CRISPR Therapeutics AG (CRSP) Earnings Call Transcript & Summary

Good morning, and welcome, ladies and gentlemen, to the CRISPR Therapeutics Clinical Update Conference Call. At this time, I would like to inform you that this conference call is being recorded. [Operator Instructions] At the request of the company, we will open up the call for a brief question-and-answer period at the end of the presentation. I would like to introduce Susan Kim, CRISPR Therapeutics' Vice President of Investor Relations and Corporate Communications. Please go ahead.

Good morning, and thank you for joining us as we report results from the CARBON trial, an ongoing Phase I study of CTX110, a healthy donor-derived, gene-edited allogeneic CAR-T therapy for the treatment of CD19+ B-cell malignancies. We recommend that you access the webcast slides on our website as you listen to this call. This conference call is being recorded, and a replay will be able on our website. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy and safety of our product candidates, our research and development plans, regulatory plans and our plans to present or report additional data. These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve risks and uncertainties that may cause the actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the SEC, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date. The company disclaims any obligation to update such statements. Joining me this morning are Sam Kulkarni, our Chief Executive Officer; Ewelina Morawa, our Vice President of Clinical Development; Dr. Joe McGuirk, Professor of Medicine and Division Director of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Medical Center and one of the investigators on the study; and Tony Ho, our Head of Research and Development. With that, I'm pleased to turn the call over to Sam Kulkarni, who will make some introductory remarks.

Thank you, Susie. Good morning, and thank you all for joining us today. Earlier this morning, we reported the first clinical results from our Phase I CARBON trial of CTX110 for the treatment of B-cell malignancies. We are proud to share this data just a few days after our scientific founder, Dr. Emmanuelle Charpentier, was awarded the Nobel Prize in Chemistry for the development of CRISPR/Cas9 as a method for genome editing, along with the collaborator, Dr. Jennifer Doudna. Over the past 5 years, we have made tremendous progress in building the leading CRISPR company with 4 clinical programs, over 300 employees and over $1 billion in cash balance. In 2019, we were the first to demonstrate the power of CRISPR gene editing in patients with rare diseases with our lead program, CTX001, which we believe could provide a functional cure for patients suffering from sickle cell disease and beta thalassemia. Building beyond CTX001, we have advanced 3 gene-edited allogeneic CAR-T programs into the clinic in just 4 years, the first of which we will talk more about today. We could not have accomplished all of this without the right team. We have an incredible group of people at CRISPR, and together, we have created a sustainable innovation engine to develop transformative medicines using our gene editing platform. Today, we are excited to present early data that suggests CRISPR gene editing can go beyond rare genetic diseases and have transformative effect on more prevalent serious diseases like cancer. We initiated our efforts in oncology based on the belief that multiplex gene editing, which CRISPR enables to a greater extent than earlier technologies, will be essential to capturing the full promise of cell therapies in oncology. Current autologous CAR-T therapies have shown this promise, but much room for improvement remains. Allogeneic CAR-T, in which the T cells from a healthy donor are used as a starting material instead of a patient's own cells, could overcome many of the challenges of the first generation of CAR-T therapies. The advantages of allogeneic CAR-T include: immediate dosing, ability to redose, more consistent product attributes and more scalable manufacturing, ultimately allowing a much broader patient population to benefit from these therapies. We believe that, over time, allogeneic therapies represent a whole new class of medicines that can become the first line of defense in the fight against cancer. Creating a safe and effective allogeneic CAR-T therapy requires the editing of multiple genes within the T cell simultaneously and at high efficiency, a task for which CRISPR is ideally suited. To create CTX110, we make 3 simultaneous edits to the genome of healthy donor T cells that are designed to avoid Graft-vs-Host disease, target the CAR-T cells to the tumor and evade a patient's immune system. To our knowledge, we are the first company to test the beta2M knockout strategy as a means of allowing allogeneic persistence without the need for more toxic pre-conditioning regimens. I will now turn the call over to Dr. Ewelina Morawa, our Vice President of Clinical Development; and Dr. Joe McGuirk, Professor of Medicine at the Kansas University Medical Center, who will go through a presentation of initial data from the CARBON trial.

