▎WuXi AppTec Content Team Report

As this year's Nobel Prize in Physiology or Medicine has been awarded to the microRNA (microRNA) field, RNA therapy and its potential for disease treatment have once again attracted widespread attention. In fact, nucleic acid-based drugs have become an important part of current new drug development, with various types of drugs such as small interfering nucleic acids (siRNA), antisense oligonucleotides (ASO), and mRNA drugs "blossoming in full swing," achieving successive breakthroughs in the treatment of different diseases.

In China, there has been significant progress in nucleic acid-based drugs. According to the official website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA),Since the beginning of this year, at least 13 innovative nucleic acid drugs have been approved for IND in China for the first time, targeting disease areasCovering types such as rare diseases, cardiovascular diseases, infectious diseases, and precancerous lesions.。Most of these drugs come from clinical-stage innovative pharmaceutical companies newly established in recent years. This article will summarize the publicly available information on these products based on open-source data.

Leaderna: A24110He Injection

Mechanism of Action: ASO Drug Targeting ANGPTL4

A24110He Injection is developed by Lipigon Pharmaceuticals.Targeting ANGPTL4ASO drug,Rona Therapeutics' drug candidate received IND approval in China this March and is being developed for the treatment of severe hypertriglyceridemia.Leaderna owns the rights to this product in the Greater China region and will jointly advance clinical development with Lipigon. ANGPTL4 is a protein highly expressed in adipose tissue and has emerged as a novel drug target for lipid-lowering therapy following recent research breakthroughs.A24110He InjectionAimed at effectively reducing triglycerides while improving insulin resistance, used for treating dyslipidemia, especially in patients with severe hypertriglyceridemia.

Jingyin Pharmaceuticals: SRSD107 Injection

Mechanism of Action: Long-acting Anticoagulant siRNA Drug

SRSD107 Injection is a double-stranded small interfering nucleic acid (siRNA) drug,Was approved for IND in China this March,Intended to be developed for the prevention or treatment of arteriovenous thrombosis. The productSpecific liver-targeting coagulation factor XI (FXI) mRNA can inhibit the protein expression of FXI, block the activation of the intrinsic coagulation pathway, thereby achieving anticoagulant/antithrombotic effects.Preclinical study data show that a single subcutaneous injection of SRSD107 can achieve nearly 100% knockdown of FXI expression.And lasted for half a year., and no bleeding was observed.Jingyin Pharmaceuticals was founded inIn 2021,Focus on the Development of Next-Generation Nucleic Acid Innovative Therapies in the Field of Cardiovascular Diseases。In October 2023, the company announced the completion of a $60 million Series B round.Financing。

Jisheng Aoma Biotech, Junshi Biosciences: IAMA-001 Nasal Spray

Mechanism of Action: Small Nucleic Acid Immunomodulator

IAMA-001 Nasal Spray is aSmall Nucleic Acid Immunomodulators, intended for the treatment of seasonal allergic rhinitis. This productGranted IND Approval in China this March. In September this year,Junshi Biosciences' controlling subsidiary, Juntop Biotech, signs with Jisheng Aoma Bio.Agreement, granting rights to research, develop, manufacture, commercialize, and otherwise utilize in Greater China (including mainland China, Hong Kong, Macao, and Taiwan regions)IAMA-001 Small Nucleic Acid Immunomodulator Nasal Spray FormulationThe exclusive license rights.The total amount of this cooperation is approximately 1.5 billion yuan., including a RMB 40 million upfront payment.

Regeneron: Cemdisiran Injection

Mechanism of Action: siRNA Drug Targeting C5 Complement

In March this year, the combination therapy of cemdisiran injection and pozelimab injection submitted by Regeneron was approved in China.Approved for Clinical Use, for the treatment of adult male and female patients with paroxysmal nocturnal hemoglobinuria (PNH) who have signs of active disease and evidence of hemolysis.Cemdisiran is a subcutaneously injectable, C5 complement-targeting siRNA drug, and pozelimab is a next-generation C5 complement antibody therapy.。RegeneronUnder DevelopmentC5 Inhibitor""Antibody + siRNA" Combination Therapy for the Treatment of Complement-Mediated DiseasesThe advantage of this combination therapy lies in its ability to achieve complete and sustained C5 inhibition at a lower dose, reduce dosing frequency, and offer convenient clinical application through subcutaneous administration.

Ruihongdi Pharmaceuticals: Injectable RGL-2102

Mechanism of Action: mRNA Replacement Therapy Drugs

RGL-2102 is the first product of Rona Therapeutics.mRNA Protein Replacement Therapy Drugs, which was approved for IND in China this April, with the indication being ischemic diseases of the lower limbs. This is an mRNA encapsulated by lipid nanoparticles (LNP),The target human protein can be translated in vivo after administration, which is expected to promote angiogenesis in the ischemic lower limbs of patients with lower limb ischemic diseases., establishing collateral circulation and improving blood perfusion in ischemic areas. Rona Therapeutics is a subsidiary of Hengrui Medicine, established in August 2021, and is a biopharmaceutical company focused on the development of AAV gene therapy, mRNA, and cell therapy drugs. In October this year, the company's AAV dual-gene therapy Class 1 new drug also received approval in China.Approved for Clinical Use, plans to develop treatments for Parkinson's disease.

