Pegzilarginase

▲10月26-27日成都中国临床试验产业发展大会免费报名 注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。 药融圈之前和大家分享了Paragon Therapeutics孵化的第一家Biotech——ApogeeTherapeutics（相关阅读：自免高热赛道“毛头小司”，一年股价涨幅曾超300%：主打长效），今天想与大家一起聊聊其孵化的第二家公司——Spyre Therapeutics。值得一提的是，虽然Paragon Therapeutics是投资机构Fairmount在2021年才创立的，但是截止2024年8月底，其已经成功孵化了四家公司，其采取的策略简单粗暴，直接针对成熟靶点开发迭代的长效抗体药物，技术上也多采用专利过期的YTE改造策略。不得不说，直到目前为止，从孵化公司的融资情况来看该策略还是比较奏效。 药融云数据，www.pharnexcloud.com：公司信息 从药融云数据库获悉，Spyre Therapeutics的成立时间可以追溯到2013年（具体缘由下面会分享），目前主要专注于开发炎症性肠病的新型单克隆抗体。Spyre Therapeutics可以说是成立于2013年底的Aeglea BioTherapeutics（专注于开发罕见代谢疾病）的救司手段，2023年6月，Aeglea宣布以换股交易的方式收购Spyre Therapeucs，交易完成后，Aeglea BioTherapeutics的股东拥有合并后公司约5.5%的股份，新公司由Aeglea和Spyre高管共同领导。在此交易之前，Aeglea BioTherapeutics正在经历临床失利和濒临破产的情况，股价从高位下跌超过95%，于是公司只得大量裁员。 药融云数据库：融资信息 合并后公司便将之前的针对罕见代谢疾病精氨酸酶1缺乏症的pegzilarginase的全球权利出售给了 Immedica Pharma，也算是正式表示其专注炎症性肠病的决心。随后公司宣布更名为Spyre Therapeucs，股价连续大涨，且在2023年和2024年分别完成了一笔1.8亿美元的融资（总计3.6亿美元）。 当前研发管线主打长效 Spyre Therapeutics的管线主要专注于炎症性肠病（IBD），IBD是一种以胃肠道炎症为特征的慢性疾病，包括溃疡性结肠炎（UC）和克罗恩病（CD）两种主要疾病。在研管线中SPY001、SPY002和SPY003均采用半衰期延长工程技术设计，SPY004则是与上述几条管线不同作用机制的单克隆抗体。目前各管线具体进展情况如下： 01 SPY001 药融云数据，www.pharnexcloud.com显示：SPY001是一种研究性新型皮下延长半衰期单克隆抗体，专为高浓度配制，可最大限度地提高诱导暴露和潜在缓解率，并实现不频繁的皮下维持给药，主要靶向整合素α4β7。整合素作为一类重要的细胞表面粘附分子，是直接介导白细胞迁移运动的重要蛋白，与炎症反应关系密切。整合素α4β7主要表达在淋巴细胞表面，负责介导淋巴细胞从血液循环进入肠道和中枢神经系统，其功能的异常与人类自身免疫疾病密切相关，如溃疡性结肠炎、克罗恩病等。在头对头的临床前研究中，SPY001在阻断MadCAM-1粘附方面显示出与vedolizumab（注射用维得利珠单抗）相当的效力，并且显示出明显更长的半衰期，有可能每两三个月才需要给药一次。 2024年6月18日，Spyre Therapeutics宣布已开始SPY001的临床试验1期研究，该临床试验1期研究是一项针对健康志愿者的双盲、安慰剂对照试验，预计将招募48名健康志愿者，包括至少四个单次递增剂量（SAD）队列和两个多次递增剂量（MAD）队列，主要终点是安全性，次要终点是药代动力学。预计该研究的中期安全性和药代动力学数据会在2024年年底前公布，并且在等待临床试验1期研究的数据之前，公司可能会在2025年开始该管线的临床试验2期研究。 前面提到的注射用维得利珠单抗是武田制药的重磅IBD治疗药物，可特异性地抑制MAdCAM-1与α4β7整合素的结合，从而阻止免疫细胞定向迁移到肠道黏膜，缓解炎症性肠病的症状。2014年在美国和欧洲上市以来销售增长强劲，是武田最畅销的产品之一。 截图自：武田财报 从武田2023年4月~2024年3月的财年年报来看，消化道是公司营收的主要来源，Entyvio（注射用维得利珠单抗）作为消化道产品管线的支柱产品，全年营收8009亿日元（约合美元55亿），占公司合并收入的19%。 02 SPY002 阻断TL1A与其同源受体DR3的相互作用已被证明可以改善CD和UC患者的疾病进程。SPY002是一种靶向TL1A的新型延长半衰期的全人lgG1单抗，对TL1A各种亚型都具有亚纳摩亲和力，可以有效抑制TL1A介导的信号传导。 2024年2月，Spyre Therapeutics在第19届年度ECCO大会上公布了SPY002主要开发候选药物的临床前数据，证明了其在非人灵长类动物（NHP）中的亚纳摩尔结合亲和力和效力，以及24天的药代动力学半衰期，与临床阶段的抗TL1A相比增加了两到三倍。预计在2024年下半年开始对两个SPY002候选药物进行FIH（首次人体试验），2025年上半年获得健康志愿者的中期数据。如果成功，公司预计一个SPY002候选药物将进入进一步的临床开发。 2023年4月，默克通过以108亿美元的价格收购了自免公司Prometheus Biosciences，以进军免疫疾病治疗市场，通过该收购也获得了靶向TL1A的药物——MK-7240，此外，Roivant Sciences（RVT-3101）和梯瓦制药（TEV-48574）也在加紧自家管线的研发进程。与上述三种临床阶段的管线相比，SPY002在NHP中的半衰期延长，也具有不需要频繁通过皮下给药的优势。 03 SPY003 SPY003是一种靶向IL-23的p19亚基的高效选择性的研究性单克隆抗体。预计在2024年下半年启动IND赋能研究，并于2025年上半年启动FIH试验。值得一提的是，IL-23也是艾伯维的Skyrizi（利生奇珠单抗）和强生公司的Tremfya（古塞奇尤单抗）靶向的蛋白质。 基于现有优质管线开展联合用药 α4β7抑制是胃肠病学家首选的一线治疗选择，因为它具有良好的安全性和肠道选择性作用机制，并且在VARSITY研究中显示出优于TNF抑制的疗效，Deanna Nguyen博士（Spyre Therapeutics临床开发高级副总裁）表示这种独特的安全性和有效性特征，结合更方便的给药频率，可以使SPY001成为IBD联合治疗的理想骨干，同时抑制其他高活性机制，包括T1LA和IL-23。 注：VARSITY研究是武田开展的一项随机双盲双模拟全球多中心的临床试验3b期研究，旨在比较维多珠单抗（静脉注射）与阿达木单抗（皮下注射）在治疗中度-重度活动性溃疡性结肠炎患者中，在第52周时的有效性与安全性。 根据最近关于与第三方产品联合疗法治疗IBD的研究结果，公司目前正在开展下一代单克隆抗体的联合治疗研究，目前正在临床前研究的联合疗法包括：（1）SPY120：SPY001和SPY002联合；（2）SPY130：SPY001和SPY003联合；（3）SPY230：SPY002和SPY003联合。 财务状况 2023年度Spyre Therapeutics研发费用为8950万美元，而上年同期只有5858万美元，这一增长主要与公司IBD产品线的临床前开发和生产费用的增加有关；一般和行政费用为3995万美元，上年同期为2853万美元；其他费用为9651万美元；2023年度净亏损6320万美元。 2024年上半年研发费用为6760万美元；一般和行政费用2440万美元；其他收入930万美元；净亏损8270万美元。分季度来看，2024年第二季度研发费用总额为3260万美元，上年同期为1740万美元，这一增长是由公司IBD产品线的临床前和临床开发和生产费用推动的，部分被与公司传统罕见病产品线相关的费用减少以及Paragon Therapeutics与SPY003开发成本相关的非经常性损益所抵消。一般和行政费用总额为1150万美元，上年同期为1210万美元。其他收入共计530万美元，主要受公司现金和有价证券所赚取的利息推动。净亏损3880万美元，而上年同期则高达2.171亿美元。 