Rifabutin

Efficacy and Safety Pro Once-Daily Vemlidy Demonstrated in Children Six Years of Age (Weighing at Least 25kg) and Older FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for Vemlidy® (tenofovir alafenamide) 25 mg tablets as a once-daily treatment for chronic hepatitis B virus (HBV) infection in pediatric patients six years of age and older and weighing at least 25 kg with compensated liver disease. Vemlidy is a targeted prodrug of tenofovir that was approved by the FDA in 2016 as a once-daily treatment for adults with chronic HBV infection with compensated liver disease. In 2022, the FDA approved Vemlidy for the treatment of chronic HBV infection in pediatric patients 12 years of age and older with compensated liver disease. Vemlidy is recommended as a preferred or first-line treatment for adults with chronic HBV with compensated liver disease by the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines. “Chronic hepatitis B can have a significant and lasting impact on the health of children. If left untreated, hepatitis B can lead to liver cirrhosis and liver cancer,” said Chaun-Hao Lin, MD, Associate Professor of Clinical Pediatrics Krek School of Medicine of USC. “As a clinician, I am well aware of the critical importance of promptly treating this disease to avoid possible complications and liver damage. The clinical trial demonstrated that tenofovir alafenamide may represent an effective treatment option for children as young as six years old affected by this chronic disease.” Vemlidy’s approval in this pediatric patient population is supported by Week 96 data from a Phase 2 clinical trial (Trial 1092) comparing treatment with Vemlidy 25 mg to placebo among 18 treatment-naïve and treatment-experienced patients aged 6 to less than 12 years weighing at least 25 kg (Cohort 2, Group 1). Participants in the Vemlidy group and in the placebo group who switched to open-label Vemlidy after Week 24 demonstrated progressive increases in the rates of virological suppression through Week 96 overall and within both study cohorts (children and adolescents). “The expanded indication for Vemlidy for the treatment of children as young as six years old is a testament to the safety, tolerability and efficacy pro this therapy,” said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “Effective and tolerable options for children require our best science and a dedicated focus. The work of our Gilead Pediatric Center of Excellence is responsible for coordinating pediatric clinical trials for treatments for cancer, HIV, hepatitis B, and COVID-19 and we will continue our research to help address unmet treatment needs for children.” Vemlidy has a boxed warning in its product label regarding post-treatment severe acute exacerbation of hepatitis B. See below for important safety information. U.S. IMPORTANT SAFETY INFORMATION AND INDICATION FOR THE USE OF VEMLIDY BOXED WARNING: POSTTREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted. Warnings and Precautions Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used. New Onset or Worsening Renal Impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome, have been reported with TAF-containing products. