Celebrating sustained sales growth, AstraZeneca quietly executes some aging mid-stage drug projects

While AstraZeneca execs clustered by the front door to discuss their third straight quarter with rising sales driven by new cancer drugs and an expanding grasp of the Chinese market, the company’s R&D janitors were sweeping its failures out the back door. And the setbacks include some longtime cancer drugs in the pipeline obtained through a slate of multimillion-dollar alliances.

This quarter’s rejects are topped by a group of Phase II projects, including prezalumab, a B7RP1 mAb for Sjogren’s syndrome, as another one of AstraZeneca’s autoimmune projects goes south on them. The IgG2k monoclonal antibody was one of the few remaining autoimmune projects at AstraZeneca, which has concentrated the pipeline heavily on oncology. The R&D team there experienced a crushing setback last summer with the Phase III failure of anifrolumab for lupus.

Its oncology exits include 3 mid-stage efforts: AZD8186, a PI3k-beta inhibitor that follows the execution of several similar drugs amid significant competition;  AZD4547, an FGFR inhibitor for solid tumors; and Imfinzi plus MEDI0680, adding a PD-1 to their PD-L1 that’s already on the market.

Back in early 2018 AstraZeneca punted its efforts to develop the PD-1 MEDI0680 as a monotherapy, leaving the combo in place. But there’s evidently no room and not much hope for their idea of matching drugs that cover both ends of a single checkpoint strategy. The pharma giant acquired the then preclinical therapy in its $500 million Amplimmune buyout — $225 million in cash and $275 million in milestones — back in 2013, as new CEO Pascal Soriot began a series of deals to remake the pipeline.

Pascal Soriot

AstraZeneca also said it is punting several Phase I projects, including one that it lists as AZD4758, a KRAS inhibitor. That is a typo, as the company acknowledged today. Their AZD4785 KRAS drug, obtained from Ionis in a $28 million licensing pact, was described as IONIS-KRAS-2.5Rx, “a Generation 2.5 antisense drug discovered by Ionis designed to directly target KRAS, one of the most frequently mutated genes in cancer.”

KRAS has been a big but tough target to crack in oncology. With AstraZeneca stepping out, expect more focus on rival efforts, including Amgen’s AMG 510 as well as Mirati’s MRTX849, which both involve the G12C mutation.

AstraZeneca’s quarterly cleanups are much easier for the company to handle as Soriot delivers on his longstanding promise to hit rock bottom and bounce back up on the revenue side. The multinational may be a long way from achieving the revenue goals laid out when the CEO was fighting off a Pfizer buyout, but the success of blockbuster cancer drugs like Lynparza, Tagrisso and Imfinzi pay for the inevitable mistakes.

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VP Oncology Biology
Skyhawk Therapeutics Waltham, MA
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Elektroki Boston, MA
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Elektroki Boston, MA
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Recursion Pharmaceuticals Salt Lake City, UT

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