RZ602 is a potential once-daily orally-administered small molecule plasma kallikrein inhibitor (PKI) in preclinical development for Hereditary Angioedema (HAE).
HAE is characterized by attacks of extreme swelling that can affect the face, hands, feet, tongue, larynx, genitalia, abdomen and intestinal wall. Attacks can be painful, debilitating, varied in frequency and even fatal due to laryngeal edema and respiratory failure. Currently available therapies target the prevention or termination of attacks, but are highly invasive and inconvenient due to the subcutaneous/intravenous routes of administration or have an undesirable side effect profile. Approximately 10,000 patients in the US and 1 in 10,000 to 50,000 patients worldwide have HAE. Rezolute plans to assess and potentially seek orphan disease status for AB602 in HAE.
Plasma kallikrein acting through bradykinin is central to the pathophysiology of HAE. Pharmacologic inhibition with PKIs reduces plasma kallikrein substrate, thereby overcoming C1-inhibitor deficiency.
In vitro studies demonstrate RZ602 rapidly blocks kallikrein activation and bradykinin formation. Oral dosing of RZ602 in dogs rapidly achieves efficacious concentrations sustained over 24 hours. Validation of activity has been achieved in several kallikrein / bradykinin–dependent animal models of vascular leakage with up to 90% reduction in vascular leakage, which we believe increases the likelihood of clinical efficacy at predicted efficacious exposures in humans. In addition, RZ602 appears to be safe and well-tolerated with broad therapeutic margins.
Rezolute is planning to continue IND-enabling studies of RZ602 in 2018 and file an IND with the FDA in H1 2019.