BAY-2927088

Bayer is applying its new operating model for key drugs elinzanetant and Nubeqa. Bayer’s massive reorganization championed by CEO Bill Anderson is bringing major changes to the German company’s pharma commercial team, shaking up its structure, personnel and operations. “We are transforming from a company that has been largely focused on hierarchy within functions to an organization—and supporting design—that really focuses on customers and products,” Christine Roth, head of global commercialization at Bayer’s pharmaceutical division, said in a recent interview with Fierce Pharma. Roth’s promotion to her current position was part of the restructuring as Bayer shrank its pharma executive team. The former oncology business chief officially started to lead a newly formed commercialization organization on June 1. The purpose of the groupwide overhaul was to reduce Bayer’s levels of bureaucracy, as job reductions were expected to mainly affect managerial roles. The new operating model, dubbed “dynamic shared ownership,” or DSO, promises fewer organizational layers and more agility for employees. While layoffs across Bayer are not expected to finish until 2025, Roth said headcount reductions in the pharma commercialization unit will largely be done at the beginning of the fourth quarter.   A new operating model As a result of the streamlining, “the span of coaching for every leader in the organization is going to double and, in some cases, triple,” Roth told Fierce Pharma on the sidelines of the American Society of Clinical Oncology annual meeting in Chicago in late May. “One of the tenets of DSO is, managers need to be less involved in the day-to-day,” Roth said. “Our role is as visionaries, architects, catalysts and coaches.” Within Bayer’s pharma unit, staff responsibilities across late-stage development, registration, commercialization and lifecycle management are being reshaped, with regulatory and development functions shifting over to the R&D organizations. For commercialization, Bayer previously had product sales teams and parallel functional teams, which may have operated on separate strategies. Now, those functions, such as marketing, market access, medical affairs and patient advocacy sit unified in the global capabilities group—instead of being dispersed across each product. Under that model, Roth explained, the product teams will set goals, and then everyone else, including Roth herself, will provide resources in service of those goals. The new DSO model still needs some honing, but Bayer expects to install people in their new jobs and functions by the end of the year across the company, Roth said.  “The beauty of this system is, we’re not perfecting it before we start,” Roth said. “We’re getting to a good place where we can start to experiment and go. And we will learn and adjust as we go.” To help test out DSO, Bayer has designated several “front-runner” teams. “The front runners have been really critical in helping us do that, because their job was to try out the new system—we did our best to completely leave them alone—to let us know what’s working to support them and what’s not working, and then feed real-time learnings back into the organization,” Roth