Good afternoon, and welcome to the Assembly Biosciences HBV Portfolio Progress Conference Call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session after the prepared remarks. As a reminder, this conference call is being recorded. I would now like to hand the call over to Amy Figueroa, Interim Investor Relations Consultant for Assembly.
Please go ahead.
Good afternoon, and thank you for joining us as we discuss the recent progress with Assembly's portfolio of clinical stage core inhibitors, which are advancing in development for the treatment of patients with chronic hepatitis B infection. This afternoon, we issued a press release reporting our financial results for the Q1 of 2020 and providing a corporate update. This press release and the slides we will refer to during the call are available in the News and Events section of our corporate website atwww.assemblybio.com. After our prepared remarks, a PDF of the slides will be available from our website. Also, a replay of today's call and webcast will be available from our website.
In a moment, I will turn the call over to Doctor. John McHutchinson, Assembly Bio's Chief Executive Officer and President, to provide a corporate update in the virologic response criteria or stopping criteria, which will be used to determine which patients begin coming off of therapy in Study 211 later this year. Then Doctor. Louisa Stamm, Chief Medical Officer, will review the criteria in more detail and provide an overview of the abstracts accepted for presentation at the virtual EASL meeting August 27th through 29, including data on our lead core inhibitor 731, 2nd generation core inhibitor 2,158 and our highly sensitive assays. Finally, John Luisa Doctor.
Richard Colono, our Executive Vice President and Chief Scientific Officer of Virology and Tom Russo, our Chief Financial Officer, will be available for the Q and A portion of the call. Before we begin, I want to remind you that we will be making forward looking statements, including statements regarding our future research and development plans, evaluation of interim data, the timing of clinical trials, trial results and therapeutic potential of our development programs. These statements are subject to the Safe Harbor protections provided under the Private Securities Litigation Reform Act of 1995. They involve certain assumptions, risks and uncertainties that are beyond our control, and actual results may differ materially from these forward looking statements. A description of these risks can be found in Slide 3 as well as our latest SEC disclosure documents and press releases.
Assembly does not undertake any obligation to update any forward looking statements made during this call. I'll now hand the call over to Assembly's CEO, Doctor. John McHutchinson.
Thanks, Amy, and welcome to everyone on the call today. I'm pleased to be speaking with you all again. Whilst we had planned to be doing this in person at EASL in London a few weeks ago, we're happy to now provide you a broader corporate update coinciding with the end of the quarter along with some other important updates as Amy has already outlined for you. In these uncertain and unpredictable times, we at Assembly remain focused. We have continued our operations thus far as permitted during the shelter in place orders.
We have rapidly adapted our operations of course and we continue to regularly assess the situation. The FDA provided guidance in March that enabled us to monitor patients in our studies in their homes, including virtual visits, laboratory testing and study products shipped directly to trial participants. As a result, we have been able to mitigate to the extent possible any potential impact to Study 211. For future studies, we are working to expand the geographic diversity of sites and bringing on countries first that are past the peak of the coronavirus outbreaks such as China. To date, our current and future planned trials have not been subject to any significant impact.
Importantly, we've also had the financial resources needed to advance our programs following the completion of our offering this past December and we continue to expect our current cash of $249,000,000 as of March 31 to fund our operations into 2022. Over the past year, we have continued to further recruit talented experienced leaders to Assembly, including our Chief Financial Officer, Tom Russo and our Chief Medical Officer, Doctor. Louise Asthem during the Q4. More recently, we have welcomed Jason Okazaki as our new Chief Legal and Business Officer. Jason comes to us with an extraordinary depth of both legal and M and A and licensing expertise.
Carl Annel has joined us to work closely with Jason, Tom and myself the Head Corporate Development. As we do more internally and externally in terms of partnerships, collaborations and other activities to grow our portfolio, both Jason and Carl will be critical to the success of the organization. Additionally, Michelle Anderson joined us to lead the regulatory group. Michelle has deep experience across multiple therapeutic areas with numerous product approvals in many geographies. These skills will put us in good standing as our programs advance globally.
