Hello. Thank you for standing by, and welcome to Allogene Therapeutics ASH 2021 Conference Call. At this time, all participants are in a listen only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star one on your telephone. If you require any further assistance, please press star zero. Please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.
Thank you, operator, and welcome to all who have joined this call. Earlier today, Allogene issued two press releases discussing data on our ALPHA, ALPHA2 and UNIVERSAL trials presented at this year's American Society of Hematology annual meeting in Atlanta. These press releases, today's webcast and corresponding slides are available on our website. We're looking forward to discussing the latest results from these programs as we progress toward our goal of making AlloCAR T therapy a reality for cancer patients. On the call today to review the data presented at ASH are Dr. David Chang, President and Chief Executive Officer, and Dr. Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer. Dr. Eric Schmidt, Chief Financial Officer, will join David and Rafael for the Q&A portion of this call. During today's call, we'll be making certain forward-looking statements.
These may include statements regarding the timing and ability to advance our clinical trials, including our ability to resolve the clinical hold on our clinical trials and advance to a pivotal trial with ALLO-501A and clinical data, among other things. These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve a number of risks and uncertainties that may cause 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 Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, and the company disclaims any obligation to update such statements. I'll now turn the call over to David.
Thank you, Christine. We are excited to be presenting updated clinical results here at ASH and perhaps even more excited to have our clinical team on site in Atlanta to see many of our investigators in our trials as we prepare for an eventful 2022. As we look back over the past year, we are very proud of all we have accomplished, not just for Allogene as a company, but also for patients in need of better therapeutic options. We feel strongly that the work we are doing, including the trail that we are blazing to better assess and understand all aspects of our AlloCAR T products, will pave the way for a bright future for allogeneic cell therapy.
Our team takes pride in this work as it is important for all those who have chosen to dedicate their livelihood to bringing the next generation of cell therapy products to patients. As we continue to push the field forward, our confidence in our platform is based on what we have already accomplished in our clinical trials. On slide three, you will see that more than 130 patients have been treated with our AlloCAR T product candidates. We continue to have a strong cash balance, which has allowed us to build and operationalize our CellForge One manufacturing facility in support of a pivotal trial, advance our research capability and pre-clinical pipeline, and strengthen our corporate infrastructure as we look ahead towards another year of clinical progress. As illustrated on slide four, the automobile began to make its presence in society in the early 1900s.
Early models were quite functional. Sears even sold them out of their iconic catalog. Assessing a new automobile was difficult. Obtaining one required waiting at the train depot, uncrating the vehicle and assembling it on your own. A few years later, Ford's Model T changed everything. It was easier to drive, more powerful, and most famously produced at scale on an assembly line. It rolled out of a factory ready to drive. Ford didn't invent the automobile or make it fashionable, but by making it accessible, Ford changed how the world thought about cars. Oncology is on the cusp of a similar transformation. Autologous CAR T therapies were a major step forward for patients with late-stage blood cancers. Several innovative new therapies that leverage an individual's own T cells to defeat cancer are changing the game, but they rely on bespoke manufacturing process that is incompatible with scale.
Much like the customers who purchased the first automobiles, patients must wait. Wait to secure a manufacturing slot, wait for harvesting of cells, wait to see if cell engineering is successful, and finally wait for their cells to return to the clinic and reinfused. The next great leap will be technology that can democratize access to cell therapy the way the Model T did, making it easier for patients to access potentially life-changing therapy. This has always been our goal at Allogene, and we believe the data we are sharing today is demonstrating that this goal is closer to a reality, with allogeneic cell therapy having the potential to revolutionize the field. Slide five is a slide we presented to you in May at our CD19 forum.
It summarizes the market research that helped to inform how we progressed our phase I trials, including areas we wanted to better understand as we prepare for a pivotal trial, our assessment of the unique attributes of an Allogene XL product, including how we might be positioned to expand the market, lead the potential benefits of consolidated dosing, and understand the importance of timely treatment for patients. The relative level of importance physicians place upon key product attributes range from efficacy, safety, dosing schedule, and delivery, are depicted here as you look at slide six. As we interrogate the levers at our disposal to fully optimize a product candidate like ALLO-501A, it became clear that efficacy parameters were the primary importance to physicians as they evaluated various NHL therapies. This included both the ability to achieve a complete response as well as maintain that response.
While efficacy and durability are the most important considerations, other factors, including some that are inherently favorable or unique to our allogeneic approach, are highly influential. These include the likelihood that a patient receives the prescribed treatment, the time to treatment, and other logistical considerations. Slide seven depicts the balance we have been aiming to achieve in our trials. Physicians have been clear in what they want in terms of an ideal product profile for an NHL. They seek an off-the-shelf option with durable efficacy and favorable safety that can be delivered quickly to all eligible patients.
We believe the data Rafael will review with you today as it relates to the ALPHA trials and the updated data for the UNIVERSAL trial demonstrates that we are on the right track in terms of achieving that optimal balance between efficacy, specifically complete responses that are durable and safety and convenience to ensure that all patients are able to access treatment. This is why we are focused and committed on our work to resolve the clinical hold on our trials and remain confident that in our ability to do so. I will now turn the call over to Rafael to review the data presented today at ASH.
