Summit Therapeutics (NASDAQ:SMMT) executives used the company’s Q4 and year-end 2025 earnings call to highlight continued clinical progress for ivonescimab, a PD-1/VEGF bispecific antibody, and to outline near-term trial milestones and commercialization preparations ahead of an FDA decision on its first U.S. biologics license application (BLA).
HARMONi-3 amended to add interim PFS analysis for squamous cohort
Management’s most detailed update centered on the company’s ongoing HARMONi-3 Phase III study evaluating ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy in first-line metastatic non-small cell lung cancer (NSCLC). The trial was previously amended to separate analyses by squamous and non-squamous histology, with primary endpoints of progression-free survival (PFS) and overall survival (OS) in each cohort.
On the call, executives explained the rationale for adding the interim analysis as a way to potentially accelerate regulatory discussions by generating primary-endpoint data earlier. They tied the decision to prior interim PFS readouts from Akeso-sponsored Phase III studies in China, including HARMONi-2 (ivonescimab vs. pembrolizumab in PD-L1-positive frontline NSCLC) and HARMONi-6 (ivonescimab plus chemotherapy vs. a PD-1 inhibitor plus chemotherapy). Summit emphasized that timing expectations for the squamous cohort’s final PFS analysis and an interim OS analysis remain in the second half of 2026.
For the non-squamous cohort, Summit maintained its expectation to complete enrollment in the second half of 2026 and to reach the pre-specified number of events for final PFS analysis by the first half of 2027.
New cooperative group Phase III head and neck study announced
Summit also announced ILLUMINE, a new Phase III trial in PD-L1-positive frontline head and neck squamous cell carcinoma sponsored by GORTEC, a French cooperative group. Initial enrollment is expected to begin early next quarter, and the study is intended to enroll approximately 780 patients across multiple countries in Europe and in China, with Summit noting it may consider expanding to U.S. sites.
The three-arm randomized study is intended to compare:
- ivonescimab monotherapy,
- ivonescimab in combination with ligufalimab (Akeso’s proprietary anti-CD47 monoclonal antibody), and
- pembrolizumab monotherapy.
Management pointed to Phase II data previously presented at ESMO 2024 in which ivonescimab plus ligufalimab showed a 60% objective response rate in 20 patients, with median PFS of 7.1 months after a median follow-up of 4.1 months, and no treatment discontinuations due to treatment-related adverse events at the time of that analysis. During Q&A, executives said the three-arm design is intended to help answer questions about “contribution of components” between ivonescimab alone and the combination versus pembrolizumab.
Combination strategy expands with Revolution Medicines and GSK collaborations
Summit said the first patient has been dosed in its clinical collaboration with Revolution Medicines. Under the collaboration, ivonescimab is being evaluated with three RAS(ON) inhibitors—daraxonrasib, zoldonrasib (KRAS G12D), and elironrasib (KRAS G12C)—across multiple solid tumor settings with RAS mutations, including pancreatic cancer, colorectal cancer, and NSCLC.
The company also reiterated a recently announced collaboration with GSK to evaluate ivonescimab in combination with GSK’s B7-H3 antibody-drug conjugate in multiple solid tumors. Management said the initial study under this collaboration is expected to begin dosing patients in mid-2026 and referenced small cell lung cancer as one of the settings previously discussed.
Regulatory pathway: BLA accepted with November 2026 PDUFA date
Summit reiterated that it submitted a BLA for ivonescimab last quarter for EGFR-mutant NSCLC after TKI therapy based on the company’s global Phase III HARMONi study, and that the FDA accepted the filing in January with a PDUFA target action date of November 14, 2026.
Executives again noted the FDA’s stated position that a statistically significant OS benefit is necessary to support marketing authorization in this setting. Summit discussed its view that the HARMONi results were “regionally consistent” and referenced additional follow-up analyses previously disclosed, including an OS hazard ratio of 0.78 with a nominal p-value of 0.0332 in a September 2025 analysis of Western patients. During Q&A, management said it submitted the full package for FDA review and that the agency is now reviewing the data.
Financial update: year-end cash, spending trends, and manufacturing readiness
Chief Operating Officer and Chief Financial Officer Manmeet Soni said Summit ended 2025 with “approximately $713 and $13.4 million” in cash and noted the company currently has no debt. (The cash figure was stated as delivered on the call.)
For Q4 2025, Summit reported:
- Total GAAP operating expenses of $225 million, down from $234.2 million in Q3, driven primarily by lower stock-based compensation expense of $19.1 million, partially offset by an $8.8 million increase in clinical trial-related spend.
- Non-GAAP operating expenses (excluding stock-based compensation) of $113.3 million, up from $103.4 million in Q3, primarily due to increased R&D spending related to HARMONi-3 and HARMONi-7.
Soni added that G&A spending has been “efficient and disciplined,” with total G&A excluding stock-based compensation of about $43 million for full-year 2025, implying a quarterly run rate of roughly $10 million to $11 million.
Operationally, the company said it accelerated enrollment of 600 squamous patients in HARMONi-3 ahead of plan, enabling the planned Q2 2026 interim analysis. Summit also said it has “successfully transferred and validated” ivonescimab production to a U.S.-based manufacturer as part of manufacturing and supply readiness, and that it is ramping commercial readiness efforts in anticipation of a potential EGFR-mutant NSCLC launch following the PDUFA date.
In closing remarks, Chairman and Co-CEO Robert Duggan emphasized Summit’s respect for the FDA and praised partner Akeso, which he said holds an ownership stake in Summit and has advanced ivonescimab through multiple Phase III readouts and approvals in China.
About Summit Therapeutics (NASDAQ:SMMT)
Summit Therapeutics plc is a clinical?stage biotechnology company dedicated to the discovery and development of precision medicines for serious and life?threatening diseases. The company applies a targeted approach to drug design, focusing on novel mechanisms of action that differentiate its candidates from existing therapies.
Summit’s lead asset, ridinilazole (formerly SMT19969), is being developed to treat Clostridioides difficile infections and has received both Fast Track and Qualified Infectious Disease Product designations from the U.S.
