Fibroblasts under the microscope
Fibroblasts (skin cells) labeled with fluorescent dyes

Recludix Pharma has announced a strategic collaboration with Sanofi to develop and commercialize first-in-class oral small molecule STAT6 (signal transducer and activator of transcription 6) inhibitors for patients with immunological and inflammatory diseases. STAT6 is believed to play a key role in multiple dermatological and respiratory diseases.

Sanofi will pay $125 million in near-term payments, potentially more than $1.2 billion subject to future milestones, and up to double-digit royalties on sales. The big pharma has seen recent success in this field: Dupixent (Sanofi and Regeneron’s dupilumab) was approved for eczema in 2017 and asthma the next year. It generated an estimated $8.7 billion in 2022 sales. More approvals are on the horizon.

“This collaboration for the advancement of a preclinical oral STAT6 inhibitor speaks to our ability to successfully solve the challenge of drugging this attractive, yet elusive, therapeutic target,” said Nancy Whiting, PharmD, CEO of Recludix. “We are proud of the breakthroughs we have made in drugging SH2 domains as demonstrated by the STAT6.”

“Recludix’s approach to targeting STAT6 has significant potential for a number of immunological and inflammatory diseases, especially where a precisely tailored oral therapy could best fit within the patient’s needs at various stages of disease,” said Frank Nestle, Global Head of Research & CSO at Sanofi.

“We are excited to partner with the Recludix team to continue to advance innovative strategies for targeting this previously considered undruggable target, aligned with our mission to best serve patients with inflammatory disease,” he added.

Under the partnership, Sanofi will have global rights to small molecule STAT6 inhibitors. Recludix will advance STAT6 inhibitors from preclinical research and development until the start of Phase II clinical trials. Sanofi will assume worldwide clinical development and commercialization responsibilities thereafter. Recludix has the option to participate in U.S. profit/loss share, which includes the ability to share equally in the costs, profits and losses, and to certain co-promotion activities for the partnered product in the U.S.

Signal 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.

Recludix is developing platform approaches to discover potent and selective inhibitors of challenging protein targets. It 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 and its most advanced programs are focused on STAT proteins where abnormal activation is found in inflammatory diseases, such as rheumatoid arthritis, asthma, atopic dermatitis, and inflammatory bowel disease, as well as numerous cancer types, such as multiple leukemias and lymphomas.

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