Zantrene (bisantrene) / Racura Oncology - LARVOL DELTA

Racura Oncology Limited…is pleased to announce that the Safety Review Committee (SRC) has completed its review of safety data from the HARNESS-1 trial single-patient first cohort, who received RC220 at 50 mg/m2 with osimertinib 80 mg daily (Racura Oncology Press Release) - "No dose-limiting toxicities or treatment-related safety concerns were identified during the safety observation period. In the past week, after the trial safety observation period had ended, the patient reported moderate (Grade 2) symptoms consistent with colitis...The SRC has recommended as a prudent precaution, that one additional patient receive RC220 at 50 mg/m2 with 80 mg of osimertinib before dose escalation to 100 mg/m2 occurs. This SRC recommendation allows continued progress of the HARNESS-1 trial and enables an eligible patient waiting to receive treatment with RC220 to be enrolled without protocol modification or delay while the cause of the Grade 2 colitis is explored. With two patients currently awaiting an open trial slot at Monash Health, recruitment is now underway to treat the next patient. The SRC is expected to meet again in the next 6–8 weeks to evaluate the safety data from the second patient."

Trial status • Non Small Cell Lung Cancer

Racura Oncology…has dosed the first patient in Phase 1 of its Harness-1 multi-centre clinical trial of development drug RC220 to treat epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). (Small Caps) - "The patient received an intravenous infusion of 50 milligrams per square metre RC220 by principal investigator associate professor Surein Arulananda and his team at Monash Health in Victoria, with no adverse events observed. Racura’s trial is evaluating whether RC220 can be safely combined with the standard-of-care tyrosine kinase inhibitor (TKI) osimertinib (sold under brand names Tagrisso or AstraZeneca) in patients with this form of cancer for whom resistance to certain TKI treatments remains a significant clinical challenge."

Trial status • Non Small Cell Lung Cancer

HARNESS-1: A Study of the Safety, Pharmacokinetics and Exploratory Efficacy ofnRC220 in Combination with Osimertinib in Adult Patients with Non-nSmall Cell Lung Cancer. (ANZCTR) - P1 | N=40 | Recruiting | Sponsor: Racura Oncology Ltd. | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2026

Enrollment open • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Racura Oncology Announces Positive Safety Review Committee Recommendation in ongoing CPACS Clinical Trial (PRNewswire) - "Following its review, the SRC recommended that the study continue, noting no safety concerns in patients treated with 40mg/m2 of RC220 as monotherapy, or 40mg/m2 of RC220 in combination with 60mg/m2 of doxorubicin, in the first patient cohort of this groundbreaking trial....Based on this positive SRC recommendation, Racura plans to proceed to screening of new eligible patients for enrolment in Cohort 2 (80mg/m2 RC220 dose level) using an updated trial protocol, which includes an initial lead-in safety monotherapy cycle of doxorubicin prior to the administration of RC220....The Company has received the SRC's formal written recommendation and has promptly notified the clinical trial sites to initiate enrolment in Cohort 2, as patients present and meet the eligibility criteria."

DSMB • Trial status • Solid Tumor

(E,E)-bisantrene Discovered to Function via Silencing of c-MYC Expression (The Manila Times) - "At the American Association for Cancer Research (AACR) Annual Meeting 2026, Racura presented new preclinical data demonstrating that (E,E)-bisantrene directly binds and stabilizes G4 DNA structures within the c-MYC gene promoter region, resulting in potent suppression of c-MYC expression and broad cytotoxic activity in a wide range of cancer models...The MYC protein functions as a master regulator of gene expression, governing thousands of genes involved in cell growth, differentiation, survival, metabolic reprogramming, chemotherapy resistance, and immune surveillance."

Preclinical • Acute Myelogenous Leukemia • Breast Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor

Racura Oncology & University of Wollongong granted NSW Government TechVoucher to study (E,E)-bisantrene in BRCA-mutated breast & ovarian cancers (Racura Oncology Press Release) - "University of Wollongong and Racura Oncology have been granted funding under the NSW Government TechVouchers program to study the efficacy of (E,E)-bisantrene in BRCA-mutated breast and ovarian cancers...This new preclinical collaboration is designed to evaluate the anticancer activity of (E,E)-bisantrene in preclinical BRCA-mutated breast and ovarian cancer models and will be led by Dr Saurabh Satija at the University of Wollongong....Results from this collaboration will emerge over the next 12 months and are expected to be published in high impact scientific journal(s)."

