Thanks everyone for joining us. On the call today from Adicet are Chen Schor, President and Chief Executive Officer, Dr. Francesco Galimi, Chief Medical Officer, Nick Harvey, Chief Financial Officer, and Dr. Blake Aftab, Chief Scientific Officer. Before we begin, I'd like to remind you that various remarks that we make on this call contain forward-looking statements that are made under the Safe Harbor provisions of the securities laws, including, but not limited to, express or implied statements regarding the potential safety, durability, tolerability, and efficacy of ADI-001.
Future progress of ADI-001 in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma or NHL, including selection of a recommended phase II dose, expectations regarding future discussions with regulators and regulatory filings for product candidates in the company's pipeline, and timing for the potentially pivotal phase II study of ADI-001 in post-CAR T LBCL patients. In addition to our prepared remarks, we may make forward-looking statements in response to questions, including, for example, statements regarding potential future trials, our financial position, and that positive interim results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies. Any statements made in this call that are not statements of historical fact may be deemed to be forward-looking statements.
Forward-looking statements involve risks and uncertainties that could cause Adicet's actual results to differ significantly from those projected, including, without limitation, the risks and uncertainties detailed in Adicet's most recent annual report on Form 10-K and subsequent filings with the SEC. We issued a press release today outlining results of our phase I clinical trial of ADI-001 in patients with aggressive NHL. The press release and the accompanying presentation can be found on the investors section of Adicet's website. This call is the property of Adicet, and any replay of this conference call cannot be made without Adicet's express written permission. With that, I'll turn the call over to Chen Schor, President and CEO of Adicet. Chen?
Thanks, Ann, thank you all for joining us on this call to discuss our latest data cut from the phase I clinical study of ADI-001 in patients with aggressive non-Hodgkin's lymphoma. Let me walk you through the agenda for today's call. I will begin with an overview of the data and provide a comparison of durable CR rates in aggressive NHL for autologous CAR T, bispecifics, and ADI-001. I will hand it over to Dr. Francesco Galimi, our Chief Medical Officer, to provide a more detailed overview of the phase I data. I'll close with a short summary of the market opportunity for ADI-001's first potential indication and our near-term corporate milestones before we open up the call for Q&A with the rest of the Adicet team. Let's go ahead and get started. Let's go to slide five.
We're excited about the ADI-001 data we announced this afternoon from our phase I study, demonstrating strong efficacy and favorable safety in 24 patients with aggressive, relapsed, or refractory B-cell non-Hodgkin's lymphoma. The data is especially impressive given that these patients were heavily pretreated with a median of 4 prior lines of therapy, and 50% of the patients had progressed on prior autologous CAR T therapy. The overall response rate we observed in the study was 71%, and the CR rate was 63% in the efficacy evaluable patients across all doses. In post-autologous CD19 CAR T patients, the overall response rate was 83%, and the CR rate was 67%. We have observed strong durability with ADI-001, with a six-month CR rate consistent with autologous CD19 CAR T therapies.
We continue to observe a favorable safety profile with no significant incidents of CRS or ICANS. Let me remind you that ADI-001 is off the shelf and rapidly available to patients. We selected DL4 as the recommended phase II dose. At this dose level, the Cmax and day 28 persistence of ADI-001 exceed that of approved CD19 autologous cell therapies. Last month, we completed our Type B meeting with FDA. We plan to transition the ADI-001 program into a potentially pivotal phase II study in post-CAR T LBCL patients in the first half of 2024, under an accelerated approval path. There is a significant and growing market opportunity for this potential indication that we will outline on a separate slide.
We believe the data you'll see today provides a strong foundation for our growing pipeline of engineered gamma delta T-cell therapies. Let's review the efficacy of the currently approved autologous cell therapies and bispecifics in aggressive NHL, so we can put some context to ADI-001 efficacy. Let's go to the next slide. If you look at published data in the New England Journal of Medicine, you'll see that CRs to cell therapies which last 6 months, are strongly indicative of long-term remission, in contrast to bispecifics. The graph in green on the left is from axi-cel's ZUMA-1 trial, published in the New England Journal of Medicine, showing duration of complete response. As you can see, the six- month CR rate represents a long tail of durable CR rate. The graph in blue on the right is from Glofitamab trial, published also in the New England Journal of Medicine.
