Allogene Therapeutics - Earnings Call - Q2 2021

Transcript

Operator (participant)

Hello. Thank you for standing by, and welcome to Allogene Therapeutics' second quarter 2021 conference call. At this time, all participants are in the listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one on your telephone. 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.

Christine Cassiano (Chief Communications Officer)

Thank you, operator, and to all on the line, welcome. We will continue to limit questions to one per person so we can get to as many as possible during the hour. After the market closed today, Allogene issued a press release that provides a corporate update and financial results for Q2 2021. This press release and today's webcast are both available on our website. Joining me on the call today are Dr. David Chang, President and Chief Executive Officer, Dr. Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer, and Dr. Eric Schmidt, Chief Financial Officer. During today's call, we will be making certain forward-looking statements.

These may include statements regarding the success and timing of our ongoing and planned clinical trials, including the timing and ability to advance our ALPHA2 trial to phase II, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, and 2021 financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our earnings press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David.

David Chang (President and CEO)

Thank you, Christine, and good afternoon. We launched Allogene in the second quarter of 2018 with a bold mission: to create and lead the Next Revolution in cancer treatment by delivering to patients the first AlloCAR T therapies for blood cancers and solid tumors. Three years later, we have made a giant leap for both Allogene and the field of cell therapy, as data from our lead program brings us one major step closer to realizing our goal of commercializing a first-in-class and best-in-class off-the-shelf cell therapy. As we enter a new stage in our life cycle, our focus turns towards advancing our lead development candidate, ALLO-501A, into a pivotal phase II trial for relapsed refractory non-Hodgkin's lymphoma by the end of 2021.

Following initial data presented at our CD19 forum in May and ASCO in June, we are increasingly confident in the safety and efficacy profile of ALLO-501A and its path forward. As we shared during the CD19 forum, the Alpha trial demonstrated that ALLO-501 can achieve deep and `durable responses in patients with relapse refractory non-Hodgkin's lymphoma who are CAR T naive, with an overall response rate of 75% and CR rate of 50%, and the six-month CR rate of 36% in patients with large B-cell lymphoma histology, which is the patient population of our first pivotal trial. The safety profile was also very encouraging: no dose-limiting toxicities or graft versus host disease, and limited ICANS and cytokine release syndromes observed.

I have been involved in the development of CAR T therapies from the early days, and the available efficacy and safety profile of ALLO-501 and ALLO-501A clearly show that all the key principles that we learned from autologous CD19 CAR T therapies are holding true in our Allogene CAR T therapy. Setting aside the limitations of drawing a cross-trial comparison, what we are seeing in our studies, both in the initial responses, durability of responses, and the safety profile from a single infusion of ALLO-501 or ALLO-501A, are on par with the data from pivotal trials of FDA-approved autologous CD19 CAR T therapies. Meanwhile, we have exceeded the bar set by the autologous therapies in other respects. Our AlloCAR T therapies can be delivered to patients within days rather than weeks, and patients who enrolled in our studies can be nearly guaranteed to receive our products.

In the ALPHA3 trial, 98% of the enrolled patients received ALLO-501 within a median time of five days from enrollment to startup therapy. By comparison, in trials deploying autologous therapies, up to 30% of patients who have undergone leukapheresis for cell manufacturing were unable to receive treatment due to interval disease progression while waiting for the CAR T cell products, or even worse, due to manufacturing failures. Given the tremendous benefit that ALLO-501A can bring to patients, we remain highly focused on execution. Top of mind today is our preparation for the industry's first Allogene pivotal trial. As our planning towards this important milestone progresses, we look forward to providing a clinical update on our CD19 program in the fourth quarter. Shortening the time to treatment and ensuring access for nearly all suitable patients is just the beginning of how we can leverage the attributes of Allogene CAR T therapies.

As we look down the line to next-generation therapies, our aim is to potentially enhance the efficacy and safety of our products beyond that of autologous therapies. Our research team is actively working on new strategies to evade premature rejection, enhance cell potency, improve product consistency, and overcome the solid tumor microenvironment. Some of these technologies, such as our Turbo-CAR T approach, have now advanced into clinical development. Others are progressing nicely behind the scenes. While the initiation of our first pivotal trial will represent a critically important milestone for Allogene, it represents just the beginning of our new product innovation cycle. We are now also preparing for the potential transition from a clinical-stage company to a commercial enterprise. We have begun to build our commercial team, which will focus on product positioning, maximizing adoption, and ensuring access.

