On May 30, 2024 Akeso, Inc. (HKEX: 9926.HK) ("Akeso," "we," or the "Company") reported that the Phase III clinical trial, HARMONi-2 or AK112-303, met its primary endpoint of progression-free survival (PFS) (Press release, Akeso Biopharma, MAY 30, 2024, View Source [SID1234643890]). HARMONi-2 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%). HARMONi-2 is a single region, multi-center, double-blinded Phase III study sponsored by Akeso with data generated and analyzed by Akeso.

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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. The PFS benefit was demonstrated across clinical subgroups, including those with PD-L1 low expression (PD-L1 TPS 1-49%), PD-L1 high expression (PD-L1 TPS >50%), squamous and non-squamous histologies, as well as other high-risk patients.

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.

The Phase III HARMONi-2 study, along with the approval of ivonescimab in China in combination with chemotherapy based on the results of the HARMONi-A trial, provides clear evidence supporting the purposefully-engineered, differentiated mechanism of action of ivonescimab, a PD-1 / VEGF bispecific antibody evidencing cooperative binding characteristics, and its opportunity to improve upon the existing standards of care for solid tumors.

"HARMONi-2 clearly demonstrates that ivonescimab has strong clinical values globally as well as commercial potentials." stated Dr. Michelle Xia , Chairwoman, President and Chief Executive Officer of Akeso. "ivonescimab is the next generation in PD-1 directed immunotherapy, and its potential to make a significant difference in the lives of patients with lung cancer and prospectively other tumors."

Conference Call

Akeso, Inc. (HKEX: 9926.HK) ("Akeso," "we," or the "Company") will host a conference call to discuss recent updates related to ivonescimab on Friday May 31, 2024, before the market opens.

About Ivonescimab

Ivonescimab, known as AK112 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 higher affinity when in the presence of both PD-1 and 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 tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro.[1] 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,[1] is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two Phase III clinical trials, HARMONi and HARMONi-3.

The safety profile of ivonescimab is manageable and consistent with known risks for PD-1 and VEGF inhibiting drugs. In the first Phase III study to be presented at ASCO (Free ASCO Whitepaper), "Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous NSCLC who progressed on EGFR TKI treatment (AK112-301): A randomized, double-blind, multi-center, phase 3 trial," 5.6% of patient discontinues ivonescimab due to adverse events.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to a placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR TKI (e.g., osimertinib).

HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.

About Lung Cancer

Lung cancer is believed to impact approximately 600,000 people across the United States, United Kingdom, Spain, France, Italy, Germany, and Japan.[2] NSCLC is the most prevalent type of lung cancer and represents approximately 80% to 85% of all incidences.[3] Among patients with non-squamous NSCLC, approximately 15% have EGFR-sensitizing mutations in the United States and Europe.[4] Patients with squamous histology represent approximately 25% to 30% of NSCLC patients.