GSK kills one of Barron's early darlings, axing 2 synthetic lethal programs and Epizyme pact

Shortly after becoming GlaxoSmithKline’s chief scientific officer, Hal Barron highlighted (PDF) GSK3326595 as one of four early-stage cancer programs to watch. Today, with Barron’s time at the company nearing its end, GSK axed (PDF) the PRMT5 inhibitor and sibling molecule GSK3368715 from its pipeline. 

Evidence that GSK was rethinking plans for PRMT1 inhibitor GSK3368715 emerged last year, when the company wrapped up an early-phase study in solid tumor and diffuse large B-cell lymphoma patients 15 months ahead of schedule. The trial enrolled 31 subjects, well down on the 215 patients GSK originally planned to recruit.

A trial of GSK3326595 in myelodysplastic syndrome and acute myeloid leukemia patients continued after GSK closed up the study of its sibling molecule. But GSK recently stopped recruiting in that clinical trial, too, having enrolled just 10% of the 302 subjects it planned to recruit at the start of the study.

GSK confirmed the removal of the programs from its phase 1 pipeline as part of its fourth-quarter results earning release. In a brief statement, GSK attributed its actions to prioritization within the synthetic lethal portfolio, adding that it will end the in-license agreement with Epizyme covering the molecules next month.

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Epizyme landed the deal with GSK in 2011. At that time, the plan was to work on small molecule HMT inhibitors against three targets. GSK dumped the third target in 2017 but forged ahead with the PRMT5 and PRMT1 programs, moving both candidates into the clinic the following year. 

Along the way, Epizyme received $89 million from GSK but the big paydays were still to come. As of the end of September, Epizyme was in line to receive up to $50 million in clinical development milestones, $197 million in regulatory payments and $128 million in sales-based paydays.