We have bolstered our internal efforts by expanding our board with the appointment of Liz Barrett and Vicky Sadow as directors. Liz, currently the President and CEO of Eurogen and former CEO of Novartis Oncology, is one of the rare executives with deep experience in the commercialization and launch of novel oncology therapies, including an autologous CAR T therapy. Vicky, a former professor in practice of molecular and cell biology at Harvard University and President of Vertex, has an exceptional track record of operational execution at several leading biotechnology companies. Our new board members will be vitally important as we prepare for the potential launch of a first-in-class product, which brings us to manufacturing.

From the beginning of Allogene, we have maintained that having in-house manufacturing capabilities would be key to controlling our ability to deliver off-the-shelf CAR T cell therapies faster, more reliably, and at greater scale to all patients. Later this month, we will host an event to inaugurate our CellForge One state-of-the-art manufacturing facility in Newark, California. The facility is intended to house commercial manufacturing, analytical testing, formulation, packaging, and distribution of cell therapies, allowing us to optimize important steps in the cell therapy production process and allow allogeneic therapies to be available to patients within days. We are excited to showcase the convergence of scientific excellence and cutting-edge manufacturing at our CellForge One facility.

The rapid build-out and operationalization of this facility is yet another example of our team's determination to let nothing, including the unforeseen challenges presented by a global pandemic, get in the way of our goal to bring the first Allogene CAR T therapy to patients. I thank them for their tireless efforts to bring this facility online in preparation for CGMP manufacturing in the second half of 2021. Positive phase I data from our ALPHA and ALPHA2, as presented at ASCO and our CD19 forum, continue to validate our Allogene platform, and we are aggressively advancing our pipeline with more confidence than ever before. We currently have five clinical trials underway: two in our CD19 program, as noted, two candidates that target BCMA, including one that incorporates our novel Turbo-CAR technology, and one program in solid tumors.

Our robust multiple myeloma program is an example of how we've been able to rapidly advance, optimize, and deliver meaningful progress across multiple strategic approaches to Allogene CAR T. Beyond our ongoing UNIVERSAL trial, we were pleased that our first Turbo-CAR clinical candidate, Allo605, received US FDA Fast Track designation for the treatment of patients with relapsed and refractory multiple myeloma. We are excited to announce that we have begun dosing patients in phase I of the IGNITE study of Allo605. We also have our sights set on confronting solid tumors, where the need is unquestionably high for a new innovation. We remain optimistic for the potential of our allogeneic platform to rise to the challenge. Our initial program targets CD70, and earlier this year, we launched our TRAVERSE trial evaluating Allo316 in clear cell renal cell carcinoma.

As we continue to treat patients, we plan to share initial data next year. Over the next 6 to 12 months, we expect to have an increasing amount of data across multiple programs that will provide critical insights and inform how we best optimize the promise of our platform. Unwavering execution has already allowed us to generate the largest set of clinical and translational data on allogeneic therapies, which we will continue to deploy towards enhancing our product candidates. We are incredibly proud of what we have achieved to date, only made possible by our team's steadfast focus on making Allogene CAR T therapy a reality for patients. While being an industry leader often entails overcoming tall obstacles, it also provides the privilege of being able to set the pace of innovation, shape important parameters in the field, and define success.

At Allogene, we believe we are up to this challenge, and we are grateful for your support as our vision for the future of Allogene CAR T therapies is continuing to materialize. I will now turn the call over to Rafael for a more in-depth look at our research and development activities.

Rafael Amado (EVP of Research and Development and CMO)

Thank you, David. As you might anticipate, our research and clinical teams have been increasingly focused on advancing our portfolio of allogeneic therapies. As David mentioned, we are on track with our plans to initiate a pivotal phase II trial for ALLO-501A in non-Hodgkin's lymphoma. We view the data that we reported in May for the ALPHA3 trial, including a 36% complete response rate at six months in large B-cell lymphoma, as a sign that we are on the right track and look forward to exploring whether the use of consolidation therapy might lead to even greater promise.

Across all non-Hodgkin's lymphoma histology, ALLO-501 demonstrated an overall response rate of 75% and a CR rate of 50% across histologies in CAR T naive patients. At the time of the data cut-off, the longest ongoing complete response was at 15 months in both large B-cell lymphoma and follicular lymphoma. Importantly, given our intent to move ALLO-501A into our pivotal studies, we were also able to demonstrate that ALLO-501A, which eliminates the rituximab recognition domains in ALLO-501 to allow for use in a broader patient population, has comparable safety and efficacy to ALLO-501. As we look to find ways to maximize all levers afforded to us by the nature of our Allogene platform, one area of distinction for us is our lymphodepletion platform, which supports consolidated dosing.