Thank you, David. I'm excited to walk everyone through the latest clinical results that are being presented at the ASH annual meeting today. We'll start first with the ALPHA trials. These data sets are highly complementary to one another, as both trials were designed to sequentially understand the key levers at our disposal for optimizing cell therapy, including cell dose, lymphodepletion, and consolidation therapy. We started exploration with ALLO-501, where patient follow-up times are a bit more mature, and then transitioned to our potential commercial candidate, ALLO-501A. As you view the results, you will see a great deal of consistency across the trials, which fosters much confidence in their conclusions. Following the ALPHA studies, I will walk you through the UNIVERSAL data, and we will end with a Q&A session. This morning, Dr.
Blatakis from the University of Miami presented data from our phase I ALPHA2 trial evaluating ALLO-501A in patients with relapsed refractory large B-cell lymphoma. Later this evening, Dr. Satya Neelapu from MD Anderson Cancer Center will present a poster containing data from our phase I ALPHA trial evaluating ALLO-501 in patients with relapsed refractory large B-cell lymphoma or follicular lymphoma. Slide nine provides a brief overview of both dosing regimens and enrollment. Perhaps most important on this slide, and in the box area, is that more than 97% of all patients who were enrolled in the trials were able to initiate treatment with a median time from enrollment to initiation being five days in ALPHA and just two days in ALPHA2. This was not unexpected given the off-the-shelf nature of our products, but nonetheless gratifying to observe.
In both trials, patients received lymphodepletion consisting of 30 milligrams of fludarabine for three days, 300 milligrams of cyclophosphamide for three days, and various doses of ALLO-647, followed by escalating doses of ALLO-501 or ALLO-501A. In the consolidation dosing phase of the studies, two different consolidation regimens were explored. Consolidation 1 used the standard cyclophosphamide dosing of 300 milligrams prior to first cell infusion. Consolidation two explored a higher cyclophosphamide dose of 500 milligrams. Patients with stable disease or better at day 28 were eligible to receive a chemotherapy-free lymphodepletion regimen consisting of ALLO-647 only, followed by a second dose of 120 million AlloCAR T cells. Slide 10 illustrates the consistent and manageable safety profile of our products.
In both trials, there were no dose-limiting toxicities or all cases of GvHD and minimal observations of grade three immune effector cell-associated neurotoxicity syndrome known as ICANS or grade three cytokine release syndrome. Of note, grade three+ infection rates were observed at a rate similar to that seen in autologous CAR T trials. In ALPHA, there were five treatment-emergent deaths in the absence of disease progression, all of which have been previously reported. In ALPHA2, there were no treatment-emergent deaths. As you know, we reported earlier on a single case of chromosomal abnormality observed in the setting of severe pancytopenia in a patient in ALPHA2 treated with consolidation two, which has resulted in a clinical hold on our trials. Overall, both ALLO-501 and ALLO-501A have been well tolerated.
Perhaps most critical is that consolidation arm in ALPHA2 and in the ALLO-501A was associated with a superior safety profile across all metrics, including lower rates of cytopenias and infections. This may reflect our ability to provide the second dose of AlloCAR T cells following lymphodepletion that is chemotherapy-free, a key differentiating feature of our platform. These safety results lay the groundwork for AlloCAR T to potentially be deployed in an outpatient setting, a paradigm that could radically transform the use of CAR T therapies. On slide 11, you can see that across the board, we are observing complete response rates on par with approved autologous CAR T therapies. In ALPHA, the overall response rate in autologous CAR T-naïve patients was 75%, and the complete response rate was 53%, with the longest CR ongoing at 18 months.
Consolidation dosing demonstrated similar safety and improved efficacy versus a single higher cell dose with an 82% ORR and a 64% CR rate in 11 patients treated to date. Similarly, in ALPHA2, roughly half of the patients responded, and 28% had a CR. With the consolidation cohort of ALPHA2, 44% had a CR. Response rates in the consolidation arm are especially encouraging given the poor baseline characteristics of the patients treated with this regimen. 62% of the patients had stage four disease, and 38% had an IPI score of 4. The longest ongoing CR is over 15 months, and the longest ongoing CRs in the consolidation cohort are more than nine months.
Slide 12 demonstrates why we believe consolidation one strikes an optimal balance between efficacy, in particular CR rates that are on the higher end of the range of approved autologous therapies, and the safety profile discussed earlier, which lends itself to outpatient treatment. Based on the clinical profile of consolidation one in both ALPHA and ALPHA2, we plan to initiate a phase II pivotal trial in relapsed/refractory large B-cell lymphoma utilizing this dosing regimen. As noted in the last slide, we continue to see ongoing and durable responses in patients dosed with ALLO-501. This tumor plot on slide 13 breaks down in detail the responses in the ALPHA trial. Among the 21 follicular lymphoma patients and 11 large B-cell lymphoma patients who were autologous CAR T-naïve, 33% and 36% respectively achieved a CR at 6 months.
