Recludix Pharma, Inc.

Gilead Sciences and LEO Pharma recently announced a strategic partnership aimed at accelerating the development and commercialization of LEO Pharma's small molecule oral STAT6 (Signal Transducer and Activator of Transcription 6) inhibitors for potential inflammatory disease treatments. According to the collaboration agreement, Gilead will gain global rights for development, manufacturing, and commercialization of the project, while LEO Pharma will be responsible for the development of potential topical formulations and is eligible for payments up to $1.7 billion.   Industry insiders note that Gilead has been actively positioning itself in the inflammation space in recent years to overcome development bottlenecks. As an emerging target, STAT6 inhibitors are still in the early stages of development. Despite competition from companies like Johnson & Johnson, Sanofi, and AstraZeneca, Gilead's involvement brings new dynamics to the market. However, whether Gilead can replicate its past successes in the antiviral field remains to be seen. Therapeutics Research Institution Global Development Status Component Type KT-621 Kyinera Therapeutics Phase I Clinical PROTAC exoASO-STAT6 Codiak Biosciences Phase I Clinical ASO, Exosome STAT6 inhibitor (Enanta) Enanta Pharmaceuticals Preclinical Small Molecule AK-1690 University of Michigan Preclinical PROTAC STAT6 inhibitor (C&C Research) Shenzhen XtalPi, Jiangtai Pharmaceutical Co., Ltd., C&C Research Labs Preclinical Small Molecule CLXR-005 Celixir Preclinical siRNA STAT-6siRNA (Roquefort) Roquefort Therapeutics Preclinical siRNA KP-723 Kaken Pharmaceutical Co., Ltd., Johnson & Johnson Preclinical Small Molecule STAT6-targeting siRNA Alnylam Pharmaceuticals Preclinical siRNA AS1810722 Astellas Pharma Preclinical Small Molecule AS1617612 Astellas Pharma Preclinical Small Molecule AS1517499 Astellas Pharma Preclinical Small Molecule BCR-0007 Hangzhou Baixin Biotech Preclinical Small Molecule STAT6 (DeepCure) DeepCure Preclinical Small Molecule STAT6 degraders (Nurix Therapeutics) Nurix Therapeutics, Sanofi Preclinical PROTAC REX-4671 Recludix Pharma Preclinical Small Molecule REX-2787 Recludix Pharma, Sanofi Preclinical Small Molecule Immune-mediated inflammatory diseases (IMID) encompass a range of common and clinically diverse disorders, including rheumatoid arthritis, ankylosing spondylitis, connective tissue diseases, inflammatory skin diseases (such as psoriasis and atopic dermatitis), inflammatory bowel disease, asthma, and autoimmune neurological disorders. STAT6 is a specific transcription factor required for the signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), both of which are clinically validated targets for various Th2-mediated inflammatory conditions. Preclinical studies targeting STAT6 have shown potential to treat a broad patient population, providing a possible oral alternative for patients currently receiving injectable biologics. Under the collaboration agreement, Gilead will pay LEO Pharma a $250 million upfront payment and up to $1.7 billion in potential milestone payments based on project progress to secure global rights for the small molecule oral STAT6 program. In addition, LEO Pharma will have the right to co-commercialize dermatological indications outside of the U.S. and retain global rights for topical STAT6 formulations. Both parties will also receive tiered royalties based on sales of the oral STAT6 product. This collaboration will expedite the development of the STAT6 project, maximizing its potential across various inflammatory diseases beyond dermatology and providing an oral option for chronic inflammatory patients. Gilead stated that it will continue to expand its inflammation product portfolio, focusing on developing next-generation therapies that support long-term relief for patients with inflammatory diseases by blocking key pathogenic pathways, clearing pathogenic cells, tolerating the immune system, and restoring cell function. Indeed, Gilead has established dominance in the antiviral field with blockbuster drugs for hepatitis C, hepatitis B, and HIV. However, with the patent cliff approaching and market conditions changing, Gilead must actively seek new growth points to maintain its leadership in related fields. In recent years, Gilead has been active in both inflammation and oncology, particularly making significant strides in inflammatory diseases. Gilead has supplemented its early pipeline assets, including the JAK inhibitor filgotinib developed in collaboration with Galapagos, and acquired XinThera, which includes early-stage inflammation/immunology MK2 small molecule inhibitors. Furthermore, Gilead has expanded its oncology research collaboration with Arcus into inflammation and acquired CymaBay for $4.3 billion, with its later-stage product Livdelzi (seladelpar) approved by the FDA, providing new treatment options for patients with primary biliary cholangitis (PBC). Despite Gilead's substantial investments in inflammation, competition in this field is fierce, and the STAT6 inhibitor space is no exception. Johnson & Johnson has exclusive licensing agreements with Kaken Pharmaceutical for an oral STAT6 inhibitor KP-723 in preclinical development, with Kaken advancing the completion of Phase 1 clinical trials before Johnson & Johnson proceeds with global clinical development and commercialization. Kaken retains commercialization rights in Japan, while Johnson & Johnson has the right to enter into co-promotion agreements with Kaken. Additionally, Kymera Therapeutics' KT-621 is leading in STAT6 drug development, expected to begin Phase 1 clinical trials in healthy volunteers by October 2024. Sanofi has reached a strategic collaboration with Recludix Pharma to jointly develop an oral small molecule STAT6 inhibitor for treating immune and inflammatory diseases. Nurix Therapeutics has extended the collaboration period for its novel STAT6 degraders with Sanofi and plans to advance the project into clinical trials within the next 12 months. Nurix also announced an extension of its ongoing collaboration with Gilead, providing Gilead the option for up to five candidate drugs targeting various pathways. In the field of inflammation, major pharmaceutical companies are increasing their investments, reflecting a current trend in the pharmaceutical industry. Although related research is still in its early stages, STAT6 inhibitors have become a "battleground" for intensified competition. Who will emerge as the leader in this field remains an open question.