During our CD19 day, we also highlighted the initial data on consolidation therapy, which leverages the unique attributes of the off-the-shelf Allogene cell therapy and our proprietary lymphodepletion regimen. We're highly encouraged by the results, especially the tolerability of consolidation and observed conversion of initial PR to CR. Pending additional follow-up, we plan to incorporate consolidation into our pivotal study design. Our approach to consolidation dosing is not currently available for autologous therapies or even other Allogene therapies as traditional lymphodepletion regimens will eliminate previously infused cells. In contrast, Allo647, as the sole lymphodepletion agent for the second dosing, is capable of supplementing the activity of the first dose, allowing for expansion and persistence after the second dose. This is an important advantage and one that we plan to fully investigate in both our CD19 and BCMA portfolios.

We are currently finalizing our proposed plan to discuss proceeding to the phase II trial with the FDA. Pending the collection of data and favorable FDA feedback on the design of the trial for the registration of both ALLO-501A and Allo647, we currently intend to initiate the phase II portion of the Alpha2 trial at the end of 2021. I have been fortunate to have been involved in the development and approval of multiple cancer therapeutics and know firsthand how much effort is involved in the preparation towards pivotal trials, including extensive and complex regulatory interactions, clinical development, and manufacturing activities. I would like to extend my thanks to the Allogene teams who are working tirelessly to lead us through the pioneering activities required for the execution of our first pivotal Allogene cell therapy trial.

Although we're further along in our CD19 program, we're committed to advancing allogeneic therapies across a broad spectrum of targets in both liquid and solid tumors. We were pleased to have received Regenerative Medicine Advanced Therapy designation granted by the FDA for Allo715 based on early clinical data and the potential to benefit patients with unmet medical needs. The UNIVERSAL trial continues to enroll patients to Allo715, including in combination with nirogacestat, a gamma secretase inhibitor from SpringWorks Therapeutics, and in consolidation therapy. We anticipate having updated data to share from the Allo715 monotherapy arm of our UNIVERSAL trial by the end of the year, and we are on course to provide updates on Allo715 in combination with nirogacestat in 2022. We're also thrilled to be dosing patients in our IGNITE clinical trial with Allo605, our first Turbo-CAR clinical candidate and part of our broader anti-BCMA strategy.

Turbo-CAR represents a next-generation cell therapy with built-in cytokine signaling, eliminating the need for systemic cytokine administration and the potential to induce broader immune system stimulation. With Turbo-CAR, we anticipate being able to improve the potency and persistence of allogeneic CAR T cells while delaying exhaustion, traits that are key to our performance in both liquid and solid tumors. Finally, we are progressing in the dose escalation portion of the TRAVERSE trial, our first venture into solid tumors with Allo316 in clear cell renal cell carcinoma. We expect to present data on this important program next year. I'd like to echo David in thanking you for your ongoing support. Our science and clinical teams are making consistent progress in advancing a promising portfolio of allogeneic candidates for patients in need, something that we could not achieve without the backing of the investment community.

I'd like to now turn the call over to Eric for an update on our financials.

Eric Shmidt (CFO)

Thank you and good afternoon. As I open my portion of the prepared remarks, I'd like to highlight progress made in our joint venture with Overland Pharmaceuticals to develop and commercialize our allogeneic therapies in Greater China, Taiwan, South Korea, and Singapore. In June, we announced the appointment of Dr. Shuyan Yao as CEO of Allogene Overland BioPharm. Dr. Yao has over 15 years of experience in cell therapy and was most recently the Chief Scientific Officer and Head of Research and Technology Development of Wuxi AppTec, where he led new technology acquisition, development, translation, and application. We are delighted to welcome Dr.

Yao to the team and are already seeing his presence translate into meaningful activities as we seek to bring the promise of Allogene cell therapies to individuals with cancer in Asia. In the second quarter of 2021, our research and development expenses were $52.3 million, which includes $10.5 million of non-cash stock-based compensation expense. General and administrative expenses were $18.8 million for the second quarter of 2021, which includes $10.6 million of non-cash stock-based compensation expense. Our net loss for the second quarter of 2021 was $70.9 million, or $0.53 per share, including non-cash stock-based compensation expense of $21.1 million. As David and Rafael mentioned, we're on track to support five clinical trials during 2021, including the initiation of a pivotal trial for ALLO-501A towards year-end. We are also looking forward to initiating manufacturing at CellForge One, our Newark manufacturing facility.

