Amazentis Announces Successful Phase IA/IB Study Results In Healthy Elderly Subjects With The Food Metabolite Urolithin A

LAUSANNE, Switzerland--(BUSINESS WIRE)--Amazentis SA, an innovative life sciences company pioneering scientific breakthroughs in nutrition to manage health conditions linked to aging, announced today Phase 1 clinical data on the safety, bioavailability, and biological activity of Urolithin A in a double-blind, randomized, placebo-controlled clinical trial in healthy elderly individuals. The study consisted of two parts, a single ascending dose (part A), followed by a multiple ascending dose for a period of 4 weeks (part B). These data are scheduled to be presented at the International Conference on Frailty and Sarcopenia Research (ICFSR) taking place in Barcelona, Spain, April 27-29, 2017.

“Orally administered Urolithin A is safe and modulates muscle and mitochondrial biomarkers in a randomized, double-blind, placebo controlled Phase 1 clinical trial in elderly”

The clinical findings demonstrated:

• Achievement of the Phase 1A/1B study’s primary safety endpoint; no serious and no product-related non-serious adverse events were reported during the conduct of parts A and B;
• Bioavailability of Urolithin A in blood and skeletal muscle;
• Upregulation of mitochondrial gene expression in elderly skeletal muscle tissue during part B; and
• Decrease of the plasma acylcarnitine metabolites during part B

“We are pleased to report these first clinical data that demonstrate both the safety of Urolithin A and the translation of its biological effects to elderly human subjects. Urolithin A holds promise for the management of age-related decline in mitochondrial and skeletal muscle function, for which there are currently no pharmaceutical therapies and where nutritional strategies have had limited impact to date,” commented Chris Rinsch, PhD, CEO and co-founder of Amazentis.

“It's exciting to see that orally administered Urolithin A is increasing mitochondrial gene expression in human muscle tissue following a 4-week treatment,” commented Johan Auwerx, MD, PhD, Professor at the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland. “Combined with the lowering of plasma acylcarnitines, this is the first evidence that Urolithin A stimulates mitochondria in the muscle of humans and is consistent with our earlier preclinical observations, which demonstrated that such molecular changes were coupled to enhanced muscle function.”

Phase 1 study of first-in-class natural bioactive to improve mitochondrial and muscle function in the elderly

Amazentis’ Phase 1 study of Urolithin A (AMAZ-02) was a single-center, multi-part (single and multiple ascending doses) double-blind, randomized, placebo-controlled study in 60 healthy elderly subjects. Part A of the Phase 1 study involved orally administering single escalating doses (250mg, 500mg, 1000mg, and 2000mg). During Part B, 250mg, 500mg, and 1000mg were selected for 4 weeks of daily oral dosing and their impact on skeletal muscle mitochondrial biomarkers was investigated along with safety and bioavailability. Additional information on the clinical trial design is available on clinicaltrials.gov.

All doses were observed to be safe and bioavailable. No serious and no product-related non-serious treatment emergent adverse events were recorded during the conduct of the Phase 1 human study. The impact of Urolithin A on plasma and muscle biomarkers following 4-week multiple ascending dosing were assessed, revealing that Urolithin A intake significantly modulated both gene expression and plasma metabolites linked to mitochondrial and muscle function.

These key clinical results will be reported in an oral presentation titled, “Orally administered Urolithin A is safe and modulates muscle and mitochondrial biomarkers in a randomized, double-blind, placebo controlled Phase 1 clinical trial in elderly,” at the ICFSR conference on April 28, 2017, at 5:45pm CEST.

Results of a second, non-interventional study conducted by Amazentis revealed the strong link between low mobility status in elderly and declining mitochondrial function in skeletal muscle. These results will also be reported in an oral presentation titled, “Mitochondrial dysfunction as a driver for age related muscle decline and frailty syndrome: A clinical study comparing active versus pre-frail elderly,” also taking place on April 28, 2017, at 4:45pm CEST. Abstracts of these presentations will also be published in a special edition of the scientific review The Journal of Frailty & Aging.

“The positive advancement of our clinical research program highlights the promise of Urolithin A and its potential health benefits driven by the strong underlying science,” explained Patrick Aebischer, MD, Chairman of Amazentis and Professor at the EPFL. “These results set the stage for Phase 2 clinical studies featuring a longer intervention period and designed to assess the impact of Urolithin A on muscle and mitochondrial function in the healthy elderly population.”

About Urolithin A (AMAZ-02)

Amazentis lead product is AMAZ-02, a proprietary form of Urolithin A, a naturally occurring metabolite that has been shown to improve mitochondrial and muscle function through a process known as mitophagy. These findings were published in a peer-reviewed article titled, “Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents” (doi:10.1038/nm.4132), which appeared last year in Nature Medicine and featured key findings from preclinical research conducted in collaboration with Prof. Auwerx's laboratory.

About Amazentis

Amazentis SA is a life science company that employs today’s leading research and clinical science to develop the next generation of bioactive ingredients derived from nature for advanced therapeutic nutrition products. The Company’s lead product candidate, AMAZ-02, an oral formulation of Urolithin A, is planned to enter Phase 2 clinical testing during 2017. For more information, please visit www.amazentis.com