Gilead Sciences Inc. has disclosed the discovery and structure of the potent, oral small molecule programmed cell death 1 ligand 1 (PD-L1) inhibitor GS-4224 (evixapodlin).

Genentech Inc. presented data on structure-based lead optimization of orally bioavailable hematopoietic progenitor kinase 1 (HPK1) inhibitors. HPK1 is a negative regulator of T-cell receptor signaling in human T cells and target inhibition significantly increases cytokine production, such as IFN-gamma, TNF-alpha and IL-2, and T-cell proliferation, suggesting HPK1 inhibition as an intracellular T-cell target for cancer immunotherapy.

The structure of a potent and selective TYK2 inhibitor, NDI-034858 (NTX-973), which was found clinically effective in autoimmune and inflammatory diseases, was disclosed for the first time by researchers from Nimbus Therapeutics LLC.

Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of multiple myeloma (MM), but its toxicity and complex manufacturing limit their broad use.

Researchers from Biomea Fusion Inc. presented preclinical data for the novel covalent menin inhibitor, BMF-219, after being evaluated in models of diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM).

Factor XIa inhibitors milvexian and asundexian, hailed as the next-generation class of anticoagulants, earned mixed reviews on phase II data presented during the European Society of Cardiology Congress 2022. However, developers Bristol Myers Squibb Co./Janssen Pharmaceutical Co. and Bayer AG, respectively, are moving into late-stage testing, citing clear mechanisms of action that put the FXIa drugs at least on par with approved factor Xa drugs in terms of efficacy while offering potentially better safety profiles that could give physicians an option for patients with stroke or atrial fibrillation who are currently undertreated with anticoagulants due to bleeding risks.