Key Takeaways Novo Nordisk remains the GLP-1 market leader but faces slower sales and rising competition.NVO cut its 2025 outlook amid weaker Wegovy and Ozempic trends.GPCR readies key obesity-drug studies, with data from its aleniglipron studies expected by year-end.Novo Nordisk (NVO) and Structure Therapeutics (GPCR) have emerged as noteworthy companies in the obesity space.A market leader in the GLP-1 space, Novo Nordisk markets its semaglutide drugs under brand names Ozempic (pre-filled pen) and Rybelsu ...

Core Insights - Several clinical-stage biotech companies experienced significant after-hours trading momentum due to anticipated trial data releases and pipeline updates [1] Company Summaries - **MBX Biosciences Inc. (MBX)**: Shares surged 33% in after-hours trading, rising from $10.00 to $13.77, following the announcement of topline results from its Phase 2 trial of Canvuparatide, expected on September 22 [2][3] - **Structure Therapeutics Inc. (GPCR)**: Stock increased 11.37% to $26.26 after closing at $23.58, driven by interest in its lead candidate aleniglipron, with topline results from two Phase 2b trials expected by the end of 2025 [4] - **Cartesian Therapeutics Inc. (RNAC)**: Shares rose 5.51% to $9.96 after a decline during the day, with preliminary data from the Phase 2 trial of Descartes-08 expected in the second half of 2025 [5][6] - **Rapport Therapeutics Inc. (RAPP)**: Stock increased 3.60% to $27.31, following positive topline results from its Phase 2a trial for RAP-219, with Phase 3 trials expected to start in 2026 [9][10] - **Rezolute Inc. (RZLT)**: Shares rose 3.77% to $7.99 after a decline during the day, with topline data from the Phase 3 sunRIZE trial for congenital hyperinsulinism expected in December 2025 [11][12]

Core Insights - Structure Therapeutics Inc. is positioned as a leading AI-driven biotech innovator focusing on oral small-molecule therapies for metabolic diseases like obesity and diabetes [1][4] - The company’s lead candidate, aleniglipron, is undergoing two Phase 2b studies, with topline results expected by the end of 2025, which will be crucial for validating its AI-enabled approach [2][4] - Financially, the company reported a net loss of $61.7 million in Q2 2025 but maintains a strong cash position of approximately $786.5 million, supporting operations through 2027 [3] Company Overview - Structure Therapeutics Inc. (NASDAQ:GPCR) is a clinical-stage biopharmaceutical company [1] - The company leverages AI-powered drug discovery to enhance the speed and precision of candidate design and optimization [1][4] Product Pipeline - The lead obesity candidate, aleniglipron (GSBR-1290), is in two Phase 2b studies, ACCESS and ACCESS II, testing doses up to 240 mg [2] - The company plans to initiate Phase 1 trials for ACCG-2671, an oral amylin receptor agonist, expanding its portfolio in metabolic diseases [2] Financial Position - Structure Therapeutics reported a net loss of $61.7 million in Q2 2025 due to significant R&D investments [3] - The company has a robust cash position of approximately $786.5 million, which is expected to sustain operations through 2027 [3] Market Position and Strategy - The AI-powered platform of Structure Therapeutics distinguishes it from traditional biotech firms by focusing on orally available therapies, enhancing patient accessibility and compliance [4] - The company is approaching pivotal Phase 2b readouts for aleniglipron and preparing for ACCG-2671 trials, showcasing the potential of AI integration in drug discovery [4]

Core Insights - Structure Therapeutics is focused on making transformative medicines accessible to the masses, particularly in the GLP-1 area [3] - The company has three different programs, with aleniglipron being the lead program, which is an oral GLP-1 small molecule believed to be potentially best-in-class [3] - The company plans to have data readouts for its programs ACCESS and ACCESS II by the end of the year [4] Company Programs - Aleniglipron is the lead program, focusing on oral GLP-1 small molecules [3] - The company is developing an oral amylin small molecule, which is noted to be the first of its kind, set to enter clinical trials by the end of the year [4] - Structure Therapeutics is also focusing on multiple oral amylin small molecules, including DACRAs and SARAs, and is emphasizing combinability in its research [4]

Summary of Structure Therapeutics FY Conference Call Company Overview - **Company**: Structure Therapeutics (NasdaqGM: GPCR) - **Focus**: Development of oral small molecules in the GLP-1 area, particularly for obesity treatment Key Points Industry and Market Dynamics - **Obesity Market**: The market is expected to evolve with a 70/30 split between injectables and oral medications, with a significant focus on oral options to enhance accessibility for patients [4][6] - **Primary Care Physicians**: They are crucial in driving market growth, preferring oral medications for their patients due to flexibility and ease of prescription [5][6] - **Discontinuation Rates**: Current injectable treatments have a 50% discontinuation rate after one year, highlighting the need for more patient-friendly options [6] Product Pipeline and Development - **Lead Product**: Eleni Glypron, an oral GLP-1 small molecule, is positioned as potentially best-in-class with data readouts expected at the end of the year [2][10] - **Phase IIa Data**: The phase IIa study showed a weight loss of 6.2% to 6.9% with low adverse event-related discontinuation rates [10] - **Phase IIb Studies**: Two studies, ACCESS and ACCESS II, will evaluate higher doses (up to 240 mg) and are set to read out at the end of the year [11][15] - **Titration Strategy**: The phase IIb study will implement a once-every-four-weeks titration scheme to improve tolerability [13][14] Safety and Efficacy - **Safety Data**: The company plans to release efficacy, tolerability, and safety data at the end of the year [19][20] - **Benchmarking**: Comparisons with orforglipron data will be made, focusing on the same titration scheme for efficacy evaluation [22][23] Future Studies and Extensions - **Open Label Extensions**: An open label extension for the ACCESS study has been announced to provide access to the treatment for those in the placebo group [29] - **Additional Studies**: Three new studies are planned, including a switch study for patients transitioning from injectables to oral medications [34][35] Strategic Considerations - **Partnerships**: The company is open to strategic partnerships to expand the indications for Eleni Glypron, emphasizing the importance of accessibility [48] - **Scalability**: Structure Therapeutics can produce enough material to supply 100 million patients at a 120 mg dose, highlighting the scalability of their oral small molecules [50][51] Amylin Development - **New Asset**: GSBR-2671, an oral amylin, is being developed with a focus on better tolerability and selective weight loss [52][53] - **Combination Therapy**: The potential for combining GSBR-2671 with Eleni Glypron for enhanced weight loss effects is being explored [57] Conclusion - **Accessibility Focus**: Structure Therapeutics aims to provide accessible treatment options for obesity, recognizing it as a pandemic that requires diverse solutions [62] Additional Important Insights - **Regulatory Environment**: Recent FDA updates have clarified requirements for chronic weight management studies, facilitating faster development of obesity treatments [41][42] - **Global Need**: By 2030, an estimated 1.3 billion people will be overweight or obese, underscoring the urgency for effective treatments [50]

Summary of Structure Therapeutics Conference Call Company Overview - Structure Therapeutics focuses on accessibility in obesity treatment, emphasizing the importance of providing patients with options in their healthcare journey [4][6][8] Key Priorities and Developments - The company is excited about the potential of oral small molecules in the obesity market, which are expected to become first-line treatments for patients transitioning from primary care physicians [5][4] - Lead molecules include aleniglapron, with two significant data readouts (Access and Access 2) expected by the end of the year [6][7] - The company is also developing an oral amylin small molecule, amylin 2671, which is set to enter clinical trials later this year [8] Clinical Trials and Data - Access and Access 2 studies are 36-week trials, with Access allowing doses up to 120 mg and Access 2 allowing doses up to 240 mg [6][7] - The company is implementing an open-label extension to trials to address high discontinuation rates in placebo groups, allowing participants to experience the drug after initial trial phases [17][18] - Recent FDA guidelines have eased requirements for chronic weight management studies, increasing confidence in the clinical trial process [25][26] Market Opportunity - The company believes that the primary care physician market will drive growth, with an estimated 70% of the market coming from this segment [39] - Oral small