Thank you, Sam. Dose escalation of CTX110 is being performed in the CARBON trial, which is currently open to enrollment globally at 7 participating institutions on 3 continents. CARBON is enrolling adult patients with relapsed or refractory large B-cell non-Hodgkin's lymphoma who have failed at least 2 lines of therapy. Patients who have received prior autologous CAR-T cell therapy are not eligible. Patients received 3 days of lymphodepleting chemotherapy, consisting of fludarabine at 30 milligrams per meter squared and cyclophosphamide at 500 milligrams per meter square, followed by CTX110 infusion. Some patients have completed screening in as few as 3 days. And all patients began LD chemotherapy within a median of 2 days of enrollment. This time line is possible because there's no need for apheresis or bridging chemotherapy on this trial, and CTX110 is available at the site before a patient is enrolled. The primary objective of CARBON is to evaluate the safety and efficacy of escalating doses of CTX110. After a dose of CTX110 is determined, the trial will proceed seamlessly into a potentially registrational, single-arm efficacy expansion cohort. As of September 28, 2020, 12 patients have been enrolled in the study and all have received CTX110. Dose escalation began at 30 million CAR+ T cells, or Dose Level 1, and escalated in approximately two- or threefold increments to the highest dose of 600 million CAR+ T cells, which is Dose Level 4. At each completed dose level, 2 lots of CTX110 manufactured from different healthy donors were used. No DLTs were observed in Dose Levels 1, 2 or 3. After the initial cohort of 3 patients were treated at Dose Level 3, the encouraging anti-tumor activity led us to enroll additional patients into both Dose Level 3 and Dose Level 4 cohorts simultaneously. Eleven patients have had at least 28 days of post-treatment follow-up and are included in the safety and efficacy analyses presented on the following slides. This study continues to enroll currently. This table summarizes the baseline characteristics for patients enrolled in CARBON across the 4 dose levels. These patient characteristics are consistent with those and other clinical trials evaluating autologous or allogeneic CD19-directed CAR-T therapy. All but 1 patient had diffused large B-cell lymphoma or transformed follicular lymphoma. All patients were heavily pretreated, having received at least 2 lines of therapy, including 4 patients with prior autologous transplant. The majority of patients had advanced-state lymphoma and were refractory to their last line of therapy before entering the study. The median time from less therapy to the start of LD chemotherapy for all 11 patients was 1.5 to 8 months. Early evidence of dose-dependent responses were seen with CTX110. Efficacy assessment was performed by centralized independent radiological review according to the 2014 Lugano response criteria. Dose escalation began conservatively at a dose of 30 million CAR+ T cells, which is approximately tenfold lower than the approved doses for commercial CD19-directed CAR-T products. Although Dose Level 1 was determined to be subefficacious, complete responses were obtained at Dose Levels 2, 3 and 4. As the dose increased, so did the percentage of patients who achieved a complete response to treatment. At Dose Level 3, 2 of the 4 patients had a complete response. To date, all of the objective responses in the study have been complete responses and were seen at the first imaging assessment at 28 days post-CTX110 infusion. Complete responses were achieved in 2 patients with diffuse large B-cell lymphoma and 2 patients with transformed follicular lymphoma as well as in patients who are primary refractory and who had relapsed after autologous stem cell transplant. This waterfall plot shows the best percentage change in tumor size for patients treated with CTX110 across the 4 dose levels. The color on the bars reflects the dose level at which the patient was treated. You can see that 7 of the 8 patients treated at Dose Level 2 or above shows evidence of decreasing tumor size and that the deeper responses are associated with higher doses of CTX110. The 4 patients with complete responses had complete resolution of extranodal disease, normalization of all nodal disease to 1.5 centimeter or smaller and a Deauville score of 2 or lower. Additionally, one of the patients with a complete response achieved complete clearance of 30% lymphoblasts in bone marrow that were seen prior to CTX110 infusion. Two of the patients highlighted will be discussed in more detail in case studies. This point-line plot shows the post-CTX110 treatment response and follow-up. New follow-up time for the 11 patients was 1.8 months. All patients treated at Dose Level 2 or 3 who had a complete response at day 28 remained in CR at the 3-month assessment. The patient that's treated at Dose Level 2 who achieved a complete response was found to have recurrence of disease on imaging approximately 5.75 months after CTX110 infusion. That patient remains otherwise clinically well and is planned to be redosed at Dose Level 3. The patient at Dose Level 4 that achieved a complete response at month 1 has subsequently died due to an adverse event after data cutoff and will be discussed in more detail later. This table summarizes the safety data for the 10 patients treated at Dose Level 3 and below that occurred following CTX110 infusion. First, there have been no cases of GvHD despite the high HLA-mismatch between CAR-T donors and patients. Second, no infusion reactions to either lymphodepleting chemotherapy or CTX110 have occurred. Focusing on treatment-emergent adverse events of special interest, 3 patients treated with CTX110 have experienced a total of 4 events of CRS. Two of these events were Grade 1 CRS per ASTCT criteria and required no intervention. Two events are Grade 2 CRS and resolved with the use of tocilizumab. Grade 2 ICANS occurred in 1 patient and improved within 24 hours of steroid administration. Two additional treatment-emergent serious adverse events have occurred that were not associated with disease progression. There were 1 event of periorbital cellulitis and 1 event of febrile neutropenia. In summary, these preliminary data suggests an acceptable safety profile at Dose Level 3 and below with no events of Graft-vs-Host Disease or Grade 3 or higher of CRS or ICANS. The 1 patient recently treated at Dose Level 4 was a 73-year-old man with transformed follicular lymphoma who relapsed following autologous stem cell transplant. Lymphodepletion and CTX110 infusion were uneventful. Five days after CTX110 infusion, the patient experienced Grade 2 CRS that responded to tocilizumab. On day 25, the patient underwent his 1-month scan in response to the incomplete response. After the 1-month scan, the clinical course became complicated. The patient was admitted for febrile neutropenia on day 26. And shortly after, on day 28, began to have short-term memory loss and confusion. The symptoms eventually progressed to significant optimization of the required intubation. The patient underwent several diagnostic procedures, including a lumbar puncture and brain MRI. He was initially treated for ICANS with high-dose steroids, anakinra and intrathecal chemotherapy without any improvement. He was later found to have reactivation of HHV-6 and HHV-6 encephalitis. Retrospective evaluation of the patient's blood collected at screening show that he was HHV-6 IgG positive, consistent with prior HHV-6 infection. The diagnosis of HHV-6 encephalitis was based on CSF examination that revealed a high HHV-6 titer of approximately 650,000 copies per ml. Subsequently, he began a course of antiviral therapy, which continued for 13 days. However, in view of the patient's status and at the request of the patient's family, the decision was made to withdraw supportive care and the patient unfortunately died at day 52 post-CTX110 infusion. We believe the exact ideology of neurological deterioration is likely due to a combination of HHV-6 reactivation in an immunocompromised patient that led to HHV-6 encephalitis and potentially ICANS. In discussion with the Safety Review Committee, we have decided to pause enrollment to Dose Level 4 while we gather additional experience with CTX110 at Dose Level 3. On this slide, we present the emerging pharmacokinetic profile of CTX110 in Dose Level 2 through 4. CTX110 cells were detected in all patients as measured by PCR. Following CTX110 infusion, there was a transient decline in CTX110, which can be attributed to distribution of cells into compartments. Peak expansion typically occurred approximately 1 to 2 weeks after administration. We are encouraged that using standard doses of lymphodepleting chemotherapy creates a window for CTX110 expansion. Finally, we have measured CTX110 as late as day 180. We continue to generate and analyze these correlative data and will provide further updates at a future scientific meeting. And with that, I would like to turn the call over to Dr. McGuirk, who will present case studies on 2 of the patients treated with CTX110.

