Precision BioSciences, Inc. (DTIL) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the Precision Biosciences CD19 Update Conference Call. [Operator Instructions] I would now like to hand the conference over to your speaker today, Alex Kelly, Chief Financial Officer. Please go ahead.

All right. Thank you, Victor, and good morning, everyone, and welcome to our webcast to discuss the promising progress that we've made on 2 strategies, to optimize the durability of allogeneic CAR T therapy in non-Hodgkin lymphoma. Before we begin, I would like to remind you that some of the statements that we make on this webcast may be considered forward-looking statements. Our forward-looking statements are within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors, including, without limitation, the risk factors in Precision's annual report Form 10-K and our first quarter 2021 10-Q. All forward-looking statements speak only as of this date and is except as required by applicable law, Precision has no obligation to update or revise any forward-looking statements made today, whether as a result of new information, future events or changed circumstances. With that, I would want to now introduce the call participants. First, we have Matt Kane, our CEO and Co-Founder. Dr. Alan List, our Chief Medical Officer, will review the latest interim data for PBCAR0191. And we also have Dr. Derek Jantz, our Chief Scientific Officer and Co-Founder, to review the status of our PBCAR19B, our immune-evading stealth cell targeting CD19. Let me now introduce Matt Kane.

Thank you, Alex, and welcome, everyone, to the call. As Alex just alluded to, we have 2 important topics for today's discussion. Our 2 strategies to optimize the durability of allogeneic CAR T therapy in non-Hodgkin's lymphoma, both of which, I'm pleased to report, are now open for enrollment. And for those of you with access to our slides, which you can find on our website, let's move to Slide 4. Over 15 years ago, Derek Jantz, Jeff Smith and I started Precision Biosciences with a dream of developing a unique genome editing tool that we call ARCUS into a technology capable of precisely rewriting DNA to overcome cancer and actually cure genetic diseases. We called this our dedication to improving life, or DTIL. Since then, we've built out an immensely talented team and class-leading internal capabilities. Now just 6 years ago, we began using ARCUS to create a novel allogeneic CAR T platform to realize the potential of an off-the-shelf therapy and a quest to greatly improve outcomes for those suffering from cancer. And just over 2 years ago, our first program, PBCAR0191 entered the clinic. Now after dosing over 50 patients with PBCAR0191, exploring different dosing cohorts, lymphodepletion strategies and our stealth cell PBCAR19B into the clinic, we have never been closer to realizing this dream. And while we won't be discussing this today, we've also quietly built what is arguably the leading in vivo gene editing platform focused on curing genetic and infectious diseases, again, leveraging our proprietary ARCUS genome editing platform. And we expect to provide an update on our in vivo editing progress later this summer. But today, Alan and Derek are going to walk you through an updated data set for PBCAR0191, combined with our enhanced lymphodepletion strategy, and the reasons why we think our stealth cell PBCAR19B gives us yet another shot on goal without prolonged immunosuppression. Let's move now to Slide 5. Our progress on PBCAR0191 and 19B is going to be the focus of today's call, but I also want to highlight that we have 2 other CAR T programs in clinical studies: PBCAR20A targeting NHL, CLL and SLL; and PBCAR269A targeting multiple myeloma. In addition, we've already lined up 2 more strategies for addressing multiple myeloma, including a combination cohort with the GSI, which is expected to commence soon, and a stealth version of PBCAR269A with a planned IND filing in early 2022. Turning next to Slide 6. Each of our CAR T programs originate from healthy donor cells, and through a patented single step process, we knock out the T cell receptor by knocking in the chimeric antigen receptor or CAR into the TRAC locus. The CAR importantly also contains our proprietary N6 co-stimulatory domain which is designed to control the expansion of our CAR T cells. Our manufacturing process delivers consistent batches of cells comprised predominantly of naive T cells and a controlled ratio of CD4 to CD8. The process itself only takes 10 days. But of course, as an allogeneic cell product, the cells are produced well in advance of patient identification. And we believe that for an allogeneic CAR T to fully reach its potential, manufacturing really is a critical component to developing a therapy that is highly effective, safe and scalable. And importantly, you cannot make CAR Ts like ours without ARCUS and Precision's intellectual property. We also believe that our work on the allogeneic CAR T platform, pipeline and the broader manufacturing capabilities places us in a uniquely strong position that we find ourselves in today. Let's move now to Slide 7. So at this point, I want to turn the call over to our Chief Medical Officer, Alan List, so that he can update you on our progress with PBCAR0191. Alan?

