Amazentis SA Announces Successful Phase 1A/1B Study Results in Healthy Elderly Subjects with the Food Metabolite Urolithin A

Oral presentation at the International Conference on Frailty and
Sarcopenia Research in Barcelona to report the successful achievement of
Phase 1 study’s primary and secondary objectives

Clinical data confirm biological activity of Urolithin A on human
skeletal muscle mitochondria

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.

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

Contacts

Amazentis SA
Chris Rinsch, Ph.D.
CEO & Co-Founder, Amazentis SA
contact@amazentis.com
or
For
Media Inquiries:

Burns McClellan
Justin Jackson,
212-213-0006, ext. 327
jjackson@burnsmc.com