Race Oncology’s new corporate strategy has been designed to maximise the inherent value of its core asset bisantrene RC220 for both its cancer-fighting and cardio-protective properties.

Clinical stage global biotech Race Oncology (ASX:RAC) has announced a new corporate strategy detailing its clinical program and key areas of discovery for bisantrene.

After taking on the role in February CEO and managing director Damian Clarke-Bruce says RAC’s core focus is to impact cancer outcomes and address challenges of chemotherapeutic cardiotoxicity.

“Our mission is being at the heart of cancer care,” Clarke-Bruce says.

Clarke-Bruce brings deep global experience in drug commercialisation and portfolio strategy, having held executive roles at all stages of the drug development process, from preclinical evaluation through to successful commercial launch.

He says bisantrene is a unique product that is a small molecule, anthracene-based chemotherapeutic that has anti-cancer benefits but additionally reduced cardiotoxicity.

“I realised we had a great opportunity to refocus the company, reshape the clinical development plan and really build a position for commercialisation and partnership opportunities,” he says.

Clarke-Bruce and the RAC team has been gaining insights from physicians globally about best trial design, unmet need, along with doing analysis on different indications with international consultants to determine their focus areas.

“We worked out what would be the best bang for our buck but also optimal for patients,” he says.

RAC has identified three key focus areas: clinical development in metastatic breast cancer (mBC) and acute myeloid leukaemia (AML); and exploration of fat-mass and obesity-associated protein (FTO).

Metastatic Breast Cancer trial

Physicians treating breast cancer frequently treat with anthracyclines, a potent class of drugs, which while effective against cancer, often harm the heart.

Studies indicate that over 50% of anthracycline-treated patients develop heart conditions within six years. Other studies have shown 10-15% showing LVEF reductions > 10%, and approximately 5% develop heart failure after anthracycline. In addition, anthracyclines are restricted by lifetime limit as cumulative exposure increases the risk of cardiomyopathy. In the US, 80-85% metastatic patients have already reached their lifetime limit.

To address the issue Clarke-Bruce says a therapeutic strategy is needed for mBC patients that safeguard the heart while allowing more doses of anti-cancer treatments.

Bisantrene emerges as a solution for mBC, addressing this unmet need.

There are approximately36,000 mBC patients in the US per year, that bisantrene has the potential to improve outcomes, which also represents a significant commercial opportunity.

Historical Phase 2 and Phase 3 clinical trial data in 471 advanced/mBC patientsdemonstrates bisantrene’s anti-cancer efficacy and reduced cardiotoxicity .

Furthermore, preclinical studies confirm bisantrene’s ability to protect the heart from anthracycline-induced cardiotoxicity.

RAC plans to conduct a Phase 1b/2a clinical trial in triple negative and HR+/HER2- breast cancer patients, combining bisantrene RC220 with the commonly used anthracycline chemotherapy agent doxorubicin.

The trial aims to determine dosing, evaluate bisantrene RC220’s dual role as an anti-cancer and cardio-protective agent, and explore endpoints like FTO expression and biomarker assessment, and is forecast to start in Q3 CY2024.

Acute myeloid leukaemia trial

RAC’s is addressing the need for improved therapies with lower toxicity for approximately 16,000 AML patients in the US per year, who are considered unfit for other treatments.

Bisantrene monotherapy has a proven track record of efficacy and safety in AML, boasting a historical 46% complete response rate across 146 patients including paediatric cohorts in 10 relapsed/refractory clinical trials. In 1988, monotherapy bisantrene was approved in France for the treatment of AML.

Supported by strong clinical historical data, compelling clinical data in two independent trials by Prof Nagler, Sheba Medical Centre, and recent preclinical data of bisantrene in combination , RAC is confident in its AML clinical program.

The Phase 1b/2a clinical trial will combine bisantrene with oral decitabine/cedazuridine in dose escalation studies, followed by a triple combination including a standard of care treatment, of azacitadine and venetoclax.

The initial phase will provide a transition from the original RC110 (central vein administration) formulation to RC220.

The AML trial is an evolution of the RAC-006 study (which will now be called RAC-009) and enables the broader recruitment cohort of unfit AML patients defined as patients who are ≥70 and/or cannot tolerate high dose chemotherapy including those with relapsed/refractory AML or extramedullary disease.

