Yamo Pharmaceuticals Enrolls Final Patient in Phase 2 Study Evaluating L1-79 to Treat the Core Symptoms of Autism Spectrum Disorder

Yamo Pharmaceuticals LLC recently announced it has completed enrollment in its Phase 2 study evaluating L1-79 in adolescents and young adults with autism spectrum disorder (ASD). Top-line data from the trial are expected in August 2024. With the completion of Phase 2 enrollment, Yamo has initiated a Phase 3 readiness program to optimize L1-79’s development timeline.

L1-79 is a tyrosine hydroxylase inhibitor designed to improve the core socialization and communication symptoms of ASD by modulating the catecholaminergic pathways implicated in ASD. In 2018, Yamo received Fast Track designation for L1-79 from the US FDA based on the promising results of its Phase 2a study. Currently, the only FDA-approved drugs for ASD are indicated for ASD-associated irritability. No medications are available to treat core symptoms of ASD, such as socialization and communication.

“We are excited that enrollment in our Phase 2 proof-of-concept study for L1-79 use in treating ASD is now complete and look forward to beginning business development discussions ahead of the data readout next summer,” said Chuck Bramlage, Yamo’s Chief Executive Officer.

“We would like to thank the families and their children for participation, as well as the research sites that have helped us get to this point. We are excited to share data from this study as it will provide further insights into the role of the catecholaminergic system in regulating social-communication function in autism,” added J. Thomas Megerian, MD, PhD, Yamo’s Chief Medical Officer.

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.

This Phase 2, multi-center, randomized, chronic-dosing (12-week) study employs a two-period placebo-controlled crossover design. The study is being conducted at eight clinical sites in the United States (US) (Including Columbia University, Cortica, Ohio State, RUSH, SARRC, Thompson Center at CHOC and University of Missouri) and targeted enrolling at least 50 patients. A total of 58 participants aged 12-21 years were 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 are randomized to receive either L1-79 or placebo BID for 12-weeks. Following the conclusion of Period 1, participants undergo a 6-week washout period and then crossover into Period 2, in which each participant that received placebo in Period 1 receives 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-3, CGI-S, and other measures of social-communication and 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 FDA 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 36 children have ASD, with boys being 3.8 times more susceptible than girls. 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.