STAT6 inhibitor(C4X Discovery)

Bengaluru: Johnson & Johnson ‍said on Friday ​it discontinued a mid-stage study ⁠of its experimental drug to treat patients with moderate to severe atopic dermatitis after ‌it failed ‌to meet efficacy goals in an ‌interim analysis. The drug, JNJ-5939 , was being tested in patients with atopic dermatitis, or eczema, a skin condition that causes inflammation, redness and intense itching. The ​drug was well-tolerated but did ‌not ‍meet the "high-bar" efficacy required to ‍advance development, the company said. Johnson & Johnson ‌said it remains committed to developing treatments for atopic dermatitis, a chronic condition that affects more than 100 million people worldwide. The company is developing other experimental ‍treatments for atopic dermatitis, including bispecific antibodies NM26, PX128 and PX130, ‍as ⁠well as ⁠an oral STAT6 inhibitor, KP-723. Eczema has multiple approved treatments, such as Sanofi and Regeneron's Dupixent, AbbVie's Rinvoq, Pfizer's Cibinqo, Eli Lilly's Ebglyss, as well as some generic drugs such as cetirizine. (Reporting by Siddhi Mahatole in Bengaluru; Editing by Shilpi Majumdar)

--Efficacy comparable to anti-IL4/IL13 antibody control --Achieved dose-dependent and durable target modulation in vivo without requiring degradation of STAT6 protein --Avoided broad JAK-mediated immune suppression --Data presented at the American Thoracic Society (ATS) International Conference SAN DIEGO, May 19, 2025 (GLOBE NEWSWIRE) -- Recludix Pharma, a leader in the discovery of inhibitors for challenging targets in inflammatory disease, today announced a poster titled “Highly Selective and Reversible STAT6 Inhibition Demonstrates Potential for Differentiated Efficacy and Safety Profile in Type 2 Allergic Inflammation” was presented at the American Thoracic Society (ATS) International Conference in San Francisco, CA. The data demonstrated that the reversible, non-degrading STAT6 inhibitor caused a significant, dose-dependent reduction of airway inflammation that is on par with anti-IL-4/IL-13 treatment in an in vivo model of asthma in both prophylactic and therapeutic dosing paradigms. “What we have demonstrated in vivo is that our reversible STAT6 inhibitor has the potential to meet or exceed the efficacy of clinically validated biologics without needing to degrade STAT6 protein, while likely avoiding the hematologic safety concerns observed with JAK inhibitors,” said Ajay Nirula, M.D., Ph.D., executive vice president and head of research and development. “We are very excited about the potential of selective STAT6 inhibition for the treatment of asthma, COPD, atopic dermatitis, and other IL-4/IL-13-dependent diseases. We are working with our partner Sanofi to swiftly advance a STAT6 inhibitor into clinical trials.” In biochemical and primary human cellular assays, the company’s STAT6 SH2 domain inhibitor demonstrated highly selective, picomolar potency for inhibiting STAT6 activation driven by IL-4. The STAT6 inhibitor disrupted TARC (thymus and activation-regulated chemokine) production, a known biomarker for type 2 inflammatory diseases, following stimulation of human PBMCs (peripheral blood mononuclear cells) with IL-4 or IL-13. The molecule replicated the selectivity of IL4/IL13 biologics by preventing differentiation of Th2 (T helper 2) cells without impacting other immune pathways. In a preclinical model of allergic asthma, blocking STAT6 activation prevented lung inflammation with efficacy comparable to antibody-mediated blockade of anti-IL-4/13 pathways. The STAT6 inhibitor suppressed phosphorylated STAT6 activity in the blood, spleen and lung with repeat dosing without any impact on total STAT6 protein levels. Unlike JAK inhibitors, reversible and selective STAT6 inhibition did not impair growth factor signaling critical for hematologic homeostasis. Poster Presentation Details: Title:Highly Selective and Reversible STAT6 Inhibition Demonstrates Potential for Differentiated Efficacy and Safety Profile in Type 2 Allergic InflammationPoster Number:P1392Session:A32 - It’s Not Easy Being Wheezy: Asthma and COPD Clinical StudiesDate and Time:Sunday, May 18, 2025; 11:30 a.m. - 1:15 p.m. PT About STAT6Signal transducer and activator of transcription (STAT) proteins are both signaling proteins and transcription factors that play a role in cell growth, differentiation and function. STAT6 is a key nodal transcription factor that selectively mediates downstream signaling of IL-4 and IL-13, dominant and central cytokines in the pathophysiology of type 2 inflammatory diseases. A STAT6 inhibitor offers the potential for a novel first-in-class targeted oral therapy for patients in the treatment of type 2 inflammatory diseases. About RecludixRecludix is a leader in developing platform approaches to discover potent and selective inhibitors of challenging protein targets. The company’s management team includes industry veterans with a track record of success, including former leaders of Seagen, Blueprint Medicines, and Lilly. Recludix has developed a unique drug discovery platform that integrates custom generated DNA-encoded libraries, massively parallel determination of structure activity relationships, and a proprietary screening tool to ensure selectivity. The company is employing this approach first in the development of SH2 domain inhibitors. Recludix’s most advanced programs are focused on STAT (signal transducer and activator of transcription) proteins where abnormal activation is found in inflammatory diseases, such as rheumatoid arthritis, asthma, atopic dermatitis, and inflammatory bowel disease. The company has a strategic collaboration with Sanofi for the development and commercialization of a STAT6 inhibitor. Recludix is also advancing potential first-in-class BTK SH2 domain inhibitors for B cell or mast cell-driven I&I diseases, STAT3 SH2 domain inhibitors for Th17-mediated I&I diseases, as well as additional programs. Recludix was named a 2024 Fierce 15 biotech company. For more information, please visit the company’s website at https://recludixpharma.com. Recludix ContactsMatt Caldemeyer Chief Business Officermcaldemeyer@recludix.com Alexandra Santos asantos@wheelhouselsa.com Aljanae Reynoldsareynolds@wheelhouselsa.com