Amezalpat (TPST-1120) in HCC - Amezalpat randomized Phase 2 data in first-line HCC showed superiority to the Standard of Care (SoC) arm[6] - Overall Survival (OS) data revealed a six-month improvement with a stable hazard ratio of 0.65 compared to the control arm[6, 32, 35, 58] - Confirmed Objective Response Rate (ORR) in the ITT population was 30% in the Amezalpat + atezolizumab + bevacizumab arm compared to 13.3% in the atezolizumab + bevacizumab arm[32] - In PD-L1 negative patients, the confirmed ORR was 27% in the Amezalpat arm versus 7% in the SoC arm[32] - In patients with β-catenin mutations, the confirmed ORR in the Amezalpat arm was 43% with 100% Disease Control Rate (DCR)[32] Clinical Development and Regulatory - The FDA and EMA have agreed on a Phase 3 plan for Amezalpat[4, 48] - A pivotal Phase 3 study is designed with over 700 subjects and a 1:1 randomization[49] - The Phase 3 study has a critical hazard ratio of <0.805 for primary efficacy and <0.729 for early efficacy[49] - FDA granted Orphan Drug Designation in December 2024 and Fast Track Designation in January 2025[52] Market Opportunity - First-Line HCC is a large market, with 234,785 treated cases across the US, EU5, and China[54]

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]

Core Viewpoint - Tempest Therapeutics, Inc. has entered into a definitive agreement for a registered direct offering of 739,000 shares at an offering price of $6.25 per share, expected to close around June 12, 2025, subject to customary conditions [1][2] Group 1: Offering Details - The offering is expected to generate approximately $4.6 million in gross proceeds before deducting fees and expenses [2] - H.C. Wainwright & Co. is acting as the exclusive placement agent for this offering [2] - The shares are being offered under a "shelf" registration statement filed with the SEC, which was declared effective on January 27, 2025 [3] Group 2: Use of Proceeds - The net proceeds from the offering will primarily support a previously announced strategic alternative process, along with working capital and general corporate purposes [2] Group 3: Company Overview - Tempest Therapeutics is a clinical-stage biotechnology company focused on developing targeted and immune-mediated therapeutics for cancer treatment [5] - The company has a diverse portfolio of small molecule product candidates, ranging from early research to later-stage investigations in global studies [5]

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]