截至2024年6月30日，Spyre Therapeutics的可用现金和现金等价物、有价证券和限制性现金为4.263亿美元，当前的资金状况预计将足以支持公司继续运营到2027年。截止2024年8月26日，Spyre Therapeutics公司市值13.71亿美元。8月30日，收盘市值为14.60亿美元。 参考： NMPA/CDE； 药融云数据，www.pharnexcloud.com； FDA/EMA/PMDA； 相关公司公开披露（除标注外，正文图片均来自企业官网）； https://spyre.com/； https://mp.weixin.qq.com/s/qkg1Cd55pgHvqPGJVORKwQ； https://mp.weixin.qq.com/s/rKoixewPMhk32GT0Z2Ab2A； https://assets-dam.takeda.com/image/upload/Global/Investor/ASR/Y2023/E_FY23_ASR.pdf； https://www.medsci.cn/article/show_article.do?id=29ed18026114； https://mp.weixin.qq.com/s/8d_bNiG15Q_HySJJDEugeQ；等等。  本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐 【关于药融圈】 药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

Announced corporate name change to Spyre Therapeutics; appointment of Cameron Turtle, DPhil, as Chief Executive Officer; and began trading on Nasdaq under the symbol "SYRE" SPY001, an anti-α4β7 antibody engineered for infrequent, subcutaneous dosing, demonstrated an updated half-life of 22 days, a greater than three-fold increase relative to vedolizumab in non-human primate pharmacokinetic data recently presented at ECCO; remains on track to begin first-in-human studies in the first half of 2024, with interim proof-of-concept data expected year-end 2024 SPY002, an anti-TL1A antibody designed for enhanced potency to both TL1A monomers and trimers, and extended half-life compared to existing molecules, remains on track to begin first-in-human studies in the second half of 2024 Raised $180 million in private placement equity financing with participation from new and existing investors $340 million of cash, cash equivalents, marketable securities, and restricted cash as of December 31, 2023, with expected runway into the second half of 2026, through multiple clinical readouts WALTHAM, Mass., Feb. 29, 2024 /PRNewswire/ -- Spyre Therapeutics, Inc. ("Spyre" or the "Company") (NASDAQ:SYRE), a biotechnology company advancing a pipeline of investigational antibody therapeutics with the potential to transform the treatment of inflammatory bowel disease ("IBD"), today announced its fourth quarter and full year 2023 financial results and provided program and corporate updates. "In 2023, we built the foundation required to advance our mission of creating IBD therapies that provide meaningful improvements in both efficacy and convenience compared to today's standard of care. Beginning with a highly unique portfolio of three promising drug candidates to what we consider the most critical targets in IBD, including α4β7, TL1A, and IL-23, we capitalized the company with nearly $400 million from top-tier investors while also attracting a talented and passionate management team and Board of Directors," said Cameron Turtle, DPhil., Chief Executive Officer. "As we look forward to 2024, our ambitions will come into focus as we enter clinical studies across multiple programs and begin to demonstrate potential best-in-class properties of our investigational medicines. We anticipate initiating Phase 2 evaluation of rational therapeutic combinations in IBD patients in 2025." Development Pipeline Overview and Update The Company's approach combines best-in-class antibody engineering, rational therapeutic combinations, and precision immunology with the goal of maximizing efficacy, safety, and convenience of its IBD treatments under development. IBD is a chronic condition characterized by inflammation within the gastrointestinal tract, including two main disorders: ulcerative colitis ("UC") and Crohn's disease ("CD"). In