Thank you, Matt, and good morning, everybody. I got to say I'm very optimistic about the potential of the allogeneic CAR T therapies, in particular, our approaching launch of the stealth program into the clinic. And it really is an exciting time for the company and really all the team. Let's go on to the next slide. The 0191 trial began in the second quarter of 2019. As I'm sure that most of you know, this is a Phase I/II study evaluating escalating doses of PBCAR0191, ranging from a starting dose of 3x 10 to the 5 cells per kilogram to 3x 10 to the 6 cells per kilogram at dose level 3 in patients with relapsed/refractory lymphoma as well as B-cell ALL. Cells were administered following what we refer to as our standard lymphodepletion regimen that consists of fludarabine 30 milligrams per meter squared per day and cyclophosphamide 500 milligrams per meter squared per day for 3 days, administered in day minus 3 through day minus 2 -- sorry, day minus 5 through day minus three. Presentation today will focus on our enhanced lymphodepletion experience in patients with relapsed/refractory lymphoma, which I will describe in further detail in just a few minutes. Let's go on to Slide #9. There are several important takeaways from our experience with the first 3 dose levels that frame the reasoning for us to explore the enhanced lymphodepletion regimen. The first are the encouraging findings that, number one, we did not experience any dose-limiting toxicity with standard lymphodepletion and nor did we see any grade 3 or greater immune effector cell neurotoxicity, or ICANS, or cytokine release syndrome. Importantly, our CD19 CAR is inserted into the TRAC locus, as you heard from Matt, so to thereby prevent generalized host recognition. And as proof of that, we had no evidence of graft-versus-host disease. And as expected, we did see a dose-dependent increase in CAR T expansion, albeit with modest peak cell expansion and rapid retraction that we attributed to host immune rejection. And finally, although we observed clear evidence of clinical activity, response durations were not sustained. Let's go on to Slide #10. So with that background, our goal was to test a strategy that could potentially improve expansion of 0191 as well as the persistence sufficiently to yield higher rates of response and more durable responses. So to accomplish that, we intensified the lymphodepletion regimen to further deepen and extend the duration of lymphodepletion compared to our standard regimen, with the intention to achieve a longer but a limited duration of lymphopenia. What we refer to as the enhanced lymphodepletion regimen includes an additional day of fludarabine on day minus 6 for a total of 4 doses and doubling the dose of cyclophosphamide to 1,000 milligrams per meter squared administered on days minus -- day minus 5 through day minus 3. All patients received the 3x 10 to the 6 per kilogram cell dose with dose level 3, which allowed us to directly compare these results to the dose level 3 with standard lymphodepletion. The objectives of this approach were to reduce host immune rejections sufficiently to give us the improvement in cell expansion and persistence that we feel is necessary to improve clinical outcomes while maintaining an acceptable safety profile. The results that we are sharing today are in patients with relapsed/refractory lymphoma, which includes patients who previously received autologous CD19-directed CAR treatments as well as prior autologous stem cell transplant. In December 2020, we shared results from the first 4 lymphoma patients. And today, we will share data from an additional 8 patients for a total of 12, who are evaluable for day 28 safety and response assessments as of our cutoff date of May 21. The data you will see presented at ASCO at 9:00 a.m. on our poster discussion session includes patients that were evaluable as of April 9. In January of this year, we modified eligibility to exclude those patients at greater risk of prolonged myelosuppression or who had a serious infection within 30 days of enrollment. Let's go on to Slide #11. As you can see on this slide, the vast majority of patients had very poor risk features and advanced disease, with more than 80% of patients having aggressive lymphoma histologies, and half the patients had prior autologous stem cell transplant, and 4 were previously treated with CD19-directed CARs. The median lines of prior therapy was approximately 7 and ranged as high as 15 prior lines of therapy. The median interval from the time of confirmation of eligibility until the initiation of lymphodepletion was only 1 day. Select adverse events of particular interest in patients treated with enhanced LD are shown here compared to the 6 patients who received the same cell dose with standard lymphodepletion. As you can see, the frequency and severity of CRS was comparable, as