Q3 2019 Earnings Call

Christine Cassiano: These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our Form 10-Q for the quarter ended June 30, 2019, as well as our upcoming Form 10-Q for the quarter ended September 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.

Good morning, ladies and gentlemen, and thank you for standing by and welcome to Halogen Therapeutics third quarter 2019 conference call. At this time all participants are in listen only mode. After the speakers presentation, there will be a question and answer session.

Ask a question. During this session you want me to press Star one on your telephone if we require any further assistance. Please press star zero.

Be advised today's conference will be recorded.

I'd like to turn the conference over to Christine Fiano, Chief Communications Officer, Ms., Cathy I know you May go ahead.

Thank you operator, and good morning before market open today Allergan issued two press releases one press release discusses an exclusive collaboration with Knox therapeutics to develop I P. S. C based aloe cart therapies and the other provides a corporate update and financial results for the quarter ended Septemberthirty 2019.

David D. Chang: Good morning, and thanks for joining us on our call today to discuss our third quarter and recent events. As we complete the end of our first full year in operation as a public company, I am very pleased with what we have accomplished at Allogene. While we were able to leverage the great research from Pfizer to give us a strong foundation, we have built Allogene from the ground up by assembling world-class capabilities across all functions. We have successfully progressed two Alokharti programs into the clinic, advanced pipeline programs toward potential IND, and optimized current Alokharti manufacturing while creating next and future generation therapies. We have initiated the build-out of in-house manufacturing capabilities. We have also completed our new headquarters, which now houses both the R&D and G&A functions under one roof. To that end, I would like to thank those who joined us in September for our open house at our new headquarters.

Press releases are available on our website at www Dot allergies dotcom.

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 are Dr., David Chang, President and Chief Executive Officer, Dr., Eric Schmidt, Chief Financial Officer, and Dr., Rafael Amado Executive Vice President of research and development and Chief Medical Officer during today's call we.

We'll 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 a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward looking statements.

David D. Chang: We are pleased to have so many analysts, investors, collaborators, and friends of Allogene join us in celebration and visit our new lab. During the event, I spoke about our journey from company inception to today, where we are now in a position to treat patients with refractory hematologic malignancies under two active INDs. I believe that the investment Allogene is making in facilities, manufacturing, and personnel provides us with a key building block to support our next phase of growth as we seek to advance allocardial therapies through clinical development and toward commercialization. As many of you know, our next phase of growth includes the construction of our state-of-the-art manufacturing facility in Newark, California. On our last quarterly call, we announced that Dr. Rafael Amado would be joining our allergen team. Since he arrived in early September, his leadership of the research and development team and integration with other cross-functional teams have been seamless.

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 June 32019, as well as our upcoming Form 10-Q for the quarter ended September 32019, you are cautioned not to place undue reliance on these forward looking statements and the company display.

James any obligation to update such statements I'll now turn the call over to Dr. David Chang.

Good morning, and Oh, thanks for joining us on alcohol today to discuss our third quarter and recent events.

As we complete their friends about first full year already in operation as a public company I'm very pleased with what we have accomplished at allergies.

While we were able to leverage the great research from Pfizer to give us a strong foundation, we have built allergan from the ground up by assembling world class capabilities across all functions.

We have successfully progress to Albuquerque programs into the clinic advance pipeline programs toward potential I envy and optimized current aloe car T manufacturing, while creating next and future generation therapies.

David D. Chang: Rafael's familiarity with engineered cell therapy allowed him to quickly step into the role of head of R&D and support us in refining the R&D strategy. I look forward to giving Rafael the opportunity to update you more fully on these efforts later in this call. We are now firmly into the clinical stage of development with lead pipeline programs. We have checked off the last of our stated 2019 program milestones as we treat patients with the initiation of our LO715 clinical trial in multiple myeloma and in our ongoing LO501 alpha trial in non-Hodgkin's lymphoma. As we have previously stated, we plan to share the data from the Allo501 Phase 1 trial in the first half of 2020.

We have initiated the buildout of in house manufacturing capabilities. We have also completed our new headquarters, which now how schools. The R&D engine a functions under one roof.

To that and I would like to thank those who joined US in September for our open house at our new headquarters.

We were pleased to have so many analysts investors collaborators and friends of Allergan join us in celebration and visit our new labs.

During the event I spoke about our journey from company inception to today, where we are now in position to treat patients with refractory hematologic malignancies under two actually buying these.

I believed that the investment algenist, making in facilities manufacturing and personnel provide us with the keep building blocks to support our next phase of growth as we seek to advance oligarchy therapies to clinical development and toward commercialization.

David D. Chang: We are committed to rapidly moving our therapies through clinical trials and advancing this nascent field of allogeneic cell therapy to generate viable commercial therapies for patients in need. We can use our first-hand knowledge and growing industry insights into autologous cell therapy to advance allogeneic development. But, as we have all learned, allergenic cell therapy is fundamentally different than autologous cell therapy.

As many of you know how next phase of growth includes the construction of our state of the Arts manufacturing facility in new work, California.

David D. Chang: To that end, our translational team is highly focused on building a robust understanding of the relationship between lymphodepletion and cell expansion and ultimately clinical outcomes including both safety and efficacy. Turning to our other news this morning, our collaboration with Notch Therapeutics is part of our broader long-term strategy to think beyond what can be achieved with currently available technologies underlying first and second generation cardiac therapy. While we believe our initial allocarditis programs derived from cells collected from healthy donors have the potential to revolutionize the field by making cardiotherapy available to many more patients, innovation cannot stop there. We are excited to partner with NARCH to develop the next generation of allocardial therapies derived from induced pre-reported stem cells, or iPSCs.

On our last quarterly call, we announced that Dr. Rafael Amado would be joining our alogent team.

Since his arrival in early September his leadership of the research and development team and integration with other cross functional teams have been seamless.

Fails familiarity and engineered cell therapy allowed him to quickly step into the role of head of R&D and support us in refining the R&D strategy.

Look forward to giving about failed the opportunity to update you more fully on these efforts later in this call.

We are now firmly into the clinical stage of development. We believe pipeline programs. We have checked off the last about stated 2019 program milestones as we are treating patients with the initiation of our outlaw 715 clinical trial in multiple myeloma.

And you know on going Oh, PPI, but one alpha trial in non Hodgkin's lymphoma.

David D. Chang: We believe this exclusive worldwide collaboration and licensing agreement with Notch, utilizing Notch's engineered thymic-niche IPSC-based platform, has the potential to create novel cell-based therapies that feature improved efficiency of gene editing, greater scalability of supply, product homogeneity, and more streamlined manufacturing. Our collaboration with NARCH includes exclusive rights to use IPS technology to develop engineered T-cells or natural killer and K-cell therapies across multiple targets in oncology and other diseases, with initial applications focused on B-cell malignancies and multiple myelomas. One of the most important aspects of this collaboration is the ability to work with scientific luminaries Dr. Juan Carlos Zuniga-Fluker and Dr. Peter Zanstra, the founders of Notch Therapeutics. JC and Peter are well-known in the iPSC field for their pioneering work in developing techniques for differentiating iPSCs into T-cells and other immune cells. Given our confidence in the team and strategic interest in the technology, we have also acquired a 25% equity position in Notch. Eric will review the financial details of this agreement later in this call. It is now my pleasure to formally welcome Rafael, who will update you on recent research and development activities.

