Summit Therapeutics Inc.
10/20/2025 | Press release | Distributed by Public on 10/20/2025 05:52
Quarterly Report for Quarter Ending September 30, 2025 (Form 10-Q)
Management's Discussion and Analysis of Financial Condition and Results of Operations.
The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our unaudited condensed consolidated financial statements and related notes included herein and our audited consolidated financial statements and related notes for the year ended December 31, 2024 included in our Annual Report.Some of the information contained in this discussion and analysis or set forth elsewhere in this filing, including information with respect to our plans and strategy for our business, includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties. All statements other than statements relating to historical matters including statements to the effect that we "believe," "expect," "anticipate," "plan," "target," "intend" and similar expressions should be considered forward-looking statements. As a result of many factors, including those factors set forth in the risks identified in the "Risk Factors" section of our other filings with the SEC, our actual results could differ materially from the results, performance or achievements expressed in or implied by these forward-looking statements.
Company Overview
Summit Therapeutics Inc. ("we", "Summit" or the "Company") is a biopharmaceutical company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs. The Company's pipeline of product candidates is designed with the goal to become the patient-friendly, new-era standard-of-care medicines, in the therapeutic area of oncology.
The Company's current lead development candidate is ivonescimab, a novel, potential first-in-class bispecific antibody intending to combine the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects of an anti-VEGF compound into a single molecule. On December 5, 2022, the Company entered into the License Agreement with Akeso pursuant to which the Company has in-licensed intellectual property rights related to ivonescimab. Through the License Agreement, the Company obtained the rights to develop and commercialize ivonescimab in the United States, Canada, Europe, and Japan. The License Agreement and transaction closed in January 2023 following customary waiting periods. On June 3, 2024, the Company entered into the Second Amendment with Akeso to expand its territories covered under the License Agreement to also include Latin America, including Mexico and all countries in Central America and South America, the Middle East and Africa. The Company's operations are focused on the development of ivonescimab and other future activities, as the Company determines.
The Company is developing ivonescimab in non-small cell lung cancer ("NSCLC"), specifically conducting Phase III clinical trials in the following proposed indications:
(a) ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor ("EGFR")-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR tyrosine kinase inhibitor ("TKI") ("HARMONi");
(b) ivonescimab combined with chemotherapy in patients with first-line metastatic NSCLC ("HARMONi-3"); and
(c) ivonescimab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression ("HARMONi-7").
In addition, the Company plans to start developing ivonescimab in colorectal cancer ("CRC") with an intention to begin a Phase III clinical study in the following proposed indication:
(d) ivonescimab combined with chemotherapy in patients with first-line unresectable metastatic CRC ("HARMONi-GI3").
The Company also intends to expand its ivonescimab clinical development program with an additional set of Phase III clinical studies, with additional color planned to be provided in the first quarter of 2026.
In October 2024, the Company completed enrollment in its HARMONi clinical trial. In May 2025, we announced topline results from our multiregional, double-blinded, placebo-controlled, Phase III study HARMONi. At the prespecified primary data analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement in progression free survival (PFS), the magnitude of which we believe to be clinically meaningful, with a hazard ratio of 0.52 (95% CI: 0.41 - 0.66;
p<0.00001). PFS was measured by blinded independent central radiology review committee ("BICR") compared to placebo in combination with chemotherapy.
We believe the PFS hazard ratio that was observed in both Asia and ex-Asia sub-populations to be clinically meaningful. The primary analysis demonstrated the consistency of the magnitude of the PFS benefit between patients randomized in Asia and ex-Asia, as well as the consistency in a single-region study (HARMONi-A) with this multiregional study. Ivonescimab in combination with chemotherapy showed a positive trend in overall survival (OS) in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI: 0.62 - 1.01; p=0.057). This trend provides further support for its use in 2L+ EGFRm NSCLC, a setting where high unmet need continues to exist with limited approved options in the United States and other western territories. Currently there are no FDA-approved regimens that have demonstrated a statistically significant overall survival benefit in this patient setting. Both Asian and North American patients demonstrated a positive trend in overall survival. The results of the primary analysis in this multiregional study were consistent with that of the single-region HARMONi-A study, which demonstrated an overall survival hazard ratio of 0.80 at 52% data maturity in a similar patient population.
Overall response rates were higher in the ivonescimab arm (45%) vs. the placebo arm (34%); median duration of response was longer in those patients administered ivonescimab plus chemotherapy (7.6 months) compared to those receiving placebo and chemotherapy (4.2 months).
In September 2025, an additional analysis was performed, whereby the western patients were followed to increase their time on study (Asian patients were locked at the time of the primary analysis). In this analysis that included longer-term follow-up of western patients (median follow-up time of western patients of 13.7 months), a hazard ratio consistent with the primary analysis was observed with an improved nominal p-value (HR=0.78; 95% CI: 0.62 - 0.98; nominal p=0.0332). Median OS for this analysis remained the same in both arms from the primary analysis. Median OS in western patients receiving ivonescimab was 17.0 months compared to 14.0 months for those receiving placebo (HR=0.84); median OS in North American patients, specifically, had not yet been reached in the ivonescimab arm compared to 14.0 months in the placebo arm (HR=0.70). The hazard ratios for western patients in totality, as well as patients from the North American and European regions individually, improved from the primary OS analysis to the analysis with longer-term follow-up of western patients. Consistent benefit was observed across pre-defined subgroups.
In a longer-term follow-up of PFS, which included all western patients and at least six months of follow-up time for all patients, ivonescimab plus chemotherapy demonstrated a consistent improvement in PFS with an observed HR of 0.57 (95% CI: 0.46 - 0.71). With the longer-term follow-up analysis, a consistent benefit in western vs. Asian patients was observed, as well as in patients with tumors with either PD-L1 positive or negative expression. This longer-term follow-up analysis of PFS was performed at the time of the primary OS analysis.