While follow-up times with consolidation dosing are shorter, the early data are encouraging. All responding follicular lymphoma and large B-cell lymphoma patients remain in remission, with the longest ongoing response being at more than seven months. Slide 14 indicates that the initial durability results from the ALPHA2 trials are mimicking those of ALPHA. six out of seven patients who achieved a CR remain in remission, with four of those patients having between nine and 15 months of follow-up. Additionally, three of the PRs in the consolidation one cohort have converted to CRs. Slide 15 depicts a closer look at the large B-cell lymphoma patients treated in both ALPHA and ALPHA2 who achieved a CR. Importantly, with the exception of the 1 patient previously noted who died of an unrelated cardiac event, all patients who achieved a CR at month six remain in complete remission.
We believe these results are compelling and similar to what has been observed in the autologous setting. They indicate that response to our therapies at six months may be a similarly good predictor of longer-term benefit. We're optimistic that as these data mature, they will support the possibility of large B-cell lymphoma patients achieving functional cures following treatment with ALLO-501A. Slide 16 shows data from ALPHA2 demonstrating that patients treated with a consolidation regimen can experience cell expansion and persistence after the second AlloCAR T dose. In other words, ALLO-647, along with our Flu/Cy chemotherapy, was sufficient to enable expansion of the second dose of CAR T cells. This is a critical and differentiated aspect of our platform with two potential benefits. One, we can spare patients the adverse events of a second course of chemotherapy.
Two, as the graph indicates, by avoiding the use of Flu/Cy, we prevent eradication of cells from the first dose of AlloCAR T, allowing for ongoing antitumor activity, which we want to preserve. Now that I have walked you through the data, I want to take a few minutes on slide 17 to put our CD19 program into context. These results have demonstrated that an allogeneic CAR T therapy may be able to match the level of efficacy achieved by approved autologous CAR T therapies for patients with large B-cell lymphoma. The ALPHA trial delivered a complete response rate of 36% at six months in large B-cell lymphoma following a single infusion of ALLO-501. In ALPHA2, a 44% complete response rate was achieved with consolidation one. These CR rates fall well within the range of what has been reported by autologous therapies.
Assuming these results can be replicated in larger trials, we believe we could have a very competitive profile in terms of both depth and duration of response while providing the benefits inherent to an allogeneic product. Meanwhile, on the bottom of the slide, you can see how our adverse event profile stacks up relative to autologous therapies. The safety of our product candidates remains a relative strength, and given the favorable tolerability of single dosing in particular, treatment in the outpatient setting may be possible. Given the design parameters of ALPHA and ALPHA 2, we have been in an enviable position to fully explore multiple means to optimize the delivery of our allogeneic cell products. This is noted on slide 18. Not only will these results inform our future trials, they will also inform the field.
We have generated robust data sets and a solid understanding of the properties of allogeneic CAR T therapy in large B-cell lymphoma, including ways to optimize patient demographics, lymphodepletion, and cell dose and schedule to deliver an outcome for patients that achieves a promising combination of efficacy, safety, convenience, and access. We're pleased we have been able to generate these learnings in just over two years since our ALPHA trial begun. With the data from ALPHA and ALPHA2 continuing to validate the promise of our AlloCAR T products as a safe and durable alternative to approved autologous CAR T therapies, we are finalizing the phase II trial design based on input from the FDA. We expect to start such phase II study on ALLO-501A in 2022, subject to FDA approval and pending the lift of the clinical hold by the FDA.
Our other ASH data set was presented by Dr. Sham Mailankody of Memorial Sloan Kettering. This is an update from our phase I UNIVERSAL trial evaluating single-dose ALLO-715 in patients with relapsed/refractory multiple myeloma. UNIVERSAL is the first AlloCAR T study in multiple myeloma. We believe that the safety and efficacy data highlighted in the oral presentation this morning provides the first and still only proof of concept data for an AlloCAR T in this disease setting. Today, BCMA-directed cell therapies, including ABECMA, the first FDA-approved therapy, and several next-generation constructs, have shown remarkable efficacy. However, several logistical challenges, including supply constraints, may be limiting access. For many patients with multiple myeloma, time is of the essence, given the prospect of rapidly progressing disease.
Allogeneic treatment offers the potential for all eligible patients to receive treatment, and as noted on slide 20, with no bridging therapy required and minimal wait times to infusion. The UNIVERSAL study has three key parts. The focus of our ASH presentation is part A, a single infusion of ALLO-715 cells preceded by lymphodepletion. This part of the study included a dose escalation phase followed by a dose expansion phase. Part B is a combination arm with ALLO-715 and nirogacestat, a gamma secretase inhibitor provided by SpringWorks Therapeutics. Part C is an evaluation of consolidation dosing with repeat administration of ALLO-715. The dose escalation phase of the trial evaluated lymphodepletion followed by ALLO-715 at one of four dose level.
