Phase 1/2 Study of KRRO-121 in Healthy Volunteers and Patients With UCD

A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KRRO-121 in Healthy Volunteers and Patients With Urea Cycle Disorders

Phase 1/2 Study of KRRO-121 is a randomized, placebo-controlled study in Healthy Volunteers (Phase 1 SAD and MAD) and Study Participants with Urea Cycle Disorders (Phase 2). The primary objective of the study is to evaluate the safety of KRRO-121.

KRRO-121 is a GalNAc-conjugated RNA editing oligonucleotide in development for the potential treatment of hyperammonemia in patients with UCDs. Utilizing Korro's proprietary OPERA® platform, KRRO-121 is designed to generate a stabilized, de novo glutamine synthetase (GS) protein, a critical enzyme involved in ammonia clearance. This synthetic rescue approach is designed to augment ammonia clearance in hyperammonemia-driven diseases such as UCDs. Korro's preclinical data support the potential for KRRO-121 to be a UCD treatment that may control ammonia levels independent of any mutational background (pan-UCD).

The purpose of this first-in-human (FIH) study is to determine the safety and tolerability of escalating doses of KRRO-121, to evaluate the pharmacokinetics of KRRO-121, and to assess the effect of KRRO-121 in healthy volunteers and in study participants with UCD. The study name is ANCHOR: AssessmeNt of Control of Hyperammonemia through Oligonucleotide-based RNA editing

Inclusion Criteria:

• Adult male or female participants, 18 to 65 years of age
• Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and screening laboratory assessments, in the opinion of the Investigator.
• Female participant of childbearing potential or male participant that is willing to use an approved, reliable means of contraception
• Willing and able to provide signed written informed consent and to comply with all study requirements

Exclusion Criteria:

• Any medical history that is clinically significant in the opinion of the Principal Investigator and Sponsor Medical Monitor
• Any laboratory value at screening or predose on Day -1 outside the local laboratory reference range that is clinically significant in the opinion of the Principal Investigator and Sponsor Medical Monitor
• Evidence of active systemic infection at Screening or Day 1 requiring antimicrobial, antiviral, or antifungal therapy
• Use of any investigational drug or device within 3 months or 5 half-lives (whichever is longer) prior to Day 1
• Concurrent participation in any other interventional clinical study