Gilead Sciences’ inflammation drug prospects have come via deals, and the latest one brings drug candidates for an elusive target that’s in pursuit by a growing number of companies. The drugmaker is paying $250 million up front to acquire preclinical small molecules from LEO Pharma. Gilead will continue development of oral formulations of these potential drugs, while privately held LEO will develop topical versions, according to deal terms announced Saturday. Denmark-based LEO could receive up to $1.7 billion in additional payments, depending on the progress of the partnered research. LEO aims to block inhibit the activity of IL-4 and IL-13, two signaling proteins that are validated targets associated with inflammation. Both proteins are already addressed by currently available injectable drugs, including Adbry, an FDA-approved IL-13-blocking antibody marketed by LEO for treating atopic dermatitis. But immunology drug research has been pursuing ways to block these targets with oral small molecules. Some of that research has focused on alternative ways of inhibiting inflammation driven by IL-4 and IL-13. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health Signal transducer and activator of transcription factor 6, or STAT6, is a protein that’s required for IL-4 and IL-13 signaling. LEO says preclinical research indicates that targeting STAT6 offers the potential to treat a broad population of patients with an oral alternative to injectable biologic drugs. The LEO drugs are small molecule inhibitors and targeted protein degraders. Gilead’s deal with LEO brings it into a burgeoning field of companies developing STAT6-targeting drugs. While Sanofi’s blockbuster Dupixent, an antibody inhibitor of IL-4 and IL-13, is a cornerstone of the pharma giant’s immunology strategy, the company also has designs on developing that product’s successor. In 2023, Sanofi paid $125 million up front to begin a partnership with privately held Recludix Pharma, a preclinical developer of small molecule inhibitors of STAT6. Recludix is scheduled to present on Wednesday during the annual J.P. Morgan Healthcare Conference in San Francisco. Sanofi has spread its STAT6 bets via a partnership with Nurix Therapeutics, developer of targeted protein degraders. Nurix is also partnered with Gilead in an alliance that spans oncology and immunology.Yet another protein degrader biotech, Kymera Therapeutics, in October began a Phase 1 test of its STAT6 degrader, KT-621. Just before the end of 2024, Johnson & Johnson announced it had licensed global rights, excluding Japan, to Kaken Pharmaceutical’s preclinical STAT6 inhibitor for autoimmune and allergic diseases. To industry observers, the flurry of STAT6 dealmaking is encouraging for the field. Leerink Partners analyst Faisal Khurshid wrote in a note sent to investors on Sunday that as the fourth major licensing deal for STAT6, Gilead’s collaboration with LEO underscores the growing strategic importance of this mechanism. An oral STAT6 degrader has the potential to be a category-defining medicine for T helper type 2 (Th2) inflammatory disorders, and could become an “oral Dupixent,” Khurshid said. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech “We see STAT6 as strategically important for companies aiming to develop small molecules for I&I (immunology & inflammation) indications and/or hold a position in Th2 inflammatory disorders (i.e., atopic dermatitis, asthma),” Khurshid said.

SAN DIEGO, Jan. 10, 2025 (GLOBE NEWSWIRE) -- Recludix Pharma, a leader in the discovery of inhibitors of challenging targets for inflammatory disease, today announced that Nancy Whiting, Pharm.D., president and chief executive officer of Recludix, will present an overview of the company’s progress and anticipated milestones for 2025 at the Annual J.P. Morgan Healthcare Conference in San Francisco, CA. The company’s presentation will be on Wednesday, January 15, 2025 at 2:00 p.m. Pacific Time. 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 partnership with Sanofi for the development and commercialization of a STAT6 inhibitor. Recludix is also advancing STAT3 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