Financial Data and Key Metrics Changes - The company ended Q3 2025 with a cash position of approximately $238.66 million [38] - Total GAAP operating expenses for 2025 were $234.2 million, a decrease from $568.4 million in the previous year, primarily due to higher stock-based compensation expenses recorded in the previous quarter [39] Business Line Data and Key Metrics Changes - The company announced the extension of its Phase III clinical development programs, including a global Phase III study in first-line colorectal cancer [3][24] - The HARMONY six study demonstrated a median progression-free survival (PFS) of 11.14 months for ivanesumab plus chemotherapy compared to 6.90 months for tislelizumab plus chemotherapy, indicating a significant improvement [12][19] Market Data and Key Metrics Changes - The HARMONY six trial included a predominantly male population with advanced squamous non-small cell lung cancer, showing a consistent benefit across various PD-L1 expression levels [11][19] - The company plans to expand its clinical trials beyond lung cancer, with the addition of the HARMONY GI III trial for unresectable colorectal cancer [24][31] Company Strategy and Development Direction - The company intends to submit a Biologics License Application (BLA) for ivanesumab based on the results of the HARMONY study, aiming to establish it as a new standard of care for advanced squamous non-small cell lung cancer [4][27] - The strategic focus includes increasing the number of ongoing Phase III clinical trials to 14, evaluating ivanesumab in multiple solid tumors [24] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the results of the HARMONY six study and its implications for future studies, highlighting the potential of ivanesumab to provide clinically meaningful improvements for patients [19][24] - The company is actively engaging with the FDA regarding the BLA submission and is confident in the strength of its data package [55][62] Other Important Information - The HARMONY six study was conducted in China and sponsored by Akeso, with all relevant data generated and analyzed by them [3][10] - The company has plans to activate clinical trial sites in the U.S. for the HARMONY GI III study by the end of 2025 [31] Q&A Session Summary Question: When could the first overall survival (OS) cut from HARMONY six be expected? - Management indicated that while they cannot provide specific timelines, they anticipate something can be reviewed in 2026, but it is event-driven [42][45] Question: What are the funding options being evaluated to extend the runway? - Management mentioned that they have an ATM out there with approximately $350 million and have received inbound interest for additional capital [49][51] Question: Can you provide any color on the BLA submission and interactions with the FDA? - Management confirmed that they are actively finalizing the BLA package and have had continued interactions with the FDA, looking forward to feedback after submission [54][55] Question: What prompted the protocol amendments to HARMONY three? - The amendments were made to accelerate the frontline lung cancer opportunity and reduce regulatory risks by separating the two histologies into individual analyses [80][84]

Financial Data and Key Metrics Changes - The company ended Q3 2025 with a cash position of approximately $238.56 million [36] - Total GAAP operating expenses for Q3 2025 were $234.2 million, a decrease from $568.4 million in Q2 2025, primarily due to a higher stock-based compensation expense recorded in the previous quarter [36][37] - Non-GAAP operating expenses for Q3 2025 were $103.4 million, an increase from $89.6 million in the previous quarter, mainly due to increased R&D expenses related to ongoing trials [37] Business Line Data and Key Metrics Changes - The Harmony Three study is enrolling ahead of goals, with over 80% of the planned 600 squamous patients cohort expected to complete enrollment in Q1 2026 [35] - The Harmony GI3 study, evaluating ivonescimab in colorectal cancer, is set to begin activating clinical trial sites in the U.S. by the end of 2025, with an expected enrollment of 600 patients [30][22] Market Data and Key Metrics Changes - The Harmony Six study demonstrated a median progression-free survival (PFS) of 11.14 months for ivonescimab plus chemotherapy compared to 6.90 months for the control group, indicating a significant clinical benefit [10][17] - The study showed consistent benefits across various PD-L1 expression levels, with hazard ratios of 0.55 for negative, 0.63 for low, and 0.71 for high PD-L1 expression [11][17] Company Strategy and Development Direction - The company plans to submit a Biologics License Application (BLA) for ivonescimab based on the Harmony study results, aiming to establish it as a new standard of care for advanced squamous non-small cell lung