resolvin E1 (TP-317) / Thetis Pharma - LARVOL DELTA

Tetrastigma hemsleyanum polysaccharides alleviate inflammatory bowel disease via the gut microbiota-SCFA-GPR43 signaling axis. (PubMed, Phytomedicine) - "THP exerts anti-colitic effects by modulating gut microbiota, activating GPR43-mediated signaling, and enhancing pro-resolving lipid mediators, showing potential for IBD treatment."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Transplantation • ARRB1

PATIENT REPORTED ATTITUDES TO INTRAVENOUS AND SUBCUTANEOUS ADMINISTERED THERAPIES FOR INFLAMMATORY BOWEL DISEASE (UEGW 2025) - "[1] Adalimumab, Golimumab, Ustekinumab & Risankizumab are administered subcutaneously (SC), Infliximab and Vedolizumab are administered intravenously (IV), and have additionally been available SC since 2020. SC Infliximab was used during the pandemic to limit exposure to hospitals & reduce risk of Covid-19, [2] as well as for convenience...6/29 (20.7%) stated SE not affected their quality of life (QoL), 12 (41.4%) little impact QoL, 10 (34.5%) moderate impact, 1 (3.4%) severe impact.96/105 (91.4%) would recommend IV routeSC survey106/113 (93.8%) completed the survey..54/106 patients were on Adalimumab (50.9%), 24 (22.6%) Ustekinumab, 13 (12.2%) Vedolizumab , 13 (12.3%) Infliximab, 2 (1.9%) Golimumab10/106 (9.4%) for 1-6 months, 21 (19.8%) for 6-12 months, 33 (31.1%) for 1-3yrs, 21 (19.8%) for 3-5 years and 20 (18.9%) for >5 years.89/106 (83.9%) rated treatment administration as easy, 10 (9.4%) intermediate, 2 (1.9%) difficult59/106 (55.7%) were previously on..."

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Novel Coronavirus Disease

Dendritic Cell-Based Biohybrid Immunomodulator Alleviates Intestinal Inflammatory Disease. (PubMed, Adv Mater) - "This biohybrid immunomodulator is engineered by conjugating resolvin E1-loaded liposomes with Fas ligand (FasL)-transfected DCs...Furthermore, the immunomodulator can be manufactured using human peripheral blood mononuclear cells and bone marrow-derived DCs, demonstrating a robust capacity to induce T cell apoptosis. This study presents a feasible and customizable strategy for mitigating intestinal inflammation, offering a promising advancement in the treatment of IBD."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CD8 • FASLG

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 2025) - "We have shown for the first time that TP-317 (RvE1) therapy reduces abdominal pain and aberrant ENS signaling networks in DNBS colitis. Colon molecular profiling reveals that TP-317 attenuates pathogenic inflammatory, immune dysfunction and transmural tissue remodeling pathways induced by DNBS. These novel mechanistic insights suggest that TP-317 offers a unique and differentiated profile to address unmet therapeutic needs in IBD."

Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Pain

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 2025) - "Based on the observation of transient neutropenia, a known effect of LTB4 and RvE1 at BLT1, TP-317 also demonstrated BLT target engagement. Oral TP-317's safety profile and pro-resolution, barrier-protective mechanism offers a unique and differentiated profile to address unmet therapeutic needs in IBD."

Clinical • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Mucositis • Neutropenia • Oncology • Pain

…TP-317, a Novel BLT1 Agonist Oral Therapy for IBD, Exhibits Anti-Inflammatory and Epithelial Barrier Protective Efficacy in Murine DSS Colitis and TNFΔARE Ileitis… (Businesswire) - "Thetis Pharmaceuticals LLC...announced the presentation...at Digestive Disease Week (DDW) 2025....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 TNFΔARE ileitis, TP-317 lowered intestinal permeability and inflammatory cytokines, reinforcing its potential as a disease-modifying therapy for Crohn’s disease and ulcerative colitis."

Preclinical • Crohn's disease • Ulcerative Colitis

…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… (Businesswire) - P1a | N=NA | "Thetis Pharmaceuticals LLC...announced the presentation...at Digestive Disease Week (DDW) 2025....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."

P1 data • PK/PD data • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

…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)… (Businesswire) - "Thetis Pharmaceuticals LLC...announced the presentation...at Digestive Disease Week (DDW) 2025....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."

