Teprotumumab Biobetters
Long-Acting Anti-IGF-1R for Thyroid Eye Disease
Overview
Thyroid Eye Disease (TED) is an autoimmune fibro-inflammatory orbitopathy that produces proptosis, diplopia, pain, and vision threat. The approved anti-IGF-1R mAb teprotumumab (Tepezza®) requires 8 IV infusions Q3W over ~24 weeks, creating a high treatment burden, and carries a labeled risk of hearing impairment.
Unmet Medical Need
A biobetter that maintains efficacy while reducing infusion frequency (Q6-8W) and enabling SC feasibility directly addresses the dominant unmet need in patient convenience and access.
Therapeutic Hypothesis
Keep the antigen-binding paratope aligned with anti-IGF-1R antibodies while engineering the Fc to extend half-life via YTE (T250Q/M428L) or LS (M428L/N434S). Use structure-based modeling for Fab:IGF-1R interface preservation and Fc:FcRn plausibility.
Computational Work Performed
- AlphaFold-Multimer-class modeling of Fab:IGF-1R and Fc:FcRn complexes
- 100ns GROMACS MD simulation showing stable RMSD and interface maintenance
- Aggrescan3D aggregation hotspot analysis
- NetSolP-1.0 solubility propensity screening
- DeepImmuno T-cell epitope screening (27,280 HLA evaluations)
- Portfolio of 3 Fc-engineered variants (A: LS, C: YTE Lead, D: Alt YTE)
Next Milestones (Success Criteria)
- 1IGF-1R KD non-inferior to teprotumumab literature benchmarks
- 2FcRn pH-dependent binding (↑ at pH 6.0; minimal at 7.4)
- 3In vivo t½ extension ≥2-4× vs IgG1 WT control
- 4High monomer content (SEC-MALS), favorable Tm/viscosity
- 5High-concentration formulation to support Q6-8W IV and SC targets
Competitive Landscape
Competitor programs pursuing anti-IGF-1R antibodies with moves toward SC dosing. SC teprotumumab formulation efforts by the innovator signal a convenience race. Our positioning: Variant C (YTE lead) offers highest binding preservation and strongest PK precedent.
Key Differentiation
- Same validated biology, fewer infusions: target Q6-8W instead of Q3W
- SC-ready: high-concentration developability screens prioritize viscosity/aggregation metrics early
- Portfolio of variants ensures options if one Fc design underperforms
Interested in This Asset?
Contact our licensing team to discuss partnership opportunities, access detailed data packages, and explore collaboration terms.