Ivonescimab Plus Chemotherapy Demonstrates a Statistically Significant Benefit in Overall Survival with a Hazard Ratio of 0.74 in 2L+ Treatment of Patients with EGFRm NSCLC in HARMONi-A Study Conducted by Akeso in China

The First Phase III Study Testing Ivonescimab Now Represents the First Statistically Significant OS Benefit Achieved by an Ivonescimab-Containing Regimen

Ivonescimab Plus Chemotherapy Demonstrates Median OS of 16.8 Months vs. 14.1 Months, Respectively, for Patients Receiving Ivonescimab Plus Chemotherapy vs. Chemotherapy Alone; OS HR of 0.74 (p=0.019)

Favorable Risk-Benefit Profile Observed in This Phase III Study

MIAMI--(BUSINESS WIRE)-- Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the “Company”) today noted that our partner, Akeso, Inc. (“Akeso,” HKEX Code: 9926.HK) published results from the Phase III HARMONi-A trial, conducted in China and sponsored by Akeso, featuring the novel, potential first-in-class investigational bispecific antibody, ivonescimab. The data was presented today as part of the Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2025) in National Harbor, Maryland (Washington D.C. metro area).

The HARMONi-A presentation, Final Overall Survival Analysis of HARMONi-A Study Comparing Ivonescimab Plus Chemotherapy to Chemotherapy Alone in Patients With EGFR+ NSCLC Progressed on EGFR-TKI Treatment, evaluated ivonescimab combined with platinum-doublet chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed after treatment with an EGFR tyrosine kinase inhibitor (TKI) against placebo plus platinum-doublet chemotherapy. This is a clinical setting with a patient population where PD-1 monoclonal antibodies have previously been unsuccessful in Phase III global clinical trials. HARMONi-A was the first Phase III study conducted with ivonescimab and now represents the first statistically significant overall survival (OS) benefit achieved by an ivonescimab regimen over a standard of care regimen.

HARMONi-A was a single region, multi-center, Phase III study conducted in China sponsored by Akeso with data generated and analyzed by Akeso. Via the results of HARMONi-A, this setting was the first of two settings which were approved by the National Medical Products Administration (NMPA), the health authority in China. In China, over 40,000 patients have been treated with ivonescimab in either a clinical or commercial setting.

In the only planned and final OS analysis of the HARMONi-A study, ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement when compared with chemotherapy alone, achieving a hazard ratio (HR) of 0.74 (95% CI: 0.58, 0.95, p=0.019). Median OS was 16.8 months (95% CI: 14.5, 20.0) in patients treated with ivonescimab plus chemotherapy compared to 14.1 months (95% CI: 12.8, 16.3) for those treated with chemotherapy alone. The data cut-off for this analysis was April 2025 with a median follow-up time of 32.5 months.

As a reminder, in May 2024, Akeso announced the approval of ivonescimab plus chemotherapy in this setting based on the results of the HARMONi-A study, which had a primary endpoint of progression-free survival. Shortly before the approval, the National Medical Products Administration (NMPA), the health authority in China, requested an administrative review of overall survival. This review of overall survival at 52% data maturity and a data cutoff of December 2023 noted a hazard ratio of 0.80 (95% CI: 0.59, 1.08).

“The overall survival results of the HARMONi-A study evidence the ability of ivonescimab to demonstrate an overall survival benefit in patients facing high unmet medical needs,” noted Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit. “This study counters the notion that testing molecules with anti-VEGF components leads to worsening OS over time. The improvement in OS with longer follow-up time and the statistically significant benefit in the HARMONi-A study provides clear differentiation in the unique mechanism of action of ivonescimab as compared to other agents available for patients today. The specifically engineered design of ivonescimab has produced four positive Phase III studies after four Phase III readouts, leading to over 40,000 patients receiving ivonescimab when considering the commercial setting in China. Ivonescimab has the potential to make a significant difference in the lives of patients facing cancer diagnoses.”

Ivonescimab continues to demonstrate an acceptable and manageable safety profile in the HARMONi-A study with this additional follow-up time, which was consistent with previous Phase III studies conducted studying ivonescimab and evidencing a favorable benefit-risk profile for ivonescimab plus chemotherapy in this setting.

At the time of the final overall survival analysis for HARMONi-A, there were 18 patients (11.2%) who discontinued ivonescimab plus chemotherapy due to treatment-related adverse events (TRAEs) compared to 10 patients (6.2%) who discontinued chemotherapy alone due to TRAEs. In both the ivonescimab plus chemotherapy arm and the chemotherapy alone arm, one patient (0.6%) each died as a result of TRAEs in this Phase III study. Excluding disease progression, there were no deaths as a result of TRAEs in the ivonescimab plus chemotherapy arm compared to one patient (0.6%) in the placebo plus chemotherapy arm. The most frequent TRAEs for ivonescimab treatment in combination with chemotherapy were common chemotherapy-related AEs, including decreased white blood cell count, anemia, and other various laboratory abnormalities, including neutrophil and platelet count decreases.

“Today’s results highlight and support ivonescimab’s differentiated efficacy and tolerability profile, and its ability to produce positive outcomes where PD-1 therapies have not shown a benefit in previous Phase III studies,” stated Robert W. Duggan, Chairman and Co-Chief Executive Officer at Summit. “Today, the current landscape includes limited options for patients after TKI therapy. The safety profile demonstrated by ivonescimab in combination with chemotherapy, both in HARMONi-A and across the four positive Phase III study readouts, is both manageable and provides compelling evidence as to the benefit-risk profile of ivonescimab for patients seeking effective therapy while minimizing quality of life-impacting adverse events. We congratulate our partners at Akeso for these outstanding results, as the first Phase III study conducted testing ivonescimab also represents the first study demonstrating a statistically significant OS benefit, highlighting the impact ivonescimab may bring to patients around the globe facing malignancies with limited treatment options today.”

Summit is sponsoring the HARMONi study, which is the first multiregional, double-blinded, placebo-controlled, Phase III study evaluating ivonescimab. HARMONi is studying ivonescimab plus platinum-doublet chemotherapy compared to placebo plus platinum-doublet chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have previously received a third generation EGFR TKI.

HARMONi was designed with two primary endpoints, PFS and OS. In the primary analyses of the HARMONi study, ivonescimab plus chemotherapy demonstrated a statistically significant PFS benefit with a hazard ratio of 0.52 (95% CI: 0.41 – 0.66; p

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