Zantrene (bisantrene) / Race Oncology - LARVOL DELTA

Racura Oncology Ltd…earlier this week confirmed it has secured AU$3.22 million to fully fund its Harness-1 Phase 1/1B lung cancer trial. (Proactiveinvestors) - "The company said the study will test its proprietary drug RC220 in combination with osimertinib, targeting EGFR-mutant lung cancer....Racura said the $3.2 million raise, supported by existing shareholders, will ensure the trial is completed without delay....Racura added that data from the Harness-1 trial will be released progressively, given the open-label design. It also noted that data from a second study — investigating RC220 in combination with doxorubicin — will be published throughout 2026."

Financing • P1 data • Non Small Cell Lung Cancer • Solid Tumor

Bisantrene in Combination with Fludarabine and Clofarabine As Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)- an Open-Label, Phase II, Study (ASH 2023) - P2 | "Background: Bisantrene (Bis), is a topoisomerase-II inhibitor with anthracycline-like activity, lower cardiotoxicity, and activity in patients (pts) with relapsed (rel)/primary refractory (PR) acute myeloid leukemia (AML) (Am J Hematol, 2021). In this Phase II study in a very advanced group of relapsed refractory AML pts resistant to multiple previous lines of chemotherapy including transplantation and with a median of 50% blasts at study initiation, Bis/Clo/Flu combination therapy was found to be safe and well tolerated without cardiac toxicity or tumor lysis syndrome. The maximum length of Bis/Clo/Flu administration was 4 days due to rapidly reversible liver toxicity, and transaminitis. As expected in this highly pretreated population, the infection rates were high."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cardiovascular • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombosis • Transplantation • KMT2A

Preclinical Evaluation of Bisantrene As Single Agent and in Combination with Decitabine for Acute Myeloid Leukemia (ASH 2023) - "Anthracyclines, particularly doxorubicin and idarubicin, together with cytarabine, have comprised standard of care induction chemotherapy in acute myeloid leukemia (AML) for almost 4 decades...Hypomethylating agents (HMA; azacytidine, decitabine) provide a less toxic alternative and have improved treatment options for the unfit...Approaches that reduce the toxicity of induction therapy and improve the efficacy of HMA treatment are emerging, e. g. combinations with Venetoclax...These data support that addition of bisantrene to HMA backbone therapy may provide an important new treatment strategy in AML. A prospective Phase Ib/II trial is being planned to evaluate this new therapeutic approach."

Combination therapy • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • IDH2 • KIT • KRAS • NPM1 • NRAS • WT1

Race Oncology secures ethics approval to launch HARNESS-1 Phase 1a/b lung cancer trial of RC220 (Proactiveinvestors) - "The St Vincent’s Hospital Melbourne Human Research Ethics Committee (HREC) has cleared the study, which will investigate the safety, tolerability and pharmacokinetics of RC220 (E,E-bisantrene, RCDS1) alongside osimertinib (Tagrisso; AstraZeneca) in adult patients with non-small cell lung cancer (NSCLC) harbouring activating epidermal growth factor receptor mutations (EGFRm)....First patient enrolment is expected in late Q4 2025 or early Q1 2026."

New P1 trial • Non Small Cell Lung Cancer

Hnrnpc and m6a RNA Methylation Control Oncogenic Transcription and Metabolism in T-Cell Leukemia (ASH 2024) - "The use of the FTO inhibitors CS1 (bisantrene) and CS2 (brequinar, Su R. et al., Cancer Cell, 2020) for the treatment of cell lines, patient samples ex vivo, and a xenograft T-ALL model showed high efficacy of the drugs in inhibiting T-ALL. Combining FTO inhibitors with dexamethasone and other chemotherapeutic agents demonstrated synergy in inhibiting T-ALL. These findings indicate that T-ALL exhibits dysregulated RNA methylation and demonstrate the potential of targeting HNRNPC and FTO as therapeutic strategies in T-ALL."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • HMGCS1 • HNRNPC • METTL3