Now turning to Slide 5 on the R and D side of the organization, we continue to execute. I'm pleased with our pipeline progress and our acceleration of activities within the last 6 months. As it relates to hepatitis B, our focus for today's call, we have submitted an end of Phase 2 meeting request and briefing document to the Chinese regulatory authorities for 731, our lead hepatitis B core inhibitor to discuss with them what a regional program for that drug might look like. We look forward to those interactions and after we'll be able to speak more about the timing and components of that program initially as a chronic suppressive therapy that we aim to link to a subsequent finite duration regimen, which is our ultimate goal. Lastly, we have now also finalized the stopping criteria for the 731 Phase 2 program and we'll outline those details and their implications today.
Also, we'll provide you a high level overview of our abstracts accepted for EASL whilst preserving more detailed scientific findings for those 4 presentations when they actually occur in August. In addition to the progress of 731, we're advancing 2 more potent second generation HBV core inhibitors into clinical development or in clinical development. 2,158 has completed Phase 1b dose ranging cohorts and remains on track to start a Phase 2 proof of concept trial in the second quarter, that is this quarter. Louisa will touch upon the final top line data from those cohorts and share the Phase 2 trial design later. Also for 3,000,000 33, we have opened the 1st in human Phase 1 study in healthy volunteers to evaluate that drug safety, tolerability and pharmacokinetics.
Let's move on to the updates in our ongoing Phase 2 program for 731 and the stopping criteria we've defined. To recap the trial design shown on Slide 6, a broad range of patients with chronic hepatitis B infection were enrolled. Included were e antigen negative or positive patients who were previously receiving suppressive nuke therapy. They were randomized in Study 201 to receive 24 weeks of therapy with the core inhibitor 731 or matching placebo for a duration of 24 weeks. Also as shown in the bottom row, another group of naive to treatment E antigen positive patients were similarly randomized.
After the 1st 24 weeks, all patients were then offered open label extension trial enrollment in Study 211, where they all received the combination of a nuke and the core inhibitor 731 for an additional period of 1 year. Of the 92 patients entering the open label extension, 84 currently remain in the study and have reached or are approaching the 76 week treatment time point. Next, as patients have progressed through Study 211, we have previously reported the proportions with progressive reductions in viral antigens and also the proportions with HBV DNA and pre genomic RNA below the thresholds of our in house sensitive assays. As many of you know, pgRNA has only one source within an HBV infected cell, the mini chromosome cccDNA. Our data to date have therefore directly and indirectly indicated prolonged and deep viral suppression are necessary, of course, to prevent relapse after any potential finite duration therapy.
Now that patients in this open label extension study are approaching the 52 to 76 week of treatments of the combination, our next step has been to determine which patients should cease therapy. The hypothesis being that with a period of prolonged viral suppression to levels below our most sensitive means of quantifying any evidence of viral replication, we have also blocked the replenishment of cccDNA and depleted that pool, which should allow therapy to be withdrawn without evidence of a viral relapse. With a drug that has continued to show a favorable and differentiated safety profile. Thus, we can evaluate patients off therapy and determine if they achieve a sustained virologic response or SVR as we coined the term initially for patients with hepatitis C. After careful internal consideration, discussions with investigators and lastly with agreement with the FDA, we've arrived at those criteria.
Slide 8 sets forth the stopping criteria as measured using our newest and most sensitive assay for detecting any evidence of residual viral replication. We defined the lower threshold for this assay as total HBV nucleic acids, its DNA and PG RNA combined, less than 20 IUs per ml. And we'll provide more detail on this assay later in the presentation. Patients will be eligible to seek therapy if they have had no evidence of quantifiable viral replication using this assay for 7 consecutive monthly visits at treatment week 76. We chose this 6 month period of negativity as it's consistent with the half life of cccDNA as we recently published in hepatology.
For patients who are e antigen positive, the detectable levels of e antigen must also have been 5 IUs per ml or less on each of those 7 visits also. After cessation of combination therapy, the next critical part of this experiment will be to closely monitor the patients and carefully document the presence or absence of a sustained virologic response. Recall that historically fewer than 5% of patients with chronic hepatitis B achieved sustained suppression of viral markers of replication after ceasing treatment or SVR. We plan to monitor patients monthly for safety and we'll measure ALT values, standard virologic markers and we'll apply our sensitive DNA and PG RNA assays as well. For patients that reach the 6 months time point without relapse and achieve SVR24 as highlighted in the middle of the slide, we'll continue to monitor them less frequently through a total follow-up period of 3 years similar to what we also did with hepatitis C patients when we were initially monitoring for SVR and its durability.
