— In a preclinical model of psoriasis, the efficacy of oral small molecule REX-7117 was comparable to an anti-IL-17A biologic
SAN DIEGO, CA, May 17, 2024 – Recludix Pharma, a leader in discovery of inhibitors of challenging targets for inflammatory disease and cancer, presented new data today in an oral plenary presentation at the Society for Investigative Dermatology (SID) Annual Meeting titled “Oral selective STAT3 inhibitors demonstrate differentiated efficacy and safety potential in preclinical models of Th17 mediated skin inflammation” (abstract #738). Recludix’s senior vice president of biology, Paul Smith, Ph.D., reviewed preclinical data on the company’s potent, selective, and orally bioavailable small molecule STAT3 inhibitors, including REX-7117. Data demonstrated that REX-7117 achieves deep, durable, and selective STAT3 inhibition and exhibits similar efficacy to biologics targeting IL-17 in in vivo models of plaque psoriasis. Data was also presented that, unlike JAK1/2 and TYK2 inhibitors, REX-7117 does not impair broader immune responses, such as interferon-dependent anti-viral immunity or growth factor signaling critical for hematologic homeostasis.
“These exciting data on our oral STAT3 inhibitors demonstrate that deep STAT3 inhibition has the potential to drive potent efficacy — such as that seen with clinically validated biologics but with improved convenience as an orally-administered medication, while high selectivity for the downstream STAT3 target may avoid some of the safety concerns observed with JAK and TYK2 inhibitors,” said Ajay Nirula, M.D., Ph.D., executive vice president and head of research and development. “Inhibiting STAT3 could be a favorable and effective approach to treating Th17- and Th1-mediated diseases, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, and inflammatory bowel disease.”
Both REX-7117 and REX-5376 are highly potent and selective orally-available STAT3 inhibitors, as demonstrated across biochemical and cellular assays, which have the potential to:
- Impair inflammatory Th17 cell function, while sparing activation of other cytokine pathways which play critical roles in the defense against viruses, bacteria, extra cellular pathogens, and parasites
- Spare STAT1 mediated-signaling, in contrast to the impact on STAT1 signaling seen with baricitinib (JAK1/2) and deucravacitinib (TYK2)
- Not impair either type I or type II interferon (IFN)-mediated antiviral activity, as shown in in vitro models
- Not impair STAT5-mediated signaling by hematopoietic growth factors, unlike some JAK inhibitors which have the risk of inducing anemia, thrombocytopenia, and neutropenia
In a murine IL-23 induced psoriasis model, REX-7117 achieved efficacy responses similar to an anti-IL-17A antibody surrogate treatment and was more efficacious than an estimated clinically relevant dose of deucravacitinib.
About STAT3
The interleukin cytokines IL-23 and IL-6 signal through STAT3 and promote the generation and function of pathogenic T helper type-17 (Th17) cells, a type of immune cell that is pro-inflammatory. Th17 cells are considered pivotal players in certain inflammatory diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease and others. Inhibiting STAT3 can also offer potential efficacy beyond Th17 / IL-17 driven diseases in clinical indications where blocking the IL-6 pathway is clinically validated. Furthermore, clinical trials inhibiting oncostatin M (OSM) and IL-22, both STAT3 dependent cytokines, have been reported as efficacious in inflammatory disease.
A selective, oral STAT3 inhibitor has potential to provide an attractive alternative to JAK/TYK2 inhibitors and biologics for multiple inflammatory diseases.
STAT3 inhibitors may also have significant opportunity in cancer settings, as STAT3 is activated in greater than 70% of human cancers.
About Recludix
Recludix 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, as well as numerous cancer types, such as multiple leukemias and lymphomas. 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 and oncology indications, as well as additional programs. For more information, please visit the company’s website at https://recludixpharma.com.
Recludix Contacts:
Alexandra Santos
asantos@wheelhouselsa.com
Aljanae Reynolds
areynolds@wheelhouselsa.com