cancer [24][19] - The clinical development program has expanded to include multiple phase three trials across various solid tumors, indicating a strategic focus on broadening the application of ivonescimab [22][30] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the results from Harmony Six and its implications for future studies, emphasizing the potential of ivonescimab to improve outcomes for patients with limited treatment options [21][19] - The company is actively engaging with the FDA and is confident in the safety and efficacy data supporting the BLA submission [52][51] Other Important Information - The Harmony Six study was conducted in China and sponsored by Akeso Inc., with all relevant data managed and analyzed by them [2][6] - The company highlighted the importance of the safety profile of ivonescimab, noting low rates of adverse events leading to discontinuation [12][17] Q&A Session Summary Question: When could the first overall survival (OS) cut from Harmony Six be expected? - Management indicated that a review in 2026 is likely, but specific timelines are difficult to disclose [41][43] Question: What options are being evaluated to extend the runway for funding? - The company has an ATM with approximately $350 million and has received inbound interest for additional capital [47][48] Question: Can you provide insights on the BLA submission and interactions with the FDA? - Continuous interactions with the FDA have been positive, and the company is preparing to submit the BLA based on the Harmony data [51][52] Question: What prompted the protocol amendments to Harmony Three? - The amendments were made to accelerate the front-line lung cancer opportunity and reduce regulatory risks by separating analyses for squamous and non-squamous histologies [70][71]

HARMONi-6 Trial Results (Ivonescimab + Chemotherapy vs Tislelizumab + Chemotherapy in Advanced Squamous NSCLC) - Ivonescimab plus chemotherapy demonstrated a statistically significant improvement in Progression-Free Survival (PFS) compared to tislelizumab plus chemotherapy, with a Hazard Ratio (HR) of 0.60, representing a 4.2-month improvement in median PFS (mPFS)[19, 21] - The median PFS (mPFS) was 11.14 months in the ivonescimab plus chemotherapy arm compared to 6.90 months in the tislelizumab plus chemotherapy arm[21] - Subgroup analysis of PFS by IRRC showed that the PFS benefit favored ivonescimab plus chemotherapy across all key subgroups, including PD-L1 TPS <1% (HR=0.55) and PD-L1 TPS ≥1% (HR=0.66)[29, 31] - The Overall Response Rate (ORR) was higher in the ivonescimab plus chemotherapy arm (75.9%) compared to the tislelizumab plus chemotherapy arm (66.5%), with a p-value of 0.008[37, 38] - The median Duration of Response (mDoR) was 11.20 months in the ivonescimab plus chemotherapy arm compared to 8.38 months in the tislelizumab plus chemotherapy arm, with a p-value of 0.0219[41] - The safety profile of ivonescimab plus chemotherapy was manageable in squamous NSCLC, with Grade ≥ 3 Treatment-Related Adverse Events (TRAEs) occurring in 63.9% of patients in the ivonescimab arm and 54.3% in the tislelizumab arm[46, 47] AK112-206 Trial Results (Ivonescimab + Chemotherapy in Colorectal Cancer) - In the AK112-206 study, the investigator-assessed ORR for ivonescimab + FOLFOXIRI was 81.8% (95% CI: 59.7-94.8) and for ivonescimab + ligufalimab + FOLFOXIRI was 88.2% (63.6-98.5)[97] - The investigator-assessed Disease Control Rate (DCR) was 100% for both ivonescimab + FOLFOXIRI (95% CI: 84.6-100) and ivonescimab + ligufalimab + FOLFOXIRI (95% CI: 80.5-100)[97] - Treatment-emergent adverse events (TEAEs) with Grade ≥3 occurred in 68.2% of patients in the ivonescimab + FOLFOXIRI arm and 66.7% in the ivonescimab + ligufalimab + FOLFOXIRI arm[102] Ongoing and Planned Trials - HARMONi-3, a Phase 3 study of Ivonescimab + Chemo vs Pembrolizumab + Chemo in 1L Metastatic Non-Small Cell Lung Cancer (NSCLC), is ongoing globally with expected enrollment of 600 squamous and 1,000 non-squamous patients[59, 74, 77] - A Phase 3 study of Ivonescimab + Chemo vs Bevacizumab + Chemo in 1L Unresectable Metastatic Colorectal Cancer (CRC) is planned with an enrollment of 600 patients[81, 83]