the United States, it is estimated that approximately 2.4 million individuals are diagnosed with IBD. The Company has four programs in preclinical development, three of which are targets in IBD validated by third parties. The fourth program is a novel, undisclosed target. The Company is also researching rational combinations of its therapeutic antibody product candidates to target IBD. All three validated targets offer the potential for effective and safe treatment of UC and CD as a monotherapy or in combination, with the potential advantage of infrequent subcutaneous dosing. SPY001 – a highly potent and selective investigational anti-α4β7 monoclonal antibody engineered with half-life extension technology and formulated for high concentration and subcutaneous, infrequent dosing. In the third quarter of 2023, the Company selected the SPY001 development candidate, which is currently progressing through IND-enabling studies and is expected to enter first-in-human ("FIH") studies in the first half of 2024. In February 2024, expanded preclinical data for SPY001 was presented at the 19th Annual Congress of the European Crohn's and Colitis Organisation (ECCO), including head-to-head non-human primate pharmacokinetic data showing an updated half-life of 22 days, a greater than three-fold increase relative to vedolizumab. This data further supports our target human half-life for SPY001 of more than 35 days predicted by allometric scaling. Interim data from a healthy volunteer study are expected by the end of 2024. The Company expects pharmacokinetic data to demonstrate proof of concept for SPY001 to potentially be dosed subcutaneously in an every-eight-week or every-twelve-week dosing interval. SPY002 – a highly potent, selective, half-life extended, anti-TL1A investigational monoclonal antibody with potential best-in-class subnanomolar binding affinity for both the monomer and trimer forms of the target. The Company believes TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. The Company has nominated two lead SPY002 development candidates and exercised its option to exclusively license related intellectual property rights under its agreement with Paragon Therapeutics. The Company's lead candidates bind both TL1A monomers and trimers and have in vitro subnanomolar potency and pharmacokinetic half-lives that potentially exceed all clinical-stage TL1A antibodies. In February 2024, preclinical data for a lead SPY002 development candidate was presented at the 19th Annual ECCO Congress demonstrating subnanomolar binding affinity and potency, as well as a pharmacokinetic half-life of 24 days in non-human primates, which represents a two to three-fold increase compared to clinical-stage anti-TL1As. The Company expects to begin FIH studies of one or both SPY002 candidates in the second half of 2024 with healthy volunteer interim data expected in the first half of 2025. If successful, one SPY002 candidate would then advance into additional clinical development. SPY003 – a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of IL-23 engineered with half-life extension technology. The Company continues preclinical development efforts on a potential best-in-class IL-23 monoclonal antibody. Recent data from the Phase 3 SEQUENCE study of risankizumab versus ustekinumab in Crohn's disease validates the Company's targeting of the p19 subunit as it demonstrated superiority to targeting the p40 subunit common to IL-12 and IL-23. The Company expects to nominate a development candidate in