Good morning, ladies and gentlemen, and thank you for standing by. And welcome to Allogene Therapeutic's Second Quarter 2019 Conference Call. Later we will conduct the question-and-answer session and instructions will follow at that time. Please be aware that today's conference is being recorded.

I would now like to turn the conference over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead..

Thank you, operator, and good morning. Before market opened today, Allogene issued a press release to provide the corporate update and financial results for the quarter ending June 30, 2019. The press release is available on our website at www.allogene.com.

We'll be discussing our ALLO-501 Phase 1 clinical trial protocol today and it's posted on our website, the slide which provides an overview of the trial. This can be found in the Investor section under news and events. We remind listeners that today's call is being webcast on our website and will be available for replay.

Joining me on the call today is Dr. David Chang, President and Chief Executive 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, regulatory filings, future research and development efforts and manufacturing capabilities, among other things.

These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve the number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements.

These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our Form 10-Q for the quarter ended March 31, 2019 as well as our upcoming Form 10-Q for the quarter ended June 30, 2019.

You are cautioned not to place undue reliance on these forward-looking statements, and the Company disclaims any obligation to update such statements. I'll now turn the call over to Dr. David Chang..

Thank you, Christine. Good morning. Thank you all for joining our second quarter earnings call. We are very pleased to be speaking with you this morning to review our recent progress.

The second quarter was an important one on many fronts from advancing our pipeline, to designing our state-of-the-art manufacturing facility and recruiting highly skilled employees who are passionate about bringing Allogeneic cell therapy to patient. To that end, our full-time headcounts now has grown to over 170 employees.

Top of mind for any of you, is the progress we are making in our clinical programs, the second quarter mark the initiation of the Allogene's first sponsored clinical trial as we began treating patients in our ALPHA study, a Phase 1/2 study of ALLO-501 in Relapsed/Refractory Non-Hodgkin Lymphoma or NHL.

We are pleased with how this dose escalation study is progressing and believe that success in this trial has the potential to derisk our anti-CD19 AlloCAR program as well as our AlloCAR T platform more broadly, including the use of our proprietary lymphodepletion strategy that is anchored around our anti-CD52 antibody, ALLO-647.

During our first quarter earnings call, we've discussed the length of protocol ALPHA study. I think it bears repeating while we view as the key components for success in this trial. First, we would hope to see good cell expansion. We would hope to good cell expansion.

We believe early expansion of CAR T cells correlates well with tumor telling activity regardless of whether the CAR T therapy is autologous or allogeneic. Second, we want to gain a better understanding of the safety profile of ALLO-501 in Phase 1 portion of this study.

Adverse events of interest will include non-risk associated with autologous CAR T therapies including cytopenia, cytokine release syndrome and CNS toxicity, as well as Graft-vs-Host Disease or GvHD, which is unique to Allogene CAR T therapies.

Third, we will evaluate patients got signs of early tumor response, bearing in mind, that in the Phase 1 dose escalation portion, the initial cohort will be receiving a fixed dose of 40 million CAR T cells which is below the approved CAR T cell dose for Kymriah and Yescarta, and relapsed and refractory DLBCL.

We know based on data from CD19 trials that tumor cell killing occurs early on and the death of initial response in the first several months is perhaps the best predict of whether a patient will experience adorable longer term remission, which leave us to the last component of ALPHA study, durability.

While we are still in the early stages of our Phase 1 trial, we look forward to following patient's overtime to understand the potential for AlloCAR T therapy to have a transformative impact on long-term patient outcomes.

We believe, we are in an enviable position and that we begin our Phase 1 study with clinical data in hands from UCART19 in relapsed/refractory acute lymphocytic leukemia. As ALLO-501 and UCART19 shared the same molecular construct, we believe the available UCART19 data informative for the ALLO-501 ALPHA study.

As presented at the ASH conference last, the UCART19 safety profile appeared manageable. The most common adverse event was cytokine release syndrome and GvHD was limited to grade one adverse event in this allogeneic setting.

The UCART19 data also demonstrated that early cell expansion and deep anti-tumor responses can be achieve when deploying a lymphodepletion regimen that content anti-CD52 antibody.

We are hopeful that data from the study will serve to reinforce what we already learned from UCART19 experience and that such data can be use to accelerate the advancements of ALLO-501 in to Phase 2 portion of the ALPHA trial expected to begin in 2020.

Beyond ALLO-501, we are developing ALLO-715, ALLO anti-BCMA allogeneic CAR T therapy for the treatment of relapsed or refractory multiple myeloma patients. We noted in our last call that we have submitted our IND for ALLO-715 and in May we were pleased to receive clearance of this IND.

