PureTech's LYT-300 (Oral Allopregnanolone) Achieved Primary Endpoint in a Phase 2a Acute Anxiety Trial in Healthy Volunteers
Orally administered LYT-300 achieved a statistically significant (p=0.0001) reduction in the stress hormone response, as measured by salivary cortisol, compared to placebo
This proof-of-concept trial demonstrating a reduction in the physiological stress response supports the further development of LYT-300 as a potential treatment for a range of anxiety disorders
Anxiety disorders affect nearly 30 percent of
LYT-300 was well-tolerated across the trial with only transient mild or moderate adverse events
Oral administration of LYT-300 achieved the trial's primary endpoint of a statistically significant reduction versus placebo in the increase from baseline to peak levels of the stress hormone salivary cortisol (p=0.0001). The LYT-300 treatment effect size versus placebo was 0.72, as measured by Cohen's d, which is one of the most common ways to measure effect size. 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 procedure2. An increase in cortisol levels after the TSST is a physiological response and an objective biomarker of acute stress. Eighty healthy volunteers were randomized and treated with either LYT-300 or placebo in a 1:1 ratio. 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.
"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," said
"These data validate that LYT-300 has potential to make a difference for people living with anxiety, where there's been a dearth of innovation and existing treatments have drawbacks," said
LYT-300 is an oral prodrug of allopregnanolone, an endogenous neurosteroid. Allopregnanolone has been recognized for its potential to treat a range of neurological and neuropsychiatric indications with a well-established rapid onset of action in mood disorders. The major hurdles associated with endogenous neurosteroids in the past have been their lack of oral bioavailability and inability to chronically administer them to patients, which means they otherwise can only be administered via a long, cumbersome intravenous infusion. To overcome the challenges with this method of administration, medicinal chemistry approaches have been applied to synthesize orally bioavailable chemical analogs of allopregnanolone. These oral analogs may have different pharmacological effects than endogenous allopregnanolone and therefore may not capture its full therapeutic potential. LYT-300 is designed to achieve oral administration of an endogenous allopregnanolone that has the potential to capture the breadth of the natural biological response.
"The data generated with
These results further validate
As part of an overall development strategy in anxiety-related indications,
LYT-300 is a clinical-stage therapeutic candidate that is in development as a potential treatment for neurological and neuropsychiatric conditions, including anxiety disorders, mood disorders and Fragile X-associated Tremor/Ataxia Syndrome. Developed using
About the Glyph™ Platform
About the Trier Social Stress Test
The Trier Social Stress Test (TSST; Kirschbaum, Pirke, & Hellhammer, 1993) is a validated clinical model of anxiety.
It is a widely used and well-established psychological and physiological laboratory test designed to induce acute psychosocial stress in human participants. It is considered the gold standard in human experimental stress research and is used by researchers to investigate how individuals respond to acute stressors, how stress affects cognitive and emotional processes, and how stress might contribute to various psychological and physiological conditions. The TSST puts the participant in situations designed to elicit unpredictable, novel, anticipatory, and social stress such as preparing and giving a speech, performing arithmetic, and being observed by judges. It models stress reactivity, which is an important component in many mood, stress and anxiety disorders, and the TSST robustly increases physiological markers of stress including salivary cortisol. Benzodiazepines, a clinically effective drug class indicated for the treatment of anxiety, reliably blunt the increased salivary cortisol in the TSST.
Juliane Hellhammer, PhD, founder and CEO of daacro (a contract research organization specialized on psychotropic drug effects) and recognized expert on the Trier Social Stress Test, is an advisor to
For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those statements that relate to our expectations around the design of and the timelines and key milestones associated with clinical trials for LYT-300 and other programs from the Glyph™ platform, including in anxiety-related indications, the therapeutic potential of LYT-300, our expectations regarding the Glyph platform including the potential for new treatment applications, our therapeutic candidates and approach towards addressing major diseases, and our future prospects, developments, and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2022 filed with the
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1] Any Anxiety Disorder. (n.d.).
2] Psychoneuroendocrinology, 31(10), 1278-1288. https://doi.org/10.1016/j.psyneuen.2006.09.009 .
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