mid-2024 and move into IND-enabling studies in the second half of 2024. Recent Corporate Updates In February 2024, the Company announced the appointment of Mark C. McKenna, former Chairman, President and CEO of Prometheus Biosciences, Inc., to its Board of Directors. Mr. McKenna's track record of corporate leadership, product development, and value creation will be instrumental to guide the Company as it advances its potentially best-in-class IBD portfolio. In December 2023, the Company announced $180 million in gross proceeds from a private placement equity financing with broad participation from both new and existing investors, extending cash runway into the second half of 2026. In November 2023, the Company announced its name change to Spyre Therapeutics and the appointment of Cameron Turtle as Chief Executive Officer and also a member of the Company's Board of Directors. The Company also announced the appointments of industry veterans Jeffrey Albers and Laurie Stelzer to its Board of Directors. In November 2023, the Company held a Special Meeting of Stockholders wherein all four proposals were approved, including the conversion of the Company's Series A Preferred Stock to common stock and an increase to the Company's authorized shares. Fourth Quarter 2023 Financial Results Cash Position: As of December 31, 2023, Spyre had available cash and cash equivalents, marketable securities, and restricted cash of $339.6 million. Net cash used in operating activities was $31.0 million for the fourth quarter of 2023. In December 2023, the Company raised $180.0 million in gross proceeds, before deducting $10.9 million in placement agent fees and other offering costs, from a private placement of equity securities. Research and Development (R&D) expenses: R&D expenses totaled $33.7 million for the fourth quarter of 2023 and $14.3 million for the fourth quarter of 2022. The increase was primarily related to increases in preclinical development and manufacturing expenses for the Company's IBD pipeline including expenses related to the annual equity grant under our agreement with Paragon, partially offset by a decrease in expenses associated with the Company's legacy rare disease pipeline. General and Administrative (G&A) expenses: G&A expenses totaled $14.1 million for the fourth quarter of 2023 and $5.1 million for the fourth quarter of 2022. This increase was primarily due to an increase in stock compensation expense, as well as legal and other professional service fees related to the Spyre acquisition. Gain on Sale of In-Process Research & Development Asset: During the fourth quarter of 2023, the Company recognized an additional $1.8 million gain on the sale of the global rights of pegzilarginase driven by the receipt of a cash reimbursement from Immedica for a previous expenditure. Other (expense) income: Other (expense) income for the fourth quarter totaled $17.3 million expense primarily driven by an increase in the Company's CVR liability related to the increased likelihood of certain milestone payments related to pegzilarginase reimbursement in European markets, partially offset by interest earned on the Company's cash and marketable securities. Net Loss: Net loss totaled $63.2 million and $18.8 million for the fourth quarters of 2023 and 2022, respectively, which includes non-cash stock compensation expense of $17.3 million and $1.4 million for the fourth quarters of 2023 and 2022, respectively. About Spyre Therapeutics Spyre Therapeutics is a biotechnology company that