Financial Performance - As of September 30, 2025, Summit Therapeutics Inc. reported total assets of $261,729,000, a decrease of 39.9% from $435,560,000 on December 31, 2024[15] - Total operating expenses for the three months ended September 30, 2025, were $234,211,000, a significant increase of 300.5% compared to $58,378,000 for the same period in 2024[17] - The net loss for the three months ended September 30, 2025, was $231,793,000, compared to a net loss of $56,254,000 for the same period in 2024, reflecting an increase of 311.5%[17] - For the nine months ended September 30, 2025, the company reported a net loss of $860,414, compared to a net loss of $160,112 for the same period in 2024, representing a significant increase in losses[30] - The company reported a comprehensive loss of $231,750,000 for the three months ended September 30, 2025, compared to a comprehensive loss of $56,063,000 for the same period in 2024[17] - The company incurred a net loss of $231.8 million and $860.4 million for the three and nine months ended September 30, 2025, respectively[186] Cash and Liquidity - The company’s cash and cash equivalents increased to $238,554,000 from $104,862,000, representing a growth of 127.7%[15] - Cash used in operating activities for the nine months ended September 30, 2025, was $220,992, up from $93,433 in the prior year[30] - The company had cash and cash equivalents of $238,554 as of September 30, 2025, compared to $94,098 at the end of the same period in 2024, indicating a substantial increase in liquidity[30] - As of September 30, 2025, the company had cash and cash equivalents of $238.6 million and an accumulated deficit of $2,075.0 million[186] - The company expects to continue to incur significant operating losses and will need to raise additional capital to fund ongoing operations and capital needs[188] - The company has established an ATM offering program with J.P. Morgan Securities LLC for up to $90.0 million as part of its liquidity strategy[191] Research and Development - Research and development expenses for the nine months ended September 30, 2025, totaled $390,382,000, up from $99,395,000 in the same period of 2024, marking a 292.5% increase[17] - Research and development expenses increased by $93.4 million (or 31.4%) and $276.0 million (or 20.0%) for the three and nine months ended September 30, 2025, respectively, compared to the same periods in the prior year[179] - The company’s lead development candidate, ivonescimab, is a bispecific antibody aimed at treating oncology patients, with rights to develop and commercialize in multiple regions including the U.S., Canada, Europe, and Japan[26] - The lead development candidate, ivonescimab, is being developed for non-small cell lung cancer (NSCLC) with ongoing Phase III trials in multiple indications[123] - The Company plans to initiate a Phase III clinical study for ivonescimab in colorectal cancer (CRC) with additional details expected in Q1 2026[124] - The company plans to expand its ivonescimab clinical development program with additional studies planned for the future[124] Stock and Equity - Summit Therapeutics Inc. issued 3,983,386 shares of common stock under stock purchase plans and exercise of stock options, raising $7,677,000[20] - The total stockholders' equity decreased to $192,263,000 as of September 30, 2025, down from $388,748,000 at the end of 2024, a decline of 50.6%[15] - The Company granted 11,417,774 stock options during the nine months ended September 30, 2025, with an outstanding total of 117,947,495 options[92] - The Company recognized stock-based compensation expense of $111,446 and $578,088 for the three and nine months ended September 30, 2025, respectively, related to the modification of performance-based stock options[93] - The Company had authorized 1,000,000,000 shares of common stock as of September 30, 2025[77] - The Company entered into a License Agreement with Akeso, making an upfront payment of $474.9 million and issuing 10 million shares of common stock valued at $25.1 million[133] Milestones and Agreements - The company entered into a License Agreement with Akeso for ivonescimab, which was amended to expand its territories to include Latin America, the Middle East, and Africa[26] - Additional potential milestone payments to Akeso could total up to $4,555,000, including regulatory milestones of up to $1,050,000 and commercial milestones of up to $3,505,000[50] - The company has potential milestone payments of $4.56 billion to Akeso, including regulatory milestones of up to $1.05 billion and commercial milestones of up to $3.51 billion[193] Operating Expenses - The Company incurred legal expenses of approximately $0.7 million and $1.4 million for the three and nine months ended September 30, 2025, respectively[112] - General and administrative expenses increased by $82.4 million (or 79.9%) and $433.1 million (or 93.2%) for the three and nine months ended September 30, 2025, respectively, compared to the same periods in the prior year[182] - Total stock-based compensation expense for the three months ended September 30, 2025, was $130,761, compared to $19,371 for the same period in 2024[95] Clinical Trial Results - The HARMONi clinical trial demonstrated a statistically significant improvement in progression-free survival (PFS) with a hazard ratio of 0.52 (95% CI: 0.41 – 0.66; p<0.00001), with median PFS of 6.8 months for ivonescimab plus chemotherapy compared to 4.4 months for chemotherapy alone[143] - Overall response rates were 45% in the