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.
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.
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.
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:
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.
According to the 10-Q SEC Filing, Arbutus Biopharma had cash, cash equivalents and investments in marketable securities of $221.8 million as of March 31, 2022. A big reason for the influx of cash is that it received $40 million as an upfront payment from Qilu Pharmaceutical Co., Ltd. due to technology transfer and license agreement for AB-729 in the greater China area. Additional funds coming in were a $15 million equity investment from Qilu and about 0.3 million of net proceeds from the issuance of common shares under Arbutus' ATM offering program.
The biotech believes that it has sufficient cash to fund its operations into Q2 of 2024. This is very good for investors, because I see no need to raise cash again until the end of 2023. Until then, it has several trial readouts to report anyway. The two notable trial data readouts are from the triple combination studies with AB-729 I have described above. Both of which are expected to be readout in the 2nd half of 2022.
The two biggest risks for Arbutus Biopharma would be the upcoming data readouts of the triple-combination studies for AB-729. Even though Vir Biotechnology established proof of concept using its RNAi drug VIR-2218 together with Peg-IFN-a, there is no guarantee that Arbutus will be able to do the same with its drug AB-729.
The other risk would be the other triple-combination study noted above of AB-729 with vebicorvir. The hope is that AB-729 being added with vebicorvir + Nrtl would have a more pronounced effect on reducing HBsAg but this remains to be seen. If such a finding is achieved whereby HBsAg is reduced in a superior fashion, then I expect both the stock of Arbutus biopharma and partner Assembly Biosciences to rise significantly.
The final risk to note would be that AB-729 has potential in triple-combination therapies, but may not work for all. I just believe it needs to find a partial/functional cure with one triple combination. There is a 3rd triple combination therapy using AB-729 with Vaccitech (VACC) VTP-300 and Nucleoside Analogue (NA) therapy. However, this study was just initiated on June 6, 2022. I don't expect initial data from this triple combination study until 2023.
I believe that Arbutus Biopharma is a great speculative biotech play to look into. That's because it has several ongoing triple combination studies using its lead RNAi drug AB-729. Two of these triple combination studies are going to be readout in the 2nd half of 2022 any day now.
Besides AB-729 the biotech is also exploring other drugs which may lead to partnerships and possibly increase shareholder value. As I noted above, AB-729 was able to reignite HBV specific T-cells. Well, another good way to possibly boost T-cell immune response would be the addition of a PD-L1 drug to AB-729. As such, it is developing its own PD-L1 drug to eventually accomplish this.
It is also exploring possible oncology indications for it as well. Why I'm really excited about the PD-L1 program is because it is being developed as an oral drug. Currently approved monoclonal antibody PD-L1 drugs are only given to patients intravenously. This could end up being a huge competitive advantage in the global PD-1/PD-L1 inhibitor market which is expected to reach $65.7 billion by 2027. Another solid program in place would be the internal development of its own pan-coronavirus oral drug program. It is advancing an oral compound that inhibits SARS-CoV-2 nsp5 main protease into IND enabling studies. This is an early stage program, but the goal is to develop a drug that works across all strains of coronavirus and not just a few.
Lastly, Arbutus and Genevant Sciences are seeking damages relating to patents which it believed Moderna (MRNA) infringed upon. It would be nice if this case was eventually settled, which is what I believe may ultimately happen, but it could take years if it is dragged out in court. Still, this is another avenue that could act as a catalyst should Arbutus succeed in court. With a few catalysts on the way in the 2nd half of 2022, plus an extensive pipeline of programs, I believe that Arbutus Biopharma is a great speculative biotech play to look into.
This article is published by Terry Chrisomalis, who runs the Biotech Analysis Central pharmaceutical service on Seeking Alpha Marketplace. If you like what you read here and would like to subscribe to, I'm currently offering a two-week free trial period for subscribers to take advantage of. My service offers a deep-dive analysis of many pharmaceutical companies. The Biotech Analysis Central SA marketplace is $49 per month, but for those who sign up for the yearly plan will be able to take advantage of a 33.50% discount price of $399 per year.
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