Atezolizumab

• Granted Both Orphan Drug & Fast Track designations for Amezalpat (TPST-1120) for the treatment of patients with Hepatocellular Carcinoma (HCC) • Announced Agreement with Roche to Support Advancement of Amezalpat Combination Therapy into First-Line HCC Pivotal Trial • Received FDA “Study May Proceed” letter for Phase 2 trial of TPST-1495 for the treatment of Familial Adenomatous Polyposis (FAP) BRISBANE, Calif., March 27, 2025 (GLOBE NEWSWIRE) -- Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-class1 targeted and immune-mediated therapeutics to fight cancer, today reported financial results for the year ended 2024 and provided a corporate update. “2024 was another year filled with significant progress and milestone achievements that position Tempest for a successful future,” said Stephen Brady, president and chief executive officer of Tempest. “Despite challenging capital markets, our lean team excelled, reporting key OS data from the ongoing randomized Phase 2 trial of amezalpat in first-line hepatocellular carcinoma. As previously announced, we have secured broad regulatory agreement with both the FDA and EMA on the Phase 3 plan and received both Orphan Drug and Fast Track designations from the FDA. We also advanced our second clinical program, TPST-1495, with a Phase 2 clinical trial for the treatment of patients with FAP, with data expected in 2026. Our focus remains on execution with excellence while securing the resources necessary to drive these promising drug candidates forward.” 2024 & Recent Accomplishments Amezalpat (TPST-1120) (clinical PPARα antagonist): Granted both Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA) for amezalpat for the treatment of patients with HCC. Received a “Study May Proceed” letter from the FDA to evaluate amezalpat in combination with atezolizumab (TECENTRIQ®) and bevacizumab (Avastin®), the current standard of care for unresectable or metastatic HCC, in a pivotal Phase 3 trial for the first-line treatment of unresectable or metastatic HCC. Announced an agreement with F. Hoffmann-La Roche Ltd. (Roche) to advance the evaluation of amezalpat in combination with atezolizumab and bevacizumab into a pivotal Phase 3 trial for the first-line treatment of unresectable or metastatic HCC. Announced positive feedback from the end-of-Phase 2 meeting with the FDA for amezalpat in combination with atezolizumab and bevacizumab to treat first-line unresectable or metastatic HCC. Reported new positive survival data from the ongoing global randomized Phase 1b/2 clinical study demonstrating that amezalpat delivered a six-month improvement in median overall survival (OS) when combined with atezolizumab and bevacizumab in comparison to atezolizumab and bevacizumab alone, the standard of care, in the first-line treatment of patients with unresectable or metastatic HCC. Published positive data from Phase 1 trial of amezalpat in patients with advanced solid tumors in the Journal of Cancer Research Communications. Data showed that amezalpat demonstrated clinical activity, including tumor shrinkage, even in PD-1 inhibitor-refractory and immune-compromised cancers. These data complement the positive Phase 1b/2 data reported in October 2023 and June 2024 from a global randomized study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC. Reported new preclinical data at the 2024 American Association for Cancer Research (AACR) Annual Meeting demonstrating that amezalpat reduces kidney cancer growth as a monotherapy, while also showing increased inhibition when combined with frontline chemotherapy and immunotherapy. These data further support the clinical benefit observed in the amezalpat Phase 1 data presented in an oral presentation at ASCO 2022. TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist) Received a “Study May Proceed” letter from the FDA to evaluate TPST-1495 in a Phase 2 Trial for the treatment of FAP. Corporate: Expanded leadership team to strengthen global clinical expertise with the appointments of Troy M. Wagner as Vice President of Quality Assurance and Sheldon Mullins as Vice President of Regulatory Affairs. Received a “Study May Proceed” letter from the FDA to evaluate TPST-1495 in a Phase 2 Trial for the treatment of FAP. Expanded leadership team to strengthen global clinical expertise with the appointments of Troy M. Wagner as Vice President of Quality Assurance and Sheldon Mullins as Vice President of Regulatory Affairs. Potential Future Milestones Amezalpat (TPST-1120) (clinical PPARα antagonist) Plan to advance amezalpat into a registrational study in first-line liver cancer patients, subject to obtaining additional resources. 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. Plan to advance amezalpat into a registrational study in first-line liver cancer patients, subject to obtaining additional resources. 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. Financial Results Year End 2024 Tempest ended the year with $30.3 million in cash and cash equivalents, compared to $39.2 million on December 31, 2023. The decrease was primarily due to cash used in operating activities, offset by proceeds from the issuance of common stock of $28.6 million from the at-the-market offering program. Net loss and net loss per share for the year were $41.8 million and $1.50, respectively, compared to $29.5 million and $1.91, respectively, for the same period in 2023. Research and development expenses for the year were $28.5 million compared to $17.5 million for the same period in 2023. The $11.0 million increase was primarily due to an increase in costs incurred from engaging contract research and manufacturing organizations in preparation for our pivotal Phase 3 trial of amezalpat for the treatment of first-line HCC. General and administrative expenses for the year were $13.6 million compared to $11.7 million for the same period in 2023. The $1.9 million increase was primarily due to an increase in stock-based compensation expense due to increased headcount as well as an increase in expenses related to legal and consulting services. 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 (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. 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 design, initiation, progress, timing, scope and results of clinical trials, including the anticipated Phase 3 study for amezalpat and Phase 2 Trial of TPST-1495; anticipated therapeutic benefit and regulatory development of the Company’s product candidates; the Company’s ability to advance into a late-stage clinical company; the Company’s ability to secure resources and funding; and the Company’s ability to achieve its operational plans. Forward-looking statements are based on information available to Tempest Therapeutics as of the date hereof and are not guarantees of future performance. Any factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; and unexpected litigation or other disputes. 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2024 and other documents filed by the Company from time to time with the Securities and Exchange Commission. 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 Contacts: Sylvia Wheeler Wheelhouse Life Science Advisors swheeler@wheelhouselsa.com Aljanae Reynolds Wheelhouse Life Science Advisors areynolds@wheelhouselsa.com 1 If approved by the U.S. Food and Drug Administration (FDA).