As you can see, there is a significant erosion in Glofitamab CR rate over time, and there is still no tail to the CR rate. What's the actual durable CR rate for Glofitamab? What we do know is that at least 50% of the CRs progress. Let's move to the next slide, so you can see the durable CR rates when you layer the number of prior lines of therapies across autologous CAR-Ts and bispecifics. This slide shows the efficacy data from the different trials at the recommended phase II dose. In purple, we plotted the durable CR rate for the ZUMA studies, which investigated axi-cel in the first, second, and third line setting.
As you can see, the durable CR rate, defined in cell therapies as the six-month CR rate, decreases from 69% in first line, to 46% in second line, to 33% in patients with a median of three lines of prior therapy. The ZUMA studies have been conducted by definition in CAR T-naive patients. In gray are the bispecific antibodies, Glofitamab and Epcoritamab. Both had the same median of three prior lines of therapy in their pivotal studies, as the ZUMA-1 study. Both bispecifics have shown an approximately 20% durable CR rate, given that the initial CR rate was approximately 40%, and at least 50% still of CRs progress, as published in the New England Journal of Medicine.
As a reminder, ADI-001 was evaluated in patients with a median of four prior lines of therapy, and 50% of the patients progressed on prior autologous CAR-T. Let's layer on our ADI-001 data on the next slide to see where we stack up. Next slide, please. As you can see here on the slide, the data for ADI-001 is outlined in the blue boxes on the right, as we tested ADI-001 in later line patients with a median of four lines of therapy. If you look at the bottom blue box, for all patients dosed, for all patients dosed at the recommended phase II dose cohort, which included 38 of patients that previously progressed on CAR-T, the durable CR rate in this group was 25%.
If you look at the top box, in post- CAR T patients at the recommended phase II dose, the durable CR rate was higher at 33%. While we have a smaller N at the recommended phase II dose, the bottom line is that ADI-001 seems to be in the same ballpark when compared to autologous cell therapies, with lower incidents of CRS and ICANS, and it's off-the-shelf, rapidly available to patients. Overall, we're very pleased with the strong, durable CR rate demonstrated by ADI-001 in these late-line NHL patients. Now, let's turn our attention to ADI-001 durable CR rate in the post- CAR T setting. Next slide please. The CD20 bispecifics have demonstrated a CR rate of approximately 34%-35% in the post- CAR T setting.
Given that at least 50% of the CRs progress with the bispecifics, the durable CR rate in the post- CAR T setting is estimated at 17% or less. With ADI-001, when you look at all doses combined, we have seen a higher complete response rate and a comparable durable CR rate, as indicated in the middle funnel. At the recommended phase II dose on the right, both the CR rate and the durable CR rate are more favorable to available therapies. In particular, although a smaller N for ADI-001, the CR rate for ADI-001 may be double that of the bispecifics, and the durable CR rate comparable, and more likely favorable at the recommended phase II dose. Additionally, it's important to point out that treatment with bispecifics required frequent infusions.
For example, for EPCO, the first 24 doses are provided weekly or bi-weekly in the hospital or clinical setting for the first nine months, tying up the patient for hours at a time for each of those 24 infusions, followed by a once-a-month infusion regimen. In the case of ADI-001, we provide a one-time treatment infusion, liberating patients from the need of frequent visits to the hospital. I'll now turn the call over to Francesco to talk about the ADI-001 data in greater detail. Francesco?
