Allogene Therapeutics, Inc. (ALLO) Earnings Call Transcript & Summary

All right. Good day, everybody. Thank you for joining us at the BofA Biotech Summit. It's typically held in Napa. Unfortunately, we're in front of computer screens, but I think there's an end in sight that -- to a future that can be held with some red wine in the evenings. But gentlemen -- and I'm pleased -- I'm Jason Gerberry, biotech -- one of the biotech analysts at BofA. I'm pleased to be introducing Allogene CEO, David Chang; and CFO, Eric Schmidt. And gentlemen, thanks so much for joining us, first off.

Thank you, Jason.

Jason, thank you very much for having us. And as you say -- I mean today is June 15, so things are opening up. So pretty soon, hopefully, we will be back to normal.

Yes. Well, great. Look, I thought a good place to start might just be an introductory for those -- varying degrees of familiarity with Allogene. If you can talk a little bit about the unique approach you guys take to cell therapy, and how the recent ASCO medical conference was an important milestone to vindicating the approach that you guys are taking?

Okay. Thanks, Jason, for the opportunity. I mean let me first give a sense of what Allogene is about. I mean I think the story of cell therapy probably now goes back to beginning of 2010 where the academic -- what used to be done in the academic setting started transitioning into the indices setting. So I was lucky enough to be involved early on in the development of CAR T, which in 2017 was approved as YESCARTA. So the CAR therapy that are currently marketed are all autologous, where it is more or less an individualized therapy. What Allogene is trying to do is take a step forward from personalized manufacturing to allogeneic platform where you can manufacture cells from healthy donor, and from 1 manufacturing process, generate enough product to treat multiple patients. I mean this is really taking cell therapy more democratized setting where the therapy can be available to more patients and also on a more timely manner. So with that, one of the many sort of areas that we are focusing on. I mean I would start -- first of all, is making the allogeneic cell therapy work. This is really a question of whether you can control safety issues related to graft-versus-host disease. And also, more importantly, can you control the rejection of the allogeneic CAR T cells by the patient's immune system. So we have been focusing on the latter, more or less, for the last 2, 2.5 years, using our differentiated approach of lymphodepleting, using ALLO-647, which is specifically used for that purpose. And what the ASCO data has shown is that, that approach is so far shown to be most effective in making the AlloCAR T cells expand and carry out antitumor effect, and this is based on more than 95 patients that we have treated across our clinical programs. And another thing that we, as a company, have really focused on is trying to streamline the manufacturing and also working towards more consistent reproducible manufacturing that can be done in scale. And this is really trying to bring down the cost of manufacturing, and we have been very successful in doing that. Right now, we estimate that from each manufacturing run, we can treat more than 100 patients very comfortably. And the yield has been going up over the last 1.5 years where we have been really focusing on this. And then in a third area that we are working on is really trying to push the innovation in the cell therapy forward with the next-generation technology such as TurboCAR. So that's more or less the backdrop. And back to your question around ASCO presentation and CD19, the presentation was focused on our lead program, ALLO-501 and ALLO-501A. And this is sort of a presentation that followed our initial presentation last year at ASCO. So at the time in 2020, we presented approximately about 20 patient data where we have demonstrated that cells can be manufactured consistently without any break in the supply chain. And also, we have shown that the cell therapy can given -- allogeneic cell therapy can given safely as well as on a timely manner, and showing the efficacy that was on par with what the autologous CD19 CAR T therapies has shown. Overall response rate, above 70% and complete remission rate in the 50% range. What we were not able to show at the time is the durability of the response because the trial was ongoing when we simply do not have enough time to follow the patient. So what we have shown in more recent ASCO is providing additional follow-up on the patients as well as additional patients that we have treated on the study. And overall, that -- what the study presentation really did was answering the last question around the durability of response by showing that in the Large B Cell Lymphoma patient, which is our lead indication, our therapy can give a 6-month complete remission rate. That sort of benchmark time frame that people are using, up 36%, which is on the upper end of what the autologous CAR T therapy has shown, somewhere between 28% to 40% is the range that autologous cell therapy has shown. And our study showed that the 6-month CR rate was 36%. So I think that answered the last lingering question, and what we are doing right at this point is based on data moving forward, preparing for the regulatory interaction, ahead of launching the Phase II study, which can be a pivotal study in the cell therapy space.

