Anacor Pharmaceuticals LLC

Paul Berns was in the middle of a haircut when his phone rang. A month earlier, he had helped steer the biotech he co-founded, Metsera, to a $7.3 billion deal with Pfizer. With the deal signed, Metsera was now focused on integrating with the giant New York drugmaker, and Berns was thinking about what he would do next. But on the other end of the phone was Novo Nordisk CEO Mike Doustdar. It was Saturday, Oct. 25, and a month earlier, Novo had offered as much as $10 billion for Metsera, but lost. Doustdar had been shocked when he was awakened early on the morning of Sept. 22 by a call from Metsera’s chairman, who told him the biotech had taken Pfizer’s lower — but more certain — bid . Now Doustdar wanted back in. “We’re going to submit an offer,” the Novo CEO told Berns, who was Metsera’s lead independent director. Berns left the hair salon with his cut half-finished. He called Metsera CEO Whit Bernard, who was spending the day with his family after intense weeks of integration meetings. And he reached out to Clive Meanwell, the board’s chairman. The three men had co-founded the company, pulling together a portfolio of weight loss assets, taking the company public and then selling it. The close of the Pfizer deal was weeks away. But now Novo was back. And Berns, Meanwell and Bernard were staring at a surprise offer worth over $1 billion more than the signed Pfizer deal. This is the inside story of a high-drama, high-stakes 14 days in which Novo tried to win back a prize it had lost, and Pfizer fought back. It’s also about two huge pharma companies trying to regain their momentum: Pfizer after the pandemic, and Novo after blowing an early lead in obesity. Pfizer won the battle, but will ultimately be judged by how the experimental drugs it obtained perform when trials read out in the next few months. The reporting here is based on interviews with people who had direct knowledge of the events described. All spoke to Endpoints News on condition of anonymity to relay private conversations and negotiations. Other details were pulled from securities filings, earlier coverage by Endpoints, or other public material. After Berns reached out to his fellow board members and their lawyers, his next call was to Albert Bourla, the CEO of Pfizer. Bourla had steered the company to triumph during the Covid-19 pandemic, fought off an attack by an activist investor, and he assumed he sealed a deal to reload the company’s pipeline with assets for the biggest drug category in industry history. Bourla picked up, and Berns told him the news. “Oh boy,” the Pfizer CEO said in his gravelly Greek accent. Pfizer’s signed deal had been blown back open. As Metsera pulled its board and lawyers into a virtual war room, it issued a press release telling the public about the new bid, declaring that Novo’s offer was “superior” to the deal it had with Pfizer. Bourla was furious. The CEO thought the companies had a deal, and that Metsera had violated it. One person involved said Bourla was as angry as they’d ever seen him. The company decided it wasn’t going down without a fight. Click on the image to see the full-sized version It immediately began planning how to push back in the courts, targeting the unusual structure of Novo’s offer, which would immediately give cash to Metsera’s shareholders and pay them for the risk that the deal might not close if US antitrust regulators stepped in. Now, Pfizer began thinking about how high it could take its offer to compete against Novo’s new bid. The day after Metsera made Novo’s offer public, Pfizer sued. It went after not just Metsera and Novo, but also sued Berns, Meanwell and other members of the board — a sign of just how angry Pfizer’s management was. Pfizer called the situation a “brazen breach of the Pfizer-Metsera Merger Agreement and disloyal, bad faith actions by Metsera’s directors.” A second lawsuit in federal