Allogene Therapeutics Inc (ALLO) 2021 Q4 法說會逐字稿

Hello, and thank you for standing by, and welcome to Allogene Therapeutics Fourth Quarter and Year-End 2021 Conference Call. (Operator Instructions) 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 join this call. After the market closed today, Allogene issued a press release that provides a business update and financial results for the fourth quarter and full year 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; Dr. Eric Schmidt, Chief Financial Officer, and a new voice on our quarterly calls, Dr. Alison Moore, Chief Technical 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, data at presentations, regulatory filings, future research and development efforts, manufacturing capabilities, and 2022 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.

Thanks, Christine, and thank you all who have joined our call. I am very excited to talk about what we believe will be an important year for Allogene, as we are working to advance 3 exciting clinical programs, from initiating our first pivotal trial in non-Hodgkin's lymphoma to progressing our mid-stage program in multiple myeloma to pivotal readiness and advancing our solid tumor clinical program to potential proof of concept. 2021 was both a year of significant pipeline achievement and unexpected challenge associated with a clinical hold, both of which played a meaningful role in moving Allogene and the fields of allogeneic cell therapy forward.

With our CD19 program, we demonstrated on the important first for our field as the Phase I data from our ALPHA trials continues to support the promise of our platform and our ability to provide safe and durable alternative to approve autologous CAR T therapies in patients with relapsed/refractory non-Hodgkin's lymphoma. Our next most advanced clinical program targeting BCMA is the leading allogeneic CAR T program in multiple myeloma. Our universal study opened the door for this modality, as the first and still only trial to demonstrate substantive proof of concept for allogeneic CAR T in this disease setting.

While we are proud to have established proof of concept, safety and efficacy data in both lymphoma and myeloma, we are even more excited about the potential for AlloCAR T products to overcome the inherent limitations of autologous therapies. Today's marketplace for autologous cell therapy is constrained by treatment delays, supply limitations, and often a requirement that patients receive within chemotherapy. No matter how compelling the data on autologous therapies might be, they are of no value to the many patients who cannot gain access.

With our AlloCAR T products, we have shown the ability to deliver treatments to patients within days rather than weeks. Patients who enrolled in our studies can be nearly guaranteed to receive our products. In the ALPHA trials 98% of enrolled patients received our products within a median time of 2 to 5 days from enrollment to the start of treatment. By comparison, in trials deploying autologous therapies for non-Hodgkin's lymphoma, up to 30% of patients who underwent successful look of braces for [CAR] manufacturing was still unable to receive treatments due to enable disease progression while waiting for CAR T cells products, due to manufacturing failures.

Treatment delays are even more critical in the multiple myeloma settings, as many patients with exactly progressing disease require bridging therapy as they wait for the manufacturing of their autologous CAR T cells, and those who are unable to tolerate effective breathing chemotherapy may not be considered candidates for autologous therapy. Shortening time to treatment and ensuring access for nearly all suitable patients is just the beginning of how we are leveraging the attributes of AlloCAR T products.

Our first allogeneic candidates are only the beginning of product innovation in the field of AlloCAR T. Our next-generation products based on our TurboCAR and other technologies that aiming to enhance the efficacy and safety of allogeneic cell therapies. Aside from the data presented in 2021, came an unexpected challenge, our clinical hold. While no company wants to be faced with a hold, the situation provided us the opportunity to retest our manufacturing processes and reconfirm the quality of our products.

In responding to and quickly resolving the hold, our team, under the depth stewardship of Rafael demonstrated the quality of leadership, collaboration, innovation, and focus required to be a pioneer in the field of AlloCAR T. I am incredibly proud of the manner in which our employees close to this challenge. In retrospect, this experience provided us with a insight that we believe will give us a competitive edge as we look to lead the field of allogeneic cell therapy. We look forward to sharing the results from our scientific investigation in a peer-reviewed forum.

As we prepare for the next stage in our lifecycle with a plan ALLO-501A pivotal trial for relapsed/refractory large B cell lymphoma in mid-2022. We are also determined to minimize hurdles that could create delays at the time of a biologic license application submission. This brings us to our technical operations, product sciences and manufacturing organization.

From the beginning, we have maintained that having in-house manufacturing capabilities is key to controlling the delivery of Off-the-shelf CAR T therapies faster, more reliably, and at a greater scale, and we have invested heavily in this area. Our state-of-the-art manufacturing facility in New York, California, called Cell Forge 1, is now fully operational and producing GMP material with the intent of supplying ALLO-501A in our planned pivotal study.