As we have previously stated we plan to share the data from the Aloe fiber one phase one trial in the first half of 2020.

We are committed to rapidly moving out therapy is through clinical trials and advancing this basin filled up allogeneic cell therapy to generate viable commercial therapies for patients in need.

We can use our first hand knowledge and growing industry insights of autologous cell therapy to advance allogeneic development.

But as we have all learned to appreciate the allogeneic cell therapy is fundamentally different than autologous cell therapy to that end translational team is highly focused on building a robust understanding of the relationship between Lymphodepletion and sold expansion and ultimately clinical outcomes, including Bull.

Safety and efficacy.

Turning your attention to out other news. This morning, our collaboration with knocks the period is part of our broader long term strategy to think beyond what can be achieved with currently available technologies underlying the first and second generation Carty therapies.

While we believe our initial aloe car T programs derived from cells collected from healthy to owners have the potential to revolutionize the field by making car T therapy available to many more patients.

Jason cannot stop there.

We are excited to partner with knots to develop the next generation of how low car T therapy is derived from induced pluripotent stem cells all IP Fcs.

We believe this exclusive worldwide collaboration and licensing agreement with notch utilizing notches engineered time, Mcnish, Hi, PSC based platform has the potential to create novel cell based therapies that feature improved efficiency up gene editing.

Rafael Amato: Thank you, David, and good morning to all of you on the call today. In my previous role, I had the pleasure of speaking with many of you, but today, I'm very happy to be speaking on behalf of Allogene and highlighting the work that has been underway by an excellent team of people in R&D. While I just recently joined Allogene in September, I was fortunate to have an opportunity to meet some of you at our open house and at various investor events. I thank you for the warm welcome and look forward to many more opportunities to see you in the months and years to come.

Greater scalability of supply product commits unity and more streamline manufacturing.

Our collaboration with notch include exclusive rights to use IP EPS technology to develop engineered T cells or natural killer or NK cell therapies across multiple targets in oncology and other diseases with initial application focused on b cell malignancies.

Rafael Amato: Our ALO501-alpha dose escalation study continues to accrue as planned. We will also be filing an amendment to the current protocol for the alpha trial to further explore the optimal dose and schedule of ALO647, allow redosing of patients, and expand enrollment criteria to include patients who have been previously treated with autologous CD19 directive therapy and whose disease has progressed. We are studying a variety of corollary parameters that are informing us about the optimal relationship between the depth of lymphodepletion, cell dose, and clinical outcomes, as David mentioned earlier. Indeed, we have made a lot of progress in setting up clinical translational assays both internally and externally to fully elucidate the optimal conditions that will lead to best outcomes in the allogeneic setting. This work is being done in close collaboration with research and process development teams that will supply the key properties of the allograft associated with optimal pharmacodynamic and clinical properties.

In multiple myeloma.

One of the most important aspect of this collaboration is the ability to work with scientific luminaries Dr., Juan Carlos Zuniga, Fluker, and Dr., Peter Zandstra, the founders of notch Therapeutics, J.C. and Peter are well known in the IP FC field for their pioneering work.

In developing techniques for differentiating hi, pfcs into T cells and other immune cells.

Given our confidence in the team and strategic interest into technology. We have also acquired a 25% equity position in notch.

Eric will review the financial details from disagreement later in this call.

It is now my pleasure to formally welcome Rafael who will update you on recent research and development activities.

Thank you David and good morning to all of you on the goal today in my previous role I've had the pleasure speaking with many of you, but today I'm very happy to be speaking on behalf of Allergan and representing the work that has seen underway by an excellent team of people in R&D.

Rafael Amato: We initiated our Allo 715 universal clinical trial during Q3, and we're actively accruing and treating patients. We are developing ALO715, our anti-BCMA allogeneic CAR T therapy, for the treatment of relapse-refractory multiple myeloma patients. We continue to get many questions about the Allo 715 Universal Trial, so I'd like to briefly remind you of its design.

Well I just recently joined Allergan in September I was fortunate to have an opportunity to meet some of you are open house and various investor event.

Thank you for the warm welcome I look forward to many more opportunities to see you in the month in years to come.

Rafael Amato: The Phase 1 study is designed to assess the safety and tolerability of increasing doses of ALO715 with the goal of identifying an optimal dose of ALO715 for a potential Phase 2 study, which could be a pivotal study for a BLA submission. As to the Allocard CD19 studies, this trial will also utilize Allo-647, our proprietary anti-CD52 monoclonal antibody, as part of the lymphodepletion regimen. In the main portion of the study, we plan to enroll up to 24 patients with relapsed refractory multiple myeloma who have failed at least three prior lines of therapy in a dose escalation 3 plus 3 trial design. The universal study is designed to allow for exploration of additional cohorts to assess a potential milder lymphodepletion regimen where the chemotherapy components, specifically fludarabine and cyclophosisphamide, will be stepwise removed.

Our aloe fiber one outside dose escalation study continues to accrue a split.

We will also be filing an amendment to the current protocol for the Alpha trial to further explore the optimal dose and schedule of Arlo six or seven allow read dosing of patients and expand enrollment criteria to include patients who have been previously treated with autologous cdnineteen directed therapy, whose disease has.

Greg.

We are studying a variety of corollary parameters that are informing us about the optimal relationship between the depth of meaningful depletion, so those and clinical outcomes that David mentioned earlier.

Indeed, we have made a lot of progress in setting up clinical translational assays, both internally and externally to fully elucidate the optimal conditions, so will lead to better outcomes in the allergenic setting.

Rafael Amato: As we look ahead, we will be assessing endpoints such as safety, tolerability, cell expansion, and anti-tumor activity as key determinants of success for ALO715 with the various lymphodepletion regimens. We anticipate sharing a first look at the data from this trial by the end of 2020. We're also pleased to announce that CEQVIA, our development partners on UCAR-19, continue to expect to move the pediatric and adult trials in ALL into Phase II in 2020. We remain very excited about the strategic direction and progress of our research and clinical programs. We're uniquely fortunate to have access to what I believe is one of the very best scientific advisory boards in the industry, and my first scientific advisory board meeting at Allogene showcased pioneering science in the allogeneic cell therapy space and was one of the most productive SADs that I have ever attended.

This work is being done in close collaboration with the research under process development team that will supply the key properties of the allograft associated with optimal Pharmacodynamic and clinical properties, we initiated our Arlo 715 universe of clinical trial during Q3 and were actively accruing intrusion.

Patients.

We are developing aloe 715, our anti VCM may allogeneic car T therapy for the treatment of relapse refractory multiple myeloma patients.

We continue to get many questions about follow soon one five universal trial selective briefly remind you of its design.

The phase one studies designed to assess the safety and tolerability of increasing dose levels of Aloe 715, with the goal of identifying an optimal dose of all of 715 for a potential phase two study, which could be a pivotal study for our pls submission.

As to the Allah Cdnineteen studies. This trial will also utilize arlo six or seven are appropriate very anti CD 52, monoclonal antibody as part of the Lymphodepletion regimen.

