ABSTRACT:
There are >37 million Americans suffering from CKD, including >495,000 patients with end stage renal disease
(ESRD) requiring hemodialysis (CKD-HD) and >17 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, >50% 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