Thank you, Chen. Hello, everyone, and thank you for joining us today to review the latest data from our phase I study, evaluating ADI-001 in aggressive B-cell malignancies. I will now review the main findings, which we believe continue to be very encouraging, and share our preliminary plans for our first potentially pivotal phase II study. Let's first give you a quick reminder of the first in-human study design on Slide 11. The dose escalation included 4 dose levels, starting at a flat dose of 30 million CAR-positive cells, and continuing to 100 million, 300 million, and 1 billion CAR-positive cells. Each enrolled patient received a five-day lymphodepletion regimen. We have explored two different lymphodepletion regimens, shown on the slide, both based on fludarabine and cyclophosphamide.
One exploratory section of the protocol, not shown on the diagram, which we call Part 1B, included patients receiving a single lymphodepletion and two infusions of dose level 3 on Day one and Day seven, for a total of 600 million CAR-positive cells. Let's go to patient characteristics on the next slide. As of the May 4th cutoff date, the trial enrolled 23 patients with aggressive B-cell lymphoma. 18 patients had large B-cell lymphoma, and five had mantle cell lymphoma. one additional patient was enrolled with follicular lymphoma, for a total of 24 evaluable patients. Most patients were heavily pre-treated with a median of four prior lines of therapy, relatively high tumor burden, and a poor prognostic outlook. Approximately 70% of patients were refractory to their last course of systemic therapy, and the remaining had relapsed.
12 patients, 50% of the total, had progressed following approved autologous anti-CD19 CAR T-cell therapies, including axi-cel, lisocabtagene maraleucel, and brexucabtagene autoleucel. Go to efficacy data for ADI-001 on the next slide. This chart summarizes the efficacy for ADI-001 as of the May data cut date. Focus on DL4, the recommended phase II dose, as shown on the first two rows on this slide. You can see that the six-month CR rate is in the same ballpark as autologous, in spite of the high prior lines of therapy and the percentage of post-CAR T patients. In dose level 4, patients had a median of four lines of prior therapy, with approximately 38% post-CAR T. This group achieved an overall response rate of 75%, with six responders out of eight patients.
The complete response rate was 62.5%, and the six-month complete response rate was 25%. Importantly, at the recommended phase II dose in patients with prior CAR T, the group achieved a 100% overall response rate. The complete response rate was 67%, and the six-month complete response rate was 33%. Let's go to the next slide. This slide shows our response data on a swim lane plot for all 24 evaluable patients as of the May 4 data cut date. Let me remind you that our patients are heavily pre-treated with a median of four prior lines, including prior treatment with autologous CAR Ts in 50% of them. In the boxes on the right, for each cohort, we break out the median number of prior lines of therapy and highlight in yellow, the percentage of post-CAR T patients.
As we saw on an earlier slide, our recommended phase II dose, DL4, included 38% of post-CAR T patients. The overall response rate was 75%, complete response rate was 63%, and the 6-month CR rate was 25%. If we look across all those levels, which included 50% of post-CAR T patients, the overall response rate was 71%, CR rate was 63%, and the 6-month CR rate was 17%. A total of 21% of patients remain cancer-free if we include the first patient in dose level 1, who had a local skin relapse, was managed with local radiation, and remains disease-free without any systemic therapy for over 20 months. We consider this patient one of the success stories for this phase I trial, even though we have to count him as a progression for Lugano criteria.
Overall, the preliminary efficacy data in this trial to date has shown high response rates comparable to the clinical experience with approved CAR Ts and comparable durability, despite the high number of prior lines of therapy and percentage of post-CAR T patients. Let's now focus on the post-CAR T patients shown on the next slide. This slide shows our response data on a swim lane plot, focusing on patients who had previously progressed on autologous CD19 CAR T therapies, which included 12 of the 24 total evaluable patients. Across all those levels, the post-CAR T patients had a median of four lines of prior therapy and saw an overall response rate of 83%, a complete response rate of 67%, a six-month complete response rate of 17%, with 25% cancer-free patients, if we include the patient with a skin lesion that I discussed earlier.