Dose level one, 40 million cells, dose level two, 160 million cells, dose level three, 320 million cells, and dose level 4, 480 million cells. Two lymphodepletion regimens, FCA, fludarabine, cyclophosphamide, and ALLO-647, or CA, cyclophosphamide and ALLO-647 only. The updated data shared today primarily focuses on the optimized DL3 dose and FCA lymphodepletion. The higher CAR T-cell doses were associated with an increased response rate and greater allo CAR T-cell expansion. The key eligibility requirements included relapsed refractory multiple myeloma with at least three prior lines of therapy, which includes all major classes of myeloma therapy. Patients were required to be refractory to the last line of therapy and free of donor-specific antibodies. Because ALLO-715 is available off the shelf, there was no need for bridging chemotherapy.
The primary objective was safety, and the key secondary objectives included the recommended phase II dose of ALLO-715, antitumor efficacy, the cellular kinetics of ALLO-715, and the pharmacometrics of ALLO-647. This slide also shows the schema for part A of the UNIVERSAL trial. Following screening, patients were enrolled, followed by lymphodepletion and a single infusion of ALLO-715. The different doses and lymphodepletion are listed here. Shown on slide 21 is the patient flow. As of the October 14, 2021 data cutoff, 48 patients were enrolled in part A, with 43 patients starting lymphodepletion, receiving ALLO-715, and evaluable for safety and efficacy. Five patients became ineligible for treatment due to rapidly progressing disease despite the short turnaround time, which speaks to the fragile nature of relapsed refractory myeloma and the immense need for timely initiation of therapy.
Patients in this arm received a single dose of ALLO-715 with a median time of enrollment to start of therapy of five days. Patients did not receive bridging therapy and proceeded with treatment soon after enrollment. This stands in contrast to the experience with autologous therapies, where bridging chemotherapy is common and wait times often amount to many weeks from enrollment to dosing. Patients who were treated at dose levels 1 and 2 were presented at ASH last year, so the focus of ASH this year were patients treated at dose level three or 320 million cells, as noted in the box area. The baseline characteristics of patients treated on this study are shown on slide 22. All patients were heavily pretreated with refractory advanced stage disease. Specifically, patients had a median of 5 prior lines of therapy and were refractory to their last line.
91% of patients were triple refractory, 84% of patients were penta-exposed, and 42% were penta-refractory, meaning the disease has ultimately become non-responsive to other approved therapies. Of this patient pool, 19% had ISS stage three, and 21% had extramedullary disease. Additionally, 37% had high-risk cytogenetics. ALLO-715 and ALLO-647 demonstrated a manageable safety profile. As shown on slide 23, there were low rates of high-grade CRS. Only one patient had a Grade three reaction, and there were no instances of Grade 4 or 5 CRS. Grade one and two CRS was reported in 23 patients but was manageable with standard therapies. Additionally, there were no cases of GvHD or Grade 3+ ICANS. In this heavily pretreated patient population, observed infection rates were in line with those seen in autologous CAR T-cell studies and occurred in 54% of patients.
This included three Grade five infections, two of which were previously reported. Grade 3+ neutropenia occurred in 70% of patients. The data presented on slide 24 demonstrate encouraging efficacy with additional patients at dose level three, which was the dose chosen for expansion. A total of 24 patients were treated at this dose level and the FCA lymphodepletion regimen. The ORR in this cohort was 71%, with 46% of patients achieving a VGPR+ and 25% of patients achieving a CR or stringent CR, namely three patients each. We are encouraged that these response rates have improved over time, including since our ASH abstract was submitted. The ORR increased from 60% reported at ASH 2020 to 71%, with 46% of patients achieving a VGPR or better, up from 40%.
We are also encouraged that response rates to ALLO-715 are similar to or better than several recently approved therapies for advanced multiple myeloma, including ABECMA. Slide 25 summarizes the key findings from ALLO-715 UNIVERSAL trial, the first study of its kind. Data presented at ASH this year demonstrates that a single dose of an off-the-shelf AlloCAR T product is capable of inducing deep, clinically meaningful responses that are similar to approved autologous CAR T therapy. Demonstration of this potential in patients with relapsed refractory multiple myeloma provides important validation of our platform in a second refractory tumor indication. In addition, off-the-shelf AlloCAR T cells have the potential to address significant unmet need in patients with rapidly progressing myeloma.
Allogeneic treatment eliminated the need for bridging therapy, allowed for quick turnaround with a median time of five days from enrollment to start of therapy, and enabled 90% of all patients being able to receive treatment. The combination of ALLO-715 with ALLO-647 was well-tolerated with low-grade CRS, low-grade reversible neurotoxicity, no GvHD, and an overall manageable safety profile. At the dose of 320 million cells with FCA conditioning, the ORR was 71% with a VGPR+ of 46%. 92% of the VGPR+ patients were also MRD negative, and the median duration of response for this cohort was 8.3 months.
