Recludix Pharma Receives FDA Clearance for First-in-Class Oral STAT6 Inhibitor REX-8756 to Enter Phase 1 Testing
核心洞察
The FDA has cleared Recludix Pharma (搜索)'s IND application for REX-8756 (搜索), an oral STAT6 inhibitor targeting the previously undruggable SH2 domain, to advance into Phase 1 clinical testing.
REX-8756 (搜索) demonstrated complete STAT6 pathway inhibition and efficacy comparable to anti-IL-4 (搜索)/IL-13 (搜索) antibody combinations in preclinical models of asthma (搜索), acute lung inflammation, and dermatitis.
The drug candidate is being developed under a strategic partnership with Sanofi, offering Recludix the option to participate in a 50:50 U.S. profit/loss share arrangement.
Recludix Pharma (搜索) announced that the U.S. Food and Drug Administration has cleared its Investigational New Drug application for REX-8756 (搜索), an oral STAT6 inhibitor, to advance into Phase 1 clinical testing. The milestone represents a significant breakthrough in targeting a previously undruggable protein domain for inflammatory diseases.
Novel Mechanism Targets Previously Undruggable Domain
REX-8756 (搜索) employs a novel therapeutic approach by targeting STAT6's SH2 domain, a key mediator of protein-protein interactions that was long considered undruggable. The oral, selective STAT6 inhibitor demonstrated complete and sustained inhibition of STAT6 activity in preclinical studies, thereby suppressing IL-4 (搜索) and IL-13 (搜索)-induced inflammatory biomarkers.
"With REX-8756 (搜索), we are excited by the opportunity to pioneer a new therapeutic class for patients with inflammatory diseases," said Nancy Whiting, Pharm.D., president and chief executive officer of Recludix. "We have demonstrated preclinically that our reversible, orally available STAT6 inhibitor can achieve efficacy comparable to that of clinically validated biologics."
Preclinical Efficacy Matches Established Biologics
In preclinical studies, REX-8756 (搜索) showed complete 100% pathway inhibition and demonstrated potent efficacy in models of asthma (搜索), acute lung inflammation and dermatitis, with results comparable to anti-IL-4 (搜索)/IL-13 (搜索) antibody combination controls. The compound maintained a favorable tolerability profile across these disease models.
STAT6 serves as a key nodal transcription factor that selectively mediates downstream signaling of IL-4 (搜索) and IL-13 (搜索), dominant cytokines in the pathophysiology of Type 2 inflammatory diseases. Because STAT6 is downstream in the disease pathway from other drug targets, its inhibition represents a more selective approach than Janus Kinase (JAK (搜索)) family inhibitors, with the potential for fewer side effects.
Strategic Partnership with Sanofi
The development program is being advanced under a strategic partnership with Sanofi, where Recludix has the option to participate in a 50:50 U.S. profit/loss share. REX-8756 (搜索) is also known as SAR448755 within the partnership framework.
Whiting emphasized the potential safety advantages of the STAT6 approach: "By targeting the pathological overactivation of STAT6 observed in many diseases -- without necessitating protein degradation and with an anticipated improved hematologic safety profile relative to JAK (搜索) inhibitors -- we believe this approach could be an important therapeutic option for patients."
Broad Therapeutic Potential
Abnormal activation of STAT6 is found in multiple inflammatory diseases, including atopic dermatitis (搜索), asthma (搜索), rheumatoid arthritis (搜索) and chronic spontaneous urticaria (搜索). 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.
Company Platform and Pipeline
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.
Beyond REX-8756 (搜索), Recludix is also advancing a potential first-in-class BTK (搜索) SH2 domain inhibitor for B cell or mast cell-driven inflammatory and immunological diseases, as well as additional discovery programs. The company was named a 2024 Fierce 15 biotech company.
The Phase 1 clinical study of REX-8756 (搜索) in healthy volunteers is expected to begin very shortly, marking the first clinical evaluation of this novel therapeutic class.