A Phase I Clinical Study on the Safety, Tolerability and Pharmacokinetics of SI-F019 Recombinant Human Bivalent ACE2-Fc Fusion Protein Injection in a Single Dose in Healthy Subjects

To evaluate the safety, tolerability and pharmacokinetic properties of a single intravenous administration of SI-F019 recombinant human bivalent ACE2-Fc fusion protein injection in healthy participants, and provide a basis for the design of subsequent clinical trials.

开始日期2021-03-30

申办/合作机构

四川百利药业有限责任公司

[+1]

NCT02492555 / Unknown statusN/AIIT

Is Relapse Rate Reduced by Home Monitoring of IBD Patients Tightly or on Demand by FC and Disease Activity?

The purpose of this study is to determine if the IBD patient doing home monitoring by web app's for disease activity (DA) and fecal calprotectin (FC) on demand (OD), compared with patients doing home monitoring scheduled interval combined with "on demand"(SI+OD) ( every 3.month).
Will home monitoring of DA and FC OD vs SI+OD reduce frequency of relapse in one year follow up? Is the frequent FC measurement in SI+OD test group predictive of an early recognition of relapse, and thus help change the naturel course of disease? Will home monitoring of DA and FC in OD vs SI+OD change the course of the disease in terms of disease activity, spread of the disease, hospitalizations and number of hospitalization days, required surgery and outpatient visits? Is there a difference in patients' compliance with treatment plan between OD vs SI+OD ? Is there difference in patients-adherence between OD vs SI+OD ?

开始日期2015-07-01

申办/合作机构-

NCT01625273 / CompletedN/A

Supplementation of Infant Formula With the Synbiotics (Lactobacillus Paracasei Ssp. Paracasei Strain F19 and Fructo- and Galactooligosaccharides).

The primary hypothesis is that Lactobacillus paracasei ssp. paracasei strain F19 in an infant formula containing FOS/GOS is safe and tolerable for use in infants from 0 to 6 months.

开始日期2010-01-01

申办/合作机构

Arla Foods AmbA

100 项与 SI-F019 相关的临床结果

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100 项与 SI-F019 相关的转化医学

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100 项与 SI-F019 相关的专利（医药）

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项与 SI-F019 相关的文献（医药）

2023-12-13·Journal of Agricultural and Food Chemistry

Synthesis, X-ray Crystal Structure, and Antimicrobial Studies of New Quinazolin-4(3H)-one Derivatives Containing the 1,2,4-Triazolo[3,4-b][1,3,4]thiadiazole Moiety and 4-Piperidinyl Linker

Article

作者: Yi, Mingyan ; An, Lian ; Wu, Nan ; Liu, Songsong ; Bao, Xiaoping ; Yan, Taisen ; Yang, Yehui ; Tian, Guangmin

A total of 35 new quinazolinone derivatives bearing the 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole scaffold and the 4-piperidinyl linker were designed, prepared, and assessed for their antibacterial and antifungal activities. Among these derivatives, the chemical structure of compound F5 was clearly verified via single-crystal X-ray diffraction analysis. The experimental results revealed that some of the compounds displayed good even excellent inhibitory effects toward the tested phytopathogenic bacteria. For instance, compound F33 was capable of strongly inhibiting Xanthomonas oryzae pv. oryzae (Xoo) in vitro with an EC₅₀ (half-maximal effective concentration) value of 4.1 μg/mL, about 16-fold more effective than the commercialized bactericide bismerthiazol. Significantly, this compound also effectively suppressed the proliferation of Xoo in the potted rice plants, showing a good in vivo protection efficacy of 47.6% at 200 μg/mL. Subsequently, the antibacterial mechanisms of compound F33 were explored by means of different biophysical and biochemical methods. Last, some of the compounds were found to possess relatively good antifungal activities in vitro, like compound F19 against Phytophthora nicotianae (with an inhibition rate of 67.2% at 50 μg/mL). In a word, the current experimental results imply that the 4-piperidinyl-bridged quinazolinone-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives possess potential as lead compounds for developing more efficient anti-Xoo bactericides.

