A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of SPY002-072 in Healthy Participants

This is a Phase 1, randomized, double-blind, placebo-controlled, single-dose, first in human safety, tolerability, and pharmacokinetic study of SPY002-072 in healthy participants.

开始日期2024-10-17

申办/合作机构

Spyre Therapeutics, Inc.

[+1]

NCT06448247 / Recruiting临床1期

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of SPY001-001 in Healthy Participants

This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose, first in human safety, tolerability, and pharmacokinetic study of SPY001-001 in healthy participants.

开始日期2024-06-06

申办/合作机构

Spyre Therapeutics, Inc.

[+1]

NCT05676853 / Terminated临床3期

A Phase 3 Open-Label Study of Safety of Weekly Subcutaneous Pegzilarginase in Subjects With Arginase 1 Deficiency

This is an open-label, multicenter study to evaluate the safety of weekly SC administration of pegzilarginase over 12 months in subjects with ARG1-D. The study consists of a screening period of up to 4 weeks, a subsequent 12-month treatment period, and a Safety Follow-Up Visit 2 weeks after the last treatment.

开始日期2023-04-04

申办/合作机构

Spyre Therapeutics, Inc.

100 项与 Spyre Therapeutics, Inc. 相关的临床结果

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0 项与 Spyre Therapeutics, Inc. 相关的专利（医药）

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项与 Spyre Therapeutics, Inc. 相关的文献（医药）

2024-07-01·Pharmaceutical Research

Stability of Protein Pharmaceuticals: Recent Advances

Review

作者: Crommelin, Daan J A ; Holcomb, Ryan E ; Liu, Hongcheng ; Matsuura, James E ; Katayama, Derrick S ; Connolly, Brian D ; Payne, Robert W ; Henry, Charles S ; Stillahn, Joshua M ; Murphy, Brian M ; Manning, Mark Cornell

There have been significant advances in the formulation and stabilization of proteins in the liquid state over the past years since our previous review. Our mechanistic understanding of protein-excipient interactions has increased, allowing one to develop formulations in a more rational fashion. The field has moved towards more complex and challenging formulations, such as high concentration formulations to allow for subcutaneous administration and co-formulation. While much of the published work has focused on mAbs, the principles appear to apply to any therapeutic protein, although mAbs clearly have some distinctive features. In this review, we first discuss chemical degradation reactions. This is followed by a section on physical instability issues. Then, more specific topics are addressed: instability induced by interactions with interfaces, predictive methods for physical stability and interplay between chemical and physical instability. The final parts are devoted to discussions how all the above impacts (co-)formulation strategies, in particular for high protein concentration solutions.'

2024-02-01·eClinicalMedicine

Efficacy and safety of pegzilarginase in arginase 1 deficiency (PEACE): a phase 3, randomized, double-blind, placebo-controlled, multi-centre trial

Article

作者: Russo, Rossana Sanchez ; Sloan, Leslie S ; Diaz, George A ; Gasperini, Serena ; Enns, Gregory M ; Bubb, Gillian ; Neuman, Linda

BackgroundArginase 1 Deficiency (ARG1-D) is a rare debilitating, progressive, inherited, metabolic disease characterized by marked increases in plasma arginine (pArg) and its metabolites, with increased morbidity, substantial reductions in quality of life, and premature mortality. Effective treatments that can lower arginine and improve clinical outcomes is currently lacking. Pegzilarginase is a novel human arginase 1 enzyme therapy. The present trial aimed to demonstrate efficacy of pegzilarginase on pArg and key mobility outcomes.MethodsThis Phase 3 randomized, double-blind, placebo-controlled, parallel-group clinical trial (clinicaltrials.govNCT03921541, EudraCT 2018-004837-34), randomized patients with ARG1-D 2:1 to intravenously/subcutaneously once-weekly pegzilarginase or placebo in conjunction with their individualized disease management. It was conducted in 7 countries; United States, United Kingdom, Canada, Austria, France, Germany, Italy. Primary endpoint was change from baseline in pArg after 24 weeks; key secondary endpoints were change from baseline at Week 24 in Gross Motor Function Measure part E (GMFM-E) and 2-min walk test (2MWT). Full Analysis Set was used for the analyses.FindingsFrom 01 May 2019 to 29 March 2021, 32 patients were enrolled and randomized (pegzilarginase, n = 21; placebo, n = 11). Pegzilarginase lowered geometric mean pArg from 354.0 μmol/L to 86.4 μmol/L at Week 24 vs 464.7 to 426.6 μmol/L for placebo (95% CI: -67.1%, -83.5%; p < 0.0001) and normalized levels in 90.5% of patients (vs 0% with placebo). In addition, clinically relevant functional mobility improvements were demonstrated with pegzilarginase treatment. These effects were sustained long-term through additional 24 weeks of subsequent exposure. Pegzilarginase was well-tolerated, with adverse events being mostly transient and mild/moderate in severity.InterpretationThese results support pegzilarginase as the first potential treatment to normalize pArg in ARG1-D and achieve clinically meaningful improvements in functional mobility.FundingAeglea BioTherapeutics.

