dystrophin x UTRN

NANTONG and SUZHOU, China, Aug. 22, 2024 /PRNewswire/ -- Ractigen Therapeutics, a pioneering developer of small activating RNA (saRNA) therapeutics, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to RAG-18, one of the company's lead saRNA product candidates. This designation follows the recent Rare Pediatric Disease Designation (RPDD) granted to RAG-18 last month, further solidifying the potential of this novel therapeutic strategy for Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) caused by any mutation of the DMD gene. These milestones establish RAG-18 as the world's first saRNA drug to achieve such significant regulatory recognition from the FDA. Orphan drug designation is granted by the FDA to a drug or biologic intended to treat a rare disease or condition, which generally includes a disease or condition that affects fewer than 200,000 individuals in the U.S. The designation provides companies with development incentives, including a seven-year marketing exclusivity from the date of market approval and a waiver of the New Drug Application fee. Dr. Long-Cheng Li, Founder and CEO of Ractigen Therapeutics, stated: "Receiving FDA Orphan Drug Designation marks a pivotal achievement for RAG-18. Combined with the recent Rare Pediatric Disease Designation, it reflects the groundbreaking work we're doing with RNA activation and reinforces our commitment to making a real difference in the lives of those affected by rare diseases. This recognition fuels our determination to push forward with RAG-18's development, aiming to bring innovative and life-changing treatments to DMD and BMD patients around the world." About RAG-18 RAG-18 is a first of its kind saRNA candidate designed to specifically target and activate UTRN gene expression in muscle cells via RNAa mechanism. The utrophin protein encoded by the UTRN gene is structurally and functionally similar to dystrophin, and its upregulation could potentially serve as a functional replacement for the missing dystrophin in DMD muscle cells, providing treatment for all DMD patients regardless of the specific mutation location. Preclinical data indicate that RAG-18, delivered through subcutaneous injection utilizing Ractigen's proprietary LiCOTM (lipid-conjugated oligonucleotide) technology, has effectively mitigated muscle damage, demonstrating significant potential in treating DMD patients. RAG-18 has recently received Rare Pediatric Disease Designation (RPDD) from the U.S. FDA in July this year. About DMD and BMD Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) are severe genetic disorders caused by mutations in the dystrophin gene, leading to the absence or insufficiency of functional dystrophin protein. This protein is essential for muscle fiber stability. Without it, muscle cells are easily damaged and cannot repair themselves, resulting in progressive muscle weakness and degeneration. The dystrophin gene, the largest in the human body, contains 79 exons. Current disease-modifying therapeutic approaches for DMD include antisense oligonucleotides (ASO) mediated exon skipping, gene therapy, and gene editing, with exon skipping being the most common strategy. However, these treatments have significant limitations, highlighting the critical need for innovative therapies that target the root cause of DMD to provide more effective and long-lasting benefits for patients. About RNAa RNAa is a clinically validated platform technology developed by Dr. Long-Cheng Li and his team. It utilizes saRNAs to target gene regulatory domains, activating gene expression and restoring therapeutic protein levels. This innovative technology holds vast potential for developing therapeutic drugs across various diseases, particularly where traditional methods fall short, including genetic disorders. About Ractigen Therapeutics A leader in saRNA drug development, Ractigen Therapeutics is at the forefront of developing saRNA drugs utilizing the RNAa mechanism to up-regulate endogenous gene expression. This innovative approach involves saRNA targeting specific genes to enhance transcription, thereby restoring normal protein functions. Ractigen's cutting-edge technology is pivotal in treating diseases unaddressable by conventional methods, such as those resulting from epigenetic silencing or gene downregulation. For more information, please visit our website at . Contact Information: Ractigen Therapeutics Email: [email protected] SOURCE Ractigen Therapeutics

JIANGSU, China, Nov. 02, 2023 (GLOBE NEWSWIRE) -- Ractigen Therapeutics, a clinical stage biopharmaceutical company founded by the pioneers in RNA activation (RNAa), presented recent preclinical results at the annual meeting of the Oligonucleotide Therapeutics Society (OTS) in Barcelona, Spain. RNAa uses short duplex RNA known as saRNA to target and ‘turn up’ transcription of endogenous genes leading to restoration of their protein function. saRNA offers the ability to modulate traditionally undruggable targets and represents one of the few available technologies that can be translated into clinic to treat diseases by stimulating the expression of therapeutic genes with insufficient expression. Key Data Highlights from OTS The poster titled "Therapeutic development of saRNA for Duchenne muscular dystrophy by targeted activation of utrophin" illustrated a novel and translatable therapeutic strategy for DMD and BMD caused by any mutation of the DMD gene. In this study, candidate saRNAs were designed to target the promoter of human UTRN gene to activate its expression. Potent lead saRNAs were identified in human skeletal muscle derived cell lines and validated in transgenic mice bearing the human UTRN promoter. In a proof-of-concept efficacy study in MDX mice bearing the human UTRN