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Arcus gets anti-CD73 small molecule buy-in

Otsuka has bought into CD73 inhibition just three months after Novartis abandoned this mechanism of action. There is one difference: Arcus’s quemliclustat, into whose Japanese development Otsuka’s Taiho subsidiary opted in yesterday, is a small molecule, while Coherus’s NVS930, scrapped by Novartis in April, was a monoclonal antibody. Arcus this year plans to start the phase 3 Prism-1 study, comparing quemliclustat plus chemo versus chemo in first-line pancreatic ductal adenocarcinoma, having reported promising survival data in the Phase 1b Arc-8 trial. The group says CD73 causes production of immunosuppressive adenosine in the tumour microenvironment, and its expression is associated with poor prognosis in several cancers. However, Lilly earlier discontinued the small-molecule CD73 inhibitor LY3475070, and the protein approach is by no means dead: AstraZeneca’s oleclumab is in phase 3, and other clinical-stage MAbs include Innate Pharma’s IPH5301, Corvus’s mupadolimab and Servier’s Sym024; Bristol Myers Squibb’s BMS-986179 and Incyte’s uprevstobart are discontinued. Taiho bought the Arcus option in 2017 for $35m, and exercising quemliclustat rights was said to include up to $275m in milestones, but the exercise fee wasn’t disclosed.

 

Clinical-stage projects with activity on CD73

ProjectCompanyStatus
Small molecules
QuemliclustatArcus BiosciencesPh1 Arc-8 trial in GI malignancies
ATG-037Antengene CorporationPh1 Keytruda combo
ORIC-533Oric PharmaceuticalsPh1 in multiple myeloma
ABSK051Abbisko TherapeuticsPh1 not yet recruiting
Monoclonal antibodies
OleclumabAstraZenecaPh3 Pacific-9 trial, Imfinzi combo in stage III NSCLC
UliledlimabI-Mab BiopharmaPh2 Tecentriq combo
JAB-BX102Jacobio PharmaceuticalsPh1/2 +/- Keytruda
IPH5301Innate PharmaPh1 Chances trial
MupadolimabCorvus PharmaceuticalsPh1 +/- ciforadenant + Keytruda
IBI325Innovent BiologicsPh1 sintilimab combo
Sym024Servier (ex Symphgen)Ph1 +/- Sym021
PT199Phanes TherapeuticsPh1 +/- Keytruda
BR101BioRay PharmaceuticalPh1
PM1015BiotheusPh1

Source: OncologyPipeline.