Rafael Amato: This extensive meeting sought feedback on our pipeline, the design of our trials, and the innovations that are the focus of our research team, including new products and innovative technology to address hematologic malignancies and solid tumors. We have already highlighted some of the work we are pursuing, including a research collaboration with Stanford University, signed in September. Under this collaboration, Allogene, in partnership with researchers Drs. Robert Weymouth, Paul Vendor, and Ronald Levy, will investigate a novel nucleic acid delivery system to more effectively, safely, and flexibly deliver RNA or DNA into lymphocytes, including T-cells, to allow efficient genetic engineering ex vivo. I am also very excited by the internal innovation that our teams are pursuing. The validation and guidance we receive from our SAVs is invaluable, and we look forward to unveiling more projects from our research efforts over the next year.

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

Universal studies designed to allow for exploration of additional cohorts to assess a potential milder lymphodepletion regimen or the chemotherapy components, specifically fludarabine and cyclophosphamide will be stepwise removed.

As we look ahead, we will be assessing endpoints such as safety Tolerability cell expansion, an anti tumor activity as key determinants of success for Allah, serving one five with the various lymphodepletion regimen.

We anticipate sharing a first look at the data from this trial by the end of 2020 .

We're also pleased to announce that said to be a our development partners on new car 19 continue to expect moving the pediatric and adult trials in MLL into phase two in 2020 .

Eric Schmidt: Thank you, Raphael. I will provide a brief overview of Allogene's financials. Additional detail on our third 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 remain strong financially, with cash, cash equivalents, and investments totaling $601.9 million as of September 30, 2019. In the third quarter, our research and development expenses were $40.0 million, which included $5.5 million of non-cash, stock-based compensation expense. R&D expense in Q3 also included a $5 million milestone payment to our partner, Selectus, which is associated with the initiation of the universal study on ALLO 715. General and administrative expenses were $15.0 million for the third quarter of 2019, which included a $7.3 million non-cash stock-based compensation expense.

We remain very excited about the strategic direction and progress of our research and clinical programs.

We are uniquely fortunate to have access to what I believe is one of the very best scientific advisory boards in the industry on my first scientific Advisory Board meeting that Allergan showcased pioneering science in the allogeneic cell therapy space and what's one of the most productive babies that I have ever attended.

These expenses meeting thought feedback on our pipeline the design of our trial and the innovations that are the focus of our research team, including new products and innovative technology to address hematologic malignancies in solid tumors.

We have already highlighted some of the work we are pursuing including a research collaboration with Stanford University sign in September .

Under this collaboration allergy in in partnership with researchers Dr., Robert Waymo Dr., Paul vendor under for Renault Levy will investigate a novel nucleic acids delivery system to more effectively safely and flexibly deliver are in a or DNA into lymphocyte, including T cells to allow efficient.

Genetic engineering ex vivo.

I'm also very excited by the internal innovation that our teams are pursuing the validation on guidance would receive from our Cvs invaluable and we look forward to unveiling more project from our research efforts over the next year.

Eric Schmidt: Our net loss for the third quarter of 2019 was $50.7 million, or $0.50 per share, including non-cash, stock-based compensation expense of $12.8 million. As we have noted in previous quarters, we continue to invest heavily in our clinical programs and advance the build-out of our manufacturing capabilities, as well as hiring across functions with now 190 full-time employees. We have also been highly focused on executing strategic business development agreements.

We'll now like to turn the call over to Eric.

Thank you Rafael I will provide a brief overview of our genes financials additional detail on our third quarter financial results can be found in our press release issued earlier today and at our 10-Q, which will be filed with the FCC. We remained strong financially with cash cash equivalents and investments totaling $601.9 million as of September thirtyth.

2019.

In the third quarter, our research and development expenses were $40.0 million, which includes $5.5 million of noncash stock based compensation expense R&D expense. In Q3 also includes a $5 million milestone payment to our partner Selectives, which is associated with the initiation of the Universal study on Aloe 715.

Eric Schmidt: As noted earlier in this call, we are very excited about our exclusive collaboration with Notch and the ability to develop next-generation IPSC-based allogeneic therapy. Under the terms of the agreement, Allogene will provide an upfront payment of $10 million, research funding over the collaboration term, and a preferred equity investment of $5 million in return for a 25 percent equity position in Notch. Preclinical research will be conducted by NOCH under the direction of a joint development committee. Allogene will lead the clinical development and commercialization of all candidates that may come out of the collaboration and will retain worldwide rights to any potential candidates. NOCH would be eligible to receive future payments upon the achievement of certain research, development, and commercial milestones, as well as tiered royalties. Including the expenses associated with a notched transaction, we remain in position to reiterate our 2019 Net Loss Guidance. Full-year net losses are expected to be between $200 million and $210 million.

General and administrative expenses were $15.0 million for the third quarter of 2019, which includes a $7.3 million noncash stock based compensation expense, our net loss for the third quarter of 2019 was $50.7 million for 50 cents per share, including noncash stock based compensation expense.

For the 12.8 million Dollarss.

As we've noted in previous quarters, we continue to invest heavily in our clinical programs and advancing the build out of our manufacturing capabilities as well as hiring across functions with now 190 full time employees. We have also been highly focused on executing strategic business development agreements.

As noted earlier in this call. We're very excited about our exclusive collaboration with notch and the ability to develop next generation IPO Sea based allogeneic therapies under the terms of the agreement our Jim will provide an upfront payment of $10 million research funding over the collaboration term and a preferred equity investment of $5 million and return for a 25% X.

Would you position a notch.

Operator: This includes an estimated non-cash stock-based compensation expense of $45 to $50 million. With that brief review of our financials, we will now open the call for your questions. Thank you. To ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key.

Preclinical research will be conducted by notch under the direction of a joint development Committee allergy and will lead the clinical development and commercialization of all candidates that may come out of collaboration and we'll retain worldwide rights to any potential candidates notch would be eligible to receive future payments upon achievement of certain research development and commercial milestones.

As well as tiered royalties.

Including the expenses associated with a notch transaction, we remain in position to reiterate our 2019 net loss guidance full year net losses are expected to be between 200 million in $210 million. This includes an estimated noncash stock based compensation expense of $45 million to $50 million with that.

Operator: In the interest of time, we ask that you please limit yourself to one question. Please stand by while we compile the Q&A roster. Our first question comes from Byron Amin with Jefferies. Your line is now open. Hi guys, thanks for taking my questions and congrats on all the progress. Maybe if I could just start with Allo501, can you just talk a little bit about how many patients you would have at the time of data collection in the first half of 2020, David? And I guess, you know, based on that analysis, what would be potential next steps?

If review of our financials, we will now open the call for your questions.

Thank you to ask a question you'll need to press star one on your telephone to withdraw your question pressed upon key.

The interest this time, we ask that you please limit yourself to one question.

Please standby probably compared to Q and a roster.

Our first question comes from buyer in the men with Jefferies. Your line is open.

Operator: Buren, we'll be happy to answer those questions, and I'm going to direct your questions to Dr. Rafael Amado. Yeah, hi.

Yeah, Hi, guys. Thanks for taking my questions and congrats on all the progress maybe if I could start with how low five on one can you just talk a little bit about how many patients you would have at the time of data in first half 2020, David and I guess.