The dual primary endpoints were allocated separate alpha levels and tested individually. The alpha was recycled from the PFS to the OS analysis upon the successful achievement of the PFS endpoint.
Based on the results of the HARMONi clinical trial, we plan to submit a Biologics License Application (BLA) in order to seek approval for ivonescimab plus chemotherapy for this proposed indication. We intend to submit the BLA in the fourth quarter of 2025. The positive results of the multiregional Phase III study are detailed further under "Product Pipeline" below. As previously noted, the FDA noted that a statistically significant overall survival benefit is necessary to support marketing authorization in this setting. After careful consideration of the safety and efficacy profile of the current FDA-approved options for patients in this setting, the positive results of the Phase III multiregional study, including regional consistency, as well as discussions with key opinion leaders and those physicians who have administered ivonescimab to patients in a clinical study setting, we believe that the safety and efficacy data generated in the HARMONi study demonstrates that patients suffering from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) in this setting can benefit from the ivonescimab regimen despite the lack of a statistically significant showing on overall survival.
Akeso Collaboration and License Agreement
Pursuant to the License Agreement with Akeso, the Company received the rights to develop and commercialize ivonescimab in the Licensed Territory. Akeso will retain development and commercialization rights for the rest of the world excluding the Licensed Territory. In exchange for these rights, Summit made an upfront payment during the first quarter of 2023 comprised of $474.9 million cash and the issuance of 10 million shares of Company common stock in lieu of $25.1 million cash pursuant to a share transfer agreement. Furthermore, on June 3, 2024, the Company entered into an amendment to the License Agreement with Akeso to expand its territories covered under the License Agreement to also include the Latin America, Middle East and Africa regions for which Summit paid an upfront payment of $15.0 million cash in the third quarter of 2024. In addition, the Company
may also pay Akeso (a) milestone payments tied to achievement of regulatory approval of ivonescimab with various regulatory authorities in the Licensed Territory, (b) milestone payments tied to achievement of annual revenue from ivonescimab in the Licensed Territory and (c) royalty payments equal to low-double-digit percentage of annual revenues from ivonescimab in the Licensed Territory. In connection with the License Agreement, the Company agreed to purchase a certain portion of drug substance and/or drug product for clinical and commercial supply and to enter into a supply agreement with Akeso.
Pursuant to the terms of the License Agreement, Summit has final decision-making authority with respect to commercial strategy, pricing and reimbursement and other commercialization matters in the Licensed Territory.
Summit has not assumed any liabilities (including contingent liabilities), nor acquired any physical assets or trade names, or hired or acquired any employees from Akeso in connection with the License Agreement.
Ivonescimab
Ivonescimab is a novel potential first-in-class PD-1 / VEGF bispecific antibody, believed to be the most advanced in clinical development in the Licensed Territory. Engineered with Akeso's unique Tetrabody technology, ivonescimab, as a single molecule, blocks programmed cell death protein 1 ("PD-1") from binding to PD-L1 and PD-L2, and blocks vascular endothelial growth factor ("VEGF") from binding to VEGF receptors. Ivonescimab is designed to potentially allow cooperative binding of the intended targets, such that the binding of PD-1 increases the binding affinity of VEGF. In view of the co-expression of VEGF and PD-1 in the tumor micro-environment ("TME"), ivonescimab may block these two pathways more effectively and enhance the antitumor activity, as compared to combination therapy through what is believed to be a unique cooperative binding mechanism.
This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the TME as compared to normal tissue in the body. As shown in Akeso's in-vitrostudies, ivonescimab's tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME with over 10 fold increased binding affinity to PD-1 in the presence of VEGF in vitro. This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities has the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.
Ivonescimab is currently being developed by both Akeso and the Company in multiple Phase III clinical trials. There are also multiple early-phase trials being conducted in multiple solid tumors. Ivonescimab has been dosed in more than 3,000 patients globally.
Product Pipeline
Summit Sponsored Ivonescimab Trials
Ivonescimab is currently being investigated in global Phase III clinical trials. Phase I and II trials were completed by or are ongoing with our partner Akeso. This pipeline reflects Phase III clinical trials that have been or are planned to be initiated by Summit in its Licensed Territory.
HARMONi
HARMONi study (NCT05184712) is a Phase III, multi-regional, potentially registration-enabling clinical trial, which enrolled patients in North America, Europe, and China. Patients enrolled in China were also enrolled as a part of the HARMONi-A study. We completed enrollment of patients in North America and Europe in October 2024. The two primary endpoints for this study are PFS and OS, and the study compares ivonescimab plus platinum-based doublet chemotherapy versus placebo plus platinum-based doublet chemotherapy in patients with advanced or metastatic EGFR-mutated NSCLC whose tumors have progressed following treatment with a third generation EGFR-TKI.
In May 2025, we announced topline results from our multiregional, double-blinded, placebo-controlled, Phase III study HARMONi. At the prespecified primary data analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement in PFS, the magnitude of which we believe to be clinically meaningful, with a hazard ratio of 0.52 (95% CI: 0.41 - 0.66; p<0.00001); median PFS was 6.8 months for those patients receiving ivonescimab plus chemotherapy compared to 4.4 months for those receiving chemotherapy. PFS was measured by blinded independent central radiology review committee ("BICR") compared to placebo in combination with chemotherapy.
