Allogene Therapeutics, Inc. (ALLO) Earnings Call Transcript & Summary

All right. Good afternoon, everyone, from the JPMorgan Healthcare Conference. My name is Cory Kasimov. I'm the senior large-cap biotech analyst. And it's my pleasure to introduce our next company, Allogene Therapeutics and CEO, David Chang. Please note that following this presentation, we'll have a Q&A session where you have the ability to submit questions via your conference portal. So with that, David, thanks for being here today, and let me turn things over to you.

Cory, thank you very much for the introduction, and happy new year. Good afternoon. I'm David Chang, CEO and Co-Founder of Allogene, a company dedicated in leading the next revolution in cell therapy. If we can go to Slide 3? It's great to kick off 2021, updating our investors and supporters about the progresses at Allogene and how we intend to continue to grow Allogene to success throughout 2021, as we march toward achieving our vision of creating and leading the next revolution in cancer treatment by delivering to patients the first AlloCAR T therapies for blood cancers and solid tumor. The next slide captures what has happened to Allogene since its founding in 2021 -- I'm sorry, 2018. I have to say we have been successful in many fronts. We have established and extended our leadership position in allogeneic CAR T therapy and that includes our successful financing, including having raised more than $1.4 billion. Our manufacturing team has delivered uninterrupted supply for all our clinical trials while building internal manufacturing capabilities at our own Newark facility, which is on track to begin the production of AlloCAR T cells this year in 2021. At the same time, our development team worked relentlessly to advance clinical programs, now having treated over 75 patients across 2 key clinical programs targeting CD19 and BCMA. I believe we have an unmatched expertise in allogeneic CAR T trials. In doing so, we steadily advanced science and unraveled the hurdles of allogeneic cell therapy, controlling graft-versus-host disease and addressing other important safety issues such as cytokine release syndrome and neurotoxicity. And also utilizing ALLO-647, our own anti-CD52 antibody to create and optimize window of cell persistence. Importantly, we have demonstrated deep responses in indications we are pursuing, non-Hodgkin's lymphoma and multiple myeloma, and continuing to utilize ongoing Phase I studies to optimize the clinical benefits of allogeneic CAR T therapy. All these efforts are setting the stage for pipeline advances we have been planned for 2021. Five clinical trials, including first pivotal study, first trial in solid tumor, first combination trial and also first next-generation TurboCAR T trials. Next slide, this is Slide 5, shows our pipeline, which I believe is industry leading. ALLO-501 and 501A, targeting CD19 for the treatment of non-Hodgkin's lymphoma. Three BCMA targeting approaches in multiple myeloma, which I will further elaborate shortly. ALLO-316 and ALLO-819 for AML. And these programs cover key targets, such as CD19, BCMA, Flt3, CD70 that can cover the major hematologic cancers, non-Hodgkin's lymphoma, multiple myeloma and AML. Our pipeline also extends to solid tumors with programs covering CD70. This will be ALLO-316 in renal cell and DLL3 as well as additional 10 undisclosed targets. Next slide covers the benefits of the allogeneic CAR T therapy. Most of you are familiar with the potential of AlloCAR T therapy. Cost: scalable and efficient manufacturing, potential to treat over 100 patients from a single manufacturing run, an opportunity to reduce ancillary cost of care associated with autologous therapy; access, potential to treat all eligible patients, repeat dosing, if needed, no need for complex logistics or bridging therapy; innovation, multiplex gene engineering editing capabilities, an opportunity for product optimization that goes beyond what can be done with autologous cell therapy; and speed and reliability, off the shelf and an on-demand treatment, very important for patient management perspective; and also products with a less variability that are made with healthy T cells that has very enriched central memory as well as stem like T-cell phenotype. So the next slide covers what we view as an essence of what needs to be done in allogeneic cell therapy. Here, for us to use cells from a different donor in many different patients, we have to overcome the so-called self and non-self recognition process, which is foundation to immunological process. We have successfully demonstrated that graft-versus-host disease is addressable by eliminating the expression of T-cell receptors in