• Leading cardiologist says bisantrene has potential to significantly change cancer treatment landscape
  • Bisantrene could minimise damage to the heart linked to many cancer therapies
  • New CEO is prioritising swift delivery of bisantrene to patients and maximising shareholder returns

For all the excitement about curing cancer or the disease going into remission, the relief for some patients can often be short-lived if the treatment leaves them with other potentially long-term health repercussions.

Cardiovascular health problems are typically the most common, but Race Oncology (ASX:RAC) is working to minimise damage to the heart linked to almost all cancer therapies with its core asset bisantrene.

The unique small molecule, anthracene-based chemotherapeutic has anti-cancer benefits, but most importantly it has reduced cardiotoxicity – meaning it is less likely to cause heart dysfunction.

University of Newcastle Professor Aaron Sverdlov is a cardiologist and clinician-scientist with a special interest in heart failure and cardio-oncology.

He told Stockhead, on average, patients living with and beyond cancer have 2-6 times the cardiovascular death/disease (CVD) risk of the general population.

“This increase in risk arises in the first year after diagnosis and persists for life,” Sverdlov says.

“The increased CVD risk among these patients results from shared risk factors (eg obesity and smoking), combined with the cardiotoxic effects of many cancer therapies.”

Sverdlov says almost all cancer therapies have been linked to cardiovascular effects, including conventional chemotherapy for example anthracyclines, microtubule inhibitors, taxanes and platins along with new targeted biological therapies and immunotherapies and chest radiation.

“Potential cardiovascular adverse effects may be acute or chronic and include hypertension, atherosclerosis, coronary artery disease, cardiac dysfunction, heart failure, myocarditis, valve disease, pericardial disease, thromboembolism, conduction defects and arrhythmias,” he says.

Sverdlov says the most studied chemotherapy agents, as far as effects on heart health is concerned, are anthracyclines with doxorubicin the most common drug in this class.

“These agents are still commonly used in the treatment of breast cancer, leukaemias and lymphomas as well as soft tissue tumours and are effective,” he says.

“Cardiotoxicity, which includes heart failure, is one of the main side effects limiting the use of these effective therapies.”

Prevalence of cardiotoxicity in cancer patients

Sverdlov says between 2005 and 2021 over 55% of all Australians treated for cancer were exposed to at least one potentially cardiotoxic anticancer medicine.

He says rates of cardiotoxicity vary from population to population and according to cancer type and treatment type, but generally are reported to be anywhere between 2% to >20% (for anthracyclines).

“Even taken at an average cardiotoxicity rate of 10%, this means that around 300,000 patients worldwide develop some form of cardiotoxicity and in Australia that number would be around 15,000 per year,” he says.

“Thus, reducing the burden of cardiotoxicity can provide benefit to tens of thousands of patients worldwide.”


The rich clinical history of Bisantrene

To understand how bisantrene can help reduce cardiovascular damage in cancer patients, here’s a little history lesson on the origins of the drug.

Bisantrene is a chemotherapy drug, originally developed in the 1970s and 1980s by a small French pharmaceutical firm called Lederle Laboratories for the treatment of a wide range of cancers, but with less dangerous side effects on the heart compared to existing chemotherapies.

RAC chief executive Daniel Tillett told Stockhead bisantrene proved very effective in patients and was even approved for the treatment of Acute Myeloid Leukaemia (AML) in France, however it suffered a serious flaw – it crystalised in the blood when injected into the patients.

“The original developers of bisantrene were able to overcome this crystallisation problem by infusing bisantrene slowly directly into the heart using what is known as a central line catheter,” he says.

“But this was unsurprisingly not popular with patients or doctors, as it is both risky and painful.

“This ultimately led to the company dropping the development of bisantrene and focusing their commercial efforts on a different chemotherapy drug.”

Years later, Tillett says, RAC scientists were able to reformulate bisantrene so the blood crystallisation problem is prevented, and the drug can be used by standard infusion via an arm or leg vein.

“This is not only less risky and painful for patients, but it provides valuable new intellectual property and patents for Race,” he says.


What bisantrene could mean for cancer patients?

