The Irak-4 approach has a wobble

Irak-4 inhibition in autoimmune disease took a knock yesterday, with Pfizer quietly discontinuing its contender PF-06650833 in hidradenitis suppurativa. Kymera paid a big price, its stock losing 24%; the Irak-4 project KT-474 is Kymera’s lead, and analysts had been looking to Pfizer’s data to handicap KT-474’s own phase 1 atopic dermatitis/hidradenitis suppurativa update, due in the second half. Then again, Kymera did not help itself, coincidentally revealing that its phase 1 protocol had been amended to increase dosing from 14 to 28 days and add clinical endpoints, and disclosing that 10-20msec QTc prolongation had been observed in the study. The last point was not serious enough to be graded an adverse event, but one risk is that it might be exacerbated by continuous dosing. Stifel analysts said Pfizer’s move called into question Irak-4 as an autoimmune target. Still, the molecules act differently: PF-06650833 is a straight inhibitor whereas KT-474 is a degrader. Sentiment will not have been helped by the FDA placing Curis’s Irak-4 inhibitor emavusertib – focused on oncology – on clinical hold last month. Pfizer continues to list PF-06650833 as a rheumatoid arthritis project, but no active trials here are ongoing.