BMS-986299

GSK may not have been surprised its anti-TIM-3 drug couldn’t secure a phase 3 win based on how its pharma peers have struggled.\n GSK’s cobolimab has become the latest anti-TIM-3 antibody to flunk a crucial oncology test, as the pharma absorbs a more than $600 million hit from its anti-TIGIT drug failure.The British Big Pharma had been evaluating cobolimab—which it acquired in the $5.1 billion Tesaro takeover in 2018—in various combinations with oncology med Jemperli and the chemotherapy docetaxel in a phase 3 study of 750 patients with non-small cell lung cancer (NSCLC).The company revealed in its second-quarter earnings this morning that the study didn’t reach its primary endpoint of improving overall survival in advanced NSCLC after prior immuno-oncology therapies.“All regimens were well-tolerated and toxicities were consistent with known safety profiles of docetaxel and immune checkpoint inhibitors,” GSK said in its July 30 earnings release (PDF). “This remains a challenging treatment setting where novel combinations have yet to improve outcomes for most patients.”The late-stage fail doesn\'t mark the end of GSK\'s hopes for cobolimab. The company is still evaluating the drug in a phase 1/2 trial in a range of pediatric cancer settings as well as in a midstage trial for advanced liver cancer.TIM-3 is expressed by immune effector cells, where it acts as an immune checkpoint, and leukemic stem cells, leading various Big Pharmas to identify the receptor as a way to simultaneously activate the immune system and suppress the proliferation of cancer cells.GSK may not have been surprised that cobolimab couldn’t secure a phase 3 win. The drug was the most advanced anti-TIM-3 antibody left standing after Novartis’ own candidate failed a late-stage study in patients with myelodysplastic syndrome or leukemia at the start of 2024.While Novartis focused on blood cancers, GSK and other big names with TIM-3 candidates had largely looked at solid tumors. Roche removed (PDF) a PD-1xTIM-3 bispecific from its pipeline in 2022, while Bristol Myers Squibb terminated a phase 1 trial of a TIM-3 candidate, BMS-986299, in 2022 because its “business objectives” had changed. Eli Lilly and Incyte have also axed their respective TIM-3 drugs. AstraZeneca appears to still have a foot in the anti-TIM-3 space, with a PD-1xTIM-3 bispecific that is due to complete a phase 1/2 study this year.TIM-3 wasn’t the only high-risk cancer target where GSK crashed and burned this quarter. The pharma revealed in the same earnings document that its decision to end development of the anti-TIGIT antibody belrestotug had resulted in a 471 million pound sterling ($629 million) impairment charge.GSK paid iTeos $625 million upfront for the rights to belrestotug four years ago. In the wake of belrestotug’s phase 2 failure, the biotech initially planned to wind down operations before accepting a buyout offer from Concentra Biosciences earlier this month.This morning’s release also revealed that GSK has discontinued a phase 2-stage adjuvanted recombinant protein vaccine for malaria dubbed GSK3437949. A spokesperson for the company put this move in the context of the pharma’s recently announced push into second-generation, multistage malaria vaccines.Meanwhile, sanfetrinem cilexetil—an oral prodrug of the antibiotic sanfetrinem—has been removed from the company’s phase 2 pipeline after having “not compared favourably in early studies to existing treatments and other tuberculosis-specific assets also in development at GSK,” the spokesperson said.