ivonescimab arm versus 34% in the placebo arm, with a median duration of response of 7.6 months for ivonescimab compared to 4.2 months for placebo[145] - The HARMONi-2 study showed ivonescimab achieved a PFS hazard ratio of 0.51, indicating a statistically significant improvement compared to pembrolizumab[166] - In the HARMONi-A study, ivonescimab demonstrated a 54% reduction in disease progression or death compared to placebo plus chemotherapy[163] - The company observed a consistent improvement in PFS with a hazard ratio of 0.57 in a longer-term follow-up analysis, indicating benefits across various patient subgroups[147] Future Outlook - The company expects to continue generating operating losses for the foreseeable future, raising concerns about its ability to fund operations without additional capital[30] - The company is actively evaluating options for financing its operations, including equity and debt offerings, collaborations, and grants[33] - The company’s ability to continue operations may be adversely affected if it cannot raise additional funds when needed[197] - The company is exposed to foreign currency exchange rate risk, particularly with the pound sterling and euro, which could impact its financial position[213]

Executive Summary & Key Announcements [Planned BLA Submission for Ivonescimab](index=1&type=section&id=Planned%20BLA%20Submission%20for%20Ivonescimab) 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](index=1&type=chunk)[2](index=2&type=chunk) - 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](index=2&type=chunk) [Expansion of Phase III Ivonescimab Clinical Development Program](index=1&type=section&id=Expansion%20of%20Phase%20III%20Ivonescimab%20Clinical%20Development%20Program) 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](index=1&type=chunk)[3](index=3&type=chunk) - 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](index=1&type=chunk)[3](index=3&type=chunk) Operational & Clinical Development Updates [Ivonescimab Program Overview](index=2&type=section&id=Ivonescimab%20Program%20Overview) 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](index=4&type=chunk) - Over **3,000 patients** have been treated with ivonescimab in global clinical studies, and over **40,000** in a commercial setting in China[4](index=4&type=chunk) - 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](index=4&type=chunk) - Summit is developing ivonescimab in **NSCLC** (HARMONi, HARMONi-3, HARMONi-7) and plans to develop it in **CRC** (HARMONi-GI3)[4](index=4&type=chunk) [HARMONi Global Phase III Study Results](index=2&type=section&id=HARMONi%20Global%20Phase%20III%20Study%20Results) 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](index=5&type=chunk) - Grade 3 or higher hemorrhage (bleeding) events were observed in **0.9%** of patients in the ivonescimab plus chemotherapy arm[5](index=5&type=chunk) [HARMONi-GI3 Global Phase III Study Initiation](index=3&type=section&id=HARMONi-GI3%20Global%20Phase%20III%20Study%20Initiation) 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](index=3&type=chunk)[5](index=5&type=chunk) - The trial will evaluate ivonescimab plus chemotherapy compared to bevacizumab plus chemotherapy as **first-line therapy** in patients with **unresectable metastatic CRC**[5](index=5&type=chunk) - The study intends to enroll **600 patients**, with **progression-free survival (PFS)** as the primary endpoint[6](index=6&type=chunk) - Clinical trial sites for HARMONi-GI3 are planned to begin activating in the **United States** prior to the end of the year[5](index=5&type=chunk) [HARMONi-6 Phase III Study Results](index=4&type=section&id=HARMONi-6%20Phase%20III%20Study%20Results) 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](index=6&type=chunk) - Ivonescimab demonstrated an **acceptable and manageable safety profile**, consistent with previous Phase III studies[6](index=6&type=chunk) - 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](index=7&type=chunk) - 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](index=7&type=chunk) [HARMONi-3 Phase III Study Update](index=5&type=section&id=HARMONi-3%20Phase%20III%20Study%20Update) 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](index=7&type=chunk) - 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](index=7&type=chunk) - 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](index=7&type=chunk) - 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](index=7&type=chunk) [Other Clinical Collaborations and Akeso's Trials](index=6&type=section&id=Other%20Clinical%20Collaborations%20and%20Akeso's%20Trials) 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](index=11&type=chunk) - 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](index=11&type=chunk) - **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](index=11&type=chunk) Financial Highlights (Q3 2025) [Cash