Good morning, ladies and gentlemen, and welcome to the Atara Biotherapeutics ATA188 Data Conference Call. My name is Liz and I will be your operator for today's call. I'd now like to turn the conference over to your host, Eric Hyllengren, Vice President of Investor Relations and Finance. You may now begin.
Thank you, Liz. Good morning, everyone, and welcome to the Atara ATA 188 Data Conference Call. Earlier this morning, we issued a press release reporting exciting data from our ongoing phase I-A clinical trial of ATA 188, presented at ACTRIMS in an e-poster this morning. This press release and the slides we will be presenting during this call are available in the Investors and Media section of atarabio.com. I'm joined today on the call by Dr. Pascal Touchon, President and Chief Executive Officer, Dr. Jakob Dupont, Executive Vice President and Global Head of Research and Development, Dr. AJ Joshi, Chief Medical Officer, and Utpal Koppikar, Chief Financial Officer. I'd like to remind listeners that the company's management will be making forward-looking statements today. Actual results could differ materially from those stated or implied by our forward-looking statements due to the risks and uncertainties associated with the company's business.
These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filings. These statements are made as of today's date, and the company undertakes no obligation to update these statements. I'll now turn the call over to Pascal for an introduction and corporate update. Pascal?
Thank you, Eric, and thank you everyone for joining us today. As Eric noted, earlier today, we issued a press release reporting exciting updated phase I data that are being presented at ACTRIMS for ATA188, or allogeneic T-cell therapy for the potential treatment of multiple sclerosis. Before we get into this data, we can see on slide four that we've made significant progress generally, and I would like to take a minute and provide a brief update on our company other key objectives. We are continuing to make strong progress with tabelecleucel and remain on track to initiate the BLA submission by the end of 2020. Importantly, the tabelecleucel interim analysis for pivotal study in relapsed refractory PTLD has now been completed, and these data support our plans to discuss the totality of tabelecleucel clinical data with FDA.
We have ongoing regular interactions with the agency and plan to have a pre-BLA meeting in Q4 2020. Pending the outcome of this pre-BLA meeting, we plan to initiate the tab cel BLA by the end of the year. In addition, we plan to begin enrollment of our Phase II multi-cohort study with tap cel in the second half of this year. As we discussed or in our Q2 quarterly call, this study could provide a significant label expansion opportunity for tap cel in the future, and we are looking forward to enrolling first patient as soon as possible. Lastly, as we announced earlier this week, the IND for ATA2271 was cleared by the FDA for the first CAR T therapy in solid tumors combining novel intrinsic PD-1 dominant negative receptor checkpoint inhibition and 1XX CAR signaling technologies.
We look forward to our collaborators at Memorial MSK enrolling the first patient in this phase I study in the very near future. As you can see on slide five, showing our achievements to date in 2020, this is truly great progress by all Atara staff members and collaborators during a still active COVID-19 pandemic. We look forward to presenting further updates on our progress later this year. We are, of course, also here today to discuss the new data readouts for exciting program in progressive multiple sclerosis, ATA188. We believe this program could potentially be a transformative therapy for patients, delivering tremendous value to patients, the healthcare system, and all shareholders. This encouraging updated data has totally deepened our conviction to invest further in ATA188. I will get into more details later.
Now, let me hand over the call to our Chief Medical Officer, Dr. AJ Joshi, to discuss the new data presented today at ACTRIMS for ATA188. AJ?
Thanks, Pascal. Good morning, everyone. I'm pleased to review the data presented at ACTRIMS by Dr. Bar-Or and also provide some additional important detail and granularity on these data. On slide eight, you see the phase I-A study design. It's an open label dose escalation study with four dose escalation cohorts where patients are assessed at three, six and 12 months. All patients are then eligible to enter an open label extension that involves annual retreatment and ongoing assessment for an additional four years. On slide 9, as background, there's growing evidence of the role of EBV infection in the pathogenesis of MS, particularly through EBV-infected memory B cells that are thought to play an important role in the propagation of the immune cascade in both relapsing and progressive forms of MS.
ATA188 is an off-the-shelf allogeneic T-cell immunotherapy made from healthy donor T- cells. Designed to eliminate EBV-infected cells by targeting specific EBV antigens believed to be important in MS. ATA188 is available as a pre-manufactured inventory that can be readily selected for a patient's HLA profile and then delivered for administration in approximately three days. Moving to slide 10. The objectives of this phase I-A study were to assess safety of ATA188 in progressive MS, also assess the clinical efficacy parameters, and select a dose for the randomized control trial. A very important parameter we assessed was sustained disability improvement, or SDI. This is a composite of clinically significant improvement in either the Expanded Disability Status Scale, also known as the EDSS, or the timed 25 Foot walk test. That improvement had to be confirmed at two consecutive time points to qualify as SDI.
This means for an individual to have SDI at six months, they were required to have disability improvement on one of these parameters at three months and confirmed on the same parameter at six months. Likewise, for SDI at 12 months, the patient must experience disability improvement at six months and have that confirmed at the 12-month time point. What's really important to remember here is that the natural course of disease in progressive MS is by definition progression of disability, and currently available therapies have really shown a modest impact at best on slowing disability progression. No treatments have proven to actually improve disability. Moving to slide 9. Here you see that information on the only agent in progressive MS that's made it to phase III studies using a primary endpoint of disability improvement.
That agent is MD1003, which unfortunately reported negative data in May of this year. What you see here is the phase II/III study on the left, which utilized a composite of disability improvement in either EDSS or timed 25 foot walk at 9 months and confirmed at 12 months. Importantly, in the phase II study on the right, this primary endpoint was measured at 12 points and then confirmed at 15 months. As you can see, our SDI measure that we're using is similar to this measure. The important point on that is the placebo numbers that you see here. The context is that you see placebo rates of 0% and 9% when you're using this kind of composite disability improvement measure.
That will be important in understanding the data that we're going to be showing you a little bit later in the next couple of slides. Moving to slide 12, we're going to go back to the phase I data now. The new information that we're showing here is cohort 4 12-month data. Starting from the beginning, first of all, we saw no new safety signals at this highest dose. In terms of the graph on the left, which is the SDI graph, both patients that experienced SDI at six months in cohort 4 maintained sustained disability improvement at 12 months. That means across this phase I study overall, each cohort had patients achieving SDI, and every patient in the study that achieved SDI at six months maintained it at 12 months.
The next point is that you see that there is a dose response showing increased sustained disability improvement in the two highest dose cohorts, which are cohorts 3 and 4. For these cohorts, 42% or five out of 12 patients achieved SDI at the 12-month time point. For us, these data affirm our decision to use a cohort 3 dose in our randomized placebo-controlled trial. We do still have the option of adding the cohort 4 dose in the future, and we'll review data in the next couple of slides to illustrate why that may still be beneficial. Moving to the right graph, it's really important to note that the SDI improvement that we've seen was driven primarily by EDSS improvement. This is key because EDSS is the most accepted and relied upon individual disability endpoint measure by the regulators.
