Empagliflozin

//  •GLP-1产品已经一只脚迈入口服时代；•使用GLP-1受体激动剂的患者在1年时有53.6%停药，2年时有72.2%停药；•小分子GLP-1受体激动剂的开发是非常具有挑战的药物化学项目；•礼来正在开展一项注射+口服的长期续贯治疗研究；•GLP-1口服赛道已经站了不少中国企业，并达成多起交易。有时候，即便是极其强调科学性的药物开发，也不得不感叹命运的翻云覆雨手。上周五（5月16日），诺和诺德宣布首席执行官周赋德（Lars Fruergaard Jørgensen）将离任的消息。援引FiercePharma的说法，更换CEO是因为“weight of market pressure”。而就在一个月前，礼来的口服小分子GLP-1产品orforglipron 3期临床试验ACHIEVE-1获得积极结果，像一把利剑刺中了诺和诺德要害。几乎同一时间，由于在安全性方面闯关失败，辉瑞宣布终止口服GLP-1受体激动剂danuglipron的临床开发。没有人知道辉瑞在这一时刻的扼腕，就像没人知道它再度重启临床试验时的决心。随着诺和诺德口服版减重司美格鲁肽Wegovy（25mg）4月21日美国上市申请获得受理，一个新故事的雏形正在展开：口服产品将如何搅动GLP-1的天下？小分子与多肽掰手腕实际上，GLP-1产品已经一只脚迈入口服时代。早在2019年，司美格鲁肽口服降糖版Rybelsus获FDA批准。2025年Q1，司美格鲁肽为诺和诺德打下了557.76亿丹麦克朗（约合78.64亿美元）的江山，成为今年第一季度的新药王。其中，降糖口服版Rybelsus卖出了56.95亿丹麦克朗（约8.03亿美元）。作为GLP-1的开山者，口服版司美格鲁肽利用SNAC吸收促进剂创新技术，越过了多肽类药物在生物利用度上的先天缺陷。那么，当礼来的orforglipron交出3期临床积极结果的时候，给诺和诺德带来的是危机，还是高手在山顶相逢的惺惺相惜？礼来公布的信息显示，在 ACHIEVE-1 研究中，orforglipron达到主要终点，即40周时，经orforglipron治疗后糖化血红蛋白（A1C）的降幅显著优于安慰剂组，A1C自8.0%的基线平均降低1.3%至1.6%（使用有效性估计目标）。同时，在关键次要终点，超过65%的患者接受最高剂量的orforglipron后A1C值降至≤6.5%，低于美国糖尿病协会定义的糖尿病阈值。在另一个关键次要终点，接受orforglipron的患者在最高剂量下平均减重7.3kg（7.9%），鉴于患者在研究结束时尚未达到体重平台期，可能表明尚未实现完全减重。诺和诺德为了证明司美格鲁肽口服剂与注射剂一样安全有效，开展了PIONEER系列3期临床试验。结果显示，在所有分组中，26周时，口服司美格鲁肽组比安慰剂组、恩格列净组或西格列汀组都显示了更大的糖化血红蛋白降低效果，与利拉鲁肽组大体持平。达到美国糖尿病协会推荐的降低糖化血红蛋白水平至7.0%（53 mmol/mol）的患者比例，口服司美格鲁肽组（7mg，42%~69%；14mg，55%~77%）高于安慰剂组（7%~31%）和其它对照药物组（25%~62%）。拓展阅读零的突破：口服司美格鲁肽的故事“一般情况下，大分子总是比不过小分子的，这就是为什么在大分子药物成功上市之后，总是会有人继续寻找小分子替代。但是反过来，从来没有人想用大分子去替代小分子。如果只看口服的生物利用度，小分子具有绝对优势。尽管这仍旧是药物化学中的一个难题，却是一个可以被攻克的难题。这是药物开发者的共识。”曾在默沙东参与糖尿病药物西格列汀研发的梁贵柏博士说。“而半衰期正好反过来。大分子药物有很多每周一次、每月一次，甚至每半年一次注射，诺和诺德的司美格鲁肽长达160个小时。小分子要做到每周一次很难。但是口服药物没有必要，每天一次是最理想的，患者依从性最好。”梁贵柏分享了他对于口服小分子和多肽类产品各自优劣的看法。安全性可能是小分子药物很难绕过的潜在风险。“小分子的毒副作用很难预见，绝大多数来源于分子本身。药物化学的解决方法是换一个化学结构不一样的先导去做优化。但是，小分子GLP-1受体激动剂很难找到好的lead。如果礼来的orforglipron 在药效与副作用方面没有明显的短板，这是一个可遇不可求的分子，其中也包括一部分运气。”orforglipron 最早由中外制药（Chugai Pharmaceutical）发现，2018年礼来以5000万美元获得这款产品的开发和商业化权益。据礼来公布的信息，orforglipron 的结构复杂，为保证药效，研发者设计开发的分子量为882.96，已接近小分子药物分子均量的上限（1000），从起始物料到制备orforglipron原料药共需要28步反应。这显然增加了抄作业的难度。回过头来看辉瑞的danuglipron，从一开始就不被业内看好，硬着头皮重启临床2期，结局可想而知。不知道它的追随者们在眼下这个十字路口将如何选择。当然，这也不是辉瑞第一次在口服GLP-1产品上折戟，前有lotiglipron因转氨酶升高的原因，于2023年停止开发。停药的情况明显今年1月，美国医学会旗下期刊JAMA Network Open刊登了一篇研究报告：一项针对125474名使用GLP-1受体激动剂患者的队列研究显示，在两年内，共有81919名患者停用了GLP-1受体激动剂。考虑到删失情况，1年时有53.6%的患者停药，2年时有72.2%的患者停药。其中，2型糖尿病患者的停药率更低（1年时为46.5%，2年时为64.1%）；而无2型糖尿病的患者在1年时停药率为 64.8%，2年时为84.4%。对此，哈佛医学院糖尿病、肥胖症与技术领域负责人Robert Gabbay博士在其社交媒体上表示，“尽管 GLP-1 类药物在减重方面效果显著，但这项研究发现，65%因肥胖而服用此类药物的患者在一年内就停止用药。目前没有很好的数据来解释这一现象。推测可能是多种因素共同作用的结果，包括成本和获取途径、副作用、无效（很多病例可能没有意识到往往需要数月才能显著减重）、用药的方便程度。”来源|JAMA Network OpenStructure Therapeutics CEO Raymond Stevens在近期的一次媒体采访中同样提到，“85%使用GLP-1患者在两年内停药，这是否暗示了口服产品将迎来全面超车？”信达生物高级副总裁钱镭博士在接受研发客采访时，提出了自己的观点。他认为，口服药和注射药物一直是“五五开”局面，有一部分人更倾向于注射类药物，一部分人选择口服。“小分子和注射类药物各自都有优缺点。前者成本低，服用方便，但很容易有脱靶风险，导致肝脏损伤。并且，容易与其他药物互相影响。注射产品成本高，而且注射治疗可能会影响顺应性。实际上，一周一次的注射治疗已经相当方便，而未来一个月一次的治疗药物顺应性会更好。当然，注射产品另一个优势是靶向精确，不容易脱靶，安全性和疗效目前来看都优于小分子。”钱镭表示。至少礼来并没有放慢注射类产品的推进速度。就在两天前，礼来公布了替尔泊肽与司美格鲁肽头对头研究（SURMOUNT-5研究）的详细结果。在第72周时，替尔泊肽达到主要终点和所有五个关键次要终点，再次叫板司美格鲁肽。拓展阅读礼来公布头对头详细结果 替尔泊肽全面优于司美格鲁肽“实际上，礼来正在开展一项研究，使用替尔泊肽把体重降下来之后，再以口服小分子药物长期续贯治疗，这也是一个非常合理的思路。”钱镭透露。在口服的路上狂奔距离辉瑞宣布danuglipron停止开发已经过去一个月。这一消息一度让Structure Therapeutics和Viking在二级市场收获了不小的涨幅。两家公司手中各自握有小分子口服GLP-1在研产品。Structure的创始人及CEO Raymond Stevens对自家的产品颇为自信。他认为，2025 年将是所有口服GLP-1小分子药物在肥胖及相关疾病治疗领域的变革之年。公司在 2024年财报中提到，小分子口服GLP-1产品aleniglipron 的ACCESS 和 ACCESSⅡ 两项研究已全部招募完毕，预计将于2025年底公布顶线数据。毫无疑问，这个跑道上已经站了不少中国企业，并达成了多起交易。其中，诚益生物的ECC5004授权给了阿斯利康，获得6000万美元首付款。这款产品应该走的是礼来orforglipron的技术路线。翰森制药的HS10535也在这条跑道上，已授权给默沙东，并获得了1.12亿美元预付款。箕星药业从闻泰医药引入了一款GLP-1小分子产品。先为达生物则在今年初与Verdiva Bio达成超24亿美元授权交易，这家公司的管线中也有一款小分子GLP-1产品。今年3月，恒瑞医药已正式启动其自主研发的口服GLP-1受体激动剂HRS-7535的3期临床研究，用于超重或肥胖人群减重适应症。华东医药的HDM1002（conveglipron），已完成体重管理适应症临床3期研究首例受试者入组。信达生物布局了口服小分子GLP-1、GIP抗体偶联GLP-1/GCG受体双激动剂、PCSK9偶联GIP/GCG/GLP-1三靶点激动剂。此外，锐格医药、德睿智药、海思科、信立泰、歌礼制药等公司的产品处在不同临床阶段。随着新选手的不断加入，会不会有更多的黑马胜出？“其实，小分子药物开发门槛低，大家都觉得自己有能力做，表面上看竞争会非常激烈。但真正有实力的并不多。小分子GLP-1受体激动剂的开发是非常具有挑战的药物化学项目，这跟GLP-1受体的结构和活化机理有关。成功的关键是一个成药性好的先导化合物。目前大家的方向是想办法绕过orforglipron的专利，争取差异化。减肥药物的市场足够大，应该可以容得下不少差异化的小分子药物。在这个过程中，AI可能会发挥它的价值，帮助大家找到更好的分子。”梁贵柏说。当然，辉瑞应该不会甘心放弃这个还在膨胀的市场，不知道它会在中国淘到哪块“金子”。编辑 | 姚嘉yao.jia@PharmaDJ.com 总第2439期访问研发客网站，深度报道和每日新闻抢鲜看www.PharmaDJ.com