The trial is planned to start in late Q4 CY 2023, with transitional phases from RC110 to RC220 in 2024.

Fat-mass and obesity-associated protein research

In July RAC executed a worldwide licence agreement to access City of Hope’s intellectual property (IP) which highlights bisantrene as a potent inhibitor of FTO.

City of Hope is one of the largest cancer research and treatment organisations in the US.

Clarke-Bruce says in 2020 City of Hope, led by Professor Jianjun Chen and his team, identified bisantrene as a potent inhibitor of the m6A pathway, linked to progression of multiple cancers.

Under the deal RAC will exclusively secure rights to a City of Hope patent application and associated know-how.

“We are working with them to understand the role of FTO, the development of biomarkers, and really what impact bisantrene will have on FTO,” he says.

He says RAC is excited to be working with City of Hope in preclinical and clinical studies and anticipate that FTO inhibition may offer a high impact, personalised medicine solution for cancer patients.

Follow-on indications

Clarke-Bruce says RAC’s concentrated efforts on mBC and AML have resulted in the identification of follow-on indications where promising data has been generated including melanoma, soft tissue sarcoma, renal cell small cell carcinoma, and lung cancer.

Early-stage breast cancer has also been included due to the potential extension of bisantrene’s use from mBC. Additionally, a paediatrics program is under consideration as bisantrene RC220’s human safety data accumulates.

The company decided on this focused approach in order to optimise resource allocation and funding.

Strong history

 Originating in the 1970s and 1980s to devise a less cardiotoxic alternative to anthracycline chemotherapy, bisantrene has proven effective and possesses a thoroughly documented safety record.

It has been scrutinised in more than 46 clinical trials and 70 peer-reviewed publications, with roughly 1,800 treated patients, demonstrating efficacy and a well characterised safety profile.

“Bisantrene was actually created by a small French pharmaceutical company named Lederle Laboratories,” Clarke-Bruce says.

He says the drug was approved in France for relapsed or refractory (R/R) AML but later withdrawn by subsequent owners of Lederle (Wyeth), not commercialised and lost to the clinical community for more than 30 years due to various M&A transactions.

He says what happened to bisantrene is not uncommon in the pharmaceutical industry with around 25% of all drugs that demonstrate good Phase 3 results end up not being approved for a range of non-clinical reasons.

However, now RAC is rediscovering bisantrene, which as a monotherapy has shown efficacy and safety.

“That’s what de-risks this program as most companies going into a Phase 1 or 2 trial are still trying to work out if their products work.

He says it is known that bisantrene kills cancer cells, provides significantly less cardiotoxicity and its safety profile is well understood.

“This just enhances our ability to take it forward in the direction we want to move forward,” Clarke-Bruce says.

“Where a chemotherapeutic is used, why would you not add bisantrene to enable that cardio-protection and increase the killing of cancer cells?”

“We has the potential to improve on the efficacy of  standard chemotherapy with improved safety.”

Reformulation of product

As key priority for RAC, Clarke-Bruce says,is the reformulation of the drug into peripheral IV dosing (bisantrene RC220), from the original central line (bisantrene RC110).

A central line or central venous catheter is much longer than a regular IV and more painful for the patient.

“If we are going into metastatic breast cancer, a central line is really not the best patient experience,” Clarke-Bruce says.

“We have a new formulation which will be completed by year end and that’s what we will be moving through to the market which will improve the ability to recruit patients, and provide a better patient experience.

“It will also provide significant IP, which will drive commercial value.”

Well-supported among physicians and patients

RAC has built global partnerships and collaborations working with leading experts worldwide including from City of Hope, Duke University, Harvard Medical School, Washington University, Memorial Sloan Kettering Cancer Center and University of Newcastle.

“We have shaped these trials through the feedback from physicians and also patients and I think sometimes that is missed early in development,” Clarke-Bruce says.

The experts say an effective cancer treatment which limits heart damage is much needed.

“It depends how carefully you look, but at least 30% of patients who are treated with anthracyclines have evidence of cardiac toxicity,” Harvard Medical School cardio-oncologist Professor Tom Neilan says.

“Toxicity is highest in the first year, but risk of heart failure remains increased for the rest of their life,” Washington University cardio-oncologist Professor Josh Mitchell says.

This article was developed in collaboration with Race Oncology, a Stockhead advertiser at the time of publishing.

This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.

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