Great. That's a great introduction. And the cell therapy space is obviously drawn a lot of capital, a lot of new companies coming into the space, a lot of different approaches. A lot of the discussion with Allogene is -- well, how does it stack up against autologous? And so maybe just a few questions along those lines. As you think about, one, you mentioned healthy donors and this idea of getting perhaps a patient with a more fit or healthy T cell, and the importance of that, say, versus autologous. I guess the hope is that these therapies move into earlier lines of therapy and even the autologous modalities have an opportunity to get a healthier fit cell in time. So I think at the -- one of the educational sessions at ASCO, I believe one of the presenters talked about this dynamic and whether or not this is really an advantage one way or the other is somewhat inconclusive. But curious if you share that view at the moment, and how important of a feature is this for your approach?

So you are really talking about the starting materials for the production of the CAR T therapy. So in autologous setting, you are getting the T cells from individual patient. For the patient population that we are going -- I mean these are people in their 60s, sometimes 70s. So the age does matter, and I'll come back to that. And also, some of the patients may have been treated with anticancer therapy, which can affect the fitness of the patient's immune system. So there is a general view, and I think the data emerging data supports that, that in the autologous setting, the starting material may not be the best. What we are doing is with the healthy donors, besides the fact that these are not patients who have undergone treatment, generally, they are much younger in age, and that matters in terms of what we consider as important parameters for the quality of the final product. I mean starting with the T-cell phenotype. I mean T cells come in many different phenotype, memory T cells and central memory, effective memory. And generally, what we consider as a juvenile phenotype, they tend to work much better when they are in -- given to the patients. And in the younger patient population, they generally have much larger proportion of cells that will be considered by the phenotype as a naive central memory or what I would characterize as juvenile cells. So that is one. And then another one is the fold expansion. And what we are seeing is that the ability to propagate the cells during the manufacturing is much better in cells derived from the younger patients, and that does matter because there's already data that's out there that the fold manufacturing -- during the manufacturing process does affect the outcome in terms of the cell expansion as well as being able to achieve the durable complete responses. So from that perspective, I think there is a very distinct advantages of using healthy donor T cells that you simply cannot do with -- in the patient population. Yes, as you go to the earlier lines, a patient may have been exposed to fewer chemotherapy, which is a great thing, and the cells may work a little bit better. But another thing that you simply cannot address within that scenario is age of the population, and that's one. And there are many other things that I can talk about why the allogeneic provides additional benefit, and that includes ability to do more than a simple gene transduction, which is the main way that the autologous cell therapy products are engineered during the manufacturing process. With the allogeneic therapy, because of the scale and because of what we are doing, we can do multiple gene editing as well as gene engineering, and that factor is greatly when you try to incorporate the newer technologies, newer manipulations that can improve the T cell fitness or the expansion capabilities.

Okay. That's really helpful. And I think we'll get to the next-generation approaches in the latter part of at least the discussion. But look, I think core to what you guys are doing is avoiding -- avoidance of bridging therapy, and we generally hear pretty consistently from hematology oncologists that, all else equal, you want to avoid bridging therapy. And so that's sort of core to your value proposition. Can you talk a little bit about practically speaking, relative to autologous, how many days do you think you can ultimately save when you factor in, presumably, you come to market all the different considerations like insurance and all the things that a patient wants to go through before they can get their allogeneic cells?

Yes. I mean Jason that's a great question. That's something that we internally debated for some time. And then eventually, we did a survey involving more than 200 patients. And from there, we learned a lot about the physician preference. Eric, do you want to cover some of the things that you found during that patient survey?

Yes. I'll certainly be happy to chime in, David. Thank you, and thanks for the question, Jason. As David mentioned, we surveyed over 200 academic oncologists who are potentially users of our product and certainly use the autologous products today. And one of the interesting things we found is that it's not just about convenience. It's not just about delays in getting CAR T therapy or the potential use of bridging chemotherapy and other potential hindrances like that. But it's really about, at the end of the day, the certainty that a patient can get is very important -- this potentially life-altering therapy at all. And as you know, Jason, when you look at the autologous data sets and the studies that were run, even a controlled randomized study where essentially you have the best physicians and the best support, somewhere between 10% and 30% of patients were not getting their therapy in time to receive that potential curative benefit. So that is a huge issue for patients and physicians. You can imagine putting yourself in a patient's shoes and signing up for one of these studies and hoping that you'll be one of the lucky ones as opposed to the unlucky ones. And the experience with our therapy that we think is going to be really materially different within our study already, a Phase I study, 98% of patients having been offered the opportunity to receive cells and receive cells in a timely fashion, within 5 days. So it's not just the inconvenience of waiting, it's the lack of certainty in waiting. And when you are dealing with very potent, very -- again, potentially life-altering therapies, like these cell therapy products, that makes all the difference in the world. So that's definitely something that I'd like to stress here.

