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Incyte announced it is discontinuing five early-stage oncology programmes, including both of its oral PD-L1 inhibitors. The decision, revealed alongside the company's second-quarter earnings results, marks the second major pipeline cut for Incyte in just over a year, highlighting an increased focus on what the company deems "high-impact clinical programmes."Specifically, Incyte is pulling the plug on the PD-L1 candidates INCB99280 and INCB99318. Both were in Phase I testing for solid tumors, with INCB99280 having entered a trial late last year as part of a combination with Bristol Myers Squibb's Krazati (adagrasib) in adult patients harbouring a KRASG12C mutation.Incyte is also scrapping a pair of partnered LAG-3 drug candidates — the monoclonal antibody INCAGN2385 in development with Agenus and the LAG-3xPD-1 bispecific INCA32459 in collaboration with Merus. Rounding out the list is the TIM-3 monoclonal antibody INCAGN2390, another product that stems from the Agenus collaboration."The restructuring was driven primarily by two things," said R&D head Pablo Cagnoni during the company's earnings call. "One, data review of the existing programmes … as well as the continued progression and promising data that we're seeing from the earlier stage pipeline that is now becoming mid-stage and will start delivering important milestones in the next 18 months."Cagnoni denied that recent positive topline Phase III data for Zynyz (retifanlimab) in squamous cell anal carcinoma (SCAC) and non–small-cell lung cancer (NSCLC) was the reason behind the pipeline restructuring. The PODIUM-303 study in SCAC and PODIUM-304 study in NSCLC met their respective primary endpoints of progression-free survival and overall survival. Incyte says it will share more details in the second half.The latest round of cuts follows a similar action last year, when the company discontinued six drugs — one in warm autoimmune haemolytic anaemia and five for different types of cancer. At that time, CEO Hervé Hoppenot had stated the decision would allow Incyte "to optimise our allocation of resources on programmes that can have a high impact for patients and for Incyte."Incyte now says its refocused R&D efforts will prioritise several key areas, chiefly its inflammation and autoimmunity portfolio, including dermatology, with a spotlight on povorcitinib and recently acquired mast cell inhibitors from its $750-million Escient Pharmaceuticals buyout. The company will also maintain its commitment to myeloproliferative neoplasms and graft-versus-host disease, as well as select oncology programmes including a CDK2 inhibitor, a KRAS G12D inhibitor, and a TGFβR2×PD-1 bispecific antibody.

Despite today’s pipeline changes, oncology remains another area of focus for Incyte. For the second quarter in a row, Incyte has used its earnings results to significantly slim down its early-stage pipeline as the Jakafi-maker channels its resources toward “high potential impact programs.”The latest list of discontinued assets includes both of Incyte’s oral, small-molecule PD-L1 inhibitors that were being assessed in phase 1 trials. One of these, INCB99280, was being evaluated in an early-stage solid tumor trial, and the biotech had already set out plans for a phase 1/1b trial in KRASG12C-mutated solid tumors in combination with Bristol Myers Squibb’s Krazati.The other scrapped PD-L1 inhibitor, dubbed INCB99318, was also in a phase 1 solid tumor trial.Also on the chopping block are a couple of LAG3 drug candidates. One of these is a LAG-3 monoclonal antibody dubbed INCAGN2385 that was being developed with Agenus. The other was a bispecific anti–PD1 and anti–LAG-3 antibody dubbed INCA32459 that was being developed with Merus and had undergone a phase 1 study in select advanced malignancies.Finally, Incyte has removed a TIM-3 monoclonal antibody dubbed INCAGN2390, which was another product of the Merus collaboration. INCAGN2390 was designed to “potently block TIM-3 to reinvigorate T and NK cells and reduce immunosuppression by regulatory T cells (Tregs),” according to Agenus’ website. Incyte said the changes, unveiled this morning in the company’s second-quarter earnings results, were part of a “strategic review of its pipeline with an increased focus on high potential impact programs.”“In R&D, we completed a strategic review of our pipeline and have further intensified our focus on clinical programs that we believe can be transformational for patients,” CEO Hervé Hoppenot explained in the release.Among the company’s highest priority candidates are povorcitinib, a selective oral JAK1 inhibitor that has already demonstrated its worth in phase 2 trials in both hidradenitis suppurativa and vitiligo so far this year. The company has also imported over a pair of budding immunology and inflammation candidates as part of its $750 million acquisition of Escient Pharmaceuticals in April.Despite today’s pipeline changes, oncology remains another key area of focus for Incyte, which will continue to channel resources into NCB123667—a CDK2-selective small molecule inhibitor in a phase 1 solid tumor trial—among others.The company’s third priority area is myeloproliferative neoplasms and graft-versus-host disease, where the biotech singled out three candidates.This morning’s pipeline changes follow a similar strategy to Incyte’s previous quarterly earnings back in May, when the biotech scrapped six drugs—one in a rare form of anemia and five in various cancers.