End-to-End Platform

The basis of Medigene’s differentiation is our End-to-End Platform of multiple, combinable, exclusive and proprietary technologies. These technologies have the potential to enhance our TCR-T drug products from a safety, durability and efficacy perspective as well as through optimizing our development processes at multiple sequential stages of development, from target screening, through TCR generation and optimization and ultimately into clinical development.

Target
Screening

TCR
Generation & optimization

TCR-T Therapy Armoring & Enhancement

Manufacturing TCR-T Drug Products

Clinical Development

= Developmental Optimization Technology
= Efficacy Enhancement Technology
= Safety Enhancement Technology

Expitope

Expitope is our improved Web-tool to assess immunotherapeutic antigens for their potential off-tumor recognition or cross-reactivity against naturally expressed proteins in human tissues. Unwanted T cell response like cross-reactivity, due to the selection of non-suitable epitopes may result in elevated off-target effects and even lethal toxicity.

Allo-HLA TCR Priming

Immune tolerance, which is also known as central and peripheral tolerance, is the active state of unresponsiveness of the immune system to specific substances or tissues to prevent autoimmune diseases. The process of negative and positive selection play a significant role in the development of central tolerance, where the immune system learns to discriminate between self and non-self. Positive selection is the elimination of T cells lacking proper binding of the T- cell receptor (TCR) to the human leukocyte antigen (HLA). Conversely, negative selection eliminates high-affinity TCRs from the T cell repertoire with a very strong binding to any self-antigens, including cancer-testis antigens (CTAs), to avoid auto-immunity.

PD1-41BB Switch Protein

The PD1-41BB costimulatory switch protein impedes tumor immune escape (“Immune evasion”), a phenomenon allowing cancer cells to proliferate and metastasize without being recognized by the host immune system. Immune evasion is one of the major challenges in immunotherapy.

CD40L-CD28 switch protein

The CD40L-CD28 costimulatory switch protein enables to overcome the immunosuppressive tumor microenvironment (TME), that represents a major challenge in immunotherapy and defines the poor outcome of different immune-therapeutic approaches.

Indicible iM-TCR

Persistent signaling can drive TCR-T cells to mediate inflammatory responses against vital tissues, especially in crucial organs like the brain. Moreover, over-activation or sustained TCR signaling can dampen the therapeutic efficacy leading to T cell exhaustion or cell death. One way to overcome persistent signaling is an inducible system to switch the TCR on and off selectively. Different approaches exist to control engineered T cells. Medigene merges its TCR with the 4OH-Tamoxifen inducible system, one of the best-characterized “reversible switch” models with numerous beneficial features.