We believe the PFS hazard ratio that was observed in both Asia and ex-Asia sub-populations to be clinically meaningful. The primary analysis demonstrated the consistency of the magnitude of the PFS benefit between patients randomized in Asia and ex-Asia, as well as the consistency in a single-region study (HARMONi-A) with this multiregional study. Ivonescimab in combination with chemotherapy showed a positive trend in overall survival (OS) in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI: 0.62 - 1.01; p=0.057). This trend provides further support for its use in 2L+ EGFRm NSCLC, a setting where high unmet need continues to exist with limited approved options in the United States and other western territories. Currently there are no FDA-approved regimens that have demonstrated a statistically significant overall survival benefit in this patient setting. Both Asian and North American patients demonstrated a positive trend in overall survival. The results of the primary analysis in this multiregional study were consistent with that of the single-region HARMONi-A study, which demonstrated an overall survival hazard ratio of 0.80 at 52% data maturity in a similar patient population.
Overall response rates were higher in the ivonescimab arm (45%) vs. the placebo arm (34%); median duration of response was longer in those patients administered ivonescimab plus chemotherapy (7.6 months) compared to those receiving placebo and chemotherapy (4.2 months).
In September 2025, an additional analysis was performed, whereby the western patients were followed to increase their time on study (Asian patients were locked at the time of the primary analysis). In this analysis that included longer-term follow-up of western patients (median follow-up time of western patients of 13.7 months), a hazard ratio consistent with the primary analysis was observed with an improved nominal p-value (HR=0.78; 95% CI: 0.62 - 0.98; nominal p=0.0332). Median OS for this analysis remained the same in both arms from the primary analysis. Median OS in western patients receiving ivonescimab was 17.0 months compared to 14.0 months for those receiving placebo (HR=0.84); median OS in North American patients, specifically, had not yet been reached in the ivonescimab arm compared to 14.0 months in the placebo arm (HR=0.70). The hazard ratios for western patients in totality, as well as patients from the North American and European regions individually, improved from the primary OS analysis to the analysis with longer-term follow-up of western patients. Consistent benefit was observed across pre-defined subgroups.
In a longer-term follow-up of PFS, which included all western patients and at least six months of follow-up time for all patients, ivonescimab plus chemotherapy demonstrated a consistent improvement in PFS with an observed HR of 0.57 (95% CI: 0.46 - 0.71). With the longer-term follow-up analysis, a consistent benefit in western vs. Asian patients was observed, as well as in patients with tumors with either PD-L1 positive or negative expression. This longer-term follow-up analysis of PFS was performed at the time of the primary OS analysis.
The dual primary endpoints were allocated separate alpha levels and tested individually. The alpha was recycled from the PFS to the OS analysis upon the successful achievement of the PFS endpoint.
The safety profile of ivonescimab in combination with chemotherapy was acceptable and manageable in the context of the observed clinical benefit with comparable rates of discontinuation and death between both arms. There were 16 patients (7.3%) who discontinued ivonescimab due to treatment-related adverse events (TRAEs) compared to 11 patients (5.0%) who discontinued placebo due to TRAEs. There were four patients (1.8%) in the ivonescimab plus chemotherapy arm and five patients (2.3%) in the chemotherapy alone arm who died as a result of TRAEs. In the ivonescimab plus chemotherapy arm, 50.0% of patients experienced Grade 3 or higher TRAEs compared to 42.2% in the chemotherapy arm. Of note, 0.9% of patients in the ivonescimab plus chemotherapy arm experienced Grade 3 or higher hemorrhage (bleeding) events. Based on the results of the HARMONi clinical trial, Summit plans to submit a Biologics License Application (BLA) in order to seek approval for ivonescimab plus chemotherapy in this setting.
HARMONi-3
HARMONi-3 study (NCT05899608) is a Phase III, multi-regional, potentially registration-enabling clinical trial for which we initiated activating sites in North America and China during the fourth quarter of 2023 and later in Europe in 2024. The two primary endpoints for this study are PFS and OS, and the study compares ivonescimab plus platinum-based doublet chemotherapy versus pembrolizumab plus platinum-based doublet chemotherapy in first-line patients with metastatic squamous NSCLC and non-squamous NSCLC. Enrollment is ongoing in all regions for patients with squamous tumors; the protocol amendment is effective and enrollment began in the United States in the fourth quarter of 2024 for patients with non-squamous tumors.
In October 2025, the Company announced a protocol amendment to separate the statistical analysis of the primary endpoints by histology. Therefore, there will be separate analyses conducted to evaluate ivonescimab plus chemotherapy compared to pembrolizumab plus chemotherapy in patients with squamous NSCLC and in patients with non-squamous NSCLC.
As a result of having two separate intention-to-treat analyses within the HARMONi-3 study, the analyses for squamous tumors and non-squamous tumors may be conducted at separate times, as each analysis will be conducted upon the prespecified numbers of events being reached in the separate cohorts.
Enrollment in the squamous cohort of HARMONi-3 is expected to complete in the first half of 2026. The Company expects to reach the prespecified number of events for the PFS primary endpoint analysis for this cohort in the second half of 2026. An interim analysis for overall survival may be conducted at a similar time.
Enrollment in the non-squamous cohort of HARMONi-3 is expected to complete in the second half of 2026. The Company expects to reach the prespecified number of events for the PFS primary endpoint analysis for this cohort in the first half of 2027. An interim analysis for overall survival is planned to be conducted based upon reaching a prespecified number of events.
In order to sufficiently power for PFS and OS in both cohorts of this study, Summit plans to enroll 600 patients with squamous NSCLC and 1,000 patients with non-squamous NSCLC.
HARMONi-7
Based on the results of HARMONi-2, the Company is enrolling in the HARMONi-7 study (NCT06767514). HARMONi-7 is a multi-regional, potentially registration-enabling Phase III clinical trial that will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic squamous and non-squamous NSCLC whose tumors have high PD-L1 expression. The sample size for this study is currently planned to have an estimated 780 patients with two primary endpoints, PFS and OS.