We are fortunate that we have enabled to apply learnings from our ALLO-501 programs, ALLO-715 program. We remain on track to initiate the ALLO-715 UNIVERSAL trial in 2019. The protocol for the ALLO-715 UNIVERSAL trial will be similar to the approach we are taking with ALLO-501.

The Phase 1 study is design to assess the safety and tolerability at increasing dose levels of ALLO-715 with the goal of identifying an optimal dose for ALLO-715 for our potential Phase 2 study which could be a pivotal study for a BLA submission.

This trial will also utilize ALLO-647, our proprietary anti-CD52 monoclonal antibody as a part of the lymphodepletion regimen.

Importantly, this trial includes the potential for secondary exploratory cohorts that will allow us to study of additional lymphodepletion regimens, including one that only uses ALLO-647 without fludarabine and cyclophosphamide.

In the main portion of this study, we plan to enroll up to 24 patients with relapsed or refractory multiple myeloma who had failed at least three prior lines of therapy in a dose escalation three plus three trial design.

Details on the starting cell dose and the initial lymphodepletion regimen will also – which are the same as in the ALLO-501 ALPHA study can be found on the slide Christine referenced earlier in this call.

The UNIVERSAL study may also include additional cohorts to assess a potentially lymphodepletion regimens where the chematherapy component specifically fludarabine and cyclophosphamide will be stepwise removed.

As we look ahead we will be looking at end points such as safety, response rate and the duration of response that's key determinants of the success for ALLO-715. Last quarter, we touched upon our initial thoughts as we explore the potential for CAR T therapy in solid tumors.

We very much think of solid tumors on a spectrum and belief that is important to first explore the viability of this modality and targets that has commonalities with blood cancers, and where we have already seen CAR T therapy be successful. Many of the targets we gain through our acquisition of assets from Pfizer [ph] in solid tumors.

So we have the options to expand our research quickly where we see opportunity. Our focus in this area today includes CD70 in renal cell carcinoma and DLL3 plus small cell lung cancer. We are also excited about the headway we're making in the build out of our manufacturing facility in New York, California.

We have completed design for the facility and look forward to starting internal manufacturing suite construction by the end of this year. Finally, we issued our press release on Monday announcing that Dr. Rafael Amado will be joining Allogene as our Executive Vice President, R&D, and Chief Medical Officer.

Rafael brings a skill set to Allogene that is as impressive and highly complementary to the rest of our leadership team. We also focus our discussion on the science and our trial, but people are the key component of success.

Our teams are largely made of people with our shared histories, passion for innovative science and communal drive to advanced, serve that therapy for the benefit of patients. Many of our team members have spent years together before taking separate journeys.

Now in a very fortunate circumstance these team members have reunited, creating an opportunities to complement each other. Rafael represents that perfectly. Many of Allogene have known Rafael for years and have work with him in his previous positions.

In fact, our [Indiscernible] Rafael, while at GCLA and he and I started our industry career through on the same time with Amgen. Subsequently, Rafael has spent years in oncology and advancing cellular immunotherapies. I know firsthand how talented Rafael is and I am thrilled that we will back on the same team.

All of our efforts to build Allogene and our intense focus on accelerating AlloCAR T therapy over the last 15 months is now beginning to bear fruit. As we advance into the clinic, we look forward to what we envision will be a very exciting next 12 months for Allogene. I will now pass the call over Eric..

Thank you, David and thanks to everyone for dialing into this call. I would provide a brief overview of Allogene's financials. Additional detail on our second quarter financial results can be found in our press release issued earlier today and in our 10-Q, which will be filed with the SEC.

We are pleased to report that we remain in a strong financial position. As of June 30, 2019, Allogene had cash, cash equivalents and investments totaling $650.2 million. In the second quarter, our research and development expenses were $31.8 million, which includes $4.7 million of non-cash stock-based compensation expense.

General and administrative expenses were $14.2 million for the second quarter of 2019, which includes $6.7 million of non-cash stock-based compensation expense. Our net loss for the second quarter of 2019 was $41.2 million, or $0.41 per share, including non-cash stock-based compensation expense of $11.5 million.

We are continuing to invest heavily in advancing our clinical programs, yielding out our manufacturing capabilities and hiring exceptional talent. As guided previously, we expect full year 2019 net loss is to be between $200 million and $210 million.

This includes an estimated non-cash stock-based compensation expense of $45 million to $50 million and excludes any impact from potential business development activities. With that brief review of our financials, we will now open the call for your questions..

Thank you. [Operator Instructions] And our first question comes from Marc Frahm with Cowen and Company. Your line is now open..

Hi. Yes. Thanks for taking my questions and congrats on the progress.

In prior calls that you've mentioned that the kind of preconditioning regimen that you're starting within the ALPHA trial based on kind of modeling from – what you've seen from UCART19, as well as other programs that you had the flexibility to adjust depending on what you actually saw in terms of lymphodepletion.