Results from MUSIC-HFpEF Phase 1/2a clinical trial show favorable safety profile and early clinical benefits with SRD-002 gene therapy BOSTON, May 19, 2025 (GLOBE NEWSWIRE) -- Medera Inc. (“Medera”), a clinical-stage biopharmaceutical company focused on targeting cardiovascular diseases by developing a range of next-generation therapeutics, today announced that positive interim data from its ongoing MUSIC-HFpEF Phase 1/2a clinical trial was presented at the Heart Failure 2025 Congress taking place in Belgrade, Serbia. The late-breaking presentation, titled "Gene therapy for heart failure with preserved ejection fraction," was delivered by Marat Fudim, MD, MHS, Advanced Heart Failure Specialist and Associate Professor at Duke University Medical Center, during the "Late-Breaking Clinical Trials in Chronic Heart Failure" session. The MUSIC-HFpEF trial is investigating SRD-002, a one-time gene therapy treatment for heart failure with preserved ejection fraction (HFpEF) delivered through a proprietary minimally invasive intracoronary infusion methodology. SRD-002 utilizes an adeno-associated type 1 virus vector carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase pump (SERCA2a) to directly target the molecular pathways underlying the core pathology of HFpEF by enhancing myocardial relaxation and reducing stiffness. The trial is evaluating the therapy in HFpEF patients with exercise-induced diastolic dysfunction, including those with LVEF ≥ 50% and symptomatic HFpEF defined by prior hospitalization or New York Heart Association (NYHA) Class II or III symptoms. The presentation highlighted interim data from the ongoing trial, which, as of the data cutoff date, has treated five patients in Cohort A with a low dose of 3x1013 viral genomes (vg) per patient and one patient in Cohort B at a dose of 4.5x1013 vg per patient. With follow-up ranging from 4 to 16 months, no gene therapy-related serious adverse events have been reported. Four out of five patients in the low-dose group have shown improvements in NYHA heart failure classification at 6 months, with clinically meaningful improvements in 6-minute walk test (6MWT), decreases/stabilization in NT-Pro-BNP, and high-sensitivity troponin observed in some patients. The enrollment of patients at the higher dose of 4.5x1013 vg per patient is ongoing. “HFpEF represents a significant unmet medical need, affecting approximately half of all heart failure patients worldwide with limited disease-modifying therapeutic options,” said Marat Fudim, MD, MHS. “These early results are encouraging and suggest that SRD-002 may offer a potentially transformative approach for patients with HFpEF by directly addressing the underlying pathophysiology of impaired myocardial relaxation.” “With our therapeutic dosages optimized by our bioengineered human mini-heart HFpEF models – approximately 100-fold less than that of IV infusion – we are pleased with the safety profile and early clinical signals observed in the MUSIC-HFpEF trial to date,” said Ronald Li, Ph.D., CEO and co-founder of Medera. “This first-in-human gene therapy approach represents an important step forward in our mission to develop innovative therapies for