Our incredible technical operations team is led by Dr. Alison Moore. In early 2018, as we are forming Allogene, I knew Alison was the person I wanted as our Chief Technical Officer. When you are building something that has never been built before, there is no blueprint, you need someone who knows technology operations inside out. Alison came to Allogene with over 25 years of experience in chemistry, manufacturing and controls was CMC at Amgen and Genentech from process and product development to manufacturing, supplies chain, global operations planning and CMC regulatory affairs. I am immensely proud to work alongside Alison and knows there is no one better to navigate the evolving CMC landscape. We are excited to have her join the call today.

I now would like to invite Rafael to preview our R&D priorities for the upcoming year.

Thank you. As David has noted, I would like to focus my remarks today on the year ahead on our clinical programs as we prepare for a pivotal trial targeting CD19 and advance our BCMA and CD70 programs. As most are aware, we issued a press release on January 10, announcing that the FDA had removed the clinical hold on our AlloCAR T clinical trials. After our extensive investigation, it was determined that the chromosomal abnormality detected in a single patient treated with ALLO-501A was unrelated to TALEN gene editing or Allogene's manufacturing process and had no clinical significance.

The abnormality was not detected in any manufactured AlloCAR T product or in any other patient treated with the same ALLO-501A lot. The abnormality developed after the cell product was administered and involved regions of the T cell receptor and immunoglobulin genes known to undergo rearrangement as part of the T cell or B cell maturation process.

During our hold, our engagement with study investigators was robust, and it was clear many were anxious for Allogene to resume study. We are pleased to have quickly resumed clinical productivities and are enrolling patients focus on our ALLO-715 and ALLO-605 for multiple myeloma, and ALLO-316 for renal cell carcinoma. We have completed accrual in the ALLO-501 ALPHA study, and the study will now continue to assess longer-term patient follow-up. As such, we will be directing the full CD19 focus on ALLO-501A and finalize with the FDA, a registrational approach prior to starting the pivotal outside to study.

Prior to the start of Phase II, we plan to resume enrollment in the Phase I study in order to offer AlloCAR T to patients in need. Our ultimate goal is to deliver the first approved allogeneic CAR T product. We remain on track to start our ALLO-501A pivotal trial mid-year. One of the most commonly asked questions from investors is about pivotal trial design. Given the competitive nature of the field, we are prioritizing the finalization of our discussions with the FDA. We will share additional details in our single-arm 501A study at the time of trial initiation.

Separately, and as Alison will discuss, we're front-loading many of the activities that address evolving CMC requirements ahead of what would be needed for a potential BLA submission. We believe our lymphodepletion regimen is differentiated through the use of ALLO-647, our anti-CD52 monoclonal antibody intended to enable enhanced expansion and persistence of AlloCAR T product candidate.

Separate from our single-arm pivotal trial with ALLO-501A, we also intend to launch a standalone registrational trial for ALLO-647 at the time of the ALLO-501A pivotal trial. These randomized trials referred to as we expand trials, is intended to demonstrate the safety of ALLO-647 and its contribution to the overall benefit of the lymphodepletion regimen. Based on the data we have previously presented at medical conferences, we believe ALLO-647 enables the highly competitive product profile for patients with large T cell lymphoma.

We also remain very excited by the potential of our anti-BCMA program. Autologous CAR T therapies targeting BCMA have recently shown unprecedented response rate, which appear well in excess of what has been achieved with any other modality in relapsed refractory myeloma. Yet, there are few allogeneic BCMA programs in development with the potential to bring cell therapy to the large population of patients in need. This has been reinforced by discussions with investigators.

Our multi-pronged strategy to address this opportunity includes the Phase I UNIVERSAL trial, which has cohorts evaluating ALLO-715 as a monotherapy, consolidated dosing and the combination of ALLO-715 with [yoga assisted]. The Phase I IGNITE trial evaluating ALLO-605 is our first TurboCAR candidate, which allows cytokine activation signaling to be engineered selectively into CAR T cells intended to improve the potency and persistence of allogeneic cell. So all activity has resumed and we plan to provide a BCMA program clinical updates by the end of 2022.

Findings from our UNIVERSAL Trial on ALLO-715 indicate that an allogeneic CAR T therapy can be delivered rapidly, and we felt a need for bridging therapy to patients with refractory multiple myeloma and that a single dose of therapy was capable of inducing deep responses. We are pleased that ALLO-715 as a monotherapy could achieve and maintain meaningful response rates, similar to the approved autologous CAR T therapy with a high rate of MRD negativity for patients achieving VGPR or better responses.