Exelixis might soon have to test the FDA’s tolerance of a lackluster overall survival showing again for Cabometyx in prostate cancer. After canceling a planned advisory committee meeting, the FDA has approved Exelixis’ Cabometyx for neuroendocrine tumors.The small-molecule drug is now allowed for patients 12 years of age and older with previously treated, advanced, well-differentiated pancreatic or extra-pancreatic neuroendocrine tumors (pNET or epNET), the FDA said Wednesday.In an interesting and unusual item in Cabometyx’s updated label, the FDA acknowledges the potential impact that control arm patient crossovers may have had on Cabometyx’s patient survival results in a phase 3 trial.The approval could be an encouraging sign for oncology drug developers because, as the likes of Novartis know too well, the FDA has not been very receptive to companies using patient crossovers to justify a signal that may hint at a potential detriment to patient survival. Even though it doesn’t mean just any company with a crossover trial design can now expect to win over the FDA, Cabometyx serves as living proof that the agency is open to that line of reasoning.In Cabometyx’s case specifically, during an updated overall survival analysis of the phase 3 Cabinet trial that Exelixis used to support its NET bid, overall survival data favored placebo in both pNET and epNET patients.The overall survival data, which were immature, tallied 48% deaths in Cabometyx arm and 52% deaths in the placebo arm, but a preliminary 1% increased risk of death for the tyrosine kinase inhibitor in pNET patients. The numbers were 63% deaths for Cabometyx and 60% for placebo in epNET patients, resulting in a 5% higher risk of death for the active drug.The lackluster overall survival data came in stark contrast with the massive 78% and 60% progression-free survival improvements that Cabometyx has shown in the two patient subgroups, respectively. Sometimes such a disconnect between a major tumor progression benefit and muted overall survival showing could be attributed to nasty side effects harming the patients’ overall wellbeing. But in the Cabinet trial case, investigators and Exelixis have pointed to a high rate of patients in the control arm who crossed over to receive Cabometyx later upon disease progression. As the FDA label shows, 52% of pNET patients and 37% epNET participants in the control group got open-label Cabometyx, “which may impact the OS endpoint.”When the FDA unveiled a meeting of external experts to discuss Exelixis’ NET application, analysts suspected that the agency had questions about the survival data. The FDA then canceled the gathering in January.The medical community has been raving about Cabometyx in a hard-to-treat tumor type, in which patients face poor prognosis. In January, the National Comprehensive Cancer Network updated its guidelines to recommend Cabometyx as a category 1—the highest—preferred regimen for the majority of previously treated well-differentiated advanced NET, plus a category 2A backing for other forms of advanced NET.The current FDA approval is limited to well-differentiated NET even though the phase 3 Cabinet trial enrolled a small number of patients with moderately-differentiated cancers. In a Wednesday, March 26 press release, Exelixis noted that an estimated 161,000 to 192,000 people are living with unresectable, advanced NET, but the company didn’t break down how many are well-differentiated cases.NET can develop in any part of the body, but those that start in the gastrointestinal tract or in the lungs are the most common, while pNET can be more aggressive. By William Blair’s estimate, the entire NET market is expected to reach $4.6 billion by 2030.Also in NET, Exelixis is preparing to start a pivotal trial coded Stellar-311 to evaluate its investigational zanalintinib, a next-generation asset, versus Novartis’ Afinitor. Exelixis has high hopes for zanalintinib, having put its 2033 U.S. sales potential at $5 billion. With the NET nod in the pocket, Exelixis might soon have to test the FDA’s tolerance of a lackluster overall survival showing again. A combination of Cabometyx and Roche’s Tecentriq previously failed to deliver a statistically significant overall survival benefit compared with a change of novel hormonal therapy in metastatic castration-resistant prostate cancer in the final analysis of the Contact-02 trial. The study did meet its other dual primary endpoint, progression-free survival.Exelixis has said it intends to file an application with the FDA but has not done so. During a recent investors’ call, Exelixis management said the company will turn to the prostate cancer indication after it gets NET across the finish line.In response to a Fierce Pharma inquiry Wednesday, an Exelixis spokesperson said the company will provide an update on its regulatory plans at an appropriate time.