Tempest Presents New Amezalpat MOA Data Reinforcing Its Potential as Novel Cancer Treatment at the 2025 AACR Annual Meeting
Rhea-AI Summary
Tempest Therapeutics presented new data for their cancer treatment candidate amezalpat at the 2025 AACR Annual Meeting, showcasing promising results in its dual mechanism of action.
Key findings include:
- Amezalpat reduces tumor-promoting immunosuppression by targeting M2 macrophages and T regulatory cells
- The drug works by inhibiting PPAR-alpha, which controls fatty acid oxidation (FAO)
- Shows promising clinical results in multiple cancers including HCC, RCC, and CCA when combined with immunotherapy
- Demonstrates ability to decrease anti-inflammatory cytokine production
According to Dr. Sam Whiting, Chief Medical Officer at Tempest, the data supports amezalpat's potential as a first-in-class cancer therapy. The treatment's effectiveness is linked to its ability to block immune suppression, which has been observed in clinical trials.
Positive
- New data supports amezalpat's dual mechanism of action in cancer treatment
- Amezalpat shows promising clinical results in multiple cancer types (HCC, RCC, and CCA)
- Drug demonstrates potential as a first-in-class cancer therapy
- Data confirms drug's ability to reduce tumor-promoting immunosuppression
- Clinical evidence shows effectiveness in combination with approved immunotherapy
Negative
- Data presented is still preclinical/laboratory-based, requiring further clinical validation
- No specific efficacy rates or clinical success metrics provided
- Competitive positioning and market potential not addressed
Insights
Tempest's amezalpat data shows immune mechanism supporting clinical approach; validates dual-action strategy in multiple cancer indications.
Tempest Therapeutics has presented new mechanism of action (MOA) data for amezalpat at the 2025 AACR Annual Meeting that substantiates the compound's scientific rationale. The data specifically demonstrates that amezalpat reduces tumor-promoting immunosuppression by affecting M2 macrophages and T regulatory cells, supporting the drug's proposed dual mechanism.
As a PPAR-alpha inhibitor, amezalpat targets fatty acid oxidation (FAO), a metabolic pathway utilized by immunosuppressive cells. The experimental results show it inhibits the development of immunosuppressive cells from precursor populations and reduces mitochondrial mass in these cells. This mechanistic action aligns with previously referenced clinical observations in hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and cholangiocarcinoma (CCA).
For a clinical-stage biotech company, having preclinical data that validates the mechanistic underpinnings of observed clinical signals strengthens their development narrative. While this presentation doesn't provide specific efficacy metrics, it offers important scientific validation for Tempest's approach. The potential "first-in-class" profile mentioned in the release could differentiate amezalpat in the competitive oncology landscape if these mechanisms translate to clinical benefits in their ongoing development program.
Amezalpat's mechanism targeting immunosuppressive cells validates its potential in creating favorable tumor microenvironment for cancer therapies.
The mechanistic data presented for amezalpat provides valuable scientific insights into how this agent modulates the tumor immune microenvironment. By inhibiting PPAR-alpha, amezalpat targets a key regulator of fatty acid oxidation that immunosuppressive cells rely on for their function and development.
The experimental findings demonstrate two significant effects: first, amezalpat inhibits the development of immunosuppressive M2 macrophages and regulatory T cells (Tregs) from precursor populations; second, it reduces mitochondrial mass in these immunosuppressive cells. The functional consequence is decreased anti-inflammatory cytokine production, effectively reversing immune suppression.
This mechanism is particularly relevant for HCC, RCC, and CCA - cancer types where immunosuppressive microenvironments often limit the efficacy of current therapies. The data explains why amezalpat might complement existing immunotherapies, as mentioned in the release's reference to promising clinical results when combined with approved immunotherapy agents.
While these findings represent preclinical mechanistic validation rather than clinical efficacy data, they provide a rational scientific foundation for Tempest's clinical development strategy. The proposed dual mechanism - directly affecting cancer metabolism while simultaneously relieving immune suppression - represents a differentiated approach that addresses multiple aspects of tumor biology.