So have you guys gotten to the point that you've confirmed that regimens doing what you wanted it to do or is it still an outstanding question for you?.

Marc, David Chang here. Let me take that question. As we have indicated a lot of those went behind how we setup the initial lymphodepletion regimen that includes not only fludarabine and cyclophosphamide, but ALLO-647 anti-CD52 antibody. Some of the questions that you're asking now it's getting into the clinical data.

And I think you'd be better be left for us to present those findings at our conference in 2020 as we have indicated in the earnings call..

Okay. And then, I guess, speaking on conditioning regimens, for the UNIVERSAL trial you mentioned possibly trying to remove either Cy and/or Flu from the regimen.

Is there something unique about BCMA and multiple myeloma in your view that would allow that? Or is that just the most convenient place to kind of test using the antibody by itself?.

Yes. That's something that we have been internally discussing for some time. I mean, we know that anti-CD52 antibody is a very important lymphodepleting agent.

The initial additional anti-CD52 is the build on the 15 lymphodepletion regimen at fludarabine and cyclophosphamide, but we do believe that we have an opportunity to further optimize with a view that at some point it may be possible to create the lymphodepletion that allows the expansion of the cells as well as protection of our AlloCAR T from destruction by the allogeneic lymphocytes simply by using anti-CD52 antibody.

And given that thought, we proactively designed universal study to have the opportunity to specifically test that hypothesis and we will be -- as I've said, a stepwise we're moving chemotherapy reagents to the point that we will have an opportunity to study anti-CD52 antibody alone.

And that's all going to be based on what we find in the initial lymphodepletion in the UNIVERSAL study..

Okay, great. Thanks a lot..

Thank you. And our next question comes from Salveen Richter with Goldman Sachs. Your line is open..

Yes. Hi. Thank you for taking the question. This is Mariana [ph] for Salveen. Following up on Marc's question about the lymphodepletion, would elimination of fludarabine and cyclophosphamide allow the possibility of AlloCAR Ts being confused as not only the academic sort of centers, but also in more community settings with just ALLO-647? Thank you..

Great question.

It's probably too early for us to go into the details of what may happen, but within the company there is a lot of thinking that's going behind, how we can continue to improve the CAR T therapy with the hope that at some point this can be done as an outpatient regimen rather than the current situation where the therapy has to given in a specialized centers or in close proximity to the transplant center.

So, taking out a full dive in a cyclophosphamide, obviously we are triangulating many different points, existing data, some of the early findings that we are getting from the ALPHA study as well as what we are hoping to achieve eventually.

So at this point, we are giving some suggestions about how we are approaching this through the study design, but let's just wait for the data to mature and as we generate additional data during the conduct of universal study..

Got it. Thank you..

Thank you. And our next question comes from Biren Amin with Jefferies Your line is open..

Yes. Hi guys. Thanks for taking my questions.

David, maybe just starting on 501; how many patients should we expect to get in the first half 2020 when you present the data on the ALPHA trial?.

Yes. So, Biren, we have previously indicated that the way that we will communicate the emerging data from the ALPHA 1 study is that we will wait for some meaningful interpretation of the data to be -- when we get to the point where we can meaningfully interpret the data we will present it in a scientific form.

So it really doesn't matter how many patients. It's really the quality of the data and the consistency of the data. When the Phase 1 study is designed can enroll up to 24 patients. But in terms of how many exact patients will be treated.

That all depends on the emerging data, including specifically around the safety findings, so the number could be very few, but could be up to 24. So let me leave it there without going into the details about how many patient data maybe expected as we present the data in early 2020..

Okay. And then, on the 715 program, given you're evaluating or potentially evaluating different lymphodepletion regimens potentially without Flu –Cy/Flu.

What your thoughts on possible redosing of patients? Because I think one thing that we've seen in the literature is a type of BCMA may have some influence on risk response or how long remission occurs, although this is still a theory, so, just thoughts on, I guess with the trial ALPHA redosing of 715 cell?.

So currently, we are building the design of the study with the assumption that a single therapy can achieve the treatment effect that we are desiring, which is a deep response in the higher proportion of patients and that's very durable.

In terms of redosing which frequently comes up especially in the Allogeneic settings because of the Allogeneic products provide such ease of redosing. We have entertain the possibility of redosing, but at this point we are keeping redosing as an option, not something that we will specifically build into the protocol from upfront..

Okay, great. Thank you..

Thank you. And our next question comes from Cory Kasimov with JPMorgan. Your line is open..

Hey. Good morning guys. Thanks for taking my questions. Two and four as well. So, first following up on ALPHA 1, given that this is using the first Gen 501, that contains the Rituxan switch.