Our data to date provides proof of concept that our AlloCAR T platform can potentially mimic results achieved with the currently approved autologous therapy while providing unique benefits in time to treatment, thereby eliminating the need for bridging therapy, as shown in slide 26. While we are very pleased with the results of our initial work with the BCMA-directed AlloCAR T product, we know that next-generation autologous approaches continue to raise the bar for the field, at least in terms of offering greater potency. As I will discuss in a moment, we too are focused on next-generation approaches designed to enhance our product profile. Before we delve into our efforts to further optimize therapy, I want to take a moment to highlight the unique advantages of our AlloCAR T products. This is highlighted on slide 27. Manufacturing is scalable, and there is less product variability.
Our product candidates can be engineered to express not just CARs, but other genetic elements that can potentially enhance antitumor activity and lend themselves to repeat dosing. The data from our Universal trial fuels our enthusiasm and supports our commitment to developing BCMA-directed AlloCAR T therapy.
Slide 28 highlights our broader anti-BCMA strategy. UNIVERSAL has established clear proof of concept for ALLO-715, and that trial is planned to progress with consolidated dosing of ALLO-647 to selectively extend the window of lymphodepletion. In addition, UNIVERSAL is evaluating ALLO-715 in combination with SpringWorks Therapeutics investigational gamma secretase inhibitor, nirogacestat. Lastly, I'm excited about ALLO-605, the company's first TurboCAR candidate. The phase I dose-escalation portion of the IGNITE trial was initiated in 2021. David started this presentation talking about how, like the Model T, AlloCAR T's have the potential to change everything, greater access on-demand dosing, scalable manufacturing, and simpler logistics.
As you look at slide 29, we intend to exploit all of the inherent benefits of allogeneic cell therapy, both from a clinical perspective as well as operationally, so we can find ways to treat every eligible patient, no matter how advanced the disease, where they live, or how quickly they need therapy. With that, we will now open the call for your questions.
Thank you. As a reminder, to ask a question, you'll need to press star one on your telephone. To withdraw your question, press the pound key. Please limit yourself to one question. Please stand by. We compile a Q&A roster. Our first question comes from Michael Yee with Jefferies. You may proceed with your question.
Hey, guys. Good afternoon, and thanks for the presentation. We had a two-part question. On the overall CD19 data, I think that people came away looking at perhaps the consolidation cohort, too, a bit puzzling with a one out of 10 CR rate. Can you put that into context for us, how to think about that? Are there a lot of sicker patients? Are there people who failed prior CAR T? Or do you think just in general, based on clinical trial design, you are just getting sicker patients these days? Maybe talk about that a bit in context. Then on durability, which I think is going to always be a question about all these things, where do you think you stand on that?
You think you've kind of cemented that sort of for a while, and you think you're on par with autologous? I'm looking at a lot of data out there. There's not much durability for anybody out there, and I guess NK data also just hit the tape, too, which is a bit, interesting. That would be great if you could comment on durability.
Hey, Michael, good afternoon, and thank you very much for that question. You know, we actually presented a lot of data today, you know, essentially summarizing past three years of work at Allogene, where we have treated over 100 patients with, you know, AlloCAR T, you know, probably the most in the field. You know, before I get to your question, you know, let me sort of, you know, reiterate some key points, specifically as it relates to the ALPHA trials. I mean, there are important lessons that we can learn from the ALPHA trials. I mean, foremost is that our allogeneic platform is allowing robust cell expansion and complete responses that are on par with autologous cell therapy.
Also, you know, consolidation, which I know has been, you know, focus of a lot of people's attention, is extremely well-tolerated, and especially in consolidation one, you know, we have raised, and even today, Dr. Lukaki reiterated a comment that, you know, this can be given as an outpatient. Overall, the complete responses that we are seeing is, we believe is on par with what we have seen in other autologous CAR Ts. Also notable is the durability of the responses that we are seeing. During Rafael's presentation, you know, we summarize the patients who have achieved CRs. There were altogether 14 of them. If you look at the durability of the response, I mean, this is just spectacular.
I mean, patients who have gone past six months, they continue to be, you know, in remission as we follow them. In fact, none of the patients who achieved CR at month six have progressed. Also, you know, other patients who haven't gotten to that, but overall, out of 14, 10 patients are in response, including the ones who have passed the, you know, seven-month time point. I think these are very important points of the allogeneic cell therapy. I mean, certainly over the past few months, we have seen data coming from other approaches from other companies, and I believe that our data stands very strong in terms of the complete response rate as well as the durability of the response.
You know, to you know answer your question specifically about the consolidation two, this was tested in the ALPHA2 study. What we did was going up slightly on Cytoxan. This is also coming after we presented the data on our CD19 day. You know, obviously, as we looked at the data, you know, consolidation two cohort stood out, and we've been looking into it very carefully. You know, we also have to you know look at the data in the context of over 60 patients with non-Hodgkin's lymphoma that we have treated between ALPHA and ALPHA2 studies. I mean, there are different ways to look at the data.
