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标题: EASL 2019预览 - 维京和春天银行抽象的早期兴趣 [打印本页]

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作者: StephenW    时间: 2019-3-29 10:20     标题: EASL 2019预览 - 维京和春天银行抽象的早期兴趣

      EASL 2019 preview – Viking and Spring Bank abstracts pique early interest            

•                                                                                  
•         Amy Brown
• 
  

  
     
                High-profile presentations from the likes of Intercept and Alnylam remain under wraps before Europe’s biggest liver disease conference next month, but the early abstract release makes for an intriguing curtain-raiser.
                        

                                                  As biopharma companies have turned their attention to liver diseases like Nash and hepatitis B over the past few years, the annual EASL/ILC conference has increasingly come onto investors’ radars. Next month’s meeting in Vienna promises to deliver important updates from small and large companies, including Intercept, Alnylam and Assembly Biosciences.
The most consequential data are being held back for the conference, but abstracts released yesterday contained some notable updates from the likes of Viking Therapeutics, Altimmune and Spring Bank Pharmaceuticals. Viking in particular caused something of a stir with data on VK2809, a thyroid hormone receptor beta agonist that counts as one of the sector’s most closely watched Nash projects.
An abstract on a phase II trial contained the first data seen with a low 5mg dose of VK2809, suggesting that this could be as effective as 10mg, with obvious safety advantages. Leerink analysts wrote that should this be confirmed in larger studies, VK2809 could be a best-in-class compound.
An update from Spring Bank concerning its hepatitis B antiviral inarigivir also attracted attention; final results from the Achieve study of the Rig-1 agonist have been selected as a late breaker at the conference. A placeholder abstract was released yesterday, describing an ongoing dose-dependent response to therapy; results from the highest dose tested in Achieve, 200mg, have yet to be fully disclosed.
Preliminary data revealed that the 200mg dose of inarigivir produced a maximum HBV DNA reduction of 3.26 logs, although this could change. The company previously announced a 2.76 log reduction with a 100mg dose. This is considered impressive efficacy for an oral monotherapy, and these latest data will raise hopes for the impending clinical programme testing an even higher dose, 400mg.
Elsewhere, an abstract from Altimmune containing full data on its therapeutic hepatitis B vaccine HepTcell make for interesting reading; the company recently said it would push into phase II. An early look at the data from this study was not encouraging – immune responses were similar in the treated and placebo arms – but at the final analysis the company concluded that two adjuvanted HepTcell arms had markedly greater increases in T-cell immunity than placebo. The full data from the trial will be presented on Friday April 12.
NGM has a number of posters on its FGF19 analogue NGM282, which has largely disappointed, so most interest is likely to focus on NGM313, an antibody activator of βklotho/FGFR1c, over which Merck & Co recently exercised an option. The company will present encouraging early data from 25 NAFLD patients, appearing to show the insulin sensitiser reducing liver fat as well as inflammatory and fibrotic markers.
On April 12 Cirius Therapeutics will present data from a phase IIb trial called Emminence, testing its insulin sensitiser MSDC-0602K in Nash patients with fibrosis. The presentation is slated as a late breaker, and is presumably a closer look at the data released last October, though curiously the company did not highlight the presentation in a press release yesterday, only mentioning a couple of abstracts concerning preclinical findings. Earlier this year Cirius filed to raise $86m in an IPO on Nasdaq.
[td]               

EASL data to watch out for
Company	Project	Details	Presentation
Late-breakers
Alnylam	Givosiran	AHP; Envision phase III	Plenary Sat April 13
Myr Pharma/Hepatera	Myrcludex B	HBV; phase II data	Plenary Sat April 13
Promathera Biosciences	HepaStem	Liver failure; phase I/II data	Plenary Sat April 13
Assembly Biosciences	ABI-H0731	HBV; phase IIa data	Late breaker Sat Apr 13
Conatus	Emricasan	Nash; phase II data	Late breaker Sat Apr 13
Genfit	Elafibranor	PBC trial; phase II	Late breaker Sat Apr 13
Other presentations
Intercept	Ocaliva	Nash; Regenerate phase III	Thu Apr 11
Viking	VK2809	Nash; phase II data	Thu Apr 11
Spring Bank	Inarigivir	HBV; Achieve phase II study	Fri Apr 12
Cirius Therapeutics	MSDC-0602K	Nash; phase IIb results	Fri Apr 12
Altimmune	HepTcell	HBV; phase Ib data	Fri Apr 12
NGM/Merck & Co	NGM313	NAFLD; phase I	Fri Apr 12
Takeda	Maralixibat/SHP627	Alagille Syndrome; phase II data	Sat Apr 13
Albireo	A4250	Alagille Syndrome; phase II data	Sat Apr 13
AHP=acute hepatic porphyrias; HBV=hepatitis B virus; NAFLD=non-alcoholic fatty liver disease; PBC=primary biliary cholangitis. Source: EASL programme.