PART I — FINANCIAL INFORMATION [Financial Statements](index=5&type=section&id=Item%201.%20Financial%20Statements) Tempest Therapeutics reported a net loss of **$10.9 million** for Q1 2025, with cash decreasing to **$21.5 million**, raising going concern doubts [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets decreased to **$32.2 million** by March 31, 2025, driven by reduced cash, leading to a decline in stockholders' equity Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 (Unaudited) | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $21,511 | $30,268 | | Total current assets | $22,433 | $31,474 | | Total assets | $32,164 | $41,488 | | **Liabilities & Stockholders' Equity** | | | | Total current liabilities | $13,177 | $14,220 | | Total liabilities | $21,031 | $22,362 | | Total stockholders' equity | $11,133 | $19,126 | [Condensed Consolidated Statements of Operations](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) Net loss increased to **$10.9 million** in Q1 2025, primarily due to a significant rise in research and development expenses to **$7.6 million** Condensed Consolidated Statements of Operations (in thousands, except per share data) | Metric | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $7,627 | $4,340 | | General and administrative | $3,309 | $3,634 | | Loss from operations | $(10,936) | $(7,974) | | Net loss | $(10,860) | $(7,904) | | Net loss per share, basic and diluted | $(3.16) | $(4.62) | | Weighted-average shares outstanding | 3,437,671 | 1,710,323 | [Condensed Consolidated Statements of Cash Flows](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased to **$8.0 million** in Q1 2025, resulting in an **$8.8 million** net decrease in cash Summary of Cash Flows (in thousands) | Activity | For the Three Months Ended March 31, 2025 | For the Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Cash used in operating activities | $(8,036) | $(7,186) | | Cash used in investing activities | $0 | $(168) | | Cash provided by (used in) financing activities | $(721) | $450 | | **Net decrease in cash** | **$(8,757)** | **$(6,904)** | [Notes to Condensed Consolidated Financial Statements](index=9&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Notes detail a 1-for-13 reverse stock split, going concern doubt, and post-quarter workforce reduction and loan repayment - The company's financial statements were prepared on a going concern basis, but management has concluded there is substantial doubt about its ability to continue operating for the next 12 months due to recurring losses and insufficient cash reserves[32](index=32&type=chunk) - On April 8, 2025, the company effected a **1-for-13 reverse stock split** of its common stock, with all share and per-share amounts retrospectively adjusted[29](index=29&type=chunk)[82](index=82&type=chunk) - Subsequent to the quarter end, in April 2025, the company reduced its workforce by **21 of 26** full-time employees, expecting to incur **$1.5 million** in severance and related costs[80](index=80&type=chunk) - On April 8, 2025, the company fully repaid its outstanding loan, including principal and fees, for a total of **$3.5 million**, terminating the loan agreement[51](index=51&type=chunk)[81](index=81&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=19&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses strategic alternatives, workforce reduction, and a **76%** increase in R&D expenses, reiterating going concern doubts - The company is exploring a full range of strategic alternatives, including mergers, acquisitions, partnerships, or other transactions, and has retained MTS Health Partners as a financial advisor[97](index=97&type=chunk)[99](index=99&type=chunk) - In April 2025, the company reduced its workforce by **21 of 26** employees to extend capital resources, anticipating **$1.5 million** in cash expenditures for severance and related costs[100](index=100&type=chunk) - The FDA has granted Orphan Drug Designation and Fast Track Designation for amezalpat for the treatment of hepatocellular carcinoma (HCC), and the company has received a "Study May Proceed" letter for its pivotal Phase 3 trial[90](index=90&type=chunk)[91](index=91&type=chunk) R&D Expenses by Program (in thousands) | Program | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | % Change | | :--- | :--- | :--- | :--- | | TPST-1120 (amezalpat) | $4,218 | $882 | 378% | | TPST-1495 | $0 | $596 | (100)% | | Personnel and other costs | $2,181 | $1,766 | 23% | | **Total R&D Expenses** | **$7,627** | **$4,340** | **76%** | [Quantitative and Qualitative Disclosures About Market Risk](index=27&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Tempest Therapeutics is not required to provide market risk disclosures - Disclosure under this item is not required as the company qualifies as a smaller reporting company[135](index=135&type=chunk) [Controls and Procedures](index=27&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls were effective as of March 31, 2025, with no material changes to internal controls - The company's management, including the CEO and CFO, concluded that as of March 31, 2025, the disclosure controls and procedures were effective at a reasonable assurance level[138](index=138&type=chunk) - No changes in internal control over financial reporting occurred during the quarter ended March 31, 2025, that have materially affected, or are reasonably likely to materially affect, internal controls[139](index=139&type=chunk) PART II — OTHER INFORMATION [Legal Proceedings](index=29&type=section&id=Item%201.%20Legal%20Proceedings) Legal proceedings information is incorporated by reference from Note 5 to the financial statements - The report refers to Note 5 of the financial statements for information on legal proceedings[142](index=142&type=chunk) [Risk Factors](index=29&type=section&id=Item%201A.%20Risk%20Factors) Key risks include going concern doubt, potential failure of strategic review, dependence on product candidates, and intellectual property challenges - There is substantial doubt about the company's ability to continue as a going concern, as existing cash is expected to fund operations for less than 12 months, and failure to secure additional funding or a strategic alternative may force the company to wind down operations[147](index=147&type=chunk)[150](index=150&type=chunk) - The process of evaluating strategic alternatives may not result in a transaction, could be costly and time-consuming, and may not enhance stockholder value[151](index=151&type=chunk) - The company's business is highly dependent on the successful development, regulatory approval, and commercialization of its lead product candidates, amezalpat and TPST-1495, which is a lengthy, expensive, and uncertain process[170](index=170&type=chunk) - The company faces risks related to its intellectual property, including the ability to obtain and maintain patent protection, potential infringement claims from third parties, and the difficulty of protecting trade secrets[308](index=308&type=chunk)[331](index=331&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=81&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered sales of equity securities were reported during the period - None[393](index=393&type=chunk) [Other Information](index=81&type=section&id=Item%205.%20Other%20Information) The company entered a retention agreement with its principal accounting officer and reported no Rule 10b5-1 trading plan changes - The company entered into a retention agreement with its principal accounting officer, providing a **$100,000** cash bonus for service through July 31, 2025[396](index=396&type=chunk) - No director or officer adopted or terminated a Rule 10b5-1 or non-Rule 10b5-1 trading arrangement during the last fiscal quarter[397](index=397&type=chunk) [Exhibits](index=82&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed as part of the Quarterly Report on Form 10-Q, including required certifications

