Merck announced the acquisition of VelosBio, a clinical–stage biopharmaceutical company developing receptor tyrosine kinase-like orphan receptor 1 (ROR1) targeted therapies. The companies entered into a definitive agreement by which Merck, through a subsidiary, will acquire all outstanding shares of VelosBio for USD 2.75 billion in cash. VelosBio’s star candidate is VLS-101, a ROR-1 targeting antibody-drug conjugate (ADC) linked to a chemotherapeutic agent called monomethyl auristatin E (MMAE). The ADC is currently being evaluated in phase 1 for the treatment of haematological malignancies and in phase 2 for the treatment of solid tumors, including triple-negative breast cancer (TNBC), hormone receptor-positive and/or HER2-positive breast cancer, and non-squamous non-small-cell lung cancer (NSCLC).
ROR1 cell surface receptors are uniquely expressed on haematological and solid tumors. VelosBio’s proprietary technology allows targeted cancer therapy delivering anti-tumorigenic drugs to cancer cells while sparing the normal healthy cells. ROR1 is physiologically expressed in early embryogenesis and its expression decreases with foetal development. Normal adult tissues lack surface expression of ROR1 while in tumor cells, the ROR1 expression reverts to an embryonic transcriptional program and leads to malignancy. The target is also unique and currently has attracted the attention of only a small set of companies, including Oncternal Therapeutics developing an anti-ROR1 monoclonal antibody Cirmtuzumab (phase1/2 stage) and an anti-ROR1 CAR-T cell therapy (preclinical stage), Triumvira Immunologics developing ROR1 targeted immunotherapies (preclinical stage) and Bristol Myers Squibb subsidiary Juno Therapeutics’ anti-ROR1 CAR-T cell therapy. Among these contenders, VelosBio’s candidate is in the lead, having begun phase 2 clinical trials by raising USD 137 million in series B financing in July 2020.
Antibody-drug conjugates (ADCs) have been known for more than a decade but the application of ADCs to targeted cancer therapy has achieved considerable success only in recent years with multiple approvals for ADCs. There are currently ten approved ADCs in the market with five of them receiving approval in the last two years, indicating a market that is rapidly gaining traction and evolving with more scientific and clinical data supporting the efficacy of targeted cancer therapy by use of ADCs. The commercial opportunity is also becoming more tangible, buoyed by active participation from the big-pharma such as AstraZeneca partnership with Daiichi Sankyo to develop and commercialize new ADCs targeting trophoblast cell-surface antigen 2 (TROP2) cell surface receptors. Gilead made headlines by its USD 21 billion acquisition of ImmunoMedics, gaining its ADC platform and the star of the deal: TrodelvyTM, a first-in-class ADC, approved for the treatment of triple-negative breast cancer. Merck forged a USD 4 billion deal with Seattle Genetics to develop ADCs targeting zinc transporter protein LIV-1. With this latest acquisition, Merck adds a potential new cancer treatment to its pipeline and strengthens its oncology portfolio with the growing list of novel cancer therapeutics.