Licensing / partnership • Preclinical • Breast Cancer • Ovarian Cancer

(E,E)-bisantrene silences c-MYC expression by stabilizing its promotor region G-quadruplex (AACR 2026) - "(E,E)-bisantrene binds to and stabilizes the G4 structure contained within the c-MYC promotor region, leading to silencing of c-MYC gene expression. These studies support clinical evaluation of (E,E)-bisantrene as a new G4-targeting drug in MYC-driven tumors."

Oncology • ATF4 • MYC

Racura Oncology Doses First Patient in Phase 1 Lung Cancer Trial of RC220 with Osimertinib (TipRanks) - "The multi-centre Phase 1a/b trial uses circulating tumour DNA to screen and enroll patients and features an accelerated dose-escalation design followed by a Bayesian Optimal Interval approach to identify the maximum tolerated dose of RC220. Once this is established, the trial will move to a randomised, double-blind Phase 1b dose-expansion stage, evaluating safety, pharmacokinetics, and key clinical outcomes such as progression-free and overall survival, with additional sites expected to come online, underscoring Racura’s clinical development momentum."

Trial status • Non Small Cell Lung Cancer

Racura teams with Purdue Uni to advance cancer drug candidate (The Australian) - "Early research at Purdue confirms (E,E)-bisantrene binds directly to the MYC-G4 DNA, forming a 2:1 drug-to-MYC-G4 complex...The collaboration will: Study how (E,E)-bisantrene binds to MYC G4 DNA and affects regulatory proteins controlling MYC transcription; Investigate the detailed molecular interactions that silence the MYC gene; Conduct high-resolution structural studies to characterise (E,E)-bisantrene binding to MYC G4...Racura said results from the research collaboration will emerge over the next 24 months and are expected to be published in a high-impact scientific journal."

Licensing / partnership • Preclinical • Acute Myelogenous Leukemia • Breast Cancer • Ovarian Cancer

Racura to Present (E,E)-bisantrene MYC Gene Silencing Data at American Association of Cancer Research Annual Meeting 2026 (Listcorp) - "Presentation supports the Phase 1 HARNESS-1 trial of RC220 in combination with osimertinib in EGFRm non-small cell lung cancer and the Phase 3 trial of RC220 in acute myeloid leukemia....The presentation will share results from preclinical studies demonstrating that (E,E)-bisantrene silences MYC gene expression by stabilizing a G-quadruplex (G4) DNA sequence in the promoter region of the MYC oncogene...Nuclear Magnetic Resonance (NMR) and molecular docking modeling demonstrate that G4 DNA stabilisation requires two molecules of (E,E)-bisantrene. RNA-Seq analysis revealed that MYC-dependent downstream target genes are potently suppressed by (E,E)-bisantrene in non-small cell lung cancer cells...(E,E)-bisantrene was found to stabilize the c-MYC promoter G4 region, producing similar increases in melting temperature to other G4 ligands (i.e., pidnarulex and pyridostatin)."

Preclinical • Trial status • Acute Myelogenous Leukemia • Non Small Cell Lung Cancer

Racura Oncology Advances Lung Cancer Program with HARNESS-1 Trial Approval (Small Caps) - "Monash Health has granted governance approval for the trial, which targets EGFR-mutant NSCLC and aims to address resistance to osimertinib. Site initiation training is scheduled for March 23, 2026, with first patient recruitment anticipated shortly thereafter....The trial will employ ctDNA screening and an accelerated single-patient dose escalation cohort, enrolling between 12 and 40 patients."

Trial status • Non Small Cell Lung Cancer

HARNESS-1: A Study of the Safety, Pharmacokinetics and Exploratory Efficacy ofnRC220 in Combination with Osimertinib in Adult Patients with Non-nSmall Cell Lung Cancer. (ANZCTR) - P1 | N=40 | Not yet recruiting | Sponsor: Racura Oncology Ltd.

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Racura Oncology Research Symposium Sydney (Racura Oncology Press Release) - "The event will provide investors with a deeper understanding of the differentiated mechanism of action of (E,E)-bisantrene, the importance of the current clinical programs, and the commercialisation strategy of the company."

Clinical • Acute Myelogenous Leukemia • Non Small Cell Lung Cancer

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