Q2 2021 Allogene Therapeutics Inc Earnings Call

Hello, Thank you for standing by and welcome to the allergy and Therapeutics second quarter 2021 conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask the question. During the session you will need to press star 1 on your telephone please.

Operator: Thank you for standing by, and welcome to Allogene Therapeutics' second quarter 2021 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be aware that today's conference call is being recorded. I would now like to turn the call over to Christine Cassiano, Chief Communications Officer. Ms. Cassiano, please go ahead.

Be aware of that todays conference call is being recorded I would now like to turn the call over to Christine Casciano, Chief Communications Officer Ms. Casiano. Please go ahead.

Christine Cassiano: Thank you, operator, and to all on the line. We will continue to limit questions to one per person so we can get to as many as possible during the hour.

Thank you operator, and so all of them on the line welcome we will continue to limit questions to 1 per person. So we can get to as many as possible during the hour.

Christine Cassiano: After the market closed today, Allogene issued a press release that provides a corporate update and financial results for Q2 2021. This press release and today's webcast are both available on our website. Joining me on the call today is Dr. David Chang.

After the market close today allergy and issued a press release that provides the corporate update and financial results for Q2.2021. This press release and today's webcast are both available on our website.

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

Christine Cassiano: 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.

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, including the timing and ability to advance our al for 2 trial to phase 2 data presentations regulatory filings future research and development efforts and manufacturing capabilities and 2.

Christine Cassiano: These may include statements regarding the success and timing of our ongoing and planned clinical trials, including the timing and ability to advance our Alpha-2 trial to Phase 2, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, and 2021 financial guidance, among other things. Such forward-looking statements are based on current information, assumptions, and expectations that are subject to change. A description of potential risks can be found in our earnings press release and latest SEC disclosure documents. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update these statements.

<unk> thousand and 21 financial guidance among other things.

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

David D. Chang: I'll now turn the call over to David. Thank you, Christine, and good afternoon. We launched Allogene in the second quarter of 2018 with a bold mission to create and lead the next revolution in cancer treatment by delivering to patients the first allococci therapies for blood cancers and thalassemia. Three years later, we have made a giant leap for both allogene and the field of cell therapy as data from our LEAD program brings us one major step closer to realizing our goal of commercializing a first-in-class and best-in-class off-the-shelf cell therapy.

I'll now turn the call over to David.

Thank you Christine and good afternoon, we launched allergy and in the second quarter of 2018 with the bold mission.

To create and lead the next revolution in cancer treatment by delivering to patients. The first allo car T therapies for blood cancers and solid tumors.

3 years later, we have made a giant leap for both the allergy and the field of cell therapy as data from our lead program brings us 1 major step closer to realizing our goal of commercializing of first in class and best in class off the shelf cell therapy.

David D. Chang: As we enter a new stage in our life cycle, our focus turns towards advancing our lead development candidate, RO501A, into a pivotal Phase II trial for relapsed refractory non-Hodgkin's lymphoma by the end of 2021. Following initial data presented at our CD19 forum in May and ASCO in June, we are increasingly confident in the safety and efficacy profiles of LO501A and its path forward. As we shared during the CD19 forum, the ALPHA trial demonstrated that ALO501 can achieve deep and durable responses in patients with relapsed refractory non-hoxygen lymphoma who are CAR T naive, with an overall response rate of 75% and CR rate of 50%, and a six-month CR rate of 36% in patients with large B-cell lymphoma histology, which is the The safety profile was also very encouraging.

As we enter a new stage and our lifecycle are focused on is towards advancing our lead develop and candidate Allo 501 day into a pivotal phase II trial for relapsed refractory non hodgkin's lymphoma by the end.

And the 2021.

Following initial data presented at our CD 19 Forum and May and ask Lee and June.

And increasingly confident in the safety and efficacy profile of Allo 501 day and its path forward.

As we share during the CD 19 Forum the.

Alpha trial demonstrated that allo 501 can achieve deep and durable responses in patients with relapsed refractory non hodgkin's lymphoma, who of car T naive.

On overall response rate of 75% and CR rate of 50% and the 6 months of VR rate of 36% and patients with large b cell lymphoma histology.

Which is the patient population about first pivotal trial.

The safety profile was also very encouraging no dose limiting toxicities of graft versus host disease, and limited ICANN and cytokine release syndrome observed.

I have been involved in the development of car T therapies from the early days and the available efficacy and safety profile of Allo 501, and Allo 501, 8 clearly show that all of the key principles day, we learned from autologous CD 19 car T therapies are holding true in our allogeneic car T.

David D. Chang: No dose-limiting toxicities or graft-versus-host disease, and limited ICANN and cytokine relief syndromes were observed. I have been involved in the development of CAR-T therapies from the early days, and the available efficacy and safety profile of ALLO501 and ALLO501A clearly show that all the key principles that we learned from autologous CD19 CAR-T therapies are holding true in our allogeneic CAR Setting aside the limitations of drawing a cross-trial comparison,

IP.

Setting aside the limitations of drawing a cross trial comparison, what we are seeing in our studies both in the initial responses.

The ability of responses and the safety profile from a single infusion of Allo 501, or Allo 501, a are on par with the data from pivotal trials of SBA approved autologous CD 19 car T therapies.

Meanwhile, we have exceeded the bar set by the autologous therapies in other respects.

David D. Chang: What we are seeing in our studies, both in the initial responses, durability of responses, and the safety profile from a single infusion of LO501 or LO501A, is on par with the data from pivotal trials of FDA-approved autologous CD19 CAR-T therapy. However, at the same time, we have exceeded the bar set by autologous therapies in other respects. Our allocarditis therapies can be delivered to patients within days rather than weeks, and patients who are enrolled in our studies can be nearly guaranteed to receive our products.

Our allo car T therapies can be delivered to patients within days rather than weeks.

And patients who enrolled in our studies can be nearly guaranteed to receive our products.

And the Alpha trial 98 per cent of the enrolled patients received allo 501 within a median time of 5 days from enrollment to startup therapy.

By comparison and trials deploying autologous therapies up to 30% of patients who have undergone leukapheresis for set of manufacturing well unable to receive treatment due to the interval of disease progression, while waiting for the car T cell products or even worse due to manufacturing failures.