Core Viewpoint - Tempest Therapeutics, Inc. reported promising developments in its clinical-stage oncology programs, particularly highlighting the amezalpat program's potential as a cancer therapy and ongoing efforts to maximize stockholder value through strategic alternatives [2][5]. Recent Highlights - The amezalpat program demonstrated its ability to reduce immunosuppression and activate the immune system against tumors, supported by positive randomized Phase 2 data [2]. - Tempest received Orphan Drug designation from the FDA for TPST-1495 for familial adenomatous polyposis (FAP) and for amezalpat for hepatocellular carcinoma (HCC) [5][6]. - The company is preparing for a Phase 2 trial of TPST-1495, expected to begin in 2025, emphasizing innovative cancer prevention strategies [6]. Financial Results - For the first quarter of 2025, Tempest reported a net loss of $10.9 million, or $3.16 per share, compared to a net loss of $7.9 million, or $4.62 per share, in the same period of 2024 [6][15]. - Research and development expenses increased to $7.6 million from $4.3 million year-over-year, primarily due to costs associated with preparing for a pivotal Phase 3 trial of amezalpat [6][7]. - The company ended the quarter with $21.5 million in cash and cash equivalents, down from $30.3 million at the end of 2024, mainly due to cash used in operating activities [6][12]. Corporate Developments - The company announced plans to explore a full range of strategic alternatives to advance its clinical-stage programs and maximize stockholder value [6]. - A reduction in force was completed on April 30, 2025, as part of its strategic initiatives [6].

[First Quarter 2025 Financial Results and Business Update](index=1&type=section&id=First%20Quarter%202025%20Financial%20Results%20and%20Business%20Update) This section provides an overview of Tempest Therapeutics' Q1 2025 financial performance and key business developments [Business and Corporate Highlights](index=1&type=section&id=Recent%20Highlights) Tempest Therapeutics advanced key drug candidates with FDA designations and pursued strategic alternatives including a workforce reduction - Amezalpat (TPST-1120) received both **Orphan Drug** and **Fast Track designations** from the FDA for the treatment of hepatocellular carcinoma (HCC)[4](index=4&type=chunk)[7](index=7&type=chunk) - **New mechanism-of-action data** for amezalpat was presented at the 2025 AACR Annual Meeting, supporting its potential as a novel cancer treatment by showing it reduces immunosuppression and activates the immune system[3](index=3&type=chunk)[4](index=4&type=chunk)[7](index=7&type=chunk) - TPST-1495 was granted **Orphan Drug designation** by the FDA for treating familial adenomatous polyposis (FAP) and received a "Study May Proceed" letter for its **Phase 2 trial**, which is expected to begin in 2025[4](index=4&type=chunk)[7](index=7&type=chunk) - The company announced it is exploring a full range of **strategic alternatives** to advance its clinical programs and maximize stockholder value, completing a related **reduction in force** on April 30, 2025[3](index=3&type=chunk)[7](index=7&type=chunk) [Financial Results](index=2&type=section&id=Financial%20Results) Tempest Therapeutics reported an increased net loss in Q1 2025, driven by higher R&D expenses, with a decrease in cash and cash equivalents [Key Financial Metrics](index=2&type=section&id=Key%20Financial%20Metrics) Key financial metrics for Q1 2025 show decreased cash, an increased net loss, and the full repayment of a $3.5 million loan | Financial Metric | Q1 2025 (Millions USD) | Q1 2024 (Millions USD) | Change (Millions USD) | | :--- | :--- | :--- | :--- | | Cash and Cash Equivalents | $21.5 | N/A | -$8.8 (vs. Q4 2024) | | Net Loss | $10.9 | $7.9 | +$3.0 | | Net Loss Per Share (USD) | $3.16 | $4.62 | -$1.46 | - The decrease in cash was primarily due to operating activities, partially offset by **$1.5 million** in proceeds from the at-the-market offering program[7](index=7&type=chunk) - In April 2025, the company repaid **$3.5 million**, fully satisfying its Loan and Security Agreement with Oxford Finance LLC[7](index=7&type=chunk) [Operating Expenses](index=3&type=section&id=Operating%20Expenses) Operating expenses rose in Q1 2025, primarily due to increased R&D costs for Phase 3 trial preparations, while G&A expenses slightly decreased | Expense Category | Q1 2025 (Millions USD) | Q1 2024 (Millions USD) | Change (Millions USD) | | :--- | :--- | :--- | :--- | | Research and Development | $7.6 | $4.3 | +$3.3 | | General and Administrative | $3.3 | $3.6 | -$0.3 | - The increase in R&D expenses was primarily due to costs from contract research and manufacturing organizations in preparation for the **pivotal Phase 3 trial** of amezalpat for first-line HCC[10](index=10&type=chunk) [Consolidated Balance Sheets](index=5&type=section&id=Consolidated%20Balance%20Sheets) The balance sheet as of March 31, 2025, shows decreases in total assets, liabilities, and stockholders' equity compared to year-end 2024 | Item | March 31, 2025 (Thousands USD) | December 31, 2024 (Thousands USD) | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $21,511 | $30,268 | | Total current assets | $22,433 | $31,474 | | **Total assets** | **$32,164** | **$41,488** | | **Liabilities and Stockholders' Equity** | | | | Total current liabilities | $13,177 | $14,220 | | **Total liabilities** | **$21,031** | **$22,362** | | **Total stockholders' equity** | **$11,133** | **$19,126** | | **Total liabilities and stockholders' equity** | **$32,164** | **$41,488** | [Consolidated Statements of Operations](index=6&type=section&id=Consolidated%20Statements%20of%20Operations) The consolidated statements of operations show increased operating and net losses for the three months ended March 31, 2025, compared to the prior year | Item | Three months ended March 31, 2025 | Three months ended March 31, 2024 | | :--- | :--- | :--- | | Research and development (Thousands USD) | $7,627 | $4,340 | | General and administrative (Thousands USD) | $3,309 | $3,634 | | **Operating loss (Thousands USD)** | **($10,936)** | **($7,974)** | | **Net loss (Thousands USD)** | **($10,860)** | **($7,904)** | | **Net loss per share (USD)** | **($3.16)** | **($4.62)** | [Company Overview and Forward-Looking Statements](index=3&type=section&id=About%20Tempest%20Therapeutics) Tempest Therapeutics is a clinical-stage biotechnology company focused on cancer treatment, with forward-looking statements subject to inherent risks and uncertainties - Tempest Therapeutics is a **clinical-stage biotechnology company** focused on advancing a diverse portfolio of small molecule product candidates with tumor-targeted and/or immune-mediated mechanisms[8](index=8&type=chunk) - The report contains **forward-looking statements** regarding strategic alternatives and the therapeutic potential of its product candidates, which are based on current management beliefs and are subject to **significant risks and uncertainties**[9](index=9&type=chunk)[11](index=11&type=chunk)