Those who do relapse will be detected early with our sensitive assays and of course standard of care new therapy will be reinitiated as is clinically indicated. So for patients in the current trial, how will this play out? As shown at the top of the slides, 10, that is, those patients that achieved these stopping criteria will stop by 731 and their new therapy at treatment week 76 and we'll continue to monitor them for SBR as we've outlined today. For those patients shown in the middle of the slide who do not meet the stopping criteria and and they will eventually complete the study. And for those patients shown at the bottom, we started in the naive patient cohort with the highest levels of DNA in pgRNA and have been responding to date with an initial virologic response, which we have defined as decline in pgRNA from baseline of at least 2.5 logs, we will be extending their duration on the combination therapy to provide them the opportunity to satisfy the stopping criteria that we have outlined today for the other groups.
For more details now and a discussion of what we have planned for EASL also, I shall hand the call over to our Chief Medical Officer, Louisa Stan.
Thank you, John. I'll follow on where you left off and walk through the treatment decisions for each patient population in Study 211. I'll speak first on Slide 11 to the virologically suppressed e antigen negative patients who entered Study 201. These patients had been receiving NRTI for a number of years and therefore had very low levels of HBV DNA and pgRNA at the time of entry into the study. All of the patients who continue on treatment have met the virologic response criteria and therefore at treatment week 76, all these patients will discontinue both 731 and NRTI.
They will then be monitored closely for safety and SVR as John described. The next group is shown on Slide 12, the virologically suppressed B antigen positive patients who entered Study 201. A proportion of these patients will meet the stopping criteria and at week 76, they will discontinue both 731 and NRTI and be monitored for SVR for up to 3 years. Those patients who do not meet the criteria will discontinue 731, but they will continue standard of care NRTI therapy. They will be monitored for 12 weeks, then complete the study.
Finally, on Slide 13, we are showing the treatment naive group of patients, all of whom were e antigen positive at enrollment into Study 202. For these patients, who are initially untreated and started the study with high levels of DNA and pgRNA, we are first evaluating the initial virologic response to determine who will continue treatment with 731 and NRTI. Specifically, patients who have had at least a 2.5 log decline in pgRNA at treatment week 76 we'll continue to receive the combination treatment with 731 and NRTI, extending for up to an additional 48 weeks. During this treatment extension, we'll continue to monitor patients who are responding and we will stop 731 and NRTI when they meet the same stopping criteria that we have outlined for the other groups in the prior slides. Patients with insufficient urologic response will discontinue 731 and continue on NRTI for 12 weeks.
As we prepare to roll out these treatment decisions, the projected flow of patients in the 3 groups is shown on Slide 14. It's important to remember that not all patients have reached 76 weeks of treatment yet. These figures include our projections based on the currently available data. The proportion shown represent the number of patients enrolled in Study 211. There are some patients who have discontinued 731 already for other reasons, most commonly withdrawal of consent.
These are shown in the light gray on the right. First, for the virologically suppressed e antigen negative patient, approximately 90% are projected to meet the stopping criteria and will discontinue 731 and NRTI after 12 or 18 months of the combination regimen. Next, almost half of the virologically suppressed e antigen positive patients are projected to meet the stopping criteria and discontinue both 731 and RTI. Lastly, for the treatment naive, the antigen positive patients, the majority or approximately 80% are projected to achieve an initial virologic response and will have their treatment with both 731 and NRTI extended to provide them an opportunity to achieve the same stopping criteria as outlined for the other group. As John mentioned at the outset, we developed these criteria after careful deliberation.
We are now excited about moving the study to the next phase and looking forward to the important data that it will generate. Moving on to EASL, we are very pleased to have 4 presentations accepted as shown on Slide 15. 1 as an oral and 3 as a poster with 2 of these being late breakers. We expect the complete abstracts will be available online about a week before the conference, which is now scheduled to take place virtually in late August. There are 2 presentations on Study 211, 1 on our highly sensitive assay and 1 on the dose ranging cohorts from the Phase 1b study with 2,158, our 2nd generation core inhibitor.
On the
next few slides, I'll provide a high level overview of what we plan to cover in this presentation. I'll begin first with our highly sensitive HBV DNA and pgRNA assays on Slide 16. These were developed by the in house scientists at assembly to monitor key viral markers in our clinical studies. The left section of the slide compares assembly of assay to the commonly used COVAS assay. We used COVAS in Study 202 for measuring DNA levels in treatment naive patients.
