STEAP2

AstraZeneca’s dealmaking in the cell and gene therapy space shows no signs of slowing. On Tuesday, the pharma agreed to spend up to $1.2 billion to acquire Chinese cell therapy company Gracell, its sixth such deal in the past year. The acquisition fills in some gaps in AstraZeneca’s cell therapy pipeline, adding a clinical-stage CAR-T therapy in development for haematologic cancers and autoimmune diseases. The pharma also gains Gracell’s FasTCAR platform, which is intended to significantly shorten manufacturing time, enhance T cell fitness, and improve efficacy.A bit of a latecomer to the CGT space, AstraZeneca began adding to its portfolio in earnest late last year with the $320-million takeout of Neogene and its T-cell receptor (TCR) candidates for solid tumours. The pharma has since signed a $2-billion deal with Quell Therapeutics to develop regulatory T (Treg) cell therapies for autoimmune diseases; acquired a slate of preclinical gene therapies from Pfizer for up to $1 billion; and last month, formed a broad strategic alliance with Cellectis to use its TALEN gene editing platform and manufacturing capabilities to develop cell and gene therapy products.AstraZeneca also partnered this month with AbelZeta Pharma to co-develop C-CAR031, an autologous, armoured GPC3-targeted CAR-T therapy for liver cancer that’s based on a novel construct designed by the pharma. AstraZeneca’s only wholly owned and internally developed cell therapy programme is AZD0754, a preclinical TGF-beta-armoured CAR-T targeting STEAP2, which is overexpressed in prostate cancer. Under the deal terms, AstraZeneca will acquire Gracell at $2.00 per share, plus a milestones-based non-tradable contingent value right of $0.30 per share, for a total deal value of $1.2 billion. The combined price is an 86% premium to Gracell's close on December 22.Early MM data, eyes on lupusThe most prominent asset AstraZeneca gains is Gracell’s lead candidate, GC012F, a BCMA/CD19 dual-targeted CAR-T in a Phase Ib/II multiple myeloma (MM) trial.At the December American Society of Hematology (ASH) meeting, Gracell presented data from an investigator-initiated trial of GC012F to treat newly diagnosed, high-risk MM. In 22 patients, GC012F demonstrated a 100 percent overall response rate, with 21 patients achieving stringent complete response with a median follow-up of 18.8 months. Although positive, KOLs told FirstWord Pharma they weren’t overwhelmed by the data. To displace the market-leading BCMA-targeted CAR-T for MM, Johnson & Johnson’s Carvytki (ciltacabtagene autoleucel), both high response rate and quick manufacturing are needed.AstraZeneca will also have an opportunity to explore GC012F’s potential in autoimmune diseases. Gracell was cleared by the FDA in November to start a trial of GC012F in systemic lupus erythematosus (SLE). This shift was validated by data presented by a German academic group at ASH, which found impressive responses treating SLE patients with a CD19-targeting CAR-T. Gracell’s pipeline also includes three preclinical dual-targeted CAR-Ts for haematological malignancies, and one CAR-T in development for solid tumours that targets Claudin-18.2, a protein expressed in gastrointestinal cancers.