ONO 1301 / Ono Pharma - LARVOL DELTA

Slow-Release Prostacyclin Agonist-Immersed Sheet Implantation Suppresses Liver Fibrosis via Hippo Signaling Pathway Activation. (PubMed, Hepatol Res) - "Implantation of ONO1301SR-immersed sheets suppresses liver fibrosis via Hippo signaling pathway activation, suggesting that slow-release prostacyclin agonist may have potential as a promising therapeutic option for liver fibrosis."

Journal • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Transplantation

ONO-1301 enhances post-transplantation survival of human induced pluripotent stem cell-derived cardiac tissue sheet by promoting angiogenesis. (PubMed, J Heart Lung Transplant) - "Slow-release ONO-1301 scaffold provided an efficient delivery method for thick hiPSC-CM tissue. ONO-1301 promotes angiogenesis between the host and graft and improves nutritional and oxygen supply, thereby enhancing the survival of transplanted cells, effectively improving ejection fraction, and therapeutic effects."

Journal • Post-transplantation • Cardiomyopathy • Cardiovascular • Fibrosis • Immunology • Myocardial Infarction • Transplantation

Enhanced myocardial blood flow in ischemic cardiomyopathy by a slow-release synthetic prostacyclin agonist combined with coronary artery bypass grafting: The first human study in a Phase I/IIa clinical trial. (PubMed, Front Cardiovasc Med) - "YS-1402, which is a polymerized form of the synthetic prostacyclin agonist ONO-1301, has been proven in several preclinical studies to induce therapeutic effects for patients with ischemic cardiomyopathy (ICM)...Significantly increased myocardial blood flow (MBF) and cardiac function were observed in the YS-1402 group 26 weeks postoperatively, although no improvement in MBF occurred in the placebo group. This Phase I/IIa parallel group-controlled, dose-escalation study of YS-1402 combined with CABG for ICM demonstrated the safety, tolerability, and potential efficacy of YS-1402."

Journal • P1/2 data • Cardiomyopathy • Cardiovascular

A novel prostaglandin I agonist, ONO-1301, attenuates liver inflammation and suppresses fibrosis in non-alcoholic steatohepatitis model mice. (PubMed, Inflamm Regen) - "The results of our study highlight the potential of ONO-1301 to reverse the progression and prevent the occurrence of liver tumors in NASH using in vivo and in vitro models. ONO-1301 is a multidirectional drug that can play a key role in various pathways and can be further analyzed for use as a new drug candidate against NASH."

Journal • Preclinical • Fibrosis • Gastrointestinal Cancer • Hepatology • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Liver Cancer • Myocardial Infarction • Non-alcoholic Steatohepatitis • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • Solid Tumor • HGF

Combined administration of laminin-221 and prostacyclin agonist enhances endogenous cardiac repair in an acute infarct rat heart. (PubMed, Sci Rep) - "Interstitial fibrosis reduced and functional recovery was prominent in LM221- and ONO1301-administrated hearts as compared with those in ONO1301-administrated or control hearts. LM221 and ONO1301 combination enhanced recruitment of PDGFRα and CD90 double-positive cells, maturation of vessels, and functional recovery in rat acute myocardial infarction hearts, highlighting a new promising acellular approach for the failed heart."

Journal • Preclinical • Cardiovascular • Fibrosis • Immunology • Myocardial Infarction • PDGFRA • THY1

Cardiac fibrosis models using human induced pluripotent stem cell-derived cardiac tissues allow anti-fibrotic drug screening in vitro. (PubMed, Stem Cell Res) - "A prostacyclin agonist, ONO-1301 (ONO), camostat mesilate (Cs), and pirfenidone (Pf) significantly decreased fibrotic ECM expression, and improved contraction/relaxation in the model stimulated with TGF-β. Consistent with the in vitro assay, the administration of ONO, Cs, or Pf for 8 weeks in J2N-k hamsters preserved the left ventricular ejection fraction and decreased cardiac fibrosis compared with the controls. The in vitro model simulating fibrotic cardiac tissue showed precise screening of anti-fibrotic drugs which indicated the expected therapeutic response in an in vivo heart failure model, suggesting that the in vitro model presented in this study is a useful tool for the screening of anti-fibrotic drugs."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • TGFB1

Growth factor mimetics for skin regeneration: In vitro profiling of primary human fibroblasts and keratinocytes. (PubMed, Arch Pharm (Weinheim)) - "A combined small molecule FGF-2/VEGF mimicry may not only improve angiogenesis-related microcirculation but also reduce early fibrosis while facilitating wound remodeling at later stages. SUN11602 and ONO-1301 represent valuable tools for improving the management of difficult-to-heal wounds, particularly for the design and development of small molecule-functionalized, next-generation, engineered skin substitutes."

Journal • Preclinical • Fibrosis • Immunology • FGF2 • MMP1

Innovative therapeutic strategy using prostaglandin I agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension. (PubMed, Sci Rep) - "However, a significant area of nanoparticles was detected in the lungs of PAH rats. ONONS effectively ameliorated PAH, with selective delivery to the damaged lung."

