Zantrene (bisantrene) / Race Oncology - LARVOL DELTA

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

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 • HMGCS1 • HNRNPC • METTL3

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

Race Oncology’s new study highlights bisantrene's efficacy in treatment for acute myeloid leukemia (Proactiveinvestors) - "Race Oncology Ltd...has struck another blow in the fight against acute myeloid leukemia (AML) with the release of a study investigating the potent anticancer activity of the company’s lead asset, bisantrene....The study...reveals that bisantrene not only excels in eradicating AML cells derived from patients but also significantly enhances anticancer activity when combined with the standard care drug, decitabine. This synergy between bisantrene and decitabine was evident in both laboratory and animal models, highlighting the potential of this combination as a low-intensity treatment option for AML patients."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Race Oncology receives $4 million R&D tax refund (Proactiveinvestors) - "Race Oncology Ltd...has received a $4 million R&D tax incentive from the Australian Taxation Office (ATO) for FY2023...'We are grateful to receive this refund and look forward to utilising the funds to accelerate the clinical development of bisantrene in 2024 and beyond.'"

Financing • Hematological Malignancies • Oncology • Solid Tumor

Preclinical evaluation of bisantrene alone and in combination with decitabine for Acute Myeloid Leukemia (NDLR 2024) - No abstract available

Combination therapy • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

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 • Cardiovascular • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3 • IDH2 • KIT • KRAS • NPM1 • NRAS • WT1

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 • Hepatology • Immunology • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombosis • Transplantation • KMT2A

Race Oncology to present “highly positive” AML clinical trial outcomes at American Society of Hematology annual conference (Proactiveinvestors) - P2 | N=29 | NCT04989335 | "Race Oncology Ltd...has fielded 'impressive' Phase 2 clinical trial results from its Acute Myeloid Leukaemia (AML) clinical trial....Of the 15 evaluable patients, six responded to bisantrene/clofarabine/fludarabine treatment, with five complete responses and one partial response, with three of the clinical responders having active extramedullary disease (EMD). Five of the six treatment-responsive patients were able to be bridged to a stem cell transplant within one to three months of treatment....The two other patients remain disease-free and in complete remission....The trial abstract has been peer-reviewed and the interim results have been selected by the conference committee for presentation at the prestigious American Society of Hematology 65th Annual Conference, December 9-12, 2023."

P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

BISECT: A Study of Bisantrene Combined With Cytarabine or With Decitabine for Adult Subjects With Extramedullary AML and MDS (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Race Oncology Ltd | N=60 ➔ 0 | Trial completion date: Jun 2027 ➔ Aug 2023 | Recruiting ➔ Withdrawn | Trial primary completion date: Jul 2025 ➔ Aug 2023

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Repeatability of quantitative individual lesion and total disease multiparametric whole-body MRI measurements in prostate cancer bone metastases. (PubMed, Br J Radiol) - "Lesion mean ADC RC was 12.5%, mean b900 SI RC 137%, normalised mean b900 SI RC 110%, rFF% RC 3.2 and target MD RC 5.5 mm (16.3%)...APC bone metastases' ADC, rFF% and maximum diameter, tDV and gADC show good repeatability. APC bone metastases' mean ADC and rFF% measurements of single lesions and global disease volumes are repeatable, supporting their potential role as quantitative biomarkers in metastatic bone disease."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Race Strategic Update August 2023 (PRNewswire) - "Race plans to take bisantrene RC220 into a Phase 1/2 clinical trial in combination with the anthracycline doxorubicin, the most widely used chemotherapy agent in mBC. This trial will be initiated once GMP RC220 is available, and after the completion of toxicology studies, ethics submission, and regulatory approvals. The expected timeframe for trial commencement is Q3 CY 2024....Race plans to take bisantrene into a Phase 1b/2a clinical trial where it will be investigated in combination with oral decitabine/cedazuridine in dose escalation studies, followed by a triple combination with a standard of care treatment. The initial phase will provide a transition from the original RC110 (central vein administration) formulation to RC220. The trial is planned to start in late Q4 CY 2023, with transitional phases from RC110 to RC220 in 2024."

New P1 trial • Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Oncology

Race executes agreement with Ardena for GMP manufacturing of RC220 (PRNewswire) - "Race Oncology Limited ('Race') is pleased to announce that it has signed an agreement with leading global contract development and manufacturing organisation (CDMO), Ardena Holding NV (Ardena) to provide additional Good Manufacturing Practice (cGMP)-standard manufacturing capability for Race's flagship intravenous (IV) formulation of bisantrene, RC220....The partnership strengthens Race's existing manufacturing programs by serving as a primary source for EU compliant supplies of RC220 required for EU clinical studies. It also provides a backup source for US and Australian clinical programs."

Licensing / partnership • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Comment on "Fluorimetric sensing of ATP in water by an imidazolium hydrazone based sensor" by S. Farshbaf and P. Anzenbacher Jr., Chem. Commun., 2019, 55, 1770. (PubMed, Chem Commun (Camb)) - "Encouraged by the results presented in the parent study, we aimed to apply this strategy for physiologically relevant water-based buffers and - preferably - intracellular application. Here we present the results of our investigations and point to the limitations of bisantrene applications in vivo as the ATP sensor."

Journal

Race Oncology receives positive guidance on Zantrene at pre-IND meeting with FDA; shares rise (Proactiveinvestors) - "Race Oncology Ltd...has received confidential and constructive guidance during a pre-investigational new drug (pre-IND) meeting with the US Food and Drug Administration (FDA) for its asset Zantrene (bisantrene dihydrochloride)....In written correspondence, the FDA provided what the company called 'insightful and helpful feedback' on the proposed clinical development plan for Zantrene and acknowledged that acute myeloid leukemia (AML) continues to have significant unmet clinical needs which require new treatment solutions....Importantly, the FDA agreed that Race had adequately addressed outstanding clinical hold issues from an earlier IND application submitted in 2019....The FDA provided guidance on the data requirements for opening an IND for Zantrene, including helpful counsel related to the AML patient populations that should be studied."

FDA event • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

"#Race Develops Improved IV Formulation of #Zantrene https://t.co/SGJrytPKkN" (@1stOncology)

BISECT: A Study of Bisantrene Combined With Cytarabine or With Decitabine for Adult Subjects With Extramedullary AML and MDS (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Race Oncology Ltd

Combination therapy • New P1 trial • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology