Summit Therapeutics (SMMT) - 2025 Q3 - Quarterly Results

Executive Summary & Key Announcements Planned BLA Submission for Ivonescimab Summit plans a Q4 2025 BLA submission for ivonescimab plus chemotherapy in EGFR-mutant NSCLC, based on HARMONi trial results, despite lacking statistically significant overall survival benefit - Summit plans to submit a BLA for ivonescimab plus chemotherapy in Q4 2025, based on HARMONi clinical trial results[1][2] - The company believes the safety and efficacy data from HARMONi demonstrates patient benefit in EGFR-mutant NSCLC, despite lacking statistically significant overall survival (OS) benefit, after considering FDA-approved options and discussions with key opinion leaders[2] Expansion of Phase III Ivonescimab Clinical Development Program Summit expands ivonescimab clinical development with HARMONi-GI3, a new global Phase III study for first-line unresectable metastatic CRC, and will announce more Phase III studies in Q1 2026 - Summit announces the initiation of HARMONi-GI3, a new global Phase III study in first-line unresectable metastatic colorectal cancer (CRC)[1][3] - The company intends to expand its ivonescimab clinical development program with an additional set of Phase III clinical studies, with details to be provided in Q1 2026[1][3] Operational & Clinical Development Updates Ivonescimab Program Overview Ivonescimab (SMT112) is an investigational bispecific antibody combining PD-1 blockade with anti-angiogenesis (VEGF blockade), having treated over 3,000 patients globally and 40,000 commercially in China, with Summit holding Western development and commercialization rights - Ivonescimab (SMT112) is an investigational, potentially first-in-class bispecific antibody combining PD-1 blockade with anti-angiogenesis effects (VEGF blockade)[4] - Over 3,000 patients have been treated with ivonescimab in global clinical studies, and over 40,000 in a commercial setting in China[4] - Summit holds rights to develop and commercialize ivonescimab in the United States, Canada, Europe, Japan, Latin America, the Middle East, and Africa, while Akeso retains rights for the rest of the world, including China[4] - Summit is developing ivonescimab in NSCLC (HARMONi, HARMONi-3, HARMONi-7) and plans to develop it in CRC (HARMONi-GI3)[4] HARMONi Global Phase III Study Results The HARMONi study in EGFR-mutated NSCLC patients demonstrated statistically significant PFS improvement with ivonescimab plus chemotherapy (HR 0.52, median PFS 6.8 months), observed a positive OS trend (HR 0.79), and maintained an acceptable safety profile HARMONi Study: Progression-Free Survival (PFS) | Metric | Ivonescimab + Chemo | Chemo Alone | | :------------------------------------ | :-------------------- | :---------- | | Median PFS (Primary Analysis) | 6.8 months | 4.4 months | | Hazard Ratio (HR) | 0.52 (95% CI: 0.41-0.66; p<0.00001) | | | HR (Longer-term Follow-up, Western Patients) | 0.57 (95% CI: 0.46-0.71) | | HARMONi Study: Overall Survival (OS) | Metric | Ivonescimab + Chemo | Placebo + Chemo | | :------------------------------------ | :-------------------- | :-------------- | | Median OS (Primary Analysis) | 16.8 months | 14.0 months | | Hazard Ratio (HR) | 0.79 (95% CI: 0.62-1.01; p=0.057) | | | HR (Longer-term Follow-up, Western Patients) | 0.78 (95% CI: 0.62-0.98; nominal p=0.0332) | | HARMONi Study: Overall Response Rate (ORR) & Duration of Response (DoR) | Metric | Ivonescimab + Chemo | Placebo + Chemo | | :------------------------------------ | :-------------------- | :-------------- | | ORR (%) | 45% | 34% | | Median DoR (months) | 7.6 months | 4.2 months | - The safety profile of ivonescimab in combination with chemotherapy was acceptable and manageable, with comparable rates of discontinuation and death between both arms[5] - Grade 3 or higher hemorrhage (bleeding) events were observed in 0.9% of patients in the ivonescimab plus chemotherapy arm[5] HARMONi-GI3 Global Phase III Study Initiation Summit expands into colorectal cancer with the global Phase III HARMONi-GI3 trial, evaluating ivonescimab plus chemotherapy versus bevacizumab plus chemotherapy as first-line therapy for unresectable metastatic CRC, targeting 600 patients with PFS as the primary endpoint - Summit announced the expansion of its Phase III clinical development program into colorectal cancer (CRC) with the planned initiation of the global Phase III HARMONi-GI3 trial[3][5] - The trial will evaluate ivonescimab plus chemotherapy compared to bevacizumab plus chemotherapy as first-line therapy in patients with unresectable metastatic CRC[5] - The study intends to enroll 600 patients, with progression-free survival (PFS) as the primary endpoint[6] - Clinical trial sites for HARMONi-GI3 are planned to begin activating in the United States prior to the end of the year[5] HARMONi-6 Phase III Study Results The Akeso-sponsored HARMONi-6 study in China met its primary endpoint of PFS, demonstrating statistically significant improvement with ivonescimab plus chemotherapy (HR 0.60) over tislelizumab plus chemotherapy in squamous NSCLC, with an acceptable safety profile HARMONi-6 Study: Progression-Free Survival (PFS) | Metric | Ivonescimab + Chemo vs. Tislelizumab + Chemo | | :------------------------------------ | :--------------------------------------------- | | Hazard Ratio (HR) | 0.60 (95% CI: 0.46, 0.78; p<0.0001) | - Both the overall response rate (ORR) and duration of response (DoR) were higher in patients treated with ivonescimab plus chemotherapy[6] - Ivonescimab demonstrated an acceptable and manageable safety profile, consistent with previous Phase III studies[6] - This marks the first known Phase III trial in NSCLC to show significant improvement over PD-(L)1 inhibitor therapy combined with chemotherapy in a head-to-head setting[7] - Grade 3 or higher hemorrhage events were observed in five patients in the ivonescimab plus chemotherapy arm compared to two patients in the tislelizumab plus chemotherapy arm[7] HARMONi-3 Phase III Study Update Summit amended the HARMONi-3 study protocol to separate primary endpoint analyses (PFS and OS) by histology, with squamous cohort enrollment completing in H1 2026 and non-squamous in H2 2026, targeting 600 and 1,000 patients respectively - The protocol for the HARMONi-3 study has been amended to separate the statistical analysis of primary endpoints (PFS and OS) by histology (squamous and non-squamous NSCLC)[7] - Enrollment in the squamous cohort is expected to complete in the first half of 2026, with PFS data readout expected in the second half of 2026[7] - Enrollment in the non-squamous cohort is expected to complete in the second half of 2026, with PFS data readout expected in the first half of 2027[7] - Summit plans to enroll 600 patients with squamous NSCLC and 1,000 patients with non-squamous NSCLC to sufficiently power each of the dual primary endpoints in both cohorts[7] Other Clinical Collaborations and Akeso's Trials Summit continues clinical collaborations with leading organizations, including a new partnership with Revolution Medicines to evaluate ivonescimab with RAS(ON) inhibitors, while Akeso conducts several single-region Phase III studies in China for various indications - Clinical trial collaborations with leading organizations (e.g., MD Anderson, Memorial Sloan Kettering) continue to progress, evaluating ivonescimab in solid tumor settings outside of metastatic NSCLC[11] - In June 2025, Summit announced a clinical collaboration with Revolution Medicines to evaluate ivonescimab in combination with three RAS(ON) inhibitors in solid tumor settings with RAS mutations, with trials expected to begin in early 2026[11] - Akeso, Summit's partner, is enrolling several single-region Phase III studies exclusively in China for multiple indications, including biliary-tract cancer, triple-negative breast cancer, head and neck squamous cell carcinoma, colorectal cancer, and pancreatic cancer[11] Financial Highlights (Q3 2025) Cash and Cash