PDE9A

Cardurion also plans to use the funding to expand the indications outlined for the two candidates and acquire additional assets for treating cardiovascular disorders. Image Credit: VectorMine / Shutterstock. US-based cardiology biotech Cardurion Pharmaceuticals has raised $260m in Series B financing to advance its drug pipeline. The proceeds will fund the late-stage trials for two of the company’s lead candidates, CRD-750, a phosphodiesterase 9 (PDE9) inhibitor for heart failure; and CRD-4730, a calmodulin-dependent protein kinase II (CaMKII) inhibitor for treating catecholaminergic polymorphic ventricular tachycardia. Both therapies are being evaluated in Phase II trials. The company also plans to use the fund to expand the number of indications being explored for the two candidates and acquire additional assets for treating cardiovascular disorders. The investors in the Series B round included Bain Capital, Ascenta Capital, and other US-based investment companies. CRD-750 is being evaluated in two Phase II trials (NCT06215586 and NCT06215911) to treat two types of heart failure – heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Both placebo-controlled trials are currently recruiting patients across multiple locations in the US and Canada. In May, the company presented positive data for another PDE9 inhibitor, CRD-740, in patients with heart failure. The CARDINAL-HF Phase IIa trial (NCT05409183) met its primary endpoint in patients with HFrEF by demonstrating a statistically significant median increase in plasma cyclic guanosine monophosphate (cGMP). See Also: Sumitomo Pharma’s DSP-5336 gains FDA fast track for AML AstraZeneca completes Amolyt Pharma acquisition CRD-4730 is being evaluated in a Phase II trial (NCT06005428) as a treatment for catecholaminergic polymorphic ventricular tachycardia—a rare genetic arrhythmic disease. The company also plans to develop CaMKII inhibitors to target additional cardiovascular indications. There has been an increased interest in developing novel cardiovascular therapies in recent months. In February, Novo Nordisk agreed to pay up to $1.46bn to license multiple molecular glue degraders for treating cardiometabolic disorders and rare diseases from Neomorph. As part of the agreement, Neomorph would bear discovery and preclinical research responsibilities while Novo Nordisk would have exclusive rights to further clinical development and commercialisation. Another approach that has emerged as a promising treatment in the cardiovascular space is drugs targeting the glucagon-like peptide-1 (GLP-1) receptor. Last year, Novo Nordisk reported that its GLP-1 therapy Wegovy (semaglutide) reduced the incidence of cardiovascular events in obese and overweight patients by 20% compared to placebo.

2月20日，药捷安康宣布完成2.6亿元人民币D+轮融资。本轮融资由国鑫投资领投，三一创新投资、国联金投启源、南京江北国资、中银资本、百益德投资、瑞桐创投、敦行资本跟投。 药捷安康是一家处于临床阶段的生物制药公司，专注于发现和开发肿瘤、炎症及心血管疾病领域的小分子创新疗法，解决临床难治性疾病。目前，药捷安康共有7款在研产品处于不同的临床研发阶段。 其中，药捷安康的核心产品tinengotinib（TT-00420）是一款创新的激酶谱选择性抑制剂，通过靶向肿瘤细胞和改善肿瘤微环境发挥抗肿瘤作用，有望解决FGFR抑制剂耐药等多个临床问题。目前，该产品正在中国和美国开展多项2期临床研究，正在开发的适应症还包括三阴乳腺癌、胆道系统癌症、转移性去势抵抗性前列腺癌等。该产品还曾获得美国FDA授予针对胆管癌的孤儿药资格和快速通道资格。 根据药捷安康公开资料，该公司的在研产品还包括：1）TT-00973，一款新型AXL/FLT双靶点抑制剂；2）TT-01688，药捷安康从LG chem公司引进的一款全新的SIPI受体小分子调节剂；3）TT-01488，一款非共价可逆BTK抑制剂；4）TT-00434，一种新型的、高活性和高选择性FGFR1/2/3抑制剂；5）TT-00920，一款高选择性PDE9抑制剂；6）TT-01025，药捷安康从LG chem公司引进的一种新型的氨基脲敏感性胺氧化酶/血管黏附蛋白1（SSAO/VAP-1）抑制等等。这些产品正在开发的适应症包括多种实体瘤、血液系统恶性肿瘤、特应性皮炎、心力衰竭等。 药捷安康创始人、董事长吴永谦博士表示，本轮融资的顺利完成，标志着各方投资者对药捷安康创新理念和价值创造的认可。它们将继续加速公司国际化、商业化的进程，守正创新，打造有国际影响力的生物技术公司。 参考资料：[1]药捷安康宣布完成D+轮融资. Retrieved Feb 20 , 2023. From https://mp.weixin.qq.com/s/SxcTjsH0z0ouImgIKq9vbQ[2]药捷安康官网. From http://www.transtherabio.com/En/Index/index 内容来源于网络，如有侵权，请联系删除。

