TREX1 inhibitor / Tempest Therap - LARVOL DELTA

Generation of novel potent human TREX1 inhibitors facilitated by crystallography (AACR 2023) - "Lead compounds demonstrated good bioavailability and achieved exposures necessary for target engagement in mouse models and resulted in tumor growth inhibition when combined with sub-therapeutic doses of doxorubicin. We present the identification and characterization of a potential first-in-class TREX1 inhibitor with nanomolar potency against human and mouse TREX1. We present the identification and characterization of a potential first-in-class TREX1 inhibitor with nanomolar potency against human and mouse TREX1. Treatment with TREX1 inhibitors conferred profound anti-tumor activity when combined with DNA-damaging agents. Here we demonstrate that targeting TREX1 can specifically and locally engage the STING pathway in the tumor microenvironment, enhance tumor-specific immunity, and provide therapeutic benefit."

Oncology • CD8

Tempest Announces New Translational and Preclinical Data Presented at the 2023 AACR Annual Meeting (GlobeNewswire) - "Tempest Therapeutics, Inc....announced that new data from its TPST-1120 and TREX1 programs were highlighted in two poster presentations at the 2023 American Association for Cancer Research (AACR) Annual Meeting taking place April 14-19, 2023 in Orlando, FL...The presentation for Tempest’s preclinical TREX1 inhibitor program, designed for tumor-selective activation of the STING pathway, is the first public demonstration of human TREX1 enzyme—TREX1 inhibitor X-ray co-crystal structures, which has facilitated the development of potent and specific TREX1 inhibitors with drug-like properties. Lead series molecules resulting from this activity demonstrated therapeutic benefit in tumor-bearing preclinical models."

Preclinical • Oncology • Solid Tumor

Tempest to Present New Translational and Preclinical Data at the 2023 AACR Annual Meeting (GlobeNewswire) - "Tempest Therapeutics...announced that two abstracts have been accepted for poster presentation at the 2023 American Association for Cancer Research (AACR) Annual Meeting taking place April 14-19, 2023 in Orlando, FL. The presentations will highlight biomarker data from the Phase 1 trial of TPST-1120, an oral selective PPAR⍺ antagonist and preclinical data from TREX1 inhibitor, a tumor-selective STING pathway activator."

Biomarker • P1 data • Preclinical • Oncology • Solid Tumor

Tempest Reports First Quarter 2022 Financial Results and Provides Corporate Highlights (GlobeNewswire) - "Tempest Therapeutics, Inc...today reported financial results for the quarter ended March 31, 2022 and provided a corporate update....TPST-1120 (clinical PPARα antagonist): (i) first presentation of clinical data from a Tempest program at the oral presentation of the Phase 1 monotherapy and combination data at the ASCO 2022 Annual Meeting; and (ii) objective response data from the first 40 HCC patients in the first-line randomized study expected by year end or early 2023. TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): (i) selection of monotherapy RP2D expected in the first half of 2022; (ii) presentation of 'trial in progress' poster at ASCO 2022 Annual Meeting; and (iii) data from Phase 1 monotherapy and combination dose and schedule optimization arms expected by year end or early 2023. TREX1 Inhibitor (preclinical tumor-selective STING pathway activator): planned selection of development candidate in the second half of 2022."

P1 data • P1/2 data • Pipeline update • Trial status • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Hepatocellular Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer

Systemic small molecule TREX1 inhibitors to selectively activate STING in the TME of metastatic disease (AACR 2022) - "We observed significant anti-tumor activity in mice with CT26 tumors given a combined therapy of low dose doxorubicin to induce dsDNA breaks and increase TME TREX1 expression along with lead series TREX1 molecule inhibitors. Recognizing that TREX1 is a DNA repair enzyme, we also showed that TREX1 inhibitors were cytotoxic in DNA repair deficient human tumor cell lines, informing advancement of this new class of STING therapeutics as a clinical approach to both activate the cGAS/STING pathway to initiate immune recognition, as well as to inhibit DNA repair orthogonal to existing tumor-driver DNA repair mutations."

Oncology • CD8 • STING

Tempest Presents Promising Preclinical Data on Two Oncology Programs at the 2022 AACR Annual Meeting (GlobeNewswire) - "The inaugural presentation for the TREX1 program summarized the approach to develop selective TREX1 inhibitor small molecules with picomolar potency. TREX1 inhibitors were profiled in various human and mouse cell-based assays, demonstrating that inhibition of TREX1 nuclease activity resulted in increased cGAS/STING pathway signaling and production of a reporter or interferon β. The anti-tumor activity of TREX1 inhibitors was evaluated in mice given sub-therapeutic doses of doxorubicin to effect double-stranded breaks in tumor cell DNA and induce the production of TREX1, resulting in significant anti-tumor efficacy and survival."

Preclinical • Oncology • Solid Tumor

Tempest Reports Year End 2021 Financial Results and Provides Business Update (GlobeNewswire) - "Planned Near-Term Milestones: TREX1 Inhibitor (preclinical tumor-selective STING pathway activator): (i) presentation of the first data demonstrating therapeutic benefit in tumor-bearing mice treated with systemically-administered proprietary targeted molecules at the American Association for Cancer Research (AACR) 2022 Annual Meeting; and (ii) planned selection of development candidate in the second half of 2022."

Pipeline update • Preclinical • Oncology