Two Ivonescimab (PD-1/VEGF) Results including Phase 3 Monotherapy versus Pembrolizumab Monotherapy in First-Line Treatment for PD-L1 Positive NSCLC to Be Presented at WCLC 2024

Rhea-AI Summary

Akeso, Inc. (HKEX: 9926.HK) announced two upcoming oral presentations of ivonescimab (PD-1/VEGF bispecific antibody) at the IASLC 2024 World Conference on Lung Cancer (WCLC24). A key presentation will feature results from the HARMONi-2/AK112-303 study, comparing ivonescimab monotherapy to pembrolizumab in patients with PD-L1 positive non-small cell lung cancer (NSCLC).

Ivonescimab has shown significant milestones, including:

• Marketing approval for EGFR-mutated NSCLC treatment in May 2024
• Statistically significant improvement in progression-free survival compared to pembrolizumab
• Acceptance of supplemental New Drug Application by China NMPA for first-line treatment of PD-L1 positive NSCLC

These developments position ivonescimab as a promising treatment option in the field of lung cancer therapy.

Positive

• Ivonescimab received marketing approval for EGFR-mutated NSCLC treatment in May 2024
• Ivonescimab showed statistically significant improvement in progression-free survival compared to pembrolizumab in a Phase III trial
• Supplemental New Drug Application for ivonescimab as first-line treatment for PD-L1 positive NSCLC accepted by China NMPA with priority review
• Strategic collaboration agreement with MD Anderson Cancer Center to accelerate development in various cancer types

Negative

• None.

Oncology Researcher

This announcement is a significant milestone for Akeso's ivonescimab. The head-to-head Phase III trial against pembrolizumab, a standard-of-care immunotherapy, in first-line NSCLC treatment is groundbreaking. Achieving statistically significant and clinically meaningful improvement in PFS over pembrolizumab is unprecedented and could potentially reshape the NSCLC treatment landscape.

The upcoming presentation at WCLC 2024 will likely provide important details on efficacy and safety profiles. Of particular interest will be the hazard ratio, which was reported as "significantly better than expected." This could indicate a substantial improvement in patient outcomes. The study's focus on PD-L1 positive patients aligns with current trends in precision oncology, potentially offering a more targeted approach to NSCLC treatment.

Pharmaceutical Industry Analyst

Ivonescimab's progress represents a potential market disruption in the lucrative NSCLC space. As the world's first approved PD-1/VEGF bispecific antibody, it offers a novel mechanism of action that could capture significant market share. The recent marketing approval for EGFR-mutated NSCLC and the priority review status for the new indication underscore regulatory confidence and could accelerate market penetration.

The collaboration with MD Anderson Cancer Center expands ivonescimab's potential beyond lung cancer, possibly into renal cell carcinoma, colorectal, skin and breast cancers. This diversification strategy could significantly enhance the drug's commercial prospects. Investors should closely monitor the full data release, as positive results could catalyze Akeso's stock performance and potentially impact competitors in the immuno-oncology space.

Medical Research Analyst

The HARMONi-2 study's design, comparing ivonescimab monotherapy to pembrolizumab monotherapy, is particularly intriguing. This approach allows for a clear assessment of ivonescimab's efficacy without the confounding effects of combination therapy. The focus on PD-L1 positive patients (TPS ≥1%) is broader than some recent trials, which have focused on higher PD-L1 expression levels.

The additional Phase 2 study on perioperative use in resectable NSCLC is also noteworthy. If successful, this could expand ivonescimab's utility across different stages of NSCLC treatment. The bispecific nature of ivonescimab, targeting both PD-1 and VEGF, represents an innovative approach that could potentially offer superior efficacy by simultaneously addressing two critical pathways in cancer progression.

• First Release of Phase III Head-to-Head Clinical Study Data of Ivonescimab versus Pembrolizumab in NSCLC
  
• Ivonescimab Is the First Drug to Achieve Clinically Meaningful Benefit over Pembrolizumab in a Randomized Phase III Clinical Trial in NSCLC

HONG KONG, Aug. 11, 2024 /PRNewswire/ -- Akeso, Inc. (HKEX: 9926.HK) ("Akeso,") today announced two upcoming oral presentations of ivonescimab (PD-1/VEGF bispecific antibody) at the IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer ("WCLC24"), taking place in San Diego, USA from September 7-10, 2024. Among these is a late-breaking Presidential Symposium presentation featuring results from the HARMONi-2/AK112-303 study, which evaluated monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression (PD-L1 TPS ≥1%).

The late-breaking result of HARMONi-2/AK112-303 will be presented by Professor Zhou Caicun, the principal investigator of HARMONi-2 and director in the Department of Medical Oncology at Shanghai Pulmonary Hospital, Tongji University.

Presentations during WCLC 2024

Abstract Title	Presentation Details
Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment for PD-L1-positive Advanced NSCLC: Primary Analysis of HARMONi-2	Session: PL02 Presidential Symposium 1 (LIVESTREAMED) Form: Plenary oral Presenter: Caicun Zhou, MD. Ph.D, China Shanghai Pulmonary Hospital Abstract release time: embargoed until the presentation day
A Phase 2 Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer	Session: Perioperative Strategies 1—Early-Stage Non-Small Cell Lung Cancer Sunday, September 8, 2024, 11:17 AM-11:27 AM Form: Oral Presenter: Xiaoliang Zhao, MD, China Tianjin Medical University Cancer Institute & Hospital Abstract release time: August 14, 2024

Akeso will also participate as an exhibitor, actively engaging with professionals from diverse fields.

