Tempest Therapeutics(TPST) - 2024 Q4 - Annual Report

Part I Business Tempest Therapeutics is a clinical-stage biotechnology company developing first-in-class cancer therapies, with lead candidates for hepatocellular carcinoma and Familial Adenomatous Polyposis - The company is a clinical-stage biotechnology firm with a portfolio of targeted and immune-mediated product candidates for treating various cancers[15] - The company's strategy includes advancing amezalpat into a pivotal Phase 3 study, exploring TPST-1495 in a Phase 2 study for FAP, enhancing the pipeline through in-licensing, and exploring business development opportunities to maximize program potential[28][33] - As of December 31, 2024, the company had 25 employees, with 18 holding advanced degrees (Ph.D., M.D., etc.)[164] Product Development Pipeline | Product Candidate | Target | Indication | Development Stage | | :--- | :--- | :--- | :--- | | Amezalpat (TPST-1120) | PPARα | First-Line Hepatocellular Carcinoma (HCC) | Phase 3 Ready (Pivotal Study) | | TPST-1495 | EP2/EP4 | Familial Adenomatous Polyposis (FAP) | Phase 2 (2025) | | Discovery Research | Novel Targets | Oncology | Preclinical | Amezalpat (TPST-1120) Amezalpat, an oral PPARα antagonist, showed a six-month median overall survival benefit in a Phase 1b/2 study for first-line HCC and has received positive FDA feedback for a Phase 3 trial design - In a global randomized Phase 1b/2 study for first-line HCC, amezalpat combined with atezolizumab and bevacizumab showed a six-month improvement in median overall survival (OS) compared to the standard of care alone, with a hazard ratio (HR) of 0.65[18] - The FDA has granted amezalpat Orphan Drug Designation (ODD) and Fast Track Designation (FTD) for HCC, and issued a 'Study May Proceed' letter for the pivotal Phase 3 trial[20] - The company owns worldwide rights to amezalpat, with patents expected to expire between December 2033 and November 2043[59] Amezalpat Randomized HCC Trial Efficacy (Feb 14, 2024 Cutoff) | Metric | Amezalpat Arm (n=40) | Control Arm (n=30) | | :--- | :--- | :--- | | Median Overall Survival (OS) | 21.0 months | 15.0 months | | Hazard Ratio (HR) | 0.65 | - | | Confirmed ORR | 30% | 13.3% | | Complete Response (CR) | 1 patient | 0 patients | | Confirmed ORR (β-catenin mutated) | 43% | Not provided | | Confirmed ORR (PD-L1 negative) | 27% | 7% | TPST-1495 TPST-1495, a dual EP2/EP4 antagonist, is advancing to a Phase 2 trial for Familial Adenomatous Polyposis (FAP) following positive preclinical data and FDA authorization - TPST-1495 is a first-in-class, oral, small molecule dual antagonist of the EP2 and EP4 prostaglandin receptors[60] - In March 2025, the FDA authorized the initiation of an NCI-funded Phase 2 clinical trial to evaluate TPST-1495 in patients with Familial Adenomatous Polyposis (FAP), expected to begin in 2025[23][441] - The company owns worldwide rights to TPST-1495, with U.S. patents expected to expire between April 2038 and April 2039[69] License Agreements The company maintains a collaboration with Roche for the amezalpat HCC study and has secured a supply agreement for its planned Phase 3 trial - A collaboration agreement with Roche is in place for the Phase 1b/2 clinical study of amezalpat in HCC; Roche manages study operations, and Tempest retains global development and commercialization rights[71] - In October 2024, Tempest entered into a master clinical supply agreement with Roche, under which Roche will supply atezolizumab free of charge for the planned Phase 3 trial of amezalpat[74] Government Regulation and Healthcare Reform Operations are subject to extensive FDA regulation and impacted by healthcare laws like the ACA and the Inflation Reduction Act, which affects drug pricing - Pharmaceutical products are subject to extensive regulation by the FDA, covering research, development, testing, manufacturing, approval, and marketing; the approval process involves preclinical studies, an effective IND, and adequate and well-controlled clinical trials[95][96] - The company may utilize expedited FDA programs; amezalpat has received Fast Track Designation, which allows for more frequent FDA interaction and potential for rolling review and priority review[120] - Amezalpat has received Orphan Drug Designation for HCC, which provides potential for seven years of market exclusivity in the U.S. if it is the first to receive approval for that indication[118] - The Inflation Reduction Act of 2022 (IRA) directs HHS to negotiate prices for certain high-expenditure drugs under Medicare and imposes rebates for price increases that outpace inflation, which could