Servier leaves Macrogenics again

Were it not for the lingering doubts about Macrogenics’ lead asset, margetuximab, Servier’s ending of a licensing deal for flotetuzumab yesterday would be a non-event. As it is, however, investors have another reason to fret over a share price that, since enthusiasm over margetuximab peaked in February, has slumped 40%. Flotetuzumab is an anti-CD123 bispecific, a mechanism that has proved extremely tricky to exploit without toxicities, as numerous companies have found (Xencor’s bispecific hold reignites debates over approach and target, February 21, 2019). Servier is not a major oncology player, so its decision might not mean much beyond the loss of $308m of possible milestone payments; $35m had already been received in up-front and option fees. Four years ago Servier pulled out of a separate deal covering Macrogenics’ anti-B7-H3 MAb enoblituzumab. Meanwhile, margetuximab, an anti-Her2 MAb, remains mired in concerns revealed at this year’s Asco that its highly touted Sophia trial is unlikely to show an overall survival benefit. The next evidence for or against flotetuzumab will emerge at December’s Ash conference, where a monotherapy trial in acute myelogenous leukaemia and myelodysplastic syndromes should yield updated results.

Selected CD123-targeting projects
Project  Company  Mechanism  Notes 
Elzonris Stemline Protein/drug conjugate  Two deaths in BPDCN cohort despite protocol modification
Phase III
Talacotuzumab Xencor/J&J MAb  Trial scrapped; J&J evaluating data to determine further steps
Phase I
UCART123   Cellectis/Allogene Allogeneic CAR-T   Clinical hold after patient death (Sep 2017), now lifted
MB-102   Fortress/Mustang Autologous CAR-T    
MIH911   Novartis   Autologous CAR-T   Study terminated for "lack of funding"
SGN-CD123A   Seattle Genetics  Antibody-drug conjugate   
IMGN632 Immunogen/Jazz Antibody-drug conjugate   
Flotetuzumab   Macrogenics   Bispecific MAb  Servier deal terminated
JNJ-63709178   Genmab/J&J Bispecific MAb  Two clinical holds (Sep 2016 & Aug 2018), both lifted
XmAb14045   Xencor/Novartis Bispecific MAb  Clinical hold after 2 patient deaths (Feb 2019), now lifted
KHK2823   Kyowa Hakko Kirin   MAb   
APVO436 Aptevo/Ligand Bispecific MAb   
SAR440234 Sanofi Bispecific MAb   
Source: EvaluatePharma. 

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