Oligonucleotide Industry Dynamics: China and Global Landscape – December 2024 Highlights

Dec 20, 2024 11:00 CST Updated 11:00

Sirius Therapeutics

Oligonucleotide Drug Developer

SANEGENEBIO

Small Nucleic Acid Drug Developer

Innovation in China

01 BIBITE

SANEGENEBIO Collaborates with Mr. Cai Lei to Establish a Joint Laboratory, Aiding in ALS Drug Development

Bebetter's First siRNA Innovative Drug BEBT-507 Approved for Clinical Trials

On November 29, 2024, according to the official website of the Center for Drug Evaluation of the National Medical Products Administration, BEBT-507 Injection, a small nucleic acid (siRNA) innovative drug independently developed by Guangzhou Bebetter Pharmaceutical Co., Ltd. ("Bebetter Pharmaceutical" for short) for the treatment of polycythemia vera, has received clinical tacit approval, with the acceptance number CXHL2400967.

BEBT-507 Injection is the first siRNA drug developed by Bibeit Pharma based on its self-developed small nucleic acid drug research and development platform. It aims to treat diseases with abnormal iron metabolism, such as polycythemia vera, by regulating iron levels in the body. Preclinical study results show that BEBT-507 can efficiently inhibit target activity over the long term, demonstrating significant and sustained efficacy as well as good safety in animal models.

02 Sirius Therapeutics

Novel Anticoagulant FXI-siRNA Therapy — Sirius Therapeutics Announces Positive Clinical Trial Data

On December 10, 2024, Sirius Therapeutics presented the latest data from the Phase I clinical trial of SRSD107 at the 66th American Society of Hematology (ASH) Annual Meeting.

This trial is a single-center, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneous SRSD107 in 40 healthy subjects.In the study, SRSD107 demonstrated good safety and tolerability, with significant changes observed in pharmacodynamic biomarkers compared to baseline.At the highest administered dose, the maximum reductions in FXI antigen and FXI activity exceeded 90%, and the increase in aPTT was over 100% (i.e., aPTT ratio > 2.0).The pharmacodynamic effect persists after a single dose, maintaining FXI antigen and FXI activity in a nearly 90% suppressed state for over 16 weeks.

About SRSD107 Injection: SRSD107 injection is a double-stranded small interfering RNA (siRNA) drug independently developed by Sirius Therapeutics. By specifically targeting the liver-directed human coagulation factor XI (FXI) mRNA, it inhibits the protein expression of FXI, blocking the activation of the intrinsic coagulation pathway, thereby achieving an anticoagulant effect. Preclinical trial data shows that a single subcutaneous injection of SRSD107 can reduce peripheral blood FXI concentration by nearly 100%, with effects lasting up to half a year without any observed bleeding.

03 SANEGENEBIO

SANEGENEBIO Announces Phase I Clinical Data of siRNA Drug for the First Time

On December 10, 2024, SANEGENEBIO announced positive results from preclinical and partial Phase I clinical trials of its small nucleic acid (siRNA) drug SGB-9768 targeting complement factor C3 at the 8th Complement Drug Development Conference held in Boston, USA.

This drug aims to treat various complement-mediated diseases by reducing complement factor C3, including IgA nephropathy, C3 glomerulopathy, immune complex-mediated membranoproliferative glomerulonephritis, dry age-related macular degeneration, paroxysmal nocturnal hemoglobinuria, and other renal and hematological disorders.

As of December 1, 2024, a total of 55 subjects have been randomly assigned to receive SGB-9768 and placebo treatments. Trial data show that after a single subcutaneous injection, SGB-9768 demonstrated good safety and tolerability, while a dose-dependent, significant, and sustained reduction in C3 levels and complement pathway activity was observed. Compared with other siRNA products targeting the same site, SGB-9768 exhibited higher knockdown efficacy of the target protein C3 at a lower dose.

04 ViaGen

ViaGenBio Completes First Patient Dosing in Phase III Clinical Trial of VSA003 for Homozygous Familial Hypercholesterolemia in China

On December 18, 2024, SANEGENEBIO announced that the first patient dosing in the Phase III clinical trial of its investigational new drug VSA003 injection (hereinafter referred to as VSA003) was successfully completed at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. This trial is a randomized, double-blind, placebo-controlled, multi-center Phase III clinical trial aimed at evaluating the efficacy and safety of VSA003 injection in Chinese adolescent and adult patients with homozygous familial hypercholesterolemia (HoFH) (CTR20244397).

VSA003 is an siRNA drug that specifically targets ANGPTL3 mRNA in hepatocytes, effectively reducing the production of ANGPTL3 protein and decreasing the levels of ANGPTL3 protein in the liver and circulation. This, in turn, inhibits the secretion of TRL (including VLDL, a precursor to LDL synthesis) from the liver into the bloodstream, thereby lowering blood LDL-C and TG levels.

