PB0368 - Development and First Human Transfusion of Allogeneic iPSC-Derived Platelet Product (MEG-002)

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Kazumasa Takao, PhD (he/him/his)

Project Leader
Megakaryon Corporation
Kyoto, Kyoto, Japan

Co-Author(s)

HH

Hidenori Hirose

Expert, preclinical research & clinical pharmacology
Megakaryon Corporation
Kyoto, Kyoto, Japan
HK

Hiromichi Konno

Manager, clinical operations
Megakaryon Corporation
Kyoto, Kyoto, Japan
NS

Naoshi Sugimoto

Associate Professor
Center for iPS Cell Research and Application, Kyoto University
Kyoto, Kyoto, Japan
JK

Junya Kanda

Associate Professor
Department of Hematology, Kyoto University Hospital
Kyoto, Kyoto, Japan
YS

Yuya Sato

Expert, CMC process engineering
Megakaryon Corporation
Kyoto, Kyoto, Japan
YH

Yasuko Hazama

Expert, CMC analysis & quality control
Megakaryon Corporation
Kyoto, Kyoto, Japan
MU

Michiko Ueda

Scientist
Megakaryon Corporation
Kyoto, Kyoto, Japan
YH

Yamato Haraguchi

Scientist
Megakaryon Corporation
Kyoto, Kyoto, Japan
MS

Mizue Suzuki

Scientist
Megakaryon Corporation
Kyoto, Kyoto, Japan
JT

Junko Tomizuka

Scientist
Megakaryon Corporation
Kyoto, Kyoto, Japan
MN

Masayuki Nogawa

Researcher
Keio University School of Medicine
Tokyo, Tokyo, Japan
NW

Naohide Watanabe

Associate Professor
Keio University School of Medicine
Tokyo, Tokyo, Japan
AS

Akira Sawaguchi

Professor
Department of Anatomy, Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
AT

Akifumi Takaori-Kondo

Professor
Department of Hematology, Kyoto University Hospital
Kyoto, Kyoto, Japan
YK

Yoshihiro Kumagae

Chief Technology Officer
Megakaryon Corporation
Kyoto, Kyoto, Japan

Background: Although platelet concentrates are essential to treat or prevent bleeding in thrombocytopenia, maintaining an adequate supply is challenging due to their short shelf life, ageing society and finding compatible donor for alloimmunized patients. Recently, iPLAT1, a clinical trial on autologous transfusions of an induced pluripotent stem cell-derived platelet product (iPSC-PLTs) was completed. Here we report development of MEG-002, iPSC-PLTs for allogeneic use.

Aims: To establish efficacy and safety of MEG-002 in preclinical studies. We also present preliminary results of the first-in-human trial of MEG-002.

Methods: MEG-002 is produced from an immortalized megakaryocyte cell line, imMKCL, master cell bank derived from an iPSC line, YZWJs513 which is a homozygous of the most frequent human leukocyte antigen haplotype in Japan. MEG-002 was manufactured using turbulent-flow bioreactors following the previously published method. Hemostatic efficacy and blood circulation of MEG-002 were examined in a rabbit model of thrombocytopenia and splenectomized rabbits, respectively. Preclinical safety studies included a general toxicity study in immunocompromised mice. The clinical trial was approved by Kyoto University Hospital Institutional Review Board. MEG-002 at a dose of 0.6 x 10^11 was infused to a thrombocytopenic patient after obtaining informed consent.

Results: MEG-002 with sufficient quality and quantity for clinical use was successfully manufactured. MEG-002 demonstrated hemostatic efficacy and blood circulation comparable to donor-derived platelets in animal models. Results of preclinical safety studies showed no sign of toxicity. In the clinical study, no adverse event was reported and there were no clinically relevant changes in vital signs, laboratory tests etc. An increase in platelet counts was observed after the transfusion. Moreover, by using flow cytometry, iPSC-PLTs were counted separately from endogenous platelets, thereby confirming the circulation of iPSC-PLTs.

Conclusion(s): The efficacy and safety of MEG-002 was established in a series of preclinical studies. An exploratory clinical trial was initiated, and preliminary results are promising.