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 CD73ProjectCompanyStatusSmall moleculesQuemliclustatArcus BiosciencesPh1 Arc-8 trial in GI malignanciesATG-037Antengene CorporationPh1 Keytruda comboORIC-533Oric PharmaceuticalsPh1 in multiple myelomaABSK051Abbisko TherapeuticsPh1 not yet recruitingMonoclonal antibodiesOleclumabAstraZenecaPh3 Pacific-9 trial, Imfinzi combo in stage III NSCLCUliledlimabI-Mab BiopharmaPh2 Tecentriq comboJAB-BX102Jacobio PharmaceuticalsPh1/2 +/- KeytrudaIPH5301Innate PharmaPh1 Chances trialMupadolimabCorvus PharmaceuticalsPh1 +/- ciforadenant + KeytrudaIBI325Innovent BiologicsPh1 sintilimab comboSym024Servier (ex Symphgen)Ph1 +/- Sym021PT199Phanes TherapeuticsPh1 +/- KeytrudaBR101BioRay PharmaceuticalPh1PM1015BiotheusPh1Source: OncologyPipeline.
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
