Q4 2020 Allogene Therapeutics Inc Earnings Call

Ladies and gentlemen.

Operator: Ladies and gentlemen, today's conference is scheduled to begin shortly. Please continue to stand by, and thank you for your patience. [inaudible] BF-WATCH TV 2021. Good afternoon, ladies and gentlemen.

Today's conference is scheduled to begin shortly please continue to standby and thank you for your patience.

Operator: Thank you for standing by, and welcome to the Allogene Therapeutics fourth quarter and year-end 2020 conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1 on your telephone. Be aware that today's conference call is being recorded. I would now like to turn the conference call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.

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Christine Cassiano: Thank you, Operator, and to all on the line. Welcome to our first afternoon conference call. As we look ahead to the rest of 2021, we will now be conducting these calls in the afternoon, and we will continue to limit questions to one per person in order to answer all of your questions during the hour. After market close today, Allogene issued a press release that provided a corporate update and financial results for Q4 and Q4 2020.

Christine Cassiano: This press release and today's webcast are both available on our website. Joining me on the call today are Dr. David Chang, President and Chief Executive Officer, Dr. Rafael Amado, Executive Vice President of Research and Development and Chief Medical Officer, 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, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, and 2021 financial guidance, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change.

Yeah.

Good afternoon, ladies and gentlemen, thank you for standing by and welcome to the on which in therapeutics with the water order in 2000 20000 for 'twenty Conference call. At this time all participants are in listen only mode. After the speaker's presentation, there will be a question and.

Answer session. The ask a question during the session you'll need the press star one on your telephone please be aware of that todays conference call is being recorded.

I'd now like to turn the conference call over to Christine <unk>, Chief Communications Officer, Ms. Cathy I don't please go ahead.

Thank you operator instead of on the line welcome to our first afternoon conference call. As we look ahead to the rest of the 'twenty 'twenty. One we will now be conducting these calls in the afternoon net and we will continue to limit questions to one per person in order to answer all of your questions during the hour.

Christine Cassiano: A description of potential risks can be found in our earnings press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements. I'll now turn the call over to David. Thank you, Christine.

After market close on grain.

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But I guess for most all of them.

For you for them.

For 'twenty, one or 'twenty, 20th press released from today's webcast are both available on our website.

Joining me on the call today are Dr. David Chang, President and Chief Executive Officer, Dr. Rafael Amado Executive Vice President of research and development and Chief Medical Officer, and Dr. Eric Schmidt Chief Financial Officer.

David D. Chang: As we head into our third full year as a company, we are pleased to provide an update on our progress in 2020 and a look ahead at what to expect in 2021. By any measure, 2020 was a standout year for biology. We have succeeded in building a company that is capable of highly efficient execution across all research, development, manufacturing, and DNA functionalities. Our strong corporate foundation underpins our ability to deliver meaningful clinical data sets at two major medical meetings in 2020.

During today's call, we will be making certain forward looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials data presentations regulatory filings future research and development efforts manufacturing capabilities in 'twenty and 'twenty, one financial guidance among other things.

These forward looking statements are based on current information assumptions and expectations that are subject to change the description of potential risks can be found on our earnings press release and latest SEC disclosure documents you are cautioned not to place undue reliance on these forward looking statements and Allergan disclaims any obligation to update these.

I'll now turn the call over to David.

Thank you Christine.

As we head into our third full year as a company. We are pleased to provide an update on our progress in 2020 and the look ahead at what to expect in 2021.

David D. Chang: Each of these trials demonstrated the potential of an allocardial therapy and provided proof of concept for our proprietary lymphodepletion platform. We've delivered uninterrupted supply for all clinical trials and have now treated over 75 patients with our allogeneic cell therapy. We believe our clinical experience in the allogeneic field is unparalleled in scope, and we expect our leadership position to widen as we anticipate having five clinical trials underway in 2021. This goal would include full FIRST for Allogene Therapeutics. The Traverse Trial, our first thalassemia trial with ALO316 in renal cell carcinoma

By any measure.

On 20th was a standout year of biology, we have succeeded in building a company that is capable of highly efficient execution across all research development manufacturing and G&A functions.

Our strong corporate foundation underpins, our ability to deliver meaningful clinical datasets at two major medical meetings in 2020.

Each of which demonstrated the potential of on Allo car T therapy and provided proof of concept for our propriety NIM for depletion platform.

With deliberate uninterrupted supply for all clinical trials and have now treated all of about 75 patients with our allogeneic cell therapies.

David D. Chang: The Universal Trial, where we have now initiated our first combination of exploring ALOS-715 plus neurogastritis and multiple myeloma. The IGNITE trial, our first therbocard trial investigating ALO605 in multiple myeloma, and the ALPHA-2 trial, potentially our first pivotal trial with ALO501A in large B-cell lymphoma. Our ability to conduct multiple clinical trials in parallel and the rational optimization strategy that we are pursuing gives us confidence in our ability to overcome hurdles inherent in the allogeneic field.

We believe our clinical experience in the allogeneic Peel the is unparalleled in school.

And we expect our leadership position to widen as we anticipate having five clinical trials underway in 2021.

This call would include full first for allergy debt.

For burst trial.

The first solid tumor trial with all of 316 in renal cell carcinoma. The.

Universal trial, where are we now initiated our first combination on the exploring allo 715, plus neuro guests debt in multiple myeloma.

David D. Chang: As we advance our increasingly broad Alokharti pipeline towards multiple industries first, we are also investing heavily in next-generation technologies designed to keep us at the forefront of innovation in the field. As part of these efforts, we have expanded our research to execute on novel strategies designed to increase cell potency, overcome tumor microenvironment considerations, and delay immune rejection. We have made a considerable investment in TurboCars, a highly innovative and proprietary technology with widespread applications.

The ignite trial, our first turbo car trial investigating allo six of <unk> in multiple myeloma and the Alpha trial potentially our first pivotal trial with Allo 501, eight in large b cell lymphoma.

Our ability to prosecute multiple clinical trials in parallel and the rationale optimization strategy that we are pursuing gives us confidence in our ability to overcome hurdles inherent in the allogeneic field.

David D. Chang: Our initial therapeutic cards, which we plan to introduce into the clinic beginning this year, have the ability to increase potency, improve T-cell fitness, and augment persistence via the addition of a cytokine stimulation domain. Meanwhile, next-generation therbocots are already being designed to overcome immune-suppressive factors in the tumor microenvironment, particularly in solid tumors, by engineering T-cell stimulatory domains that are activated by certain factors such as PD-L1 and TGF-beta that normally inhibit T-cell function.

As we advance our increasingly growth allo car T pipeline towards multiple industry. First we are also investing heavily in next generation technologies designed to keep us at the forefront of innovation in the field.

As part of these efforts we have expanded our research to execute on novel strategies designed to increase cell potency.

Other come tumor micro environment considerations and delayed immune rejection.

We have made a considerable investment behind turbo cars.

Wiley innovated and proprietary technology with widespread application.

David D. Chang: Our focus on new technologies extends to the progress we are making in our partnership with Notch Therapeutics, directed at IPSC-derived therapeutics. NACCHI is applying its scalable, engineered thymic-niche platform to develop homogeneous and universally sourced stem cell drive therapies. They have assembled a world-class scientific team and are building a fully integrated, rigorously controlled platform for generating and editing immune cells from clonal stem cells to enable the development of a range of T-cell therapeutics.

Our initial cobalt cars, which we plan to introduce into the clinic beginning this year have the ability to increase potency improved T cell fitness and admin persistence be out of the addition of a cytokine stimulation domain.

Meanwhile, next generation of turbo costs are already being designed to overcome immunosuppressive factors in the tumor micro environment, particularly in solid tumors by engineering T cell stimulatory domains that are activated by certain factors.

David D. Chang: While our current focus with NARCH is to develop fully functional T-cell therapies for initial applications in non-Hodgkin's lymphoma, leukemia, and multiple myeloma, our agreement also gives us the right to pursue natural killer (NK) cell therapies should we opt to do so. Additionally, our work allows us to consider next-generation anti-rejection strategies that might complement our proprietary anti-CD52 platform. We are advancing preclinical programs based on what we call dagger approaches. For example, in concert with Baylor College of Medicine.

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Our focus on new technologist extends to the progress we are making in our partnership with notch therapeutics directed at Ips C drive therapies.

Chase applying its scalable engineered thymic niche platform to develop a homogeneous and universally source stem cell drive therapies.

They have assembled a world class science Big team and building a fully integrated rigorously control platform for generating and editing immune cells from Cornell stem cells to enable development of a range of T cell therapeutics.

David D. Chang: We are exploring the use of alloimmune defense receptors, or ADRs, to recognize and destroy alloreactive host immune cells that would otherwise be capable of rejecting the allogeneic CAR-T cells, thereby providing enhanced persistence of allogeneic CAR-T cells.

While our current focus with notch is to develop fully functional piece of therapies for initial applications in non Hodgkin's lymphoma.

David D. Chang: In addition, we are advancing cloaking approaches that seek to hide allogeneic cells from detection by the host immune system. We hope to advance one or more novel strategies into the clinic by 2023. Based on the strong foundation we have created, we believe we are in a great position to broaden our reach, both in terms of pursuing new targets as well as expanding our geographic footprint. Let's first talk about new targets. We have previously spoken about our first foray into solid tumors with LO316 in renal cell carcinoma.