molecules are expected to expand the market, providing flexibility and ease of use compared to injectables [39][36] Competitive Landscape - Structure Therapeutics positions itself as having the second most advanced oral GLP-1 small molecule, aleniglapron, and is focused on a multigenerational approach to drug development [40][41] - The company is actively monitoring competitive developments, particularly in markets like China, and is committed to maintaining a strong intellectual property portfolio [65][66] Formulation and Combinability - The company has invested in advanced formulation technologies, including extended-release and gastric retention technologies, to enhance the efficacy and tolerability of its drugs [45][46] - Aleniglapron is designed for combinability with other treatments, allowing for flexible dosing ratios to optimize efficacy and tolerability [64][49] Long-term Strategy and Partnerships - Structure Therapeutics aims to partner for commercialization to expand its reach and capabilities in conducting multiple phase three studies [67][69] - The company emphasizes the importance of making medicines accessible to all, aligning its mission with the growing need for effective obesity treatments [67][66] Conclusion - Structure Therapeutics is positioned to capitalize on the growing demand for obesity treatments through innovative oral small molecules, strategic clinical trial designs, and a focus on accessibility and flexibility in treatment options [4][39][67]

Company Overview - Structure Therapeutics Inc. is a clinical-stage global biopharmaceutical company focused on developing novel oral small molecule therapeutics for metabolic diseases, particularly obesity [1][3] - The company utilizes a next-generation structure-based drug discovery platform to create a robust GPCR-targeted pipeline, featuring multiple proprietary clinical-stage oral small molecule compounds [3] Upcoming Events - Management will participate in the Cantor Global Healthcare Conference on September 3 at 3:55 p.m. ET in New York, NY, featuring a fireside chat and 1x1 meetings [2] - The company will also attend the Morgan Stanley 23rd Annual Global Healthcare Conference on September 10 at 10:45 a.m. ET, also in New York, NY, with a similar format [2] - Live and archived webcasts of these events will be available on the company's website for 90 days [2]

Group 1: Core Insights - Goldman Sachs' latest report focuses on "2Q25 EPS updates," analyzing biotech companies such as Amylyx (AMLX.US), CG Oncology (CGON.US), GPCR (GPCR.US), and Ideaya Biosciences (IDYA.US), concluding that operational data largely meets expectations with minor adjustments to target prices due to cash flow or clinical milestones [1] Group 2: Amylyx (AMLX.US) - In Q2, Amylyx reported operating expenses of approximately $43 million, slightly above market consensus of $41 million and Goldman Sachs' estimate of $40 million, primarily due to higher R&D costs of $27 million compared to the expected range of $22 million to $25 million [2] - The management reiterated the timeline for the Phase III clinical trial for post-bariatric hypoglycemia (PBH), aiming for enrollment completion in 2025, data readout in the first half of 2026, and potential market entry in 2027, with an estimated patient population of around 160,000 [2] - Goldman Sachs maintains a "Buy" rating with a target price of $10 [2] Group 3: CG Oncology (CGON.US) - CG Oncology's BOND-003 Phase III trial data showed a complete response rate of 75.5% for its bladder cancer gene therapy, with 12-month and 24-month sustained response rates of 50.7% and 42.3%, respectively [3] - The company has $661 million in cash, sufficient to support operations until mid-2028, and Goldman Sachs maintains a "Buy" rating with minor model adjustments [3] Group 4: GPCR (GPCR.US) - GPCR's Q2 R&D expenses were approximately $54 million, significantly higher than market expectations of $36 million and Goldman Sachs' estimate of $44 million, attributed to workforce expansion and increased trial costs [4] - The company has $787 million in cash, expected to last until 2027, and plans to read out Phase 2b ACCESS data in 2025 [4] Group 5: Ideaya Biosciences (IDYA.US) - Ideaya reported Q2 R&D expenses of about $74 million, slightly above market expectations of $71 million and Goldman Sachs' estimate of $68 million, with cash reserves of $992 million projected to last until 2029 [5] - The core pipeline includes darovasertib in combination with crizotinib for HLA-A2 negative metastatic uveal melanoma, with Phase 2/3 results expected by year-end [5] Group 6: Terns Pharmaceuticals (TERN.US) and RNA (RNA.US) - Terns Pharmaceuticals plans to release preliminary data for its leukemia drug TERN-701 and obesity drug TERN-601 in Q4 2025, with cash reserves of $315 million sufficient until 2028 [6] - RNA has signed a manufacturing agreement with Lonza to ensure product supply stability from 2026 to 2028, with BLA submissions expected for its treatments by the end of 2025 and mid-2026 [6] Group 7: AI in Biotech - Goldman Sachs emphasizes the core role of biotechnology R&D, highlighting collaborations with institutions like OpenAI to drive innovation, while also focusing on the pricing potential of rare disease drugs and opportunities for indication expansion [7] Group 8: Overall Industry Outlook - The biotech sector is expected to see over 15 key clinical data readouts from late 2025 to early 2026, with a focus on companies like AMLX, CGON, and RNA for their potential breakthroughs [8] - Despite some companies facing increased short-term losses due to R&D spending, pipeline progress remains in line with expectations, and cash flow is generally secure [8]

[PART I. FINANCIAL INFORMATION](index=10&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) This section provides the unaudited condensed consolidated financial statements and management's discussion and analysis of the company's financial condition and results of operations [Item 1. Financial Statements (Unaudited)](index=10&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) This section presents the unaudited condensed consolidated financial statements, including the balance sheets, statements of operations and comprehensive loss, statements of shareholders' equity, and statements of cash flows, along with detailed notes explaining the company's financial position, performance, and significant accounting policies for the periods ended June 30, 2025, and December 31, 2024 [Condensed Consolidated Balance Sheets](index=10&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This statement presents the company's financial position, including assets, liabilities, and equity, at specific reporting dates Condensed Consolidated Balance Sheets (in thousands) | Metric | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | | :-------------------------------- | :----------------------------- | :------------------------------- | | Cash and cash equivalents | $147,024 | $169,510 | | Short-term investments | $639,472 | $714,008 | | Total current assets | $799,298 | $891,211 | | Total assets | $816,443 | $903,330 | | Total current liabilities | $39,033 | $36,021 | | Total liabilities | $44,362 | $38,487 | | Total shareholders' equity | $772,081 | $864,843 | - Total assets decreased from **$903.3 million** at December 31, 2024, to **$816.4 million** at June 30, 2025, primarily due to a reduction in cash, cash equivalents, and short-term investments[16](index=16&type=chunk) [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) This statement details the company's revenues, expenses, and net loss over specific reporting periods, reflecting operational performance Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands) | Metric | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | :------------------------------------------ | :------------------------------------------ | | Research and development | $54,710 | $22,050 | $97,577 | $42,729 | | General and administrative | $15,741 | $11,266 | $29,185 | $22,602 | | Total operating expenses | $70,451 | $33,316 | $126,762 | $65,331 | | Loss from operations | $(70,451) | $(33,316) | $(126,762) | $(65,331) | | Interest and other income, net | $8,929 | $7,335 | $18,505 | $13,343 | | Net loss attributable to ordinary shareholders | $(61,661) | $(26,034) | $(108,494) | $(52,070) | | Net loss per share, basic and diluted | $(0.36) | $(0.18) | $(0.63) | $(0.36) | - Net loss attributable to ordinary shareholders significantly increased for both the three and six months ended June 30, 2025, compared to the same periods in 2024, primarily driven by a substantial rise in research and development expenses[19](index=19&type=chunk) [Condensed Consolidated Statements of Shareholders' Equity](index=12&type=section&id=Condensed%20Consolidated%20Statements%20of%20Shareholders%27%20Equity) This statement outlines changes in the company's equity accounts, including net losses, share-based compensation, and share issuances Condensed Consolidated Statements of Shareholders' Equity (in thousands) | Metric | December 31, 2024 (in thousands) | March 31, 2025 (in thousands) | June 30, 2025 (in thousands) | | :-------------------------------- | :------------------------------- | :---------------------------- | :--------------------------- | | Total Shareholders' Equity | $864,843 | $824,638 | $772,081 | | Accumulated Deficit | $(329,098) | $(375,931) | $(437,592) | - Total shareholders' equity decreased from **$864.8 million** at December 31, 2024, to **$772.1 million** at June 30, 2025, primarily due to net losses and unrealized losses on investments, partially offset by share-based compensation and proceeds from share issuances[21](index=21&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=13&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This statement summarizes the cash inflows and outflows from operating, investing, and financing activities over specific periods Condensed Consolidated Statements of Cash Flows (in thousands) | Cash Flow Activity | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Net cash used in operating activities | $(106,787) | $(60,473) | | Net cash provided by (used in) investing activities | $82,975 | $(203,097) | | Net cash provided by financing activities | $1,326 | $515,405 | | Net change in cash and cash equivalents | $(22,486) | $251,835 | | Cash and cash equivalents, end of period | $147,024 | $381,627 | - For the six months ended June 30, 2025, net cash used in operating activities increased to **$106.8 million**, while investing activities provided **$83.0 million**, primarily from net maturities of short-term investments. Financing activities provided **$1.3 million**, resulting in a net decrease in cash and cash equivalents of **$22.5 million**[23](index=23&type=chunk) [Notes to Unaudited Condensed Consolidated Financial Statements](index=14&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed explanations and supplementary information for the figures presented in the unaudited financial statements - The company is a clinical-stage global biopharmaceutical company incorporated in the Cayman Islands with operating subsidiaries in the United States and China, focused on developing novel oral therapeutics for chronic diseases[24](index=24&type=chunk) Summary of Financing Events | Financing Event | Net Proceeds (approx.) | | :---------------- | :--------------------- | | Initial Public Offering (Feb 2023) | $166.7 million | | Private Placement (Oct 2023) | $281.5 million | | Follow-On Offering (June 2024) | $512.7 million | - As of June 30, 2025, the company had **$786.5 million** in cash, cash equivalents, and short-term investments, which it believes will be sufficient to fund projected operations for at least 12 months[31](index=31&type=chunk) Research and Development and General and Administrative Expenses (in thousands) | R&D Expense Category | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Discovery research and development | $48,031 | $20,392 | | Clinical research and development | $40,306 | $17,696 | | Other research and development expenses | $9,240 | $4,641 | | General and administrative | $29,185 | $22,602 | | Total operating expenses | $126,762 | $65,331 | - A **$3.0 million** milestone payment was achieved and paid under the Aconcagua-Schrödinger Agreement as of June 30, 2025. Additionally, Basecamp Bio Inc. entered into an Asset Purchase Agreement with Exelixis, Inc. on August 5, 2025, for early-stage assets, with potential initial payments of **$10.0 million** and up to **$90.0 million** in contingent milestones[80](index=80&type=chunk)[81](index=81&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=32&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides an overview of the company's clinical-stage biopharmaceutical business, its pipeline of oral small molecule therapeutics targeting GPCRs for chronic diseases, and a detailed analysis of its financial performance, liquidity, and capital resources. The company reported increased net losses driven by higher R&D expenses, particularly for aleniglipron, and discussed its funding strategy and future capital needs [Overview](index=32&type=section&id=Overview) This section introduces the company's clinical-stage biopharmaceutical business, its drug discovery platform, and its pipeline of oral small molecule therapeutics - The company is a clinical stage global biopharmaceutical company focused on developing novel oral small molecule therapeutics for chronic diseases, utilizing a differentiated technology platform that leverages structure-based drug discovery and computational chemistry against G-protein coupled receptors (GPCRs)[84](index=84&type=chunk) - Aleniglipron (GSBR-1290), an oral GLP-1R agonist, is the most advanced product candidate, currently in two Phase 2 clinical studies (ACCESS and ACCESS II) for obesity and overweight. Positive topline Phase 2a data showed a **6.2% placebo-adjusted mean weight decrease** at 12 weeks. Enrollment for ACCESS and ACCESS II was completed in February 2025, with topline data expected in Q4 2025[85](index=85&type=chunk)[86](index=86&type=chunk)[89](index=89&type=chunk) - The pipeline also includes ACCG-2671 (oral amylin receptor agonist, IND-enabling studies ongoing, Phase 1 expected by year-end 2025), ANPA-0073 (oral APJ receptor agonist, Phase 2 ready), and LTSE-2578 (oral LPA1R antagonist for IPF, completed Phase 1 in July 2025)[85](index=85&type=chunk)[92](index=92&type=chunk)[95](index=95&type=chunk) - The company relies on third parties for manufacturing product candidates and is diversifying suppliers outside of China. It has incurred significant net operating losses (**$108.5 million** for six months ended June 30, 2025) and had an accumulated deficit of **$437.6 million** as of June 30, 2025[97](index=97&type=chunk)[98](index=98&type=chunk)[100](index=100&type=chunk) - Existing cash, cash equivalents, and short-term investments (**$786.5 million** as of June 30, 2025) are expected to fund operations through at least 2027, including Phase 3 readiness for aleniglipron (excluding registrational studies). Substantial additional capital will be needed for Phase 3 and future growth[101](index=101&type=chunk)[102](index=102&type=chunk) [Impact of Geopolitical and Macroeconomic Factors](index=38&type=section&id=Impact%20of%20Geopolitical%20and%20Macroeconomic%20Factors) This section assesses the potential effects of global geopolitical and macroeconomic developments on the company's operations and financial outlook - While no significant financial impact was observed for the six months ended June 30, 2025, the company acknowledges potential future impacts from geopolitical and macroeconomic developments, including disruptions in access to bank deposits, tariffs, global pandemics, and US-China tensions[103](index=103&type=chunk)[105](index=105&type=chunk) - The One Big Beautiful Bill Act (OBBBA), signed on July 4, 2025, repeals the requirement to capitalize domestic R&D expenditures for federal income tax purposes for taxable years beginning after December 31, 2024, and allows **100% bonus depreciation**. The company preliminarily does not anticipate a material change to its effective income tax rate due to a full valuation allowance[106](index=106&type=chunk) [Components of Our Results of Operations](index=40&type=section&id=Components%20of%20Our%20Results%20of%20Operations) This section outlines the primary categories of expenses and income that constitute the company's financial performance - Research and development expenses primarily consist of costs for discovery, engineering, preclinical and clinical studies, including personnel, consulting, clinical trial expenses, and regulatory costs. These expenses are expected to increase substantially as product candidates advance[107](index=107&type=chunk)[109](index=109&type=chunk) - General and administrative expenses include personnel costs for executive, legal, finance, and administrative functions, professional fees, and other operating expenses. These are expected to increase due to headcount expansion and public company operating costs[110](index=110&type=chunk)[111](index=111&type=chunk) - Interest and other income, net, primarily comprises interest earned on cash, cash equivalents, and short-term investments, including amortization/accretion of premiums/discounts, and foreign currency exchange gains/losses[114](index=114&type=chunk) [Results of Operations](index=42&type=section&id=Results%20of%20Operations) This section analyzes the company's financial performance, highlighting key changes in revenues, expenses, and net loss over the reporting periods Results of Operations - Three Months Ended June 30 (in thousands) | Metric | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | Change ($) | Change (%) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | :--------- | :--------- | | Research and development | $54,710 | $22,050 | $32,660 | 148% | | General and administrative | $15,741 | $11,266 | $4,475 | 40% | | Interest and other income, net | $8,929 | $7,335 | $1,594 | 22% | | Net loss | $(61,661) | $(26,034) | $(35,627) | 