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Axial Biotherapeutics Reports Findings of Elevated 4-Ethylphenylsulfate (4-EPS) in Replicate Analyses of Serum Samples from Children with Autism Spectrum Disorder (ASD)

First Results from Axial’s ASD Program Presented at the International Society for Autism Research (INSAR) conference

BOSTON and Pasadena, Calif., May 9, 2018 – Axial Biotherapeutics, a biotechnology company building a unique class of microbial-inspired therapeutics for neurological diseases, today announced that Srinivas Rao, M.D., Ph.D., Axial’s Chief Medical Officer, will present new data from Axial’s research of the link between the human gut microbiome and Autism Spectrum Disorder (ASD) at the International Society for Autism Research (INSAR) conference held May 09 – 12, 2018 in de Doelen ICC Rotterdam, Netherlands. The findings showed that concentrations of the bacterial metabolite, 4-ethylphenylsulfate (4-EPS) were elevated as much as six-fold in serum samples from children with ASD compared to healthy controls in replicate analyses.

This research builds on previous work published by Axial’s Co-founder and Caltech Professor, Sarkis Mazmanian, Ph.D., that demonstrated causality between 4-EPS and anxiety-like behaviors in the “maternal immune activation” (MIA) mouse model of ASD. The MIA model recapitulates key features of the autism phenotype, including increased anxiety, stereotypic behaviors, and decreased vocalizations and social behaviors. Dr. Mazmanian found changes in the gut microbiome (dysbiosis), increased intestinal permeability (IP), and elevated levels of the putative bacterial metabolite 4-EPS in MIA mice, compared to controls. Oral treatment with B. fragilis, a human commensal gut bacterial species, resulted in restoration of gut microbial profiles, decreased IP, and markedly reduced serum concentrations of 4-EPS.

The current study aimed to evaluate 4-EPS levels in children with ASD compared to samples from control children. Two analyses were performed, a 4-EPS targeted analysis in 103 pediatric subjects and a non-targeted serum metabolomics study involving 230 children (cohorts from the “Childhood Autism Risks from Genetics and the Environment” study ongoing at the Univ. of California Davis). 4-EPS concentrations were found to be significantly elevated in children with ASD vs. healthy controls in both analyses. In addition, elevated levels were associated with worse social performance on two separate measurements. The impact of this elevation on behavior, and the impact of treatment with B. fragilis and with Axial’s small molecule therapeutic, AB-2004, will be the subject of subsequent human clinical studies.

“Our clinical biomarker results, derived from one of the largest ASD serum metabolomics studies conducted to date, are encouraging,” said David H. Donabedian, Ph.D., Co-founder & CEO of Axial Biotherapeutics. “These data, which are the first we have presented from our ASD program, present a major advancement in our mission to develop microbiome inspired therapeutics as a potential new approach to treating neurological diseases and disorders like ASD.”

Poster Presentation Details:

Title: Elevation of a Putative Bacterial Metabolite in a Pediatric ASD Population
Abstract No: 28205
Date/Time: Friday, May 11, 2018 / 5:30 PM-7:00 PM
Location: Hall Grote Zaal (de Doelen ICC Rotterdam)

About Axial Therapeutics

Axial Therapeutics is a clinical-stage biopharmaceutical company focused on the discovery and development of gut-restricted, small molecule therapeutics for central nervous system (CNS) disorders. The company is leveraging its expertise in the gut-brain axis and its unique drug development platform to advance novel therapies that have the potential to transform the treatment paradigm in neurological diseases. Axial is advancing a pipeline of small molecule product candidates with lead clinical programs that address underlying pathology and resulting symptoms in Autism Spectrum Disorder (ASD) and Parkinson’s Disease (PD), and additional preclinical initiatives in small molecules in other areas of autism and PD, as well as oncology and rare CNS diseases.

Contacts for Axial Therapeutics


Mike Beyer
Sam Brown, Inc.


Jeffrey Young, CFO

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