OncoFAP-GlyPro-MMAE / Philogen - LARVOL DELTA

Combination with Immunocytokines Enhances the Anticancer Activity of Small Molecule Drug Conjugates and Radioligand Therapeutics Targeting Fibroblast Activation Protein. (PubMed, Mol Pharm) - "A therapy experiment in immunocompetent mice bearing low FAP-expressing tumors showed that the combination with L19-hIL2 potentiated the antitumoral activity of 177Lu-OncoFAP-23 and OncoFAP-GlyPro-MMAE. These results provided the motivation for the clinical development of these combinations for treating FAP-positive solid tumors."

Journal • Oncology • Solid Tumor • FAP

Development of multivalent FAP-targeted Small Molecule-Drug Conjugates with tailored MMAE release kinetics. (PubMed, Mol Cancer Ther) - "We compared the kinetic profiles of the monovalent and trivalent derivatives of OncoFAP through in vivo and ex vivo biodistribution and therapy studies. The distinct in vivo MMAE release obtained for OncoFAP-GlyPro-MMAE and TriOncoFAP-GlyPro-MMAE did not lead to substantial differences in therapeutic efficacy in a preclinical FAP-positive cancer model."

Journal • Oncology • Solid Tumor • FAP

Delivery of Monomethyl Auristatin F to the Tumor Microenvironment with Noninternalizing Fibroblast Activation Protein-Cleavable Small Molecule-Drug Conjugates Elicits Potent In Vivo Anticancer Activity. (PubMed, Bioconjug Chem) - "The novel OncoFAP-GlyPro-MMAF and the previously described OncoFAP-GlyPro-MMAE were compared in a head-to-head therapeutic experiment in mice bearing FAP-positive tumors. Surprisingly, the MMAF conjugate mediated potent antitumor activity, despite its poor cellular permeability."

Journal • Preclinical • Oncology • Solid Tumor • FAP

In vivo activation of FAP-cleavable small molecule-drug conjugates for the targeted delivery of camptothecins and tubulin poisons to the tumor microenvironment. (PubMed, J Control Release) - "The Glycine-Proline FAP-cleavable technology was directly benchmarked against linkers found in Adcetris™, Enhertu™, and Trodelvy™ structures by means of in vivo therapeutic experiments in mice bearing tumors with cellular or stromal FAP expression. OncoFAP-GlyPro-Exatecan and OncoFAP-GlyPro-MMAE emerged as the most efficacious anti-cancer therapeutics against FAP-positive cellular models. OncoFAP-GlyPro-MMAE exhibited a potent antitumor activity also against stromal models, and was therefore selected for clinical development."

Journal • Preclinical • Tumor microenvironment • Oncology • Solid Tumor • FAP

Optimisation of FAP-targeted small molecule drug conjugates for the delivery and release of cytotoxic payloads in solid tumors (ESMO-TAT 2024) - "Conclusions OncoFAP-GlyPro-MMAE emerged as a highly promising candidate for the selective delivery and release of the MMAE cytotoxic payload at the site of disease. The compound has been selected for clinical development and is planned to enter phase I studies shortly."

Oncology • Solid Tumor • FAP