April 6, 2017
BlackThorn Therapeutics Announces Results of Preclinical Study of BTRX-335140, Demonstrating Therapeutic Potential in Modulating Brain Circuits Commonly Dysregulated in Neurobehavioral Disorders
New Research Presented at 2017 Kappa Therapeutics Conference Highlights BTRX-335140 as a Potent, Selective, Short-acting KOR Antagonist
South San Francisco, Calif. – April 6, 2017 – BlackThorn Therapeutics, a clinical-stage biopharmaceutical company discovering and developing targeted treatments for neurobehavioral disorders, today announced preclinical study results demonstrating that its investigational novel kappa opioid receptor (KOR) antagonist BTRX-335140 is selective and short-acting. Results of the study, which was conducted by BlackThorn and researchers at the University of California, San Francisco (UCSF), were presented this week at the Fourth Conference on the Therapeutic Potential of Kappa Opioids in Philadelphia. BlackThorn is building its proprietary KOR antagonist program through a partnership with The Scripps Research Institute.
The KOR is located within brain regions that regulate the negative effects of stress on behavior. Activation of the KOR pathway inhibits release of the neurotransmitter dopamine in brain regions that govern emotion. The anatomical and physiological roles of the KOR suggest that blocking it could be therapeutically useful for a range of neurobehavioral disorders, including depression and obsessive compulsive disorder.
“Progress in the field has been limited by the inability to identify antagonists that are highly selective for the kappa opioid receptor and achieve high brain penetration with short-term reversible pharmacological activity,” said Bill Martin, Ph.D., chief scientific officer of BlackThorn Therapeutics. “While additional studies are ongoing, these preclinical results support the potential of BTRX-355140 as a therapeutic for targeting neurobehavioral disorders characterized by dysregulation of brain circuits in which kappa receptors are expressed.”
The aim of the study was to characterize the electrophysiological properties of BTRX-335140 and other historical KOR antagonists on dopamine neurons located within the ventral tegmental area (VTA), a brain region that is integral in regulating cortical and subcortical circuits. Study results were presented by lead investigator Elyssa B. Margolis, Ph.D., associate professor in the Department of Neurology at UCSF and a researcher at UCSF’s Wheeler Center for the Neurobiology of Addiction. Results showed:
- BTRX-335140 reduced kappa agonist-induced outward currents in a concentration-dependent manner, and showed full recovery to baseline within 10 minutes of drug discontinuation.
- In contrast, the effects of a historical KOR antagonist failed to reverse after drug washout over the duration of the experiment.
- BTRX-335140 had no effect on responses to a saturating dose of a mu opioid receptor agonist or a delta opioid receptor agonist at a concentration that fully blocked the kappa agonist-induced responses.
- BTRX-395750, another investigational KOR antagonist in BlackThorn’s program, also attenuated kappa agonist-induced outward currents. Preclinical studies with this compound are ongoing.
About BlackThorn Therapeutics, Inc.
BlackThorn Therapeutics is a clinical-stage biopharmaceutical company dedicated to transforming the lives of people with neurobehavioral disorders through the discovery and development of novel, targeted treatments. BlackThorn is building a robust pipeline of first- and best-in-class treatments, and is redefining the industry approach to drug discovery and development by linking brain physiology to behavior. Through BlackThorn’s network of collaborations with leading academic investigators and technology alliances, the company is developing and deploying a set of technologies that will enable focused, rapid, resource-efficient translational studies for drug development. The company is headquartered in South San Francisco, Calif. For more information, please visit http://www.blackthornrx.com/.