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients – See Dosage and Administration. Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (TDF). Discontinue VEMLIDY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations. Adverse Reactions Most common adverse events in the week 96 pediatric population reported in ≥5% were: nasopharyngitis, headache, COVID-19, pyrexia, diarrhea, upper respiratory tract infection, cough, respiratory tract infection viral, abdominal pain upper. Overall, abdominal pain upper and metabolic nephropathy were the only study drug–related adverse events, which occurred in > 1 participant, reported in 2.3% (2/88 participants) each. Drug Interactions Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions. Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption. Coadministration of VEMLIDY with carbamazepine, the tenofovir alafenamide dose should be increased to two tablets once daily. Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments. Dosage and Administration Testing Prior to Initiation: HIV infection. Prior to or When Initiating, and During Treatment: On a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Dosage: 1 tablet taken once daily with food. Renal Impairment: Not recommended in patients with end-stage renal disease (ESRD; eCrCl <15 mL/min) who are not receiving chronic hemodialysis; in patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after completion of hemodialysis treatment. No data are available to make dose recommendations in pediatric patients with renal impairment. Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment. Indication VEMLIDY is indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients six years of age and older and weighing at least 25 kg with compensated liver disease. About the 1092 Study Study 1092 is an ongoing Phase 2 clinical trial that randomized 88 treatment-naïve and treatment-experienced patients with chronic hepatitis B infection between the ages of 12 to less than 18 years weighing at least 35 kg to receive either Vemlidy 25 mg (N=47) or placebo (N=23) and 6 to less than 12 years weighing at least 25 kg to receive either Vemlidy 25 mg (N = 12) or placebo (N=6) once daily. The study met its primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall, 19% (11/59) of patients treated with Vemlidy 25 mg achieved HBV DNA < 20 IU/mL at Week 24 compared to 0% (0/23) of