Q4 2019 Earnings Call

Good morning, ladies and gentlemen, thank you for standing by and welcome to the housing Therapeutics fourth quarter 2009 conference call. At this time, all participants are to listen only mode. After the speakers presentation. There will be a question and answer session to ask a question during the session issued a press star one on your telephone if you require further assistance.

Operator: Good morning, ladies and gentlemen, thank you for standing by, and welcome to the Allogene Therapeutics Fourth Quarter 2009 Conference. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you need to press star 1 on your telephone. If you require further assistance, please press star then 0.

First our than zero.

Operator: Please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.

Please be aware that todays conference call is being recorded I would now like turn the call over the course, the interest Seattle Chief Communications Officer, Scott Seattle. Please go ahead.

Thank you operator, and good morning before market open today allergy issued a press release it provides a corporate update and finance results for the fourth quarter and full year ended December 31 funny thing.

Christine Cassiano: Thank you, Operator, and good morning. Before the markets opened today, Allogene issued a press release that provides a corporate update and financial results for the fourth quarter and full year ended December 31, 2019. This press release is available on our website at www.allogene.com. We remind listeners that today's call is a 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. Rafael Amato, Executive Vice President of Research and Development and Chief Medical Officer, and Dr. Eric Schmidt, Chief Financial Officer. During today's call, we will be making certain forward-looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials, regulatory filings, future research and development efforts, manufacturing capabilities, and 2020 financial guidance, among other things.

In the press releases are available on our website at www dot allocating dot com.

We remind listeners that today's call. It a 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., Rafael Amado Executive Vice President of research and development and Chief Medical Officer, Dr., Eric Schmidt Chief Financial Officer.

During todays call, we will be making certain forward looking statements.

These may include statements regarding a success and timing of our ongoing and planned clinical trials regulatory filing future research and development efforts manufacturing capabilities and 2020 financial guidance among other things.

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 statement. 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 September 30, 2019, as well as our upcoming Form 10-K for the year ended December 31, 2019. Your questions deny the plate's 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.

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 does contained in the forward looking statements.

These and other risks are described in our periodic filings made with the Securities Exchange Commission, including our form 10-Q for the quarter ended Septemberthirty 2018, as well as our upcoming form 10-K for the year ended December 31, 29 aim.

Youre cautioned not to place undue reliance on these forward looking statements and the company disclaims any obligation to update.

I'll now turn the call over to Dr. David thing.

David D. Chang: Good morning, and thank you for taking time to join us on our call today to discuss our fourth quarter and the year ahead. I am extremely pleased with what we have accomplished in 2019. We completed the hiring of senior management, built work-class capabilities across critical functions, and initiated the build-out of our GMP cell manufacturing facility in Newark, California, making steady progress towards bringing the facility online in 2021. Most importantly, we initiated two clinical programs, ALO501 for relapsed and refractory non-Hodgkin lymphoma and ALO715 for relapsed and refractory multiple myel Our research team is also working towards advancing additional programs and next-generation cell engineering technologies, which we plan to introduce into clinical trials in the coming years. It is still early in 2020, but we are continuing the momentum we created last year and working at an accelerated pace.

Good morning, and thank you put taking time to join us on our call today to discuss how fourth quarter and a year ahead.

Hi, I'm extremely pleased with what do we have accomplished in 2019, we completed the hiring of senior management.

The old World class capabilities of course critical functions.

And initiated the deal that allergy M T cell manufacturing facility in New York, California, making steady progress towards bringing the facility online in 2021.

More importantly, we initiated two clinical program Hello fiber, one in relapsed and refractory non Hodgkin lymphoma, and almost 715 in relapsed and refractory multiple myeloma.

Oh research team is also working towards advancing additional programs and next generation sell engineering technologies, which we plan to introduce into clinical trials in the coming years.

It's still early in 2020, but we are continuing the momentum we created last year and working at an accelerated pace.

David D. Chang: This year, we anticipate reporting initial data for two key clinical programs, ALO501 in the second quarter of this year and ALO715 in the fourth quarter. We also look forward to expanding our clinical portfolio as we progress our next IND candidate, TALO316, which targets 3D7B. All 200-plus employees at Allogene remain singularly focused on one goal, making allergy therapy and its life-saving potential a reality for patients.

Let's see here, we anticipate reporting initial data for two key clinical programs helped by the one in the second quarter up is here and now seven one spot in the fourth quarter.

We also look forward to expanding out clinical portfolio as we progress on our next I. Indeed ended at three months, six which target cdseventy.

All 200, plus employees that Allergan remain singularly focused on one goal, making follow car T therapy, and Dan lifesaving potential hey reality for patients.

David D. Chang: The team at Allogene intends to strengthen our leadership position in allocardiotherapy, and we recently laid out our three-part strategy to achieve this goal. Number one, establish a platform that will be foundational to the success of allocardial therapy. Number two, validate the platform through the rapid clinical development of multiple product candidates. And number three, transform the future of allopathy by advancing next-generation technologies to enhance the potency and selectivity of our cells. Let me walk you through our concept of platform validation and transformation.

The team at Allergan intends to strengthen our leadership position in that'll car T therapy, and we recently laid out our brief parts strategy to achieve this fall.

Number one establish a platform there will be foundational queued up success of Albuquerque therapy.

Number two validate the platform to the rapid clinical development of multiple product candidates and number three transform that future Battle car T by advancing next generation technologies to enhance the potency and selectivity about Phil.

When you walk you through our concept a platform validation that transformation.

David D. Chang: While there are similarities between allogeneic and autologous cell therapy, there are key immunological phenomena that need to be addressed to allow the unrestricted use of allogeneic CAR-T cells manufactured from one healthy donor for a large number of patients independent of HLA-type. Specifically, one needs to control the risk of graft-resource disease and prevent early graft rejection. Once these issues that are key to the success of allogeneic cell therapy are addressed, the inherent benefits of allococci therapy can be realized, namely the ability to deliver therapy faster and more conveniently to all appropriate patients as an off-the-shelf therapy at a reduced cost of manufacturing. Our novel platform approach to creating an allogeneic cell therapy is based on talent in editing, state-of-the-art cell manufacturing, and the use of a novel lymphodepletion strategy. Talent technology and our proprietary manufacturing processes allow us to efficiently edit out the T cell receptor from alokar T cells. Early data from studies on our UCAR-19 candidates, as well as data being generated by others in the field, support the view that cells lacking the T cell receptor have limited ability to mount the graft-versus-host response.

While there are similarities between allogeneic, an autologous cell therapy, yeah. She immunological phenomenon not that needs to be addressed to allow unrestricted use of allogeneic car T cells. Many baxter from one healthy doner, what a large number of patients independent hmm.

Specifically, one needs to control the risk of graft versus host disease, and pretty bad really graph projection.

Once these issues that keytruda success of allogeneic cell therapies that the inherent benefits of Albuquerque, 30 can be realized, namely the ability to deliver therapy faster and more convenient lead to all appropriate patients as an off the shelf therapy at a reduced cost up manufacturing.

Oh novel last call my thoughts to creating on allogeneic cell therapy is based on talent gene editing state of the arc self manufacturing and the use of a novel Lymphodepletion strategy.

Talents technology, and I'll propriety manufacturing processes allow us to officially ended out the T cell receptor from Albuquerque felt.

Early data from studies, well now you cards 19 candidates as well as data being generated by others in the field support that view that sells lacking T cell receptor have limited ability to now be graft versus host be spot.

David D. Chang: The second challenge, the ability to overcome early graft rejection, is critical to enabling allocarditis and requires a novel strategy that goes beyond the use of traditional chemotherapy-based lymphodiplation. We believe our lympho-depletion strategy, based upon the use of ALO647, our anti-CA52 antibody, as a selective and controllable lympho-depleting agent, differentiates us from others and is well-suited We use ALO647 for the purpose of creating a selective and durable period of lymphoid depletion to facilitate expansion and persistence of our ALO CAR T cells, which have been modified to be resistant to the effect of ALO647. The initial proof of concept for ALIS-647 comes from the UCAR-19 study.

The second challenge the ability to overcome early craft injection is critical to enabling Albuquerque and requires a novel novel strategy that goes beyond the use of traditional chemotherapy based lymphodepletion.

We believe our Lymphodepletion strategy based upon to use that alis six or seven I'll add that he could be to anybody that's a selected uncontrollable input depleting agent differentiates us from others and is well suited to crude them early rejection of Iowa Aloe car T cells.

We use alis six or seven for the purpose of creating a selected and durable period up Lymphodepletion two facility expansion and persistence, although a little car T cell, which have been notified to be resistant to the effect of the analytics with seven.

The initial proof of concept, what alis six or seven tons from the used car 19 studies.

