TIDES Weekly Digest | Global Peptide and Oligonucleotide Therapeutics Highlights (Nov 18–29)
Rona Therapeutics
Nucleic Acid Drug Developer
Leaderna
Nucleic Acid Drug Developer
November 202416th，Rona Therapeutics, a leader in innovative RNA therapies, announced positive results from the Phase I clinical trial of its novel GalNAc-conjugated PCSK9 siRNA drug RN0191 at the American Heart Association (AHA) Annual Scientific Sessions. The drug aims to significantly reduce low-density lipoprotein cholesterol (LDL-C) and other lipid markers.
This Phase I study is a randomized, single-dose escalation, placebo-controlled trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects with elevated LDL-C levels. The trial subjects are aged between 18 and 60 years, with a Body Mass Index (BMI) ranging from 19 to 30 kg/m². The data cut-off date was October 14, 2024. A total of 32 subjects were randomly assigned to receive doses of 60mg, 200mg, or 400mg.g and 600mg treatment. The average LDL-C level at baseline was between 110-130 mg/dL.
About Rona Therapeutics
Rona Therapeutics is a global leading nucleic acid innovative drug platform company, focusing on the treatment of metabolic diseases and nervous system disorders. Rona Therapeutics is committed to developing best-in-class and first-in-industry siRNA drugs with differentiation and innovation to address unmet clinical needs and improve treatment outcomes for cardiovascular diseases, obesity, and metabolic disorder-associated nonalcoholic steatohepatitis (NASH). In addition, Rona Therapeutics is fully unlocking the enormous potential of extrahepatic delivery technologies for nervous system disorders and fat-muscle delivery targeting various metabolic syndrome treatments.
2November 202418th，Leaderna Therapeutics Ltd. (hereinafter referred to as "Leaderna") announced that the first subject has been enrolled in a Phase I clinical trial in China for its self-developed LDR2402 injection, a small nucleic acid drug targeting angiotensinogen (AGT), at the Sichuan Provincial People's Hospital, marking the beginning of a new generation of primary hypertension treatment drugs in China.This is the second clinical study of small nucleic acid drugs conducted by Leaderna.
About LDR2402 Injection
LDR2402 Injection is a novel small nucleic acid drug developed based on RNA interference (RNAi) technology. In preclinical experiments, it significantly reduces the level of angiotensinogen (AGT), with effects lasting over six months after a single injection. AGT is the origin of the renin-angiotensin-aldosterone system (RAAS) mechanism. LDR2402 selectively enters the liver, silencing AGT expression at the source to achieve blood pressure reduction. In clinical treatment, LDR2402 may improve patient compliance by extending the dosing interval (once per quarter or every six months). It also provides steady blood pressure reduction within 24 hours, decreases blood pressure variability (BPV), and offers greater cardiovascular benefits to patients with hypertension.
November 202418th，Ratio Therapeutics Announces Global Exclusive License and Collaboration Agreement with Novartis. The collaboration leverages Ratio's expertise in radioligand therapy discovery and development along with its technology platform to develop targeted somatostatin receptor 2 (SSTR2) radiopharmaceutical candidates for cancer treatment.
About Novartis
Novartis is committed to reimagining medicine to improve people's quality of life and extend human lifespan. Leveraging our technological leadership in research and development, along with innovative accessibility initiatives, we deliver high-value medicines that alleviate the greatest disease burdens on society. In our pursuit of new drugs, we continuously innovate, maintaining a leading position in global R&D investment within the industry. Novartis employs approximately 106,000 people from over 140 countries and regions worldwide, and nearly 800 million patients globally benefit from Novartis products.
On November 18, 2024, Johnson & Johnson announced positive topline results from the pivotal Phase 3 ICONIC study of Icotrokinra (JNJ-2113, formerly known as PN-235). The potential "first-in-class" IL-23 receptor (IL-23R) targeted antagonist peptide icotrokinra (JNJ-2113) met both primary endpoints of the trial, significantly improving symptoms in adult and adolescent patients aged 12 years and older with moderate to severe plaque psoriasis (PsO). Icotrokinra is the first investigational targeted oral peptide designed to block IL-23R.
About Johnson & Johnson
Johnson & Johnson was founded in 1886 and is one of the most comprehensive healthcare enterprises globally, with a broad range of operations spanning three major areas: medical devices, pharmaceuticals, and consumer goods. Headquartered in New Brunswick, New Jersey, USA, the company owns more than 260 operating companies across 60 countries and regions worldwide, with over 130,000 employees globally. In 2020, its global revenue reached $82.6 billion, with global R&D investment amounting to $12.2 billion.