Bolim Pharmaceuticals: BW-20507 Injection

Mechanism of Action: siRNA Drug Targeting HBV

Bowlin Pharmaceuticals, a subsidiary of Bowang Pharmaceuticals, received IND approval in China in May this year for its BW-20507 Injection, which is being developed for the treatment of...Chronic Hepatitis B Virus InfectionBowang Pharmaceutical is a clinical-stage biotechnology company established in 2021, dedicated to developing a new generation of siRNA drugs. Public information shows that BW-20507 is asiRNA drugs targeting Hepatitis B Virus (HBV),The product has currently initiated Phase 1 clinical research in China.

RAG-17 Injection by Rona Therapeutics

Mechanism of Action: siRNA Drug Targeting SOD1

RAG-17 Injection, developed by Rona Therapeutics, was approved for IND in China this May and is intended for the treatment ofAdults due to superoxide dismutase 1 (SOD1) Mutation-induced Amyotrophic Lateral Sclerosis (ALS, commonly known as "Lou Gehrig's disease")。Ractagen was founded in 2017 and is committed to developing innovative small nucleic acid drugs and disease treatment methods.RAG-17 is a product under research by the company.InSOD1Double-stranded siRNA drugs targeting genes, by reducingSOD1Gene Expression for TreatmentSOD1ALS patients caused by mutations. RAG-17 utilizes the delivery platform independently developed by Rona Therapeutics.To achieve efficient delivery to the central nervous system. The product has been granted orphan drug designation by the FDA for the treatment of "ALS."

Ima Biotech: ER2001 Injection

Mechanism of Action: siRNA Therapy

ER2001 Injection, developed by iMab Biopharma, was approved for IND in China this June and is proposed for development to treatEarly Manifest Huntington's Disease。Exon Bio mainly focuses on the fields of central nervous system diseases, infections, and tumors.Synthetic Biology Self-Assembled Exosome Nucleic Acid DrugsThe development. ER2001 injection is the first product of the company's in vivo self-assembling exosome delivery (IVSAED) technology platform. It utilizes the body's own organs and tissues as bioreactors to be "processed" into the active form of siRNA in vivo, and is assembled into endogenous exosomes targeting the central nervous system that are simultaneously produced by the "bioreactor."Transported to neuronal cells via exosomes to degrade the mRNA of mutant huntingtin protein (mHTT), thereby exerting therapeutic effects.. The product has been granted Orphan Drug Designation by the FDA for the treatment of Huntington's disease.

SinoBio: SGB-9768 Injection

Mechanism of Action:RNAi Drug Targeting Complement C3 Protein

SGB-9768 Injection, a Class 1 New Drug by Shengyin BioIn June this year in ChinaApproved IND，Proposed Development TreatmentComplement-Mediated Kidney Disease, including adult patients with IgA nephropathy, C3 glomerulopathy, and immune complex-mediated membranoproliferative glomerulonephritis. According to publicly available information from St. Inno Biologics, this is aRNAi Drug Targeting Complement C3 Protein，Adopted innovative technology to deliver to liver cells,Inhibition of Hepatic C3 Synthesis via RNAi. The productCan achieve a dosing frequency of once every 3 months or 6 months, with the advantages of low treatment frequency, good patient compliance, and long-lasting efficacy.。

SinoBio, Innovent Bio: SGB-3908 Injection

Mechanism of Action:siRNA Drug Targeting AGT

SGB-3908 Injection, a Class 1 new drug applied by Shengyin BioIn July of this year in ChinaApproved IND, intended for the treatment of primary hypertension. Public information shows,This isSinoBio and Innovent Bio jointly developedsiRNA Drug for the Treatment of Hypertension, ItsAim toTargeting the treatment bottleneck of hypertension,Directly reduce the expression of AGT, with the differentiated advantages of long-lasting drug efficacy, good safety, and high patient compliance.`, which is expected to bring better treatment options and long-term benefits to patients.`

SinoBio was founded in 2021 and is dedicated to developing novel small nucleic acid drugs based on RNA interference (RNAi) technology. In December last year, SinoBio announced the completion of an over US$80 million (nearly 600 million RMB) Series A+ financing round led by Tencent Investment and YuanSheng Venture Capital.Financing，Has attracted significant attention in the industry。

Gema Biotech: LY01620

Mechanism of Action:HPV mRNA Therapeutic Vaccine

GlycoBio, a holding subsidiary of Luye Pharma, independently developedHuman Papillomavirus (HPV) mRNA Therapeutic VaccineLY01620 was approved for IND in China this August and is intended for the treatment of HPV16-related high-grade squamous intraepithelial lesions of the cervix. LY01620Utilizing mRNA to express HPV-specific antigens E6/E7, inducing the body to produce specific T-cell immunity to eliminate HPV-infected cervical epithelial cells., blocking the carcinogenic process and restoring the cervical epithelial cells to normal. The productExpected to be applied in different stages of the disease course after HPV infection.

G-Mab Biotech is a research and development company under Luye Pharma, focusing on lipid nanoparticle delivery of small molecule chemical drugs and nucleic acid drug delivery. Its product pipeline covers anti-tumor drugs, analgesics, mRNA vaccines, novel adjuvants, and nucleic acid drugs.

Xuanjing Bio: RG002C0106 Injection

Mechanism of Action: TargetedsiRNA Drug Targeting Complement Factor C3

Xuanjing Biotech's自主研发的小干扰核酸（siRNA）1类创新药RG002C0106注射液于今年8月在中国获批IND，拟用于治疗补体参与介导的原发性或继发性肾小球疾病。这是一款siRNA Drug Targeting Complement Factor C3It is also the first pipeline of Xuanjing Bio to enter the clinical trial stage. Xuanjing Bio was established in 2022 and focuses on the research, development, and industrialization of innovative small nucleic acid drugs.

[1]Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.Retrieved Oct 22，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2] Official websites of various companies and public materials