David D. Chang: These studies, which used both low- and high-dose fludarabine and cyclophosisphamide-based lymphodepletion, provided compelling evidence that chemotherapy-based lymphodepletion alone may not be sufficient. While the majority of patients who received an anti-CD52 antibody as part of their lymphoid depletion regimen experienced clinical benefits, those who only received flu-type failed to demonstrate cell expansion and were not responsive to therapeutic treatment We believe Allo647 provides us with a unique opportunity to selectively control the depth and length of lymphoid depletion, thereby allowing us to explore and determine the optimal window for Allocard-T cell expansion and persistence in a variety of clinical settings. In summary, we believe we have the only lymphoid depletion platform capable of inducing durable lymphoid depletion without impacting the viability of allocardi Our lymphodepleting agent, Salo-647, is not associated with a broader cytokinetic effect for chemotherapy because it is targeted only at cells that express CD52 and can be flexibly dosed. No other platform can do that.

These studies, which used both low and high dose fludarabine and cyclophosphamide piece to Lymphodepletion provided compelling evidence that chemotherapy based lymphoma policemen, along may not be sufficient.

Wow that majority of patients who received an anti CD 52 anybody at part of their Lymphodepletion regimen experienced clinical benefit those who only received well I failed to demonstrate solid expansion and whatnot responsive to therapy.

We believe Alis six plus seven pro by thoughts with a unique opportunity to selectively controlled that that and length of lymphodepletion, thereby allowing us to explore and determining the optimal window for aloe car T cell expansion and persistence in up variety of clinical setting.

In summary, we believe we had the only lymphodepletion platform capable of inducing durable lymphodepletion without impacting the viability of idle car T cells.

Our lymphoma depleting agent Alis six plus seven is not associated with the broader therapeutic effects of chemotherapy because it is targeted only itself that expense feeding 52 and can be flexibly doors.

No other platform and do that.

This leaves us to the validation that we hope to obtain from a clinical trial.

David D. Chang: This leads us to the validation that we hope to obtain from a clinical trial. We are on track to present initial data from the ALO501 Alpha trial in relapsed and refractory non-Hodgkin's lymphoma in the second quarter and our ALO715 trial for relapsed and refractory muscular myeloma in the fourth quarter this year. These phase one trials are designed to test safety and establish an appropriate allocardial cell dose. In addition, these trials are designed to test different doses and dosing schedules of ALLO647 to optimize lymphodepletion in preparation for Phase II trials. We believe our ongoing trials could validate our lymphodepletion strategy and thereby be leveraged across our broader pipeline. Later in this call, Rafael will provide additional color on our progress in the Phase 1 Alpha trial for ALLO501. In addition, we have made progress to introduce our next generation ALLO501A construct into clinical testing. As you recall, LL501A, previously referred to as LL501.1, was created to eliminate the retoxicum recognition domain in LL501 with the intent of using LL501A broadly across different subtypes of non-Hodgkin's lymphoma and in a pivotal trial.

We are on track to present initial data from Aloe fiber, one I'll touch while in relapsed and refractory non Hodgkin's lymphoma in the second quarter and our seven to one side trial for relapsed and refractory multiple myeloma into fourth quarter disappear.

These phase one trials are designed to assess safety and established an appropriate Palo car T cell dose.

In addition, these trials are designed to test different dose and dosing schedules well Dallas to explore seven to optimize lymphodepletion in preparation for phase two trials.

We believe our ongoing trials could validate our lymphodepletion strategy and thereby leveraged to close our broader pipeline.

Later in this call my fellow provide additional color on our progress in the baseline Alpha trial, well Allo Bible. One. In addition, we have made progress to introduce our next generation Aloe fiber one a cost cuts into clinical testing.

As you May recall ALC Bible, one a previously referred to that Oh by the 1.1 was created to eliminate the tough some recognition domain in aloe fiber one with the intent of using outlook Bible, one a broadly across different sub I spoke non hodgkin's lymphoma, and you know.

In a pivotal trial.

David D. Chang: We have submitted and gained clearance for a new IND and expect to initiate an abbreviated phase one portion of the LL501A trial in the second quarter of this year. The learnings from ongoing alpha studies, including our work to optimize the dose of L0647 and L0501, will be leveraged to rapidly explore and confirm the safety and efficacy of L0501A in a limited number of patients before we seek to advance the program to potentially pivotal phase two. This now takes us to transformation.

We have submitted and gain Clarence part of me line D and expect to initiate an abbreviated baseline unfortunate Allo Bible one eighth trial in the second quarter of this year.

Learnings from ongoing Alpha study, including I'll work to optimize the dose of Alis, six or seven and aloe fiber one will be leveraged to rapidly explore and confirmed the safety and efficacy of L. fiber one a limited number of patients before we seek to advance the program to a potential.

The pivotal phase two.

This now takes us to transformation.

David D. Chang: Our goal is to always remain at the forefront of innovation in the field of allopathy therapy. This will require us to research and develop next-generation technologies derived from internal and external sources. Our internal research team has developed a novel technology that mimics the effect of cytokine stimulation selectively within allocardial t-cells. We call this technology TurboCard.

Our goal is to always remain at the forefront of innovation in the field of our car T therapy.

This will require us to research and develop next generation technology is derived from internal and external sources.

Our internal research team has developed a novel technology that mimics the effect of cytokine stimulations selectively within Aloe car T cells, we call this technology Carbo Cox.

David D. Chang: TurboCars has the potential to improve the overall fitness of our low-carb key cells, thereby enhancing their potency, expansion, and persistence. Preclinical research has demonstrated that turbo cars increase antitumor efficacy in an in vivo model, and we are excited to move this approach to the next stage of preclinical development, starting with advancement of a BCMA-directed turbo car. More recently, we have entered into clinical collaboration with SpringWorks Therapeutics to evaluate ALO715 in combination with their investigational gamma-secretase inhibitor, Naroget-Cepstat, in patients with relapsed and refractory multiple myeloma.

Turbo cars has the potential to improve the overall fitness that aloe car T cells, thereby enhancing their potency expansion and persistence.

Preclinical research has demonstrated that cerebral cars increase anti tumor efficacy in an in vivo model and we are excited to move this approach to the next stage of preclinical development, starting with the advancement of a B C. M- directed terrible car.

Well recently, we have entered into clinical collaboration with spring works therapeutics to evaluate aloe 715 in combination with their investigation I Gamma secretase inhibitor narrow get tested in patients with relapsed and refractory multiple myeloma gamma secretase is an enzyme that please.

Yeah, It may come to surface the myeloma itself.

Rafael Amato: In preclinical models, Narogatested has been shown to prevent the cleavage and shredding of BCMA, leading to an increase in the cell surface density of BCMA and reduced levels of soluble BCMA. In addition, emerging clinical data suggest that gamma secretase inhibition may augment the anti-tumor efficacy of BCMA-targeted autologous carcinoids. We expect to initiate combination trials of nitroglycerin and NAL715 in the second half of this year. In the long term, our collaboration with NACCH Therapeutics is off to a strong start. Our research team is working together to develop a process for the production of allopathy cells derived from induced free protein stem cells, or iPSC-based starting material. Success on this front could enable a more streamlined supply chain, greater cell product consistency, and the potential to create more highly engineered therapies. We are looking forward to keeping you updated on our progress in this emerging field. I will now turn the call over to Rafael, who will update you on our research and development activities. Thank you, David, and good morning to all of you on the call today.

In preclinical models that are being assessed it has been shown some pretty bad the cleavage and setting up be Sam a leading to an increase in the cell surface density IBCM may and reduced levels of solubility scanning.

In addition, emerging clinical data suggest that gamma secretase inhibition may have men the anti tumor efficacy bcm its targeted but pilots car T therapy.

We expect to initiate combination trial of natural gas faster and now seven one by in the second half of this year.

In the long term collaboration would not therapeutics is off to a strong start.

Research team are working together to develop a process for the production of our park you saw us drive induced pluripotent stem cells or IP FCB starting material.

Access on this front could enable more streamlined supply chain greater cell product consistency and the potential to create more highly engineered therapies.

We are looking forward to keeping you updated on our progress in this emerging field.

I'll now turn to call over to Rafael who will update you on our research and development activities.

Thank you David and good morning to one of the on the call today.

Rafael Amato: I'd like to start with a quick update on our LEAD program, LO501, for relapsed, refractory, non-Hodgkin's lymphoma. As David noted earlier, our Phase 1 trial for ALO501 is ongoing, and we're looking forward to sharing initial data from this alpha trial at a medical meeting in the second quarter. While the focus of any Phase 1 dose escalation trial is appropriately on safety, we're also using this trial as an opportunity to optimize our lymphodepletion strategy. There are two things to consider.

Let's start with a quick update on our lead program, although fiber one for relapsed refractory non Hodgkin's lymphoma.

David noted earlier, our phase one trial for fiber one is ongoing and we're looking forward to sharing initial data from these alpha trial medical meeting in the second quarter.

