December 23rd, 2020 - Alphamab Oncology (stock code: 9966 HK) announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to KN026 (anti-HER2 bispecific antibody) in combination with KN046 (PD-L1/CTLA-4 bispecific antibody) developed and fully owned by Jiangsu Alphamab Biopharmaceuticals Co., Ltd. (“Jiangsu Alphamab”), a wholly-owned subsidiary of the company, for the treatment of HER2-positive or low expressing gastric or gastroesophageal junction cancer. This is the third ODD granted to Alphamab Oncology by FDA after the first ODD granted to the subcutaneous PD-L1 antibody KN035 by FDA for the treatment of biliary track cancer in January 2020 and the second ODD granted to KN046 for the treatment of thymic epithelial tumors (TET) in September 2020.
The Orphan Drug Designation from US FDA originates from the Orphan Drug Act which was enacted to encourage the development of innovative drugs to treat orphan diseases with target patient population less than 200,000 in the US. Drug candidates with Orphan Drug Designation qualify for seven-year market Orphan Drug Exclusivity (ODE). In addition, US FDA also rewards ODD drugs with comprehensive incentives including tax credit of 50% clinical trial cost, waiver of BLA user fee, subsidies for R&D costs, protocol assistance and expedited regulatory approval pathway. In 2019, 21 (44%) out of the 48 new drugs approved by US FDA are Orphan Drugs; and 8 out of the top 10 best-selling cancer drugs in US, have received Orphan Drug Designation for certain indications.
Gastric cancer (GC)/, gastroesophageal junction cancer (GEJ) is the fifth most common cancer and the third leading cause of cancer death worldwide. There are approximately 950,000 new cases diagnosed and 720,000 deaths worldwide annually. The complete prevalence of gastric cancer, including gastroesophageal junction cancer, in the U.S. was estimated as 116,525 according to the SEER Cancer Statistics Review 1975-2017. Fluoropyrimidine and platinum based regimen is commonly used as the first line therapy. Available second or later line therapies include paclitaxel plus ramucirumab, paclitaxel, docetaxel or irinotecan monotherapy, and best supportive care, inducing approx. 15-25% objective response rate. Median overall survival is only about 8-9 months at second line and 4-6 month at late line.
KN026 and KN046 are innovative bispecific antibodies developed and fully owned by Alphamab Oncology. Both of them have shown good safety, tolerability and anti-tumor efficacy in multiple clinical trials. The efficacy of combo has been demonstrated in an IIT trial. Initial data indicates the objective response rate of KN046 in combination with KN026 in HER2-positive tumors was 64.3% (9/14, 95% CI 35.1~87.2%) and disease control rate 92.9% (13/14, 95% CI 66.1~99.8%). This results has been presented in SITC this year.SEARCH-01 is an phaseⅡ registration clinical study to evaluate the efficacy, safety and tolerability of KN026 in combination with KN046 for HER2-positive solid tumors. This study is planned to be conducted in 20-30 clinical centers in China and 10-20 US clinical centers with advanced HER2-positive solid tumors, including HER2-positive gastric and gastroesophageal junction cancer etc. We want to believe that KN046 plus KN026 will provide a new approach to address the unmet medical need in near future.
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 alone or in combination, 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 excellent safety, tolerance and potentially superior anti-tumor activity in HER2-positive breast cancer patients who progressed after multiple lines of anti-HER2 treatment.
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, TNBC, ESCC, HCC and pancreatic cancer in Australia and China. 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. Two registrational clinical trials are currently being conducted.
About Alphamab Oncology
Alphamab Oncology is a biopharmaceutical company focusing on innovative biologics medicine for oncology. On December 12, 2019, the Company was listed in the mainboard of Hong Kong 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 eight tumor monoclonal antibodies and bispecific antibodies and a Covid-19 multifunctional antibody. Four products have advanced into phase I-III clinical trials or pre-marketing stage in China, the United States, Japan and Australia. The BLA for KN035(Envafolimab) has been accepted by the National Medical Products Administration (NMPA) on December 17.
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 an 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.
Visit http://www.alphamabonc.com for more information.
Alphamab Oncology Forward-Looking Statements
This press release contains statements related to our future business and financial performance and future events or developments involving Alphamab Oncology that may constitute forward-looking statements. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. These statements may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. We may also make forward-looking statements in other reports, in presentations, in material delivered to shareholders and in press releases. In addition, our representatives may from time to time make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Alphamab Oncology’s management and business operation, many of which are difficult to predict and generally beyond Alphamab Oncology’s control. These are subject to a number of risks and uncertainties, including but not limited to, uncertainties inherent in research and development, future clinical data and analysis, decisions by regulatory authorities regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, Alphamab Oncology's ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of shares outstanding and Alphamab Oncology’s disclosures. Should one or more of these risks or uncertainties materialize, or should underlying expectations not occur or assumptions prove incorrect, actual results, performance or achievements of Alphamab Oncology may (negatively or positively) vary materially from those described explicitly or implicitly in the relevant forward-looking statement. Other than as required by applicable law, Alphamab Oncology undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.