IBD Program

A clinical-stage, oral BLT1 agonist that adds epithelial repair to inflammation blockade

Breaking the Therapeutic Ceiling in IBD

The Challenge

▶ Monotherapy remission rates have plateaued across all major classes
▶ Core franchises face loss of exclusivity

Therapeutic Ceiling: <50% Remission

Adapted from Raine & Danese, Gastroenterology 2022;
Alsoud et al., Lancet Gastroenterol Hepatol 2021

Industry Response: Combinations

▶ Goal is to raise remission rates and extend exclusivity with combinations approved as new products
▶ 14 combinations and bispecifics in Phase 2 or 3, all pairing inflammation blockers

Limitations of Current Combinations

▶ Current combinations leave epithelial repair unaddressed
▶ Stacking immunosuppressive mechanisms could increase infection and malignancy risk

Inflammation Blockade Limits Damage – TP-317 Drives Repair

Inflammation Blockade

TNF · IL-23 · JAK · α4β7 · miR-124 · TL1A

▶ Blocks immune activation and gut homing
▶ Reduces downstream epithelial injury
▶ No direct effect on epithelial repair or collagen cross‑linking

TP-317: Repair and Resolution

BLT1 agonist · non-immunosuppressive

▶ Drives epithelial migration and proliferation
▶ Reduces collagen deposition and cross‑linking
▶ Dampens LTB4-driven neutrophil signaling

Clinical Development

Phase 1a 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

Phase 1a Results

✓ TP-317 was safe and well-tolerated across all dose levels
✓ Exposure increased with dose; the 80 mg dose reached 5.4-fold the EC50 of RvE1 at BLT1 at Cmax
✓ Target engagement supported by transient neutrophil margination,
a well-established effect of BLT1 activation

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