Targeting pancreatic cancer metastases with Targefrin

ABSTRACT
We intend to devise a novel therapeutic strategy based on a specific cancer cell receptor named EphA2, which
is abundant on the surface of metastatic pancreatic cancers and other solid tumors including breast, lung,
prostate, ovarian, and renal cancers. Over the past several years our studies focused on testing the anti-cancer
potential of agents targeting the receptor in suppressing cell migration and invasion in cellular studies, as well
as in inhibiting tumor metastases using in vivo models. Very recently we have derived the most effective agonistic
agent reported to date (Targefrin-dimer) that potently targets the EphA2 receptor and causes its degradation. In
the completed SBIR phase I studies, the agent is remarkably effective in inducing EphA2 degradation in several
pancreatic cancer cells lines and in suppressing pancreatic cancer cell migration, and possesses favorable
pharmacokinetics and safety in vivo. Based on these data we conclude that Targefrin-dimer has a great potential
as possible therapeutic in combination with standard of care, where it could degrade a major driver for cell
migration and tumor metastases, in particular in pancreatic cancers (PCa), This phase II SBIR intends to conduct
all necessary manufacturing and IND enabling studies for IND filing with the DFA and subsequent phase I/II trials
with pancreatic cancer patients.

Grant Number: 2R44CA277917-02
NIH Institute/Center: NIH
Principal Investigator: Carlo Baggio