Antibody Drug Conjugates – Acquisitions and Partnering

Stemcentrx’ Rova-T, also known as SC16LD6.5, is addressing small cell lung cancer (SCLC) and other neuroendocrine cancers such as large cell neuroendocrine carcinoma. Rova-T has received orphan drug designation from the FDA for treatment of small cell lung cancer. Rova-T targets delta-like protein 3 (DLL3), which is expressed in >80% SCLC patient tumors and is not present on healthy tissue. Rova-T comprises a D6.5 pyrrolobenzodiazepine (PBD) payload conjugated to cysteine residues on the SC16 antibody, a maleimide-containing linker with an eight-carbon polyethylene glycol spacer, cathepsin B–cleavable valine-alanine dipeptide, and self-immolating group, with an average drug-to-antibody ratio (DAR) of 2. Rova-T represents a multi-billion dollar peak revenue opportunity with expected commercialization in 2018. The acquisition expands AbbVie’s oncology pipeline with four additional early-stage clinical compounds in solid tumor indications and Stemcentrx’ portfolio of preclinical assets.

Together with CytomX, AbbVie will co-develop a PDC against CD71. PDCs contain a masking peptide designed to decreasing target binding to healthy tissue and remain inactive until the molecules are activated proteolytically in the tumor microenvironment, thereby minimizing toxicities. The target, transferrin receptor 1 (TfR1), also known as CD71, is ubiquitously expressed on dividing, normal or healthy cells plus a number of hematologic and solid malignant cancer cells. CD71 mediates transferrin-iron complex uptake, an essential process for cell division and therefore also for tumors. CD71 is homogeneously and highly expressed (3+ expression assessed by IHC) in almost all tumor types, including metastatic tumors. The current PDC approach should avoid targeting the many healthy cell types that also express CD71.

Additionally, Regeneron Pharmaceuticals and MedImmune (wholly owned subsidiary of  AstraZeneca) entered into a licensing agreement under which Regeneron will use MedImmune’s PBD-based payload and linker technology to develop ADCs against a number of cancer targets. MedImmune will have the option to develop and commercialize certain products created with this technology in territories outside of the United States.