Leukemia and multiple myeloma.

Our agreement also gives us the rights to pursue of natural killer for NK cell therapies should we ought to do so.

Our work allows us to consider of next generation anti rejection strategies that might complement our propriety anti CD 52 of platform.

We are advancing great clinical programs based on what we call of dagger approaches for it.

Example, in concert with Baylor College of Medicine.

We are exploring the use of allo immune defense receptors for a D ours to recognize and destroy allo reactive host immune cells that would otherwise be capable of rejecting the allogeneic car T cells, thereby providing enhanced persistence to allogeneic car T cells.

David D. Chang: We believe this disease state is ripe for innovation as current therapies are based on a few mechanistic targets and complete response rates are low. Our goal is to deliver the potentially transformative impact of CAR Therapy to patients with kidney cancer. We are pleased last year to receive clearance for our IND and are now preparing to launch our TRAVERSE trial. We would expect to share initial data from this trial in 2022. Finally, as we look at both expanding development and our footprint, we are excited about the joint venture we announced late last year with Overland Pharma, named Allogene Overland BioPharm. This first-of-its-kind collaboration for an allogeneic cell therapy will focus on our candidates targeting PCMA. CD 70.

In addition, we are advancing clocking approaches that seek to hide allogeneic cells from detection by the host immune system.

We hope to advance one or more novel strategies into clinic by 2023.

Based on the strong foundation, we have created we believe we are in a great position to broaden our reach both in terms of pursuing new targets as well as expanding our geographic footprint.

Let's first talk about new targets.

We have previously spoken about first of all right into solid tumors with allo 316 in renal cell carcinoma.

We believe this disease state is ripe for innovation as current therapies that based on the field mechanistic targets and complete response rates are low.

David D. Chang: CLIT 3 and DLL 3. Not only will this JV give us access to a large and rapidly growing pharmaceutical market in China, but it may also give us the opportunity to accelerate the clinical development of certain alokharki pipeline candidates. Based upon my experience over the past eight years of developing successful and life-saving cell therapies, the pursuit of a disciplined, methodical, and data-driven approach to the most challenging obstacles facing the field of this modality can sometimes be unheralded. However, I personally believe that a rigorous scientific approach is of critical importance to long-term success in the field.

Our goal is to deliver the potentially transformative impact of car T therapy to patients with kidney cancer.

We are pleased last year to receive clearance for all of <unk> D and are now preparing to launch our <unk> trial.

We would expect to share initial data from this trial in 2022.

Finally, as we look at bulk expanding development and all of footprint. We are excited about the joint venture we announced late last year with Oberland pharma name Allergen Oberland Biopharm.

This first of its kind of collaboration for an allogeneic cell therapy will focus on our candidates targeting the CMA.

David D. Chang: Only companies that commit to such scientific excellence and to rational decision-making will be able to make the necessary progress to reliably deliver radically transformative and durable therapies to patients. To accomplish such formidable tasks, one should surround himself with a world-class team of scientists, clinicians, and cell therapy manufacturing experts. I am blessed to have Dr. Barbara Sasu, our Chief Scientific Officer, Dr. Rafael Amado, our Executive Vice President of Research and Development and Chief Medical Officer, and Dr. Allison Moore, our Chief Technical Officer, on the Allogene Leadership Team, and I'm proud that the teams have embraced these same principles.

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Flit three N D L L III.

Not only will this JV give us access to a large and rapidly growing pharmaceutical market in China, but it may also give us the opportunity to accelerate clinical development of certain allo car T pipeline candidates.

Based on upon my experience over the past eight years of developing successful and lifesaving cell therapies, the pursuit of a disciplined net.

Article and data driven approach to the most challenging obstacles facing the field of this modality can sometimes be unheralded.

However, I personally believe that of rigorous scientific approach is of critical importance to long term success in the field.

David D. Chang: We greatly appreciate your support as we seek to make allocardiotherapy accessible to more patients with advanced cancer. I will now turn the call over to Rafael for further updates on our research and development activities. Thank you, David.

Only companies that commit to such scientific excellence and two rationale of decision, making will be able to make the necessary progress to reliably deliver radically transformative and durable of therapies to pesos.

Rafael Amado: I'd like to first discuss our C19 program with ALO501 and ALO501A in non-Hodgkin's lymphoma as we look ahead to our next data presentation at a medical forum in Q2 of this year. While our policy has been to not get ahead of meeting announcements, to alleviate any speculation with regard to timing, we're targeting ASCO for this update. At ASCO 2020, we presented initial data on 22 non-Hodgkin's lymphoma patients treated with ALLO501, of which 19 were evaluable for efficacy.

To accomplish such formidable task lunches are on one cell with a world class team of scientists clinicians and cell therapy manufacturing experts.

I'm Blessed to have doctors bottler of SaaS to our Chief Science Officer Dr.

Rafael Amado, our executive Vice President of research and development and Chief Medical Officer.

And that's the Alison Moore, our Chief Technical officer on the allergy and the leadership team and then proud that the teams embraced these same principles.

We greatly appreciate your support as we seek to make allo car T therapy accessible to more patients with <unk> cancer.

Rafael Amado: Updated ALO501 data from the alpha trial will reflect longer-term follow-up from those patients previously presented, as well as more recent data, which will include additional patients who received higher doses of ALO647. We will also examine biomarker results such as minimal residual disease or MRD status. As we expect to have a more meaningful data set, we also intend to provide information on patient subsets. As you might recall, our ALO501A Alpha 2 trial was designed to potentially move into a pivotal phase should the data support it. As a result, this trial was designed to enroll a homogeneous patient population focused on relapsed refractory large P cell lymphoma.

I will now turn the call over to Rafael for further updates on our research and development activities.

Thank you David I'd like to first discuss our seen 19 program with all of final one on Allo 501 day in non Hodgkin's lymphoma. As we look ahead to our next startup presentation in the medical for them in Q2 of this year while the.

The policy has been to not get ahead of meeting the announcements to alleviate any speculation with regards to timing, we're targeting Oscar for the sub base.

As for 2020, we presented initial data on 22, non Hodgkin's lymphoma patients treated with all of the one of which 19 were evaluable for efficacy.

Updated allo five of the one data from the Alpha trial will reflect longer term follow up from those patients previously presented as well as more recent data, which will include additional patients who received higher doses of our listings for seven.

Rafael Amado: As noted in our press release this afternoon, ALLO501A was granted fast-track designation for the treatment of this population. The abbreviated Phase 1 dose escalation portion of this trial was designed to recapitulate initial findings from the ALPHA trial with a modified construct where the rituximab recognition domains have been removed. Dose escalation was completed late last year, and as such, durability will be limited from the Alpha 2 trial when data are first presented.

We will also of some in biomarker results, such as minimal residual disease or it might be studies.

We expect to have a more meaningful data set we also intend to provide information on patient subset.

As you might recall, our allo five of <unk> outside the trial, what's the sign to potentially move into a pivotal phase should the data supports it.

Rafael Amado: As we continue enrollment in this trial, much like the ALSA trial, we're now focused on enrolling patients into the consolidation portion of this study. In both of these trials, consolidation consists of two infusions of 120 million Alokar T cells. The first infusion follows lymphodepletion with fludarabine and cyclophosisphamide, as well as ALOS647, and an initial tumor assessment is performed on day 28. If a patient is in complete response, partial response, or stable disease on day 28, a second infusion is given approximately five to six weeks after the first infusion.

The service so the straw was designed to enroll a homogeneous patient population focus on relapsed refractory large b cell lymphoma.

As noted in the in our press release. This afternoon Allo five of one day was granted fast track designation for the treatment of this population the.

The abbreviated phase one dose escalation portion of this trial once you sign to recapitulate. The initial findings from the Alpha trial with a modified construct where the rituximab recognition domains have been removed.

Dose escalation was completed late last year on of such durability will be limited from the outside to the trial when data of our first presented.

As we continue enrollment in the straw unless like the Alpha trial, we're now focused on enrolling patients into the consolidation of portion of this study for <unk>.

Rafael Amado: Prior to the second cell infusion, a patient will be eligible to receive a modified lymphodepletion consisting only of ALO647. The consolidation protocol will evaluate whether an additional dose of cells can further improve the complete response rate and translate into durable complete response. Approved autologous CAR T therapies have demonstrated a best overall response rate of 70% to 80%. However, over half of these patients fall out of response.

Each of these trials consolidation will consist of two infusions of 120 million of Allo car T cells the <unk>.

First infusion for listening for the depletion with Fludarabine and cyclophosphamide spoiler for Allo, six or seven and then the initial tumor assessment of pro forma on day 28 for.

The pace of anything complete response partial response or stable disease of day 28.

On the infusion is given approximately five to six weeks of the first infusion.

Relative to the second selling infusion of based on will be eligible to receive a modest filing for the ablation, consisting only of allo six for seven.

Rafael Amado: The intention of the consolidation protocol is to see if we can potentially induce responses in a higher proportion of patients over the long term. As the duration of follow-up from these consolidation protocols in both ALPHA and ALPHA-2 will be short, we look forward to assessing the best course of action for a pivotal trial in the second half of the year. At ASH in December 2020, we were pleased to present the initial data from our ALO715 program in relapsed refractory multiple myeloma. This was the first data set ever presented on an allogeneic cell therapy targeting DCMA.

