Medigene cellular immunotherapy platform
underpins latest ?Vant in potential $1B deal
By Cormac Sheridan, Staff Writer
DUBLIN ? Medigene AG is banking $10 million up front and could earn up to $1 billion more in
milestones from a multiproduct immuno-oncology alliance with Cytovant Sciences, a newly launched
?Vant that will develop cell therapies for cancer patients across East Asia.
Included in the deal are two existing Medigene assets, a research-stage T-cell-receptor-modified T-cell
(TCR-T) therapy targeting NY-ESO-1 and a clinical-stage dendritic cell-based cancer vaccine directed at tumors expressing Wilm?s tumor protein 1 (WT-1) and Prame (Preferentially Expressed Antigen in Melanoma).
Hong-Kong-based Cytovant has licensed rights to develop, manufacture and commercialize those therapies in greater China, South Korea and Japan.
In addition, Cytovant and Medigene are also engaging in a research collaboration to discover and develop two further TCRbased cell therapies. ?They choose the antigens, we discover the
receptors,? Dolores Schendel, CEO and chief scientific officer of Martinsried, Germany-based Medigene, told BioWorld.
The deal has obvious echoes of Medigene?s 2016 pact with Cambridge, Mass-based Bluebird Bio Inc., which initially covered four TCR-based cellular therapies directed against
Bluebird-nominated antigens, in return for which Medigene received $15 million up front plus up to $1 billion in milestones.
?That was extended last year to an additional two targets,? Schendel said. Medigene received an additional $8 million up front and could earn up to $500 million more in milestones. (See
BioWorld Today, Sept. 30, 2016.)
Medigene has conducted extensive research on its NY-ESO-1- targeting TCR, but it is not planning to progress the asset in its present form into clinical development in Western markets, given the lead enjoyed in that segment by London-based Glaxosmithkline plc, which in-licensed a similar therapy from Adaptimmune Ltd. Now called GSK-3377794, the latter is undergoing several trials across a range of indications.
Medigene has recently in-licensed from the Helmholtz Zentrum Munich research institute a co-stimulatory fusion protein, comprising PD-1 and 4-1BB, which it may deploy in a future NY-ESO-1-directed TCR-T, Schendel said, as it may break the strong immunosuppression associated with solid
tumor microenvironments. In the meantime, it will, she said, learn more about NY-ESO-1-expressing tumors from Cytovant?s work in Asia. Given that TCR-T therapies are majorhistocompatibility-
complex (MHC)-restricted, it will need to be re-engineered for the predominant MHC types in Eastern Asian populations.
In Medigene?s dendritic cell vaccine, Cytovant is gaining a clinical-stage asset. ?They were interested in having a more mature immunotherapy, which they can fast-forward in China,? Schendel said.
It is currently undergoing a European phase II trial in patients with acute myeloid leukemia. ?The phase II will read out at the end of this year,? Schendel said.
As it is an autologous cell therapy, Cytovant will be responsible for its manufacturing in China. It is ? by no means ? the first dendritic cell vaccine to reach the clinic, but Schendel differentiated it sharply from Provenge (sipuleucel-T), the once prostate cancer therapy that gained approval almost a decade
ago. It is something of a fallen icon, given its cumbersome production process and its modest survival benefits.
Medigene?s DC vaccine can be manufactured in lots that can be frozen for up to two years. What?s more, it is based on the selective loading of isolated mature dendritic cells rather than
a mixed population of white blood cells containing both mature and immature dendritic cells.
?There?s a dramatic difference between an immature dendritic cell and a mature dendritic cells, in terms of therapeutic potential,? she said. Only mature dendritic cells sense danger signals and activate a cytotoxic T-cell response, whereas their immature counterparts mediate immune tolerance.
Medigene is also in the clinic with its lead in-house TCR-T therapy, MDG-1011, which comprises autologous T cells engineered to express a TCR directed against Prame. ?The first patient was treated in February,? Schendel said. The phase I/II dose-escalation study, which initially recruited three clinical
centers in Germany, will eventually expand to Europe and the U.S. It has a target enrollment of 92 patients.
Shares of Medigene (Frankfurt:MDG1) closed Thursday at ?10.39 (US$11.66) up 13.3 percent on the previous close.
Cytovant was jointly established by Basel, Switzerland-based Roivant Sciences Ltd. and its Chinese Sinovant Sciences Ltd., of Shanghai.
John Xu, co-founder and former president and chief scientific officer of Mab-Legend Biotech Co. Ltd., of Shanghai, has been named as Cytovant?s president.
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