Yes. I mean Jason -- I mean in many ways -- I mean you're dealing with a patient with a progressing disease. The waiting can have many consequences, including patient getting into complications from disease that is progressing and advancing. And bridging therapy is really just as the word says, trying to sort of keep the patient without getting into any worse situation before the cell product manufacturing is complete and can be given to the patient. And that really adds a lot of uncertainty to the treating physicians as well as patients. So we view not having to use the bridging therapy to be a very distinct advantage of the allogeneic CAR-T therapy.

Got it. Great. Okay. Now the ability for dose consolidation is also an important differentiating attribute for ALLO-501, 501A. Mindful that it's still a little bit early, but -- and the data are still accruing. But how do you think investors should be thinking about your ability for dose consolidation for 501A? And maybe can you point to what gives you confidence that mounting a stronger immune attack against the malignancy in that first 28-day period is really the key, right, to a better and more durable CR, which is something that you really aspire to? And obviously, I think you guys have kind of framed single infusion is comparable, competitive to auto, but consolidation might be kind of a swing factor ultimately from a competitive positioning perspective.

Yes, great question. And there was a sort of a hypothesis that we really wanted to test in our clinical program. So when you think about any anticancer therapy, the goal should be really trying to eliminate or eradicate the last cancer cells in the body. And this is where we frequently talk about the depth of initial response or whether we talk about the response is MRD-negative at 10 to the minus 4 or 10 to the minus 6. Everybody is looking for a deeper response. And the reason is, when you look at all the existing data, patients who are able to achieve deep response tend to have much durable duration of response. So where we sort of came in terms of conceiving the idea of consolidation is that with our allogeneic, cell manufacturing is not an issue because we have an off-the-shelf product. And then two, we also have very differentiated lymphodepletion approach using ALLO-647 where we felt the lymphodepletion, which is needed before the cell infusion, can be done differently with the second infusion, without having to use the chemotherapy. So all these were the different sort of supporting idea behind us moving into the consolidation. And what we have shown in the data presentation where we discussed more than 8 patient who have been enrolled in the consolidation, 6 patient received the second dose, a month after the first cell infusion. And most importantly, one, it was feasible; and two, the second infusion was well tolerated by the patient where physician treating -- investigators themselves were talking to us about, "You should really consider doing the second infusion as an outpatient. I don't see any need to keep them in the hospital after cells are infused." So those were both great information that we got from this early stage of testing consolidation. And also extremely encouraging to us was what we saw in efficacy. There were several patients whose initial response after cell therapy was only partial response, and we saw those responses converting to complete response after the second cell infusion. So that's where we stand. And certainly, we are collecting more data and also enrolling more patients into the consolidation. I think this is something that is quite unique to what the allogeneic therapy can do. I don't think it's easily doable with autologous. It can really push the response deep. And I should also tell the -- some of the correlative findings in the autologous cell therapy is that patients with bulky tumors, their responses tend to be less durable or sometimes they cannot achieve complete responses. So we have a potential to address that segment of patients with a bulky tumors, with a consolidation where we can push them into the complete responses. So I think there are many sort of tantalizing ideas. So initially, we are sort of thinking about autologous cell therapy with all the benefits of off-the-shelf. We need to be somewhere close to the -- what the autologous cell therapy has been shown in efficacy. So far, we have shown that with a single infusion. And what the consolidation brings up is a potential to push the efficacy boundary beyond what the autologous cell therapy has been doing. So we are very eager to really generate additional data and incorporate consolidation scheme into our pivotal study design.

And mindful that I'm probably not going to get you to front run your FDA meeting here in this venue, but are you thinking about second consolidation outpatient for your pivotal trial? And can you remind us, have any of the autologous approaches been evaluated? Outpatient [ availed ] and inpatient, I assume?

