艾格生物制药是治疗病毒性肝炎的领导者？

StephenW

Eiger BioPharmaceuticals A Leader In Treatment Of Viral Hepatitis?Jun. 20, 2018  8:15 AM ET|
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About: Eiger BioPharmaceuticals, Inc. (EIGR)


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SummaryEiger BioPharmaceuticals is a small biopharma focused on rare diseases.
I will discuss HBV/HDV co-infection and how there is a pressing need for new drugs.
I will focus on EIGR's development of drugs for treating HBV/HDV co-infections.
I will also discuss in depth Lonafarnib, one of Eiger BioPharmaceuticals' lead compounds that they are developing for treatment of rare disease hepatitis delta virus (HDV) and progeria.



Introduction

In this article, I will focus on Eiger BioPharmaceuticals (NASDAQ:EIGR) and its development of treatment for HBV/HDV co-infections. I will discuss the science behind Eiger's two lead compounds and which one I believe is the better bet. While there are other companies working on treatments for HBV/HDV co-infections, Eiger is well ahead in clinical trials. Lastly, I will discuss lonafarnib as a treatment for HDV and the future of Eiger BioPharmaceuticals.

Hepatitis B (HBV)/delta (HDV) viral co-infections are the most aggressive form of viral hepatitis

Globally, it is estimated that 257 million people are chronically infected with hepatitis B virus (HBV) of which approximately 20 million are co-infected with hepatitis delta virus (HDV). HBV/HDV chronically infected patients develop rapid and severe hepatitis due to their infection. These patients have a 600-fold higher likelihood of developing hepatocellular carcinoma, aka liver cancer, than HBV mono-infected patients which already have an elevated risk as compared to the healthy general population.

HDV is a small RNA virus that requires an HBV co-infection in order to spread in the patient's liver and to form infectious virions. As such, people that have received the HBV vaccine are also protected against infection with HDV. HDV encodes only a single gene, the HDAg, that has two forms performing two different functions. While it is very small and is considered "simple", this is actually not the case in terms of treatment. As the virus highjacks the host machinery (DNA polymerase, RNA polymerase, …etc) to replicate its genome, it is difficult to develop inhibitors of HDV that do not also make patients incredible sick. One key part of the HDV life-cycle is that the HDAg must be prenylated, the addition of a hydrophobic lipid to the protein, in order for HDV to form a virus particle. As such, this is a good potential target to inhibit HDV.

HBV/HDV co-infections are considered by the FDA as a rare disease. As such, the approval process for HDV treatments is accelerated. In addition, there are currently no approved treatments for HBV/HDV co-infections. Eiger currently is the only company that has two treatments in development for the treatment of HDV. It should also be noted it is unclear the number of HBV/HDV co-infected patients in the United States (less than 200,000 reported as it is considered a "rare disease") but the Centers for Disease control (CDC) estimates that HDV diagnosis might be underreported by 20%.

Eiger's HDV treatments in development

Eiger has two different compounds in development. The first is pegylated interferon lambda (IFN-lambda), an innate immune stimulator. It is a human protein that activates the type III interferon receptor pathway which activates the JAK-Stat pathway leading to viral suppression. Pegylated interferon alpha (IFN-alpha) was the standard of care for HBV for almost 2 decades. IFN-alpha activates type I interferon receptors but still acts through the JAK-Stat pathway. IFN-alpha is now used only rarely in the treatment of HBV as it results in very terrible side effects and, as such, patients tend not to adhere to their treatment regimen. Type I IFN receptors are on several cell types, type III is on fewer cell types, and as such, Eiger argues that this will reduce the off-target side effects increasing efficacy and also patient compliance. In phase I/II fast track, trial showed that overall there was good tolerance. Eiger BioPharmaceuticals is moving into phase III trials. Keep close attention to updates about these phase III trials as they get underway.