On January 29, 2024, VSA003 injection was included in the list of breakthrough treatment drugs by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). The drug is intended for the treatment of Homozygous Familial Hypercholesterolemia (HoFH).

Overseas Hotspots

01 Alnylam

Alnylam Announces FDA Acceptance of Supplemental New Drug Application (sNDA) for Vutrisiran in Treatment of ATTR Amyloidosis with Cardiomyopathy

On November 25, 2024, Alnylam Pharmaceuticals announced that the FDA had accepted the company's supplemental New Drug Application (sNDA) for vutrisiran for review.

Vutrisiran utilizes the GalNAc delivery system for the treatment of hATTR amyloidosis with polyneuropathy. Compared to the company's earlier LNP-delivered Onpattro, Amvuttra has low manufacturing costs, long-lasting effects, and does not require frequent dosing, offering the convenience of subcutaneous injection, which has led to a rapid and significant increase in sales after its market launch.

In 2023, the global net product revenue of AMVUTTRA® (vutrisiran) reached 5.578 billion US dollars, and this year has seen even more impressive growth. By the end of Q3 2024, the global net product revenue has exceeded 6.84 billion US dollars (1.95+2.3+2.59).

02 Silence

Sirius Therapeutics Announces Additional Results from Phase I Clinical Study in Patients with Polycythemia Vera (PV)

On December 9, 2024, Silence Therapeutics announced additional results from the open-label Phase I portion of the SANRECO study at this year's American Society of Hematology (ASH) Annual Meeting. The study focuses on divesiran, an siRNA targeting TMPRSS6, for use in patients with polycythemia vera (PV).

Consistent with the results reported in June, HCT continued to decrease during treatment and had a favorable impact on iron metabolism indicators. Heparin levels increased and remained within the physiological range across all dose groups, demonstrating consistent target engagement. Importantly, divesiran has been well-tolerated to date, with no dose-limiting toxicity observed. The Phase I clinical portion of the SANRECO study has enrolled 21 patients and will continue until all patients complete follow-up, expected to conclude in February 2025. Additionally, Silence announced that the Phase II portion of the SANRECO study has dosed its first subject.

03 Arrowhead

Arrowhead Announces Interim Data from ARO-CFB Phase 1/2a Clinical Trial

On December 11, 2024, Arrowhead presented interim results from the Phase 1/2a clinical study of ARO-CFB at the 8th Complement-Based Drug Development Summit. ARO-CFB achieved an average 90% reduction in serum CFB after a single 400 mg dose; ARO-CFB nearly completely inhibited the hemolytic activity and functional activity of the alternative pathway, which should be competitive with other treatments targeting the alternative pathway; The duration of effect supports a dosing regimen of at least once every 3-4 months via subcutaneous administration; ARO-CFB is a GalNAc conjugate designed to target and silence liver CFB mRNA, inhibiting the production of complement factor B. CFB plays a key regulatory role in amplifying the activation of the alternative complement pathway and has been identified as a promising therapeutic target.

About Oulibio

Oli Biopharmaceuticals (Suzhou) Co., Ltd. is a professional medicinal nucleic acid CRDMO.The company provides customers with "one-stop" services including nucleic acid drug discovery, laboratory R&D, process and analytical development, CMC services, API production, and drug registration. The technical team of Oulibio comes from one of the earliest teams in China to engage in the development of nucleic acid drug production processes and CMC research, possessing extensive experience in project development and product registration. Currently, the company has established four industry-leading core technology platforms: solid-phase synthesis of nucleic acids, chemical modification and conjugation, process development and analysis, and CMC pharmaceutical research. It has also initiated in-depth collaborations with multiple pharmaceutical and biotechnology companies both domestically and internationally.

In 2023, the company's 3,000㎡ pilot platform compliant with GMP standards officially began offering services, focusing on helping customers address "bottleneck" issues such as small nucleic acid drug process scale-up and CMC pharmaceutical research. The company will continue to provide compliant, high-quality, reliable, and efficient services to help customers enhance R&D efficiency, accelerate product registration and market entry, jointly supporting the entire process of small nucleic acid drugs from preclinical to commercial production.

Contact Us

Email: order@olipharma.com

Phone: 15336788818

Official Website: www.olipharma.com

R&D Center: No. 168, Yuanfeng Road, Yushan Town, Kunshan City, Jiangsu Province

Production Base: Building C3, Phase I Factory, No. 999 Yishanhu Road, Guoxiang, Wuzhong District, Suzhou City, Jiangsu Province

Common Technology Platform: Room 202, 2nd Floor, Building 2, No. 21 Baoshen South Street, Beijing Daxing District Biomedical Industry Base