impact future product pricing[159][160] Risk Factors The company faces significant financial, clinical, and regulatory risks, including the need for additional funding, a history of losses, and reliance on third parties - The company will require substantial additional funding for operations, and failure to obtain this capital may force delays, limitations, or termination of product development[172][175] - The company has a history of operating losses, incurring net losses of $41.8 million in 2024 and $29.5 million in 2023, with an accumulated deficit of $207.1 million as of December 31, 2024[186] - The loan agreement with Oxford Finance provides Oxford with a lien against all company assets, including intellectual property, and contains restrictive covenants[174][187] - Success in preclinical and early clinical trials may not be indicative of results in later-stage trials, which could delay or prevent regulatory approval[174][205] - The company relies on third parties for manufacturing, which poses risks related to supply, quality, and regulatory compliance[174][251] - The company's common stock is thinly traded and has been volatile, which could lead to substantial losses for investors[176][385][390] Unresolved Staff Comments The company reports no unresolved staff comments from the SEC - None[410] Cybersecurity Cybersecurity risk management is led by the CFO and overseen by the board's audit committee, utilizing internal processes and third-party providers - The company's information security function is led by the Chief Financial Officer & Head of Corporate Strategy (IT Lead), who reports to the CEO and is supported by a third-party security provider[412] - The board of directors' audit committee is responsible for overseeing the company's cybersecurity risk management processes[416] - Cybersecurity measures include risk assessments, system monitoring, access controls, asset management, and employee training[414] Properties The company leases approximately 20,116 square feet of laboratory and office space in Brisbane, California for its corporate headquarters - The company leases approximately 20,116 square feet of laboratory and office space at 2000 Sierra Point Parkway, Brisbane, California, which serves as its headquarters[421] Legal Proceedings As of the report date, Tempest Therapeutics is not a party to any material legal proceedings - The company is not currently a party to any material legal proceedings[424] Mine Safety Disclosures This item is not applicable to the company - Not applicable[425] Part II Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities The company's common stock trades on Nasdaq as "TPST", with 45,483,384 shares outstanding as of March 21, 2025, and no history of paying dividends - The company's common stock is listed on the Nasdaq Stock Market under the ticker symbol "TPST"[427] - As of March 21, 2025, there were 45,483,384 shares of common stock outstanding[427] - The company has never declared or paid cash dividends and intends to retain future earnings to fund business development[428] Management's Discussion and Analysis of Financial Condition and Results of Operations The net loss increased to $41.8 million in 2024, driven by higher R&D expenses for the amezalpat trial, while cash reserves are deemed sufficient for the next 12 months - The $11.0 million (63%) increase in R&D expense was primarily due to increased costs for contract research and manufacturing in preparation for the pivotal Phase 3 trial of amezalpat[460] - As of December 31, 2024, the company had $30.3 million in cash and cash equivalents and an accumulated deficit of $207.1 million[463] - Management believes existing cash is sufficient to fund operations for at least the next 12 months, but acknowledges that the Phase 3 clinical trial for amezalpat will require significant additional capital[464][451] Results of Operations (2024 vs. 2023) | Line Item | 2024 (in thousands) | 2023 (in thousands) | Change (%) | | :--- | :--- | :--- | :--- | | Research and development | $28,476 | $17,498 | 63% | | General and administrative | $13,550 | $11,659 | 16% | | Operating loss | ($42,026) | ($29,157) | 44% | | Net loss | ($41,843) | ($29,491) | 42% | Cash Flow Summary (2024 vs. 2023) | Cash Flow Activity | 2024 (in thousands) | 2023 (in thousands) | | :--- | :--- | :--- | | Cash used in operating activities | ($33,027) | ($27,357) | | Cash used in investing activities | ($435) | ($170) | | Cash provided by financing activities | $24,500 | $35,602 | Quantitative and Qualitative Disclosures About Market Risk This section is not required as the company is a