It’s a good week to be working on drugs targeting STAT6. Kymera Therapeutics Inc.’s, KT-621, the first oral STAT6 degrader candidate to enter the clinic, surpassed expectations with impressive safety, pharmacokinetic and biomarker data from a phase I trial, while potential fast-followers from Nurix Therapeutics Inc. and Recludix Pharma Inc. advanced via respective partnerships with Sanofi SA.
Sanofi SA has exercised its option to exclusively license Nurix Therapeutics Inc.’s STAT6 program, including the drug development candidate NX-3911, an oral, highly selective STAT6 degrader.
Recludix Pharma Inc. has nominated a lead development candidate, REX-8756, an oral, selective and reversible small-molecule inhibitor of STAT6, and completed GLP toxicology studies for the compound. REX-8756 has potential for patients with type 2 immune-related inflammatory diseases.
Bronchodilators are front-line weapons against asthma and chronic obstructive pulmonary disorder. The search continues for next-generation dilators, which so far has largely produced compounds that are no better than existing ones and that often present safety problems.
Teva Pharmaceutical Industries Ltd. has commenced IND-enabling studies with BD-9, a dual-specific multibody targeting thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13). By simultaneously blocking two key drivers of TH2-driven inflammation, BD-9 has the potential to improve outcomes for patients with conditions such as atopic dermatitis and asthma.
Interleukin-4 receptor α (IL-4Rα), a shared receptor subunit for both IL-4 and IL-13, along with thymic stromal lymphopoietin (TSLP), are key drivers of the type 2 inflammatory cascade involved in asthma and other inflammatory disorders.
STAT6 plays a central role in regulating Th2-driven immune responses. Recent studies have identified gain-of-function mutations in the STAT6 gene that are associated with early-onset, severe allergic diseases. As a result, STAT6 has emerged as a promising therapeutic target in conditions such as asthma, eosinophilic inflammation, food allergies and atopic dermatitis, particularly in cases that are refractory to standard therapies.
Chronic obstructive pulmonary disease (COPD) is a prevalent and heterogeneous respiratory disorder with limited effective treatments. IL-33 and IL-4Rα are key mediators of airway inflammation in COPD and hence represent potential therapeutic targets.
A recent study in Respiratory Research further investigated the expression and role of the myristoylated alanine-rich C kinase substrate (MARCKS) protein in a horse model of asthma.
Despite missing a phase II study’s primary endpoint in moderate to severe asthma, Sanofi SA sees a way forward to a phase III program in the crowded disease space. Preliminary results showed the annualized exacerbation rate endpoint wasn’t met at the highest dosage of amlitelimab. Those numbers, at week 48, showed nominal significance at the medium dose.