2022-12-01·Orphanet Journal of Rare Diseases2区 · 医学

Arginase 1 Deficiency: using genetic databases as a tool to establish global prevalence

2区 · 医学

ArticleOA

作者: Catsburg, C ; Anderson, S ; Bechter, M ; Upadhyaya, N

AbstractBackground/objectiveArginase 1 Deficiency (ARG1-D) is a rare inherited metabolic disease with progressive, devastating neurological manifestations with early mortality and high unmet need. Information on prevalence is scarce and highly variable due to limited newborn screening (NBS) availability, variability of arginine levels in the first days of life, and high rates of misdiagnosis. US birth prevalence was recently estimated via indirect methods at 1.1 cases per million live births. Due to the autosomal recessive nature of ARG1-D we hypothesize that the global prevalence may be more accurately estimated using genetic population databases.MethodsMEDLINE and EMBASE were systematically searched for previously reported disease variants. Disease variants in ARG1-D were annotated wherever possible with allele frequencies from gnomAD. Ethnicity-specific prevalence was calculated using the Hardy–Weinberg equation and applied to generate country-specific carrier frequencies for 38 countries. Finally, documented consanguinity rates were applied to establish a birth prevalence for each country.Results133 of 228 (58%) known causative alleles were annotated with ethnic-specific frequencies. Global birth prevalence for ARG1-D was estimated at 2.8 cases per million live births (country-specific estimates ranged from 0.92 to 17.5) and population prevalence to be 1.4 cases per million people (approximately 1/726,000 people). Birth prevalence estimates were dependent on population demographics and consanguinity rate.ConclusionBirth prevalence of ARG1-D based on genetic database analysis was estimated to be more frequent than previous NBS studies have indicated. There was a higher degree of confidence in North American and European countries due to availability of genetic databases and mutational analysis versus other regions. These findings suggest the need for greater disease education around signs and manifestations of ARG1-D, as well as more widespread testing and standardization of screening for this severe disease in order to appropriately identify patients prior to disease progression.

112

项与 Spyre Therapeutics, Inc. 相关的新闻（医药）

2024-10-30

·PRNewswire

Spyre Therapeutics to Participate in Upcoming November Investor Conferences

WALTHAM, Mass., Oct. 30, 2024 /PRNewswire/ -- Spyre Therapeutics, Inc. (NASDAQ: SYRE), a clinical-stage biotechnology company utilizing best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches to target improved efficacy and convenience in the treatment of Inflammatory Bowel Disease ("IBD"), today announced that management will participate in the following upcoming investor conferences: Event: Guggenheim's Inaugural Healthcare Innovation Conference Date: Wednesday, November 13, 2024 Time: 2:30pm ET Event: Stifel 2024 Healthcare Conference Date: Monday, November 18, 2024 Time: 1:15 pm ET Event: Jefferies London Healthcare Conference Date: Wednesday, November 20, 2024 Time: 10:30 am GMT Live audio webcasts and replays of these events will be available on the Spyre investor events website at . About Spyre Therapeutics Spyre Therapeutics is a clinical-stage biotechnology company that aims to create next-generation inflammatory bowel disease (IBD) products by combining best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches. Spyre's pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, visit Spyre's website at . Follow Spyre Therapeutics on social media: @spyretx and LinkedIn SOURCE Spyre Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2024-10-30

