FAP-2286 and Peptide-Targeted Radiotherapy 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 alpha (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. 

An abstract describing the first presentation of FAP-2286 preclinical data in animal models has been accepted for the 2020 ESMO Virtual Congress, and during Q4 2020, Clovis intends to submit two Investigational New Drug (IND) applications for FAP-2286 for use as imaging and treatment agents respectively. Upon activation of the INDs by the U.S. FDA, Clovis will initiate a Phase 1 study to determine the dose and tolerability of the FAP-targeting therapeutic agent, with expansion cohorts planned in multiple tumor types. The FAP-targeting imaging agent will be utilized to identify tumors that contain FAP for treatment in the Phase 1 study.

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

To learn more, view the presentation provided below.

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

Introduction to FAP Program and PTRT Platform

October 2019