CR845, A Novel Peripherally Acting Kappa Opioid Receptor Agonist for the Treatment of Pain and Pruritus
Stephen O'Connor
Senior Director, Chemistry Research and CMC, Cara Therapeutics, Inc.
Peptides with high affinity and selectivity for the kappa opioid receptor have been known for more than 20 years, but peptides suitable for clinical development have not been forthcoming. CR845 is a potent and selective synthetic peptide kappa opioid receptor (KOR) agonist being developed as both intravenous (IV) and oral formulations (enteric-coated tablets). CR845 is currently in mid- to late stage clinical development (Phase 2-3) to assess the safety and efficacy of this drug in patients with post-operative pain, osteoarthritis or uremic pruritus using the IV or oral formulation depending upon the particular indication. CR845 has full agonist activity at rodent and human kappa opioid receptors (EC50 = 0.16 nM) with no other detectable off-target activities. Non-clinical pharmacological studies indicate that CR845 has combined analgesic, antipruritic, and anti-inflammatory properties which support the therapeutic indications of pain and pruritus being pursued with this compound. CR845 is composed of 5 unnatural amino acids and does not readily cross the blood-brain barrier. Consequently, CR845 predominantly activates KORs expressed in peripheral neurons and on immune cells. CR845 is primarily excreted unchanged into the urine and bile with no major metabolites identified. The safety data available to-date and the potential benefit of CR845 treatment support continued study and development of this compound.
I have been with Cara Therapeutics for 9 years primarily focused on the GMP manufacturing of CR845 drug substance and drug product for the clinical development program. Prior to Cara, I was at Bayer (in West Haven, CT) for 8 years working in both the research (Medicinal Chemistry) and Development (Project Management). I began my professional career with Abbott Laboratories as a Medicinal Chemist in 1993.