2023-08-15·Pharmaceuticals (Basel, Switzerland)

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Review

作者: Zahid, Wajeeha ; Shabir, Ghulam ; Muneeba ; Saeed, Aamer ; Riaz, Zainab ; Naseer, Fatima ; Albericio, Fernando ; Khalil, Nafeesa

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding ability of fluorinated drug target proteins has also been reported in some cases. An emerging line of research on F substitution has been addressed by using ¹⁸F as a radiolabel tracer atom in the extremely sensitive methodology of positron emission tomography (PET) imaging. This review aims to report on the fluorinated drugs approved by the US Food and Drug Administration (FDA) from 2016 to 2022. It cites selected examples from a variety of therapeutic and diagnostic drugs. FDA-approved drugs in this period have a variety of heterocyclic cores, including pyrrole, pyrazole, imidazole, triazole, pyridine, pyridone, pyridazine, pyrazine, pyrimidine, triazine, purine, indole, benzimidazole, isoquinoline, and quinoline appended with either F-18 or F-19. Some fluorinated oligonucleotides were also authorized by the FDA between 2019 and 2022.

2023-04-01·Probiotics and Antimicrobial Proteins

Brewer’s Spent Grain Enhanced the Recovery of Potential Probiotic Strains in Fermented Milk After Exposure to In Vitro-Simulated Gastrointestinal Conditions

Article

作者: Herkenhoff, Marcos Edgar ; Vieira, Antonio Diogo Silva ; Battistini, Carolina ; Saad, Susana Marta Isay ; Bedani, Raquel ; de Souza Leite, Marcela

Brewer's spent grain (BSG) is a beer industry by-product with interesting functional properties by its high fiber content and bioactive compounds, which may be possibly employed as a prebiotic ingredient. The fermentability of BSG by ten probiotics and two starter cultures was evaluated, and the co-culture of Lacticaseibacillus paracasei subsp. paracasei F-19® (probiotic) and Streptococcus thermophilus TH-4® (starter) was selected to produce a potentially probiotic fermented milk (FM). Four formulations of FM were studied: FM1 (control), FM2 (probiotic - /BSG +), FM3 (probiotic + /BSG -), and FM4 (probiotic + /BSG +). The viability of the microorganisms in the FM was monitored throughout 28 days of storage. The resistance of the microorganisms in the FM to in vitro-simulated gastrointestinal tract (GIT) conditions was also evaluated. Even though the BSG did not influence the fermentation kinetics or increase the populations of both microorganisms in the FM, a significant improvement on the survival of TH-4® against in vitro-simulated GIT stress was observed in the formulations containing BSG alone or in combination with F-19®. All formulations showed potential as probiotic FM, since total probiotic populations were kept above 10¹⁰ CFU in a daily portion of 200 mL, and a minimum of 10¹⁰ and 10⁸ CFU equivalent of, respectively, TH-4® and F-19® was recovered after the GIT stress. Therefore, TH-4® has potential as a probiotic strain in addition to its starter feature, while BSG may be employed as a possible prebiotic ingredient in a synbiotic approach. Nonetheless, further studies to evaluate possible health benefits are needed.

