Esperion Therapeutics, Inc.

About four years ago, Sheldon Koenig was thinking about retiring. After spending decades in leadership roles at different pharmaceutical companies, hed led a successful career focused largely on cardiovascular therapeutics. Along the way, hed endured his own personal challenges with healthincluding a battle with cancer, which led him to discover he also had high cholesterol.But before he made the decision to leave the workforce, he was offered a job with Esperion Therapeutics and saw the potential to make an even greater impact on heart health. The opportunity to lead a company with both the challenges and the potential to provide a much-needed alternative to current treatments in cardiology was too great to turn down, says Koenig. He joined the company as chief operating officer in 2020 and in 2021 was promoted to president and chief executive officer.The years that hes been at the helm of Esperion have been a period of transformation for the company, which recently received FDA approval for broad new label expansions for its products. Koenig sat down with BioPharma Dive to talk about whats changedand whats nextwith the ever-evolving Esperion.What drew you to working at Esperion in 2020?I have been fortunate to spend most of my professional career working in cardiovascular health and it is a personal passion of mine to bring life-saving medicines to patients in need. People forget that cardiovascular disease remains the No. 1 cause of death for both men and women in the U.S. and worldwide. At Sanofi S.A., I served as senior vice president and head of the cardiovascular franchise. Prior to that, I was vice president and global brand leader for the cardiovascular division of Merck & Co. taking on roles of increasing responsibility within the companys cardiovascular and thrombosis franchises.Esperion CEO, Sheldon KoenigHowever, it is my own battle with cancer, where I have truly witnessed the transformative power of medical breakthroughs and the invaluable role they play in prolonging and improving the lives of countless individuals. This personal connection has only strengthened my resolve to contribute to the advancement of medical knowledge and the development of progressive treatments.When I was approached by Esperion, I was serving as executive vice president and chief commercial officer at Portola Pharmaceuticals until it was acquired by Alexion in August 2020. At that time, I was toying with the idea of retirement, but when I was presented with the Esperion opportunity it made me realize I still had more to accomplish.How has your experience with cancer, and your overall health journey, shaped you as a business leader?Ironically, it was while I was under treatment for cancer that my oncologist recommended I see a cardiologist about my high LDL cholesterol. From my professional experience I was well aware of the risks of elevated LDL. Today, I can speak with customers, investors and colleagues not