Ivonescimab Plus Chemotherapy Demonstrates Consistent Global Benefit: HARMONi Data Update Shows OS HR=0.78, Nominal P=0.0332

• The overall survival (OS) hazard ratio (HR) in the HARMONi trial was 0.78, with a nominal p-value of 0.0332
• In the North American patients, the OS HR was 0.70
• The HARMONi trial has already demonstrated clinically meaningful and statistically significant progression-free survival (PFS) outcomes
• In the HARMONi trial, clinical endpoint benefits, including OS and PFS, were consistent across Western and Asian patient populations, and these results were also in alignment with the clinical data from the HARMONi-A trial conducted in China

HONG KONG, Sept. 7, 2025 /PRNewswire/ -- Akeso, Inc. (HKEX: 9926.HK) is pleased to share today that its global partner, Summit Therapeutics Inc. (NASDAQ: SMMT), announced the updated overall survival (OS) results from the global Phase III HARMONi clinical trial of ivonescimab, a novel PD-1/VEGF bispecific antibody, at the Presidential Symposium in the 2025 World Conference on Lung Cancer (WCLC).

Longer-term follow-up of western patients showed improving, favorable trend in OS, yielding a hazard ratio (HR) of 0.78 and a nominal p-value of 0.0332.

Meanwhile, Akeso recently announced that the HARMONi-A study conducted in China has also recently reached the OS clinical endpoint, achieving clinically meaningful and statistically significant OS benefit. The OS data from this study will be presented at upcoming academic conferences.

The results from the first international multi-center Phase III HARMONi study of ivonescimab, along with those from the Phase III HARMONi-A study conducted in China, demonstrated consistent and robust clinical efficacy in both progression-free survival (PFS) and OS. These findings provide strong evidence that ivonescimab not only offers significant advantages in terms of rapid onset of action and effective disease control in cancer treatments but also provide survival benefits to patients. The data further support ivonescimab's consistent efficacy and safety across diverse global populations, including both international and Chinese cohorts, reinforcing its potential for broad therapeutic benefit for cancer patients worldwide.

Approximately 38% of patients were recruited from western countries.

The trial results were presented by Jonathan Goldman, MD, Professor of Medicine at UCLA in the Hematology/Oncology Division, UCLA Director of Clinical Trials in Thoracic Oncology, Associate Director of Early Drug Development, and Chair of University of California Lung Cancer Consortium.

Clinically Meaningful Efficacy

As previously disclosed, ivonescimab in combination with chemotherapy showed a positive trend in 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). The statistical analysis plan for the study required a p-value of 0.0448 in order to achieve statistical significance at the time of the primary analysis of overall survival. Median overall survival was 16.8 months for those patients administered ivonescimab plus chemotherapy vs. 14.0 months for those receiving placebo plus chemotherapy. It was noted at the time of the primary analysis that the median follow-up time for western patients was 9.2 months and less than the median overall survival at the time of the primary analysis, and these patients may continue to be followed for long-term outcomes.

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.

As previously disclosed at the prespecified primary data analysis for PFS, ivonescimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement 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. Median PFS for ivonescimab vs. placebo plus chemotherapy was 6.8 months vs. 4.4 months, respectively. The PFS analysis was event driven and was conducted with 345 patients enrolled. There was a consistent observed benefit 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, clinically meaningful 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.

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)

Ivonescimab demonstrated a favorable safety and tolerability profile with no new safety signals identified. The safety results from the HARMONi study were consistent with those observed in the HARMONi-A trial.

Ivonescimab has shown positive results in the HARMONi-2 trial, a randomized, double-blind, head-to-head Phase III study against pembrolizumab monotherapy, which led to its approval for first-line treatment of PD-L1-positive NSCLC (its second approved indication). Besides that, ivonescimab plus chemotherapy has now also demonstrated significant positive outcomes in another head-to-head Phase III study against tislelizumab plus chemotherapy in first-line squamous NSCLC. This clinical outcome demonstrates that ivonescimab shows significant clinical breakthroughs, whether compared to PD-1 monotherapy, or compared to PD-1 in combination with chemotherapy (the optimal standard of care for many cancer treatments), or compared to VEGF-related therapies in the area of anti-angiogenesis. This highlights the remarkable capability of ivonescimab to make leapfrog advancements in cancer treatment.