Thank you, Ewelina. This first case highlights the challenges of early drug development in oncology and the importance of learning everything you can from each patient. This patient of mine is a 62-year-old male with transformed follicular lymphoma who previously received 2 lines of therapy, including R-CHOP and dose-adjusted R-EPOCH. The patient relapsed, and we enrolled him on this trial and treated at Dose Level 3. He had an uncomplicated course after CTX110 infusion, did not have any CRS, ICANS or infections. The patient had a clear response to CTX110 on physical exam, with decreasing size of lymph nodes. In fact, I can see this patient's lymph nodes from across the exam room. And at day 8, following CTX110 infusion, I could no longer see them or palpate them. The patient similarly could no longer feel these enlarged lymph nodes on self-examination. We were very hopeful for the 1-month imaging based on the clinical findings. However, although on the CT scan there was a decrease in size of the lymph nodes, on PET, the lymph nodes remained FDG avid. Per Lugano criteria, this would be considered stable disease. At that point, we decided to obtain a lymph node biopsy and we compared it to the results prior to CTX110 infusion. As you can see, while at screening, the expression of CD19 was positive per immunohistochemistry. It was CD19 negative by immunohistochemistry when rebiopsied. This suggests that the CAR-T cells had cleared the CD19-positive population and only the CD19 negative remained and gave rise to subsequent persistence of disease. While disappointing, this case speaks to the on-target activity of CTX110 and could potentially be addressed by future iterations of CAR-T products with the CRISPR/Cas9 editing technology. We will be pursuing allogeneic stem cell transplant for this patient. I'm excited to present the second case study of a 62-year-old woman who is diagnosed with diffuse large B-cell lymphoma. She had initially received 6 cycles of R-CHOP, exceeding only a partial response. She then received RICE [ DHAP ] with chemotherapy. And similarly, it is only a partial response before receiving busulfan-cyclophosphamide conditioning, followed by an autologous stem cell transplant. This year, she relapsed and was referred to our center for further management. She presented with an approximately 6-centimeter mesenteric lymph node mass that was Deauville 5 PET scan at baseline, who is confirmed to be diffuse large B-cell lymphoma on biopsy. She was enrolled on this trial and treated at Dose Level 3, hit an uncomplicated course without any CRS, ICANS or infection. I'm excited to report that at 1-month assessment, there was no evidence of lymphoma by either PET or CT. The subject is clinically very well. I just saw her about a month ago for a 3-month follow-up, and she remains in complete remission with no toxicity.