promotor, systemic administration of a lead saRNA conjugated to Ractigen’s proprietary LiCOTM delivery system ameliorated muscle damage. The study also highlighted their LiCOTM technology which enables duplex RNAs (e.g., saRNA and siRNA) delivery to, and exerts durable activities in, the skeletal muscles and heart. "We are very excited about the preclinical results of our utrophin activating saRNA and believe that our approach could represent an ideal therapeutic strategy that benefits all DMD and BMD patients," said Long-Cheng Li, CEO of Ractigen Therapeutics. "We are fast-tracking this program and aim to initiating phase I trial in early 2025" At the same OTS meeting, Ractigen presented a second poster titled, "SCAD: a platform technology for CNS delivery of duplex RNA by intrathecal administration," which reports the development and validation of its proprietary duplex RNA delivery platform SCADTM (smart chemistry aided delivery) in rodents and nonhuman primates. SCADTM enables the delivery of saRNA and siRNA to the CNS via local injection (e.g., intrathecal) with broad biodistribution and potent and durable activity. The SCADTM platform has propelled Ractigen’s leading RNA program to the clinic for the treatment of ALS patients with SOD1 mutation. About RAG-18 RAG-18 is a therapeutic saRNA designed to upregulate the expression of utrophin to compensate the function of dystrophin and treat Duchenne muscular dystrophy (DMD) and Becker muscular dystrophin (BMD) regardless of the location of DMD mutation. RAG-18 utilizes Ractigen’s proprietary Lipid-conjugated oligonucleotide (LiCOTM) delivery platform, which enables durable and potent activity in the skeletal muscle and heart via systemic administration. Data from preclinical studies indicate RAG-18 could be delivered to the skeletal muscles and heart to activate the expression of endogenous utrophin gene and ameliorated muscle damage caused by the mutation of mouse DMD gene. About SCADTM SCADTM (smart chemistry-aided delivery) is Ractigen’s proprietary breakthrough platform technology for delivering dsRNA to the central nervous system (CNS) by conjugating a non-targeting single-stranded accessory oligonucleotide (ACO) to a duplex with “self-delivering” properties. SCADTM has broad distribution, and durable and potent activity in different parts of the CNS by intrathecal injection. The efficacy and safety of SCADTM delivery system is being validated in the clinic. About Ractigen Ractigen Therapeutics, founded in 2017 by pioneers of the RNA activation (RNAa) technology, is a clinical pharmaceutical company devoted to creating groundbreaking therapies based on oligonucleotide technologies including RNAa and RNAi. Supporting therapeutic development, Ractigen Therapeutics has also created a portfolio of delivery platforms including its SCADTM and LiCOTM system, which allows efficient delivery of therapeutic oligonucleotides to hard-to-reach extrahepatic tissues and empowers pipeline development across several disease areas. The Company has completed +$50M Series A/A+ venture financing rounds with participation from reputed investors including Hillhouse Venture Capital, SDIC Venture Capital, Eisai Co., LC Ventures, CSSD Capital, Xianghe Capital, CCB Healthcare Growth Fund, Boyi Capital, and Longmen Capital. For more information on Ractigen, please visit . For more information, please contact: Ractigen Therapeutics Email: pr@ractigen.com

LEXINGTON, Mass., Oct. 04, 2023 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. (“Keros”) (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta (“TGF-ß”) family of proteins, today announced results from preclinical studies evaluating the treatment effect of a research form of KER-065 (“RKER-065”) in a mouse model of Duchenne muscular dystrophy (“DMD”) and in prednisolone-treated mice, which were presented at the 28th International Annual Congress of the World Muscle Society (“WMS”) on Wednesday, October 4, 2023. “We are pleased to present promising preclinical data from our KER-065 program at WMS this year, showing that treatment with RKER-065 led to a robust increase in muscle mass, muscle function and bone mass in a mouse model of DMD and in prednisolone-treated mice,” said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer of Keros. “We believe these data support the potential of KER-065 to treat multiple pathophysiologies of DMD and other neuromuscular diseases, and we look forward to commencing a Phase 1 clinical trial of KER-065 in healthy volunteers in the first quarter of 2024.” RKER-065 treatment led to a robust increase in muscle mass, functional strength, and bone formation in a DMD mouse model RKER-065 ameliorated muscle and bone loss in a progressive murine model of Duchenne muscular dystrophy Keros studied the effect of RKER-065 in a progressive and phenotypically severe DMD mouse model. DMD mice were dosed with vehicle or 10 mg/kg of RKER-065 once weekly for four or six weeks. A cohort of healthy mice received only vehicle. In DMD mice, treatment with RKER-065 led to significant increases in body weight and lean mass by four weeks compared to vehicle-treated DMD mice. Additionally, an increase in forelimb grip strength was observed, which is supportive of improved muscle function. DMD mice treated with RKER-065 demonstrated significant increases in muscle mass in the pectoralis and tibialis anterior (“TA”) as compared to vehicle-treated DMD mice. In addition, expression of utrophin, a functional analog of dystrophin, was higher in the TA of DMD mice treated with RKER-065 compared to vehicle-treated DMD mice. Concomitant with neuromuscular decline, vehicle-treated DMD mice had significant decreases in bone mineral density (“BMD”), while DMD mice treated with RKER-065 showed no significant