EGFR
Epidermal growth factor receptor
Design a conditional EGFR binder
EGFR is one of the most clinically validated targets in oncology, and also one of the clearest illustrations of why affinity alone is not enough. This challenge asks for three properties that current EGFR therapeutics achieve only partially: binding human EGFR, binding the orthologs used in preclinical studies, and binding selectively in acidic tissue.
Submissions are open until Tuesday, October 6, 23:59 AoE.
EGFR extracellular region with a cetuximab Fab mutant · PDB 6ARU
Target information
Design against human EGFR’s extracellular region. We recommend targeting a functional epitope such as domain III.
Human EGFR
Extracellular region- UniProt reference
- P00533-1 ↗
- Target residues · UniProt
- 25–645 / 621 aa
- Recommended epitope
- Domain III
- Structure reference
- 6ARU · Chain A ↗
Amino acid sequence
LEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSThree objectives
This challenge consists of 3 main objectives, and each will be accounted for when selecting the best designs.
01
Binding affinity
Design a binder against human EGFR. We recommend targeting a functional epitope such as domain III, which is also targeted by the therapeutic antibodies cetuximab and panitumumab.
We’ll measure its binding affinity using the full extracellular region of the human receptor.
02
Mouse cross-reactivity
In the next objective, you should design a binder that recognises both human and mouse EGFR. On top of the validation from Objective 1, we will test binding against the mouse EGFR.
Binding both species would make it easier to study the same design in mouse models before moving to human studies, without developing a separate mouse-specific binder.
How designs are ranked
- 1
pH-selective binding
Does the design bind EGFR at pH 6.5 but show no detectable binding at pH 7.4?
- 2
Mouse cross-reactivity
Does the same sequence bind mouse EGFR as well as human?
- 3
Affinity
Affinity against human EGFR.
Timeline
Sep 28 – Oct 6, 2026
- 1nowSubmit designs
Submissions open
Design, review, and submit. Submissions close Tuesday, October 6 at 23:59 Anywhere on Earth (AoE).
- 2
Submissions closed
The window is closed. No further designs are accepted for this challenge.
- 3
Selection in progress
Anthropic and Adaptyv select designs for synthesis using a Claude-based workflow, published after the competition.
- 4
Wet-lab validation in progress
Selected designs go to Adaptyv's automated lab for experimental validation.
Submission requirements
- Length
- 10–250 amino acids
- Format
- Single chain protein, nanobody, scFv, or Fab
- Designs per participant
- Up to 40 for Track 1, up to 20 for Tracks 2 and 3
- Design
- De novo designs only