Lonafarnib (LNF) is a prenylation inhibitor which inhibits the lipid prenylation of the HDAg. As such, the HDV virion is not able to exit from the infected hepatocyte preventing spread of the virus and could most likely reduce HDV viral load over time. This has been borne out by the clinical data showing that HDV RNA is the serum of patients reduces over the course of several weeks. However, the effect is not long lasting as when treatment is stopped, the virus is able to rebound. As such, Eiger is also performing phase II clinical trials where they combine LNF with pegylated IFN-lambda. This combination therapy, in theory, should prevent HDV spread and should reduce and possibly clear the HDV viral RNA from infected hepatocytes as the pegylated IFN-lambda would activate interferon stimulated genes resulting in targeting of the HDV genomic RNA for degradation.

The major issue with LNF is that it causes gastrointestinal (GI) issues in patients. This is usually manifested as diarrhea and discomfort. It remains to be seen if these side effects are going to become more severe with longer treatment regiments of LNF. Another option is that, with combination therapy with pegylated IFN-lambda, the amount of LNF used could be reduced and as such, the GI side effects will consummately also be lowered.

Eiger is also developing LNF for a different indication, the treatment of progeria. Progeria is a devastating rare disease where patients age at an accelerated rate. Patients with progeria have a significantly lowered life expectancy as well as quality of life. There is also no treatment currently available for progeria. It has been shown in phase II trials that LNF and prenylation inhibition can improve the quality of life and symptoms of patients with progeria. As such, it may extend the lives of these patients.

Can Eiger make it past the finish line?

Eiger has $33.2 million in the form of cash, cash equivalents, and short-term debt. Its two lead compounds are heading into phase III trials (LNF and pegylated interferon lambda). Eiger's cash burn rate for the first quarter of 2018 was $8.8 million. As such, Eiger has enough cash to complete its phase III trial for LNF. However, to complete the two additional phase III trials, Eiger is about to undergo with pegylated interferon lambda mono-treatment and the co- LNF and pegylated interferon lambda study the company will most likely have to dilute shareholders by offering more of the company for sale in order to finance these adventures.

Advocacy by special interest groups for LNF treatment

Eiger BioPharmaceuticals' two lead compounds are pegylated IFN-lambda in phase III and LNF both for the treatment of HBV/HDV infection. In addition, LNF is being developed for the treatment of progeria, a terrible genetic disorder. Eiger BioPharmaceuticals has a very strong collaborative relationship with two advocacy groups that will help with its approval of both of these treatments. The first is the HBV Foundation, the other is The Progeria Foundation. These are both powerful lobbying advocacy groups that will help Eiger get approval for these two compounds as they would be the first treatment for HDV and progeria.

Conclusion

I think that it is imminent that Eiger will get approval of its pegylated IFN-lambda treatment for HDV as the phase I/II data showed efficacy in being able to suppress HDV in the serum of infected patients. As such, I believe that the phase III trials will be successful and will end later this year 2018 or early next 2019. This may soon be followed by approval of LNF in 2019-2020. In addition, Eiger is also working on approval of a combination therapy using its two compounds pegylated IFN-lambda and LNF. The phase II preliminary data looks promising for this combination therapy and should be completed 2018-2019. This creates a significant advantage as Eiger has three different therapies in development for HDV. There are other companies, MYR Pharma is one that is also developing its own therapies for treating HBV/HDV infection. However, Eiger is so far ahead in its development of LNF and pegylated interferon lambda that it will most likely be first to market. As such, all other potential drugs will be compared to Eiger's for efficacy. I predict that Eiger will be a leader in HDV treatment and is a great investment as a result. In addition, LNF might be approved for progeria indication creating another revenue stream for the company.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Editor's Note: This article covers one or more stocks trading at less than $1 per share and/or with less than a $100 million market cap. Please be aware of the risks associated with these stocks.