cardiovascular diseases with limited treatment options.” The Heart Failure Congress is the world's leading event covering the entire spectrum of heart failure, from prevention to diagnosis and treatment. It is the annual meeting of the Heart Failure Association of the European Society of Cardiology. For additional information about the MUSIC-HFpEF trial, visit ClinicalTrials.gov using the study identifier NCT06061549. On September 5, 2024, Medera and Keen Vision Acquisition Corporation ("KVAC") (NASDAQ:KVAC, KVACW), announced they had entered into a definitive merger agreement. About Heart Failure with Preserved Ejection Fraction (HFpEF) Heart failure (HF) is a global pandemic with an estimated 64.3 million cases worldwide and a rising prevalence trend. Accounting for 50% or more of the overall HF population, HFpEF is an age-related condition that has become increasingly prevalent in recent years. This surge is partly due to better awareness and identification of the condition and partly due to lifestyle changes affecting cardiac myocytes. Individuals affected by HFpEF experience similar morbidity and mortality to patients with HF with reduced ejection fraction (HFrEF). Despite the growing epidemic of this emerging syndrome, HFpEF-focused interventional trials have had little success, except for the use of sacubitril-valsartan (Entresto™) and the sodium glucose transporter-2 (SGLT-2) inhibitor empagliflozin (Jardiance™) for reducing cardiovascular mortality and heart failure hospitalization. However, these agents are not disease-modifying, highlighting the critical need for therapeutic interventions targeting the physiological mechanisms involved in HFpEF. About Medera Medera is a clinical-stage biopharmaceutical company focused on targeting difficult-to-treat and currently incurable diseases by developing a range of next-generation therapeutics. Medera operates via its two preclinical and clinical business units, Novoheart and Sardocor, respectively. Novoheart capitalizes on the world’s first and award-winning “mini-Heart” Technology for revolutionary disease modelling and drug discovery, uniquely enabling the modelling of human-specific diseases and discovery of therapeutic candidates free from species-specific differences in accordance to the FDA Modernization Act 2.0. Novoheart's versatile technology platform provides a range of state-of-the-art automation hardware and software as well as screening services, for human-specific disease modelling, therapeutic target discovery and validation, drug toxicity and efficacy screening, and dosage optimization carried out in the context of healthy and/or diseased human heart chambers and tissues. Global pharmaceutical and academic leaders are using Novoheart's technology platform for their drug discovery and development purposes. The Novoheart platform has facilitated and accelerated the development of Sardocor's lead therapeutic candidates that are currently in clinical trials. Sardocor is dedicated to the clinical development of novel next-generation therapies for Medera. Leveraging Novoheart’s human-based drug discovery and validation platforms, Sardocor aims to expedite drug development and regulatory timelines for its gene and cell therapy pipeline. Sardocor has received Investigational New Drug (IND) clearances from the FDA for three ongoing AAV-based cardiac gene therapy clinical trials targeting Heart Failure with Reduced Ejection Fraction (HFrEF), Heart Failure with Preserved Ejection Fraction (HFpEF) with the Fast Track Designation, and Duchenne Muscular Dystrophy-associated Cardiomyopathy (DMD-CM) with the Orphan Drug Designation. Additionally, Sardocor's pipeline includes four preclinical gene