court argued that a deal with Novo would give a key obesity asset to a company that was already part of a weight loss duopoly and make “a mockery of the US antitrust laws.” But in private, the two sides were still keeping channels open. Bourla and Berns had a decade-long relationship, which started when Berns was CEO of Anacor Pharmaceuticals and sold the company to Pfizer for $5.2 billion. Before each lawsuit dropped, Bourla called Berns to tell him it was coming. The conversations grew heated at times, and reminded Meanwell of the elite rugby he’d played when he was younger, both teams pounding each other on the field, then shaking hands after. On Tuesday, Nov. 4 — the day after filing its second lawsuit — Pfizer was back with a raised offer. It pledged $60 per share, plus a potential $10-per-share future payment. Novo immediately retaliated with an even higher bid totaling $86.20 a share. The next few days were a whirlwind of negotiations and legal developments . (Berns also made it back to the salon and completed his half-finished haircut.) As one party raised its offer, the other would counter, like heads-up poker for a billion-dollar stake. Pfizer had been counting on its relationships in Washington to help it win the deal. All year, Bourla had been courting President Donald Trump, flying on the company’s private jet to see him in Washington or in Florida, or dining with him at his club in New Jersey. Bourla had struck the first of the industry’s “most favored nation” deals with the administration, and an Oval Office announcement publicly sealed the close relationship between the two leaders. And Pfizer’s advisors were hinting that the Trump-Bourla relationship would work in their favor, pointing to an unusual announcement by the FTC — despite the government shutdown — that it had blessed Pfizer’s takeover of Metsera. But Novo was now playing the game in Washington, too. Trump was fascinated by the weight loss injections, sometimes calling them the “fat shot” and telling tales of friends who had used them to shed pounds. As the companies negotiated early that week, Endpoints broke the news that Novo and its rival Eli Lilly had a deal with the administration to cut the price of their weight loss drugs. Two days later, Doustdar was in the Oval Office , smiling and touting the deal in a public press conference. At the event that Thursday, Endpoints’ Max Bayer asked Trump what he thought of the fight for Metsera and if he favored one buyer over the other. Trump called Doustdar to the lectern that was set up in the room. Click on the image to see the full-sized version “As of today, our bid is higher,” Doustdar said. “Our message to Pfizer is if they would like to buy the company, then put your hand in the pocket and bid higher. It’s a free market and at the end of it, it has to do with the price.” Pfizer’s team was watching closely to see if Trump might throw a wrench in the situation by weighing in. But he didn’t, and it was unclear if he was even familiar with the volatile deal. The next day, on Nov. 7, Novo had raised its total price to $86.25 a share, with much of it in upfront cash. In total, it was worth around $10 billion, more than $2 billion higher than the initial deal with Pfizer. In a call to Metsera that Friday, a Novo executive told Berns that the company wanted the deal, and wanted it badly. It liked the pipeline and thought it could do well with the company. But it was also at its limit on price. Then came a call from the FTC. Novo believed that while its deal structure was innovative, it was not illegal. But Daniel Guarnera, the antitrust regulator’s director of the Bureau of Competition, told Metsera’s legal team that if it took the Novo deal, the FTC would sue. Hours later, Pfizer did what Doustdar had suggested. It reached into its wallet and raised the bid, matching Novo’s $86.25 a share, with $65.60 a share in cash and $20.65 a share in