TPST-1495 / Tempest Therap - LARVOL DELTA

Tempest Reports Third Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "'In addition, we look forward to the start of the TPST-1495 Phase 2 in collaboration with the NCI and the Cancer Prevention Clinical Trials Network...'"

New P2 trial • Solid Tumor

Pilot Window of Opportunity Trial (POET) (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: University of Oklahoma | Trial primary completion date: Sep 2025 ➔ Dec 2025

Trial primary completion date • Colorectal Cancer • Endometrial Cancer • Oncology • Solid Tumor

TPST-1495-001: Phase 1a/1b Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors (clinicaltrials.gov) - P1 | N=89 | Completed | Sponsor: Tempest Therapeutics | Active, not recruiting ➔ Completed | N=175 ➔ 89

Enrollment change • Trial completion • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • PIK3CA

Pilot Window of Opportunity Trial (POET) (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: University of Oklahoma | Trial completion date: Apr 2026 ➔ Sep 2026 | Trial primary completion date: Apr 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Colorectal Cancer • Endometrial Cancer • Oncology • Solid Tumor

Tempest Receives Orphan Drug Designation from the FDA for TPST-1495 to Treat Patients with FAP (GlobeNewswire) - "Tempest Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to TPST-1495, the company’s novel dual receptor inhibitor of prostaglandin (PGE2) signaling, for the treatment of patients with Familial Adenomatous Polyposis (FAP)....A Phase 2 study evaluating TPST-1495 in patients with FAP is set to begin this year, conducted by the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute (NCI) Division of Cancer Prevention. Data from this study are expected in 2026."

Orphan drug • P2 data • Genetic Disorders

Tempest Reports Year End 2024 Financial Results and Provides Business Update (GlobeNewswire) - "TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): Plan to advance TPST-1495 into a Phase 2 study in patients with FAP under the auspices of the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute (NCI) Division of Cancer Prevention in 2025, with data expected in 2026."

New P2 trial • P2 data • Genetic Disorders

FDA Study May Proceed Notice Received for Phase 2 Trial of TPST-1495 for the Treatment of Familial Adenomatous Polyposis (FAP) (GlobeNewswire) - "Tempest Therapeutics, Inc...today announced that the Cancer Prevention Clinical Trials Network received a 'Study May Proceed' letter from the U.S. Food and Drug Administration (FDA) to evaluate TPST-1495, the company’s novel dual receptor inhibitor of prostaglandin (PGE2) signaling, in a Phase 2 clinical trial for the treatment of patients with Familial Adenomatous Polyposis (FAP)...The Phase 2 study in patients with FAP will begin this year and will be run by the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute ('NCI') Division of Cancer Prevention."

FDA event • New P2 trial • Rare Diseases

Blockade of the PGE2 pathway inhibits the growth of PTEN deficient HNSCC tumors. (PubMed, Mol Cancer Ther) - "Here, we assessed PGE2 signaling in PTEN-deficient HNSCC and evaluated the effect of aspirin or TPST-1495, a dual EP2/EP4 antagonist, on the growth of PTEN knockout (KO) and PIK3CA-altered HNSCC tumors in immunocompetent mice. To date, there are no FDA-approved therapies for PI3K pathway-altered HNSCC. Our findings suggest that NSAIDs demonstrate anti-tumor activity in PTEN-deficient or PI3K-altered tumors whereas EP2/EP4 targeting may augment FDA-approved anti-PD1 therapy in HNSCC."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PIK3CA • PTEN

An Investigational Drug (TPST-1495) in Patients With Familial Adenomatous Polyposis (clinicaltrials.gov) - P2 | N=38 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Feb 2025 ➔ May 2025

Trial initiation date • Genetic Disorders • CTNNB1 • PTGS2

Tempest Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Other Potential Future Milestones - TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): (i) Expect to disclose data from the TPST-1495 Phase 1 combination arm in patients with advanced endometrial cancer in 2025."

P1 data • Endometrial Cancer

An Investigational Drug (TPST-1495) in Patients With Familial Adenomatous Polyposis (clinicaltrials.gov) - P2 | N=38 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P2 trial • Genetic Disorders • CTNNB1 • PTGS2

Tempest Reports Second Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Potential Future Milestones: (i) Amezalpat (TPST-1120) (clinical PPARα antagonist): Plan to advance amezalpat into a registrational Phase 3 study in first-line HCC patients, subject to obtaining feedback from the FDA; (ii) TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist):...Expect to report data from the combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer, where prostaglandin signaling is implicated, in 2024."

New P3 trial • P1 data • Endometrial Cancer • Hepatocellular Cancer

Tempest Reports First Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Potential Future Milestones:...TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist:...Expect to report data from the combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer, where prostaglandin signaling is implicated, in 2024."

P1 data • Endometrial Cancer

TPST-1495-001: Phase 1a/1b Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors (clinicaltrials.gov) - P1 | N=175 | Active, not recruiting | Sponsor: Tempest Therapeutics | Recruiting ➔ Active, not recruiting | Phase classification: P1a/1b ➔ P1 | Trial primary completion date: Apr 2024 ➔ Sep 2024

Combination therapy • Enrollment closed • Phase classification • Trial primary completion date • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • PIK3CA

Tempest Reports Year End 2023 Financial Results and Provides Business Update (GlobeNewswire) - "TPST-1495...Expect to report data from the combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer in 2024."