The consolidation protocol will evaluate whether on the additional dose of cells come further improves the complete response rate and translate into durable complete responses.

Bruce Autologous car T therapies have demonstrated the best overall response rate in the 70% to 80% range.

However over half of these patients fallout of response.

The intention of the consolidation of protocol is to see if we can potentially induce responses in a higher proportion of patients over the long term that's the.

Duration of follow up from this consolidation protocols in both Alpha and IL two will be short.

Rafael Amado: We were very pleased with the initial look at the universal trial and the proof of concept generated by allocard T therapy in this indication. In this initial data readout, 31 patients treated with ALO715 were evaluable for safety, and 26 patients were evaluable for initial efficacy. As has previously been observed in multiple myeloma, higher CAR-T cell doses were associated with an increased response rate and greater alloCAR-T cell expansion.

We look forward to assessing the best course of action for a pivotal trial in the second half of the year.

At Ash in December 2020, we were pleased to present initial data from our allo seven one plus program in relapsed refractory multiple myeloma.

What's the first set of said ever presented on the allogeneic cell therapy targeting the CMA.

We're very pleased with the initial look at the Universal trial on the proof of concept generated by Allo car T therapy in the syndication.

And this initial data readout 31 patients treated with Allo 715 were Evaluable for safety and 26 patients were evaluable for initial efficacy.

Rafael Amado: In the DL3 cohort of 320 million allocard T-positive cells, the overall response rate was 60%, with 40% of patients achieving a very good partial response or better, which we refer to as VGPR+. MRD was assessed in 5 of 6 patients with a VGPR+ response, and all 5 were MRD negative. Approximately 90% of patients were treated within 5 days of study enrollment, and importantly, no bridging therapy was required. In terms of safety, there was no graft-versus-host disease or immune-effector cell-associated neurotoxicity syndrome observed. Grade 1 or 2 cytokine release syndrome was reported in 14 patients and was manageable with standard therapy.

<unk> previously been observed in multiple myeloma higher car T cell doses were associated with an increased response rate and greater allo car T cell expansion.

In the D O three cohort of 320 million on Olive garden, the posted the cells. The overall response rate was 60% with 40% of patients achieving a very good partial response or better, which we referred to as VP of applause MRV was assessed in five of six patients with visa.

PR plus response.

On all five where it might be negative.

Approximately 90% of patients with treated within five days of study enrollment and importantly, no bridging therapy was required.

In terms of safety, there was no graft versus host disease or immune effector cell associated neurotoxicity syndrome observed great.

Great. One of just cytokine release syndrome was reported in 14 patients on was manageable with standard therapies.

Rafael Amado: The rate of grade 3 plus infection events was similar to what has been reported in other advanced multiple myeloma studies. Grade 3 plus adverse events reported as serious adverse events occurred in 19% of patients, which included the previously disclosed single grade 5 event related to progressive myeloma and a reduced intensity conditioning regimen. This proof-of-concept data was an important step forward in the field as an on-demand option may be critical for patients with multiple myeloma, knowing that many either cannot wait for an autologous option or may need to be healthy enough to tolerate and respond to bridging therapy in order to receive autologous CAR-T.

The rate of grade three plus the infection events was similar to what has been reported in the other advanced multiple myeloma studies.

Breaking plus adverse events reported of serious adverse events occurred in 19% of patients which included the previously disclosed single grade five events related to the progressive myeloma and are reducing the conditioning regimen.

This proof of concept data what's on importance the forwarding the seal of Sun on the non option may be critical for patients with multiple myeloma, knowing the many either cannot wait for in a total of this option or may need to be healthy enough to tolerate and respond to bridging therapy in order to receive a total.

All of us kind of cheap.

The findings from the Universal Phase one dose escalation trial positions us to move onto the next steps in this study, namely optimizing of so does it mean for the depletion potentially repeat administration of all of southern one five.

Rafael Amado: The findings from the Universal Phase I Dose Escalation Trial position us to move on to the next steps in this study, namely optimizing cell dose, lymphodepletion, and potentially repeat administration of ALO715. Our plan is to provide an update on ALO 715 later this year. We're also exploring ALO 715 in combination with the gamma secretase inhibitor nirogastrostate from our partner ScreenWorks

Our plan is to provide an update on all of sudden one five later this year.

We're also exploring all of 715 in combination with the gunman separate base inhibitor narrow gaseous debt from our partners screen works Therapeutics. We're pleased to report that we have now initiated this cohort our first clinical milestone for 2021.

Rafael Amado: We are pleased to report that we have now initiated this cohort, our first clinical milestone for 2021. Continuing in the BCMA program, we remain on track to submit our IMD-40605 in the IGNITE trial, our first turbo car targeting multiple myeloma, in the first half of the year. We continue to believe that the innovation behind turbo cars represents a breakthrough as this technology has the potential to overcome T-cell exhaustion and expand allo-car T-cell viability and efficacy while reducing car T-cell dose requirements. These properties may enable CAR T to succeed in harder-to-treat hematologic malignancies and solid tumors and may enable us to raise the bar in multiple myeloma.

Continuing in the <unk> program, we remain on track to submit our IND for Allo 605 in the ignite trial, our first durable car targets in multiple myeloma in the first half of the year.

We continue to belief of the innovation behind Supercars represents a breakthrough of this technology has the potential to overcome T cell exhaustion and extend the allo car T cell viability on efficacy, while reducing car T cell dose requirements.

These properties may enable of part D to succeed and harder to treat hematologic malignancies and solid tumors. The may enable us to raise the bar in multiple myeloma.

Lastly, in what is one of our most exciting programs were eager to initiate our first solid tumor trial.

Rafael Amado: Lastly, in what is one of our most exciting programs, we're eager to initiate our first polytumor trial. The TRAVERSE trial with the anti-CD70 CAR-T allo-316 in clear cell renal cell carcinoma is initially designed to explore allo-316 dosing at 40, 160, 320, and 480 million allo-CAR-T positive cells. The protocol will also evaluate components of the lymph depletion regimen, including ALOS647. Safety, tolerability, depth and duration of lymphodepletion, cell expansion, and anti-tumor activity will be assessed.

The diverse trial with the anti CD 70 car T. All of 316 in clear cell renal cell carcinoma is initially designed to explore all of the three won't see dosing for.

41, 63, 20, 480 million Olive garden deep book with yourselves.

The protocol will also evaluate components of the names of the depletion regimen, including allo six for seven.

The endpoints being assessed the safety tolerability depth and duration of thing for depletion cell expansion on anti tumor activity.

Rafael Amado: Given the high prevalence of renal cell carcinoma and the lack of curative therapies for advanced disease, we look forward to working closely with leading kidney cancer centers and CAR-T specialists in the innovative development of allogeneic cell therapy for this disease.

Given the high prevalence of renal cell carcinoma on the lack of curative therapies for the disease. We look forward at the working closely with leading kidney cancer centers on part D, especially in the innovative development of allogeneic cell therapy for this disease.

With free trials underway on two more on the horizon, we remain very enthusiastic about on olive garden seed platform and its potential for patients.

Rafael Amado: With three trials underway and two more on the horizon, we remain very enthusiastic about our AllocRT platform and its potential for paging. I'd like to now turn the call over to Eric to discuss the financials. Thank you, Raphael, and good afternoon. Before I provide a brief overview of our financials for the quarter and year-end, I'd like to spend a few minutes on some of our recent business development activities. In particular, at the end of the year, we announced the formation of Allogene Overland BioPharm, our joint venture with Overland Pharmaceuticals to develop and commercialize our aloecar T therapies in Greater China, Taiwan, South Korea, and Singapore. Overland, which is backed by Hill House Capital, owns 51% of the joint venture through its investment of $117 million.

And now I'll turn the call over to Eric to review the financials.

Thank you Raphael and good afternoon.

Before I provide a brief overview of our financials for the quarter and year end I'd like to spend a few minutes on some of our recent business development activities in particular at the end of the year, we announced the formation of allergy overland Biopharm, our joint venture with overland pharmaceuticals to develop and commercialize our allo car T therapies and greater.

China, Taiwan, South Korea, and Singapore.

Overland, which is backed by Hillhouse capital owns 51% of the joint venture through its investment of $117 million. This investment includes an upfront payment of allergy of $40 million. The majority of which we expect to book as revenue in Q1, and the commitment of $77 million of capital to support operations.

Eric Schmidt: This investment includes an upfront payment to Allogene of $40 million, the majority of which we expect to book as revenue in Q1, and the commitment of $77 million in capital to support operations at Allogene Overland BioFarm. In addition to the upfront payment, Allogene, which owns 49% of the joint venture, will be eligible to receive approval milestones as well as tiered low-to-mid single-digit royalties on in-territory Overland will provide operational support, while Allogene will provide technical and manufacturing expertise.

Patients that allergy and overland Biopharma.

In addition to the upfront payment allergy, which owns 49% of the joint venture will be eligible to receive approval milestones as well as tiered low to mid single digit royalties on in territory net sales.

Overland will provide operational support while allergy and will provide technical and manufacturing expertise.