StephenW

艾格生物制药是治疗病毒性肝炎的领导者？
2018年6月20日8:15 ET |
2条评论
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关于：艾格生物制药有限公司（EIGR）
Augury投资
Augury投资
长期以来，深度价值，以合理的价格增长，研究分析师
（60位追随者）
概要

艾格生物制药是一种专注于罕见疾病的小型生物制药。

我将讨论HBV / HDV合并感染以及新药如何迫切需要。

我将重点讨论EIGR开发治疗HBV / HDV共感染的药物。

我还将深入讨论Lonafarnib，艾诺生物制药的先导化合物之一，它们正在开发用于治疗罕见疾病的肝炎三角洲病毒（HDV）和早老性痴呆症。
介绍

在本文中，我将重点介绍艾格生物制药公司（纳斯达克股票代码：EIGR）及其开发的治疗HBV / HDV合并感染的方法。我将讨论艾格背景下的两种先导化合物，以及我认为哪种更好的选择。虽然还有其他公司正在从事HBV / HDV共同感染的治疗，但艾格在临床试验中遥遥领先。最后，我将讨论lonafarnib作为治疗HDV和艾格生物制药未来的方法。
乙型肝炎（HBV）/三角洲（HDV）病毒合并感染是病毒性肝炎的最积极形式

估计全球有2.57亿人长期感染乙型肝炎病毒（HBV），其中约2000万人与丁肝病毒（HDV）共同感染。 HBV / HDV慢性感染患者由于感染而发展为快速和严重的肝炎。与健康人群相比，这些患者发生肝细胞癌的可能性高出肝癌的600倍，而HBV单发感染患者的风险已经升高。

HDV是一种小RNA病毒，需要HBV共感染才能传播到病人的肝脏并形成传染性病毒颗粒。因此，接受过乙肝疫苗的人也可以免受HDV感染。 HDV只编码一种基因HDAg，它有两种形式执行两种不同的功能。虽然它很小，被认为是“简单的”，但在治疗方面实际上并非如此。由于病毒会劫持宿主机器（DNA聚合酶，RNA聚合酶等）以复制其基因组，所以很难开发H​​DV抑制剂，这种抑制剂也不会令患者难以置信地患病。 HDV生命周期的一个关键部分是HDAg必须被异戊二烯化，向蛋白质中添加疏水性脂质，以便HDV形成病毒颗粒。因此，这是抑制HDV的良好潜在目标。

FDA / HDV共同感染被FDA认为是一种罕见疾病。因此，加速了HDV治疗的批准过程。另外，目前还没有经过批准的HBV / HDV共同感染治疗。艾格目前是唯一一家有两种治疗HDV治疗方法的公司。还应该注意的是，目前还不清楚美国HBV / HDV共感染患者的数量（据报道少于20万，因为它被认为是“罕见疾病”），但疾病控制中心（CDC）估计HDV诊断可能低报20％。
艾格开发的HDV治疗

艾格在研发中有两种不同的化合物。第一种是聚乙二醇化干扰素λ（IFN-λ），一种先天免疫刺激剂。它是激活III型干扰素受体途径的人类蛋白质，其活化JAK-Stat途径导致病毒抑制。聚乙二醇干扰素α（IFN-α）是近二十年来用于治疗HBV的标准。干扰素-α激活I型干扰素受体，但仍然通过JAK-Stat途径起作用。 IFN-α现在仅用于治疗HBV的情况很少，因为它会导致非常可怕的副作用，因此患者往往不坚持治疗方案。 I型IFN受体在几种细胞类型上，III型在较少的细胞类型上，因此，Eiger认为这将减少脱靶副作用，增加效力并且也符合患者依从性。在第一阶段/第二阶段的快速通道中，试验表明总体上有良好的宽容度。艾格生物制药正在进入III期临床试验阶段。密切关注这些III期临床试验的最新进展。
Lonafarnib（LNF）是抑制HDAg脂质异戊烯化的异戊烯化抑制剂。因此，HDV病毒体不能从受感染的肝细胞中排出，防止病毒传播，并且可能随时间推移最有可能减少HDV病毒载量。临床数据显示，HDV RNA是患者血清在数周内减少的结果。但是，当治疗停止时，效果不会持久，病毒可以反弹。因此，艾格还正在进行II期临床试验，将LNF与聚乙二醇化IFN-λ结合起来。理论上，这种组合疗法应该能够预防HDV扩散，并且应该减少并可能从感染的肝细胞中清除HDV病毒RNA，因为聚乙二醇化的IFN-λ会激活干扰素刺激的基因，从而导致HDV基因组RNA的降解。