AlloCAR T cells. Now much of our focus is controlling the graft rejection. And this is done -- and this is Slide 8. Anchoring on our ALLO-647, which provides selective biologic process for lymphodepletion. We have a proprietary position of using CD52 monoclonal antibody, together with editing out CD52. And we also have full access to anti-CD52 monoclonal antibody to use across different AlloCAR T clinical trials. And Phase I trials have demonstrated the ability of ALLO-647 to selectively enhance the lymphodepletion, which we believe is key to the cell expansion and persistence. And this really leads to the differentiation approach that we are doing in the lymphodepletion anchored by ALLO-647. An important aspect of cell therapy is manufacturing of the cells. And this, I'm going to cover both in terms of our strategy behind technical operations as well as our infrastructure that's enabling to do that. Slide 9 covers the strategy. We, as a company, are singularly focused on AlloCAR T platform development, which enables speed as well as minimizing the cost. And we have invested heavily in partnership with clinical suppliers to ensure availability of emergent and high-demand materials. We are leveraging a process known as QTPP framework for a product understanding to improve process performance and support comparability, as we advance the programs, and we also have the ownership in manufacturing now with a Cell Forge 1, which is online and begin to develop -- begin to produce allogeneic cell therapy products. And we have ALLO-647, which allows our differentiated lymphodepletion approach, which all allows the cost of goods manufactured in a very favorable way. And at the end, what we are aiming is reliable product delivery. In terms of the infrastructure, which is covered on the next slide, we have Cell Forge 1, which is a state-of-art manufacturing facility that has completed construction and this facility is designed for both clinical as well as commercial manufacturing, analytical testing and distribution of cell therapy, covering all the needs that we have to make sure that the clinical supply as well as future commercial supplies are uninterrupted. As I said, construction of the facility was complete last year, and first GMP production is projected to occur in this year. We also have a facility in South San Francisco that carries out manufacturing process and product development as well as development of analytical methods for process and product understanding and release. And also South San Francisco facility takes care of the need of quality assurance and quality control. As we are finalizing our own internal facility, we are still dependent on external network, which we have managed very successfully, and that includes both contract manufacturing and supplier network, and also incorporating external expertise for starting materials, drug substance and drug product manufacturing. And also important for us is packaging, labeling and logistics and clinical distribution, which, so far, we have been very successful in managing. Next few minutes, I will start covering our pipeline programs. Slide 11 starts with our first lead program, CD19. ALLO-501 and 501A, we are really focusing advancing ALLO-501A to potential pivotal study in 2021. What's -- much of the data that we have generated with the proof-of-concept, construct ALLO-501, is captured in this slide. The key points that I want to make is that study as presented at ASCO 2020 showed early efficacy that is competitive with Autolus CAR T therapy, 83% objective response rate including 67% complete remission rate at high dose ALLO-647. And the treatment was well tolerated with no evidence of graft-versus-host disease and manageable cytokine release syndrome and early safety data, which overall compares favorably to the Autolus CAR-T therapy. And we showed that with the allogeneic CAR T, on-demand dosing is possible. Essentially, only time that it takes from the enrollment to the treatment was 5 days compared to what it takes in autologous cell therapy setting, which can range anywhere between weeks, sometimes getting close to a couple of months. The study also showed biomarker validation demonstrating correlation between ALLO-647 lymphodepletion and ALLO-501 cell expansion and tumor response. And we are continuing this program with the retreatment and consolidated dosing to potentially optimize the outcome. Shown on the right panel is what I have said, what was seen in the ALLO-501 study. And comparing to the autologous data coming from 2 different non-Hodgkin's lymphoma, one capturing Phase I data and the other one capturing Phase II data on the top as well as the safety data across key safety issues