Now onto our financials in the fourth quarter of research and development expenses were $52 $2 million, which includes $7 $9 million of noncash stock based compensation expense for the full year 2020 research and development expenses were $193 million.

Eric Schmidt: Now on to our financials. In the fourth quarter, our research and development expenses were $52.2 million, which included $7.9 million of non-cash stock-based compensation expense. For the full year of 2020, research and development expenses were $193 million, which included $31.3 million in expenses associated with non-cash stock-based compensation. General and administrative expenses were $17.1 million for the fourth quarter of 2020, which included $8.6 million of non-CAS stock-based compensation expense. For the full year of 2020, G&A expenses were $65.3 million, which included $34 million of non-cash stock-based compensation expense.

Which includes $31 $3 million in expenses associated with noncash stock based compensation.

General and administrative expenses were $17 $1 million for the fourth quarter of 2020, which includes $8 $6 million of noncash stock based compensation expense for the full year of 2020, G&A expenses were $65 $3 million, which includes $34 million of non.

Cash stock based compensation expense.

Eric Schmidt: Our net loss for the fourth quarter of 2020 was $68.6 million, or $0.53 per share, including non-cash stock-based compensation expense of $16.5 million. For the full year of 2020, our net loss was $250.2 million, or $2.08 per share, including non-cash stock-based compensation expense of $65.3 million.

Our net loss for the fourth quarter of 2020 was $68 $6 million or <unk> 53 per share, including noncash stock based compensation expense of $16 $5 million for the full year of 2020, our net loss was $252 million or $2 <unk>.

<unk> per share, including noncash stock based compensation expense of $65 $3 million.

Eric Schmidt: As we look toward financial guidance for 2021, David and Raphael have noted that we expect to have five programs in the clinic, including a potentially pivotal trial for Allo501A. To support the advancement of these programs and to prepare for initial GMP production at our Newark manufacturing facility, known as CellForge1, we anticipate that we will need to make substantial incremental investments in R&D. On the other hand, our focus on maintaining an efficient corporate infrastructure should enable more limited growth in G&A spend.

As we look toward financial guidance for 2021, they've been Raphael have noted that we expect to have five programs in the clinic, including of potentially pivotal trial for allo five of <unk> to support the advancement of these programs and to prepare for initial GMP production at our Newark manufacturing facility known as self.

For one we anticipate that we will need to make substantial incremental investments in R&D on the other hand, our focus on maintaining an efficient corporate infrastructure should enable more limited growth and G&A spend.

Eric Schmidt: Overall, we expect our full-year 2021 operating expenses to be between $300 and $330 million. This includes an estimated non-cash stock-based compensation expense of $80 to $90 million and excludes any impact from potential future business development activity.

Overall, we expect our full year 2021 operating expenses to be between 303 hundred $30 million. This includes an estimated non cash stock based compensation expense of $80 million to $90 million and excludes any impact from potential future business development activities.

With that we will now open the call to your questions.

Operator: With that, we will now open the call to your questions. And thank you. As a reminder, to ask a question, you'll need to press star one on your telephone. To withdraw your question, press the pound.

And thank you as a reminder to ask the question you'll need of press star one on your telephone to withdraw your question press. The pound key please standby we compile the Q&A roster and we ask that you. Please limit yourself to one question.

Operator: Please stand by; we have compiled a Q&A roster, and we ask that you please limit yourself to one question. And our first question comes from Salveen Richter of Goldman Sachs. Your line is now open. Hi everyone. This is Andrea on behalf of Salveen. Maybe a question for you, David, or for Eric. Just with respect to the Oberlin JV, can you provide additional color on your thinking here, why the structure was so appealing, and if you think this is a strategy you'll look to employ in other ex-US geographies?

And our first question comes from solving Mr from Goldman Sachs. Your.

Your line is now open.

Hi, Andrew Your line. This is Andrew on for Zalviso on maybe a question for you Dave There for Eric just with respect to the overland JV interest can you provide additional color on your thinking here why the ex <unk>.

Structure wise still appealing and if you think this is the strategy on what can play in other ex U S geography.

Andrea Thanks for that question. Obviously, we are very excited about the joint venture debt got started and.

David D. Chang: Yeah, Andrea, thanks for that question. Obviously, we are very excited about the joint venture that got started. And, you know, Eric worked very hard on this. So, let me ask Eric to explain why we did it the way that we did with this joint venture.

Eric worked very hard on this so let me ask Gary to explain why we did it the way that we have done with this joint venture Eric.

Eric Schmidt: Yes, thanks. Thanks, David. And thanks, Andrea, for the question. We are very proud of what we've been able to accomplish here. I think that China is a little bit of a unique market, honestly.

Yes, thanks, Thanks, David and thanks, Andrea for the question. We are very proud of what we've been able to accomplish here I think the China's a little bit of a unique market honestly one thing that we really liked about China is it's a very large growth opportunity and it's one where we think manufacturing on the ground can be.

Eric Schmidt: One thing that we really liked about China is that it's a very large growth opportunity, and it's one where we think manufacturing on the ground can be a huge competitive advantage. So the structure of this joint venture, you know, allows us through our equity position of 49% to really benefit from the growth in China, while we use the influx of capital from our partners at Overland to support much of the buildout. So for China, it makes a lot of sense.

On a huge competitive advantage. So the structure of this joint venture allows us through our equity position of 49%, it's really benefit from the growth in China, while we use the influx of capital from our partners at all the land to support much of the Buildout of so for China. It makes a lot of sense.

Eric Schmidt: We'll see in other territories. Obviously, I should reiterate that our focus in the major markets of the U.S. and Europe is really to keep rights commercially to all of our products. Got it. Thanks. Thank you. And our next question comes from Byron Amin from Jeffreys. Your line is now open.

You'll see in other territories, obviously I should reiterate that our focus on the major markets of the U S and Europe is really the keep.

On the rights commercially to all of our products.

Got it thanks, so much.

Thank you.

And our next question comes from Byron on Min from Jefferies. Your line is now open.

Operator: Yeah, hi guys, thanks for taking my question. Regarding the Alpha-2 trial and the consolidation dose of 120 million cells, is that strictly for dose level two, or would patients be eligible to receive consolidation at dose level three? And are you using a similar consolidation regimen for LO715?

Yeah, Hi, guys. Thanks for taking my question.

Regarding the alpha to the trial and the consolidation.

Dose of 120 millions of those is that strictly for dose level, two or would patients be eligible to receive consolidation at the <unk>.

On the Curry and are you using a similar consolidation of regiment for Alex some of them one five.

Okay.

Rafael Amado: Okay, Biren, thanks for that question. We have spoken a little bit about consolidation, but let me just reiterate what we are trying to do with a consolidation regimen, which I think is a very unique opportunity that comes with allogeneic off-the-shelf cell therapy. This is not something that I see that can be done easily within the autologous setting.

Thanks for the question, we have spoken a little bit of the consolidation.

Let me just reiterate what we are trying to do with the consolidation regimen, which I think is a bit of a unique opportunity that comes with the allogeneic off the shelf cell therapy. This is not something that I can I see that can be that easily wins the autologous setting.

David D. Chang: So, you know, as we have done throughout the development of 501, I mean, we are checking every possible leverage to optimize and improve what we get with the allogeneic cell therapy, starting with a cell dose, lymphodepletion, where we saw very positive findings as we increased the 647 dose, and what's really left is the consolidation. The details, obviously, with the consolidation are a little bit complicated, and Raphael went through that, but let me ask Raphael to explain exactly what's being done with the consolidation in 501A. Yes, Byron.

So as we have done throughout the development of fiber one I mean, we are checking every possible levers to optimize and improve what we get with the allogeneic cell therapy, starting with the cell dose limit for depletion, where we saw very positive finding as we increase of $6 seven dose and what's real.

The left is the consolidation the details obviously with the consolidation of its little bit complicated and Rob sales linked to that but let me ask for opt out to explain exactly what's being done with the consolidation and fiber one Inc.

Yes, so iron.

Rafael Amado: So, consolidation, as I described in my opening remarks, is where we are enrolling at the moment in both Alpha and Alpha 2. And Alpha 2 is only large-cell lymphoma. And patients are enrolled, they're treated with the usual lymph depletion regimen, including ALO647, and then, at day 28, they are assessed. The initial dose is 120 million, and the second dose is 120 million. We're not exploring any additional doses because we believe that the dose response that, for instance, tends to be observed in myeloma is not something that we have observed in lymphoma.

For the consolidation is a free described in the opening remarks.

Is.

Where we are in growing up the moment in both all the fun of hard too.

And I'll talk to is on the large b cell lymphoma.

And patients are in growth.

They are treated with.

On the usual, earning for depletion regimen.

Including all of the six for sovereign and then on day 28, there are for us.

The initial dose of 420 million on the second dose and time line from Dominion, we're not exploring any additional doses because we believe that the <unk>.

Its response on the <unk>.

Since the re observing the myeloma is not something that we have observed from lymphoma and you know that gets the dose of for a total of stronger on 40 million cells in total and here again as David mentioned, we're trying to do is to see whether we can increase the responses.

Rafael Amado: And, you know, that gives us a dose of 240 million cells in total. And here, again, as David mentioned, what we're trying to do is to see whether we can increase the responses, increase the durability. And we're looking at a variety of biomarkers to try to give us some surrogate information that this is superior to single-dose. Great, thank you.