Interestingly, although the numbers are small, there's a suggestion that the cohort four dose may have done best in terms of the pure EDSS improvement. Moving to slide 13. Here, we're showing you all the patients that developed SDI during the study with granular detail on the three disability measures that we assessed. We've already mentioned EDSS and timed 25 foot walk. We've added here the 9 hole peg test, which is really a measure of upper limb disability. Before I get into the details, and it's not on a chart, but we should note that in these seven patients, there were both males and females showing SDI, both patients with PPMS and SPMS showing SDI, and people who were naive to anti-CD20 therapy, as well as people who failed anti-CD20 therapy having SDI.
For orientation on this chart, the rows go from cohort 1 through 4, top to bottom, and the columns on the right represent data for the disability measures at three, six, and 12 months. The data shaded in the darker green are clinically significant improvements in those parameters. The lighter green are transient improvements in those parameters, and in the case of EDSS, either improvements or stability. The light pink are transient decline. The first important thing that jumps out is that we're seeing a lot of green. Secondly, we also see that at the three-month time point, six out of seven of these SDI patients were already showing clinically significant disability improvement, suggesting that the treatment effect can be seen early in most subjects.
What's interesting here is that we have additional data on cohort 4 on the next slide suggesting that subjects may begin to show disability improvement for the first time a bit later than expected. On slide 14, we've provided some of that added detail for cohort 4. The first two subjects, which are F and G in this table, are carried over from the prior slide and represent those two subjects that achieved SDI. Subjects Y and Z are two additional subjects from cohort 4. Notice all the way over to the 12-month time point, where for the first time, subject Y has disability improvement in the timed 25 foot walk test, and subject Z has a 1-point improvement in EDSS from 5.5-4.5 at that 12-month time point.
If these improvements are now confirmed at the 15-month time point in the open label extension portion of the study, both of these cohort 4 patients would also have achieved SDI now at the 15-month time point. Move to slide 15. We also have data on five other measures in the phase I-A study. Now, the green data points that you see on the plot represent patients that achieved SDI, and the blue data points are those that did not. Now, prior to this slide, we focused on physician and investigator-assessed measures of disability. Here, we're now focusing on patient-reported outcomes in the three green boxes that you see highlighted. Notice that the patients achieving SDI had a statistically significant improvement in the Fatigue Severity Scale, which is important given the prominence of fatigue as a significant issue for MS patients.
There was also a trend for SDI patients to have greater improvement in both the Multiple Sclerosis Impact Scale and the Multiple Sclerosis Walking Scale. In the case of MRI and 9 hole peg test, SDI patients appear to be doing better on the plot. For example, brain volume MRI is known to require a large number of patients to assess, given the inherent variability in this measure. We'll need more data to properly assess this as we go forward. Moving to slide 16, we're now going into the OLE study, and this is the open label extension. Here we have data from six out of 15 patients that were retreated in the open label extension that at the time of the August data cut, had reached their first post-dose assessment.
Patients are represented here from cohorts 1 through 3. All of them received the randomized control trial dose, which is the cohort 3 dose, as part of this open-label extension. Importantly, we see no new safety signals with repeat dosing and the longer-term observation in the open-label extension. On this table, we have subjects from cohorts 1 through 3, top to bottom, and the time point for open-label extension administration of ATA188 is highlighted in yellow for each of the patients. For most of these patients, the time point should be 12 months. As you can see, subjects H from cohort 1 and B from cohort 2 received it later, and that's because the RCT dose hadn't been selected when they reached their 12-month time point.
As we look at the data overall, the top four subjects in the table, which are H, B, D, and E, have all achieved SDI, either in the phase I-A portion or in the open-label extension. Specifically, subject H was from cohort 1, and they finished their 12 months in the phase I-A without achieving SDI. No additional assessments were done until the subject entered the open-label extension at 21 months. Remember, that was the time we were able to select the cohort extension dose. At that point, interestingly, they had disability improvement recorded for the first time. This improvement was likely from the initial treatment that they received in the phase I-A, we confirmed this improvement at the 24 months. They qualified for SDI for the first time at the 24-month time point.
These three other patients that achieved SDI achieved it earlier at the six-month time point and then maintained it at all future time points through the open label extension. Interesting from this group of three, there's a subject E that had further improvement in EDSS at the 15-month time point. Lastly, I'll draw your attention to subject I, who hadn't achieved SDI in the Phase 1a portion of the study. At the 15-month time point, they had their first disability improvement by EDSS. That's another patient who could develop SDI at the next time point. Moving to slide 17. I'd like to just close here with just a few summary points. First, we continue to see a favorable safety profile for ATA 188 with all doses and now with retreatment and extended observation in the open label extension.
Secondly, a greater portion of patients showed sustained disability improvement with higher doses, particularly in cohorts 3 and 4. All patients who achieved SDI maintained it at all future time points throughout the phase I-A and open label extension. Next point is that in the phase I-A study, 42% of patients, which is 5 out of 12, achieved SDI at 12 months in our high-dose cohorts 3 and 4. Important in cohort 4, there are two additional patients who achieved their first disability improvement measured at 12 months. That means if all of those patients maintain SDI at 15 months, there's potential that 58%, which is 7 out of 12, of patients from the 2 high-dose cohorts would have achieved SDI at the 15-month time point.
Obviously, this is a small study, the results do need to be confirmed in a larger randomized control trial, which as you know, is already underway. With that, I will turn it over to our head of R&D, Dr. Jakob Dupont, who will take us through the MS treatment landscape and ATA188 future development plans. Jakob?
Thanks, AJ. I would now like to take a few moments to provide an overview of the current and future treatment landscape for multiple sclerosis, as well as present an update on the development plans that we have for ATA188. On slide number 19. As a reminder, there remains a significant unmet need for MS patients worldwide, especially for those patients with the progressive form of the disease. Approximately 2.3 million patients worldwide are diagnosed and living with MS, with approximately 1 million of these patients with progressive MS. These patients, unfortunately, have a poor prognosis as a continual decline is expected. The current treatment options for these patients have only delivered modest results in progressive disease. Slide 20. Current approved therapies for progressive MS, like ocrelizumab and siponimod, only slightly delay progression of the disease but do not fundamentally alter its course.
We believe there is significant opportunity to provide better treatment options in this area to benefit patients. ATA188 could be such a therapy. Slide 21. As a reminder, ATA188 is an off-the-shelf allogeneic T-cell immunotherapy that targets EBV-infected cells, and we believe there is growing evidence that EBV plays a significant role in multiple sclerosis. Data to date has shown that EBV infection is strongly associated with the pathogenesis of MS, and EBV infection has been reported in up to 100% of MS patients. We've also seen that the risk of developing MS is extremely low among individuals not infected with EBV, but that risk increases sharply in the same individuals following an EBV infection. We feel this provides further support for the potential for ATA188 to be successful. Slide 22.
