Granulocyte-macrophage colony-stimulating factor(Emergent BioSolutions, Inc.)

Results of a prospective, randomized, placebo-controlled study of inhaled Leukine® in non-hospitalized patients at risk for severe COVID-19 LEXINGTON, Mass., Dec. 20, 2023 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx) announced today that Open Forum Infectious Diseases recently published the results from the SCOPE study (doi.org/10.1093/ofid/ofad500.351).1 These data were also presented at IDWeek 2023. The study was a prospective, multicenter study of 600 non-hospitalized COVID-19 patients randomized to receive either inhaled Leukine® (sargramostim; yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) or placebo. SCOPE included patients diagnosed with symptomatic mild/moderate COVID-19 who were at high risk for progression to severe disease. Of the 600 patients, 93 were vaccinated. Inhaled sargramostim, administered daily for five days, was well tolerated, no cytokine changes were observed, and adverse events were generally similar across both arms. The primary study endpoint was to determine if inhaled sargramostim could prevent progression to more severe disease as determined by any emergency room visit, hospitalization, or death by day 28. No difference was found in the primary endpoint between treatment arms. However, the sargramostim arm had a greater reduction in overall symptom score (a secondary endpoint) than the placebo arm. Results of prior studies of sargramostim in patients hospitalized with COVID-192,3 showed inhaled sargramostim plus standard of care led to greater improvement in P(A–a)O2, a measure of oxygenation, compared to standard of care alone. Exploratory analyses of a biomarker cohort (n=101, containing both vaccinated and unvaccinated patients) revealed potential immunomodulatory effects of sargramostim. Humoral and cellular immune signatures adjust to a multiplying SARS-CoV-2 viral load during the progression from mild to severe COVID-19.4,5 SCOPE investigators observed that treatment with inhaled sargramostim enhanced SARS-CoV-2 viral load clearance, modulated the humoral kinetics and magnitude against SAS-CoV-2 antigens, and suggested enhanced IgG4 expression and FcGR2B binding.2 The effect of sargramostim on humoral immune response was more pronounced in patients who have received a COVID-19 vaccination. The translational data from this study show modulation of humoral immunity with sargramostim treatment. Ila Joshi, Ph.D., Director of Biology, Pre-Clinical and Translational Research and Development at PTx observed, "The exploratory results from the biomarker cohort provide evidence of the potential for sargramostim to act as a virus-agnostic, host-directed immunomodulator. The combined effect of sargramostim and a COVID-19 vaccination observed on the humoral response, humoral kinetics, and viral load highlight a synergistic immune response against virus-specific antigens." This effort was funded by the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) under project agreement MCDC2006-012. Included references to commercial products do not constitute an endorsement by the U.S. Defense Department or the JPEO-CBRND. Leukine® is not approved to treat COVID-19. ABOUT IDWEEK IDWeek is the joint annual meeting of the Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, the HIV Medicine