Tetra’s Fragile X Clinical Trial – The Most Successful So Far

FRAXA Research Foundation Berry-Kravis, Elizabeth • Cogram, Patricia • Research Updates September 7, 2021March 5, 2025cyclic AMP, drug tolerance, FRAXA-DVI, NIH, PDE4, Tetra Therapeutics, World Fragile X Day

Dr. Mark Gurney, CEO of Tetra Therapeutics, discusses how one of the earliest clues to the biology of Fragile X led to the most successful Fragile X clinical trial to date. Following the initial finding of decreased cyclic AMP levels in Fragile X patients, FRAXA funded many studies in the mouse and fly models of Fragile X implicating phosphodiesterase 4 (PDE4), the enzyme which breaks down the key intracellular messenger, cAMP, as a major treatment target.

FRAXA and Tetra began working together after one of these key FRAXA-funded studies caught the attention of Dr. Gurney. Through the FRAXA Drug Validation Initiative, Dr. Patricia Cogram was able to conduct preclinical validation experiments with Tetra’s lead compound (BPN14770) in record time, paving the way for clinical trials. These studies showed that the drug rescued nearly all abnormalities examined in the mouse model, with no development of tolerance, and long term benefit even after the drug was stopped. Shortly after this preclinical validation, FRAXA, Tetra, and Dr. Elizabeth Berry-Kravis began planning an initial clinical trial of BPN14770 in Fragile X subjects. Despite the pandemic, this trial finished on schedule, with 30/30 subjects completing the protocol. The results were a resounding success!

Tetra is now launching a larger follow up trial for more individuals with Fragile X at medical centers around the US.

This excerpt came from the Fragile X Syndrome: In Pursuit of a Cure webinar that took place on World Fragile X Day 2021. It was hosted by WuXi AppTec in partnership with FRAXA Research Foundation. Feel free to watch the webinar in its entirety.