Eidos Therapeutics has announced results from Phase I clinical trials of their lead molecule AG10, which will be advancing to Phase II in patients with cardiac amyloidosis. The trials are supported by $91 million of venture capital funding to Eidos Therapeutics.

Co-founded by Mamoun M. Alhamadsheh, PhD, associate professor of pharmaceutics and medicinal chemistry, and Isabella Graef, MD, assistant professor of pathology at Stanford University, Eidos’ mission is to develop a therapeutic treatment that addresses the root cause of transthyretin (TTR) amyloidosis. Currently there is no FDA-approved treatment for the rare, fatal disease that affects more than 250,000 people worldwide.


AG10 is a small molecule which was initially discovered by Dr. Alhamadsheh while working at Stanford University. In collaboration with Dr. Graef, their research demonstrated the stabilizing properties of AG10 on TTR.

“We are excited by the positive results from our Phase I clinical study which demonstrate that AG10 could be a best-in-class therapy,” said Dr. Alhamadsheh. “We are also grateful to have the experienced team at Eidos and the new funding to advance AG10 into Phase II.”

TTR is a relatively abundant protein found in the blood. It is normally a four-part molecule, but genetic mutations or environmental factors can cause it to become unstable. If the protein destabilizes, it can misfold, which creates amyloid fibrils which are the cause of the disease. AG10 binds to the TTR molecules, stabilizing the structure and preventing the disease-causing amyloid fibrils from forming.

Unstable TTR can result in TTR cardiomyopathy or TTR polyneuropathy, both of which are progressive, fatal diseases. TTR cardiomyopathy can be caused by a genetic mutation, the most common mutation, V122I-TTR, is found in approximately 4 percent of African-Americans. The only disease-modifying treatment currently available is a liver and heart transplant. For patients with TTR polyneuropathy, misfolded TTR amyloid fibrils accumulate in the peripheral nervous system, which affects movement and sense of touch, as well as digestive and cardiovascular functions.


Pacific faculty and students have been instrumental in demonstrating the early potential of AG10. Dr. Alhamadsheh has been assisted in his research by William K. Chan, PharmD, PhD, professor and chair of the Department of Pharmaceutics and Medicinal Chemistry, Miki Susanto Park, PhD, professor of pharmaceutics and medicinal chemistry, Sravan C. Penchala ’16, PhD, Wabel Albusairi ’17, PhD, Mark Miller ’18 and Arindom Pal ’19. Dr. Alhamadsheh continues to be involved in Eidos as a scientific advisor.

By Anne Marie H. Bergthold
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