Tides Weekly | Global Peptide and Oligonucleotide Therapeutics News Roundup

On April 3, 2024, Ractigen Therapeutics, an innovative biopharmaceutical company at the global forefront in the field of small activating RNA (saRNA) drugs, announced that the first human trial participant dosing of its self-developed pioneering saRNA drug RAG-01 was completed at GenesisCare in Australia.

RAG-01 is a first-in-class saRNA drug designed to activate the tumor suppressor gene p21 in patients with non-muscle-invasive bladder cancer (NMIBC), thereby inhibiting the recurrence and progression of bladder cancer. This trial is an open-label, multi-center study aimed at evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy of RAG-01 in NMIBC patients who have failed Bacillus Calmette-Guérin (BCG) treatment. Preclinical data indicate that RAG-01 can effectively inhibit bladder cancer tumor growth in model animals and has demonstrated good safety. Ractigen Therapeutics owns the independent intellectual property rights for the RAG-01 product. 

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 master both intrahepatic and extrahepatic delivery technologies, having developed several internationally leading small nucleic acid drug delivery platform technologies with independent intellectual property rights, such as SCADTM and LiCOTM. Based on RNA activation technology and its self-developed Smart-TTC saRNA drug development platform, the company has established a highly differentiated small nucleic acid drug pipeline. Indications cover neurodegenerative and neuromuscular diseases, cancer, metabolic and hematological disorders, providing innovative therapeutic solutions for undruggable targets and currently incurable diseases across various disease areas.

On April 7, 2024, Ionis Pharmaceuticals announced the full results of the Phase III Balance study of Olezarsen for the treatment of familial chylomicronemia syndrome (FCS). The monthly 80mg Olezarsen treatment group achieved the primary endpoint of significantly reducing patients' triglyceride levels at 6 months. In addition, Olezarsen continued to reduce apolipoprotein-III (apoC-III) levels. More importantly, compared with placebo, Olezarsen reduced the incidence of acute pancreatitis during the 12-month treatment period.

The Balance study is a global, multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial that enrolled 66 adult patients with FCS who were receiving background therapy including statins, fibrates, and omega-3 fatty acids. In the study, patients were randomized 1:1:1 to receive subcutaneous injections of 50 mg or 80 mg Olezarsen or placebo once every 4 weeks for 53 weeks. The primary endpoint was the percentage change in fasting triglyceride levels from baseline at 6 months in the treatment group compared with placebo. Secondary endpoints included patient triglyceride levels at 12 months and the incidence rate of acute pancreatitis events.

About Ionis Pharmaceuticals, Inc.

For more than 30 years, Ionis has been a leader in the field of RNA-targeted therapeutics, pioneering new markets and transforming treatment standards. Ionis currently has four marketed drugs and a promising late-stage pipeline, with a focus on cardiovascular and neurology franchises. Our scientific innovation began and will continue because we know that patients are counting on us, driving our vision to become a leader in genetic medicine by utilizing a multi-platform approach to discover, develop, and deliver life-changing therapies.

On April 7, 2024, Alnylam and Roche jointly announced that the Phase II KARDIA-2 study of the RNAi therapy zilebesiran for the treatment of hypertension had met its primary endpoint. Data showed that adding zilebesiran to the standard treatment regimen significantly reduced patients' 24-hour average systolic blood pressure (SBP) at the third month. Notably, some patients who received a single dose of zilebesiran still maintained the sustained blood pressure-lowering effect at the six-month follow-up.

KARDIA-2 is a randomized, double-blind, placebo-controlled Phase 2 clinical trial designed to evaluate the efficacy and safety of zilebesiran in combination with standard antihypertensive drugs in adult patients with mild to moderate hypertension. This global multicenter study enrolled 672 adult patients with hypertension. They were first randomly assigned to three different cohorts to receive open-label treatment with the antihypertensive drugs olmesartan, amlodipine, or indapamide for at least four weeks. Eligible patients were then randomly assigned to receive either 600 mg of zilebesiran or a placebo, in addition to standard antihypertensive drug therapy, for six months.