Rafael Amato: Hi there. So, the trial is progressing quite well as planned. We've decided that our first presentation will be one that contains enough information to be able to evaluate the allogeneic approach, and we will continue guiding to the same time, which is the first half of this year. So our expectation is that we will have enough patients to be able to make statements about efficacy, safety, and corollary parameters.

Based on that analysis, what would be a potential next steps.

Yes, we'll be happy to answer those questions and I'm going to correct audio questions to file an idle.

Operator: Thank you. Our next question comes from Phil Nadeau with Cowan & Company. Your line is now open.

Yes, hi, there so.

Charlie is progressing.

Well.

As planned.

Operator: Morning. Thanks for taking my question. My question is also about the ALLO501 alpha trial. During your prepared remarks, you mentioned a couple times that you were working to figure out how the depth of lymphodepletion affects cell expansion. And, in fact, from the alpha trial, you mentioned that you were going to change the dose and schedule of 647. So can we read into those comments that you've decided to investigate these changes because of what you've seen in the initial patients? And, I guess specifically, what dose and schedule change are you contemplating for 647, and what are you trying to accomplish? Thanks.

We decided that our first presentation would be one contained enough information to be able to.

Great.

The.

Allogeneic approach.

And.

We will continue to gain to the.

The same time, which is the first half of this year. So our expectation is that we will have.

No patients.

Yeah, well too.

Make statements about.

Efficacy safety and corollary parameters.

Thank you. Our next question comes from Phil Nadeau with Cowen and company. Your line is now open.

Good morning. Thanks for taking my question. My question is also on our fiber one all for trial. During your prepared remarks, you mentioned a couple of times that you were working to figure out.

How the depth of Lymphodepletion effect so expansion.

David D. Chang: Yeah, Phil, good morning. Let me take that question. This is David Chang.

And in fact from the Alpha Charlie you mentioned that you're going to change the dosing schedule 647. So can we read into those comments that you decided to.

David D. Chang: So, some of the questions about, you know, things that we are looking at. I mean, this is a Phase I study, and we always view the Phase I study to really test So, we're going to talk about some of the key unknowns as well as confirm some of the assumptions that went into the design of the Phase I study. And, you know, in Phase I, as we have talked about, flexibility is key because there are so many different questions that we want to ask. And at the end, the goal of, you know, Phase I is coming up with the right doses and schedule that will enable us to move into Phase II and, you know, progress on Phase II as quickly as possible.

Investigate these changes because what you've seen in the initial patients and I guess, specifically, what what dose and schedule change are you contemplating for 647 and what are you trying to accomplish thanks.

Yes. So good morning, let me take that question. This is David Chang So some of the questions about.

Things said, we are looking at I mean, this is a phase one study and we always viewed.

The phase one study to really tests.

Unknowns as well add to come from some of the assumptions that went into the design of the phase one and.

In phase one as we have talked about flexibility as a key but there's so many different questions that we want to ask and SDN to Golar phase one.

David D. Chang: So, a lot of times, you know, in Phase I, we sometimes start with a lot of flexibility. In the case of, you know, our 501 alpha study, given that it was our first, you know, clinical study as a company, we elected to go with a very simple protocol and take the opportunity to amend the studies as it goes. So, none of these, you know, the things that we are talking about are a reflection of what we are seeing, but it is all part of the original plan that we had.

Is coming up with the right grocers and schedule that will enable us to move into the phase two.

And in a progress on the phase two as quickly as possible. So a lot of times.

In phase one we from the beginning sometime starts with a lot of flexibility in the case.

Hi, Bill one study given that it is our first.

Clinical study as a company we elected to globally, the very simple protocol and picked up its ability to amend the studies as it goes so none of these.

Operator: Thank you. Our next question comes from Corey Kasimov with J.P. Morgan. Your line is now open. Hi, this is Gavin on behalf of Corey.

David D. Chang: Just wanted to get your thoughts on the Notch deal, kind of what drove the decision there? Did you see, you know, was it clinical or preclinical data? And just any thoughts on the timing, why did you decide to do the deal now? Thanks.

Things that we're talking about is a reflection of what we are seeing but as it is all part of the original plan that we had.

Thank you. Our next question comes from Cory Kasimov with JP Morgan. Your line is now open.

Hi, This is gathering on for Corey just.

David D. Chang: Yeah, this is David Chang. Let me take that.

David D. Chang: I mean, you know, I think, you know, we have talked about, you know, how we are thinking about CAR-T therapy, in general, several times. This is a field that started, you know, from the autologous, and now we are trying to advance that into the allogeneic using the healthy donor. And we also have talked numerous times about where the future may lie, you know, as we advance the allogeneic CAR-T therapy. And we believe that eventually, using an iPSC-derived renewable cell source has the potential to really, you know, fine-tune the gene engineering as well as make the manufacturing more, you know, scalable. So, you may say, why now? I think this is something that we always have to be somewhat opportunistic about.

Just wanted to get your thoughts on the notch deal kind of.

What what drove the decision there did you see the clinical or preclinical data and just any thoughts on the timing why why do you decide to do the deal now thanks.

Yes. This is David Chang, let me take that I mean, I think we have talked about.

How we're thinking about the car T therapy in general.

At times.

This is a feel that.

From the pilots and now we are trying to advance that into the allogeneic.

Using the houses owner.

We also have Paul numerous times about where that future may lie ads, we advanced allogeneic car T therapy, and we believe that eventually using the IPO see drive renewable cell source has the potential to really.

David D. Chang: And some of the reasons that drove us to this deal are, you know, our belief that the scientific founders of Notch, Dr. J.C. Zuniga-West and then also Dr. Peter Zemstra, really define the differentiation of iPSC into T-cells. And so far, you know, the platform that they are bringing, you know, the ENT platform or the... Thank you very much.

Fine tuning the gene engineering, as well as making the manufacturing.

More scalable. So you may say why now I think this is something that we always have to be somewhat opportunistic and some other reasons that drove us to this deal is.

Out at least at scientific founders have nots this is that.

C.

Depending on that and then also.

Yeah.

Operator: Thank you. The next question comes from Tyler Van Buren with Piper Jaffray. Your line is now open. Hey, good morning guys. Congratulations on all the progress during the quarter. I just had another question regarding an amendment that was discussed in the prepared remarks with your guys' decision to include patients who were previously treated with CD19. I was just curious what resulted in that change, if there were any observations pre-clinically or clinically that you're willing to talk about.

Astra and so these two.

Hey, founder selling day really fine the differentiation of IP at sea into the T cells and so far.

Yeah.

Platform that they're bringing.

Yes, you platform or.

Engineer Knox's engineered timing niche really provides us a CRM free self rebased synthetic platform that allows the differentiation IP Etsy has a functioning T cells and Thats really what drove us to get into this deal.

The founders what they have and what we believed to be scalable and potentially more GMT amendable manufacturing process.

