Repotrectinib: Why Did BMS Pay $4.1 Billion for Turning Point Therapeutics?

In May 2024, several significant transactions worth millions and billions of dollars took place to advance next-generation neuroplastogens, KRAS G12C inhibitors, Pompe disease treatments, and molecular glues. We also highlight positive clinical readouts for hot targets such as tetrameric transthyretin (TTR) stabilizers, Hedgehog pathway inhibitors, plasma kallikrein inhibitors, dipeptidyl peptidase 1 (DPP-1) inhibitors, and PCSK9 inhibitors. Here's a recap of the most notable news highlights from May 2024!

Companies inked notable high-profile transactions in March 2024, including AbbVie's purchase of Landos Biopharma for $137.5M, AstraZeneca's $2.4B acquisition of Fusion Pharmaceuticals, and its subsequent deal to buy Amolyt for up to $1.05B. The FDA approved the first treatment for MASH. In parallel, expectations are high for the approval of Xcovery's ALK inhibitor, ensartinib. Praxis made headlines with PRAX-628, a next-generation oral NaV modulator, which showed anti-seizure efficacy in a Ph. IIa trial. Read below for more details on these and other drug discovery news stories from March 2024

STC15 is Storm Therapeutics' first-in-class and first-to-clinic inhibitor of the post-transcriptional RNA modifier, METTL3, which progressed from HTS hit to clinical development in less than three years. METTL3 inhibitors have been previously identified, but no METTL3 inhibitors have entered clinical development until now. In this article, we explore METTL3 as a therapeutic target, highlight the discovery story of STC15, its fascinating mechanism of action, provide the latest clinical development update, and much more.

PRMT5 is an epigenetic “synthetic lethality” target that has attracted much attention among drug hunters. The first generation of PRMT5 inhibitors was limited by systemic toxicities resulting in a cooling of industry interest, until the recent identification of tumor-specific inhibitors. These second-generation compounds target the MTA:PRMT5 complex in MTAP-deleted cancers—15% of all tumors—leading to a revival of the target. Read on to find out which companies are prevailing in the search for a first-in-class PRMT5 inhibitor and how their clinical compounds differentiate.

One of the key challenges in CNS projects is achieving sufficient unbound brain exposure to engage the target. To predict CNS exposure, scientists employ metrics like CNS MPO scores from Pfizer and Merck, Bayesian models, and methods for balancing physicochemical properties. However, these in silico metrics often fail to correlate well with experimental data. Schrödinger's team has discovered the energy of solvation (E-sol) metric, which accurately predicts Kp,uu and has been validated with CNS-penetrant DLK inhibitors. Explore more in this detailed Drug Hunter article.