Journal • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases • HGF • IL1B • IL6 • PCNA

[VIRTUAL] Administration of Laminin511 Combined With Prostacyclin Agonist Enhances Endogenous Stem Cell Recruitment in Acute Myocardial Infarction Model Rat (AHA 2020) - "The combined administration of LM511 and ONO1301 promotes arteriogenesis by enhanced endogenous repair with declined infarct size and improved cardiac function in rat acute myocardial infarction model, proposing new therapeutic strategy for ischemic cardiomyopathy."

Cardiomyopathy • Cardiovascular • Myocardial Infarction • PDGFRA

[VIRTUAL] Angiogenic Agent Ono-1301 Enhanced Cardiac Contractile Proteins in Hipsc Derived Cardiac Tissue-like Construct With Functional Angiogenesis (AHA 2020) - "In vitro experiments have shown that supernatant of iPS-CM with ONO-1301 underwent a rise in VEGF during a 3 to 6 day culture (Figure B). The VEGF concentration in ONO-1301 positive group is much higer than ONO-1301 negative group (P=0.022) on day3. This difference narrows down over time."

Cardiovascular • Myocardial Infarction • Transplantation

Synthetic Prostacyclin Agonist Attenuates Pressure-Overloaded Cardiac Fibrosis by Inhibiting FMT. (PubMed, Mol Ther Methods Clin Dev) - "Results showed that ONO-1301 co-incubation significantly suppressed TGF-β-induced α-SMA expression and collagen synthesis, and significantly inhibited TGF-β-induced CF proliferation and migration. Our findings suggest that ONO-1301 ameliorates pressure overloaded cardiac fibrosis by inhibiting TGF-β-induced FMT."

Journal • Fibrosis • Immunology • CTGF • HGF • VIM

Single injection of sustained-release prostacyclin analog ONO-1301-MS ameliorates hypoxic toxicity in the murine model of amyotrophic lateral sclerosis. (PubMed, Sci Rep) - "At late disease stages, the motor function and the survival of motor neurons of ONO-1301-MS-treated mSOD1 mice was significantly improved compared to vehicle-treated mSOD1 mice. Our data suggest that vasodilator therapy modulating local blood flow in the spinal cord has beneficial effects against ALS disease progression."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders • Immunology • Inflammation

ONO-1301 loaded nanocomposite scaffolds modulate cAMP mediated signaling and induce new bone formation in critical sized bone defect. (PubMed, Biomater Sci) - "They also promoted new bone formation in large sized calvarial defects in rats compared to the scaffold alone, but did not show any impact on angiogenesis. Hence, this study suggests the chemotactic and osteoinductive capability of ONO-1301 for the repair and regeneration of critical sized bone defects."

Journal

Prostacyclin mimetics afford protection against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice. (PubMed, Toxicol Appl Pharmacol) - "We indicate that IP receptor activation with PGI2 mimetics can rescue the damage in the liver induced by LPS/GalN by undermining activation of STAT3 and leading to a lower production of ROS. Our findings point to PGI2 mimetics, especially ONO-1301, as a potential novel therapeutic modality for the treatment of acute liver injury."

Journal • Biosimilar

Bioinspired nanocomposite fibrous scaffold mediated delivery of ONO-1301 and BMP2 enhance bone regeneration in critical sized defect. (PubMed, Mater Sci Eng C Mater Biol Appl) - "It also augmented bone tissue regeneration in critical sized rat calvarial defect at 12 weeks; mainly with lower dose of ONO-1301. However, synergistic effect on osteogenic differentiation and bone regeneration were not obtained through the concurrent release of BMP-2 and ONO-1301."

Journal

Oral Administration of Synthetic Prostacyclin Agonist ONO-1301 Improves Survival Rate With Prevention in Deteriorated Pathophysiology of Dilated Cardiomyopathy Model Hamsters (AHA 2019) - "Oral administration of synthetic prostacyclin agonists improved survival rate with prevented histological and functional degeneration in the delta-sarcoglycan-deficient hamster, suggesting that this drug may inhibit the progression of the disease pathology in DCM."

A prostacyclin agonist and an omental flap increased myocardial blood flow in a porcine chronic ischemia model. (PubMed, J Thorac Cardiovasc Surg) - "ONO-1301SR combined with a pedicled omental flap synergistically promoted myocardial angiogenesis, leading to function recovery in a porcine chronic myocardial infarction model."

Journal • Preclinical

Prostacyclin Analogue-Loaded Nanoparticles Attenuate Myocardial Ischemia/Reperfusion Injury in Rats. (PubMed, JACC Basic Transl Sci) - "Consequently, ONO-1301NP-injected rats exhibited a smaller infarct size, better-preserved capillary networks, and a better-preserved myocardial blood flow at 24 h after I/R injury, compared with those in vehicle-injected or ONO-1301 solution-injected rats. ONO-1301NPs attenuate the myocardial I/R injury via proangiogenic and anti-inflammatory effects of the drug."

Journal • Preclinical