lphamab Oncology (stock code: 9966.HK) and CSPC Pharmaceutical Group Co., Ltd. (stock code: 1093.HK) jointly announced that two posters highlighting data from two clinical studies of the anti-HER2 bispecific antibody KN026 were presented at the 44th San Antonio Breast Cancer Symposium (SABCS 2021).

Title: Preliminary Safety and Efficacy Results of KN026 (a HER2-targeted Bispecific Antibody) in combination with KN046 (an anti-PD-L1/CTLA-4 Bispecific Antibody) in Patients with Metastatic HER2-positive Breast Cancer: a Phase II Trial
Publication Number: P5-16-04
First author: Professor Jieqiong Liu, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

Professor Chuangui Song, Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China

KN026-203 is an open-label, multi-center, phase II study to evaluate the efficacy, safety and tolerability of KN026 in combination with KN046 in subjects with HER2-positive solid tumors. The primary endpoint is the objective response rate (ORR) assessed by the investigator according to RECIST 1.1. The preliminary results from this ongoing study is reported in patients with HER2-positive metastatic breast cancer (MBC). Female patients with HER2-positive MBC who were previously treated with at least one HER2-targeted combination therapy were enrolled to receive KN026 (iv. 30 mg/kg Q3W) plus KN046 (iv. 5 mg/kg Q3W).

As of August 10, 2021, a total of 36 patients were enrolled, with a mean age of 53.0 years (range, 33-67 years). 30 patients (83.3%) had received > 2 lines of HER2-targeted combination therapy. 33 patients were evaluable for overall response, the objective response rate (ORR) was 48.5% (16/33, 95% CI: 30.8-66.5), and 1 patient achieved complete response (CR); the disease control rate (DCR) was 78.8% (26/33, 95% CI: 61.1-91.0).

36 patients were evaluable for safety, of whom 32 (88.9%) experienced at least one treatment-related adverse event (TRAE) and 5 (13.9%) experienced ≥grade 3 TRAE. The most common (≥ 10%) TRAEs were infusion-related reaction (41.7%), pruritus (22.2%), diarrhea (19.4%), rash (16.7%), elevated alanine aminotransferase (16.7%), elevated aspartate aminotransferase (16.7%), hypothyroidism (13.9%), decreased weight (11.1%), and abnormal hepatic function (11.1%). No treatment-related deaths were observed.

Title: First-in-human HER2-targeted bispecific antibody KN026 for the treatment of patients with HER2-positive metastatic breast cancer: Results from a phase I study
Publication Number: P2-13-10
First author: Professor Jian Zhang, Fudan University Shanghai Cancer Center

Dr. Dongmei Ji, Fudan University Shanghai Cancer Center

This first-in-human Phase I study evaluated the safety, tolerability, pharmacokinetics (PK), preliminary efficacy of KN026 administered as monotherapy to HER2-positive metastatic breast cancer (MBC) patients. Female patients with HER2 positive MBC who failed prior anti-HER2 therapies received intravenous KN026 monotherapy at 5 mg/kg (QW), 10mg/kg (QW), 20 mg/kg (Q2W), or 30 mg/kg (Q3W). Dose escalation was guided by a 3+3 dose escalation rule followed by dose expansion. The primary endpoint of the study was to assess safety and ascertain the recommended phase 2 dose (RP2D).

63 patients were enrolled with a median of 3 prior lines of systemic therapies and 2 prior lines of HER2 targeted therapies. Treatment was well tolerated with no DLTs observed. KN026 is well tolerated, with a favorable safety profile and promising anti-tumor activity in the context of its class in patients with HER2-positive breast cancer.

The most common treatment related adverse events (TRAEs) were pyrexia (23.8%), diarrhea (22.2%), aspartate aminotransferase increased (22.2%), alanine aminotransferase increased (22.2%). 4 patients reported Grade 3 TRAEs.

Results from exposure-response analysis supported the selection of the RP2Ds at 20 mg/kg Q2W or 30 mg/kg Q3W, which had corresponding median progression-free survival (PFS) of 5.5 and 7.4 months, respectively.

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 and Taiwan, China).

About KN046

KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Alphamab. Its innovative designs include: a different 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 China, the US and Australia. The results of these clinical trials have shown an advantage in survival for patients. Alphamab 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 registrational 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.

About CSPC

CPSC, listed on the Hong Kong, S.A.R., China Stock Exchange (stock code: 1093), was selected as a constituent stock of the Hang Sang Index in 2018 and was the first constituent stock in the pharmaceutical sector since the launch of the index. Currently, it is one of constituent stocks of Hang Seng Composite Index, Hang Seng Healthcare Index, Hang Seng Mainland Healthcare Index, Hang Seng Stock Connect Index, Hang Seng (Hong Kong, S.A.R., China-listed) 100 Index and Hang Seng China Enterprise Index. As of the date of this announcement, CPSC has total assets of more than RMB30billion and more than 23,000 employees. CSPC has a national top research and development team with research and development bases in Shijiazhuang, Shanghai, Beijing and the United States, focusing on the discovery, research and development of small molecule targeted drugs, nanodrugs, monoclonal antibody drugs, bispecific antibody drugs, antibody-drug conjugates, mRNA vaccines, small nucleic acid drugs and biological drugs in the immune field.

Source: Alphamab Oncology