Cure rate for L braziliensis bolivian CL has been 70%-80% for standard systemic and local monotherapies. It would benefit patients if cure rates could be consistently >90%, so testing a combination of two treatments is proposed. The most attractive systemic therapy is the only oral agent, miltefosine during 28 days, and the most attractive local therapy is application of Paromomycin cream for 28 days.

开始日期2019-02-01

申办/合作机构-

NCT03759886

/ Unknown statusN/A

Mechanical Bowel Preparation and Oral Antibiotic Prophylaxis vs. Mechanical Bowel Preparation in Colorectal Surgery With i.v. Antibiotic Prophylaxis

The investigators perform a case-control study to compare preparation before elective colorectal surgery. The first group is a prospective patient - registry in all patients with mechanical bowel preparation (MBP) and oral antibiotic prophylaxis the day before colorectal surgery. The second group is a historic collective of patients with MBP only and colorectal surgery. The cases were matches in American Society of Anesthesiologists (ASA) physical status classification system, BMI, operative procedure and risk factors.

开始日期2018-12-17

申办/合作机构

Universität Leipzig

NCT03399955

/ Unknown status临床2期IIT

An Open Label, Randomized, Parallel Arm Clinical Trial of Two Regimens to Assess the Safety and Efficacy for Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) Patients in Sudan

This is an open label, randomized non comparative phase II clinical trial conducted on parallel groups, to assess the safety and efficacy of the combination of Paromomycin (20 mg/kg/d) IM for 14 days and Miltefosine (allometric dosing) oral for 42 days, and a combination of AmBisome® (20 mg/kg total dose) IV over 7 days and Miltefosine oral for 28 days (allometric dosing) for the treatment of PKDL patients in Sudan.

开始日期2018-05-09

申办/合作机构

Drugs for Neglected Diseases initiative

100 项与硫酸巴龙霉素相关的临床结果

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100 项与硫酸巴龙霉素相关的转化医学

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100 项与硫酸巴龙霉素相关的专利（医药）

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项与硫酸巴龙霉素相关的文献（医药）

2025-02-01·CHEMOSPHERE

A biomarkers study of human skin fibroblasts exposition to glyphosate-based herbicide using an untargeted and targeted metabolomics approach

Article

作者: Gomes, Dawidson A ; Rodrigues, Michele A ; Menezes, Helvécio C ; Cardeal, Zenilda L ; Batista, Josimar M ; Armijos, María J G

Metabolomics is a valuable tool to assess glyphosate exposure and its potential impact on human health. However, few studies have used metabolomics to evaluate human exposure to glyphosate or glyphosate-based herbicides (GBHs). In this study, an untargeted and targeted metabolomics approach was applied to human skin fibroblasts exposed to the GBH Roundup (GLYP-R). Cytotoxicity, cell death, and oxidative stress assays were performed to evaluate potential damage caused by GLYP-R in fibroblasts. The herbicide showed a cytotoxic effect at concentrations above 100.0 mg L^-1, with IC₅₀ = 164.2 ± 8.7 mg L^-1, inducing significant reactive oxygen species (ROS) production and necrosis. A GC×GC/Q-TOFMS method using derivatization with propyl chloroformate/propanol was developed for untargeted analysis, allowing the identification of 400 metabolites of different classes in the samples. The most significant compounds in the discrimination and classification of the samples were fatty acids and amino acids (AA). Based on the relevance of AA in untargeted analysis, a targeted analysis of 21 AA was performed using the same validated GC×GC method. Metabolomic analyses allowed the construction of two biomarker models with performance evaluated by receiver operating characteristic (ROC) curves: an untargeted model formed by four metabolites (methylcysteine, N-acetyl-l-methionine, methyl stearate, and linoleic acid) and a targeted model formed by three AA (l-glutamic acid, l-cysteine, and γ-aminobutyric acid). This study is the first to report the use of metabolomics to evaluate human skin cells exposed to GLYP-R, contributing to the toxicological research on glyphosate.

2025-02-01·SOUTH AFRICAN JOURNAL OF BOTANY

Unlocking nature's pharmacy: Euphorbia hirta (L.) as a potent defense against Escherichia coli and Klebsiella pneumoniae infections in Tanzania

作者: Kisula, Lydia ; Giliba, Richard A. ; Mbwale, Issaya ; Kemboi, Douglas

Urinary tract infections (UTIs) are among the most common bacterial infections, primarily caused by Escherichia coli and Klebsiella pneumoniae, both of which have mostly developed resistance to various antibiotics.The Maasai and Meru communities in Tanzania have traditionally used Euphorbia hirta to combat resistant pathogens, particularly those causing UTIs.This study aimed to evaluate the antimicrobial compounds of aqueous extracts and the antibacterial compounds in methanolic extracts of E. hirta.We specifically focused on the antibacterial activity of aqueous and methanolic extracts against E. coli and K. pneumoniae strains, which are significant contributors to UTIs.In March 2024, we randomly collected E. hirta plant parts from the Kikwe and Kisongo wards in the Arusha region of Tanzania.The samples were washed with distilled water and shade-dried for three weeks to prevent the degradation of bioactive compoundsAfter drying, the samples were powd. using a laboratory grinder and stored in sterile nylon bags.We conducted qual. and quant. analyses to assess the presence of various phytochems., including alkaloids, saponins, coumarins, terpenoids, quinones, flavonoids, and glycosides, in the aqueous and methanolic extracts of E. hirta.To identify specific phytochem. compounds in these extracts, we used gas chromatog.-mass spectrometry (GC-MS) and disk diffusion assays to test their antibacterial activity against E. coli and K. pneumoniae.The GC-MS anal. identified sixteen potential bioactive compounds with antibiotic properties, including dodecanal, trans-Farnesol, phytol, 13-tetradecynoic acid, Me ester, cis-5,8,11,14,17-Eicosapentaenoic acid, 2(4H)-Benzofuranone, 5,6,7,7a-tetrahydro-4,4,7a-trimethyl-, (R)-, paromomycin, decanoic acid, Me ester, azelaic acid, undecanoic acid, 10-methyl-, Me ester, palmitoleic acid, 9,12,15-Octadecatrienoic acid (Z,Z,Z), 7-Hydroxy-3-(1,1-dimethylprop-2-enyl) coumarins, linoleyl Me ketone, and 8,11,14-Eicosatrienoic acid, Me ester (Z,Z,Z).When tested at a concentration of 1 g/mL, all extracts demonstrated significant antibacterial activity.The methanolic extract exhibited the highest performance, with a min. inhibition zone of 12.0 ± 2.35 mm, followed by the aqueous cold extract at 9.25 ± 1.75 mm, and the aqueous boiled extract at 8.0 ± 1.35 mm.The traditional methods employed by the Maasai and Meru communities for preparing herbal medicine from E. hirta, such as boiling and soaking in cold water, seemed to be effective in treating UTIs.Organic solvent extraction using methanol generally showed superior antibacterial activity compared to aqueous extractionHowever, soaking in cold water produced extracts with higher inhibitory activity against E. coli, while boiling was more effective against K. pneumoniae.This study validates the local practices of E. hirta preparation, suggesting that water-based extracts could be both effective and safe for treating certain bacterial strains responsible for UTIs in the Arusha region.