and Cash Equivalents and Short-term Investments](index=6&type=section&id=Cash%20and%20Cash%20Equivalents%20and%20Short-term%20Investments) 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)](index=6&type=section&id=Operating%20Expenses%20(GAAP%20and%20Non-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](index=12&type=chunk) - The increase in Non-GAAP operating expenses was due to the **expansion of clinical studies and development costs** related to ivonescimab[12](index=12&type=chunk) [Research and Development (R&D) Expenses (GAAP and Non-GAAP)](index=6&type=section&id=Research%20and%20Development%20(R%26D)%20Expenses%20(GAAP%20and%20Non-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](index=12&type=chunk) - The increase in Non-GAAP R&D expenses is primarily related to the **expansion of clinical studies and development costs** for ivonescimab[12](index=12&type=chunk) [General and Administrative (G&A) Expenses (GAAP and Non-GAAP)](index=7&type=section&id=General%20and%20Administrative%20(G%26A)%20Expenses%20(GAAP%20and%20Non-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](index=15&type=chunk) - The increase in Non-GAAP G&A expenses is related to **building infrastructure** to support the development of ivonescimab[15](index=15&type=chunk) [Net Loss (GAAP and Non-GAAP)](index=7&type=section&id=Net%20Loss%20(GAAP%20and%20Non-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](index=8&type=section&id=About%20Ivonescimab) 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](index=17&type=chunk) - 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](index=17&type=chunk)[18](index=18&type=chunk) - 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](index=27&type=chunk) - Over **3,000 patients** have been treated with ivonescimab in clinical studies globally, and over **40,000** in a commercial setting in China[19](index=19&type=chunk) [About Summit Therapeutics](index=9&type=section&id=About%20Summit%20Therapeutics) 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](index=28&type=chunk) - The company was founded in **2003**, and its shares are listed on the **Nasdaq Global Market (symbol "SMMT")**[29](index=29&type=chunk) - Summit is headquartered in **Miami, Florida**, with additional offices in **Menlo Park, California**, and **Oxford, UK**[29](index=29&type=chunk) Financial Statements & Non-GAAP Reconciliations [GAAP Condensed Consolidated Statements of Operations](index=12&type=section&id=GAAP%20Condensed%20Consolidated%20Statements%20of%20Operations) 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](index=12&type=section&id=GAAP%20Condensed%20Consolidated%20Balance%20Sheet%20Information) 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](index=13&type=section&id=GAAP%20Condensed%20Consolidated%20Statement%20of%20Cash%20Flows%20Information) 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](index=14&type=section&id=Schedule%20Reconciling%20Selected%20Non-GAAP%20Financial%20Measures) 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](index=16&type=section&id=Notes%20on%20Non-GAAP%20Financial%20Information) 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](index=42&type=chunk)[43](index=43&type=chunk) - 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](index=42&type=chunk) - 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](index=45&type=chunk) Additional Information [Forward-looking Statements](index=10&type=section&id=Forward-looking%20Statements) 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](index=31&type=chunk) - 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](index=31&type=chunk) - The Company specifically **disclaims any obligation to update** any forward-looking statements included in this press release[31](index=31&type=chunk) [Contact Information & Legal Notices](index=10&type=section&id=Contact%20Information%20%26%20Legal%20Notices) 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](index=31&type=chunk) - Summit Therapeutics and its logo are **trademarks** of Summit Therapeutics Inc., with **copyright** held by Summit Therapeutics Inc. (**2025**)[32](index=32&type=chunk)

Financial Performance - Summit Therapeutics Inc. reported a GAAP net loss of $231.8 million or $0.31 per share in Q3, compared to a loss of $56.3 million or $0.08 per share in the same quarter last year [1] - The non-GAAP net loss for the third quarter was $101.0 million or $0.13 per share, up from a loss of $36.9 million or $0.05 per share in the prior year [1] Clinical Development - Based on the results of the HARMONi clinical trial, Summit plans to submit a Biologics License Application (BLA) for ivonescimab plus chemotherapy, targeting submission in Q4 2025 [2] - The company intends to expand its ivonescimab clinical development program with additional Phase III clinical studies [2] Market Reaction - Shares of Summit Therapeutics are down 5% in pre-market trading on Monday [2]

