In this update of small molecules in the news for February 2023, we will cover recent: - Molecules in Motion : clinical trial updates and FDA filings - Negative Readouts : halted, discontinued or altered clinical trials - Million-Dollar Molecules : recent M&A’s, IPOs, and other fundraising - Potential Approvals : recent NDA filings and [...]

Our Drug Hunter subscribers at Curie.Bio recently made headlines with the launch of their new >$500M venture fund with a new model for early-stage biotech financing to help founders launch therapeutics companies. Curie.Bio intends to act not only as an investor, but also as a day-to-day operating partner to help founders choose targets [...]

A Ph. IIb TYK2 inhibitor from Nimbus (just bought by Takeda) that may be more efficacious than deucravacitinib, the first and only approved CGRP receptor antagonist nasal spray for the treatment of acute migraines from BMS/Pfizer, a pomalidomide-derived Ph. I/Ib oral, IKZF2-selective molecular glue degrader for the treatment of advanced solid tumors from Novartis are just some of the examples for this month's MOTM.  Learn more about the molecules by navigating to the full reviews on the right (when released) which cover: why the molecules matter, how they were discovered, the key steps behind...

The first approved non-covalent BTK inhibitor. As the nexus of the B cell receptor (BCR) signaling pathway , BTK has been a hotly pursued target in B-cell-mediated cancers and immunological diseases , as evidenced by the many BTK inhibitors we’ve highlighted in just the past few years. Recently, pirtobrutinib (Jaypirca, LOXO-305) received [...]

What is it? Elacestrant ( Orserdu ) is an oral, selective estrogen receptor modulator and degrader (SERM/SERD) that was recently approved for ER-positive, HER2-negative, estrogen receptor ɑ (ESR1)-mutated advanced or metastatic breast cancer (345 mg PO QD) based on progression-free survival (PFS) data from EMERALD ( NCT03778931 ). As the [...]

What is it? Baxdrostat ( RO6836191 , CIN-107) is an oral aldosterone synthase (CYP11B2) inhibitor in several Ph. II trials (0.5-2 mg QD) for hypertension, CKD, and primary aldosteronism. The molecule is highly selective ( >100x ) against a cortisol synthesis enzyme, CYP11B1, allowing it to avoid negative effects due to cortisol reduction in [...]

PF-6870961 is a growth hormone secretagogue receptor 1a (GHSR1a) inverse agonist biased for inhibition of 𝜷-arrestin signaling, in contrast to its parent compound, PF-5190457, an unbiased GHSR1a inverse agonist. PF-6870961 was discovered as a major metabolite of [...]

A protein-protein interaction inhibitor for a challenging-to-drug master transcription factor. OICR12694 is an oral protein-protein interaction inhibitor targeting the challenging-to-drug oncogenic transcription factor, B cell lymphoma 6 (BCL-6) . As a master regulator of B cell differentiation in germinal centers and hence a common driver of [...]

What is it? MK-8189 is a Ph. II clinical candidate for schizophrenia targeting PDE10A, a long-pursued but uncracked target for psychosis. With potentially better target engagement over prior molecules, it could become the first in the class to demonstrate efficacy in this challenging therapeutic area. The discovery and medicinal chemistry [...]

Newly disclosed HIV-1 antiretroviral is the first integrase-LEDGF/p75 allosteric HIV-1 inhibitor to clear Ph. I safety trials. Biodim has recently disclosed a small molecule candidate, BDM-2 , that demonstrates nanomolar activity against HIV-1 replication in vitro and showed promising safety in healthy subjects in a 2020 Ph. I clinical trial [...]

What is it? GB0139 is a selective, inhaled inhibitor of galectin-3 and galectin-1 in Ph. II for IPF and COVID-19 pneumonitis, and is Galecto’s ($GLTO) lead asset. Galecto was founded in 2011 with Lund University academic galectin research leaders Ulf Nilsson and Hakon Leffler, and has had a research focus on galectin-3 modulators to treat [...]

What is it? Saridegib (IPI-926, patidegib) is a Smoothened receptor (SMO) antagonist and hedgehog pathway inhibitor currently in Ph. III trials for Gorlin syndrome. The molecule is a semisynthetic analog of the naturally-occuring SMO antagonist , cyclopamine, and has a long history and originates from Infinity Pharmaceuticals . After a [...]

Mirati’s “Breakthrough” KRAS G12C inhibitor, adagrasib, was granted accelerated approval by the FDA in 2022. As it follows Amgen’s first-in-class KRAS G12C inhibitor, sotorasib, adagrasib is constantly scrutinized for any evidence it may be different, or better, than sotorasib. This deep dive reviews the current understanding on how adagrasib [...]

Here’s a preview of two molecules acquired in January 2023 among 14 mentioned in this article: deuruxolitinib (CTP-543) This molecule, a deuterated version of JAK1/2 inhibitor ruxolitinib (Opzelura, Incyte), has received Breakthrough Therapy designation from the FDA and is being acquired by Sun Pharma via Concert in a $0.576B transaction [...]

We recently explored how the lipophilicity (logP) of drugs has changed over time and found that, on average, drugs have become more lipophilic through the decades, primarily attributable to the industry’s move away from natural products. Despite this shift, it is clear from a broad qualitative comparison of structures from past decades to [...]

Our latest roundup of small molecules in the news includes two potential upcoming approvals: rezafungin Rezafungin (CD-101) is a once-weekly IV antifungal agent and next-generation echinocandin (glucan synthase inhibitor) that demonstrated non-inferiority vs. standard of care caspofungin (IV QD) (NCT03667690). An FDA AdCom voted 14 to 1 in [...]

Two past Molecules of the Month inductees had significant updates recently, showing they’re still moving forward: upacicalcet This September ‘22 Molecule of the Month is an IV calcium-sensing receptor (CaSR) agonist first identified in flavor studies of peptides. It is already approved in Japan for secondary hyperparathyroidism (SHPT), and [...]

Our latest roundup of small molecules in the news includes three molecules moving into development for the first time: MRTX1133 Mirati’s reversible, long-acting KRASG12D inhibitor, and December ‘21 Molecule of the Month, is going into the clinic as an oral compound. While initial disclosures referred to its potential as an IV agent, Mirati [...]