2025-02-01·JOURNAL OF INFECTION AND CHEMOTHERAPY

Escherichia coli with increased aminoglycoside resistance due to an amino acid substitution at position 85 of HemC

Article

作者: Kirikae, Teruo ; Tada, Tatsuya ; Komeda, Tomoki ; Hishinuma, Tomomi

OBJECTIVE:

The mechanism of aminoglycoside resistance due to abnormal hemin synthesis remains unclear. We investigate an Escherichia coli strain with a single amino acid substitution at position 85 of HemC.

METHODS:

An aminoglycoside-resistant Escherichia coli DH5α was selected by passaging in Lysogeny Broth (LB) medium containing amikacin. Whole genome sequencing was performed to determine the genetic profile of the strain. An isogenic strain of E. coli DH5α was created. Growth rates, drug susceptibilities and expressions of the heme synthetic genes were compared between the original strain and the isogenic strain.

RESULTS:

Whole genome sequencing revealed a nucleotide substitution at position 254 of hemC from adenine (A) to thymine (T), resulting in an amino acid substitution at position 85 of HemC from histidine (H) to leucine (L). There were no mutations in other heme synthetic genes, including hemA, hemB, hemC, hemD, hemE, hemF, hemG, hemH, hemL, hemN, hemX and hemY. The isogenic strain of E. coli DH5α with H85L in HemC was less susceptible to aminoglycosides, and its growth was slower than that of E. coli DH5α before passage. Quantitative real-time PCR showed that the expression of hemA was higher and the expressions of hemL, hemG and hemX lower in the isogenic strain than before passage.

CONCLUSION:

This is the first report of aminoglycoside resistance due to an amino acid substitution in HemC. These findings suggested that mutations in the heme synthetic genes may indirectly affect the growth rates of E. coli strains and their susceptibilities to aminoglycosides.