Preclinical • Colorectal Cancer

…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… (Businesswire) - "Thetis Pharmaceuticals LLC...announced the presentation...at Digestive Disease Week (DDW) 2025....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."

Preclinical • Inflammatory Bowel Disease • Ulcerative Colitis

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 TNF^ΔARE Ileitis (Businesswire) - "In a two-cycle DSS colitis model, oral TP-317 treatment significantly reduced disease activity index (DAI) scores, histologic inflammation, and crypt damage, demonstrating strong anti-inflammatory and mucosal barrier-protective effects; In TNF^ΔARE ileitis models, TP-317 lowered intestinal permeability and reduced pro-inflammatory cytokines, reinforcing its potential as a disease-modifying therapy for Crohn’s disease and ulcerative colitis; In a visceral pain study, TP-317 reduced pain responses to colorectal distension to levels comparable to prednisolone, suggesting potential benefits for IBD-associated abdominal pain."

Preclinical • Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis

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 (ECCO-IBD 2025) - "Methods DSS colitis : 8-wk old C57Bl6/J mice (n=12/group) were given two 5-day cycles of DSS (1%, 2%) separated by a 10-day recovery period, followed by 7 days of daily oral treatment starting on day 20 with TP-317 (0.04, 0.4 or 4 mg/kg), cyclosporin (25 mg/kg), the JAK1 inhibitor filgotinib (36 mg/kg), or vehicle. These findings align with reports of have exacerbated DSS colitis in BLT1-/- mice and RvE1’s promotion of BLT1-dependent wound repair in an in vitro model using human intestinal epithelial cells. 1 2 Together, these studies support positioning of TP-317 as a novel, oral BLT1 agonist for treating ileal and colonic disease in IBD patients."

Preclinical • Immunology • Inflammation • Inflammatory Bowel Disease • IL17A

Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Oral Resolvin E1-based Therapy in Inflammatory Bowel Disease (IBD): Translating Resolvin E1 Activation of BLT1 in Experimental Models to Healthy Volunteers (ECCO-IBD 2025) - "Transient neutropenia observed with TP-317, a known effect of BLT1 activation by LTB4 and RvE1, suggests target engagement in humans. Oral TP-317’s safety profile and unique pro-resolution, barrier-protective mechanism warrant further clinical studies in IBD patients."

Clinical • PK/PD data • Immunology • Inflammation • Inflammatory Bowel Disease

Thetis Pharmaceuticals Secures an Additional $8.975 Million in Program-Related Investment Funds from the Helmsley Charitable Trust to Advance TP-317, an Oral BLT1 Agonist, into a Phase 1b Trial in Ulcerative Colitis Patients (Businesswire) - "Thetis Pharmaceuticals LLC...today announced that the company has secured an additional $8.975 million in program-related investment funding in the form of a loan from The Leona M. and Harry B. Helmsley Charitable Trust ('Helmsley'), bringing Helmsley’s total program-related investment in support of oral applications of TP-317 as a potential therapy for Crohn’s Disease patients to $14,044,660. The newly approved funding will support a Phase 1b trial of TP-317 in ulcerative colitis patients to identify safe and efficient dosing."

Financing • Ulcerative Colitis

Thetis Pharmaceuticals Announces Positive Initial Results From Phase 1a Study of TP-317 in Healthy Subjects (Businesswire) - P1a | N=24 | "Thetis Pharmaceuticals...announced positive top-line results from its Phase 1a study of TP-317 in healthy subjects. The study showed that TP-317 was safe and well tolerated, with pharmacokinetics that support dose selection for a follow-on Phase 1b trial in ulcerative colitis patients. Full results will be presented at a medical conference in 2025....A Phase 1b study in ulcerative colitis (UC) is planned for 2025 that will further evaluate safety and pharmacokinetics, with exploratory endpoints including clinical and endoscopic response, clinical remission, and biomarker analysis."

New P1 trial • P1 data • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Chemokine‑like receptor 1‑positive cells are present in the odontoblast layer in tooth tissue in rats and humans. (PubMed, Exp Ther Med) - "Following treatment of dental pulp stem cells with lipoteichoic acid, which imitates Gram-positive bacterial infection, resolvin E1 did not suppress the expression of cyclooxygenase-2 or of the odontoblast differentiation marker, dentin sialophosphoprotein. Furthermore, resolvin E1 induced the differentiation of dental pulp stem cells into odontoblasts even in the presence of the inflammatory stimulus."