said. The team for Bayer’s prostate cancer drug Nubeqa is one of the front-runners groups. Bayer has pegged the androgen receptor inhibitor to reach peak sales of more than €3 billion a year. Bayer is trying to expand Nubeqa’s reach in part through the phase 3 ARANOTE trial in metastatic hormone-sensitive prostate cancer. The study reached primary completion on June 7, according to clinicaltrials.gov. A Bayer spokesperson said the company plans to announce the topline results soon. While preparing for potential regulatory filings for ARANOTE, the team identified many unnecessary processes from the old practice, including around 80 tables that would have previously been produced. Eliminating those processes will save time and costs, Roth said. DSO is also coming into play with Bayer’s possible launch of the hot flash drug elinzanetant, which has three positive phase 3 trials in the bag and an FDA filing on the horizon. The new model has allowed the elinzanetant staffers to tap into digital resources that traditionally have not been dedicated to a specific product team, Roth said. Novel channel marketing resources were brought in “because they see this launch as not so much the traditional boots-on-the-ground, reach-and-frequency, face-to-face with physician, but much more patient engagement and much more policy engagements,” Roth said. Direct-to-consumer patient marketing will be critical for elinzanetant launch, Roth added. Bayer wants to empower women to have an open dialogue with doctors about their symptoms and potential treatment options, and to make sure medical policies are in place so that patients can have access to the meds. Bayer is evaluating DSO system in 90-day cycles. According to Roth, employees are getting the hang of the new model and need no more convincing. “We are going to have to get our hands dirty and let teams really struggle through some of these things before we see what kind of adjustments we need to make,” Roth said. “What I am very focused on achieving between now and the end of the year is, as people complete multiple 90-day cycles, I will be listening and checking to make sure that it feels different for employees. They feel empowered. They feel like there are fewer barriers to getting the job done. They feel like they’re closer to the customer.”   Bayer’s oncology ambition: ‘A moving target’ Roth had experience working in women’s health and cardiometabolic diseases. But before she came to lead Bayer’s entire pharma commercial operations, she had spent nearly two decades in oncology, including at GSK, Novartis and Bristol Myers Squibb. Last year, Bayer laid out an ambition to reach $10 billion in revenue from cancer drugs by 2030 and to become a top 10 oncology player. It’s a bold target considering none of the pharma division’s top 3 products last year were in oncology, while Nubeqa is expected to hit above $1 billion sales this year. So at last year’s ASCO annual meeting, Roth told Fierce Pharma that Bayer would need a “midsize acquisition” to reach its revenue goal. This time around, Roth argued that there’s no magic formula on how to achieve an ambitious target in pharma, and that a midsize deal may not be absolutely necessary. “I would not