only about the strong science behind our brands but also from my personal experience and success taking an Esperion product, myself.Since becoming president and CEO in 2021, what are some of your proudest accomplishments?While there have been many accomplishments leading up to 2024, this has been a truly transformational year for the company. First, we received FDA approval for an expanded label for our products that significantly increased the potential patient population of the previous highly restrictive indication. Simultaneous with pursuing the expanded label approval, we doubled Esperions existing sales force to prepare for the launch of the expanded indications. We also developed and launched an innovative and primarily digital marketing campaign to target and reach the widest possible audience of healthcare providers and patients utilizing impactful characters known as the Lipid Lurkers.Outside the U.S., we also solidified our relationship with our European partner, Daiichi Sankyo Europe (DSE), which led to DSE obtaining a label expansion for both brands in Europe. In Japan, our partner, Otsuka Pharmaceuticals, met the primary endpoint in Phase 3 clinical trials, moving the approval forward for that country. These are all exciting developments that illustrate how Esperion is poised for growth.What are your goals for 2025?I have three goals for 2025 that will lead us into an even brighter future. First, to continue to inform healthcare providers about our currently marketed products as well as expanding patient access and education for patients on their treatment options for uncontrolled LDL cholesterol. Second, continue to solidify our presence outside the U.S. by working with current partners and launching into other desirable world markets. Third, expanding our portfolio both through new partnerships and our Next Gen Program, which is exploring new therapeutic opportunities in ATP-citrate lyase (ACLY) biology, with the goal to develop next-generation inhibitors optimized to address multiple life-threatening diseases.Looking further ahead, whats your vision for Esperion?Esperion is priming to become more than a cardiovascular company by exploring broad spectrum opportunities in categories with no current standard of care. While I cant say too much on that topic yet, I can say that what lies ahead is incredibly exciting.In the more immediate future, we are thrilled to be presenting at the 2025 JPM Healthcare Conference. Esperion will have some news to share, including details on our upcoming R&D Day in the spring and developments in our pipeline. We look forward to meeting other innovators in the industry at the conference. For those who are unable to attend, our presentation will be available to anyone through a link on esperion.com.Esperion discovers, develops and commercializes innovative medicines to help improve outcomes for patients with or at risk for cardiovascular and cardiometabolic diseases. To learn more visit esperion.comand esperionscience.com. '