The 25% of cancer-free patients includes three out of the 12 post-autologous CAR T patients. Two were large B-cell lymphoma and one was mantle cell lymphoma. Given that there were 10 large B-cell lymphomas and two mantle cell lymphomas post-autologous CAR T patients, while this is a very small N, this suggests that 20% of the large B-cell lymphoma post-autologous patients and 50% of the mantle cell lymphoma post-autologous post-CAR T patients remain cancer-free at six months. As you can see, at dose level 4, our recommended phase II dose, patients had an overall response rate of 100%, with a complete response rate of 67% and a six-month complete response rate of 33%. Let's move to the next slide to talk about PK.
Slide 16 depicts the PK analysis of blood samples using two different techniques: flow cytometry for CAR-positive cells on the left, and the dPCR for the CAR transgene on the right. For the latter, at this point, we have data only for dose level 4. By both methods, Cmax and day 28 persistence exceed the levels reported for approved autologous CD19 CAR Ts, like axi-cel, tisagenlecleucel, and lisocabtagene maraleucel. Also similar were the peak values for ADI-001, occurring between days seven and 10. Persistence at dose level 4 was also clearly detectable at high levels through day 28. Of note, both Cmax and persistence in dose level four 4 were much higher than dose level 3 and dose level 3 times 2, providing supporting data to our recommended phase II dose selection.
Please note that this PK, measured in peripheral blood, may be only the tip of the iceberg, considering gamma delta 1 T cells tropism for tissues. Altogether, we believe these are the most compelling pharmacokinetic data reported to date for any allogeneic CAR T platform. This data set is also very promising for its implications for our upcoming pipeline programs. Let's go to the next slide. This slide shows a summary of key safety data collected so far. There was one CRS and one ICANS reported in grade three or above in dose level 3, and dose level 3 times 2, respectively. We have not seen any event of graft-versus-host or any dose-limiting toxicities. The occurrence of infection in the study appears to be rather low, in spite of the use of enhanced lymphodepletion.
Overall, ADI-001 was remarkably well tolerated throughout the dose escalation, including patients dosed at dose level 4 especially in comparison with the safety profile of approved autologous CD19 CAR-Ts. Let's go to the next slide. Let me show you this diagram again, which visualizes how we describe the lay of the land when it comes to recent advances in non-Hodgkin's lymphoma immunotherapy. As you can see, ADI-001, shown by the blue dots, compares well to both the axi-cel experience shown in purple and the two recent accelerated approvals of bispecifics shown in gray. We are convinced that our data set bodes well for further characterization in our future clinical program. Let's move to the next slide.
Last month, we met with the FDA for our Type B meeting, and we are now advancing our plan to initiate our potentially pivotal phase II study in post-CAR T large B-cell lymphoma. The phase II study will evaluate a single infusion of ADI-001 at our recommended phase II dose of 1 billion CAR-positive cells in a single arm clinical trial in post-CAR T large B-cell lymphoma patients. We expect to enroll approximately 100 evaluable patients. The primary endpoint of the trial is expected to be complete response. Manufacturing is underway to supply clinical material for our potentially pivotal phase II study, which we plan to initiate in the first half of 2024. In addition, given the highly favorable data we have observed in post-CAR T mantle cell lymphoma patients, we're also evaluating our plans for this indication.
In summary, we are very pleased with the CR rate, durability, and safety data demonstrated with ADI-001 in this study. With that, I thank you all for your attention, and I'll turn it back over to Chen.
Thanks, Francesco. We believe the latest clinical data set provides us with a strong foundation for future development. The data we've shown you today demonstrate that ADI-001, at a high CR rate, at least comparable to approved CD19 autologous CAR T therapies. ADI-001 showed strong durability in late-line patients with high percent of post-CAR T, and the Cmax and day 28 persistence exceeds the value of reported for approved CD19 autologous CAR T. We've already published the superior cell-killing potency of ADI-001 compared to the Alpha Beta CAR-T. Finally, a favorable safety profile with no significant incidents of CRS and ICANS, which is expected to enable dosing in outpatient setting. Let's move to the next slide to discuss the market opportunity.