The increase the durability.

Looking at a variety of Biomarkers to try to give us some surrogate information.

This is superior to single dose.

Great. Thank you.

Thank you.

Operator: Thank you. And our next question comes from Mark Frahm from Collin, and your line is now open. Thanks for taking my questions. Focusing back on the ASCO presentation from ALPHA, maybe you could give us a little bit more granularity on how many patients you would expect to be at six months and then just kind of the relative breakdown of new data in the abstracts versus the presentation itself. Which of those is probably the bigger event that we should be focusing on?

And our next question comes from Marc Frahm from Cowen <unk> Company. Your line is now open.

Thanks for taking my questions Inc.

Just focusing back on the <unk> presentation from from the Alpha.

Maybe can you just a little bit more granularity on how many patients you would expect to be at six months and then just kind of relative breakdown of new data in the abstracts versus the.

For the presentation of thoughtfully, which of those is probably the bigger event that we should be focused on.

Alright.

Mark.

David D. Chang: All right, you know Mark, you're going straight into a data presentation that we plan to do targeting ASCO. I mean, we're getting pretty close, so in terms of what we will say is somewhat limited, but let me ask Raphael to recap, you know, what are the salient findings from the ASCO presentation and what has happened over the last, essentially, about six months since the data presentation, which will be sort of underlying the content of what is to be expected at 2021 ASCO. Rafael?

Going straight into data presentation that we plan to do targeting asked call I mean, we're getting pretty close so in terms of what we will say is somewhat limited, but let me ask Rafael to recap what of the sale and findings from the <unk> presentation and what has happened.

And all of the lost essentially about six months since the data presentation, which will be sort of underlying the contents of what it is to the expected in 2020 on asphalt right now.

Sure So mark.

Rafael Amado: Sure. Marc, you may recall that at ASCO we enrolled 22 patients, and as I mentioned before, 19 were eligible for efficacy. We did see a dose response with regard to ALO647 with 50% of patients in complete response when we used 90 mg. Thus, higher doses of ALO647 can cause better lymphodepletion and retard the recovery of endogenous lymphocytes in the patient and, therefore, allow for a longer dwelling time of the donor cells.

You may recall that at our scope, we enrolled 22 patients on as I mentioned before 19, we're eligible for quarter of efficacy.

We did see a dose response with regards to out of six or seven.

50% of patients in complete response, when we use 90 milligrams.

So we.

We believe the higher doses for about six or seven current cost better lean for depletion and retard the.

Recovery of endogenous lean.

Lymphocytes in the patient and therefore allow for a longer.

Dwelling time of the dawn of ourselves. So in the meantime, after that of course, we have continued to follow those patients. So you kind of expect the longer follow up of both the 39 milligrams in the 90 milligram patients and then we'll continue to explore the higher doses of all the six or seven.

Rafael Amado: So, in the meantime, after that, of course, we'll continue to follow those patients, so you can expect a longer follow-up for both the 39 mg and the 90 mg patients. And then we've continued to explore higher doses of ALO647 as a single dose. We've treated a number of patients at that dose, and then after that exploration, we commence the consolidation treatment. In alpha, we've enrolled both follicular and large cell, and in alpha 2, as I said before, we've only enrolled large cell lymphoma. And then, just to make the point that the consolidation started much later, obviously, is the last thing that we started exploring.

As the single dose.

Three of the number of patients.

At that dose.

And then after that exploration then we commenced the consolidation of treatment in alpha with Enbrel, both follicular on large cell and in part two as I said before we finally enroll.

Large cell lymphoma, and then just to make the point that the consolidation started much later, obviously is the last thing debt debt.

<unk>.

We started exploring and therefore, the follow up in dose patients will be naturally shorter so.

Rafael Amado: And, therefore, the follow-up in those patients will be naturally shorter. So, you can expect longer follow-up from the initial patients from ASCO, additional patients treated with higher doses of ALO647, and some data on consolidation. Thank you. And our next question comes from Tyler Van Buren from Piper Sandler. Your line is now open.

So you can expect longer follow up from the initial patients from Moscow additional patients treated with doses of.

The other six or seven.

The data some data on consolidation.

Okay. Thanks.

Thank you.

And our next question comes from Tyler Van Buren from Piper Sandler Your line is now open.

Hey, guys. Thanks. Good afternoon, just wanted to focus on the second dose specifically with the consolidated dosing regimen.

Operator: Hey, guys. Thanks. Good afternoon.

Operator: Just wanted to focus on the second dose specifically with the consolidated dosing regimen. You know, previously, at the last data update, you guys showed a lower CRS rate than the other therapies and no ICAMs. And so I wanted to... (inaudible) you know, in the broader context of just using ATLOS 647 and not doing conditioning again.

Previously.

The last day to update you guys showed lower crs rate than the other therapies and no I cans and so one of the.

Ask you about the second dose in the <unk>.

Penalty or the potential for it to potentially increase some of those safety events.

And I guess.

The in the broader context of just using allo 647, and not doing conditioning again.

David D. Chang: So Tyler, I'm trying to better understand the question. You know, Rafael, as he stated, I mean, the second dose is the same as the first cell dose of 120 million cells. So the question is around, you know, why 120?

Yeah.

So of Tyler.

Trying to better understand the question.

Sales as he stated I mean, the second dose.

Is the same as the per cell dose of $120 million.

The cells. So the question is around 120 or.

David D. Chang: Or I want to better understand exactly what you're asking. Oh, sorry. Does the second dose add new safety events or make tolerability worse based upon your experience of patients that you've dosed with the consolidated dosing regimen to date? Okay, I got it.

And I understand exactly what you're asking for.

Sorry.

The second dose.

Add new safety events or make tolerability worse based on your experience of patients that we've dosed with the control of the dosing regimen to date.

Okay I got my apologies I think that is a relatively simple question and let me take debt.

David D. Chang: My apologies. I think, you know, that's a relatively simple question. And let me take, I think we are getting to have more and more information on re-dosing, certainly in the days of early Otocar T, when we were re-dosing patients after their first dose of Yaskara, and that's several months later. And one thing that was quite noticeable at the time was that re-dosing, you know, was relatively well tolerated among patients.

I think we are getting to have a growing inflammation with the re dosing certainly in the days of.

Early or the car T, where when we were re dosing patients after first dose with Scott and the several months later and one thing that was quite noticeable at the time was the.

Re dosing was relatively well tolerated among the patients and I think.

David D. Chang: And I think not just us, others are seeing similar trends where re-dosing is much better tolerated the first time. We don't know what the reason is, but I think, you know, there are many things that we can speculate about, but that's not important.

Not just us other yourself seeing similar trend, where we dosing is a much better tolerated than the first time we.

We don't know what the reason is but I think they're on many things that we can speculate about that's not important.

David D. Chang: The way we see it, you know, in terms of consolidation, it's more, you know, concentrated in terms of the time window between the first and second dose. And I feel pretty confident that, you know, reducing as we're doing in consolidation will be relatively well tolerated. And certainly, we are testing that in a phase one setting, which is the right setting to really assess both safety and efficacy. Thanks for taking the question. Thank you. And our next question comes from Michael Schmidt from Guggenheim. Your line is now open.

Way, we see it in terms of consolidation, it's more concentrated in terms of the kind of window between first and second dose, but overall when we look at the data and based on the all my experience.

I feel pretty confident that the reader.

<unk> dosing as way of doing the consolidation of will be relatively well tolerated and certainly we are testing debt in the phase one setting which is the right setting to really.

Yes, most of the both safety and efficacy.

Thanks for taking the question.

Yes.

Thank you.

And our next question comes from Michael Schmidt from Guggenheim. Your line is now open.

Hey, guys I had a question on your Allo 301 sixth program that is now start.

David D. Chang: Hey guys, I had a question on your Allo 316 program that is now starting in phase one. I guess, what type of efficacy and safety profile do you think might be necessary for this in a solid tumor context, specifically in RCC, to ultimately be successful at a minimum? To what degree do you think this could be achieved with this product candidate? already, or whether you think, you know, additional optimization may be necessary down the road, maybe similar to what I've been doing with 501. Thanks so much. Okay, Michael, thank you for those excellent questions. I mean, there are two parts to the question. I mean, one is really, you know, what are we expecting?

Starting in phase one I.

I guess, what what type of efficacy safety profile do you think.

Might be necessary for this and the solid tumor contacts specifically in RCC.

Similarly be successful at a minimum and to what degree do you think.

This could be achieved with this product candidate.

The already or whether you think additional optimization, maybe necessary down the road, maybe so much of what I've been doing the 501. Thanks so much.

Hey, Michael Thank you for those excellent questions.

There are two of parts to the question I mean, what is really.

What what what are we expecting I mean in a solid tumor we have to realize when you look at the renal cell cancer. Despite all of the advances debt has occurred over the last decade still complete responses out there anywhere I mean, if you look at the history of how.

David D. Chang: I mean, in a solid tumor, you know, we have to realize that when you look at renal cell cancer, despite all the advances that have occurred over the last decade, complete responses are still very rare. I mean, if you look at the history of how the solid tumor is currently managed, it's just buying additional time from one treatment to another and continuing that. What we, what to expect from the, you know, the solid tumor trial with 316, which we're very excited about, I mean, I think, you know, time will tell.