November 202418Arrowhead Pharmaceuticals ("Arrowhead") announced that the company has submitted a new drug application to the U.S. Food and Drug Administration (FDA) for plozasiran, a small interfering RNA (siRNA) drug intended for the treatment of familial chylomicronemia syndrome (FCS).
Familial Chylomicronemia Syndrome (FCS) is a severe and rare disease, typically caused by various monogenic mutations. FCS leads to extremely high triglyceride (TG) levels, usually exceeding 880 mg/dL. This severe elevation can result in various serious symptoms and signs, including acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues. Currently, there are no sufficient treatment options available in the United States to adequately manage FCS.
Plozasiran (ARO-APOC3) is a first-in-class RNAi therapy designed to reduce the production of apolipoprotein C-III (APOC3), a component of triglyceride-rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 increases triglyceride levels in the blood by inhibiting the lipoprotein lipase breakdown of TRLs and the hepatic receptor uptake of TRL remnants. The goal of plozasiran treatment is to lower APOC3 levels, therebyReduce triglycerides and restore lipids to a more normal level.
About
Arrowhead Pharmaceuticals Develops Drugs to Treat Refractory Diseases by Inhibiting Pathogenic Genes. Arrowhead's therapies leverage a broad combination of RNA chemistries and efficient delivery modalities to trigger the RNA interference (RNAi) mechanism, inducing rapid, deep, and long-lasting knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that suppresses the expression of specific genes, thereby affecting the production of specific proteins. Arrowhead Pharmaceuticals' RNAi-based therapies harness this natural pathway of gene silencing.
November 202419th，Huadong Medicine Co., Ltd. (Stock Code: 000963.SZ, hereinafter referred to as "Huadong Medicine") released two announcements on the progress of innovative drug research and development.
The clinical trial application for HDM1005 injection (a long-acting agonist targeting GLP-1/GIP) submitted by Sinomed, a wholly-owned subsidiary of Zhongmei Huadong, has been approved by the FDA, allowing Phase I clinical trials to be conducted in the United States for the indication of metabolic-associated steatohepatitis (MASH).
The clinical trial application for DR10624 injection (a long-acting agonist targeting FGF21R/GLP-1R/GCGR) submitted by the holding subsidiary Daor Biologics has been approved by the National Medical Products Administration (NMPA) to conduct clinical trials for metabolic associated fatty liver disease (MAFLD) / metabolic associated steatohepatitis (MASH) indications.
On November 19, 2024, Innorna, a clinical-stage biopharmaceutical company focused on the development of Lipid Nanoparticle (LNP) delivery technology and innovative RNA therapies, announced that its investigational mRNA drug IN015 has been granted Orphan Drug Designation (ODD) by the U.S. FDA, following the Rare Pediatric Disease Designation (RPDD) received on November 1, 2024.
IN015 for the Treatment of Progressive Familial Intrahepatic Cholestasis (PFIC), a Life-Threatening Genetic Disorder. The simultaneous granting of RPDD and ODD will significantly accelerate the clinical development and market approval process of IN015, benefiting patients sooner. In July 2024, another mRNA drug targeting PFIC, IN016, developed by Shenzhen Biotech, also received RPDD and ODD. IN015 and IN016 target different functional proteins, aiming to achieve more comprehensive therapeutic effects for PFIC. IN015 is the third mRNA therapy product from Shenzhen Biotech to receive orphan drug designation, highlighting the urgent need for new and effective treatment options for PFIC patients.Sex and Importance.
About DeepTrust Bio
DeepTrust Bio was founded in 2019 and is committed to developing a world-leading LNP delivery technology platform and innovative RNA therapies to address unmet clinical needs. DeepTrust Bio has established a Diversity-Oriented LNP Library (DOLL) containing more than 5,000 ionizable lipids, which can be applied to the development of various innovative therapies, including mRNA vaccines and drugs, in vivo gene editing therapies, and cell therapies.
November 202419thRactigen Therapeutics announced that its self-developed FUS gene-targeting small interfering RNA (siRNA) therapy, RAG-21, has successfully received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for the treatment of Amyotrophic Lateral Sclerosis (ALS).
RAG-21 is a siRNA therapy specifically targeting FUS gene mutations, effectively reducing the level of FUS protein and addressing the root cause of motor neuron degeneration. The drug functions through the RNA interference (RNAi) mechanism, alleviating the mislocalization and abnormal aggregation of FUS protein by lowering its levels. Preclinical studies have shown that RAG-21 exhibits significant knockdown effects and favorable safety. As a novel RNA therapy, RAG-21 brings new hope for improved prognosis to FUS-ALS patients who currently lack disease-modifying treatments. This marks an important milestone in our ALS research.The second FDA orphan drug designation, following the previous designation of RAG-17 for SOD1-ALS, demonstrates our firm commitment to conquering ALS.