The benefits of an allogeneic option are especially valuable in aggressive disease like relapsed refractory multiple myeloma, even with new potential therapies in the horizon. Through ample discussions with investigators, the need for more therapy options is clear, and they often emphasize that an allowable margin for efficacy is offset by benefits provided by the official alternative.

Before I welcome Alison to discuss our technical operations, I would like to comment briefly on our clinical development of ALLO-316, our anti-CD70 AlloCAR T candidate for solid tumors. Clinical trial activities have resumed for our Phase I TRAVERSE trial which is designed to evaluate the safety, tolerability and anti-tumor efficacy of ALLO-316 in patients with advanced or metastatic clear cell renal cell carcinoma.

Metastatic solid tumors have historically been a challenge regardless of treatment modality. The 5-year survival rate for patients with advanced kidney cancer is less than 15%. This underscores not only the unmet needs but also the necessity for scientific innovation. CAR T therapies in general have faced significant challenges in solid tumors, which can be summarized in 3 areas: target recognition and selectivity, trafficking and survival within the tumor.

We're working to overcome these issues with our AlloCAR T platform, including several next-generation approaches to overcome the inhibitory signals of the tumor microenvironment. Meanwhile, we look forward to generating data from our ongoing Phase I dose-escalation trial.

I would now like to turn the call over to Alison.

Thank you, Rafael. I've been fortunate in my career to build high performing teams, bring multiple medicines to market, build state-of-the-art manufacturing facilities, and redefine the scope of process development. However, a career highlight and something I am most proud of has been the progress we've made in making AlloCAR T a reality for patience. When I joined Allogene in 2018, we were a small team working to do something that had never been done before, create off-the-shelf CAR T products for patients with cancer from the T cells of healthy donors.

Our first clinical data presentation in 2020 provided initial proof-of-concept for the industry, showing that our allogeneic product have the potential to improve patients lives. It represented 2 years of rigorous work, creativity, problem solving, and collaboration. Understanding product quality is paramount to the development of safe and effective products.

In our increasingly complex world of biopharmaceutical development, the design and control of product quality is far from simple and we've seen time and time again in cell therapy, how manufacturing delays or issues translate into patients not getting treatment. That is why excellent CMC science is so critical. It is the convergence of multiple disciplines coming together to solve some of our most difficult challenges.

I've been fortunate to have worked on many modalities, including monoclonal antibodies, viruses and bispecifics, but I'm particularly excited about advancing cell therapies. While we stand on the shoulders of the autologous pioneers, the field continues to evolve dramatically as the science, the industry and regulators become increasingly sophisticated. The evolution is clear. In the emerging cell and gene therapy field, the CMC work toward a BLA submission cannot be an afterthought. It is critical for demonstrating the quality of our product, the reproducibility of the process and the control strategy. Any gaps or weaknesses can compromise the entire submission.

In the development of monoclonal antibodies, for instance, teams may have years during Phase II and Phase III clinical development in which we could study performance of the process and methods and the opportunity to optimize production. In the development of CAR T therapy for late-stage cancer, we have the privilege of starting pivotal trials relatively quickly, following the recognition that these product candidates have game-changing potential for patients. This expedited timeline is unique for CMC practitioners, and ensuring the right experience within our teams is of utmost importance.

Failure to understand the evolving landscape and FDA requirements can be a common pitfall and a cause of delay for new product approvals. The ability to produce safe and effective biologic products from complex raw materials is the difference between hope and reality for patients in need. While the start of any pivotal trial is exciting, approval is the ultimate goal.

At Allogene, we are focused on mitigating risks as we look ahead to the BLA submission by moving up the timeline for important CMC validation work prior to the start of the pivotal program. This improves our measurement of quality attributes and enables robust characterization for approval. Strong process and product validation support our ability to deliver a well-characterized biologic with minimized variability. We believe this will work to our advantage in the long term and set us up for success.

Understanding a live product requires collaboration across many disciplines, including process development, clinical, research, translational sciences, and biometrics. I am so proud of the proactive work being done by our incredible team to eliminate the potential downstream delays and to more importantly, be able to say with confidence that we can safely and effectively deliver to patients the promise of our AlloCAR T products.

We look forward to advancing this important area of drug development and building a robust regulatory dossier that effectively communicates the strategic design and strong execution of our CMC activities.

I will now turn the call over to Eric.