Well the focus of any phase one dose escalation trial is appropriately on safety. We're also using these trial as an opportunity to optimize our lymphodepletion strategy.

There are two things to consider first unlike the autologous phase one trial that kind of the benefit of extensive academic and drug development research to informed me of at least in diligently feel the starting from a much earlier point and there is little precedence regarding the optimal so those are looking for the leasing regimen.

Rafael Amato: First, unlike the autologous Phase 1 trials that have the benefit of extensive academic and drug development research to inform lymphodepletion, the allogeneic field is starting from a much earlier point, and there is little precedent regarding the optimal cell dose and lymphodepletion regimen. The second consideration is how we can best harness one of the most differentiating tools in our platform, ALO647, our anti-CD52 antibody, to produce the best possible We have recently completed enrollment in the three cell-dose escalation cohorts in this 3 plus 3 trial and have moved to enrolling additional patients that allow us to better understand the impact of varying allo-647 doses or schedules. Our translational oncology team is collecting the data necessary to evaluate several potentially important parameters. This includes the depth and duration of lymphodepletion, patterns of host lymphocytes, including NKB and T-cell depletion, recovery, and allocard T-cell expansion and persistence.

Second consideration is how we can bet harness one of the most differentiating tool in our platform, although six or seven our anti CD 52 antibody to reduce the best possible outcomes.

We have recently completed enrollment on the three cell dose escalation cohorts can be replaced the trial will have moved to enrolling additional patients that allows us to better understand the impact of varying aloe six or seven doses or schedule.

Translational oncology team is collecting the data necessary to evaluate several potentially important parameters.

Includes the depth and duration opening for depletion patterns of post lymphocytes, including NK D and E file depletion recovery and Arlo car T cell expansion and persistent.

Rafael Amato: We believe a methodical, exhaustive, scientific approach to understanding these biomarkers and their correlation with anti-tumor activity is essential to create the best possible outcomes for patients. We are leveraging strong momentum in the execution of this trial, and we intend to fully explore and elucidate the optimal treatment regimen prior to advancing ALOF501A, as mentioned in David's remarks, into a Phase II trial. The work being done in the ALPHA trial will inform our ALPHA 2 trial, which will start the clinical transition from ALO501 to ALO501A. The ALO501 construct being studied in the ALPHA trial shares the same gene engineering as UCAR-19 and includes the rituximab binding epitope as a safety off switch. The clinical candidate, which Allogene acquired from Pfizer, was designed to be used in acute lymphoblastic leukemia.

We believe a methodical exhausted scientific approach to understanding this biomarkers and their correlation with anti tumor activity is essential to create the best possible outcomes for patients.

We are leveraging strong momentum and execution of this trial and we intend to fully explore analysts today the optimal treatment regimen prior to advancing outlook by the one a mentioning David's remarks into a phase two trial.

The work being done in the outlet trial will inform our alpha to trial, which will start the clinical transition from olive fiber one to all of fiber one eight.

The other five a lung cancer drugs being studied in the Alpha trials shares the same gene engineering as you go 19 and includes the lead customer binding epitope, that's a safety of switch the clinical candidate, which I'll, let gene acquired from Pfizer was designed to be used in acute lymphoblastic leukemia.

Rafael Amato: Early on, Allogene elected to take a parallel path by beginning clinical trials on ALO501 in relapsed refractory non-Hodgkin's lymphoma. This allowed us to test our lymphodepletion strategy while engineering a modified next-generation product, which we now refer to as ALO501A. While we expect the initial data from our 501 alpha trial to facilitate the identification of an optimal dosing and lymphodepletion strategy, we recognized early on that the rituximab off switch would limit commercial potential in a clinical setting where rituximab is commonly used. For this reason, ALO501A is devoid of the rituximab off switch, which would allow us to serve a broader patient population, including those non-Hodgkin lymphoma patients with recent rituximab exposure.

Leon Alesina elected to take a parallel path by beginning clinical trials on our fiber one in relapsed refractory non Hodgkin's lymphoma.

This allowed us to settling for the business strategy, while engineering, a modified next generation products, which we now referred to at 5.18.

But we expect the initial data from our fiber one outside trial to facilitate identification of an optimal dosing underneath that at least in strategy. We recognize fairly on the reduction of switch with limited commercial potential clinical setting would be tough enough is commonly used.

For this reason Hello fiber one a is the void of the reduction of off switch, which would allow us to serve a broader patient population, including those non hodgkin lymphoma patients with recent pre talking about exposure.

Rafael Amato: As David noted earlier, we're happy to report that we have made rapid progress with the preclinical development of ALO501A, and our IND has been cleared by the FDA. We anticipate that the abbreviated Phase 1 portion of the Alpha 2 trial will commence in the second quarter of this year. We expect to enroll approximately 10 patients, and we'll apply the optimized dosing of Apollo 647 elucidated in the alpha trial as we move toward a potential phase two clinical trial. In our second clinical program, we have created a robust anti-DCMA strategy that includes TALOS 715 as a platform therapy for the treatment of relapsed refractory multiple myeloma. Universal, our Phase 1 trial with ALOS 715, continues to actively accrue and treat patients. This trial will also explore optimal dosing of all components of the lymph depletion regimen, including allo-647, fudarabine, and cyclophosisphamide.

As David noted earlier, we're happy to report that we have made rapid progress with the preclinical development of followed by the Renee and our I envy has been here by the FDA.

We anticipate that the abbreviated phase one portion of the I'll have to trial will man in the second quarter of this year.

We expect to enroll approximately 10 patients will apply the optimal dosing of follow suit for seven elucidated, India, but trial as we move store a potential phase two trial.

In our second clinical program, we have created a robust anti VCM eight strategy, which includes Carlo said on one side at the platform therapy for the treatment of relapse refractory multiple myeloma.

You need Birstall, our phase one trial with Alex 715 continues to add because we accrue to treat patients.

This trial will also explore optimal dosing of all components of the Lymphodepletion regimen, including follow suit for seven Fludarabine and cyclophosphamide.

Rafael Amato: We will be assessing endpoints such as safety, tolerability, the depth and duration of lymphodepletion, cell expansion, and antitumor activity as key determinants of success for ALO715. We are on track to report initial data from this trial in the fourth quarter of 2020. Our anti-DCMA program will also investigate ALO715 in combination with the SpringWorks Investigational Gamma Secretase Inhibitor Narrow Gas Distab. We will determine the best route to initiate a combination trial and expect to begin it in the second half of this year. The third leg to our multiple myeloma strategy was unveiled earlier this year as part of a broader look at our pipeline. We have named ALO625 as our lead anti-DCMA turbo CAR candidate, which in preclinical models increases ALO CAR T cell activation and enhances their phenotype and function.

We will be assessing endpoints, such as safety tolerability, the depth and duration of into the Gleason cell expansion and anti tumor activity a ski determinants of success for our low 715.

We are on track to report initial data from this trial in the fourth quarter of Twentytwenty.

Our on diabetes May program will also investigate aloe 715 in combination with the spring works investigation on gamma Secretase inhibitor narrow that this path.

We will determine the best routes to initiate a combination trial unexpected beginning the second half of this year.

The third leg to our multiple myeloma strategy with them Vale earlier this year as part of the broader looks at our pipeline.

We have name Alex So five after lead on Friday May tool Park candidate, which in preclinical models increases, although part T cell activation and enhancements that phenotype on function.

Let's see so five is advancing into clinical development with an eye in the plan for Twentytwenty water.

Lastly, we continue to progress the preclinical work and have officially nominated almost anyone thick, our anti Cdseventy program, that's our net oligarchy clinical candidate.

Rafael Amato: ILO 605 is advancing in preclinical development with an IND plan for 2021. Lastly, we continue to progress our preclinical work and have officially nominated ALOC 316, our anti-CD70 program, as our next ALOC RT clinical candidate. We're excited by the opportunity to bridge hematologic malignancies and solid tumors with ALON316. Our focus for this product will be on acute myeloid leukemia, T-cell malignancies, and renal cell carcinoma. We expect to submit an IND by the end of this year. In closing, I'm very excited about the strong momentum of both our discovery and clinical allogeneic programs. Both are progressing as planned, and we look forward to providing initial clinical results later this year. I'd like to turn the call over now to Eric to review our financials.

Excited by the opportunity to bridge hematologic malignancies in solid tumors with Oliver through Wednesday.

Our focus for this product will be on acute myeloid leukemia T cell malignancy and renal cell carcinoma.

Expect to submit an eye Andy by the end of this year.

In closing I'm very excited with the strong momentum of both our discovery and clinical allogeneic programs. Both are progressing to plan and we look forward to providing initial clinical results later this year.

I'd like to turn now the call over to Eric to review our financial.

Thank you Raphael and good morning. In addition to the brief financial overview I will provide on the call. Today, you can read additional detail on our fourth quarter and year end financial results in our press release issued earlier today and is our 10-K, which will be filed with SEC.