Milestones of ivonescimab:

May 2024:
Ivonescimab was granted marketing approval for the treatment of epidermal growth factor receptor ("EGFR") mutated locally advanced or metastatic non-squamous non-small cell lung cancer ("nsq-NSCLC"), making it the world's first approved PD-1/VEGF bi-specific antibody.

May 31:
At a prespecified interim analysis conducted by an independent Data Monitoring Committee, ivonescimab demonstrated a statistically significant and clinically meaningful improvement in PFS by blinded independent radiology review committee (BICR) compared to pembrolizumab, and the hazard ratio (HR) was significantly better than expected. There are no known Phase III clinical trials in NSCLC which have shown a statistically significant improvement compared to pembrolizumab in a head-to-head setting.

June 01:
Interim result of the Phase III study of ivonescimab combined with platinum-doublet chemotherapy in patients with  EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR-TKIs treatment (HARMONi-A ), was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, and the study was ranked as the top report on the TOP 10 list of lung cancer at ASCO by OncoAlert, an international cancer support organization. On the same day, the research findings were also published simultaneously in the JAMA journal.

July 25:
Akeso's partner, Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit,") announced a strategic five-year collaboration agreement with The University of Texas MD Anderson Cancer Center (MD Anderson) for the purpose of accelerating the development in certain types of renal cell carcinoma, colorectal cancer, skin cancer, and breast cancer.

July 29:
The supplemental New Drug Application (sNDA) for ivonescimab as a monotherapy for first-line treatment of PD-L1 positive (PD-L1 TPS≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC), has been accepted by the China National Medical Products Administration (NMPA). This new indication application for ivonescimab is based on the HARMONi-2 (AK112-303) study.

August 02:
The supplemental New Drug Application (sNDA) for ivonescimab monotherapy for first-line treatment of PD-L1 positive (PD-L1 TPS≥1%) locally advanced or metastatic NSCLC was accepted by China NMPA with priority review.

About Ivonescimab (AK112/SMT112)
Ivonescimab is a novel global first-in-class PD-1/VEGF bi-specific immunotherapy drug independently developed by Akeso. Ivonescimab is known as SMT112 in Summit Therapeutics' license territories, including the United States, Canada, Europe, Japan, Central America, South America, the Middle East and Africa. Ivonescimab was granted marketing approval by NMPA for the treatment of EGFR mutated locally advanced or metastatic non-squamous NSCLC patients who have progressed after EGFR TKI treatment. Currently, ivonescimab's first indication has been approved in China, and Akeso is conducting 5 Phase III trials including 2 global MRCTs and 4 registrational trials versus anti-PD-1 therapeutics. The Company is also conducting multiple clinical trials of ivonescimab covering 16 indications including gastrointestinal cancer, hepatocellular carcinoma and colorectal cancer.

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, with 19 drug candidates in the clinical stage, including 8 multispecific antibodies. Akeso has successfully promoted the commercialization of three innovative biological drugs, and marketing applications of multiple indications are submitted for 4 new drugs. 安尼可®, approved for marketing in August 2021, is currently the only differentiated PD-1 monoclonal antibody that applies the IgG1 subtype with modified Fc-null domain. 开坦尼® (PD-1/CTLA-4 bi-specific antibody, Cadonilimab injection) was granted marketing approval in June 2022, making it the world's first bi-specific antibody drug for tumor immunotherapy and the first bi-specific antibody new drug in China.In May 2024, 依达方® (PD-1/VEGF bi-specific antibody, Ivonescimab injection), the first-in-class PD-1/VEGF bi-specific antibody independently developed by Akeso, was granted marketing approval for the treatment of epidermal growth factor receptor ("EGFR") mutated locally advanced or metastatic non-squamous non-small cell lung cancer ("nsq-NSCLC"), making it the world's first approved PD-1/VEGF bi-specific antibody. The drug had been granted three Breakthrough Therapy Designations for the treatment of lung cancer by the Center for Drug Evaluation (CDE). In December 2022, a license agreement with total potential deal value of USD $5 billion, plus a low double-digit royalty of product net sales in the authorized countries of the new drug, 依达方®, set a new record in overseas licensing for the transaction amount of a single innovative drug in China.

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.

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SOURCE Akeso, Inc.

FAQ

What is the HARMONi-2/AK112-303 study for ivonescimab (SMMT)?

The HARMONi-2/AK112-303 study is a Phase 3 clinical trial comparing ivonescimab monotherapy to pembrolizumab monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression (PD-L1 TPS ≥1%).

When was ivonescimab (SMMT) granted marketing approval for NSCLC treatment?

Ivonescimab was granted marketing approval in May 2024 for the treatment of epidermal growth factor receptor (EGFR) mutated locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC).

What significant result did ivonescimab (SMMT) achieve in the Phase III trial against pembrolizumab?

In a prespecified interim analysis, ivonescimab demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to pembrolizumab, with a hazard ratio (HR) significantly better than expected.

What is the current regulatory status of ivonescimab (SMMT) for first-line NSCLC treatment in China?

The supplemental New Drug Application (sNDA) for ivonescimab as a monotherapy for first-line treatment of PD-L1 positive locally advanced or metastatic NSCLC has been accepted by the China National Medical Products Administration (NMPA) with priority review.