HARMONi-GI3
In October 2025, the Company announced it intends to start HARMONi-GI3, a Phase III, multi-regional, clinical trial evaluating ivonescimab plus chemotherapy compared to bevacizumab plus chemotherapy as first line therapy in patients with unresectable metastatic colorectal cancer (CRC). The primary endpoint for this study is PFS and Summit plans to enroll 600 patients. Clinical trial sites for HARMONi-GI3 are planned to begin activating in the United Stated prior to the end of the year.
Potential Future Clinical Development and Additional Current Activities
Summit is conducting its current clinical trials, and plans to design and conduct additional clinical trial activities for ivonescimab within its Licensed Territory, to support and submit relevant regulatory filings. We intend to explore further clinical development of ivonescimab in solid tumor settings outside of metastatic NSCLC and metastatic CRC, our current areas of focus in its Phase III clinical trials.
In the fourth quarter of 2023, we began collaborating with multiple institutions globally and opened our investigator- sponsored trials program across several disease areas. We continued to expand this program in 2024 in order to discover additional opportunities for ivonescimab, including in several tumors outside of our current development plan.
We plan to review the data generated from these clinical trials as a part of our consideration for advancing our clinical development pipeline for ivonescimab in the Licensed Territory.
Additional Ivonescimab Development: Akeso-Sponsored Trials
Akeso is currently developing ivonescimab in NSCLC and other solid tumor settings. Ivonescimab is currently approved in China in combination with chemotherapy for patients with EGFR-mutated NSCLC whose tumors have progressed following an EGFR-TKI based on the results of the HARMONi-A clinical trial that was first announced and presented in 2024. In addition, a supplemental application was submitted in China by Akeso for ivonescimab as monotherapy based on the results of the HARMONi-2 study in first-line, PD-L1 positive NSCLC, and was approved by the National Medical Products Administration ("NMPA") in April 2025 for this indication as well. Also in April 2025, Akeso announced positive results for the HARMONi-6 study in first-line squamous NSCLC. Further details related to these three trials, in addition to other Phase II clinical data presented during 2024, are described further below. Akeso is currently conducting Phase III clinical trials in combination with chemotherapy in first-line biliary tract cancer ("HARMONi-GI1"), in first-line advanced PD-L1 low or negative triple-negative breast cancer ("HARMONi-BC1"), in first-line advanced microsatellite stable colorectal cancer ("HARMONi-GI3") and in NSCLC for patients whose tumors have progressed following PD-(L)1 inhibitor based therapy ("HARMONi-8A"), as well as in combination with ligufalimab, a proprietary Akeso-owned investigational CD-47 monoclonal antibody, in first-line recurrent / metastatic PD-L1 positive head-and-neck cancer ("HARMONi-HN1") and in combination with ligufalimab plus chemotherapy in first-line advanced pancreatic cancer ("HARMONi-GI2").
HARMONi-A
Based on data published by Akeso at the American Society of Clinical Oncology ("ASCO 2024") and in a publication in the Journal of the American Medical Association (JAMA) in the HARMONi-A study, in a single-region (China), randomized, double-blinded Phase III study in patients with NSCLC who have progressed following an EGFR-TKI, ivonescimab achieved its primary endpoint of PFS when combined with doublet chemotherapy (pemetrexed and carboplatin). Patients experienced a 54% reduction in disease progression or death as compared to placebo plus doublet-chemotherapy (HR: 0.46, 95% CI: 0.34 - 0.62; p<0.001). In a pre-specified subgroup analysis of patients who received a previous third-generation TKI, a hazard ratio of 0.48 was observed. A median Overall Survival ("mOS") in this study of 17.1 months was observed, reflecting a 20% reduction in death as compared to placebo plus chemotherapy in the study (HR: 0.80, 95% CI: 0.59 - 1.08). The Phase III study was considered to have demonstrated a tolerable safety profile and a low discontinuation rate for adverse events.
In August 2025, Akeso announced that in the final OS analysis of HARMONi-A, ivonescimab met the OS clinical endpoint, demonstrating a statistically significant and clinically meaningful OS benefit. As the first Phase III final analysis for ivonescimab, these results not only reinforce its breakthrough value in PFS, but also highlight its ability to deliver significant OS improvement, a key endpoint in global oncology drug development.
HARMONi-2
After announcing positive qualitative results for the HARMONi-2 trial, also referred to as AK112-303, a randomized, single-region (China) Phase III study sponsored by Akeso, on May 30, 2024, the Company announced, on September 8, 2024, quantitative data from the primary analysis of the Phase III HARMONi-2 trial featuring ivonescimab that was presented as part of the Presidential Symposium at the International Association for the Study of Lung Cancer's ("IASLC") 2024 World Conference on Lung Cancer ("WCLC 2024"). The HARMONi-2 presentation evaluated monotherapy ivonescimab compared to monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression. HARMONi-2 is a single region, multi-center, double-blinded Phase III study conducted in China sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso.
In the HARMONi-2 primary analysis, ivonescimab monotherapy demonstrated a statistically significant improvement in the trial's primary endpoint, PFS by Independent Radiologic Review Committee ("IRRC"), when compared to monotherapy pembrolizumab, achieving a hazard ratio of 0.51 (95% CI: 0.38, 0.69; p<0.0001). A clinically meaningful benefit was demonstrated across clinical subgroups, including patients with tumors with high PD-L1 expression. Overall survival ("OS") data was not yet mature at the time of the data cutoff of the primary analysis.
Ivonescimab demonstrated an acceptable and manageable safety profile, which was consistent with previous studies. There were three patients (1.5%) who discontinued ivonescimab due to treatment-related adverse events ("TRAEs") compared to six patients (3.0%) who discontinued pembrolizumab due to TRAEs. There was one patient in the ivonescimab arm and two patients in the pembrolizumab arm who died as a result of TRAEs in this Phase III study.
