Tides Weekly | Global Peptide and Oligonucleotide Therapeutics News Roundup
Dyne Therapeutics
Developer of Targeted Therapies for Muscle Diseases
Ractigen
Innovative Drug R&D Developer
On May 20, 2024, Dyne Therapeutics announced the latest clinical progress of two Antibody Oligonucleotide Conjugates (AOC) drugs. The data showed that both drugs significantly impacted disease biomarkers, improved function, and demonstrated good safety.
About AOC
AOC is a type of conjugated antibody, similar to ADC, with the difference being that AOC is constructed by conjugating oligonucleotides (such as siRNA, ASO, etc.) via site-specific or non-site-specific conjugation onto a targeted antibody or antibody fragment.
About ACHIEVE
ACHIEVE is a Phase 1/2 global clinical trial evaluating DYNE-101, including a 24-week multi-dose escalation (MAD) randomized placebo-controlled period, a 24-week open-label extension period, and a 96-week long-term extension period. The trial, which is designed for registration, is enrolling adult DM1 patients aged 18 to 49. The primary endpoint...The primary endpoints are safety and tolerability, with secondary endpoints including pharmacokinetics, pharmacodynamics, splicing changes from baseline, and measurements of muscle strength and function.
About Dyne Therapeutics
Dyne is a clinical-stage muscle disease company focused on advancing innovative, life-changing treatments for patients with genetically driven diseases.
On May 21, 2024, Ractigen Therapeutics announced that its self-developed small activating RNA (saRNA) drug, RAG-01, received Fast Track Designation (FTD) from the U.S. Food and Drug Administration (FDA) for the treatment of BCG-unresponsive non-muscle invasive bladder cancer. Previously, the clinical trial application for RAG-01 for the treatment of non-muscle invasive bladder cancer had been approved by the FDA. Meanwhile, a Phase I clinical trial of RAG-01 has been initiated in Australia, with three subjects already enrolled and dosed. The Fast Track Designation granted by the FDA will significantly expedite the development process of this drug during the clinical trial period. RAG-01 is also the world’s first saRNA project to receive FDA Fast Track Designation.
About RAG-01
RAG-01 is a first-in-class double-stranded saRNA drug that specifically targets and activates the tumor suppressor gene p21. It enhances the expression of the p21 gene through the RNAa mechanism to inhibit tumor cell proliferation and induce apoptosis and senescence. Preclinical efficacy studies have shown that, via Ractigen Therapeutics' self-developed small nucleic acid delivery system LiCO™, RAG-01 treatment significantly inhibits the growth of bladder cancer tumors in animal models while demonstrating robust safety.
About Ractigen
Ractigen Therapeutics is a platform-based new drug research and development company based in China and targeting the global market. It is committed to developing breakthrough small nucleic acid drugs and disease treatment methods. Ractigen Therapeutics is one of the few global small nucleic acid drug companies that simultaneously possess both intrahepatic and extrahepatic delivery technologies, and has developed multiple proprietary, internationally leading small nucleic acid drug delivery platform technologies, including SCAD™ and LiCO™.
On May 24, 2024, Eli Lilly announced that it had more than doubled its investment in the Lebanon, Indiana manufacturing site, with a new investment of $5.3 billion, increasing the company’s total investment at this site from $3.7 billion to $9 billion. This expansion will enhance Eli Lilly's capacity to produce the active pharmaceutical ingredients (API) for tirzepatide, namely Zepbound and Mounjaro injections, allowing more patients suffering from chronic conditions such as obesity and type 2 diabetes to benefit.
About Tirzepatide
Tirzepatide is a once-weekly GIPR and GLP-1R agonist. GLP-1 and GIP are two natural incretins, and studies have shown that GIP can reduce food intake and increase energy expenditure, thereby reducing body weight. When GIP is used in combination with a GLP-1 receptor agonist, it may have an impact on patients' blood glucose levels and body weight.A greater impact.
About Eli Lilly and Company
Eli Lilly and Company is a globally leading pharmaceutical company engaged in the research, development, production, and sale of medicines, dedicated to improving human health through innovation. Founded more than a century ago by Colonel Eli Lilly in 1876 in Indiana, USA, the company’s founder committed to producing high-quality medicines to meet genuine medical needs.
Recently, Novo Nordisk's latest data from the large Phase III clinical trial FLOW for semaglutide in treating chronic kidney disease combined with type 2 diabetes was published in the New England Journal of Medicine. The primary endpoint of the study was kidney disease (CKD) events (renal failure such as dialysis, transplantation, eGFR<15ml/min/1.73m², or a decrease in eGFR from baseline by more than 50%, or death).
The FLOW clinical trial is a randomized, double-blind, placebo-controlled clinical trial designed to examine the effects of a 1.0 mg subcutaneous injection of Ozempic compared to placebo as an adjunct to standard treatment in preventing the progression of kidney damage and reducing the risk of renal and cardiovascular death in patients with CKD and type 2 diabetes. The trial enrolled 3,533 patients with CKD and type 2 diabetes. The primary endpoint is a composite endpoint consisting of multiple components, including: time to onset of a sustained ≥50% decline in estimated glomerular filtration rate (eGFR) from baseline; time to eGFR decline to <15 mL/min/1.73 m²; initiation of chronic kidney replacement therapy (dialysis or kidney transplantation); and death due to kidney disease or cardiovascular disease in patients with type 2 diabetes and chronic kidney disease. Key secondary endpoints include the annual rate of change in eGFR, major adverse cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death), and all-cause mortality.
