Peer-Reviewed Study in Cell Validates eFFECTOR Therapeutics’ Novel Small-Molecule Approach to Cancer Treatment

Research at University of California, San Francisco Demonstrates Powerful Effects of Targeting Translation of Disease-Causing Proteins

SAN DIEGO, June 19, 2015 – eFFECTOR Therapeutics co-founder Davide Ruggero, Ph.D., has published ground-breaking research in the preeminent biomedical journal Cell which demonstrates preclinical promise for a cancer treatment approach that’s centered on selectively regulating the cell’s protein synthesis process, known as translation.

Dr. Ruggero, the Helen Diller Family Chair in Basic Research in Urologic Cancer at University of California, San Francisco (UCSF), reveals in his study that targeting a key factor involved in translating messenger RNA (mRNA) into proteins may be an effective therapeutic approach for cancer. His findings are published online in an article titled, “Differential requirements for eIF4E dose in normal development and cancer” and will appear in the July 2 print edition of Cell.

“We know that cells have a precisely orchestrated process for translating mRNA into proteins, and a small subset of proteins in a cell, frequently those involved in driving key cellular functions, are subject to tight translational regulation,” said Steve Worland, Ph.D., President and CEO of eFFECTOR. “If this process becomes dysregulated, key driver proteins can be made inappropriately leading to cancer and other serious diseases. The study published in Cell provides important validation of eFFECTOR’s approach to treat disease by selectively restoring control to the translational landscape.”

Dr. Ruggero’s research shows that cells normally have a surplus of a key regulator of translation control, eukaryotic initiation factor 4E (eIF4E), such that a 50 percent reduction in eIF4E levels does not affect normal development or global protein synthesis. However, the expression of a small subset of proteins required for transformation and cancer cell survival is significantly down regulated when eIF4E levels are reduced. This suggests that eIF4E may be a suitable target for therapeutic intervention—in line with eFFECTOR’s approach to drug discovery and development. The results demonstrating highly selective effects of eIF4E reduction on translation of a small subset of mRNA were obtained using techniques eFFECTOR applies to the characterization of targets and drug effects. Applications of these techniques in the area of pharmaceutical R&D were exclusively licensed by eFFECTOR from UCSF.

The study findings showing selective impact on cancer promoting proteins were confirmed both in animal models and in human tumor cell lines, suggesting that selectively targeting eIF4E may be a safe way to shut down the production of proteins known to cause cancer while leaving normal cellular processes unaffected. (Read the full article in Cell to learn more.)

eFFECTOR is leveraging this cutting-edge approach in several programs as it advances a new class of small-molecule therapies for oncology and other serious diseases.

Heidi Chokeir, Ph.D.