related to cytokine -- I'm sorry, to the cell therapy as well as graft-versus-host disease. Important to note is we have not seen any cases of graft-versus-host disease and also the infection, which is one of the known complications of cell therapy, that looks very favorable compared to what has been seen with axi-cel, tisa-cel or liso-cel. Next slide, and this is Slide 12, shows the waterfall plot demonstrating that with ALLO-501, we can achieve a deep responses. And most of the responses can be complete responses. And shown on the right is PET/CT scan image of a patient who has undergone the cell therapy with our ALLO-501. Baseline is shown on the left and 4 months after the cell therapy patient demonstrating a complete response. And this is a response that's still ongoing. So what have we learned from the ALPHA study of ALLO-501, which is captured on the next slide, this is Slide 13. I think we have successfully answered some of the key questions. Can ALLO-501 be successfully manufactured? The answer was yes. Can ALLO-501 be safely administered without closing clinically relevant graft-versus-host disease? We have answered that. Can ALLO-647 be safely administered and allow a sufficient window of lymphodepletion to -- for ALLO-501 expansion and persistence to occur? We have shown that. And can ALLO-501 provide complete responses across multiple histologies? And we have also shown that. And we are continuing the follow-up of the patients who have been treated to demonstrate whether ALLO-501 can provide durable response. Next few slides, I'll cover the multiple myeloma. It is worth reminding ourselves -- this is Slide 14, why allogeneic cell therapy matters in multiple myeloma. Multiple myeloma is progressive disease with no noncurative therapy and prognosis of the patient worsens all the time. If you look at the available data on time to progression, what's shown on the right panel is time progression of 18 months in the first front-line setting. And that's with the treatment providing up to 74% complete response or very good partial responses. As you go to the second and subsequent lines of therapy, time to progression shortens and also the ability to achieve complete remission or very good partial response diminishes. And when you get to the point of penta-refractory, so these are patient population that is being targeted with a CAR T therapy. The response rate, complete remission and very good partial response is below 10% with available therapy. This really highlights the unmet need that exists in multiple myeloma. And also important is that speed of disease progression in later lines of therapy cases a clinical challenge for patients waiting for Autolus CAR-T therapy who often require bridging therapy to control the disease. And this comes at the risk of potentially increasing cumulative or synergistic toxicity. Time is of the essence for patients with rapidly progressive disease, and we believe allogeneic CAR T therapy can provide a potential solution. Next slide, Slides 15, really highlights our approach to address the need in multiple myeloma. We are taking a franchise approach first with ALLO-715 anti-BCMA AlloCAR T monotherapy. And the second is using ALLO-715 in combination with nirogacestat, which is a gamma secretase inhibitor to potentially increase antitumor efficacy. We announced the clearance of IND to start the combination study, and we are in the process of site activation, which is ongoing, and we are hoping to enroll -- start enrolling patients shortly. Another important part of this franchise is ALLO-605, which is next-generation anti-BCMA CAR T therapy that incorporates the TurboCAR T technology that is designed to selectively enhance the potency of AlloCAR T cells. Now covering each of these 3 franchise programs, one by one. Slide 15 summarizes the data that we presented at recent ASH meeting at the -- a month ago. ALLO-715, and as the data were presented, this is the first allogeneic CAR T data to demonstrate feasibility in multiple myeloma. There was a clear benefits associated with off-the-shelf therapy. 