Wolfgang Miesbach: Discussing Immunological Challenges in Hemophilia at GTH 2026
Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared a post on LinkedIn:
“A standout session at GTH was ‘The immunogenicity of therapeutic proteins in hemostasis – an overview’ by Sebastien Lacroix-Desmazes.
The talk clearly highlighted the immunological challenges in haemophilia — from classical FVIII inhibitors to gene therapy and anti-drug antibodies (ADAs) against newer engineered therapies.
One especially interesting point: FVIII-mimetic bispecific antibodies do not seem to share the same immunogenic profile
- Emicizumab։ ADA signal reported
- NXT007։ ADA signal also observed in early studies
- Mim8։ no ADA signal in the study presented
A likely reason is molecular design:
- Emicizumab is a humanized and highly engineered bispecific antibody; such optimization can improve function, but may also introduce non-self sequences or neoepitopes.
- NXT007, as a further optimized derivative, may retain or add immunogenic determinants.
- Mim8, with a more fully human design strategy, may reduce immune recognition
Take-home message:
Shared mechanism does not equal shared immunogenicity. Even when therapies target the same pathway, immune responses can differ because of humanization strategy, sequence design, and epitope architecture.”
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