was ICANS, with the exception of 1 grade 3 event that resolved to grade 2 and lower within 2 days. As with standard lymphodepletion, there was no evidence of graft-versus-host disease. The frequency of grade 3 or greater neutropenia and thrombocytopenia was observed with enhanced lymphodepletion, occurring in 2% or 17% of the patients. Prolonged grade 3 neutropenia that persisted at day 28 was also observed in 2 patients and grade 3 thrombocytopenia in 1 patient. Accompanying this was a higher frequency of infection documented in 4 patients overall, 3 of which were grade 3 or higher. You may recall that there was 1 infection-related death at day 54 that was disclosed in December, and that was deemed possibly related by the treating physician. Two other deaths have occurred. One at day 50, that was attributed to pneumonia; and 1 on day 28, following -- having a cardiac arrest following a choking incident. The latter 2 deaths were deemed unrelated. The latter patient never had response assessment, but is included in our intent-to-treat response data. The other 2 patients had both achieved a complete response. I might add that the median number of prior lines of therapy among the studied deaths was 9 lines of treatment. Let's go on to the next slide. Cell expansion [ contents ] are shown here with assessment by flow cytometry in the figure on the left and PCR on the right. As you can see from the flow data, peak cell expansion was profoundly improved, with a 72-fold increase with enhanced lymphodepletion compared to the standard lymphodepletion patients. This was accompanied by a 56-fold increase in the total area under the curve with good persistence at day 28. Persistence appears higher in the PCR figure, as you might expect, which is due to the greater sensitivity of the PCR assay. Okay. The next slide, #14, shows the overall responses. The best response assessed at day 28 or later, as shown on here. And as you can see, among all the study subjects, 9 or 75% of patients had an objective response and 6 or 50% achieved a complete response. I might remind you that 1 patient did not have a day 28 response assessment, but is included in the intent-to-treat estimates and response. Overall, complete response rates were identical among CD19 CAR naive patients and among those who received prior CAR treatments. 3 of the 4 CD19 CAR treated patients had also undergone a prior autologous stem cell transplant. Slide #15 shows the swim plot which illustrates the depth of response, the duration of response and the time of progression or death. The color coding for the prior CD19 CAR in autologous stem cell transplant treatments is in the lower left-hand corner of the slide. Overall, 5 patients remain progression-free with ongoing response as reflected by the arrows on the right-hand side of the lines, including 4 responses that are more than 4 months duration. Among 9 patients with diffuse large B-cell lymphoma or high-grade lymphoma, 3 remain progression-free, 1 patient went on to receive an allogeneic stem cell transplant while remaining in CR at approximately day 150. In addition, 1 of 3 patients who received both a prior CD19 CAR and an autologous stem cell transplant continues in response. Among the 6 patients who had a prior autologous stem cell transplant, 4 or 66% responded, including 2 complete responses and 2 partial responses. Let's go on to Slide 16, which is my last slide. So to summarize the clinical data that we just shared with you, we found that enhanced lymphodepletion mitigated PBCAR0191 rejection to markedly increase the cell expansion, 72 fold, and the AUC, 59 fold, compared to standard lymphodepletion. There was a similar frequency of ICANS and CRS compared to standard LD, while myelosuppression was increased. We continue to see no evidence of graft-versus-host disease, which is consistent with the knockout of the T cell TRAC locus in the CARs. Also reflecting the profound improvement in CAR kinetics, a single dose of PBCAR0191 yielded higher rates and depth of response with ORR and complete response rates of 75% and 50%, respectively in both CD19 CAR naive subjects as well as those who were previously treated with CD19-directed CAR therapies. We see preliminary evidence of durability with 5 of 9 responders or 56% remaining progression-free, including 4 for over 4 months. The median interval from confirmation of eligibility to the start of lymphodepletion was 1 day, which reinforces the feasibility of applying PBCAR0191 as an off-the-shelf allogeneic cell therapy for lymphoma patients at high risk for rapid disease progression. As of today, a total of 15 patients are enrolled in the enhanced lymphodepletion cohort, and our plans are continued follow-up of response duration with the goal of achieving durable responses of 6 months or longer in more than 1/3 of patients. And now I'll turn it over to Derek.

