[宣传]Arbutus：EASL 數據發布後值得期待的 2 個關鍵催化劑

StephenW

2022 年 6 月 29 日下午 3:36 ETArbutus Biopharma Corporation (ABUS)ASMB、MRNA、VACC、VIR 4 條評論1 喜歡
概括

    預計 2022 年下半年將進行兩項使用 AB-729 治療乙型肝炎患者的三聯療法研究。
    一種 PD-L1 藥物正在研發中，以最終添加到與 AB-729 的三聯方案中；此外，有可能將相同的藥物用於腫瘤學。
    泛冠狀病毒計劃正在推進到 2022 年的 IND 授權研究，如果進展順利，我預計此後將啟動 1 期研究。
    截至 2022 年 3 月 31 日，Arbutus 擁有 2.218 億美元現金；有足夠的現金為 2024 年第二季度的運營提供資金。
    這個想法與我的私人投資社區生物技術分析中心的成員進行了更深入的討論。學到更多 ”

日冕病毒爆發期間在實驗室進行分析的醫務人員 — 科學與保健概念

Alessandro Biascioli/iStock 來自 Getty Images

Arbutus Biopharma Corporation（納斯達克股票代碼：ABUS）是一家值得研究的投機性生物技術公司。我之所以這麼說是因為它最近在最近的 EASL 國際肝臟大會上發布了 AB-729 用於治療乙型肝炎患者的新數據。

首先，會議上展示的 AB-729 本身就令人印象深刻。迄今為止，在 8 至 24 週的隨訪中，在患者停止接受 AB-729 劑量後，沒有證據表明病毒學或臨床復發。這需要監測超過 24 週，但如果這些患者繼續維持這樣的水平 1 年或更長時間，他們可能會部分功能性治愈乙型肝炎。這僅在 AB-729 的背後.

這讓我想到了下一點，即 2022 年下半年有兩個關鍵催化劑即將到來，我相信這可以為股票增加顯著價值。這是因為有數據將來自 AB-729 的兩項三聯研究。一種三聯組合是 AB-729 與 Assembly Biosciences (ASMB) vebicorvir 加 Nrtl 標準護理療法，第二種是 AB-729 與 Nrtl 加短期聚乙二醇化干擾素 alfa-2a。僅 AB-729 就在慢性乙型肝炎的部分/全部功能治愈方面取得瞭如此巨大的潛力，我相信這些三重組合研究中的一項可能會更好。
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因此，股票交易在每股 2.60 美元左右的風險/回報是相當理想的。特別是，由於 Vir Biotechnology (VIR) 也在使用一種 RNAi 藥物，如 AB-729，當與 PEG-IFN-α 一起放置時，與 VIR-2218 相比，乙型肝炎表面抗原 ((HBsAg)) 的下降幅度要大得多獨自的。我對這種三重組合更有信心，因為 RNAi 藥物和 PEG-IFN-a 組合在一起似乎效果很好。基於這兩個關鍵催化劑的臨近，這就是我認為 Arbutus 是一個值得研究的投機性生物技術公司的原因。
AB-729 數據揭示了恢復 HBV 特異性 T 細胞的能力

Arbutus Biopharma 最近在上週的 2022 年 EASL 國際肝臟大會上公佈了其 AB-729 RNA 干擾（（RNAi））藥物的最新結果。結果表明，僅 AB-729 就能夠使患者實現強勁的 HBsAg 下降。這在 HBeAg + 和 HBeAg- 患者中都觀察到，甚至更好。 32 名患者中約有 16 名 (50%) 在最後一次服用 AB-729 後 24 週內將 HBsAg 水平維持在 100 IU/mL 以下。這些數據表明，僅 AB-729 就非常強大，這是生物技術賴以發展的堅實基礎。

然而，我發現最有趣的是，迄今為止，停止 AB-729 加核苷類似物 (NA) 治療的前 5 名患者在 8 至 24 週的隨訪期間沒有病毒學或臨床復發的證據。為什麼這很關鍵？這是因為到目前為止，它證明 AB-729 即使在停止治療後仍繼續發揮作用。需要注意的一點是，這是初步的，為了確認乙型肝炎患者的部分/全部功能治愈，必須監測 1 年或更長時間。

儘管如此，單獨使用 AB-729 作為治療乙型肝炎患者的基石療法仍然是可靠的。由於本研究中的其他患者符合停止標準，他們也可能能夠同時停止 AB-729 和 NA 治療。從那裡，Arbutus 將監測所有此類其他患者，以查看在較長時間後是否發生病毒學或臨床復發。 AB-729如何繼續工作？這可能是因為 AB-729 繼續恢復 HBV 特異性 T 細胞並減少耗盡的 T 細胞。這種疾病的一個主要問題是 T 細胞已經耗盡並且對它的反應很弱。即使在停止治療後，隨著時間的推移，這可能會被證明是有用的。
2022 年下半年值得關注的兩個關鍵催化劑