patients treated with placebo. The overall percentage of patients with HBV DNA < 20 IU/mL progressively increased in the Vemlidy 25 mg group relative to the Week 24 time point at both Week 48 (37% [22/59 subjects]) and Week 96 (61.0% [36/59 subjects]). The overall median change from baseline in ALT values for the Vemlidy and placebo-Vemlidy treatment groups, respectively, was -39.5 U/L and -46.5 U/L at Week 96. At 96 weeks, ALT normalization (AASLD criteria) was achieved for 54% of Vemlidy-treated patients and 57% of patients who switched from placebo to Vemlidy. Serum ALT is an enzyme used to monitor liver damage. Importantly, the mean percent changes in bone mineral density from baseline to Week 24 were similar for Vemlidy-treated patients and placebo-treated patients (1.6% (N=48) and 1.9% (N=23) for lumbar spine, and 1.9% (N=50) and 2.0% (N=23) for whole body, respectively). At Week 24, mean changes from baseline BMD Z-scores were 0.01 and -0.07 for the lumbar spine, and -0.04 and -0.04 for whole body, for Vemlidy and placebo groups, respectively. About Hepatitis B Hepatitis B (HBV) is a serious disease that attacks the liver and can cause chronic (lifelong) infection, cirrhosis of the liver, liver cancer, and death in up to a third of patients. Hepatitis B is spread through infected blood or body fluids, sexual contact, injection drug use, or perinatally from mother to child. Early symptoms may include loss of appetite, fever, generalized aches and pains, fatigue, itching, urticaria (hives), and joint pain. The disease is often asymptomatic, which may lead to undiagnosed individuals. Later symptoms may include nausea and vomiting, halitosis (bad breath), dark brown urine, jaundice (yellowing of the skin and eyes), and right-sided abdominal pain (especially with external pressure or palpitation). About Gilead Sciences in Liver Disease For more than 20 years, Gilead has sought to address some of the biggest challenges in liver disease. The company has transformed the trajectory of multiple liver diseases through a relentless pursuit of innovation and pioneering access programs to bring meaningful therapies to people around the world. More work is required, and Gilead is committed to advancing innovative therapeutics to address the most pressing unmet needs in liver disease and overcoming barriers to better care. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19 and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties, and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Vemlidy; the risk that physicians may not see the benefits of prescribing Vemlidy for the treatment of chronic HBV in pediatric patients; and any assumptions underlying any of the foregoing. These risks, uncertainties, and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and