A novel ADC targeting HER2 pathways based on Alteogen's NexMab ADC technology.
Alteogen Inc. (“Alteogen”) (196170.KS) today announced it has entered into an exclusive licensing deal with 3SBio Inc. (“3SBio”) (01530.HK), a leading China-based biotechnology company focused on researching, developing, manufacturing and marketing biopharmaceutical products, for the development, manufacturing and marketing of ALT-P7, a novel antibody-drug conjugate (“ADC”) targeting HER2 pathway for cancer in the territory of Mainland China, Hong Kong and Macau. The deal included undisclosed upfront, milestone and royalty payments.
Approximately 20% of breast cancers and 15% of gastric cancers are characterized by amplification of the human epidermal growth factor receptor 2 (HER2) gene and over-expression of HER2, which leads to increased signal transduction and activation of the MAPK and PI3K/Akt pathways. In contrast to normal cells which express approximately 20,000 HER2 receptors on the cell membrane, each HER2-positive breast cancer cell expresses approximately one to two million HER2 receptors, making HER2 an attractive candidate for targeted therapy. Trastuzumab, a humanized monoclonal antibody directed against the extracellular juxtamembrane domain IV of HER2, combined with chemotherapy, has significantly improved OS in patients with breast cancer and gastric cancer. In order to remove the inevitable toxicity of chemotherapy, Genentech developed ado-trastuzumab emtansine (T-DM1) to improve safety and efficacy with traditional cytotoxics. T-DM1 is an antibody-drug conjugate of trastuzumab, and a potent microtubule inhibitor, DM1 (derivative of maytansine), which has been approved for treatment-refractory HER2-positive metastatic or locally advanced breast cancer by FDA.
Still T-DM1 has its own limitations: non-specific conjugation of DM1 may leads to 1) the formation of heterogeneous mixture of ADC isomers; 2) chemical modification of amino acids on the surface of Mab, and 3) difficulty in reproducibility of product manufacturing. Therefore, site-specific conjugation and improved conjugation yield are critical requirements for next-generation ADC. ALT-P7, developed based on Alteogen’s proprietary NexMab™ ADC technology, is expected to be more efficacious and stable compared with first generation ADC products. Preclinical proof-of-concept, including in vitro binding assays and in vivo efficacy in animal models, has demonstrated superiority of ALT-P7 over current drugs in murine models of HER2-positive breast cancer.
“We are very pleased to start our partnership with 3SBio,” Dr. Soon Jae Park, CEO of Alteogen commented, “3SBio is a well-established industry leader with long-term vision in the innovative biological field in China, which makes them an ideal partner for strategic collaborations in the long term. ALT-P7 is a novel ADC with great potential to treat refractory tumors. We are looking forward to working with them to develop this drug in China, so that tens of thousands of patients suffering for cancers can benefit from this drug candidate.”