Some of the speculation that we can come up with about consolidation two is really time period as well as some of the excitement by the investigators, especially after seeing the consolidation one safety data as we presented in our CD19 day. When we look at consolidation two cohort more closely, patients in general had more poor prognostic factors, including majority of them having very high LDH, which is a well-known negative predictor to treatment outcome. This together with number of prior CD19 treatment that consolidation two cohort got, and that's in our presentation that Dr. Lukachky made earlier today.
At the end, you know, we have to look at this in the context of overall data, and, you know, we believe the consolidation too , for the reasons that I have, you know, said is a little bit of an outlier, but also is an important lesson for us as we look into this data. You know, we are sort of taking few lessons about how we can better control the patient characteristics, who will be enrolled into our phase II study. You know, we feel very confident about what we are seeing in the ALPHA and ALPHA2 study. You know, the issues with the consolidation, at this point, you know, we are viewing that as an outlier.
Okay. Okay, just to be clear, and I'm sorry for taking this on, but it's three out of 10 people had prior CAR T. Was that number in the slides or what?
Yeah. I think in the presentation, in the ALPHA2, I think there were altogether 10 patients. Our clinical data indicates that, you know, five of them have prior CD19 therapy, and we're trying to find the details, and we don't have that information yet about how many of those are prior CAR Ts versus other anti-CD19 therapy. Stay tuned.
Thank you.
Thank you. Our next question comes from Tyler Van Buren with Cowen. You may proceed with your question.
Hey, guys. Thanks for taking the question and for the presentation. Just wanted to further parse out the difference, potential difference in consolidation in ALPHA2 versus single dose in ALPHA. It's difficult for me to believe that the increased expansion and persistence after a second CAR T dose isn't going to add something, and clearly the initial CR rates appear similar. I guess, is it just too early to really tell if there's gonna be an improvement in terms of durability with consolidation dosing? I guess if you look at the 14 CRs, which conveniently is split seven and seven, you do appear to have, you know, three progressors in ALPHA versus only one in ALPHA2. Is there maybe a hint there?
Just the second question, related to the same topic is why would consolidation dosing potentially have an improved safety profile? What's the hypothesis there?
Okay, Tyler, thank you for very insightful questions on, you know, our data. I mean, certainly you're looking at every, you know, angle. I mean, in terms of consolidation, you know, if I pass this on to my, you know, Rafael to answer some of the specific questions that you're asking. We are providing cell infusion, you know, over four-five weeks, two different cell infusions. Certainly we are seeing evidence of cell expansion with the second cell infusion, which I think is the most exciting findings. A lot of times, you know, we, you know, constantly talk about the importance of, you know, persistence. You know, as we beginning to talk about, I think the real question is importance of functional persistence of the CAR T cells.
That's exactly what the consolidation is doing. You're giving a fresh cell in a batch of cells for the second infusion. When those cells expand, they are functionally active. Not only we are, you know, improving the overall persistence, I think we are having a pretty significant effect on the functional persistence of the CD19 CAR T cells. You know, to the specifics about, you know, the patients and the CRs and the duration of response, I'm gonna pass off to Rafael.
Yeah, Tyler. I mean, we are pretty excited about C1, particularly C1. We did this experiment of increasing cyclophosphamide and you know the number of patients that we've accrued has allowed us to look at different dosing and schedule and also the availability of ALLO-647 allows us to do these kinds of experiments because we don't use chemotherapy to eliminate the first batch of cells that's given at day zero. I like to look at the data in an overall fashion both on ALPHA and ALPHA2. You know, the responses, when you just parse out C1, are in the 70s overall and you know north of 40% CRs.
It's a little early to know the durability, but you know, we are starting to get durability that is surpassing 9 months. You know, that is actually boding well for you know, potentially adding to that slide 15 graph that you were referring to before. I think you were pretty insightful when you were talking about why should it be safer. We think that you know, part of it may be because we give 60 milligrams first and then the rest of the 30 milligrams are given 28 days later without chemotherapy. We managed to give 90 milligrams, which we think is optimal in a split fashion. We also give cells that we expand.
you know, I think taken together, you know, there's really the best balance, I think, between efficacy and safety, particularly with C1. you know, although ALLO-647 given in 90 mg is probably, you know, the ideal dose, and the split dose allows for better safety.
Thanks very much.
Thank you. Our next question comes from Salveen Richter with Goldman Sachs. You may proceed with your question.
Hey, everyone. Thanks for taking the question. This is Andreon for Salvine. Maybe one for Rafael or David. Just wondering if you could comment on how the profiles that have emerged from the consolidation treatment compared to your initial expectations. Do you believe there are still other levers that need to be optimized here?
I think. As I said before, what we've been most impressed with is the tolerability, particularly with the consolidation one, both the initial dosing and more importantly, the second dose, which is pretty easy to give, you know, patients can receive as outpatients. It allows us to, you know, get higher doses of cells and split ALLO-647 in a way that, you know, that supports the safety that I just talked about. You know, we will continue obviously to accrue, particularly large B-cell lymphoma in ALPHA2 with consolidation one, because we think that it strikes the best balance between safety and efficacy. That's really what this is about.
