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Oncothyreon halts at Sentinel's checkpoint: Deal could be worth up to $174M


By Cormac Sheridan
Staff Writer

Sentinel Oncology Ltd. could earn up to $174 million from an alliance with Oncothyreon Inc., on its preclinical drug development program targeting checkpoint kinase 1 (Chk1).

The two companies did not provide further details on the deal structure, but Sentinel CEO Bob Boyle told BioWorld Today that it was not back-end loaded. "There are payments throughout the whole deal," he said. Seattle-based Oncothyreon also will fund additional drug discovery work on backup compounds at Cambridge, UK-based Sentinel.

The timing of the agreement is a good fit with Sentinel's commercial strategy. "We are a company that wants to keep things to the end of preclinical development. That's our sweet spot," Boyle said.

The deal, though sizeable for a preclinical alliance, falls some way short of the $28 million up-front payment and $685 million in milestones that Boulder, Colo.-based Array Biopharma Inc. could earn from a 2011 agreement on GDC-0575 with the Genentech arm of Basel, Switzerland-based Roche Holding AG.

"The deal Array did with Genentech was fantastic," Boyle said. "This was a compound ready to go first-in-man." Sentinel's candidate Chk1 inhibitor is not far from the clinic he said, but it is not yet ready to enter it. "The formal IND studies have not been completed at this point in time."

Chk1 has long been identified as a potential cancer target – its crystal structure was reported back in 2000 – but progress in developing selective drug molecules has been slow. It plays a key role in a signal cascade that temporarily halts the cell cycle as part of the DNA damage response. It is phosphorylated by a sensor kinase called ataxia telangiectasia and Rad3 related (ATR), which responds to single-stranded DNA breaks. Inhibition of Chk1 prevents cell cycle arrest at the intra S and G2/M checkpoint, leading to catastrophic cell division and apoptosis.

Originally conceived as sensitizers to both chemotherapy and radiotherapy, Chk1 inhibitors also are being studied as single-agent drugs in defined patient populations. Any cancer that is compromised for DNA repair should exhibit enhanced sensitivity to Chk1 inhibition, Boyle said, including those with p53 mutations.

Most drug development efforts targeting Chk1 are early stage. Those in the clinic include Genentech, which is conducting a phase I multiple-ascending-dose trial of GDC-0575 alone and in combination with Gemzar (gemcitabine) in about 90 patients with refractory solid tumors or lymphoma. GDC-0425, which it discovered in-house and which is included in the Array alliance, is also undergoing a similar trial in about 75 patients.

Indianapolis-based Lilly is conducting two phase I trials of LY2603618 in patients with non-small-cell lung cancer and advanced solid tumors. The National Cancer Institute is the sponsor of a phase II study of MK-8776 (formerly SCH900776) in patients with acute myeloid leukemia. Whitehouse Station, N.J.-based Merck & Co. Inc. previously terminated a phase I study of the same drug in patients with various leukemias. Exelixis Inc., of South San Francisco, terminated development of XL844, a dual inhibitor of Chk1 and Chk2. London-based Astrazeneca plc terminated development of AZD7762 several years ago because of cardiotoxicity problems.

Avoiding that issue was a key focus of the Sentinel program, Boyle said. The company's candidate Chk1 inhibitor is a "high-quality drug substance" and is competitive with other known compounds, he said.

For Sentinel, a company founded in 2005, the Oncothyreon deal will boost its visibility in the U.S. All of its alliances to date have been with European firms, Boyle said. Those include an agreement with Cambridge, UK-based Horizon Discovery Ltd. on the development of an inhibitor of an undisclosed kinase target. That molecule now has been taken on by an unnamed big pharma firm.