About Rona Therapeutics
Ractigen Therapeutics is a platform-based new drug research and development company rooted in China and targeting the global market, committed to developing breakthrough small nucleic acid drugs and disease treatment methods.
November 2024Day 21Four Rings Pharmaceutical announced that its non-wholly owned subsidiary Huisheng Bio has reached an exclusive licensing agreement with its non-wholly owned subsidiary Meiyán Space for the development of a semaglutide biosimilar targeting overweight or obesity indications.
About Huisheng Bio
In May 2019, HuiSheng Biopharmaceuticals Co., Ltd. was established under the strategic transformation of Four Rings Medicine, focusing on the treatment of diabetes and its complications. It is committed to providing comprehensive and full-process treatment solutions for patients and is a biopharmaceutical company with a complete product pipeline for diabetes and its complications.
November 2024Day 21，The Drug Clinical Trial Registration and Information Disclosure Platform shows that Vantia Therapeutics has initiated the first Phase III clinical trial of the small molecule GLP-1 receptor (GLP-1R) agonist VCT220. This drug is the second domestically produced small molecule GLP-1R agonist to enter the Phase III stage.
This study is a 52-week multicenter, randomized, double-blind, placebo-controlled clinical trial planning to enroll overweight or obese subjects aged 18-75 with a BMI ≥ 28 kg/m² or 24 kg/m² ≤ BMI < 28 kg/m² and at least one additional condition (prediabetes, hypertension, dyslipidemia, fatty liver, weight-bearing joint pain, obesity-induced dyspnea, obstructive sleep apnea syndrome) to evaluate the efficacy and safety of VCT220 tablets (20 mg or 40 mg, once daily) in this population. The primary endpoint is the change in body weight from baseline at week 34.≥5% of the proportion of subjects.
AboutWen Tai Pharmaceuticals
Wen Tai Pharmaceuticals is an innovative pharmaceutical company co-founded by several Ph.D.s from the Chinese Academy of Sciences. The core team has years of in-depth experience in related fields and a wealth of entrepreneurial expertise. It has out-licensed or transferred multiple new drugs for liver diseases and NASH, and possesses experience in leading and advancing new drugs from research and development through clinical trials to market.
November 2024Day 21Guangdong Zhongsheng Pharmaceutical Co., Ltd.'s controlling subsidiary, Guangdong Zhongsheng Ruichuang Biotechnology Co., Ltd. (hereinafter referred to as "Zhongsheng Ruichuang"), has independently developed RAY1225 Injection, an innovative peptide drug for overweight/obese patients. The Phase II clinical trial recently obtained the topline analysis data of a sub-study. Preliminary results indicate that RAY1225 Injection demonstrated positive efficacy and good safety in Chinese adult participants who are overweight or obese. The trial results were ideal and met the expected objectives.
RAY1225 Injection is a product independently developed by Rona Therapeutics, with global intellectual property rights.Innovative structured peptide drugs, belonging to long-acting GLP-1 class drugs, possess dual agonist activity for both GLP-1 receptors and GIP receptors.
AboutZhongsheng Pharmaceutical
November 2024Day 23，Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of ChinaThe official website shows that the marketing application of Leaderna's Inogruotide has been accepted.
This study is a multicenter, randomized, placebo-controlled Phase II clinical trial conducted in China, with participation from over 20 hospitals qualified for diabetes clinical research. The study enrolled 145 adult Chinese patients with type 2 diabetes whose condition had not been effectively controlled despite at least 3 months of lifestyle modifications or oral hypoglycemic treatment. These patients were divided into four cohorts, each receiving a once-weekly subcutaneous injection at a dose of0.4mg, 0.8mg, 1.2mg Ecnoglutide Injection (Ecnoglutide, XW003) and placebo treatment for 20 weeks. The primary endpoint of the study was the change in HbA1c from baseline at week 20.
AboutLeaderna
Xianweida Bio is a clinical-stage biopharmaceutical company focused on researching and developing innovative therapies for metabolic diseases. Its R&D pipeline includes first-in-class and best-in-class drug candidates, such as the long-acting GLP-1 peptide injectable Ecnoglutide, oral GLP-1 peptide Ecnoglutide, and the oral small-molecule GLP-1 receptor agonist XW014.
November 202422Recently, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration showed that the marketing application for a new indication of Eli Lilly's tirzepatide injection, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has been accepted.