Epitranscriptomic reprogramming and enzalutamide resistance in prostate cancer (PCF 2025) - "Novel small molecule inhibitors of METTL3 are in phase I clinical trials and derivatives of drugs and candidates such as entacapone, meclofenamic acid, brequinar and bisantrene that inhibit FTO are in development. Targeting m6A and its regulators may provide a novel mechanism to alter androgen and androgen receptor signalling offering therapeutic potential on its own and in combination with other therapies including enzalutamide. Funding Acknowledgements:This work has been funded by Prostate Cancer Foundation and John Black Charitable Foundation Challenge Awards: 20CHAL04 and 22CHAL11; and Prostate Cancer UK Research Innovation Award RIA21-ST2- 002; the University of Nottingham, unrestricted gifts from the Stanyard, Moody and Kenyon families to support prostate cancer research and the BBSRC doctoral training program award: BB/I024291/1. Conflicts of Interest Disclosure Statement: No conflicts of interest to disclose."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ALKBH5 • METTL3

Race Oncology extends patent protection and advances Phase 1 RC220 trial in September quarter (Proactiveinvestors) - "Race expects increased recruitment in Q2 FY26 as up to five more sites come online across Hong Kong and South Korea, supported by MFDS IND approval in Korea late in the quarter....Race filed three patents covering the composition, manufacture, formulation and use of the active (E,E)-bisantrene isoform — potentially resetting patent life with up to 20 years of protection over the API in RC220 and opening a pathway for RC110 to move toward a pivotal AML Phase 3 (partner-dependent)."

Patent • Trial status • Acute Myelogenous Leukemia • Solid Tumor

Discovery of bisantrene as a dual-cardioprotective and anticancer agent in combination with doxorubicin (ESMO 2025) - P1 | "An improved proprietary formulation of Bis, RC220, is being evaluated in combination with Dox in a Phase I trial of patients with diverse solid tumors (NCT06815575). Legal entity responsible for the study Race Oncology Ltd Funding Race Oncology Ltd"

Combination therapy • Breast Cancer • Oncology • Solid Tumor

Race Oncology flags dual cardioprotection and anticancer effects for (E,E)-bisantrene combo at ESMO 2025 (Proactiveinvestors) - "Adding bisantrene to doxorubicin lowered the IC50 across a panel of 111 human cancer cell lines spanning 22 tissue types, indicating higher potency than doxorubicin alone. In a 4T1 syngeneic breast cancer mouse model, the combination improved survival versus either agent alone...Bisantrene reduced doxorubicin-induced cytotoxicity in primary human cardiomyocytes and neonatal rat ventricular myocytes and mitigated doxorubicin-driven beat-rate increases in induced pluripotent stem cell–derived cardiomyocytes...Race reports the cardioprotective effect follows a clinically validated pathway — reducing topoisomerase-2β–mediated double-strand DNA breaks in cardiomyocytes — similar to the mechanism of FDA-approved dexrazoxane."

Preclinical • Breast Cancer

Race Oncology to host investor webinar on (E,E)-bisantrene mechanism discovery (Proactiveinvestors) - "During the webinar, executive hair Dr Pete Smith and managing director & CEO Dr Daniel Tillett will present supporting data on the mechanism, explain its significance for Race’s clinical and commercial plans, and address investor questions."

Clinical • Acute Myelogenous Leukemia • Breast Cancer

Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling. (PubMed, J Clin Immunol) - "Our iPSC-based disease modeling and drug investigation approach provides a robust platform for validating the efficacy and toxicity of candidate therapeutic agents for rare and intractable human diseases such as type I interferonopathy."

Journal • Aicardi Goutieres Syndrome • Genetic Disorders • Inflammation • Interferonopathies • IFIH1 • IFNA1 • OASL

Race Oncology…has received Investigational New Drug (IND) approval from the Republic of Korea’s Ministry of Food and Drug Safety (MFDS) to begin a Phase 1 clinical trial of RC220, its novel formulation of (E,E)-bisantrene (Proactiveinvestors) - "The approval allows patient recruitment to start at three leading Korean hospitals - Samsung Medical Center, Asan Medical Center and EWHA Woman’s University Medical Center - all of which already hold ethics approval. A fourth site, Severance Hospital, is expected to come online following Institutional Review Board clearance in the coming weeks."