Just curious and your thoughts on how representative the patients might be if the broader relapsed/refractory NHL patient population?.

Great question. So, I think you are asking about the fact that from 501 as we advanced the program into the pivotal Phase 2 stage, we will be making the one minute change of taking out the Rituxan switch. We went in details about why this Rituxan switch still exists in our 501? That's really a historical reason.

And we had planned from the beginning to take the switch out. And we also have outlined the speed and the sequence events that will allow us to introduce ALLO-501.1 which is now a second generation that lacks the Rituxan switch.

For now, because of the Rituxan switch there are certain criterias that we have set to screen out the patients who does not have high levels of rituxan from the previous treatment. So far despite that unique requirement we have not gone into any significant issues with the patient enrollment.

And currently, the patients that we have enrolled, I would say is very representative that we've relapsed and refractory large cell lymphoma patient population..

Okay, great. And then to follow up on that, can you just help us understand when you go to 501.1, the manufacturing differences there.

Is it a very simple switch and does it change the total manufacturing time or how much of a change to the process itself?.

Yes. So the main change is taking off the switch, means that you have to use a new antiviral vector. Other than that the manufacturing process essentially the same..

Okay. Terrific. Thanks a lot for taking the questions..

Thank you. And our next question comes from Mark Breidenbach with Oppenheimer. Your line is open..

Hey, good morning guys. Thanks for taking the questions.

David, I was wondering if you just quickly comment on how you chose the 40 million cells starting dose in the UNIVERSAL study, especially given what we know about the autologous BCMA CAR T and where they start showing efficacy? And also I'm wondering if the UNIVERSAL protocol or future version of it might leave any room for including a maintenance therapy for patients who respond to treatment and if it will be worth trying something like a lenalidomide potentially extend PFS beyond what we've seen in other BCMA CAR T trials?.

Hi, Mark. Great questions. In terms of the starting cell dose, 40 million cells, I mean, that includes the vial size for the production of the cells, as well as what we believe can be potentially active dose, but obviously in this dose escalation study we want to start at relatively low dose and grow up the dose escalation.

I mean that's the sort of underlying premise where we came up with a 40, could it's been 60, could it’s been 20. I think it's a choice that we made. And 40 we felt was a reasonable number. To it of course of the study, we can definitely more than double the dose as we grow up does escalation.

So we will be able to explore a range of doses that will inform us in how we choose the recommended Phase 2 as we advance the program into the pivotal stage. In terms of the second question of maintenance, I mean, I think the question is really reflecting the treatment paradigm in multiple myeloma.

This is a field that underwent revolution over the last 20 years with the introduction of many novel and highly effective agents and both the combination as well as a maintenance therapy is very much in play.

And that's something that we are closely working with investigators, as well as key opinion leaders to how to position the CAR T therapy in this complex setting multiple myeloma treatment. So we're keeping all these options open. However, initially this study will be done as ALLO-715 as a single agent in relapsed and refractory patient population..

Okay. And just a quick follow-up. I'm also wondering if there would be any value or if you have any plans to share ALLO-647 with Servier or selective so you could potentially gain some clinical experience in a broader range of indications beyond what you're testing in your own trials? Thank you..

Yes. So ALLO-647 which is for proprietary anti-CD52 antibody, I mean, it has a potential broader use in a setting where you are utilizing the deletion of CD52 genes in the product as a selectively lymphodepletion approach.

And we are obviously developing, advancing for our own use, not just for ALLO-501 and ALLO-715, but as a platform approach on any other programs where we had the leading anti-CD52 genes. And as we go forward, our plan is that we will make these ALLO-647 available for others to use.

I mean, I think that's really a business development discussion within the company. And our goal is to advance ALLO CAR T and anything that we can do not just within the company but for the field we will be trying to push the field..

All right. Thank you for taking questions, and congrats on progress..

Thank you..

Thank you. And our next question comes from Dane Leone with Raymond James. Your line is open..

Hi. Thank you. Congrats on all the progress and update. So, few from me. So, when we think about the UNIVERSAL program, obviously there's lot of BCMA agents and clinical testing right now ranging from CAR T to ADCS bispecifics.

What's kind of been the feedback as you're working with your PIs to understand what the phenotype is going to be for the patients likely enrolled in this study?.

Hi, Dane. So, let me take this question and I'm going to also ask Susie Jun, our Chief Development Officer for the feedback from the investigators. I mean, certainly as we advanced the study we have held multiple different discussion.

In terms of BCMA and multiple myeloma, I mean despite multiple new drugs being out there, none of the current therapy are curative, and essentially patients go from one treatment to another.

So there is always an opportunity to find the right clinical setting to conduct the studies, as well as to introduce new agents in this spectrum of different regimen that the patient will undergo. When it comes to the BCMA, our product, ALLO-715 as we envision, it will be differentiated by the fact that is an allogeneic and it is off the shelf.