I should be clear. I mean all the autologous cell therapy label, including YESCARTA, allows outpatient dosing of the cells. And it's really -- what happens with the safety findings that investigator decides whether a patient can go home after cell infusion, in which case, a lot of them will have to be readmitted to manage the adverse events that are a few days later. Or some physicians just keep the patients in the hospital so that they don't have to worry about making an emergent admission back to the hospital. I mean what we are talking about here is a little bit different, which is potential of not just giving the cell infusion, product infusion as an outpatient, but also trying to see whether the hospitalization requirement can be significantly reduced. So there are many different factors that we have to consider in this. But to the exact approach that we're going to make with FDA, let's stay tuned on that. We'll sort of discuss that once we come out of the FDA meeting.

Great. Maybe for Eric, conceptually thinking about the concept of allogeneic opening up the market, expanding the market for cell therapy relative to what we've seen with autologous approaches. I know that BiTEs are also in the NHL setting very topical. What -- from the work you guys have done, what do you think are sort of the key features to really opening up the market and the proportion of prescribers who are really capable of giving a cell therapy versus -- we oftentimes hear about true community docs who are just ill equipped to kind of deal with -- be it either monitoring for CMV or some of the other considerations that go along with administering cell therapy?

Yes. Good question, Jason. I think one of the findings from our survey was that what physicians really, really care about, their top #1, 2, even 3 priority, is efficacy, right? These patients, unfortunately, have a very poor prognosis. And if they can use the most potent therapy available to them, they tend to reach for that therapy first. So all of the data we think that's been emerging around the cell therapy field to date speaks that this modality has the potential to be as potent, if not more potent than all others. And we think an allogeneic therapy will follow in the footsteps of autologous, like David has already mentioned. I think we're all ready with a single dose. We're in the ballpark of matching the efficacy of an autologous therapy in NHL and hopefully, with consolidated dosing regimen, we can see if we can push that envelope further. So when you compare our ability to provide that most potent of therapies in an off-the-shelf manner, in a product matter, not a therapy or procedural matter like the autologous products we are provided with today. But really, an in-a-vial pharmaceutical distribution model, a true drug that matches how BiTEs or bi-specifics or other drugs are delivered to these patients with NHL today. I think we have the potential to bring the best of both worlds, that top-notch potency as well as the convenience of a pharmaceutical distribution model, product that could be delivered within days to all patients. So that's really our competitive strategy of going at this market.

For the baseball fans. If you build it, they will come, right? If you can offer something single infusion that has the hope and potential for a curative outcome, you think the markets will sort it out and fall for the innovation and what you're expiring for therapeutically?

Okay. Yes. I mean...

And then -- sorry, go on.

No, please.

No. No. I was going to jump to the next question. But if you had a follow-up point, go ahead.

I think the other point that David mentioned is scalability of manufacturing, right? And again, we can produce in a scalable way and continue to enhance that efficacy, that efficiency of production to drive down those cost of goods in a way that, again, is very pharmaceutical-like. So obviously, that's the other focus point in our go-to-market strategy.

Yes. Could you put a little context around that right now with autologous? What are we talking $50,000 a dose? Or it might even be $100,000 a dose? And obviously, you've got some things that you're working through and possibly even with consolidation. You've got flexibility through your lower cost of goods. So could you put a little bit more practical context around what sort of advantage you have there?

I think we've heard similar ranges as you in terms of what could autologous cost of goods might be today. That $50,000 to $100,000 range certainly, seems to us, to be ballpark. So obviously, we don't have any firsthand knowledge, and what we do know is our own manufacturing production costs. And as David has already spoken to, a single manufacturing run of an allogeneic product can produce material for 100 or more patients. Now it is fair to say each manufacturing run that we perform is more expensive than an autologous run because it has those additional gene editing steps. So we are more expensive than an autologous manufacturing run. But we're certainly not a hundredfold more expensive, and the ability to create that scalability in our system that is unable to be created in an autologous system where each individual patient provides his or her own material. That scalability is something we really strive to continue to reap yield from. So we think whether it's 1 or 2 doses, we'll be in a certainly, a very good place with a lot of flexibility when it comes to cost to manufacturing.

So I think the punch line is -- not getting into specifics, but is a meaningful step change different relative to autologous?

I think that's correct.

Okay. Well, maybe we can jump more specifically to CD19 program. And I guess -- David, now that you've got your data out there, you've got an FDA meeting, you'll be evaluating some incremental data before making final decisions on pivotal trial protocol. Maybe specific to this program, some of the -- what you see as outstanding challenges and opportunities that lie ahead of you as you kind of contemplate a really important and potentially differentiating pivotal protocol?