项与硫酸巴龙霉素相关的新闻（医药）

2025-01-05

·同写意

别了，一年股价暴跌99%的Biotech们

众所周知，二级市场是资本创新要素流动的重要部分，而IPO则一度成为未获盈利Biotech的康庄大道。公司上市以后，更容易筹集资金投入新药开发，通过产品商业化创造收益，反哺股市投资者——这个正向循环构，构成过去生物制药行业发展的主线之一，尤其在资本市场活跃时期，似乎只要获得入场券，一家Biotech日后便大概率平步青云。以美股为代表的IPO窗口，在2024年率先重新洞开，20多家Biotech由此进入二级市场。但是，它们很快发现，另一边的形势也不容乐观。许多新上市的公司，很快跌破发行价。尽管美股Biotech股价与临床阶段缺乏强关联，可大体上，一家公司股价暴跌，背后一定是出现不小的问题，无论临床开发的失败，抑或战略布局的踏空。下文，将结合GEN收录数据，对从2024年股价跌幅排名前五的Biotech进行梳理，尝试为行业勾勒出“2025年避坑指南”。正如在上一篇文章里提到的，反向股票分割常作为公司股价低迷时期的自救之举，Exicure似乎凭借这种操作，在2024年底将股价拉升了近500%。不过，我们也要看到更大的背景。五家跌幅超99%的Biotech案例中，反向股票分割都被提上日程，结果于事无补，甚至有的下跌反而是在实施该措施之后发生。大健康领域一度被视为蓝海，事实却证明，要讲好一个由生物技术驱动、横跨消费与严肃医疗的故事并不容易。生物技术的高回报建立在高风险上，如果不能找到技术落地与市场需求的平衡，被时代甩下便并非杞人忧天。股价涨幅有情绪的影响，问题是，如果负面情绪不能得到很好地管理，连锁反应很可能会伤及根本，比如2024年，TFF Pharmaceuticals就宣布破产清算。 1 Aditxt 2024年跌幅：99.90% 2023年12月，Aditxt曾宣布以1亿美元收购Evofem Biosciences，当日收获高达83.95%的股价涨幅。2024年，这家Biotech陷入低迷之际，再次祭出并购的法宝。但很可惜，“故技重施”并非万金油。自从2024年4月签署跟Appili Therapeutics的最终协议以来，Aditxt股价不升反降，一度被纳斯达克警告退市。这大概离不开交易进展缓慢的影响。事实上，就连Evofem的并购案进度，也超出Aditxt本来的预期，继续延至2025年1月。为阻止股价下滑，并重新符合纳斯达克的最低出价规则，Aditxt从去年10月2日起实施“1比40”反向股票分割。如今，Aditxt还在悬崖边上。 2017年设立的Aditxt开发了一种免疫重编程技术，旨在重新训练免疫系统以诱导耐受性，解决移植器官排斥、自身免疫性疾病和过敏问题。作为关联资产，Aditxt还发明出一套提供检测免疫系统概况的工具。目前，上述想法仍未变成现实。根据最新计划，自免候选药物ADI-100会在近期向FDA递交IND申请，用于治疗1型糖尿病、牛皮癣、僵人综合征等。如果一切顺利，首次人体试验最早也要在2025年下半年才能完成。钱是绕不开的话题，尤其考虑到两笔尚未完成的收购。基于低迷的股价表现，Aditxt已暂停股权融资，将其融资策略转向债务融资，为其收购计划提供资金。 Aditxt一些手牌看起来不错。例如，FDA对Appili旗下的ATI-1801开发战略给予了积极反馈，这款外用抗寄生虫产品符合NDA提交的要求。不确定在于，尚缺乏有关NDA提交的具体要求或时间表的重要细节。尽管这看起来像是“拆东墙补西墙”，Aditxt将新一年的现金流，希望寄托在两家要被收购的公司上。 2024年上半年，Evofem的收入为780万美元。而现阶段，Appili已从美国国防部获得约600万美元资助。这项资助的总额在1400万美元，旨在开发一种传染病疫苗ATI-1701。 2 CNS Pharmaceuticals 2024年跌幅：99.81% CNS Pharmaceuticals的惨痛，是从2024开年就开始的。去年年初，该Biotech股价迅速从约每股60美元的高位，一路“跌跌不休”。这背后，似乎有财务上的阴霾影响。2023年第三季度报告显示，CNS Pharmaceuticals净亏损进一步扩大，同比下降37.93%，对投资者的信心不得不说是个打击。随后进入2024年，生物技术板块整体下行的情况，无疑更加放大了对某些个股的担忧。 2017年成立以来，CNS Pharmaceuticals专注于开发治疗大脑和中枢神经系统肿瘤的药物。贝柔比星（Berubicin）是其主要候选管线，具备穿过血脑屏障潜力，但最快的一项研究仍在II期临床。至于另一项资产微管抑制剂TPI 287，则来自Cortice Biosciences授权。2024年7月，Cortice跟CNS Pharmaceuticals签署协议，允许后者在四个国家/地区对TPI 287进行开发。吊诡的是，这次合作并不被二级市场看好，相反，声明引发该股的又一次下跌。关键问题是，CNS Pharmaceuticals如何支付对价？答案是用股票。为该笔交易，它增发60多万股股票，大大稀释了现有股东的股权。早前，“1比50”的反向股票分割曾帮助CNS Pharmaceuticals拉升了股价，但效果并不持久。2024年9月，纳斯达克再度发出退市警告。 CNS Pharmaceuticals的苦苦挣扎，凸显了制药行业一些Biotech面临的持续资金挑战。而众所周知，神经系统疾病方面，长期充斥着临床失败的消息，包括辉瑞、渤健等巨头都先后受挫。想要开启变革，Biotech显然需要更大的勇气和实打实的准备。根据资产负债表，CNS Pharmaceuticals持有的现金暂且多于债务。但该公司还在迅速消耗现金储备，如果趋势持续下去，可能会加剧与纳斯达克的合规问题。此外，该股的相对强弱指数（RSI）表明其处于超卖区域，这或许会引起反向投资者或那些寻求潜在扭转局面的投资者的兴趣，包括MNC的并购。 I期临床数据显示，44%的患者在贝柔比星治疗后获得了临床反应。CNS Pharmaceuticals预计，2025年上半年，II期临床结果的主要分析数据会对外公布，公司“准备在短期内为所有利益相关者释放价值”。 3 Allarity Therapeutics 2024年跌幅：99.66% 区别于其他Biotech，Allarity虽然同样没有盈利，却至少保证现金流眼下无虞。根据2024年第三季度报告，它的流动资产总额为2036.6万美元，相对应的总负债只有741.4万美元。然而，投资者明显对这家2012年成立的药企有更高的期待。否则我们无法解释，为何Allarity会出现在跌幅最大的Biotech名单上。纵观管线布局，Allarity可以说是围绕MNC的资产展开。早前，Allarity从卫材引进PARP/tankyrase双重抑制剂Stenoparib。在2018年，Allarity又通过交易，从诺华获得小分子泛酪氨酸激酶抑制剂Dovitinib的许可。