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

Rafael Amato: Hi, this is Rafael. So, as we progress with the study, we've been thinking about ways to potentially test the allogeneic approach in other settings. So, as you know, in non-Hodgkin's lymphoma, although the outcomes are excellent for patients that have no other options, there are still two-thirds of patients that don't benefit. And there are patients that progress really quickly or don't respond within the first three months. And many of those patients actually have poor grafts. Although they meet the release requirements, the T cells are either exhausted, or they don't have the right phenotype. And so, provided that the patient's tumor was still CD19 positive, and that the CARLA that was used before had a different single-chain FV, trying an allogeneic approach in these patients would make sense.

Hey, good morning, guys. Congratulations on all the progress during the quarter just had a another question regarding an amendment those discussed in the prepared remarks. What's your guys. This decision to include patients were previously treated with CD 19 was just curious what resulted in that change. If there was any observations preclinically or or clinically that you are willing to talk.

So.

Yes, Hi, this is right now so.

As we progress from this study we've seen thinking about.

Ways to eventually pad the Allergan a brokerage in although setting so as you know a non hodgkin's lymphoma, although the outcomes are excellent for patients that no. Other options are still two thirds of patients and dong benefit.

And there are patients that progress really quickly or.

Donges Bon within the first three mountain many of those.

It's actually have poor graph, although they need release requirement.

Rafael Amato: It would be, first of all, a source of patients, but also, more importantly, a proof of concept as to whether allogeneic therapy can work in patients that have failed autologous therapy, which is, I think, something that would be of great benefit to the field. So that was the rationale behind it, and particularly knowing that this is a sizable patient population that once they fail autologous CAR-T, they have very few

On the T. so.

There are exhausted or they don't have the right phenotype.

So we thought that provided that the patient's tumor was still cdnineteen positive and at the kind of what you see for how to a different.

Single chain at the.

Tying that allogeneic approach in these patients would make sense.

It would be first of all.

Source of patients, but also more importantly, a proof of concept as to whether allogeneic therapy can work in basins I have failed Oliver therapy, which is I think.

Operator: Thank you. Our next question comes from Amanda Murphy with BTIG. Your line is now open. Hi, good morning.

It would be based benefits in the field. So that was the rationale the rationale behind it and particularly knowing that this is a sizeable.

David D. Chang: I'm not sure you had a question on 501 as well. Curious, I don't know if you've been able to talk to the centers and get a sense, to the extent that you do get complete responses, how are the physicians thinking about transplants in this setting. You know, do you have any idea if they'll go to transplant or, you know, try to see how long the CAR T or the durability of the CAR T can last?

Patient population that one thing I'll call. This RFP they have very few options.

Thank you. Our next question comes from Amanda Murphy with BTI G. Your line is open.

Hi, good morning.

That does she had a question on fiber one as well curious I don't know if you've been able to.

David D. Chang: Amanda, this is David. Let me take your question. Good morning. So, as we do the study, I mean, we have to act very closely with the investigators. And, you know, some of the changes that we have talked about...

Talk to the centers and get a sense. It today said that you do get complete response is how our Howard that physicians thinking about.

Transplants in this setting or do you have any sense of dealt gun transplants or try to see how long he cartier and durability of the car T can that can last.

Matt This is David let me take your question good morning. So.

David D. Chang: And as Rafael just talked about, the inclusion of the patients who previously received CD19, it reflects the growing interest in the field as identifying previously treated patients who previously received CD19 CAR-T as an autologous treatment and have not responded as being one unmet need. So we were definitely interested in sort of going with the investigator and pursuing that avenue. You know, with respect to the other things, I mean, I would say the support of the investigator and, you know, the rate of enrollment. I think this is very much proceeding, you know, according to the plan. But I cannot be happy with, you know, how we are progressing with the clinical studies.

As we did a study I mean, we attacked very closely with investigators and some of the amendment that we have talked about that also factors in the investigators interest and advice that we are getting on that and as Rob just have talked about the.

Inclusion of the patients who previously we see cdnineteena. It reflects the growing interest in the field as identifying the previously treated patients previously we see Cdnineteen car T ethanol colleges treatment and have not responded as being less than that.

David D. Chang: I mean, I know that many of you are asking questions about, you know, what we are seeing in the clinical study. And, you know, on this one, we're going to really maintain the position that we have been maintaining over the last three quarters, which is that, you know, we would like to really, you know, provide a meaningful update in due time. And we project it, as we have stated in the prepared statement, to be in the first half of 2020.

Needs. So we will definitely interested in sort of going with the investigator and pursuing.

Avenue.

With respect to the other things I mean, I, let's say the support of the investigator and.

The rate of enrollment I mean, I think this is very much proceeding according to the plan and I cannot be happy with how we are progressing with a clinical studies I mean, I know that many of you are asking questions about the what we're seeing in the clinical study and this fund we go.

Operator: Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. Your line is now open. Hey, good morning, guys. Let me ask you a two-part question, if I can. First of all, do you think

Really maintain that position that we had in maintaining over last three quarters, which is that we would like to really provide a meaningful update in due time and we project as we have stated in the prepared statement to be in the first half of 2000 Bonnie.

Operator: I think that the exploratory...

David D. Chang: So, do you think that the two depletion regimens that are being amended into the ALSPR protocol are going to be very similar to what's being tested in Universal, or do you think that the two protocols will diverge from each other in terms of the lymphodepletion regimens? And the second part of the question really is focusing on the Notch collaboration. It sounds like Notch's core technology focuses on program differentiation of iPSCs into T-cells and maybe NK-cells as well, but I'm wondering if they also have proprietary methodology for iPSC induction, and if so, can you just quickly comment on how that avoids treading on some of the existing IP that's out there from Notch's competitors? Thank you.

Thank you. Our next question comes from Mark Beaton Buck with Oppenheimer. Your line is now open Hey, Good morning, guys. Let me ask a two part question if I can first of all.

Do you think that the exploratory lymphodepletion regimens that are being amended into the protocol are going to be very similar to what's being tested in universal or do you think that the two verticals will diverged from each other in terms of Lymphodepletion regimen and the second part of the question really is focusing on on the non.

Collaboration.

Like not just core technology focuses on program differentiation of IPO seized into T cells, and maybe NK cells as well, but I'm wondering if they also have a proprietary methodology for IDFC induction and if so can you just quickly comment on how that avoids treading on some of the existing IP that's out there from from not just competitors. Thank you.

David D. Chang: So, Marc, let me take both of those questions. You know, the first question about some of the exploration that we are doing in the 501 study with respect to the lymphodepletion. I mean, you know, this is one of the key areas of the allogeneic. You know, how to do proper lympho-depletion that will control the rejection of Alokar T, which is something that has to be overcome for any allogeneic archaeotherapy to work. I mean, we are using, you know, essentially what is viewed as a selective biological lympho-depletion agent, our Allo-647, which really gives us many different ways to think about lympho-depletion. Some of that we have outlined, as you have pointed out, in our Allo-715 universal study. And in the 501 study, we are sort of testing it, exactly how we are doing it. I don't think this is the right place to go into it, but conceptually, you know, both programs will.

So let me.

Excellent. Thanks.

Both of those questions. The first question.

Some of the exploration dead, we are doing in the fiber one study with respect to the Lymphodepletion I mean, yes. This is one of the key areas of the allogeneic hospitals.

Proper Lymphodepletion, then well control the.