Association, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. IDWeek 2023 was held October 11-15, 2023, in Boston. ABOUT Leukine® Leukine® (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. Leukine® is indicated: To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia. For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients. For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients two years of age and older. For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients two years of age and older. For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients two years of age and older. To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome). Important Safety Information for Leukine® (sargramostim) Contraindications Do not administer Leukine® to patients with a history of serious allergic reaction, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factor, sargramostim, yeast-derived products, or any other component of Leukine®. Warnings and Precautions Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with Leukine®. If a serious allergic or anaphylactic reaction occurs, immediately discontinue Leukine® therapy, and institute medical management. Discontinue Leukine® permanently for patients with serious allergic reactions. Leukine® can cause infusion-related reactions that may be characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease; dose adjustment or discontinuation may be needed. Leukine® should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy. Edema, capillary leak syndrome, and pleural or pericardial effusions have been reported in patients after Leukine® administration. Leukine® should be used with caution in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure. Such patients should be monitored. Supraventricular arrhythmia has been reported in uncontrolled studies during Leukine® administration, particularly in patients with a history of cardiac arrhythmia. Use Leukine® with caution in patients with preexisting cardiac disease. If absolute neutrophil count > 20,000 cells/mm3 or if white blood cell counts > 50,000/mm3, Leukine® administration should be interrupted, or the dose reduced by half. Monitor complete blood counts with differential twice per week. Discontinue Leukine® therapy if tumor progression, particularly in myeloid malignancies, is detected during Leukine® treatment. Treatment with Leukine® may induce neutralizing anti-drug antibodies. Use Leukine® for the shortest duration needed. Avoid administration of solutions containing benzyl alcohol (including Leukine® for injection reconstituted with Bacteriostatic Water for Injection, USP [0.9 % benzyl alcohol]) to neonates and low birth weight infants. Drug Interactions Avoid the concomitant use of Leukine® and products that induce myeloproliferation. Monitor for clinical and laboratory signs of excess myeloproliferative effects. Adverse Reactions Adverse events occurring in >10% of patients receiving Leukine® in controlled clinical trials and reported at a higher frequency than in placebo patients are: In recipients of autologous bone marrow transplantation–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder. In recipients of allogeneic blood and marrow transplant–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, gastrointestinal hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin. In patients with acute myeloid