Overall, we continue to expect our full year 2021 operating expenses to be between $300 million and $330 million, implying a meaningful ramp in expenses during the second half of the year. This includes an estimated non-cash stock-based compensation expense of $80 million-$90 million and excludes any impact from potential business development activities. With that, we will now open the call for your questions.

Operator (participant)

As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. We ask that you please limit yourselves to one question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Michael Yee from Jefferies. Your line is now open.

Dennis Ding (Biotech Equity Research Analyst)

Hi, good afternoon. This Dennis Ding on for Mike. I just have a quick question around the lymphoma data coming at year-end.

Can you just comment on what type of data we will get and specifically for consolidation? Can you help us kind of set expectations for that data relative to what we've seen at ASCO? Thank you.

David Chang (President and CEO)

Hi, this is David Chang. I usually take a lot of questions, but much of today's discussion I expect to be around CD19. I'm going to ask our Chief Medical Officer, Rafael, to comment on the expectations of what data we'll be presenting at the year-end.

Rafael Amado (EVP of Research and Development and CMO)

Sure. At the ASCO time point, we had 10 patients that had received consolidation, and we were pretty encouraged by what we saw: 80% of patients responding with 7 out of the 10 in complete response. More importantly, we saw conversions from PRs to CRs. That gave us impetus to continue to accrue.

Investigators have been very enthusiastic about the ability of consolidation to actually boost up complete response rates, which may be a surrogate to longer durability. What you may expect towards the end of the year is longer follow-up on those ASCO patients, as well as more patients that we've continued to accrue both on Alpha and Alpha2 and follicular lymphoma and diffuse lymphoma. The durability will be variable, obviously, but at least we'll include those patients that we presented at ASCO. I think they will be sufficient to obviously make an adjustment as to the merits of consolidation. I can't give you an exact number, but it will be obviously more volume of what we showed at ASCO because we've continued this approach.

Operator (participant)

Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open.

Pardon me, Salveen Richter from Goldman Sachs. Your line is now open. Please check your mute button. Our next question comes from the line of Marc Frahm from Cowen & Company. Your line is now open.

Marc Frahm (Biotechnology Equity Research Analyst)

Thanks for taking my questions. On your comments about defaulting to using the consolidation dosing, your kind of default assumption, would you expect that the pivotal trial is going to be just a single dose using that consolidation approach, a single arm, or might the FDA require a kind of a randomized trial for the consolidation piece of it to kind of definitively establish the utility of that second dose?

I guess, related to that, as you evaluate the early data that's coming out of the trial, what's your latest thoughts on kind of the minimum kind of difference in durable CR rate that you need to see to justify that second dose?

Rafael Amado (EVP of Research and Development and CMO)

Yes, Marc, those are very good questions. I mean, in general, the fact that one gets more than one dose of a product doesn't necessarily lead to mandates from regulators to test single dose in a randomized fashion. Obviously, the agency's negotiations need to happen, but just akin to what may happen with a vaccine or with a product that requires periodic dosing, whether it's every two weeks or every five weeks or dosing for a year or dosing to progression, et cetera, the sponsor establishes the regimen and proposes that as the regimen to go forward.

I don't foresee that there will be a mandate for us to actually establish whether consolidation is better than single dose or not. It will be up to us to decide whether we believe that that is the case, which leads me to the second part of your question. The evidence would be a composite of the high CR rate, the durability of the responses, and we are accumulating more and more months on some of these patients, as I mentioned before, and also some of the surrogates like minimal residual disease, and then the ability to continue to expand and observe persistence of the CAR positive cells, which we've already seen after the second dose.

So far, we're excited about what we're seeing, and that's why we believe that it's likely that we will incorporate consolidation in our pivotal trial, but we'll continue to observe the data prior to making the decision.

David Chang (President and CEO)

Marc, this is Dave Chang. If I can add on to that, I take it there will be a lot of questions about the study design that we will go forward with the FDA meeting. I kindly ask you to stay tuned, and certainly, we have to have the FDA discussion. As we come out of it, we will clarify exactly what will happen for our pivotal study.

Operator (participant)

Thank you. Our next question comes from the line of Luca Issi from RBC. Your line is now open.

Luca Issi (Senior Biotechnology Analyst)

Oh, terrific. Thanks so much for taking my question. Congrats on all the progress. Maybe a quick one.

I think Sage Therapeutics is planning to show some, for the first time, I think, clinical data for the CD19 CAR NK cells in the next two weeks. I'm wondering if you can comment on what are your expectations getting into that data and maybe a bigger picture, what's your latest thinking on the debate between CAR T cell versus CAR NK cells? Thanks so much.