Equivalents and Short-term Investments Aggregate cash and cash equivalents and short-term investments decreased from $412.3 million at December 31, 2024, to $238.6 million at September 30, 2025 Cash and Cash Equivalents and Short-term Investments | Metric | September 30, 2025 (Millions) | December 31, 2024 (Millions) | | :------------------------------------ | :------------------- | :------------------ | | Cash & Cash Equivalents & Short-term Investments | $238.6 million | $412.3 million | Operating Expenses (GAAP and Non-GAAP) GAAP operating expenses increased significantly to $234.2 million in Q3 2025 from $58.4 million in Q3 2024, mainly due to a $111.4 million increase in stock-based compensation, while Non-GAAP operating expenses also rose to $103.4 million from $39.0 million due to clinical study expansion Operating Expenses (Q3 2025 vs Q3 2024) | Metric | Q3 2025 (Millions) | Q3 2024 (Millions) | Change (YoY) (Millions) | | :---------------------- | :----------------- | :----------------- | :----------- | | GAAP Operating Expenses | $234.2 | $58.4 | +$175.8 | | Non-GAAP Operating Expenses | $103.4 | $39.0 | +$64.4 | - The increase in GAAP operating expenses was primarily due to a $111.4 million increase in stock-based compensation expense related to modification of performance-based stock option awards[12] - The increase in Non-GAAP operating expenses was due to the expansion of clinical studies and development costs related to ivonescimab[12] Research and Development (R&D) Expenses (GAAP and Non-GAAP) GAAP R&D expenses increased to $131.1 million in Q3 2025 from $37.7 million in Q3 2024, largely due to a $34.8 million increase in stock-based compensation, while Non-GAAP R&D expenses also increased to $90.5 million from $31.9 million, primarily due to ivonescimab clinical study expansion R&D Expenses (Q3 2025 vs Q3 2024) | Metric | Q3 2025 (Millions) | Q3 2024 (Millions) | Change (YoY) (Millions) | | :-------------------- | :----------------- | :----------------- | :----------- | | GAAP R&D Expenses | $131.1 | $37.7 | +$93.4 | | Non-GAAP R&D Expenses | $90.5 | $31.9 | +$58.6 | - The increase in GAAP R&D expenses was due to a $34.8 million increase in stock-based compensation expense[12] - The increase in Non-GAAP R&D expenses is primarily related to the expansion of clinical studies and development costs for ivonescimab[12] General and Administrative (G&A) Expenses (GAAP and Non-GAAP) GAAP G&A expenses rose to $103.1 million in Q3 2025 from $20.7 million in Q3 2024, mainly due to a $76.6 million increase in stock-based compensation, while Non-GAAP G&A expenses increased to $12.9 million from $7.1 million, attributed to building infrastructure for ivonescimab development G&A Expenses (Q3 2025 vs Q3 2024) | Metric | Q3 2025 (Millions) | Q3 2024 (Millions) | Change (YoY) (Millions) | | :-------------------- | :----------------- | :----------------- | :----------- | | GAAP G&A Expenses | $103.1 | $20.7 | +$82.4 | | Non-GAAP G&A Expenses | $12.9 | $7.1 | +$5.8 | - The increase in GAAP G&A expenses was due to a $76.6 million increase in stock-based compensation expense[15] - The increase in Non-GAAP G&A expenses is related to building infrastructure to support the development of ivonescimab[15] Net Loss (GAAP and Non-GAAP) GAAP net loss significantly widened to $231.8 million (or $(0.31) per share) in Q3 2025 from $56.3 million (or $(0.08) per share) in Q3 2024, while Non-GAAP net loss also increased to $101.0 million (or $(0.13) per share) from $36.9 million (or $(0.05) per share) Net Loss (Q3 2025 vs Q3 2024) | Metric | Q3 2025 (Millions) | Q3 2024 (Millions) | Change (YoY) (Millions) | | :-------------------- | :----------------- | :----------------- | :----------- | | GAAP Net Loss | $(231.8) | $(56.3) | $(175.5) | | GAAP Net Loss Per Share | $(0.31) | $(0.08) | $(0.23) | | Non-GAAP Net Loss | $(101.0) | $(36.9) | $(64.1) | | Non-GAAP Net Loss Per Share | $(0.13) | $(0.05) | $(0.08) | About Ivonescimab & Summit Therapeutics