Tyra Biosciences’ lead asset, TYRA-300, is a potent, selective, and orally bioavailable FGFR3 inhibitor designed to mitigate the toxicities commonly seen with pan-FGFR inhibitors. A key objective of the program was to meet the safety standards required for advancing into pediatric populations for the treatment of ACH (achondroplasia) and other skeletal dysplasias. TYRA-300 is currently being evaluated in Ph. I clinical trials for advanced urothelial cancers and other solid tumors and, importantly, has received IND clearance to initiate a Ph. II clinical trial in pediatric ACH patients.

The Bristol Myers Squibb (BMS) HPK1 kinase inhibitor, “compound 24” is an oral tool compound intended for cancer immunotherapy, with >50x selectivity against family members including GLK. The starting point was an IRAK4 kinase inhibitor identified from historical kinome selectivity data. A homology-model based on MST1 was used for [...]

PRN1008 (rilzabrutinib, Sanofi) is an oral, reversible covalent Bruton’s tyrosine kinase (BTK) inhibitor in a Ph. III trial for immune thrombocytopenia. A simultaneously published inhibitor, PRN473, is in development as a topical treatment for atopic dermatitis. Following target discovery in 1993, and subsequent approval of the first [...]

Sovleplenib (HMPL-523) is an orally bioavailable Syk inhibitor being developed by HUTCHMED and is currently in Ph. II and Ph. III clinical trials for several autoimmune diseases. Derived from an HTS hit and SAR optimization, the discovery story of sovleplenib serves as an excellent case study on how to design a next-generation Syk inhibitor devoid of off-target kinase activity, mitigated hERG activity, and more.

NT-0796 is NodThera's pro-drug inhibitor of the NLRP3 inflammasome. NT-0796 is currently in a Ph. Ib/IIa trial in obese individuals at risk of developing atherosclerotic cardiovascular diseases. NT-0796 has the potential to reduce neuroinflammation in Parkinson’s disease. The NLRP3 inflammasome has emerged as a hot target due to its connection to Alzheimer’s disease, Parkinson’s disease, gout, and other diseases. Here is a detailed review of the role of NLRP3 inhibition in treating atherosclerosis, how NT-0796 was identified, and what makes it special, clinical development, and more.