近日，Padlock Therapeutics的前股东起诉了百时美施贵宝（BMS），指控其使用欺诈手段，以逃避支付2016年收购协议中的3.75亿美元里程碑付款。 Padlock成立于2014年，是一家致力于开发自身免疫病药物开发的公司，由风险投资公司Atlas Venture成立并孵化。 在2016年，Padlock与BMS达成了收购协议，其中首付款是2.25亿美元，如果达到某些开发和监管里程碑，BMS将向Padlock的股东额外支付3.75亿美元付款。 Padlocks的前股东包括了Atlas Venture以及Padlock的首席执行官Michael Gilman。 针对Padlock的诉讼，BMS打算在法庭上进行回应。 与Celgene的纠纷 与BMS扯上里程碑纠纷的不止Padlock。 至今，BMS与Celgene前股东之间持续三年多的CVR（或有价值权）纠纷仍未了结。 CVR通常是一种用于解决买卖双方就目标公司价格条款难以达成一致的价格缓冲工具。买方通过承诺在满足特定条件时，支付额外对价，来换取卖方同意交易的价格和条款。 就付款模式而言，CVR与许可引进（license-in）一样，其兑付也与特定的milestone挂钩。买方承诺在满足特定条件时，向卖方支付额外的收购价款。 在BMS与Celgene当初达成的收购协议中，也包含一项CVR，据双方协议约定，在完成交割后，如果BMS能在规定时间内完成三款药物—Zeposia、Zeposia和Abecma在美国的上市批准，则将向Celgene前股东额外支付64亿美元（共计7.15亿股，每股约9美元）。反之CVR协议将作废，持有人将不会获得任何付款。 其中Zeposia和Abecma两款药物均在规定的截止日期前获得了FDA的批准，偏偏Breyanzi批准延期了，获批日期比截至日期晚了36天（2021年2月5日获批），导致Celgene最终与64亿美元失之交臂。 2021年6月，Celgene前股东委托UMB Bank NA向法院提起诉讼，指控BMS未能做到尽职努力”（Diligent ），导致Breyanzi未能在截至日期前获得批准，违反了CVR条款。 在之前几起CVR诉讼中，Celgene的诉讼请求都遭到了法院驳回。上个月，Celgene前股东再次对百时美施贵宝（BMS）提起了新一轮诉讼。 拿不到的里程碑 在一场BD交易中，相比实实在在能拿到的首付款，里程碑付款存在着相当大的变数，在医药领域，里程碑付款通常将取决于被许可方是否完成相应里程碑事件，如取得临床批件、关键临床受试者给药、取得上市批准等等。 随着交易/项目的推进，涉及到的争议或潜在争议也逐渐凸显，里程碑成为极易产生履约纠纷的部分。 今年7月，诺华被其收购的Calypso Biotech公司指控故意拖延IL-15项目（CALY-002）的研发，使其无法收到里程碑付款。按照当时的并购协议，如果所有开发里程碑都达到了，Calypso的股东将再可获得诺华支付的1.75亿美元。不过Calypso的股东们认为，依据诺华对其收购所获得管线的推进情况来看，短期内看不到里程碑款项的希望。 因对于触发里程碑事件的界定分歧，Esperion与第一三共也产生了纠纷。 2019年1月，第一三共以1.5亿美元和最高9亿美元里程碑的代价，获得Esperion的Nexletol和Nexletol复方制剂在欧洲等地区的独家商业化权益。协议规定，在某些情况下（label expansion），第一三共将向Esperion支付里程碑款项。 2022年12月，Nexletol的一项III期临床CLEAR Outcomes达到主要终点MACE-4目标，基于此临床结果，Esperion认为按照合作协议，其将收到第一三共的3亿美元里程碑付款。但是第一三共认为CLEAR试验数据不足以触发里程碑事件，拒绝付款。最终Esperion起诉了第一三共。 参考出处 https://www.statnews.com/2024/12/12/padlock-therapeutics-bristol-myers-lawsuit/ https://news.bloomberglaw.com/esg/bristol-myers-squibb-sued-for-450-million-over-drug-acquisition

FDA今年很忙，但是再忙也未敢忘批药，截至2021年1月1日，FDA批准了53款新药，其中有38个小分子药物，作为化学人一定会很好奇这些化合物有啥特点，结构是啥，小编今天就带大家先睹为快。 1，Avapritinib (BLU-285) 阿伐普利尼 Avapritinib (BLU-285)是一种小分子激酶抑制剂，可有效抑制PDGFRα D842V突变体的活性、在细胞背景下抑制PDGFRα D842V自我磷酸化（IC50=30 nM）；同时也是KIT突变（KIT D816V）的抑制剂（IC50=0.5 nM）。 2，Tazemetostat (EPZ-6438) Tazverik(tazemetostat)  (EPZ-6438) 是组蛋白赖氨酸甲基转移酶（Histone-Lysine N-methyltransferase）EZH2的抑制剂。 3，Pizensy(乳糖醇) Pizensy是一种口服的乳果糖类似物。它是一种渗透性泻药（osmotic laxitaive），可促进水分流入肠道，进而在结肠内达到通便作用。 4，Nexletol (bempedoic acid) bempedoic acid由美国Esperion Therapeutic 公司研发，是一种治疗血脂异常及降低其他心血管疾病风险的新型小分子化合物。 合成路线如下： 5，Barhemsys(氨磺必利) 氨磺必利是一个多巴胺D2和D3受体阻断剂，上世纪80年代开始应用于精神分裂症治疗。 6，Nurtec ODT（rimegepant） Biohaven公司的口服CGRP抑制剂rimegepant，用于成人偏头痛的急性治疗。 7， Isturisa(osilodrostat) 3月6日，FDA批准库欣综合征（Cushing syndrome，CS）一线用药Osilodrostat上市，商品名：Isturisa，患者无论是否接受受过垂体切除手术治疗，都可应用Osilodrostat作为治疗药物。Osilodrostat是FDA批准的首个11-β羟化酶抑制，可直接阻断肾上腺皮质醇合成。 8，Zeposia(ozanimod) ozanimod（商品名ZEPOSIA），用于成人复发性MS（RRMS）患者的治疗。 9，Selumetinib（司美替尼） Selumetinib （司美替尼）（ARRY-142886 ; AZD6244）是一种MEK 1/2抑制剂和潜在的新药，由AlstraZeneca于2003年获得Array BioPharma Inc.的许可。阿斯利康和MSD于2017年签订了selumetinib的共同开发和联合商业化协议。 