is cautioned not to place undue reliance on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statement. U.S. Prescribing Information for Vemlidy, including BOXED WARNINGS, is available at Vemlidy, Gilead, and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@GileadSciences), or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. View source version on businesswire.com: Contacts Meaghan Smith, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com Source: Gilead Sciences, Inc. View this news release online at:

03月13日的《热心肠日报》，我们解读了 15 篇文献，关注：胆汁酸代谢，抗肿瘤免疫，抗性淀粉，IBD，工程酵母，COPD，瘤胃菌群，神经退行性变，肠道病原体，纳米医学，联川生物，默沙东Keytruda，Regor，华东医药，RedHill。 该篇日报由R·AI辅助创作生成，人工审核校对。 朱书+潘文等Cell子刊：肠菌胆汁酸代谢可影响抗肿瘤免疫，促肠癌 Immunity——[32.4] ① 中国科学技术大学朱书、潘文与团队发表最新研究，揭示了肠菌代谢物脱氧胆酸（DCA）通过抑制CD8+ T细胞功能促进结直肠癌（CRC）的机制，为防治CRC提供新的思路和靶点；② 该研究对肠道菌群代谢物文库进行筛选，发现次级胆汁酸DCA可抑制CD8+ T细胞效应功能，削弱其介导的抗肿瘤免疫，促进小鼠CRC生长；③ 机制上，DCA可结合质膜钙ATP酶（PMCA，钙离子外排泵）并增强其活性，以减少胞内钙离子积累，进而抑制钙离子-活化T细胞核因子2（NFAT2）信号通路，减少NFAT2入核和转录活性，从而削弱CD8+ T细胞功能；④ CRC患者中，DCA浓度及其细菌合成基因 baiF 表达水平，与CD8+ T细胞效应功能负相关；⑤ 携带DCA合成基因、能生成DCA的肠菌可抑制CD8+ T细胞效应功能，促进小鼠肿瘤生长，这种作用可通过靶向肠菌DCA代谢（胆汁酸螯合、敲除细菌DCA合成途径、噬菌体干预）来消除。 【原文信息】 Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions 2024-03-12 , doi: 10.1016/j.immuni.2024.02.014 Cell：超大数据资源库揭示胆汁酸多样性 Cell——[64.5] ① 胆汁酸和相关类固醇在动物生理中至关重要，参与营养元素的转运、细胞器功能、信息传导、免疫调节等等，也参与许多病理过程，但目前的研究对胆汁酸的识别、修饰及其功能的认识有限，这项研究对此提供了丰富的资源和信息；② 研究采用了近期研发的质谱查询语言MassQL，通过分析筛选12亿个公开的串联质谱(MS/MS) 中的胆汁酸选择性离子模式，创建了一个可重复使用的MS/MS图谱，进而发现了动物、人体和微生物培养物中分布的数千种胆汁酸修饰；③ 利用这一资源库，研究人员还发现了源自多胺生物合成途径的代谢物与胆汁酸的酰胺化产物，这些多胺胆汁酰胺在食肉动物中普遍存在，在人类中也存在；④ 而人类体内多胺胆汁酰胺的水平会随着其饮食类型从地中海转变为美国饮食而改变，揭示了胆汁酸修饰的巨大多样性，强调了胆汁酸在健康和疾病中作用的研究潜力。 【原文信息】 The underappreciated diversity of bile acid modifications 2024-03-11 , doi: 10.1016/j.cell.2024.02.019 膳食抗性淀粉增加小鼠肠道胆酸含量 Gut Microbes——[12.2] ① 本研究探究膳食抗性淀粉（RS）对小鼠肠道内脱氧胆酸（DCA）丰度的影响；② 与等热量对照饲料相比，补充RS显著增加肠道内DCA的含量，但不改变肠道内胆酸（CA）的丰度；③ 补充RS不影响肝脏胆酸生成酶或回肠胆酸转运蛋白的mRNA表达，以及发挥7-α-脱氢酶功能的细菌的相对丰度；④ Phnomibacter ginsenosidimutans 和多形普雷沃菌与肠道内DCA丰度呈正相关，且补充RS可增加其丰度；⑤ 综上，膳食纤维在调节DCA产生中发挥关键作用，膳食RS补充剂通过非经典细菌增加肠道细菌DCA的产生。 【原文信息】 Dietary resistant starch supplementation increases gut luminal deoxycholic acid abundance in mice 2024-02-20 , doi: 10.1080/19490976.2024.2315632 国内团队：肠道菌群介导的胆汁酸代谢可影响克罗恩病免疫治疗 Gut Microbes——[12.2] ① 广西医科大学吕小平团队综合多组学研究揭示肠道菌群通过改变胆汁酸代谢来调节克罗恩病患者抗α4β7整合素免疫治疗反应的关键机制；② 抗α4β7整合素治疗能显著缓解实验性结肠炎小鼠的疾病表型、改变肠道菌群组成及胆汁酸代谢，尤其增加次级胆汁酸的水平；③ 缓解小鼠中益生菌属如乳酸杆菌属和梭菌属显著富集，且与胃肠道中石胆酸和脱氧胆酸等胆汁酸水平增加有关；④ 临床上，抗α4β7整合素治疗为临床缓解者提供持续的治疗益处，且与微生物相关的胆汁酸的持续变化相关；⑤ 本研究为开发激活抗炎胆汁酸代谢途径的靶向益生菌，从而提高免疫疗法反应提供了新的策略。 