leukemia–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema. ABOUT PARTNER THERAPEUTICS Partner Therapeutics, Inc., an integrated biotechnology company, focuses on development and commercialization of late-stage therapeutics to improve health outcomes in treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit . ABOUT THE JPEO-CBRND The Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) mission is to provide an integrated layered chemical, biological, radiological, and nuclear defense capabilities to the Joint Force across combined Joint All-Domain Operations. JPEO-CBRND's goal is to enable the Joint Force to fight and win unencumbered by a CBRN environment. To learn more about JPEO-CBRND, visit: , or follow JPEO-CBRND on social media @JPEOCBRND. References: 1 Joshi I, Garner F, Roychowdhury DF, et al. Inhaled Sargramostim (rhu GM-CSF) Leads to Enhanced SARS-CoV-2 Virus-Specific Immune Response and Viral Clearance: Results of the Biomarker Cohort of a Randomized, Double-Blind, Placebo-Controlled Phase 2b Trial in Non-Hospitalized Patients with COVID-19. Open Forum Infectious Diseases. 2023;10(Supplement 2). doi:10.1093/ofid/ofad500.351 2 Paine R, Chasse R, Halstead ES, et al. Inhaled Sargramostim (Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor) for COVID-19-Associated Acute Hypoxemia: Results of the Phase 2, Randomized, Open-Label Trial (iLeukPulm) [published online ahead of print, 2022 Dec 2]. Mil Med. 2022;188(7-8):e2629-e2638. doi:10.1093/milmed/usac362 3 Bosteels C, Van Damme KFA, De Leeuw E, et al. Loss of GM–CSF–Dependent Instruction of Alveolar Macrophages in COVID–19 Provides a Rationale for Inhaled GM–CSF Treatment. Cell Rep Med. 2022:100833. doi: 10.1016/j.xcrm.2022.100833 4 Galipeau Y, Greig M, Liu G, Driedger M, Langlois MA. Humoral Responses and Serological Assays in SARS-CoV-2 Infections. Front Immunol. 2020;11:610688. Published 2020 Dec 18. doi:10.3389/fimmu.2020.610688 5 Zhou X, Ye Q. Cellular Immune Response to COVID-19 and Potential Immune Modulators. Front Immunol. 2021;12:646333. Published 2021 Apr 30. doi:10.3389/fimmu.2021.646333 SOURCE Partner Therapeutics, Inc.

近几个月来，公开募资的生物技术公司的市值急剧下降，而私营公司继续吸引资金，并正在获得技术许可以及扩大员工人数。随着经济放缓，公司通常会放弃早期项目，专注于更先进的潜在候选产品。这些变化将开始影响对CDMO 服务的需求。并购市场也可能受到进一步影响，因为已经有些CDMO 处于最佳收购位置。这里，让我们看看最近的一些交易以及哪些公司可能会在这里范围内。最近一些值得关注的交易过去一年的大部分投资活动都集中在细胞和基因治疗(CGT) 领域。事实上，仅在过去 9 个月内就有近 20 家CGT CDMO被收购。其中一些交易来自典型的生物药公司，但正在CGT 领域扩大能力和产能。例子包括 WuXi Advanced Therapies 收购OXGENE 以及 ArchiMed 收购质粒 DNA 生产商Xpress Biologics。其它一些更有趣，例如 Recipharm 收购微生物组 CDMO Arranta Bio 以及病毒载体CDMO Vibalogics，这使该公司从传统的小分子和无菌生产进入了CGT 领域。SK Inc.（SK pharmteco 是 SK CDMO 业务控股公司，总部位于加利福尼亚，其包括 AMPAC Fine Chemicals、SK biotek、SK biotek Ireland 和 Yposkesi）在突破性药物中心 (CBM) 的3.5 亿美元投资也值得注意。CBM 将利用股权融资创建它所声称的全球最大的、涵盖质粒 DNA、病毒载体和 CGT 生产的端到端细胞和基因治疗CDMO。一旦 CBM 建成，该组织可能会成为美国最大的独立团体。然而，它将面临来自 FUJIFILM Diosynth Biotechnologies 的竞争，该公司最近宣布通过与姊妹公司FUJIFILM Wako Chemicals U.S.A., Corp. 的合作，将其位于三角研究园生物工艺创新中心现有实验室的占地面积增加一倍。其它日本企业集团也很活跃。例如，旭化成（Asahi Kasei）最近收购了 Bionova。AGC Biologics 从Novartis Gene Therapies购买了位于科罗拉多州Longmont的最先进的 CGT 商业生产设施。JSR Group旗下的KBI Biopharma是日本另一家大型机构；尽管它在过去几年没有达成任何交易，但它似乎可能正在考虑机会。另一家一直专注于传统生物制药领域的公司是Curia，该公司通过收购 LakePharma 和 Integrity Bio 继续其扩张努力。在经济冲击的背景下所有这些最近的活动今天都必须通过当前经济状况创造的镜头来看待。最大的变化是公共资助的生物技术公司的股价大幅下跌 -在某些情况下高达 95%。5 月份有小幅反弹，但仍普遍下跌90%。然而，私营领域的情况并非如此，几乎没有出现疲软。这些组织的估值已经下降，但在上市公司中看到的 下降100 倍的情况并不存在，资金继续流入私营领域。拥有私人资金的生物技术公司继续增长，引进新技术并扩大员工人数。