IBD Program

TP-317: First-in-Class, Oral BLT1 Agonist for Inflammatory Bowel Disease

The Challenge in IBD

30-50%

Primary Response

Clinical remission rates with
current advanced therapies

~50%

Secondary Failure

Biologic responders fail
within two years of initial treatment

▶ Therapeutic Ceiling
Advanced therapies — anti-TNFs, IL-23 inhibitors, JAK inhibitors, anti-integrins — have transformed IBD care, but durable remission remains elusive for many patients.
▶ Epithelial Repair Gap
While these therapies promote mucosal healing by suppressing inflammation, they do not directly engage epithelial cells to restore barrier function.
▶ Compounding Immunosuppression
Because advanced therapies suppress immune function, combining them to increase response and durability can compound safety issues.

TP-317 Activates Resolution Biology Complementary to Inflammation Blockade

▶ Epithelial Repair
Activates epithelial BLT1, engaging the Src/FAK pathway to promote repair and barrier restoration — shown in human intestinal epithelial cell models
▶ Fibrosis Prevention
Attenuates pro-fibrotic signaling including collagen and lysyl oxidase pathways — shown in acute colitis models
▶ Inflammation Resolution
Drives resolution by promoting neutrophil apoptosis and clearance, displacing LTB4-driven immune cell recruitment, and limiting microbial translocation

Phase 1a Data Supports Advancing into IBD Patients

Study Design

Design: Randomized, placebo-controlled, single-ascending dose
Population: Healthy volunteers
Cohorts: 3 dose levels n=8 per cohort (3:1)
Doses: 10, 40, 80 mg oral, single dose

Key Results

✓ TP-317 was safe and well-tolerated across all dose levels
✓ Dose-proportional PK with blood levels sufficient to activate BLT1 at all doses based on the EC50 of RvE1 at BLT1
✓ Target engagement supported by transient neutrophil margination in all treated subjects monitored

What TP-317 Brings to Combination Therapy

Epithelial Repair

Adds direct barrier repair to mucosal  healing  achieved  by  blockade 

Inflammation Resolution

Resolves drivers of IBD pathology unaddressed by inflammation blockade

Non-Immunosuppressive

Allows combination therapy without additional safety burden on patients

Layered Patent Estate

Enables runway extension for
combination approaches

References

RvE1 Biology

Quirós M, et al. Resolvin E1 is a pro-repair molecule that promotes intestinal epithelial wound healing. Proc Natl Acad Sci U S A. 2020;117(17):9477-9482. https://doi.org/10.1073/pnas.1921335117

Hayashi S, et al. Intestinal epithelial BLT1 promotes mucosal repair. JCI Insight. 2022;7(23):e162392. https://insight.jci.org/articles/view/162392

El Kebir D, Gjorstrup P, Filep JG. Resolvin E1 promotes phagocytosis-induced neutrophil apoptosis and accelerates resolution of pulmonary inflammation. Proc Natl Acad Sci U S A. 2012;109(37):14983-14988. https://doi.org/10.1073/pnas.1206641109

Merlin J, et al. Multipathway In Vitro Pharmacological Characterization of Specialized Proresolving G Protein-Coupled Receptors. Mol Pharmacol. 2022 Apr;101(4):246-256. https://pubmed.ncbi.nlm.nih.gov/35125345/

Arita M, et al. Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol. 2007;178(6):3912-3917. https://doi.org/10.4049/jimmunol.178.6.3912

Pellas TC, et al. LTB4-induced transient neutropenia in the rat: a model for evaluating efficacy and bioavailability of LTB4 receptor antagonists. J Pharmacol Toxicol Methods. 1993 Nov;30(3). https://doi.org/10.1016/1056-8719(93)90036-e

TP-317 Conference Abstracts

Verstockt B, et al. TP-317, a novel BLT1 agonist oral therapy for inflammatory bowel disease, exhibits anti-inflammatory and epithelial barrier protective efficacy in murine DSS colitis and TNFΔARE Ileitis. Journal of Crohn's and Colitis. 2025;19(Supplement_1). https://doi.org/10.1093/ecco-jcc/jjae190.0243

Brierley S, et al. 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. DDW ePoster Library. 05/06/2025; 4157089

Sands B, et al. Pharmacokinetics, pharmacodynamics, safety, and efficacy of oral Resolvin E1-based therapy in inflammatory bowel disease: translating RvE1 activation of BLT1 in experimental models to healthy volunteers. DDW ePoster Library. 05/03/2025; 4154830

Selected IBD References

Danese S, Solitano V, Jairath V, Peyrin-Biroulet L. The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment). Gut. 2022;71(12):2380-2387. https://doi.org/10.1136/gutjnl-2022-327025

Beaugerie L, Kirchgesner J. Balancing Benefit vs Risk of Immunosuppressive Therapy for Individual Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2019;17(3):370-379. https://doi.org/10.1016/j.cgh.2018.07.013