About Ivonescimab Ivonescimab (SMT112/AK112) is a novel, investigational bispecific antibody combining PD-1 blockade with anti-angiogenesis (VEGF blockade), approved in China (May 2024) and granted FDA Fast Track designation for the HARMONi clinical trial setting - Ivonescimab is a novel, potential first-in-class investigational bispecific antibody combining PD-1 blockade with anti-angiogenesis effects (VEGF blockade) into a single molecule[17] - It displays unique cooperative binding to its targets with multifold higher affinity to PD-1 in the presence of VEGF, and its tetravalent structure enables higher avidity in the tumor microenvironment[17][18] - Ivonescimab was initially approved for marketing authorization in China in May 2024 and was granted Fast Track designation by the US FDA for the HARMONi clinical trial setting[27] - Over 3,000 patients have been treated with ivonescimab in clinical studies globally, and over 40,000 in a commercial setting in China[19] About Summit Therapeutics Summit Therapeutics Inc. is an oncology biopharmaceutical company founded in 2003, focused on discovering, developing, and commercializing patient-friendly medicinal therapies, with shares listed on Nasdaq (SMMT) and headquarters in Miami, Florida - Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-friendly medicinal therapies[28] - The company was founded in 2003, and its shares are listed on the Nasdaq Global Market (symbol "SMMT")[29] - Summit is headquartered in Miami, Florida, with additional offices in Menlo Park, California, and Oxford, UK[29] Financial Statements & Non-GAAP Reconciliations GAAP Condensed Consolidated Statements of Operations For Q3 2025, GAAP operating expenses were $234.2 million, leading to a net loss of $231.8 million (or $(0.31) per share), while for the nine months ended September 30, 2025, total operating expenses were $869.5 million, resulting in a net loss of $860.4 million (or $(1.16) per share) GAAP Condensed Consolidated Statements of Operations (Unaudited) | Metric (in millions, except per share data) | Three Months Ended Sep 30, 2025 | Three Months Ended Sep 30, 2024 | Nine Months Ended Sep 30, 2025 | Nine Months Ended Sep 30, 2024 | | :------------------------------------------ | :------------------------------ | :------------------------------ | :----------------------------- | :----------------------------- | | Research and development | $131.1 | $37.7 | $390.4 | $99.4 | | Acquired in-process research and development | | | | $15.0 | | General and administrative | $103.1 | $20.7 | $479.1 | $46.0 | | Total operating expenses | $234.2 | $58.4 | $869.5 | $160.4 | | Other income, net | $2.4 | $4.6 | $9.1 | $9.0 | | Interest expense | | $(2.5) | | $(8.7) | | Net loss | $(231.8) | $(56.3) | $(860.4) | $(160.1) | | Net loss per share, basic and diluted | $(0.31) | $(0.08) | $(1.16) | $(0.22) | GAAP Condensed Consolidated Balance Sheet Information As of September 30, 2025, Summit reported $238.6 million in cash, cash equivalents, and short-term investments, a decrease from $412.3 million at December 31, 2024, with total assets at $261.7 million, total liabilities at $69.5 million, and total stockholders' equity at $192.3 million GAAP Condensed Consolidated Balance Sheet Information (in millions) | Metric | Unaudited September 30, 2025 | December 31, 2024 | | :------------------------------------------ | :----------------------------- | :------------------ | | Cash and cash equivalents and short-term investments | $238.6 | $412.3 | | Total assets | $261.7 | $435.6 | | Total liabilities | $69.5 | $46.8 | | Total stockholders' equity | $192.3 | $388.7 | GAAP Condensed Consolidated Statement of Cash Flows Information For the nine months ended September 30, 2025, net cash used in operating activities was $(221.0) million, net cash provided by investing activities was $310.8 million, and by financing activities was $43.7 million, resulting in a $133.6 million increase in cash, cash equivalents, and restricted cash GAAP