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.
Wall Street Breakfast
Wake up with Wall Street Breakfast
Get your daily take on the financial markets with Seeking Alpha's flagship newsletter.
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:
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.