About Alnylam Pharmaceuticals

Alnylam Pharmaceuticals (Nasdaq: ALNY) is pioneering the translation of RNA interference (RNAi) into a wholly new class of innovative medicines with the potential to transform the lives of people suffering from rare and prevalent diseases with unmet needs. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for producing transformative medicines.

On April 8, 2024, Arnatar (Angtuo Bio), a company dedicated to the development of nucleic acid drugs, announced that it had recently completed a Series A financing round exceeding 50 million US dollars. This round of financing was jointly completed by Eight Roads Capital, 3E Bioventures Capital, Cowin Capital, Gao Rong Capital, Lyfe Capital, New Alliance Capital, Yi Jing Capital, Legend Star, Hong Sheng Capital, and Zhuanhua Capital. The proceeds from this financing will mainly be used to accelerate the in-depth layout of the company's drug pipeline, rapidly advance clinical trials, and support the operational establishment of its China-based company. Previously, Angtuo Bio completed a nearly 100-million-yuan seed financing round led solely by Apricot Capital in September 2022.

Antorna Therapeutics was founded in 2022 by a global team of scientists in the field of nucleic acid drugs. It has established a breakthrough innovative nucleic acid drug platform and continues to explore novel mechanisms of nucleic acid-based drugs, covering multiple therapeutic areas.

According to the official website of Antorna Biotech, the company is leveraging innovative antisense nucleic acid technology (Antisense Technology) and utilizing RNA interference (RNAi) and antisense oligonucleotide (ASO) platforms to modulate the expression of target genes, thereby providing opportunities for the treatment of liver, extrahepatic organ diseases, as well as common and rare diseases.

On April 8, 2024, Suzhou Ribo Life Science Co., Ltd. ("Ribo Life Science") announced that the European Medicines Agency (EMA) has approved the Phase II clinical trial of its self-developed small nucleic acid drug RBD1016 injection for the treatment of Hepatitis Delta Virus (HDV). The trial will evaluate the efficacy and safety of RBD1016 in treating HDV infection.

HDV virus requires the presence of HBV virus to reproduce and cause infection, therefore, hepatitis D virus specifically infects patients with hepatitis B. Currently, about 5% of chronic hepatitis B patients are also infected with HDV virus. HDV/HBV co-infection accelerates the progression of liver disease, leading to a several-fold increase in the incidence of cirrhosis and hepatocellular carcinoma in co-infected patients. At the time of diagnosis, 30-70% of hepatitis D patients are already diagnosed with cirrhosis, and 50% of patients die within 10 years of diagnosis (JAMA . 2023 Dec 6;330(24):2376-2387). Therefore, hepatitis D is the most severe chronic viral infection.Types of hepatitis, with significant unmet clinical needs.

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 enterprise dedicated to developing RNA interference (RNAi) drugs and is a leading 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 research and development centers in Beijing and Gothenburg, Sweden.

Recently, Novo Nordisk announced the results of the Phase 3 trial STEP HFpEF DM at the 2024 American College of Cardiology (ACC), with the trial results simultaneously published in The New England Journal of Medicine. Analysis shows that, compared to placebo, once-weekly subcutaneous injections of its weight-loss therapy Wegovy (semaglutide) significantly reduced heart failure-related symptoms and physical limitations while improving exercise function in obese heart failure patients with preserved ejection fraction (HFpEF) who also have type 2 diabetes (T2D).

STEP HFpEF DM is a Phase 3 randomized trial primarily aimed at investigating the effects of once-weekly subcutaneous administration of 2.4 mg Wegovy compared to placebo on symptoms, physical function, and weight in obese (BMI ≥ 30 kg/m²) patients with T2M HFpEF. The trial enrolled 616 patients, with co-primary endpoints being changes in body weight and the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) from baseline to Week 52. The KCCQ-CSS score measures symptoms and physical limitations in HFpEF patients, ranging from 0-100, with higher scores indicating better health status.The fewer symptoms and physical limitations the patient has.

AboutNovo 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 and other serious chronic diseases such as obesity, rare blood disorders, and endocrine disorders. To achieve this goal, we lead scientific breakthroughs, expand the accessibility of our medicines, and are committed to preventing and ultimately curing diseases. Novo Nordisk has approximately 47,000 employees across 80 countries and regions worldwide, providing products and services to more than 168 countries and regions globally.