In May 2022, Tirzepatide was first approved by the FDA for marketing to treat type 2 diabetes. In May this year, Tirzepatide was approved for marketing in China for the first time to be used in adult patients with type 2 diabetes (T2DM) whose blood glucose levels are not well controlled by metformin and/or sulfonylurea drugs despite dietary control and exercise. In July this year, Tirzepatide received approval in China for a new indication: long-term weight management in adults with a body mass index (BMI) meeting the following criteria, based on dietary control and increased physical activity: BMI ≥28 kg/m² (obesity), or BMI ≥24 kg/m² (overweight) accompanied by at least one weight-related comorbidity (e.g., hypertension, dyslipidemia, highBlood glucose, obstructive sleep apnea, cardiovascular diseases, etc.).
About Eli Lilly and Company
Eli Lilly and Company is a globally leading pharmaceutical company engaged in the research, development, production, and sales of medicines, dedicated to improving human health through innovation. Founded by Colonel Eli Lilly in 1876 in Indiana, USA, the company has grown over more than a century with its founder committed to producing high-quality medicines to meet genuine medical needs.
November 26, 2024
The transaction is expected to be completed in early 2025. Upon completion of the transaction, Arrowhead will receive
About
November 202426Day,Amgen announced positive results from the Phase II clinical trial of its GLP-1R agonist/GIPR antagonist MariTide (maridebart cafraglutide, AMG 133) for the treatment of obesity and type 2 diabetes. For obese or overweight patients without type 2 diabetes, treatment with MariTide at week 52 resulted in an average weight loss of 20%.
MariTide is a GLP-1R agonist/GIPR antagonist. Compared with semaglutide and tirzepatide, MariTide has a lower administration frequency and can be administered monthly or even longer.Administered once at intervals. As an antibody-peptide conjugate drug with a long half-life and dual mechanism of action, MariTide can reduce the likelihood of weight regain after discontinuation. Preclinical studies have shown that simultaneously activating GLP-1R and inhibiting the GIP pathway leads to better weight loss effects compared to targeting GLP-1R or GIPR alone.
About Amgen
Amgen is committed to benefiting patients worldwide who suffer from serious diseases by unlocking the potential of biology. To achieve this vision, Amgen has long focused on the exploration, research and development, production, and sales of innovative human medicines. By leveraging cutting-edge tools such as human genetics, Amgen strives to uncover the complexity of diseases and gain insights into the fundamental mechanisms of human biology.
Recently, Otsuka announced a collaboration with Ionis Pharmaceuticals to obtain the global exclusive rights to the latter's investigational antisense oligonucleotide (ASO) drug ulefnersen (development code: ION363). This product is being developed for the treatment of amyotrophic lateral sclerosis caused by mutations in the fused in sarcoma (FUS) gene.Patients with amyotrophic lateral sclerosis (ALS, commonly known as "Lou Gehrig's disease").
Under the terms of the agreement, Otsuka will pay Ionis a $10 million upfront payment, along with milestone payments based on the achievement of regulatory approvals and sales targets. Ionis is also eligible to receive royalties from product sales. Otsuka will...Approval from regulatory authorities is required, and the company will exclusively handle the global production and sales of the product.
About Ulefnersen
Ulefnersen (ION363) is an antisense oligonucleotide (ASO) developed by Ionis that targets the sixth intron of the fus sarcoma fusion protein (FUS) transcript, silencing FUS in a non-allele-specific manner. It is currently in Phase 3 clinical trials. Ulefnersen aims to reduce the production of fus sarcoma fusion protein to treat ALS patients caused by FUS gene mutations. Ulefnersen can lower postnatal levels of FUS protein in the brains and spinal cords of ALS-FUS disease-related mouse models, thereby delaying motor neuron degeneration.
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.
Recently,The official website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) shows that the Investigational New Drug (IND) application for MWN105 Injection, a Class 1 new drug developed by Minwei Biotech, has received tacit approval. The indications are Type 2 diabetes and overweight or obesity. According to publicly available information, this drug is a GIP/GLP-1/FGF21 tri-target fusion protein.
The function of GLP-1 is to stimulate insulin secretion and inhibit glucagon secretion; GIP is a bifunctional hormone, promoting insulin secretion during hyperglycemia and stimulating glucagon release during hypoglycemia to stabilize blood glucose; the metabolic activities of FGF21 include stimulatingGlucose uptake, blocking the obesity development in transgenic animals, and inhibiting hyperglycemia and hyperlipidemia.
About Minwe Bio
Shanghai Minwei Biotechnology Co., Ltd. was founded in 2021 and is located in the Zhoupu Medical Park of Pudong New Area, Shanghai, an area densely populated with innovative biopharmaceutical and medical device R&D companies. The company focuses on cutting-edge "multi-core macromolecule biopharmaceuticals" innovation and platform development, aiming to create globally competitive novel drugs.