Yes. So in terms of challenges that leading to the FDA meeting, I think what we are dealing is nothing unusual. I mean it's more or less on par. I mean like any other players in this space, I mean you are dealing with data that you have already on hand as well as additional -- because the Phase I studies are still ongoing, additional data that we'll be generating while we are preparing. So -- and here, particularly the consolidation, we want to know a little bit more on those 6 patient as well as want to have a few more patients treated. So I think that is very much built into the plan. And the second assumption that we have made early on, and this is something that we have already had some in form of discussions is, is the study going to be a single-arm study or whether this is going to be a controlled study. We are working with the assumption that this will be a single-arm study of 70 to 100 patient using the response rate as the primary endpoint, and duration of response and safety as a key -- other consideration. Just like how other autologous cell therapy that have been approved in this space have used. So -- and then we have to take care of some manufacturing, clean up all the details on the manufacturing and have to present to the FDA. So this is very much on course. I think where the opportunity -- this is going back to -- when we think about it, single infusion data look very good and competitive enough with the autologous. I mean we are seeing potential tremendous benefit that could come from the consolidation, and we want to leverage that to make sure that at the end, our product, if it has ability to push up the efficacy beyond what the autologous cell therapy has done, we will try to pursue that. And certainly, the convenience and others, being able to treat everybody -- I mean in our Phase I study that we presented, we treated almost everybody. There was a 1 patient who could not be treated, but we treated 41 out of 42 patients who were enrolled. And we want to do that kind of being able to provide therapy to everybody. So this is a very exciting time for Allogene. Not just Eric and I, who's in this call, but every employee at Allogene, they are very excited about seeing the data and moving towards the Phase II study.

And if I can just follow up on that FDA point. What underpins your confidence that you can have a regulatory path with a lesser clinical burden as you talked about, single arm? When I think -- when investors in oncology hear about having a potentially -- a therapeutic with a comparable profile to something that's been approved for a while, they typically think of having to do an active comparator trial. And so obviously, you offer higher certainty of treatment, you're a newer modality. So just maybe some of the considerations, regulatory-wise? Mindful that nothing certain with FDA, and you're not making promises, but just sort of how you think about the argument as to how that pathway is feasible?

Yes. So here -- one thing that we did at -- when we were at Kite -- and for those who may not know, I was Head of R&D at Kite Pharma. One thing we established is what the standard of care provides in the second plus line setting. I mean this is a study called SCHOLAR-1, that sets the benchmark for the available therapy other than CAR T therapy. So using that benchmark, I believe that if our allogeneic cell therapy can provide substantial benefit, and certainly Phase I data gives a lot of assurance that the response rate as well as the durability represents a substantial benefit compared to what the SCHOLAR-1 patient population has done, that could support the study moving forward as Phase I. So that's the assumption that we are looking for. And FDA, on this matter, has also shown several examples where as long as the treatment provides a substantial benefit, a single-arm study can support the registration. And this is not just in CAR T, but in more conventional pharmaceutical drugs as well. So there are other precedents. So we are not working in isolation in terms of how we are thinking about the nature of the Phase III pivotal -- the Phase II pivotal study.

Not to belabor the point, but substantial benefit is matching the ORR and the durability of benefit? Or the substantial benefit is the unique attributes of ALLO-501A?

Substantial benefit here would really entail the efficacy, and Eric can comment on this. And that's another thing that, when we did the patient survey, came out as the key thing that everyone is looking for.

Okay. I wasn't sure if Eric was going to make a comment there, but I'll jump to durability of efficacy here. Obviously, it's a key feature. It comes up -- we -- our firm has done a recent physician survey. So obviously, this is a critical variable. I guess technically, you're a couple of years behind autologous. What -- in oncology, at least, multiyear follow-up tends to be a disadvantage of later movers, right? And so what gives you confidence that the 6-month CR will give oncologists sort of a level of comfort and confidence that you can have a durable CR similar to what you get with autologous?

