Amplia Therapeutics (ASX:ATX): Battling pancreatic cancer with an FAK inhibitor

Amplia Therapeutics (ASX:ATX) is another ASX oncology biotech company, attempting to battle cancer. At first glance, it may not a unique company but when you dig deeper…it is. It is using an ‘FAK inhibitor’ to fight pancreatic cancer (and potentially other indications down the track).

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Amplia Therapeutics recapped

The company bearing the name Amplia was founded in 2000 but only pivoted to its current program in 2018. It in-licensed two compounds AMP945/narmafotinib and AMP886 which had been discovered via the Cancer Therapeutics CRC (CTx). AMP945 has been the company’s key focus and works as a FAK inhibitor. Before we go further, we need to explain what that means.

What the FAK?

FAK stands for Focal Adhersion Kinase. A Kinase is an enzyme that adds phosphate groups to other molecules. Focal adhesions are specialised protein complexes within cells that act as a connection point between the extracellular matrix (ECM) and the cell’s internal actin cytoskeleton. They (FAKs) are crucial for cell adhesion, migration, growth, and differentiation by transmitting mechanical forces and initiating signaling pathways that influence a cell’s behaviour and function.

In many cancers, FAK is overexpressed or over-activated and this contributes to tumour growth and the microenvironment. This is particularly true in pancreatic cancer because it is a fibrotic cancer – FAK generates and maintains stiff and protective micro environments. The science behind FAK inhibitors is that by using it, you can make tumours more accessible to immune cells and drug penetration and reduce signalling supporting tumour survival. It is important to note AMP945 is not a sole agent (in other words, it is not a treatment in itself), it sensitises tumours to receive standard therapies.

It has been granted Orphan Drug Designation in the US as well as IND. Amplia has been pursuing drug development against metastatic pancreatic cancer, a cancer with a 5-year survival of 3% and where the current standard only provides an overall surival of less than a year.

Phase 1 worked well and Phase 2 did too, but have investors given it credit for this?

AMP945 was tested in a Phase 1 trial in healthy volunteers. It was well tolerated at all doses tested (single oral dose & repeated daily dosing over 7 days). The pharmacokinetics showed that levels achieved in the blood are sufficient to inhibit FAK; and the results support once‑daily oral dosing.

Then, Amplia moved to the ACCENT trial which is Phase 1b/2a. AMP945 is combined with modified Folfirinox (a popular chemotherapy regimen) in advanced pancreatic cancer. Back in August, interim data was released and the company claimed the results were a success, but investors were not so sure. The Progression Free Survival (PFS) was 7.6 months vs 6.4 months with Folfirinox chemo alone and 5.5 months in another famous trial (the MPACT trial, run in the early 2010s which was the first phase 3 study in MPC to report 3-year survival rates).

We think this is the key concern for Amplia investors – it seems it only helps patients survive for a month or two extra. Above all else, investors need to keep in mind this is only interim data. Also, there were 17 confirmed responses including 1 confirmed complete response and 1 pathological complete response. The objective response rate was 31% – this may not appear high but is easily better than any trial to data.

But will this make a difference?

Yes. Just Google Peter Molding and you’ll see a story in the Australian about how the drug helped him – there was no residual cancer left. But what about from the commercial perspective? Will M&A suitors ‘pay up’ for a drug that only improves survival by 1-2 months. Yes, but even if there is debate there, this trial remains ongoing.

What’s more is that:

• The tolerability has been excellent with many side effects not seen at all or seen to a far lesser degree,
• There’s no evidence the drug has negative interactions with others, and
• The drug is a once a day capsule, administered orally and can be stored at room temperature.

What’s next?

The aim with this trial is to identify an appropriate dosing regiment for a formal Phase 2 study. But data will continue to flow over the next 6-12 months and the company hopes to initiate a later study in the 2nd half of next year. Also watch out for potential regulatory filings, including in Europe, as well as clinical work in other indications. Amplia investors have a lot to look forward to, so should hang tight for the next few months!