Sian Biosciences Submits IND Application for LDR2402, an Ultra-Long-Acting Small Nucleic Acid Drug for Hypertension Treatment
Leaderna
Nucleic Acid Drug Developer
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September 2, 2024
eMedClub News
Recently, Leaderna Therapeutics Ltd. (hereinafter referred to as "Leaderna") submitted a targeted angiotensinogen (AGT)）The Investigational New Drug (IND) application for LDR2402 Injection, a novel small nucleic acid drug, has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.
LDR2402 Injection is a novel small nucleic acid candidate drug developed based on RNA interference (RNAi) technology for the treatment of hypertension.
Hypertension is a common chronic disease.Currently, more than 1 billion people worldwide suffer from the disease.Hypertension not only increases the risk of cardiovascular and cerebrovascular diseases but also may lead to complications such as kidney damage and vision loss. With the aging population and the prevalence of risk factors like obesity, lack of physical activity, and unhealthy diet, the prevalence of hypertension continues to rise globally.
Currently, there are effective antihypertensive treatments available in clinical practice, but antihypertensive medications need to be taken daily. Since hypertension is not easily detectable when symptoms are not severe, patients may forget to take their medication, leading to poor compliance. This has become a major challenge in the treatment of hypertension, with less than 20% of hypertensive patients achieving long-term effective control.Targeting the treatment bottleneck of hypertension, siRNA drugs can directly act to reduceAngiotensinogen (AGT)Expression, with the differentiated advantages of long-lasting drug effects, good safety, and high patient compliance, is expected to bring better treatment options and long-term benefits to patients.
AGT is the most upstream precursor of the renin-angiotensin-aldosterone system (RAAS), synthesized and secreted in the liver. Through a series of bio-signaling processes, it leads to an increase in blood pressure. siRNA targeting AGT, when conjugated with N-acetylgalactosamine (GalNAc), specifically binds to the asialoglycoprotein receptor (ASGPR) on the surface of hepatocyte membranes, enters the hepatocytes, and degrades AGT mRNA, thereby reducing blood pressure by inhibiting the synthesis of AGT.
Leadena stated,LDR2402In preclinical animal experiments, it demonstrated the potential for stable and sustained efficacy lasting over six months after a single dose, with excellent safety.In clinical treatment, it may be possible to improve patient compliance by extending the dosing interval (once per quarter or every six months), and potentially reduce blood pressure variability (BPV) by maintaining 24-hour blood pressure control, providing cardiovascular benefits to patients with hypertension. Therefore, LDR2402 has the potential to break the traditional hypertension treatment model and become a new generation of hypertension therapy.
It is worth mentioning that,InLDR2402The day before the IND application was accepted,Leadena Therapeutics Ltd. announced the completion recentlyNearly 100 Million Yuan in New Round of FinancingThe financing will be used to advance the clinical progress of its small nucleic acid new drug pipeline, further expand the preclinical pipeline, and strengthen the talent team.
References:
1.Leadena
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