David Chang (President and CEO)

Yeah, Luca, thank you very much for that question. Certainly, our focus now is really advancing our Allogene CAR T program, ALLO-501A, into the pivotal study. We have treated a number of patients, and we have a good understanding coming from the large number of patients, the emerging data we have from the 501, where most of the single dose experience are coming from, as well as the consolidation dosing, which we are very interested in.

As you know, the Allogene cell therapy field is a very active place. I think a lot of companies see the promise of the off-the-shelf therapy with the potential of providing very deep and durable responses. Companies are taking a different approach. We believe in the CAR T therapy, especially therapy that leverages T cells. We eagerly wait to see what other companies, especially those leveraging the NK cells, will provide in their data updates. Let's have another conversation after the data presentation, which I believe is planned for sometime in August.

Operator (participant)

Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open.

Salveen Richter (Biotechnology Equity Research Analyst)

Yes, sorry for earlier. Just two questions here. Could you talk about CD17 and what you would see as a clinical bar here and first data with your CAR T program?

On the BCMA side, do you have an understanding here of the optimization levers required to get you closer to the autologous profile?

Rafael Amado (EVP of Research and Development and CMO)

Yes, Salveen, this is Rafael. On CD17, that program has begun not that long ago. As you know, we have to treat patients and observe them before we can go through those escalations. We are treating patients that have failed all pathway-directed therapies, so that is checkpoint inhibitors and angiogenesis inhibitors. Many of them are progressing as they come into the study. We hope to get some early evidence of potential activity that we can show next year. In terms of the bar, I think it is premature to talk about it, but many of these patients are already refractory. As you know, the data in solid tumors with CARs still needs to mature and progress.

I think certainly any complete responses or partial responses will be of interest, and we will follow the field very closely. There are a number of surrogate markers that we're also looking at that will help us with other targets in solid tumors, such as trafficking into the tumor, the tumor microenvironment effect, resistance, et cetera. In terms of BCMA optimization, we have continued dosing. As you know, we were in DO4. We have finished our dose escalation. We've continued to follow patients. We are starting consolidation as well. We were very glad to see the RMAT designation being awarded to the product. In part, that was in recognition for the effect of the product, but also the ability to treat very quickly and to avoid bridging therapy, which are two important features that you don't see in the autologous setting.

We clearly want to get closer to the autologous bar. There's no question that the cell has set a pretty high bar. We're continuing with consolidation, the use of nirogacestat, and obviously the Turbo-CAR that we referred to in the prepared remarks that we just started. It's a matter of staying tuned and seeing what these potential optimizations' results are.

Operator (participant)

Thank you. Our next question comes from the line of Michael Schmidt from Guggenheim Securities. Your line is now open.

Kelsey Goodwin (Senior Associate)

Hey, this is Kelsey on for Michael. Thanks for taking our question. Maybe building on the multiple myeloma side, I guess, what should we be expecting at ASH in terms of when you implemented the consolidation regimen? Will there be a meaningful amount of patients that we can interpret single agent versus consolidation?

Would we see any initial data points from the nirogacestat combination? That is it for me. Thank you.

David Chang (President and CEO)

Yeah. The consolidation, Kelsey, just started relatively recently. There will be patients, but there may not be a long follow-up. There will be more follow-up on the higher doses, which we have already noted were more effective than the lower doses. We have treated in DO3 and DO4, and we will have more patients on those as well as longer follow-up. Nirogacestat is accruing well, but we will need to have sufficient patients and sufficient follow-up. We believe that will probably be a 2022 type data release, just like 605. Most likely, it will be much more mature data with the higher doses on 715 that we will present towards the end of the year.

Kelsey Goodwin (Senior Associate)

Perfect. Thank you.

Operator (participant)

Thank you.

Our next question comes from the line of Jason Gerberry from Bank of America. Your line is now open.

Jason Gerberry (Equity Research Analyst)

Hey, guys. Thanks for taking my questions. Another BCMA question just heading into ASH. Obviously, as you guys have mentioned, autologous has had a high bar. Your data last year at ASH were immature for the 480 million cell dose. Just curious, do you think you might be at a point at ASH to determine whether or not single dose is the right path forward or whether you need to shift the focus to gamma secretase or Turbo-CAR programs or dose consolidation? Just sort of curious if you feel like the data might be mature enough for single dose to make that pivot or prioritization. Thanks.