Given the tremendous benefit that allo 501 day can bring to patients we remain highly focused on execution.

David D. Chang: In the alpha trial, 98% of the enrolled patients received Allo501 within a median time of five days from enrollment to start of therapy. By comparison, in trials deploying autologous therapies, up to 30% of patients who have undergone leukopoiesis for thumb manufacturing were unable to receive treatment due to interval disease progression while waiting for the CAR-T cell products, or even worse, due to manufacturing failure.

Top of mind today is our preparation for the industry's first allogeneic pivotal trial.

As our planning towards this important milestone progresses, we look forward to providing a clinical update on our CD 19 program and the fourth quarter.

Shortening the time to treatment and ensuring access for nearly all suitable patient is just the beginning of how we can leverage the attributes of allogeneic car T therapies.

As we look down the line for next generation therapies. Our aim is potentially enhance the efficacy and safety of our.

David D. Chang: Given the tremendous benefit that ALLO501A can bring to patients, we remain highly focused on execution. Top of mind today is our preparation for the industry's first allogeneic pivotal trial. As our planning towards this important milestone progresses, we look forward to providing a clinical update on our CD19 program in the fourth quarter. Shortening the time to treatment and ensuring access for nearly all suitable patients is just the beginning of how we can leverage the attributes of allogeneic cardiotherapy.

Products beyond that of the autologous therapies.

Our research team is actively working on new strategies to ebay premature injection.

The enhanced cell potency and improved product consistency and overcome the solid tumor microenvironment.

Some of these technologies such as our Turbo car T approach have now advanced into clinical development.

Others are progressing nicely behind the scenes so while the initiation of our first pivotal trial will represent a critically important milestone for allergy and it represents just the beginning of our new product innovation cycle.

We are now also preparing for the potential of transition from a clinical stage company to a commercial enterprise.

We have begun to build our commercial team, which will focus on product positioning maximizing adoption and ensuring access.

David D. Chang: As we look down the line to next-generation therapies, our aim is potentially enhanced efficacy and safety of our products beyond that of autologous therapies. Our research team is actively working on new strategies to evade premature ejection, enhance cell potency, improve product consistency, and overcome the thalatumor microenvironment. Some of these technologies, such as our therapeutic approach, have now advanced into clinical development. Others are progressing nicely behind the...

We have bolstered our internal efforts by expanding our board with the appointments of Liz Barrett and biggest saddle as directors is currently the president and CEO of the origin and former CEO of Novartis oncology is 1 of the rare executives with deep experience in the commercial.

The nation and launch of novel oncology therapies, including and autologous car T therapy.

The key a former professor and practice of molecular and cell biology at Harvard University, and President of vertex has an exceptional track record of operational execution at several leading biotechnology companies.

The new board members will be vitally important as we prepare for the potential launch of the first in class product.

David D. Chang: So, while the initiation of our first pivotal trial will represent a critically important milestone for Allogene, it represents just the beginning of our new product innovation cycle. We are now also preparing for the potential transition from a clinical stage company to a commercial enterprise. We have begun to build our commercial team, which will focus on product positioning, maximizing adoption, and ensuring access. We have bolstered our internal efforts by expanding our board with the appointment of Liz Barrett and Becky Saddle as directors.

Which brings us to manufacturing from the beginning of allergy and we have maintained the us heading in house manufacturing capabilities with the key to controlling our ability to deliver off the shelf car T cell therapies faster more reliably and at greater scale to all patients.

Later this month.

We will host an event to inaugurate our sales force 1 state of the art manufacturing facility in Newark, California.

The facility is intended to house commercial manufacturing and analytical testing formulation and packaging and distribution of cell therapies.

David D. Chang: Liz, currently the president and CEO of Urgent and former CEO of Novartis Oncology, is one of the rare executives with deep experience in the commercialization and launch of novel oncology therapies, including an autologous CAR T-therapy. Vicky, a former professor in practice of molecular and cell biology at Harvard University.

Wowing us to optimize the important steps in the cell therapy of production process and allow allo car T therapies to be available to patients within days.

We're excited to showcase the convergence of scientific excellence and cutting edge manufacturing it ourself for which 1 facility the.

And the rapid Buildout and Operationalization of this facility is yet again. Another example of our team's determination to let nothing including the unforeseen challenges presented by a global pandemic hit and the way of our goal.

David D. Chang: And President of Vertex has an exceptional track record of operational execution at several leading biotechnology companies. Our new board members will be vitally important as we prepare for the potential launch of a first-in-class product. Which brings us to many facts.

And to bring the first allogeneic car T therapy to patients.

I. Thank them for this tireless efforts to bring this facility online in preparation for cgmp manufacturing and the second half of 2021.

Positive phase 1 data from our alpha and offer to as presented at Ash coal and our CV 19 Forum continues to validate our allogeneic platform and.

David D. Chang: From the beginning of Allogene, we have maintained that having in-house manufacturing capabilities would be key to controlling our ability to deliver off-the-shelf, cut-key cell therapies faster, more reliably, and at greater scale to all patients. Later this month, we will host an event to inaugurate our CellForge®-1 state-of-the-art manufacturing facility in Newark, California. The facility is intended to house commercial manufacturing, analytical testing, formulation, packaging, and distribution of cell therapies, allowing us to optimize important steps in the cell therapy production process and allow allocardiotherapies to be available to patients within days.

And we are aggressively advancing our pipeline with more confidence than ever before we currently have 5 clinical trials underway.

And our CD 19 program as noted 2 of candidates that target the CMA, including 1 that incorporates our novel Turbo car technology, and 1 program and solid tumors.

Our robust multiple myeloma program is an example of how we've been able to rapidly advance optimize and deliver meaningful progress across multiple strategic approaches to allogeneic car T.

Beyond our ongoing universe of trial, we were pleased that our first turbo car clinical candidate Allo 6 of <unk>, We received U S. FDA fast track designation for the treatment of patients with relapsed and refractory multiple myeloma we.

We are excited to announce that we have begun dosing patients in phase 1 of the ignite study of Allo 605.