Thank you, Alan, and good morning, everyone. If you could all please turn to Slide 18. As Alan mentioned, the challenge that we're trying to overcome is rejection of our allogeneic CAR T cells by the patient's immune system. And there are 2 general ways that we can think about doing that. The first is to try and address the problem at the level of the patient's immune system by adding lymphodepleting drugs upfront to hold the immune system back and essentially buy the CAR T cells more time to do their job. The enhanced lymphodepletion data that Alan just walked us through is a good example of that. Using an anti-CD52 antibody is another example. But the second and potentially much better approach is to modify the CAR T cells themselves so that they avoid detection by the immune system in the first place. And that's exactly what we're hoping to do with our second-generation CAR T platform that we call stealth cell. On Slide 19, our first idea was to knock out a gene called beta-2-microglobulin. B2M is a component of MHC Class I, which is the protein complex on the surface of the CAR T cells that the patient's T cells are looking at to try and figure out if the CAR T cell is foreign or not. That is the interaction that's shown on the left-hand side of this slide. So in principle, if we knock out B2M in our CAR Ts using our ARCUS gene editing technology, the patient's T cells should be unable to recognize and kill them. However, MHC Class I also plays a role in preventing rejection by natural killer cells, which are another type of immune cell. And that's the interaction shown on the right-hand side of the figure. So the concern that we had based on basic immunology was that if we use ARCUS to knock out B2M and thereby eliminate MHC Class I entirely, we might save ourselves from rejection by the patient's T cells, but we will now induce an NK response and be rejected by NKs instead. And in fact, that's exactly what we saw in preclinical experiments, as shown on Slide 20. We made CAR T cells with B2M knocked out and we tested them in mixed lymphocyte experiments in which we mixed the CAR T cells with either T cells or NKs from unmatched donors and we looked to see whether or not the CAR T cells were killed. As we expected, we found that the standard CAR T cells are efficiently killed by T cells, which is shown on the left, but they're not killed by NKs, as shown on the right. And then the opposite is true of the B2M knockout CAR-Ts which are not killed by T cells, but are very efficiently eliminated by NKs. So this signal to us that just knocking out B2M probably wasn't going to be enough to prevent rejection. Now it did occur to us that perhaps the patient's NK cells don't actually recover as quickly as their T cells do following lymphodepletion. So perhaps, we didn't actually need to worry about the NKs because they aren't actually there. So we looked at some of the patient blood samples that were drawn in our first-generation trial, and this data is shown on Slide 21. What we found is that, in fact, the patient's NK cells, which are shown in the light blue trace, recover back to pretreatment levels on about the same time line as the T cells, which are shown in orange. So any strategy for immune evasion is going to have to take into account both the T cells and the NKs. So to that end, if you want to turn to Slide 22, one of our scientists had the very clever idea to knock down B2M instead of knocking it out. Gene editing is very black and white. You either knock the gene out to 100% or you don't. But we can use RNAi to just suppress expression of the gene to varying degrees so that each cell still makes some, but not as much as normal. So we made a series of new CAR T vectors in which we incorporated a variety of different shRNAs that suppress B2M expression to different extents. And we evaluated them for resistance to killing by either T cells or NKs. So if you look first at the plot on the lower left, the orange line indicates how much B2M is on the surface of each CAR T cell variant. Our standard CAR Ts are in gray, the B2M knockout CAR T is in red, and the 3 B2M shRNA clones are in blue. What you can see is that as we go down in B2M surface expression, we see a corresponding and almost linear reduction in killing by T cells. But if you look at the plot on the right, which is killing by NKs, the shRNA clones don't really look any different from the standard CAR T, and we don't induce a strong NK response until we knock out B2M entirely. What they said to us is that there's sort of a sweet spot around 10% to 20% of normal B2M levels, which is what we can achieve with shRNA #3 where the CAR T cells are largely resistant to rejection by both T cells and NKs. And we named that vector with shRNA #3 a stealth cell and we moved that into development. But then we saw something unexpected, and this is shown on Slide 23. As we were collecting the preclinical data for that first version of the stealth cell, we found that not all NK cells are alike. We found that NK cells that were taken from certain donors or that were activated using certain more potent protocols were more aggressive and would kill our B2M knockdown CAR Ts despite the presence of some MHC class I on the cell surface. For example, the data that's shown on this slide shows an experiment comparing NKs activated using a mild protocol, which is a 24-hour incubation in IL2, versus NKs activated using a stronger protocol of 48 hours in IL-15. Whereas the less activated NKs on the left, more or less ignore the B2M knockdown CAR Ts, the more highly activated NKs on the right kill it quite efficiently. And unfortunately, we don't actually know which one of these situations more accurately reflects what is going on in the patient at the time that our CAR T cells would be facing rejection. So we made the decision to pause so that we could add a second layer of defense against NKs with the more aggressive phenotypes. And this is shown on Slide 24. We added a gene called HLA-E. HLA-E is a form of MHC Class I that is invariant between individuals. So like other forms of MHC Class I, it can interact with NKs to turn them off and avoid rejection. But unlike other forms of MHC Class I, it looks the same between the donor used to make the CAR T cells and the patient. So it won't be recognized as foreign and induce the T cell response. The final result of all of this is shown on the next slide, Slide 25. PBCAR19B, which is our stealth cell version of the CD19 CAR T, incorporates the anti-B2M shRNA as well as a transgenic copy of HLA-E. The vector configuration is shown on the slide. It actually took some very sophisticated molecular biology to get this thing made such that it would be stable and completely compatible with our existing manufacturing process. And as you can see from the data at the bottom of the slide, the stealth cell, which is the orange trace, is resistance to both T cells and NKs even at very high effector to target ratios and using potent activation protocols. So we are hopeful that it will give us a significant boost in cell expansion and persistence time in patients such that we won't need a stronger lymphodepletion regimen and the associated infection risk. An update on the 19B program is given on Slide 26. The study is now open for enrollment. We will be evaluating 3 doses of CAR Ts. But in this case, we will use a flat dose, unlike our first-generation CAR T in which we dosed by weight. And dose level 1 of the study, which is a flat dose of 2.7x 10 to the 8 cells, is approximately equivalent to dose level 3 of the first-generation 0191 study, which is the data that Alan just talked about. So we do hope to see significant clinical benefit even at the first dose level. That said, obviously, we are just getting it started, so I wouldn't expect to see any stealth cell data until next year. A few concluding thoughts are on the last slide. We feel like we now have multiple viable paths to realizing the potential of allogeneic CAR T. PBCAR0191, the first-generation CD19, is looking very promising when paired with our enhanced lymphodepletion regimen. It's obviously still early, and we need more patients and more follow-up, but we think that program is tracking very, very well. And we're obviously very excited to see the data for PBCAR19B, which is our second-generation stealth cell platform which may be able to achieve similar or potentially better levels of efficacy but without the need for prolonged immunosuppression. Our plan right now is to continue both programs in parallel and follow the data to determine which is the best approach to avoiding rejection before we pick a program to advance to pivotal. There are a few other things that you should probably have on your radar. Later this year, we plan to give clinical updates on our first-generation CD20 and BCMA programs. In addition, we are just about to start treating patients in a trial of our allogeneic BCMA CAR T in combination with the gamma secretase inhibitor. And we plan to file an IND for a stealth cell version of our BCMA CAR T early next year. So there's a lot of activity with BCMA right now. And one final thing to be on the look out for is an R&D event that we will be hosting later in the summer, focused on our gene editing pipeline that we haven't talked about at all today. We'll be sharing time lines and data updates for a number of our rare disease gene editing projects that are really starting to get a lot of attention. So please attend that if you can. We haven't announced the date yet, but we will do so soon. And with that, Matt and Alan and I can take any questions you might have.