Condensed Consolidated Statement of Cash Flows Information (in millions) | Metric | Nine Months Ended Sep 30, 2025 | Nine Months Ended Sep 30, 2024 | | :------------------------------------------ | :----------------------------- | :----------------------------- | | Net cash used in operating activities | $(221.0) | $(93.4) | | Net cash provided by (used in) investing activities | $310.8 | $(288.8) | | Net cash provided by financing activities | $43.7 | $404.8 | | Effect of exchange rate changes on cash | $0.1 | $0.1 | | Increase in cash, cash equivalents and restricted cash | $133.6 | $22.7 | Schedule Reconciling Selected Non-GAAP Financial Measures This section provides detailed reconciliations of GAAP to Non-GAAP measures for R&D, G&A, operating expenses, and net loss, primarily by excluding stock-based compensation, with Q3 2025 adjustments totaling $40.6 million for R&D, $90.2 million for G&A, and $130.8 million for total operating expenses and net loss Reconciliation of GAAP to Non-GAAP Financial Measures (Q3 2025 vs Q3 2024, in millions) | Metric | Q3 2025 GAAP | Stock-based Comp. | Q3 2025 Non-GAAP | Q3 2024 GAAP | Stock-based Comp. | Q3 2024 Non-GAAP | | :------------------------------------ | :------------- | :---------------- | :--------------- | :------------- | :---------------- | :--------------- | | Research and Development | $131.1 | $(40.6) | $90.5 | $37.7 | $(5.8) | $31.9 | | General and Administrative | $103.1 | $(90.2) | $12.9 | $20.7 | $(13.6) | $7.1 | | Operating Expenses | $234.2 | $(130.8) | $103.4 | $58.4 | $(19.4) | $39.0 | | Net Loss | $(231.8) | $130.8 | $(101.0) | $(56.3) | $19.4 | $(36.9) | | Net Loss Per Basic and Diluted Common Share | $(0.31) | $0.18 | $(0.13) | $(0.08) | $0.03 | $(0.05) | Notes on Non-GAAP Financial Information Non-GAAP financial measures, which exclude non-cash charges and stock-based compensation, are used by management for internal budgeting and forecasting, and are considered useful for investors in comparing prior periods and analyzing business trends, with acquired in-process R&D expenses no longer excluded from Q4 2024 - Non-GAAP financial measures adjust GAAP financial measures by excluding non-cash charges and costs associated with stock-based compensation[42][43] - Summit management uses these Non-GAAP measures for internal budgeting and forecasting purposes and to evaluate financial performance, believing they are useful for investors in comparing prior periods and analyzing ongoing business trends[42] - Beginning in the fourth quarter of 2024, the Company's Non-GAAP financial measures will no longer exclude acquired in-process research and development expenses ("IPR&D")[45] Additional Information Forward-looking Statements The press release contains forward-looking statements regarding future expectations, clinical development, BLA submissions, financial outlook, and potential acquisitions, which are subject to various risks and may differ materially from actual results, with the company disclaiming any obligation to update them - Statements about future expectations, clinical development, BLA submissions, financial outlook, and potential acquisitions constitute forward-looking statements[31] - Actual results may differ materially from forward-looking statements due to various important factors, including clinical trial results, regulatory discussions, market conditions, and funding availability[31] - The Company specifically disclaims any obligation to update any forward-looking statements included in this press release[31] Contact Information & Legal Notices This section provides contact details for Summit Therapeutics' investor relations and media inquiries, along with legal notices regarding trademarks and copyright - Contact information for Summit Investor Relations (Dave Gancarz, Nathan LiaBraaten) and media inquiries is provided[31] - Summit Therapeutics and its logo are trademarks of Summit Therapeutics Inc., with copyright held by Summit Therapeutics Inc. (2025)[32]