On April 25, 2025, Akeso announced that ivonescimab was approved in China by the NMPA, the Chinese Health Authority, for a second indication based on the results of the HARMONi-2 trial. As a part of the review of the supplemental marketing application submitted by Akeso seeking a label expansion of ivonescimab in China, the NMPA requested that Akeso perform an interim analysis of OS. Akeso announced that the results of this interim overall survival analysis included a clinically meaningful hazard ratio of 0.777. The analysis was conducted at 39% data maturity, with a nominal alpha level of 0.0001.
HARMONi-6
After announcing positive qualitative results for the HARMONi-6 trial, on April 23, 2025, detailed clinical trial results of the study were presented as part of the Presidential Symposium at the European Society for Medical Oncology's 2025 Congress ("ESMO 2025"). The HARMONi-6 study evaluated ivonescimab in combination with platinum-based chemotherapy compared to tislelizumab (a PD-1 inhibitor) in combination with platinum-based chemotherapy in patients with previously untreated advanced NSCLC irrespective of PD-L1 expression. HARMONi-6, also referred to as AK112-306, is a single region, multi-center, double-blinded Phase III study conducted in China sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso.
In the HARMONi-6 planned PFS interim analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint, PFS, by IRRC, when compared to tislelizumab in combination with chemotherapy, achieving a hazard ratio of 0.60 (95% CI: 0.46, 0.78; p<0.0001). A clinically meaningful benefit was demonstrated across clinical subgroups, including those with either PD-L1 negative or positive expression, as well as high-risk patients. OS data was not yet mature at the time of the data cutoff and will be evaluated in the future.
Ivonescimab demonstrated an acceptable and manageable safety profile in the HARMONi-6 study, which was consistent with previous blinded Phase III studies conducted studying ivonescimab. Nine patients (3.4%) discontinued ivonescimab plus chemotherapy due to treatment-related adverse events (TRAEs) compared to 11 patients (4.2%) receiving tislelizumab plus chemotherapy due to TRAEs. There were eight patients in the ivonescimab plus chemotherapy arm and 10 patients in the tislelizumab plus chemotherapy arm who died as a result of TRAEs in this Phase III study.
Additional Phase II Data Sets
In addition to the HARMONi-2 data announced at WCLC 2024, Akeso also announced Phase II trial results from AK112-205, for patients with Stage II or III resectable NSCLC. Further, the Company announced data for ivonescimab was presented as a part of the 2024 European Society for Medical Oncology Annual Congress ("ESMO 2024") featuring updated Phase II ivonescimab data in advanced triple-negative breast cancer ("TNBC"), recurrent / metastatic head and neck squamous cell carcinoma ("HNSCC"), and metastatic microsatellite-stable ("MSS") colorectal cancer ("CRC"). At ASCO 2024, Akeso presented ivonescimab Phase II data in biliary-tract cancer ("BTC"). Earlier, at the 2024 European Lung Cancer Conference ("ELCC 2024"), Akeso announced updated data from AK112-201 (Cohort 1), a Phase II study for patients with first-line advanced NSCLC. Each trial from which the data was generated was a multi-center Phase II study conducted in China sponsored by Akeso, with data generated and analyzed by Akeso.
Results of Operations
Amounts reported in millions within this Quarterly Report on Form 10-Q are computed based on the amounts in thousands, and therefore, the sum of components may not equal the total amount reported in millions due to rounding.
The following table sets forth our results of operations for the three and nine months ended September 30, 2025 and 2024:
| Three Months Ended September 30, | Nine Months Ended September 30, | |||||||||||||||||||||||||||||||||||||
| (in millions) | 2025 | 2024 | $ Change | 2025 | 2024 |
$ Change
|
||||||||||||||||||||||||||||||||
| Operating expenses: | ||||||||||||||||||||||||||||||||||||||
| Research and development | $ | 131.1 | $ | 37.7 | $ | 93.4 | $ | 390.4 | $ | 99.4 | $ | 291.0 | ||||||||||||||||||||||||||
| Acquired in-process research and development | - | - | - | - | 15.0 | (15.0) | ||||||||||||||||||||||||||||||||
| General and administrative | 103.1 | 20.7 | 82.4 | 479.1 | 46.0 | 433.1 | ||||||||||||||||||||||||||||||||
| Total operating expenses | 234.2 | 58.4 | 175.8 | 869.5 | 160.4 | 709.1 | ||||||||||||||||||||||||||||||||
| Other income, net | 2.4 | 4.6 | (2.2) | 9.1 | 8.9 | 0.2 | ||||||||||||||||||||||||||||||||
| Interest expense | - | (2.5) | 2.5 | - | (8.7) | 8.7 | ||||||||||||||||||||||||||||||||
| Net loss | $ | (231.8) | $ | (56.3) | $ | (175.5) | $ | (860.4) | $ | (160.1) | $ | 700.3 | ||||||||||||||||||||||||||
Operating Expenses
Research and Development expenses
The table below summarizes our research and development expenses by category for the three and nine months ended September 30, 2025 and 2024, respectively.
| Three Months Ended September 30, | Nine Months Ended September 30, | |||||||||||||||||||||||||||||||||||||
| (in millions) | 2025 | 2024 | $ Change | 2025 | 2024 | $ Change | ||||||||||||||||||||||||||||||||
| Oncology | $ | 75.2 | $ | 23.0 | $ | 52.2 | $ | 179.4 | $ | 64.8 | $ | 114.6 | ||||||||||||||||||||||||||
| Acquired in-process research and development | - | - | - | - | 15.0 | (15.0) | ||||||||||||||||||||||||||||||||
| Compensation related costs, excluding stock-based compensation | 15.3 | 8.9 | 6.4 | 37.7 | 22.8 | 14.9 | ||||||||||||||||||||||||||||||||
| Stock-based compensation | 40.6 | 5.8 | 34.8 | 173.3 | 11.8 | 161.5 | ||||||||||||||||||||||||||||||||
| Total | $ | 131.1 | $ | 37.7 | $ | 93.4 | $ | 390.4 | $ | 114.4 | $ | 276.0 | ||||||||||||||||||||||||||
The entry into the License Agreement represents a significant change in our strategy from anti-infectives to the therapeutic area of oncology. We invested our resources in the clinical development of ivonescimab in the periods presented.