However, for virologically suppressed patients in 201, who had already reached the lower limit of quantification or LLLQ of the cobas assay, DNA was measured by Assembly's quantitative PCR gel assay. This assay's limit of detection of 5 IU per ml allows for improved accuracy, enabling measurement of deeper viral inhibition in these patients. The center of the slide shows our improvement in measuring PgRNA. For comparison, the DBL assay measures all HBV RNA, not just pgRNA, with an LLOQ of 11,000 copies per ml. The assembly assays more specifically measured pgRNA and also had improved sensitivity with LLOQs of 802 100 copies per ml used in the treatment naive patients in Study 202 and the virologically suppressed patients in Study 201 respectively.
For your reference, we previously referred to the LLOQs in these assays as 135 units per ml in Study 202 and 35 units per ml in Study 201. On the right, you'll see our latest highly sensitive assay, which is the one we will be using in the stopping criteria for Study 211. This simpler composite assay measures total HBV nucleic acid, both PG RNA and DNA. It has a quantitative readout with a LLOQ of 20 IUs per ml, more sensitive than our prior quantitative assays. Next, I'll review the updated data from Study 211 using these new more sensitive assays.
On Slide 17, you'll see an update on the virologically suppressed e antigen patients from study 201 to 111. The proportions of these patients whose HBV DNA is not detectable by the sensitive assay with the 5 IUs per ml limit of detection is shown on the left. As we presented at ASLD last year, at baseline, a small proportion of these patients had undetectable HBV DNA shown in light gray. With the addition of 731, this proportion increases to over 70%, shown in light and dark blue. We are pleased to see that with longer durations of combination therapy, we have continued improved deeper viral suppression of viral replication.
On the right side is the data with the new composite DNA and pgRNA assay, which has been incorporated into Study 211 from week 24 of treatment onward. For patients shown in gray, who initially received placebo and NRTI through the 1st 24 weeks of treatment, you can see a light in light blue, a far greater proportion with DNA and pgRNA less than LLOQ after addition of NRTI after addition of 731 to NRTI. For the patients who received 731 and NRTI throughout the studies shown in dark blue, we see the proportion after 24 weeks of combination treatment was similar, and this continues to increase further over the next 24 weeks and after. Recall from earlier in this presentation that about half of these patients are now projected to meet the stopping criteria and discontinue both drugs at week 76 because they also had e antigen less than 5 IU per ml. For the naive e antigen positive patients from Study 202211 not included here, we have planned to do a data cut in late June and provide a detailed update in August at EASL.
To remind you, this group started with the highest levels of DNA and PG RNA. And overall, they are continuing to progress with approximately 80% meeting the initial virologic response criteria. These patients are responding and we are extending their therapy. Now, let me turn to Slide 18 and the data from the virologically suppressed e antigen negative patients, a population which we will present in detail for the first time at EASL. Of note, these patients enrolled in Study 201 after prolonged NRTI treatment with a mean duration of 4 years.
Also, most, 88%, had e antigen seroconverted and had detectable anti HBE antibodies. So it's not surprising that at baseline, a high proportion of these subjects had already achieved undetectable HBV DNA reflective of deeper level of viral suppression compared to the e antigen positive population on the prior slide. Even with this, we see on the left deeper suppression during treatment with 731, as measured by our sensitive DNA assay. The increasing proportions of patients in both groups achieving undetectable DNA with longer duration combination therapy. On the right side are the data with the composite DNA and pgRNA assay.
All patients in this population consistently have had DNA and pgRNA less than 20 IU per ml. Recall from earlier in the presentation that these patients have all met the stop band criteria for at least 6 months. And therefore, all will discontinue 731 and NRTI after 12 or 18 months of combination therapy and will be observed for SCR. Now let's move to CABR2,158, our 2nd generation more potent core inhibitor and the data from the completed Phase 1b dose ranging cohort that will be presented at EASL. In this study, the antigen positive patients received 14 days of placebo or 2,158 with a once daily dose of 100, 300 or 500 milligrams.