10，Tukysa(Tucatinib) Tukysa（Tucatinib）妥卡替尼 /图卡替尼 (ONT-380)是一种口服TKI(酪氨酸激酶)抑制剂，对HER2具有高度特异性，但对同属人表皮生长因子受体家族的EGFR没有明显抑制作用。 11，Pemigatinib （帕米加替尼） Pemigatinib（INCB054828）是一种口服有效的，选择性FGFR抑制剂，它对FGFR1，FGFR2，FGFR3，FGFR4的IC50值分别为0.4 nM，0.5 nM，1.2 nM和30 nM。 12，Ongentys(opicapone)  13，INCB28060 (Capmatinib) 卡马替尼；苯扎米特 INCB28060是一种新型， ATP竞争性的c-MET抑制剂，IC50为0.13 nM，抑制RONβ， EGFR和HER-3活性。 14，Selpercatinib (LOXO-292) 塞尔帕替尼 Selpercatinib（LOXO-292）是一种有效的，特异性RET抑制剂。 15，Ripretinib 瑞普替尼 Ripretinib（DCC-2618）是一种具有口服活性的，选择性的KIT和PDGFR-alpha抑制剂。 16， Cerianna (fluoroestradiol F18) 17，Artesunate（青蒿琥酯） 青蒿琥酯是一类控制疟疾症状的抗疟药。 18，Tauvid（flortaucipir F18） Tauvid（flortaucipir F18）是第一种获得FDA批准，帮助对大脑中的tau病理进行成像的药物。Tauvid是一种放射性诊断试剂，用于需要接受阿尔茨海默病评估的认知障碍成人患者。 19，Lurbinectedin（卢比克替定） lurbinectedin是PharmaMar研发的海鞘素衍生物，为肿瘤创新药。目前，绿叶制药与PharmaMar在华合作共同开发该药物。 20，Dojolvi（triheptanoin）三庚酸甘油酯 Dojolvi（triheptanoin）三庚酸甘油酯，是一种高纯度、人工合成的7碳脂肪酸甘油三酯，在甘油骨架上通过多个化学合成步骤添加了三个7碳脂肪酸形成。专门为LC-FAOD患者提供中链、奇数碳脂肪酸作为能源和代谢产物替代品。 21，Fostemsavir(BMS-663068) Fostemsavir (BMS-663068) 是 BMS-626529 的原药，能结合gp120，抑制 HIV-1 与细胞 CD4 受体的结合。 22，Byfavo（Remimazolam）瑞米唑仑/雷米马唑仑 Byfavo（Remimazolam）瑞米唑仑/雷米马唑仑 是一种起效和失效迅速的静脉注射苯二氮卓（benzodiazepine）镇静剂。可用于在时长不超过30分钟的有创医疗程序中，例如结肠镜检查和支气管镜检查。 23，Inqovi(cedazuridine+地西他滨) Inqovi（cedazuridine/decitabine[地西他滨]，口服C-DEC，ASTX727），该药用于骨髓增生异常综合症（MDS）和慢性骨髓单核细胞白血病（CMML）成人患者的治疗。 24，Xeglyze(Abametapir) Xeglyze（Abametapir）0.74％ 洗护剂 是一种金属蛋白酶抑制剂，金属蛋白酶是对虫卵发育和若虫和成虫虱子存活，至关重要的生理过程所必需的酶。 25，Nifurtimox (Synonyms: 硝呋替莫) Nifurtimox 是一种用于锥虫病 (Trypanosoma cruzi) 的抗虫剂。Nifurtimox 有潜力用于神经母细胞瘤细胞的研究。Nifurtimox 影响乳酸脱氢酶 (LDH) 活性。 26，Olinvyk（oliceridine） Olinvyk的活性药物成分为oliceridine，这是一种首创的（first-in-class）静脉镇痛药。oliceridine是首个G蛋白选择性激动剂，与静脉注射吗啡相比，镇痛效果更好。oliceridine以μ阿片受体为靶点，通过一种优化作用机制（MOA），优先参与负责疗效的信号通路，减少引起不良反应的信号通路的激活。 27， Evrysdi(risdiplam) risdiplam是治疗所有3种类型SMA的首个口服药物。 28，Winlevi(clascoterone) Clascoterone（又称CB-03-01）是一种局部雄激素受体（AR）抑制剂，该新的化学实体正在开发治疗痤疮（暂定品牌名为Winlevi）和男女性脱发（暂定品牌名Breezula）。根据美国FDA审查其1%浓度治疗痤疮以及后期开发其高浓度溶液治疗男性雄激素雄性脱发的结果，其被认为是一种“first-in-class”药物。值得一提的是，这是近40年来针对痤疮治疗的首个新机制药物。 29，Detectnet（Cu 64 DOTATATE）放射性诊断试剂 铜64盐酸盐 Detectnet是首款将Cu 64放射性同位素与生长抑素类似物DOTATATE偶联的诊断试剂。 30，Pralsetinib 普雷西替尼 Pralsetinib (Blu-667) 是新一代的，高效的，选择性RET抑制剂，对于WT RET，RET突变体V804L，V804M，M918T和CCDC6-RET的IC50为0.3-0.4 nM。 31，瑞德西韦（Remdesivir） 2020年10月22日，美国食品药品管理局（FDA）批准了吉利德科学的抗病毒药物瑞德西韦用于治疗新冠住院患者，成为美国首个正式获批的新冠治疗药物。 32，Lonafarnib (Synonyms: Sch66336) Lonafarnib 是一种口服有效的法尼基蛋白转移酶 (FPTase) 抑制剂，作用于 H-ras，K-ras 和 N-ras，IC50 分别为 1.9 nM，5.2 nM 和 2.8 nM。Lonafarnib 具有抗肝炎三角洲病毒 (HDV) 的活性。 33， Imcivree(Setmelanotide) setmelanotide是一款首创、寡肽类MC4R激动剂，开发用于治疗罕见肥胖遗传性疾病。 34，Gallium 68 PSMA-11 35，Orladeyo（Berotralstat）贝罗司他 rladeyo（Berotralstat）贝罗司他  是一种新型、口服、每日1次、强效、选择性人血浆激肽释放酶抑制剂，通过抑制激肽释放酶来阻止缓激肽的生成从而预防水肿发作。Orladeyo （berotralstat）用于预防12岁及以上儿童和成人遗传性血管性水肿（HAE）发作，Orladeyo是首个预防HAE发作的口服非甾体药物。 36，Tirbanibulin (Synonyms: KX2-391; KX-01) 37，Relugolix 瑞卢戈利 Relugolix，也称为TAK-385，是一种口服活性的黄体激素释放激素（LH-RH）受体拮抗剂，IC50为0.12 nM。 38,Gemtesa（vibegron） vibegron可治疗膀胱过度活动症导致的急迫性尿失禁，尿急和尿频等症状。