P1 data • Endometrial Cancer

Pilot Window of Opportunity Trial (POET) (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: University of Oklahoma | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Biomarkers associated with blockade of prostaglandin E2 signaling by TPST-1495: a novel, dual-antagonist of E-prostanoid receptors 2 and 4 (SITC 2023) - P1a/1b | "Elevated baseline COX-2 levels may be a predictive biomarker of response in patients. Currently, the combination of TPST-1495 and pembrolizumab is being assessed in endometrial cancer patients, a malignancy expressing comparatively high levels of EP2, EP4 and COX-2."

Biomarker • Endometrial Cancer • Oncology • Solid Tumor • CD8 • GZMB • PTGS2 • TNFA • TPST1

Pilot Window of Opportunity Trial (POET) (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: University of Oklahoma

New P2 trial • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Dual Blockade of EP2 and EP4 Signaling is Required for Optimal Immune Activation and Antitumor Activity Against Prostaglandin-Expressing Tumors. (PubMed, Cancer Res Commun) - "Dual EP2/EP4 PGE2 receptor antagonists increased tumor microenvironment lymphocyte infiltration and significantly reduced disease burden in multiple tumor models, including in the adenomatous polyposis coli (APC) spontaneous colorectal tumor model, compared with celecoxib...Here we describe TPST-1495, a first-in-class orally available small-molecule dual EP2/EP4 antagonist. Prostaglandin (PGE2) drives tumor progression but the pathway has not been effectively drugged. We demonstrate significantly enhanced immunologic potency and antitumor activity through blockade of EP2 and EP4 PGE2 receptor signaling together with a single molecule."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • TPST1

Tempest Reports Second Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "Potential Upcoming Milestones: (i) TPST-1120 (clinical PPARα antagonist): we expect to be able to discuss an updated and comprehensive data set from the formal review of the ongoing, global, randomized Phase 1b/2 study in first-line liver cancer patients in the second half of 2023; (ii) TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): we plan to report data from the combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer in 2024."

P1 data • P1/2 data • Endometrial Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Liver Cancer • Oncology • Solid Tumor • Uterine Cancer

Tempest Announces Publication in Cancer Research Communications Highlighting TPST-1495 Significantly Increased Potency Against Prostaglandin-Driven Tumor Models by Blocking EP2 and EP4 Together (GlobeNewswire) - "Tempest Therapeutics, Inc...announced today that in vivo and in vitro data on the unique mechanism of TPST-1495, the company’s novel dual receptor inhibitor of prostaglandin E2 (PGE2) signaling, were published in Cancer Research Communications, a journal of the American Association for Cancer Research....'Our innovation with TPST-1495 shows for the first time the effect of blocking PGE2 signaling through the EP2 and EP4 pro-tumor receptors while maintaining the important anti-tumor signaling of PGE2 through the EP1 and EP3 receptors, which could be an important advance to inhibiting PGE2'."

Preclinical • Oncology

A phase 1 study of TPST-1495 as a single agent and in combination with pembrolizumab in patients with advanced solid tumors. (ASCO 2023) - P1a/1b | "In preclinical models, dual EP2/EP4 inhibition with TPST-1495 increased anti-tumor efficacy, reduced immune suppression, and activated immune effector response significantly better than single EP2 or EP4 antagonists and the COX-2 inhibitor celecoxib. PGE2 is an important target for cancer and immunotherapy but remains ineffectively drugged. TPST-1495 is a novel oral therapy that inhibits signaling only at the tumor promoting EP2/EP4 receptors. In patients with heavily treated solid tumors, primarily MSS CRC, TPST-1495 had pharmacodynamic activity, a manageable safety profile, and a potential signal of activity consistent with the preclinical data and IO combination mechanism."

Clinical • Combination therapy • IO biomarker • Metastases • Anemia • Endometrial Cancer • Fatigue • Hematological Disorders • Oncology • Pain • Pancreatic Cancer • Solid Tumor • CD8 • PTGS2 • TNFA • TPST1

Tempest to Present Phase 1 Monotherapy and Combination Data at ASCO for TPST-1495 in Patients with Advanced Cancers (GlobeNewswire) - P1a/1b | N=175 | NCT04344795 | Sponsor: Tempest Therapeutics | "The data showed that in a diverse and treatment-refractory patient population, treatment with TPST-1495 as a monotherapy and in combination with pembrolizumab resulted in tumor shrinkage and prolonged stable disease in certain patients, as well as a durable confirmed partial response (PR) in a combination therapy patient with microsatellite stable colorectal cancer (MSS CRC), an indication not normally responsive to immunotherapy....On the recommended once-daily schedule, the disease control rate (DCR) by RECIST v1.1 was 44% for patients on monotherapy TPST-1495 and 40.9% for patients on TPST-1495 with pembrolizumab (including a confirmed PR in a patient with MSS CRC and a stable disease rate of 36.4%)."

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Tempest Reports First Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): we plan to report data from (i) the Phase 1 dose and schedule optimization trial studying monotherapy and combination therapy with an anti-PD1 therapy, pembrolizumab, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, and (ii) a separate combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer in 2024."

P1 data • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Tempest Announces TPST-1495 Poster Presentation at the 2023 ASCO Annual Meeting (GlobeNewswire) - "Tempest Therapeutics, Inc...today announced the acceptance of an abstract on TPST-1495, a EP2/EP4 prostaglandin receptor dual antagonist, for a poster presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 2-6, 2023 at the McCormick Place Convention Center in Chicago, IL."

P1 data • Oncology • Solid Tumor