Oncology clinical trial related costs represent our investment in the clinical development of ivonescimab, known as SMT112 in the Licensed Territory.
Research and development expenses increased by $93.4 million and $276.0 million during the three and nine months ended September 30, 2025, compared to the same periods in the prior year. This increase was in part due to the increase in stock-based compensation expense of $34.8 million and $161.5 million for the three and nine months ended September 30, 2025, respectively, as a result of the modification to our performance-based stock option awards during the second quarter of 2025. In addition, our continued investment in oncology expenses for ivonescimab, known as SMT112 in our Licensed Territory, resulted in an increase of $52.2 million and $114.6 million for the three and nine months ended September 30, 2025, respectively, and an increase in compensation related costs of $6.4 million and $14.9 million, respectively, for the three and nine months ended September 30, 2025 to support the clinical development of ivonescimab as we continue to hire additional clinical resources in the oncology field. We expect oncology-related research and development costs to continue to increase as we progress with the development of ivonescimab.
In June 2024, we entered into a second amendment (the "Second Amendment") to the License Agreement with Akeso to expand our licensed territories to include Latin America, Middle East and Africa regions. Considered an extension of the original License Agreement, we agreed to make an upfront payment to Akeso in the amount of $15.0 million for these expanded territories which we paid in the third quarter of 2024. This was recorded in our unaudited condensed consolidated statement of operations and comprehensive loss as Acquired in process research and development expenses for the nine months ended September 30, 2024.
General and Administrative Expenses
The table below summarizes our general and administrative expenses by category for the three and nine months ended September 30, 2025 and 2024, respectively.
| Three Months Ended September 30, | Nine Months Ended September 30, | |||||||||||||||||||||||||||||||||||||
| (in millions) | 2025 | 2024 |
$ Change
|
2025 | 2024 |
$ Change
|
||||||||||||||||||||||||||||||||
| Compensation related costs, excluding stock-based compensation | $ | 6.2 | $ | 4.1 | $ | 2.1 | $ | 16.4 | $ | 10.1 | $ | 6.3 | ||||||||||||||||||||||||||
| Stock-based compensation | 90.2 | 13.6 | 76.6 | 447.4 | 28.2 | 419.2 | ||||||||||||||||||||||||||||||||
| Legal fees and professional services | 3.3 | (0.1) | 3.4 | 9.3 | 3.0 | 6.3 | ||||||||||||||||||||||||||||||||
| Other general and administrative expenses | 3.4 | 3.1 | 0.3 | 6.0 | 4.7 | 1.3 | ||||||||||||||||||||||||||||||||
| Total | $ | 103.1 | $ | 20.7 | $ | 82.4 | $ | 479.1 | $ | 46.0 | $ | 433.1 | ||||||||||||||||||||||||||
General and administrative expenses increased by $82.4 million and $433.1 million for the three and nine months ended September 30, 2025, respectively, compared to the same periods in the prior year. The increase was primarily due to the increase in stock-based compensation expense of $76.6 million and $419.2 million for the three and nine months ended September 30, 2025, respectively, as a result of the modification to our performance-based stock option awards during the second quarter of 2025. In addition, compensation related costs, excluding stock-based compensation, increased by $2.1 million and $6.3 million for the three and nine months ended September 30, 2025, respectively compared to the same periods in the prior year as the Company is focused on building its executive management team, and legal fees and professional services increased by $3.4 million and $6.3 million for the three and nine months ended September 30, 2025, respectively, compared to the same periods in the prior year to continue supporting the development of ivonescimab. We expect general and administrative expenses to continue to increase as we scale our infrastructure and management to support development of ivonescimab.
Other Income, net
The table below summarizes our other income by category for the three and nine months ended September 30, 2025 and 2024, respectively.
| Three Months Ended September 30, | Nine Months Ended September 30, | |||||||||||||||||||||||||||||||||||||
| (in millions) | 2025 | 2024 |
$ Change
|
2025 | 2024 |
$ Change
|
||||||||||||||||||||||||||||||||
| Foreign currency (loss) gain | $ | (0.4) | $ | 0.2 | $ | (0.6) | $ | (0.5) | $ | 0.2 | $ | (0.7) | ||||||||||||||||||||||||||
|
Investment income
|
2.8 | 4.3 | (1.5) | 9.6 | 8.7 | 0.9 | ||||||||||||||||||||||||||||||||
| Other income, net | $ | 2.4 | $ | 4.5 | $ | (2.1) | $ | 9.1 | $ | 8.9 | $ | 0.2 | ||||||||||||||||||||||||||
Other income, net decreased by $2.1 million in the three months ended September 30, 2025, compared to the same period in the prior year, primarily due to a decrease of $1.5 million in interest income due to lower cash and investments balance during three months ended September 30, 2025. For the nine months ended September 30, 2025, other income, net increased by $0.2 million, compared to the same period in the prior year, primarily due to an increase of $0.9 million in interest income due to higher yield on cash equivalents and short-term investments balance.
