Vivreon Biosciences, LLC
4940 Carroll Canyon Rd., Ste. 110
San Diego, CA 92121
milton@vivreonbiosciences.com
NIAMS PA-21-259
Project Summary
Hidrosis is the normal physiological sweat response that contributes to thermoregulation during heat stress.
Hyperhidrosis is the uncontrolled and excessive production of sweat due to dysregulation of normal sweat control
mechanisms. This is an unpleasant and embarrassing condition that affects nearly 5% of the US population and
causes significant reduction in performance and economic contribution amongst individuals from all walks of life,
and it contributes substantially to debilitating mental health issues like anxiety and depression. Current
treatments include powerful anti-perspirants, and topical cholinergic antagonists (Qbrexza¿) and BOTOX¿ that
block innervation pathways that drive primary hyperhidrosis (PHH). These treatments are neither fully effective
nor embraced by the patients due to issues such as inefficacy, inconvenience, side effects, and high cost. New
solutions are needed to offset the social and emotional impact of PHH.
The PHH response is strictly dependent on function of the Ca2+ release activated Ca2+ (CRAC) channels in the
sweat gland, and all signals that initiate PHH immediately engage the CRAC pathway to elevate intracellular
Ca2+ levels in the eccrine sweat gland for sustained periods regardless of the initial stimulus. This elevated Ca2+
in turn drives monovalent ion fluxes, creating the osmotic gradient that leads to water release into the gland duct
and movement of sweat to the surface for cooling. As such, the CRAC channel is an ideal target for control of
hyperhidrosis. Here, Vivreon Biosciences proposes to evaluate a small molecule candidate that potently
modulates CRAC channels as a therapeutic candidate for treating PHH. Aim 1 will determine any genotoxic or
phototoxic potential using the Ames, chromosomal aberration, and UV-dependent cytotoxicity assays. Aim 2 will
develop a suitable topical formulation and measure the topical penetration of the formulation using human skin
biopsies. Aim 3 will measure compound efficacy following topical application alone and in combination with a
currently approved therapy against a sweating response elicited in a standard model of hyperhidrosis. Successful
conclusion of this project will trigger Vivreon to seek additional funding to advance the PHH program through
required development steps culminating in an IND filing and exploration of partnership opportunities with
dermatological product companies.
