Core Viewpoint - The announcement by Valiant Biosciences-B (09887.HK) regarding the successful administration of the first patient in the Phase II clinical trial of Opalizumab (PD-L1/4-1BB bispecific antibody LBL-024) for first-line treatment of hepatocellular carcinoma marks significant progress in the expansion of its core product indications [1] Group 1: Clinical Trial Details - The Phase II clinical trial is an open-label, multicenter study led by Professor Zhou Jian from Zhongshan Hospital affiliated with Fudan University, currently being conducted in multiple hospitals across the country [1] - The trial aims to evaluate the efficacy and safety of Opalizumab in combination therapy for patients with hepatocellular carcinoma [1] Group 2: Related Events - Valiant Biosciences-B (09887.HK) has been included in the MSCI Global Small Cap Index [1]

Core Viewpoint - Systemic treatment is the best option for patients with unresectable or advanced hepatocellular carcinoma (HCC), but its efficacy is limited by drug resistance [2][3]. Group 1: Research Findings - Ferroptosis is a unique form of regulated cell death that plays a crucial role in the systemic treatment of HCC [3]. - A study published in Nature Cancer reveals that SCRN1 confers resistance to ferroptosis in HCC by stabilizing GPX4 through STK38-mediated phosphorylation, providing potential therapeutic targets and strategies for HCC treatment [4][8]. - The research team found that high expression of SCRN1 is closely related to ferroptosis resistance and poor prognosis in HCC [7]. Group 2: Mechanism of Action - SCRN1 enhances the interaction between STK38 and GPX4, promoting the phosphorylation of GPX4 at the S45 site, which impairs HSC70's recognition of GPX4 and reduces its degradation via chaperone-mediated autophagy, thereby alleviating lipid peroxidation and ferroptosis [7][8].

Core Viewpoint - The company has completed the first patient dosing in a Phase II clinical trial evaluating the combination of Tinengotinib with Kanfang Biotech's anti-cancer drugs for advanced hepatocellular carcinoma [1][2] Group 1: Clinical Trial Details - The trial is an open-label, multicenter Phase II study conducted in China, aimed at assessing the efficacy and safety of Tinengotinib in combination with Kanfang's drugs, Kadyuoni (PD-1/CTLA-4) and Yidafang (PD-1/VEGF) [2] - The primary objective of the trial is to evaluate the safety and effectiveness of the combination therapies compared to Tinengotinib monotherapy in patients with advanced hepatocellular carcinoma who have not received prior systemic anti-tumor treatment or have failed standard treatment [2] Group 2: Collaboration and Development - The company has established a collaboration agreement with Kanfang Biotech to jointly develop clinical combination therapies in the field of hepatocellular carcinoma [2]

Core Viewpoint - The company announced the initiation of a Phase II clinical trial for its core product, Tinengotinib (TT-00420), in combination with other therapies for the treatment of advanced hepatocellular carcinoma (HCC) [1] Group 1: Clinical Trial Details - The trial is an open-label, multicenter Phase II study conducted in China [1] - The primary objective is to evaluate the safety and efficacy of Tinengotinib in combination with Kanfar Biotech's Katanib (PD-1/CTLA-4) and Yida Pharma's Yivofisi (PD-1/VEGF) [1] - The target population includes patients with advanced HCC who have not previously received systemic anti-tumor therapy or have failed standard treatment [1] Group 2: Collaboration and Development - The company has entered into a collaboration agreement with Kanfar Biotech to jointly develop clinical combination therapies in the field of hepatocellular carcinoma [1]

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]