We continue to be in a strong financial position with cash cash equivalents and investments totaling $588.9 million as of December 31st 2019.

In the fourth quarter, our research and development expenses were $49.4 million, which included $6.4 million noncash stock based compensation expense.

For the full year 2019 research and development expenses were $144.5 million, which includes $10 million and expenses associated with the signing of our Knox collaboration.

Eric Schmidt: Thank you, Rafael, and good morning. In addition to the brief financial overview I will provide on the call today, you can read additional detail on our fourth quarter and year-end financial results in our press release issued earlier today and in our 10-K, which will be filed with the SEC. We continue to be in a strong financial position with cash, cash equivalents, and investments totaling $588.9 million as of December 31, 2019. In the fourth quarter, our research and development expenses were $49.4 million, which included $6.4 million of non-cash stock-based compensation expense. For the full year 2019, research and development expenses were $144.5 million, which included $10 million in expenses associated with the signing of our NOTCH collaboration. The total research and development expenses for the year included $19.4 million of non-cash, stock-based compensation.

Total research and development expense for the year includes $19.4 million of noncash stock based compensation expense.

General and administrative expenses were $15.2 million for the fourth quarter 2019, which includes $7.5 billion of noncash stock based compensation expense for the full year 2019 general and administrative expenses were $57.5 million, which includes $26.6 million Don.

Cash stock based compensation expense.

Our net loss for the fourth quarter of 2019 was $61 million were 58 cents per share, including noncash stock based compensation expense at $13.9 billion for the full year 2019, our net loss was $184.6 million or $1.83 cents per share, including non cash.

Stock based compensation expense of $46.1 million.

Turning now financial guidance for 2020.

We will continue to invest heavily in our clinical programs by the end of this year. Our goal is to complete enrollment in the phase one our fiber one trial progress our phase one aloe 715 trial and initiate phase one trials for our fiber one day and the outlook everyone. Five combination study with merit based that.

Eric Schmidt: General and administrative expenses were $15.2 million for the fourth quarter of 2019, which included $7.5 million of non-cash stock-based compensation expenses. For the full year 2019, general and administrative expenses were $57.5 million, which included $26.6 million of non-cash stock-based compensation expenses. Our net loss for the fourth quarter of 2019 was $61 million, or 58 cents per share, including non-cash stock-based compensation expense of $13.9 million. For the full year 2019, our net loss was $184.6 million, or $1.83 per share, including non-cash stock-based compensation expense of $46.1 million.

As noted in David's earlier comments, we also look to advance the build out of our Newark manufacturing facility.

As a result, we expect our full year 2020, net losses to be between 260 million and $280 million. This includes an estimated noncash stock based compensation expense of 70 million to $75 million and excludes any impact from potential business development activities with that we will.

Now open the call for your questions.

Ladies and gentlemen, if you have a question or comment at this time. Please press the star than the one key on your touched on telephone. If your question has been answered you were seeing with yourself from the Q. Please press the pound cake.

Our first question comes from Mark from Cowen and company.

Hey, Thanks for taking my questions.

So maybe things to this update we're going to get in the second quarter from the at the Alpha trial, recognizing that ultimately you do need to switch over to the five on a program, but we'll just data set the mature enough that warrant for fiber one a you'd be able to make the decision to move forward into a phase two and I have this next steps late.

Eric Schmidt: Turning now to financial guidance for 2020, we will continue to invest heavily in our clinical programs. By the end of this year, our goal is to complete enrollment in the Phase 1 ALO501 trial, progress our Phase 1 ALO715 trial, and initiate Phase 1 trials for ALO501A and the ALO715 combination study with Nira Gaystack. As noted in David's earlier comments, we also look to advance the build out of our Newark manufacturing facility. As a result, we expect our full-year 2020 net losses to be between $260 million and $280 million. This includes an estimated non-cash stock-based compensation expense of $70 million to $75 million and excludes any impact from potential business development activities.

Okay.

Or if it's still going to be you kind of work in progress that you need more maturity on some of these different preconditioning regimen and the different cohorts.

Yes.

Mark.

This is David I'll take your question I mean, the question that you asking is a very important one and and certainly there are many different aspects that goes into answering the question.

Incomes.

Couple of things that you know how you should be thinking about is.

Internally Lymphodepletion is something that we see as generalizable concept and that is one of the reason that into Alpha study, we're spending a considerable amount of effort to optimize the lymphodepletion and as we know yes, you know we had been.

Operator: With that, we will now open the call to your questions. Ladies and gentlemen, if you have a question or a comment at this time, please press the star and then the one key on your touchtone telephone. If your question has been answered, or you wish to move yourself from the queue, please press the pound key. Our first question comes from Mark Frahm with Cowan & Company. Thanks for taking my questions. Maybe things like this update we're going to get in the second quarter from the alpha trial, recognizing that ultimately you do need to switch over to the 501A program, but will this data set be mature enough that if it weren't for 501A, you would be able to make a decision to move forward into phase two and kind of have those next steps laid out? Or is it still going to be kind of a work in progress that you need more maturity for some of these different preconditioning regimens and the different cohorts? Yeah, you know.

Bearing the Alex expose seven both dose and dosing schedule to do that and we'll certainly have a lot of data by the time that we present.

Findings in the second quarter and with respect to the question of making the transition from al fiber, one and two while five on a one has to realize that primary antigen receptor portion of the cost but remains identical only thing that has changed is taking out the reduction switch.

Which in fiber one was expressed as a separate protein. So we consider just as a relatively minor change and we believe that the learnings from the fiber one study will be directly translate or both as we move forward with our fiber one eight and that is the reason that we believe that.

And be done as an abbreviated phase one study as we have said in our prepared statement.

David D. Chang: Mark, this is David. I'll take your question. I mean, you know, the question that you're asking is a very important one, and, you know, certainly, there are many different aspects that go into answering the question. In terms of, you know, a couple of things that, you know, what you should be thinking about is, internally, you know, lymphoid depletion is something that we see as a generalizable concept. And that is one of the reasons that, in the alpha study, we're spending a considerable amount of effort to optimize lymphoid depletion. And as we know, as we know, we have been using both dose and dosing schedule to do that. And we'll certainly have a lot of data by the time that we present the findings in the second quarter.

Okay. Okay. When you when you say abbreviated phase one I mean can you give us some clarification as to what exactly does that mean does that mean, yes. I mean do you have to start from as little bit dose as you did it in the Alpha trial, but you can go up in single patients do you go one does down can you just do the exact regimen that you selected from Alpha.

And just reconfirm PK like like what what does abbreviated me.

I think one thing that I have learned over the years that I've been involved in the car T trial is that.

Anything that we do in preclinical setting we like to come from in the clinical studies. So when we talk about abbreviated approach you exactly set up point I mean dose escalation will be somewhat simplified and the real intent is to confirm whatever we so in fiber one.

David D. Chang: And with respect to the question of making the transition from ALO501 and to ALO501A, one has to realize that the primary antigen receptor portion of the construct remains identical. The only thing that has changed is taking out the reduction switch, which in 501 was expressed as a separate protein. So we consider this a relatively minor change, and we believe that the learnings from the 501 study will be directly translatable as we move forward with ALO501A. And that is the reason that we believe that this can be done as an abbreviated phase one study, as we have said in our prepared statement.

Can be we produced in the fiber one case study so.

With that certainly there will be a more color to it as we presented data and which I think cast too you have to wait for that.

Okay. Thank you.

Our next question comes from Salveen Richter with Goldman Sachs.

Thanks, Good morning.

So with regard to NHL study, hi, though one where we're going to see data in hand.

In the first half CR second quarter and are you primarily 14 have ace hearing ASCO as the presentation coatings from Goldman Sachs and that for this datasets and then secondly, as you look to taking other programs into the clinic. So the multiple myeloma program that program with framework.

David D. Chang: Okay, when you say abbreviated phase one, can you give some clarification as to what exactly that means? Does that mean, for example, you have to start from a, you know, as low of a dose as you did in the alpha trial, but you can go up in single patients? Do you go one dose down? Or can you just do the exact regimen that you've selected from alpha and just reconfirm PK? Like, what does abbreviated mean?

Others. How are you think about thinking about leveraging further steps and optimization be yet the preconditioning regimen, where you could play with timing of dosing.

As well as duration of dosing in another aspect.

And any kind of non preconditioning effort tier.

Okay sobbing I'm going to take the first part of the question and Oh.

We'll ask about fail to ask the second question regarding how we are leveraging the learnings from the Alpha study in our other programs.

David D. Chang: You know, I think one thing that I have learned over the years that I've been involved in the CAR-T trial is that, you know, anything that we do in the preclinical setting, we like to confirm in clinical studies. So when we talk about an abbreviated approach, exactly to the point, I mean, these escalation will be somewhat simplified, and the real intent is to confirm whether whatever we saw in 501 can be reproduced in the 501A study. So, you know, with that, certainly there will be more color to it as we present the data, and which I think has to, you know, you have to wait for that. Okay, thank you.

