Rezolute, Inc, with Handok and Genexine as its largest shareholders, announced positive topline results from its first-in-human Phase Ia clinical study of RZ402 on May 4, 2021.

RZ402 is an oral plasma kallikrein inhibitor (PKI) for the treatment of diabetic macular edema (DME) currently being developed by Rezolute. Results of a study of single-dose oral administration of RZ402 demonstrated the potential for once daily dosing and supported the advancement of development activities toward Phase II, including a Phase Ib multiple-ascending dose study. RZ402 was generally safe and well-tolerated at all doses tested, without dose-limiting toxicities.

RZ402-101 is a clinical study in which RZ402 was administered to healthy adults for the first time. The study was conducted as a single-center, randomized, double-blind, placebo-controlled, and single ascending dose (SAD) study. The objective of the study was to characterize the safety profile and pharmacokinetics of RZ402 administered as single oral doses. The study was conducted on 30 patients who received doses of 25 mg, 100 mg, and 250 mg.

Robert B. Bhisitkul, M.D., Ph.D., Professor of Clinical Ophthalmology and retinal specialist at the University of California San Francisco School of Medicine’s Department of Ophthalmology and member of Rezolute’s Scientific Advisory Board, said, “We’re in need of new treatments in the clinical care of patients with diabetic eye diseases. Pioneering research has strongly implicated the kallikrein-kinin system in the development of diabetic retinopathy and macular edema. A novel plasma kallikrein inhibitor has the potential to give patients with diabetic macular edema an alternative therapeutic option. Oral delivery would provide the possibility of earlier treatment intervention and enable a patient-controlled regimen with advantages in comfort, convenience, and continuous drug levels in the retinal microvasculature. I look forward to the continued development of RZ402 for patients at risk of losing their sight from DME.”

“We are excited to share these encouraging results from the first clinical trial of the systemic delivery of an oral plasma kallikrein inhibitor for the treatment of DME. Given that DME is a consequence of diseased microvessels at the back of the eye, we believe that systemic exposure may be crucial in treating the disease,” said Brian Roberts, M.D., Rezolute’s Head of Clinical Development. “It is noteworthy that a single oral dose of RZ402 safely, durably, and substantially exceeded target blood concentrations that have been shown in animal models of DME to reduce retinal inflammation and fluid leakage, the physiological hallmarks of this microvascular disease. These results support the advancement of RZ402 into a Phase Ib multiple ascending dose study, which we expect to initiate in the third quarter of this year.”

Rezolute is a U.S. bio-venture developing targeted treatments for rare diseases and metabolic illnesses and was listed on the Nasdaq in 2020. Major R&D pipelines include RZ358, currently in Phase IIb clinical trials and a treatment for the rare pediatric endocrine disease of congenital hyperinsulinism, and RZ402, an oral plasma kallikrein inhibitor for the treatment of diabetic macular edema (DME) that is currently in Phase I clinical trials. Handok and Genexine jointly invested in Rezolute in 2019 to become its largest shareholders. Handok reinforced its drugs pipeline for diabetes and rare diseases by acquiring domestic commercialization rights for RZ402 and RZ358 in 2020.