The autologous CD19 CAR T market is estimated at over $2.2 billion annual run rate. The market is expected to grow significantly, given the recent approval of autologous CD19 CAR T therapies in the second-line setting. In the second-line and third-line setting, 60%-70% of patients progress following autologous CD19 CAR T. We believe this provides a significant opportunity for Adicet and for ADI-001. Let's go to the next slide to talk about the near-term milestones. Looking ahead, we're well-funded and have significant near-term milestones ahead. Based on these first-in-human findings, we expect to initiate a potentially pivotal phase II study for ADI-001 in post-CAR T LBCL in the first half of 2024.
We plan to provide a clinical update from additional post- CAR T LBCL patients, including efficacy, six months CR rate, and safety data in the second half of 2024. We also expect to evaluate opportunities for a second pivotal study. Our second pipeline candidate is ADI-925, which we believe has the potential to introduce a fundamental advance to the fields of cell therapy and innate immunity, by significantly enhancing the intrinsic, innate, and adaptive antitumor activity of our gamma delta 1 T cells. We continue to expect to submit an IND for ADI-925 in the second half of this year, and initiate the phase I clinical study in AML in the first half of next year.
Our third pipeline candidate, ADI-270, for which we expect to submit an IND next year, provides multiple levels of differentiation for CD-expressing tumors, such as renal cell carcinoma. One, our CAR construct uses CD27 to bind to CD70, enabling us to target tumors with low antigen density at very high specificity. Two, Gamma Delta 1 T cells have tissue tropism to the renal tissue, unlike other immune cell types. Three, the innate antitumor activity inherent in our gamma delta T cell platform may help address tumor heterogeneity in renal cell carcinoma. We're excited about the data we discussed today, which demonstrate that ADI-001 has the potential to generate meaningful responses in patients where other treatments have failed. We're developing a pipeline of programs targeting additional hematologic and solid tumors. We appreciate your continued support, and look forward to updating you on our progress.
With that, I'll turn it back to the Operator to open it up for Q&A. Operator?
We will now begin the Q&A session. Please note that this call is being recorded. If you would like to ask a question, you can use the Raise Hand button at the bottom of your Zoom window, or if you've dialed in by phone, by dialing star nine, and star six will allow you to unmute. Our first question comes from John Newman from Canaccord. You may unmute your line to ask your question.
Hi there. Thanks very much for taking my question, and congrats on the continued progress here. I just wanted to confirm, the pivotal study will only be enrolling large B-cell lymphoma patients. I'm also wondering, if you considered at all, perhaps enrolling patients that had prior exposure to CD19 bispecifics, or if at this time it's just going to be prior CAR T exposure. Thanks.
Yeah, absolutely. Francesco, why don't you take this one?
Yeah. Thank you, John. Yes, to answer your first question, yes, we plan to enroll patients with post-CAR T large B-cell lymphoma. In terms of CD19 bispecifics, you are alluding to the agents in development?
Yeah
Anything in mind in particular? We don't plan to exclude patients with prior exposure to anti-CD19 bispecifics. That's not our current plan.
Just to add to that, the same is for [audio distortion] is quite stable, antigen, so also these patients will be allowed to the pivotal study.
Great. Then if I could ask just one additional question. Over time, for development of the CAR T therapies, the FDA has generally required somewhere around six months follow-up just to get a sense of durability. I've noted that you your primary endpoint here will be complete response. Should we assume that you'll be following the patients for say, 6-12 months also to get a sense of the durability there as well?
Yeah, John, you're right. It's very, very traditional for the FDA, you know, in cell therapies to ask for follow-up with the six months. Indeed, the primary endpoint is expected to be complete response, and we expect to file with a follow-up data of six months for patients in the study. Absolutely.
Great. Thank you.
Our next question comes from Asthika Goonewardene. You may dial star six to unmute and ask your question.
Hey, Asthika.
Hi, guys.
Yep. I can hear you.
Yes, you can hear me all right?
Yeah.