Much of the data that investors are waiting for, however, has not been released in advance.
On the first day full results from Intercept’s Regenerate study will be the big draw. The company released ostensibly positive topline data in early March, but many remain to be convinced by the product’s profile, particularly regarding safety (Intercept's Nash hopes rest on Ocaliva's borderline hit, February 19, 2019).  
Most of the high-profile late breakers will emerge on the Saturday. The plenary session on Saturday morning will see Alnylam get its moment in the spotlight with the Envision study of givosiran, with all eyes once again on the toxicity profile (Alnylam touts givosiran win despite toxicity fears, March 6, 2019).
The private Russian company Hepatera has also bagged a plenary spot with its hepatitis B therapy Myrcludex B, a viral entry inhibitor, alongside Promathera Biosciences’ stem cell-based liver failure therapy HepaStem.
Other late breakers on Saturday will feature Conatus’s Encore-PH trial of emricasan, which is known to have failed, a study of Genfit’s elafibranor in PBC, and an update on a phase IIa trial of Assembly Biosciences’s hepatitis B project ABI-H0731. Assembly is expected to report six-month data in a couple of patients for the first time, and a strong reading could see investors gain appreciation for this largely overlooked project.
There is everything still to play for in both hepatitis B and Nash. Although much of the data at EASL this year is from early trials, investors will hope for some important glimpses into several of the most promising pipeline projects.

            

         

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作者: StephenW    时间: 2019-3-29 10:22

EASL 2019预览 - 维京和春天银行抽象的早期兴趣

    艾米布朗

来自Intercept和Alnylam等公司的高调演讲在下个月欧洲最大的肝脏疾病会议之前仍未完成，但早期的抽象发布令人眼花缭乱。
肝脏的例证红灯的反对黑暗的背景

由于生物制药公司过去几年将注意力转向纳氏和乙型肝炎等肝脏疾病，年度EASL / ILC会议越来越多地投入到投资者的视线中。下个月在维也纳举行的会议有望提供包括Intercept，Alnylam和Assembly Biosciences在内的大型公司的重要更新。

最重要的数据被阻止参加会议，但昨天发布的摘要包含来自Viking Therapeutics，Altimmune和Spring Bank Pharmaceuticals等公司的一些值得注意的更新。 Viking特别引起了VK2809数据的轰动，这是一种甲状腺激素受体β激动剂，被认为是该部门最受关注的Nash项目之一。

II期试验的摘要包含了低剂量VK2809的第一个数据，表明这可能与10mg一样有效，具有明显的安全性优势。 Leerink分析师写道，如果在更大规模的研究中证实这一点，VK2809可能是一流的化合物。

春秋银行关于乙型肝炎病毒抗病毒药物的更新也引起了人们的关注;实践研究的Rig-1激动剂的最终结果被选为会议的后期破坏者。昨天发布了一个占位符摘要，描述了对治疗持续的剂量依赖性反应;在Achieve中测试的最高剂量200mg的结果尚未完全公开。

初步数据显示200mg剂量的inarigivir最大HBV DNA减少3.26 log，尽管这可能会改变。该公司此前宣布以100mg剂量减少2.76对数。这被认为是口服单一疗法的令人印象深刻的功效，这些最新数据将为即将进行的临床计划测试提供更高剂量400mg的希望。

