Armida Labs, Inc., a University of California, Riverside startup company located in the incubator space on campus, has been awarded a $2.25 million Small Business Innovation Research, or SBIR, grant from the National Cancer Institute of the National Institutes of Health. The grant will support preclinical investigational new drug (IND) application studies, which are critically required before human clinical trials can be initiated.

The company will use the funding to advance the development of Targefrin, a new anti-metastatic agent designed to target and degrade EphA2 (ephrin type-A receptor 2), a protein frequently overexpressed in many cancers, including pancreatic, prostate, lung, breast, ovarian, and colorectal cancers. EphA2 spreads cancer by allowing malignant cells to migrate from the primary tumor into circulation and eventually adhere to other tissues.

Targefrin was discovered in the laboratory of Maurizio Pellecchia, a distinguished professor of biomedical sciences in the UCR School of Medicine and co-founder of Armida Labs. The IND studies will be led by Carlo Baggio, Armida Labs' co-founder, chief technology officer, and principal investigator on the grant.

Baggio, formerly a senior scientist in Pellecchia's research group, said developing targefrin as a potent and effective EphA2-targeting agent has been the group's focus for several years.

"EphA2 drives the aggressive spread of pancreatic cancer, and patients with high EphA2 levels tend to have a poor prognosis. Targefrin works by degrading EphA2 in cancer cells, making tumors significantly less aggressive," he said. "This Phase II award builds on a prior $600K SBIR Phase I grant that enabled Armida Labs to successfully advance the development of Targefrin."

Pellecchia said the team at Armida Labs is excited to develop a molecule that was originally conceived in his laboratory at the UCR School of Medicine; he hopes the grant will allow Armida Labs to develop it all the way to a potential clinical candidate.

"Our initial applications will focus on pancreatic cancer, a largely unmet medical need, but the agent, if successful, could be deployed against several solid tumors that present aberrant EphA2 expression," said Pellecchia, who holds the Daniel Hays Endowed Chair in Cancer Research and is director of the Center for Molecular and Translational Medicine at the UCR School of Medicine. "Continued fundraising efforts will remain critical to complement this valuable grant and help bring this promising anti-metastatic agent into clinical testing."

Pellecchia explained that Targefrin is a dimeric peptide mimetic - a synthetic molecule designed to imitate the structure and function of natural peptide ligands. Specifically, it mimics ephrins, the natural binding partners of EphA2. Through a biological process known as dimerization (the binding of two identical or similar molecules to form a "dimer"), Targefrin induces EphA2 to dimerize, which effectively eliminates EphA2 from the surface of cancer cells.

"EphA2 plays a dual role in cancer biology," Pellecchia said. "When bound to its natural ephrin ligands, EphA2 acts as a tumor suppressor, inhibiting cell migration and proliferation. However, in cancers such as pancreatic, prostate, breast, lung, and ovarian tumors, EphA2 is frequently overexpressed without corresponding ligand availability, turning it into a pro-oncogenic driver of cancer cell invasion and metastasis. Targefrin corrects this imbalance by mimicking ephrins and targeting EphA2 for degradation."

The development of Targefrin in Armida Labs followed an iterative design and optimization process, with each chemical modification aimed at improving its binding affinity and specificity for EphA2.

"With support from the NIH and additional fundraising efforts, we at Armida Labs are positioned to advance Targefrin toward clinical trials," he said. "Our initial focus is pancreatic cancer as well as potential expansion to other EphA2-driven malignancies."