Thank you, Alison. During meetings with investors, we often get a multitude of questions on manufacturing and the evolving gene and cell therapy CMC landscape. So we're quite privileged to have Alison someone so experienced and visionary at the helm of our operations technology group.

Before I provide a brief overview of our financials for the quarter and year-end, I'd like to spend a few minutes on a topic that's been at the forefront of the industry and stays very challenging market environment, cash runway. We are very fortunate to be in a strong financial position ending the year with $810 million in cash, cash equivalents and investments and no debt.

As you may have been able to discern from comments by David, Rafael and Alison, one of the most critical elements of our corporate and financial strategy is to efficiently deploy our capital resources to support value-enhancing programs that will drive long-term growth. In 2022, we have taken important measures designed to keep our cash burn below $300 million. This means focusing on our most critical activities, including #1 starting of our ALLO-501A pivotal trial; #2, capitalizing on the tremendous opportunity in multiple myeloma; and #3, continued exploration of the role of AlloCAR T in solid tumors. We strongly believe we have the operational capabilities, scientific prowess, and resources needed to succeed in all 3.

Taking into account the incremental investment needed to support our first pivotal trial and fully operationalized Cell Forge 1, we expect our full year 2022 GAAP operating expenses to be between 360 and $390 million, including estimated non-cash stock-based compensation expense of $90 million to $100 million. This guidance excludes any impact on potential business development activities. As we review our financials for 2021, for the full year of 2021, research and development expenses were $220.2 million, which includes $39.6 million in expenses associated with non-cash stock-based compensation.

For the full year of 2021, general and administrative expenses was $74.1 million, which includes $41.2 million of non-cash stock-based compensation expense. For the full year of 2021, our net loss was $257.0 million or $1.89 per share, including noncash stock-based compensation expense of $80.8 million.

With that, we will now open the call for your questions.

(Operator Instructions) Our first question comes from Michael Yee with Jefferies.

We got 2 questions. One was appreciating all the color you discussed around CMC and manufacturing. I guess maybe you could shed some light without giving too much away competitively on what you're working on and what competitive advantage or what insights you can provide us on that advantage that you will have confidence that you will start the pivotal CD19 study by mid-year? In other words, you're commenting about all of this and those are the key factors. Maybe give us some color on that.

And the second relates to later this year, there is a myeloma update. Can you just remind us on expectations, presumably, that's mostly data on the first generation, but not likely to have real data on TurboCAR?

Hey Michael, this is David. Thanks for those 2 questions. Obviously, the CMC question, that's not something that we have spoken about in our previous earnings call. And also this is an area that probably is very complex. And we don't want to tip too much of our head about revealing too much. But since Alison has joined in, I'll ask her to provide some high level response to your questions about what's being done on the CMC side. Alison?

Yes, obviously, on the CMC side, we are really excited to advance product from Cell Forge 1. Cell Forge 1 was designed and built to support commercial supply and we're so excited that, that is already generating GMP material. And we are working with the agency to ensure that we can realize our goals are of supply from Cell Forge 1.

Also, we are really interested and excited, as I described in my comments to really demonstrate that we understand our product really well. We think that this helps all the way through developments. It helps me provide the best support for our clinical colleagues. And it allows us to make modifications, optimizations, and refinements as it go towards BLA filings.

Thank you. It sounds like it's really about Cell Forge 1, that's a big part of this given that that's a kind of support commercialization. And then on myeloma?

Yes. So just on that, I mean, as Alison had said, we are trying front load as much CMC activity ahead of the BLA filings. So we are taking very careful measures to address what's known as well as potential issues that may come up down the line. And being able to launch the pivotal study with the materials coming from the CF 1 is one of the big things that we are trying to do. So with that on the myeloma data, Rafael?

Yes. Thanks, Mike. And so as you know, we presented at ASH data on 43 patients, and in my remarks, I spoke about how excited we were about the data. And how it did really compares very well to the approved product that's out there in terms of responses VGPR+ as well as durability. The interesting thing is that the follow-up was actually not long, so we continue to follow-up these patients and the durability may still improve.

We are really excited about the fact that it's been really well received both by investigators and non-investigator key opinion leaders in terms of the results that are obtained with a product that essentially is able to treat virtually every patient as opposed to the autologous product. So we look forward to providing an update, as I mentioned before, that would be towards the end of the year. And it would include the patients that we have treated with nirogacestat.

We are now treating all of the (inaudible) patients with 605, and depending on the number of patients from the follow-up, and we may be able to include some of those patients in that update towards the end of the year. So stay tuned, it's a really exciting program that we are testing several approaches, and it will be a big decision point for us this year.