The solid tumor is currently manage is just buying additional time from one treatment to another and continuing debt.

What we should expect.

From the the solid tumor trial with two year on six which we're very excited about I mean, I think time will tell.

David D. Chang: I think we are looking at more than just, you know, response. Certainly, whether we get a complete remission in solid tumors will be very important information. And secondly, amongst those who get responses, you know, how long does the response last?

I think we are looking at more than just the response.

Certainly whether we get a complete remission in solid tumor there will be a very important information and second one is really amongst those who get responses. How long does the response loss. So I think we have to factor of many different elements of what we would consider as the.

David D. Chang: So, I think we have to factor in many different elements of what we would consider as a meaningful clinical benefit, which we can, we believe that cell therapy can provide in solid tumors. So, you know, 316 is one of the early and probably the first allogeneic CAR T programs that is going into solid tumors, so stay tuned. The second question is really an important question, you know; what else can we do?

The meaningful clinical benefit, which we can we believe that the cell therapy can provide in solid tumors. So 316 is one of the early and probably the first allogeneic car T programs debt, it's going into the solid tumor so stay tune for the second question is really on important question.

What else can we do a certain.

David D. Chang: Certainly, you know, there's a lot of innovation that's awaiting to occur in the cell therapy space. TurboCAR is one of them, and, you know, TurboCAR is actually a platform approach that we are making to make the allogeneic CAR T cells work better, and we have several different tricks that we are exploring in the preclinical setting that are almost ready to go into the clinic.

Certainly.

There is a lot of innovation that's of waiting to occur in the cell therapy space terrible car is one of them and terrible Kai as you know.

Actually a platform approach that we are making to make the allogeneic car T cells to work better and we have several different tricks that we're exploring in the preclinical setting that is almost ready to go into the clinic, so stay tuned, but we at that point.

David D. Chang: So, stay tuned, but we are definitely planning to continue to innovate from the first generation to the second generation, always looking for the best. Thank you. And thank you. And our next question comes from John Newman from Canaccord. Your line is now open.

Planning to continue to innovate from depressed generation for the second generation always looking for the test.

Thank you.

And thank you and our next question comes from John Newman from Canaccord. Your line is now open.

Hi, guys. Thanks for taking my question question is regarding the.

Operator: Hi guys. Thanks for taking my question. My question is regarding the, I'm just curious, David, if you have an opportunity or if there would perhaps be a need to explore different dose levels of Nerogasistat in the future? If it's more likely that you might simply continue to explore higher doses of 646. You know, great question.

L 715, plus guests debt cohort.

I'm just curious David if you'll have an opportunity or if there would be perhaps.

Need to explore different dose levels of near gas its debt in the future or.

If it's more likely that you might.

Simply continue to explore higher doses of 647.

Great question, that's why we're doing these things in a phase one setting where we had the option of exploring different things and the question of what are too.

David D. Chang: You know, that's why we are doing these things in a phase one setting, where we have the option of exploring different things. And, you know, the question of whether to explore different doses of gamma secretase inhibitor or different doses of cell therapy is really fundamental to any combination therapies being tested. I mean, the hypothesis for these combination studies is very straightforward.

Slower different doses of <unk>.

Tamara secret tastes inhibitor or different doses of cell therapy, that's really fundamental to any combination therapies being tested the hypothesis for the combination study is very straightforward and the way that the study is designed it gives us optionality to.

David D. Chang: And the way that the study is designed, you know, it gives us the option to explore different doses of gamma secretase inhibitors. So, we are very excited, you know, that we were able to clear the IND in record time, and also in the process of activating the sites. So, you know, these are the questions that we will know in the very near future. So, stay tuned. Great, thank you.

For different doses of camera secrets Ace inhibitors. So we are very excited that we were able to clear the dean of record time and also in the process of activating the sites. So this is these are the questions that we will know in very near future. So stay.

Tunes.

Great. Thank you.

David D. Chang: Thank you. And our next question comes from Mark Breidenbach from Oppenheimer. Your line is now open. Hey, guys. Thanks for taking the question. I want to jump back to ILO 316 for a second and that reverse trial.

Thank you and our next question comes from Mark Breidenbach from Oppenheimer. Your line is now open.

Hey, guys. Thanks for taking the question I wanted to jump back to L.

The one six for a second and the reverse trial.

Rafael Amado: I'm wondering if you think you'll need to identify distinct lymphodepletion conditions that are very different from what seems to be working in HEMON settings. And would you consider including IL-2 cytokine support given that IL-2 is already approved in our RCC, you know, aside from a future turbo product? You know, I always get amazed at the sophisticated questions that you ask. Let me, you know, ask Rafael to answer those very important questions. Rafael?

I'm wondering if you you think youll need to identify distinct links of the depletion conditions that are very different from what seems to be working in haemonchus settings, and would you consider including IL two cytokine support given that all of what she was already approved in RCC.

Our side from a future turbo kind of approach.

And I always get amazed of.

The such as the gate of sophisticated questions that you're asking let me ask Rafael to answer goes very important questions.

For a while.

Yeah.

Yes sure so.

Rafael Amado: Yes, Marc. So, I mean, we are definitely planning to follow a variety of translational parameters. Obviously, the initial information that we're seeking is tolerability, so, you know, it's a dose escalation trial. But we will be looking at what happens to these cells, do they traffic to the tumor, do they encounter antigen, do they expand, and do they eventually cause, you know, cytolysis to the tumor cells. We have thought about many combinations.

I mean, we are definitely.

Planning to follow a variety of.

Translational.

Parameters, obviously the initial.

Information that will see gaming for liability so it's a dose escalation trial.

But we will be looking on what happens to the south the the traffic to the tumor do the encounter antigen.

Do they expand.

And do eventually cost side.

Side of the license to the tumor cells.

We have thought about combination this is an immunogenic tumor as you know and.

Rafael Amado: This is an immunogenic tumor, as you know, and whether it's IL-2 support or PD-1, those are things that may come in the future, along with potential modifications of the construct itself, such as what David was referring to before. In terms of the lymphodepletion, that's an unknown, and we will be testing that in the Phase 1 study. One thing that I would say is that CD70 is also in lymphocytes. It's actually a marker that was discovered in lymphocytes, and it's actually expressed in activated lymphocytes. So it is possible that alloreactive lymphocytes may be susceptible to depletion by the CAR.

On whether its child to support or.

The PD one.

Those are things that may come in the future along with potential.

Modifications of the construct itself.

Such as what David was referring to before.

So the link for the ablation.

That's an unknown and we will be testing that.

In the Phase one study one thing that I would say is the C. 17 is also in lymphocytes, it's actually a market of whats discovering lymphocytes.

It's actually expressed in activated lymphocytes. So it is possible debt Hello, reactive lymphocytes, maybe susceptible to depletion by by the car so because of that.

Rafael Amado: So because of that, we are obviously starting, you know, carefully with doses, and then we will continue to escalate as we see that the program is safe. So it's a fascinating question, you know, what kind of lymphodepletion we will need because of the biology of the target, and as well as the biology of the tumor, what kind of partner, perhaps, we will need to be using with the CAR to make it effective and lead to a complete response. Yeah, and I would just add, you know, besides those things, the patient's prior treatment history. Thank you very much. Super, thank you.

Obviously, starting carefully with the doses.

And then we will continue to escalate that's we see that the.

For me safe.

It's a it's a fascinating question.

What kind of linked for depletion, we wouldn't need because of the biology of the target.

And as well as the biology of the tumor or on what kind of partner of perhaps we will need to be using with the car to make it.

Effective on.

The need to complete responses.

Yeah and I'll just.

Besides those the patients prior treatment history.

Debt also influences patients underlying base of conditions about their immune system, which is relevant as we think of that the Olympic depletion. So.

Rafael Amado: And thank you. And our next question comes from Corey Kazimoff from J.P. Morgan. Your line is now open. Hey, guys. Thanks for taking my question. This is Matthew.

We rely on a lot on our translational and clinical groups to find answers to these important questions as we are studying.

Taking a new path in solid tumors.

Super Thank you.

And thank you and our next question comes from core CASM off from J P. Morgan. Your line is now open.

Operator: And, Corey, just a quick one for me. Can you remind us if you're looking at anti-CAR antibodies in your Alpha and Alpha 2 studies and whether we might get some of this data at ASCO? Okay, Rafael, you want to cover that? Yeah, just very simply, we are looking for, and we plan to disclose, you know, a variety of translational markers, including anti-car antibodies. Great, thank you. Thank you. And our next question comes from Luca Isi. From RBC, your line is now open. Oh, hi everyone.

Hey, guys. Thanks for taking my question. This is Matthew on for Cory.

Sorry, just a quick one for me can you remind us if you are looking at anti <unk> antibodies and you're all set on the two studies on whether we might get some of the Dana at Harsco.

Okay.

Rafael covered net.

Yeah, just very simply we are looking and we plan to.

On this close.

A variety of translation of markers, including including anti <unk> antibodies.

Great. Thank you.

Thank you and our next question comes from Luca <unk> ISI.

From RBC. Your line is now open.

Hello, Hi, everyone great. Thanks for taking our question. This is at least for Walter on some of the Easter from RBC I just wanted to get it can't continue the conversation on the game and if I could tell from other areas. So.