Trial status • Solid Tumor

Race Oncology moves to secure IP protection for ‘breakthrough' bisantrene discovery (Proactiveinvestors) - "The company’s scientists found that bisantrene is composed of three light-sensitive photoisomers, with one — the (E,E)-bisantrene isomer — showing significant anticancer activity. Based on this discovery, Race has submitted patent applications covering the isomer’s chemical structure, as well as its manufacturing, formulation and use. If granted, the patents would extend composition of matter protection until 2045."

Patent • Acute Myelogenous Leukemia • Solid Tumor

Results of Phase 2 of RC110 Bisantrene for AML Published in the British Journal of Haematology (Race Oncology Press Release) - P2 | N=19 | NCT04989335 | "Up to 17 patients to be enrolled into a Phase 2 expansion efficacy cohort using a 2-stage Simon design with the first nine patients enrolled and treated with the recommended Phase 2 dose of Bis/Clo/Flu...As previously disclosed, six of the 15 evaluable patients (40%) in the Phase 2 efficacy stage clinically responded to the Bis/Clo/Flu treatment (five complete responses, one partial response), with three of the clinical responders having active extramedullary disease...Five of the six treatment-responsive patients were bridged to a potentially curative stem cell transplant within one to three months of receiving treatment. Of the five stem-cell transplanted patients, three have since died: one from graft-versus-host disease at Day 45 after transplant, one from disease relapse four months after transplant, and one from infection at Day 610 after treatment. One patient remains alive and free of disease more than 2 years after Bis/Clo/Flo treatment."

P2 data • Acute Myelogenous Leukemia

Bisantrene in combination with fludarabine and clofarabine as salvage therapy for adult patients with refractory or relapsed acute myeloid leukaemia (AML)-An open-label, phase I/II study. (PubMed, Br J Haematol) - P2 | "Responses were transient, but six patients, including four undergoing second allo-HSCTs, proceeded to allo-HSCT within 1-3 months post-treatment. The Bis/Clo/Flu regimen demonstrated a tolerable safety profile and potential as a bridging therapy in high-risk, heavily pretreated AML."

Journal • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cardiovascular • Hematological Malignancies • Hepatology • Leukemia • Oncology • Transplantation

Race Oncology doses first patient in trial of RC220 + doxorubicin for solid tumours (Proactiveinvestors) - "Race Oncology Ltd...has successfully dosed the first patient with the combination of its lead drug RC220 and doxorubicin in its Phase 1 clinical trial targeting advanced solid tumours. The treatment, administered at the Southside Cancer Care Centre in Miranda, NSW, marks a significant milestone in the company's clinical development program."

Trial status • Oncology • Solid Tumor

Race Oncology hails key milestone with first patient safely dosed in RC220 solid tumour clinical trial (Proactiveinvestors) - "Race Oncology Ltd has kicked off its flagship oncology trial, dosing the first patient in its Phase 1 clinical trial investigating RC220 for the treatment of advanced solid tumours....With a total of 20 additional patients anticipated for the second stage, the study will also assess early indicators of anticancer activity and cardioprotection. Trial sites have been opened in Australia, with expansion planned to Hong Kong and South Korea."

Trial status • Oncology • Solid Tumor

A Safety and Pharmacokinetics Study of RC220 Combined With Doxorubicin in Adult Participants With Solid Tumours. (clinicaltrials.gov) - P1 | N=53 | Recruiting | Sponsor: Race Oncology Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Race opens first Australian clinical site for RC220 Phase 1 solid tumour trial (BiotechDispatch) - "Race Oncology...has announced the site activation of Southside Cancer Care Centre in Sydney after receiving governance approval enabling the commencement of patient enrolment for its Phase 1 clinical trial of RC220 in combination with doxorubicin in advanced solid tumours patients...The company said the Phase 1 trial will be open-label and conducted across multiple sites in Australia, Hong Kong and South Korea....The trial will use ascending doses of RC220 in up to 33 patients to determine the safety, tolerability, pharmacokinetics, maximum tolerated combined dose (MTCD) in combination with doxorubicin, and effects on a range of clinical biomarkers."