You know, potentially being able to bring this not only to the vast majority of patients, but also, potentially to, you know, community setting and outpatient setting.
Yeah, Andreon, let me just add on to that. I mean, you know, when I think about what we did at Allogene over the last 2.5 years is really trying to get to the right balance of safety and efficacy. I mean, you know, our studies are, you know, complex. You know, I think we have heard that from, you know, several today after we provided some additional updates. Part of the reason is we tested not only the cell dose, but many different lymphodepletion regimen, because we believe that the requirement of lymphodepletion for the allogeneic will be substantially different than what has been used in the autologous. I mean, that was the early, you know, recognition which led us to test many different regimens.
At the end, I think we have a clear understanding that the standard lymphodepletion is not gonna be sufficient. We need something more, and that something more is really being provided, and we have optimized it quite a bit with ALLO-647, our anti-CD52 antibody.
Thank you. Our next question comes from John Newman with Canaccord. You may proceed with your question.
Hi, guys. Thank you for taking the question, and thanks for the presentations today at ASH. You know, I was a bit surprised that you were allowing some of the very difficult patients in the consolidation study. I think you previously mentioned you had several patients that had prior CD19 experience. Should we expect that in the pivotal study, those patients might be excluded? Also would there be other parameters, you mentioned LDH, that would better allow you to treat a similar patient population, if possible, as the patients that are currently receiving autologous CD19? Thanks.
Thanks, John. This is Rafael. Excellent question. I think the timing to explore multiple variables is in phase I. You know, sometimes we explore variables that you know may result in patients not responding or having a lower response rate. You know, that's the case for instance of prior autologous therapy, which is really true also in the autologous setting, by the way, as you know. Patients with very high LDH also do very poorly in the autologous setting. Patients with extranodal disease also do poorly. You know, some of these patients made it into our trial, particularly in consolidation too. They were allowed in part, you know, because of the enthusiasm of physicians, particularly patients that couldn't wait, you know, to receive autologous therapy.
you know, for us to understand, you know, what are the limits of the therapy with regards to activity. you know, your point about learning on these phase I studies, what are the best patients that may benefit from therapy is a really good one, and it's certainly going to inform the design of our pivotal trial.
Okay. Thank you.
Thank you. Our next question comes from Luca Issi with RBC. You may proceed with your question.
Oh, great. Thanks so much for taking my question. Maybe the first on the clinical hold, wondering if you can comment on whether you have provided the appropriate responses to the FDA and maybe a bigger picture of what gives you confidence that the clinical hold will ultimately be lifted. The second maybe on cyclophosphamide, can you remind us why you almost doubled the dose from 300 mg to 500 mg for consolidation? Should we assume that that experiment is essentially over or you're maybe planning to explore a dose in between the two? Thanks so much.
Hey, look, let me take, you know, both the questions. In terms of the clinical hold, I mean, we have made, you know, several comments in different situations. We believe that we are in control of the, you know, situation in terms of generating the data supporting our hypothesis as well as expanding the data set by analyzing some of the patient samples. It's to us, you know, I strongly believe it's not the question of whether, you know, we will get out of the clinical hold or not, it's just a matter of when. On that regards, we not saying much because in part, the final arbiter of our argument would be the FDA.
Let's stay tuned, and I do not wanna, you know, say ahead of what FDA may or may not say. That's one. The second question about, you know, why did you go up on the cyclophosphamide? I think this is really, you know, driven by some of the preclinical work as well as available data in terms of, you know, lymphodepletion. When we do the lymphodepletion, we simply follow the peripheral blood count. There is also, you know, cells in the tissue, lymph nodes, and elsewhere. There is data that would suggest that high-dose cyclophosphamide, you know, is more effective in eliminating the lymphocytes than maybe in the tissue, not in circulation or in the bone marrow. That was the hypothesis.
As Rafael has suggested, you know, if we were gonna test that, you know, phase I study would be in the, you know, setting that we have done, we would do it, and that's exactly what we did. Your last question, are we still gonna go back and forth? At this point, I think after spending about 2.5 years and going through many different, you know, iterations of you know, the lymphodepletion, I think we are getting fixed with the consolidation one as we are looking forward to the start of our pivotal study.
Super helpful. Thanks so much, David.
Thank you. Our next question comes from Michael Schmidt with Guggenheim. You may proceed with your question.
Hey, guys. Thanks for taking my questions. I had one on durability. It's obviously nice to see that many of the CRs in ALPHA and ALPHA2 were relatively durable. Just curious, in the UNIVERSAL study, if you could just comment on durability of CR. You know, I thought it was interesting, I think in the ABECMA studies we saw some of the responses deepening over time, and I was just curious if that's something that perhaps you've observed as well. And the second part of the question, again, on myeloma, just wondering how you're weighing next development steps with the two other programs still ongoing.