如上所述，AB-729 能夠恢復 HBV 特異性 T 細胞並減少耗盡的 T 細胞。接下來是什麼？嗯，將在 2022 年下半年公佈兩項三聯研究。這些研究很重要，因為它們正在添加額外的藥物，與單獨的 AB-729 相比，這些藥物可能會產生更明顯的反應。第一個三聯療法是 AB-729 + Assembly 的 vebicorvir + Nrtl 標準護理療法。早在 2021 年 2 月，就針對這種組合啟動了一項 2 期隨機開放標籤臨床試驗。將招募約 60 名 HBeAg 陰性慢性乙型肝炎病毒 (HBV) 病毒學抑制患者。研究的武器如下：

    AB-729 + Vebicorvir + Nrtl
    AB-729 + Nrtl
    維比可韋 + Nrtl

從本質上講，上述 AB-729 + vebicorvir + Nrtl 的三重組合與單獨的兩種雙重組合相比必須達到更好的結果。安全將是首先要觀察的最重要的發現。之後，將觀察其他指標，例如 HBV DNA、HBV pgRNA 和 HBsAg 水平。

預計在 2022 年下半年發布的第二個數據將是 Arbutus 自己運行的三重組合研究。這是一項 2 期研究，於 2021 年 7 月獲得授權。這是一項隨機開放標籤的 2a 期研究，正在測試 AB-729 與正在進行的 NA 治療和短期 Peg-IFNa-2a 治療慢性病患者乙型肝炎。正在招募大約 40 名穩定的 NA 抑制 HBeAg 陰性非肝硬化 CHB 患者。患者每 8 週服用 60 毫克 AB-729，共 24 週。之後，患者將被隨機分配到不同的給藥組。

底線是 AB-729 + NA + 每週 Peg-IFNa-2a 的三重組合將與 NA + 每週 Peg-IFNa-2a 進行比較。目的是觀察 AB-729 的三聯組合是否對降低這些乙型肝炎患者的 HBsAg 和其他措施具有更顯著的效果。我對這種三重組合更有信心，這是一個主要原因。原因在於，Vir Biotechnology 已經建立了將 RNAi 藥物與 Peg-IFN-a 一起使用的概念證明。

究竟證明了什麼？添加帶有免疫調節劑聚乙二醇化干擾素 α 的 RNAi 藥物，可能導致 HBsAg 的下降不止累加。這讓我相信，由於 AB-729 不僅是一種像 VIR-2218 一樣的 RNAi 藥物，而且隨著它被添加到 Peg-IFNa-2a 和 Nrtl 中，它也應該在讀取數據時實現 HBsAg 的這種附加下降。這還有待觀察，但由於 Vir 已經建立了一些概念證明，這就是為什麼我對 Arbutus Biopharma 的這種三重組合比另一種更有信心的原因。

StephenW

Arbutus: 2 Key Catalysts To Look Forward To After EASL Data Release
Jun. 29, 2022 3:36 PM ETArbutus Biopharma Corporation (ABUS)ASMB, MRNA, VACC, VIR4 Comments1 Like
Summary

    Two triple-combination studies using AB-729 for treatment of patients with Hepatitis B are expected in the 2nd half of 2022.
    A PD-L1 drug is being advanced in the pipeline to eventually add to a triple combination regimen with AB-729; In addition, potential to advance very same drug for oncology use.
    Pan-coronavirus program is being advanced into IND-enabling studies in 2022, should it go well I expect a phase 1 study to be initiated thereafter.
    Arbutus had $221.8 million in cash as of March 31, 2022; Enough cash to fund its operations into Q2 of 2024.
    This idea was discussed in more depth with members of my private investing community, Biotech Analysis Central. Learn More »

Medical workers doing analysis in laboratory during corona virus outbreak- Science and healthcare concept

Alessandro Biascioli/iStock via Getty Images

Arbutus Biopharma Corporation (NASDAQ:ABUS) is a great speculative biotech to look into. The reason why I state that is because it just recently released new data at the most recent EASL International Liver Congress for AB-729 for the treatment of patients with Hepatitis B.

For starters, AB-729 shown at the conference was impressive in itself. Thus far between 8 and 24 weeks of follow-up, after patients stopped receiving doses of AB-729, there was no evidence of virologic or clinical relapse. This needs to be monitored for longer than 24 weeks, but if these patients continue to maintain such levels for a 1-year or more they could reach a partial of functional cure of Hepatitis B. This is just on the back of AB-729 alone.

