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Merck KGaA, Artios Collaborate to Discover DNA Damage Response Drug Targets

NEW YORK – Merck KGaA, Darmstadt, Germany, and Artios Pharma on Thursday announced a three-year research pact to discover and develop precision oncology drugs that inhibit the biological mechanisms that cancer cells use to repair DNA damage and proliferate.

Under the terms of their deal, Merck and Artios will jointly conduct discovery research, and Merck will have exclusive worldwide rights to develop and commercialize up to eight targets discovered within this partnership. Artios is eligible to receive $30 million in up-front and near-term payments, and up to $860 million per target if Merck chooses to exercise its option to license any of the drug targets. Artios is also eligible to receive double-digit royalty payments on the net sales of each product commercialized by Merck and has opt-in rights to jointly develop and commercialize these products.

Within the partnership, Merck and Artios will use Artios' proprietary nuclease targeting discovery platform to identify synthetic lethal targets that can be interrogated by therapeutic candidates. Cancer cells, in response to DNA damage, rely on enzymes called nucleases to survive. However, some cancer cells' ability to repair DNA damage is already diminished due to mutations in the DNA damage repair pathway, and in these settings drugs shutting down the activity of nucleases can effectively kill tumor cells, resulting in what is known as synthetic lethality.

Merck is already involved in advancing drugs that cause synthetic lethality. For example, the company acquired berzosertib from Vertex Pharmaceuticals a few years ago and the drug has shown promising activity in early studies in cancer patients with aberrations in DNA damage repair pathways. 

However, the deal with Merck does not impact the lead Polθ and ATR inhibitor programs underway at Artios, to which it will retain all rights. "The partnership puts us in an exceptional position to focus internal efforts on our leading portfolio of assets which includes a small-molecule ATR inhibitor and a Polθ program, both in candidate IND evaluation," Artios CEO Niall Martin said in a statement.

Cambridge, UK-based Artios licensed an ATR inhibitor from MD Anderson Cancer Center last year in collaboration with SangPharma Innovation. The company plans to advance its Polθ inhibitor program into human studies next year.