Thank you, Dr. McGuirk. We are very encouraged by this initial clinical data for our CTX110 program, which represents the first report of complete responses achieved with a CRISPR-edited allogeneic cell therapy engineered for immune patients. We see initial evidence of dose-dependent anti-tumor activity with complete responses achieved in 4 patients. While we have seen early signs of durability, we will continue to monitor the ongoing complete responses. We see an acceptable safety profile at Dose Level 3 and below, with no GvHD and low grade and rates of CRS and ICANS. Furthermore, no additional lymphodepleting agents beyond a standard [ fluda ] regimen were required to achieve these responses. Finally, the advantage of the allogeneic approach are already becoming evident, with 100% of enrolled patients receiving treatment without need for bridging chemotherapy or worry about manufacturing failures. Furthermore, we observed responses across multiple lots of CTX110 manufactured from different donors, suggesting that, as anticipated, this approach can't fail benefit as many patients as possible. In all, we believe this data validates our CRISPR-edited allogeneic CAR-T approach and makes us excited to progress CTX110 as well as CTX120, CTX130 and additional allogeneic CAR-T programs forward as rapidly as possible. To that end, we are moving full steam ahead on CTX110. We plan to proceed interim expansion cohort in the near term, following selection with an optimal dose. In addition, we have now included redosing as an option for patients who relapsed or do not achieve a complete response. And we have already redosed 1 patient. We believe that the ability to redose with CTX110 provides an additional advantage that will increase our ability to achieve durable complete responses in as many patients as possible. We continue to make rapid progress on CTX120 and CTX130, with dosing ongoing across trials in multiple myeloma, renal cell carcinoma and T- and B-cell lymphomas. We expect to release initial data for both programs next year. Finally, we continue to build our pipeline beyond CTX110, CTX120 and CTX130, which includes both novel targets and novel edits. And we plan to announce additional programs in 2021. When we initiated our allogeneic CAR-T efforts 4 years ago, we set out a concrete strategy: first, validate the allogeneic platform with proven targets; then expand from hematologic cancers into solid tumors; and finally, unlock the full potential of immuno-oncology cell therapy through CRISPR multiplex editing. Our I/O pipeline reflects that strategy. Today, we have presented initial data indicating that we have achieved our first step towards accomplishing this ambitious goal by validating our allogeneic platform in the clinic. We are looking forward to continuing to innovate novel CAR-T design and investigating them in the clinic with the aim of bringing multiple transformative off-the-shelf CAR-T therapies to patients. None of this will be possible without our investigators, site staff and, above all, the patients and their family who have had the courage to participate in this ground-breaking clinical research. We thank them for their undaunted efforts and bravery. We are now happy to take questions. Operator?

[Operator Instructions] We'll take our first question from Maury Raycroft of Jefferies.

Congrats on the updates. I just had a 1 2-part question. So I'm wondering if you can talk about whether you're seeing NK cell proliferation or activity? And is this related to CRS or any other safety observations? And for the Grade 2 ICANS or other SAEs, can you provide more specifics or comments on potential influence from baseline characteristics, including CNS involvement or number of immune cells in CSF at baseline? And can you mitigate for these issues going forward?