David Chang (President and CEO)

Thanks, Jason. Thanks for a great question. I mean, I think you're asking all the right questions.

I mean, certainly, from the beginning, we set up the BCMA program slightly different than the way that we set up the CD19 program. I mean, yes, there are different levers that we can test, including higher cell dose and more stronger lymphodepletion leveraging what we have, specifically Allo647, and consolidation. All these are the parameters that we tested in the CD19 program. We have a lot of knowledge about how to best utilize different levers to optimize the benefits of Allo715. Also, we have taken a sort of somewhat unusual step of concurrently developing the next generation Allo605 that utilizes the Turbo-CAR technology. In terms of the question about when we will know about what to do with our different BCMA approaches that we are making, we're going to take all different information that we are generating. All these trials are ongoing and enrolling patients.

We are in a pretty good position, I believe, that sometime in 2022, there will be a convergence of data that will help us to map out the path for the BCMA program.

Operator (participant)

Thank you. Our next question comes from the line of John Newman from Canaccord. Your line is now open.

John Newman (Managing Director)

Hi, guys. Thanks for taking the question. Follow-up on the last question, actually. Just curious, for Allo715, in terms of combining with nirogacestat, I'm wondering if you're considering giving multiple doses of nirogacestat sometime in the future if it may be beneficial to dose initially in combination with 715 and 647, and then maybe after that to give another dose or two. Just curious if that's something that you're considering for the future. Thanks.

Rafael Amado (EVP of Research and Development and CMO)

Hi, John. This is Rafael. Yeah, good question.

I mean, we haven't gone into how we're dosing nirogacestat for competitive reasons, obviously. I can tell you that we don't just give one dose. Our intent is to try to maximize the benefit of BCMA expression that nirogacestat can afford. We will be testing that potential. It may take the form of several doses. This is something that is currently under exploration. Stay tuned for the results.

Operator (participant)

Thank you. Our next question comes from the line of Mark Breidenbach from Oppenheimer. Your line is now open.

Mark Breidenbach (Senior Analyst)

Hey, guys. Thanks for taking my question. Just a quick one from me. I know the main focus of the upcoming pivotal trial will be on large B-cell lymphomas, but I'm wondering if you have plans to continue development of 501A in follicular lymphoma, or is that off the table for now?

David Chang (President and CEO)

Yes, Mark. I mean, this is something that we are crafting right now, which is a comprehensive program that includes a suite of studies across various lines of therapies as well as histologies. As you know, there are second-line results that have come up, and we are thinking about follow-on trials that would address that need with the ALLO-501A therapy, and likewise to follow on with follicular lymphoma and potentially other histologies. Right now, we are very focused on the third-line histology and in discussions and preparations to get that study started. There will be a lot of activity around ALLO-501A to really form a comprehensive program.

Operator (participant)

Thank you. Our next question comes from the line of Reni Benjamin from JMP Securities. Your line is now open.

Reni Benjamin (Managing Director)

Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress. It's just one for me.

When we go to Allo316, can you just remind us why RCC as opposed to, let's say, any other solid tumors? When I think about RCC, I always think about it in combination with checkpoints. I guess I'm curious as to where you guys are in the development of evaluating these Allogene cell therapies in combination with checkpoints, whether it's with RCC or any of the other indications or in the 501 test kitchen that you guys have.

David Chang (President and CEO)

Reni, great question. As you're pointing out, with our Allo316 targeting CD70, there are several different development opportunities. CD70 as a target, it is very attractive in both heme as well as autologous tumor indications. Certainly, renal cell carcinoma and I'll go into why we chose the renal cell as well as other types of tumors, solid tumors. Also, there's a lot of interest.

We are certainly getting a lot of inbound interest in advancing 316 in the AML indication, where there is some earlier proof of concept coming from using antibody alone for the treatment of AML. We have many different options to consider. At the end, from the corporate perspective, we wanted to advance the Allogene CAR T into the solid tumor, which is the reason that we chose the renal cell as the first indication. As a part of your question, I mean, is there an opportunity to combine CAR T therapy with a checkpoint inhibitor? I mean, that's definitely a topic that has been explored in other CAR T settings as well. We will be considering that once we sort of generate the safety and efficacy data from the single agent treatment of Allo316.

Also, at the same time, as we get more proof of concept from 316, stay tuned. We will be advancing that program into other indications as well.

Operator (participant)

Thank you. Our next question comes from the line of Raju Prasad from William Blair. Your line is now open.

