Enrollment Completed in Phase II Clinical Study of KN026 Combined with KN046

Alphamab Oncology (stock code: 9966.HK) announced that the phase II clinical study of KN026 (HER2 bispecific antibody) combined with KN046 (PD-L1/CTLA-4 bispecific antibody) (KN026-203) has successfully completed the enrollment of all patients in China, and the interim analysis is expected in the second quarter of 2022.

KN026-203 is an open-label, phase II, multi-center clinical study to evaluate the efficacy and safety of KN026 combined with KN046 in the treatment of HER2-positive solid tumors. Enrollment of all 102 patients, including HER2-positive GC/GEJ, breast cancer and other HER2-positive solid tumors, has been completed at 25 study centers nationwide.

Previously published clinical data showed that KN026 in combination with KN046 initially demonstrated good efficacy in HER2-positive solid tumors. The preliminary results from KN026-203 is reported in patients with HER2-positive metastatic breast cancer (MBC) as poster at SABCS 2021, female patients with HER2-positive MBC who were previously treated with at least one HER2-targeted combination therapy were enrolled, the ORR was 48.5% (16/33, 95% CI: 30.8-66.5), and 1 patient achieved CR; the DCR was 78.8% (26/33, 95% CI: 61.1-91.0). Data from a Phase Ib study (KN046-IST-02) of KN026 plus KN046 for GI with HER2 positive/mutation/low-expression are presented as Poster at the ESMO congress 2021. In 27 HER2-positive patients, the ORR was 51.9% with median DOR 11.2 months; Among those 27 patients 21 were GC/GEJ, the ORR was 71.4% for treatment naïve patients (n=7), 42.9% for 14 patients who had been exposed to systemic therapy and 40.0% for 10 patients who had received trastuzumab. With more patient enrolled, similar trend for efficacy and safety has been observed.

Professor Shen Lin from Peking University Cancer Hospital, the principal investigator, commented: "Overexpression of HER2 occurs in multiple tumor types such as breast, gastric, and intestinal cancers. There are urgent needs to develop effective treatment for those tumors. A number of preclinical and clinical studies have shown the potential efficacy of anti-HER2 therapy in combination with immunotherapy. Combination of KN026 and KN046 is a exploration with global edge and potential to change treatment landscape forHER2-positive tumor. We are looking forward the data from interim analysis to confirming clinical value of the combo."

About KN026

KN026 is an anti-HER2 bispecific antibody developed by Alphamab Oncology using the proprietary Fc-based heterodimer bispecific platform technology called CRIB (Charge Repulsion Induced Bispecific). KN026 can bind two non-overlapping epitopes of HER2 simultaneously, leading to a dual HER2 signal blockade. KN026 has demonstrated potentially equivalent efficacy compared with Trastuzumab and Pertuzumab in combination, and was superior to either single agent, such as increased binding affinity, as well as better tumor inhibition in HER2-positive tumor cell lines. Additionally, KN026 has also shown inhibitory effect on tumor cells with medium or low HER2 expression or Trastuzumab-resistant cell lines.

KN026 received IND approval from the National Medical Products Administration (NMPA) of China and U.S. Food and Drug Administration (FDA) in 2018. Currently, it is in multiple phase I/II clinical trials in China and phase I clinical trial in the United States. The results of Phase I clinical trials show KN026 has good safety, tolerance and potentially superior anti-tumor activity in HER2-positive breast cancer patients who progressed after multiple lines of anti-HER2 treatment.

In August 2021, the company entered an agreement with JMT-Bio, a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. (stock code: 1093.HK), for the development and commercialization of KN026 in Mainland China. According to the terms of the agreement, JMT-Bio will obtain the exclusive license rights of KN026 for the development and commercialization in the indications of breast cancer and gastric or gastroesophageal junction cancers (GC/GEJ) in Mainland China (excluding Hong Kong, S.A.R., China, Macau, S.A.R., China, S.A.R., China and Taiwan, China,China).

About KN046

KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Alphamab. Its innovative designs include: a novel mechanism - CTLA-4 fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression, and Treg (suppress tumor immunity) clearing function.

There are about 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, thymic cancer, pancreatic cancer, HCC, ESCC and TNBC in Australia, the US and China. The results of these clinical trials have shown an advantage in survival for patients. Alphamab Oncology has received FDA clearance to enter phase II trial of KN046 based on the clinical results in China and Australia. Moreover, KN046 has obtained the U.S. FDA's orphan drug designation for thymic epithelial tumor in September 2020. Four pivotal clinical trials are currently being conducted.

About Alphamab Oncology

Alphamab Oncology is focusing on innovation, production and commercialization of anti-tumor drugs. On December 12, 2019, the Company was listed in the mainboard of Hong Kong, S.A.R., China Stock Exchange with stock code 9966.

Alphamab has fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline includes fifteen tumor monoclonal antibodies and bispecific antibodies and a COVID-19 bispecific antibody. Four products have advanced into phase I-III clinical trials or pre-marketing stage in China, the United States, Japan and Australia. In November 2021, Envafolimab received marketing authorization from the Chinese National Medical Products Administration (NMPA) for the treatment of previously treated MSI-H/dMMR advanced solid tumors.

The Company also has state-of-the-art manufacturing capabilities designed and built to meet NMPA and EU/FDA's cGMP standards and a complete quality system which has passed the on-site inspection of a European Union qualified person. Alphamab Oncology is committed to building a global leading, multi-dimensional drug development and commercialization platform, focusing on multifunctional biological innovative drugs, and to benefit patients in China and around the world.

Source: Alphamab Oncology