July 19, 2022 12:00 UTC CARDINAL-HF is the first Phase 2 proof-of-concept trial of a PDE9 inhibitor in heart failure Large-scale trial builds upon encouraging data generated in Cardurion’s Phase 1b trial CARDINAL-HF will examine the effects of CRD-740, Cardurion’s PDE9 inhibitor, in both types of heart failure and in key subsets of these patients BOSTON--(BUSINESS WIRE)-- Cardurion Pharmaceuticals, Inc. (“Cardurion” or “the Company”), a clinical-stage biotechnology company developing next-generation therapeutics for the treatment of cardiovascular diseases, today announced it has opened multiple sites and commenced dosing patients in a Phase 2 clinical trial of CRD-740, a phosphodiesterase-9 (“PDE9”) inhibitor for the treatment of heart failure. Initiated in May 2022, CARDINAL-HF is the first Phase 2 proof-of-concept trial of a PDE9 inhibitor in heart failure, and will assess the effects of CRD-740 on key subsets of these patients. Based on the mechanism of PDE9 action, inhibition by CRD-740 is expected to have benefit both alone and in combination with all standard of care heart failure treatments. CARDINAL-HF is a randomized, placebo-controlled trial that will enroll over 650 patients at more than 100 trial sites around the world. The trial will include chronic, stable patients with both reduced (HFrEF) and preserved ejection fraction heart failure (HFpEF). In addition, CRD-740 is being tested on a background of standard of care therapies to provide important information on the potential for benefit of CRD-740 when combined with guideline-directed treatments. The target of CRD-740 is PDE9, the enzyme that metabolizes cardiac cGMP generated by the natriuretic peptide receptor (NPR) pathway. Activation of this pathway is of proven clinical benefit in both forms of heart failure. PDE9 activity is increased in heart failure patients, which limits the beneficial effects of the NPR pathway. PDE9 inhibition with CRD-740 is a novel approach capable of maximizing NPR pathway activation and the beneficial effects of cGMP generated by this pathway, by blocking its breakdown by the PDE9 enzyme. “The launch of this large-scale trial is a significant milestone for Cardurion and for millions of patients who suffer from heart failure and are underserved by currently available therapies. We are gratified to have assembled a world-class group of cardiovascular experts to help oversee its execution,” said Peter Lawrence, Chief Executive Officer of Cardurion Pharmaceuticals. “We believe that CARDINAL-HF will rigorously test CRD-740 in both HFrEF and HFpEF, allowing us to assess the value of PDE9 inhibition in these patient populations, including important subgroups of patients who are on other heart failure medications. The data from this trial will be extensive and allow for robust decision-making for Phase 3.” The Executive Committee for the trial includes Dr. James Udelson, Principal Investigator and Chief of Cardiology at Tufts Medical Center; Dr. Scott Solomon, Professor of Medicine at Harvard Medical School; and Dr. John McMurray, Professor of Medical Cardiology and Deputy Director of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow. Drs. Udelson, Solomon and McMurray, along with Dr. Eugene Braunwald, the Distinguished Hersey Professor of Medicine at Harvard Medical School, also lead Cardurion’s Clinical Advisory Board. The CARDINAL-HF Steering Committee is further comprised of leading international heart failure trialists. “CARDINAL-HF has been carefully designed to evaluate how a broad range of heart failure patients will respond to this novel drug candidate, which has the potential to address significant unmet medical need when added to the current standard of care,” said Dr. Jim Udelson, Principal Investigator for the CARDINAL-HF trial. “The design will also provide a rich data set to inform the structure of a Phase 3 program and help evaluate a potential patient selection biomarker.” About Chronic Heart Failure Heart failure is a prevalent and growing condition that is responsible for substantial morbidity and mortality. Approximately 6.5 million people in the U.S. suffer from heart failure, and 50 percent of these patients die from the condition within five years of diagnosis. One in five patients are hospitalized annually, and 25% of hospitalized heart failure patients will be admitted again within a month of discharge. Approximately half of heart failure patients have reduced ejection fraction and half have preserved ejection fraction. Despite the availability of drugs indicated to reduce morbidity and mortality in both types of heart failure, substantial unmet medical need remains. About Cardurion Pharmaceuticals Cardurion Pharmaceuticals is a clinical-stage biotechnology company focused on the discovery and development of novel, next-generation therapeutics for the treatment of heart failure and other cardiovascular diseases. Founded by physician-scientist Michael E. Mendelsohn, M.D., and built by a team of physician-scientists and industry leaders with extensive experience in cardiovascular science, drug development and business development, Cardurion Pharmaceuticals is pursuing unique drug discovery and development programs to target major unmet needs in cardiovascular medicine. Cardurion Pharmaceuticals has facilities in Boston and Burlington, Massachusetts and Shonan, Japan. For more information, please visit the company’s website at .