Unicycive Therapeutics, Inc. announced that several presentations were delivered on the Company's two product candidates, Oxylanthanum carbonate (OLC) and UNI-494, at the 61stEuropean Renal Association (ERA) Congress. OLC is a next-generation lanthanum-based phosphate binding agent utilizing proprietary nanoparticle technology being developed for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD). UNI-494 is a novel nicotinamide ester derivative and a selective ATP-sensitive mitochondrial potassium channel activator initially targeting acute kidney injury (AKI).

Oxylanthanum Carbonate (OLC)Presentation Details: Title: Enhanced Urinary Phosphorous Reduction: Comparative Study of Oxylanthanum Carbonate and Tenapanor in Rats: Lead Author: Satya Medicherla, Ph.D., Vice President, Preclinical Pharmacology, Unicycive; Results: This oral presentation evaluated the effects of tenapanor and OLC on phosphate excretion in rats. Tenapanor is a sodium hydrogen exchanger inhibitor used to reduce serum phosphate in adults with CKD on dialysis as an add-on therapy with phosphate binders. In this study, modeled after an earlier study with tenapanor and sevelamer, OLC demonstrated a significant reduction in urinary phosphate excretion compared to vehicle treated animals which was 3X greater than the reduction in urinary phosphate excretion observed with tenapanor which was not statistically different from vehicle.

OLC and tenapanor utilize two different mechanisms of action to manage phosphate levels. Subsequent analyses will focus on examining the combination of tenapanor and OLC as the combination may lead to synergistic effects on lowering phosphate levels while providing patients with the benefit of reduced pill burden with OLC. Title: Oxylanthanum Carbonate for Hyperphosphatemia in End Stage Kidney Disease (ESKD): Tolerability Trial in Progress.

Lead Author: Pablo E. Pergola, M.D., Ph.D., Renal Associates, P.A. Results: This poster describes a pivotal trial in progress to evaluate the tolerability of clinically effective (serum phosphate =5.5 mg/dL) doses of OLC in patients on hemodialysis. OLC is a new lanthanum-based nanotechnology product in development with a high in vitro binding capacity as compared to other phosphate binders. OLC is formulated as a small pill that is swallowed whole instead of being chewed.

This open-label, single-arm, multicenter, multidose study will enroll up to 90 patients on hemodialysis who require phosphate binder therapy and have mean historical serum phosphate levels between =4.0 and =7.0 mg/dL for =8 weeks. Participants will undergo up to 3 weeks of phosphate binder washout until their serum phosphate levels reach >5.5 and =10.0 mg/dL. During the 6-week Titration Period, all patients will receive 1,500 mg/day OLC (500 mg TID with meals/snacks) for the initial two weeks, with subsequent titration every two weeks until achieving a target serum phosphate level (=5.5 mg/dL) or to a maximum OLC dose of 3,000 mg/day.

After titration, patients will enter a 4-week Maintenance Period at the effective OLC dose. The primary endpoint of the study is tolerability as assessed by the incidence of discontinuations due to treatment-related AEs; the pharmacokinetics of OLC will also be evaluated. UNI-494 Presentation Details: Title: Oral Administration of UNI-494 Ameliorates Acute Kidney Injury in a Rat Model of Delayed Graft Function; Lead Author:Satya Medicherla, Ph.D., Vice President, Preclinical Pharmacology, Unicycive.

Results: This oral presentation evaluated the in vivo efficacy of oral (PO) UNI-494 to prevent damage in the unilateral renal ischemia-reperfusion (I/R) rat model of AKI, which is a well-established model of DGF. In the study, a single oral dose of UNI-494 at 50 mg/kg/PO or 100 mg/kg/PO significantly reduced important kidney functional markers including tubular injury, and proximal tubular injury scores. Additionally, kidney functional biomarker serum creatinine and tubular injury biomarker urinary neutrophil gelatinase-associated lipocalin (NGAL).

Additionally, these two biomarkers were very well supported by kidney histology data on proximal tubular injury scores at both low and high doses reflecting a non-dose related trend with biomarkers and dose-dependency for proximal tubule injury scores. The study concluded that UNI-494 is a potential candidate for prevention of DGF and other clinical conditions dealt with AKI. Title: UNI-494 Phase I Tolerability and Pharmacokinetics: Trial in Progress.

Lead Author:Guru Reddy, Ph.D., Vice President of Preclinical R&D, Unicycive; Results: This oral presentation described the ongoing Phase 1 dose-escalating single-center, double-blind, placebo-controlled, randomized clinical trial in healthy volunteers. The trial consists of two parts: Part 1 is a single ascending dose (SAD) study to determine the maximum tolerated dose (n=40); Part 2 is a multiple ascending dose (MAD) study to understand the effect of multiple doses administered of UNI-494 (n=20). The trial is designed to evaluate the safety, tolerability, and pharmacokinetics of UNI-494 in healthy subjects.

The SAD study was successfully completed, and a dose of 80 mg twice a day (BID) was carried over to the MAD study, which is currently ongoing. Results of this study are expected in the second half of 2024.