Raju Prasad (Equity Research Analyst)

Thanks for taking the question. I wanted to get your thoughts on the ZUMA-7 trial and TRANSFORM results as it relates to how the LBCL landscape might change by the time ALLO-501 goes through its pivotal trial. Just curious to kind of hear the thoughts on CAR-Ts moving into the earlier lines of therapy given the CAR-T naive data that you've shown to date. Thanks.

David Chang (President and CEO)

Raju, thanks for that question. I personally was involved in the ZUMA-7 study, and I have to say that I was really thrilled when the preliminary data came out.

Certainly, that highlights what the CAR T therapy can do. I mean, there are a lot of questions about, is the CAR T therapy going to be just for the relapse refractory setting, or can it move up to the earlier line? I think the ZUMA-7 study sets a clear example that the CAR T therapy can be more effective and work better in the earlier lines of therapy. We see that as an opportunity for Allogene to follow what was set by the autologous CAR T therapy. Having been involved in both autologous and Allogene CAR T therapy, as I said in the prepared statement, what we are seeing in the Allogene CAR T therapy coming out of the 501 and 501A data is so many consistencies with what we saw in the autologous CAR T.

I mean, that's one of the reasons that we are very, I guess, somewhat bullish and confident about the future of ALLO-501A. The future for ALLO-501A will not stop in the relapse refractory setting. We will definitely advance that into other indications, especially in the earlier lines, as Rafael has earlier alluded to.

Operator (participant)

Thank you. Our next question comes from the line of Dane Leone from Raymond James. Your line is now open.

Dane Leone (Managing Director)

Hi. Thank you for taking the questions. Congrats on all the progress. Looking forward to some of the updates later this year. One question for me. Just wanted to focus on the primary inbound that we get in terms of your data set and aggressive B-cell lymphoma right now. That's really focused on understanding the infection risk profile. I guess maybe a multi-part question here, sorry.

One, could you just remind everyone how the lymphodepletion works for the consolidation regimen that you're now using that we should see more data on later this year? Two, maybe comment on your expectations for infection rates for that consolidation regimen relative to maybe what we saw reported around ASCO between the 90 milligram of Allo647, which seemed to be a bit higher than the 60 milligram dose. Lastly, how that could play into discussions with FDA about clinical trial design if you do go forward with the consolidation dose or not, what they would want to see in terms of maybe patient numbers to understand that infection risk potentially relative to other salvage line therapies for those patients. Thank you.

David Chang (President and CEO)

Yeah, thanks for the question. This is a complex question, and I'll do my best to do it justice.

Just to start with consolidation, we give dose intensity that is the same as the 90 mg that you've been seeing with the single dose in that we give 60 mg in three doses upon the first infusion. Then on the second infusion, which is done after day 28, we give 30 mg. The total dose intensity is the same, but it's split into two doses. We've been incredibly pleased with the tolerability of both the initial and the consolidation infusion. What we hear and what we see is that particularly with consolidation, patients do find there's been really no class effects, and the tolerability has been quite good to the point that we're considering whether this could be done as an outpatient.

The overall infection risk, I mean, if you look at the USPI of the three products that are approved in the autologous setting, I mean, it's very clear that it is similar to the infection risk that we see, which is in the 20%—it ranges between 19% to the mid 20% in terms of grade 3 plus infection rates. That's really what we see. We do not believe that the way that we're using Allo647 is leading to a higher rate of infection. It is really a common feature, which is really highlighted by the guidelines of how to treat these patients and how to prophylax them. It is possible that the split dosing may lead to even lower rates, but this is something that we really have to wait and see.

Even with the single dose, the rates have not been higher than what we see in the autologous setting.

Rafael Amado (EVP of Research and Development and CMO)

Yeah. And Dane, if I can just add on to that, as a clinician and as somebody who's been involved in the CAR T study, I mean, I can understand some of the concerns that are being raised about the infection rate. Now we have treated over 100 patients across different programs with our Allogene CAR T, AlloCAR T, 501, 501A, and 715. I think at this point, the clinical data speaks for itself in terms of the infection rate that we are seeing. I have to say that in 100 patients that we have treated, despite some of the concerns that are being raised, I mean, the data does not really indicate that the infection rate is any higher than what has been reported in the autologous CAR T therapy.

Operator (participant)

Thank you. Our next question comes from the line of Ben Burnett from Stifel. Your line is now open.

Carolina Ibanez (Equity Research Senior Associate)

Hello. Good afternoon. This is Carolina Ibanez, on for Ben. Thank you for the questions. For your solid tumor program with ALLO-316, how should we think of cell expansion data, and what time points can we expect to be supported by tissue biopsy data?

