Tempest Presents Data Showing TPST-1120-Induced Pharmacodynamic Changes Consistent with Clinical Benefit Observed in Patients with Cancer
- TPST-1120 Late-breaking Poster Presentation at SITC Annual Meeting
- Second Poster Presentation Demonstrates that Dual Blockade of EP2 and EP4 PGE2 Receptors with TPST-1495 is an Optimal Approach for Drugging the Prostaglandin Pathway
SOUTH SAN FRANCISCO, Calif., Nov. 10, 2022 (GLOBE NEWSWIRE) -- Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company focused on developing first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, today announced the presentation of data on TPST-1120, an oral selective peroxisome-proliferator activated receptor-alpha (PPAR-α) antagonist, and TPST-1495, a dual antagonist of both EP2 and EP4 prostaglandin (PGE2) receptors, at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting taking place November 10-12, 2022 in Boston, MA.
The biomarker results presented from the TPST-1120 Phase 1 clinical study demonstrate pharmacodynamic changes in circulating blood in patients who received clinical benefit from therapy that are consistent with blocking the activity of PPAR-α. In addition, data presented from TPST-1495 showed that its dual antagonism of EP2 and EP4 generated significantly greater immune activation in human immune cells and anticancer activity in mouse tumor models than single inhibitors of either receptor, or the COX-2 inhibitor, celecoxib.
“As we advance the Tempest pipeline, we continue to generate results that validate and differentiate the novel approaches of our product candidates,” said Tom Dubensky, Ph.D., president of Tempest. “For patients who responded to treatment with TPST-1120 in our Phase 1 study, we have identified potential biomarkers in the peripheral blood of immune activation and alleviation of immune suppression. These discoveries may enable us to identify patient populations in future clinical studies that are most likely to benefit from treatment with TPST-1120.”
TPST-1120: “Pharmacodynamic and Predictive Biomarkers Associated with Response in Cancer Patients Treated with TPST-1120: a First-in-class, Small Molecule Antagonist of Peroxisome-Proliferator Activated Receptor-Alpha”
In a late-breaking poster presentation, data from a Phase 1 trial with monotherapy and nivolumab combination arms were used to assess gene expression changes in post-treatment whole blood from 30 patients and to perform baseline mutational analysis on ctDNA to identify potential biomarkers. The data showed that seven genes were modulated by TPST-1120 exposure (p<0.05), including genes associated with enhanced immune responsiveness (CXCL16, TNFRSF1A), stimulation of monocytes or macrophages (ITGAX, FCGR2A) and PPAR-α blockade (NCF4). The results were consistent across monotherapy and combination arms. Patients in the combination arm who had a partial response (PR) to treatment had significant elevations (p<0.05) in multiple genes, including those associated with Th17 development (RORC), lipid transport (APOE) and down-regulation of CD155, a TIGIT ligand. Mutational analysis revealed that patients with a PR or stable disease were more likely to bear mutations in isocitrate dehydrogenase (IDH) and phosphatase and tensin homolog (PTEN) compared to patients with progressive disease.
TPST-1495: “Dual Blockade of the EP2 and EP4 PGE2 Receptors with TPST-1495 is an Optimal Approach for Drugging the Prostaglandin Pathway”
In a second presentation, the data demonstrated that TPST-1495 was more effective than EP2 and EP4 single antagonists, and the COX-2 antagonist, celecoxib, in mouse and human whole blood assays. TPST-1495 conferred a near complete restoration of immune function in cellular assays, even in the presence of high PGE2 concentrations. In lung carcinoma tumors and in a spontaneous tumor mouse model of CRC, TPST-1495 decreased tumor size and number of tumors. Immunohistochemistry analysis of the resected small intestine tumors revealed increased immune infiltrate and an enhanced adaptive immune transcriptional profile.
About Tempest Therapeutics
Tempest Therapeutics is a clinical-stage oncology company advancing small molecules that combine both tumor-targeted and immune-mediated mechanisms with the potential to treat a wide range of tumors. The company’s two novel clinical programs are TPST-1120 and TPST-1495, antagonists of PPARα and EP2/EP4, respectively. Both programs are advancing through clinical trials designed to study the agents as monotherapies and in combination with other approved agents. Tempest is also developing an orally available inhibitor of TREX1, a target that controls activation of the cGAS/STING pathway. Tempest is headquartered in South San Francisco. More information about Tempest can be found on the company’s website at www.tempesttx.com.
This press release contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended (the “Securities Act”)) concerning Tempest Therapeutics, Inc. (“Tempest Therapeutics”). These statements may discuss goals, intentions, and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Tempest Therapeutics, as well as assumptions made by, and information currently available to, management of Tempest Therapeutics. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “could”, “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions. All statements that are not historical facts are forward-looking statements, including any statements regarding the results of studies, future clinical study plans, commencement of, or availability of data from, clinical trials, or the benefits that may be derived from any future products. Forward-looking statements are based on information available to Tempest Therapeutics as of the date hereof and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation, the progress, scope or timing of the development of our product candidates. These and other risks are described in greater detail in the Form 10-Q filed by Tempest Therapeutics with the Securities and Exchange Commission on November 8, 2022. Except as required by applicable law, Tempest Therapeutics undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. These forward-looking statements should not be relied upon as representing Tempest Therapeutics’ views as of any date subsequent to the date of this press release and should not be relied upon as prediction of future events. In light of the foregoing, investors are urged not to rely on any forward-looking statement in reaching any conclusion or making any investment decision about any securities of Tempest Therapeutics.
Wheelhouse Life Science Advisors
Wheelhouse Life Science Advisors