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Murray Ward
While many cancer companies spend billions trying to make stronger chemotherapies, Melbourne-based Amplia Therapeutics is taking a different path, developing a “shield-breaking” treatment that makes other multi-billion-dollar drugs work better.
Following the world’s premier American Society of Clinical Oncology (ASCO) conference in Chicago, where a new class of drugs known as “kRAS inhibitors” took centre stage, Amplia’s chief executive officer Dr Chris Burns laid out a compelling case for its lead drug, narmafotinib, to play a pivotal role in one of the hottest new areas of cancer treatment.
Excitement followed the presentation of phase three data for a groundbreaking drug called daraxonrasib, which showed significantly improved survival rates in pancreatic cancer patients. The results reinforced the view that targeting the mutant kRAS protein, found in around 90 per cent of pancreatic cancers, can meaningfully slow disease progression.
However, discussions at ASCO made it clear these new agents are not a complete answer on their own. Whilst promising, they are not curative, often involve significant side effects and can quickly become subject to treatment resistance. There is growing recognition that the full potential of kRAS inhibition will likely be realised only through combination therapies.
And this is where Amplia believes it is particularly well placed.
Pancreatic tumours are notoriously difficult to treat because they surround themselves with a dense wall of scar-like tissue that acts as a biological fortress, blocking chemotherapy drugs from penetrating the cancer core. Amplia’s drug, narmafotinib, is an inhibitor of a protein known as Focal Adhesion Kinase, or “FAK”, and is designed to dismantle that defensive shield.
Preclinical data show narmafotinib can boost the effectiveness of kRAS inhibitors and may even dismantle the protective protein shell surrounding cancer cells, potentially shutting down a key escape route that enables drug resistance.
Amplia Therapeutics chief executive officer and managing director Dr Chris Burns said: “Over the past two years, we have been steadily building our understanding of the potential value of combining FAK and kRAS inhibitors… More recent findings also indicate that narmafotinib may block known resistance pathways to these drugs. Importantly, both preclinical and clinical data from other FAK inhibitors continue to support this approach and strengthen our confidence in the opportunity.”
The company’s confidence is underpinned by some seriously impressive results from its own ACCENT clinical trial in pancreatic cancer. An independent analysis of that study, which combined narmafotinib with standard chemotherapy, showed a median overall survival of 11.1 months – a solid two-month improvement over the 8.5 to 9.2 months typically seen with chemotherapy alone.
Perhaps more startling was the trial’s complete response rate. The study recorded five confirmed complete responses from 64 patients, a rate of 7.8 per cent. For a notoriously aggressive disease such as pancreatic cancer, where historical data for chemotherapy alone shows a complete response rate of just 0.2 per cent, that figure is a genuine head-turner.
With more than 60 kRAS-targeting drugs now in clinical development, a massive commercial opportunity is opening up. Narmafotinib could potentially offer those drug developers a way to improve patient outcomes and differentiate their products from the pack. The company says its business development unit was on the ground at ASCO, meeting with several potential partners.
While the kRAS combination story builds, Amplia is also charging ahead with its own pivotal Phase 2b trial for narmafotinib in pancreatic cancer. As the world’s major drug companies pile into the kRAS space, they may well need a partner to make their drugs dance. Amplia looks like it’s already on the dance card.
Is your ASX-listed company doing something interesting? Contact: mattbirney@bullsnbears.com.au