Yes. Thank you, Maury. We're quite excited to present these data today and very excited about the complete responses we're seeing. To your 2 questions on the pharmacokinetics and the NK cells as well as ICANS, we're collecting all sorts of information on these patients, whether they're cell proliferation of our CAR-Ts, what happens to the host immune system. And at the right medical meeting, we'll present all the data holistically. So you'll see more on that. We're very excited, though, the fact that our CAR-Ts persist for a very long time and can be detectable up to 180 days, which was one of the key hypotheses in making the beta2M edit. I think, as for the questions on the neurotoxicity, I'll turn it over to Ewelina to answer that question.

Yes. Thanks for the question. There aren't any specific characteristics that we have noticed, thus far, that potentially increase the risk of ICANS. In addition, the inclusion/exclusion criteria for our trials is very similar to what's been done with other autologous CAR-T cell trials, where ICANS has been seen as well.

Our next question is from Gena Wang of Barclays.

I also wanted to add my congratulations to the data. So I also have a few parts of the question. First, on the -- I wanted to confirm, I think I heard follicular lymphoma. I just wanted to confirm how many patients with follicular lymphoma versus the DLBCL, particularly in the Dose Level 2 through 3? And then also regarding more the technical parts. So I wanted to ask you regarding the co-stimulatory domain, was that CD28 or 4-1BB? And then lastly, very quickly on the IP, do you have IP on beta2M knockout technology?

Yes. Thank you, Gena. And I'll start with your last question first, which is we've filed extensively in terms of IP on our CAR-T constructs, whether it's the beta2M edit or other aspects. CRISPR gene editing is -- just makes better quality T cells and CAR-Ts. They're healthier and more robust in terms of cytotoxicity. So that's something that we filed extensively on, including the whole construct. At this point, we have not disclosed what the co-stim domain is, whether it's CD28 or 4-1BB. But I think we, again, protect the overall construct with IP with many different filings that you'll see over time. I think to your first question on the patient mix, I think we've provided in our press release. What we said is we see complete responses in both DLBCL and transformed follicular. And I just want to emphasize transformed follicular aspect. We're looking at very serious follicular patients, not indolent follicular patients here. And we see complete responses in both DLBCL and transformed follicular.

We'll take our next question from Geoff Meacham of Bank of America.

This is Greg Harrison on for Geoff. So it looks like the complete response from the Dose Level 2 patient was about out to 6 months or so. Is that what you would also expect to see in the ongoing CRS in Dose Level 3? Or is there any reason you could believe that they might have a longer duration of response?

Yes. Thank you, Greg. Our hope is that we would see long durable responses. Let me just remind you and contextualize the fact that durability ultimately is a function of both how deep the responses are and the persistence of our CAR-Ts. The fact that we saw such a long response at DL2, which is a suboptimal dose, gives us great confidence that when we see deeper responses at DL3 and above, we eventually should translate into durability in the clinic. That's something we're obviously monitoring closely as we enroll more patients and we progress in the trial. But I think what we see so far gives us great confidence.

The next question is from Salveen Richter of Goldman Sachs.

Just given the small ends in each of the dose cohorts, can you just discuss your work on the Ford here to better determine dose response and additional levers that you'll play with, like repeat dosing or testing post-autologous CAR-T? And then if you could give us more details on 2 items. One is on the patient that was redosed, what triggered that? And then what dose is patient 12 on?

Thank you, Salveen. I'll start with some -- with a top line answer, and then I'll ask Ewelina to provide more details here. I think the end is small, but I think it's very encouraging. I think of the 4 patients that we've dosed at Dose Level 3 and the patient at Dose Level 4, I think seeing the complete response was -- in these patients, whether they're DLBCL or tFL, or whether they're primary refractory or relapsed gives us great confidence. And I think this is a very important update for the trial as we look to expand the number of sites, as we look to bring more patients in. At this point, I think the way the trials are designed, I think we want to complete the dose escalation to determine the optimal dose and then expand rapidly with the hope that, that can become the registrational trial, assuming the data continue to hold. I think we haven't said exactly what that expansion dose is going to be, and we will continue to update The Street as we go along in the trial. But at this point, I think we're full steam ahead on this trial once we complete the dose response, and we want to get into expansion. I think to the second question around the redosing of that patient, I will turn it over to Ewelina.

