Rona Therapeutics Inc., a global leader in RNA-targeted therapeutics, announced today that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for RN0361, an APOC3-targeted small interfering RNA (siRNA) therapeutic. This clearance allows the company to initiate a Phase 2 clinical study for the treatment of severe hypertriglyceridemia (SHTG), mixed dyslipidemia, and familial chylomicronemia syndrome (FCS).
The decision to advance RN0361 into Phase 2 development follows promising results from a 6-month single-dose Phase 1 clinical trial, which demonstrated a favorable safety profile and sustained triglyceride (TG) reduction in patients with hypertriglyceridemia.
Innovative siRNA Technology Targeting APOC3
RN0361 leverages Rona's proprietary siRNA conjugate and oligonucleotide chemistry platform, GAIA, to enable robust and durable hepatocyte-specific silencing via subcutaneous administration. The therapeutic achieves gene silencing through optimized chemical modifications that significantly reduce APOC3 mRNA and protein expression.
APOC3 is a key regulator of triglyceride metabolism, and its inhibition has emerged as a promising approach for managing lipid disorders. By targeting APOC3, RN0361 aims to address the underlying mechanisms of hypertriglyceridemia, potentially offering a more effective and convenient treatment option for patients.
Phase 2 Study Design and Objectives
The upcoming Phase 2 study will be a randomized, double-blind, placebo-controlled, multicenter global trial. It will evaluate RN0361's efficacy, safety, and duration of effect in patients with hypertriglyceridemia over a nine-month follow-up period.
"This IND submission underscores our commitment to advance transformative RNAi therapies for patients with severe lipid disorders," said Stella Shi, CEO and Founder of Rona Therapeutics. "RN0361's Phase I data validate its potential as a best-in-class siRNA with durable efficacy and patient-friendly dosing. We look forward to collaborating with global investigators and agency to accelerate its development."
Clinical Significance and Unmet Need
Hypertriglyceridemia affects millions of people worldwide and is associated with increased risk of cardiovascular disease and acute pancreatitis. Current treatment options often have limitations in efficacy, tolerability, or convenience, creating a significant unmet need for novel therapeutic approaches.
Dr. Alex M. DePaoli, CMO and EVP of translational medicine at Rona Therapeutics, expressed enthusiasm about the potential impact of RN0361: "This Phase 2 study of RN0361 in dysmetabolic patients with hypertriglyceridemia will build on the evidence for RN0361 as an important therapeutic for multiple populations with significant hypertriglyceridemia and its pathologic consequences."
He added, "The remarkable potency and durability of triglyceride reduction already seen in the First in Human single dose study offers patients a potential powerful tool in the management of a substantial unmet need."
Potential Clinical Applications
RN0361 is being developed for multiple indications related to elevated triglycerides:
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Severe Hypertriglyceridemia (SHTG): Characterized by triglyceride levels ≥500 mg/dL, which significantly increases the risk of acute pancreatitis.
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Mixed Dyslipidemia: A condition involving abnormal levels of multiple lipid types, including elevated triglycerides.
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Familial Chylomicronemia Syndrome (FCS): A rare genetic disorder causing extremely high triglyceride levels and recurrent, potentially life-threatening pancreatitis.
About Rona Therapeutics
Rona Therapeutics is positioning itself as a global leader in nucleic acid innovative drug development, specializing in treatments for metabolic and neurological diseases. The company is committed to developing differentiated, first-in-class siRNA drugs to address unmet needs in cardiovascular diseases, obesity, and metabolic dysfunction-associated steatohepatitis (MASH).
Beyond its work in liver-targeted therapies, Rona is also exploring the potential of extra-hepatic delivery for neurological disorders and adipose/muscle delivery for various metabolic syndromes, expanding the potential applications of its RNA interference technology platform.
