Yamo Pharmaceuticals has announced positive Phase 2 results for L1-79, a novel therapeutic candidate targeting the core symptoms of autism spectrum disorder (ASD). The findings, presented at the International Society for Autism Research (INSAR) 2025 Annual Meeting, demonstrated statistically significant and clinically meaningful improvements in social functioning among adolescents and young adults with autism.
The 12-week randomized, double-blind, placebo-controlled crossover study enrolled 58 participants aged 12-21 years. Results showed L1-79 produced a 7.94-point advantage over placebo on the Vineland-3 Socialization Standard Score (VSSS), a gold-standard instrument for measuring real-world social skills (p=0.01). This improvement nearly doubled the 4-point minimal clinically important difference recognized by experts in the field.
"These results are extremely encouraging for the autism community," said J. Thomas Megerian, MD, PhD, Chief Medical Officer at Yamo Pharmaceuticals. "Seeing nearly an 8-point jump in Vineland Socialization scores is remarkable. To our knowledge, this is one of the largest positive effects observed to date on an adaptive-behavior measure in ASD for any medication."
Comprehensive Efficacy Across Multiple Measures
Beyond the primary endpoint, L1-79 demonstrated significant improvements across several secondary outcome measures. Investigator-rated Clinical Global Impression-Severity (CGI-S) improved by approximately 0.6 points versus placebo (p<0.02), indicating a meaningful reduction in overall socialization symptom burden.
Caregivers also reported notable improvements in their family members' most bothersome symptoms. On the Caregiver Global Impression of Change in the three most bothersome symptoms of ASD (CaGI-3P), families reported mean improvements of 0.48–0.61 points (p<0.05).
"These global impression scales matter because they capture day-to-day life," explained Dr. Megerian. "For example, a parent might cite difficulty engaging in back and forth conversation, seeking friendship, showing flexibility, or engaging in repetitive behaviors or speech as top concerns—and on L1-79 we saw improvement across all of them. That kind of broad positive shift defines meaningful benefit in autism treatment."
Novel Mechanism of Action
L1-79's efficacy may stem from its unique mechanism of action. The drug inhibits tyrosine hydroxylase, the rate-limiting enzyme for dopamine and norepinephrine production. Overactive catecholamine signaling has been linked to ASD-related social and sensory difficulties; by tempering this activity, L1-79 aims to rebalance neural circuits governing social interaction and communication.
"Rather than chasing downstream symptoms, we're modulating a core neural pathway," noted Dr. Megerian. L1-79 is the first autism therapy to directly target catecholamine synthesis—an approach now supported by emerging research.
Safety and Tolerability Profile
The drug demonstrated a favorable safety and tolerability profile throughout the trial. No serious adverse events were reported, and no participants discontinued L1-79 treatment due to side effects—a significant consideration for a condition where existing approved medications often carry substantial side effect burdens.
Addressing a Critical Unmet Need
Currently, no FDA-approved medications address the core symptoms of autism spectrum disorder. Existing treatments such as risperidone and aripiprazole target associated irritability but often come with significant side effects.
ASD affects approximately 1 in 31 children in the United States, according to CDC estimates, with boys affected nearly four times more often than girls. The condition is characterized by persistent difficulties in social communication and interaction, along with restricted or repetitive behaviors and interests.
Path Forward
"With these compelling Phase 2 data, we are moving full speed into Phase 3 planning and FDA discussions," said Chuck Bramlage, Chief Executive Officer of Yamo Pharmaceuticals. "Our mission is clear: bring the first medicine that meaningfully improves social functioning in autism to patients as quickly and responsibly as possible."
The FDA previously granted L1-79 Fast Track designation in May 2018, potentially expediting its development and review process.
Founded in 2015, Yamo Pharmaceuticals is supported by strategic partners including the Autism Impact Fund. The company completed its Phase 2 study in 2024 and is now preparing for pivotal Phase 3 trials that could potentially lead to the first approved therapy specifically targeting core social symptoms of autism spectrum disorder.