so much focus on the $10 billion anymore,” Roth said during this year’s ASCO conference. “The goal is to become a top oncology player, and it’s a moving target anyway.” “All we need, to be quite honest with you, is [for] one of the assets from Vividion—one of the assets in our pipeline—to be our next $2-to-$3-billion drug,” she said hypothetically. “And all of a sudden, the picture changes.” Bayer acquired Vividion Therapeutics in 2021 and made the discovery engine an independently operating subsidiary. In oncology, the unit is working on candidates to inhibit NRF2 and STAT3, and it has an anti-WRN program in collaboration with Roche. But all of those programs are in early-stage testing and currently don’t have data in their clinical profiles. Roth also pointed to Bayer’s HER2 program, a reversible tyrosine kinase inhibitor coded BAY 2927088, which recently received an FDA “Breakthrough Therapy” designation in previously treated HER2-mutated non-small cell lung cancer. It also has a new PSMA-targeted radioligand therapy coded BAY 3563254. But those are also in phase 1 development. Compared with other therapeutic areas, Bayer’s oncology pipeline is composed of newer assets that are relatively unproven. In women’s health, the company is looking to introduce elinzanetant soon. And it just bought European rights to BridgeBio’s near-to-market heart disease drug acoramidis. But in oncology, it has no phase 2 or phase 3 therapeutic programs in sight for novel molecules, while Nubeqa was first introduced about five years ago.   The Bayer pharma team has had discussions with CEO Anderson—a pharma veteran—about the need to balance between early-stage and later-stage assets in the oncology pipeline, Roth said. For one thing, the DSO model is expected to advance early-stage programs faster. “The core of the strategy is really to continue investing and filling the funnel,” Roth said. As for M&A deals, Roth argued that the ongoing restructuring wouldn’t impair Bayer’s ability to pursue external transactions in oncology, pointing to the BridgeBio deal. But the drugmaker simply hasn’t identified the right target. “[If] we find the right one, I’m fairly optimistic that we’ll be successful if that’s what we want to bring in,” Roth said. “We’ve looked at a lot of things that have transacted recently and just decided for one reason or another that they weren’t the right deal for us.”

岁月不居，时节如流。2024 年，新药研发稳中求进。在这半年间，各大药企争分夺秒，力求尽早推出具有竞争力的创新药品，从而在市场上占据一席之地。 那么，有哪些值得期待的新药呢？在这里我们基于 Insight 数据库，整理了 2024 上半年各个药企在国内新进入 III 期临床试验阶段（包括 2/3 期临床）的化药小分子新药。这些项目或将成为最接近申报上市的新药，代表着化药领域的最新突破和蓬勃发展。 研发热度不减，抗肿瘤新药仍占大头 作为全球最大的细分赛道，肿瘤领域一直都是各大药企的「兵家必争之地」，今年也是如此。从目前来看，肿瘤领域共有 11 款新产品，其适应症涵盖了肺癌等癌症类型，同时为了避免「同质化」，靶点也更为多样化。在这里我们选取几款具有代表性的新药进行分析。 在肺癌领域，既有拜耳这样的国际药企加入赛道，也有首要控股、加科思等国内药企积极发力。 其中，BAY 2927088 是拜耳开发的酪氨酸激酶抑制剂（TKI），主要针对携带 HER2 激活突变的非小细胞肺癌（NSCLC）患者。今年 2 月和 6 月，该药物先后获得 FDA 和 CDE 的「突破性疗法」认定，并于 6 月启动针对这一患者群体的一线治疗 III 期临床试验。 首药控股的 CT-3505 属于国产第三代 ALK 抑制剂。它在靶向 ALK 的同时还靶向 FAK、LTK 和 PTK2B 等关键蛋白，旨在克服单一靶点药物容易产生的耐药性问题。今年 1 月，首药控股启动 CT-3505 在 ALK 阳性 NSCLC 患者中的 III 期临床试验，并在 3 月 25 日完成首例受试者的入组工作。 CTR20240005 试验历史时光轴截图来自：Insight 数据库官网 JAB-3312 是加科思自主研发的高选择性 SHP2 变构抑制剂，也是全球第二个获得 FDA 批准进入临床的同类产品。2020 年 9 月，FDA 授予该新药治疗食道癌（包括食管鳞癌）的孤儿药资格认定。