In allergic diseases, STAT6 is a critical transcription factor in the IL-4 and IL-13 signaling pathways and the key driver of Th2 inflammation. Because STAT6 functions through protein-protein and protein-DNA interactions, selectively and potently inhibiting STAT6 with traditional small-molecule inhibitors has been a challenge. However, it is well suited for a targeted protein degradation approach, whereby a binding event is adequate to direct degradation.
Apogee Therapeutics Inc.’s phase I home run put IL-13-targeting antibody APG-777 on an accelerated development path in atopic dermatitis, and the company touted its similarity to further-along IL-13 competitor lebrikizumab, from Eli Lilly and Co., as a likely indicator of further success.
Derm-Biome Pharmaceuticals Inc. is preparing to initiate IND-enabling studies with DB-007-4, a first-line topical treatment for inflammatory skin diseases, such as acne, atopic dermatitis and rosacea. The company will shortly begin a GLP toxicology study.
On the verge of top-line data from its phase IIb trial with oral small-molecule CC chemokine receptor 4 (CCR4) antagonist zelnecirnon in atopic dermatitis (AD), due around the middle of this year, Rapt Therapeutics Inc. said the U.S. FDA has imposed a clinical hold on that study with the otherwise promising drug, also known as RPT-193, in AD as well as the phase IIa trial with the same compound in asthma.
DP Technology Ltd. has nominated DPT-0218, a novel small molecule targeting Kv1.3, as a preclinical candidate for the treatment of various autoimmune diseases, including inflammatory bowel disease and atopic dermatitis.
Allakos Inc. terminated all development of its lead drug, anti-Siglec-8 antibody lirentelimab (AK-002), and is cutting its workforce in half, following phase II failures for atopic dermatitis and chronic spontaneous urticaria. The San Carlos, Calif.-based company will now focus on phase I trials for anti-Siglec-6 antibody AK-006 as part of a restructuring that stretches the runway into mid-2026. Shares (NASDAQ:ALLK) sank by 60.2%, down $1.80, to close at $1.19 on Jan. 16.
Kymera Therapeutics Inc. has unveiled two new first-in-class oral degrader programs for immune-mediated diseases: KT-621, a STAT6 degrader, and KT-294, a TYK2 degrader.
JAK1 signaling promotes skin inflammation and is a major therapeutic target for atopic dermatitis-related itching. But in a study appearing in the Jan. 4, 2024, print issue of Cell after earlier publication online, researchers at the Icahn School of Medicine at Mount Sinai, led by dermatologist Brian Kim, found that intrinsic JAK1 signaling in sensory neurons had an immunoprotective effect in the lung. The findings suggest a more precise and personalized approach is required to potentially expand JAK inhibitor use to a wider range of allergy and inflammatory disorders.