Thanks, Sam. So as Sam mentioned, our hope, and we're incredibly encouraged by what we're seeing right now, is that redosing may not be necessary, but it's an option on our trial. And we provide this option to patients that have either relapsed or patients that have had some kind of a response, but not full complete remission. And the 12th patient dose was on Dose Level 3.

Our next question is from Ted Tenthoff of Piper Sandler.

Thank you very much on a positive update. Are those learnings from this study that you think imply to the other CAR-Ts? And how do you see this as building the foundation to start to do multiplex with respect to additional target?

Yes. Thank you, Ted, and I'll start. And then I'll ask Tony to make some comments as well. But I think this is very exciting for the company and for the portfolio. I think -- I'll just remind folks, I think, as a company, we only were -- have been around for 5 years. It's a brick-and-mortars company. And within that time, we came up with the CTX001 program, disclosed that data last year, which can be transformative. And then in parallel, have developed a host of 3 different CAR-Ts, which are all in clinical trials right now and enrolling rapidly. I think we're moving along on CTX120, which is targeted towards BCMA; and CTX130, which is targeted towards CD70. So I think the notion that we're seeing very encouraging data and responses at -- with CTX110 does give us great confidence in what we may see with CTX120 and CTX130. We will have data updates for those 2 programs next year as well as additional data on CTX110. And I think that, that one give us confidence that these initial-version products could be transformative and have an important place in the lines of treatment for these patients that have limited options. I think beyond that, I think the thesis always has been having the CRISPR tool and engine gives us tremendous ability to continue to innovate come and up with new generations of products, and our research team continues to work on that. Let me ask Tony to make a couple of comments on the continuing work and how we see this over the next 5, 10 years.

Sure. I think, and as you have seen, our initial data give us a lot of confidence. We saw sort of deep complete response in these patients. And in addition, we also see the persistence of our cell in both blood and the bone marrow out to day 180 really sort of validated our allogeneic immune-invasive platform. So we're very excited to sort of build on the chassis to add additional edit and also additional target. These could be edits that resist tumor microenvironment, [ they add caution ] to resistance and select targeting. And also we can build things that illicit immune -- endogenous immune response. So I think this is just a start, and we're looking forward to continue to build our platform.

Our next question is from Raju Prasad of William Blair.

Just a couple of questions on the cell product. Can you just disclose what the number of lots used to treat the patient? And any signs you're seeing kind of engraftment with regards to peak or durability in your responses? And then anything you can say on percent of the B2M knockout or knockdown would be helpful.

Thank you, Raju. I think what we did disclose in this presentation is that we've used multiple lots from healthy donors on our patients. I think one of the things we wanted to make sure was we are seeing effect in patients and responses regardless of the healthy donor lot that we're using more than one. And obviously, we take a lot of robust characterization to select healthy donor lots that we want for this manufacturing. But we have used multiple healthy donor lots to make these drug products, and we're seeing responses across multiple lots. So that's very encouraging. I think to the questions you're asking about the beta2M positive versus beta2M negative, I think that we will disclose that very important data. And as you can imagine, it's highly competitive data. I think the beta2M edit gives us a distinct advantage over other players in the allogeneic field. And we're filing IP on various aspects of it as we go along. We will disclose the data of how the cells behave with or without beta2M edits. But it's very encouraging, as Tony was saying, that we see these cells persist for a very long time. I think, finally, to your question on other NK parameters as well, I think we will be providing holistic data at the medical meeting where we show the comparison, the pharmacokinetics, et cetera.

Our next question is from Ben Burnett of Stifel.

Congrats on the data. I was wondering if you could provide any additional color on the expansion that you're seeing. And I guess are you seeing better expansion in patients who respond? And are you seeing better expansion at higher dose levels?

Yes. Let me turn that question over to Tony to respond. I think -- at a high level, I think -- Ben, and as I was telling Raju, I think we're going to have a holistic package on cell expansion and how that looks for the cell type versus responders or nonresponders. We haven't disclosed that information at this point. But I think we did show a chart showed the cell expansion chart. And you do see a curious expansion. In the first 7 to 10 days, you see a lot of the expansion happening. And I think a lot of the activity of the CAR-T is happening very early on. And that is an interesting profile for these allogeneic therapies. But let me turn it over to Tony and see if he has any additional comments to make. But the holistic data presentation will come at medical meetings.