Our current development plan for ATA188 is focused on achieving sustained disability improvement over time for patients with progressive MS. We believe that if that were to be achieved, it would represent a significant transformation in the current treatment paradigm. As a reminder, the natural course of disease for patients with progressive MS is a decline over time. As I mentioned earlier, current available treatments only offer about six-month delay in progression. We believe that halting or, more importantly, reversing the progression of disability would represent a truly transformational advancement for patients. Slide 23. When we talk about the optimal characteristics of a progressive MS treatment, there are several things to consider. First, the treatment must be well-tolerated by patients. Second, we believe that the treatment should halt or, better yet, reverse progression of disability.
The treatment should penetrate the CNS and target specific cell populations like B cells and plasma cells. Finally, the treatment should address the underlying biology of the disease. We are targeting all aspects of these characteristics with ATA188. Slide 24. As you've heard from AJ today, we are conducting an open label extension of the phase I-A study. This allows patients to continue on the study and to be retreated annually with ATA188. In the OLE, we learn more about the safety and potential efficacy of ATA188 over a longer duration of treatment. We currently have 15 patients who are participating in the OLE, and we will be presenting the ongoing results from these patients continually over the next years. Slide 25. Based on encouraging clinical data, we are increasing our investment in the ATA188 program.
We are expanding the size of the currently enrolling randomized double-blind placebo-controlled study to at least 64 patients. We are changing the primary endpoint of the study to disability improvement while maintaining biological endpoints in the double-blind placebo-controlled study. The increase in the number of patients is driven by our decision to move to SDI as our primary clinical endpoint and will provide a broader data set, which we believe will create more opportunity to deliver value. Moreover, we are conducting additional clinical biomarker studies to provide further support for the product and investing in our novel stirred-tank bioreactor manufacturing scale-up. We do intend to meet with the FDA by the end of this year or early next year to discuss our encouraging clinical data for ATA188 to discuss the updated design of our double-blind placebo-controlled study.
We want to explore with the agency opportunities for accelerated development of ATA188 for multiple sclerosis patients. Slide 26. As I just mentioned, we've increased our investment and updated the primary and secondary endpoints in the randomized placebo-controlled study. We now plan to enroll at least 64 progressive MS patients in the study and will conduct a primary analysis at 12 months. The key endpoints are also updated to include primary clinical endpoints of SDI at 12 months, as well as secondary clinical endpoints of EDSS at 12 months and SDI and EDSS at 15, 18, 21, and 24 months. In addition, we have secondary biological endpoints around CSF IgG index at eight months. Importantly, we will consider whether we should be conducting the primary endpoint at 12 months or 15 months within the near future.
We will also be making the dose decision for the randomized control study between either continuing with the cohort 3 dose or transitioning to the cohort 4 dose in Q4 of this year, following the analysis of the 15-month data from cohort 4 in the phase I-A study. Slide 27. Also, we are planning to conduct additional clinical biomarker studies for pharmacokinetics, pharmacodynamics, and mechanism of action biomarkers. These biomarker studies will focus on testing blood and CSF for ATA188 persistence, panel soluble factors, EBV-positive cell quantification, and B-cell receptor characterization, and is targeted at further supporting the successful development of ATA188. Slide 28. We have also demonstrated each element of our manufacturing platform to support a biologic-like supply chain for ATA188 at commercial scale.
Notably, we have proven scalable bioreactor manufacturing capabilities that confirms we can produce up to 40,000 doses of ATA188 from one healthy donor leukapheresis. At commercial scale, this level of productivity is expected to deliver a biologic-like cost of goods manufactured. Slide 29. In summary, we believe that ATA188 is a bold vision to dramatically transform multiple sclerosis patient treatment. We have demonstrated a favorable safety profile to date, we believe there is the potential for ATA188 to improve disease in progressive MS. We're excited about the future of this program, we look forward to provide updates in the near future. Pascal?
Thank you, Jakob. I would like to take a few moments to provide an update on key expected program milestones for ATA188 and also provide context around what type of value a transformative therapy could bring to patients, the healthcare system, and shareholders. On Slide 31, as Jakob mentioned, on an ongoing basis over the next year, we will have a regular cadence of upcoming data readouts for at least 15 patients continuing in our ATA188 phase I-A open-label extension, including all patients from cohort 3 and 4. It is important to note this regular cadence of data readouts since this will occur while we are conducting the randomized control study. Such data readouts will provide further insight into how these patients progress over time, we look forward to sharing this data with you on a regular basis.
Moving to Slide 32, and also as mentioned by Jakob, we plan to consider adapting those in timing of primary analysis for the randomized placebo-controlled study in the fourth quarter of 2020 once we see the cohort 4 data at 15 months. Now that we have a set of encouraging data for ATA188, we plan to have interactions with the FDA to discuss future potential regulatory pathway in Q4 2020 or Q1 of next year. One of the topic we intend to cover is the possibility of an accelerated development. We expect to conduct an interim analysis on the primary endpoint and also analyze the CSF IgG biological secondary endpoint for the randomized placebo-controlled study in 2022. If our encouraging early clinical data are confirmed through our randomized controlled trial, ATA188 could very well be a unique transformative therapy in progressive MS and possibly beyond.
Moving on to Slide 33. A transformative therapy in progressive MS could be tremendously impactful to these patients as they are largely underserved, especially as disease progresses. In PMS, over 60% of patients remain untreated, which presents a remarkable opportunity to make an impact. Slide 34. We believe that based on this high unmet need, the transformative therapy in progressive MS could be a multi-billion dollar opportunity. Independent and reputable data are projecting that in five years, the U.S. market size for progressive MS will grow to between $5 billion and $7 billion, through a 9% compound annual growth rate. We believe that there is a dire need for better treatment options than currently available, and a transformative therapy could increase the treatment rates of these underserved patients by 25%-50%, reaching the treatment level of relapse remitting MS.
Next, we believe a potential transformative therapy market share could be at least 45% based on the current share of anti-CD20 therapies in progressive MS. Altogether, these data suggest a potential annual revenue opportunity for a transformative therapy of at least $3.5 billion in the U.S. alone, with potential for further upside when including ex-U.S. revenues or also with higher market share levels. As a note, every 10% increase in market share would translate to an additional $750 million- $1 billion of revenue in the U.S. based on 2025 market projections. While it is still early in the development cycle of ATA188, with today's small number of patients treated in an open study so far, we are excited by the sustained disability improvement we've seen thus far and are very hopeful that ATA188 can become a transformative therapy for multiple sclerosis patients worldwide.