Across the cohorts, 2,158 was well tolerated and demonstrated potent antiviral activity. With the 300 milligram dose, the decline from baseline on
Based on this data and the less than
dose proportional increase Based on this data and the less than dose proportional increases in the pharmacokinetic parameters as shown in the table, the 300 milligram daily dose has been selected for the upcoming Phase 2 trial, the design of which is shown on Slide 20. This trial, which is expected to initiate this quarter, will enroll treatment naive patients with e antigen positive chronic hepatitis B without cirrhosis. 80 patients will be randomized 3:one to receive 2,158, 300 milligrams or placebo and entecavir once daily for 72 weeks. The objective of this proof of concept study is to evaluate the safety and efficacy of longer duration treatment with this combination. The endpoints of this study include safety and changes from baseline in HBV DNA, pgRNA along with viral antigen.
The data will be used to indirectly compare our 1st and second generation core inhibitors in terms of their efficacy to prevent the generation of new cccDNA. I'll now turn the call back over to John.
So thanks, Louisa. Before we open the Q and A session, I'd like to recognize how fortunate we are to be in a strong position now. We've now put into place an experienced team. We raised the resources to be well capitalized and we remain on track to execute on our plans. Looking ahead into the rest of this year, as shown on Slide 21, we have several important milestones we anticipate in the coming months.
These include, as shown, the start of our Phase 2 proof of concept clinical trial for 2,158 this quarter that Luisa has just outlined. Also the first preclinical data from our immuno oncology microbiome program that will be presented virtually at this month's next month's AACR. 4 presentations that you heard about today relating to our hepatitis D portfolio at EASL in late August our ongoing regulatory interactions in China and the U. S. As we aim to initiate studies to enable registration, And of course, we continue to evaluate potential partnership opportunities in China that might help us move this along.
And importantly, beginning to take patients off therapy in Study 211 later this year to monitor patients for sustained viral response as Luisa has outlined for you today. So we are now happy to take your questions. Operator, you may now start the Q and A session.
Your first question comes from the line of Brian Skorney from Baird. Please ask your question.
Hey, good afternoon, guys. Thanks for taking the question and congrats on getting the go ahead on moving forward with the stopping criteria. I guess maybe just kind of high level, I know we don't have a lot of historical data on patients who achieve cures, a lot of it's still kind of guesswork. But when you kind of consider the 3 buckets of patients, the naive, NUXTressed D positive and NUXT suppressed E negative patients, is there anything to kind of take away from the historical characteristics and anything you think is a more likely cohort to achieve? For carry another treatment naive sort of a likely a blinded hybrid of the nuc suppressed e antigen positive and e antigen negatives.
But any sort of theoretical reasons why one should be more likely to achieve functional cure than the other?
Brian, thank you for your comments about getting clearance and approval from everybody, our investigators and the regulators and internally for us to move forward with the stopping criteria, we thought a lot about them. Look, it's a fantastic question, which group are most likely to be cured. And you're always looking back historically at very low rates of sustained viral suppression of therapy, not cure, in patients who were treated with interferon or a new one, it's 1% to 5%. Now the rates are higher if you look at A negative people who've been suppressed for patients on nukes for a long period of time many, many years and a lot of that data comes from China. And in those that have reductions in other viral antigens such as the antigen and now we're looking at PG RNA, which has really not been been influenced in the short term in any way shape or form by our prior nuke based therapies.
So we don't know the answer to your question. It's part of the experiment we're doing. I believe that the e antigen negative patients have started low and been suppressed for a long time. We know, as Louisa said to you today, we've suppressed both DNA and pgRNA with our sensitive assays for many months and we'll see how they go. Obviously, it's going to take longer for the naive patients who started much higher.
So it's the experiment we're doing. We're not exactly sure what the answer is. Biologically, I think the A negative patients might have the best chance. Look, whatever it is, whatever group it is, the important point is, as I've said before, that anything that's at least 10% better than standard of care, which is 1% to 5%, respectively, for the 2 approved therapies is something that is important for patients and important for doctors to tell their patients and will change prescribing patterns. So if we get around 15% across the board here, I'll be happy about that.
So a long answer, but I hope I've given you our thought process on the science around this. Thanks for your question. Thank you.
Your next question comes from the line of Geoffrey Porges from SVB Leerink. Please ask your question.