Our next question comes from Salveen Richter with Goldman Sachs.

Could you just speak to the ongoing discussions that you're having with the FDA that have to be finalized prior to commencing the pivotal ALPHA2 trial? And then secondly, with the CD70 program, how should we think about what the bar is here for what you'd want to see to -- for that to be kind of a positive step to then move forward?

Salveen, you're making my job easy. I can refer again to Rafael to answer both of those questions. Rafael?

Yes. So we've been having discussions with FDA during the fall, which I think speaks to the interest and -- mutual interest on moving this allogeneic program forward. And we as you know are co-developing ALLO-647 as well. So we have had discussions as well in terms of how to develop that product. And 647 gives us a lot of precision with (inaudible) lymphodepletion. But in order for it to be approved as co-development, the agency obviously requires evidence of benefit risks. So those discussions are being finalized. We're actually quite advanced on them. And we are very confident that the study will start -- the 501A study will start by mid-year follow shortly by the ALLO-647 trials. So both trials are going to be in execution mode.

And obviously, we are working very closely with Alison and her team to ensure that we work together in sync and that we finish this trial without any issues with regards to designs or any issues with regards to CMC that may jeopardize our ability to complete the trial. So stay tuned. But the discussions are proceeding according to plan, and we have full confidence on our ability to start by mid-year.

On the CD70 program, CD70 program has resumed, it's really exciting program, we had started treating patients and we're continuing now. There's excitement in the investigator community about this program, it's in renal cell carcinoma as you know, but it's got a lot of potential in other solid tumors and hematologic malignancies.

And with regards to the bar, as I said before, these patients, unfortunately, once they fail checkpoint inhibitors and angiogenesis inhibitors, even if they get more than one line of therapy, their 5-year survival is quite low in the order of 10%, 15%. So, obviously, it's early for us to have discussions with regards to what is it that would be a meaningful regulatory threshold for approval. But this is something that we will, obviously, evaluate as we see it. But clearly, investigators will be happy with response rates, because really after patients are accepting these therapies, the release and very much that works. So we will have those discussions first, we know a little bit more, it's a little bit early in the program for us to be able to tell.

Our next question comes from Tyler Van Buren with Cowen.

Related to the separate ALLO-647 registrational trials, beyond safety, can you provide more specifics on what needs to be demonstrated for approval?

And then the second question is, it should allow you guys to comprehensively detail the safety profile and demonstrate if it's adding any safety events to the AlloCAR T regimen, which could be beneficial given the historical theoretical concerns of infections, right? So, other than endpoints required for approval, is this a significant purpose of the trial in your eyes?

Yes. So as we said before, 647, we view it as a competitive advantage, as you know lymphodepletion is critical in the allogeneic space, and 647 has provided us with incredible precision with regards to T cell depletion, which is required in the allogeneic settings for the avoidance of rejection. So -- but because it's co-development and I've been involved in the development of many drugs including co-development drugs, FDA requires the benefit risks to be shown and demonstrated for each one of the components, both 647 and 501A, so hence the second study that's required.

It is going to be a randomized trial, they will compare it to FC, we are pretty confident that 647 leads to better outcomes. And the need for lymphosuppression hasn't shown not just in our program, but in other programs as well. And 647 is -- it's been a component that has been studied at multiple doses in our program. So we're very confident that this is a study that's going to show the 647 show superiority to FC alone.

And importantly the safety of it is actually very comparable with regards to what we used to see in the autologous setting. So we have naturally seen with the use of 647, more infections or Grade 3+ infections are then -- are seen in the autologous setting. So you're absolutely right. We expect to demonstrate 647 a superior to FC alone, and also that the tolerability of FCA is on par with what's seen with autologous CAR Ts.

Our next question comes from Michael Schmidt from Guggenheim Securities.

Hey. This is Kelsey on for Michael. I guess just to confirm one thing, will there be any update on the Phase I datasets from the CD19 program? And then secondly on BCMA, I guess, will you wait to see the ALLO-605 data before making a go-forward decision for the franchise, or would you consider advancing both 715 and 605?

Hi, Kelsey. I'm going to ask Eric to respond to both of your questions. Eric?

Thanks, Kelsey. In terms of the CD19 updates, yes, you can expect that will present a longer-term follow-up dataset at some future medical meeting as we continue to observe and monitor patients that have been previously dosed in that study, we don't exactly know the forum for that yet. But just as a reminder, we've been really pleased with the durability in particular that we have been able to show as of the ASH data cut-off, gratifying to see 10 out of the 14 patients who achieved a complete response, still in a complete response. So we're keen to see just how much longer those responses can last.