Which brings me to the next point, which is that there are two key catalysts approaching in the 2nd half of 2022, which I believe could add significant value for the stock. It is because there is data coming which will be released from two triple-combination studies with AB-729. One triple combination is AB-729 with Assembly Biosciences (ASMB) vebicorvir plus Nrtl standard of care therapy and the second one is AB-729 with Nrtl plus short courses of pegylated interferon alfa-2a. With AB-729 alone having achieved such great potential towards a partial/full function cure of chronic hepatitis B, I believe one of these triple combination studies could be even better.
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As such, the risk/reward with the stock trading around $2.60 per share is quite ideal. Especially, since Vir Biotechnology (VIR) is also using an RNAi drug like AB-729, which, when placed with PEG-IFN-α, achieved a far more substantial Hepatitis B surface antigen ((HBsAg)) decline compared to VIR-2218 alone. I have more confidence in this triple combination since an RNAi drug and PEG-IFN-a seems to have worked well when put together. Based on these two key catalysts approaching, these are the reasons why I believe Arbutus is a great speculative biotech play to look into.
AB-729 Data Sheds Light On Ability To Restore HBV-specific T-cells

Arbutus Biopharma just recently presented updated results for its AB-729 RNA interference ((RNAi)) drug at the EASL International Liver Congress 2022 this past week. It was shown that AB-729 alone was able to allow patients to achieve robust HBsAg declines. This was observed in both HBeAg + and HBeAg- patients, which is even better. About 16 out of 32 patients (50%) maintained HBsAg levels below 100 IU/mL 24 weeks after their last dose of AB-729. These data show that AB-729 alone is quite strong, which is a solid foundation for the biotech to build upon.

However, what I found most intriguing is that the first 5 patients thus far who discontinued both AB-729 plus Nucleoside Analogue (NA) therapy had no evidence of virologic or clinical relapse between 8 to 24 weeks of follow up. Why is this crucial? That's because thus far it proves that AB-729 continues to work even after treatment is stopped. One thing to note is that this is preliminary and in order to confirm a partial/full functional cure of Hepatitis B patients will have to be monitored for 1 year or more.

Still, AB-729 alone is solid as a cornerstone therapy for the treatment of patients with Hepatitis B. As other patients in this study meet stopping criteria, they too may also be able to stop both AB-729 and NA therapy. From there, Arbutus will monitor all such other patients to see if a virologic or clinical relapse occurs after an extended period of time. How can AB-729 continue to work? This may be possible due to the fact that AB-729 continues to restore HBV specific T-cells and decrease exhausted T-cells. One major problem with this disease is that T-cells are exhausted and are weak to respond to it.With AB-729 alone being able to restore T-cell function, even after treatment is stopped, this may prove to be useful as time goes on.
Two Key Catalysts To Watch For 2nd Half Of 2022

As I described above, AB-729 was able to restore HBV-specific T-cells and decrease exhausted T-cells. What comes next? Well, there are going to be two triple-combination studies which will be readout in the 2nd half of 2022. These are important, because they are adding additional drugs which may create a more pronounced response compared to AB-729 alone. The first triple combination would be AB-729 + Assembly's vebicorvir + Nrtl standard of care therapy. A phase 2 randomized open-label clinical trial was initiated back in February of 2021 for this combination. About 60 virologically-suppressed patients with HBeAg negative chronic Hepatitis B Virus (HBV) will be recruited. The arms of the study are as follows:

    AB-729 + Vebicorvir + Nrtl
    AB-729 + Nrtl
    Vebicorvir + Nrtl

In essence, the triple combination above of AB-729 + vebicorvir + Nrtl must achieve superior outcomes compared to either of the two double combinations alone. Safety will be the most important finding to observe first. After that, other measures will be observed such as HBV DNA, HBV pgRNA and HBsAg levels.

The second data readout expected in the 2nd half of 2022 would be a triple-combination study that Arbutus is running itself. This was a phase 2 study that received authorization back in July of 2021. This is a randomized open-label phase 2a study which is testing AB-729 in combination with ongoing NA therapy and short courses of Peg-IFNa-2a in patients with chronic Hepatitis B. About 40 stably NA-suppressed HBeAg negative non-cirrhotic CHB patients are being recruited. Patients are to be given 60 mg of AB-729 every 8 weeks for a total of 24 weeks. After that, patients will be randomized into different dosing groups.

The bottom line is that the triple combination of AB-729 + NA + weekly Peg-IFNa-2a will be compared to NA + weekly Peg-IFNa-2a. The goal is to see if the triple combination of AB-729 has a more pronounced effect on reducing HBsAg and other measures in these Hepatitis B patients. I have more confidence in this triple-combination and it is for one primary reason. That reason being, is that Vir Biotechnology already established proof of concept of using an RNAi drug together with Peg-IFN-a.

What was proven exactly? Adding an RNAi drug with an immunomodulatory agent pegylated interferon alfa, resulted in potentially more than additive declines in HBsAg. This leads me to believe that since AB-729 is not only an RNAi drug like VIR-2218 but with it being added to Peg-IFNa-2a and Nrtl, that it should also achieve such an additive decline in HBsAg when data is readout. This remains to be seen, but since some proof of concept has been established from Vir, this is why I have more confidence for this triple-combination from Arbutus Biopharma compared to the other one.