SBIR/STTR Award attributes
ABSTRACT: There are rt37 million Americans suffering from CKD, including rt495,000 patients with end stage renal disease (ESRD) requiring hemodialysis (CKD-HD) and rt17 million affected by advanced CKD (stages 3-5) who are not dialysis dependent (CKD-nonHD). About one third of both CKD-HD and CKD-nonHD patients experience moderate-to-severe chronic itch a.k.a. uremic pruritus. Intense and generalized systemic itching is associated with poor sleep quality, depression, reduced quality of life (QoL), increased risk of infection, and increased risk of death. It is important to note that, in addition to pruritus, rt50% of both CKD-HD and CKD-nonHD patients also experience chronic pain, and that 30-50% of these patients are prescribed opioids resulting in additional comorbidities and reduced QoL. Until recently, there was no approved drug for uremic pruritus in the US and there is still no approved non-addictive analgesic to replace opioids for CKD-associated chronic pain. Difelikefalin is a peripherally restricted and short-acting tetrapeptide KOR agonist that was recently approved by the FDA for moderate-to-severe uremic pruritus in CKD-HD patients. It is the first and only approved drug for this indication in the US. Difelikefalin has significant shortcomings, including kidney-mediated clearance and short half-life in patients with functioning kidneys limiting its development outside the CKD-HD patient population. Using a proprietary peptide-antibody conjugate (PAC) technology, we have created PAC-KOR agonists with a unique target product profile (TPP) characterized by the following key features: (i) potent and selective KOR agonist to ensure efficacy while minimizing dose and cost of goods (COGS), (ii) peripherally-restricted to avoid CNS side-effects and ensure safety, and (iii) long half-life enabling once-weekly to once-monthly subcutaneous (SC) dosing by autoinjector to maximize convenience, adherence, exposure, and efficacy. This application seeks to confirm the pharmacodynamic (PD) and pharmacokinetic (PK) profile of our clinical candidate and create stable cell lines to support future development. Impact and