Hi, this is Brad Canino on for Jeff today. And I'd like to send my congratulations as well on achieving all of this and really staying on track during these difficult times. And I'd like to ask again on this e positive virally suppressed population, and you're saying you're going to discontinue 42% of them because they didn't achieve the responses you wanted. But you're willing to extend treatment further in the treatment naive population. So why would you not be extending treatment for the e positive patients?
Brad, it's John to start and then I'll hand it over to Louisa. I think your question was related to the E positive suppressed patients that have some small amount of E antigen left. Why aren't we continuing them on? So I'll let we've talked about that a lot and I will let Louisa answer it. Thanks for your nice comments about staying on track and being able to do all that during the events over the last few months.
So Louisa, some comments and clarity around why we chose the cutoff of 5 international units for E and perhaps a little bit more data?
Sure. Thank you, Jeff, for the question. I think first to what John just mentioned, the cutoff of 5 IUs per ml for the discontinuation of treatment in the e antigen virologically suppressed population. As you know, there's no expected cutoff for what's low and meaningful with regard to e antigen and predicting SVR for patients receiving treatment with a core inhibitor and NRTI. What I can tell you is that the 21e antigen positive patients who are less than 5 and predicted to stop treatment, 2 thirds have less than 1 and all but 1 are less than 3.
So we're really conducting this experiment in a broader population to assess the importance of an absolute change in E antigen. This will maximize our learning about the contribution of 731 to NRTI. And then moving forward, we'll take the results and refine our criteria for future study. I think part of your question, if I understand it correctly, is also why would we discontinue those who are why would we continue NRTI and discontinue 731 and the other patients in the cohort. And this really reflects the maturity of the data now and where we are in this open label extension, where most patients have already received or all patients will have received 12 or 18 months of therapy.
So we think this is a reasonable amount of time to assess the impact of core inhibitor on top of standard of care NRTI.
So Brad, it's John again. Just one other point, 2 other points I'd like to make is a lot of these patients are trickling along with very, very, very low levels of E for a long period of time. It raises this issue of what does that mean and we'll do this experiment and we'll find out what it means, but the majority are very, very low as Louise described. Whether that comes from an integrant or not, we don't know. There's great debate as Rich has talked to you many times before about whether E integrins are relevant and important.
We'll do that experiment now. Look like the other thing about the naive, so I'd just like to mention and pick up to you is they started with such high levels of RNA and DNA. They're at least a year behind all of these other patients. So that's why they're continuing on. And as Louisa said, we'll do this experiment in the eNEXT, ePOS suppressed now.
Thank you. Brad?
Operator, we're ready for that question.
Thank you. Your next question comes from the line of Michael Yee from Jefferies. Please ask your question.
Hi, guys. Hey, John. Hope you can hear me okay. Couple of quick ones. A lot of information there.
So thanks for all that new disclosure. And question 1, I think I heard you right or saw that 49 percent of people met the stopping criteria in the e positive, obviously, which is huge new information. When are you actually going to take patients off and then when would you report how many do or don't rebound? You're going to wait 6 months after that. So maybe describe the timing when we would get that huge answer.
Question 2, on the 2nd generation 1, are you going to implement the stopping criteria there too or you're just going to try and see if you can get higher than 49% who meet the stopping criteria? I guess that would be the goal of that study. And then question 3, on the China study, is that potentially for an FDA submission by running that or a China submission? Maybe just clarify that. Thank you so much.
Thanks, Mike. We heard your 3 questions. So the first question is when are we going to stop start taking people off therapy and when we're going to report it. So let's work through this one by one, Luisa. So when will we start taking people off therapy?
Yes. So as we mentioned on that slide, Michael, it's a projection right now. I can say that as of last week, about onethree of individuals on study have reached treatment week 76. So we plan to start taking people off of treatment by June.
And then in terms, Mike, of the second part of that first question, in terms of when we're going to report this, The answer is when we're sure we have the right answer, which is not meant to be cryptic, but there's 2 major factors. It's having a significant number of patients where you feel it's a real representation of the cohort. And then it's having the 6 month follow-up in that cohort. So it's really both of those factors. Look, we could report that at a scientific meeting.
We could report it. It's material to us. We could report it as a press release separate from the scientific meeting. Some of you have felt that it might be at AASLD later this year. That's a real stretch and I'd be thinking about this into next year for all of you.
