A Small-Molecule Drug Conjugate Targeting FAP Exhibits Potent Activity in Dogs with Spontaneous Tumors

  • J Med Chem. 2026 May 28;69(10):12634-12646. doi: 10.1021/acs.jmedchem.6c00682.
Andrea Galbiati  1 ,  Paola Roccabianca  2 ,  Silvia Dell'Aere  2 ,  Matilde Bocci  1 ,  Luigi Auletta  2 ,  Roberta Ferrari  2 ,  Alessandra Ubiali  2 ,  Elisa M Gariboldi  2 ,  Emanuele Marsala  1 ,  Pinuccia Faviana  3 ,  Francesco Bartoli  4 ,  Beatrice Zoanni  1 ,  Ettore Gilardoni  1 ,  Maurizio Longo  2 ,  Dario Neri  5  6 ,  Damiano Stefanello  2 ,  Samuele Cazzamalli  1
Affiliations
  • 1. Philochem AG, R&D department, Otelfingen CH-8112, Switzerland.
  • 2. Department of Veterinary Medicine and Animal Sciences, University of Milan, Lodi IT-26900, Italy.
  • 3. Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa 56126, Italy.
  • 4. University of Pisa and Azienda Ospedaliero Universitaria Pisana, Department of Translational Research and Advanced Technologies in Medicine and Surgery, Pisa 56126, Italy.
  • 5. Swiss Federal Institute of Technology, Department of Chemistry and Applied Biosciences, Zurich CH-8093, Switzerland.
  • 6. Philogen S.p.A, Siena I-53100, Italy.
PMID: 42142054 DOI: 10.1021/acs.jmedchem.6c00682
Abstract

Antibody-drug conjugates have transformed the treatment of Cancer, yet their clinical utility can be limited by suboptimal tumor penetration, complex manufacturing, and safety concerns. Replacing antibodies with low-molecular-weight ligands enables the generation of small molecule-drug conjugates with enhanced tumor-targeting performance. Here, we report the results of a proof-of-concept study in canine Cancer patients with OncoFAP glidotin, a small molecule-based targeted cytotoxic directed against Fibroblast Activation Protein. OncoFAP glidotin was evaluated in a dose-escalation trial in eight client-owned pet dogs bearing spontaneous FAP-positive tumors. The agent displayed an excellent safety profile, with no severe treatment-related adverse events. Six (75%) patients responded to the therapy. A tumor volume reduction of up to ∼88% in target lesions was observed on whole-body computed tomography, after only 4 weeks of treatment. These findings support further translational development activities of OncoFAP glidotin for both human and veterinary Cancer patients.

Products