【原文信息】 Integrated multi-omics reveal gut microbiota-mediated bile acid metabolism alteration regulating immunotherapy responses to anti-α4β7-integrin in Crohn's disease 2024-02-05 , doi: 10.1080/19490976.2024.2310894 国内团队：定制化工程酵母补充肠道丁酸，治疗炎症性肠病 Gut Microbes——[12.2] ① 天津大学的李炳志、康广博和天津医科大学的曹晓沧团队合作发表文章，通过改造酿酒酵母基因组，使其在肠道中产生丁酸，旨在为炎症性肠病（IBD）患者提供一种合理的丁酸补充治疗方法，以调节肠道菌群和促进黏膜修复；② 构建一系列具有不同丁酸合成能力的工程酵母株，最强株系丁酸产量可达1.8 g/L；③ 通过与轻中度溃疡性结肠炎患者肠道菌群共培养，证实了这些工程酵母株能够根据其丁酸合成能力不同程度地调节肠道菌群和丁酸含量，其中工程酵母株能显著提高益生菌如双歧杆菌和乳酸杆菌的丰度，降低了如Candidatus Bacilloplasma等有害菌的丰度；④ 在三硝基苯磺酸（TNBS）诱导的小鼠结肠炎模型中，这些酵母通过恢复丁酸含量显著改善结肠炎症状；⑤ 丁酸合成能力第二高的工程酵母株在调节IBD患者肠道菌群和治疗结肠炎小鼠模型方面显示出最显著的效果. 【原文信息】 A tailored series of engineered yeasts for the cell-dependent treatment of inflammatory bowel disease by rational butyrate supplementation 2024-02-21 , doi: 10.1080/19490976.2024.2316575 张允雷+尹佳+张秀伟：或可改善慢性阻塞性肺病的新益生菌 Gut Microbes——[12.2] ① 慢性阻塞性肺病（COPD）患者的CAT和SOD等抗氧化酶水平显著降低，抗氧化治疗可缓解COPD进展，南京医科大学张允雷和张秀伟、湖南师范大学尹佳与团队发表研究，揭示了具有抗氧化功能的戊糖片球菌SMM914在延缓COPD进展方面的潜在功效；② 香烟烟雾和臭氧诱导的COPD模型小鼠中，口服SMM914能降低氧化应激，显著改善呼吸功能，减轻机体炎症反应；③ SMM914使肠道菌群发生改变，特别是产短链脂肪酸和抗氧化代谢物的有益菌丰度明显增加；④ SMM914能够分泌L-色氨酸甲酰胺、5-羟基-L-色氨酸和3-硫基-L-丙氨酸，这些物质增强了色氨酸-褪黑素途径，进而提高了小鼠肺中6-羟基褪黑激素和亚牛磺酸的含量；⑤ 这种调节机制不仅增强了内源性抗炎因子的分泌，还减少了巨噬细胞向M1表型的极化，最终有效减轻了COPD小鼠的氧化应激反应。 【原文信息】 Modulation of chronic obstructive pulmonary disease progression by antioxidant metabolites from Pediococcus pentosaceus: enhancing gut probiotics abundance and the tryptophan-melatonin pathway 2024-03-06 , doi: 10.1080/19490976.2024.2320283 国内团队：生命早期瘤胃菌群衍生的3-IAld和PGD2促进瘤胃发育 Genome Biology——[12.3] ① 南京农业大学刘军花团队揭示了生命早期瘤胃菌群衍生的吲哚-3-甲醛（3-IAld）和前列腺素D2（PGD2）促进瘤胃发育，为理解早期营养-菌群-宿主互作机制提供了新见解；② 以淀粉质玉米-大豆为主食的羔羊瘤胃上皮最厚，而以富含纤维的苜蓿干草为主食的羔羊瘤胃肌肉最厚；③ 瘤胃代谢物3-IAld和PGD2与瘤胃上皮和肌肉发育相关；④ 假长双歧杆菌可将色氨酸转化为3-IAld，而白色念珠菌主要产生PGD2；⑤ 机制上，3-IAld通过AhR-wnt/β-连环蛋白信号促进瘤胃上皮细胞增殖，而PGD2通过Ca2+信号加速瘤胃平滑肌细胞增殖；⑥ 注射3-IAld和PGD2可促进羔羊瘤胃上皮和肌肉发育。 【原文信息】 Early-life ruminal microbiome-derived indole-3-carboxaldehyde and prostaglandin D2 are effective promoters of rumen development 2024-03-04 , doi: 10.1186/s13059-024-03205-x 港大Cell子刊：丙酸可缓解PD中α-突触核蛋白诱导的死亡和运动缺陷 Cell Reports——[8.8] ① 香港大学的郑超固作为通讯作者在Cell reports发表最新研究，通过构建人类α-突触核蛋白A53T突变蛋白的神经元转基因PD模型，发现丙酸含量降低；② 维生素B12缺乏会诱导丙酸分解，丙酸补充则能抑制神经退行性变和逆转PD相关的转录组异常；③ α-突触核蛋白聚集会诱导肠道线粒体蛋白质反应，导致丙酸水平降低，触发肠道的转录重编程并影响能量产生，进而加剧神经退行性变；④ 通过基因手段增强丙酸产生或在肠道中过表达丙酸下游的代谢调节器可以挽救神经退行性变，这一过程不依赖于减少α-突触核蛋白聚集。 【原文信息】 Metabolic rescue of α-synuclein-induced neurodegeneration through propionate supplementation and intestine-neuron signaling in C. elegans 2024-02-26 , doi: 10.1016/j.celrep.2024.113865 国内团队：肠道冠状病毒劫持丙酮酸作为代谢中枢，引发非瓦博格效应 Redox Biology——[11.4] ① 华中农业大学肖少波、周艳荣团队发现，与常见的病毒感染引发的Warburg效应不同，猪δ冠状病毒（PDCoV）感染细胞时，通过劫持丙酮酸作为代谢中心，展现出一种非Warburg效应的新型中心碳代谢（CCM）模式；② PDCoV感染需要糖酵解过程，但降低了糖酵解通量，导致丙酮酸积累；③ 机制上，PDCoV通过增强丙酮酸激酶活性促进丙酮酸的合成，并同时产生ATP；④ PDCoV还通过劫持丙酮酸的分解过程，增加非必需氨基酸的生物合成，表明丙酮酸是PDCoV劫持宿主能量和代谢物的关键枢纽；⑤ PDCoV促进谷氨酰胺分解促进非必需氨基酸和嘧啶的合成，从而实现最佳增殖；⑥ 本研究揭示病毒感染后的一种新型CCM模型，并为抗PDCoV药物的开发提供了潜在靶点。 