David D. Chang: We are excited to showcase the convergence of scientific excellence and cutting-edge manufacturing at our CellForge1 facility. The rapid build-out and operationalization of this facility is yet another example of our team's determination to let nothing, including the unforeseen challenges presented by a global pandemic, get in the way of our goal to bring the first allogeneic RT therapy to patients. I thank them for their tireless efforts to bring this facility online in preparation for CGMP manufacturing in the second half of 2021.

We also have our sights set on confronting solid tumors, where the need is unquestionably the high for a new innovation we remain.

And optimistic for the potential of our Allo car T platform to rise to the challenge.

Our initial program target CD 17, and earlier this year, we launched our true burst trial evaluating allo, 3.1 and 6 in clear cell renal cell carcinoma.

As we continue to treat patients we plan to share initial data next year.

Over the next 6 to 12 months, we expect to have an increasing amount of data across multiple programs that will provide critical insight and.

David D. Chang: Positive Phase I data from our Alpha and Alpha-2, as presented at ASCO and our CD19 forum, continue to validate our allogeneic platform, and we are aggressively advancing our pipeline with more confidence than ever before. We currently have five clinical trials underway, two in our CD90 program, as noted, two candidates that target BCMA, including one that incorporates our novel turbo car technology, and one program in solitum.

And the informed how we best optimize the promise of our platform.

Unwavering execution has already allowed us to generate the largest set of clinical and translational data on our car T therapies.

Which we will continue to deploy towards enhancing our product candidates.

We are incredibly proud of what we have achieved to date only made possible by our team's steadfast focus on making allogeneic car T therapy, a reality for patients.

1 of being an industry leader often entails overcoming obstacles and it also provides the privilege of being able to set the pace of innovation.

David D. Chang: Our robust multiple myeloma program is an example of how we've been able to rapidly advance, optimize, and deliver meaningful progress across multiple strategic approaches to allogeneic heart disease. Beyond our ongoing universal trial, we were pleased that our first turbo car clinical candidate, ALOF605, received USFDA Fast-Track designation for the treatment of patients with relapsed and refractory multiple myeloma. We are excited to announce that we have begun dosing patients in Phase 1 of the IGNITE study of Allo605.

Shape important parameters in the field and define success.

And allergy and we believe we are up to this challenge.

And we are grateful for your support as the vision for the future of Allogeneic car T therapies is continuing to materialize.

I will now turn the call over to Rafael for more in depth look at our research and development activities.

Thank you David as you might anticipate on research and clinical teams have been increasingly focused on advancing our portfolio of allo car T therapy.

As David mentioned, we are on track with our plans to initiate the pivotal phase II trial for Allo, 500, RNA and non Hodgkin's lymphoma.

We view the data that we reported in May for the Alpha trial, including out of 36% complete response rate of 6 months and large T cell lymphoma is a true.

David D. Chang: We also have our sights set on confronting solid tumors where the need is unquestionably high for new innovation. We remain optimistic about the potential of our Allocardi platform to rise to the challenge. Our initial program targets CD70, and earlier this year, we launched our Traverse Trial Evaluating Allose 316 in clear cell renal cell carcinoma. As we continue to treat patients, we plan to share initial data next year. Over the next 6 to 12 months, we expect to have an increasing amount of data across multiple programs that will provide critical insights and inform how we best optimize the promise of our platform.

And that we are on the right track and look forward to exploring whether the use of consolidation therapy might lead to even greater promise.

And of course, all non Hodgkin's lymphoma, histology Allo 501 demonstrated on overall response rate of 75% and a C.

The rate of 50 per saying of course, histology and car T naive patients with the <unk>.

Time of the data cut off the longest ongoing complete response was at 15 months and both large b cell lymphoma, and Follicular lymphoma, and importantly, given our intent to move out of <unk> into our people don't study.

So able to demonstrate that all of <unk>, which eliminates the rituximab recognition domains and allo 501 to allow for use and a broader patient population have comparable safety and efficacy to all of fibre 1.

As we look to find ways to maximize all levers of afforded to us by the nature of our allogeneic platform..1 area of distinction for US is arlene for depletion platform, which supports consolidator of dosing.

David D. Chang: Unwavering execution has already allowed us to generate the largest set of clinical and translational data on allocardial therapy, which we will continue to deploy towards enhancing our product candidates. We are incredibly proud of what we have achieved to date. Only made possible by our team's steadfast focus on making allogeneic heart disease therapy a reality for patients. While being an industry leader often entails overcoming tall obstacles, it also provides the privilege of being able to set the pace of innovation, shape important parameters in the field, and define success.

During the season and 19 day, we also highlighted the initial data on the consolidation therapy, which leverages the unique attributes of the off the shelf allogeneic cell therapy and our.

The early and for depletion regimen.

We're highly encouraged by the results, especially the tolerability of consolidation on <unk>.

On the observed conversion of initial PR to CR.

Pending additional follow up we plan to incorporate consolidation into a pivotal study the fine.

And our approach to consolidation dosing is not currently available for autologous therapies or even all of the allogeneic therapies of traditional Inc. For the accretion regimens will eliminate previously and for yourself.

In contrast, our 6 or 7 at the <unk>.

All of them for the placement agent for the second dosing is capable of supplementing the activity of the first dose, allowing for expansion and persistence. After the second dose. This is an important advantage of on 1 that we plan to fully investigate in both of our C 19, and the CMA portfolios.

David D. Chang: At Allogene, we believe we are up to this challenge, and we are grateful for your support, as our vision for the future of allogeneic cardiac therapies is continuing to materialize. I will now turn the call over to Raphael for a more in-depth look at our research and development activities. Thank you, David.

We are currently finalizing our proposed plan to discuss proceed into the phase II trial with the FDA and.

Rafael Amado: As you might anticipate, our research and clinical teams have been increasingly focused on advancing our portfolio of allocardial therapy. As David mentioned, we are on track with our plans to initiate a phase 2 trial for ALO501A in non-Hodgkin's lymphoma. I view the data that we reported in May for the ALPHA trial, including a 36% complete response rate at 6 months in large T cell lymphoma, as a sign that we are on the right track and look forward to exploring whether the use of consolidation therapy might lead to even greater promise.