·药研网

康方生物PD-1/VEGF双抗：海外又有2家初创锚定

10月28日，总部位于英国的Ottimo Pharma走出隐形模式。前Seagen公司的首席执行官David Epstein，在辉瑞以430亿美元收购Seagen后，现已加入一个新的生物技术公司Ottimo Pharma。 Ottimo Pharma还任命了前罗氏高管、现任BioMarin首席商务官James Sabry为副主席，以及勃林格殷格翰的资深人士Mehdi Shahidi为首席医学官。 Ottimo Pharma在过去三年中一直致力于Jankistomig的临床前开发，Jankistomig是一种双功能抗体，靶向PD1和VEGFR2，这两种受体参与帮助肿瘤生长和逃避免疫系统的分子途径。Ottimo Pharma一直在对该分子进行全面的临床前表征，并预计在2025年底提交IND。 10月29日，GlycoMimetics宣布已与Crescent Biopharma 公司达成收购协议。交易完成后，公司计划以Crescent Biopharma的名义运营，推进旨在治疗实体瘤的肿瘤疗法。Crescent Biopharma的主导项目CR-001是一款PD-1 x VEGF双特异性抗体。 Crescent是第五家利用 Paragon Therapeutics 发现和开发的资产上市的公司。Paragon此前孵化了Apogee Therapeutics、SPYRE THERAPEUTICS、ORUKA THERAPEUTICS和JADE BIOSCIENCES多个自免药物开发上市公司。 Crescent Biopharma 管线 Crescent Biopharma注与实体瘤药物的开发，目前管线中装入了三款药物: PD-1/VEGF双抗CR-001，另外两款为拓扑异构酶的ADC药物 CR-002 和 CR-003。 CR-001是一种四价PD-1 x VEGF双特异性抗体，其形式和药理学与康方生物的ivonescimab相匹配。与目前的市场领导者pembrolizumab相比，ivonescimib具有更优的疗效。该公司预计 CR-001 的 IND 将于 2025 年Q4或 2026 年Q1提交，患者的中期 1 期数据预计将于 2026 年下半年获得。除了 CR-001，Crescent还在开发 CR-002 和 CR-003，它们是使用拓扑异构酶抑制剂有效载荷针对未公开靶点的抗体-药物偶联物 (ADC)；与具有替代有效载荷的 ADC 相比，具有拓扑异构酶抑制剂有效载荷的 ADC 显示出更高的疗效和安全性。CR-002 是 Crescent 的首个 ADC 项目，旨在成为同类最佳项目，预计将于 2026 年启动第 1 阶段；Crescent计划在项目进入临床阶段时披露 CR-002 的目标。该交易预计将于 2025 年Q2完成。预计公司交割时的现金余额将为2027年的运营提供资金，包括推进公司的主要项目 CR-001，预计在 2026 年下半年通过对实体瘤患者的初步概念验证临床数据进行推进。 PD-1/VEGF潜力巨大。去年11月，BioNTech超10亿美元引进普米斯PD-L1/VEGF双抗，2024年9月，该双抗产品PM8002注射液的新药研究申请（IND）成功获得CDE的批准。目前，PM8002注射液已在国内针对TNBC、SCLC、非小细胞肺癌（NSCLC）等多个瘤种开展了多项临床试验研究，相关临床研究数据也陆续在重要的国际学术会议上发布，展示了其广阔的应用前景和潜在的巨大临床价值。超10亿美元，BioNTech引进普米斯PD-L1/VEGF双抗今年5月，康方生物宣布，全球首创PD-1/VEGF双抗依沃西单抗头对头对比Keytruda一线治疗PD-L1阳性NSCLC的三期临床HARMOIN-2（HARMONi-2或AK112-303）达到无进展生存期（PFS）的主要研究终点，显示强阳性结果。里程碑! 国产PD-1/VEGF双抗，头对头击败K药！ PD-1/VEGF双抗的大获成功再次引起了人们的关注。今年8月，宜明昂科将旗下PD-L1xVEGF双特异性抗体IMM2510大中华区以外的开发和商业化权利以5000万美元首付+20亿美元里程碑付款授予Instil Bio。由此可见，该领域的竞争激烈程度不言而喻。 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载/商务/投稿 | 联系微信15618157102（sum_Gmi）商务合作稿件征集点击了解详情往期回顾 1 8月 | 高达22家药企裁员 2 国产首款四价HPV疫苗拟纳入优先审评 3 3. 7亿美元!今年规模最大的生物医药融资诞生

抗体药物偶联物临床申请并购免疫疗法临床1期

2024-10-29

·EndPoints

Paragon launches another company in hot PD-1xVEGF space that goes straight to reverse merger

Antibody maker Paragon Therapeutics has formed another company, this time in the bustling cancer space of PD-1xVEGF, and it will go straight onto the public markets. The new biotech, named Crescent Biopharma, will take the place of GlycoMimetics on the Nasdaq, the companies said Tuesday morning. GlycoMimetics has failed multiple mid- and late-stage trials in recent months, including one for acute myeloid leukemia . The PD-1xVEGF space has become quite popular in recent months thanks to Keytruda-beating data from Summit Therapeutics and its Chinese partner Akeso. Former Seagen CEO David Epstein also joined a preclinical biotech, named Ottimo Pharma , on Monday that hopes to get bought out after Phase 1 data. BioNTech is also in the race. Crescent’s program, codenamed CR-001, will have initial proof of concept data in the second half of 2026, the company said. It also has two antibody-drug conjugates, another en-vogue area for oncology R&D. “This transaction and financing enable a potentially rapid development path for CR-001, and for the antibody-drug conjugate programs CR-002 and CR-003,” Crescent interim CEO Jonathan Violin said in a statement. Violin is also a venture partner at Fairmount, which is one of the investors supporting a concurrent $200 million financing for the merger, which will keep the R&D engine humming “through 2027,” the company said. Paragon has formed multiple autoimmune-focused biotechs over the past two years. Apogee went public via a traditional IPO, whereas other startups from its universe have landed on the public markets by way of reverse mergers, including Oruka and Spyre . In August, Paragon debuted another offshoot, named Jade Biosciences , with just a chief scientific officer and $80 million. Crescent’s shareholders will own almost all of the combined company, at 96.9%. The deal is anticipated to close in the second quarter of 2025.

IPO抗体药物偶联物

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药物(靶点)	适应症	全球最高研发状态

Pegzilarginase (Aeglea Biotherapeutics) ( Arginine )	高精氨酸血症更多	申请上市
SPY-001 ( α4β7 )	-	临床1期
SPY-230 ( IL-23 x VEGI )	炎症性肠病更多	临床前
SPY-003 ( IL-23 )	-	临床前
SPY-130 ( IL-23 x α4β7 )	炎症性肠病更多	临床前