In the past two months, news events in the field of precise targeting of "small nucleic acids" have attracted considerable attention
On September 30, Heggia Biochem, a new small nucleic acid drug, declared its second innovative drug
On September 23, Yujia, A leader in small nucleic acid drug research and development, completed A+ round of financing of tens of millions of yuan, which was used to promote the IND application of liver fibrosis project YJH-0425 and preclinical research of other product pipelines
On September 19, Angto Biomedical completed the seed round investment of nearly 100 million yuan, which was used to build the unique two-way regulation technology platform of antisense nucleic acid, and promote the early research and development and layout of multiple innovative drug pipelines
On September 19, the first domestic PCSK9siRNA drug was approved for clinical use
On August 10, Huadong Pharmaceutical planned to hold Hualin Technology for 396 million yuan, adding small nucleic acid drug layout
On August 5, Alnylam announced phase 3 data from Patisiran, its siRNA drug for transthyretin amyloidosis cardiomyopathy (ATTR-CM), demonstrating significant efficacy and safety. The company's shares jumped nearly 48%, pushing its market value to $25.5 billion
x small nucleic acid drugs target nucleic acid and achieve disease treatment through the regulation of protein translation process. They have the advantages of abundant targets, short research and development cycle, long efficacy and high success rate of clinical development. After more than 40 years of research and accumulation, small nucleic acid drugs have made continuous progress in chemical modification and drug delivery.
In the past two years, the development of small nucleic acid drugs has been accelerated. Especially during the epidemic period, the advantages of COVID-19 mRNA vaccines in research and development efficiency and drug efficacy have made people see the great potential of nucleic acid drugs, which is expected to become the third wave of modern pharmaceutical.
As a representative of the new generation of technology in the industry, a number of representative enterprises have emerged in the field of small nucleic acid drugs. Overseas, Ionis, Alynlam and Sarepta are becoming three major small nucleic acid drugs.
Among them, Alynlam is recognized as the hegemon of RNAi drugs. Currently, the four RNAi drugs on the market in the world are all developed by the company and its partners. In 2018, the company successfully launched Onpattro, the world's first approved RNAi therapy, which also means that the Nobel Prize achievement has been successfully brought from concept to practical clinical application. In 2021, Alnylam posted full-year revenue of $662 million and briefly topped $20 billion in market capitalization.
Ionis is a global leader in the research and development of antisense nucleic acid drugs, with a pipeline of more than 40 products in development. Its drug Spinraza (Nusinersen) has been approved for sale in many countries around the world, including the United States and China, and is the largest small nucleic acid drug in the world.
In addition, as the small nucleic acid drug discovery technology is becoming more and more mature, pharmaceutical giants Roche, Sanofi, Novartis have also come off the market, looking for the next "blockbuster" drug opportunities.
Overseas nucleic acid drugs are in full swing, and the domestic industry has also entered a period of rapid growth. In China, 24 small nucleic acid drug candidates have entered clinical trials, and most small nucleic acid drug companies are still in the early stage of development or rising.
Among them, the domestic enterprise with the most drugs in clinical stage is Rebo Biotics, which has 5 products into clinical.
SR062 is domestic first small nucleic acid drugs for type 2 diabetes treatment, developed by Ionis, rainbow biological research, development and cooperation for the treatment of type 2 diabetes, at present in domestic in phase 2 clinical stage, is expected to once every two weeks for medicine, greatly reduce the dosing frequency, such slow disease treatment for diabetes has important clinical significance.
RBD7022 injection is the first domestic PCSK9siRNA drug approved for clinical use. The drug is a GalNAc conjugate siRNA drug for hyperlipidemia, developed by Ribobio based on the RIBOGalSTARTM platform with proprietary intellectual property rights. Preclinical trial data showed that RBD7022 had good safety characteristics and strong lipid-lowering effect, and its lipid-lowering effect showed the characteristics of stable lipid-lowering level and long-lasting effect. After a single administration, the effect could be maintained for several months, and the inhibition of LDL-C could reach more than 50%.
RBD1016(SR016) is the first anti-hepatitis B siRNA drug based on GalNAc liver targeted delivery technology independently developed by Rebobio in China, which can effectively and long-term inhibit hepatitis B surface antigen and is expected to achieve functional cure of chronic hepatitis B. The current phase 1 clinical study is nearing completion.
SR063, the first ASO drug for the treatment of patients with AR-V7 positive prostate cancer, has inhibitory effects on both androgen-dependent and androgen-independent AR pathpath-related metastatic castration-resistant prostate cancer (mCRPC). Currently, it has completed phase 1 clinical study, and will carry out phase 2a clinical study in China.
In addition, in 2012, a joint venture company, Rebo Quark, was established between Rebo Bio-and Quark. In 2020, Rebo Bio-acquired Rebo Quark as a controlling subsidiary and renamed Rebo Gul. The subsequent research and development of SR061 in the licensed area is led and undertaken by Rebo Bio-. SR06 is a small nucleic acid drug with rapid development in China. It is an optic neuroprotective drug targeting Caspase2. Its first clinical indication is non-arteritis anterior ischemic optic neuropathy (NAION), and it is suitable for many ophthalmic indications related to optic nerve injury, including glaucoma. SR061 is currently being analyzed for phase 2/3 clinical data for NAION indications. For glaucoma indications, phase 2a clinical studies have been completed abroad.
In addition, STP705, a leader in the field of tumor RNAi therapy, is the most advanced product of Sunro, which has entered phase 2 clinical trials in the United States. It adopts two siRNA strategies that simultaneously deliver TGF-β1 and Cox-2 to target tumor tissues by intratulotumor injection. Previously published data from the phase 2 interim trial showed 100% complete clearance in the 180-μg dose cohort.
HT-101 injection is a GalNAc-siRNA drug developed by Xing Yao Kunze, a subsidiary of Fosun Pharmaceutical, for the treatment of chronic hepatitis B virus infection. In preclinical efficacy trials, a single dose reduced the expression of multiple key components of hepatitis B virus and sustained inhibition of viral replication for more than 70 days.
In 2021, through the acquisition of Tianlong Pharmaceutical, Yuekang Pharmaceutical began to actively layout mRNA vaccines and small nucleic acid drugs, and comprehensively cut into the nucleic acid track nucleus. Currently, the most advanced small nucleic acid drug CT102 is an antisense nucleic acid (ASO) drug targeting the human insulin-like growth factor type 1 receptor (IGF1R) gene for the treatment of primary hepatocellular carcinoma. The phase 1 clinical study was completed in January 2022, and the clinical 2a trial was initiated in March.
VIR-2218 is a subcutaneously administered siRNA targeting HBV introduced by Tensengbo. It is also the first clinical siRNA to include enhanced stabilization chemoplus technology to enhance stability and minimize off-target activity, indicated for hepatitis B.
As can be seen from the above contents, domestic small nucleic acid drugs began to have an outbreak momentum.