And obviously, that is a moving target. As you follow the study for longer, that information will be updated. And we -- in the recent sort of announcement, it's made it known that we will be updating the 501A -- our CD19 program clinical data in -- at the year-end in a meeting. So having said that, I think there's a lot of learnings coming from the autologous cell therapy. I mean in terms of what correlates with a durable response. I mean I had already talked about a few things. Whether you see a good cell expansion or not, that's an important parameter. The initial tumor volume of the patients and also initial response, whether you're getting the CR or a partial response, I mean all these things matter. So yes, 6-month CR rate is 1 number. But in a -- clinical trialist and most physicians will look at the totality of the data. And one thing that we haven't talked about in our ALLO-501 and 501A data, one thing that gives us a lot of assurance is the consistency of different data points that we are getting. What we are getting with our proprietary lymphodepletion in terms of depth of win for depletion and the speed of the T cell recovery, the kind of cell expansion and persistence that we see. The initial response, some of which we are characterizing at the molecular level, and also the 6-month CR rate, which has been really used as a landmark time point to see whether the patient will likely to be -- to have a long term, going many years in response or not. And the fact that our 6-month CR rate, together with all other important parameters coming very consistently with what we know from the autologous CAR T therapy, I mean that's certainly, what our investigators like. I mean we definitely see that as a big plus in terms of how we are preparing for the pivotal study. And In terms of the -- your final answer is -- what's the durability going to be like a year from now. I mean that's something that we -- you just have to follow the patients.

Yes. Okay. Now just thinking about the role of consolidation a little more specifically. I'm just a little unclear, I guess, what you're really looking for from here. And I think at a recent competitor broker conference, you talked about -- even if it's a little bit better, right, that warrants further clinical evaluation. So just wondering to what extent is a pending FDA meeting important to sort of the decision that how quickly you would move forward with consolidation. I know you mentioned sort of the ability to convert a patient with bulky tumor to CR. I don't know, of the 6 patients that you're evaluating, if they have bulky tumor. Any kind of color you can just provide on maybe what you'll learn incrementally between now and sort of the decision to kind of move forward with pivotal protocol?

Yes. I mean before talking about additional information that we are looking for, internally we debated about this issue for some time. I mean well, single infusion is good enough, at least what -- that's what the 501 data that we presented at ASCO has shown. Why complicate the matter by doing consolidation? Now, which is a very valid question. I mean as a drug developer, you want to go as simple, as speedy way as possible. But another thing that many in the company are aspiring to do is come up with a therapy that's better than the existing therapy, and I think that's really one of the key drivers for embracing the consolidation as we sort of think about the next step. I mean there is an opportunity to make the outcome of the CAR T therapy better, with ALLO-501A administered as a consolidation. So for those who may not be familiar with consolidation, what's really being done here is that we give the cell infusion, and we wait for a month. And at that point, unless someone has a disease that's progressing, which tells you that they may have disease that's refractory to CAR T therapy, everybody else, patients who are in stable disease, partial response or even complete response, they will be receiving the second infusion of our CAR T cells. And as I've said, a limited number of patients where we have a clinical data, this appears to be very safe. And the preliminary data, being able to convert partial responses to complete response -- responder after the second infusion, that's a big change. I mean for the autologous CAR T therapy, the response rate that's out there is somewhere around 80% to 90%. About 30% of them are partial responses. And those partial responders, they progress pretty rapidly. If we are able to rescue some of those patients with a consolidation, that will be a great benefit to the patient. And having been in this field for the last 10 years, I mean I personally rather take a little bit of chance going for that kind of benefit that we can provide to the patients rather than just taking an easy course out going with a single infusion approach. And to your question, what are we looking for. It's really coming down to already we have shown the partial responses can be converted to the complete responses. We are looking a little bit more at that and a few more patients safety data to be -- to really convince ourselves that the second infusion is really safe.

Okay. That makes a ton of sense. I really appreciate that. And then from a safety monitoring perspective, [ I assume ] was a topic that sort of with investors after the update. And if you can talk a little bit about practically speaking, I guess, unique might be the [Technical Difficulty] practically speaking, given the level of [Technical Difficulty] Should I go to the computer?

And just as clear as previously.

Okay. All right. Great. Yes. So yes, it was about sort of [Technical Difficulty] So it's really about the level of monitoring -- safety monitoring with -- for CMV. And from what we hear from physicians, it's really that, hey, if I'm an allo transplant guy, I know how to monitor this. This is very straightforward. I guess it's more of a concern perhaps more broadly with the community. Will they be able to kind of deal with the extra layer of managing for CMV that's unique to this? So how do you guys kind of address that concern or topic?