Unlike current BPCM CAR T program, most of them are autologous. So from that perspective we have heard many positive feedbacks and excitement amongst the investigators about having opportunity to study and to treat patients with the allogeneic off the shelf CAR T product.

And certainly, this gets into the consideration of how we view our product versus bispecific, which have shown some encouraging data. I think it's too – it's little bit too early for us to comment.

But the general view that we have taken is that multiple myeloma is such a large indication, we can work out ways to introduce different novel reagents during that different parts of the management of patients from the initial diagnosis to second, third or sometimes in the refractory lines of therapy.

So having said that let me ask, Susie to specifically comment about what the KOLs are been saying about opportunities..

Yes. Thank you. So the feedback we've been getting from the myeloma experts currently that may or may not want to participate in our studies. They are very strongly encouraged by the role of cell therapy for the treatment of myeloma.

And they really do feel as David has just said that having it off the shelf option would give these patients more -- give more of these patients an opportunity to get some therapy because of the elimination of the long-lead time from the autologous approach.

And I think you're hearing that as well with some of the support they've been giving to the bispecifics. So overall, I'd say the feedback from our potential investigators has been very positive and they're very engaged in the conversations that we've been having..

Okay, great. And maybe just another branch off of that question, if we assumed that the patient prior experience or refractory status would be something similar to what we've seen in the initial studies with the Bluebird and Celgene agent where these patients have had seven, eight lines to prior therapy.

Usually they're coming in fairly beat up with kind of penia across the board.

Just curious have you received any concern questions about risk of infection or anything like that if you're going to hit them with anti-CD52 as a preconditioning agent?.

I think overall everyone understands that CD52 antibody is a potent lymphodepleting agent. And their experience at least in the hematologic malignancies field with [Indiscernible] gives everybody a strong sense of caution around the potential for other infectious or the opportunistic infections that come with a prolonged lymphopenia.

But that being said, our dose that we're using in the lymphodepletion regimen is much lower than what was used with Campa [ph] and is even lower than what the currently prescribed dose for multiple sclerosis with alemtuzumab. So caution is good. But I don't think anyone's too concerned given how low dose we're using..

Okay. And then finally for me, kind of like a two part single question, sorry about that. The commentary about Flu/Cy potentially moving away from Flu/Cy or not eating it or experimenting with what not using it, is interesting for a couple of reasons.

One, if we go back to the classic CD19 example, there is a -- I think at this point you might disagree with me. I'd be interested to hear your thoughts. A pretty close tie to that the Flu/Cy regimen and of itself helped with the initial of the bulking which also help control CRS and potentially neurotoxic rates.

Obviously, we haven't seen those types of rates and the BCMA spectrum of multiple myeloma treatment, but curious for your thoughts on that? And then secondly, it seems like it and this is pure speculation on my part that if you were able to move away from Flu/Cy preconditioning that might actually be favorable to what clinicians really going to want to get in with any treatment in multiple myeloma is bridging that patient to actually a transplant therapy.

Would that actually be potentially helpful you think in terms of making a CAR T a bridge to transplant within multiple myeloma if you moved away from Flu/Cy?.

Yes. So, Dane, let me take that question. I think there are several different concepts that that are intermixed in your question. Yes. Flu/Cy chemotherapy and there has always has been questions about whether the tumor killing coming from the lymphodepletion regimen.

And I think this has been asked and this has been looked at very carefully across many different studies. There are many. There may be some slight reduction but the general overwhelming findings are that in the refractory patient population as the CAR T study – CAR T programs has been studied. Flu/Cy has a very minimal impact on as an anti-tumor agent.

It's really for the purpose of allowing the CAR T cells to expand which is a critical component of how the cell therapy is really impacting tumor killing so rapidly and so deeply. So personally I don't think the Flu/Cy should be looked at as anything other than agents will wait to lymphodeplete, also that the cells can expand.

And that's really where previously the idea of using CD52 antibody for the lymphodepletion That's really didn't come up because CD52 antibody unless you knock out CD52 in the CAR T cells will not discriminate the lymphocyte in patients or looking at the CAR T cells which are T cells.

So there is no selective way of creating lymphodepletion with anti-CD52 antibody. However, the approach that we are taking which is editing out the CD52 in our ALLO CAR T cells, that's now creates an opportunity for selective lymphodepletion.

So I think this is a really unique opportunity for us to continuously advance the field and continuously we find how we administer the CAR T cells and certainly we will have to test this in humans, but we have enough indications that CD52 antibody alone can provide that deep lymphodepletion.

And certainly I think at this point my answer -- my response to this is let's just hold onto this very important question as we generate that data through ALLO-715 study.