Perfect. Cool. Thanks for taking my questions. Congrats on the progress as well. Just wanted a couple of clarification questions here on the pivotal study here. Chen, I believe I heard you say that you might have preliminary data in the second half of 2024. I just want to clarify, did I hear that correctly, or was there a wax in my ears?
Yeah, yeah, absolutely. Let me separate. Regarding the initiation of the potentially pivotal phase II, we expect to initiate it in the first half of 2024. That's number one. Regarding the clinical update with additional post-CAR T LBCL patients, this will include efficacy, six-month CR rate, as well as safety. This update, we expect it to be provided in the second half of next year. It will include additional post-CAR T LBCL, that we will enroll into the currently ongoing phase I, as well as patients that will be enrolled to the expected pivotal study.
Got it. Okay. Can you maybe, parse out how you will be prioritizing recruiting patients, if you have both of these sort of ongoing? Would you kind of have it as you'll continue enrolling patients into the phase I all the way until you really kick off the phase II study?
Francesco?
Yes, we will continue enrolling patients in our existing phase I, and we will also, start enrolling patients in our upcoming phase II, which we are currently, writing and finalizing. The answer is yes, we'll be doing both.
Okay. Francesco, can you, can I ask you to maybe put a little bit of color on maybe some of the differences in the baseline factors, or sort of like the inclusion/exclusion criteria we can expect to see for the pivotal study, compared to what was for the Phase I, and how do you think that would impact outcomes?
Yeah. Let me rephrase my answer. We will add more patients to the ongoing phase I, and then at some point, of course, we'll switch to phase II, which we are currently finalizing. The eligibility criteria for the existing phase I, as you know, are broader. In the phase II, we'll focus, as we said, in the post-CAR T population of large B-cell lymphoma patients.
Right. Okay. Just the last one, how would you define prior CAR T exposure? Would you define it in any particular way, like maybe patients should have had a prior response to CAR T, or will you allow patients who have best response of PD to prior CAR T?
We, let's talk about semantics for just a minute. We call patients who did not respond to their prior autologous CAR T experience, we call those primary refractory. We don't expect to enroll a significant number of those in the upcoming pivotal study. The broader definition of refractory in the literature is patients who relapse within six months from their prior CAR T experience, we do have quite a few of those already in our phase I, we plan to have some of those in the upcoming pivotal. Some of it has to do with the definition that is used in the literature to define the refractory population.
Got it. Excellent. Guys, thanks for taking my questions. I'll jump back in queue.
Thank you so much.
Our next question comes from Reni Benjamin, from JMP. Feel free to unmute and ask your question.
Hey, guys. Thanks for taking the questions. A couple here. Just, you know, you had a nice comparison between the bispecifics and 001 in terms of durable CR. Can you comment a little bit about the median duration of response for both assets?
you know, it's, I'll start, and Francesco might be able to comment. It's tougher to compare median duration of response, because when you look at the bispecifics, you can see this very significant erosion in the CR rates. When you think about eventually people are looking for a cure, you're trying to understand what percent of the patients are actually cured. You look at cell therapy, you look at the six-month CR rate, and that gives you a sense of what are the percent of patients that can get a cure. That is the best way for us to try to calculate it. Of course, when we expand the study and we'll have many more patients in DL4, we can start, you know, understanding that better. That's what I can share so far. Yeah.
I don't think we have anything to add.
Okay. How do you strategically plan to evaluate patients with lesser lines of prior therapies? Are you— you know, 'cause we're hearing, obviously, the CAR T therapy moving up in terms of administration, right? Sometimes in the second line. Is there a way to, as you continually point out, that, you know, in your set of patients, they've had at least four prior lines. Is there any way in your ongoing pivotal study, move that up in your inclusion criteria to have only two or three lines prior study, and potentially get your CR rate higher?
