Encysive Pharmaceuticals, Inc.

心脏，是人体最重要的器官之一。一直以来，心脏的药物研发都充满了竞争，各大医药厂商都希望能抢先发现新一代突破性药物。心脏手术术后并发症，却是心脏药物研发的空白领域。2015年，Renibus Therapeutics（以下简称“Renibus”）成为率先踏足这一领域的药企。Renibus是一家总部位于美国德克萨斯的临床阶段新药研发企业，致力于为心肾疾病开发突破性药物。目前，Renibus已有四条药物管道，其首个项目RBT-1（SnPP / FeS）是Nrf2、IL-10和铁蛋白的有效诱导剂，处于心脏外科用于降低心胸外科手术并发症风险的2期实验阶段。近期，Renibus宣布完成3300万美元的过桥融资，其中包括2300万美元的SAFE（未来股权简单协议）发行和根据与Oxford Finance LLC（"Oxford"）签订的3000万美元定期贷款的第一部分1000万美元。   两个项目被收购，创业从未停止说起D.Jeff Keyser和Alvaro Guillem的缘分，已有20余年。1998年，二人先后来到德克萨斯加入Adams Respiratory Therapeutic，Keyser和Guillem同时担任副总裁制定并执行研发及监管战略，带领团队成功发明出Mucinex，这是一种感冒类OTC非处方药。在之后的几年里，二人与团队成功将Mucinex推向市场。2008年，巨头利洁时宣布以23亿美元的高价收购Adams Respiratory Therapeutic，同年，其推出的Mucinex在美国感冒药市场销售额排名第一。第一个项目被收购后，两人便打开了创业的大门。2008年，他们共同创办肾病药物生产公司ZS Pharma，开发出一种治疗高钾血症（HK）的药物ZS-9（sodium zirconium cyclosilicate，Lokelma）。高钾血症是慢性肾脏病（CKD）和心力衰竭（HF）患者中的一种常见疾病，影响24%至48%的中晚期CKD或HF患者。2015年，阿斯利康以27亿美元的溢价收购ZS Pharma，获得ZS-9的药物开发权。这款药物在三年后获得CE、FDA批准用于治疗高钾血症成人患者。2020年在中国获批，填补了高钾血症药物治疗领域长达60年的空白。也是2015，Keyser和Guillem继续出发，在美国德克萨斯创办心肾药物开发企业Renibus，Keyser担任总裁和首席运营官，Guillem担任CEO和董事长。短短几年间，Renibus已拥有四个候选药物管道，融资总额达7800万美元。除了一直在创业路上，Keyser和Guillem在其他领域的挑战也并未停止。目前，Keyser在Encysive Pharmaceuticals，Medeva Americas，Marion Merrell Dow和Abbott Laboratories均有任职。自2019年起，Keyser担任Lantern Pharma董事长，这是一家已上市的AI制药企业。Guillem，作为弗吉尼亚联邦大学的化学博士，在Genzyme/Bone Care，Wyeth， Boeringher Ingelheim和Medeva Americas均有任职。2022年年中，Guillem宣布不再担任Renibus的CEO和董事长，改由Frank Stonebanks接任。Frank Stonebanks拥有超过20年的从业经验，曾创办Triphase LP、Zosano Pharma两家公司，作为高级财务顾问、产品经理在赛诺菲等多家世界500强公司供职。目前，Frank还是Wavemaker 360 Health的健康特别顾问。RBT-1：30天再入院率减少90%，已进入FDA快速通道心脏外科手术包括心脏搭桥术、先天性心脏病手术、瓣膜置换术、冠状动脉旁路移植术等。心脏外科手术也是最常见的外科手术之一，据中国体外循环论坛消息，2021年我国心脏大血管手术量和体外循环手术量再创新高，分别达到了278056例和176496例，总量较2020年增长25%。心脏外科手术的高风险几乎成为人们的共识。其面临着患者ICU天数延长、呼吸机依赖及30天再入院率升高的风险，携带的手术并发症包括急性肾损伤、感染、心力衰竭、心脏术后出血等。作为外科领域较为年轻的学科，尽管历经多次技术升级，但心脏外科手术的术后并发症仍然严重威胁患者健康。而心脏外科术后ICU护理主要以支撑性为主，难以改善手术恢复状况，可能造成长期预后不良，使得住院时间增加，从而增加更多的医疗成本及费用。针对这种状况，Renibus开发出新型药物RBT-1。RBT-1是针对心脏外科手术术后并发症的首创药物，通过诱导参与器官损伤的抗氧化剂（Nrf2）、抗炎因子（IL-10）和铁代谢（铁蛋白、铁调素）水平起到减少术后并发症、降低30天再入院等风险的作用。RBT-1作用模型2022年11月，Renibus在美国心脏协会（AHA）2022科学会议上公布的2期临床试验结果。2期研究是一项随机、多中心安慰剂对照试验，目标是评估RBT-1对接受冠状动脉旁路移植术（CABG）或心脏瓣膜手术患者的影响。结果显示，RBT-1具有多器官预处理的潜力，有效降低呼吸机和ICU使用的天数，30天再入院率减少了90%以上（P＜0.0027）。目前，RBT-1已进入FDA快速通道指定，3期研究将于2023年初启动。RBT-3（FeS）是一种新型低分子量铁纳米颗粒，是RBT-1的组成部分之一，设定目标为降低顺铂诱导的肾毒性风险。RTB-3作用模型2021年Renibus在《science》上的一篇同行评议指出，RBT-3的临床前动物模型试验证明，其可能将顺铂诱导的肾毒性降低50%。顺铂是一种基于铂的化疗药物，在癌症治疗中可引起高达30%的人群肾毒性反应。RBT-3将于2023年投入临床开发。RBT-9（SnPP）是一种具有抗病毒特性的强效抗炎和抗氧化药物，也是RBT-1的组成部分之一。一项涉及42名患者的2期临床实验已将其作为住院患者的单药治疗进行了研究，使住院时间缩短约70%。心肾药物联合开发或成未来趋势除了针对心脏疾病的药物外，Renibus还开发了一种减缓慢性肾病（CKD）进展的药物RBT-2。RBT-2是一种抗氧化天然产物的活性代谢物，通过恢复细胞稳态和减少炎症及纤维化发展来减缓CKD进展。临床前研究表明，RBT-2还具有保护心脏的作用。目前，RBT-2正在进行IND申请，预计将在2023第三季度开启临床研究。 RBT-2作用模型近年来，心肾疾病的相关性引起了人们的广泛关注。美国心脏学会（AHA）2001年会上对心肾疾病相关性进行了总结，认为CKD是急性冠状动脉综合征患者发生心源性死亡、不良心血管事件的危险因素，与其他危险因素（如既往冠心病史、中风、心力衰竭、MI病史等）相比，CKD更具独立相关关系。2003年临床K/DXQI临床应用指南里也指出，所有CKD病人均应视为CVD的高危人群，对所有的CKD病人都应进行CVD危险因素评价，在防治或纠正各种危险因素时，均应考虑到CKD的存在。国内也有多篇论文指出，高血压性心肾的损害、冠心病与慢性肾脏病的相关性。中医也早已提出过肾脏疾病影响心脏病变发病机理。过去，心脑血管疾病常常作为统称被提及，也常有药企开发联合药物。如今，对心肾疾病相关性的探索也在不断推进中，心肾药物的联合开发或许成为未来药物的开发趋势之一。如果您想对接动脉网所报道的企业，请扫描小程序码进入VB100人脉圈查看。近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