And the collection of data and the favorable FDA feedback on the design of the trial for the registration of both all of <unk> and Allo 6 for 7 we currently intend to initiate the phase II portion of the all types of the trial at the end of 2021.

I have been fortunate to have been involving the development and approval of multiple accounts for therapeutics and know firsthand how much effort gets involved and the preparation towards people total trials, including extensive and complex regulatory interactions clinical development and manufacturing activities.

I'd like to extend my thanks to the allergy and teams who are working tirelessly to lead us to the the pioneering activities required for the execution of our first give us the allogeneic cell therapy trial.

Okay.

Although we're furthest along and our 2019 program, we're committed to advancing all of car T therapies across a broad spectrum of targets in both liquid and solid tumors.

Rafael Amado: Across all non-Hodgkin's lymphoma histology, ALA501 demonstrated an overall response rate of 75% and a CR rate of 50% across histologists and CAR-T naive patients. At the time of the data cutoff, the longest ongoing complete response was at 15 months in both large fistula lymphoma and follicular lymphoma.

And we were pleased to have received the degenerative medicines advanced therapy. The <unk> granted by the FDA for Allo 715 based on early clinical data and the potential to benefit patients with unmet medical need.

The Universal trial continues to enroll patients 2 of allo 715, including in combination with neuroblastoma that governments of good taste inhibitor from spring work therapeutics and in consolidation therapy.

Rafael Amado: Importantly, given our intent to move ALO501A into our published study, we were also able to demonstrate that ALO501A, which eliminates the rituximab recognition domains in ALO501 to allow for use in a broader patient population, has comparable safety and efficacy to ALO501. As we look to maximize all levers afforded to us by the nature of our Allogene platform, one area of distinction for us is our lymphodepletion platform, which supports consolidated dosing.

Anticipate having updated data to share from the almost 715 monotherapy on of our Universal trial by the end of the year and we are on course to provide updates on all of 7.1 filing combination with no gas the start in 2022.

We're also thrilled to be dosing patients in our ignite clinical trial with Allo 6 of our first 2 book current clinical candidate and part of our broader on diabetes Ma strategy.

Total car represents on next generation cell therapy with built in Kalydeco and signaling eliminating the need for systemic cytokine of administration and the potential to induce broader immune system stimulation with turbo car, we anticipate being able to improve the potency and persistence of olive garden T cells, while the lane.

Got it and trades that are key to our performance in both liquid and solid tumors.

Rafael Amado: During our CD19 day, we also highlighted the initial data on consolidation therapy, which leverages the unique attributes of off-the-shelf allogeneic cell therapy and our proprietary lymphodepletion regimen. We are highly encouraged by the results, especially the tolerability of consolidation and observed conversion of initial PR to CR.

And finally, we're progressing and the dose escalation portion of the reverse trial, our first venture into solid tumors with all of 3.1 and 6 in clear cell renal cell carcinoma, we expect to present data on this important program next year.

I'd like to Echo, David and thanking you for your ongoing support.

The science and clinical teams are making consistent progress.

1 thing a promising portfolio of allo car T candidates for patients in need.

Something that we could not achieve without the backing of the investment community.

I'd like to now turn the call over to Erik for an update on our financials.

Rafael Amado: Pending additional follow-up, we plan to incorporate consolidation into our pivotal study design. Our approach to consolidation dosing is not currently available for autologous therapies or even other allogeneic therapies because traditional lymphodepletion regimens will eliminate previously infused cells. In contrast, ALO647, as the sole lymphodepletion agent for the second dose, is capable of supplementing the activity of the first dose, allowing for expansion and persistence after the second dose. This is an important advantage and one that we plan to fully investigate in both our CID-19 and VCMA portfolios.

Thank you and good afternoon, and say I hope and my portion of the prepared remarks, I'd like to highlight progress made and our joint venture with the overland pharmaceuticals to develop and commercialize our allo car T therapies of greater and greater China, Taiwan, South Korea, and Singapore and June we announced the appointment of Dr. <unk> Shew Jan Yao.

The CEO of allergy and overland and Biopharma. Dr. Yao has over 15 years of experience and cell therapy and was most recently the chief Scientific officer and head of research and technology development of the Wuxi advanced therapies, and Wuxi uptick where he led new technology acquisition development translation and application.

We are delighted to welcome Doctor you out of the team and are already seeing his presence translate into meaningful activities as we seek to bring the promise of allogeneic cell therapies to individuals with cancer and Asia.

And the second quarter of 2021 of research and development expenses were $52.3 million, which includes $10.5 million of noncash stock based compensation expense.

Rafael Amado: We are currently finalizing our proposed plan to discuss proceeding to the Phase 2 trial with the FDA. Depending on the collection of data and favorable FDA feedback on the design of the trial for the registration of both ALO501A and ALO647, we currently intend to initiate the Phase II portion of the ALPHA-2 trial at the end of 2021. I have been fortunate to have been involved in the development and approval of multiple cancer therapeutics and know firsthand how much effort is involved in the preparation for pre-motile trials, including extensive and complex regulatory interactions, clinical development, and manufacturing activities.

General and administrative expenses were $18.8 million for the second quarter of 2021, which includes $10.6 million of noncash stock based compensation expense, our net loss for the second quarter of 2021 was $79 million or <unk> 53 per share, including non <unk>.

Cash and stock based compensation expense of $21.1 million as David and Raphael mentioned, we're on track to support 5 clinical trials during 2021, including the initiation of a pivotal trial for Allo 501 day towards year end. We are also looking forward to initiating manufacturing itself for each 1 our Newark.

Sure and facility.

Overall, we continue to expect our full year 2021 operating expenses to be between 303 hundred $30 million, implying a meaningful ramp and expenses during the second half of the year. This.

Rafael Amado: I would like to extend my thanks to the allogene teams who are working tirelessly to lead us to the pioneering activities required for the execution of our first pivotal allogeneic cell therapy trial. Although we're furthest along in our CD19 program, we're committed to advancing allocarditis therapies across a broad spectrum of targets in both liquid and solid tumors. We are pleased to have received Regenerative Medicine Advanced Therapy designation granted by the FDA for ALO715 based on early clinical data and the potential to benefit patients with unmet medical needs.