Journal • Preclinical • Dental Disorders • Infectious Disease • Inflammation • DSPP

The Effect of Resolvin E1 and Resolvin D1 Specialised Pro-resolving Mediators on the Inhibition of Osteoclastogenesis (ACR Convergence 2023) - "In summary, this study highlights the capacity of RvE1 and RvD1 to specifically modulate OC differentiation in primary human cells in either health or RA. Combined, these findings suggest a potential for SPMs as novel treatment for RA."

Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD14 • CSF1 • FPR2

Thetis Pharmaceuticals Secures $4.2 Million From the Helmsley Charitable Trust to Advance Its First-in-Class Resolvin Oral Therapy for Crohn’s Disease (BioSpace) - "Dr. Bruce Sands...commented, 'Mechanistically, TP-317 has the potential to address a critical unmet need for safe, oral therapies for Crohn's disease patients without the side effects associated with immune suppression.'"

Media quote

Thetis Pharmaceuticals Secures $4.2 Million From the Helmsley Charitable Trust to Advance Its First-in-Class Resolvin Oral Therapy for Crohn’s Disease (BioSpace) - "Thetis Pharmaceuticals...has secured $4.2 million in non-dilutive financing from The Leona M. and Harry B. Helmsley Charitable Trust. Structured as a program-related investment in the form of a loan, the Helmsley funding supports the early clinical development of TP-317."

Financing • Crohn's disease • Inflammatory Bowel Disease

Thetis Pharmaceuticals Receives Orphan Drug Designation from FDA for Resolvin E1 Therapy for Pancreatic Cancer (BioSpace) - "Eileen O'Reilly, MD...commented, 'Pancreatic cancer is the fourth leading cause of cancer-related mortality worldwide and has an overall five-year survival rate of nine percent. Although the use of multi-agent cytotoxic combinations has improved outcomes for advanced pancreatic cancer, overall survival for most patients is less than a year. Thus, new therapeutic options are needed. Based on encouraging preclinical efficacy data and its differentiated mechanism of action addressing pro-tumor inflammation, TP-317 could offer a major benefit as adjuvant to existing standard of care and as monotherapy in the maintenance setting.'"

Media quote

Thetis Pharmaceuticals Announces Completion of Pre-IND Meeting with FDA for Development of its Resolvin E1 Candidate, TP-317, for Inflammatory Bowel Disease - "Thetis Pharmaceuticals ('Thetis')...announced today that it completed a Pre-IND (Investigational New Drug) meeting with the U.S. Food and Drug Administration for its lead candidate, TP-317, a Resolvin E1 oral, small molecule therapy being developed for inflammatory bowel disease (IBD). FDA has provided guidance on Thetis' nonclinical and clinical plans, including its proposed Phase 2a clinical trial in ulcerative colitis patients....Dr. William Sandborn...commented, 'TP-317 has the potential to address a critical unmet need for safe, oral therapies for IBD patients with a differentiated, non-immunosuppressive mechanism of action focused on mucosal healing. I am excited to see the TP-317 program advancing toward clinical investigation.'"

FDA event • Media quote

Thetis Pharmaceuticals receives funding from the Crohn's & Colitis Foundation to support investigational mucosal healing therapy for inflammatory bowel disease (Yahoo Finance) - "Thetis Pharmaceuticals...announced receipt of funding from the Crohn's & Colitis Foundation's IBD Ventures program to support development of TP-317, a first-in-class, oral therapy for inflammatory bowel disease (IBD)."

Financing

A Novel Salt of Resolvin E1 Controls Disease Activity in the Dextran Sulfate Sodium Colitis Mouse Model and Reduces Inflammation in Colon Tissue Explants from Ulcerative Colitis Patients (DDW 2019) - "Treatments were administered by oral gavage from Day 20-27 and were as follows vehicle (Groups 1&2), 1.5, 15, or 150 čg/d TP-317 (Groups 3-5), 0.63 mg/d cyclosporin (Group 6), 0.75 mg/d filgotinib (Group 7), 0.63 mg/d 5-ASA (Group 8), or 1.5 čg/d TP-317 and 0.63 mg/d 5-ASA (Group 9). Figure 1. Effects of TP-317 on cytokine expression in primary ulcerative colitis patient colon tissue explants."