Core Viewpoint - Tempest Therapeutics presented new data at the 2025 AACR Annual Meeting supporting the immune-mediated anti-cancer activity of amezalpat, reinforcing its potential as a novel cancer treatment [1][2]. Group 1: Amezalpat's Mechanism and Efficacy - Amezalpat reduces tumor-promoting immunosuppression by M2 macrophages and T regulatory cells, leading to immune activation [2]. - The drug is an inhibitor of PPAR-alpha, which regulates fatty acid oxidation, a pathway utilized by immunosuppressive cells associated with poor cancer prognosis [2]. - Clinical data indicate that amezalpat shows superiority in overall survival when combined with atezolizumab and bevacizumab in advanced HCC patients compared to standard care [3]. Group 2: Company Overview - Tempest Therapeutics is a clinical-stage biotechnology company focused on developing small molecule therapeutics with tumor-targeted and immune-mediated mechanisms [4]. - The company is headquartered in Brisbane, California, and is advancing a diverse portfolio of product candidates aimed at treating various tumors [4].

BRISBANE, Calif., April 21, 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 announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to TPST-1495, the company's novel dual receptor inhibitor of prostaglandin (PGE2) signaling, for the treatment of patients with Familial Adenomatous Polyposis (FAP). "Receiving orphan d ...

Core Viewpoint - Tempest Therapeutics, Inc. is exploring strategic options to enhance stockholder value, which may include mergers, acquisitions, partnerships, or licensing arrangements [1] Company Development Plans - Tempest is developing amezalpat (TPST-1120), a PPAR-alpha antagonist, for first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC) [2] - The company is also working on TPST-1495, a selective EP2-EP4 dual antagonist, for treating familial adenomatous polyposis (FAP) [2] - Tempest has partnered with Roche to evaluate amezalpat in combination with Roche's Tecentriq and Avastin for HCC treatment [5] - The FDA has cleared Tempest to begin a pivotal phase III study for amezalpat in combination with Roche's therapy for HCC [6] - Ongoing studies have shown that amezalpat combined with Roche's therapy resulted in a six-month improvement in median overall survival compared to the standard therapy alone [7] - The FDA has granted Fast Track and Orphan Drug designations to amezalpat for HCC treatment [7] - Tempest has received a "Study May Proceed" letter from the FDA for a phase II study on TPST-1495, expected to start in 2025 [9] - The FDA has also granted Orphan Drug designation to TPST-1495 for FAP treatment [9] - Management believes that amezalpat has blockbuster potential in HCC, while TPST-1495 also shows promise [10] Stock Performance - Following the announcement of strategic options, Tempest's shares rose by 6.3% in after-hours trading on April 9 [2] - Year-to-date, Tempest's shares have decreased by 34.1%, compared to a 14.6% decline in the industry [3]