The question around exactly when the data presented we do get that question. Yes, we are very close to the second quarter and at this point.

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I think it will be fair to say that.

The higher get full out presentation.

Is either asked cool or E meeting.

Great.

The.

Thank goodness rockpile on I'm going to address your Visteon me.

And so there's no question.

The learning.

From five alone counting form to be in a program.

Any impact some of it changes.

For the depletion that are introducing five alon amendments in the.

The second one five program you may recall that they're older changes in for at least and are willing to do at the beginning of the outfitting that study, which are designed to ascertain the.

David D. Chang: Our next question comes from Salveen Richter with Goldman Sachs. Good morning. So, with regard to NHL study 501, where we're going to see data in the first half here, second quarter, are you primarily thinking of ACR and ASCO as the presentation settings for these data sets and then for this data set? And then secondly, as you look to take other programs into the clinic, so the multiple myeloma program, the program with SpringWorks and others, how do you think about thinking about leveraging further steps in optimization, be it the preconditioning regimen where you could play with timing of dosing as well as duration of dosing and other aspects and any kind of non-preconditioning efforts here?

Value of finding type of cost them items without having to on into some oh, I'm, sorry, and use it for seven by itself.

We will be thats being higher doses of 96% on.

In that study as well and obviously things such as.

Some of that kinetic PK PD interaction.

So recovery expansion and other parameters we expect.

That the learnings from five alone will translate into 715 and therefore.

I think it will help accelerate a decision making as we see the data.

Thank you.

David D. Chang: Okay, Salveen. I'm going to take the first part of the question and, you know, I will ask Rafael to answer the second question regarding how we are leveraging the learnings from the alpha study in our other programs. The question around exactly when the data are presented, we do get that question. We are very close to the second quarter, and at this point, you know, I think it would be fair to say that, you know, the target for our presentation is either the ASCEL or EHA meeting. This is Rafael.

Our next question comes from Barbour and have been with Jefferies.

Yes, hi, guys. Thanks for taking my questions, maybe if I could start with fiber one final one a heavier yields change.

With fiber one name versus five on given your transfection efficiency is likely going to increase since you're not requiring to switch.

Aaron I mean, you're going straight into the very technical question.

Yes, when we changed the when you make the changes to kind of stuck in a vital tighter and other things do change and that's where you know we have a very strong process development team as well as manufacturing team and all these issues have been all worked out and I can.

Rafael Amato: I'm going to address your BCMA question. There's no question that the learnings from 501 can inform the BCMA program. In fact, some of the changes in infodepletion that are introduced in 501 are mimicked in the 715 program. However, you may recall that there are other changes in infodepletion that were introduced at the beginning, at the outset of that study, which are designed to ascertain the value of adenocyclofosamide and fluzarabine to amg647 by itself. But we will be testing higher doses of amg647 in that study as well. Obviously, things such as pharmacokinetics, PKPD interactions, cell recovery, expansion, and other parameters; we expect that the learnings from 501 will translate into 715. Therefore, I think it will help us accelerate decision making as we see the data.

More or less value that the yield that we are getting from their manufacturing is really exceeding our expectations. So I don't really see this being a major issue.

Okay, and then I guess.

When you present, the fiber one data.

Second quarter I, just want to ask.

Whether there's a risk where you're going to see themselves undetectable. So one of your Cdnineteen compares presented early Dana dash, where they use an asset where the cells were undetectable. So what's the risk of seeing similar should rise and fall one.

Well I mean, you are going into the data portion of our presentation, which I you know, we're not quite ready to talk about it.

Rafael Amato: Thank you. Our next question comes from Byron Amin, who said, Yeah, hi, guys. Thanks for taking my questions. Maybe I could start with 501 and 501A. How do your yields change with 501A versus 501, given your transaction efficiency is likely going to increase since you're not requiring the switch?

Let me just tell you incomes, though sales that kinetics and the Beckwith copy number. This is a topic that we had at least I personally have been working off a number of years and a we took some of the necessary steps to make sure that we can get reliable biomarker data in our study.

David D. Chang: Buren, I mean, you're going straight into the very technical question. Yes, you know, when we change the, when you make the changes to construct, you know, viral titer, and other things, you know, do change. And, you know, that's where we have a very strong process development team as well as a manufacturing team. And, you know, all these issues have been worked out. And I can more or less tell you that the yield that we are getting, you know, from the manufacturing is really exceeding our expectations. So, I don't really see this being a major issue. Okay.

Yes so.

So let me just stop there without rebuilding too much about exactly what we will be present, but the deco copy number is one of the important components of the translational.

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Research.

Okay, and then any second ask question on the Cama.

She has client program.

When do you I guess I guess when do you expect to start the season log will it be after the Q4 data from having one fives and I guess.

How are you planning on dosing.

The GE insight.

David D. Chang: Okay, and then, I guess, you know, when you present the 501 data in the second quarter, I just want to ask whether there's a risk that you're going to see the cells undetectable. So one of your CD19 competitors presented early data at ASH where they used an assay where the cells were undetectable. What's the risk of seeing a similar issue arise in 501?

With with the car and I guess, you know David at Ash arms few months ago. Fred Hutch also presented there is you have side and the assumption really good responses, but also observe neurotoxin thinking about six uptime patients. This is do you anticipate that the safety profile will change with you use of June side.

Great question I'm going to ask about how to answer that question. I mean, rockpile has been looking into this particular area very intensely and I feel we have pretty well prepared to embark on the phase one study well.

David D. Chang: Well, I mean, you're going into the data portion of our presentation, which I, you know, we are not quite ready to talk about, but, you know, let me just tell you, in terms of cellular kinetics and the vector copy number, this is a topic that we have, you know, at least I personally have been working on for a number of years, and we took some of the necessary steps to make sure that we could get reliable So, you know, let me just stop there without, you know, revealing too much about exactly what we will represent, but the vector copy number is one of the important components of translational research.

Yes, Thanks, David.

So we plan to study the study in the second half of the year.

We have a great collaborations with spring where.

We're pretty excited about our initial interactions with them.

We've seen demolished Gill.

God really good.

PK PD profile he doesn't penetrate the blood brain barrier. So you know the thesis doesn't north of two city.

I have not really being observed this treated over 100 patients, though the profile.

Safety wise pretty well understood with its very useful when you're doing a combination trial.

And as you know this quarter Raystation back with John.

Rafael Amato: Okay. And then maybe I could ask a question on BCMA. So for the GSI program, when do you – I guess – when do you expect to start phase one? Will it be after the Q4 data from 7.1.5?

The helps with regards to potential cover development.

So by the time, we do this combination we probably wouldn't know a lot about both being for the depletion and dosing and we think it will be the right time to start.

Rafael Amato: And I guess, you know, how are you planning on dosing the GSI with the CAR? And I guess, you know, David and Ash. A few months ago, Fred Hutch also presented their GSI data. They spoke of some really good responses, but they also observed neurotoxin, I think, in about six of 10 patients. So do you anticipate that the safety profile would change with the use of GSI?

Flying the combination to try to understand.

Whether increasing dcms expression actually resulting superiority of our product.

But so far the preclinical data is pretty strong in.

We look forward to food testing this combination, which hopefully will translate into better outcomes for patients.

Great. Thank you.

Our next question comes from Cory Kasimov from JP Morgan.

Hi, guys does not count for Korean Thanks for taking my questions. So from my first question. Just wondering if you can discuss what do you expect to having a hand in terms of aloe for.

Rafael Amato: Great question. I'm going to ask Rafael to answer that question. I mean, Rafael has been looking into this particular area very intensely. And, you know, I feel we are pretty well prepared to embark on the Phase I study.

Hello, 6004, seven facelift vote accretion thats levels at the time of that appreciated five or one hey trial initiation.

Rafael Amato: Yeah, thanks, David. So we plan to start the study in the second half of the year. We have a great collaboration with SpringWorks. We're pretty excited about our initial interactions with them. We think the molecule has got a really good, you know, PK, and PD profile. It doesn't penetrate the blood-brain barrier. So, you know, these issues of neurotoxicity have not really been observed.

Basically I'm wondering.

Whether you expect cell lymphoma depletion data to be mature enough to result in a more narrow range of dose levels for that prevailed at 5.1, Hey study.

So Matt this is David let me take that question I mean, we have been saying bed, we will be leveraging the learnings from the Bible one in other programs, including fiber one eight and also definitely in the seven one by programs I mean, Lymphodepletion you know.

