2. Academic Validation
  3. A Small-Molecule Drug Conjugate Targeting FAP Exhibits Potent Activity in Dogs with Spontaneous Tumors

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

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.

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