Operator: Great. Thanks for taking our question. This is Lisa Walter on for Luke at UC from RBC. I just wanted to continue the conversation on the gamma secretase inhibitors. So, the gamma secretase inhibitor obviously induces the expression of BCMA.

Again, the secretary of inhibitor, obviously increases the expression of the CMA. So do you think that it will just improve the response rate, but not maybe not necessarily of the duration of response the.

David D. Chang: So, do you think that it will just improve the response rate but maybe not necessarily the duration of response? The reason why I'm asking is because, you know, we've seen some impressive data from Fred Hutch at ASH 2019, but we haven't seen an update on the data since then. So, just wondering if you have any thoughts on this. Thank you.

The reason line asking is because we've seen from <unk> question.

From Fred Hutch at Ash 2019, but we haven't seen an update on the data from San So just wondering if you have any thoughts on the thank you.

So Lisa let me take that question.

David D. Chang: You know, what the field has seen, and I think this is something that we have seen from the early days of the CAR-T trial, where, you know, others who generate the data keep finding this similar pattern. You know, one, cell expansion tends to correlate with the response, especially the depth of the response, and it correlates with the durability of the response. So, you know, one of the sort of underlying hypotheses that we want to test in the combination study is whether as we increase the density of the DCMA on the multiple myeloma cells, we can get a deep response.

You know what the appeal of has seen and I think this is something that we have seen from the early days on car T trial, where.

Others, who will generate the data keep.

Find the similar pattern one.

Cell expansion tend to correlate with the response and the response, especially the depth of response tend to correlate with the durability of the response.

So one of the sort of underlying hypothesis that we want to test in the combination study is as we increase the density of the DCA may on the multiple myeloma cells.

Can we get a deep response. So response as you know partial response very good partial response or complete remission stringent complete response and also <unk> status I think all of these different levels of responses that we can look into and I think they will tell part of debt and.

David D. Chang: So response, as you know, partial response, very good partial response, complete remission, stringent complete response, and also, you know, MRD status. I think all these are different levels of responses that we can look into, and I think they will tell us quite a bit. And, you know, the question about, you know, response and durability, that are somewhat linked in cell therapy, in my experience. So, you know, excellent question.

The question about response, and the durability debt somewhat linked in the.

In the south therapy in my experience so excellent question.

David D. Chang: The second part to your question about updates from Fred Hutch, I don't know what's going on there. I think they will update at some time in the near future, but this is a very interesting hypothesis, and this is a very interesting concept that we feel that we have to test as we advance our BCMA CAR programs in multiple myeloma. Great, thanks for taking the questions. Thank you. And our next question comes from Ren Benjamin from JMP Security. Your line is now open.

The second part to your question about updates from Fred Hutch, I don't know, what's going on there hopefully they will update in sometime in the future but.

This is the very interesting hypothesis and this is a very interesting concept that we feel that we have to test as we advance our be CMA car programs in multiple myeloma.

Great. Thanks for taking the question.

Thank you.

And our next question comes from Ren Benjamin from JMP Securities. Your line is now open Hey.

Operator: Hey, good afternoon, guys. Thanks for taking the questions. I guess one for me, just from a manufacturing perspective, Cellforge One is going to be up and running. Can you just talk a little bit about how the products get integrated into the existing trials? Does it kind of just come on full-blown with the pivotal study or slowly get integrated?

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

Just one for me just from a manufacturing perspective sales force one is going to be up and running can you just talk a little bit about how the products get integrated into the existing trials does it for the kind of just come on for one with the pivotal study or.

Slowly get integrated how many.

Eric Schmidt: How many facilities do you think, how many Cellforges do you think you might ultimately have across the US as well? Eric, CellForge Fund. This is something that you're paying close attention to. Do you want to cover the answer about the capacity, and I'll come back and cover the questions about integration?

Facilities do you think how many cell for just do you think you might ultimately have across the U S as well and what's the capacity.

You know Eric South for trial. This is something that you're paying close attention to do you want to cover the answer about the share.

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So by the integration.

Eric Schmidt: Okay. I mean, in terms of capacity, REM is a very large facility. I think, as we've talked before, it's 120,000 square feet.

Okay. I mean in terms of capacity ran that's the very large facility I think as we've talked before it's a 120000 square feet the.

Construction is essentially complete and we're now in a position where we can begin to activate and operationalized manufacturing of the facilities. So a lot of effort a lot of investment has gone in to make the state of the art.

Eric Schmidt: The construction is essentially complete, and we're now in a position where we can begin to activate and operationalize manufacturing in the facility. So a lot of effort and a lot of investment have gone in to make this state-of-the-art facility, and we're very proud of its becoming operational this year. In terms of the capacity, we've spoken in the past about being able to commercialize, on a global basis, multiple products from It's modular in its design, so it's quite flexible and quite large and can certainly suit us for the foreseeable future.

And we're very proud.

It's becoming operational this year.

In terms of the capacity we've spoken in the past about being able to commercialize on a global basis multiple products from this facility. Its modular design, so its quite flexible and quite large and can certainly suit us for the foreseeable future David back to you.

David D. Chang: David, back to you. Yes, so the first question is a very important one, you know, which is, you know, really rephrasing your question. You know, right now, we are making the cell product using a contract manufacturer. Now you have the process going over to our own facility, CellForge1, how do you source the clinical studies with, you know, different manufacturing sites? I mean, this is something that, you know, we have, you know, I personally have a lot of experience having done that at KITE, where we went from the contract manufacturer to our own manufacturing facility.

Yes. So the first question is a very important line, which is really in a rephrasing. The question you know right now we are making the south product using the contract manufacturer now you're of the process going over to our own facility south for which one.

How do you source of the clinical studies with the different.

<unk> manufacturing I mean, this is something that we have.

And I have a lot of experience having done that at kite.

Where we went from the contract manufacturer to al on manufacturing facility and in terms of how to do that and what's also required part of which is.

David D. Chang: And you know, in terms of how to do that and what's also required, part of which is, you know, being able to characterize your product, analytic assay capability, which we have been building internally within our tech ops group.

Being able to characterize product analytic assay capability, which we have been building internally within our tech ops growth. So very important question something that we have a lot of experiences and and I feel very confident debt, we will be able to handle this very smoothly.

David D. Chang: So a very important question, something that we have a lot of experience with, and I feel very confident that, you know, we will be able to handle this very smoothly. Terrific. Thank you. Thank you. And our next question comes from Ben Burnett from Stiefel. Your line is now open. Hi, good afternoon. This is Carolina Ibanez on behalf of Ben Burnett.

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Terrific. Thank you.

Thank you.

And our next question comes from Ben Burnett from Stifel. Your line is now open.

Hi, Good afternoon. This is kind of lean I believe its on for than book net Thank you for taking our question.

Operator: Thank you for taking our question. As a follow-up to the previous questions on ARLOS 715 in combination with neurogastrostat, can you provide additional details on the type of patients you are enrolling, whether or not you plan to test both low- and high-dose ARLOS 607, and when do you expect to have initial data? Thank you. Raphael.

The follow up to the previous questions on Allo seven.

And one five in combination with the needle cash Pat kind of can provide additional details on the type of patient journey from probing with or not.

Do you plan to test ball.

So on high dose on the success of Samsung.

And when do you expect to have initial data. Thank you.

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Rafael.

Rafael Amado: Sure. So the study is... Exploring ALO647 and also doses of neurogastrostat as well, the cell dose is going to be relatively small. We'll study a limited number of cell doses because we have an idea from 7.1.5 of what doses are active. In terms of when we will have data on this, the study just started, and as I said, there's some exploration that we need to do in dose escalation on a variety of parameters. We anticipate to have data probably not this year but early next year. That's our projection.

Sure. So the study.

Uh huh.

The exploring all of six for seven and also of doses so from Europe ex the status as well.

The cell doses.

The relatively.

Thanks will.

Study.

The limited number of cell dose that's because we have an idea from 715 of what doses are.

Active.

In terms so when we will have data on this on the study just started on.

I said there is some.

On exploration that we need to do in dose escalation in a variety of parameters. So we anticipate to have data probably not this year, but early next year that the.

Our projection.

Rafael Amado: Thank you. And our next question comes from Jason Gerberry from Bank of America. Hi, this is Sadi Rahman on behalf of Jason.

Thank you.

And our next question comes from Jason <unk> from Bank of America.

Hi, This is Saudi on line on for Jason Thanks for taking our question.

David D. Chang: Thanks for taking our question. For the CD19 update at ASCO, I know you started enrolling pretty recently. So can you talk about the pace of enrollment and give some idea of the number of patients we might see that are treated with both doses of the consolidation regimen? I'm trying to understand how meaningful the update could be and if there would be enough patients followed at least a month after the second dose to gauge how response rates might improve compared to the single infusion. Excellent question. This is David.

For the CD 19 update on ESCO.

He started enrolling pretty recently, so can you talk about the pace of enrollment and get some idea on.

The number of patients we might see that are treated with both doses of the consolidation regimen.

I'm trying to understand how meaningful that could be in there would be enough patients follow the got at least of months. After the second dose to gauge how response rates.

The improved compared to the single infusion.

Ex.

