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Design and characterization of Zweimab and Doppelmab, high affinity dual antagonistic anti-TSLP/IL13 bispecific

Sathyadevi Venkataramani1, Sarah Low1, Bernd Weigle2

  • 1Boehringer Ingelheim Pharmaceuticals Inc, 900 Ridgebury Rd, Ridgefield, CT, USA.

Biochemical and Biophysical Research Communications
|August 22, 2018
PubMed

Insights

Novel bispecific antibodies targeting both TSLP and IL13 cytokines were developed. These dual-action therapies aim to overcome steroid resistance and reduce exacerbations in severe Th2 asthma patients unresponsive to single-pathway treatments.

Area of Science:

  • Immunology
  • Respiratory Medicine
  • Biotechnology

Background:

  • Severe Th2 type asthma is characterized by steroid resistance and frequent exacerbations.
  • Current therapies targeting single pathways offer limited efficacy in many patients.
  • Redundant signaling pathways may contribute to treatment unresponsiveness.

Purpose of the Study:

  • To design and develop novel bispecific antibodies targeting both thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL13).
  • To investigate the potential of concurrently inhibiting TSLP and IL13 signaling for improved asthma treatment.
  • To address the limitations of current therapies in managing severe, steroid-resistant asthma.

Main Methods:

  • Development of novel monovalent bispecific antibodies (Zweimabs) and bivalent bispecific antibodies (Doppelmabs).
  • Design focused on concurrent inhibition of TSLP and IL13 signaling pathways.
  • Utilized advanced antibody engineering techniques to create potent dual-targeting agents.

Main Results:

  • Successfully designed and developed highly potent bispecific antibodies (Zweimabs and Doppelmabs).
  • These antibodies are engineered to concurrently inhibit TSLP and IL13 signaling.
  • The dual-targeting approach addresses multiple redundant pathways implicated in severe asthma.

Conclusions:

  • Novel bispecific antibodies (Zweimabs and Doppelmabs) offer a promising therapeutic strategy for severe Th2 asthma.
  • Concurrent inhibition of TSLP and IL13 may overcome steroid resistance and reduce exacerbations.
  • Targeting multiple redundant pathways represents a potential advancement in asthma treatment.
Keywords:
AsthmaBispecificEpitope mappingIL13SPRTSLP

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