Rafael Amato: They've treated over 100 patients. So the profile, safety-wise, is pretty well understood, which is very useful when you're doing a combination trial. And as you know, they've got a registration path, which.., obviously helps with regards to, you know, potential co-development. So, by the time we do this combination, we probably will know a lot about both things, the depletion and dosing, and we think it will be the right time to start, you know, applying, you know, the combination to try to understand whether increasing DCMA expression actually results in superiority of our product, but so far, the preclinical data is pretty strong and, you know, we look forward to testing this combination, which, you know, hopefully will translate into better outcomes for patients.

Cost, it's really dealing with.

The horse lymphocyte count.

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Before that fell by given.

This is quite in our view a generalizable findings so any learnings will be a fine that and to your question as we have said in the pre bit prepared remarks, we have completed the dose escalation of aloe fiber one and we are actively recruiting.

Patients into the often that lymphodepletion regimen cohort so.

Current projection is that we will definitely have some inflammation and there will be leveraged in how we move forward with al fiber one study.

David D. Chang: Great, thank you. Our next question comes from Corey Kazma of J.P. Morgan. Hey guys, this is Matthew. I'm for Corey, and thanks for taking my questions. So, for my first question, just wondering if you can discuss what you expect to have in hand in terms of ALO-647-based lymphodepletion dose levels at the time of the abbreviated 501A trial initiation. Basically, I'm wondering whether you expect the lymphodepletion data to be mature enough to result in a more narrow range of dose levels for the abbreviated 501A study.

Great. Thanks, and then I guess for the Alpha trial, what should we keep in mind when comparing the initial data that two phase one data sets from the CD 19 autologous space.

So.

Can you repeat the question sorry.

Just wondering for the initial alpha data.

That.

What should we keep in mind when comparing this to either initial phase one data sets from the CD 19, autologous car T space.

David D. Chang: So, Matt, this is David. Let me take that question. I mean, you know, we have been saying that we will be leveraging the learnings from the 501 in other programs, including 501A, and also definitely in the 715 programs. I mean, lymphodepletion, you know, because it's really dealing with the host lymphocyte count before the cells are given, this, you know, is quite, in our view, a generalized finding. So any learnings will be applied to that. And, you know, to your question, as we have said in the prepared remark, we have completed the dose escalation of 501, and we are actively recruiting patients into the ultimate lymphodepletion regimen cohort. So, you know, the current projection is that we will definitely have some information, and that will be leveraged in how we move forward with our 501 study.

You know.

No, we're just being a little bit cost us about not talking too much about what will be presented at when we present the fiber one data I mean, the question that you I asking is a very important one certainly we are trying to.

Get the allogeneic cell therapy in terms of the safety and outcome.

The point that is similar if not better than what has been reported with autologous, but you also have to realize that in a phase one setting will be dealing with a relatively small number of patients as well as the fact that we have bearing the lymphodepletion. So there is some you know you know that defined set of inflammation.

David D. Chang: Great, thanks. And then, I guess for the alpha trial, what should we keep in mind when comparing the initial data set to phase one data sets from the CD19 autologous phase?

So.

Not.

Just wait till we presented data.

Great. Thanks for taking my question.

Our next question comes from Carload bedroom with Piper Sandler.

David D. Chang: So, can you repeat the question? Sorry.

Hey, guys. Good morning, Congrats on the progress so with respect to the Alpha data update next quarter is impossible to just confirmed the rough number of patients we should expect and approximately what the split between DLP seal in footwear lymphoma is and and with respect to 647, I think you mentioned youre enrolling patients in the final Lymphodepletion regimens.

Operator: Just wondering, for the initial alpha data set, what should we keep in mind when comparing this to other initial Phase I datasets from the CD19 autologous CAR-T space?

David D. Chang: You know, we are just being a little bit cautious about not talking too much about what will be presented when we present the 501 data. But I mean, the question that you are asking is a very important one. Certainly, we are trying to get allogeneic cell therapy to a point where it is similar, if not better, than what has been reported with orthopaedic patients. But you also have to realize that in the Phase I setting, we'll be dealing with a relatively small number of patients, as well as the fact that we are varying the lymphoid depletion. So there are some different sets of information. Just wait till we present the data.

Can you give us a sense of where six or seven is in terms of the 39 to 90 big range.

So we're going too much into the details of what is to be presented so I'm going to gain or try to limit what I say.

But let me just try to get some color to your question I mean in the prepared statement. We said that we completed the dose escalation that alone should give up pace a number of nine patients minimum and certainly we are going beyond those.

David D. Chang: Great. Thanks for taking my call. Our next question comes from Tyler Van Buren with Pipeline.

David D. Chang: Hey guys, good morning. Congrats on the progress. With respect to the alpha data update next quarter, is it possible to just confirm the rough number of patients we should expect and approximately what the split between DLBCL and follicular lymphoma is? And with respect to 647, I think you mentioned you're enrolling patients in the final lymphodepletion regimen, so can you give us a sense of where 647 is in terms of the 39 to 90 big range?

Nine patients into dose escalation, so hopefully that give some color about what you may see and let me also emphasize that we get asked a lot about you know what the duration data that you may present, but that is going to be very dependent on when the patient gets enrolled and.

There are lot of sort of dynamic nature of how the data is evolving bought a when the presentation happens we will be presenting older available data to the time of the data cut.

David D. Chang: So, you know, we're going too much into the details of what is to be presented, so I'm going to again, you know, try to limit what I say, but let me just, you know, try to get some color to your, you know, question. I mean, in the prepared statement, you know, we said that we completed the dose escalation. That alone should give a patient number of nine patients minimum, and certainly we are going beyond those, you know, nine patients in the dose escalation. So, you know, hopefully that gives some color about, you know, what you may see, and let me also emphasize that we get asked a lot about, you know, what's the duration data that you may present, but, you know, that is going to be very dependent on when the patient gets enrolled, and, you know, there are a lot of sort of dynamic nature of, you know, how the data is evolving, but when the presentation happens, we will be presenting, you know, all the available data to the time of the data cut.

Okay. That's helpful and then for Turbo car can you.

Say anything more about it with respect to what cytokine you guys, maybe using or maybe how it compares to some of the other approaches using relatively well known cytokine and while you guys chose to start with myeloma and if you plan to go into non hodgkins.

Yeah.

For competitive reasons, we're not going to.

Talk about which cytokine.

You know over the years, we have seen many different ways to enhance then provide extra I spoke about the signal created that is driven by the cytokine to the engineered T cells and while we are seeing what I'm seeing and in the in the third because so far is.

Far better than anything else that I've seen before so we quite excited about this turboprop.

David D. Chang: Okay, that's helpful. And then for TurboCar, can you say anything more about it with respect to what cytokine you guys may be using or maybe how it compares to some of the other approaches using relatively well-known cytokines and why you chose to start with myeloma and if you plan to go into non-Hodgkin's.

That's very exciting thank you.

Our next question comes from Mark Breidenbach with Oppenheimer.

Hey, good morning, guys and thanks for taking the questions.

David I'm, just wondering is it realistic to expect that the lymphodepletion depth and duration requirements.

David D. Chang: Yeah, you know, for competitive reasons, we're not going to talk about which cytokine, but, you know, over the years, we have seen many different ways to enhance and provide extra, you know, so-called signal three that is driven by cytokines to the engineered T-cells. And what we are seeing, what I'm seeing in the Therbocot so far is, you know, far better than anything else that So we are quite excited about this thermocot. That's very exciting. Thank you.

Likely be universal across different indications AOL, NHL and multiple myeloma or do you think it's more probable that we'd see sort of different lymphodepletion requirements, depending on the disease.

Great question, you know I wish I knew though answer I mean.

Over the years of doing clinical trials thing that I am always surprised about the patient to patient or indication by indication differences and thats exactly what we have to doing the phase one studies so.

David D. Chang: Our next question comes from Mark Breidenbach with Op... Hey. Good morning, guys, and thanks for taking the questions. David, I'm just wondering whether it is realistic to expect that the lymphodepletion depth and duration requirements will likely be universal across different indications, ALL, NHL, and multiple myeloma, or do you think it's more probable that we see sort of different lymphodepletion requirements depending on the disease?

The way that used to be thinking about it as we understand the lymphodepletion and as we optimize the six or seven we will have a very good framework to use that inflammation and simplified the lymphodepletion exploration in other indications. So that's how we are really leveraging.

David D. Chang: Great question. You know, I wish I knew the answer.

David D. Chang: I mean, you know, over the years of doing clinical trials, I am always surprised about patient-to-patient or indication-by-indication differences, and that's exactly what we have to do in the Phase I studies. So the way that you should be thinking about is as we understand lymphodepletion and as we, you know, optimize the 647, we will have a very good framework to use that information and simplify lymphodepletion exploration in other indications. So that's how we are really leveraging the learnings from 501 in other programs, and I think that approach will be very effective in simplifying the lymphodepletion exploration in other indications.

They're learning from fiber wanting other programs and I think that approach will be very effective in simplifying the lymphodepletion exploration in other indications.

