On April 3, it was jointly announced that the two companies, Ipsen and Sutro Biopharma, had reached a global exclusive licensing agreement totaling up to USD 900 million for Sutro's antibody-drug conjugate (ADC) STRO-003. STRO-003 will be the first ADC candidate drug in Ipsen's portfolios.
STRO-003 is a new-generation ROR1-targeted ADC, which could generate highly stable conjugates with exatecan payloads by utilizing Sutro's site-specific technology. The strong single-drug efficacy and differentiated safety that STRO-003 shown in preclinical trials of both solid tumors and hematological malignant tumors has given it the potential to be "best-in-class" drugs.
According to the terms of the agreement, Ipsen will prepare for the STRO-003 Phase I clinical trial, including the submission of an IND application, as well as all subsequent clinical development and global commercialization activities. Sutro is eligible to receive potential upfront, developmental, regulatory, and commercial milestone payments totaling up to USD 900 million, including an immediate payment of around USD 90 million, contingent upon the successful development and commercialization of the drug.
ROR1: New Potential Anti-tumor Targets
ROR1, short for receptor tyrosine kinase-like orphan receptor 1, is a kind of transmembrane protein in ROR receptor family. In recent years, due to its high expression characteristics in various malignant tumors, ROR1 has become a research hotspot in biomedicine and is considered to be a new drug target with broad-spectrum anticancer potential.
Unlike less-expressed or non-expressed in normal human tissues, ROR1 is highly expressed in many malignant tumors or tissues. Take diseases such as chronic lymphocytic leukemia (CLL), breast cancer, ovarian cancer, melanoma, and lung adenocarcinoma for example, the characteristics of high expression in tumors but low expression in healthy cells make ROR1 an attractive drug R&D objective. After binding to ligand Wnt5a, ROR1 is able to mediate the signaling of non-classical Wnt signaling pathway, which will play an important role in promoting tumor growth and metastasis, inducing drug resistance and inhibiting apoptosis of tumor cells.
MSD, BI and CStone Pharmaceuticals Made Significant Investments in ROR1 ADC
Southwest Securities Research Report predicts that the market is expected to obtain tens of billions of dollars once ROR1 ADC is developed into a drug. Such a huge market size has naturally attracted many MNCs' attention. In the short span of three months from October to December 2020, CSTONE Pharmaceuticals, MSD, and Boehringer Ingelheim made significant investments to acquire three kinds of ROR1 ADCs. CSTONE Pharmaceuticals introduced the ROR1-targeted ADC drug CS5001 that developed by the Korean biopharmaceutical company LCB with USD 10 million advance payments and up to USD 353 million milestone payments and additional tiered royalties. MSD spent USD 2.75 billion to acquire VelosBio, whose core pipeline is a kind of ROR1 ADC drug, called zilovertamab vedotin; Boehringer Ingelheim spent EUR 1.18 billion to acquire NBE-Therapeutics, focusing on acquiring a kind of ROR1 ADC drug, called NBE-002. There are only three kinds of ROR1 ADCs that have entered the clinical stage in the world at present.
Zilovertamab vedotin (MK-2104) is composed of a monoclonal antibody targeting ROR1 connected to the chemotherapeutic agent MMAE. The combination of the antibody to MK-2140 and the ROR1 on cancer cells can release MMAE to destroy cancer cells. VLS-101 has shown great anti-tumor efficacy in mouse models of human hematological malignant tumors and solid tumors. Previously, the FDA granted VLS-101 orphan drug designation and fast track status for the treatment of Mantle Cell Lymphoma (MCL).
At the European Society for Medical Oncology in 2021 (ESMO 2021), the escalation result of the first-in-human dose in Phase I patients that MK-2140 used in treatment of malignant tumor lymphatic system were announced. Data indicated that the candidate drug induced objective tumor responses in 7 out of 15 Mantle Cell Lymphoma patients, with an objective response rate (ORR) of 47%, comprising 4 partial r...
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