Rejection of our current tea, which is something that has to be overcome but any allogeneic car T therapy to work and we are using essentially what is viewed as a selective biological lift for these litigation, our Alis 647, which really gives us a many.

Finding ways to think about their lymphodepletion. Some of that we have outlined as you pointed out in our allo 715, Universal study and in the Bible. One study, we have sort of testing it exactly how they're doing it I don't think is this is the right place to go into it but conceptually.

Both programs will.

Test and review different.

Locations that we can do with Alis six or seven so some of the key things that we are bearing is really around the use of this biologic.

David D. Chang: you know, test and review different... There are a few modifications that we can do with the LO-647, so some of the key things that we are bearing are really around the use of this biological selective lymphodeplaning agent. The second question around, you know, what's really unique about the NOTCH, I think, you know, there are many different aspects, as I've said. We always think about, in any partnership, you know, the people behind, you know, the partner.

Selected depleting agent.

The second question around you know, what's really unique about the notch I think there are many different aspect as I've said.

Yes, we always think about in any partnership people behind the partner and Knox Therapeutics as I've said, we believe in the scientific Bonders, who really created sealed I see differentiation into the T cells.

David D. Chang: And NOTCH Therapeutics, as I've said, we believe in the scientific founders who really created the field of ITSC differentiation into T-cells. Along with that, as I've said, their platform, the EPN platform, provides, you know, serum-free, cell-free, and a synthetic method of differentiating iPSCs into T-cells. And I think this is where, you know, the real attraction of the NOTCH collaboration lies, you know, being able to differentiate iPSCs into T-cells in a scalable way and eventually looking towards manufacturing those in sufficient quantity and quality to conduct clinical studies and, hopefully, some day, looking towards commercializing iPSC-derived cell therapies.

Along with that as I've said.

Platform end platform provides.

Serum free cell free.

And a synthetic net.

Differentiating hi, PSC is to T cells, and I think this is where.

We feel the attraction of the notch collaboration lies being able to differentiate IPO sees into T cells.

Scalable way and eventually I'm towards our manufacturing goes in sufficient quantity and quality conduct clinical studies and hopefully someday.

Looking towards commercializing IPO see drive cell therapies.

Operator: And Mark, this is Eric. On the IP side, as you can appreciate, we're not gonna be discussing patent matters, but we have a strong legal team here who've performed much due diligence on this venture. Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. Our next question comes from Raju Prasad with William Blair. Your line is now open.

Mark This is Eric on the IP side as you can appreciate we're not going to be discussing patent matters that we have a strong legal team here has underperformed.

Much due diligence on this bench.

Thank you as a reminder to ask a question you will need to press star one on your telephone.

Our next question comes from Russia, pesticide with William Blair. Your line is now open.

Thanks for taking my question Congrats on the progress I guess, maybe just a follow up on.

David D. Chang: Thanks for taking the question, and congrats on the progress. I guess maybe just a follow-up on preconditioning. Can you just provide a little bit of color on maybe how you're thinking about which assays you're putting higher in the hierarchy when making the decisions? Is it more alloreactivity-based or engraftment-based? And then when you're thinking about changing the regimens, would it be more along the lines of reducing fluci? Before you touch 647, I'm just trying to get a sense of, you know, how you're thinking about changing the regimens, if you do, and what will guide that. Thanks.

Preconditioning can you just provide a little bit of color on.

And maybe how you're thinking about which assay is you're putting its kind of hiring the hierarchy when making the decisions is it more other reactivity based or Engrafting based and then when you're thinking about changing the regimens would it be more along the lines of reducing flu site.

Before you touch 647, I'm, just trying to get a sense of how you're thinking about changing the regiments. If you do and what will guide that thanks.

Okay.

David D. Chang: Okay, Raj, thanks for that question. In fact, there are a lot of questions about, you know, the protocol amendment that we are making. As I've said, the protocol amendment is something that we have internally been discussing for some time, and, in fact, we have indicated in previous communications that we will be making some adjustments to the protocol to test different hypotheses. So this is really, you know, driven from that end, not necessarily based on the clinical data that we are seeing. And you know, we're going to stay relatively silent about, you know, clinical data that's coming out of the ALO501 study. But I will say that, to one of your questions, our main focus of, you know, adjusting the lymphoid depletion is really centered around maximizing the potential benefit of ALO647.

Hi, Raj. Thanks for that question seems like there are a lot of questions about the protocol amendment that we are making.

As I've said.

So amendment. This is something that we have not only be discussing from some time and in fact, we have indicated in previous.

Communications that we will be making some adjustments is a protocol to test different hypothesis. So this is really Steven and not necessarily based on the clinical data that we are seeing and we've got a stayed relatively silent about clinical data.

That's coming out of our fiber one study.

I will say that to one of your questions. Our main focus of adjusting the lymphodepletion is really centered or.

Maximizing the potential benefit of our six or seven as you know this is propriety lymphodepletion agent. It is unique and differentiated from what's out there and the fact that we can provide a selective lymphodepletion. We believed that this is.

David D. Chang: As you know, this is our proprietary lymphoid depletion agent. It is unique and differentiated from what's out there. And the fact that we can provide selective lymphoid depletion, you know, we believe that this is, you know, potentially a significant differentiating factor in our strategy. So obviously, we want to maximize that aspect of ALO647. And that underlies some of the options and, you know, different things that we plan to test in the ongoing ALPHA study.

Potentially significant differentiating factoring in our our strategy. So obviously, we want to maximize that aspect of.

Atlas explore seven and debt on the line some of the.

The options and different things that we plan to test in the ongoing outlets study.

Thank you and next question comes from John Newman with Canaccord. Your line is now open.

David D. Chang: Thank you. Our next question comes from John Newman with Canaccord. Your line is now open.

Hey, good morning, guys. Thanks for taking my question.

Operator: Hey, good morning, guys. Thanks for taking the question. Excuse me.

Unique.

Just curious.

Operator: Just curious, sorry to ask another question about the amendment, but I'm just curious if you will be... For more information, please visit www.cdc.gov. You will be adding some additional patients to the study in order to maintain the current protocol and way of doing things as well as investigate any potential changes. See how those turn out, thank you.

Ask another question about the amendment, but I'm just curious if you will be.

Instituting the changes regarding.

Lymphodepletion going forward for.

You will be adding some additional patients to the study in order to.

Maintains the current.

Protocol and way of doing things as well as has been the gate.

Potential changes.

So for now.

So from Alan.

Rafael Amato: So, this is Rafael, and... I'm not entirely sure I understood the question, but I think you were asking whether we are going to continue enrolling with making these changes or investigate this. I don't want to go into all the details of how we're going to do this, but I'm going to, Essentially, I mean, just to reiterate what David said, this is a phase one study. The first thing that it was designed for is to design the cell doses. And the choice of allo-647 was actually, you know, the lowest possible dose. As you may know, there are different doses. Thank you. It's only fitting that in a phase one study, before you launch a phase two study, you want to optimize both cell dosing and lymphodepletion, both for the maximum benefit and the least amount of toxicity. So, in order to do that, obviously...

Not entirely sure understood.

And then.

Yes, I think you were asking whether we are going to continue enrolling.

We are making making these changes or investigate is.

Changes in six or seven.

Perhaps in earlier cohort.