今年 5 月，JAB-3312 与戈来雷塞联合用于晚期非鳞状 NSCLC 患者的临床试验正式启动。 在血液肿瘤方面，Golcadomide 是 BMS 子公司新基医药开发的新型 E3 泛素连接酶 Cereblon 调节剂（CELMoD）分子。该药物针对非霍奇金淋巴瘤（NHL）的特性进行了优化，显著增强其在淋巴器官中的分布。目前，Golcadomide 正在开展针对多种类型 B 细胞淋巴瘤的 III 期临床研究。 此外，BCL2 作为调节细胞凋亡的关键蛋白，在慢性淋巴细胞白血病（CLL）和小淋巴细胞淋巴瘤（SLL）等血液系统恶性肿瘤中呈现高表达。针对这一靶点，亚盛医药和诺诚健华均进行了战略布局。 亚盛医药的 Lisaftoclax 是首个在国内进入临床阶段、本土研发的 BCL2 抑制剂，它在上半年连续启动了 2 项中国内地 III 期临床试验。目前唯一获批上市的 BCL2 抑制剂是艾伯维的维奈托克（Venetoclax）。 Lisaftoclax 国内 III 期临床试验截图来自：Insight 数据库官网 除肺癌及血液肿瘤外，来凯医药的 AKT 抑制剂 Afuresertib 也在今年 5 月展开了针对局部晚期或转移性 HR+/HER2- 乳腺癌患者的 III 期临床研究。 聚焦内分泌与代谢疾病，六款新药实现突破 在内分泌与代谢领域，靶向新药的开发正日益受到重视。接下来，我们将聚焦于表格中提到的几款新药，来探讨其临床潜力。 首先，糖尿病作为该领域的热门话题，其庞大的患者基数促使多个药企纷纷抢占市场。此次在国内新进入 III 期临床的新药包括诺和诺德的 Cagrilintide 和中国科学院上海药物研究所研发的 LH-1801。 Cagrilintide 是一种基于胰淀素模板的衍生多肽，目前正在进行 2 型糖尿病的 III 期临床研究。除此之外，Cagrilintide 与「减肥神药」司美格鲁肽的组合疗法也在 2023 年进入了 肥胖治疗的 III 期临床研究。 Cagrilintide III 期临床研究截图来自：Insight 数据库官网 其次，痛风领域长期缺乏疗效显著的新药，具备了创新的土壤。URAT1 作为降尿酸的热门靶点，目前全球在研新药达 40 种，其中大多数由国内药企开发。海创药业的 HP501 以及一品红和美国 Arthrosi 公司合作研发 AR 882 都是靶向 URAT1 的创新药物，前者于今年 3 月正式启动治疗原发性痛风伴高尿酸血症的 Ⅱ/Ⅲ 期临床试验，后者则在 4 月展开适应症为痛风的 Ⅱ/Ⅲ 期临床研究。 最后，恒瑞医药自主研发的 HRS9531 和 SHR-6508 也备受关注。HRS9531 是靶向 GIPR 和 GLP1R 的双重受体激动剂，通过增加胰岛素分泌、抑制食欲和促进体重减轻来治疗肥胖。SHR-6508 则是用于治疗继发性甲状旁腺功能亢进症的新分子药物，尽管其具体靶点尚未公开，但其创新的作用机制有望为这一疾病提供新的治疗选择。 打破桎梏，心血管疾病治疗又添「新将」 心血管疾病涉及心脏和血管的多种病理生理机制，每种机制都可能对治疗效果产生重大影响。此外，临床试验设计的严格要求、庞大的样本量需求以及长期的随访观察，都增加了新药研发的复杂性。因此，针对这一领域的新药，我们将对其中两款展开评述。 脂蛋白(a) [Lp(a)] 是心血管疾病的要遗传因素，而 LPA 基因负责编码构建 Lp(a) 的载脂蛋白(a)。Lepodisiran 是基于小干扰 RNA（siRNA）技术设计的药物，其原理是通过阻断或「沉默」LPA 基因，降解编码载脂蛋白(a) 的信使 RNA (mRNA)，从而抑制 LPA 基因的翻译，降低血液中 Lp(a) 的水平。 目前尚无针对 Lp(a) 的药物获得监管部门的批准，Lepodisiran 的研发填补了这一空白。今年 3 月，在 Lp(a) 水平升高且确诊为动脉粥样硬化性心血管疾病或具有首次心血管事件高风险的成年人中进行的 III 期临床研究正式启动，旨在评估 Lepodisiran 对主要不良心血管事件的影响。 Lepodisiran 最初由 Dicerna 制药公司研发。2018 年，礼来公司与 Dicerna 达成战略合作协议，共同开发多种 siRNA 疗法，其中 Lepodisiran 是这一合作中的第二条管线产品。 Lepodisiran 医药交易截图来自：Insight 数据库官网 CYP11B2 是负责编码醛固酮合成酶的基因，参与了醛固酮的合成过程。Baxdrostat 作为醛固酮合成酶抑制剂（ASI），通过靶向 CYP11B2 以用于高血压和慢性肾病的治疗。今年 2 月和 3 月，Baxdrostat 针对这两项适应症的 III 期临床研究分别正式启动。 Baxdrostat 针对高血压和慢性肾病的 III 期临床研究截图来自：Insight 数据库官网  据悉，Baxdrostat 最初由罗氏着手开发。2019 年 CinCor 收购该药物并接管其全部开发、制造和商业化工作。2023 年阿斯利康又通过收购该药物来加强其心肾疾病治疗产品线。 呼吸系统、皮肤及眼科新药，同样不容错过 呼吸系统、皮肤及眼科领域的新药竞争同样相当激烈。从研发机构和靶点出发，以下几款新药值得关注。 在呼吸系统领域，阿斯利康的沙丁胺醇与布地奈德组合药物（PT027）是靶向 ADRB1、ADRB2、ADRB3 和 GR 的复方药物。作为首款且唯一经 FDA 批准的哮喘抗炎缓解药，它在国内已进入治疗哮喘的 III 期临床研究，有望为我国患者带来生存获益。 Camlipixant 是一种选择性口服 P2X3 受体拮抗剂，通过靶向 P2RX2 和 P2RX3 用于治疗慢性咳嗽。其作用机制是抑制嘌呤能受体，从而减少咳嗽反射的频率和强度。对于那些受到顽固性咳嗽困扰的患者来说，Camlipixant 提供了全新的治疗选择。 Camlipixant 最初由 BELLUS Health 开发。2023 年 4 月，GSK 以 20 亿美元收购了 BELLUS Health，将 Camlipixant 纳入其产品管线。 在皮肤和眼科这两个小众赛道，靶向新药也在不断涌现。芦可替尼乳膏通过抑制 JAK1 和 JAK2 的活性，阻断 JAK-STAT 信号通路，用于治疗非节段型白癜风和特应性皮炎。 Incyte Corporation 是芦可替尼乳膏的开发者。2022 年 12 月，康哲药业与 Incyte 达成协议，负责芦可替尼乳膏在中国市场的开发、注册和商业化推广。 此外，AR 在调节皮脂腺功能和维护皮肤健康方面也发挥着重要作用。三生制药与 Cosmo 合作开发的克拉考特通过抑制 AR，减少皮脂腺的活性，降低皮脂分泌，从而防止毛囊堵塞和炎症反应，有效控制痤疮的发展。 眼科疾病方面，莱恩医药研发的洛索洛芬通过抑制 COX，减少前列腺素生成，有效缓解眼部术后炎症和疼痛。维眸生物的 VNV001 靶向整合素 ITGAL 和 ITGB2，减少炎症细胞在眼表面的积聚，减轻干眼症症状。博瑞制药的阿托品作为 CHRM 激动剂，通过调节眼球生长和发育，延缓近视进展。 其他 此外，上半年新进入 III 期临床的化药小分子新药还涉及精神障碍、镇静止痛和感染性疾病等多个领域，参与研发的企业包括吉贝尔药业、Zevra Therapeutics、立品药业和恩华药业等。 封面来源：站酷海洛 Plus 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。 PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验 点击阅读原文，立刻解锁！