项与 SI-F019 相关的新闻（医药）

2023-01-09

·药渡Daily

百利天恒登场，“激进”的研发策略国内绝无仅有

百利天恒已于1月6日登陆科创板，首日收盘于32.05元/股，上涨29.76%。随着百利天恒的到来，科创板迎来开门红，一扫过去一年Biotech屡屡破发的尴尬局面。但事实上，百利天恒并不能归类为严格意义上的Biotech，因为其是一家有着26年历史的“老牌”药企。诞生于90年代民营药企野蛮生长的时期，本可以在仿制药时代“躺赚”，但得益于其创始人的高瞻远瞩和创新情怀，百利天恒选择放弃安逸，倾情投入创新药的研发中，令人敬佩。01履遭集采重挫四川百利天恒药业股份有限公司（“百利天恒”）是一家集药品研发、生产与营销一体化的、拥有化药、中成药和创新药业务板块现代生物医药企业。经过26年的发展，百利天恒已具备包括小分子化学药、大分子生物药及抗体偶联药物的全系列药物研究开发生产能力；拥有中美两地研发中心（美国：Systimmune；中国：百利药业和多特生物等）、1个大分子生物药及ADC药物生产企业（多特生物）、2个化药制剂生产企业（百利药业和国瑞药业）、1个化学原料药生产企业（精西药业）、1个化学中间体生产企业（海亚特科技）以及2个药品营销公司（百利天恒和拉萨新博）。来源：官网2019-2021年，百利天恒总营收分别为12亿元、10.11亿元和7.95亿元；同期，净利润分别为774.23万元、3792.29万元和-9999.13万元。其中，2019-2021年，仿制药板块收入分别为9.62亿元、8.21亿元和6.06亿元，分别占同期总收入的79.84%、81.24%和76.20；中成药制剂收入分别为2.43亿元、1.9亿元和1.89亿元。百利天恒近年来业务收入组成来源：招股书如果从仿制药的收入结构看，百利天恒与海思科有几分相似，均是以麻醉类产品为营收主力，以肠外营养产品为辅助。2021年，百利天恒的麻醉类产品收入4.02亿元，占化药营收的66.3%，占总营收的50.6%；肠外营养收入1.16亿元，占化药营收的19.14%，占总营收的14.59%。麻醉类产品中，百利天恒的主打产品为丙泊酚系列产品。丙泊酚主要用于麻醉诱导和维持、无痛胃肠镜检查领域以及ICU镇静领域，是麻醉镇静领域王牌产品。据统计，在2021年国内样本医院中丙泊酚销售额为10.88亿元，占整体全麻药35.75%。其中，外企爱施健（Aspen Pharma）和费森尤斯卡比（Fresenius Kabi）进口产品占比较大，市场份额分别为42.01%和25.72%。2019年-2021年，百利天恒生产的丙泊酚产品市场占有率分别为8.56%、10.78%和7.54%，市场占有率排名分别为第4、第3和第4，除去外企进口产品后在国内企业中排名第2、第1和第2。但是在2021年第四批国家集采中，百利天恒丙泊酚中/长链脂肪乳注射液未中标，因此我们可以看到其该产品自2021年收入较上年大幅下滑67.77%，并在2022年上半年再次下滑87.39%，可见集采威力之大，落标几乎等于退出市场。同样的剧情也发生在右美托咪定身上，2019年的“4+7”集中采购中，仅扬子江药业一家中标。2012-2021年国内样本医院丙泊酚市场份额来源：招股书除了化药板块，百利天恒独特的中药制剂也为其赢下了不错市场和收入。好好黄芪（黄芪颗粒）由其子公司百利药业生产，2019-2021年，来自好好黄芪（黄芪颗粒）销售收入分别为1.9亿元、1.57亿元和1.61亿元，在国内样本医院中市场占有率分别为94.28%、94.68%和97.25%，均排名行业第一。柴黄颗粒在医院市场主要用于中成药类感冒用药，2019-2021年，柴黄颗粒在国内样本医院中的市场份额分别为81.53%、82.86%和80.92%，均排名行业第一。单从仿制药和中药板块的收入组成来看，百利天恒的体量规模在国内不算特别突出，在集采的冲击下，其收入也在不断遭到蚕食。在这样的背景下，百利天恒第一次冲击创业板以失败告终。但好在，百利天恒在很早以前就开始布局创新药的研发，而且瞄准的都是Best-in-class和First-in-class的项目。这样的胆识和气魄，在当时的环境下可谓绝无仅有，就连恒瑞医药都无法望其项背。也因此，百利天恒得以成功冲刺科创板。那么，百利天恒的创新药研发管线能为其带来怎样的估值？02是否过于激进？2010年，整个中国医药行业几乎没人做生物医药创新，百利天恒当时的销售额已到亿元以上，每年有几千万的现金流稳定入账。但彼时百利天恒已提前嗅到了行业转变的风向，早早就开始布局。在经历了三年的探索后，百利天恒逐渐确立了自身路线，2012年和2014年，百利天恒分别整合研发团队和资源，入驻成都天府生命科技园区、在美国西雅图成立Systimmune Inc.，聚焦抗肿瘤创新抗体药物，由此形成了中美两地双研发中心的布局。2015年，百利天恒即申请了第一个双特专利、第一个ADC专利，并立项多特异性抗体研发。截至IPO前，百利天恒已自主研发了16个创新生物药，其中9个已进入临床研究阶段，7个候选生物药已进入临床前药理、毒理等研究阶段。