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 have completed a single ascending dose and multiple ascending dose Phase 1 study in healthy volunteers in which BTRX-335140 exhibited favorable pharmacokinetics and was well tolerated. Target receptor occupancy studies are underway with results expected in the second half of 2019. The first Phase 2 study for this program is expected to start in 2020 and will investigate BTRX-335140 in treating symptom domains that have transdiagnostic relevance.
Our portfolio includes a second novel KOR antagonist in development to treat stress-related migraine prophylaxis.
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.