Reni, I think this is a great question. Actually, there's nothing that we need to do, because, so far, most of the patients we've seen in this study were a median of four line of therapies. When you think about it, something happened relatively recently, and it's the autologous CAR T got approved in the second-line setting, and are really becoming the standard of care in the second-line setting. Effectively, in this upcoming potentially pivotal study, it would not be surprising if most of the patients would progress on two lines of therapies, including post-autologous CAR T, and we'll see ADI-001 in the third-line setting. From that perspective, it's really not a result of our effort, but rather a result of the nice data that the autologous CD19 have shown in the second-line setting.
When you look at these patients, have you been following at all CD20 expression, and, you know, any sort of correlation between the six-month duration or six-month CR rate and CD20 expression, versus those that are, you know, progressing faster?
Not really. You know, in the post-autologous CAR T, about 95% of the patients continue to express CD20, the data is too small to try to correlate the level of CD20 expression to the quality of the response. At least most of them do express CD20. It's a very stable antigen that's being expressed on the B-cell. Francesco, anything to add?
No, I would just like to point your attention to the fact that CD20 has a well-deserved reputation as a very resilient target, we do expect possible fluctuations, but we consider CD20 expected to be expressed throughout the treatment.
Yep. Got it. Just one final one for me. The only durable CR that you saw was in an MCL patient, you know, not an LBCL. How should we be thinking about that kind of discrepancy, especially at the recommended phase II dose? What kind of six-month CR rate do you expect to be achieved in LBCL, you know, at the recommended phase II dose?
Sure. Absolutely. Great question. When you look at the post-CAR T setting, Are you talking about the post-CAR T? I just want to clarify.
Yes, the post-CAR T.
Perfect. If you look at the post- CAR T setting, we see two durable CRs. One of them is an MCL, and one of them is a DLBCL, and one patient that, you know, it's almost a CR, we call it cancer-free, because he had this minor skin lesion. The bottom line is three patients out of the 12 patients remain cancer-free. If you try to dissect it, in LBCL, you have one patient who is in a complete response, i.e., 10%, and one patient who is essentially cancer-free. It's 10%-20% CR rate, six months CR rate in LBCL. If you look at MCL, on the other hand, it's 50%, one out of the two, with a six-month CR.
The truth is probably somewhere in the middle, that when you combine all these data, you see the overall, six-month CR rate in this cohort, in all those, is a 17%, and in, the recommended phase II dose, 33%. If you ask me what we expect, it's probably somewhere in the middle, between 17%-33%, would be a reasonable expectation. Probably more favorable to the B specifics.
In your discussions, Chen, with the FDA, this is, you know, you had this Type B meeting. Have they kind of signed off on this trial and kind of the expectations? Like, how did they, you know, what was their language, I guess?
Sure.
Color you can provide regarding the regulatory counter?
Yeah, absolutely. First of all, we had the Type B meeting with the FDA, and essentially, the key feedback was the following: Regarding the trial design, they agreed that the accelerated approval path is available. Regarding the size of the study, they agreed that 100 patients is appropriate, and regarding the endpoint, they're okay with us using the CR rate. Overall, I want to say there was pretty good alignment on the design of the pivotal study. We do expect to send them the protocol, and we'll see if they have any additional comments, but that's to the best of our knowledge, that's the expected design.
Great. Thanks for taking the question.
Absolutely. Thank you.
Our next question comes from Kelly Shi from Jefferies. You may unmute your line and ask your question. If you joined by phone, star six will allow you to unmute.
Thank you for taking my question. Just curious, the lymphodepletion regimen to be used in pivotal trial?
Yes, we'll be using the enhanced lymphodepletion, which is again, Cy/Flu, at the doses that you'll find on one of our slides. We're comfortable with that selection, and our clinical advisors are also supportive.
Okay, great. Also a follow-up is, have you talked to doctors, and what has been their feedback regarding for the allogeneic CAR T, whether they will compromise efficacy bar compared to autologous because of the short wait time?