137% | Results of Operations - Six Months Ended June 30 (in thousands) | Metric | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | Change ($) | Change (%) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | :--------- | :--------- | | Research and development | $97,577 | $42,729 | $54,848 | 128% | | General and administrative | $29,185 | $22,602 | $6,583 | 29% | | Interest and other income, net | $18,505 | $13,343 | $5,162 | 39% | | Net loss | $(108,494) | $(52,070) | $(56,424) | 108% | - The increase in R&D expenses was primarily due to preclinical research, clinical trial costs, employee expenses (personnel increase), and a **$3.0 million** milestone payment under the Aconcagua-Schrödinger Agreement[116](index=116&type=chunk)[121](index=121&type=chunk) Product Candidate R&D Expenses - Three Months Ended June 30 (in thousands) | Product Candidate R&D Expenses | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Aleniglipron (GSBR-1290) | $28,365 | $9,943 | | ACCG-2671 | $9,649 | $2,429 | | ANPA-0073 | $1,048 | $1,635 | | LTSE-2578 | $1,493 | $2,181 | | Other | $14,155 | $5,862 | | Total R&D Expenses | $54,710 | $22,050 | Product Candidate R&D Expenses - Six Months Ended June 30 (in thousands) | Product Candidate R&D Expenses | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Aleniglipron (GSBR-1290) | $53,350 | $19,478 | | ACCG-2671 | $15,259 | $4,412 | | ANPA-0073 | $2,154 | $2,749 | | LTSE-2578 | $2,919 | $4,343 | | Other | $23,895 | $11,747 | | Total R&D Expenses | $97,577 | $42,729 | [Liquidity and Capital Resources](index=44&type=section&id=Liquidity%20and%20Capital%20Resources) This section discusses the company's ability to generate and manage cash, its funding sources, and future capital requirements - The company has funded operations through equity financings, including an IPO (**$166.7 million** net proceeds in Feb 2023), a Private Placement (**$281.5 million** net proceeds in Oct 2023), and a Follow-On Offering (**$512.7 million** net proceeds in June 2024)[125](index=125&type=chunk) - As of June 30, 2025, cash, cash equivalents, and short-term investments totaled **$786.5 million**, with an accumulated deficit of **$437.6 million**. The company believes existing capital is sufficient for at least 12 months, covering projected operations and key clinical milestones through 2027 (excluding Phase 3 registrational studies)[125](index=125&type=chunk)[126](index=126&type=chunk)[127](index=127&type=chunk) - Substantial additional capital will be needed for Phase 3 clinical studies of aleniglipron and future operations, with funding expected from equity sales, debt, grants, or collaborations[102](index=102&type=chunk)[129](index=129&type=chunk)[131](index=131&type=chunk) Cash Flow Summary (in thousands) | Cash Flow Activity | Six Months Ended June 30, 2025 (in thousands) | Six Months Ended June 30, 2024 (in thousands) | | :-------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Net cash used in operating activities | $(106,787) | $(60,473) | | Net cash provided by (used in) investing activities | $82,975 | $(203,097) | | Net cash provided by financing activities | $1,326 | $515,405 | | Net (decrease) increase in cash and cash equivalents | $(22,486) | $251,835 | - Contractual obligations as of June 30, 2025, include **$8.6 million** in facilities lease payments, with **$3.1 million** due within the next 12 months[141](index=141&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=51&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section states that there were no material changes to the company's quantitative and qualitative disclosures about market risk during the six months ended June 30, 2025, compared to those reported in its Annual Report - No material changes to quantitative and qualitative disclosures about market risk were reported during the six months ended June 30, 2025[145](index=145&type=chunk) [Item 4. Controls and Procedures](index=51&type=section&id=Item%204.%20Controls%20and%20Procedures) Management, including the Chief Executive Officer and Chief Financial Officer, concluded that the company's disclosure controls and procedures were effective at a reasonable assurance level as of June 30, 2025. No changes in internal control over financial reporting were identified that materially affected, or are reasonably likely to materially affect, internal control during the quarter - The Chief Executive Officer and Chief Financial Officer concluded that disclosure controls and procedures were effective at the reasonable assurance level as of June 30, 2025[147](index=147&type=chunk) - No changes in internal control over financial reporting were identified during the quarter ended June 30, 2025, that materially affected, or are reasonably likely to materially affect, internal control over financial reporting[148](index=148&type=chunk) [PART II. OTHER INFORMATION](index=53&type=section&id=PART%20II.%20OTHER%20INFORMATION) This section provides additional disclosures beyond financial statements, including legal proceedings, risk factors, and other required information [Item 1. Legal Proceedings](index=53&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any material governmental investigations, private lawsuits, or other legal proceedings that would have a material adverse effect on its financial position, results of operations, or cash flows - The company is not currently the subject of any material governmental investigation, private lawsuit, or other legal proceeding[151](index=151&type=chunk) [Item 1A. Risk Factors](index=53&type=section&id=Item%201A.%20Risk%20Factors) The company faces numerous risks, including its limited operating history, significant ongoing losses, and substantial capital requirements for product development. Key risks also involve the uncertain and lengthy drug development and regulatory approval processes, reliance on third parties for manufacturing and clinical studies, intense competition, and challenges in achieving market acceptance and reimbursement. Furthermore, the company's international operations, particularly in China, expose it to geopolitical, regulatory, and intellectual property risks, while its public company status adds compliance costs and potential stock price volatility [Risks Related to Our Limited Operating History, Financial Position and Capital Requirements](index=53&type=section&id=Risks%20Related%20to%20Our%20Limited%20Operating%20History%2C%20Financial%20Position%20and%20Capital%20Requirements) This section highlights financial risks stemming from the company's early operational stage, consistent losses, and significant future capital needs - The company has a limited operating history, has incurred significant operating losses since its inception, and expects to incur significant losses for the foreseeable future, with an accumulated deficit of **$437.6 million** as of June 30, 2025[153](index=153&type=chunk)[154](index=154&type=chunk) - Substantial additional capital will be required to finance operations, particularly for Phase 3 clinical studies of aleniglipron, and this capital may not be available on acceptable terms or at all, potentially forcing delays or termination of product development programs[156](index=156&type=chunk)[157](index=157&type=chunk)[159](index=159&type=chunk) - Raising additional capital may dilute shareholder ownership, restrict operations through debt covenants, or require relinquishing rights to technologies or product candidates through collaborations[161](index=161&type=chunk) [Risks Related to the Discovery, Development and Regulatory Approval of Product Candidates](index=57&type=section&id=Risks%20Related%20to%20the%20Discovery%2C%20Development%20and%20Regulatory%20Approval%20of%20Product%20Candidates) This section details the inherent uncertainties, high costs, and lengthy processes involved in drug discovery, clinical development, and obtaining regulatory approvals - The company's structure-based drug discovery platform is unproven, and there is no guarantee of developing commercially valuable products. Failure of one program could negatively impact perception of others[162](index=162&type=chunk) - The company is in early development stages with only four product candidates (aleniglipron, ACCG-2671, ANPA-0073, LTSE-2578) in early clinical development, and all other programs are preclinical or discovery stage. Successful advancement, regulatory approval, and commercialization are uncertain and subject to significant delays[165](index=165&type=chunk)[168](index=168&type=chunk)[169](index=169&type=chunk) - Clinical and preclinical drug development is a lengthy, expensive, and uncertain process. Prior results are not necessarily predictive of future outcomes, and product candidates can fail at any stage[170](index=170&type=chunk)[174](index=174&type=chunk) - Difficulties or delays in clinical studies, such as data collection omissions, patient enrollment challenges, or regulatory hurdles, could increase costs, delay revenue generation, and adversely affect commercial