Accelerating a novel glioma therapeutic

CAMBRIDGE, U.K.—PhoreMost Ltd., a biopharmaceutical company dedicated to drugging “undruggable” disease targets, and Sentinel Oncology, in early November announced an expansion of their collaboration to accelerate the progression of SOL686, a novel allosteric Polo-like kinase 1 (PLK1) inhibitor through preclinical development and IND-enabling studies for the treatment of glioma.

Mitotic PLKs are widely recognized as playing crucial roles in disease causing pathways, including K-Ras mutant cancers, the companies notes. Traditional approaches to drugging PLK enzymes have focused on targeting their active site; however this tactic has been hindered by toxicity-associated adverse events. Sentinel Oncology’s allosteric PLK1 inhibitor takes the novel approach of targeting the Polo-box domain of the PLKs, thereby aiming to mitigate adverse events seen by active site inhibitors.

The program has reportedly demonstrated a promising combination of specific drug-like properties, mode of action and target validation data obtained so far. Originating from the laboratory of Prof. Ashok Venkitaraman at the University of Cambridge, PhoreMost subsequently developed the lead chemical series. Sentinel Oncology then optimized drug-like properties for the series and guided therapeutic positioning. Both PhoreMost and Sentinel Oncology received funding from Innovate UK for the drug discovery program.

“We are delighted to deepen our long-standing association with Sentinel Oncology, and excited to be progressing this drug discovery program towards the clinic,” said Dr. Chris Torrance, CEO of PhoreMost. “This lead compound exemplifies the value of PhoreMost’s strategy to use functional protein-protein interactions to drive the development of novel therapies, and to capitalise on its SITESEEKER platform to change the model of drug discovery through innovation, strategic partnerships and collaboration.”

Commented Robert Boyle, CEO of Sentinel Oncology: “We are very excited about the prospects for this program, and to be collaborating with PhoreMost to advance our allosteric PLK1 inhibitor. The program adds to our neuro-oncology pipeline, has started formal preclinical studies and is well positioned to enter clinical development as a glioma treatment by 2021.”