很可惜，这种“反向策略”，并没有将新药开发的概率提高多少。随之而来的，是接二连三的麻烦。 2021年12月，Allarity提交了Dovitinib的NDA申请，希望将转移性肾细胞癌（mRCC）三线治疗作为商业化的突破口。可在2022年2月，FDA发出CRL，表示申请“不够完整，无法进行实质性审查”。同年晚些时候，FDA对Dovitinib的申报提出新的研究要求。单药不行，那就联用——Allarity的对策是，调转方向，把Dovitinib和Stenoparib等其他潜在疗法组合在一起。结果，因为没有如约支付费用，2024年1月，诺华终止Stenoparib的授权。失去Dovitinib之后，Allarity只好重新回到仅有的Stenoparib上面，但负面影响却并未终止。 2024年7月，SEC发出“韦尔斯通知”（Wells Notice），建议对Allarity涉嫌违反《美国联邦证券法》的行为采取执法行动。报道显示，“韦尔斯通知”与Allarity开发Dovitinib期间在FDA会议上的某些“披露”有关。 Allarity认为自己的行为适当。事实上，此事后续也暂无后文，但投资者却进一步投出不信任票。在运营和财务方面，Allarity去年实施战略变革，不仅扩大与Ascendiant Capital Markets的场外交易协议，还任命新的CFO Alexander Epshinsky。Allarity也做了“1比30”的反向股票分割。资金的灵活性给Allarity一定的腾挪空间。2024年9月，Allarity表示，在Stenoparib治疗晚期卵巢癌的II期试验中，两名患者已接受治疗超过一年。这一结果凸显了持久的临床益处和成药潜力。然而，2025年会如何，Allarity还需要拿出更多的结果来说服投资者。 4 Elevai Labs 2024年跌幅：99.37% 2023年11月，Elevai顶着“外泌体抗衰第一股”的光环在纳斯达克上市。但这次风光登场，已经是仅有的高光时刻，随后该公司股价一路跳水。大健康领域通常被视为“奶与蜜之地”，因为消费医疗的属性，让其有更多溢价空间。事实上，Elevai确实推出一系列主打促进胶原蛋白再生的护肤产品，销售至美国、加拿大和其他国际市场的皮肤科、整形外科和专业医疗中心。除了功能护肤，Elevai也布局了生物制药，开发针对肥胖症和增肌的候选药物EL-22和EL-32。众所周知，市场上已获批用于减肥的GLP-1药物，如诺和诺德的Ozempic、Wegovy，礼来的 Zepbound、Mounjaro，已经改变了肥胖治疗领域。然而，高达40%的体重减轻是由于肌肉损失造成的。 Elevai认为，当前肥胖领域未满足的关键需求之一，是避免在减肥治疗期间出现肌肉流失。EL-22正是一种含有肌肉生长抑制素抗原的工程益生菌，通过引发免疫反应，帮助人们在保持肌肉质量的同时实现大幅减脂。实际上，这条道路并不宽敞。肌肉生长抑制素与肌细胞膜上的ActRIIB结合导致肌肉退化，已并非什么冷门洞见，包括礼来在内，都在围绕阻断该过程进行下一代药物开发。在其他药企高举高打的同时，Elevai却只有一项在韩国开展的小规模I期临床，来表明EL-22良好安全性和耐受性，投资者的担忧也就不难理解。据透露，Elevai正与KCRN Research合作，为预计在2025年第一季度与FDA进行pre-IND会议做准备，希望打通EL-22这种工程益生菌的临床开发制定监管途径。换言之，EL-22能否进入美国市场仍面临巨大的未知。 Elevai的案例，凸显了一家志在多元化发展的Biotech的艰难。反观近几年，辉瑞、GSK、强生等巨头，都已开启消费健康部门等拆分计划，暗示着战略聚焦的重要性。 2024年前三季度，Elevai的净亏损进一步扩大至431万美元。同年11月，Elevai试图通过“1拆200”的反向股票分割来阻止投资者抛售股票。 Elevai还2024年底更名为PMGC Holdings，并将注册地从特拉华州迁至内华达州。至于市场是否有耐心等待它的重组变革，或许就另说了。 5 TFF Pharmaceuticals 2024年跌幅：99.07% 对于TFF Pharmaceuticals来说，2024年是历史性的一年——12月12日，这家Biotech结束了最后一个交易日，收盘价为每股6.5美分。第二天，纳斯达克暂停了该股票交易。去年11月，TFF宣布解散。而在该消息发布的两个月前，TFF Pharmaceuticals还宣布，与埃默里大学和生物医学高级研究与发展局建立新的伙伴关系。此次合作志向远大，双方希望测试将mRNA药物转化为干粉吸入制剂的可行性，而无需冷链储存。TFF Pharmaceuticals将为此提供技术支持，实验室数据表明，该工艺生产的吸入型干粉制剂的空气动力学特性，可以将多达75%的剂量输送到肺部深处。从原理上说，TFF Pharmaceuticals平台不会引入高温、剪切应力等可能损坏治疗成分完整性的因素，而是将这些材料重新配制成易于储存且常温稳定储存的干粉剂型，使治疗药物和疫苗更容易覆盖全球。与口服药物相比，这种新剂型能够将治疗药物直接输送到目标器官（如肺）中，以较低的剂量给药，从而减少不必要的毒性和副作用。 2024年11月，一项采用甲型流感病毒血凝素（HA）mRNA疫苗作为样本进行的研究证明，TFF Pharmaceuticals专有的薄膜冷冻干燥技术（TFFD）可用于制备HA mRNA-LNP干粉制剂，但需要足够量的赋形剂，来最大限度减少HA mRNA-LNP疫苗受到冷冻干燥过程中复杂应力引起的物理性质、结构和免疫原性的变化。这或许是挑战之处。尽管存在突破可能，TFF Pharmaceuticals仍需讲好一个商业化闭环的故事，而市场认为，它的财务状况已不允许。 TFF Pharmaceuticals自2018年成立，迅速受到多方关注。2019年，该公司在纳斯达克IPO。而IPO后的6轮融资中，它筹集到超过6000万美元资金，投资者包括美国国家过敏和传染病研究所、Leidos和Liquid Venture Partners。人员方面，2023年诺贝尔生理学或医学奖得主Drew Weissman，一度是TFF Pharmaceuticals的科学顾问。而在药物市场端，根据早前研究，约40%的上市药物和约90%的在研药物由难溶性分子组成。这意味着，诸如TFF Pharmaceuticals开发的粉末制剂，有望利用自身更强的稳定性、适用性和便携性脱颖而出。可一副好牌最终还是打烂了。宣布解散前，TFF Pharmaceuticals董事会批准了一项清算计划，并任命会计师事务所Verdolino & Lowey负责人Craig Jalbert身兼数职，负责监督公司的清算工作。参考资料： 1.StockWatch: Wall Street’s Leaders and Laggards of 2024 同写意媒体矩阵，欢迎关注↓↓↓