Yes. So I'm a little bit surprised about the concerns being raised about this particular issue of the viral reactivation monitoring because having worked on the autologous CAR T therapy, what we are doing is exactly what gets done in the autologous setting. Patients are susceptible to infection. They are also susceptible to so-called viral reactivation, such as CMV reactivation. And for that reason, the standard of care after cell therapy is that for a period of time, patients receive prophylactic antiviral therapy to avoid any kind of viral reactivation, and that's exactly what we do. And when we look at our clinical safety data, especially those are clinically relevant. So these are Grade 3 or higher infection rate. What we are seeing in our study is that the numbers -- I mean we have treated enough patients, close to 100 patients. The numbers don't lie, and the numbers tell you that our Grade 3 infection rates on par with what has been seen with the autologous CAR T therapy. So I think, definitely, my lesson and our lesson from this sort of comments that we are hearing is that we need to better educate some of the people. But what we are doing in terms of monitoring is the same thing that the autologous CAR T players -- therapies require. So thanks for reminding that there is some education that we have to do.

Great. Okay. Maybe shifting gears to BCMA. This seems like it will probably be the most tangible data update going in for the rest of the year. The updates regarding CD19 seem like they're more regulatory in nature. But correct me if I'm wrong. So I guess some of the questions coming out of ASH with BCMA. What questions do you think you'll be able to address and answer? You had small numbers, maybe some people kind of wonder what's the best and optimal dose here, if the lower dose performed better than the higher dose. So perhaps maybe we just need to see more mature data and more to come is the message. But just sort of curious if you can kind of set the stage. Obviously, ASH is a little bit of a ways away, but just some of the controversies and your perspective, it would be appreciated.

Yes. ASH is still in a bit of a way. But I mean I think still -- I mean the abstract has to go in pretty soon, so this is an ongoing discussion. Eric, do you want to sort of cover this topic of the BCMA data update that we promised for year-end 2021?

Sure, David. Let me start. I mean before we leave the CD19 realm, we are, Jason, committed to providing another data update toward year-end as well. And we think that's important because as we start a potentially pivotal Phase II study, we want to show the investment community the latest data in support of that study. So do also keep an eye out for those data. But yes, in particular, we promised a BCMA update, namely our ALLO-715 program at ASH 2021. You'll recall, we last showed data from this program at ASH 2020. We showed a little over 30 patients worth of data. And I think the conclusions from that trial, at that time, were that we could first, produce and administer cells to essentially all patients who need benefit of our allogeneic platform, of course. Second, that we could do so safely. Again, much like you and David have already discussed, the safety profile of 715 seems quite good. And if anything, erring on the side of being a little bit better tolerable than the autologous products. And third, that we could get some deep responses. We had several patients with MRD-negative responses at the time of our last ASH update. One thing that we saw that was a little bit different with 715 was it was -- it seemed a dose dependency of the cells. In other words, higher cell cohorts perform better than lower cell dose cohorts. And at the time of our ASH presentation, we're still escalating both cell doses as well as our ALLO-647 lymphodepletion antibody dose. So for ASH 2021, we would expect to certainly have longer-term follow-up on the patients we dosed as of a year ago, and then we provide additional data on those higher dose cohorts as well as higher ALLO-647 dose cohorts. As you know, as part of our BCMA strategy, we have a couple of other things that we're interrogating. Namely, the combination of 715 with nirogacestat, GSI, gamma secretase inhibitor. And also, we're very keen to start to vest our ALLO-605 program, which is our TurboCAR directed at BCMA. That program will start clinical studies shortly, but will not be able to be reported data as of the time of ASH this year.

And quickly just on -- as you guys think about bogey for getting yourself established as comparable to autologous, similar to the CD19 setting. I guess the one thing that always has flummoxed investors, they look at legends data, it looks a lot more competitive on efficacy parameters, yet -- even BofA did a recent survey of oncologists and they actually [indiscernible] on par, if not, gave a slight edge over cell to cell. So just kind of curious, from your perspective, what sort of metrics you might point to sort of help -- give comfort that you've got a profile, at least with single infusion comparable to auto?

Yes. So the 2 products, 1 already approved and 1 under review for the targeting of BCMA in multiple myeloma. I mean the data -- I mean obviously, larger data set is needed to really influence the clinical practice, but the clinical trial data [Technical Difficulty]