Okay, and just a quick follow up with regard to.

Output trial, I'm wondering if you're seeing a lot of screening failures due to recent retired some out of exposure and if so would you expect enrollment in alpha to to proceed at a faster rate than what you've been able to achieve and alpha.

Hi, Yes, Mark this is roughly 11 answer the question I think.

That is a very perceptive observation and Asia about reduction of exposure, but in spite of that.

Rafael Amato: Okay, and just a quick follow-up. With regard to the alpha trial, I'm wondering if you're seeing a lot of screening failures due to recent rituximab exposure, and if so, would you expect enrollment in alpha 2 to proceed at a faster rate than what you've been able to achieve in alpha?

Our goal has been very brisk and we've been very fortunate to work with great investigators that happening very committed and we were improving actually plan and.

We are exactly where we want to be with that study.

Rafael Amato: Yes, Mark, this is Rafael. I'll answer the question.

Now, we'll with fiber one name clearly the an easier study to group for the reasons that you mentioned and we anticipate that it would go faster, but investigators are able to find patients for fiber one and I think.

Rafael Amato: I think that is a very perceptive observation, you know, the issue about reduction of exposure, but in spite of that, our accrual has been very brisk, and we've been very fortunate to work with great investigators that have been very committed. And we were accruing, actually, as planned, and, you know, we are exactly where we want to be with that study. Now, with 501A, clearly, it will be an easier study to enroll in for the reasons that you mentioned, and we anticipate that it would go faster. So, I mean, you're right on your observation, but it's actually not really limiting our ability to, you know, enroll in 501.

Fantastic, because it's allowing us to actually elucidate all these parameters that hopefully.

We'll be it will allow us to move with fiber won a.

Quicker.

So and you're right on your observation bodies, but he's actually in not really limiting our ability to units when volume fiber one.

Rafael Amato: Okay, terrific, thanks for taking the questions. Our next question comes from John Newman with Canaccord. Hi, guys. Good morning. Thanks for taking my question. I just had a general question, David. I know you don't want to get into too much detail about the 501 study, but is there a chance that we might see some redosing data when we get a look at the data in the second quarter?

Okay terrific. Thanks for taking the questions.

Our next question comes from John Newman with Canaccord.

Hi, guys. Good morning, Thanks for taking my question.

Just had to a general question, David I know you don't want to get into much.

Too much of the two homes above the.

Level, one study, but is there a chance that we might see.

Re dosing data.

You can look at data.

David D. Chang: You know, great question. We don't think it's one of the changes that we introduced into the protocol, and certainly, you will see some data. Exactly how many patients, I'm not going to say, but you will definitely see some redosing data.

Quarter.

Yeah. Great question, you know, we don't thing is one of the changes that we introduced into the protocol and certainly.

You will see some data exactly how many patients I'm not going to say, but you'll definitely see some we dosing data okay.

David D. Chang: Okay. Great. One follow-up question. This is a little bit broader. I'm sure you remember very well when Kite and Novartis both had their CD19 CAR-T products in development in the autologous setting, and there was a big debate about whether longer persistence with Novartis' product with the 4-1 BB CAR was going to result in better efficacy versus the co-stem that Kite was using, which was CD28, and it ultimately turned out that the efficacy was almost the same

And then.

One follow up question. This is a little broader.

Im sure you remember very well back.

When kite Novartis, both had their sheet 19.

Archie product development in the autologous setting and that was the big debate about whether.

[music].

Longer persistence with Novartis this product with the forward BB car.

What's going to result in a better efficacy versus the co stem that kite was using which was GBP 28, and ultimately turned out that the efficacy was almost the same I know that we're dealing with.

David D. Chang: I know that we're dealing with...

David D. Chang: A very different product here because this is allogeneic, but... Can you maybe talk a little bit about how we should be thinking about persistence and detection of these cells if there are certain... thresholds that we should be thinking about, because I know that this is different, we have to worry about close versus graft here, but just

Very different products here, because this is alan generic but.

Can you maybe talk a little bit about.

How we should be thinking about persistence and detection of b cells as there are certain.

Threshold that we should be thinking about because I I know that.

This is different we have to worry about hosts for scrapped here, but just curious how you're thinking about that.

David D. Chang: I'm just curious to know how you... Yeah, you know, John, the question that you are asking is a very, you know, complicated question to answer. I'm going to sort of answer it in a different way, which is really coming from the existing experience in non-Hodgkin's lymphoma. In non-Hodgkin's lymphoma, I mean, if you have a response, you know, at month three, the likelihood that that response will be maintained in a longer follow-up is very high, which means that whatever the initial killing of the tumor cells, that really has a great impact on the durability of the response. And that's more or less how we are thinking about cell persistence in this setting.

Yeah, you know.

John You know the question that you asking you know that is a very complicated question to answer.

Im going to sort of and studied in summit in a different way, which is really coming from the existing experienced in non Hodgkin's lymphoma.

In non Hodgkin's lymphoma, I mean, if you have a response you know at month free.

The likelihood that that response will be maintained in you know you no longer follow up is very high.

Which means that.

Whatever it the initial filling.

The tumor cells that really has a great impact on the durability of the response.

And that's more or less how we are thinking about the south persistence in this setting and if you look at somewhat they'll Carlos car T data, especially with the CD 28, close to mostly domain containing constructs you're talking about the cell expansion and persistence.

David D. Chang: And if you look at some of the autologous CAR-T data, especially with the CD28-closed tumor-to-domain containing constructs, you're talking about cell expansion and persistence for probably two to three months, sometimes a little bit longer. And if we look at our own UCAR-19 data, that level of cell persistence is something that was able to be achieved in the UCAR-19 study. And certainly, when we present the data, we'll detail more findings on cell persistence that we see in the 501 study. Thank you.

Probably.

Two to three months, sometimes little bit longer and if we look at all on new card 19 data that level of cell persistence is something that was able to be achieved in the U. card 19 study and certainly when we presented data will detail mall findings on software systems that we seem to fiber one stuff.

Right.

Great. Thank you.

Our next question comes from run Benjamin with JMP Securities.

David D. Chang: Our next question comes from Ren Benjamin with JMP Security. Hi, good morning.

Hi, good morning, Thanks for taking the questions and congrats on the progress I guess is just a broader picture question regarding.

Rafael Amato: Thanks for taking the questions and congrats on the progress. I guess this is just a broader question regarding your iPSC programs and how you're seeing the allogeneic space evolve. Is this something that evolves where there's space for both, you know, healthy donor cells and iPSCs? Do you think that iPSCs will ultimately take over? How do you see this, you know, kind of shaping out? Moving forward.

Your IP FC programs, and how you're seeing that allogeneic space evolve as this is this something that evolves where their space for for both healthy donor cells and IPO sees do you think that I just see is ultimately take over how do you see this you know kind of shaping out.

Rafael Amato: Hi Ren, this is Rafael.

Moving forward.

Hi, Ryan This is Rafael I'll give that tried bad I mean, what you are asking.

Rafael Amato: I'll give it a try, but, I mean, what you are asking is still an answer. I think, obviously, the IPSC field is extremely exciting. For one, you know, it allows us, or will allow the field to have a homogeneous product that is well-characterized and inexhaustible in theory, which would transform the field. I think the characteristics of the T-cells that emerge after IBSP differentiation are still being worked out. I mean, will they be similar in terms of function, persistence, et cetera, as post-spinic T-cells? Can they be engineered and still maintain their T-cell differentiation capacity? Will they have the same molecules, cytokines, receptors, and ligands to penetrate and travel to the tumor?

It's still add ons there.

I think.

Obviously, the IBSD field. These extremely exciting for one you know it allows the or you will allow the field to have a homogeneous product very well characterized.

And.

Inexhaustible in theory.

Yes, good transformed this deal.

I think they.

Three six of the T cells that emerged after IDFC differentiation.

Bill is being worked out I mean will they be similar in terms of function persistence et cetera.

So both finding piece, though.

Can they be engineered and still maintain that piece. So differentiation capacity will they have the same molecule cytokine receptors and ligands to penetrate and traffic. The tumor I think all of this thing will need to be evaluated but we're starting to see.

Rafael Amato: I think all of these things will need to be evaluated, but we're starting to see what happens in the NK space differentiation for IBSP, and we see that promise, and we're pretty excited about it. And as you know, we're working pretty hard with NOS, and that collaboration is off to a really good start. And so, in terms of how it will compare to autologous healthy donors, I think, you know, we will have to see how the future evolves. At the moment, you know, our focus in terms of clinical trials is using allogeneic donors, and, you know, we are, I think, leading in recruiting and ascertaining what are the best parameters for dosing, meaningfully pleading, you know, issues such as the ones that have been asked, persistence, et cetera.

What happens in the engage space differentiation from IBSD, and we see that problem it and we're pretty excited about it and that's you know we're working pretty hard.