therapy and three preclinical small molecule candidates targeting various cardiac, pulmonary, and vascular diseases. For more information, please visit www.medera.bio. About Keen Vision Acquisition Corporation Keen Vision Acquisition Corp ("KVAC"), listed on Nasdaq, is a blank check company incorporated for the purpose of effecting a merger, share exchange, asset acquisition, share purchase, reorganization or similar business combination with one or more businesses or entities. KVAC is focused on biotechnology, consumer goods or agriculture opportunities, which are also evaluated on their sustainability, environmental, social, and corporate governance ("ESG") imperatives. For more information, please visit www.kv-ac.com. Forward-Looking Statements Certain statements included in this press release are not historical facts but are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this press release are forward-looking statements. Any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are also forward-looking statements. In some cases, you can identify forward-looking statements by words such as "estimate," "plan," "project," "forecast," "intend," "expect," "anticipate," "believe," "seek," "strategy," "future," "opportunity," "may," "target," "should," "will," "would," "will be," "will continue," "will likely result," "preliminary," or similar expressions that predict or indicate future events or trends or that are not statements of historical matters, but the absence of these words does not mean that a statement is not forward-looking. Forward-looking statements include, without limitation, KVAC's, Medera's, or their respective management teams' expectations concerning the outlook for their or Medera's business, productivity, plans, and goals for future operational improvements and capital investments, operational performance, future market conditions, or economic performance and developments in the capital and credit markets and expected future financial performance, including expected net proceeds, expected additional funding, the percentage of redemptions of KVAC's public shareholders, growth prospects and outlook of Medera' operations, individually or in the aggregate, including the achievement of project milestones, commencement and completion of commercial operations of certain of Medera's projects, as well as any information concerning possible or assumed future results of operations of Medera. Forward-looking statements also include statements regarding the expected benefits of the transactions contemplated by the merger ("Transaction"). The forward-looking statements are based on the current expectations of the respective management teams of Medera and KVAC, as applicable, and are inherently subject to uncertainties and changes in circumstance and their potential effects. There can be no assurance that future developments will be those that have been anticipated. These forward-looking statements involve a number of risks, uncertainties or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to, (i) the risk that the Transaction may not be completed in a timely manner or at all, which may adversely affect the price of KVAC's securities; (ii) the risk that the Transaction may not be completed by KVAC's business combination deadline and the potential failure to obtain an extension of the business combination deadline if sought by KVAC; (iii) the failure to satisfy the conditions to the consummation of the Transaction, including the adoption of the Merger Agreement by the shareholders of KVAC and the receipt of certain regulatory approvals; (iv) market risks; (v) the occurrence of any event, change or other circumstance that could give rise