Thetis Pharmaceuticals Presents New Preclinical and Clinical Data forTP-317 at DDW 2025

Business Wire

05-05-2025

ESSEX, Conn.--(BUSINESS WIRE)--Thetis Pharmaceuticals LLC ('Thetis'), a clinical-stage company developing TP-317, a first-in-class, small molecule drug candidate targeting the BLT1 receptor to treat inflammatory bowel disease (IBD) and solid tumor cancers, today announced the presentation of four data sets at Digestive Disease Week (DDW) 2025, held May 3-6 in San Diego, California. The data support TP-317's advancement as a novel oral therapy for both IBD and microsatellite stable (MSS) colorectal cancer (CRC).
'With encouraging preclinical results in IBD and MSS colorectal cancer and positive safety and PK/PD data from our Phase 1a study, TP-317 is well-positioned for Phase 2 clinical development in both indications.'
'These data show how TP-317 can meaningfully impact immune-mediated diseases by activating the BLT1 pathway. In IBD, TP-317 promotes epithelial repair and resolves mucosal inflammation. In solid tumors, TP-317 promotes antigen presentation to enhance the efficacy of immune checkpoint inhibitors in tumors that are resistant to immunotherapy,' said Gary Mathias, CEO of Thetis Pharmaceuticals. 'With encouraging preclinical results in IBD and MSS colorectal cancer and positive safety and PK/PD data from our Phase 1a study, TP-317 is well-positioned for Phase 2 clinical development in both indications.'
Colorectal Cancer: Immune Reprogramming and Combination Potential
In the oral presentation, ' TP-317, an Oral BLT1 Agonist, Enhances Immune Checkpoint Inhibitor Therapy by Stimulating Tumor Antigen Presentation in a Microsatellite Stable (MSS) Tumor Model of Colorectal Cancer (CRC), ' TP-317 demonstrated potent anti-tumor activity and synergy with checkpoint inhibitors. Key findings include:
TP-317 activated STING and IFN-γ pathways and boosted antigen presentation, converting immunologically 'cold' MSS tumors into 'hot,' immune-responsive ones.
TP-317 demonstrated robust single-agent efficacy and enhanced activity in combination with chemotherapy and checkpoint inhibitors in MSS CRC models.
Tumor control was BLT1-dependent, with broad innate and adaptive immune activation.
IBD: Barrier Protection and Mucosal Homeostasis
In a second oral presentation, ' TP-317, a Novel BLT1 Agonist Oral Therapy for IBD, Exhibits Anti-Inflammatory and Epithelial Barrier Protective Efficacy in Murine DSS Colitis and TNF ΔARE Ileitis,' data from multiple colitis models showed TP-317 restored epithelial barrier function and reduced inflammation. Key findings include:
In DSS colitis, TP-317 significantly reduced disease activity, histologic inflammation, and crypt damage, demonstrating strong anti-inflammatory and mucosal barrier-protective effects on par with a JAK inhibitor and cyclosporine.
In TNF ΔARE ileitis, TP-317 lowered intestinal permeability and inflammatory cytokines, reinforcing its potential as a disease-modifying therapy for Crohn's disease and ulcerative colitis.
Clinical Safety and PK/PD Profile
In the poster presentation, ' PK/PD, Safety, and Efficacy of Oral Resolvin E1-based Therapy in IBD: Translating Resolvin E1 Activation of BLT1 in Experimental Models to Healthy Volunteers,' data from a Phase 1a study confirmed TP-317's safety and target engagement:
Single oral doses up to 80 mg were well tolerated with no treatment-related adverse events.
Resolvin E1 (RvE1) exposure was dose-proportional and exceeded the EC50 for BLT1 activation.
Transient neutrophil margination that reversed within two hours (a known pharmacodynamic effect of RvE1 at BLT1) was observed at the 80 mg dose in all subjects, indicating target engagement.
Inflammation and Pain Biomarkers Modulation
A second poster presentation, 'TP-317, an Oral BLT1 Agonist, Reduces Abdominal Pain to Colorectal Distension and Reduces Key Biomarkers of Colitis in a Mouse Model of Inflammatory Bowel Disease,' further demonstrated TP-317's dual efficacy:
Significantly reduced visceral pain responses in DNBS colitis mice.
Broad transcriptomic suppression of genes associated with inflammation, epithelial-to-mesenchymal transition (EMT), and enteric nervous system signaling.
Compared favorably to prednisolone across visceral pain endpoints and modulation of gene expression pathways.
These findings build a compelling case for TP-317 as a Phase 2-ready candidate with broad potential to address unmet needs in IBD.
About Thetis Pharmaceuticals
Thetis is a clinical-stage pharmaceutical company focused on developing innovative treatments for chronic inflammatory diseases and cancer. Its lead candidate, TP-317, is a first-in-class oral Resolvin E1 drug candidate that targets the LTB4-BLT1 pathway to mobilize the body's natural ability to resolve disease and restore immune homeostasis. For more information, please visit www.thetispharma.com, and follow us on LinkedIn.