The second part about whether this is going to make easy for patients to undergo transplant and that really is -- I don't think that really even the Flu/Cy at the doses that we are using that's really not going to impact whether the patient undergo a transplant or not.

The purpose is that really to facilitate the transplant, but it's really to simplify the lymphodepletion. And I would say just taking out the cyclophosphamide and Fludarabine in the immediate short period after the -- during the cell therapy.

Now that's going to -- I'm hoping that will reduce neutropenia or other impact that cyclophosphamide will have on platelets as well as white blood cells that can -- that requires additional management during the early days. So, simplification that could lead to the easier administration of the CAR T without losing the cell expansion or the efficacy.

That's the main goal of testing different depletion resident..

Excellent. Thank you very much and congrats on the progress..

Thank you..

Thank you. And our next question comes from Raju Prasad with William Blair. Your line is open..

Thanks for taking the question. Just a kind of conceptual one on the ALPHA and UNIVERSAL trials in regard to precondition. So, in both trials you'll have kind of the optionality to tinker with the precondition regimen.

Is there like conceptually a way that there could be two different preconditions regimens you end up coming out with based on indication or do you think that it'll kind of be synergistic and kind of determining the best precondition regimen from both trials to move forward with increasing graph [ph] and persistence?.

Great question. I think from the Flu/Cy perspective, I don't think there has been a clear indication whether there is any difference in how lymphodepletion can be achieved in patients with lymphoma versus multiple myeloma. I think if you continue to expand that question into other tumors and solid tumors, at this point I think we still have to see.

I mean, that's a question that really has not been tested in a meaningful way. So hold on to that.

I mean certainly in the ongoing ALPHA study we are carefully monitoring the depth of lymphodepletion not just measuring the lymphocytes but specifically measuring T cells subsets, NT cell subsets and B-cell subsets and we are generating very interesting data.

And this is really informing how we are thinking about lymphodepletion and also forming the basis for us to think about a different lymphodepletion regimen..

Great. And then one just a small question, on the UNIVERSAL trial is added to the upper bound of doses 320 times ten [ph] to the six.

And then ALPHA 360, is there a reason for that?.

Raju, looking at those information very carefully, we are wondering whether somebody will catch the difference between 320 and 360. It really is coming down along how we are thinking about the BIO-SIZE of the frozen product. I mean, that went in. There's many different sort of considerations about how we are setting the gross range.

So that's probably the main reason. I mean personally, do I think that we need to go up as high as 320 or 360. I don't think so. All the indications are that the CAR T cells will be effective somewhere between 500 and 40 million to 50 million to about 200 million in that range.

But as I said previously in the Phase 1, we really want to get some dynamic range of those to information which is one of the reasons that we are bracketing doses that we are testing across a wide range..

Okay. Thanks..

Thank you. And our next question comes from Tyler Van Buren with Piper Jaffray. Your line is open..

Hey, guys. Good morning. Thanks for taking the questions. A follow-up on the potential of a pure ALLO-647 regimen.

Can you speak towards what potential magnitude of dose would be required to completely remove Flu/Cy? And as you think about the initial upfront doses of three days or expanding beyond that and dosing longer, what do you think might be more optimal when you think about a pure anti-CD52 regimen and at what time points? Can you remind us at what time points you're measuring cell counts by a flow cytometry and how that could inform how you move forward? Thank you..

So that's a very loaded question in terms of the dose ALLO-647. As we have indicated in previous calls, the current dose that we are using which is 13 milligrams daily for three days, which comes up to about 39 milligrams about -- now we say 40 milligrams. And we believe that this will achieve a deep lymphodepletion.

Certainly, as we have not tested a CD52 antibody, ALLO-647 along with fludarabine and cyclophosphamide, that needs to be confirmed in studies as the way that we have designed ALLO-715 study. So let's hold off on some of the -- what may happen on actual clinical data beyond current speculations that we are making based on modeling and other things.

In terms of dosing, I think you correct me if I'm wrong. You are asking the potential of dosing ALLO-647. That's something that we have definitely considered.

And because of the selective lymphodepletion nature created by how we are engineering cells that opportunity that excess and certainly that's an option that we can also explore as we continue to try to refine and improve their lymphodepletion.

And in terms of the last question, the time point and frequency of the measurements of anti T cells and B cells. Early on what I mean, early on within first two weeks we do know fairly frequent measurements. And as time goes on it becomes less frequent.

But the details, I would defer to the scientific presentations on exactly how we are following the extent depth and duration of lymphodepletion..

Okay. That's helpful. And if I'm not mistaken what are your potential large competitors with respect to the DLL3 program paused their CAR T program.

Do you have insights into why they pause it as we think about the potential implications for Allogene's program?.