to the termination of the Merger Agreement; (vi) the effect of the announcement or pendency of the Transaction on Medera's business relationships, performance, and business generally; (vii) the outcome of any legal proceedings that may be instituted against Medera or KVAC related to the Merger Agreement or the Transaction; (viii) failure to realize the anticipated benefits of the Transaction; (ix) the inability to maintain the listing of KVAC's securities or to meet listing requirements and maintain the listing of Medera's securities on Nasdaq; (x) the inability to implement business plans, forecasts, and other expectations after the completion of the Transaction, identify and realize additional opportunities, and manage its growth and expanding operations; (xi) risks related to Medera's ability to develop, license or acquire new therapeutics; (xii) the risk that Medera will need to raise additional capital to execute its business plan, which may not be available on acceptable terms or at all; (xiii) the risk of product liability or regulatory lawsuits or proceedings relating to Medera's business; (xiv) uncertainties inherent in the execution, cost, and completion of preclinical studies and clinical trials; (xv) risks related to regulatory review, and approval and commercial development; (xvi) risks associated with intellectual property protection; (xvii) Medera's limited operating history and risk that it may never successfully commercialise its products; (xviii) Medera expects to continue to incur significant losses and may never achieve or maintain profitability; and (xix) the risk that additional financing in connection with the Transaction may not be raised on favorable terms. The foregoing list is not exhaustive, and there may be additional risks that neither KVAC nor Medera presently knows or that KVAC and Medera currently believe are immaterial. You should carefully consider the foregoing factors, any other factors discussed in this press release and the other risks and uncertainties described in the "Risk Factors" section of KVAC's Annual Report on Form 10-K for the year ended December 31, 2023, which was filed with the SEC on March 29, 2024, the risks to be described in the registration statement, which will include a preliminary proxy statement/prospectus, and those discussed and identified in filings made with the SEC by KVAC from time to time. Medera and KVAC caution you against placing undue reliance on forward-looking statements, which reflect current beliefs and are based on information currently available as of the date a forward-looking statement is made. Forward-looking statements set forth in this press release speak only as of the date of this press release. Neither Medera nor KVAC undertakes any obligation to revise forward-looking statements to reflect future events, changes in circumstances, or changes in beliefs. In the event that any forward-looking statement is updated, no inference should be made that Medera or KVAC will make additional updates with respect to that statement, related matters, or any other forward-looking statements. Any corrections or revisions and other important assumptions and factors that could cause actual results to differ materially from forward-looking statements, including discussions of significant risk factors, may appear, up to the consummation of the Transaction, in KVAC's public filings with the SEC, and which you are advised to review carefully. Important Information for Investors and Shareholders In connection with the Transaction, KVAC and Medera filed a registration statement with the SEC, which includes a prospectus with respect to the securities to be issued in connection with the