Bart VandekerckhoveGhent University

Production of investigationaladvanced therapy medicinal products for phase I clinical trials

CERTAIN TUMORS ARE IMMUNOGENIC

R.T. Prehn, J.M. Main

Immunity to

methylcholanthrene-induced

sarcomas

J. Natl. Cancer Inst., 18 (1957)

2

Adaptive immune resistance.

Daniel Morgensztern, and Roy S. Herbst Clin Cancer Res

2016;22:3713-3717

©2016 by American Association for Cancer Research3

IMMUNOGENIC TUMORS ARE CURABLE BY IMMUNE ACTIVATION

4

MUTATIONS GENERATE IMMUNOGENIC TUMORS

Number of somatic mutations in

representative human cancers,

detected by genome-wide

sequencing studies.

B Vogelstein et al.

Science 2013;339:1546-1558

Published by AAAS

5

CERTAIN TUMORS ARE IMMUNOGENIC

| MIDRIXNEO : MPLA-Interferon-activated neoantigen-targeted dendritic cell vaxine

GM-CSF

IL-4

IFNγ

MPLA

| A truly personalized approach

Sahin U and Türeci Ö. Science 2018.

Slide courtesy of Mark Lowdell, UCL

| Good manufacturing practices

GMP environment:

Controlled environment

Risk reduction

RISKS?

Starting

materials

ATMPmRNA

Apheresis

product

Drug substance:

mRNA electroporated

DC

Drug products: frozen

mRNA EP DC

Full documentation in the Investigational Medicinal Product Dossier

GMP facility and production process audited and licensed by FAGG

▪ Research

▪ Open systems

▪ Bovine serum

▪ GMP

▪ Closed systems

▪ No animal products

| Translation into a GMP compliant protocol

| Clean room: clean, cleaner, cleanest

Clean room environment atGMP unit 3 Cell Therapy UZ Ghent

• Qualified personnel

• Controlled environment

• Strict clothing requirements

• Control of devices

13

14

?

| MIDRIXNEO team

Principal investigatorsProf. Karim VermaelenProf. Bart Vandekerckhove

GMP productionProf. Bart VandekerckhovePam DevrekerSaskia DesmetNele LootensSarah Vanrenterghem

BioinformaticsProf. Bjorn MentenProf. Kathleen ClaesLaurenz De Cock

ImmunologyDr. Elisabeth BrabantsJoline IngelsKelly Heyns

ImmunopeptidomicsProf. Francis ImpensDr. Rupert Mayer

FarmacyProf Stefaan DE SmedtDr Ine LentackerDr Heleen De witte

SponsorsKom op tegen KankerUniversity of Ghent