Not which isn't that that collaboration is off to I really would start and yeah. So in terms of Holly will compared to autologous a healthy donors. I think you know we will have to see how that you sort of all on the moment.

Our focus in terms of the clinical trials using allogeneic donors and.

We are I think leading in recruiting and ascertaining you know what are the best parameters for dosing meaningfully bleeding issues, but just want to have the now versus down et cetera.

Rafael Amato: And we plan to bring that forward to the clinic, but it will be an iterative process. We're working in parallel, and, you know, we expect that this technology will evolve, and it may become the future, or it may coexist with normal donor gene therapy as well. So, I think it's, you know, it's a matter of sort of watching this space, and it's great. At least, I feel it's fantastic that there are so many opportunities and that, you know, the technologies are advancing to make it easier, you know, more available to patients, which would be the case in the IPSC setting.

And we plan to bring that forward to the clinic, but it'll be any did brought that we're working in parallel and we expect that this technology will evolve and maybe become.

The future borrowing make books this week.

With normal donor.

Gene therapy as well so I think it is.

It's a matter to sort of watching this space.

And it's great at least you know I feel that it's fantastic that theres, so many opportunities and Doug.

The technologies are advancing to make it easier or more.

Level to basins, which would be located in the idmc setting.

David D. Chang: And just as a follow-up, you know, regarding donor cells and healthy donors, you know. I know there's a lot of work going into the lymphoid depletion regimens and things along those lines. Is there still a lot of work being done in terms of the ideal donor cells and types of donors that you want, or do you feel that that's largely pretty much anchored down, and, you know, everything else is, you're focusing on later stage parameters to change?

And just as a follow up regarding donor cells and healthy donors is you know I know theres a lot of work going into the Lymphodepletion regimens and things along those lines zero is there still lot of work being done in terms of the ideal donor cells and.

And types of donors that you want or do you feel that that's that's largely.

The much anchored down and everything else, you're focusing on later stage freighters to change.

Randy Let me take that question I mean based on the sort of successes that we're having with a manufacturing I think we feel that even though not selection became a little bit up a less of an issue, but that is an interesting topic that we are continuing to.

David D. Chang: Ren, let me take that question. I mean, based on the sort of successes that we are having with the manufacturing, you know, I think, you know, we feel that, you know, doughnut selection has become a little bit of a less of an issue, but, you know, that is an interesting topic that we are continuing to investigate. And certainly, as we do more manufacturing runs, we'll have more data points to really understand whether there are such individuals as super donors. But ultimately, you know, all these learnings will be applied to how we improve, continuously improve the manufacturing process. I mean, you know, we cannot build a program based on, you know, super donors out there. That knowledge will translate into our manufacturing improvement. That's how we see it.

Investigate and certainly as we do more manufacturing runs will have a more data point to really understand whether there is such individuals that the super donor, but ultimately.

All these learnings will be applied to how we improve continuously improved manufacturing process. I mean, we can not feel the program based on you know super donors out there that knowledge will translate into our manufacturing improvement Thats, how we see it.

Rafael Amato: Got it. And just one final one for me, just going back to the re-dosing question. Can you just talk us through what are the, I guess, alternative re-dosing protocols that you're evaluating?

Got it and just one one final one for me just going back to the read dosing question can you just talk us through what are the.

I guess, all kind of read dosing.

Protocols that you're evaluating.

Rafael Amato: So, I'll take that question. So, the amendment that we announced at the last call, that's a lot for reducing. In addition to dosing patients that have received autologous CARs in the past, we will see probably a few patients, we're enrolling some patients that are being re-dosed, these are patients, So, if a patient is a patient who has been in the protocol for 19 months and has developed some of the symptoms that have benefited or, you know, eventually developed stable disease, there's some parameters in the protocol that allow for re-dosing and, of course, the patient has to continue to express the 19 and, you know, we have to rule out that there are antibodies against the donor, but if they meet the conditions, they're eligible for re-dosing, which is, you know, fairly simple in the allogeneic setting.

So.

I'll take that question so the amendment.

That we announced the last call that's allow for reducing.

In addition to dosing basins bad have received a fellow of cars in the back.

The you know we will see.

Only a few patients.

You know, we're enrolling some patients that are being read those.

These are patients.

Have benefited or.

Eventually develop stable disease, there's some parameters in the product code that allow for read those seen on of course. The basin has to continue to express cdnineteen and we'd have to rule out the they're onto bodies.

Since the donor, but if they need the conditions, they're eligible for Reed dosing, which is fairly simple India allogeneic setting.

Rafael Amato: If they are very close to the length of depletion, it could be given using the same length of depletion. However, if it's longer than a period of time where the cells have recovered, then they need to be conditioned again. So, we will see some of those patients and, you know, it will be, I think, very informative to see, you know, how patients behave after a second dose and also, you know, likewise, how they behave after having progressed from prior therapy, which are, you know, two of the changes that we made in the amendment. They are stem cells that allow for recovery of, you know, granular sites and playlets relatively quickly and remains, So, that is really our singular focus now: what is the optimal length of the depletion regimen?

If they are very.

Very close to the Lymphodepletion it could be given using the same lymphodepletion if it's in longer than a period of time, where the tariffs have recovered than they need to be condition again. So we will see some of those patients. Then you will be I think very informative to see how basis behave thus there that condos.

And and also likewise, how do they behave after having progress Empire part therapy, which are.

You know two as a potential that we made any amendments you know we look forward to seeing what those have you know what what happens with those.

Patients, but our main objectives remain to understand the optimal lymphodepletion and to utilize to the maximum benefit the flexibility of our I listed for sale an antibody.

Which we've seen good.

It gives us a lot of Flexibilities bears themselves that allows for recovery of of.

Granular side, some playlists relatively quickly and remain maintains thing for at least into a lot putting grafman. So that is really a singular focus not only what is the optimizing for the patient regimen.

Rafael Amato: Thank you and congratulations on the progress. Our next question comes from Sammy Corwin with William Blair. Hi there, Samyon Faraj.

Great. Thank you and congrats on the progress.

Our next question comes from semi chrome with William Blair.

Hi, there Sammy on for Reisz, Thanks for taking my questions and congrats on the progress. After a couple of quick ones from me I was curious I know, it's still early but are you guys thinking that the turbo car Alis six so five program well eventually replace aloe seven one.

David D. Chang: Thanks for taking my questions and congrats on the progress. A couple of quick ones for me. I was curious, I know it's still early, but are you guys thinking that the TurboCar Allo 605 program will eventually replace Allo 715, or are you kind of thinking that those two programs will advance in parallel? And then, in regards to the re-dosing, are you re-dosing at the same dose, or are you giving patients a higher dose upon the re-dosing? And then I have a quick housekeeping follow-up.

Five or are you kind of thinking those two programs will advance in parallel and then in regards to de <unk>, Joe saying are you read dosing at the same Joe's or are you getting patients a higher dose of Ponderay dosing and then I have a quick housekeeping follow up.

David D. Chang: Sammy, this is David Chang, and I will take the question around 605 and 705 (it's a great question, but at this point, it's too early in terms of, you know, how we can answer it because we will really have to examine different approaches and, you know, how different approaches lead to different patient outcomes. And ultimately, you know, based on that, we will make a decision on whether we go with one or more than one. Multiple myeloma indication provides a lot of different opportunities, and I certainly believe that this is a field that can accommodate not just the first generation but the next generation in some simultaneous ways. So that's one of the reasons that we are really advancing our approach towards the BCMA in multiple myeloma.

Yeah. Sammy this is David sang and I'll take the question around Sixtyl by then 75.

Great question, but at this point is too early in terms of how we can answer it because we will really have to.

Examine different approaches and the you know how different approaches leaves two different patient outcome and ophthalmology you know based on that you know we will make a decision on whether we go with one or more than one.

Multiple myeloma indication provides a lot of different opportunities and I certainly believe that this is a field that can accommodate not just the first generation, but the next generation in some odd simultaneously. So that's one of the reason that we are really banting up our approach.

Tours bcm a in multiple myeloma.

Good.

Thank you. This concludes the question and answer session, how electrode the conference call back over to management for any additional comments.

Operator: Thank you. This concludes the question and answer session. I would like to turn the conference call back over to management for any additional comments.

Well. Thank you for joining us on this call today and your continued support of Allergan is what we know will be an exciting year, well allogeneic cell therapy. Operator, you may now disconnect.

Operator: Well, thank you for joining us on this call today, and your continued support of Allogene is what we know will be an exciting year for allogeneic cell therapy. Operator, you may now disconnect.

Operator: Thank you, ladies and gentlemen. Thank you for participating in today's conference. This does conclude the program. You may all log off and disconnect.

Thank you ladies and gentlemen.

Thank you for participating in todays conference. This does conclude the program you may all log off of disconnect.