Billion-Dollar Biotransformations: On the Metabolism of Ozanimod
Today, ozanimod is a likely megablockbuster drug approved for ulcerative colitis and multiple sclerosis. But before it became the first S1P modulator approved in ulcerative colitis, it received a scary, headline-making “Refuse to File” letter from the FDA due to insufficient preclinical characterization of an active metabolite RP112273 (CC112273). Addressing the refusal to file letter…
Why Did Bristol Myers Squibb (BMS) Pay $4.1 Billion for Turning Point Therapeutics?
Turning Point Therapeutics ($TPTX) was recently acquired by BMS for a whopping $4.1 billion in cash. Turning Point’s most advanced molecule is repotrectinib, a potential best-in-class ROS1/TRK/ALK tyrosine kinase inhibitor in Ph. I/II studies for cancer. This article explores the science behind repotrectinib, one of our 2021 Molecules of the Month, what properties make it…
Molecule Spotlight: Risdiplam, the First Approved Small Molecule Splicing Modulator for Spinal Muscular Atrophy
Spinal Muscular Atrophy (SMA)—the leading genetic cause of childhood mortality—is a disease in which the gene SMN1 is deleted or mutated. The highly similar gene SMN2 can undergo alternative splicing to generate functional protein transcripts of the SMN1 gene product, although native levels of the protein are too low to overcome the pathology. Here we…
Ten Examples of Best-in-Class Drugs
It’s best to be first, but drugs that are approved later with the same mechanism of action can also create significant value for patients and society by being best-in-class (BIC), or what clinicians refer to as “gold standard.” Recently we highlighted key factors that can make a follow-on drug be considered a best-in-class drug. This…
Why Did GSK Pay $1.9B for Momelotinib, an Oral Ph. III Myelofibrosis Candidate?
Momelotinib, an oral JAK1/2 inhibitor for myelofibrosis, is going to GSK as part of a $1.9 billion acquisition of Sierra Oncology. Anyone that’s ever worked on a kinase program probably looked at this structure and raised their eyebrows. $1.9 billion for another JAK2 inhibitor? It’s probably not super selective either, you might think… and you’d…
Small Molecule of the Year – 2021
We asked the global drug discovery community to nominate and vote on their favorite molecule from 2021, and the results are in. The 2021 choice for Drug Hunter’s Small Molecule of the Year is Pfizer’s CoV-2 Mpro Inhibitor, PF-07321332 (nirmatrelvir, Paxlovid). Published in a November 2021 Science article, the molecule was praised for its impressive…