Yes. I mean, I think you're referring to the comments made by Amgen in their earnings call last week. We don't have any more details than that. I think the comments generally we refer to that, it was their strategic decision and considering that they have both bispecific and the CAR T.

Beyond that we don't really have the details on how the decision was made..

Thanks very much for taking the questions..

Thank you. And our next question comes from Ben Burnett with Stifel. Your line is open..

Thanks so much. I appreciate it. I have a follow up on the second gen ALLO-501 program. I guess would you anticipate needing to do any dose ranging for this specific product before moving the second gen product into registration all studies? And then I guess also has the all switch ever been used in the 501 or UCART19 program thus far.

So, I guess in other words, has there ever been an instance where physician needed to eradicate the CAR T cells with rituximab?.

So, let me answer second question. The simple answer is, no. The whole idea – we go to sort of think about now which will be almost seven, eight, possibly 10 years ago when people were initially designing the CAR T construct. All different doses went in and some are very cautious as well as sort of right decision to have some kind of safety switch.

And to the extent where the safety switch need to be triggered I'm just thinking that just in terms of the UCART19 programs, but other programs that have sort of similar switch. I don't think there has been in many incidences. And to my knowledge I'm not aware of any specific case where the switch had to be triggered for the safety reasons.

I mean, people certainly have used high dose steroids in the case of severe cytokine release syndrome. And certainly it appears that the steroid now with the growing evidence that it doesn't really impact the efficacy. It's being more widely used. And sort of recalling my early conversations with Dr.

Steve Rosenberg in NCI around the switch, and he frequently said, what, why didn't he switch high dose steroids, I mean they are very lymphocytic and they will do the same as out as a switch.

But frankly, we have never had a reason to trigger this switch in the UCART19 program to my knowledge and certainly in the ongoing 501 ALPHA study we have had more great locations to consider using the switch..

Okay..

And now, I forget your first question with you..

Sorry about that.

The other question I was just asking is, were you -- do you anticipate needing to do any dose ranging with a second gen product before moving that into the Phase 2 registration study?.

Yes. I think that possibly – that possibility does exist. I mean there are many different ways that we can handle that. And frankly, we're not going into too much into those details. I feel very comfortable that we will be able to ease in ALLO-501 into the ongoing ALPHA study without any delay in the timeline.

And as I've said in the prepared statement, we currently project that the pivotal part of the ALPHA study will start in 2020..

Got it. Okay. Thank you. And then just one last one if I may. Just on the CALM and PALL studies I guess when can we expect to see additional data either longer term follow up data or data from the new patients entering the study.

When might the next readout be?.

Yes. so CALM and PALL study, these are the UCART19 study in ALLO that's sponsored and led by Servier. And earlier this year there was some manufacturing issues that delayed the study. But those issues have been resolved and the studies -- both studies are currently enrolling the patient.

And given that there may be some incremental hard data that gets presented in the upcoming scientific presentations, but let's hold off on the details of what may be presented because it's really Servier that's making the decision on when and what to present..

Got it. Thanks so much for taking the questions..

Thank you. And our next question comes from Tony Butler with Roth Capital Markets. Your line is open..

Thanks very much, David. Three brief questions if I may. One is, given the dose 647, what is the half life of the antibody? That's question one.

Number two, in ALPHA and Universal the first 24 patients in the dose finding stage, could I ask, will they be eligible to rollover for the Phase 2 portion? And then the third question is as you alluded to thinking that the real dose for let's say 715 might be between 40 million and 50 million, could be 200 million.

So I'm going to ask, what is the -- when you think about that next dose as you're escalating is that like 160 or are you going to push in further or you're going to incrementally move from 40 to 50 to the 80 or just a couple of thoughts around that would be very helpful because it does relate to timing needing to wait and to see what those patients look like before you move further? Thanks for the time..

Okay. So I'm the half life of 647 which is a complex question. I'm going to ask our Chief Development Officer, Susie to answer your question. But let me just answer the easy ones first. So, I'm going to go to a third question about how we are dose escalating.

I mean, we haven't specifically stated how many cohorts will be starting in the dose escalation phase of ALPHA study or UNIVERSAL study. But when we say we will study up to 24 patients. Usually in terms of how most protocols will say in three plus three dose escalation study, they always assume the maximum possibility in each cohort which is six.

So from there you can more or less sort of figure out how many of those cohorts may be studied. So it's not going to be incremental 10 million to 20 million dose increase as we go to the next cohort. It'll be two to three fold increases in the cell dose as we go from the initial dose of 40 million to the next and to the next dose cohort.

Now, as the morning gets late I'm sort of at your second question.

Can you repeat the second question?.

Yes. Sure, David. Thanks for that. It's actually the third one I guess. But the question was, the 24 patients that are dosed do they get to roll over to the Phase 2 portion? Thank you..

