Chronic Pain is defined as pain persisting beyond 1 month post-treatment of an underlying illness or pain lasting beyond 3 months. Chronic Pain one of the largest and most widely-acknowledged unmet medical needs in the world, affecting over 100 million people in the USA alone. The origin of pain will further segment this broad category into Nociceptive Pain (Stimulation of somatic or visceral nociceptors), Neuropathic Pain (resulting from nerve damage) and Mixed Pain (of both Nociceptive & Neuropathic origins). Current treatment options from anti-inflammatory agents and anti-epileptics to SNRI’s and opioids are only minimally effective and can have intolerable side-effects including constipation, depression and addiction.
CSP Conopeptide is a 13 amino acid peptide conotoxin derived from the venom of a cone snail. KPI is developing CSP Conopeptide as a subcutaneous injection for a broad spectrum of Neuropathic Pain indications (IE. Chemotherapy-Induced Neuropathic Pain and Diabetic Peripheral Neuropathy) and Burn Pain. Follow-on development work is assessing not only an oral dosage formulation, but confirmation of efficacy towards the treatment of Cancer Pain and Sciatica; both within the Mixed Pain segment.
CSP Conopeptide is a potent and highly selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR), a novel pain target. This target is suggested to be expressed in both nociceptors and inflammatory cells. Blocking the α9α10 nAChR will reduce over-excitation of nociceptors and/or recruitment of inflammatory cells, therefore blocking pain signaling and reducing pain sensation. The discrete expression of α9α10 in the peripheral nervous system and the general inability of peptides to cross the blood-brain barrier support the notion that CSP Conopeptide will not elicit negative CNS side effects. And in addition to showing analgesic and anti-inflammatory effects, potentially the most significant attribute of our CSP Conopeptide is its ability to prevent nerve damage. Limiting nerve damage means preventing additional pain and possibly preventing acute pain from becoming chronic.
The preclinical development program for the CSP Conopeptide includes safety pharmacology and toxicology programs. In-vitro safety pharmacology studies suggest that the CSP Conopeptide is highly selective for its target when compared to cardiac and nervous system ion channels. Moreover, the CSP Conopeptide was well tolerated with no overt toxicity in chronic studies having a greater than 50-fold safety margin than that of the anticipated therapeutic dose of the drug. This suggests that the CSP Conopeptide will likely have large safety margins when compared to competitive treatments. Additionally, preliminary in-vivo safety data have identified no initial target organs of toxicity.
Drug lead optimization is underway to ensure the optimal target product profile including, but not limited to, route of administration and duration of action.