This includes an estimated noncash stock based compensation expense of the $80 million to $90 million and excludes any impact from potential business development activities.

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

As a reminder, and task of question you will need to press star 1 on your telephone to withdraw.

For all of your question press the pound key.

So you please limit yourself to 1 question per.

Please standby, while we compile the Q&A roster.

Our first question comes from the line of Michael Yee from Jefferies. Your line is now open.

Hi, Good afternoon. This is Dennis thing on for Mike.

I just have a quick question around the lymphoma data coming at year end can you just comment on what type of data, we will get and specifically for consolidation can you help us kind of set expectations for that data.

Rafael Amado: The universal trial continues to enroll patients on ALO715, including in combination with Neurogastrostat, a gamma secretase inhibitor from SpringWorks Therapeutics, and in consolidation therapy. We anticipate having updated data to share from the ALO715 monotherapy arm of our universal trial by the end of the year, and we are on course to provide updates on ALO715 in combination with Neurogastrostat in 2022. We're also thrilled to be dosing patients in our IGNITE clinical trial with Allo605, our first turbo car clinical candidate and part of our broader anti-BCMA strategy.

Relative to what we've seen at Pasco. Thank you.

Hi, This is David Chang.

And usually it takes a lot of questions but.

Much of today's discussion and I expect to be around the <unk> 19, and I'm going to ask.

And our Chief Medical Officer, Rob payoff the comment on the expectations.

Data, we will be presenting at the year and.

Sure.

At the.

Time point, we have 10 business the 1.

<unk> received the consolidation and we're pretty encouraged by where we saw 80% of pace and service bonding with 7 out of the 10 and complete response and more importantly, we from conversions from PR to CR So Doug.

What.

It gave us the incentive to continue to accrue and investigators have been.

Very enthusiastic about the.

Ability of consolidation to actually boost.

The complete response rate, which may be necessary to longer durability.

Rafael Amado: TurboCAR represents a next-generation cell therapy with built-in cytokine signaling, eliminating the need for systemic cytokine administration and the potential to induce broader immune system stimulation. With TurboCAR, we anticipate being able to improve the potency and persistence of all of our T-cells while delaying exhaustion, traits that are key to our performance in both liquid and solid tumors.

And so when you may expect towards the end of the year is longer follow up on dose escalation as well as more business and we've continued to accrue both on our current answer too.

Follicular lymphoma, and diffuse large b cell lymphoma, the durability will be variable obviously, but at least we'll include those patients.

On that we present that on Oscar and I think there were.

Will it be sufficient to obviously make the adjustment and us too.

The merits of of <unk>.

For innovation, so kind of give you an exact number but it will be.

We see more volume of for we showed on US with continued this approach.

Rafael Amado: Finally, we are progressing in the dose escalation portion of the TRAVERSE trial, our first venture into solid tumors with ALOS316 in PR cell renal cell carcinoma. We expect to present data on this important program next year. I'd like to echo David in thanking you for your ongoing support. Our science and clinical teams are making consistent progress in advancing a promising portfolio of Holocard T candidates for patients in need, something that we could not achieve without the backing of the investment community. I'd like to now turn the call over to Eric for an update on our front. Thank you and good afternoon.

Thank you. Our next question comes from the line of solving Richter from Goldman Sachs. Your line is now open.

Yeah.

Pardon Me tell me and Victor from Goldman Sachs. Your line is now open please check your mute button.

Our next question comes from the line of Marc Frahm from Cowen and company. Your line is now open.

Hi, and thanks for taking my questions and I guess.

On your comments about defaulting to using the consolidation dosing is kind of a.

And you're kind of default assumption.

Would you expect the the pivotal trial is going to be just a single dose do you think that consolidation that from.

The approach or a single arm or you might the FDA require of kind of a randomized trial for the consolidation piece of it to kind of definitively.

Eric Schmidt: As I open my portion of the prepared remarks, I'd like to highlight progress made in our joint venture with Overland Pharmaceuticals to develop and commercialize our aloe CAR T therapies in Greater China, Taiwan, South Korea, and Singapore. In June, we announced the appointment of Dr. Shuyan Yao as CEO of Allogene Overland BioPharm. Dr. Yao has over 15 years of experience in cell therapy and was most recently the Chief Scientific Officer and Head of Research and Technology Development of Wuxi Advanced Therapies at Wuxi AppTech, where he led new technology acquisition, development, translation, and application. We are delighted to welcome Dr. Yao to the team and are already seeing his presence translate into meaningful activities as we seek to bring the promise of allogeneic cell therapy to individuals with cancer in Asia.

Definitively establish the utility of the second dose and then I guess related to that as you evaluate the.

Early data that's coming out of the trial and just what's your latest thoughts on the kind of the minimum kind of difference and durable CR rate that you need to see to justify that type of test.

Yes, Mark for a very good question.

And I mean in general.

The fact, the 1 gives more than 1 dose of of brought on 7 early.

The lead to a mandate from regulators too.

The 2 test.

Single dose and a randomized fashion.

The 3 of the agencies.

The <unk> needs to happen, but just the.

Just the keen to make hunting within athene or we've.

Product requires periodic dosing, where there is every 2 weeks or the 5 weeks or.

Dosing.

Now for a year or gross income progression and et cetera.

For.

Establishes the regimen and <unk>.

For both of the start of the.

The regimen to go forward. So I don't foresee that there will be a mandate for us to actually establish whether it's consolidations better the single dose or not and there will be up to us to decide whether we believe that is the case, which leads me to the second part of your question.

Eric Schmidt: In the second quarter of 2021, our research and development expenses were $52.3 million, which included $10.5 million of non-cash stock-based compensation expense. General and administrative expenses were $18.8 million for the second quarter of 2021, which included $10.6 million of non-cash stock-based compensation. Our net loss for the second quarter of 2021 was $70.9 million, or $0.53 per share, including non-cash, stock-based compensation expense of $21.1 million. As David and Raphael mentioned, we're on track to support five clinical trials during 2021, including the initiation of a pivotal trial for ALO501A towards year end.