RADNOR, Pa., Oct. 10 /PRNewswire/ -- The following statement was issued today by the law firm of Schiffrin & Barroway, LLP: Notice is hereby given that a class action lawsuit was filed in the United States District Court for the Southern District of Texas on behalf of all securities purchasers of Encysive Pharmaceuticals Inc. ("Encysive" or the "Company") from February 19, 2004 through March 24, 2006, inclusive (the "Class Period"). If you wish to discuss this action or have any questions concerning this notice or your rights or interests with respect to these matters, please contact Schiffrin & Barroway, LLP (Darren J. Check, Esq. or Richard A. Maniskas, Esq.) toll-free at 1-888-299-7706 or 1-610-667-7706, or via e-mail at info@sbclasslaw.com. The Complaint charges Encysive and certain of its officers and directors with violations of the Securities Exchange Act of 1934. More specifically, the Complaint alleges that the Company failed to disclose and misrepresented the following material adverse facts which were known to defendants or recklessly disregarded by them: (1) that stride tests involving Thelin failed to demonstrate a statistically significant advantage over Bosentan, another drug used to treat pulmonary arterial hypertension ("PAH"); (2) that, in order to portray Thelin's supposed superiority, defendants manipulated the stride tests to achieve statistically significant results; (3) that defendants' claims regarding the potential market for Thelin were based upon overinflated patient numbers; (4) that, as a result of the defendants' manipulations, United States Food and Drug Administration ("FDA") approval for Thelin would not be forthcoming because the FDA would require additional clinical trials before approving the drug; and (5) as a result of the above, the Company's statements concerning Thelin were lacking in any reasonable basis when made. On March 24, 2006, after the market closed, Encysive stunned investors when the Company announced that, contrary to its previous statements concerning the bright future of Thelin, the Company's new drug for the treatment of PAH, the approvable letter which it received from the FDA requested additional information concerning Thelin, including a request for additional clinical trial work. On this news, shares of Encysive plummeted $4.48, or 49.3 percent, to close, on March 27, 2006, at $4.60 per share, on unusually heavy trading volume. On July 24, 2006, after the market closed, Encysive announced that one issue raised in the FDA's March 2006 approvable letter concerning Thelin remained unresolved. On this news, shares of Encysive sank an additional $2.49, or 40.3 percent, to close, on July 25, 2006, at $3.69 per share, on unusually heavy trading volume. Plaintiff seeks to recover damages on behalf of class members and is represented by the law firm of Schiffrin & Barroway, which prosecutes class actions in both state and federal courts throughout the country. Schiffrin & Barroway is a driving force behind corporate governance reform, and