smaller reporting company - Not required for smaller reporting companies[491] Financial Statements and Supplementary Data The audited financial statements show a 2024 net loss of $41.8 million, with the auditor providing an unqualified opinion and noting accrued R&D expenses as a critical audit matter - The independent auditor, Ernst & Young LLP, issued an unqualified opinion on the consolidated financial statements[497] - The auditor identified accrued research and development expenses as a critical audit matter due to the significant judgments and estimates required to determine the accrual balance[501][502] Consolidated Balance Sheet Highlights (as of Dec 31) | Account | 2024 (in thousands) | 2023 (in thousands) | | :--- | :--- | :--- | | Cash and cash equivalents | $30,268 | $39,230 | | Total assets | $41,488 | $51,603 | | Total liabilities | $22,362 | $24,835 | | Total stockholders' equity | $19,126 | $26,768 | Consolidated Statement of Operations Highlights (Year Ended Dec 31) | Account | 2024 (in thousands) | 2023 (in thousands) | | :--- | :--- | :--- | | Research and development | $28,476 | $17,498 | | General and administrative | $13,550 | $11,659 | | Net loss | ($41,843) | ($29,491) | | Net loss per share | ($1.50) | ($1.91) | Changes in and Disagreements with Accountants on Accounting and Financial Disclosure The company reports no changes in or disagreements with its accountants on accounting and financial disclosure - None[603] Controls and Procedures Management concluded that the company's disclosure controls, procedures, and internal control over financial reporting were effective as of December 31, 2024 - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2024[605] - Management concluded that the company's internal control over financial reporting was effective as of December 31, 2024[607] - No changes in internal control over financial reporting occurred during the fourth quarter of 2024 that materially affected, or are reasonably likely to materially affect, internal controls[609] Other Information No director or officer adopted or terminated a Rule 10b5-1 trading arrangement during the fourth quarter of 2024 - During the three months ended December 31, 2024, no director or officer adopted or terminated a Rule 10b5-1 trading arrangement[610] Disclosure Regarding Foreign Jurisdictions that Prevent Inspections This item is not applicable to the company - Not applicable[611] Part III Directors, Executive Officers and Corporate Governance Information on directors, officers, and corporate governance is incorporated by reference from the company's 2025 Proxy Statement - Information is incorporated by reference from the registrant's definitive Proxy Statement for its 2025 Annual Meeting of Stockholders[613][614] Executive Compensation Information regarding executive compensation is incorporated by reference from the company's definitive 2025 Proxy Statement - Information is incorporated by reference from the registrant's definitive Proxy Statement for its 2025 Annual Meeting of Stockholders[616] Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters Information on security ownership and equity compensation plans is incorporated by reference from the company's 2025 Proxy Statement - Information is incorporated by reference from the registrant's definitive Proxy Statement for its 2025 Annual Meeting of Stockholders[617][618] Certain Relationships and Related Transactions, and Director Independence Information on related party transactions and director independence is incorporated by reference from the company's 2025 Proxy Statement - Information is incorporated by reference from the registrant's definitive Proxy Statement for its 2025 Annual Meeting of Stockholders[619][620] Principal Accountant Fees and Services Information regarding principal accountant fees and services is incorporated by reference from the company's definitive 2025 Proxy Statement - Information is incorporated by reference from the registrant's definitive Proxy Statement for its 2025 Annual Meeting of Stockholders[621] Part IV Exhibits and Financial Statement Schedules This section lists the exhibits filed with the report, including material contracts and required certifications, while financial schedules are omitted - The financial statements are included in Item 8; all financial statement schedules are omitted as inapplicable or the information is otherwise included[623] - A list of exhibits filed with the report is provided, including material contracts and required certifications[624][625] Form 10-K Summary This item is not applicable to the company - Not applicable[628]