Oncology and Autoimmune Diseases
STRO-002Indications——Recurrent ovarian cancer、non-small cell lung cancer、triple-negative breast cancer and other solid tumor.
Product Introduction STRO-002 is a third-generation antibody-drug conjugate (ADC) developed by Sutro with global intellectual property rights. In December 2021, Tasly Biopharma and Sutro Biopharma signed the License Agreement on STRO-002. Under the provisions of the License Agreement, Tasly Biopharma will obtain the exclusive rights in the development, registration, and commercialization of STRO-002 in the Greater China region (including the Chinese mainland, Hong Kong, Macao, and Taiwan, hereinafter referred to as the “Territory”). The synthesis of the antibody part of STRO-002 targeting folate receptor α (FRα) employs the industry-leading cell-free protein synthesis technology (XpressCF). This technology inserts non-natural amino acids (XpressCF+) at specific sites in the protein sequence, and the side chains of non-natural amino acids of the resulting antibody can be loaded with cleavable linker-payload through click chemistry reaction, hence achieving site-specific conjugation of the ADC. Conjugation methods for ADCs mainly include non-site-specific conjugation and site-specific conjugation. Non-site-specific conjugation was the method used in early ADC development. Overall, the final product of non-site-specific conjugation is a mixture, including different DAR values(drug-antibody ratio) and different conjugation sites, which have poor stability and are prone to aggregation, and cytotoxin is easy to exfoliate and produce non-therapeutic toxic side effects with a narrow therapeutic window; in addition, it is a technical problem to analyze, identify and control the differences between production batches. STRO-002 is prepared by site-specific conjugation technology, with a DAR value (drug-to-antibody ratio) of 4 and a high product homogeneity, STRO-002 has the potential to solve the problems in CMC quality and pharmacology of conventional ADC products due to non-site-specific conjugation. In addition, the small molecule payload of STRO-002 is a derivative of the marine extract Hemiasterlin, which is a novel microtubule inhibitor and a weak substrate for the P-glycoprotein pump, with the potential to avoid drug resistance.
Mechanism of Action FRα, the target of STRO-002, is tumor cell-specific, which can be highly expressed in tumors such as ovarian cancer, endometrial cancer, breast cancer, and non-small cell lung cancer, with no expression or very low expression in normal tissues; therefore, targeting FRα has the potential to treat a variety of solid tumors including ovarian cancer, non-small cell lung cancer (NSCLC), breast cancer and endometrial cancer.
Clinical Progress STRO-002 is currently in Phase I clinical study in the US for recurrent ovarian cancer and endometrial cancer, the pre-clinical study for NSCLC is ongoing.