Excellent question. Let me. This is David let me take the question as I've said, we're getting pretty close to ask what time. So we're not kind of go too much into the details of.

David D. Chang: Let me take the question. As I've said, we're getting pretty close to ASCO time, so we're not going to go too much into the details, but I would sort of look at our record of study enrollment. We have highlighted the fact that since we started the clinical programs across CD19, we have an outstanding clinical team that is managing the enrollment and also patient follow-up issues. So we are still enrolling, and we are hoping that we can provide a meaningful update, as we have done in the past two presentations. Okay, thank you. Thank you. And our next question comes from Dane Leon from Raymond James. Your line is now open. Hey guys, this is Bowen on for Dane.

But I would sort of look at our record.

<unk> enrollment.

We have highlighted the fact debt.

Since the since we started the clinical programs.

Across the CD 19, and day CMA, we have enrolled 75 plus patients.

And we have the outstanding clinical team that is managing the enrollment and also of patient follow up of issues. So.

We are still enrolling and we are hoping that we can provide a meaningful update as we have done in the past two presentations.

Yes.

Okay. Thank you.

Thank you.

And our next question comes from Dane Leone.

From Raymond James.

Your line is now open.

Hey, guys just as Boeing on for Dane. Thanks for taking our question just one from us on our seven five.

Operator: Thanks for taking our question. Just one from us on ALS 705 So when we're talking about redoing patients, can you just give a little bit more color on the criteria you would be using there? Okay, Rafael. I would ask Rafael to respond to a question. Yeah, so we have not yet started consolidation in the ALOS 715, that's why, you know, it wasn't mentioned in the opening remarks. You know, we saw meaningful responses as well as BGPR+, as I mentioned earlier, at 60% and 40%, respectively, with 320 million cells. And now we have finished the dose escalation with ALOS 647, as well as the cell dose. So we are starting the Augusta stat, as we've been discussing today.

So when we're talking about the dosing patients can you just give them a little bit more.

Color on the criteria you would be using there.

Okay Rockdale.

I would ask for ourselves to respond the questions.

Yeah. So we have not yet started.

Consolidation in the all of 715, that's the way it wasn't mentioned.

And in the opening remarks.

We we so meaningful responses as well.

The EPS plus as I mentioned.

Earlier.

And the 60% on 40% respectively.

With 320 million cells.

And now.

We have finished the.

The dose escalation with the allo six for seven.

For a loss.

On the cell dose. So we are restarting yogurts the status we've been discussing today, we're looking forward to start 600 price and the next thing to explore.

Rafael Amado: We're looking forward to starting 605. And the next thing to explore in 715 is consolidation, and that is something that we're looking forward to doing. It may be slightly different in design than the ALPHA study due to the nature of the disease, but stay tuned for that in an upcoming update. Great. Thank you. Thank you. And our next question comes from Raju Prasad from William Blair. Your line is now open.

Explored and seven one times this consolidation and that is something that we're looking forward to doing it maybe slightly different in designed on the alpha.

The study due to the nature of the of the disease.

But stay tuned to that in the upcoming update.

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Great. Thank you.

Thank you.

And our next question comes from Raju Prasad from William Blair. Your line is now open.

Operator: Thanks for taking the question. There's been some discussion in the BCMA space on antigen escape and anti-drug antibodies from some of the autologous data that's been analyzed. Can you maybe just talk a little bit about that aspect and how you anticipate, you know, neurogasasset and, more importantly, the turbo car to potentially help mitigate some of those potential concerns? Thanks. Yeah, let me take that question. I think the first question concerns the antigen escape, which is a DCMA loss that I think you're referring to. If anything, I mean, I think this is something that the field has been looking for some time.

Thanks for taking the question there's been some discussion in the dcms space on it.

Antigen escape and anti drug antibodies from some of the autologous data. That's been analyzed can you maybe just talk a little bit about that aspect and.

How you anticipate neuro gases that and more importantly, the turbo car to potentially.

On help mitigate kind of some of those.

The potential concerns.

Yeah, Let me take the question I think the first question of the antigen escape, which is E. CMA losses, I think you're referring to.

If anything I mean, I think this is something that the field has been looking for some time.

David D. Chang: And, you know, also the data that was published in the New England Journal of Medicine on BB21 certainly tells you that antigen escape is, you know, a relatively infrequent event in multiple myelomas. So, obviously, we are learning about the biology of different tumors, but that's the status of it. And we will continue to follow in our study about the occurrence of antigen loss. You know, the second question around the anti-drug antibody.

And also the data that was published in New England Journal Medicine on the.

The.

PV 'twenty one 'twenty one.

Certainly tells you that the antigen escape.

Yes.

On a relatively infrequent event in multiple myeloma so.

Obviously, we are learning about the biology of different tumors, but.

What's the status of it and we will continue to follow.

<unk> about the occurrence of the antigen loss.

The second question around the anti drug antibody.

David D. Chang: You know, that is somewhat difficult to respond to because there are some variability in how different companies measure anti-drug antibodies, and this is something that, you know, we knew for some time from the early days of Ocollis-Kharki therapy. In terms of, you know, whether the anti-drug antibodies affect, you know, the response and all those things, I think at this point there's no evidence that anti-drug antibodies have any negative consequences, but this is something that we will be testing in our own studies, and we will look for any evidence of, you know, what the anti-drug antibody, if it occurs, will do to the...

That is somewhat difficult to respond to because there are some variability in how different companies measured anti drug antibodies.

And this is something that we knew for some time from the early days of what college of car T therapy.

In terms of letter the anti drug antibodies effect.

Net debt the.

The response in all of those things I think at this point, there's no evidence that anti drug antibodies had any negative consequences, but this is something that we will be testing in our studies and we will look for any evidence of.

You know what the anti drug antibody if it occurs will do to the efficacy so stay tuned.

David D. Chang: So, stay tuned. Thank you. And our next question comes from Asthika Goonewardene from Truist Security. Your line is now open. Hi, guys. Good evening, and thanks for squeezing me in. So I want to talk a little bit about expectations for homing and penetration with Allo316.

Thank you.

And our next question comes from Africa, Ghana, Barney from true Securities.

Your line is now open.

Hi, guys good evening and thanks for squeezing me in.

So I wanted to talk a little bit about.

Expectations for homing in penetration.

Our 316 I'm wondering if you can discuss what your preclinical experiments have shown you and how would you sort of expectations for that and also what kind of persistence you expect based on preclinical data of.

Rafael Amado: I wonder if you can discuss what your preclinical experiments have shown you and how you have set expectations for that, and also what kind of persistence you expect based on preclinical data of 316 in a tumor microenvironment. Thanks a lot. Now, Rafael, do you want to take that question?

360 of the tumor microenvironment, thanks, a lot.

Rafael do you want to take the question.

Sure so.

Rafael Amado: Sure. So, the product in preclinical studies performs incredibly well. So, we do a variety of in vitro assays as well as animal modeling. In vitro assays, we obviously challenge the product with CD17 positives for our cells, and, you know, we continue to re-challenge, and we continue to see killing. The cells diminish in terms of persistence until they get re-challenged again, and then you see a resurgence. This is more pronounced in general in the case of turbo cars, but it's seen also in 316.

The the product in preclinical studies performs.

Incredibly well so we do a variety of in vitro assays as well of animal modeling.

You mean the draw phase.

Obviously the challenge.

The product with <unk>.

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All of US and we continue to re challenge and we've continued to see killing.

The south diminish in terms of persistence until they get challenged again and then you see again.

A resurgence.

This is more pronounced.

In general in the case tubal cars, but as seen also in the in Q1 six.

Rafael Amado: In animal models, we have done a variety of them, including PDX models that are, you know, animals, immunocompromised animals that contain human tumors, and we've seen penetration of the CARB T-positive cells into the tumor, into the stroma, and disappearance of these tumors. And again, these are not xenografts or cell lines. These are actual cells or tumors rather that come from metastasis procured from surgical excisions.

In animal models, we have done a variety of them, including Pdx model already.

On the malls.

Compromised animals could contain.

On a human tumors and we've seen our penetration of the car T positive sales linked to the tumor into.

Into the stroma and.

On disappearance of these tumors on again deciding on the.

No graft on cell lines sort of actual sales or two months, rather that come from metastases procure from surgical acquisitions.

Rafael Amado: So, if the preclinical data is a good omen for what's going to happen in the clinic, we're pretty pleased with what we've seen thus far. Great, thank you. And I would now like to turn the call back over to management for closing remarks. Thank you for joining us on our earnings call and for many outstanding questions. As we close out the call, I'd like to thank our team at Allogene and our many partners and collaborators who overcame the global challenges of 2020 to make the progress we highlight today possible. Operator, you may now disconnect. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect. Everyone have a great day. Thank you for watching.

So.

The preclinical data as the boot all meant to what's going to happen in the clinic.

We're pretty pleased with what we've seen thus far.

Great. Thank you.

Thank you.

And I would now like to turn the call back over to management for closing remarks.

Thank you for joining us on our earnings call and for many outstanding questions as we close out the call I'd like to thank our team at Allergan and our many partners and collaborators who overcame the global challenges of 2020 to make the progress we highlight today possible.

Operator, you may now disconnect.

Thank you ladies and gentlemen. This concludes today's conference call. Thank you for participating and you may now disconnect everyone have a great day.

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