difference compared to healthy adult mice. RKER-065 treatment led to a significant increase in trabecular bone volume fraction by six weeks as compared to vehicle-treated DMD mice and a significant increase in trabecular thickness as compared to healthy mice. The RKER-065-treated DMD mice also had a significant decrease in trabecular spacing and a significant increase in trabecular number compared to both healthy mice and vehicle-treated DMD mice. Overall, treatment with RKER-065 led to a robust increase in muscle mass, functional strength and bone formation in the DMD mouse model. These studies suggest that KER-065 has the potential to benefit DMD patients who suffer from severe muscle loss and impaired muscle function and are at higher risk of fractures. RKER-065 increased muscle mass, improved muscle function and prevented bone loss in prednisolone-treated mice RKER-065, a novel ActRII ligand trap, counteracted the negative impact of glucocorticoid treatment on bone and muscle in mice In order to evaluate if RKER-065 can prevent the negative effect of glucocorticoids, the standard of care for DMD, on bone and muscle mass function, Keros treated healthy mice, divided into two groups matched by body weight, with 5.0 mg/kg prednisolone daily (“Pred”) and 10.0 mg/kg of RKER-065 weekly (“Pred-RKER-065”) or Pred daily and vehicle weekly (“Pred-vehicle”) for 9 weeks. A cohort of vehicle-treated mice were fed daily with cherry syrup. The Pred-vehicle mice exhibited reduced weight gain relative to vehicle – which is consistent with the use of glucocorticoid treatment – while weight gain was maintained in Pred-RKER-065-treated mice. The Pred-vehicle mice also exhibited reduced lean mass gain relative to vehicle, while Pred-RKER-065-treated mice had a robust increase in lean mass compared to Pred-vehicle mice. The observed increase in lean mass in the Pred-RKER-065 mice was associated with an increase in forelimb grip strength compared to Pred-vehicle and vehicle, which was apparent by day 34. At day 32, both right femoral and whole-body BMD in the Pred-vehicle mice were lower than vehicle. No difference in BMD reduction was observed between the Pred-RKER-065 and vehicle cohorts, suggesting that RKER-065 treatment prevented prednisolone-associated BMD reduction. A similar trend was observed at day 52. Additionally, Pred-RKER-065-treated mice showed increases in trabecular bone parameters relative to both vehicle and Pred-vehicle cohorts. These data demonstrate that RKER-065 can increase muscle mass, improve muscle function, and prevent bone loss in prednisolone-treated mice. These data further support that targeting activin and myostatin can potentially increase muscle and bone strength in muscular dystrophic patients under glucocorticoid therapy. About KER-065 KER-065, Keros’ fourth product candidate, is designed to bind to and inhibit select TGF-ß ligands, including myostatin and activin A, which are negative regulators of muscle and bone mass and strength. Through inhibition of these TGF-ß ligands, we believe that KER-065 has the potential to induce muscle and bone anabolic effects, increase fat metabolism and reduce fibrosis. KER-065 is being developed for the treatment of neuromuscular diseases, with an initial focus on DMD. About Keros Therapeutics, Inc. Keros is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the TGF-ß family of proteins. We are a leader in understanding the role of the TGF-ß family of proteins, which are master regulators of the growth, repair and maintenance of blood cells and a number of tissues, including bone, skeletal muscle, adipose and heart tissue. By leveraging this understanding, we have discovered and are developing large and small molecules that have the potential to provide meaningful and potentially disease-modifying benefit to patients. Keros’ lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes and in patients with myelofibrosis. Keros’ lead small molecule product candidate, KER-047, is being developed for the treatment of functional iron deficiency. Keros’ third product candidate, KER-012, is being developed for the treatment of pulmonary arterial hypertension and for the treatment of cardiovascular disorders. Keros’ fourth product candidate, KER-065, is being developed for the treatment of neuromuscular diseases, with an initial focus on DMD. Cautionary Note Regarding Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as “believe,” “can,” “look forward,” “potential” and/or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: Keros’ expectations regarding its growth, strategy, progress and the design, objectives and timing of its clinical trial for KER-065; and the potential of KER-065 to treat DMD and other neuromuscular diseases. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Keros’ limited operating history and historical losses; Keros’ ability to raise additional funding to complete the development and any commercialization of its product candidates; Keros’ dependence on the success of its product candidates, KER-050, KER-047, KER-012 and KER-065; that Keros may be delayed in initiating, enrolling or completing any clinical trials; competition from third parties that are developing products for similar uses; Keros’ ability to obtain, maintain and protect its intellectual property; and Keros’ dependence on third parties in connection with manufacturing, clinical trials and preclinical studies. These and other risks are described more fully in Keros’ filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q, filed with the SEC on August 7, 2023, and its other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Keros undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Investor Contact:Justin Frantzjfrantz@kerostx.com 617-221-6042