在其他地方，来自Altimmune的摘要包含其治疗性乙型肝炎疫苗HepTcell的完整数据，可用于阅读;该公司最近表示将进入第二阶段。早期研究这项研究的数据并不令人鼓舞 - 免疫反应在治疗组和安慰剂组中相似 - 但最终分析结果表明，两种有佐剂的HepT细胞臂的T细胞免疫力明显高于安慰剂组。试验的全部数据将于4月12日星期五公布。

NGM在其FGF19类似物NGM282上有许多海报，这些海报很大程度上令人失望，因此最感兴趣的可能是NGM313，一种βklotho/ FGFR1c的抗体激活剂，Merck＆Co最近在其上运用了一种选择。该公司将提供来自25名NAFLD患者的令人鼓舞的早期数据，似乎显示胰岛素敏感剂减少肝脏脂肪以及炎症和纤维化标记物。

4月12日，Cirius Therapeutics公司将展示一项名为Emminence的IIb期试验数据，在Nash纤维化患者中测试其胰岛素敏化剂MSDC-0602K。该演示文稿被定为晚期破坏者，并且可能是对去年10月发布的数据进行仔细研究，但奇怪的是该公司昨天没有在新闻稿中突出显示该演示文稿，只提及了几个关于临床前研究结果的摘要。今年早些时候，Cirius在纳斯达克上市首次公开募股筹集了8600万美元。
要注意的EASL数据
公司项目详情介绍
晚断路器
Alnylam Givosiran AHP;设想第三阶段全体会议4月13日星期六
Myr Pharma / Hepatera Myrcludex B HBV;第二阶段数据全体会议4月13日星期六
Promathera Biosciences HepaStem肝功能衰竭;第一阶段/第二阶段数据全体会议4月13日星期六
Assembly Biosciences ABI-H0731 HBV;阶段IIa数据延迟断路器4月13日星期六
Conatus Emricasan Nash;第二阶段数据延迟断路器周四4月13日
Genfit Elafibranor PBC试验;第二阶段晚期破坏者4月13日星期六
其他演讲
拦截Ocaliva Nash;再生第三阶段Thu Apr 11
维京VK2809纳什;第二阶段数据4月11日
春季银行Inarigivir HBV; 4月12日周五进行第二阶段研究
Cirius Therapeutics MSDC-0602K纳什;阶段IIb结果4月12日星期五
Altimmune HepTcell HBV;阶段Ib数据4月12日星期五
NGM / Merck＆Co NGM313 NAFLD;第一阶段4月12日星期五
Takeda Maralixibat / SHP627 Alagille综合症;第二阶段数据4月13日星期六
Albireo A4250 Alagille综合症;第二阶段数据4月13日星期六
AHP =急性肝卟啉症; HBV =乙型肝炎病毒; NAFLD =非酒精性脂肪性肝病; PBC =原发性胆汁性胆管炎。资料来源：EASL计划。

然而，投资者等待的大部分数据尚未提前发布。
在第一天，Intercept的Regenerate研究的全部结果将是最大的吸引力。该公司在3月初公布了表面上积极的一线数据，但很多人仍然对该产品的形象深信不疑，特别是在安全性方面（Intercept的Nash希望依靠Ocaliva的边界线，2019年2月19日）。

大多数备受瞩目的晚期断路器将在周六出现。星期六早上的全体会议将看到Alnylam在Envision对givosiran的研究中成为焦点，所有的目光再一次关注毒性特征（Alnylam在尽管有毒性恐惧的情况下宣传了givosiran，2019年3月6日）。

俄罗斯私人公司Hepatera还与Promathera Biosciences的基于干细胞的肝衰竭疗法HepaStem一起，将其乙型肝炎疗法Myrcludex B（一种病毒进入抑制剂）与其进行了全面讨论。

星期六的其他晚期断路器将采用Conatus的encore-PH试验，其中已知失败的emricasan，对PBC的Genfit的elafibranor的研究，以及装配生物科学的乙型肝炎项目ABI-H0731的IIa期试验的更新。预计大会将首次报告几个患者的六个月数据，并且强烈的阅读可以让投资者对这个被忽视的项目获得赞赏。

乙型肝炎和纳什都有一切可以发挥作用。虽然今年EASL的大部分数据来自早期试验，但投资者希望对几个最有前景的管道项目有一些重要的看法。

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