Zasocitinib

OSAKA, Japan & CAMBRIDGE, Mass.--( BUSINESS WIRE )--Takeda ( TSE:4502/NYSE:TAK ) will host an investor R&D Day today beginning at 8:30 a.m. JST in Tokyo. The meeting will focus on programs in the company’s late-stage pipeline, the transformative value they could deliver to patients, and the market opportunities they represent. “We are focused on advancing our innovative pipeline and accelerating late-stage programs to deliver sustainable revenue growth to 2030 and beyond, building upon the strong momentum of our Growth and Launch Products,” said Christophe Weber, Takeda chief executive officer. “The first three Phase 3 programs will read out in 2025, initiating a cadence of potential filings across multiple indications over the next several years.” Eight Regulatory Filings in FY2025 – FY2029 The late-stage pipeline includes oveporexton (TAK-861), zasocitinib (TAK-279), rusfertide (TAK-121), mezagitamab (TAK-079), fazirsiran (TAK-999) and elritercept (TAK-226). Combined these programs have potential peak revenue 1 of $10B - $20B. Data from three Phase 3 programs is expected to read out in 2025: oveporexton, a potential best-in-class and first-in-class investigational oral orexin receptor 2 agonist will report Phase 3 results in narcolepsy type 1; zasocitinib, an investigational next-generation, highly selective and potent oral allosteric tyrosine kinase 2 (TYK2) inhibitor will deliver Phase 3 results in psoriasis; and rusfertide, an investigational injectable hepcidin mimetic in development with partner Protagonist Therapeutics, will have Phase 3 results in polycythemia vera. Filings for these three indications are expected in fiscal years 2025 and 2026. Five additional indication filings for late-stage programs are on pace for fiscal years 2027 through 2029: zasocitinib in psoriatic arthritis; mezagitamab, an investigational anti-CD38 antibody providing rapid, selective and sustained depletion of disease-causing immune cells that could set a new standard for the treatment of immune thrombocytopenia (ITP) and immunoglobulin A neuropathy (IgAN); fazirsiran, an investigational RNA interference (RNAi) therapy that stops the production of misfolded abnormal protein Z-AAT directly addressing the pathology of alpha-1 antitrypsin deficiency liver disease (AATD-LD) and; elritercept, an investigational activin inhibitor designed to treat anemia associated with certain hematologic cancers, including myelodysplastic syndromes (MDS). Takeda recently signed an exclusive licensing agreement with Keros Therapeutics to further develop, manufacture and commercialize elritercept worldwide outside of mainland China, Hong Kong and Macau. The agreement is subject to customary closing conditions, including completion of antitrust reviews. “Takeda has established an exciting, late-stage pipeline of transformative therapies that we believe will deliver value to our company and, most importantly, to the patients we serve around the world,” said Andy Plump, president of R&D at Takeda. “As we continue scaling our capabilities and maximizing R&D investment to deliver the late-stage pipeline, we are also progressing an exciting early-stage pipeline, supporting a cutting-edge research organization, and focusing on creative business development across our therapeutic areas to sustain Takeda’s future and continue to meet significant unmet patient needs.” 