I'd like to take this moment to offer our sincere thanks to our staff and especially also to the patients who are participating in our trials of ATA188, their families, the investigators, and the support teams at the clinical site. Finally, I would like to extend our gratitude to our corporate partners at QIMR who have helped us bring ATA188 to patients. Thank you. Finally, on slide 35, we look forward to provide a further update on our company progress later this year. We are very proud of the accomplishment we've made to date and are excited about the future. That concludes our prepared remarks this morning, and I would like now to turn the call back over to the operator so we can go ahead and take your questions. Operator?
Ladies and gentlemen, if you'd like to ask a question, please press the star, then the number one key on your touchtone telephone. To withdraw your question, press the pound key. Again, that's star, then one if you'd like to ask a question at this time. Our first question comes from John Newman with Canaccord Genuity. Your line is now open.
Hi there. Good morning. Congrats on a very nice data update here for an exciting therapy for MS. Just a few quick questions. The first one is on slide 12, you mentioned that the SDI that was driven by EDSS improvement appeared to be a bit stronger for cohort 4. I just wondered if you could walk us through again why EDSS is viewed as the most relevant and important measure there, as compared to timed 25 foot walk. Also, in terms of the decision to expand the randomized study to 64 patients, I'm just curious if you could talk a bit about how the enrollment is going in the study thus far, and if that played into your decision to expand the size there. Thank you.
Thank you, John, for your questions and for your thanks there. AJ, do you want to take these questions?
Sure. In terms of the cohort, the SDI and the timed 25 foot walk portions here, EDSS is the more established measure out of this composite score. It's been used in lots of different trials for targeting for approval for multiple different therapies. Timed 25 foot walk, on the other hand, has really only been used by one therapy to officially get an approval. EDSS, from a regulatory perspective, has had more precedent, but also from what it covers. EDSS covers, I think it's eight or nine functional domains. You're assessing a lot of different things for the MS patient. It's a much more global and well-recognized measure, versus timed 25 foot walk is really just assessing walking speed, if you think about it. It's not to minimize timed 25 foot walk. It is an important point.
However, EDSS improvement or EDSS in general is really the main most important endpoint that people are going to be looking at when you think about anything that's happening with a disability. That's why EDSS is so important, and that's why it was really important for us to see that you see seven patients on the left-hand side of slide 12 having sustained disability improvement in the study. On the right-hand side, you see five out of those seven were driven by EDSS, and specifically in cohort 4, that was the cohort where all of the SDI was EDSS patients. In terms of the enrollment and things in the randomized controlled trial, we're not going to be commenting, as you might imagine, on the enrollment rate.
What we will comment on is that I think Jakob had mentioned a bit earlier that we are continuing to invest in this study. We're adding more sites so that we can make that enrollment as rapidly as possible to deliver on those timelines that Pascal mentioned a bit earlier.
Okay, great. Thank you very much.
Our next question comes from Salim Syed with Mizuho. Your line is now open.
Great. Thanks so much for the call, guys, congrats on the data. Three from me, if that's okay. The first is, I didn't see any detail in the slides regarding which patients were SPMS or PPMS. I was wondering if you could maybe opine on that if you are seeing a trend now that we have the longer 12-month cohort 4 data. Are you seeing a trend where the data is behaving better in one versus the other, SPMS versus PPMS? Second question is on the interim analysis that you plan to provide. Just curious if that's some sort of futility analysis or if there's even any room here to stop for if you see a ridiculous amount of efficacy versus placebo. Just lastly, on the 15-month primary that you said you may switch to that. Just curious what the criteria is for that.
Do you need to see both of those patients in cohort 4 that have shown disability improvement at month 12 but not yet at sustained disability? Would you just, if you saw the EDSS patient alone, the one that showed disability improvement on the EDSS, that one alone but not the other patient, would that qualify enough data to move it to a 15-month primary endpoint for the randomized trial? Thank you.
Thank you, Salim, for these number of questions. Let's start with question number 1. AJ, do you want to take question number 1? Jakob will address question number 2 and number 3. AJ?
Sure. In terms of the breakdown, the seven patients that we have that showed a sustained disability improvement, five of them were PPMS and two were SPMS. If you look at the cohorts 3 and 4, there were five total patients, and three of them were PPMS, two were SPMS. We do have a good mix of improvement in both of those settings. If you're curious, for cohort 4, where we had those two potential additional patients at that 12-month time point, one was SPMS and one was PPMS. As you can see, we're not seeing a trend. We're seeing actually good effect across both MS populations. As noted earlier, we're also seeing good effect across males and females as well as prior anti-CD20 treatment. I should say anti-CD20 failure versus anti-CD20 naive patients.
Far at least, across all of those subpopulations, we've seen SDI.
Thank you, AJ. Jakob, do you want to take question number 2 and 3?
Yes, absolutely. I think I'll start with the dose selection question in the randomized control trial. As you know, Salim, currently we're using the cohort 3 dose, and we have been enrolling the randomized control trial for several months based on the data. As you've seen today, there are some encouraging signs coming out from the cohort 4 dose, including a very good safety profile, as well as some encouraging signals of efficacy. Those two patients that showed disability improvement and not yet sustained disability improvement, we want to see how those patients are going to do when we do the follow-up assessment here at 15 months. If they do convert to sustained disability improvement, which would mean we would have now four out of six patients in cohort 4 with SDI, I think that would be very compelling to us.
I think it's also important to think about the OLE data that AJ has shown, where there's also some evidence of continual improvement at the higher doses as well. I think that could factor into our decision-making on switching to the cohort 4 dose. We will be able to make that decision here before the end of the year. Additionally, I think we need to take a look at the safety profile here again in 15 months. To this point, the cohort 4 safety profile has been very excellent, and we anticipate that it will continue to be so. We need to see that data when we review here at 15 months. In terms of the interim analysis for the randomized control study, we do plan on looking at CSF and the biological endpoints. We also plan on looking at the clinical efficacy.
At that point in time, the primary goal of the interim analysis will likely not be futility. We do think that we have, again, excellent data in the phase I-A to this point, so we do not anticipate that futility will be an issue. Again, we will take a look at the data. If there is exceptional efficacy at the point of the interim analysis, we will consider that. I think it's also important to remember that we plan to have an FDA meeting before the end of this year or early next year, depending on the availability of the agency.
The intent of that meeting is to share the data from the phase I-A study and then also to share with them the design of the randomized control study, because we want to assess potential for rapid development of the drug in progressive MS, so that if there are potential to advance this trial as a pivotal study in progressive MS, then we want to work with the agency to understand that further, and that can certainly affect the way that we treat the interim analysis. I will say that the FDA meeting coming up here shortly will be important in terms of how we handle the interim analysis as well.
Got it. Thanks so much for the color, guys.