And the.

Evidence will be a composite of the.

High CR rate.

On the durability of the responses and we're accumulating more and more months on some of these patients as I mentioned before.

And also some of the third is true minimal residual disease, and then the ability to continue to expand and.

And on observed persistence of the current positive sales, which we've already seen after the second dose.

So so far we're excited about where we are seeing.

And that's why we believe that it's likely that we will incorporate the consolidation and iron.

And with those from where we'll continue to observe the day.

Data prior to making the decision.

And Mark This is day thing if I can add on to that.

I take it there will be a lot of questions about the study design that we will go forward with the.

And the FDA meeting and I kindly ask you to stay tuned and uncertainty we have to have the FDA discussion and as we come out of it we will clarify exactly what will happen for all.

Eric Schmidt: We are also looking forward to initiating manufacturing at CellForge1, our Newark manufacturing facility. Overall, we continue to expect our full-year 2021 operating expenses to be between $300 and $330 million, implying a meaningful ramp-up in expenses during the second half of the year. This includes an estimated non-cast stock-based compensation expense of $90 million and excludes any impact from potential business development activities.

The pivotal study.

Thank you. Our next question comes from the line of Luke I E. C from RBC. Your line is now open.

Hello, and terrific. Thanks, so much for taking my question. Congrats on all of the progress and maybe a quick 1 I think fate therapeutics just planning to show some for the first time I think of clinical data for <unk> CD 19 car NK cells for the next 2 weeks I was wondering if you can comment on what of your expectation getting into the data and maybe a bigger picture of what's your latest thinking on.

The debate between a car T cell versus car NK cells. Thanks, so much.

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

Luke.

Thank you very much for that question.

Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. We ask that you please limit yourself to one question. Please stand by while we compile the Q&A roster.

And certainly our focus now is really advancing our allogeneic car T program on all 5 of <unk> into the pivotal study.

Have treated number of patients and we have a good understanding coming from the <unk>.

And the large number of patients the emerging data we have from the 501, where most of the single dose experienced and are coming from and <unk>.

Well as the consolidation of dosing, which we are very interested and.

Operator: Our first question comes from the line of Michael Yee from Geoffrey's. Your line is now open.

You know the allogeneic cell therapy field is a very active place I think a lot of companies see the promised the.

David D. Chang: Hi, good afternoon. This is Dennis Bing on behalf of my company. I just have a quick question around the lymphoma data coming at year-end. Can you just comment on what type of data we will get, and specifically for consolidation, can you help us kind of set expectations for that data relative to what we've seen at ASCO? Thank you. Hi, this is David Chang.

Off the shelf therapy with the potential providing a very deep and durable responses and.

And companies are taking different approach, we believe in the current key therapy, especially therapy debt leverage the T cells, and we eagerly wait to see what on.

Other companies, especially those leveraging the NK cells, who will provide and their data updates so.

David D. Chang: I usually take a lot of questions, but much of today's discussion I expect to be around CD19. And I'm gonna ask our chief medical officer, Raphael, to comment on the expectations for what data we will be presenting at the year-end. Sure.

Let's start on other conversation after the data presentation, which I believe is planned for sometime in August.

Yeah.

Thank you. Our next question comes from the line of choline recur from Goldman Sachs. Your line is now open.

And sorry for for earlier and 2 questions here could you talk about <unk> 17, and what you would see as the clinical bar here.

Rafael Amado: So at the ASCO time point, we had 10 patients that had received consolidation, and we were pretty encouraged by what we saw. Eighty percent of patients responded, with 7 out of 10 in complete response, and more importantly, we saw conversions from PRs to CRs. So that gave us impetus to continue to accrue, and investigators have been very enthusiastic about the ability of consolidation to actually boost complete response rates, which may be a surrogate for longer durability.

And first data with your car T program and then on the <unk> side do you have and understanding here of the optimization levers required to get you closer to the autologous profile.

Yes, sorry, I mean for a parallel.

The 70.

That program.

The began not that long ago and then.

And as you know.

And we'd have to.

Treat patients and observe them before we can go through the dose escalation.

And at a pretty and basis on a sale.

Of pathway directed therapies for Rite aid.

Rafael Amado: So what you may expect towards the end of the year is longer follow-up on those ASCO patients, as well as more patients that we've continued to accrue, both on alpha and alpha 2, and follicular lymphoma and diffuse plasma lymphoma. The durability will be variable, obviously, but at least it will include those patients that we presented at ASCO, and I think, you know, there will be enough to obviously make a judgment as to the merits of consolidation. So I can't give you an exact number, but it will obviously be more volume than what we showed at ASCO because we've

The point inhibitor, it's an androgen inhibitors and then.

Any of them.

And are progressing.

Coming to the studies, so we hope to get some early evidence.

The potential activity that we can show next year.

In terms of the bar I think it's premature to talk about about it but many of these patients are already refractory.

And as you know the data and solid tumors with cars.

And it still needs to mature and progress.

But I think certainly any incomplete responses of partial responses will be of interest.

We will follow the appeal of very closely and there is the.

The number of surrogate markers that we're also looking at that will help us with other targets and solid tumors such as traffic gain into the more of the tumor microenvironment. The fact that system.

Operator: Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open. Pardon me, Salveen Richter from Goldman Sachs. Your line is now open. Please check your mute button.

And et cetera.

And the rest of the CMA optimization rehab.

We have continued dosing from there.

And you had.

When the deal for our finished dose escalation and with.

Continuing to follow patients.

We are starting the consolidation as well and.

And we were very glad to see the arm of the submission being awarded the 2.

Of the product and part of that what.

Operator: Our next question comes from the line of Marc Frahm from Cowan & Company. Your line is now open.

And the recognition for the effect of the product, but also the ability to treat very quickly and to avoid the bridging therapy.

Rafael Amado: Thanks for taking my questions. On your comments about defaulting to using the consolidation dosing, your kind of default assumption, would you expect that the pivotal trial is going to be just a single dose using that consolidation approach, a single arm, or you might say FDA require a kind of a randomized trial for the consolidation piece of it to kind of definitively establish the utility of that second dose, and then I guess related to that, as you evaluate the, early data that's coming out of the trial, just what's your latest thoughts on kind of the minimum kind of difference in durable CR rate that you need to see to justify that, Yes, Mark, those are very good questions.

