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PIPELINE > TRIAL OVERVIEW

Molecule Overview
PTK7 Antibody-Drug Conjugate
LY4175408
PTK7 MoA

Golubkov VS, et al1; Fu Z, et al2; Dessaux C, et al3

Target

Protein tyrosine kinase 7 (PTK7) is a catalytically inactive transmembrane receptor tyrosine kinase. It is implicated as a modulator of several signaling pathways, most notably Wnt.3 PTK7 is highly expressed in primary tumors (eg, ovarian cancer, NSCLC, and triple-negative breast cancer) as well as in tumor-initiating cells (TICs).4

Molecule

LY4175408 is a PTK7-targeting antibody-drug conjugate (ADC) composed of a fully human Fc-silenced IgG1 monoclonal antibody, a proprietary polysarcosine hydrophobicity masking agent with a cleavable linker, and the topoisomerase I inhibitor payload exatecan. It has a drug-antibody ratio (DAR) of 8:1. In preclinical models, LY4175408 has shown activity against a range of PTK7-expressing tumors, including low and moderate PTK7-expressing tumors.5

Clinical Development

LY4175408 preclinical data support further evaluation in clinical trials.5

References

  1. Golubkov VS, et al. J Biol Chem. 2010;285(46):35740-35749.
  2. Fu Z, et al. Signal Transduct Target Ther. 2022;7(1):93.
  3. Dessaux C, et al. Oncogene. 2024;43(26):1973-1984.
  4. Damelin M, et al. Sci Transl Med. 2017;9(372):eaag2611.
  5. Sagar D, et al. Abstract presented at: EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics; October 23-25, 2024; Barcelona, Spain. Abstract 520 LBA.
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