I think it's important, Salim, to keep in mind that what we're doing there in postponing for a few months the decision on the dose and considering adapting the time points from 12 to 15 months is not having an impact whatsoever in the enrollment we're doing right now. We are full speed on enrollment on that study, and things are moving very well. It's not having an impact in our current view on enrollment and follow-up of patients onto the possibility to have significant data in 2022.
Got it. Thanks, Pascal.
Our next question comes from Salveen Richter with Goldman Sachs. Your line is now open.
Good morning. Thanks for taking my questions. One is just around how to think about what's important within the secondary endpoints for the randomized trial, just bigger picture here, as you look to run part D and think about the overall regulatory path to approval, could you maybe just walk us through that and how you envision that playing out?
Yeah, thank you. AJ, do you want to take the first question on the secondary criteria in the randomized controlled trial and their importance? Jakob, the question on the regulatory path and interaction with the FDA to come.
Sure. In terms of the secondary endpoints, there's a few. Some of the more intriguing ones are the biological endpoints. For example, we've focused in on the CSF IgG. It's a biological endpoint that really most other therapies have not been able to show a reduction in CSF IgG. Almost by definition, that means you're getting your therapy into the central nervous system, and you're having a direct impact on something related to MS, because increases in CSF IgG are really almost pathognomonic for some of the pathology that you see in MS. The ability for a therapy to reduce that would be significant when you think about the mechanism of action. It's an important endpoint. We did see some early evidence of that in the autologous version, ATA190 study that was done previously.
That endpoint is something we are tracking, and that would be one of the important secondaries. As you've seen, we're also tracking some of the measures that we're talking about now, the individual disability measures at different time points as secondaries, because that will also help us figure out the best time point in terms of overall treatment effect. Lastly, there are some additional secondary endpoints that will be related to MRI and other factors, that are also harder endpoints beyond the clinical ones.
I would like as well, before handing over to Jakob, that during that RCT, we will have, of course, samples of the blood and the CSF that will be used for the secondary criteria that AJ just mentioned. We are also investing in a number of translational work. It's going to be very important to clarify aspects related to the pharmacokinetics and dynamic of ATA188, so how the cells are expanding, trafficking, persisting, but also on the mode of action and how they're working in a very targeted way, in a very selective way on these B cells that are infected by the EBV virus. It's going to be very exciting, this investment, do a lot of translational work there. Jakob, do you want to answer Salveen's question on the regulatory interaction?
Absolutely, Pascal. Salveen, thanks for the question. Regarding our regulatory interactions with the FDA, as I mentioned, we do plan to have a meeting with them either in Q4 of this year or Q1 of next year, depending on their availability. We do want to share the phase I-A data that we've shown you today. We also want to share with them the design of the currently enrolling randomized placebo-controlled study that we've described today. We have, as you've heard, made additional investments in that study, and taken that internal decision based upon what we think are very encouraging data in phase I-A. Those additional investments make our program more rigorous, we believe. First and foremost, we're increasing the sample size up to at least 64 patients in a one-to-one randomization between ATA188 and placebo.
Again, this is a double-blind experiment, really a definitive proof of concept experiment. We've also changed the primary endpoint to a disability improvement here, a clinical endpoint. We think that these factors make the study much more rigorous. What we want to discuss with the FDA are, number one, what do they think about our current data in phase I-A? Does this qualify us potentially for accelerated development paths like Fast Track or Breakthrough Therapy or RMAT. We want to talk to them about how we can optimize our speed to development of the randomized control study so that we really get agreement around that. Now, the final piece is we're also investing in our manufacturing process to make it a more robust and rigorous process closer to what would be commercial-like material.
That investment allows us to go into additional regions for enrollment, but it also may provide more ease of getting qualifications like RMAT and so forth. We think that these additional investments that we're making now actually fit very well with our discussions with the FDA and potential for more accelerated paths to development.
Great. Thank you very much.
Thank you.
Our next question comes from Michael DiFiore with Evercore ISI. Your line is now open.
Hi, guys. Thanks so much for taking my question. Congrats on the very encouraging data thus far. A few from me. Number one, looking at slide 13 to 14 and just noticing that the response kinetics among the seven patients who did have SDI vary on EDSS. Meaning that in either there's an abrupt decrease in EDSS which remains there, or a patient could have a gradual improvement in EDSS, or it could occur very late in the game. All that being said, I wanted to see if there's any biomarker correlation to these different response kinetics and whether you could use this info to enrich the randomized controlled portion of the study, as well as future trials of these patients. That's number one. Second is more of a kind of a scientific question.
What could possibly biologically explain the super late onset of patients, in some patients versus the early response in others? Finally, with regards to adding the cohort 4 dose in the randomized control portions, if you decide to proceed that way and switch current patients who have been dosed with cohort 3 dose over to cohort 4, will this redosing using the cohort 4 dose somehow confound the results? Just want to get some color on that if possible. Thank you.
Thank you, Mike. AJ, do you want to take the first two questions and Jakob, the last one?
Sure. Good question on the biomarker correlation. In the phase I-A portion of the study, when you look for a biomarker for something like this, there's really not a lot. The best biomarkers are going to be related to what's happening to those EBV-infected B cells. The state of technology has not existed to allow you to measure just those small numbers. Because if you think about B cell depletion in general, for the anti-CD20s, for example, they'll report out of 99% depletion of peripheral B cells. That's because you're looking at the entire population. What we're looking to eliminate is just those EBV-infected cells. Trying to isolate those, the assay technology has not really existed. Now, we have developed that. We've developed it. We're in the process of validation, and that will then actually be used in the randomized control study.
We will have that information with the randomized control study. It's just that there's been technological limitations, so we really don't have that for the phase I-A. To your second point about how do we explain this late phenomenon versus the early phenomenon. If you look at some of these patients, what's really interesting is, for example, you mentioned slide 13. If you look on slide 13, there was that patient 3C. The cohort 3 patient where they didn't develop SDI, or their first disability improvement happened at the six-month time point, and then they became officially SDI at 12 months. They were a little bit later than most patients who start at three months.
If you look at the first time point at three months for that patient, even though their EDSS score was still six, if you look at the individual data sets, that patient was clearly improving on disability. They just hadn't crossed over the bar to get to that full improvement. Really, when you think about what's happening biologically, it seems like for the majority of these patients, something is happening early on fairly consistently for these folks. It's just a question of how much time does it take to officially trigger the sustained disability improvement measure that we've put into place here. I think that's the biggest reason you're seeing some of the variability here.
Thank you. Jakob, could you clarify the cohort 4 possible addition into the RCT?
Absolutely. With our upcoming decision on whether to switch to the cohort 4 dose, I think a few key statements. Number 1, if we do decide to incorporate cohort 4 dose going forward, we do not intend to switch those cohort 3 patients over to cohort 4. We're going to retain them on the dosing that they have been receiving. We don't want to create that type of confounding. I do think that we have ways to handle the analysis of the study going forward, so we can certainly do sensitivity analyses. When we look at the result, where we look at whether or not there is an effect of the cohort 3 doses, we can certainly increase the sample size a little bit more to account for those patients in the study that received the cohort 3 dose.