Transaction and a proxy statement to be distributed to holders of KVAC's ordinary shares in connection with KVAC's solicitation of proxies for the vote by KVAC's shareholders with respect to the Transaction and other matters to be described in the Registration Statement (the "Proxy Statement"). After the SEC declares the registration statement effective, KVAC plans to mail copies to shareholders of KVAC as of a record date to be established for voting on the Transaction. This press release does not contain all the information that should be considered concerning the Transaction and is not a substitute for the registration statement, Proxy Statement or for any other document that KVAC may file with the SEC. Before making any investment or voting decision, investors and security holders of KVAC are urged to read the registration statement and the Proxy Statement, and any amendments or supplements thereto, as well as all other relevant materials filed or that will be filed with the SEC in connection with the Transaction as they become available because they will contain important information about, Medera, KVAC and the Transaction. Investors and security holders will be able to obtain free copies of the registration statement, the Proxy Statement and all other relevant documents filed or that will be filed with the SEC by KVAC through the website maintained by the SEC at www.sec.gov. In addition, the documents filed by KVAC may be obtained free of charge from KVAC's website at https://www.kv-ac.com or by directing a request to info@kv-ac.com. The information contained on, or that may be accessed through, the websites referenced in this press release is not incorporated by reference into, and is not a part of, this press release. Participants in the Solicitation KVAC, Medera and their respective directors, executive officers and other members of management and employees may, under the rules of the SEC, be deemed to be participants in the solicitations of proxies in connection with the Transaction. For more information about the names, affiliations and interests of KVAC's directors and executive officers, please refer to KVAC's annual report on Form 10-K filed with the SEC on March 29, 2024, which can be found at https://www.sec.gov/ix?doc=/Archives/edgar/data/1889983/000121390024027973/ea0201104-10k_keenvision.htm and registration statement, Proxy Statement and other relevant materials filed with the SEC in connection with the Transaction when they become available. Additional information regarding the participants in the proxy solicitation and a description of their direct and indirect interests, which may, in some cases, be different than those of KVAC's shareholders generally, will be included in the registration statement and the Proxy Statement and other relevant materials when they are filed with the SEC when they become available. Shareholders, potential investors and other interested persons should read the registration statement and the Proxy Statement and other such documents carefully, when they become available, before making any voting or investment decisions. You may obtain free copies of these documents from the sources indicated above. No Offer or Solicitation This communication shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities in the Transaction shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933, as amended. Contacts:Keen Vision Acquisition CorporationAlex DavidkhanianChief Financial OfficerEmail: alex.davidkhanian@kv-ac.com MederaInvestor RelationsStephanie CarringtonICR HealthcareStephanie.Carrington@icrhealthcare.com(646) 277-1282 Media RelationsSean LeousICR HealthcareSean.Leous@icrhealthcare.com(646) 866-4012