药物涵盖双/多特异性抗体、ADC药物、融合蛋白等不同类型，聚焦于肿瘤治疗等领域，用于治疗非小细胞肺癌、乳腺癌、胃癌等临床亟需解决的重大疾病。与近两年已登陆资本市场的Biotech明显不同的是，百利天恒的研发策略更加激进，也因此，更具价值。百利天恒研发管线来源：招股书03核心产品：SI-B001（EGFR×HER3双抗）SI-B001是百利天恒基于自主建立的SEBA平台，独立研发的具有完全自主知识产权和全球权益的双特异性抗体分子。可同时靶向EGFR和HER3两个肿瘤治疗相关靶点，拟用于非小细胞肺癌、结直肠癌、头颈鳞癌、食管鳞癌及其他EGFR基因驱动型肿瘤的治疗。目前已在非小细胞肺癌、结直肠癌、食管鳞癌、头颈鳞癌等多个上皮肿瘤上开展6个II期临床研究。SI-B001可同时结合肿瘤细胞上的EGFR×EGFR同源二聚体和EGFR×HER3异源二聚体，阻断EGFR及HER3与其各自配体的结合，从而进一步阻断EGFR和HER3及其下游通路的药理活性，实现抑制和杀伤肿瘤的目的。SI-B001作用机制来源：招股书04SI-B003（PD-1×CTLA-4双抗）SI-B003可同时靶向并阻断PD-1与CTLA-4靶点，发挥抗肿瘤的药理活性。一方面，SI-B003可通过阻断APC细胞（抗原呈递细胞）上B7与T细胞CTLA-4的结合，以及PD-L1/2与PD-1的结合，解除免疫抑制，激活T细胞免疫。另一方面，SI-B003也能在肿瘤微环境中，解除肿瘤细胞上PD-L1/2与T细胞PD-1的结合，恢复T细胞免疫应答。通过以上协同作用，SI-B003可充分激活T细胞，从而获得更强的T细胞抗肿瘤活性。05双价ACE2-Fc（n2）融合蛋白SI-F019产品ACE2为新冠病毒SARS-CoV-2感染人体细胞最重要的受体，也是传播感染的必由环节。SI-F019具有ACE2结构域，可以代替人ACE2蛋白与新冠病毒在细胞外结合，从而阻断新冠病毒感染人体细胞，实现对病毒的中和作用。另一方面，基于ACE2是多种冠状病毒感染人体细胞的受体这一特征，SI-F019采用了双价ACE2的设计，能够以较高的亲和力中和多种以人ACE2蛋白为受体的病毒，既防止病毒突变逃逸，又能够广谱应用于其他以ACE2为受体的病毒。06四抗候选药物GNC-038、GNC-039、GNC-035GNC-038、GNC-039和GNC-035均为四特异性抗体，由于结构和作用机制的特殊性，四特异性GNC分子具有三种相同的肿瘤“靶向免疫治疗”相关结构域（CD3结构域、4-1BB结构域、PD-L1结构域）和一种不同的结合肿瘤抗原（如TAA，tumor-associated antigen，肿瘤相关抗原）结构域。GNC-038的肿瘤抗原为CD19结构域，该候选药物除了靶向CD3×4-1BB×PD-L1靶点外，还能特异性靶向CD19靶点，未来拟用于非霍奇金淋巴瘤、急性淋巴细胞白血病等血液系统肿瘤的治疗。GNC-039的肿瘤抗原为EGFRvIII结构域，该候选药物除了靶向CD3×4-1BB×PD-L1靶点外，还能特异性靶向EGFRvIII靶点，未来拟用于高级别脑胶质瘤的治疗。GNC-035的肿瘤抗原为ROR1结构域，该候选药物除了靶向CD3×4-1BB×PD-L1靶点外，还能特异性靶向ROR1靶点，未来拟用于乳腺癌、非霍奇金淋巴瘤等复发/难治性肿瘤的治疗。07双抗ADC药物BL-B01D1BL-B01D1是具有抗肿瘤活性的重组人源化双特异性抗体药物偶联药物，一方面可同时结合肿瘤细胞上的EGFR和HER3，实现对两个肿瘤相关靶点的同时阻断，以此获得靶向性和增强的抗肿瘤活性；另一方面，BL-B01D1分子经EGFR、HER3的结合、内吞作用后进入细胞内部，由水解酶酶切释放小分子毒素ED04（拓扑异构酶抑制剂），阻止肿瘤细胞的DNA复制和RNA合成，并破坏DNA结构，从而进一步杀伤肿瘤细胞。除了上述候选产品外，百利天恒的研发管线中还包含多款尚未披露具体靶点的多特异性抗体以及ADC在研产品。百利天恒这条精心打造的管线有多激进，我们通过其核心的几个在研产品便能一窥一二。截至IPO前，全球范围内处于临床研究阶段的EGFR×HER3双抗仅有SI-B001；全球范围内进入临床研究的四特异性抗体，仅百利天恒的GNC-038、GNC-039、GNC-035；全球范围内尚未有双抗ADC获批上市，百利天恒的BL-B01D1是全球第三个、中国第一个进入临床研究阶段的双抗ADC药物，也是全球第一个进入临床研究阶段的EGFR×HER3双抗ADC药物。激进的研发策略，风险巨大，但同时也意味着机会更大。08结语在刚刚过去的2022年，中国首款国产双抗获批，国产ADC创下破纪录的巨额交易，国内的Biotech正在以爆发的方式向世界宣告属于中国的生物制药时代已经来临。虽然目前市场上的主流仍是Fast-follow，但还是有一些勇士，敢于挑战最前沿的科技。正是这些勇士撑起了中国生物科技未来的想象力，百利天恒就是这样的勇士之一。或许收获可能还为时尚早，但等待终将值得。后续发展如何，我们还将持续关注。参考资料百利天恒招股书《手握多个全球独家，仿制药企转型急先锋百利天恒冲刺IPO》，梧桐树下，2022-12-19关注药渡数据媒体矩阵

