Bexotegrast is a dual-selective αvβ6-αvβ1 integrin inhibitor with surprising efficacy and safety data from a Ph. II trial in idiopathic pulmonary fibrosis (IPF). The αv integrins have been studied for decades in indications such as cancer and IPF. Both small molecule and antibody-based integrin inhibitors have demonstrated preclinical toxicities in non-human primates. This article highlights the unmet need for effective therapies for IPF and related conditions, a comparison of bexotegrast with other integrin binders, and possible reasons why bexotegrast is different in terms of safety.

LUNA18 is an orally bioavailable, cell-penetrant, macrocyclic peptide pan-RAS inhibitor (Chugai ’21Q3 earnings call) intended for the treatment of KRAS-mutant cancers. It disrupts the protein-protein interaction between KRAS and SOS, preventing RAS activation.

BI-0115 inhibits the C-type lectin family member lectin-like oxidized LDL-receptor-1 (LOX-1) by stabilizing an inactive tetrameric form of the protein. Interestingly, co-crystollography demonstrates that inter-ligand interactions between two BI-0115 molecules contribute to the dimerization of LOX-1 homodimers.

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.

BridgeBio’s acoramidis (Attruby), an oral, second-generation stabilizer of the TTR protein, has been approved by the FDA for the treatment of ATTR-CM (transthyretin amyloid cardiomyopathy). Amyloid deposits in the heart muscle characterize the rare but potentially fatal disease. This case study reviews the history of TTR modulation, early experiments validating the therapeutic potential of TTR stabilization, the binding mechanism of acoramidis to TTR, the importance of binding enthalpy for differentiation, and the molecule’s impressive 30-month clinical data following an early scare.