Yes. So generally in pivotal study we do not do that, because we tend to tweak the pivotal studies separate from the Phase 1. But keep in mind, the pivotal study in the CAR T space it's going to be relatively small size anywhere between, I'm just throwing up the number not going to give you the exact number that we are planning.

But it's going to be somewhere between 70 to 80, 90 in that range. From that sense what the experience from the Phase 1 study gets used is as additional efficacy information, as well as additional safety information. So, at the end we will use all the available information coming from Phase 1 and Phase 2.

And no matter how you dissect the total number of patients that we are talking about for the CAR T is going to be relatively small number of patients. And now I'm going to refer to Susie for the most challenging question about the half life..

Yes. For the half life ALLO-647 that's certainly something we don't really have a clear answer on yet. We're testing ALLO-647 for the first time in our ALPHA study. So we will measure all the pharmacokinetics parameters as we would for most or any other typical monoclonal antibody. So the answer is I'll figure it out as we go.

But if we think about alemtuzumab which is what we based bit of off. The half life for alemtuzumab is slightly different depending on which disease indication you look at. So the expected range of the half life is somewhere between six to 21 days..

And this one on the half life issue about the CD52. Antibody is, I mean, the reason that the half life can vary depending on the indication and depending on the setting is that there is a phenomenon known as target dependent sort of clearance of the antibodies.

So if there are a lot of targets, a lot of B cells are T cells, CD52 antibody will clear little bit faster than somebody who starts the treatment with slightly being lympho-thymic [ph]. So there is some variability. But I would say know this is not anything unusual compared to the clearance of other antibodies as we know..

Very helpful, David. Thank you. Thank you, Susie..

Thank you. And our next question comes from Michael Schmidt with Guggenheim Securities. Your line is open..

Hi. This is Kelsey Goodwin on for Michael. Thanks for taking the questions. Just a couple of quick ones, I think you've previously said you plan to use multiple manufacturing lots to complete the Phase 2 portion of ALPHA.

I guess can you just provide some color on kind of the regulatory checkpoints for multiple runs maybe kind of how and when the specs would be assessed? And then more broadly just could you provide some color on quality assurance and control burden for allogeneic cell therapies from a regulatory point of view, maybe how that compares to autologous? Thanks..

So, in terms of quality assurance and release criteria for the allogeneic CAR T, I mean, it follows the standard CMC rules about how we prepare the drugs. I mean, that includes the purity, identity, potency, among many other things.

So there are many different assays that we incorporate to make sure that the product that we use in patients are safe and well controlled.

Given that these are safe products, I mean the variability that we will see in the cell products that will be in general much greater than the kind of variability that we are used to seeing in small molecule where people talk about product identity and antibodies or biologics where people will talk about the equivalence of one antibody or one biologic from another.

So there are many different considerations and this is something that FDA is keenly aware of and are working very closely with different sponsors to set appropriate standard for release criteria.

So this is an area that we -- I personally, some other peoples who have joined our Allogene from pharma has experiences and this is will be an ongoing discussion as we advance the program from Phase 1 to pivotal to eventually and hopefully into the marketing space.

So, that's an ongoing discussion and I would say that we have a pretty good understanding and we are continuously addressing the issues that will come up throughout the product development. In terms of whether there are any differences between the criteria that get used for the allogeneic versus autologous.

The main thing that really goes in here relates to the additional engineering that we do in the allogeneic. We use gene editing and with gene editing there is always a concern for off target cuts and changes in non intended bites and that we already have developed assays to test that pretty well. And I think that's issue that doesn't concern me a lot.

That doesn't mean that we are continuing to work on that. And then the other one that we pay attention to is the degree of editing of the T cell receptor and any residual T cell receptor positive cells that still maybe present in the final product. And that's something that we've been working on for several years.

And I would say that we have pretty much that under control. So from a product perspective we will go through the usual path, but there's nothing that really stands out as an outstanding issue. And that doesn't mean that there isn't a lot of work that we need to do.

We have a lot of work that's cost for us, but that's one of the reasons that we are investing heavily in building the highest quality CMC Pick School to address these issues that we know as of today as well as additional issues that we may run into as we advanced the manufacturing process..

Okay, great. That was really helpful. Thank you..

Thank you. That concludes our question and answer session. I'd like to turn the conference back over to Dr. Chang for any additional comments..

Well, thank you for your continued interest in Allogene and support as we now move firmly into the clinical stage of our key pipeline programs. We will look forward to seeing many of you in the near future as we plan ahead into the fall conference schedule. Operator, you may now disconnect..

Thank you. Ladies and gentlemen, thank you for participation in today's conference. This concludes the program. You may now log off and disconnect. Everyone have a great day..