Core Insights - Summit Therapeutics Inc. plans to submit a Biologics License Application (BLA) for ivonescimab in Q4 2025 based on the results of the HARMONi clinical trial [1] Financial Results - The financial results for the third quarter ended September 30, 2025, were reported, although specific figures were not detailed in the provided content [1] Operational Progress - The company is making operational progress with the planned BLA submission for ivonescimab, which is intended to be used in combination with chemotherapy [1]

Core Insights - Ivonescimab combined with chemotherapy demonstrated a 40% reduction in the risk of disease progression or death compared to Tislelizumab plus chemotherapy in the first-line treatment of patients with squamous non-small cell lung cancer (NSCLC) in the HARMONi-6 study [1][5][33] - The median progression-free survival (PFS) was 11.14 months for Ivonescimab plus chemotherapy versus 6.90 months for Tislelizumab plus chemotherapy, with a hazard ratio of 0.60 [1][5][6] - The safety profile of Ivonescimab was comparable to Tislelizumab, with similar rates of serious treatment-related adverse events (TRAEs) and discontinuation due to TRAEs [1][7][9] Study Overview - The HARMONi-6 trial was a Phase III, multi-center study conducted in China, evaluating Ivonescimab in combination with platinum-based chemotherapy against Tislelizumab plus chemotherapy in patients with advanced squamous NSCLC, regardless of PD-L1 expression [2][4][33] - The study was sponsored by Akeso, Inc., with all relevant data generated and analyzed by Akeso [2][4] Efficacy Results - Ivonescimab showed a statistically significant improvement in PFS, with a hazard ratio of 0.60 (95% CI: 0.46, 0.78; p<0.0001) [5][6] - The overall response rate (ORR) was 75.9% for Ivonescimab plus chemotherapy compared to 66.5% for Tislelizumab plus chemotherapy [6] - Duration of response (DoR) was also longer for Ivonescimab at 11.20 months versus 8.38 months for Tislelizumab [6] Safety Profile - The safety profile of Ivonescimab was manageable, with 3.4% of patients discontinuing due to TRAEs compared to 4.2% for Tislelizumab [9][11] - Serious TRAEs occurred in 32.3% of patients receiving Ivonescimab and 30.2% for Tislelizumab [11] - Grade 3 or higher immune-related adverse events were reported in 9.0% of Ivonescimab patients versus 10.2% for Tislelizumab [11] Future Studies - The HARMONi-3 global study will analyze squamous and non-squamous NSCLC cohorts separately, with enrollment completion expected in the first half of 2026 for the squamous cohort and the second half of 2026 for the non-squamous cohort [1][19][20] - An interim analysis for overall survival is planned for both cohorts upon reaching the prespecified number of events [19][20] Publication and Presentation - The results of the HARMONi-6 trial were published in The Lancet and presented at the European Society for Medical Oncology (ESMO) 2025 Congress [1][13][24]

Core Viewpoint - Summit Therapeutics Inc. is a biopharmaceutical company focused on developing innovative therapies in antibiotics and oncology, facing competition in the biotech sector [1] Financial Performance - The company is set to release its quarterly earnings on October 20, 2025, with Wall Street expecting an earnings per share of -$0.14 and projected revenue of approximately $77.2 million [2][6] - Summit has a negative price-to-earnings (P/E) ratio of -21.87, indicating current unprofitability [3][6] - The enterprise value to operating cash flow ratio is -77.47, suggesting difficulties in generating cash flow from operations [4][6] - The earnings yield is negative at -4.57%, further highlighting the company's lack of profitability [4] Financial Stability - Despite financial challenges, Summit maintains a low debt-to-equity ratio of 0.02, indicating minimal reliance on debt [4] - The current ratio stands at 5.13, demonstrating a strong ability to cover short-term liabilities with short-term assets [5]

Core Viewpoint - Summit Therapeutics Inc. (NASDAQ:SMMT) is recognized as a biotech stock with high potential, but it faces mixed ratings from analysts, indicating uncertainty in its investment outlook [1][2][3]. Analyst Ratings - Leerink Partners maintained a Sell rating on Summit Therapeutics without a price target as of September 29 [1]. - Barclays also issued a Sell rating with a price target of $13 on September 25 [2]. - In contrast, Asthika Goonewardene from Truist Financial maintained a Buy rating without a price target on the same day [2]. - Citi's Yigal Nochomovitz expressed a bullish outlook, assigning a Buy rating with a price target of $35 on September 24 [3]. Company Overview - Summit Therapeutics is a biopharmaceutical company focused on developing novel medications for infectious and cancerous diseases [3].