90% of the patients were treated within short time, 5 days after study enrollment, without the need for the breeding therapy prior to dosing. Therapy was well tolerated across different dose levels with no evidence of graft-versus-host disease or neurotoxicity and all the cytokine release syndrome manageable at Grade 1 or 2. Also, just as in the ALLO-501, our non-Hodgkin's lymphoma program, infection rate was on par with other studies in advanced multiple myeloma. And we also saw dose-dependent activity in heavily pretreated refractory patients. ALLO-715 cell persistence was observed through month 4 in many patients. And at 320-milligram cell dose level, with FCA lymphodepletion, we are seeing overall response rate of 60%, with 5 of 6 very good partial response or complete remission patients achieving the MRD-negative status. On the right is a patient with a bone marrow data. And the top immunohistochemistry at baseline shows bone marrow that's heavily infiltrated with CD138 positive multiple myeloma cells. Within short time after cell infusion, the follow-up on there that was done on day 28 shows total eradication of these myeloma cells, while preserving the normal cellular components, which can be seen in the H&E staining on the bottom. The next slide, Slide 17, summarizes and compares to what we saw in ALLO-715 Phase I study to other autologous cell therapy, starting with a safety comparison on the top as well as efficacy initial response comparison on the bottom. I'm not going to go through the details, but when you look at the overall safety profile, what we are seeing in the ALLO-715 is on par or compares favorable to what was reported in Ide-Cel, Orva-Cel or Cilta-Cel clinical trials. And on the bottom, and our ongoing Phase I study, which hasn't completed the dose exploration as well as optimization of the lymphodepletion shows very encouraging response rate, which I think tracks very well with what has been reported with more mature studies in the autologous cell therapy. Slide 18, the next slide, covers our planned combination study of 715 with the nirogacestat. The study schema shown on the right patient undergoes lymphodepletion followed by a single infusion of ALLO-715, during which patients will also be treated with nirogacestat. Patient will be evaluated for the safety and response and then will be subjected to a longer-term follow-up. The planned doses of nirogacestat as well as lymphodepletion regimen that is planned is listed below in the table. Like any other Phase I study, primary endpoint is safety and tolerability and secondary endpoint includes antitumor activity as well as cellular kinetics and looking at the pharmacokinetics of ALLO-647 as well as nirogacestat. And certainly, we will be evaluating the BCMA expression in bone marrow in patients undergoing treatment with a nirogacestat. Key eligibility criteria are listed below, and this would be pretty standard for the CAR T studies that have gone into the multiple myeloma. Next slide, this is Slide 19, covers our ALLO-605. This will be the first program that will incorporate TurboCAR T technology. Why TurboCAR T? This is an engineering that is designed to recapitulate cytokine signaling selectively in the CAR T cells. In doing so, it does not stimulate host immune cells, which could lead to systemic toxicity or potentially rejection of AlloCAR T cells. And also, it delivers a survival benefit selectively to the AlloCAR T cells. And this could lead to the improved -- improvement in the efficacy of AlloCAR T cells, potentially reducing the cell dose requirement as well as potential to overcome exhaustion and allow CAR T cells to work more effectively, especially as we eye our AlloCAR T programs into the solid tumors. On the left is the sort of schematics of what the technology entails. It is really allowing the dimerization constitutively of the cytokine signaling domain, thereby enabling AlloCAR T cells to benefit from the cytokine signaling. And the result in the preclinical studies are captured on the bottom. Three lines of -- that are shown on the left is tumor growth in mice without any treatment that's no CAR treating with a standard BCMA CAR as well as treating the mice with a TurboCAR. And what is very apparent? And having done this kind of experiment many times and reviewing this data, we are really struck by what the TurboCAR T cells can do in terms of achieving the response as well as maintaining the response in the preclinical model. We are extremely excited about the AlloCAR T programs, and we are looking forward to submitting the IND and starting the clinical study with ALLO-605 in multiple myeloma, thereby completing our franchise approach towards addressing the unmet need in multiple myeloma. Next slide is really where we are going as a company? I mean last 1.5 years, much of our attention was trying to get entrenched in 2 key indications, non-Hodgkin's lymphoma and multiple myeloma. And we have done that very successfully. With that, we are beginning to shift our focus to -- from hematologic malignancy. I would say, shifting the focus by adding -- so augmenting our focus to include solid tumors. Why solid tumor? This is really driven by the unmet medical need that exists in solid tumors. When you look at the incidents as well as deaths attributable to hematologic malignancy