About Novo Nordisk
Novo Nordisk was founded in 1923 and is a global leading biopharmaceutical company headquartered in Copenhagen, the capital of Denmark. Our goal is to drive change to defeat diabetes, obesity, rare blood disorders, endocrine disorders, and other serious chronic diseases.
On May 28, 2024, Bio-Thera Solutions announced that the Biologics License Application (BLA) for its self-developed dulaglutide injection (BA5101) has been accepted by the Center for Drug Evaluation of China's National Medical Products Administration for the treatment of blood glucose control in adult patients with type 2 diabetes. BA5101 is the first biosimilar of Trulicity® (Chinese name: Duoyida®) to be submitted for marketing approval in China. The international registration and clinical trials for this product are also being actively advanced.
Dulaglutide is a long-acting GLP-1 (glucagon-like peptide-1) receptor agonist administered once weekly. Compared with other types of hypoglycemic agents, dulaglutide improves the function of pancreatic β-cells, providing stable and effective reduction of blood glucose and glycated hemoglobin (HbA1c) levels. Additionally, its unique mechanism of action is less likely to cause hypoglycemia and can reduce body weight, lipid levels, and the long-term risk of cardiovascular disease, benefiting renal health.Dirt also has a protective effect. Multiple clinical studies have also shown that: The once-weekly dosing method of dulaglutide can reduce the inconvenience for patients when taking medication, resulting in higher medication adherence.
About Boan Biotech
Boan Biotech (6955.HK) is a fully integrated biopharmaceutical company dedicated to the development, manufacturing, and commercialization of biologics, with a focus on oncology, autoimmune diseases, ophthalmology, and metabolic disorders. The company's new drug discovery efforts are centered around multiple platforms, including a fully human antibody transgenic mouse and phage display technology platform, a bispecific T-cell engager technology platform, an antibody-drug conjugate (ADC) technology platform, and a cell therapy platform.
Recently, NS Pharma announced the failure of the Phase III clinical trial for its Duchenne muscular dystrophy candidate drug viltolarsen (brand name: Viltepso).
Viltepso is an antisense oligonucleotide that works by skipping exon 53. It was approved in Japan in March 2020 for the treatment of DMD patients confirmed to have exon 53 skipping mutations. In August 2020, Viltepso received accelerated approval from the U.S. FDA, becoming the second antisense oligonucleotide (ASO) therapy for the treatment of DMD amenable to exon 53 skipping. The first one was Golodirsen (brand name: Vyondys 53®), a drug developed by Sarepta, which received FDA approval in December 2019.
These two drugs are both ASO therapies, a type of small nucleic acid therapy, and they share the same mechanism of action.Through the ScreenSkipping Exon 53 in the Dystrophin Gene to Promote FunctionalityProduction of anti-myotonic dystrophy protein.
AboutDuchenne Muscular Dystrophy（DMD）
Duchenne Muscular Dystrophy (DMD) is a fatal rare X-linked degenerative neuromuscular disorder and one of the most common lethal genetic diseases. Its pathogenesis is due to mutations in the gene encoding dystrophin, leading to the absence or functional defect of dystrophin. Shortly after birth, DMD patients exhibit inflammatory responses, resulting in muscle fibrosis as well as muscle atrophy and degeneration. Due to respiratory and/or cardiac failure, the life expectancy of patients typically does not exceed 40 years. Globally, 1 in every 3,500-5,000 male infants is affected by DMD.
On May 29, 2024, Suzhou Ribo Life Science Co., Ltd. ("Ribo Life Science") announced that its self-developed RBD4059, the world’s first anti-thrombotic siRNA drug targeting FXI, had recently received Phase II clinical trial approval from the European Medicines Agency (EMA). This trial is a randomized, double-blind, placebo-controlled Phase II clinical study designed to evaluate the safety, efficacy, and pharmacokinetics of RBD4059 in patients with stable coronary artery disease. The trial has also been approved to be conducted at Ribo Life Science's European R&D center in its own Phase II clinical facility, which complies with European and American regulatory standards.
Anticoagulant drugs are fundamental medications for the prevention and treatment of thrombosis, with a wide range of indications including coronary artery disease, peripheral artery disease, end-stage renal disease (ESRD), atrial fibrillation (AF), venous thromboembolism (VTE), and the prevention and treatment of conditions such as post-operative care in orthopedic surgery. Currently used anticoagulants in clinical practice, such as direct oral anticoagulants (DOACs), VKAs, and heparin, all carry a certain risk of bleeding. Therefore, there is a significant clinical demand for new anticoagulant drugs that are potent, long-acting, and have a low risk of bleeding.
About Suzhou Ribo Life Science Co., Ltd.
Suzhou Ribo Life Science Co., Ltd. ("Ribo Life Science") was established in 2007. It is an innovative R&D company dedicated to developing RNA interference (RNAi) drugs and is the main pioneer and leader in China's small nucleic acid technology and small nucleic acid pharmaceuticals industry. The company's headquarters is located in Kunshan, Jiangsu, with R&D centers in Beijing and Gothenburg, Sweden.