Advancing Targeted Therapeutics for Autism Spectrum Disorder and Neurodevelopmental Disorders

Allos Pharma develops therapeutics informed by decades of translational neuroscience, genetically defined disease biology, and clinical experience across Fragile X syndrome and autism spectrum disorder.

SCIENCE

Increases in relative excitatory:inhibitory balance are commonly observed in humans with, and animal models of, autism spectrum disorders
Arbaclofen selectively activates GABA-B receptors to decrease presynaptic release of excitatory neurotransmitters while simultaneously decreasing excitability of the postsynaptic neuron.
Activation of GABA-B receptors effectively normalizes excitatory: inhibitory balance in animal models of ASD and FXS.
Arbaclofen treatment produces broad phenotypic improvements in animal models and humans
​Arbaclofen is a potent and selective agonist of GABA-B receptors
Preclinical: Arbaclofen is 10 times more potent than GABA itself

Arbaclofen significantly reduced irritable aberrant behavior in a Phase 3 trial in FXS. 

Excellent safety & tolerability confirmed in 360 humans with fragile X syndrome, including >200 subjects treated for over a year

Pipeline

Allos Pharma is advancing arbaclofen across genetically informed and clinically defined neurodevelopmental disorders, with an initial focus on Autism Spectrum Disorder and Fragile X Syndrome. The company’s development strategy builds on decades of translational neuroscience, clinical experience, and mechanistic understanding of inhibitory signaling pathways relevant to social and behavioral function.

ABOUT US

Allos Pharma is committed to delivering science-based treatments for underserved neurodevelopmental and neurological disorders. Arbaclofen is the first therapy to show replicated improvements in social functioning and irritability in children with Fragile X Syndrome and ASD — with additional promise in genetically defined subgroups like 16p11.2 deletion syndrome.

Leadership

Mark Bear, PhD, Co-founder

 Chair Scientific Advisory Board, Board Director

Dr. Mark Bear is Picower Professor of Neuroscience in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. He was an Investigator of the Howard Hughes Medical Institute for 22 years from 1994 to 2015 and served as Director of the Picower Institute from 2007 to 2009. Prior to moving to MIT in 2003, Dr. Bear was on the faculty of Brown University School of Medicine for 17 years.

Dr. Randy Carpenter’s career experience includes leadership positions in academic medicine, pharmaceutical companies and patient advocacy organizations. He previously founded Seaside Therapeutics to translate scientific discoveries into therapeutics for individuals with autism. He is currently a member of the Translational Medicine Advisory Board of the Rett Syndrome Research Trust, the advisory boards of EU-AIMS and the Translational Neuroscience Center of Boston Children’s Hospital, and is a research affiliate in the Department of Brain and Cognitive Sciences at MIT.

While in industry, he led translational medicine teams responsible for eight IND submissions and dozens of GCP-compliant clinical trials. Prior to joining industry, he held academic faculty appointments at the University of Washington and Wake Forest University, where he specialized in anesthesiology, pain management, and translational medicine.

Randall Carpenter, MD, Co-founder

CEO & Chief Medical Officer, Board Director

Fragile X Syndrome:

National Fragile X Foundation – www.fragilex.org
FRAXA Research Foundation – www.fraxa.org

RESOURCES

Autism Spectrum Disorder:

Autism Speaks – www.autismspeaks.org
Autism Science Foundation – autismsciencefoundation.org
SFARI – www.sfari.org

Selected publications

  • Arbaclofen in Children and Adolescents with Autism Spectrum Disorder: A Randomized, Controlled, Phase 2 Trial.Veenstra-VanderWeele JM, Cook EH, King BH, Zarevics P, Cherubini M,Walton-Bowen K, Bear MF, Wang PP, Carpenter RL. Neuropsychopharmacology. 2016, 1-9 Oct 17. doi: 10.1038/npp.2016.237 [Epub ahead of print]
  • STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study. Erickson CA, Veenstra-Vanderweele JM, Melmed RD, McCracken JT, Ginsberg LD, Sikich L, Scahill L, Cherubini M, Zarevics P, Walton-Bowen K, Carpenter RL, Bear MF, Wang PP, King BH. J Autism Dev Disord. 2014 44(4):958-64.
  • Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: A randomized, controlled, Phase 2 trial. Berry-Kravis E, Hessl D, Rathmell B, Zarevics P, Cherubini M, Walton-Bowen K, Gonzales-Heydrich J, Wang P, Carpenter RL, Bear MF, Hagerman R. Science Translational Medicine. 2012 19;4(152):152ra127.
  • Reversal of disease phenotypes in the Fragile X mouse model by selective activation of GABA-B receptors.Henderson C, Wijetunge L, Nakamoto Kinoshita M, Shumway M, Postma FR, Brynczka C, Hammond RS, Rush R, Thomas A, Paylor R, Warren ST, Vanderklish PW, Kind PC, Carpenter RL, Bear MF, Healy AH. Science Translational Medicine. 2012 19;4(152):152ra128.
  • R-baclofen reverses cognitive deficits and improves social interactions in two lines of 16p11.2 deletion mice.Stoppel LJ, Kazdoba TM, Schaffler MD, Preza AR, Heynen A, Crawley JN, Bear MF. Neuropsychopharmacology. 2018 Feb;43(3):513-524​
  • Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Chang S, Bray SM, Li Z, Zarnescu DC, He C, Jin P, Warren ST. Nat Chem Biol.2008 Apr;4(4):256-6

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