and solid tumor, it is very apparent that solid tumor is biggest unmet medical need in the entire oncology space, incidents of numbers -- incidence in heme malignancies by about 10-fold as well as death due to solid tumor is close to 9x over the death due to heme malignancies. And this is also reflected in the commercial opportunity, where cancer drug spending in 2018, which accounted for about $150 million -- billion, majority of which was coming from the spending in the solid tumor. So we see significant opportunity to expand benefits of CAR T therapies into larger areas of unmet medical need. What needs to be done in solid tumor is captured on the schematics on the right. Our strategy is grounded on target selection and validation. And working towards optimizing the T-cell fitness using both gene engineering as well as manufacturing process. And also trying to address the immunosuppressive tumor microenvironment that exists in solid tumor using technologies such as TurboCAR as well as lymphodepletion strategies. And also, important in solid tumor is how cells traffic into the solid tumor. And we believe we have a good control of this situation. That's leading to our first program in solid tumor, which is captured on Slide 21, ALLO-316. This is -- will be -- this is the first and will be one of the many that we have in plans to introduce AlloCAR T into the solid tumor. CD70 is a target that's selectively expressed in several cancers, notably renal cell cancer, where majority, if not all, the cancers express CD70 and the expression of CD70 is very unique in that it's very limited to the tumor. And virtually, there's no normal tissue other than certain blood cells that express CD70. And CD70 has a place in tumor types other than solid tumors, namely continued our interest in hematologic malignancies as well as CD70 expression can be seen up to 96% of the tumors. We announced at the last year a clearance of IND and we are in the process of activating the clinical site ahead of the enrollment, which we plan to do in the first half of this year. Schematics of the study design as well as the planned cell dose levels are shown on the right panel. Next slide, Slide 22. It's really talking about what we are doing. So far, we have covered all the things that we are doing organically at Allogene. However, important in our space is leveraging the external innovation and capability. This site serves to recognize and thank some of our partners who have been instrumental in helping us to advance our pipeline as well as technology, Servier, Cellectis, Notch Therapeutics, which we are -- whom we are collaborating to advance the iPSC drive technologies. Maxcyte, SpringWorks, whom we are collaborating for the ALLO-715 gamma secretase combination study as well as MD Anderson and many other academic partners. I'd like to point out that we recently entered into a partnership with Overland Pharma to create a joint venture in China. Moving to Slide 22 (sic) [ Slide 23 ] . This joint venture, Allogene Overland Biopharma is created to advance allogeneic CAR T in Greater China, Taiwan, South Korea and Singapore. This is a first in kind collaboration and has the right to develop AlloCAR T therapies in these geographic areas. Allogene is contributing the assets as well as technology, especially on the manufacturing. Overland Pharma backed by Hillhouse Capital is providing the local expertise and funding, which includes an upfront payment of $40 million to Allogene as well as setting aside $77 million in operating budget. As I said, this is our first in kind collaboration, and we are excited to expand the allogeneic CAR T therapy programs beyond the western countries, which we are -- we have been doing into Greater China as well as other countries in that region. I want to conclude my presentation with the last slide, Slide 23, which really highlights what is in plan for 2021. In the first half, 3 key events: initiating ALLO-715 gamma secretase inhibitor combination study; advancing our solid tumor by initiating ALLO-316 study in renal cell cancer; and also submitting ALLO-605 TurboCAR IND for multiple myeloma indication. And also, we plan to update the status of our ALLO-501 and 501A clinical study in the first half. Second half is going to be very important not only we will be manufacturing our own CAR T programs from our GMP manufacturing facilities. We are working towards initiating ALLO-501A pivotal study in the second half of 2021. Much of last 2.5 years have been very busy, and we are looking forward to another busy and exciting year in 2021. And with that, thank you very much for your attention, and I look forward to updating you on our progress throughout the years.

