Pfizer bows out of the Tyk2 race

2021 had once looked like the year of the Tyk2 inhibitors, but some shine is coming off this member of the Jak family. Pfizer today disclosed plans to offload two projects with activity against Tyk2, not long after the lead proponent of this approach, Bristol Myers Squibb, reported disappointing data with deucravacitinib in ulcerative colitis. Pfizer did not give a reason for its Tyk2 exit, which will see brepocitinib and PF-06826647 licensed to a new company that Pfizer is forming in partnership with an unnamed autoimmune player; the pharma giant will have a 25% stake in this venture and retain certain ex-US rights. Perhaps the decision was spurred by toxicity concerns with the Jak inhibitors, which solidified in September into a class warning; however, Pfizer is keeping hold of its Jak1 abrocitinib – which is still awaiting an FDA decision in atopic dermatitis – and the Jak3/Tec inhibitor ritlecitinib. Still, other mechanisms now look like a priority: Pfizer highlighted several immunology projects in its third-quarter presentation, including a “high potency” topical PDE4 inhibitor, PF-07038124, for atopic dermatitis and psoriasis; PF-06480605, a TL1A inhibitor for ulcerative colitis; and the interferon-beta Inhibitor PF-06823859 in dermatomyositis.