FAP-2286 and Peptide-Targeted Radionuclide Development Program

In September 2019, Clovis and 3B Pharmaceuticals GmbH (3BP) entered into a global licensing and collaboration agreement with an initial focus on developing FAP-2286, a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas.1

Peptide-targeted radionuclide therapy involves a small amount of radioactive material (radionuclide) that is combined with a cell-targeting moiety peptide for the treatment of cancer; PTRT is considered a form of radiopharmaceuticals. The targeting peptide is able to recognize and bind to specific features of tumors, such as antigens and cell receptors. When injected into the patient’s bloodstream, the peptide attaches to cancer cells or cancer-associated stromal cells, delivering a high dose of radiation to the tumor while sparing normal tissues.

Clinical studies of small molecule imaging agents targeting FAP have validated this target in a diverse number of cancer indications and support the further evaluation of peptide-targeted radionuclide therapy. FAP-targeted radiopharmaceuticals have at least two potential modes of anti-tumor activity: radiation crossfire, in which tumor cells are irradiated due to their close proximity to CAFs; and depletion of CAFs, disrupting the communication between the tumor cells and the tumor stroma. In addition, in certain tumor types, such as sarcoma and mesothelioma,  FAP is expressed on the tumor cells themselves, and in those tumors, FAP-targeted radiopharmaceuticals may have a direct antitumor effect. 

Clovis plans to initiate a broad clinical development program for FAP-2286 as a FAP-targeting therapeutic agent in the first half of 2021.

Clovis has also acquired global rights to discovery program directed at three unnamed preclinical targets for radiopharmaceutical therapy.  Clovis holds global rights for the discovery program and for FAP-2286 holds U.S. and global rights, excluding Europe. 

1 Rettig, 1993, Cancer Research

FAP-2286 Scientific Presentations

Preclinical evaluation of FAP-2286, a peptide-targeted radionuclide therapy to fibroblast activation protein alpha

Poster Presentation 2020 ESMO Virtual Meeting