Core Insights - Tempest Therapeutics has received approval from the National Medical Products Administration (NMPA) in China to initiate a pivotal trial for amezalpat (TPST-1120) in combination with atezolizumab and bevacizumab for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC) [1][2][3] Company Overview - Tempest Therapeutics is a clinical-stage biotechnology company focused on developing targeted and immune-mediated therapeutics for cancer treatment [8] - The company is headquartered in Brisbane, California, and has a diverse portfolio of small molecule product candidates [8] Drug Development - Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist that shows promise in treating cancer by targeting tumor cells and modulating the tumor microenvironment [7] - The planned Phase 3 study will be a global, blinded, 1:1 randomized trial comparing amezalpat plus atezolizumab and bevacizumab against a placebo combination for first-line treatment of HCC [3] - The company has received agreement from both the FDA and EMA on the study design and statistical plan for the Phase 3 trial [3] Hepatocellular Carcinoma (HCC) Insights - HCC is an aggressive cancer with over 900,000 new diagnoses globally each year, and it is projected to become the third leading cause of cancer death by 2030 [4] - The highest incidence and mortality rates of HCC are found in East Asia, with increasing rates in Europe and the US [4] - Chronic liver diseases, including hepatitis B and C, NAFLD, NASH, and cirrhosis, account for 90% of HCC cases [5] Clinical Trial Context - The ongoing global randomized Phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab has shown clinical superiority in overall survival compared to the standard of care [7] - Early-stage HCC patients face a 70-80% recurrence rate post-surgery, which is associated with poorer prognosis [6]

Company Overview - Tempest Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing first-in-class targeted and immune-mediated therapeutics for cancer treatment [1][8] - The company is headquartered in Brisbane, California, and has a diverse portfolio of small molecule product candidates [8] Drug Development and Designations - The European Medicines Agency (EMA) has granted Orphan Drug Designation (ODD) to amezalpat (TPST-1120), an oral, small molecule, selective PPAR⍺ antagonist for hepatocellular carcinoma (HCC) [1][6] - Earlier in the year, the FDA also granted ODD and Fast Track Designation (FTD) to amezalpat for the same indication, highlighting the urgent need for new treatment options [2][6] - Amezalpat has shown positive outcomes in a global randomized Phase 1b/2 clinical study, demonstrating a six-month improvement in median overall survival (OS) with a hazard ratio (HR) of 0.65 when combined with standard-of-care therapies [2][4] Disease Context - Hepatocellular carcinoma (HCC) is an aggressive cancer with over 900,000 new diagnoses globally each year, projected to become the third leading cause of cancer death by 2030 [3] - The majority of HCC cases are linked to chronic liver diseases, with a high recurrence rate of 70-80% even after early-stage diagnosis [3][4] Mechanism of Action - Amezalpat is designed to target tumor cells directly while also modulating immune suppressive cells and angiogenesis within the tumor microenvironment [4] - The drug has shown clinical superiority across multiple study endpoints, including overall survival in both the entire population and key subpopulations compared to standard care [4][6] Regulatory Benefits - The EMA's ODD provides benefits such as potential 10 years of market exclusivity following regulatory approval in the EU, reduced regulatory fees, and a centralized EU approval process [7]