payments based on events such as FDA approvals and starting a key Phase 3 trial. That night, the Metsera board met again. The choice seemed clear. It had two equal offers, but one could be tied up in lawsuits from the government and Pfizer, potentially stretching on for months or years, slowly strangling the company. As the lawyers guided them through the debate, they agreed to take the Pfizer deal. Doustdar woke up on Saturday morning to Metsera’s press release announcing the deal, and knew Novo had lost. But Novo’s ceiling had always been $10 billion; it had gone as high as it could. The final deal was a triumph for Metsera’s owners, including the investor ARCH Venture Partners, which could clear more than $2.3 billion from its stake in the company. Berns, Bernard and Meanwell, also stand to generate significant wealth from the sale, through a combination of their own stock holdings and other incentives. The deal closed this week.

最近（11月13日官宣），创新药物研发公司浙江扬厉医药技术有限公司（下称“扬厉医药”）完成亿元级B轮融资，本轮融资由启明创投独家投资。 扬厉医药技术是一家专注于前沿创新药物研发的高新技术企业。公司专注于研发具有全球知识产权的同类首创（first-in-class)和同类最优（best-in-class)国家1类创新药物，聚焦抗肿瘤和慢性病疗法，有多个产品已进入临床2期和3期。 VB19：高选择性醛固酮合成酶抑制剂VB19055，IND已经受理，针对耐药性高血压（rHTN）和未控制高血压（uHTN）等。大约20%的高血压患者联用3种现有疗法也无法达标，而产生心血管事件，患者需要新的疗法使得血压达到正常水平。醛固酮（英语：aldosterone）是由肾上腺分泌，调节人体水和电解质平衡的激素，为肾素-血管紧张素-醛固酮系统（RAAS）的一部分，来维持血压稳定。醛固酮合成分泌过多时，就会导致血压升高。VB19055调节醛固酮的合成达到血压稳定的作用。 TFX05：临床2期（CTR20220957）在研，针对肝癌，胆道恶性肿瘤，肾上腺皮质癌等。多种实体瘤高表达醛酮还原酶家族1成员C3 （AKR1C3），TFX05是扬厉医药研发的具有全球知识产权的小分子前药，在高表达AKR1C3肿瘤细胞内还原释放烷化剂选择性杀伤肿瘤细胞。初步临床结果显示具有更长的中位总生存期(mOS)。 TFX06：临床2期（CTR20230789）在研，针对ER+/HER2-的乳腺癌。ER+/HER2-乳腺癌占据乳腺癌的70%，内分泌疗法（例如芳香化酶抑制剂来曲唑等）是基石疗法。但是ESR1基因突变是内分泌疗法的主要耐药机制，占据30-40%，目前除了elacestrant之外没有其他有效的疗法。 TFX06是扬厉医药研发的具有全球知识产权的选择性雌激素受体的完全拮抗剂和降解剂（CERAN/SERD），针对现有内分泌疗法耐药后ER+/HER2-乳腺癌伴ESR1基因突变或未突变患者。TFX06的初步安全性，有效性和PK特征已在国际会议公开。TFX06对乳腺癌脑转患者的脑部病灶具有显著缩瘤效果。 VB15：临床1期（CTR20243267）在研，针对同源重组修复缺陷（BRCAm/HRD）的实体瘤。临床应用的PARP抑制剂（例如olaparib等），是泛PARP抑制剂，具有明显血液毒性，导致患者不耐受停药/减量影响疗效。PARP1选择性抑制剂带来更优的疗效和安全性。 VB15010是扬厉医药研发的具有全球知识产权的PARP1高选择性抑制剂，和同类竞品比较具有更强的DNA捕获能力，更高的自由药物比例，临床每天一次给药无蓄积风险。现有临床结果初步展现良好的安全性及有效性，针对olaparib无响应患者有持久疗效。 VB18：选择性CDK2/4双重抑制剂在临床前研发，针对ER+/HER2-乳腺癌等。临床广泛应用的CDK4/6抑制剂的副作用是血液毒性,研究发现CDK6的抑制而不是CDK4的抑制才是血液毒性的原因。另外CDK4/6抑制剂临床耐药机制之一是细胞周期素E （cyclinE）的高表达和CDK2结合逃逸CDK4/6抑制剂的作用。因此，CDK2/4双重抑制剂有望更安全、更有效取代CDK4/6抑制剂。 扬厉医药技术能够在短时间内撑起多线创新药，与他们药明康德背景有关。 其管理团队中，有多名高管曾在药明康德担任要职。 丁照中博士是扬厉医药的联合创始人兼总裁。他拥有超过30年的药物研发及管理经验，为VyBio带来了宝贵的研发经验。在创立扬厉医药之前，他曾担任上海药明康德的副总裁，负责服务全球制药公司的药物发现研究。他带领的科学家团队为客户发明了40多个新化学实体分子（NCE）。加入药明康德之前，他曾担任Anacor Pharmaceutical, Palo Alto, California的药物化学总监，该公司后来被辉瑞公司以56亿美元收购。他的职业生涯始于1992年作为高级研究员加入Bristol-Myer Squibb, Princeton, New Jersey做新药研发。他参与研发了Iruplinalkib等多款上市药物。丁博士毕业于纽约州立大学，获得博士学位，并在美国西北大学师从Richard B. Silverman教授进行博士后研究。 方东博士为VyBio带来了逾20年的药物发现与开发经验。他曾作为亚盛医药临床前开发高级副总裁，主导了全球第二个获得监管机构批准的BCL-2抑制剂Lisaftoclax的临床前开发工作。方博士还在诺华中国生物医学研究所担任肿瘤药理学与转化研究负责人。他还曾担任药明康德肿瘤事业部执行总监，并在美国辉瑞和塞雷拉公司担任过药物研发科学家。方博士拥有四川大学华西医科大学医学博士学位，并在香港大学获得肿瘤生物学博士学位。 方博参与了多个已上市抗肿瘤新药的研发，包括Lisaftoclax、Olverembatinib、Iruplinalkib和Glasdegib并成功主导或推动数十项向中国国家药品监督管理局（NMPA）和美国食品药品监督管理局（FDA）提交的新药临床试验申请。此外，他发表了40多篇同行评审的科学论文，并且是20多项专利的发明者。 另外值得注意的是，浙江扬厉医药技术有限公司并非一家原生于杭州的公司。2024年11月，他们从深圳搬到了杭州。 拓展阅读，看杭州如何成为生物医药创新高地： 复旦校友在杭州创立的启元生物，最近完成2亿元融资 杭州新元素药业申请港股上市，目前暂无销售收入 杭州先为达生物申请港股上市，核心产品是时下流行的减肥药 杭州专注乙肝治愈的浩博医药，获得6300万美元B2轮融资 杭州专注开发肿瘤及神经系统类疾病药物的亦立医药，完成超亿元人民币天使+轮融资 杭州专注体内基因疗法的神拓生物，刚刚融资数千万元 杭州耀加速医用同位素完成数千万天使轮融资，加速国产α核素商业化突破 杭州美股上市药企天境生物获6亿元C2轮融资 核心团队成员来自辉瑞、强生、施贵宝和赛诺菲等，杭州创新药研发公司多域生物完成新一轮融资 合肥盯上杭州这家女性赛道医疗公司 杭州AI医药公司高维医药完成数千万元融资

今天，我在看辉瑞的产品线时，注意到克立硼罗软膏这个产品。 克立硼罗是一种磷酸二酯酶4（PDE-4）抑制剂，用于轻中度特应性皮炎，原研是Anacor Pharmaceuticals，后来卖给了辉瑞。 产品因独特的作用机制，相比于传统激素类外用药，有更好的疗效和安全性。算是这个领域的明星品种。 2020年7月，原研获批进口，后来通过谈判进入医保。 最新的零售价是158.8元每支。 2024年医院市场销售额1.5亿不到，零售市场还有5千万销售额。 在皮肤病专科领域，算是不错的品种。 2024年9月，南京万融健诚首仿获批。 很快，江苏万禾、齐鲁等仿制陆续获批。 也就一年左右时间，总计已有8家仿制获批。 最夸张的是，后面还有几十批仿制申请受理号，涉及40来个相关企业的申请，处在审评审批中，按这个节奏，等下次国采时，少说也有15家仿制。 先获批的企业，如果没有强大的销售能力，很难把先机转化为优势啊。 摩熵药筛小程序重磅改版，查询产品信息更快捷！ 11批国采交流群已建，加客服微信，入群交流！