一个很好的例子是Inceptor Bio，它拥有三个基于 CAR-T、CAR-NK 和CAR-M 技术的平台。下一篇：关闭早期生物技术投资That's Nice 的高级治疗总监Jason Rahal 表示，经济放缓将影响内部生物制药投资，他在CDMO 生物制药和 CGT 领域拥有 25 年的经验。随着资金的减少 -继 2020 年和 2021 年的绝对爆炸式增长之后，生物技术公司正专注于其最新阶段的开发项目并将其转移到临床试验中。多个临床前和早期试验的几乎所有资金都将被撤出并转移，以支持公司在II 期的主要候选产品。大部分将停止临床前和早期临床材料的外包。这一“运动”将在 2022 年Q3/Q4和2023 年Q1/Q2真正”生效”。除此之外，如果通货膨胀继续上升，并且利率继续上升以致最优惠利率达到 6%，大多数公司债务将在 8到8.5%，并且可以预期完全关闭对 IND 前项目的生物技术投资。机会仍然很大2022 年初，交易设定了10 个收入的新上限。尽管生物技术公司估值下降，但最近 -无论是专注于老式哺乳动物和微生物技术的生物制药CDMO还是新模式的公司 - 收购了年收入为 2-5百万美元的企业，以15-20 的收入出售。这与生物技术市场的发展方式完全不成比例，但机会显然是巨大且具有爆炸性的。生命科学产业仍然很“性感”一个保持特别强劲的行业是生命科学行业。在考虑经济上下波动期间个人投资的总体趋势时，这是有道理的。当经济强劲、利率低时，人们更愿意承担风险以获得更高的收益，并投资于新想法和创新公司。然而，当经济低迷时，趋势是投资于生产基本产品的老牌公司 -一种“实体”的心态，可以说是。如今，在生物制药领域也观察到了类似的行为，这就是为什么从投资和收购的角度来看，生命科学产业仍然很有吸引力。例如，提供支持CRISPR 基因编辑和类似技术的工具和服务的公司继续获得大量资金。间充质干细胞(MSC) 和MSC 分泌的细胞外囊泡 (EV) 是另一个备受关注的前沿领域。mRNA CDMO 的激动人心的时刻COVID-19 mRNA 疫苗的成功表明该技术可以在人类身上发挥作用。因此，现在大大小小的生物制药公司都对开发基于RNA 的疗法和疫苗产生了浓厚的兴趣。这为mRNA CDMO 创造了巨大的机会。Vernal BioSciences 是第一个专门的mRNA CDMO，它是一家制造新闻的公司，最近获得了由Ampersand Capital 牵头并得到Dynamk Capital 支持的 2100 万美元投资。预计至少有两个或三个其它 CDMO 将被创建为纯 mRNA 原料药公司，这将为这一领域增添活力。不仅是mRNA，其它核酸、寡核苷酸、适体和类似的、涉及复杂化学的新模式都是新的前沿，将推动新的治疗方法，每个人都应该关注。这包括支持药物生产过程各个方面的公司，如脂质纳米颗粒(LNP) 等递送工具。Avanti Polar Lipids 是一家高纯度极性脂质制造商，产品用作复杂的下一代药物的递送系统，于2020 年 8 月被 Croda International Plc 收购。鉴于生产 COVID-19 mRNA 疫苗对这些脂质的需求，该交易恰逢其时。提供改进的 LNP 生产方法的公司也在不断涌现。一个例子是小公司 Diant Pharma，它开发了一种气流磨（jet-mil）技术，用于生产更均匀的LNP。显著降低 LNP 粒径的可变性可实现更一致的体内释放曲线。事实上，我们在这个领域看到的是，设备制造商正在与纳米颗粒辅料公司合作，而纳米颗粒辅料公司正在与原料药公司合作，所有这些目标都是为了提供最佳的mRNA 疗法和疫苗。CDMO 将在联合这些努力和将新药推向市场方面发挥关键作用。一些传统的生物药 CDMO兴奋不仅限于 mRNA，即使传统的生物制药领域已经相当成熟，有些公司也为合适的买家提供了有吸引力的机会。Emergent BioSolutions 就是其中之一。它已经损失了 90% 的市值，但作为生物防御合同商，Emergent拥有相当大的原料药和药品生产能力，其中大部分是最先进的。然而，公司的文化被打破了，唯一的出路是采用一个新的管理系统，该系统需要一个由新所有者支持的新团队运行。Emergent 2021 年的市盈率在 4 到 6 之间，而行业平均水平为20-40。估值的显著下降使该公司成为一个明显的收购目标。Goodwin Biotechnologies 是另一家公司。它成立于 30 多年前，是美国首批生物制药CDMO 之一。该公司在新产能、技术和模式方面的投资缓慢，并且难以成长为佛罗里达州领先的生物制造CDMO。尽管 Signet Healthcare 最近进行了投资，但它仍然是一家独立公司，我们预计Goodwin 将在 2023 年Q2重新焕发活力。一旦商业化产能上线，Goodwin将成为最新的目标收购机会之一。在欧洲，位于立陶宛的 Northway Biotech 也是一个明显的目标。这个组织已经存在超过15 年。除所有者外，立陶宛EDC也对该公司进行了投资。Richter-Helm 是一家生产创新产品的生物制药公司，但最近扩大了其CDMO 服务，可能对一些买家具有吸引力。回到美国，一家令人兴奋的新公司是INCOG Biopharma Services，该公司由一个在建立CDMO 并将其出售给市场领先企业（Baxter Biopharma Solutions 和Catalent）方面拥有良好记录的团队创立。INCOG 资金充足，拥有一支经验丰富的优秀管理团队。它已经与 Resilience 签署了一项协议，提供集成式工艺开发、原料药和药品生产服务。鉴于 INCOG 创始人的历史，这家公司可能会很快被收购。病毒载体 CDMO 可能也在目标范围内有几家病毒载体 CDMO 可以被视为有吸引力的收购目标。在美国，Genezen Laboratories 最近被 Ampersand Capital 收购，并正在投资进行大规模的GMP 扩建。它已经吸引了潜在买家的兴趣，并可能在2023 年出售。韩国公司 CHA Biotech 的美国 CDMO 附属公司Matica Biotechnology 刚刚在德克萨斯州开设了一家新的GMP 病毒载体工厂。在欧洲，Biomay、Biovian、FinVector、HALIX 和PlasmidFactory 都是潜在的目标。PlasmidFactory 是北美公司特别感兴趣的潜在目标，这些公司希望在欧洲站稳脚跟，建立GMP 产能。关于无菌灌装领域鉴于 COVID-19 疫苗生产合同将于 2022 年底到期，因此值得看一下无菌灌装领域的情况。这些灌装产能是专为大规模商业化灌装而设计的大容量系统。目前市场上很少有生物药产品 - 鉴于越来越关注孤儿适应症和个性化药物 - 需要如此大容量的灌装解决方案。结果，我们开始看到一些产能过剩和变化。最近一笔大交易是 PCI Pharma Services 在 2021 年底以超过 50 EBITDA 收购了新英格兰冻干服务公司(LSNE)。在美国，一家正式宣布不出售的公司是 Argonaut Manufacturing Services。在欧洲，Cenexi在多个设施中拥有相当不错的产能。在接下来的几个月中，一些较大的 CDMO 可能会收购一些具有无菌灌装产能的小型 CDMO。一旦希望为临床运行外包较小灌装量的生物制药公司意识到可用的大容量产能对其应用来说效率太低，这就会发生。本文为以下文章内容简介，详细内容，请参考原文。本文旨在知识、信息分享，转载请注明出处和原文。原文：N.Walker, Who's Left to Acquire in CDMO Biomanufacturing? A Select Few. https://www.pharmasalmanac.com/, 2022.线上培训推荐|生物制品CDMO委托全流程及转化放大专题识别微信二维码，添加生物制品圈小编，符合条件者即可加入微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。