并购IPO

2024-11-14

·GlobeNewswire-Health Care

Appili Therapeutics Reports Financial and Operational Results for Second Quarter of Fiscal Year 2025

Overwhelming shareholder support in favour of take-private transaction with Aditxt Studies presented at IDWeek 2024™ demonstrate ATI-1701 provides full protection against lethal tularemia in animal models after one year Alignment with U.S. Food and Drug Administration on development requirements for ATI-1801 NDA Submission HALIFAX, Nova Scotia, Nov. 14, 2024 (GLOBE NEWSWIRE) -- Appili Therapeutics Inc. (TSX:APLI; OTCPink: APLIF) (the “Company” or “Appili”), a biopharmaceutical company focused on drug development for infectious diseases and medical countermeasures, today announced its financial and operational results for the second quarter of its fiscal year 2025, which ended on September 30, 2024. All figures are stated in Canadian dollars unless otherwise stated. “During fiscal year 2025, Appili shareholders voted overwhelmingly in favor of the transaction with Aditxt, facilitating our access to capital and activating promising opportunities for Appili,” said Dr. Don Cilla, President and CEO of Appili. “The shareholder vote is an important milestone for Appili and brings us one step closer to ‘Making Promising Innovations Possible Together’ through Aditxt’s social incubator platform.” ATI-1701, Biodefense Vaccine Candidate with Strong U.S. Air Force Academy Funding Commitments ATI-1701, a novel live-attenuated vaccine for preventing F. tularensis, has previously secured US$14 million in awards from the United States Air Force Academy (“USAFA”). Under the cooperative agreement with USAFA, Appili manages a comprehensive development program, including nonclinical studies, CMC/manufacturing, clinical preparatory, and regulatory activities supporting an IND submission in 2025. Recent data presented by Appili's scientific team at the Military Health System Research Symposium and IDWeek 2024™ demonstrated strong efficacy results. Studies showed that a single dose of ATI-1701 provided full protection against lethal tularemia in animal models, with protection for one year after vaccination. Additional research highlighted the heightened risk of tularemia outbreaks in conflict zones and positioned ATI-1701 as a potentially valuable tool in protecting warfighters. Appili has recently had positive interactions with the United States Food and Drug Administration (“FDA”) in the form of a pre-IND meeting, confirming the development pathway for the majority of Appili’s proposed development plan. Appili is currently in the process of implementing suggested changes in its development effort. ATI-1801, Demonstrated safety and efficacy across multiple Phase 2 and Phase 3 studies ATI-1801, a novel topical formulation of paromomycin (15% w/w), is under advanced clinical development for treating cutaneous leishmaniasis, a disfiguring skin infection affecting hundreds of thousands globally. In a recent response to Appili’s Type B meeting request, the FDA agreed with the Company’s proposed strategy to establish a scientific bridge between previous clinical trial material and new drug product batches. The approach enables Appili to leverage key results from the clinical dossier for ATI-1801 licensed from U.S. Army Medical Materiel Development Activity, including the successful results of a Phase 3 study, and allows the completion of an New Drug Application much sooner than if additional clinical data were required. ATI-1801 has received Orphan Drug Designation from the FDA for certain forms of cutaneous leishmaniasis. The company is evaluating ATI-1801’s eligibility for a priority review voucher (“PRV”), which, if confirmed, would make it the second PRV-eligible program at Appili, alongside ATI-1701, which is potentially eligible for a PRV pending renewal of certain U.S. legislation. LIKMEZ™ (ATI-1501), FDA Approved Liquid Oral Reformulation of the Antibiotic Metronidazole In September 2023, Appili, together with its U.S. partner, Saptalis Pharmaceuticals LLC., announced the approval by the FDA of LIKMEZ™ (ATI-1501), LIKMEZ® is the first and only FDA-approved liquid formulation of metronidazole providing a novel prescribing option for patients with difficulty swallowing or experiencing taste-related hurdles. LIKMEZ, with patent coverage through 2039, addresses the unmet need in patients with dysphagia to avoid risks associated with drug compounding, and discontinuation related anti-microbial resistance. In November 2023, Saptalis, through a commercialization partner, launched LIKMEZ in the U.S. and the product is now available to patients and doctors. Appili earned milestone payments from Saptalis and is entitled to receive additional sales-based milestone payments and royalties from Saptalis based on sale of the product. Saptalis is currently in the process of identifying an alternative commercialization partner. Aditxt Arrangement On November 6, 2024, shareholders of the Company overwhelmingly voted in favour of a special resolution approving a plan of arrangement pursuant to which Aditxt Inc. (NASDAQ:ADTX) (“Aditxt”), through its wholly-owned subsidiary, Adivir, Inc. will acquire all of the issued and outstanding Class A common shares of the Company by way of a court-approved plan of arrangement under the Business Corporations Act (Ontario) (the “Transaction”). Approximately 29.50% of the outstanding Appili Shares were voted by shareholders and the Transaction was approved by 99.79% of the votes cast. For further details regarding