Cambridge, Massachusetts-based Foghorn Therapeutics, is developing a novel class of therapeutics targeting the chromatin regulatory system in oncology. This system regulates which genes a cell expresses and when it expresses them.

Dysregulation of the chromatin system is implicated in up to half of all cancers, Merck said, adding that disease dependencies associated with the system are estimated to affect over 2.5 million patients across Europe, the US and Japan. The chromatin regulatory system is further implicated in neurological, autoimmune and other serious diseases.

The partners will apply Foghorn’s proprietary Gene Traffic Control product platform to discover and develop novel therapeutics against a transcription factor target believed to be relevant to a broad range of cancer patients. The platform, said Foghorn’s president and CEO Adrian Gottschalk, opens vast potential to discover and develop novel cancer treatments.

Nick Haining, vice president, discovery oncology & immunology at Merck Research Laboratories, added: “There is broad evidence for the role of dysregulated transcription factors in multiple cancer types, but these have been difficult targets to drug.”

Foghorn will grant exclusive global rights to commercialize drugs that target dysregulation of a single transcription factor. In turn, it will receive an upfront payment and research milestones and will also be eligible to receive payments potentially totaling up to $425 million along with royalties on sales of any approved product.

The Cambridge, Massachusetts-based company launched by venture capital firm Flagship Pioneering in March 2018 with an initial capital commitment of $50 million is currently advancing more than 10 small molecule and protein degrader programs across a wide range of cancers. It expects to file an Investigational New Drug application with the US Food and Drug Administration for its first program later this year.

Merck’s second collaboration is with Zymeworks, a clinical-stage biopharma. This deal is an extension of a partnership that dates back to 2011 and which was previously expanded in 2014. The latest agreement grants Merck the right to develop additional multispecific antibody therapeutic candidates using Zymeworks’ Azymetric and Efect platforms.

Azymetric therapeutics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies while Efect is a library of antibody Fc modifications engineered to activate or suppress the antibody-mediated immune response. The Efect platform is compatible with traditional monoclonal as well as Azymetric bispecific antibodies, further enabling the customization and optimization of therapeutic responses for different diseases.

Zymeworks will grant Merck a worldwide, royalty-bearing license to research, develop and commercialize up to three new antibodies. In exchange, Zymeworks will receive payment of an undisclosed upfront sum. Should each of the three programs result in an approved product, Zymeworks could receive up to $891 million in option exercise fees and various milestone payments as well as tiered royalties on global sales.

In addition, Merck will also receive a worldwide, royalty-bearing license to research, develop and commercialize up to three multispecific antibodies in the animal health field for additional payments and royalties.

“It is an exciting time for the field of bispecific and multispecific therapeutics with candidates like ZW25 demonstrating great promise in clinical trials,” said Ali Tehrani, president and CEO of Zymeworks. ZW25 is a novel Azymetric bispecific antibody currently in Phase 2 development. The company’s second clinical candidate is ZW49, a bispecific antibody-drug conjugate currently in Phase 1 development.

Zymeworks is also advancing a deep preclinical pipeline in oncology, including immuno-oncology agents, and other therapeutic areas. As well as Merck, the company has strategic partnerships with BeiGene, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Daiichi-Sankyo, Iconic Therapeutics, Janssen Biotech (part of Johnson & Johnson) and Leo Pharma.