26 October 2018 - - US-based oncology company TP Therapeutics and precision medicine company Almac Diagnostic Services have inked a global collaboration agreement to develop and commercialise a next-generation sequencing companion diagnostic for repotrectinib, TP Therapeutics' investigational therapy rationally designed to target ROS1, NTRK1-3 and ALK gene fusions in advanced solid tumors, the companies said.

Under the agreement, Almac will develop the NGS diagnostic based on the ArcherDx's Anchored Multiplex PCR chemistry, with the intent of submitting it for regulatory approval in the United States. 

The companion diagnostic will initially allow Almac's CLIA-accredited laboratory in Durham, N.C. to identify tumors with the targeted gene fusions, enabling physicians to select appropriate patients for treatment with repotrectinib.

Repotrectinib is an investigational, next-generation tyrosine kinase inhibitor developed for the treatment of patients with advanced solid tumors harboring ROS1, NTRK1-3 or ALK molecular rearrangements.

Repotrectinib is a rationally designed, low molecular weight, macrocyclic TKI that is much smaller than current ROS1, TRK family and ALK inhibitors with the objective to systematically overcome the clinically acquired resistance mutations of ROS1, TRK family and ALK kinases, especially the gatekeeper and solvent front mutations.

Co-development of CDx and therapeutic products is critical to the advancement of targeted therapies and precision medicine.

Companion diagnostics are tests designed to confirm the presence of a specific biomarker to assist physicians in selecting effective therapies for their patients, based on the individual molecular characteristics of each person.

Incorporating a companion diagnostic strategy into a drug development program may help generate more effective treatments with improved safety profiles for patients.

The financial terms of the agreement were not disclosed.

Almac Diagnostic Services is a global stratified medicine company specializing in biomarker driven clinical trials.

The company is focused on the discovery, development and commercialisation of diagnostic and companion diagnostic tests.

Repotrectinib (TPX-0005) is a potent and orally bioavailable investigational small-molecule inhibitor of ALK, ROS1 and TRK family kinases.

The clinical benefits of targeting ALK, ROS1 or TRK fusion kinases have been demonstrated with multiple kinase inhibitors already approved for the treatment of ALK+ non-small cell lung cancer (NSCLC), in addition to crizotinib for ROS1+ NSCLC, and larotrectinib and entrectinib in clinical studies for TRK+ cancers.

The successes of these therapies are overshadowed by the development of acquired resistance. The acquired solvent front mutations including ALK G1202R, ROS1 G2032R, TRKA G595R and TRKC G623R render a common clinical resistance to the current ALK, ROS1, and TRK inhibitors.

Repotrectinib has demonstrated potency against wildtype and mutated ALK, ROS1 and TRK family kinases, especially the clinically significant solvent front mutations, gatekeeper mutations, and emerging compound mutations after multiple lines of treatment.

According to the company, Repotrectinib may provide a new opportunity to inhibit the abnormal signaling of ALK, ROS1, or TRK family kinases in solid malignancies, and overcome multiple resistance mechanisms seen in refractory patients.

Repotrectinib is currently being evaluated in a Phase 1/2, open-label, multi-center, first-in-human study of the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements (TRIDENT-1 study).

TP Therapeutics is a clinical-stage precision oncology company forging a new path for targeted cancer care.

Founded in October 2013 by Dr. J. Jean Cui, the lead inventor of Pfizer's oncology drugs crizotinib and lorlatinib, the company is developing a pipeline of novel drugs that aim to tackle treatment resistance and give new hope to patients who have stopped responding to available targeted therapies.