A unique drug technology platform developed by Monash University researchers in partnership with Boston-based biotherapeutics company, PureTech Health plc (Nasdaq: PRTC, LSE: PRTC), has reached another exciting milestone with the successful completion of a Phase 2a clinical trial of 'LYT-300' an oral version of the drug allopregnanolone.
The randomised, placebo-controlled, proof-of-concept trial has achieved a statistically significant reduction in stress hormone response among healthy volunteers, compared to placebo.
Designed to evaluate the salivary cortisol (a hormone that manages stress) response in the Trier Social Stress Test (TSST) - a validated clinical model of anxiety in healthy volunteers - the trial enlisted eighty volunteers who were randomised and treated with either LYT-300 or placebo in a 1:1 ratio.
Oral administration of LYT-300 achieved the trial's primary goal of a statistically significant reduction (versus placebo) in the peak levels of the stress hormone cortisol in saliva (p=0.0001).
LYT-300 showed a similar effect size to previously observed results for alprazolam, a benzodiazepine drug indicated for treatment of anxiety disorders, when assessed following the TSST procedure[1]. Importantly, however, LYT-300 is based on an endogenous neurosteroid and therefore has different pharmacology to traditional benzodiazepines.
LYT-300 employs PureTech's GlyphTM platform, initially developed by Professor Chris Porter and his team at the Monash Institute of Pharmaceutical Sciences (MIPS) and exclusively licensed to PureTech Health in 2017.
"Allopregnanolone has been recognized for its potential to treat a range of neurological and neuropsychiatric indications and has a well-established rapid onset of action in mood disorders. However, historically there have been major hurdles associated with the development of endogenous neurosteroids as medicines. Most notably, a lack of oral bioavailability and a need to administer intravenously. This makes convenient dosing to patients over an extended period of time in chronic diseases extremely difficult," said Professor Porter
"The Glyph platform harnesses the body's natural lipid absorption and transport process to enable the oral administration of therapeutics like allopregnanolone that otherwise cannot be administered orally. These data validate that LYT-300 has the potential to become a simple oral capsule for people living with anxiety, a condition where there's been a dearth of innovation," said Professor Porter.
Murray Stein, MD, MPH, FRCPC, Distinguished Professor of Psychiatry and Public Health at the University of California San Diego and an advisor to PureTech said: "Anxiety disorders are an area of significant unmet medical need and current standard-of-care treatments leave much room for improvement due to inconsistent efficacy and adverse events. We know that benzodiazepines, like alprazolam, can reduce the salivary cortisol response to stress in the TSST. Cortisol is an important marker of the physiological response to stress, and reduction of stress overreactivity may be an important mechanism for treating anxiety and stress-related disorders."
"LYT-300, a non-benzodiazepine neurosteroid, blunts this stress response, highlighting its novel pharmacology and potential for helping patients in serious need of new treatment options."
In the trial, LYT-300 was well tolerated, with all treatment-related adverse events transient, mild or moderate and consistent with the known pharmacology profile of allopregnanolone. Additional data from the study will be presented in a scientific forum.