I think that would be the right way to think about it. Will we implement the stopping criteria for 2,158 as we did? Yes, we might modify them if we learn from the stopping criteria, But by that stage, we plan on implementing the same. Louisa, a few words on that?
Yes. So the way the protocol is currently written, there are no stopping criteria. As I mentioned, what we'll do is take the results from the 731 study, refine the stopping criteria and then we plan to amend the protocol and apply it to the 2,158 program.
And Mike, the last question just to finish up for you is the China submission and will that be part of a global submission? Too early to talk about all the details. We've submitted we have our plan. We've submitted our end of Phase 2 request for a meeting in China. As you know, these things have to be discussed and negotiated and eked out in greater detail.
We'll present all of those findings once we have it sort of tied down, but it'll be like most other Phase 3 programs, 2 studies, maybe they'll be the same, maybe they'll be different populations. As I said today, finite potentially bridging to suppressive therapy, subsequently bridging to finite. So and whether we use that data for global submission, that would ideally be our goal. So thanks for your three questions.
Thank you. Appreciate it. Great.
Your next question comes from the line of Salim Syed from Mizuho. Please ask your question.
Great. Thanks so much for all the color, John and team. Super helpful. A couple from me. On just a high level one here.
On the your discussions with the FDA and I presume other KOLs, things like from the slides, obviously, it's largely focused on pgRNA versus the what people historically have focused on SA antigen. Have you sensed this shift at all at the FDA or amongst your KOL discussions, people taking focus off S antigen and focusing more on pgRNA as the right marker? That's question 1. And then the second question was just on Slide 9. It looks like from the patient follow ups for after year 1, it will be every 3 months.
I just want to make sure I'm interpreting that correctly. Thank you.
So I don't want to speak about shift in terms of FDA really Salim or what they're thinking. I think we are seeing in the scientific community a shift in this. And I think it might be a good opportunity to have Rich talk about the assays and how they've evolved over time and how they're somewhat reliant and importantly reliant on pgRNA. And then I'll follow-up with the second part of the question. So Rich, we haven't had an opportunity to talk much about all this work you guys have done on these assays and why.
Yes, sure. Thank you and hi, everybody. Yes, I think clearly there is a shift, I think not like just in the agencies, but also investigators in terms of the importance of S antigen, especially given all the data that the vast majority of S comes from integrins. That's a scientific fact now. And especially as you go to the antigen negative patients, it's close to 100%.
So then what is the next criteria that one uses for success in monitoring patients on treatment as we are doing in the study? And that's where you see the shift now much more to sort of TOR of pgRNA. We are not totally there yet. It's still DNA to a great degree. But pgRNA is the primary marker of cccDNA And everybody now scientifically, I think, does agree that look, at the end of the day, the cure patients, you're going to have to get rid of cccDNA.
And pgRNA is the greatest marker for that. So our emphasis is on pgRNA. We're very happy to be one of the leaders in the scientific field on this and developing the science behind that. And I think there is a lot of uptake now on a lot of different parts of the treatment world that pgRNA is probably a very important element to this. And if you can get the DNA and pgRNA down to these very low undetectable levels, then you have checked 2 major boxes.
You've stopped our replication and you've depleted cccDNA. So anyway, so that's where it is. So there's no definitive answer to it. There's no EDIC that's come down from the FDA or anybody else to say they're going to forget about S antigen. But I think there's clearly a trend now where everybody's moving in that direction.
Thanks.
Thanks, Rich. Fortunately, with our combination therapy, we've been driving both DNA and PG RNA down. So we've created these more and more sensitive assays to try and measure what was previously unmeasurable or below the level of protection. That's a testament to what the combination is doing, virology-one hundred and one. But look, the other thing I would say, Selim, before we get on to the second question is just in doing this internally, our lead investigators are completely on board with this conceptually.
Important experiment that nobody's ever done before. If somebody had done it before, we wouldn't be discussing it, right? It would be everybody would know the outcome. So that's important. And the regulators have interacted with us and agreed upon this plan to go forward and monitor people when we take them off therapy.
The other important point about this where the FDA, I can't speak for the FDA, but their guidance document clearly says there's 2 ways to a finite therapy. 1 is absence of HBV DNA for 6 months after stopping therapy using the CoBass or the commercially available assay. That doesn't talk about surface antigen. That talks about the importance of controlling viral replication as measured by DNA. And then the second component of that is about surface antigen.