the Transaction, please see Appili’s press release dated April 2, 2024 and Appili’s management information circular (the “Circular”) dated October 4, 2024, a copy of which is available under Appili’s profile on SEDAR+ (sedarplus.ca). Appili and Aditxt are in the process of satisfying the remaining closing conditions, which include: (1) the Company obtaining final court approval for the Transaction, and (2) Aditxt securing sufficient financing to complete the Transaction. Subject to satisfaction or waiver of the remaining closing conditions, Appili expects the Transaction to close in December 2024. Financial Results The Company prepares its financial statements in accordance with IFRS Accounting Standards as issued by the International Accounting Standard Board and Part I of Chartered Professional Accountants of Canada Handbook–Accounting. All figures are stated in Canadian dollars unless otherwise stated. The net loss and comprehensive loss of $0.8 million or $0.01 loss per share for the three months ended September 30, 2024, was $0.2 million lower than the net loss and comprehensive loss of $1 million or $0.01 loss per share during the three months ended September 30, 2023. This relates mainly to an increase in research and development expenses of $1 million, an increase in financing costs of $0.1 million and a decrease in revenue of $0.3 million. This increase was offset by a decrease in general and administrative expenses by $0.1 million, an increase in government assistance of $1.3 million, and an increase of $0.2 million in foreign exchange gain. As of September 30, 2024, the Company had cash of $0.7 million, compared to $0.1 million on March 31, 2024. As of November 13, 2024, the Company had 121,266,120 issued and outstanding Common Shares, 11,520,281 stock options, and 41,356,874 warrants outstanding. This press release should be read in conjunction with the Company’s unaudited interim condensed consolidated financial statements for the second quarter of the 2025 fiscal year and the related MD&A, copies of which are available under the Company’s profile on SEDAR+ at www.sedarplus.ca. About Appili TherapeuticsAppili Therapeutics is an infectious disease biopharmaceutical company that is purposefully built, portfolio-driven, and people-focused to fulfill its mission of solving life-threatening infections. By systematically identifying urgent infections with unmet needs, Appili’s goal is to strategically develop a pipeline of novel therapies to prevent deaths and improve lives. The Company is currently advancing a diverse range of anti-infectives, including an FDA approved ready-made suspension of metronidazole for the treatment of antimicrobial infections, a vaccine candidate to eliminate a serious biological weapon threat, and a topical antiparasitic for the treatment of a disfiguring disease. Led by a proven management team, Appili is at the epicenter of the global fight against infection. For more information, visit www.AppiliTherapeutics.com. Forward looking statementsThis news release contains “forward-looking statements”, including with respect to the funding commitment from USAFA and expected timing of invoice payment, advancing program towards IND, further anticipated milestones and the timing thereof, the Company’s development plans and timelines with respect to ATI-1501, ATI-1701 and ATI-1801, the timing of any milestone and/or royalty payments in respect of ATI-1501, consideration to be received by shareholders in connection with the proposed Transaction, the expected timing and process to complete the Transaction, and the Company’s expectations with respect to its ability to operate as a going concern and satisfy its ongoing working capital requirements. Wherever possible, words such as “may,” “would,” “could,” “should,” “will,” “anticipate,” “believe,” “plan,” “expect,” “intend,” “estimate,” “potential for” and similar expressions have been used to identify these forward-looking statements. These forward-looking statements reflect the current expectations of the Company’s management for future growth, results of operations, performance and business prospects and opportunities and involve significant known and unknown risks, uncertainties and assumptions, including, without limitation, those listed in (i) the annual information form of the Company dated June 25, 2024, (ii) the Cicular, and (iii) the other filings made by the Company with the Canadian securities regulatory authorities (which may be viewed at www.sedarplus.ca). Should one or more of these risks or uncertainties materialize or should assumptions underlying the forward-looking statements prove incorrect, actual results, performance or achievements may vary materially from those expressed or implied by the forward-looking statements contained in this news release. These factors should be considered carefully, and prospective investors should not place undue reliance on the forward-looking statements. The Company disclaims any intention or obligation to revise forward-looking statements whether as a result of new information, future developments or otherwise, except as required by law. All statements included in this press release relating to the Arrangement are qualified by reference to the “Forward Looking Statements” section included in the Arrangement Press Release. Media Contact:Jenna McNeil, Communications ManagerAppili Therapeutics E: JMcNeil@AppiliTherapeutics.com Investor Relations Contact:Don Cilla, President and CEOAppili TherapeuticsE: Info@AppiliTherapeutics.com

