Diversified pipeline of radiopharmaceuticals in development to address unmet needs in cancer
THE FUSION PIPELINE
Fusion is progressing an earlier-stage product candidate, FPI-1966, into clinical development. FPI-1966 is designed to target and deliver 225Ac to tumor sites expressing FGFR3, a protein that is overexpressed in head and neck and bladder cancers. FPI-1966 utilizes our Fast-Clear linker to connect a human monoclonal antibody that targets FGFR3 with 225Ac. Fusion plans to submit an investigational new drug application to the FDA.
FPI-2059 is a small molecule radioconjugate in development as a targeted alpha therapy for various solid tumors. The molecule targets neurotensin receptor 1 (NTSR1), a promising target for cancer treatment, that is overexpressed in multiple solid tumors. FPI-2059 combines Ipsen’s IPN-1087, which Fusion acquired in 2021, with actinium-225. IPN-1087 was previously in Phase 1 clinical development as a lutetium-177-based radiopharmaceutical for pancreatic ductal adenocarcinoma, colorectal cancer and gastric cancers expressing NTSR1.
Fusion is currently conducting a Phase 1, non-randomized, multi-center, open-label clinical trial in patients with solid tumors expressing IGF-1R to investigate the safety, tolerability and pharmacokinetics of FPI-1434 as well as to establish the maximum tolerated dose and potentially the recommended Phase 2 dose. FPI-1434 is a targeted alpha radioimmunoconjugate that consists of a humanized monoclonal antibody targeting the insulin-like growth factor-1 receptor 1 (IGF-1R), our Fast-Clear™ linker technology, a bifunctional chelate, and actinium-225 (225Ac).
As part of the screening process for the trial, all patients are administered a single injection of 185 megabecquerel, or MBq, of FPI-1547, the imaging analogue of FPI-1434 which contains 111In instead of 225Ac, and SPECT and planar imaging is used to evaluate tumor uptake of the imaging isotope. In accordance with the trial protocol, patients that meet predefined uptake and dosimetry criteria for FPI-1547 are advanced into the trial and administered a single dose of FPI-1434 within approximately fourteen days of receiving the imaging analogue.
Based on the mechanisms of action of FPI-1434 and data from preclinical studies, Fusion is also evaluating the combination potential of FPI-1434 with checkpoint inhibitors as well as DNA damage repair inhibitors (DDRi’s), which include poly (ADP-ribose) polymerase, or PARP, inhibitors.
The first planned study is to evaluate FPI-1434 in combination with Merck’s anti-PD-1 (programmed death receptor-1) therapy, KEYTRUDA® (pembrolizumab), in patients with solid tumors expressing IGF-1R.