September 14, 2018 Antibody-drug conjugate resurgence continues with Lumoxiti Jacob Plieth With today’s approval of Astrazeneca’s Lumoxiti the US market has two antibody-drug conjugates against the CD22 antigen. While the first, Pfizer’s Besponsa, was approved a year ago for treating relapsed adult acute lymphoblastic leukaemia (ALL), Astra has positioned Lumoxiti against hairy cell leukaemia, a relatively rare malignancy. Both these haematological cancers affect B cells, hence the relevance of hitting CD22, an antigen present on this cell lineage. An important difference between Besponsa and Lumoxiti is the cytotoxic payload each carries – respectively calicheamicin, the same as that used in Pfizer’s Mylotarg, and Pseudomonas exotoxin A. And both drugs’ labels carry boxed warnings, respectively for liver damage and capillary leak syndrome, the toxicity that briefly derailed Stemline’s anti-CD123 conjugate SL-401. The next anti-CD22 asset to test the regulators could be Immunomedics’ epratuzumab, though as this is a standard “naked” antibody it is unlikely to match the efficacy of more advanced constructs like conjugates and bispecifics. The big competitor could emerge in the form of CD22-directed CAR-T therapy, though this is still some way off being commercialised. Anti-CD22 antibody-drug conjugates 2024e Lead Project Pharmacology class Company sales indication ($m) Approved Besponsa Anti-CD22 MAb-calicheamicin conjugate Pfizer/ UCB ALL 519 (inotuzumab ozogamicin) Lumoxiti (moxetumomab Hairy cell Anti-CD22 MAb-PE38 conjugate Astrazeneca 218 pasudotox) leukaemia Phase II Anti-CD22 MAb-monomethyl auristatin E Roche/ Seattle Pinatuzumab vedotin NHL NA conjugate Genetics Phase I Immunomedics/ BAY1862864 Anti-CD22 MAb-thorium 227 conjugate NHL NA Bayer Preclinical Anti-CD22 MAb-pyrrolobenzodiazepine ADC ASCT-602 NHL, ALL NA conjugate Therapeutics Triphase TRPH-222 Anti-CD22 MAb-4AP drug conjugate Accelerator/ NHL NA Celgene ALL=acute lymphoblastic leukaemia; NHL=non-Hodgkin lymphoma; NA=not available. Source: EvaluatePharma. More from Evaluate Vantage Evaluate HQ 44-(0)20-7377-0800 Evaluate Americas +1-617-573-9450 Evaluate APAC +81-(0)80-1164-4754 © Copyright 2021 Evaluate Ltd..