【原文信息】 Enteric coronavirus PDCoV evokes a non-Warburg effect by hijacking pyruvic acid as a metabolic hub 2024-03-04 , doi: 10.1016/j.redox.2024.103112 国内团队：双重作用蛋白质“冠”助力肠道穿透 ACS Nano——[17.1] ① 西北工业大学刘德春团队联合陕西科技大学姚晓琳团队揭示了粘液源蛋白冠在调节转铁蛋白功能化纳米粒子跨细胞转运中既能充当“盾”也能作为“矛”的双重作用；② 在粘液分泌细胞中，转铁蛋白修饰的纳米粒子（Tf-NPs）吸附更多来自粘液层的蛋白质，这些蛋白质掩盖、取代并减弱Tf-NPs的主动靶向效果，从而降低内吞作用和跨细胞转运效率；③ 在无粘液细胞中，Tf-NPs在细胞内运输过程中吸附更多蛋白质，从而增强与跨细胞运输相关的功能；④ 粘液源蛋白冠预涂Tf-NPs（M@Tf-NPs），可限制与上皮粘膜界面形成的“被动蛋白冠”的负面影响，并改善内吞途径的有利性；⑤ M@Tf-NPs可吸附更多与内质网-高尔基体功能相关的蛋白，促进细胞内转运和胞吐作用；⑥ 本研究为提高口服纳米药物的效率提供了理论基础和设计平台。 【原文信息】 Protein Coronas Derived from Mucus Act as Both Spear and Shield to Regulate Transferrin Functionalized Nanoparticle Transcellular Transport in Enterocytes 2024-02-28 , doi: 10.1021/acsnano.3c11315 联川生物IPO辅导验收拟冲刺北交所 ① 近日，杭州联川生物技术股份有限公司完成上市辅导验收，拟在北交所上市，辅导机构为国金证券；② 联川生物计划公开发行股票不超过1162.5万股，若考虑超额配售选择权则不超过1336.88万股；③ 联川生物专注于基因科技领域，提供基因检测科研技术服务及解决方案，并且逐步拓展至临床基因检测领域；④ 财务方面，2019年-2021年联川生物分别实现营收7861.26万元、1.52亿元和2.05亿元，相对应的归母净利润分别为-429.31万元、2277.63万元和3739.44万元。 【原文信息】 联川生物IPO辅导验收，拟冲刺北交所 2024-03-12 , 医药魔方 默沙东Keytruda一线治疗HER2阴性胃癌韩国获批 ① 3月11日，默沙东宣布，Keytruda（帕博利珠单抗）治疗胃癌扩展适应证在韩国获得批准；② Keytruda此次获批适应证为：与氟嘧啶和铂类化疗药物联用，治疗手术不可切除的局部进展或转移性、HER2阴性胃癌或胃食管连接部腺癌患者；③ Keytruda成为韩国首款能够治疗所有胃癌类型、无论HER2阴性或阳性的肿瘤免疫制剂；④ Keytruda联合化疗方案在总体生存期（OS）上显著优于单独化疗，中位OS为12.9个月，相比化疗组的11.5个月死亡风险降低了22%。 【原文信息】 Keytruda approved as 1st-line treatment for HER2-negative gastric cancer to vie with Opdivo 2024-03-11 , Korea Biomedical Review 华东医药HDM1005注射液治疗2型糖尿病和超重或肥胖中国临床获批 ① 近日，华东医药对外表示，旗下子公司开发的HDM1005注射液临床试验申请获得国家药监局批准，拟定适应证为治疗2型糖尿病，以及超重或肥胖人群体重管理；② HDM1005是一款具有全球知识产权的1类化学新药，为GLP-1和GIP双靶点长效激动剂；③ 临床前研究显示，HDM1005能显著改善糖耐量、降糖和减重，且具有良好的成药性和安全性；④ 本次临床试验批准是HDM1005研发进程中的重要里程碑，有助于提升华东医药在内分泌治疗领域的核心竞争力。 【原文信息】 华东医药GLP-1/GIP双靶点长效激动剂HDM1005注射液的2型糖尿病和超重或肥胖人群体重管理适应症中国IND获得批准 2024-03-11 , 华东医药 Regor宣布启动其候选药物RGT-075的2期试验 ① 3月8日，临床阶段的生物制药公司Regor宣布，其用于治疗肥胖症的口服药物RGT-075的2期临床试验启动，并完成第一个受试者的第一次访视（FPFV）；② 该试验为多中心、随机、双盲、安慰剂对照研究，旨在评估RGT-075的安全性、耐受性、药代动力学和药效学；③ 计划招募约60名成人，治疗周期为12周，预计2024年下半年公布其顶线数据；④ RGT-075是每日一次口服的小分子GLP-1受体激动剂，其1期单次递增剂量和多次递增剂量研究结果显示出良好的安全性和临床耐受性； 【原文信息】 Regor Initiates Phase 2 Study of Oral Once-daily GLP-1 Agonist RGT-075 for the Treatment of Obesity 2024-03-08 , BioSpace RedHill抗幽药物Talicia获得新专利授权 ① 3月11日，RedHill Biopharma公司宣布，旗下抗幽门螺杆菌药物Talicia一项新专利获得美国专利商标局授权，产品保护期延长至2034年2月12日；② Talicia由阿莫西林，奥美拉唑和利福布汀组成，是当前获FDA批准的唯一一款含利福布汀的抗幽门螺杆菌感染疗法；③ 美国约有35%的成年人口罹患幽门螺杆菌感染，Talicia是美国胃肠病学家首选的抗幽门螺杆菌一线治疗品牌；④ 新专利进一步加强了Talicia的知识产权组合，该组合包括药物组成和其它相关专利，以及FDA授予的独占权等。 【原文信息】 RedHill Announces New USPTO Patent Covering Talicia® Through 2034 2024-03-11 , PR Newswire 感谢本期日报的审核者：mildbreeze，好雨，圆圈儿，章台柳，九卿臣，Richard，Alex Zhang 点击阅读过去10天的日报： 0312 | 65分综述详解ILC3：守护肠道健康的重要免疫细胞 0311 | 分析81万人数据：根除幽门螺杆菌，还能防肠癌？ 0310 | 癌症治疗中的饮食干预：评估252项临床试验有何发现？ 0309 | AGA最新指南：基于粪便菌群的疗法在胃肠疾病中的应用 0308 | Lancet综述：炎症性肠病患者的孕期指南 0307 | 今日Nature：白色念珠菌"定居"肠道的秘诀 0306 | 肠道菌群如何代谢胆汁酸？17页高分综述一文读懂 0305 | Cell子刊：肠炎如何影响肠菌DNA"开关"？ 0304 | 《自然·医学》新发现：菌株水平的肠菌特征，为跨癌症免疫治疗提供助力 0303 | 7天不吃饭，人体发生哪些变化？Nature子刊研究带来新知