You know, what I can tell you is, at least for the expected pivotal study, which is, in the post-CAR T setting, which is, you know, the subject of discussions with the physicians. We see a lot of interest for, from about 50 sites. You know, right now, in this phase I, we have seven sites, and we're seeing 50 sites expressing interest. I think it's really given the unmet medical need in the post-CAR T settings, and even with the data with the B specifics, given the limited CR rate and durability, we see a, I want to say, very, very high interest level in the study. We have never heard any comment about this.
Thank you.
Absolutely. Thank you, Kelly.
Our next question comes from Justin Zelin from BTIG. You may unmute and ask your question.
Hi, thanks for taking the question, and congrats on the data here. maybe just first on the pivotal trial, you'll enroll both mantle cell and DLBCL patients, and will you stratify them, Francesco?
Our lead indication for the first pivotal trial will be post-CAR T large B-cell lymphoma. I alluded to, though, in light of our data in mantle cell, which are quite interesting, we will consider mantle cell for an indication expansion opportunity. You know, it's a small indication, but it's very compelling to us.
Got it. Okay, that makes sense to me. Can you comment on outpatient administration with the drug?
Yeah.
Are you planning on looking into that, or is there a possibility?
Yeah, it's early days, and you know, when you, when you see the lower incidence of CRS and ICANS, this certainly opens the potential for outpatient settings. Really, that's something that we expect to explore in the future, in the upcoming studies.
Okay, great. Can you comment just on, have you seen any manufacturing failures or, you know, anything of the sort? I know that you kind of manufacture ahead of time, but maybe if you could just highlight just how the manufacturing has gone thus far in the trial.
Yeah, absolutely. We have two CDMOs that we're working with. They manufacture on an ongoing basis. You know, every now and then, you have a manufacturing failure for different reasons. It can be that, you know, something broke during the manufacturing, but overall, we have the same release testing and potency testing from all the manufacturing, and we continue to supply for the studies.
Great. Thanks for taking my questions, and congrats once again.
Absolutely. Thank you.
Our next question comes from Soumit Roy, from Jones Trading. You may unmute your line to ask your question. For phone connections, star six will allow you to unmute.
Hi, everyone. Thank you for taking the question, and congrats on all the progress. I'm trying to focus on the dose level for both in the CAR T-naive or CAR T relapse patient. Is there, specific to the DLBCL patients, that is not showing a longer term durability of response, can you characterize a little bit, like, high tumor burden or too many lines of therapy? The MCL patient seems to be reacting much better to the drug. Any thoughts would be appreciated.
Let me start, and Francesco will expand here. First of all, we're very confident in DL4. The reason is, again, you step back, it's very small, it's very easy to go into, you know, very few patients and jump to a conclusion based on this etiology or that etiology. Bottom line, DL4 was the dose level where we enrolled the highest number of patients, when you step back, it's four median lines of therapies, 38% of the patients were post-CAR T. You look at the CR rate, it's about 63%. You look at the six-month CR rate, it's 25%. You look at the post-autologous CAR T, it's 33%.
I think probably even more important, even as, or I want to say as important, when you look at the exposure, you see that the Cmax of ADI-001 at DL4, is about 10-25 higher compared to a DL3 or DL3 x 2. When you look at day 28, persistence is about 100-fold higher than DL3, so it's a much higher dose. Regarding once you start to dissect, indeed, you see the data there for LBCL a little on the lower side, but we believe it's smaller, and the big picture is that this seems to be the best dose level, and should play out very well in the coming study.
Got it. The second question on any color from the FDA meeting, when they are deciding on the primary endpoint to be the complete response, that's the three-month complete response, or did they say for an accelerated approval, they would like to see three-month or six-month CR?
No. No. The endpoint is complete response, whenever it happens. When you submit the BLA, you just want to show six months follow-up for the FDA. That's all. As you know, our CRs are very, very quick, so we would expect that the CRs, for the most part, will come at day 28, but there might be a few delays.
Okay. Thank you for taking the questions, and congrats again.
Absolutely. Thank you, Soumit.
We have no further questions at this time. I will hand the call back to Chen.
Well, thank you all for joining us today. We appreciate your support, and have a wonderful evening. Goodbye.