Race Oncology Ltd (ASX:RAC, OTC:RAONF) has today shared an update on its clinical and preclinical programs.
Today’s update follows last month’s fully funded updated clinical development strategy focused on anthracycline cardioprotection plus anti-cancer activity in solid tumours. The program is designed to deliver proof-of-concept clinical data on the cardioprotection opportunity for bisantrene within the constraints of the current capital market.
Bonus options
Also announced last month was a bonus option issue, awarding shareholders one option for every 20 shares held with an exercise price of 75 cents and exercise date before June 4, 2024. The exercise of these options provides a further three piggyback options for every bonus option exercised with an exercise price of $1.25 and exercise date before May 29, 2026.
The bonus options are intended to reward loyal shareholders and provide funding to support future clinical trials of RC220, Race’s reformulated bisantrene, in AML and solid tumours.
The company thanked shareholders that have exercised their bonus options early, saying funds from these early option exercises will be used to accelerate and further de-risk the clinical development of bisantrene and undertake additional preclinical studies.
Preclinical activities
RC220 development
Race says significant progress has been made in the manufacturing of RC220 by Societal CDMO, who issued a certificate of testing for the first engineering batch of Race’s proprietary bisantrene formulation, RC220, confirming that the drug product meets manufacturing quality specifications.
This clears RC220 for use in good laboratory practice (GLP) toxicology and safety pharmacology studies and significantly de-risks the RC220 current good manufacturing practice (cGMP) campaign underway at leading global contract development and manufacturing organisation, Ardena.
Race’s innovative RC220 bisantrene formulation is designed to enable safe administration of bisantrene to patients via peripheral vein — arm or leg — intravenous infusions. More than 1,500 vials of RC220 were manufactured by Societal.
The company confirms that progress of the final cGMP batch of RC220 continues at Ardena and delivery remains on track for release in the coming quarter, enabling clinical trials to begin once the non-clinical toxicology data package is finalised.
Non-clinical toxicology program
Race notes it has signed contracts with Attentive Science (USA) and Agilex Biolabs (Australia) to complete a package of good laboratory practice toxicology and safety pharmacology studies.
These studies are required to support human clinical trials of Race’s flagship bisantrene formulation for peripheral infusion, RC220. Extensive historical and modern clinical data has been collected around the safety and efficacy of bisantrene in humans.
While RC220 contains the same active pharmaceutical ingredient as previous formulations, regulators consider it a new ‘drug product’. All new drug products must pass a panel of toxicology and safety pharmacology preclinical studies to show that they are safe for use in humans and to establish a safe starting dose for Phase 1 dose-escalation studies.
The data for RC220 will be used in all regulatory submissions requesting approval for its use in clinical trials, including any US FDA Investigational New Drug (IND) applications.
The company says that the non-clinical data program is progressing well and remains on track to be finalised by late Q2 2024.
AML
Scientists at Race in collaboration with researchers from the University of Newcastle submitted a mouse study exploring low dose bisantrene in combination with decitabine as a treatment for AML for presentation at the 65th American Society of Hematology Annual Meeting. The study abstract was not able to be accepted as a presentation at the ASH meeting due to space constraints but it was published in the prestigious journal, Blood.
The in vitro activity of bisantrene was initially assessed in a range of human and mouse AML cell lines covering the major molecular and clinical subtypes. All cells were sensitive to bisantrene. When tested against primary patient AML samples, 30.6% responded strongly to bisantrene treatment ex vivo.
The in vivo efficacy of bisantrene alone and in combination with decitabine were examined. Bisantrene significantly reduced leukemic burden and increased median survival compared to vehicle control, and significantly reduced leukemic burden and increased median survival in a dose and schedule-dependent manner in the patient-derived xenograft model.
The combination of bisantrene and decitabine significantly improved survival relative to vehicle control. The combination also reduced leukemic infiltration to extramedullary sites (spleen, liver, uterus, brain).
The data is highly supportive of the proposed investigator initiated clinical trial of RC220 in combination with oral decitabine as a low intensity treatment for AML and is expected to be published in a high impact peer reviewed journal in 2024.
Clinical activities
Sheba 2
Interim results were released from an ongoing investigator-initiated Phase 2 trial of bisantrene in combination with fludarabine and clofarabine in relapsed or refractory acute myeloid leukaemia (R/R AML) patients.
The trial is running at the Sheba Medical Centre, Israel, under the supervision of key opinion leader Professor Arnon Nagler. Results of this trial were chosen by the conference committee for presentation at the American Society of Hematology 65th Annual Conference held on the 9-12 December 2023.
The oral poster presentation describes clinical results from the first 15 evaluable patients treated since August 2021.
The results of the trial were highly positive, with six of the 15 evaluable patients responding 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 able to be bridged to a stem cell transplant within one to three months of treatment.
Of the five stem-cell transplanted patients, three have since died; one from graft-versus-host disease, one who relapsed within four months of transplant, and one of infection after two years. The two other patients remain disease free and in complete remission.
The trial is continuing to recruit the final two patients and shareholders can expect to be updated when the final patient finishes treatment in the first half of 2024. It is expected the study will be published in a high impact peer reviewed journal in 2024.
Cardio-protection and m6A RNA Solid Tumour Phase 1a/b Trial of RC220
Race says significant progress has been made towards initiating the Phase 1a/b trial in the second half of 2024 exploring the use of bisantrene as a cardio-protective anti-cancer agent for use in patients where an anthracycline treatment is indicated. Strong clinical interest has been fielded from a range of Australian oncologists interested in participating in the trial.
The company expects to provide regular updates on contract research organisation selection, investigator and site selection, human ethics and governance approvals, along with first patient treatment in 2024.
Investigator Initiated Trial of RC220 in AML
Race received a proposal from an experienced haematologist to undertake an investigator-initiated Phase 1/2 trial of RC220 in combination with oral decitabine in Australia, building on the preclinical mouse work untaken by Race’s collaborators at the University of Newcastle and the recent Sheba Phase 2 AML results.
This trial offers Race a low-cost clinical proof-of-concept of bisantrene in AML compatible with modern clinical practice. Initiation of this trial depends on available funding from the bonus option.