Enrollment open • Trial status • Solid Tumor

Anticancer drugs targeting topoisomerase II for antifungal treatment. (PubMed, Sci Rep) - "Idarubicin, epirubicin, and bisantrene appeared to be even more effective inhibitors of yeast enzyme than its human counterpart. In fungal cells idarubicin exhibited a multifaceted mechanisms of action, including nuclear DNA fragmentation, disruption of mitochondrial network architecture and mitochondrial DNA aggregation as well as oxidative stress induction. Our results indicate that fungal topoisomerase II targeting is worth considering in antifungal treatment and the reported drugs may serve as a starting point for the reinnovation of a new molecule."

Journal • Oncology

Race Oncology garners ethics approval for RC220 Phase 1 solid tumour trial (Proactiveinvestors) - "Race Oncology Ltd has the ethics green light from Bellberry Human Research Ethics Committee (HREC) for its Phase 1 dose escalation clinical trial assessing RC220 bisantrene alone and in combination with doxorubicin, in patients with solid tumours....The trial will assess the safety, tolerability and pharmacokinetics of RC220 and will proceed under the supervision of principal investigator Dr Mahmood Alam as an open-label, multi-centre, Phase 1 study conducted in two stages....Race expects that most Australian sites will be activated by George Clinical in Q1 or Q2 of the 2025 calendar year. The Hong Kong and South Korean sites have a longer regulatory review process, and activation is expected in Q3 2025."

Trial status • Solid Tumor

A patenting perspective of fat mass and obesity associated protein (FTO) inhibitors: 2017-present. (PubMed, Expert Opin Ther Pat) - "Remarkedly, the FTO inhibitor CS1 (Bisantrene) has advanced to clinical trials for treating acute myeloid leukemia (AML). The successful advancement of CS1 into clinical trials would continuingly stimulate researches on RNA epigenetic enzymes targeted first-in-class anticancer drug discovery."

Journal • Genetic Disorders • Hematological Malignancies • Leukemia • Obesity • Oncology

Race Oncology partners with George Clinical for multi-site Phase 1 trial (Proactiveinvestors) - "Race Oncology Ltd has executed a Work Order (WO) contract with Contract Research Organisation (CRO) George Clinical International to support the Phase 1 RAC-010 trial of RC220 bisantrene in combination with doxorubicin. The total contract value is A$8,582,117....The study, conducted across sites in Australia, Hong Kong, and South Korea, aims to assess human safety and pharmacokinetics, establish the maximum tolerated combined dose, and provide initial clinical data on RC220’s cardioprotective, anticancer, and m6A RNA activity."

Commercial • Oncology • Solid Tumor

A Safety and Pharmacokinetics Study of RC220 Combined With Doxorubicin in Adult Participants With Solid Tumours. (clinicaltrials.gov) - P1 | N=53 | Not yet recruiting | Sponsor: Race Oncology Ltd

New P1 trial • Oncology • Solid Tumor

Race Oncology awarded Orphan Drug designation extension for RC220 for acute myeloid leukemia; shares up (Proactiveinvestors) - "Race Oncology Ltd...has welcomed the extension of the company’s proprietary formulation of bisantrene, RC220, as an Orphan Drug Designation (ODD) by the US Federal Drug Administration (FDA) for the treatment of acute myeloid leukemia (AML)...'Orphan Drug Designation is a major asset beyond AML as it enables Race to work closely and constructively with the FDA on all of our RC220 bisantrene clinical programs as we progress towards opening an FDA IND in 2025'..."

IND • Orphan drug • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology