BTRX-335140

BlackThorn Kappa Opioid Receptor (KOR) Antagonist

Our novel kappa opioid receptor antagonist (KORA)

In partnership with The Scripps Research Institute, we have discovered BTRX-335140, a potentially best-in-class KOR antagonist.

The KOR pathway – located within brain regions that regulate the negative effects of stress on behavior – has emerged as a significant therapeutic target.1-3 Activation of the KOR pathway results in downstream dysregulation of neurotransmission in brain regions that govern anxiety, reward processing, mood and cognition.1,4 As such, KOR antagonists show great promise for treating a variety of neurobehavioral disorders in which neurotransmission is disrupted.

BTRX-335140 is a potent, selective and reversible KOR antagonist. We are conducting a Phase 2 proof-of-concept study of BTRX-335140 in a subpopulation of patients with major depressive disorder. Phase 1 studies in healthy volunteers showed that BTRX-335140 was well tolerated, exhibited favorable pharmacokinetics and engaged KORs in the brain at levels projected to be effective in treating symptoms relevant to depression and other CNS disorders.

Our portfolio includes a second novel KOR antagonist in development to treat stress-related migraine prophylaxis.


References
1. Crowley NA, Kash TL. Kappa opioid receptor signaling in the brain: circuitry and implications for treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2015;62:51-60.
2. Carroll FI, Carlezon WA. Development of κ opioid receptor antagonists. J Med Chem. 2013;56(6):2178-95.
3. Xie JY, et al. Kappa opioid receptor antagonists: A possible new class of therapeutics for migraine prevention. Cephalalgia. 2017;37(8):780-794.
4. Carroll FI, Carlezon WA. Development of κ opioid receptor antagonists. J Med Chem. 2013;56(6):2178-95.