Ignyta agrees new terms with Lilly for troubled cancer alliance

Eighteen months ago, Eli Lilly cut a $53 million deal with Ignyta setting up an alliance to develop cancer therapy taladegib. Now, the San Diego-based biotech has followed through on plans to pare down the alliance and focus more on another drug.

The first signs that all was not well with the collaboration emerged last year, when Lilly started to voice its concerns that Ignyta "may not have satisfied certain … obligations under the license agreement."

Now, the two companies have agreed a way forward for the small-molecule Hedgehog pathway inhibitor, which is being developed initially for a form of skin cancer called basal cell carcinoma (BCC)—although it may be that Ignyta does not end up developing the drug itself.

In an SEC filing, Ignyta said it had agreed a revision of the terms of its license agreement with Lilly for an oral formulation of taladegib that has cleared a phase 1 dose-ranging study, as well as a topical formulation in preclinical development which was shelved last February.

Under the new terms, Ignyta will continue to develop potential combinations of taladegib with other products for residual disease, and will try to sub-license or sell the drug as a single-agent therapy to "dermatology-focused companies who may have an interest in superficial, nodular, and advanced BCC."

According to the biotech's CEO Jonathan Lim, Ignyta has "received inbound interest on these assets in these BCC indications, and will be weighing the merits of these potential partnerships with other opportunities to develop taladegib internally for the benefit of patients with rare cancers outside of BCC." 

This is not the first occasion that Ignyta has opted to slim down its pipeline. Last year, it dumped three cancer candidates including two licensed form Teva and a couple of preclinical programs in order to concentrate its efforts on taladegib and entrectinib. At the time, Lim said the aim of that exercise was to focus on projects most likely to generate positive results.

The latest decision may speak more to Ignyta's growing excitement about entrectinib—a first-in-class , a kinase inhibitor now in phase 2 testing—rather than any fundamental issue with taladegib, although there seems to have been little progress made with the drug since Ignyta in-licensed the drug towards the end of 2015.

It is also likely a factor that taladegib is playing catch-up with two other hedgehog pathway inhibitors—Roche's Erivedge (vismodegib) and Novartis' Odomzo (sonidegib)—which are already FDA-approved to treat BCC.

Entrectinib targets fusions in the NTRK, ROS1 and ALK gene families which are commonly seen in solid tumors, and has already been shown to stimulate objective responses in patients with non-small cell lung cancer (NSCLC), colorectal cancer and melanoma in the ALKA-372-001 and STARTRK-1 trials.

Among the recent findings was an overall response rate of 86% in 14 patients with ROS1-rearranged solid tumors (NSCLC and melanoma), including two complete responses, and a median response duration of more than 17 months.

Analysts at Credit Suisse have previously predicted entrectinib could reach the market in 2019 for NSCLC caused by NTRK fusion mutations and colorectal cancer, pulling in more than $300 million in the following year.