BlackThorn Therapeutics Reports Data Supporting Phase 2 Development of KOR Antagonist, BTRX-335140, in Depression and Other CNS Disorders

BlackThorn Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing targeted medicines to treat central nervous system (CNS) disorders, today announced data supporting Phase 2 development of its lead drug candidate, BTRX-335140 (BTRX-140), a selective kappa opioid receptor (KOR) antagonist. New results from a positron emission tomography (PET) occupancy study in healthy volunteers confirmed that BTRX-140 engages KORs in the brain at levels that are projected to be effective in treating symptoms relevant to depression and other CNS disorders. The data were presented during a poster session at the 58^th Annual Meeting of the American Neuropsychopharmacology (ACNP) Annual Meeting, taking place December 8-11 in Orlando.

"The KOR neuropeptide system is an important mediator of the negative effects of stress-induced alterations on mood, emotional regulation and motivation," said Charles Chavkin, Ph.D., Professor of Pharmacology at the University of Washington and leading expert in neuropharmacology of neuropeptide transmitters. "KOR antagonism is a novel therapeutic approach, which offers the potential to address key drivers of disability, such as depressed mood, anxiety, anhedonia and cognitive impairment. These clinical symptoms commonly occur in multiple CNS disorders, but are not adequately addressed by currently available medications for many people seeking therapy."

BlackThorn presented results for the first time from a PET study of BTRX-140 showing that a single oral 160 mg dose achieved approximately 90% KOR occupancy in the brain. A model developed from the PET study describing the relationship between plasma exposure and KOR occupancy projects that an 80 mg dose at steady state will also achieve approximately 90% KOR occupancy.

"These data extend our confidence in our lead program by confirming BTRX-140 target engagement, which informs the dose to carry forward into our planned Phase 2 trial," said Bill Martin, Ph.D., BlackThorn's president and chief executive officer. "Today, more people are suffering from brain disorders than ever before, but effective, therapeutic interventions for many of these disorders are still limited. We believe that by targeting the KOR system with BTRX-140, we may be able to address symptoms associated with these disorders that have not been addressed in the past. We look forward to initiating our Phase 2 trial of BTRX-140 by the end of the year, using our pathfindertm technology to identify patients with major depressive disorder who are most likely to benefit from the treatment."

In addition, the ACNP poster presentation included data previously reported by BlackThorn showing that BTRX-140 was well tolerated in a Phase 1 trial in which healthy volunteers were administered single or multiple doses of drug. BTRX-140 exhibited favorable pharmacokinetics showing increased plasma exposures after a single oral dose (5 mg to 240 mg) and after daily oral dosing for 10 days (20 mg to 160 mg).

About BlackThorn's Lead Clinical Program: BTRX-140

BTRX-140 is a potent, selective KOR antagonist being investigated for the treatment of neurobehavioral disorders including major depressive disorder. Activation of the KOR system under conditions of stress and disease can contribute to symptoms associated with depressed mood, anhedonia, anxiety and cognitive impairment, which are key drivers of disability in numerous psychiatric and neurological disorders. BTRX-140 is intended to reduce stress responses and restore dysregulated brain networks underlying these symptom domains, providing a novel therapeutic approach to treating neurobehavioral disorders. BTRX-140 was discovered as part of a research collaboration with The Scripps Research Institute.

About BlackThorn Therapeutics

BlackThorn Therapeutics is a clinical-stage biopharmaceutical company focused on the discovery and development of targeted medicines for the treatment of central nervous system (CNS) disorders. With pathfindertm, our computational psychiatry platform, our approach is based on generating a quantitative, brain-based understanding of neurobehavioral disorders. These data-driven insights are applied to create treatments targeted to biologically based subtypes of patients to increase the precision of therapeutic intervention. Our clinical pipeline is designed to restore balance to dysregulated brain circuits and empower individuals with CNS disorders to live better lives. BlackThorn is headquartered in San Francisco, California. For more information, please visit blackthornrx.com.