And now your second question, the evaluation of our BCMA program. It's nice to be back in control of this program, back in the clinic with the ability to execute across our multi-pronged strategy. And yes, we think 2022 is going to be a critical year for generating datasets across many of our strategies. And hopefully by the end of the year, as Rafael has already mentioned, we'll have enough data to begin to make a decision on next program steps.

Our next question comes from Mark Breidenbach with Oppenheimer.

I know you said you wouldn't tell us much about the pivotal study design, but I'll try anyway. Just given the closeness between the ORR and the CR rates you've seen in ALPHA2. I'm wondering if you're currently viewing CR rate as a potential or likely registrational endpoint in that study. And if so, I'm just wondering if you can point us any precedents that have recent approvals in [B cell] or large B cell lymphomas that might serve as kind of a model to build this trial after.

Hey, Mark, let me take on that question. So, as Rafael has said, ALLO-501A that's proceeding as a single-arm pivotal study. And in any single-arm study, 2 important elements that efficacy measure is the response rate -- objective response rate. And then the second one is the durability of the response. So, that has been part of the discussion with FDA. And we expect that those 2 primary and co-primary endpoint will be the key weigh in measures of efficacy. And certainly, safety is another part, which will be also part of, I expect to be the data review.

Our next question comes from Reni Benjamin with JMP Securities.

It's 2 for me. Just going back to the ALLO-647 study. Is -- can you talk a little bit about it for some reason, it's a randomized study and that trial fails, how that might impact the entire application of 501A and 647. And if it works, just kind of thinking out of the box here. Could this gen -- could this be used as a general lymphodepletion regimen, potentially even with autologous therapies? So almost, sort of Antion.

I'm kind of curious, when you're striking these relationships, is this something that -- how do you plan on uncovering the value, or is this just something that you want to kind of keep abreast on, because it's pretty novel new technology? And any update on Overland, the joint venture, if there is a deliverable this year, we can keep track of?

So all 3 great questions. The question about the 647, this is a drug core development, where we have to demonstrate the contribution of 647 to lymphodepletion. This is an area that we have, at this point more than enough datasets coming from both CD19 501, 501A program, as well as multiple myeloma program. Certainly, there is a possibility of study failure, but all the information that we have right now, we feel very comfortable and confident that the study will demonstrate the contribution of 647 in a meaningful way.

And the second question, this is something that we frequently have a discussion internally, which is really, how can we best leverage the potential benefit of 647, not just in our own allogeneic setting, but to a extend to other settings such as autologous. I will not rule that out, but for now, our main focus is optimizing the use of 647.

And also, in some of our studies, we are trying to see whether we can tease out and lower the chemotherapy-based lymphodepletion, moving more towards the biologic lymphodepletion which we find to have several benefits. So that will be our initial attention. But certainly your question of can this be used in autologous setting is something that we are also looking into. But that will not be immediate. And third question I'm going to ask, Eric to respond to.

Okay, thanks, Reni. I guess I get your third question, all 3, or 4 or 5 sub parts, many were in there, relating to our technology partners. Yes, at this point in time, we've formed a number of relationships that we really feel give us as much access to gene engineering and cell engineering as we could probably want, including some of the relationships you've mentioned with Notch, Antion and the joint venture, but others that have been undisclosed that provide additional domain expertise and engineering modality, relationships.

In terms of Notch, in particular, we're looking at the ability to make fully functional T cells from an IPSC source, that partnership is going really quite well. Notch has made a lot of progress in almost 2 years now since we've been working with them. And much of the work is focused on continued engineering and scale up of their products.

On the Antion side, new relationship for us where we're partnering to look at their multiplex knockdown technology to add greater functionality to some of our gene and cell engineering capabilities. Very new relationship, but we view them as leaders in this space and very pleased that we think Allogene will be a focus project for them. And then lastly, on the joint venture with Allogene Overland in China, giving us access to an important commercial territory. That entity has begun building out a manufacturing facility in China which will be required to commercialize our therapies and they're making quite good progress as well. We'd hope to be able to launch that facility later this year. Thank you for the question.

Our next question comes from Luca Issi with RBC.

Great. Maybe on 647, obviously the FDA is asking you to say the contribution of 647. Is this something that is just limited to non-Hodgkin lymphoma, or should we expect the FDA may ask you for similar trials also for multiple myeloma and solid tumors?

