BlackThorn Therapeutics Presents Preclinical and Clinical Data from Its First-in-Class NOPR Antagonist at American College of Neuropsychopharmacology Annual Meeting

Circuit-based translational results support ongoing Phase 2a trial in major depressive disorder and highlight opportunity to expand clinical evaluation to patients with Parkinson’s disease

South San Francisco, Calif. – December 7, 2017 – BlackThorn Therapeutics, a clinical-stage biopharmaceutical company discovering and developing targeted treatments for neurobehavioral disorders, today announced preclinical and clinical data from its lead program, BTRX-246040, a first-in-class antagonist of the nociceptin receptor (NOPR) that is currently being evaluated in a Phase 2a clinical study in patients with major depressive disorder (MDD). The data were presented during panel and poster sessions at the American College of Neuropsychopharmacology (ACNP) Annual Meeting in Palm Springs, Calif.

“The data presented at the ACNP conference underscore our unique approach to CNS drug development, which involves linking brain circuits to behaviors and applying this understanding to guide the development of novel therapeutics,” said Greg Vontz, chief executive officer of BlackThorn Therapeutics. “These results highlight the promise of BTRX-246040. Preclinical studies demonstrated for the first time that NOPR modulation has a significant influence on brain regions related to emotional processing, and clinical data demonstrate our ability to identify certain patient subtypes, both of which may improve our potential for clinical success.”

Preclinical Study Findings

Preclinical study findings, presented by Tanya Wallace, Ph.D., head of biology for BlackThorn Therapeutics, revealed that NOPR antagonism can modulate brain regions and behaviors associated with emotional processing, consistent with the development of the company’s Phase 2a study of BTRX-246040 in MDD. Preclinical study results also showed that NOPR antagonism improved motor symptoms in a non-human primate model of Parkinson’s disease.

NOPRs are expressed in brain regions that regulate emotional and motivational processing, which are implicated in MDD. One of the preclinical studies evaluated the effects of BTRX-246040 and ketamine, an NMDA receptor antagonist, in non-human primates given a decision-making task or a visuospatial working memory task. Results showed that both BTRX-246040 and ketamine reduced the punishing effect of losses during the decision-making task, but only BTRX-246040 did so without impairing working memory. These results suggest that BTRX-246040, an antagonist to NOPR, a receptor widely distributed in brain regions associated with reward processing, might modulate the behavioral effect of aversive outcomes.

Symptoms of Parkinson’s disease are mediated by brain circuits that express NOPR. Another of the preclinical studies evaluated the anti-Parkinsonian effect and impact of BTRX-246040 on dyskinesia (involuntary, uncontrolled movements) in an animal model of the disease. Results showed that BTRX-246040 significantly improved motor symptoms and increased “good ON time” scores (defined as improving Parkinson’s disease symptoms without troublesome dyskinesia) compared with L-DOPA therapy.

“These preclinical data support our rationale for advancing BTRX-246040 into the clinic in Parkinson’s disease, where NOPR antagonism may improve both the motor and depression symptoms associated with that disease,” said Annette Madrid, M.D., chief medical officer of BlackThorn Therapeutics. ”We plan to initiate a Phase 2a clinical trial in Parkinson’s disease in 2018. In the meantime, we are making important progress in enrolling patients in our Phase 2a MDD study, which is seeking to improve symptoms in patients with particular subtypes of MDD that are hypothesized to be positively responsive to NOPR modulation.”

Ongoing Phase 2a Study of BTRX-246040 in MDD

Blinded interim data from the first 15 patients randomized in the Phase 2a study were presented by Atul R. Mahableshwarkar, MBBS, vice president of clinical development for BlackThorn Therapeutics. This double-blind, placebo-controlled, multicenter study is evaluating the efficacy, safety and tolerability of BTRX-246040 administered once daily for eight weeks in adults (ages 18 to 65 years) with MDD with or without anhedonia (the inability to experience pleasure). The primary objective of the study is to evaluate the effects of BTRX-246040 on symptoms of depression in adults with MDD as measured by the Montgomery-Asberg Depression Rating Scale (MADRS).

The Phase 2a study is seeking to identify objectively defined subtypes of patients with MDD to determine which subtype may be most responsive to NOPR antagonism. Interim results showed that all 15 randomized patients reported experiencing anhedonia as assessed by the Structured Clinical Interview for DSM Disorders (SCID-CT), and 14 of 15 patients reported having anhedonia of significant severity based on a study protocol-defined score of 5 or greater on the Snaith Hamilton Pleasure Scale (SHAPS). The baseline data suggest that passively collected “dry biomarkers” (digital assessments used to monitor for a treatment effect) correlate with specific symptom domains, including anhedonia.

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 has a robust pipeline of first- and best-in-class treatments. The company approaches 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 San Francisco, Calif. For more information, please visit


Julie Normart
Pure Communications

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