Which are 2 important features.

On.

And then the color with training, but we clearly want to get closer to the air total risk bar. There is no question.

Sales of Ferro has set a pretty high bar and.

And so we are continuing with consolidation of the use of Neovasc the stat and obviously the total current and we've referred to in the prepared remarks, there and.

And we just started so.

As a matter of things 2 and seeing what the potential of the mutations.

And I don't know if this whole time.

Thank you. Our next question comes from the line of Michael Schmidt from Guggenheim Securities. Your line is now from.

And it seems that Kelsey on for Michael Thanks for taking our question and.

And maybe building on the multiple.

Multiple myeloma side, I guess, what should we be expecting at ash in terms of when you implemented the consolidation regimen will there be a meaningful amount of patients and we can interpret a single agent versus the consolidation and and would we see any initial data points from the near against the Stat combination.

Rafael Amado: I mean, in general, the fact that one gets more than one dose of a product doesn't necessarily lead to a mandate from regulators to test single doses in a randomized fashion. Obviously, the agency's negotiations need to happen, but just, you know, just akin to, you know, what may happen with a vaccine or with a product that requires periodic dosing, whether it's every two weeks or every five weeks, or, you know, dosing for a year, or dosing based on progression, et cetera.

And that's it for me thank you.

Yeah. So the consolidation of Chelsea. This started relatively recently so there may be the will be basins, but there may not the loans.

Loans follow on.

And there will be more follow up on the higher doses, which we've already noted that we're more effective on the lower doses, so true and the city and deal for and so we will have more patients on dose as well as sort of a follow up.

And that's the status of Green wells, but we will need to have sufficient patients and sufficient follow up and so we believe that that will probably of the.

2022 times debt of relief display system price.

So on.

Rafael Amado: The sponsor establishes the regimen and proposes that as the regimen to go forward. So, I don't foresee that there will be a mandate for us to actually establish whether consolidation is better than single dose or not. It will be up to us to decide, you know, whether we believe that that is the case. Which leads me to the second part of your question.

And most likely it would be much more mature data with the.

Higher doses on the.

7.1 times debt, we will per center and of the year.

Perfect. Thank you.

Thank you. Our next question comes from the line of Jason Goldberg from Bank of America. Your line is now open.

Hey, guys. Thanks for taking my questions and other.

The CMA question just heading into <unk>.

Cash <unk> obviously.

You guys had mentioned autologous and set a high bar your data last year at Ash were immature for the $480 million.

David D. Chang: The evidence would be a composite of the high CR rates, the durability of the responses, and we are accumulating more and more data on some of these patients, as I mentioned before, and also some of the surrogates, like minimal residual disease, and then the ability to continue to expand and observe persistence of the CAR positive cells, which we've already seen after the second dose. So, you know, so far, we're excited about what we're seeing, and that's why we believe that it's likely that we will incorporate consolidation in our field trial, or we'll continue to observe the data prior to making the decision.

So just curious do you think you might be at a point.

At ash to determine whether or not single dose is the right path forward or whether you need to shift the focus to gamma secretase or turbo car programs or dose consolidation just just sort of curious if you feel like the data might be mature enough for single dose to to make that pivot or prioritization. Thanks.

Thanks, Jason.

Thanks for Great question, and I think Youre, asking all of the right questions on and certainly.

From the beginning.

We set up the the CMA programs slightly different and delay day, we set up the C.

And 19 program and yes, there are a dip.

And from levers that we can test including <unk>.

David D. Chang: And, Mark, this is Dave Chang. If I can add to that, you know, I take it there will be a lot of questions about the study design that we will go forward with at the FDA meeting, and I kindly ask you to stay tuned. We certainly have to have the FDA discussion, and as we come out of it, we will clarify exactly what will happen for our pivotal study.

Higher cell dose and more stronger Lim for depletion on leveraging what we have of specifics of the our fixed for 7.

And consolidation and.

All of these are the parameters that we tested and the CD 19 program and we have a lot of knowledge about how to best utilize different levers to optimize the benefits of.

Our 71.5.

Also we have taken a sort of somewhat unusual step from currently developing the next generation our 6 of applied that utilizes the turbo kind of technology. So in terms of the question about when we will know about what to do with our debt.

Operator: Thank you. Our next question comes from the line of Luca Issi.

From the CMA approaches that we are making we got to take all of different information that we are generating and all and all of these trials are ongoing and enrolling patients and we are in a pretty good position I believe debt.

Operator: That comes from the line of Luca Issi from RBC. Your line is now open. Oh, terrific. Thanks so much for taking my question. Congratulations on all the progress. Maybe a quick one.

Some time in 2022, there will be a convergence of data that will help us to map out the path for the <unk> program.

Thank you. Our next question comes from the line of John Newman from Canaccord. Your line is now open.

David D. Chang: I think SAIT Therapeutics is planning to show some, for the first time, clinical data for the CD19 CAR-NK cells in the next two weeks. I'm wondering if you can comment on what your expectations are for that data and maybe a bigger picture of what's your latest thinking on the debate between CAR-T cells versus CAR-NK cells. Thanks so much.

Hi, guys. Thanks for taking the question.

A follow up on the last question actually just curious for Allo 715 in terms of combining with the near guests debt.

I'm wondering if you're considering giving.

Giving multiple doses of near and gas debt sometime in the future.

And if may be beneficial to the dose initially and combination was 715 and 6 for 7.

And then maybe after that given other dose or 2 of just curious if that's something that you are.

David D. Chang: Yeah, Luca, thank you very much for that question. Certainly, you know, our focus now is really advancing our allogeneic heart key program, LL501A, into the pivotal study. We have treated a number of patients, and, you know, we have a good understanding coming from the large number of patients, the emerging data we have from the 501, where most of the single dose experience is coming from, as well as the consolidation dosing, which we are very interested in.

Considering for the future.

Hi, Joe.

Rafael.

Yes. Good question I mean, we haven't gone into how we're dosing neurovascular stab and.