And maybe on business development, we've seen a couple deals recently, where companies have decided to monetize some of their extra manufacturing capability to extend the runway, including [Uttara, Fujifilm or homology, Oxford]. So wondering what was your reaction to those deals, and this is something that you may consider.

And lastly, for CD70, I think I've seen a clinicaltrials.gov that the size of TRAVERSE actually has increased from 48 patients to 120 patients a couple of weeks back. So wondering if you have any color on that?

Okay. What's the first question?

Yes. So yes, the 647, you're asking whether for different indications, there is a need to do additional studies. I mean, we see the lymphodepletion is something that is generalizable and extendable to other indications. I mean, that's our current position. We have not had any specific discussion with the regulatory agencies about how to deal with the contribution of 647 for depletion in different indication. So stay tuned.

Our manufacturing plans, Luca, no, is the short answer there. As you heard from Alison Moore, we view ownership of the CF 1 facility, our Cell Forge 1 facility is absolutely critical to our ability to function and commercialize across a slew of product opportunities. So given our strong cash position, $800 million, plus we don't see any need or interest in monetizing that in any ways to perform just the opposite, we're going to continue to invest.

And then on the TRAVERSE clinicaltrials.gov listing, I wouldn't read much into that, honestly, the clinical team often includes a number of different parameter changes to our studies. And those changes are designed to provide the utmost and flexibility going forward. But certainly, we don't have plans at this stage to enroll the full cohort of patients that you referenced.

(Operator Instructions) Our next question comes from Asthika Goonewardene with Truist.

I want to pick on Alison since she is on the call today, if I may. Alison, a while back, especially, talking about the goal of the allogeneic cell therapy to get maybe around 1,000 or more batches out of a single donor draw. But you had some ways to go in reaching that. And a little while back, I think, I remember you're telling us that, you were getting around maybe 100 batches withdraw. Where are you on that today?

And then also, related more generally, as you are -- are you able to get these incremental innovations to manufacturing incorporated into the production of cell therapies that are already in the clinic, or does that essentially require a lot of new work and maybe even a new IND?

Thank you. Yes, great question. So our goal at Allogene has been to, from a single luciferase that enable approximately 100 doses. That has been our goal, but still what we are working towards, I can say that we know that we can do that. And already we have been very successful in optimizing yield. And I think that our focus right now is to ensure supply across all of these programs, but certainly, as a process developer, I can see that there is extensive potential for us to continue to optimize yield.

So I would answer you by saying that, we have more than an adequate performance there in terms of doses. But there is definitely the opportunity for further improvement there in the future. Then, regarding your question, with respect to the introduction of novel technologies, this is certainly not just a -- this is a question across all biologics products. And it really relates to the magnitude of the technology change, and how well you understand your product and your process.

And we certainly have been able to introduce some novel technologies that we're very excited about. But we will always do that in collaboration with the agency and with the very best analytical measures. And that's why, focusing on product quality and the measurement of product quality is always in our best interest.

Our next question comes from John Newman with Canaccord.

So my question is, just wondering if you're confident that you can get the patient population in the pivotal study that is representative of patients that are currently receiving the autologous therapies? And the reason I'm asking is, I feel like you're -- some of the most recent updates, you've had some patients that have already had treatment with CD19 therapies and failed them.

And I feel like to get a true, accurate picture of the true potential of this product -- the ALLO-501 product, the agency might be curious as to what it looks like in a population similar to the autologous therapy. So without getting into too much detail about the design, just curious if you're confident that you'll be able to do that in a pivotal trial.

Thanks, John, for the question. It's a great question. I can tell you that in a Phase I study, we go through a variety of clinical situations with regards to the kinds of patients that we enroll. So one of the questions obviously is what happens to patients who have received CD19 drug therapy, as an example, which you mentioned. We -- that doesn't mean that the population that we put into Phase I study where we're looking at doses and we're looking at populations, etc., is going to be the one that is actually in the pivotal study.

So, those discussions, as I said, will take place and have been taken place with FDA. But we fully expect and our investigators are backing us up with regards to this, that there will be representative of the patients that are entering into all the therapies with the caveat that obviously they will enter sooner and obviously, that (inaudible) and will be able to get the therapy to majority of the patients. So we have absolutely no doubt that this is achievable.

Our next question comes from Raju Prasad with William Blair.