2024 R&D Day Agenda The meeting includes the following presentations and speakers: A Global, Innovation-Driven Biopharmaceutical Company Christophe Weber, President & CEO R&D Strategy and Pipeline Highlights Andy Plump, President, Research and Development Neuroscience: Deep-Dive on Orexin Franchise Sarah Sheikh, Head of Neuroscience Therapeutic Area Unit and Head of Global Development Ramona Sequeira, President of Global Portfolio Division Gastrointestinal and Inflammation: Deep-Dive on Zasocitinib, Rusfertide, Mezagitamab, Fazirsiran Chinwe Ukomadu, Head of Gastrointestinal and Inflammation Therapeutic Area Unit Ramona Sequeira, President of Global Portfolio Division Oncology: Deep-Dive on Elritercept – Newly Announced Business Development Deal Teresa Bitetti, President Global Oncology Business Unit P.K. Morrow, Head of Oncology Therapeutic Area Unit Webcast Details A live webcast of the meeting begins at 8:30 a.m. JST December 13 (6:30 p.m. EST December 12). Presentations are available on the Investor Relations section of Takeda’s website where a video replay will be available following the meeting. About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com . Important Notice For the purposes of this notice, “press release” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. This press release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this press release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This press release is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws. The companies in which Takeda directly and indirectly owns investments are separate entities. In this press release, “Takeda” is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words “we”, “us” and “our” are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies. Forward-Looking Statements This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could”, “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof. These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations, including global health care reforms; challenges inherent in new product development, including uncertainty of clinical success and decisions of regulatory authorities and the timing thereof; uncertainty of commercial success for new and existing products; manufacturing difficulties or delays; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s); and other factors identified in Takeda’s most recent Annual Report on Form 20-F and Takeda’s other reports filed with the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/sec-filings-and-security-reports/ or at www.sec.gov . Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results. Peak Sales and PTRS Estimates References in this press release to peak revenue potential ranges are estimates that have not been adjusted for probability of technical and regulatory success (PTRS) and should not be considered a forecast or target. These peak revenue potential ranges represent Takeda’s assessments of various possible future commercial scenarios that may or may not occur. References in this press release to PTRS are to internal estimates of Takeda regarding the likelihood of obtaining regulatory approval for a particular product in a particular indication. These estimates reflect the subjective judgment of responsible Takeda personnel and have been approved by Takeda’s Portfolio Review Committee for use in internal planning. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. Elritercept license agreement Elritercept is included for reference only. Takeda entered into an exclusive license agreement with Keros for global rights, in all territories outside of mainland China, Hong Kong and Macau, to Elritercept. The closing of the transaction is subject to receipt of regulatory approval(s), expected in the first calendar quarter of 2025. Takeda does not currently have rights to Elritercept. ___________________________ 1 References in this presentation to peak revenue potential are estimates that have not been adjusted for probability of technical and regulatory success (PTRS) and should not be considered a forecast or target. These peak revenue ranges represent Takeda’s assessments of various possible future commercial scenarios that may or may not occur.

12月4日，益方生物发布公告：公司宣布在近日完成D-2570针对银屑病的二期临床试验并取得积极的结果。 D-2570是益方生物自主研发的一款靶向TYK2的新型口服选择性抑制剂，用于治疗银屑病等自身免疫性疾病。D-2570的二期之所以值得引起市场重视，基于其所处赛道的潜在巨大市场空间，以及其展现的Best in class潜力。 过去JAK家族上市药物除了初代的JAK抑制剂，主要以泛JAK抑制剂、迭代高选择抑制剂为主，这两个策略前者获得治疗领域拓宽的同时不可避免出现较大毒性问题，后者虽降低了初代JAK抑制剂的副作用问题但还是难逃FDA的黑框警告。 TYK2是JAK家族中的“异类”，TYK2在调节IL-23、IL-12和1型IFN等细胞因子时，其它细胞因子不会受到影响（几乎只影响免疫相关信号传导），同时新一代TYK2变构抑制剂可靶向TYK2的“假激酶”调控域JH2能够高选择性地抑制TYK2，从而不影响其他JAK激酶活性有效避免毒副作用，这在治疗自免疾病中尤为重要。值得注意的是，已经获批TYK2抑制剂BMS的氘可来昔替尼是全球唯一一个不带黑框的JAK家族抑制剂，2023年上市首年卖出1.7亿美元，BMS预测其销售峰值有望达到40亿美元。 由此，TYK2靶点药物也成了MNC巨头购物清单中的重点目标之一，大额BD交易频出，益方生物D-2570二期数据一出，BD预期日愈强烈。 01 TYK2大额交易频出 在众多“带着黑框”的JAK抑制剂前辈的商业化光芒下（2023年芦可替尼、乌帕替尼销售额分别为43美元、39.7亿美元），相信潜在安全性更佳的TYK2抑制剂市场潜力无用赘叙。 近年来，全球TYK2抑制剂的BD交易频发，高光制药就临床前阶段TYK2/JAK1抑制剂与Biohaven达成授权合作的总金额近10亿美元，武田选择以“天价”60亿美元（其中40亿美元首付款）收购Nimbus当时处于二期临床的潜在同类最佳TYK2抑制剂，更早实现TYK2抑制剂授权的海思科已经在稳定收取Alumis稳定推进海外临床带来的数千万美元里程碑。 尽管以氘可来昔替尼为代表的TYK2抑制剂具备较其他JAK家族靶点抑制剂安全性更佳、口服依从性强等的优点，但在市场看来TYK2抑制剂的疗效优势相比IL-17A等生物制剂“不够明显”。 于是氘可来昔替尼的“Me better”受到市场欢迎，Nimbus卖给武田的TYK2抑制剂TAK-279便是Fast follow或Me better策略的产物。从TAK-279的中重度银屑病二期临床数据分析（该临床设计与氘可来昔替尼的二期研究IM011-011趋近），15mg组患者12周达到PASI 75为67.9%、PASI 90为45.3%，PASI 100为15.1%，最高剂量30mg组患者相比15mg组PASI 100数值上更高为32.7%。