Summit Therapeutics Announces Q3 and Nine-Month 2025 Financial Results and Operational Updates

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10/20/2025 – 06:45 AM

Summit Plans to Submit a BLA in Q4 2025 for Ivonescimab Based on HARMONi Global Phase III Study Results

Expansion of Summit’s Global Phase III Development Program Starts with Initiation of HARMONi-GI3, a New Study in 1L CRC: Summit to Initiate an Additional Set of Phase III Clinical Trials with Details to Come in Q1 2026

Ivonescimab with Chemotherapy Reduces the Risk of Disease Progression or Death by 48% Compared to Chemotherapy Alone in Global Phase III HARMONi Trial Evaluating Patients with EGFRm NSCLC after EGFR TKI Therapy with Consistent Data across Regions

Ivonescimab with Chemotherapy Reduced the Risk of Disease Progression or Death by 40%, Median PFS of 11.14 Months, Compared to Tislelizumab (PD-1 Inhibitor) Plus Chemotherapy, Median PFS 6.90 Months, in 1L Treatment of Patients with Squamous NSCLC in Phase III HARMONi-6 Study Conducted by Akeso in China

HARMONi-3 Global Phase III Study Analyses Will Be Split by Histology: Squamous NSCLC Cohort Expected to Complete Enrollment First Half of 2026 with Data Readout Expected Second Half 2026; Non-Squamous NSCLC Cohort Expected to Complete Enrollment Second Half of 2026

MIAMI — Summit Therapeutics Inc. (SMMT) is making significant strides in its oncology pipeline, specifically with its bispecific antibody, ivonescimab. The company announced plans to submit a Biologics License Application (BLA) to the FDA in the fourth quarter of 2025 for ivonescimab combined with chemotherapy as a treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI).

This decision follows compelling results from the global Phase III HARMONi trial, which demonstrated a statistically significant improvement in progression-free survival (PFS) in patients receiving the ivonescimab regimen. While the overall survival (OS) benefit did not reach statistical significance in the primary analysis, a positive trend was observed, and longer-term follow-up data in Western patients showed an improved nominal p-value.

Strategic Expansion of Clinical Development

Beyond the planned BLA submission, Summit is strategically expanding its ivonescimab clinical development program. The company will initiate HARMONi-GI3, a new global Phase III study in first-line unresectable metastatic colorectal cancer (CRC). Furthermore, Summit intends to unveil plans for an additional set of Phase III clinical studies in the first quarter of 2026, signaling a robust commitment to exploring ivonescimab’s potential across various cancer types. This expansion illustrates a broader strategy to leverage ivonescimab’s unique mechanism of action beyond NSCLC.

Ivonescimab’s Efficacy and Safety Profile

The HARMONi trial results highlighted a 48% reduction in the risk of disease progression or death with ivonescimab plus chemotherapy compared to chemotherapy alone. Moreover, in the Akeso-conducted HARMONi-6 study in China, ivonescimab combined with chemotherapy demonstrated a 40% reduction in the risk of disease progression or death compared to tislelizumab (a PD-1 inhibitor) plus chemotherapy in first-line squamous NSCLC. The median PFS was 11.14 months for the ivonescimab arm versus 6.90 months for the tislelizumab arm.

Notably, the safety profile of ivonescimab in combination with chemotherapy was deemed acceptable and manageable, with comparable rates of discontinuation and death between the treatment arms. This is a crucial factor for regulatory approval and market adoption.

HARMONi-3 Study Amendment

Summit has amended the protocol for the HARMONi-3 Phase III clinical trial, which is evaluating ivonescimab plus chemotherapy versus pembrolizumab (another PD-1 inhibitor) plus chemotherapy in first-line metastatic NSCLC. The statistical analysis of the primary endpoints (PFS and OS) will now be separated by histology (squamous versus non-squamous NSCLC). This strategic adjustment will allow for more precise data analysis and potentially faster data readouts for each cohort. The squamous NSCLC cohort is expected to complete enrollment in the first half of 2026, with data readout expected in the second half of 2026.

• Since in-licensing ivonescimab (SMT112), from Akeso Inc. (Akeso, HKEX Code: 9926.HK) in January 2023, over 3,000 patients have been treated with ivonescimab in clinical studies globally, and over 40,000 patients when considering those treated in a commercial setting in China as noted by Akeso. Summit has rights to develop and commercialize ivonescimab in the United States, Canada, Europe, Japan, Latin America, including Mexico and all countries in Central America, South America, and the Caribbean, the Middle East, and Africa while Akeso retains development and commercialization rights for the rest of the world, including China.

• Summit is developing ivonescimab in NSCLC, specifically conducting Phase III clinical trials in the following proposed indications:
  • HARMONi: Ivonescimab combined with chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR tyrosine kinase inhibitor (TKI)

  • HARMONi-3: Ivonescimab combined with chemotherapy in patients with first-line metastatic NSCLC

  • HARMONi-7: Ivonescimab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression

• In addition, Summit plans to start developing ivonescimab in CRC with an intention to begin a Phase III clinical study in the following proposed indication:
  • HARMONi-GI3: ivonescimab combined with chemotherapy in patients with first-line metastatic CRC

Financial Position

Summit reported its third-quarter 2025 financial results, highlighting a decrease in cash and cash equivalents and short-term investments to $238.6 million as of September 30, 2025, compared to $412.3 million at the end of 2024. This decrease is attributable to the expansion of its clinical development programs.

GAAP operating expenses for the third quarter were $234.2 million, a significant increase from $58.4 million in the same period last year. This surge was primarily due to a $111.4 million increase in stock-based compensation expense related to modifications in performance-based stock option awards.

Non-GAAP operating expenses for the third quarter were $103.4 million, up from $39.0 million in the prior year, reflecting the growth in clinical studies and development costs for ivonescimab.

Summit’s strategic focus on ivonescimab, coupled with its ongoing clinical trials and planned BLA submission, position the company as a key player in the evolving oncology landscape. The expansion into CRC and the refined approach to the HARMONi-3 study signal a data-driven strategy with potential for significant clinical and commercial impact.

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al., SITC, 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al., SITC, 2023) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.