Nature Medicine Publishes Full Results from Axial Therapeutics’ Phase 1b/2a Clinical Trial in Autism Spectrum Disorder (ASD)

Open-label study showed Axial’s Lead Candidate, AB-2004, is safe and well-tolerated in an adolescent ASD cohort

AB-2004 lowered blood and urinary levels of gut-derived metabolites and significantly improved irritability and anxiety

Research supports company’s clinical development strategy focused on gut-targeted therapeutics for managing irritability associated with autism

Woburn, Mass., February 14, 2022 – Axial Therapeutics, a clinical-stage biopharmaceutical company dedicated to improving the lives of people with neurological disorders and conditions, today announced the publication in Nature Medicine of full results from its Phase 1b/2a clinical trial of AB-2004. AB-2004 is being studied as a potential new treatment for managing irritability associated with Autism Spectrum Disorder (ASD) in children and is the company’s lead gut-targeted, molecular therapeutic.

The article, titled “Safety and target-engagement of an oral small molecule sequestrant in adolescents with Autism Spectrum Disorder: an open-label phase 1b/2a trial”, is available online at

The Phase 1b/2a studywas designed to evaluate the safety and tolerability of AB-2004 in an open-label, single cohort, multiple ascending dose clinical trial, and explored target engagement of AB-2004 for reducing specific gut-derived microbial metabolites which are produced by bacteria commonly found in the gastrointestinal (GI) tract. The study also evaluated several initial efficacy endpoints aimed at guiding future clinical development. The trial enrolled 30 adolescents with ASD and GI symptoms in Australia and New Zealand.

The article highlights mechanistic evidence supporting the potential of AB-2004 as a novel therapeutic approach for treating co-occurring conditions associated with ASD, including irritability and anxiety, that can severely impact the quality of life of children with autism. Lead author of the publication, A. Stewart Campbell, Ph.D., is chief executive officer and head of Research & Development of Axial Therapeutics, and additional authors include a large team of clinical and basic research collaborators.

Based on a growing body of scientific research, including recently published preclinical work from its scientific founder Prof. Sarkis Mazmanian of Caltech, Axial believes that certain gut-derived neuroactive microbial metabolites (NMM’s™) enter the bloodstream and can adversely impact behavior by altering oligodendrocyte maturation and myelination in certain regions of the brain.

Key findings from the Phase 1b/2a trial include:

  • AB-2004 was shown to have strong safety and tolerability across all dose levels, and no drug-related serious adverse events were identified.
  • AB-2004 showed target engagement as measured by significantly reduced levels of key gut bacterial metabolites, including 4-ethylphenyl sulfate (4EPS), in both urine and plasma.
  • AB-2004 reduced anxiety and irritability based on scores on the Aberrant Behavior Checklist – Irritability domain (ABC-I) and the Pediatric Anxiety Rating Scale (PARS). Individuals with high baseline irritability (scores ≥ 15), which represents the top quartile of severity, displayed a greater than 9-point decrease in ABC-I over 8 weeks.

“As we continue to advance AB-2004 through clinical development, we are excited to share these results which continue to support our previously published scientific research and preclinical data on the role of the gut-brain axis and its impact on neurological conditions,” said Dr. Campbell. “The data highlighted in Nature Medicine further support our novel therapeutic strategy focused on specific targets in the gut microbiome. We strongly believe that AB-2004 can improve the quality of life of many children with autism.”

Based on the positive results from the Phase 1b/2a clinical trial, Axial has commenced a global, randomized, double-blind, placebo-controlled Phase 2 study of AB-2004 for the treatment of irritability associated with ASD. The Phase 2b trial ( will evaluate the efficacy, safety, and tolerability of AB-2004 in children aged 13 to 17 who have been diagnosed with ASD and gastrointestinal symptoms. The study will enroll an estimated 195 subjects who will receive low or high doses of AB-2004 or placebo for 8 weeks. More information about the Phase 2b trial is also available at, identifier NCT04895215.

“The lack of safe and effective treatment options for co-occurring conditions associated with ASD, such as irritability and anxiety, exacerbate the daily challenges faced by children and their families,” said Robert L. Hendren, D.O., professor, psychiatry, Weill Institute for Neurosciences at the University of California, San Francisco, School of Medicine, and a principal investigator for the AB-2004 Phase 2 trial. “A gut-targeted therapeutic approach that safely mitigates the role of bacterial metabolites on traits associated with autism would be an ideal option for addressing the significant unmet treatment need. I am encouraged by the data from the first human study of AB-2004 and I look forward to assessing its potential as a safe alternative to atypical antipsychotics currently used to treat irritability associated with autism.”

About AB-2004

AB-2004 is a first-in-class, molecular therapeutic that targets the microbiome gut-brain axis and its role in autism. AB-2004 has a unique mechanism of action that selectivity sequesters certain gut-derived metabolites before they enter the bloodstream and reach the brain. Axial believes this gut-targeted approach minimizes the potential for side effects in part due to a lack of systemic exposure to the drug.

About Autism Spectrum Disorder (ASD)

According to the Centers for Disease Control and Prevention (CDC), approximately 1 in 44 children has been identified with ASD. Core features of ASD include impairments in social interaction, communication, and the presence of stereotyped repetitive behaviors. Co-occurring conditions that impact quality of life are extensive and diverse, and include irritability, anxiety, ADHD, allergies, autoimmune disorder, neuroinflammation, and epilepsy. Based on research, of the 1.1 million children with ASD in the United States, as many as 50% seek treatment to manage irritability. Physicians have reported irritability impacts a large portion of children with ASD. The presentation of ASD-associated irritability can vary with severity and age and can be caused by a broad array of different factors, including lack of sleep, the inability to communicate pain, and mental health conditions.

About Axial Therapeutics

Axial Therapeutics is a clinical-stage biopharmaceutical company dedicated to improving the lives of people with neurological disorders and conditions. The company is a scientific leader in the biological role of the microbiome-gut-brain axis and its influence on the central nervous system. Harnessing its unique expertise in the microbiome, Axial is developing small molecule drugs with defined mechanisms of action that act on new targets to mitigate the impact of metabolites and bacteria in the gut linked to neurological disorders and disease pathology, progression, and symptoms. The company is advancing a pipeline of “microbial-inspired therapeutics™” for conditions with significant unmet patient need, including autism and Parkinson’s disease, and is also pursuing pre-clinical discovery of gut-targeted therapies in oncology. Axial’s lead product candidate is AB-2004, a molecular therapeutic in Phase 2b clinical trials for the treatment of irritability in children with autism. For more information, visit

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