（氘可来昔替尼二期数据PASI 75、PASI 90、PASI 100患者比例分别为67%-75%、43%-44%、9%-25%）如果不考虑IM011-011研究43%的生物制剂经治患者比例高于TAK-279二期研究，那么其二期临床的疗效接近氘可来昔替尼。 TAK-279暂时从二期的临床数据层面没有让市场找到其强于氘可来昔替尼的验证或其达成60亿美元价值，市场在期待更强的TYK2抑制剂出现，去打破其创造的BD记录。 02 D-2570，Best in class潜力十足 天命人会是D-2570吗？ 益方生物公布的D-2570二期数据，让投资者看到了“Best in class”的潜力，同时其在国产TYK2抑制剂研发进度层面处于领先者的位置。 和BMS的氘可来昔替尼走的路线一样，D-2570是靶向TYK2假激酶结构域JH2部位的新型TYK2抑制剂，以此来避免产生与JAK1-3抑制剂相关的毒性。D-2570通过抑制TYK2激酶的活性，进而阻断TYK2依赖的细胞因子信号传导介导的STAT蛋白的磷酸化，抑制炎症因子释放，参与免疫调节。 D-2570临床前研究数据显示，一方面D-2570的口服生物利用度较高，另一方面对JAK1的选择性高达近1000倍，预示在临床上会有更大的安全窗口。 同样氘可来昔替尼对JAK1的JH1选择性较好，D-2570这样设计主要原因可能是高选择性JAK1抑制剂会减少了抑制其他JAKs可能带来的潜在风险，降低炎症因子的产生，从而改善自身免疫性疾病的症状和体征，增加了治疗药物安全性。 （图源：兴证医药） D-2570最新公布的治疗中重度银屑病临床二期显示，161名患者分为中、低、高三个剂量组，12周后三个剂量组PASI 75应答率为85.0%-90.0%（安慰剂组为12.5%），PASI 90应答率为70.7%-77.5%（安慰剂组为5.0%），PASI 100应答率为39.0%-50.0%（安慰剂组为2.5%），sPGA 0/1应答率（皮损完全清除或基本清除）为80.5%-87.5%（安慰剂组为20.0%）。 目前尚不清楚益方生物最大爬坡剂量为多少毫克，但基于临床前数据其安全窗口较大；该项临床试验中，益方生物尚未公布161名患者中有多大比例的生物制剂经治患者（临床招募和数据发布电话会议明确有生物制剂经治患者）。单从D-2570展现的疗效数据分析（非头对头临床比较，供参考），其二期疗效显著优于氘可来昔替尼、TAK-279，说是潜在“Best in class”TYK2抑制剂丝毫没有问题。 安全性方面，观察到的治疗期间不良事件（TEAE）绝大多数为一级或二级，三级以上非常少，没有四级事件和严重不良反应（SAE）。12周治疗期后没有病人停药，未来有更长时间观察长期安全性。 D-2570现有的PASI 75、PASI 90、PASI 100、sPGA 0/1应答率的疗效数据已经媲美现有疗效最佳的IL-17A生物制剂，结合D-2570作为TYK2抑制剂自身的口服、安全性优势，未来出海价值拉满。 03 益方生物价值或严重低估 益方生物作为潜在同类最佳TYK2抑制剂D-2570的创新Biotech，其现有68.29亿市值显然是严重低估的。 除了D-2570之外，目前公司已商业化管线有第三代EGFR贝福替尼，KRAS G12C抑制剂D-1553已经处于NDA阶段（国产第二款），口服选择性ER降解剂D-0502处于临床三期（进度领先）和URAT1抑制剂D-0120处于二期临床。 从管线梯队来看，益方生物短期内存在商业化放量的预期填充，中长期也具备有核心竞争力的管线催化，不仅布局非常紧凑，而且发展后劲十分足。 首先分析贝福替尼，尽管第三代EGFR抑制剂在国内有红海格局化的趋势，但益方生物的合作伙伴贝达药业在肺癌领域和EGFR抑制剂赛道有很强的商业化能力，贝达药业的埃克替尼在2023年销售额仍维持在10亿以上，综合考虑到贝达药业将部分埃克替尼转化为贝福替尼和贝福替尼进入医保后的放量，保守估计销售峰值达到10-15亿相对合理，结合益方生物15%的销售分成对应1.5-2.25亿利润。 KRAS G12C抑制剂D-1553距离商业化临门一脚，这个赛道虽然是个“乱局”（三家国产前后商业化），但初始市场不小并且鹿死谁手尚未可知。在KRAS G12C抑制剂获批前，国内缺乏针对KRAS G12C突变的治疗手段（以PD-1和化疗为主），同时KRAS G12C突变占到非小细胞肺癌患者大约12%，市场并不算小。另外，益方生物国内合作伙伴是正大天晴，商业化能力过硬。方正证券测算，2030年D-1553以15%的市占率达到销售额11.58亿，结合与正大天晴合作的潜在里程碑，以及假设15-20%的销售分成，亦能获得每年稳定的利润分成。 D-0502作为国内唯一一个进入三期的口服SERD，有望享受优良竞争格局和背后乳腺癌巨大市场的蛋糕。70%的乳腺癌患者为雌激素受体阳性（ER+）乳腺癌，内分泌治疗是作为前线治疗的重要手段（SERD是其中一类常用药物，典型药物为氟维司群），而氟维司群作为专利过期药物2022年在国内院内销售仍能超过9亿元，可以判断D-0502成药后大概率也是过十亿的品种。目前，D-0502已有单药治疗ER+\HER2-的乳腺癌患者一期临床中展现出初步疗效，CBR为47.1%、ORR为15.7%。 URAT1抑制剂D-0120同样是潜在市场巨大的创新分子，其针对高尿酸血症和痛风患者，过去URAT1抑制剂实际已经得到了苯溴马隆、雷西纳德等药物的疗效验证，但真正重头戏在于安全性层面。从D-0120国内IIa期临床看到，其治疗用量不仅剂量极大低于雷西纳德的上市剂量，在4mg的剂量下即可达到200mg雷西纳德的降尿酸效果，安全性和耐受性良好（一二期均未出现肝毒性），而且在每日给药4mg剂量下患者的血尿酸达标率达80%。（当初AZ对雷西纳德寄予厚望，认为其能够超过10亿美元销售额，后因雷西纳德展现肾毒性而落下帷幕）可以说D-0120的成药有一定难度，需要通过大三期验证，但一旦成药，市场非常广阔。 结语：益方生物在手的一款商业化药物和一款即将商业化药物实际上给了公司设立了一个稳固的基本盘，即便什么都不做，公司未来都能稳定的躺着收分成。而口服SERD、URAT1抑制剂而是公司的中坚预期力量，但凡其中一个成药都将是10亿级以上的品种；而D-2570目前则是展现了BIC潜力，未来进一步的二期详细临床数据披露，其BD交易价值起步在10亿美元以上。显然，这样拥有优良管线储备和未来短期能快速见到商业化收入的创新药公司，低于百亿市值显然是被严重低估的，或许可以静待市场给出评判。 免责声明： 文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部责任。本公众号发布的各类文章重在分享，如有侵权请联系我们，我们将会删除。 联系我们 SIT 2025 展位火热预定中！ 扫码立即咨询 电话：13816031174 （同微信） 赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。 点击此处“阅读全文”咨询更多精彩