-REX-7117 is an oral, potent and selective STAT3 SH2 domain inhibitor, which demonstrated strong efficacy in an in vivo model of inflammatory arthritis
-STAT3 inhibition does not impair the interferon-mediated antiviral defense or hematopoietic growth factor signaling, as seen with JAK/TYK2 inhibitors
SAN DIEGO, CA, November 14, 2024 – Recludix Pharma, a leader in discovery of inhibitors of challenging targets for inflammatory disease, today announced pre-clinical inflammatory arthritis data for REX-7117, an oral, reversible, SH2 domain-targeting STAT3 inhibitor, will be presented at the American College of Rheumatology (ACR) Convergence meeting being held November 14–19, 2024 in Washington, D.C. In multiple in vivo models of inflammatory arthritis, REX-7117 achieved deep, durable, and selective STAT3 inhibition, decreased inflammatory biomarkers such as c-reactive protein (CRP), and achieved statistically significant efficacy compared to vehicle and comparable efficacy to a high-dose of the JAK inhibitor, baricitinib. Unlike both JAK1/2 and pan-JAK inhibitors, REX-7117 did not impair innate interferon-dependent viral replication or growth factor signaling critical for hematologic homeostasis.
“We have multiple preclinical datasets in inflammatory diseases confirming the differentiated therapeutic potential of selectively targeting STAT3,” said Ajay Nirula, M.D., Ph.D., executive vice president and head of research and development. “In these most recent studies for arthritis, we have demonstrated that by inhibiting STAT3, we can potently dampen inflammatory cytokines that drive rheumatologic diseases. Importantly, we are able to do so while avoiding the pathways that trigger the safety concerns seen with JAK/TYK2 inhibitors. A selective STAT3 inhibitor could be a promising therapy for diseases such as rheumatoid arthritis, psoriasis, psoriatic arthritis, and inflammatory bowel disease.”
REX-7117 was found to:
- Be highly selective to STAT3, including across the SH2 domain family and other STAT proteins;
- Achieve deep and durable STAT3 inhibition;
- Dose-dependently reduce arthritis disease clinical scores, similar to the highest dose of baricitinib tested;
- Significantly reduce serum CRP, an IL-6 dependent biomarker of inflammatory activity;
- Effectively reduce histopathological changes, including inflammation, cartilage damage, pannus formation, periosteal proliferation and bone resorption;
- And, not impair either type I or type II interferon-mediated antiviral activity.
In contrast, the JAK inhibitors tofacitinib and baricitinib broadly inhibited multiple phosphoSTAT pathways. JAK/TYK2 inhibitors are associated with on-target safety signals, including opportunistic infections and dysregulated hematologic homeostasis (anemia, thrombocytopenia).
Poster Presentation Details:
| Title: | REX-7117 Is a Highly Potent and Selective Oral STAT3 Inhibitor That Demonstrated Potential Efficacy and Safety Differentiation versus JAK/TYK2 Targeting in Preclinical Models of Inflammatory Arthritis |
| Poster Number: | 0947 |
| Session: | Poster Session B, RA – Animal Models Poster |
| Date and Time: | Sunday, November 17, 2024; 10:30 a.m. – 12:30 p.m. ET |
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.
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. 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 Contacts
Matt Caldemeyer
Chief Business Officer
mcaldemeyer@recludix.com
Alexandra Santos
asantos@wheelhouselsa.com
Aljanae Reynolds
areynolds@wheelhouselsa.com