So clearly, they recognize both of those. Long winded answer to your question, but I think it's important information. And then Louisa, if you could answer Selene's second question about the timing of follow-up after the 1st 24 weeks.
Sure. Thank you. As you referred to on Slide 9, we'll be looking very closely over the 3 year duration. We'll initially be looking monthly as indicated on the slide and then we'll slowly be spacing those out. We appreciate this is a long study and we'll be going first to every 2 months and then finally in the last year to every 3 months.
So that gives you a little bit of an idea about the cadence of our plans in terms of monitoring these individuals off of therapy.
Got it. Thanks so much guys.
Your next question comes from the line of Raju Prasad from William Blair. Please ask your question.
Thanks for taking the question and congrats on the alignment. Can you just provide a little more color on the assumptions that went into the 211 projections on, I think it's Slide 14? And then as far as 2,158, just wanted to understand, there's a treatment naive e antigen positive study. Do you plan on studying in the e antigen negative and how the development of that program is going to be helpful as well? Thank you.
Thanks, Raj. I'll ask Louisa to answer both of those first. Appreciate your comments about alignment, which was great for us to see. But then how did we calculate the projections of the patient flow on Study 14? Louisa can give you some more details about that.
And then in terms of the 2,158 question about other populations, which is on our agenda as well.
So as I mentioned, the data on the slide is the projections on the slide are accurate as we project them currently through the data cut of last week. And I mentioned that about a third of them have reached treatment week 76. So it's really a mix of confirmed and potential treatment decisions. Those that have the 3rd that have missed have already reached week 76 are confirmed. The others, which are projected to come off therapy, have 3 to 6 assessment out of the 7 meeting criteria.
So they're on track and projected to come off of therapy.
That's good. And 2,158, we started the Phase 2 proof of concept study in e antigen positive naive to compare to 731, but what about other populations?
Yes. Our initial assessment, as John has mentioned, will be to compare that case to proof of concept to the 202 population. We think that's really important to get that longer dosing efficacy data to do a head to head comparison of our 1st and second generation CAR inhibitors. Beyond that, we certainly will look at other populations, including treatment naive E antigen negative patients.
So just remember that Rich and his team developed 2,158, Roche to be more potent than it is more potent in cell based systems at preventing the generation or formation of new cccDNA. So that's not something we're going to see in the 14 day antiviral study. What we saw in the 14 antiviral study is what we expected to see and we saw safety. It's about the same as 731. But to look at this effect against the potency of preventing the generation of new cccDNA, that's why we have to do a longer duration study.
So we can look at the tails of all these antigens and compare it back to 731. So that's the plan, an important point, it's in distinction. But we'd like to look at other populations. Let's start with this, where we're sort of we're still on track to get this trial up and running this quarter despite all the coronavirus issues. So we didn't want to over complicate anything else at the current time.
Great. Thanks, John. And maybe just one more, if I can. Obviously, didn't want to comment on the S antigen kind of story, but do you from your discussions with the FDA, does this seem as though kind of moving forward, this kind of composite endpoint is how they'll be looking at core inhibitors from here on out? Thanks.
I can't comment on that, Raj, or what they're thinking about that. I think did you mean composite endpoints, were you meaning DNA and RNA and so forth or I'm not sure exactly what you were referring to?
Yes. Yes.
Look, I
Yes, the endpoint.
I'm always reticent to talk about somebody else's opinion, particularly our regulators, and let us have all the discussions with them and have those things finalized before we would talk about them publicly. I think that's fair to them and fair to us as well. But it's a good question.
Okay. Thanks. Congrats.
There are no further questions at this time. I will now turn the call back to Assembly's CEO and President, Doctor. John McCatchenson for closing remarks.
Thank you again for joining the call today everybody. In closing, I'd like to thank our dedicated employees, not only those in the hepatitis B programs, but across the organization. The focus today was hepatitis B, of course, but also our microbiome team, which continues to do great work and equally committed to our mission. I'd also like to recognize the investigators involved in our trials, the patients participating in the studies and the shareholders who support our work. They are all essential to the progress we are making toward our vision of a cure for hepatitis B.
I'm confident we have the resilience and the resources to push forward our goals for this year and afterwards and beyond that as well. So we look forward to updating you in the future, sharing our continued progress. And thank you today for your time. And this concludes our call.