Amplia Therapeutics Ltd (ASX:ATX) is continuing to advance the development of its Focal Adhesion Kinase (FAK) inhibiting drug candidates AMP886 and AMP945 for potential use in multiple indications including oncology and chronic fibrosis.
These assets represent attractive compounds for clinical development possessing significant potency and drug-like properties, biological selectivity, bioavailability, and manufacturing scale-up potential.
AMP945 Phase 1 trial achieves primary endpoints
In May 2021, Amplia completed dosing in its Phase 1 clinical trial of AMP945 in healthy volunteers.
The trial achieved its primary endpoints by demonstrating that AMP945 is safe and well-tolerated at the doses tested when it is administered as a single oral dose or as repeated, daily oral doses over seven days.
Furthermore, oral administration produced levels of AMP945 in the bloodstream that are required to inhibit the drug's intended target, FAK, and the pharmacokinetic data supports once-daily, oral dosing of AMP945.
Research collaboration with Garvan
In June 2021, Amplia finalised the commercial terms and executed a research collaboration agreement with the Garvan Institute of Medical Research in Sydney.
This collaboration provides the company with access to Garvan’s research strength in FAK biology and its extensive clinical research network.
Amplia has been working with Professor Paul Timpson, a world-renowned expert in FAK biology, from the Garvan for over two years and appointed him to the company’s Scientific Advisory Board in February 2020.
FAK inhibitors for pancreatic cancer
Amplia reported promising new preclinical data in June 2021 generated by Professor Timpson’s laboratory showing a statistically significant, 27% improvement in survival in a highly aggressive animal model of pancreatic cancer (the KPC mouse model).
These results provided further support and validation of the scientific rationale for incorporating FAK inhibitors into treatment regimens for pancreatic cancer and indicate that they have the potential to have a positive impact on the clinical outcomes for these patients.
Phase 2 clinical trial of AMP945 in pancreatic cancer
In September 2021, Amplia announced the design of its Phase 2 clinical trial of AMP945 in pancreatic cancer patients.
The trial will add AMP945 to chemotherapy with gemcitabine and Abraxane®, which is a standard of care currently used to treat the majority of newly diagnosed advanced pancreatic cancer patients.
Conducting the Phase 2 trial in first‑line patients is expected to expedite recruitment for the trial and provide the best opportunity to detect an efficacy signal.
The ability to test AMP945 in a first‑line setting is made possible in part by the excellent safety and tolerability profile demonstrated in Amplia’s recent Phase 1 clinical trial.
The company plans to initiate patient recruitment at Australian sites in the first quarter of calendar 2022 and currently estimates that full recruitment will take 18‑24 months.
Improved response in tumours
Amplia reported in September that its collaborators at the Garvan Institute of Medical Research had published a paper in Science Advances, a high impact peer-reviewed journal, reporting that, in an animal model of human pancreatic cancer, pre-treatment with a FAK inhibitor resulted in tumours being more responsive to gemcitabine/Abraxane® chemotherapy.
Furthermore, the FAK-priming reduced tumour metastasis to secondary sites such as the liver.
These findings are based on the same treatment regimen and rationale that has underpinned the design of Amplia’s Phase 2 clinical trial in pancreatic cancer patients.
While these are data from preclinical animal studies, they support the strategy the company is taking and the fundamental biology underpinning this approach.
Generic drug name for AMP945
Amplia remains on track to receive a newly manufactured batch of the AMP945 active pharmaceutical ingredient (API) by the calendar year end.
This will provide clinical-grade material for formulations used in the preclinical, chronic animal toxicology studies to support the ILD clinical trials and for use in Phase 2 clinical trials.
Amplia has also initiated the process for securing a generic drug name for AMP945.
This process involves the development and selection of a number of candidate names that simultaneously satisfy multiple naming conventions, an extensive search on their suitability for global use, and then an extensive review and registration process.
This can take up to 24 months to complete but is an important part of developing a new drug for commercial use.
AMP945 trial in fibrotic lung disease
Amplia has also advanced its plans toward initiating a clinical trial of AMP945 in patients with fibrotic Interstitial Lung Diseases (ILDs).
The company expects to start the first clinical trial of AMP945 in patients with fibrotic lung disease in the second half of 2022.