Terrific. Thank you, David. We'll have about a little less than 10 minutes for Q&A. It was nice of Siri to make a cameo there as well.

Yes. My apologies. I mean that's...

Oh, no, it's always good, always good. So just -- we'll get to a few questions, and we'll touch on a couple of your different programs. Starting with the 501, 501A update, though, in the first half of this year and recognizing that you answered a lot of questions about the approach and everything last year, durability is one of the key on answer ones and that takes some time to play out. Your -- the update you'll be able to provide the first half of this year, do you think we'll get a good read at that point to durability? Or is this something that's going to take even more time just like a larger sample size a little bit more follow-up?

Yes. I mean that's a great question. I mean the way that we have been coordinating the CD19 program is with 2 different clinical studies. One with ALLO-501, where we have treated a number of patients and all the treatment -- majority of the patients have been patients who have been studying the 501 was to optimize the cell dose as well as to optimize the lymphodepletion. And these patients will definitely have a much longer follow-up. And we plan to provide some updates on the status of the longer follow-up from that study. 501A, which is the construct that we will take it into the pivotal study. That study started a little bit later after 501, and we are advancing that clinical study initially with a very abridged dose escalation but now enrolling patients into the consolidation regimen and targeting the large B-cell lymphoma patients. So here, there will be 2 different studies that will provide critical answers, both in terms of the durability, the 501 study as well as whether the consolidation can improve the initial response rate beyond what we have shown already with the 501. So you will see towards the end of first half, but we are quite ready to -- we believe, as we have done in the past, our data update will be very meaningful.

Do you have a hunch with the data you've generated to date, whether the consolidation approach or the sort of the onetime treatment approach is going to be the most optimal path forward?

I mean we have seen very encouraging data with a single treatment. But we are also trying to do a few additional things. I mean one of the benefits of the allogeneic off-the-shelf therapy is the ease of redosing. And we also know from all the autologous cell trials in the non-Hodgkin's lymphoma. It is groundbreaking benefit to the patients. But still, majority of the patients, over 60% of the patients do not stay in response. So I think -- we believe that there is a great opportunity. So we are trying to leverage that opportunity by going with the consolidation approach where we would treat the patient with a CAR T, allogeneic CAR T consecutively over a 2-month period, thereby achieving much deeper response, which we believe will translate to much durable responses. Obviously, we will have to generate the data, but we are very excited and we are very encouraged by some of the redosing data that we have already generated from the 501 study.

Okay. And then on the BCMA front, there was recently another company that presented data for a fast CAR approach, where an auto CAR T can be manufactured in a matter of days. If the industry were to trend there from where autos could be produced much faster than they currently can, does that change the value proposition at all for an allogeneic CAR T? Or is that like a healthy donor cell and a key component that really doesn't get altered?

I mean speed is one of the many elements of the benefits of the allogeneic CAR T therapy mean, the speed, even if it's 1 or 2 days, doesn't come close to off-the-shelf concept of having things ready rather than dealing with the uncertainty about whether the manufacturing will be successful or not. And also dissociating the manufacturing from the patient need allows us to not only use the healthy donor cells, where we can generate products with much better T cell fitness, but we can also do more complex gene editing and gene engineering. And that's really the crux of how we can move to the next generation where the engineering goes beyond simple introduction of the CAR T construct. But as we are doing engineering with a TurboCAR as well as gene editing that can be incorporated into the cell therapy products. So the innovation, I believe, comes much better and more opportunities with allogeneic CAR T therapy.

Okay. And in our last minute, just working this audience question is, do you [Audio Gap] next BCMA AlloCAR T update?

So we have -- we are really trying to provide a meaningful update. Our BCMA data presentation was only a month ago. So it's a little bit too early to talk about when the next data presentation is. But it will be sometime in 2021, but I think it's too early to say exactly when.

Okay. Perfect. And with that, we are out of time. So David, thank you very much. Really appreciate your time and your insight here today.

And thank you very much, and thanks for very insightful questions, and have a nice day, Cory.

Thank you.