Ivonescimab continues to validate its clinically meaningful profile and potential with a strategically expanded development program targeting key immuno-oncology settings:

Phase III trials for Lung cancer (8 registrational/Phase III trials, 4 already met primary endpoints):

• First-line NSCLC, squamous and non-squamous (versus pembrolizumab + chemotherapy; global trial)
• First-line squamous NSCLC (versus tislelizumab + chemotherapy)
• NSCLC after progression on EGFR-TKI therapy (HARMONi-A and HARMONi studies)
• First-line PD-L1-positive NSCLC (versus pembrolizumab monotherapy)
• First-line PD-L1-high expressing NSCLC (versus pembrolizumab)
• IO-resistant NSCLC
• Consolidation therapy for limited-stage small cell lung cancer (LS-SCLC) without progression after concurrent chemoradiotherapy (cCRT)

Phase III trials for core immuno-oncology indications (first-line therapy):

• First-line biliary tract cancer (versus durvalumab + chemotherapy)
• First-line PD-L1-positive head and neck squamous cell carcinoma (HNSCC) in combination with ligufalimab (anti-CD47) versus pembrolizumab

Phase III trials for cold tumors and more：

• First-line triple-negative breast cancer (TNBC)
• First-line MSS/pMMR colorectal cancer (representing about 95% of CRC cases)
• First-line pancreatic cancer
• Additional global Phase III trials are in advanced stages of planning

An extensive clinical foundation includes over 20 Phase II studies across more than 10 additional tumor types, generating compelling efficacy and safety data to enable rapid transition to further registrational studies worldwide.

Ivonescimab uniquely targets both PD-1 and VEGF, producing a synergistic anti-tumor effect. This dual mechanism not only combines the benefits of PD-1 and VEGF inhibition but also overcomes the efficacy and safety limitations of each target alone, resulting in pronounced clinical benefits. These advantages have been confirmed across multiple Phase III trials and real-world use, rapidly establishing ivonescimab as a next-generation leader in immunotherapy and anti-angiogenic therapy.

Akeso is implementing a dual-path strategy to maximize the value of ivonescimab world wide: accelerating domestic commercialization and label expansion in China, while simultaneously advancing global development in partnership with Summit Therapeutics.

Forward-Looking Statement of Akeso, Inc.

This announcement by Akeso, Inc. (9926.HK, "Akeso") contains "forward-looking statements". These statements reflect the current beliefs and expectations of Akeso's management and are subject to significant risks and uncertainties. These statements are not intended to form the basis of any investment decision or any decision to purchase securities of Akeso. There can be no assurance that the drug candidate(s) indicated in this announcement or Akeso's other pipeline candidates will obtain the required regulatory approvals or achieve commercial success. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in P.R.China, the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Akeso's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Akeso's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Akeso does not undertake any obligation to publicly revise these forward-looking statements to reflect events or circumstances after the date hereof, except as required by law.

About Akeso

Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research, development, manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012, the company has created a unique integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the core, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode, and has gradually developed into a globally competitive biopharmaceutical company focused on innovative solutions. With fully integrated multi-functional platform, Akeso is internally working on a robust pipeline of over 50 innovative assets in the fields of cancer, autoimmune disease, inflammation, metabolic disease and other major diseases. Among them, 24 candidates have entered clinical trials (including 15 bispecific/multispecific antibodies and bispecific ADCs. Additionally, 7 new drugs are commercially available. Through efficient and breakthrough R&D innovation, Akeso always integrates superior global resources, develops the first-in-class and best-in-class new drugs, provides affordable therapeutic antibodies for patients worldwide, and continuously creates more commercial and social values to become a global leading biopharmaceutical enterprise.

For more information, please visit https://www.akesobio.com/en/about-us/corporate-profile/ and follow us on Linkedin.

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