Finally, we can also speak with the FDA about how to handle these patients. If they say, "Listen, we would like this analysis to be predominantly on the cohort 4 patients," we can always make sure in our statistical analysis plan that we do a designated analysis just on the patients that get the cohort 4 dose. I think we're well aware of this feature, and we will certainly proactively manage it. I think at the end of the day, what we really want to do is make sure that we conduct this randomized controlled trial with the dose that we think is going to be optimally most effective and provide the most benefit for patients with progressive MS.
Yeah. Very helpful. Thank you.
Thank you, Mike. Thank you for your question. Next question?
Our next question comes from Phil Nadeau with Cowen and Company. Your line is now open.
Morning. Thanks for taking my questions. A few from me. First on the data, congratulations again on the sustained benefits. I guess the question that comes to mind is, one of the challenges with evaluating EDSS in an open label study is at a baseline of five or six, it's really an exertion-dependent endpoint, meaning the difference between EDSS of six versus five is whether a patient needs a cane or not, and whether they can walk 100 meters or 200 meters. What provisions were put into the evaluation of these patients such that that exertion was equivalent from baseline to three months, six months, 12 months? I guess where you'd worry is patients know they're receiving a drug and they might just try harder later on.
Was there anything put in place to mitigate that potential confounding effect of the impact of exertion on EDSS at these type of baselines?
Thank you. AJ, do you want to answer that question, explain how that was done with the clinical investigators assessment?
Sure. It's a good question. There's very standardized approaches to having the same investigator and very specific approaches that investigator must take to assess each patient for EDSS. Again, that's well established in the space. The main thing is that you have to make sure that each one of the investigators at each site is properly trained to perform these analyses and to account for some of those variables. To some extent, there's always going to be, because of the way the nature of the variables, there is going to be differences. That's also why we actually require the confirmation of any change in EDSS on two consecutive time points.
If you don't do that, then really the measure is not a useful measure because of that known variation. The way to look at it is, one, everybody knows that there is variability, so the folks who are doing the assessments are well-trained, and there's a standardized methodology around this to minimize any of those effects that you mentioned. Two is, even if that happens, you account for that by making sure that you've got a confirmed assessment on two consecutive time points so that there, again, that's that second mitigation for any of the variability that could be introduced.
That's very helpful. Thanks. Second question is on the phase II. With the expanded enrollment and SDI endpoint, what is the powering of this study now to detect a difference on that SDI endpoint?
Yeah, I think at this stage, we are not giving details on these. Jakob, do you want to explain what is our intent there?
Yeah, absolutely. In terms of the phase II, when we think about increasing our sample size to at least 64 patients, that number is really based upon the treatment effect that we're seeing in the phase I-A data. Again, we look at the treatment effect, and we say, what's a reasonable estimate to go after in the randomized controlled trial? It's really based on that. Then some of the other points about type 1 error and power and so forth, we're not commenting on. I think the design is realistic based on the data that we've seen so far. I just want to add a comment to what AJ described in your question around variability of EDSS.
I think the other data that AJ shared today, which is in slide 15, shows these other scales of physical well-being for patients, including the Fatigue Severity Scale, the 9 hole peg test, the Multiple Sclerosis Impact Scale, and the Multiple Sclerosis Walking Scale. I think these are all additional metrics where we can see, independent of the EDSS assessment, how the drug is performing. I think as you saw in the data that AJ presented, that there appears to be a clear distinction in the patients who have sustained disability improvement on these other factors. To me, that really provides some confidence in the consistency of the data here beyond just the EDSS assessment. I think that's another key point to take out of the data that we presented today.
That's very helpful. Last question. Pascal, I apologize, I might have totally misunderstood what you said. Did you say in your very early remarks that the TABS cell interim analysis has been conducted and based on the data, you remain in a position to initiate a meeting with the FDA in Q4?
Yes. What I said exactly, that the tabelecleucel interim analysis has now been completed. Data support our plan to discuss, as we said before, the totality of the data with the FDA. We continue to interact with the FDA and plan to have a pre-BLA meeting with the FDA in Q4 2020. Pending the outcome of the pre-BLA meeting, we plan to initiate tabelecleucel BLA by the end of 2020.
Any updated thoughts on how you'll disclose that interim analysis to investors?
As we said, we want to discuss that with the FDA because we want to preserve the integrity of that study. Part of the interaction with the FDA will be also to discuss with them when and what can be disclosed in the appropriate way.
Perfect. Thanks for taking my questions.
You're welcome.
Our next question comes from Ben Burnett with Stifel. Your line is now open.
Hey, thanks very much and congrats on this update. I also just want to get a clarification on one thing. You said that you're still looking and assessing dose level 4. I guess could you just clarify how patients in cohort 4 of the phase I-A study will be handled in the open-label extension portion? Will those patients get redosed at dose level 4?
Yeah, that's an interesting question. AJ, do you want to answer that one?
Yeah. The way the protocol is designed, if we choose to add the cohort 4 dose into the study, the first certain number of patients will need to be still dosed at the cohort 3 dose before we switch over to cohort 4 in the open-label extension. There may actually be a couple of cohort 4 patients that are treated with cohort 3 dose before we make that cohort 4 decision. Sounds a little strange, but at the end of a open-label extension, cohort 3 dose for all patients. If we make the decision to switch to the cohort 4 dose, at that point, that would allow potentially to move over to the cohort 4 dose and open-label extension.
Anyone who has not gotten to open label extension retreatment, once we make that decision, could then get their cohort 4 dose, but otherwise everybody will still receive the cohort 3 dose and open label extension.
Yeah. That means that the 15 patients that are the OLE today, they have received cohort 3 dose in the first redosing.
Okay.
Does it answer your question, Ben?
That's very helpful. Thank you. Maybe just one quick one, just one last one. I know in the past you've talked about clinical improvements, just in terms of improving on two clinical measures for two consecutive time points. I recall that this was met in cohort 3. Has the FDA given any guidance on the use of SDI as a measure of efficacy? I know that's something that's being planned for the phase I-B.
AJ, do you want to answer that one?
The question was related to FDA guidance around use of SDI. Was that it?
Yes. Yeah, exactly. As an endpoint.
Okay, great. Thank you. No. We haven't had those conversations with FDA ourselves, at this point. As Jakob noted, that's going to be coming in Q4 of this year or Q1 of the next year. I think the important point that we wanted to emphasize with the MD1003 data was that clearly an endpoint very, very similar to what we're talking about here has been discussed with the FDA because they were late in phase III with that particular endpoint. There's clearly experience at the FDA with that, and there's got to be some comfort level given how far that study went. We know that FDA is going to at least have a good, strong working knowledge of that, and obviously we'll have to see what they're feeling like when we have those conversations, but clear experience, phase III level experience with that endpoint.