Sverdlov says various cardiovascular medications, including renin-angiotensin-aldosterone system inhibitors, β-blockers and statins, have all been suggested, and tested for prevention of cardiotoxicity.

He says, however, the efficacy of these cardioprotective agents has not been consistently demonstrated and bisantrene represents a novel approach to cardioprotection.

“It is an anti-cancer medication effective against a number of different cancer types, yet has shown an ability to protect the heart from toxic side effects of anthracycline chemotherapy,” he says.

“This is a very novel approach for cardioprotection and if confirmed in clinical trials, it has the potential to significantly change the treatment landscape.”

He says more patients would be able to receive and complete their chemotherapy with less cardiovascular side effects.

Potentially more patients would also be able to receive life-saving chemotherapy, where in the past their cardiovascular risk would have been deemed too high to take the risk.

“The addition of bisantrene could reduce that risk and allow them to be given the combination therapy more safely,” he says.


Clinical trial show positive results

RAC recently released positive interim clinical results from an ongoing investigator-initiated Phase II study of bisantrene in combination with fludarabine and clofarabine in relapsed or refractory Acute Myeloid Leukaemia (R/R AML) patients.

From the first 15 patients in the Israel trial that could be evaluated, 40% showed an excellent response to treatment that made them eligible for a potentially curative stem cell (bone marrow) transplant.

“The patient response in the trial is especially impressive as the patients in the trial had all failed many different treatment therapies, an average of more than four with some patients failing up to nine prior treatments,” Tillett says.

“Without effective treatment all the patients faced a very bleak future with a life expectancy of only weeks.

“The final two patients in the trial are expected to be treated in the coming months and we will update our investors when the trial completes.”

Tillett says the company is looking to start the new Phase 1 trial for solid tumours in the second half of 2024 using its new formulation of bisantrene called RC220.

“While the trial is considered a Phase 1 trial because RC220 is considered a new drug, it is important to note that bisantrene has been used in 50 clinical trials with more than 1,500 patients,” he says.

He says this makes the risk profile of bisantrene very different to the usual Phase 1 drug which has never been used in humans.

“We know the dose the patients can tolerate, we know the drug works in humans and not just mice, and we know what side-effects to expect,” he says.

“A good analogy is being able to bet on the outcome of a horse race just after the winner has crossed the line.

“Yes, there is some risk that the winner might be disqualified by the stewards, but you have a pretty good bet.”


‘Large as is possible’ market opportunity

Tillett says reformulation of an existing drug can be very valuable, which combined with an enormous need for cancer treatment with less cardiotoxicity, makes the potential for bisantrene “as large as is possible in the pharmaceutical industry”.

“The results of the primary market research we tasked to external consultants and shared with the market in April 2023, conservatively calculated the annual sales for bisantrene to be more than US$5 billion per year if approved,” he says.

Tillett says a good example of a reformulated drug is development of Abraxane, which is a reformulation of the anti-cancer drug Taxol.

He says the original formulation of Taxol was very toxic because of the extra chemicals needed to keep the active drug (Paclitaxel) soluble in the blood.

“The developers of Abraxene were able to solubilise paclitaxel without needing these harsh chemicals making it safer to use in patients.”

Abraxane was acquired for US$2.9 billion by Celgene in 2010.


Attractive drug for large Pharma

Tillett has been chief executive of RAC since November, having previously served the company as chief scientific officer, executive director and as a consultant.

He says the focus of his leadership is on getting bisantrene to patients as quickly as possible and achieving the greatest return for shareholders.

“Historically, the best returns for investors in small pharmaceutical companies occur when the company is acquired by a large pharmaceutical company after Phase 2 results have been released,” he says.

“Small companies are nimble and innovative, but large companies have the financial and marketing resources to sell so combining the two can create a best of both worlds outcome.

“If Race generates the sort of impressive Phase 1 and 2 results that we believe are possible based on our preclinical studies and past clinical trials, then I am confident bisantrene will be a very attractive drug for large pharma.”


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At Stockhead, we tell it like it is. While Race Oncology is a Stockhead advertiser, they did not sponsor this article.