MRD(+) patients Endpoints MRD status post-Bisantrene Treatment post-transplant survival Goal Early FDA approval of Bisantrene for MRD(+) patients 4 Breast cancer combination trial Phase I/II proof-of-concept (POC) trial in breast cancer Will use drug combinations which preclinical data show synergise with Bisantrene (preclinical studies underway with U. Newcastle) Use optimal dosing, administration and combination of Bisantrene Historical breast cancer trials used sub-optimal dosing and administration of Bisantrene (but still showed good activity!) Goal Opens up much larger cancer market than AML (2 million cases each year) Show equivalent efficacy to existing treatments but with fewer serious side effects (less damage to the heart) Displace current anthracyclines used in breast cancer treatment 5 Ovarian cancer combination trial Phase I/II proof of concept (POC) trial in ovarian or other cancer Preclinical trials to be performed to identify those cancers that respond most to Bisantrene and which drug combinations show synergy Use optimal dosing, administration & combinations of Bisantrene Historical non-AML cancer trials all used sub-optimal dosing and did not use combinations, but still showed activity for Bisantrene Goal Open up much larger cancer market than AML (200,000 cases each year) POC trial to attract pharmaceutical partner for approval trials L40 140 William St, Melbourne, VIC 3000 info@raceoncology.com +61 3 9098 8750