David Chang (President and CEO)

We in 316 follow cell. We do in the rest of our programs, which is pretty closely early on. Obviously, we spread it out as time goes on, but we continue to follow until we cease to see cell expansion. The data are premature, and we have not obviously shared any data with 316 yet, but we have seen cell expansion or cell persistence all the way out to six months and beyond.

There is one feature of 316 that we've mentioned in the past, which is that it is expressing activated T cells. We believe that the autoreactive T cells may express CD70 and may be susceptible to actually cell kill by the allogeneic CAR bearing cells. It is possible that the persistence may actually be even superior. This is something that we are looking at and taking a look very closely. In terms of the tissue, we definitely want to see what's happening in the tissue, particularly migration of the CAR positive cells to the tissue. We do biopsies very early on at entry into the study and then within the first 10 days. We look for CAR presence. We look obviously for CD70, PD-1, PD-01, and other markers to tell us what's happening with the tumor microenvironment.

So far, the data are premature, but we are accumulating these results, and it will be part of what will be presented when the data matures.

Rafael Amado (EVP of Research and Development and CMO)

Stay tuned.

Operator (participant)

Thank you. Our next question comes from the line of Asthika Goonewardene from Truist. Your line is now open.

Asthika Goonewardene (Senior Biotechnology Analyst)

Hi, guys. Thanks for taking my questions. Just want to follow back up on Allo715 plus the gamma secretase inhibitor. Guys, previously, you did mention that you might see this data in early 2022. I just want to check if that early part is still in play here. If not, could you maybe give a little bit more granularity as to when?

And then related to that, I guess besides response rates, MRD levels, soluble BCMA levels, etc., what other measurements and data can we expect in this first look of this combination that will help support the rationale for putting these two together? Thank you very much.

David Chang (President and CEO)

Yeah. I mean, we haven't said exactly when the data will be shown. I mean, we said it will be 2022, and I think we will make the decision once we consider that we have a meaningful data set. Stay tuned. All I can say, running this excellent team, is that accrual has not been a problem and that the execution continues actually at a very brisk pace. Hopefully, we'll accumulate data as soon as possible and be able to share it with you. Yeah. I mean, obviously, we're looking at BCMA expression in the plasma cells. We're looking at soluble BCMA.

We're looking at MRD. We're looking at persistence. We're looking at something that's important in this field also, which is extramedullary disease and the ability to prevent relapses outside of the bone marrow. Perhaps the most important factor is the mechanistic reason for giving the nirogacestat, which is, do we actually see a meaningful increase in BCMA, and does that result in a better enhanced activity of the CAR T Allo715? That's what we're focused on. We're doing all the right biomarkers that you mentioned.

Operator (participant)

Thank you. Our next question comes from the line of Kalpit Patel from B. Riley Securities. Your line is now open.

Kalpit Patel (Senior Biotech Research Analyst)

Yes, hi. Thanks for taking the question. Maybe one for David or Rafael.

In the study for renal cell, obviously, safety is a priority first, but at what dose level should we expect to see some signals of clinical activity based on your preclinical PK/PD modeling? And then can you remind us if the lymphodepleting doses that you're using in renal cell are essentially the same as what you use in your liquid tumor trials? Thanks.

David Chang (President and CEO)

Yeah. Let me take the whole cell dose question. From the preclinical to clinical, we all learned that in CAR T field, it is not as predictable. In terms of what is to see in clinics, I mean, it really has to be done in carefully planned clinical study, which is currently being done. Stay tuned. I mean, it could happen in the first dose level, or it could happen in the second. The planned dose is three dose levels in the 316 study.

The second question was

Kalpit Patel (Senior Biotech Research Analyst)

the administration of

David Chang (President and CEO)

the lymphodepletion for the solid tumor versus heme malignancies. For different reasons, I apologize for not answering the question. We are trying to remain relatively silent on the lymphodepletion strategy that we are making. Just wait for the data presentation. As we said in the prepared statement, we expect 316 data presentation to occur in 2022, next year.

Operator (participant)

Thank you. That concludes our question and answer session. I would like to turn the conference back over to management for any additional comments.

David Chang (President and CEO)

Thank you. It is an exciting time for Allogene as we look ahead to two near-term events that begin the journey towards commercialization, the planned initiation of our first pivotal trial, and taking control of our manufacturing with CellForge One, our first world-class facility.

With that, thank you for joining us today and for taking part in our journey to define the future of allogeneic cell therapy. Operator, you may now disconnect.

Operator (participant)

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.