has recovered billions of dollars on behalf of institutional and individual investors from the United States and around the world. For more information about Schiffrin & Barroway, or to sign up to participate in this action online, please visit . If you are a member of the class described above, you may, not later than November 27, 2006, move the Court to serve as lead plaintiff of the class, if you so choose. A lead plaintiff is a representative party that acts on behalf of other class members in directing the litigation. In order to be appointed lead plaintiff, the Court must determine that the class member's claim is typical of the claims of other class members, and that the class member will adequately represent the class. Under certain circumstances, one or more class members may together serve as "lead plaintiff." Your ability to share in any recovery is not, however, affected by the decision whether or not to serve as a lead plaintiff. You may retain Schiffrin & Barroway, or other counsel of your choice, to serve as your counsel in this action. CONTACT: Schiffrin & Barroway, LLP Darren J. Check, Esq. Richard A. Maniskas, Esq. 280 King of Prussia Road Radnor, PA 19087 1-888-299-7706 (toll-free) or 1-610-667-7706 Or by e-mail at info@sbclasslaw.com Schiffrin & Barroway, LLP CONTACT: Darren J. Check, Esq. or Richard A. Maniskas, Esq., both ofSchiffrin & Barroway, LLP, +1-888-299-7706, +1-610-667-7706, orinfo@sbclasslaw.com Web site:

US drugmaker Encysive says it has received a nod from European regulators to market its hypertension drug Thelin (sitaxentan sodium), pushing shares in the firm up more than 11% to $4.60 in after-hours trading on the Nasdaq. The news follows the thumbs up by an advisory panel last month, but the company is waiting for a formal letter from the European Commission before it will provide further details, it said in a statement. Encysive’s shares have been on a rollercoaster since March this year, when the US Food and Drug Administration unexpectedly issued its first approvable letter for Thelin instead of the anticipated all clear, a move which swiped around 50% off the group’s share price a the time. This was followed by a second request for further information in July, again pushing shares down as investor confidence in the drug waned further. But Encysive remains confident in the future of Thelin in the US, saying the matter raised by the FDA in its latest 'approvable' letter would not require any additional clinical trials, and that is a matter of judgment that does require negotiations with the agency to see if agreement can be reached. One group basking in Encysive’s misfortune is Actelion, maker of rival drug Tracleer (bosentan), its stock enjoying a nice boost on news of Thelin’s delay. Sales of Tracleer were $335 million in the first half of this year, but had been expected to come under pressure in the second half on competition from Thelin as well as Pfizer's Revatio (sildenafil) and Myogen's ambrisentan, also due for approval in the USA before the end of the year. Thelin has been tipped as a $200 million product at peak.