prospects[175](index=175&type=chunk)[177](index=177&type=chunk)[179](index=179&type=chunk)[189](index=189&type=chunk) - Serious adverse events or unexpected properties of product candidates identified during development or after approval could lead to discontinuation of programs, refusal of regulatory approval, or revocation of marketing authorizations[191](index=191&type=chunk)[192](index=192&type=chunk)[193](index=193&type=chunk) - The company lacks experience in conducting later-stage clinical studies or submitting New Drug Applications (NDAs), which are lengthy, time-consuming, expensive, and inherently unpredictable processes[196](index=196&type=chunk)[198](index=198&type=chunk) - There is a risk of expending limited resources on product candidates or indications that may be less profitable or have a lower likelihood of success, potentially missing greater commercial opportunities[202](index=202&type=chunk) - The company may not be able to obtain or maintain orphan drug designations or exclusivity for its product candidates, which could limit their potential profitability[203](index=203&type=chunk)[206](index=206&type=chunk) - Clinical studies conducted outside the United States (e.g., Australia, China) may not be accepted by the FDA or other foreign equivalents, leading to delays and increased costs[207](index=207&type=chunk)[208](index=208&type=chunk) - Preliminary, topline, and interim data from clinical studies are subject to change and audit, and may differ materially from final data, potentially harming business prospects[209](index=209&type=chunk)[210](index=210&type=chunk) [Risks Related to Commercialization of Our Product Candidates](index=98&type=section&id=Risks%20Related%20to%20Commercialization%20of%20Our%20Product%20Candidates) This section addresses challenges in bringing approved product candidates to market, including regulatory compliance, market acceptance, reimbursement, and competitive pressures - Even if product candidates receive marketing approval, they will be subject to ongoing regulatory obligations and review, potentially leading to significant additional expenses, labeling restrictions, or market withdrawal[255](index=255&type=chunk)[256](index=256&type=chunk)[259](index=259&type=chunk)[260](index=260&type=chunk)[261](index=261&type=chunk) - Market acceptance by physicians, patients, and third-party payors is crucial for commercial success, and failure to achieve adequate acceptance could prevent significant product revenue[263](index=263&type=chunk)[264](index=264&type=chunk) - Coverage and adequate reimbursement may not be available for approved product candidates, making profitable sales difficult and impacting demand and pricing[265](index=265&type=chunk)[267](index=267&type=chunk)[268](index=268&type=chunk) - The company faces substantial competition from major pharmaceutical and biotechnology companies, including those utilizing AI for drug discovery, which may result in others commercializing products more successfully[269](index=269&type=chunk)[270](index=270&type=chunk)[271](index=271&type=chunk)[273](index=273&type=chunk)[274](index=274&type=chunk)[276](index=276&type=chunk) - If market opportunities for product candidates are smaller than estimated, revenue may be adversely affected[277](index=277&type=chunk) - The company currently lacks a marketing and sales organization and experience in commercializing products, requiring significant investment or reliance on third parties, which may not generate sufficient product revenue[279](index=279&type=chunk) - Commercializing products in foreign markets exposes the company to additional regulatory burdens, economic, political, and other risks[280](index=280&type=chunk) [Risks Related to Our Business Operations and Industry](index=110&type=section&id=Risks%20Related%20to%20Our%20Business%20Operations%20and%20Industry) This section covers operational challenges, regulatory compliance, personnel dependency, and external factors affecting the company's business and the broader industry - Operating results may fluctuate significantly due to various factors, making future predictions difficult and potentially causing results to fall below expectations[281](index=281&type=chunk)[282](index=282&type=chunk) - High dependence on senior management and the ability to attract and retain qualified personnel. Failure to do so could harm business operations and growth[283](index=283&type=chunk)[286](index=286&type=chunk)[287](index=287&type=chunk) - The need to expand the organization and manage growth could disrupt operations and divert management attention[289](index=289&type=chunk)[290](index=290&type=chunk) - Operations in Australia, conducted through wholly-owned subsidiaries, are subject to risks including the potential loss or refund of research and development tax credits[292](index=292&type=chunk)[294](index=294&type=chunk) - Relationships with healthcare providers and third-party payors are subject to federal and state healthcare fraud and abuse laws, false claims laws, and health data privacy and security laws. Non-compliance could lead to substantial penalties[295](index=295&type=chunk)[296](index=296&type=chunk)[297](index=297&type=chunk)[298](index=298&type=chunk)[299](index=299&type=chunk)[300](index=300&type=chunk) - Healthcare legislative reform measures, such as the ACA, IRA, and OBBBA, may negatively impact the business and results of operations, particularly regarding drug pricing and reimbursement[301](index=301&type=chunk)[302](index=302&type=chunk)[303](index=303&type=chunk)[304](index=304&type=chunk)[305](index=305&type=chunk)[306](index=306&type=chunk)[307](index=307&type=chunk)[310](index=310&type=chunk) - The use of hazardous and biological materials by third-party manufacturers could lead to liability for damages, fines, or operational interruptions[311](index=311&type=chunk) - Product liability lawsuits related to clinical testing or commercialized products could result in substantial liabilities, decreased demand, and harm to reputation[312](index=312&type=chunk)[315](index=315&type=chunk) - Compromises or disruptions to information technology systems or data, including those of third parties, could lead to significant financial, legal, regulatory, business, and reputational harm[316](index=316&type=chunk)[317](index=317&type=chunk)[318](index=318&type=chunk)[320](index=320&type=chunk)[321](index=321&type=chunk)[322](index=322&type=chunk) - Misconduct by employees, principal investigators, consultants, or commercial partners, including non-compliance with regulatory standards or insider trading, could lead to regulatory sanctions and reputational damage[323](index=323&type=chunk) - Governments outside the United States may impose strict price controls on prescription pharmaceuticals, adversely affecting potential revenues[324](index=324&type=chunk) - The company is subject to stringent and evolving U.S. and foreign data security and privacy laws (e.g., GDPR, CCPA, PIPL), with non-compliance potentially leading to government enforcement actions, litigation, fines, and business disruptions[325](index=325&type=chunk)[327](index=327&type=chunk)[328](index=328&type=chunk)[329](index=329&type=chunk)[330](index=330&type=chunk)[331](index=331&type=chunk)[332](index=332&type=chunk)[335](index=335&type=chunk)[336](index=336&type=chunk)[337](index=337&type=chunk)[338](index=338&type=chunk)[339](index=339&type=chunk)[342](index=342&type=chunk) - Tax risks are associated with cross-border arrangements and activities between the company and its subsidiaries, with potential challenges to transfer pricing and increased tax liabilities[343](index=343&type=chunk)[344](index=344&type=chunk)[345](index=345&type=chunk)[346](index=346&type=chunk) - Changes in tax laws or regulations, such as the One Big Beautiful Bill Act, could adversely affect the business, cash flow, financial condition, or results of operations[348](index=348&type=chunk) [Risks Related to Doing Business in China and Our International Operations](index=132&type=section&id=Risks%20Related%20to%20Doing%20Business%20in%20China%20and%20Our%20International%20Operations) This section outlines the specific political, economic, regulatory, and legal risks associated with the company's operations and business relationships in China and other international markets - Changes in political and economic policies or relations between China and the United States may affect the company's business, financial condition, results of operations, and the market price of its ADSs[349](index=349&type=chunk)[351](index=351&type=chunk) - Compliance with China's Data Security Law, Cyber Security Law, Cybersecurity Review Measures, and Personal Information Protection Law (PIPL) may entail significant expenses and affect business operations, with uncertainties in interpretation and implementation[352](index=352&type=chunk)[353](index=353&type=chunk)[354](index=354&type=chunk)[355](index=355&type=chunk)[356](index=356&type=chunk)[357](index=357&type=chunk)[358](index=358&type=chunk)[359](index=359&type=chunk) - Approval, filing, or other procedures with the CSRC or other