Just wanted to get a sense of the bar on the BCMA program in terms of maybe patient numbers and durability at the kind of go-forward dose that you're looking at before taking whichever program forward. Just curious to know how much data that you need from the [neuro-gas] set program as well as 605 to really make that decision. And how much the potential efficacy improvements of the approved autologous therapy, [if autologous approval in 28] plays a role into kind of a decision making process.

Great question. I'm going to ask Eric to respond to that.

Yes. Thanks for that, Raj. So first, again, I think we're in a fortunate position to be evaluating multiple different strategies, starting off with a strong foundation with what we've already shown on ALLO-715. And specifically, there is -- as Rafael has already commented, that 715 profile essentially being right on par with the approved autologous therapies. So obviously, we're trying to build off that foundation with either the combination approach that you mentioned or consolidation therapy, or the ALLO-605 TurboCAR that we're also very keen on.

In terms of where the bar is going forward, you referenced I think the cell-to-cell PDUFA date, which is upcoming here. We and everyone else are very persuaded by the compelling results that the Johnson in Legend have been able to produce with our product. And it really highlights what's possible with an autologous cell therapy and the results are unprecedented, but, it also is quite clear that even the most efficacious drugs -- excuse me are empathetic that can't be delivered to patients in need. And as you know, the current market for autologous therapies is quite capacity constrained. And while we would expect supply to increase, we don't know by how much without approval.

And even more importantly, the autologous cell therapies are unlikely to ever be applicable to certain patient subset populations. Specifically, I guess, I'm thinking about those patients who can't wait the weeks to months to be scheduled for collection and manufacturing and also those patients who can't tolerate the bridging chemotherapy which is being given to the majority of patients in the autologous study. So, for those reasons, we really think we have a pretty clean opportunity with our off-the-shelf product. And we're very focused on making the most of that opportunity as we collect the data and move forward.

Our next question comes from Jason Gerberry with Bank of America.

Hi. This is [Terry] on the line for Jason. I have 2 parts, one is regarding manufacturing, the other is kind of on the broader BCMA development. So for in-house manufacturing, I guess, are you expecting your in-house capabilities to fully support both the pivotal as well as the commercial demand for 501?

And then also does in-house manufacturing address vector supply, or is that something that's partnered with the third-party manufacturer? And then regarding BCMA development, there's -- think about the broader spaces, some of your targets market leaders are moving into third -- the third line one setting, potentially having data by the time that you started pivotal in one of your approaches. And I'm wondering, is there potential to start a pivotal trial in the third line setting? Given the way that the space is evolving towards earlier lines?

Alison, do you want to take the manufacturing question?

I'll take the manufacturing question very quickly. Our facility is designed and built to be focused on CAR T at this time. Although, the build is modular, and we could do other things, in addition. And the answer is, yes, it will have the capacity to supply commercial product for 501A. Regarding other raw materials, including critical raw materials, we have a broad network of third-party suppliers that we work with on a daily basis.

Yes, and I think the point that you make about BCMA is a good one, these therapies will make their way into earlier lines of therapy. As you know, they start in layer lines of therapy first, but just like we plan to do in lymphoma, if we -- once we make the decision, then we will be developing a comprehensive program on BCMA.

In the interest of time, we can take one more question and that is from Dane Leone with Raymond James.

One kind of related question. Do you -- and it's just something we get asked almost in every meeting with investors. Do you have an updated view on the impact of prior CD19 therapy like rituximab within the lymphoma program that was an outstanding question that needs to be discussed since the presentation, the update of the ALPHA program turning ASH.

And within that vein of developing in multiple myeloma, does your team have a view of why or why not prior CD -- BCMA are targeted therapy would have a similar potential detrimental effect in responses to an allogeneic cell therapy product, like, has been discussed in lymphoma for CD19?

It was directed to CD19 cell therapy, I mean, the data in autologous is actually, very telling as well. Many patients do not respond, particularly if they were primary refractory or they relapse relatively quickly. And this is something that we are seeing as far as in the allogeneic setting. So we are not keen on involving these patients, going forward. With regard to BCMA, we actually don't have much experience with BCMA experienced patients. So we can't really answer the question that whether there are parallels with CD19 in BCMA. I think that's a question to be answered. But currently, we want to study BCMA naive patients.

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

Thank you again for joining the call today. Based on our strong execution since inception, coupled with healthy cash position, and our focused approach and drug development, I believe we remain positioned to transform and lead the field of allogeneic CAR T. We look forward to sharing our continued progress with you throughout the year. Operator, you may now disconnect.

Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program, you may now log off and disconnect.