Breakthrough estrogen discovery in Milwaukee

Approximately 6.2 million Americans are living with Alzheimer’s Disease, which is the leading cause of dementia. The two key risk factors in the development of Alzheimer’s Disease are age and sex. According to the Alzheimer’s Association, nearly two-thirds of those living with Alzheimer’s are women. That difference sparked researchers to study the effects of estrogens in the brain. Simply boosting estrogen levels in aging women would not safely prevent the adverse side effects of estrogen depletion. They noted traditional estrogen therapies work to alleviate the troublesome symptoms of menopause, like hot flashes, but also come with an increased risk of stroke and the development of cancer.  Something more needed to be done to protect the health of women as they aged, and the team at Estrigenix Therapeutics, Inc. embraced that challenge.

Dr. William Donaldson and Dr. Daniel Sem met while faculty members at Marquette University. Donaldson was making compounds to selectively target estrogen receptor beta, a protein associated with the beneficial effects of estrogens on brain function but not the cancer-causing effects of other estrogen receptors. This work intrigued Sem, and eventually the pair began to collaborate in the lab. While looking to add a specialist to test the cognitive effects of their compounds, the professors were introduced to Dr. Karyn Frick, one of the leading specialists in the study of estrogen’s impact on the brain. The scientists began working together in 2015 to find a safe solution to this perplexing problem faced by nearly half of the world’s population.

After years of work, the group created a modified version of estrogen that binds very specifically to estrogen receptor beta, sparing its user from the negative effects of traditional estrogen therapies. They patented this lead compound under the name EGX358. EGX358 works to stimulate the growth of neural connectors, resulting in improved memory in pre-clinical studies. These studies also suggest that it provides relief from hot flashes. If similar results are seen in clinical trials, EGX358 may be the breakthrough needed to help alleviate some of the worst side effects of menopause. The group formed Estrigenix Therapeutics, Inc. in 2018 with the goal of turning this discovery into a safe treatment for menopausal women in pill form.

 “I think it’s everyone’s goal- to live our life to the fullest until it’s over, right?,” Frick said. “And nobody wants to live with Alzheimer’s; it’s a long goodbye. Nobody wants to end their lives that way and put their families through the pain of watching them disappear.”

Frick is a renowned neuroscientist who wears many hats. Beyond teaching, running a federally-funded research lab and co-directing the university’s new Neuroscience major, she is the Chief Scientific Officer at Estrigenix Therapeutics. Frick began her studies as a pre-med major with a keen interest in biology. While in college, she discovered her passion for psychology, which led her to the burgeoning field of neuroscience. For more than 30 years she has studied the effects of hormones on the brain.

Estrigenix Therapeutics had a newly designed molecule, but no way to get it into the hands of the women who could use it. To move their discovery from the laboratory to the boardroom, Donaldson and Frick enrolled in the Milwaukee I-Corps, the local chapter of a National Science Foundation-supported program that links new venture and business mentors with academics to help commercialize research ideas. They’ve gone through the program twice.

““The first time we went through it, the process was enormously helpful and illuminating for two academics who know nothing about business to start understanding the language of business value propositions and such,” she said. ““This whole notion of the I-Corps model basically uses a scientific method approach to understanding your customers and your business, and was really very appealing for scientists. Develop a hypothesis, meet with people, collect data, then reevaluate your hypothesis and make a decision to “Go” or “No Go”.”

Their seed money has primarily come in grant form. The team was awarded two National Institutes of Health (NIH) grants and two UWM Research Foundation (UWMRF) grants, and won funds from the UW System Regent Scholar Award program to test EGX358 in a mouse model of Alzheimer’s disease. The group plans to apply for a Small Business Innovation Research grant in January and has received interest from several angel investors as they make their plans to begin Series A funding. The preliminary Series A funding goal is $3 million. Estrigenix estimates it will need to raise $10 million to take their work from the Phase I, pre-clinical stage to FDA approval, a process that will likely take seven years.

“The more we can do to keep ourselves mentally sharp and physically healthy, the longer into our lives, the better,” Frick said. “It’s going to be better for everybody.”

To follow the progress on this ground-breaking development in estrogen replacement therapy, connect with Estrigenix on their website, LinkedIn, or Facebook.