[Operator Instructions] Our first question will come from the line of Andrea Tan from Goldman Sachs.

Two for me, please. Just the first, can you comment whether the other levers that you've discussed before, such as increased CAR T cell doses or repeat dosing, are still under consideration?

Thanks, Andrea. Go ahead , Alan?

No, I was just going to mention that right now, we're focused on the single infusion. And we have a total of 15 patients enrolled in that right now. So we're going to be following those for response and most importantly, durability. We have looked at other lymphodepletion strategies, as you mentioned, repeat dosing. We went with the eLD because we felt that was the most promising for us. And the -- our goal really is to, right now, focus on 1 single infusion, just like we do with autologous CAR T cells. We feel that the bar for allogeneic CAR is going to be -- have to be equal or beat the autologous approach. So using a single cell infusion, we feel, is going to be the best approach for us.

Got it. And then, Alan, maybe 1 other question for you. Just wondering if you could speculate on how 0191 is maybe differentiated from other allo CAR T products just given that it is able to elicit a response here in patients with prior auto CAR T therapies when we haven't necessarily seen that with other products.

Yes. I mean we're very excited about that. To be able to see that patients that had prior CD9 directed CARs is very good. Very good response rate in the patients that had autologous stem cell transplant. We did that with only 1 infusion of the CARs. Obviously, with this, our only immunosuppression or preparation of the patient is with the lymphodepletion regimen alone. Our -- the T cells begin to recover right around day 28 or later or shortly thereafter. So we don't get a prolonged period of lymphodepletion or lymphopenia to put the patient at risk. So a little bit of different approach to compare to, for example, what Allogene is doing.

Our next question will come from the line of Tom Shrader from BTIG.

