AACR 2023 – Relay takes the wooden spoon

AACR was to have seen Relay’s novel approach to PI3K blockade prove itself clinically, but instead the company might have taken the wooden spoon for the meeting's most disappointing dataset. After being halted Relay’s stock fell 32% yesterday on a presentation showing that RLY-2608 did precisely what it was supposed to mechanistically, but that this did not result in meaningful efficacy. Targeting PI3Kα rather than pan-PI3K activity became an important strategy in Her2-negative breast cancer with the advent of Novartis’s Piqray, but nevertheless even Piqray is associated with toxicity due to its action on wild-type PI3Kα. The case for RLY-2608 is that it inhibits only mutated PI3Kα, and yesterday’s AACR presentation showed 80% target inhibition with minimal impact on glucose homeostasis in the phase 1 Rediscover trial. But across 27 subjects with PIK3CA-mutant breast cancer there was only one partial response, and that was unconfirmed; there were no responses at all in a further 15 subjects with other tumour types. Cowen analysts blamed the share price fall on overblown expectations, and the bull case is that remissions will emerge at higher doses or with longer follow-up. For now this is a distant hope, however.