Yes. Thank you, Sam. So certainly, we're still learning from these data. Most importantly, we saw CTX110 were detected in multiple time points all the way to day 180 in all patients. And following CTX110 infusion, there was a transient decline of CTX110, which can be attributed to the distribution of the cell to different compartments, including the tumor. Then we saw a peak expansion, as you have seen on the curve. It occurs for approximately 1 to 2 weeks after administration. We're encouraged to use that -- just using a standard doses of lymphodepleting chemotherapy and able to create a window for CTX110 expansion. And as Sam was saying, we will continue to analyze this data, and we'll provide further update in a scientific meeting.

Our next question is from Arlinda Lee, Canaccord Genuity.

Congratulations on the data. I had a couple of questions. [ If you can talk a little bit of the further investments you have ]. Has the FDA seen the ICANS data? Are they concerned about it? Have you seen anything in your 120 or 130 with regards to that? Or have you changed your protocols with regards to that? And then maybe for Dr. McGuirk, how do you see CTX110, is it as bridge to another treatment? Or are you looking for a greater [indiscernible] (00:47:26)

Thank you, Arlinda. Let me start with the second part of your question first and turn it over to Dr. McGuirk on how he sees CTX110 in the treatment paradigm.

No, I -- we're looking toward CTX110 as being a definitive therapy, not as a bridge to a subsequent therapy. We, from a clinical perspective, in a program that has done a lot of cell therapy, now in clinical trials and in the commercial space, we see this as the next generation of therapies for our patients with specific advantages to these constructs. And that it's, we think, importantly a more fit population of T cells that have not failed to control tumor growth in the first place because they're not from the patient. And the therapy is readily available to our patient population. And we think, with the CRISPR edits that are very specific, we think it's a more physiologically active and less likely to become exhausted population of cells that will persist, as you've heard from the scientists at CRISPR, discussed here just a moment ago. So we're very much encouraged with the signals that we're seeing in terms of both efficacy. And these early-dose cohorts are already seeing complete responses, including some of our patients that we -- one of whom we've discussed today, has a durable complete response. And our experience with the autologous constructs is that majority of patients who go into complete remission or staying in complete remission long term, we expect -- and I'll just extrapolate, we expect that we're going to see the same thing here. And so we're greatly encouraged about the potential here. We really think, again, this is the next generation. This is the future for our patients, that's why we're participating in this important study.

Thank you, Dr. McGuirk. And Arlinda, to the second part of your question around the ICANS, I think we've -- Ewelina disclosed the course of the clinical complications and the course of treatment for that patient. Obviously, safety is our top priority. And we work closely with regulators, our DSMB and our Safety Review Committee to make the right decisions. I think we've all looked at the case. We're comfortable moving forward in the trial, and we continue to enroll patients at Dose Level 3.

And we'll take our next question from Joon Lee of Truist Securities.

Congrats on the data as well. For one of the questions (sic) [ patients ] in Dose Level 2 who may have relapsed, is that the patient who got redosed? And on the safety side, were the different doses associated with different levels of AEs?

Let me -- yes, let me turn it over to Ewelina to answer that question.

Yes. So thanks for the question. So the patient in Dose Level 2 is not the patient that was redosed. I previously mentioned to one of your colleagues that -- we previously mentioned that the patient that was redosed with Dose Level 3. In terms of the safety profile, we are not seeing any sort of a correlation based on dose and safety at this moment. I think Dose Level 4 was an unfortunate case that occurred and had very complicated neurological course that was both the result of lymphodepletion, HHV-6 encephalitis and ICANS. And as Sam mentioned, so we're going to continue evaluating as we treat patients. And I just wanted to point out that all the patients treated at Dose Level 3 had no CRS and no ICANS. So very -- we're continuing to hope that, that continues, and we'll continue monitoring very closely.

Yes. Thank you, Ewelina. And I will just add, Joon, to your questions. You heard from Dr. McGuirk. I really think, as we look at the early responses here, these are -- looks like early autologous CAR-T data. And I think with all the benefits you have with an allogeneic therapy, I think you have a great chance of leapfrogging some of the autologous therapies and build the chassis for the next generation of allogeneic cell therapies, which can have impact on these patients that have very limited options. I think on the safety as well, I think we see a relatively acceptable safety profile. And we're full steam ahead on these trials. And we look forward to providing you more updates as we go forward in the trial on this one as well as providing you updates on CTX120 and CTX130.

Due to brevity of time, this does conclude our question-and-answer session as well as our conference call for this morning. You may now disconnect your lines. And everyone, have a good day.