It looks like pretty clean results. Slide 13, on the right panel, the expansion data. That looks like what you wanted. I'm curious what we're looking at there. Is that all the patients? Is that a couple of patients? How many patients got expansion that looked like that, that really is robust still at 28 days?

Thanks, Tom.

This is Alan.

Go ahead, Alan.

I'm just going to -- and Derek can comment too, if you like. So these are all the patients who had had enhanced lymphodepletion shown there in the blue and 6 patients who had the standard lymphodepletion shown there in the green. So the end, obviously, for the enhanced lymphodepletion is very strong. And you can see, again, very good persistence at day 28, which is -- really was our goal of using the enhanced lymphodepletion. Now PCR, obviously, is 2 logs more sensitive than flow. And that's why you can see the persistence of the cells at lower doses there.

Yes, got it. It's certainly what you wanted.

All right. Derek, were you going to comment?

Yes. I was just going to say, in terms of patient to patient variability, obviously, you can see the yellow bars on the data. But one of the advantages of the eLD protocol is we are seeing more consistent cell expansion and persistence really across patients. So as you say, exactly what we were hoping to be.

And if I could just ask a second question on Slide 15, in the middle of the curve, it looks like you have 3 very similar CRs about the same duration. How much data do you have on those patients? Are those really deep CRs? Are they MRD? And any idea what's going on there? Because that looks great also, but the duration is just unusual, and they look very consistent.

I'm sorry, I was on mute. So Matt, did you want me to comment on that?

Please, Alan.

Yes. I mean the -- so these are not ALLs. So we don't have the MRD data there, but we are looking at that. All this has been collected, and it's going to be batched, and we'll get that molecular data very soon. So and you're right, I think that would be fantastic if we had, at day 28, CRs that we know that are MRD-negative by molecular analysis. If that translates into durability, that would be a great biomarker for us for taking forward with the FDA. We don't have that as yet. But yes, these are -- these responses have been looking very, very durable. I might point out that one of these lymphomas, the follicular, 1248-007, that one is going to be illustrated in the 9:00 poster discussion session. So you'll see the PET CT scans of that. It was initially called a CR by the investigator, but the radiologist thought he saw 1 submandibular node and it turns out that the patient was having dental issues. So we feel like these are very deep responses that we're seeing. And so far, are durable beyond 6 -- beyond 4 months. But our goal is to see 6 months or longer.

Great.

And actually, Tom, I'll -- this is Derek. I'll just add a little bit more color to the question about the patients around the middle of the plot. In particular, you see that there are 2 patients on this slide that had complete responses until about day 60 and then progressed. And those are 1179-001 and 1140-002. One of those patients progressed with CNS disease, which we do believe that treating CNS disease with an allo CAR T is going to be very challenging because the lymphodepletion drugs don't cross the blood-brain barrier. And the second patient progressed with CD19 negative disease. So really, the CAR Ts, in that case, did all they could, but then the progression was CD19 negative.

Our next question will come from the line of Raju Prasad from William Blair.

How should we anticipate the extended lymphodepletion regimen being utilized in potentially future trials given what you've seen today?

Thanks, Raj. Appreciate the question. Alan, do you want to take that one?

Yes. Thank you, Matt. So the enhanced lymphodepletion we've had a lot of success with, with 0191. With stealth, which is now open, we're using the standard lymphodepletion. And the reason behind that is simply that the strategy to suppress -- or I should say, to evade immune response of the host was -- is built into the stealth cell itself, as you heard from Derek, with the beta-2-microglobulin knockdown and the HLA-E knock in. So we fully expect we won't need to have an enhanced lymphodepletion approach with the stealth cell. Now the other programs it could be applied in, particularly in like CD20, if we wanted to. We don't have plans to take this into myeloma at this point. But right now, the focus is on the lymphoma patients with the -- in the first generation studies.

Great. And in one of the slides, you looked at a mixed donor with NK cells. And I was just curious, maybe, Derek, if you could comment on if you saw any specific attributes to the NK cells that were doing the killing in that experiment or whether it was kind of just random.

Yes. Great question. And certainly, we have looked to see if there are particular phenotypic markers that would indicate -- and that would identify these more aggressive NK cell phenotypes. And at this point, we haven't been able to identify anything obvious. So it's been very difficult to predict which of the NK cell subtypes would be able to reject that first generation version of the stealth cell, which is why we made the decision to add the HLA-E transgene. And since we added in the HLA-E, it doesn't seem to matter anymore whether the NKs or the more aggressive phenotypes or not. The stealth cell -- the current version of the stealth cell is more or less resistant to all of them.