We feel pretty comfortable that, when we go with them, they're going to be at least receptive to the concept of the SDI.
Yeah. Also that composite disability is something that is now accepted by the FDA. Even when you see the other treatment being developed in MS that are all looking not at improvement. Nobody else is looking at improvement. They're all looking at limiting the progression. It's becoming more and more composite disability progression. It will make sense that the field is evolving into this composite disability type of scales.
Okay. That's helpful color. Thanks very much.
Our next question comes from Anupam Rama with JP Morgan. Your line is now open.
Hey, guys. Thanks for taking the question and congrats on the update. How do you think about the Timed 25 and 9 hole peg test baselines across the different dosing cohorts? Were they roughly similar or any differences to note? Just trying to put the changes that we see in slide 13 and 14 into context a little bit. Thanks so much.
Thank you, Anupam, for your question. AJ, do you want to answer that one?
Yeah. There wasn't much in terms of any pattern on the timed 25 foot walk and 9 hole peg test in terms of baseline. Really baseline, the most important things for those two are the % change that you see, irrespective of the baseline. There's a little bit of variability there, but the most important thing is % change. EDSS is a little bit different where the baseline does matter. For example, at the higher levels of EDSS, a small change is significant versus lower levels of EDSS, you do need a bigger change to be significant. The measures behave a little bit differently from baseline versus change. For timed 25 foot walk and 9 hole peg test, we really didn't see any patterns there.
Great. Thanks for taking the question.
Thank you .
Our next question comes from Yigal Nochomovitz with Citi. Your line is now open.
Hi, this is Samantha on for Yigal. Thanks very much for taking our questions and appreciate all the detail and the updates. Had a question on the frequency of redosing. Is it possible that you could extend the redosing timeline out past 12 months? You have one patient, I think it's Subject H, that started to show their first EDSS improvement at 21 months. What are your thoughts on maybe making that dosing frequency longer than one year?
Thank you for your question, Samantha. AJ, or Jakob maybe, do you want to have a crack at this?
Maybe I'll start, and Jakob, please jump in. In terms of the dosing frequency issue, that's always possible. I think right now, we're going to learn a lot from this randomized control study. The annual frequency, at least for what we're seeing, feels like a good spot to be in. That said, we talked about we're going to be having a lot of additional measures in randomized control study that will include a variety of pharmacokinetic and pharmacodynamic parameters. Those data will help us determine, does it make sense to further extend out? Certainly, these clinical data suggest we may be able to, but I think it'll be nice to have that translational information to make that more of a data-driven decision with those translational data. Jakob, I don't know if there's anything else you'd like to add.
Yeah. Just to add, I do think this is also where the OLE study is very valuable because we are getting more experience with longer treatment with patients, where we are redosing on an annual basis here, and we're going to keep generating that safety and efficacy data. Certainly, we're very enthusiastic about the fact that it looks like redosing and continual dosing here over a longer period of time is safe, and there may even be some evidence that we're picking up additional responses when you continue to dose. I think AJ's absolutely right that we want to look at some of the translational data. How long do these cells persist in patients after treatment? We're going to certainly get that data. To some degree, I don't want to mess with success, if you know what I mean.
If we know that we can do this safely, if we know that we're getting excellent treatment effect, then I want to be a little bit careful about not making too many modifications. I think as we're going to keep learning about the drug and we're going to learn about the persistence of the cells and so forth, where perhaps less frequent dosing may not be necessary. At this point, we're sticking with the yearly dosing.
Got it. That's helpful.
Thank you.
You also highlighted the placebo response in the phase III trial for MD1003. To what extent did this data point factor into your redesign of the phase I-B with the increase in the enrollment and even the change in the primary endpoint? Just curious on what your assumptions of the placebo arm in the phase I-B are now.
Yeah. Jakob, do you want to answer that one?
Yeah, sure. I think it's a great question. The availability of the MedDay data, which came out at EAN around the time that we were also presenting our cohort 3 and 4 data there, was very timely for us. It certainly gives this benchmark of zero to 9% in the phase II and III experiments. Now, I do want to mention that with the MedDay data, these patients were also receiving background therapy, which is actually different than what we have in our study where the patients in placebo are actually not getting any treatment. Perhaps, that 9% in the MedDay study may actually be reflective of some of the background therapy. That's speculation, of course. I do think that we consider this as some historical data that we can reference.
It does factor in a little bit in terms of when we think about the percent improvement that we're looking for in SDI in the randomized control study. Again, we did design the study to give the drug a chance to succeed. I think, yes, we consider the current data that we have for phase I-A, and yes, we consider this historical data that we have from the phase III and two MedDay studies, and we look for what may be a reasonable improvement with the administration of ATA188 over placebo.
Got it. Then you mentioned the interim analysis. I appreciate that you're still maybe working out some of the details there. Have you discussed any triggers, or what would trigger that interim analysis that you're planning for 2022? Is it a number of follow-up or a certain number of patients? Just curious on your thoughts there.
Yeah. AJ, do you want to answer that one or Jakob?
I apologize because I lost the question. It went out. Jakob, have you heard it?
I can. Yeah, I can respond. The interim analysis. The way that we're thinking about it is that it's going to be triggered by a certain number of patients enrolled with a certain amount of follow-up. Absolutely, this is a rigorously defined analysis point.
Great. Just one last really quick one from me. In the pre-BLA meeting that you're scheduled for tabelecleucel in the fourth quarter, is that already on the docket or is that something that you've now just requested?
Yeah. We have regular interaction with the FDA because we have a BTD situation there that allows to have regular interactions there. We're planning to have the pre-BLA by the end of the year.
Okay, great. Thanks very much for taking the question.
Thank you, Samantha.
Our next question comes from Matt Phipps with William Blair. Your line is now open.
Hi. Good morning. This is Rob Andrew and Matt Phipps here. Just couple of questions on the data. On slide 15, where you show the SDI responders versus non-responders, I know you mentioned earlier in the call here you've got a good mix of prior CD20, PPMS, SPMS, and males and females. Is there anything that can be said about these patients in terms of differences at baseline scores or characteristics between the responders and the non-responders here?
Thank you, Rob. AJ, do you want to answer that one?
Yeah. It's a good question. I think right now we're not seeing any real specific trends in terms of baseline characteristics between those two groups. Obviously, it's only 24 patients. You may not see those early on, but right now it's just looking like broad-based effect across all the populations that we're seeing so far.
Okay, great. On the 15 patients that are enrolled so far in the OLE, slide 16, we see six. Can you just clarify which cohorts those additional patients have been enrolled from? Of those patients that haven't enrolled in the OLE, what are the main reasons? I assume in the earlier cohorts, it's mainly just due to the length of time to develop the recommended phase II dose, any additional clarification there?