LNF的主要问题是它会导致患者胃肠（GI）问题。这通常表现为腹泻和不适。在LNF治疗方案较长的情况下，这些副作用是否会变得更加严重仍有待观察。另一种选择是，用聚乙二醇化IFN-λ联合治疗，可以减少LNF的使用量，因此GI副作用也将被完全降低。

艾格还正在开发针对不同症状的LNF，即progeria的治疗。 Progeria是一种破坏性罕见疾病，患者年龄增长速度加快。早衰患者的预期寿命和生活质量显着降低。目前还没有针对progeria的治疗方法。在II期试验中已经表明LNF和异戊烯基化抑制可以改善早衰患者的生活质量和症状。因此，它可能会延长这些患者的生命。
艾格能否超越终点？

艾格以3320万美元的现金，现金等价物和短期债务形式出现。其两种先导化合物正在进入III期试验（LNF和聚乙二醇干扰素λ）。艾格在2018年第一季度的现金消费率为880万美元。因此，艾格拥有足够的现金来完成对LNF的第三阶段试验。然而，为了完成另外两项III期临床试验，艾格将要接受聚乙二醇化干扰素λ单一治疗，并且联合LNF和聚乙二醇化干扰素拉米达研究公司将很可能不得不通过提供更多的公司出售稀释股东以资助这些冒险。
由特殊利益团体提倡LNF治疗

艾格生物制药公司的两种先导化合物是聚乙二醇化的III期IFN-λ和LNF，用于治疗HBV / HDV感染。此外，LNF正在开发用于治疗可怕的遗传疾病 - 早衰。艾格生物制药与两个倡导团体建立了非常强大的合作关系，这将有助于批准这两种治疗方案。第一个是HBV基金会，另一个是Progeria基金会。这些都是强大的游说倡导团体，这将有助于艾格获得这两种化合物的批准，因为它们将是HDV和progeria的第一种治疗方法。
结论

我认为，随着I / II期数据显示能够抑制受感染患者血清中的HDV，Eiger将获得聚乙二醇化IFN-λ治疗HDV的批准即将到来。因此，我相信III期临床试验将取得成功，并将于2018年底或2019年年底之后结束。随后2019-2020年可能会批准LNF。此外，艾格还正在研究使用其两种聚乙二醇化IFN-λ和LNF的联合疗法。第二阶段的初步数据看起来很有希望用于这种联合治疗，并应在2018-2019年完成。由于艾格有三种不同的治疗HDV的发展，这产生了显着的优势。还有其他公司，MYR制药公司也正在开发治疗HBV / HDV感染的自身疗法。然而，艾格在LNF和聚乙二醇干扰素拉姆达的研发中遥遥领先，因此很可能首先将其推向市场。因此，所有其他潜在的药物将与艾格的疗效进行比较。我预测艾格将成为HDV治疗领域的领导者，并因此成为一项巨大的投资。此外，LNF可能被批准用于progeria指示，为公司创造另一个收入来源。

披露：我/我们没有提到任何股票的头寸，也没有计划在未来72小时内发起任何头寸。

我自己写了这篇文章，它表达了我自己的观点。我没有获得赔偿（除了来自Seeking Alpha）。我与本文提到的任何公司都没有业务关系。

编者按：本文涵盖了一只或多只股票，每只股票的交易价格低于1美元和/或市值不足1亿美元。 请注意与这些股票相关的风险。

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