aims to create the next-generation of inflammatory bowel disease (IBD) products by combining best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, please visit . Follow Spyre Therapeutics on social media: @spyretx and LinkedIn. Safe Harbor / Forward Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical fact are forward-looking statements. These forward-looking statements include statements regarding the Company's future results of operations and financial position, business strategy, including the Company's potential success of developing therapeutics for IBD, the sufficiency of the Company's funding to support the development of its assets, the length of time that the Company believes its existing cash resources will fund its operations, its market size, its potential growth opportunities, its preclinical and future clinical development activities, including the expected timing of nomination of development candidates and submission of investigational new drug applications, the efficacy and safety profile of its product candidates, the potential therapeutic benefits and economic value of its product candidates, the timing and results of preclinical studies and clinical trials, including the commencement of FIH studies, the timing of data and whether the data demonstrates proof of concept, and the Company's planned regulatory activities including filing of INDs to support development and potential commercialization of product candidates. The words "believe," "may," "will," "potentially," "estimate," "continue," "anticipate," "predict," "target," "intend," "could," "would," "should," "project," "plan," "expect," the negatives of these terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including the expected or potential impact of macroeconomic conditions, including inflationary pressures, rising interest rates, general economic slowdown or a recession, changes in monetary policy, the prospect of a shutdown of the U.S. federal government, volatile market conditions, financial institution instability, as well as geopolitical instability, including the ongoing military conflict in Ukraine, conflict in Israel and surrounding areas, and geopolitical tensions in China on the Company's operations, the potential impacts of the BIOSECURE Act bill if passed into law and those risks described in the Company's Quarterly Reports on Form 10-Q, Annual Reports on Form 10-K, as well as in other filings and reports that the Company makes from time to time with the Securities and Exchange Commission. Moreover, the Company operates in a very competitive and rapidly changing environment, and new risks emerge from time to time. It is not possible for the Company's management to predict all risks, nor can the Company assess the impact of all factors on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements it may make. In light of these risks, uncertainties, and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. The Company undertakes no obligation to update publicly any forward-looking statement for any reason after the date of this press release to conform these statements to actual results, to reflect changes in the Company's expectations, or otherwise, except as required by law. You should read press release with the understanding that the Company's actual results, levels of activity, performance, events, outcomes, and the timing of results and outcomes, and other circumstances may be materially different from what the Company expects. SOURCE Spyre Therapeutics, Inc.