Biocurious: Behind Race Oncology’s quest to prevent chemo from being worse than the disease

Race Oncology hopes its drug candidate can protect the heart from the dangerous effect of chemotherapy.

Chemo can kill the cancer - and the heart as well. Pic via Getty

• Cancer survival has dramatically increased, but chemotherapy can lead to lasting organ damage

• Race plans to launch a cardioprotective study of a repurposed cancer drug, bisantrene

• Following an innovative options issue, Race is well cashed up to meet its objectives

Here’s the good news: more patients are surviving cancer and living longer after treatment.

In 2022 there were 18 million cancer survivors in the US and more than one million in Australia.

“Twenty to 30 years ago, if you were told you had metastatic, late-stage cancer you would have months to live at best,” says Race Oncology (ASX:RAC) CEO Dr Daniel Tillett.

“There’s been enormous progress in treating patients, so that many patients will live the rest of their lives and die of something else.”

And therein lies the bad news: the “something else” is likely to be heart failure or kidney and liver damage resulting not from the cancer, but the chemotherapy.

A classic case of the cure being worse than the disease.

“As a result, the damage inflicted by cancer treatments has become increasingly important,” Tillett says. “Regulators and drug companies are zeroing in on ways to mitigate or avoid the damage.”

You can teach an old drug new tricks

Race is tackling the problem of chemo-induced heart damage – the clinicians’ key priority – with its reformulated drug candidate called bisantrene (RAC-220).

The drug made it to market in France in 1988 and had clinical success in treating breast cancer and leukemia sans the heart damage.

The trouble is – and there’s always a problem – the drug crystallised in the blood after being injected. Ledle (now Pfizer) persevered and treated 2000 patients in clinical trials before losing interest.

In 2021 Race discovered that if were combined with doxorubicin, the leading anthracycline, the heart could be protected.

The most widely used chemotherapy, anthracyclines were discovered more than five decades ago. They’re still popular because they are effective and – being generic – they are cheap at $100 to $200 per dose.

“Usage is still growing, which is very unusual for an old drug that has been around for so long,” Tillett says.

But doctors typically give a maximum four doses because of the heart damage risk.

Heading to the clinic

Race has completed two acute myeloid leukemia (AML) trials with the old formulation, RC-110.

Now, a phase 1 trial of RAC-220 will use with cardio protection as the primary endpoint.

The study is on track to start in 2025 at the Sydney’s Southside Cancer Care Centre, the lead site, with targeted enrolment of 25 to 40 patients across ten local and offshore sites.

Because the drug is not targeting a specific cancer the trial is “all comers” and can accept any patients with any type of cancer.

Pending ethics approval, the first patient should be recruited in the March quarter.

In essence, the study aims to show that positive animal model results translate into humans. As they say in the biotech milieu, ‘everything works in mice’.

Race’s work was ‘back translated’, which means it originally was identified in people with the animal models developed to confirm the effect.

“We know in multiple different animal species that it works and how it works,” Tillett says.

The company hopes the data will be strong enough to support an application to carry out a follow-on trial in the US.

Tackling leukemia

Meanwhile, a completed phase 1b/2 investigator-sponsored trial studied the original bisantrene formulation, RC-110 to treat acute myeloid leukemia (AML).

Carried out at the at Israel’s Chaim Sheba Medical Centre, the phase 2 efficacy stage saw 40% of the patients with relapsed or refractory (treatment-resistant) AML responding to RC-110, in combination with the chemo drugs clofarabine and fludarabine.

“The results have stimulated further clinician interest in taking the drug forward in new AML trials,” Race executive chairman Dr Peter Smith told shareholders at the company’s AGM.

“We are still discussing future clinical trials with an Australian investigator in the AML field and will update our shareholders when we received a formal request for support.”

Investors enjoy the piggyback ride

Race is well cashed up, with $14.6 million in the bank as of the end of September 2024.

In an unusual ‘buy now, pay later’ fund raising, in November 2023 Race announced two tranches of bonus options, aimed at raising up to $36.7 million.

Investors got one option for every 20 shares, exercisable at 75 cents each, up to June 2024. For each option exercised, punters get three ‘piggyback’ options exercisable at $1.25 by May 2026.

The exercise of the in-the-money June 2024 options raised $5 million in November, with the potential for piggybacks to raise up to $25 million before they expire in June 2026.

In December, Race also pocketed a $5.25 million R&D tax refund.

The cardio protection trial has been costed at $9 million if the maximum 40 patients are recruited.

“Race is fully funded to the end of the decade if we run it correctly,” Tillett says. “We are run with a real eye on costs.”

Shortening the odds of success

Tillett says biotech is all about minimising risk at every turn, given any new drug candidate only has a 3% chance of making it to market.

Given bisantrene is “derisked and clinically proven”, the odds of success are more like 80%.

“We know the drug works and is safe,” Tillett says. “From an investor perspective, that’s better than throwing darts with your eyes shut.”

As a 10% Race shareholder, Tillett is heavily invested in Race’s success.

“All of that money has come out of my pocket, I haven’t been given and freebies along the way,” he says.

“Every time we spend a dollar, I know 10 cents of that is my money and I want to get it back.”

Fair enough!

The stakes are high for Race, which has a market cap of around $240 million after this year’s 64% share surge.

In 2023 doxorubicin was a US$1.5 billion-a-year market and the company estimates that expanding to cardio protection would expand the opportunity to US$7 billion.

If the heart protection angle fails to fly, at least bisantrene stands up as a more effective chemotherapy adjunct.

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

Originally published as Biocurious: Behind Race Oncology’s quest to prevent chemo from being worse than the disease