BRISBANE, Calif., April 28, 2025 (GLOBE NEWSWIRE) -- Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, today announced that a presentation of new data supporting the immune component of amezalpat’s purported dual mechanism of action that reinforces its potential as a novel cancer treatment at the 2025 American Association for Cancer Research (AACR) Annual Meeting.
“The data presented at the AACR Annual Meeting show that amezalpat reduced tumor promoting immunosuppression by M2 macrophages and T regulatory cells resulting in immune activation. These data support the immune-mediated anti-cancer activity of the proposed dual MOA of amezalpat,” said Sam Whiting, M.D., Ph.D., chief medical officer and head of R&D at Tempest, “and are consistent with clinical data showing promising results in patients with HCC, RCC and CCA including in combination with approved immunotherapy. The results reinforce amezalpat’s novel and potentially first-in-class profile as a cancer therapy.”
Amezalpat is an inhibitor of PPAR-alpha, the key regulator of fatty acid oxidation (FAO), which is a key metabolic pathway used by immunosuppressive macrophages and regulatory T cells (Tregs). Both cell populations are associated with poor prognosis in multiple cancer indications. Data presented demonstrated that amezalpat inhibits the development of these cells from precursor populations and is associated with reduced mitochondrial mass, the site of FAO, in immunosuppressive macrophages. Additionally, treatment of Tregs or immunosuppressive macrophages with amezalpat in the presence of tumor and cytotoxic T cells decreases anti-inflammatory cytokine production, indicating blockade of immune suppression that likely contributes to the efficacy of amezalpat observed in clinical trials.
About Amezalpat
Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Data suggests that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In a global randomized phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the amezalpat arm showed clinical superiority across multiple study endpoints, including overall survival in both the entire population and key subpopulations, when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by additional positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors, including renal cell carcinoma and cholangiocarcinoma.
About Tempest Therapeutics
Tempest Therapeutics is a clinical-stage biotechnology company advancing a diverse portfolio of small molecule product candidates containing tumor-targeted and/or immune-mediated mechanisms with the potential to treat a wide range of tumors. The company’s novel programs range from early research to later-stage investigation in a randomized global study in first-line cancer patients. Tempest is headquartered in Brisbane, California. More information about Tempest can be found on the company’s website at www.tempesttx.com.
Forward-Looking Statements
This press release contains forward-looking statements, as that term is defined under the federal securities laws, that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking terminology such as “may,” “will,” “should,” “would,” “could”, “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions. Forward-looking statements contained in this press release include but are not limited to statements relating to: the initiation, timing and results of the Phase 2 study for TPST-1495; and the ability of TPST-1495 to benefit from the ODD designation, including potential tax credits and market exclusivity. Any forward-looking statements in this press release are based on Tempest Therapeutics’ current expectations, estimates and projections about its industry as well as management’s current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks relating to: changes in the regulatory environment resulting in potentials delays in the clinical development and regulatory approval of our product candidates, including TPST-1495; the volatility and uncertainty in the capital markets for biotechnology companies; and our ability to raise additional capital or other pursue our plan to identify and complete a strategic transaction on attractive terms or at all. These and other factors that may cause actual results to differ from those expressed or implied are discussed in greater detail in the “Risk Factors” section of the company’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission (SEC) on March 27, 2025, as well as in other filings the company may make with the SEC in the future. 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.
Investor & Media Contacts:
Sylvia Wheeler
Wheelhouse Life Science Advisors
swheeler@wheelhouselsa.com
Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com
_______________________
i If approved by the FDA
FAQ
What new data did Tempest (TPST) present at AACR 2025 about amezalpat?
How does Tempest's (TPST) amezalpat work against cancer cells?
What types of cancer is Tempest's (TPST) amezalpat being tested for?
What makes Tempest's (TPST) amezalpat a first-in-class cancer treatment?
What are the key findings from Tempest's (TPST) amezalpat research at AACR 2025?