I don't want I'm going to all the details of.

How we're going into this but.

Essentially I mean, just to reiterate what David said I mean this is a phase one study the first thing that was.

It was designed for is to design to two exciting some dosing and the choice of.

Almost 6% on what's actually that the lowest possible doses you may know, there's different doses dependent of that and all of those borrowed which is down the path.

That's right.

So.

Rafael Amato: So I think that hopefully answers your question, and if it doesn't, just please ask me to clarify.

It solely sitting down in a phase one study before you are going to launch as a society you want to optimize.

Operator: Thank you. Our next question comes from Michael Schmidt with Guggenheim Securities. Your line is now open. Hey, this is Kelsey on behalf of Michael.

Both sell dosing and Lymphodepletion, both for the maximum benefit and the least amount toxicity. So.

Operator: Thanks for taking our question. There's obviously been kind of a high bar set by anti-PCMA frontrunners, and we've seen two anti-PCMA clinical stage assets now suspended due to the competitive market. I guess, what do you think the bar is for 7.1.5, and maybe does this bar differ between Otto versus Allo CAR-T approaches, given their advantages and disadvantages? Thank you.

In order to do that.

Lastly, we needed to have some.

Some patients treated and the study has been crew that mine and we found is the time to make the amendment is not something that wasn't on plan.

And.

We'll be rolling now, we don't anticipate going back to very early does is when when it rolls out.

So I think that.

David D. Chang: Kelsey, thanks for the question. This is David, and I'll answer that.

Hopefully answers your question and if he doesn't just leave plenty to bonafide.

David D. Chang: I mean, you know, based on what we know from scientific preclinical experiments and how we perceive the LFRT should be working in the clinics, our baseline assumption is that allogeneic approaches should provide about the same level of safety and efficacy as autologous CAR-T. I mean, so that is based on, you know, on a treated basis. So from that perspective, you know, that's our baseline expectation. I mean, obviously, we will have to see in the clinical studies. I mean, there are certain things that could lead to better efficacy, but we haven't really factored that into our baseline assumption.

Thank you.

Next question comes from Michael Schmidt with Guggenheim Securities. Your line is now open.

Hey, I'm Mrs Kelcy on for Michael Thanks for taking my question.

There's obviously been kind of a high bar set by if you may front runners and you need to add to became a clinical stage assets now suspended due to the competitive market I guess, what do you think the bar is for seven one side of that maybe does this bar differ between auto burst Aloe car T approaches given kind of the advantages in this.

Beverages. Thank you.

David D. Chang: I would, however, add that one of the limitations of current autologous therapy is patients who cannot wait to receive the CAR-T therapy. If you go back and review the registrational studies in the 3D19, you know, CAR-T space, the autologous CAR-T space that led to the approval of Kymriah and Yaskara, you know, 10 to 30 percent of the patients who enrolled in the clinical studies are unable to receive the cells because they simply cannot wait until the cells are being manufactured. And obviously, as we go into Allogene, you know, our model basically would say that the cells can be readily made available to the patients once the decision is made to treat the patients with a CAR-T. And I think that could potentially lead to more patients being treated. And if we look at the data based on intent to treat, I think there are several potential improvements in efficacy simply from that logistical aspect that Allogene CAR-T cells could provide.

Oh Chelsea. Thanks for the question. This is David and I'll answer that I mean.

We view based on what we know from the scientific preclinical experiments and how we perceive.

All right he should be working the clinics.

Our baseline assumption is that allogeneic approach should provide.

The same level of safety and efficacy as to what palace car T.

I mean, so that is based on.

Yes in a number on it treated basis.

So from that perspective, that's our baseline expectation I mean, obviously, we will have to seem to clinical studies I mean, there are certain things that could lead to a better efficacy, we haven't really factored that into the our baseline assumption.

However at that one of the limitations of current autologous therapy is patients who cannot wait to received.

Operator: Thank you. Our next question comes from Ben Burnett with CFO. Your line is now open. Ben, if your line is muted, please unmute.

Operator: Thank you. Apologies. Good morning and congratulations on the progress. I also had a question about the competitive landscape. So there's a CD19 program from Precision Biosciences, and they've messaged that they could potentially have data potentially within the window that you've talked about releasing ALO501 data. And I guess I wanted to ask, can you talk about some of the more technological details that differentiate ALO501 from Precision Biosciences' CD19 CAR-T candidate? Thanks so much.

Car T therapy, if you go back and reviewed the Registrational studies in the CD 19.

Hi, Keith space.

Hi piece, they said lifted approval of key Maya and gets tighter.

10% to 30% of the patients who enrolled into clinical studies are unable to receive the cells because they simply cannot wait till the cells that being manufactured and obviously as we go into the allogeneic.

Our model basically would say that the cells can be really.

David D. Chang: Yeah, so, you know, we are aware of Precision Biosciences and what they're doing and what they have said. And I think this is all, you know, good for the field.

The made available to the patients once the decision is made to speak to patients with a car T and I think that could potentially led led to lead to more patients being treated and if we look at the data based on intend to treat I think there are several potential improvement in the efficacy.

David D. Chang: I mean, obviously, we have seen tremendous growth in the allogeneic field over the last year, year and a half since we created Allogene. And I think this is really telling you the interest of the clinicians and the field in advancing cell therapy from autologous to allogeneic. As you know, there are some subtle differences in how different companies are making their allogeneic approach. And I think this is, you know, in the end, this is going to accelerate the creation of the allogeneic cell field as we learn from each other and from different approaches that we are taking. So, you know, we remain very confident in the approach that we are taking.

We are simply from that logistical aspect that allogeneic car T cells could provide.

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

Then if your line is muted piece I mean.

Thank you Bob apologies good morning, and congrats on the progress I also had a question on the competitive landscape.

So there's a cdnineteen program from precision bio sciences, and they've message that they could have data potentially within the window that did you have talked about releasing our fiber one data I guess I wanted to ask it can you talk to some of the more technological details that differentiates hollow fiber one from precision Bio Sciences Cdnineteen car T candidate. Thanks, so much.

David D. Chang: And as we have said, you know, our approach is based on UCAR-19, which has treated a number of patients in the ALL setting. And when I review the data, the genetic engineering that controls the graft-versus-host disease also allows cell expansion and provides early efficacy in the UCAR-19 studies. I mean, these are the key things that are essential to make sure that the approach is viable. And, you know, I think that is one of the strengths that we are taking forward as we advance our 501 and our 715 programs.

<unk>.

Yeah. So.

We are aware of precision biased sciences, and what they're doing and what they have said and I think this is all good for the field I mean.

Obviously, we haven't seen tremendous growth in the allogeneic fields over the last a year yonhap since we created challenging and I think this is really telling you know left the interest of the clinicians and the field is in advancing the south therapy from autologous to the allogeneic.

Operator: Thank you. Our next question comes from Tony Butler with Roth Capital Partners. Your line is now open.

As you know that subtle differences in how different companies I'm, making out there allogeneic approach I think this is not at the end just going to accelerate the creation of allogeneic cell feel as we learn from each other as and and from different approaches.