Interest Expense
Interest expense decrease for the three and nine months ended September 30, 2025 compared to the same period in the prior year, primarily due to the repayment in full of the promissory note in October 2024.
Liquidity, Capital Resources and Going Concern
During the three and nine months ended September 30, 2025, we incurred a net loss of $231.8 million and $860.4 million and cash flows used in operating activities for the nine months ended September 30, 2025 was $221.0 million. As of September 30, 2025, we had an accumulated deficit of $2,075.0 million, and cash and cash equivalents of $238.6 million. We expect to continue to generate operating losses for the foreseeable future.
Going Concern
Our cash and cash equivalents are not sufficient to fund our planned operations for a period of at least one year from the date these unaudited condensed consolidated financial statements are issued.
Until we can generate substantial revenue and achieve profitability, we will need to raise additional capital to fund our ongoing operations and capital needs. We continue to evaluate options to further finance our operating cash needs for our product candidates through a combination of some, or all, of the following: equity and debt offerings, collaborations, strategic alliances, grants and clinical trial support from government entities, philanthropic, non-government and not-for-profit organizations, and marketing, distribution or licensing arrangements. There is no assurance, however, that additional financing will be available when needed or that we will be able to obtain financing on terms acceptable to us. If we are unable to obtain funding when required in the future, we could be required to delay or reduce research and development programs, product portfolio expansion, or future commercialization efforts, which could adversely affect our business prospects. These conditions raise substantial doubt about our ability to continue as a going concern.
Sources of Liquidity
To date, we have financed our operations primarily through issuances of our common stock, including our most recent private placement issued in September 2024 for gross proceeds of $235.0 million and the raise of $76.8 million gross proceeds from our Distribution Agreement, issuance of debt, and receipt of payments to us under license, and collaboration arrangements.
We have devoted substantially all of our efforts to research and development, including clinical trials. We have not completed the development of any drugs. We expect to continue to incur significant expenses and increasing operating losses for at least the next few years. The net losses we incur may fluctuate significantly from quarter to quarter and year to year, due to the nature and timing of our research and development activities. We expect that our research and development and general and administrative expenses will continue to be significant in connection with our ongoing research and development efforts. In addition, if we obtain marketing approval for any of our product candidates in the United States or other jurisdictions where we retain commercial rights, and if we choose to retain those rights, we would expect to incur significant sales, marketing, distribution and outsourced manufacturing expenses, as well as ongoing research and development expenses. In addition, our expenses will increase if and as we:
•invest in clinical development of ivonescimab in our Licensed Territory;
•conduct research and continue development of additional product candidates;
•maintain and augment our intellectual property portfolio and opportunistically acquire complimentary intellectual property;
•seek further regulatory advancement for ivonescimab;
•invest in our manufacturing capabilities for ivonescimab and any other products for which we may obtain regulatory approval;
•seek marketing approvals for any product candidates that successfully complete clinical development;
•ultimately establish a sales, marketing and distribution infrastructure in jurisdictions where we have retained commercialization rights and scale up external manufacturing capabilities to commercialize any product candidates for which we receive marketing approval;
•perform our obligations under our collaboration agreements;
•pursue business development opportunities, including investing in other businesses, products and technologies;
•experience any delays or encounter any issues with any of the above, including but not limited to failed studies, complex results, safety issues or other regulatory challenges
•hire additional clinical, regulatory, scientific and administrative personnel;
•expand our physical presence;
•add operational, financial and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts; and
•borrow capital to fund our resources and have to pay interest expenses on such borrowings.
From time to time, we may raise additional equity or debt capital through both registered offerings off of a shelf registration, including ATM offerings, and private offerings of securities. On February 20, 2024, we filed a shelf registration statement on Form S-3 with the SEC, which the SEC declared effective on February 27, 2024. Through our shelf registration statement we may, from time to time, sell up to an aggregate of $450 million of our common stock, preferred stock, debt securities, depository shares, warrants, subscription rights, purchase contracts, or units. Of the $450 million of liquidity available to us under this shelf registration statement, on May 13, 2024, we had established an ATM offering program with J.P. Morgan Securities LLC, as sales agent, in the amount of up to $90.0 million.
On August 11, 2025, we entered into an amendment (the "Amendment") to the distribution agreement, which amended that certain distribution agreement, dated May 13, 2024, by and between us and sales agent (the "Original Distribution Agreement" and, as amended by the Amendment, the "Distribution Agreement"). Pursuant to the Amendment, the Original Distribution Agreement was amended to, among other things, increase the aggregate offering price of shares of the Company's common stock, par value $0.01 per share, from time to time, through the sales agent, by up to an additional $360.0 million. The remaining gross proceeds available under the Distribution Agreement as of September 30, 2025 was approximately $373.2 million.
In addition to the payments already made to Akeso under the License Agreement and Second Amendment, there are additional potential milestone payments of $4.56 billion, as Akeso will be eligible to receive regulatory milestones of up to $1.05 billion and commercial milestones of up to $3.51 billion. In addition, Akeso will be eligible to receive low double-digit royalties on net sales. Until we can generate substantial revenue and achieve profitability, we will need to raise additional capital to fund ongoing operations and capital needs, including the payment of the milestone payments referenced above.