Chinese regulatory authorities may be required for issuing securities to foreign investors, and the ability to obtain such approvals or complete procedures is uncertain[360](index=360&type=chunk)[362](index=362&type=chunk)[363](index=363&type=chunk) - Pharmaceutical companies operating in China are subject to extensive regulations and permit requirements, and the ability to obtain and maintain these approvals is uncertain, with future government regulation potentially placing additional burdens[364](index=364&type=chunk)[366](index=366&type=chunk) - As a company with operations and business relationships outside the United States, the business is subject to economic, political, regulatory, and other risks associated with international operations[367](index=367&type=chunk)[369](index=369&type=chunk) - Failure to comply with Chinese environmental, health, and safety laws and regulations could lead to fines, penalties, or costs that materially adversely affect the business[370](index=370&type=chunk)[371](index=371&type=chunk) - Developments in the Chinese legal system, which is a civil law system with evolving laws and regulations, could materially and adversely affect the company[372](index=372&type=chunk) - Exposure to the U.S. Foreign Corrupt Practices Act (FCPA), U.S. domestic bribery laws, and similar anti-corruption and anti-bribery laws in China and other countries, as well as export controls and trade sanctions, could limit competitiveness and harm reputation[373](index=373&type=chunk)[375](index=375&type=chunk)[376](index=376&type=chunk) - Chinese regulatory requirements on currency exchange may limit the ability to receive and effectively use financing in foreign currencies for Chinese subsidiaries[377](index=377&type=chunk)[378](index=378&type=chunk) - Chinese regulations relating to the establishment of offshore special purpose companies by residents in China may subject beneficial owners or subsidiaries to liability or penalties, and limit capital injection or profit distribution[379](index=379&type=chunk)[380](index=380&type=chunk)[381](index=381&type=chunk) - Classification as a China resident enterprise for China income tax purposes could result in unfavorable tax consequences, including a **25% EIT** on global income and withholding taxes on dividends and gains for non-Chinese shareholders[382](index=382&type=chunk)[384](index=384&type=chunk)[385](index=385&type=chunk) - Uncertainties exist in China regarding indirect transfers of equity interests in China resident enterprises, potentially subjecting such transfers to income tax[386](index=386&type=chunk)[388](index=388&type=chunk) - Failure to comply with Chinese regulations regarding registration requirements for employee equity incentive plans may lead to fines and sanctions[389](index=389&type=chunk) [Risks Related to Our Intellectual Property](index=151&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) This section addresses the critical risks associated with obtaining, maintaining, and enforcing intellectual property rights, including patents, trade secrets, and trademarks - Inability to obtain and maintain sufficient or broad intellectual property protection for platform technologies and product candidates could allow competitors to develop similar products, adversely affecting commercialization[390](index=390&type=chunk)[392](index=392&type=chunk)[393](index=393&type=chunk)[394](index=394&type=chunk)[395](index=395&type=chunk) - Patent rights relating to pending applications may not issue, or issued patents may be challenged, invalidated, or rendered unenforceable, leading to loss of exclusivity or narrowed protection[396](index=396&type=chunk)[398](index=398&type=chunk)[399](index=399&type=chunk)[401](index=401&type=chunk) - Reliance on trade secrets and proprietary know-how is vulnerable to disclosure or misappropriation, which can be difficult to trace and enforce, harming the business and competitive position[402](index=402&type=chunk)[403](index=403&type=chunk) - Reliance on in-licenses from third parties means losing these rights or disputes with licensors could materially adversely affect the business and ability to develop/commercialize products[404](index=404&type=chunk)[405](index=405&type=chunk)[406](index=406&type=chunk)[407](index=407&type=chunk)[409](index=409&type=chunk)[410](index=410&type=chunk)[411](index=411&type=chunk) - Intellectual property licensed from third parties may be subject to retained rights by licensors or government agencies (e.g., Bayh-Dole Act), potentially limiting the company's ability to exploit or enforce patents[412](index=412&type=chunk)[414](index=414&type=chunk) - Obtaining and maintaining patent protection requires compliance with various procedural, document submission, and fee payment requirements; non-compliance could lead to loss of patent rights[415](index=415&type=chunk)[416](index=416&type=chunk) - Patent terms may be inadequate to protect competitive position for a sufficient amount of time, especially given the lengthy development and regulatory review process[417](index=417&type=chunk)[419](index=419&type=chunk)[420](index=420&type=chunk) - Intellectual property rights have limitations and may not adequately protect the business from various threats, such as competitors developing similar compounds not covered by claims or independent development[421](index=421&type=chunk)[424](index=424&type=chunk) - Third parties may initiate legal proceedings alleging infringement, misappropriation, or other violations of their intellectual property rights, leading to uncertain outcomes, substantial litigation expenses, and potential limitations on commercialization[422](index=422&type=chunk)[425](index=425&type=chunk)[426](index=426&type=chunk)[427](index=427&type=chunk)[428](index=428&type=chunk)[429](index=429&type=chunk) - Lawsuits to protect or enforce patents or other intellectual property could be expensive, time-consuming, and unsuccessful, potentially resulting in loss of patent protection or an inability to stop infringers[430](index=430&type=chunk)[431](index=431&type=chunk)[432](index=432&type=chunk)[434](index=434&type=chunk)[435](index=435&type=chunk)[436](index=436&type=chunk) - Changes in U.S. patent law (e.g., Leahy-Smith Act) or foreign patent law could diminish the value of patents, increasing uncertainties and costs for protecting inventions[437](index=437&type=chunk)[438](index=438&type=chunk)[439](index=439&type=chunk)[440](index=440&type=chunk)[441](index=441&type=chunk) - Inability to protect intellectual property rights throughout the world, particularly in countries with weaker enforcement, could negatively impact the business and competitive advantage[442](index=442&type=chunk)[443](index=443&type=chunk)[444](index=444&type=chunk) - Claims that employees, consultants, or advisors have wrongfully used or disclosed trade secrets of former employers, or claims asserting inventorship or ownership of the company's intellectual property, could lead to litigation and loss of valuable rights[445](index=445&type=chunk)[446](index=446&type=chunk)[447](index=447&type=chunk)[448](index=448&type=chunk) - Failure to identify relevant third-party patents or incorrect interpretation of their relevance, scope, or expiration could adversely affect the ability to develop and market products[449](index=449&type=chunk)[450](index=450&type=chunk) - Inadequate protection of trademarks and trade names could prevent building name recognition and adversely affect the business[451](index=451&type=chunk)[452](index=452&type=chunk) [Risks Related to Our ADSs](index=179&type=section&id=Risks%20Related%20to%20Our%20ADSs) This section addresses risks specific to the company's American Depositary Shares (ADSs), including market volatility, delisting potential, and shareholder rights - The trading price of the company's ADSs is likely to be highly volatile and subject to wide fluctuations due to various factors, including clinical study results, regulatory decisions, competition, and general market conditions, potentially leading to a loss of investment[453](index=453&type=chunk)[455](index=455&type=chunk) - There is a risk of delisting under the Holding Foreign Companies Accountable Act (HFCA Act) or Accelerating Holding Foreign Companies Accountable Act (AHFCA Act) if the SEC identifies that the company's audit work is performed by an auditor not subject to PCAOB inspection, although currently, the company's auditor is PCAOB-inspected[456](index=456&type=chunk)[457](index=457&type=chunk)[458](index=458&type=chunk)[460](index=460&type=chunk)[461](index=461&type=chunk)[462](index=462&type=chunk) - The company previously identified and remediated material weaknesses in internal control over financial reporting as of June 30, 2024. Future material weaknesses could lead to material misstatements in financial statements or failure to meet reporting obligations[463](index=463&type=chunk)[464](index=464&type=chunk)[465](index=465&type=chunk)[466](index=466&type=chunk) - Principal shareholders and management own approximately **45%** of the voting power, allowing them to exert significant control over matters requiring shareholder approval, potentially conflicting with other shareholders' interests[467](index=467&type=chunk) - Substantial future sales of ADSs by existing shareholders or through equity offerings could cause the market price to drop significantly[468](index=468&type=chunk)[469](index=469&type=chunk) - Holders of ADSs have fewer rights than ordinary shareholders and must act through the depositary to exercise voting rights, potentially limiting their ability to vote or receive distributions[470](index=470&type=chunk)[471](index=471&type=chunk)[473](index=473&type=chunk) - ADS holders may not be entitled to a jury trial for claims arising under the deposit agreement, which could result in less favorable outcomes for plaintiffs[472](index=472&type=chunk) - The right to participate in future rights offerings may be limited, potentially causing dilution to holdings[474](index=474&type=chunk) - The company does not anticipate paying cash dividends in the foreseeable future, making capital appreciation the sole source of gains for investors[475](index=475&type=chunk) - The company is subject to tax in both the Cayman Islands and the United States, potentially leading to a material adverse effect on financial condition and results of operations[476](index=476&type=chunk)[477](index=477&type=chunk)[478](index=478&type=chunk) - The ability to use net operating loss carryforwards and certain other tax attributes may be limited by ownership changes (Sections 382 and 383 of the Code) or state tax laws, potentially increasing future tax liability[479](index=479&type=chunk)[480](index=480&type=chunk) [General Risk Factors](index=195&type=section&id=General%20Risk%20Factors) This section covers broad risks impacting the company's overall operations, including financial infrastructure, internal controls, legal proceedings, and external disasters - Failure to build adequate finance infrastructure and improve accounting systems and controls could impair compliance with financial reporting and internal controls requirements for publicly-traded companies, leading to significant costs and potential misstatements[492](index=492&type=chunk)[495](index=495&type=chunk)[496](index=496&type=chunk)[497](index=497&type=chunk)[499](index=499&type=chunk) - Disclosure controls and procedures, or internal controls, may not prevent or detect all errors or acts of fraud due to inherent limitations[500](index=500&type=chunk)[501](index=501&type=chunk) - Future changes in financial accounting standards or practices may cause adverse and unexpected revenue fluctuations and affect reported results of operations[502](index=502&type=chunk) - Lack of or unfavorable equity research analyst coverage could negatively impact the price and trading volume of the company's ADSs[503](index=503&type=chunk) - The company could be subject to securities class action litigation or material legal proceedings, which could have a negative impact on its reputation or business[504](index=504&type=chunk)[506](index=506&type=chunk) - The company or third parties it depends on may be adversely affected by earthquakes, fires, or other natural disasters, and business continuity plans may not adequately protect against serious disasters[507](index=507&type=chunk) - Failure to comply with environmental, health, and safety laws and regulations could lead to fines, penalties, or costs that materially adversely affect the business[508](index=508&type=chunk)[510](index=510&type=chunk) - Failure to meet Nasdaq's continued listing requirements could result in a delisting of the company's ADSs, negatively affecting their price and liquidity[511](index=511&type=chunk)[512](index=512&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=203&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales of equity securities during the three months ended June 30, 2025 - No unregistered sales of equity securities occurred during the three months ended June 30, 2025[513](index=513&type=chunk) [Item 3. Defaults Upon Senior Securities](index=203&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reported no defaults upon senior securities during the period - No defaults upon senior securities were reported[514](index=514&type=chunk) [Item 4. Mine Safety Disclosures](index=203&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) The company reported no mine safety disclosures - No mine safety disclosures were reported[515](index=515&type=chunk) [Item 5. Other Information](index=203&type=section&id=Item%205.%20Other%20Information) The company reported no other information - No other information was reported[515](index=515&type=chunk) [Item 6. Exhibits](index=204&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including organizational documents, specimen certificates, the deposit agreement, certifications of principal officers, and XBRL interactive data files - The exhibits include the Amended and Restated Memorandum and Articles of Association, Registrant's Specimen Certificate for Ordinary Shares, Form of Deposit Agreement, and certifications of the Principal Executive Officer and Principal Financial Officer[517](index=517&type=chunk) [Signatures](index=205&type=section&id=Signatures) The report was duly signed on August 6, 2025, by Raymond Stevens, Ph.D., Chief Executive Officer, and Jun Yoon, Chief Financial Officer, on behalf of Structure Therapeutics Inc - The report was signed by Raymond Stevens, Ph.D., Chief Executive Officer, and Jun Yoon, Chief Financial Officer, on August 6, 2025[520](index=520&type=chunk)

Executive Summary & Business Update [Q2 2025 Overview and Key Highlights](index=1&type=section&id=1.1%20Q2%202025%20Overview%20and%20Key%20Highlights) Structure Therapeutics reported strong Q2 2025 results, advancing aleniglipron and ACCG-2671, backed by $786.5 million cash for operations through 2027 - Topline data from oral small molecule GLP-1 receptor agonist aleniglipron ACCESS and ACCESS II studies are on track for **year-end 2025** readouts[1](index=1&type=chunk)[2](index=2&type=chunk) - Aleniglipron clinical development program expanded to optimize competitive positioning and Phase 3 program design[1](index=1&type=chunk)[2](index=2&type=chunk) - Oral small molecule amylin receptor agonist (ACCG-2671) Phase 1 initiation anticipated by **year-end 2025**[1](index=1&type=chunk)[2](index=2&type=chunk) Cash Position as of June 30, 2025 | Metric | Amount (Millions) | | :------------------------------------ | :---------------- | | Cash, cash equivalents and short-term investments | $786.5 | - The strong financial position is expected to fund projected operations and key clinical milestones through at least **2027**[1](index=1&type=chunk)[13](index=13&type=chunk) Recent and Upcoming Milestones [Aleniglipron (GSBR-1290) Development](index=2&type=section&id=2.1%20Aleniglipron%20(GSBR-1290)%20Development) Structure Therapeutics updated on aleniglipron, with ACCESS/ACCESS II data due year-end 2025 and new studies initiated for competitive positioning [Ongoing ACCESS and ACCESS II Studies](index=2&type=section&id=2.1.1%20Ongoing%20ACCESS%20and%20ACCESS%20II%20Studies) - The fully enrolled ACCESS and ACCESS II studies are on track for topline **36-week** data readouts by **year-end 2025**[3](index=3&type=chunk) - ACCESS study enrolled approximately **220 adults**, evaluating doses up to **120 mg** with a slower four-week titration schedule[6](index=6&type=chunk) - ACCESS II study enrolled approximately **80 adults**, evaluating higher doses (**180 mg** and **240 mg**) with a slower four-week titration schedule[6](index=6&type=chunk) [Expanded Data Collection from ACCESS and ACCESS II Studies](index=2&type=section&id=2.1.2%20Expanded%20Data%20Collection%20from%20ACCESS%20and%20ACCESS%20II%20Studies) - ACCESS Open Label Extension (OLE) allows patients to roll over for longer-term weight loss effects and expanded safety data[4](index=4&type=chunk) - ACCESS II Extension continues patients on assigned doses to **44 weeks**, providing an additional **eight weeks** of double-blinded safety, tolerability, and efficacy data, particularly for higher dose arms (**180 mg** and **240 mg**)[4](index=4&type=chunk) [Additional Aleniglipron Studies](index=2&type=section&id=2.1.3%20Additional%20Aleniglipron%20Studies) - Three new aleniglipron clinical studies are being conducted to generate additional data for competitive positioning and Phase 3 program design[5](index=5&type=chunk) - A Phase 2 study to assess a maintenance switching strategy from an approved injectable GLP-1 receptor agonist to oral aleniglipron is expected to start in **Q3 2025**[7](index=7&type=chunk) - A Phase 2 body composition study to assess the effect of aleniglipron on body fat loss over **40 weeks** is expected to start in **Q3 2025**[7](index=7&type=chunk) - A Phase 2 study in patients with type 2 diabetes mellitus (T2DM) is anticipated to start in **Q4 2025**, with data potentially supporting a T2DM cohort in the Phase 3 obesity program[8](index=8&type=chunk) [Other