财报抗体药物偶联物

100 项与 SI-F019 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床2期	中国	四川百利天恒药业股份有限公司	2022-07-05
肺动脉高压	临床2期	中国	四川百利天恒药业股份有限公司	2022-07-05
呼吸窘迫综合征	临床2期	中国	四川百利天恒药业股份有限公司	2022-07-05

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临床结果

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分期

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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


Pubmed \| Scand J Gastroenterol	N/A	肠易激综合征	131	Probiotic mixture (Lactobacillus paracasei ssp paracasei F19, Lactobacillus acidophilus La5, and Bifidobacterium Bb12)	(糧襯範遞遞醖鬱蓋衊艱) = 顧構選繭構願憲簾廠繭廠膚淵遞構選築築鑰遞 (觸獵壓膚願獵蓋鬱鬱窪 )	不佳	2013-10-01
				Placebo	(糧襯範遞遞醖鬱蓋衊艱) = 願醖範顧願膚範簾壓廠廠膚淵遞構選築築鑰遞 (觸獵壓膚願獵蓋鬱鬱窪 )
Pubmed \| Pediatr Infect Dis J	N/A	-	-	Palivizumab (Immunocompromised children)	網觸觸範衊夢繭積糧鹹(構窪膚築觸襯繭窪餘鏇): HR = 1.7 (95% CI, 0.9 ~ 3.4)	-	2020-06-01
				Palivizumab (CMD)