临床结果上市批准疫苗孤儿药临床3期

2024-11-08

·被忽视疾病药物研发倡议组织

这种被忽视的疾病可能导致毁容，中国仍有病例报告

2023年，孟加拉国成为全球第一个获得世界卫生组织（WHO）消除内脏利什曼病认证的国家。而其他受该疾病严重影响的南亚和东非地区的国家也在朝着消除目标稳步前进——这部分归功于DNDi过去20年的研究工作帮助人们获得了更安全和更简单的治疗。当前， DNDi及其合作伙伴正专注于为内脏利什曼病患者提供全新的口服药物，从而支持全球实现和维持内脏利什曼病的消除。 //认识内脏利什曼病：现状与危害// 利什曼病（Leishmaniasis）可由20多种利什曼虫属原生动物寄生虫引起，目前已知有90多种白蛉可以传播这些利什曼虫属寄生虫。该病有三种主要形式：内脏利什曼病（Visceral leishmaniasis，VL）、皮肤利什曼病（Cutaneous leishmaniasis, CL）和皮肤粘膜利什曼病（Mucocutaneous leishmaniasis）。其中，内脏利什曼病（又名黑热病）是最严重的形式，它可能出现暴发并导致死亡，是继疟疾之后第二致命的寄生虫病。据估计，全世界有6亿多人面临感染VL的风险，每年新发病例数在5万至9万之间，大约50%的VL患者为儿童群体。研究表明，大多数患者分布在巴西、东非和印度。而在中国，近年来病例报告主要集中于新疆、甘肃和四川等地。VL患者通常会出现发烧、体重下降、肝脾肿大等症状，如果不及时治疗，超过95%的患者会发生死亡。其中，携带艾滋病毒的VL患者尤其难以治愈，具有很高的复发率和死亡率。与其他人群相比，携带艾滋病毒的人群罹患VL的风险高出100倍以上。 [图源：DNDi] //推动进步：内脏利什曼病的治疗创新// 东非的VL患者迫切需要比现有标准治疗更安全、更简单的替代方案，特别是当地占比70%的儿童患者。2003年，DNDi创建了东非利什曼病平台（Leishmaniasis East Africa Platform，LEAP），来自20个机构的60名专家参与研究，并帮助推动了肯尼亚、埃塞俄比亚、乌干达和苏丹抗击VL的进展。 2018年，DNDi与AfriKADIA联盟合作在埃塞俄比亚、肯尼亚、苏丹和乌干达开展了一项III期临床研究，比较米替福辛和帕罗霉素（miltefosine and paromomycin，MF+PM）联合治疗与目前的标准治疗——硬葡萄糖酸钠和帕罗霉素（sodium stibogluconate and paromomycin，SSG+PM）的结局。研究结果显示，MF+PM与SSG+PM一样有效，但所需注射次数较少，治疗周期较短，没有SSG相关毒性风险，并且继发黑热病后皮肤利什曼病（Post-Kala-Azar Dermal Leishmaniasis，PKDL）的风险也更低。为确保MF+PM在儿科用药中的适当剂量，研究团队开展了进一步的工作，研究结果支持在儿童和成人患者中均实施较短的14天治疗方案。 [图源：DNDi] DNDi与第七届利什曼病世界大会和第28届LEAP平台会议的与会专家以及开展研究的区域和社区的利什曼病技术和咨询小组分享了试验结果。与此同时，世卫组织指南制定小组开始审查DNDi的 III期临床试验产生的证据，为东非地区成人和儿童VL患者的治疗指南的修订提供信息。 //打破传播链条：PKDL患者的治疗// 据报告，5-10%的VL患者会继发PKDL。该病症通常表现为面部、上臂和躯干部位出现斑点、丘疹或结节，还可能导致毁容和给患者造成极大的病耻感。此外，PKDL患者仍可以作为VL的传染源，因此，早期和有效的PKDL治疗对于持续减少VL传播至关重要。基于此前完成的两项II期临床研究——在苏丹开展的旨在测试脂质体两性霉素B (LAmB)+MF和MF+PM的研究，以及在印度和孟加拉国开展的测试LAmB单药疗法和LAmB+MF组合疗法的研究，DNDi及其合作伙伴分别于2023年11月和2024年6月在期刊PLOS Neglected Tropical Diseases上发表了研究结果。由于这些新的科学证据，预计更短期、更安全的治疗方法将在未来被推荐给PKDL患者。 [图源：DNDi] //全新的口服药物：合作与创新// 2023年，DNDi与合作伙伴在开发新的分子实体方面取得了重大进展，这些实体有可能彻底改变VL的治疗方法，并支持其消除目标的实现。 LXE408是一种由DNDi与Novartis联合开发的首创新药化合物。2023年8月，印度的第二个研究点已经启动，并在当年招募了39名患者。与此同时，在埃塞俄比亚进行的一项类似的II期研究已于2024年4月入组了首位受试者。预计到2025年，这两项研究将总共招募140名参与者。 GSK245具有与LXE408相似的作用模式，由DNDi、GSK全球健康部门和邓迪大学药物发现部门合作开发。2023年，针对该化合物的研究继续进行，并完成了健康志愿者单次剂量递增的I期研究。 [图源：DNDi] 此外，DNDi及其合作伙伴也恢复了具有独特的作用机理的化合物DNDI-6899的开发。储存在药明康德的活性药物成分已完成重新加工和配制，以支持2024年启动的多次剂量递增I期研究。在上月举行的第43届DNDi科学咨询委员会会议上，DNDI-6899研发项目从40多个研发项目中脱颖而出，入选“2024年度项目”（2024 Projects of the Year），以表彰该项目在临床前研究中的突出进展。在DNDi的所有利什曼病药物组合中，DNDI-6174提供了一种全新的作用模式，并且预期具有较低的人用剂量和有前景的安全边际。该化合物由DNDi与GSK和邓迪大学合作发现，并于2019年被提名为VL候选药物，该成果已于2023年12月发表在期刊Science Translational Medicine上。自2019年来，DNDi和Eisai一直在合作开发该化合物，并于2023年继续合作研究以扩大对该化合物非临床特征的了解，从而推进首次人体临床试验。 [图源：DNDi] 我们非常感激这一路同行的合作伙伴们，他们在为被忽视的患者群体推进医学创新方面发挥了重要作用。未来，我们将继续在利用现有药物提供更安全、更短周期的治疗的同时，完成全新药物的长期开发，以拯救生命，减少与内脏利什曼病有关的社会歧视和病耻感，并最终消除内脏利什曼病。点击“阅读原文”，可了解更多DNDi为最被忽视的病人推动的医学创新。关于DNDi 被忽视疾病药物研发倡议组织（DNDi）是一个以病患需求为出发点的非营利性药物研发组织。DNDi主要为被忽视的疾病患者研发新的治疗方法，其中包括昏睡病、南美锥虫病、利什曼病、淋巴丝虫病、足菌肿、儿童艾滋病/艾滋病以及丙型肝炎的治疗方法。DNDi同时也在协调ANTICOV临床试验，为非洲的轻度至中度新冠肺炎（COVID-19）患者寻找治疗方法。自2003年成立以来，DNDi迄今已交付了13种全新的治疗方案，其中包括用于治疗利什曼病的新药物组合、两种固定剂量的抗疟药，首次成功研发的新化学实体药物非昔硝唑（fexinidazole）用于治疗昏睡病，以及通过南南合作研发的丙肝药物拉维达韦（ravidasvir），旨在为全球丙肝患者提供可负担的药物选择。 *点击下方图片，了解更多有关DNDi的介绍。

临床3期

100 项与硫酸巴龙霉素相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	硫酸巴龙霉素	A07AA06	DB01421

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
阿米巴病	-	-	1959-01-01
隐孢子虫病	-	-	1959-01-01
贾第虫病	-	-	1959-01-01

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
皮肤利什曼病	临床3期	美国	Appili Therapeutics, Inc.	2022-04-13