Operator: Thanks very much. First of all, I actually applaud the amendment, so the question really goes through the differences between universal and alpha and what learnings you may be able to capture as you vary 645 with flu-psi. Do you think it would be reasonable to assume that with each different patient population, it becomes an entirely new experiment with the combination, if you will? And, if I may, just a follow-up on Notch. Applause for that deal, but are you actually, are you convinced that iPSC-derived T-cells, or actually not T-cell imposters, but in fact, can be sufficiently educated in order to behave like normal human T-cells, that is, to kill appropriate tumors?

We are taking we remain very confident in the push that we are taking and as we have said you know how approaches based on the you part 19, which has treated number of patients in the.

Hey, I'm, not saying and when I review the data.

The genetic engineering that control, so graft versus host disease and also allows to sell expansion.

David D. Chang: Thanks very much.

David D. Chang: Okay. So, Tony, thanks for that question. Especially, I'm going to take the second question, and I'm going to defer to Rafael on the first question.

And provide the in the early efficacy in the UK 19 studies I mean these are the key things that are essential to make sure that approach is viable and I think that is one of the strength that we are taking forward as we advance aloe fiber one and our settlement bye.

David D. Chang: So, at the ITFC, the question that you're asking me is one of the most important questions. Can you generate functioning T-cells? And one of the unique advantages of cell-based therapy, especially the one that uses T-cells, is the T-cells' ability, upon recognition of the target, to expand, and with an increased number, that's where the real efficacy, the depth of the response that we get with the CAR-T, I think that is what I believe in. And as I've said, the ETN platform, which is proprietary to Notch, that And you may think, well, everybody can do that. That's not true.

Program.

Thank you and next question comes from Tony Butler with Roth Capital Partners. Your line is now open.

Thanks very much.

Yes first of all I actually applaud the amendment. So the question really goes through the differences between Universal an alpha and what the learnings you may be able to capture as you very.

645 with flu sorry.

Do you think power would be reasonable to assume that with each different patient population to becomes an entirely new experiment with the combination if you will.

David D. Chang: I mean, this is one of the areas that is really not fully answered in the IPFC, whether you can generate functioning T cells. So when we were doing due diligence and having discussions with the founders of Notch Therapeutics, and when they showed this data, I mean, that was really like an "aha moment." Besides their track record, the fact that they had a proprietary reagent, and that is really, in my view, amenable to large-scale manufacturing, and also the data that shows that they can differentiate IPFCs from functioning T cells. And that's really what drove us to jump into this research collaboration. Thank you.

If I may just a follow up one notch.

Paul So that deal, but do you actually were you convince that by PSC derived cells or actually not too so imposters, but in fact can be sufficiently educated in order to.

No.

Behave like normal human T cells that is too.

To kill appropriate tumors, thanks very much.

[laughter].

Okay. So.

Turning to answer that question.

Especially I'm going to take the second question and I'm gonna have to far too rationale for the first question. So on the idea see the question that you asking to me is one of the most important question.

Can you generally functioning T cells and one of the the unique advantages of the cell based therapies, especially the ones that using the T cells is to T cells ability open recognition of the target to expand and with that.

Operator: Thank you. This is your first question about the similarities and differences between universal and non-universal.

Rafael Amato: What I would say is that, as you know, the universal study, A, is earlier, and so we have less data than we have for alpha, naturally, and B, it's a different disease, and obviously, to maximize benefit-risk, it was designed already with the idea of trying to get the optimal lymphodepletion and DICD-62 to try to reduce alloreactivity with a minimum potential toxicity. The alpha study is further along, and as David and I mentioned before, as we move with doses, it's now time to look at lymphodepletion again with the same objective, but I think to the point that you're making, it is possible that the different studies for the phase two sort of lymphodepleting conditioning regimen may be different because of the different diseases. And that's really what we want to do is to march along very carefully during So as we see more patients and we see what happens in the alpha study, we may also make modifications to universal, but that is still speculative, and time will tell. And we'll update you in the future.

Increased number that's where the real efficacy the depth of the response that we get with a car T. I think that is what I believe in and as I've said.

The end platform, which is proprietary to not stead, we had exclusive license for the other indications that we're going after.

They have shown that using that platform. They can generate functioning T cells and you may think well that everybody can do that that's not true I mean this is one of the area that is really.

Fully answered in the ITC, whether you can generate functioning T cells. So when we were doing due diligence and having to discussions with the founders of not therapeutics and when they show. This data I mean, thats was really like our moment besides their track record the fact that.

They had impropriety reagent and that is really in my view amenable for lack scale manufacturing and also the data that shows that they can differentiate IP FCC the functioning T cells, and that's really what drove us to jump into these research collaboration.

Thanks, Tony. This is this is to your first question about.

The similarities and differences between universal on the offer sorry, what I would say that as you know the universal study or a is earlier and so we have let data than we have four alpha naturally Andy is a different disease.

David D. Chang: And Tony, by the way, this is David again. Thanks for recognizing that, you know, protocol amendment is something that is really, you know, warranted here. I mean, you know, I am somewhat surprised by the number of questions on the protocol amendment. You know, having been in this field and having been involved in so many different phase one studies, I mean, every phase one study that I have been involved in will have, you know, anywhere between five to ten amendments during the course of phase one. So, I know that you all have a lot of questions about why we are doing the protocol amendment, but I see this as more on par and as a routine that one has to do as a part of the phase one study.

These and there will obviously to maximize innocent Brad you what design already with the idea of trying to get the optimal.

For the completion and.

On Dicey 60 to try to reduce our loss activity within minimal.

Potential toxicity.

The Alpha freight further along in a David and I mentioned before we as we move with doses. It's now time to to look at the names of inflation again with the same objective, but I think to avoid that you're making it is possible them to different studies for the phase twos.

Operator: Thank you. That concludes today's question-and-answer session. I would now like to turn the call back over to you.

David D. Chang: Well, thank you for joining us on the call today, and thank you for your ongoing support of Allogene as we progress our clinical programs. We look forward to seeing many of you at ASH and other conferences as we close out 2019. Operator, you may now disconnect.

Marketing for the bleeding.

Conditioning regimen, maybe just trend because of the different diseases and Thats really what we want to do it to marched along very carefully.

In this phase one sort of phase of these two trials so that when we started the phase two studies, we have the maximum potential to to derive the greatest benefit risk.

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

So.

We see more basins and we see what happens in the on Friday, We may also make modifications universal but that is still speculative and.

Time will tell them, we'll update you in the future and Tony by the way. This is David again, thanks flow recognizing that protocol amendment is.

Something that is really in a warranted share I mean, I am somewhat surprised with a number of questions on the protocol amendment that having been in this field and having been involved in so many different phase one studies I mean every phase one studies that I have been involved in will have anywhere between five to 10.

Operator: BF-WATCH TV 2021

You know amendment during the course of the phase one so.

I know that you all of you have a lot of questions about why we are doing the protocol amendment, but I see it is as small on par and as a team that one has to do as a part of the phase one study.

Thank you that concludes today's question and answer session I would now like to turn the call back over to management for any additional comments.

Well, thank you for joining us on the call today and thank you for your ongoing support of algae as we progress our clinical programs. We look forward to seek many of you at ash and other conferences as we close out 2019, operator, you may now disconnect.

Thank you ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program you may now walk off and disconnect.