We have based the foregoing estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect. This estimate assumes, among other things, that we do not obtain any additional funding through grants and clinical trial support or through new collaboration arrangements. Our future capital requirements will depend on many factors, including:
•the costs, timing and outcome of clinical trials required for clinical development of ivonescimab;
•the number and development requirements of other future product candidates that we pursue;
•the costs, timing and outcome of regulatory review of ivonescimab and/or our other product candidates we develop;
•the costs and timing of commercialization activities, including product sales, marketing, distribution and manufacturing, for any of our product candidates that receive marketing approval;
•the extent to which we become liable for milestone payments under the License Agreement and Second Amendment for ivonescimab;
•subject to receipt of marketing approval, revenue received from commercial sales of any product candidates;
•the costs and timing of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights and defending against any intellectual property-related claims;
•our ability to establish and maintain collaborations, licensing or other arrangements and the financial terms of such arrangements;
•the extent to which we acquire or invest in other businesses, products and technologies;
•the rate of the expansion of our physical presence; and
•the extent to which we change our physical presence.
We will need to seek additional funding in the future to fund operations. Additional capital, when needed, may not be available to us on acceptable terms, or at all. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our existing stockholders may be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing stockholders. Additional debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends or other distributions. If we raise additional funds through collaborations, strategic alliances or marketing, distribution, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us. As of the date of this Quarterly Report on Form 10-Q, additional capital has not been secured.
If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves, which could materially adversely affect our business, operating results and financial condition and our ability to continue operations.
Cash Flows
The following table summarizes our cash flows for the nine months ended September 30, 2025 and 2024:
| Nine Months Ended September 30, | ||||||||||||||
| (in millions) | 2025 | 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 | ||||||||||
Operating Activities
Net cash used in operating activities for the nine months ended September 30, 2025 was $221.0 million and primarily consisted of a net loss of $860.4 million and a $23.1 million net change in working capital, partially offset by non-cash charges of $616.3 million. The non-cash charges primarily consisted of $620.6 million of stock-based compensation driven by the modification to outstanding performance-based stock option awards which removed the performance-based vesting criteria, partially offset by $4.0 million relating to amortization of the discount on short-term investments in U.S. Treasury securities. The net change in working capital was primarily due to a $17.4 million increase in accounts payable, $7.4 million increase in accrued liabilities and a decrease of $3.7 million in prepaid expenses and other current assets, partially offset by an increase of $4.5 million in other assets and a decrease of $1.0 million in accrued compensation.
Net cash used in operating activities for the nine months ended September 30, 2024 was $93.4 million and was due to a net loss of $160.1 million, which included non-cash charges of $35.5 million, an adjustment of $15.0 million cash payments to investing activities, related to acquired-in process research and development for the upfront payment to Akeso for the Second Amendment signed in June 2024 and paid in the third quarter of 2024, and a net change in working capital of $16.2 million. The non-cash charges primarily consisted of $40.0 million of stock-based compensation, offset by $4.9 million relating to the amortization of the discount of short-term investments in U.S. Treasury securities. The net change in working capital was primarily due to an increase of $9.9 million in accrued liabilities, which mostly represents the interest on the current promissory notes payable, an increase of $2.5 million in accrued compensation relating to an increase in accrued bonuses, a decrease of $2.1 million in current and other long-term assets, a decrease of $0.7 million in research and development tax receivable to reflect a true-up in estimates, an increase of $0.5 million in accounts payable, and a decrease of $0.6 million in prepaid expenses.
Investing Activities
Net cash provided by investing activities for the nine months ended September 30, 2025 was $310.8 million and was primarily due to $311.3 million received from maturities of short-term investments in U.S. Treasury securities.
Net cash provided by investing activities for the nine months ended September 30, 2024 was $288.8 million and was primarily due to $256.9 million received from the maturity, redemption and sale of short-term investments in U.S. Treasury securities, offset by $530.5 million related to the purchase of short-term investments and a $15.0 million cash payment to Akeso for the Second Amendment signed in June 2024.
Financing Activities
Net cash provided by financing activities was $43.7 million for the nine months ended September 30, 2025, was due to $31.8 million net proceeds from our current Distribution Agreement, $7.3 million of proceeds received related to the exercise of warrants and $4.6 million of proceeds received related to employee stock awards and purchase plans.
Net cash provided by financing activities was $404.8 million for the nine months ended September 30, 2024, and primarily consisted of net proceeds of $435.0 million from various private placements, $43.0 million net proceeds from our Distribution Agreement, proceeds received of $2.2 million related to employee stock awards, partially offset by $75.5 million early principal repayment on the $100.0 million promissory notes payable with a related party.
Critical Accounting Policies and Significant Judgments and Estimates
Our management's discussion and analysis of our financial condition and results of operations are based on our unaudited condensed consolidated financial statements, which have been prepared in accordance with U.S. GAAP. The preparation of our financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, and expenses and the disclosure of contingent liabilities in our financial statements. On an ongoing basis, we evaluate our estimates and judgments, including those related to research and development expenses, stock-based compensation and income taxes. We base our estimates on historical experience, known trends and events, and various other factors that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.
Our significant accounting policies are described in Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations, and in Critical Accounting Policies and Significant Judgments and Estimates in our Annual Report. There have been no material changes to our critical accounting policies and estimates that were disclosed in our Annual Report.
Except as set forth in Note 13, Commitments and Contingencies, to our unaudited condensed consolidated financial statements included in this Quarterly Report on Form 10-Q, there have been no material changes from the contractual obligations and commitments as of December 31, 2024 previously disclosed in our Annual Report on Form 10-K filed with the SEC on February 24, 2025.
We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined in the rules and regulations of the SEC.
Recently Issued Accounting Pronouncements
For a discussion of recently issued accounting pronouncements, refer to Note 2, Summary of Significant Accounting Policies and Recent Accounting Pronouncements, to our unaudited condensed consolidated financial statements included in this Quarterly Report on Form 10-Q.
Summit Therapeutics Inc. published this content on October 20, 2025, and is solely responsible for the information contained herein. Distributed via Edgar on October 20, 2025 at 11:52 UTC. If you believe the information included in the content is inaccurate or outdated and requires editing or removal, please contact us at [email protected]