Yamo Pharmaceuticals Announces Enrollment of First Patient in Phase 2 Study of L1-79 in Autism Spectrum Disorder

Yamo Pharmaceuticals recently announced the first patient has been treated in a Phase 2 study of L1-79 in adolescents and young adults with ASD at six US research centers of excellence.  L1-79 is a tyrosine hydroxylase inhibitor designed to improve the socialization and communication symptoms by modulating the catecholaminergic pathways implicated in ASD.

“The design of this clinical trial builds on the insights gained in previous clinical experience with L1-79, in which a favorable tolerability profile and positive efficacy trends were observed in a smaller 28-day pilot study.  The ongoing Phase 2 study will serve as a proof-of-concept to evaluate the impact of 2 doses of L1-79 in a placebo-controlled crossover study with two 12-week treatment periods in 50 adolescents and adults with ASD.” said Chuck Bramlage, Chief Executive Officer of Yamo Pharmaceuticals. “While the Covid-19 pandemic delayed the initiation of this study, we are very excited to have commenced enrollment at six research centers with significant experience conducting studies in ASD.”

The only FDA-approved drugs for ASD are indicated for the irritability associated with autism.  Today’s announcement signals hope for patients and families that medicines are in development to treat the core deficits in social-communication and social interaction associated with ASD.

“We expect this study to generate further insights into the role of the catecholaminergic system in regulating social-communication function in autism.  The study also incorporates several innovative approaches such as use of the Brief Observation of Social Communication Change (BOSCC), which provides a more objective measure of improvement in core symptoms, and a crossover design in order to mitigate placebo effects, which have complicated the interpretation of other trials,” said J. Thomas Megerian, MD, PhD, Yamo Pharmaceuticals’ Chief Medical Officer.

This Phase 2, multi-center, randomized, chronic-dosing (12-week) study employs a two-period placebo-controlled crossover design.  This trial is expected to enroll approximately 50 participants aged 12-21 years who will be randomized 1:1 to one of two active treatment groups: L1-79 200 mg or 300 mg.  On Day 1 of Period 1, participants in each dosing group will be randomized to receive either L1‑79 or placebo BID for 12-weeks.  Following the conclusion of Period 1, participants will washout for 6-weeks and then crossover into Period 2, in which each participant who had received placebo in Period 1 will receive L1‑79 and vice versa BID for another 12-weeks.

To be eligible to participate in the study, individuals must have been diagnosed with ASD with a score of ≥ 70 on the Wechsler Abbreviated Scale of Intelligence (WASI-II), and a score of ≥ 4 on the Clinical Global Impression of Severity of Illness (CGI-S) weighted for socialization.  Key objectives of the study are to evaluate the effect of L1-79 on the core deficits in social-communication and interaction using the Vineland Adaptive Behavior Scale Third Edition (Vineland-3), BOSCC, CGI-S, and other measures of social-communication interaction.  Please refer to study identifier NCT05067582 at www.clinicaltrials.gov for additional clinical trial details.

Evidence suggests that the core symptoms of ASD may be the result of dysfunction in the catecholaminergic system.  L1-79 is a tyrosine hydroxylase inhibitor expected to modulate the catecholaminergic pathways, and thereby improve the core ASD symptoms.  L1-79 was granted Fast Track Designation by the Food and Drug Administration in May of 2018.

Autism spectrum disorder or autism refers to a group of complex neurodevelopment disorders that is defined in the Diagnostic and Statistics Manual of Mental Disorders V (DSM-5) by “difficulties in social communication and social interaction, and restricted and repetitive behavior, interests or activities.”  In the US, it is estimated that 1 in 44 children have ASD, with boys being 4.2 times more susceptible than girls (Maenner, 2021).  Symptoms of repetitive and characteristic patterns of behavior and difficulties with social communication and interaction start early in childhood and continue throughout a person’s life.

While the causes of ASD are not known, research suggests that both genes and environment play important roles. Since the severity, specific types of symptoms, and causes of ASD vary between individuals, it is referred to as a ‘spectrum’ disorder.  Currently there are no approved pharmacological therapies which address the core symptoms of ASD.

Yamo Pharmaceuticals is a clinical stage pharmaceutical company founded in 2015 to develop L1-79, a novel therapy with the potential to improve the core symptoms of ASD.  Yamo Pharmaceuticals is a privately held company.  For more information, visit www.yamopharma.com.