Yeah, let me take that question, Michael. As you know, we've been very pleased to see the data mature and the durability of response increase now being above eight months for responders. The VGPR plus 46%, which is pretty similar to what has been seen with ide-cel. The CR rate, the data are maturing. We have patients in CR that are approaching a year, and we believe that as there's still a lot of patients that are in response that number may actually get better with time as we continue to follow these patients.
In addition to that, you know, we are starting the consolidation cohort now, which may actually add, you know, some benefit with regards to responses. Obviously, it will take some time for that data to mature, but it will hopefully increase the rate of CR and overall with time, the durability of response. You know, stay tuned, but you know, so far we're very pleased with, you know, how these numbers are improving with time.
Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. You may proceed with your question.
Hey, guys. Thanks for taking the question. I guess I'm looking at ALPHA and ALPHA2, and I'm wondering if you're generally seeing ongoing B-cell aplasia in patients who have ongoing responses, and if that differs at all from your experience with autologous CD19 CAR Ts. Like, kind of second part of the question is, there are obviously a few follicular lymphoma patients who lost their responses kind of late in the trial. You know, maybe you can comment on why that six-month CR rule doesn't really seem to hold up necessarily in follicular lymphoma in particular. Thanks for taking the question.
Yeah. This is a really important question with regards to B-cell aplasia. We follow you know the recovery of the cells very carefully and you know patients remain with B-cell aplasia for several months. You know eventually they start recovering their B cells. And likewise you know their T cells also start coming back up which you know starts coinciding with you know the decrease and disappearance of persistence. You know the B-cell aplasia it's still you know compares you know pretty similar to what we've seen with the CD28 CARs. With regards to follicular lymphoma you know the initial response rates and complete response rates are. We've been very pleased with them.
I mean, the CR rate of 75%, the six-month rate of 32% has improved from 24%, and we think that there may be perhaps, you know, an opportunity for that number to get better. It is true that some patients, you know, with long responses, a few of them, have recurred, but this is a different disease. You know, it tends to be a chronic disease, and it's possible that, you know, that there are, for some patients, you know, responses that are more limited than they are in large B-cell lymphoma, where six-month responses are very predictive. It's still a little bit of early days, but we are pleased with the way that the six-month rate is really increasing with time.
Thanks so much.
Thank you. In recognition of participant time constraints during a busy ASH meeting, our last questions will come from Ren Benjamin with JMP Securities. You may proceed with your question.
Hey, guys. Thanks for squeezing me in and taking the questions. For me, it's about the cell expansion data that you have in the second CAR T dose. Can you maybe just help explain, you know, how these expansions may be correlating to the depth of the CR? All these three patients ultimately got a CR, but clearly, you know, the expansions vary quite a bit. I'd love to just kind of get your thoughts as to how you're viewing this. Can you also tell us what's the longest you've seen the cells actually persist in a patient? And is there any thoughts to dosing according to kind of like cell number or vector copy number within a patient? Thank you.
Okay. Ren, let me take that question. In terms of, you know, second cell infusion, you know, the fact that we are seeing cell expansion is very exciting. Cell expansion, you know, that is really triggered by the presence of CD19, whether it's present in the B cells or whether it's present in the lymphoma cells, which would really trigger the activation of the CAR T cells. In the cases where we see the partial response, sort of converting to CR, we haven't asked, and we certainly have seen it in autologous setting, you know, after single infusion, because there's no, you know, chance for consolidation in autologous setting. You know, sometimes initial PR improves over a period of time to CR.
You know, those are usually, you know, some minor, you know, PET findings that prevents you from calling a good response to a CR, and you just have to wait for the PET response to go away. I mean, certainly, you know, some of the, you know, patients, you know, in our study would apply to that kind of setting. Certainly when we see the cell expansion, I mean, that's a really good indication that the consolidation is doing what it is intended to do. Your other question about, you know, how long do you see the cell persistence by vector copy number, and obviously this is by vector copy number. We don't know whether those cells are functional or not.
I mean, the only way that you would know whether CAR T cells are still functional or not is sort of following as a surrogate and you know endpoint, you know, the duration of B-cell aplasia. As Raphael said, you know, that B-cell aplasia we see in our study is pretty you know pretty you know that it's very comparable to what we have seen in the autologous setting. Having said that, you know, just if you follow by the vector copy number, we can easily get up to about 120 days, which I believe is more than enough to get the maximum benefits of the CAR T therapy. Your last question, will we ever consider you know dosing based on vector copy number?
I mean, you know, I'm not gonna say no. I mean, as we learn about the CAR T therapy, maybe in the future, but right now, that's not something that we are considering.
Terrific. Thanks, David.
Thank you. That concludes our question and answer session. I would like to turn the conference back over to management for any additional comments.
You know, ASH has been an extremely busy time for all of us, and thank you very much for joining the call today. As we said in the beginning, we are very proud of what we, Allogene, has accomplished in the AlloCAR T therapy setting. We look forward to updating the data as we follow these patients as well as you know, communicating additional data. Thank you very much for following us today.
Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program, and you may now log off and disconnect.