Pipeline Programs](index=3&type=section&id=2.2%20Other%20Pipeline%20Programs) Structure Therapeutics updated its diverse pipeline, advancing ACCG-2671 to Phase 1 and completing other early-stage studies [Oral Small Molecule Amylin Receptor Agonists (ACCG-2671)](index=3&type=section&id=2.2.1%20Oral%20Small%20Molecule%20Amylin%20Receptor%20Agonists%20(ACCG-2671)) - IND-enabling activities for ACCG-2671 are ongoing, with a first-in-human Phase 1 clinical study planned by **year-end 2025**[12](index=12&type=chunk) - New preclinical data for ACCG-2671 demonstrated high binding affinity, balanced potency, and significant, dose-dependent body weight reductions in diet-induced obese rats[12](index=12&type=chunk) - Combination therapy of ACCG-2671 with semaglutide resulted in superior weight loss compared to monotherapy of either compound[12](index=12&type=chunk) [Oral Small Molecule Metabolic Pipeline and Potential Combinations](index=3&type=section&id=2.2.2%20Oral%20Small%20Molecule%20Metabolic%20Pipeline%20and%20Potential%20Combinations) - Structure Therapeutics is developing GIPR selective agonists and antagonists, and GLP-1R/GIPR combinations to treat obesity and related diseases[12](index=12&type=chunk) - The company is also developing GCGR selective agonists and GLP-1R/GCGR combinations for obesity and related diseases[12](index=12&type=chunk) - ANPA-0073, a Phase 2 ready biased APJR agonist for selective or muscle-sparing weight loss, completed a Phase 1 study with good tolerability. Long-term toxicology studies are underway, expected by **year-end 2025**[12](index=12&type=chunk) [Oral Small Molecule LPA1R Program (LTSE-2578)](index=3&type=section&id=2.2.3%20Oral%20Small%20Molecule%20LPA1R%20Program%20(LTSE-2578)) - Structure Therapeutics successfully finished a Phase 1 single and multiple ascending dose clinical study of LTSE-2578, an oral small molecule antagonist for Idiopathic Pulmonary Fibrosis (IPF)[11](index=11&type=chunk) - The study showed no evidence of dose-dependent LTSE-2578-related adverse events, including clinical, laboratory, and electrocardiogram recordings, and no SAEs were observed[11](index=11&type=chunk) Financial Performance [Q2 2025 Financial Highlights](index=4&type=section&id=3.1%20Q2%202025%20Financial%20Highlights) Structure Therapeutics reported a strong $786.5 million cash position, but increased expenses led to a higher Q2 2025 net loss Cash Position | Metric | June 30, 2025 | | :------------------------------------ | :------------ | | Cash, cash equivalents and short-term investments | $786.5 million | - Current cash, cash equivalents and short-term investments are expected to fund projected operations and key clinical milestones through at least **2027**[13](index=13&type=chunk) Research and Development (R&D) Expenses (YoY Change) | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (YoY) | | :------------------- | :----------------- | :----------------- | :----------- | | R&D Expenses | $54.7 | $22.1 | +$32.6 million | - The increase in R&D expenses was primarily due to increases related to pre-clinical research and development, clinical trial costs, and personnel-related expenses to support the GLP-1R franchise[14](index=14&type=chunk) General and Administrative (G&A) Expenses (YoY Change) | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (YoY) | | :------------------- | :----------------- | :----------------- | :----------- | | G&A Expenses | $15.7 | $11.3 | +$4.4 million | - The increase in G&A expenses was primarily due to increases in employee expenses as infrastructure expanded to support growth as a publicly-traded company[15](index=15&type=chunk) Net Loss (YoY Change) | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (YoY) | | :------- | :----------------- | :----------------- | :----------- | | Net Loss | $61.7 | $26.0 | +$35.7 million | - Non-cash share-based compensation expense increased to **$7.5 million** in Q2 2025 from **$4.2 million** in Q2 2024[16](index=16&type=chunk) [Condensed Consolidated Statements of Operations](index=6&type=section&id=3.2%20Condensed%20Consolidated%20Statements%20of%20Operations) The condensed consolidated statements of operations show a significant increase in operating expenses, particularly in research and development, leading to a higher net loss for both the three and six months ended June 30, 2025, compared to the prior year periods Condensed Consolidated Statements of Operations (Unaudited, In thousands) | | THREE MONTHS ENDED | | | | SIX MONTHS ENDED | | | | | :-------------------------- | :--- | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | | JUNE 30, | | | JUNE 30, | | | | | | 2025 | | 2024 | 2025 | | 2024 | | Operating expenses: | | | | | | | | | | Research and development | $ 54,710 | | $ 22,050 | $ 97,577 | | $ 42,729 | | General and administrative | 15,741 | | 11,266 | 29,185 | | 22,602 | | Total operating expenses | 70,451 | | 33,316 | 126,762 | | 65,331 | | Loss from operations | (70,451) | | (33,316) | (126,762) | | (65,331) | | Interest and other income, net | 8,929 | | 7,335 | 18,505 | | 13,343 | | Loss before provision for income taxes | (61,522) | | (25,981) | (108,257) | | (51,988) | | Provision for income taxes | 139 | | 53 | 237 | | 82 | | Net loss | $ (61,661) | | $ (26,034) | $ (108,494) | | $ (52,070) | [Condensed Consolidated Balance Sheet Data](index=6&type=section&id=3.3%20Condensed%20Consolidated%20Balance%20Sheet%20Data) Total assets decreased from $903.3 million to $816.4 million due to reduced cash, with liabilities increasing and equity decreasing Condensed Consolidated Balance Sheet Data (Unaudited, In thousands) | | JUNE 30, | | DECEMBER 31, | | :---------------------------------- | :--- | :--- | :--- | :--- | | | 2025 | | 2024 | | Assets | | | | | | Current assets: | | | | | | Cash, cash equivalents and short-term investments | $ 786,496 | | $ 883,518 | | Prepaid expenses and other current assets | 12,802 | | 7,693 | | Total current assets | 799,298 | | 891,211 | | Property and equipment, net | 3,459 | | 3,478 | | Operating right-of-use assets | 7,484 | | 3,535 | | Other non-current assets | 6,202 | | 5,106 | | Total assets | $ 816,443 | | $ 903,330 | | Liabilities and shareholders' equity | | | | | | Current liabilities: | | | | | | Accounts payable | $ 8,990 | | $ 8,024 | | Accrued expenses and other current liabilities | 27,379 | | 26,299 | | Operating lease liabilities, current portion | 2,664 | | 1,698 | | Total current liabilities | 39,033 | | 36,021 | | Operating lease liabilities, net of current portion | 5,012 | | 2,164 | | Other non-current liabilities | 317 | | 302 | | Total liabilities | 44,362 | | 38,487 | | Total shareholders' equity | 772,081 | | 864,843 | | Total liabilities and shareholders' equity | $ 816,443 | | $ 903,330 | About Structure Therapeutics [Company Overview](index=4&type=section&id=4.1%20Company%20Overview) Structure Therapeutics is a clinical-stage biopharmaceutical company developing oral small molecule treatments for chronic metabolic and cardiopulmonary conditions - Structure Therapeutics is a science-driven clinical-stage biopharmaceutical company[17](index=17&type=chunk) - Focuses on discovering and developing innovative oral small molecule treatments for chronic metabolic and cardiopulmonary conditions with significant unmet medical needs[17](index=17&type=chunk) - Utilizes a next-generation structure-based drug discovery platform to establish a robust GPCR-targeted pipeline[17](index=17&type=chunk) - Aims to surpass scalability limitations of traditional biologic and peptide therapies and make treatments accessible to more patients globally[17](index=17&type=chunk) Forward-Looking Statements [Disclaimer and Risk Factors](index=5&type=section&id=5.1%20Disclaimer%20and%20Risk%20Factors) This section cautions that forward-looking statements are subject to risks and uncertainties, with no obligation to update - The press release contains "forward-looking statements" as defined by the Private Securities Litigation Reform Act of 1995[18](index=18&type=chunk) - Statements concern future plans, prospects, expected timing of data readouts, study initiations, cash runway, and potential benefits/efficacy of therapeutic candidates[18](index=18&type=chunk) - Readers are cautioned that actual results, levels of activity, safety, performance, or events could differ materially due to various risks and uncertainties, including those described in SEC filings[18](index=18&type=chunk) - The Company undertakes no obligation to update such statements to reflect events or circumstances that exist after the date on which they were made, except as required by law[18](index=18&type=chunk) Contact Information [Investor and Media Relations](index=6&type=section&id=6.1%20Investor%20and%20Media%20Relations) This section provides contact details for investor and media inquiries related to Structure Therapeutics - Investors can contact Danielle Keatley at ir@structuretx.com[23](index=23&type=chunk) - Media inquiries can be directed to Dan Budwick of 1AB at Dan@1abmedia.com[23](index=23&type=chunk)