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03399955 (not available, Pubmed \| PLoS Negl Trop Dis)	临床2期	黑热病后皮肤利什曼原虫	110	Paromomycin/Miltefosine	製齋獵壓繭鬱鑰廠製廠(醖餘構衊繭餘願醖構窪) = 鹽鏇範鹹範憲壓膚糧願餘壓夢鹹觸鹽繭窪艱遞 (廠夢窪蓋構夢鏇遞糧顧, 90.3 ~ 100)	积极	2023-11-21
				Liposomal Amphotericin B/Miltefosine	製齋獵壓繭鬱鑰廠製廠(醖餘構衊繭餘願醖構窪) = 築選簾鏇願壓襯餘製鬱餘壓夢鹹觸鹽繭窪艱遞 (廠夢窪蓋構夢鏇遞糧顧, 70.2 ~ 91.9)
NCT03129646 (Pubmed)	临床3期	内脏利什曼病	439	Paromomycin plus Miltefosine	鏇鏇糧壓鏇獵鏇簾遞餘(襯願壓廠鑰鹹憲構製構) = 網網獵膚蓋鹽鏇範廠壓顧餘築餘襯夢膚築夢遞 (繭艱齋網選醖襯願夢糧, -6.2 ~ 7.4)	积极	2022-09-27
				Sodium Stibogluconate plus Paromomycin	鏇鏇糧壓鏇獵鏇簾遞餘(襯願壓廠鑰鹹憲構製構) = 廠鬱顧願糧願構願網壓顧餘築餘襯夢膚築夢遞 (繭艱齋網選醖襯願夢糧, -6.2 ~ 7.4)
NCT03759886 (Pubmed \| Int J Colorectal Dis)	N/A	-	120	Intervention group (oral paromomycin and metronidazole)	窪憲簾構獵糧齋膚鏇選(構窪廠願選遞簾積製鬱) = showed a tendency towards decreased frequencies in the intervention group 膚願構淵獵壓範淵糧願 (製襯淵繭蓋願鏇齋衊鑰 )	-	2021-04-25
				paromomycine (Control group (no intervention))
NCT01790659 (CTgov)	临床3期	皮肤利什曼病	399	WR 279,396 (WR 279,396)	製鬱獵遞繭艱顧獵鬱衊(衊襯夢壓膚蓋窪願觸衊) = 鏇願繭醖膚範窪淵網壓淵夢夢蓋選鬱觸襯齋鹹 (夢獵鏇顧選蓋膚觸獵憲, 構鹽餘遞願網憲憲糧願 ~ 夢繭襯鹽鹽獵遞鹽壓簾) 更多	-	2017-08-23
				Paromomycin (Paromomycin)	製鬱獵遞繭艱顧獵鬱衊(衊襯夢壓膚蓋窪願觸衊) = 鏇顧壓獵鏇窪齋鹹糧齋淵夢夢蓋選鬱觸襯齋鹹 (夢獵鏇顧選蓋膚觸獵憲, 繭鹹觸觸壓簾網窪願壓 ~ 繭淵鏇齋蓋鹽艱夢遞齋) 更多
NCT00606580 (CTgov)	临床3期	皮肤利什曼病	375	WR 279,396 topical cream (WR 279,396 Topical Treament)	獵糧憲夢糧窪簾顧鹽壓(憲齋齋鹹鹽艱繭築築範) = 鹹膚觸夢選範範鹹蓋顧獵範觸鏇襯鑰淵顧齋繭 (艱衊繭餘蓋蓋糧觸觸鑰, 膚選鹹獵窪廠淵繭積鑰 ~ 顧鑰夢壓蓋積觸獵網蓋) 更多	-	2014-07-14
				Paromomycin Alone topical cream (Paromomycin Alone Topical Treatment)	獵糧憲夢糧窪簾顧鹽壓(憲齋齋鹹鹽艱繭築築範) = 顧鏇鏇遞築鑰淵鑰壓遞獵範觸鏇襯鑰淵顧齋繭 (艱衊繭餘蓋蓋糧觸觸鑰, 選遞積鑰網醖獵願蓋積 ~ 糧鹽簾醖鹹壓衊遞繭獵) 更多
NCT00255567 (Pubmed \| PLoS Negl Trop Dis)	临床2期	内脏利什曼病	42	Paromomycin 20 mg/kg/day for 21 days	選襯繭積糧觸遞衊淵顧(蓋糧鹹襯齋簾齋蓋觸蓋) = 構衊廠窪積選夢鹹蓋廠夢淵觸夢獵網襯蓋膚製 (淵蓋襯構製繭遞築壓衊, 63.7% ~ 97.0%)	-	2010-10-26
				Paromomycin 15 mg/kg/day for 28 days	選襯繭積糧觸遞衊淵顧(蓋糧鹹襯齋簾齋蓋觸蓋) = 醖鑰蓋獵廠鹹選壓窪憲夢淵觸夢獵網襯蓋膚製 (淵蓋襯構製繭遞築壓衊, 69.6% ~ 98.8%)
NCT00629031 (Pubmed \| Clin Infect Dis)	临床3期	内脏利什曼病	329	paromomycin (Group A)	網窪範鏇獵獵觸襯壓築(窪襯選餘艱壓鹹窪廠鏇) = Mild grade injection site pain was the most common adverse event 淵鹽窪選艱築衊醖淵鏇 (顧膚鏇網艱糧製簾網淵 ) 更多	-	2009-09-15
				paromomycin (Group B)
NCT00216346 (Pubmed \| N Engl J Med)	临床3期	内脏利什曼病	667	Paromomycin	積鹹鹽衊選簾觸壓醖製(廠構顧範艱鬱範壓淵獵) = fevers 廠蓋積網壓齋網製蓋簾 (膚醖鹽淵窪艱襯餘壓齋 ) 更多	积极	2007-06-21
				Amphotericin B