Teva Pharmaceutical Industries and Heptares will collaborate to develop new Heptares-discovered small-molecule calcitonin gene-related peptide (CGRP) antagonists for migraine, the companies said today.

The deal could generate up to $410 million plus for Heptares, with Teva in return receiving worldwide development and commercial rights to new CGRP antagonists co-developed by the companies.

CGRP is released during migraine attacks and can trigger migraines in patients.  As elevated levels of CGRP are found in people with migraine headaches, the companies reason that blocking CGRP activity is a validated mechanism of action for relieving pain, as well as for preventing migraines.

Teva agreed to pay Heptares $10 million upfront, and potentially up to $400 million in payments tied to achieving research, development, and commercialization milestones. Heptares is also eligible to receive royalties on net sales of products resulting from the alliance, the companies said.

“We believe small-molecule CGRP antagonists offer further opportunities that are highly complementary to our promising candidate, TEV-48125, an anti-CGRP antibody,” Michael Hayden, M.D., Ph.D., Teva’s president of global R&D and CSO, said in a statement.

TEV-48125 (formerly LBR-101/ RN-307) is a monoclonal antibody that binds to CGRP. The compound is being developed for two migraine indications; chronic migraine and high frequency episodic migraine.

On September 30, Teva said it expected to advance TEV-48125 into Phase III trials following positive results in a pair of Phase IIb studies. In results published in Lancet Neurology, Teva said TEV-48125 consistently met all primary and secondary efficacy and safety endpoints in 564 patients and across multiple doses, significantly reducing average monthly migraine days, headache days and hours relative to baseline.

Clinical improvements were exhibited after a single administration of all tested doses of TEV-48125 in both episodic and chronic migraine studies, the company added.

Heptares will apply its structure-based drug discovery (SBDD) technology platform, designed to engineer drugs for highly validated, yet historically undruggable or challenging, GPCRs. Heptares has used the platform to develop new candidates for treating Alzheimer’s disease, schizophrenia, cancer immuno-oncology, migraine, addiction, metabolic disease, and other indications.

“The commitment Teva is making allows us to expand this promising program,” added Heptares CEO Malcolm Weir.

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