AJ?
Sure, your assumption is correct because in order to maintain eligibility for the open-label extension, these patients have to continue to follow study protocol. Essentially, for example, when you see slide 16, that patient H, 15 months and 18 months, although we don't have measures, that patient had to stay off of all other therapies in order to stay eligible for the open-label extension. As you might imagine, not everybody in cohorts 1 and 2 were able to do that. Really, the ones that we know are definitely not moving forward into the study are really from cohorts 1 and 2, where they just are no longer eligible for it. For cohorts 3 and 4, we really do expect all of these patients to move through.
Some of those additional patients that we're waiting for to come through are in Australia, where they are having some COVID-related slowness there. As far as we know, all of those patients are looking to move into the open-label extension as well.
Okay, great. Just one last one, maybe just as a follow-up on the prior question. In the phase I-B part of the study, how are you dealing with patients that are progressing on the study, whether it's in the placebo arm or whether it's in the ATA188 arm in terms of additional therapies, how does that impact analysis as you move through that study?
Yeah. AJ?
Yeah. They are not allowed additional therapies while on study. There are rescue clauses for various elements of progression in case those happen for the patients, but there are no additional therapies allowed while they're on study. It does make for, hopefully, a relatively clean data review, but we also protect the patients with rescue clauses if they do run into any specific trouble.
Okay, great. Thanks for the clarification there.
Sure.
Thank you, Rob.
Our next question comes from Tony Butler with Roth Capital. Your line is now open.
Thanks very much. I appreciate you taking my questions. I appreciate the data set today. Very briefly, number one, you spoke about length of time for redosing being in a year, not necessarily extending it. My question is around actually contracting it to perhaps six months. I'm respectful of your response on an annualized redosing. Is there a rationale why you wouldn't do it at six months, for example, and/or instead of infusions at 1-8 and 15 days, maybe it's 1-8, 15, and 30? Just a thought. That's question one. Number two is, curiously, all the patients, even those that don't have SDI improvements, except for cohort 3J which seems to progress fairly rapidly from an EDSS perspective and the other parameters.
I'm curious as to if there is anything different about that particular patient, just to rule out the fact that therapy didn't necessarily cause the progression. That's number two. Finally, because these patients are EBV seropositive, I recognize that seropositivity may not be high in these patients, but is there any rationale that that actually changes over time? That is, they become seronegative. Thanks very much.
Thank you, Tony, for your question. Jakob, do you want to take the first one and then, AJ, the next two?
Yep. Sounds good. Tony, thanks for these questions. In terms of the length of time for redosing, as you know, the current design is for annual dosing. That can go over, the OLE does extend over several years, out to five years. There's again, that opportunity for the patients to keep going. We did set it at yearly dosing. Your question's an interesting one in terms of whether or not we should consider a six-month dosing schedule. That's not what our current plans are, but I think we're going to be doing a lot of translational work on the studies, so we will see things like pharmacokinetic analyses and so forth. We're going to keep learning about the program.
I think, again, if we do make a change eventually in the development of the drug, that will be more of a data-driven decision based on the biomarker data that we are generating in the clinical trials. Frankly, the randomized control study is probably the best place to be looking at these types of biomarker analyses because you've got a placebo group in there. I think for the time being, we're staying with our plans because I think they're yielding good results. That being said, we certainly are going to keep conducting science to understand the performance of our drug even better. If there are compelling reasons, then it's certainly something that we can consider for the future. In terms of, I think it's a similar response when it comes to the days of dosing where you mentioned one, eight, 15, and 30.
Again, this is going to be more of a data-driven decision. Again, we think we're seeing clinical data from a safety and an efficacy perspective that's compelling, and so we want to stay with our current regimen. Again, we're going to keep generating that data that could lead to changes in the future. Again, if we do make those changes, they're going to be data-driven decisions. For the time being, we certainly think that we have a good approach when it comes to dosing and schedule of dosing and so forth.
Yeah. Thank you. AJ, do you want to talk about the patient J?
Sure. Your question was, do we think there's anything unique about this patient? Could there be cause for regression? I don't think there's anything to suggest that. There's two patients in the entire 24-patient group that had EDSS progression during the study. If you think about other studies, for example, the Ocrevus study, and you look at their placebo population, at that 12-month time point, about 10% - 15% of patients in the placebo group had EDSS progression. Pretty consistent with what you would expect in the normal population. There's nothing unique about that patient. I think right now we're seeing what you would normally expect to see in this group. I think the second question you had was related to EBV seropositivity, and can that become negative? It's a good question. I think the likelihood is no.
The reality is that once you have EBV infection, we all know it's a lifelong infection, and EBV has been part of our systems for thousands upon thousands of years. It's a virus that's actually learned to live with us in many different ways. The ability to completely eradicate it from anyone is a very tall order. That said, the ability to control the impact that it's having is, I think, what we're really showing here with ATA188 and also some of our other programs that target Epstein-Barr virus.
I think one other comment to make here is we described here today our biomarker program. We are going to be doing extensive assessments, pharmacokinetic, pharmacodynamic, mechanism of action biomarkers. Some of the aspects that we'll be looking at as well are EBV cell quantification in the blood and CSF of patients. This is a really interesting program also from a translational perspective, because we are going to keep generating these types of data that will really help us to understand the biology of EBV infection in multiple sclerosis to a greater degree.
Thank you, Tony.
Our next question.
Any further questions?
Our next question comes from Maury Raycroft with Jefferies. Your line is now open.
Hi, everyone. Thanks for taking my questions and congrats on the progress.
Thank you, Maury.
You're welcome. Just clarifying, it sounds like you're not allowing the rescue meds in the phase I-B, but are you allowing background meds to stable at baseline?
AJ, do you want to take that one?
Yeah. Just for clarity, we are allowing rescue meds if the patient gets in trouble. We are not allowing background meds. The patient has to be completely off of existing medications before they enter into the randomized control study.
Got it. In thinking about how you're looking at SDI at two time points for the secondary endpoints and for IgG in particular, how often will you be measuring the IgG, and are you looking for changes over time, or will you be focused on the 12-month or 15-month time points?
Yeah, AJ?
Yeah, it's a good question. We are doing a fair number of lumbar punctures for the study. Patients get actually three lumbar punctures in the first year, it's a decent request of these patients. We will have all of those time points. We would expect, this is not necessarily a time point that takes, I'm sorry, not necessarily an endpoint that takes a long time to change. You might get information on that earlier than a one-year time point, but we'll be looking at all of the time points. Yes, you might get data little bit earlier than a one-year time point on the CSF.
Got it. Okay, thank you for taking my questions.
Thank you, Maury.
I'm not showing any further questions at this time. Thank you for joining the Atara Biotherapeutics ATA 188 data conference call. You may now disconnect.