And for competitive reasons, obviously, but.

I can tell you that we've done.

1 of those.

And.

The intent is to try to maximize the benefit of the CMA expressions on neurovascular that kind of afford.

So we will be testing.

The percentage of that potential.

And.

And it may take the form of several doses.

And this is something that is currently under exploration.

David D. Chang: You know, as you know, the allogeneic self-therapy field is a very active place, and I think a lot of companies see the promise of off-the-shelf therapy with the potential to provide very deep and durable responses, and companies are taking different approaches. We believe in the heart key therapy, especially therapy that leverages T-cells, and we eagerly wait to see what other companies, especially those leveraging NK cells, will provide in their data updates. So, you know, let's have another conversation after the data presentation, which I believe is planned for sometime in August.

Stay tuned for the result.

Thank you. Our next question comes from the line of Mark Breidenbach from Oppenheimer. Your line is now open.

Hey, guys. Thanks for taking my question just a quick 1 from me.

I know the main focus of the upcoming pivotal trial will be on large b cell lymphomas, but I'm wondering if you have plans for continued development of our 5 of <unk> and Follicular lymphoma or is that off the table for now.

Yes, Mark I mean.

And this is something that on.

The.

We are.

Cross team right now, which is a comprehensive program that includes the suite of studies across various.

The lines of therapies as well as the policies as you know the the second line result.

Operator: Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open. Yeah, sorry.

<unk> come up and we aren't thinking about.

For loans trials, I would address that need with the Allergan Inc.

The <unk> therapy and.

Operator: Yes, sorry for earlier. There are just two questions here.

And likewise to follow on with Follicular lymphoma, and potentially other histology. So right now we are very focused on the third line histology on and discussions and preparations for the.

Rafael Amado: Could you talk about CD17 and what you would see as a clinical bar here and for data with your CAR-T program? And then, on the BCMA side, do you have an understanding here of the optimization levers required to get you closer to the autologous profile? Yes, Salveen. This is Rafael.

It started.

There will be a lot of activity around the type of wanting to really form a comprehensive program.

Thank you. Our next question comes from the line of Ren Benjamin from JMP Securities. Your line is now open.

Rafael Amado: So on CD70, you know, that program has begun not that long ago, and as you know, we have to treat patients and observe them before we can go through those escalations. We are treating patients that have failed all pathway-directed therapies, so that is checkpoint inhibitors and endogenous inhibitors, and many of them are progressing as they come into the study. So, you know, we hope to get some early evidence of potential activity that we can show next year.

Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress there.

Just 1 from me when we go to the Allo 3.1 and 6 can you just remind us why RCC as opposed to let's say any other solid tumors and.

And when I think about RCC I always.

About and combination with checkpoints and I'm guess I'm curious as to where you guys are and the development of evaluating these allogeneic cell therapies in combination with checkpoints, whether it's with RCC or any of the other indications are and the 5 of 1 test kitchen that you guys have.

Rafael Amado: You know, in terms of the VAR, I think it's premature to talk about it, but, you know, many of these patients are already refractory, and as you know, the data in solid tumors with CARs still needs to mature and progress. But I think certainly any complete responses or partial responses will be of interest, and, you know, we will follow the field very closely. And there's a number of surrogate markers that, you know, we're also looking at that will help us with other targets in solid tumors, such as trafficking into the tumor microenvironment, resistance, et cetera.

And then.

Great question and.

And as you are pointing out with our outlook for you on 6 targeting CD 70, there are several of different development opportunities CD 70 at the target it is very attractive in.

In both him as 1 of the solid tumor indications.

Certainly renal cell carcinoma and are going to why we chose the renal cell as well as other types of tumors solid tumors and also there is a lot of interest and we are.

And getting a lot of inbound interest in <unk>.

<unk> 3.1 and 6 in the AML indication.

Rafael Amado: In terms of PCMA optimization, we have continued dosing. As you know, we were in DL4, and we have finished our dose escalation. We've continued to follow patients, and we are starting consolidation as well. And, you know, we were very glad to see the ARMA designation being awarded to the product, and, in part, that was in recognition of, you know, the effect of the product but also the ability to treat very quickly and to avoid breathing therapy, which are two important features that, you know, you don't see in the autologous setting.

Patients who are there is of some earlier proof of concept coming from using.

Antibody alone for the treatment of AML. So we have many different options to consider SDN.

From the corporate perspective, we wanted to advanced.

I was in a current team for the solid tumor which is the reason that we chose the renal cell as the.

The indication and as a part of your question I mean is there an opportunity to combine.

<unk> therapy with a checkpoint inhibitor.

And definitely pockets debt has been explored in other cities other currency settings, as well, we will be considering debt once we sort of generate the safety and efficacy data from the single agent treatment of Allo 6 and also at the same time as we get more proof of concept from.

Rafael Amado: But we clearly want to get closer to the autologous bar. There's no question that Faxil-Tefel has set a pretty high bar. And so we're continuing with consolidation, the use of neurovascular stat, and obviously the TuvoCard that we referred to in the prepared remarks that we just started. So, you know, it's a matter of staying tuned and seeing what these potential optimization results are.

<unk> 6 and stay tuned we will be advancing the program into other indications as well.

Yeah.

Thank you. Our next question comes from the line of Rajiv Prasad from William Blair. Your line is now open.

Thanks for taking the question I wanted to get your thoughts on the Zuma 7 trial and transform result.

As it relates to how the <unk> landscape might.

Change by the time and all 5 of 1 goes through its pivotal trial, just curious to kind of hit of the thoughts on cash.

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

Our teams moving into earlier lines of therapy given.

Given the car T and naive.

The data that you've shown to date thanks.

Rajiv.

Thanks for that question.

Consequently, what's involved and the Zuma 7 study and I have to say and then all of us really thrilled.

Operator: Thanks for taking our question. Maybe building on the multiple myeloma side, I guess, what should we be expecting at ASH in terms of when you implement the consolidation regimen? Will there be, you know, a meaningful number of patients that we can interpret a single agent versus a consolidation? And will we see any initial data points from the neurogastrostatic combination?

The preliminary data came out and certainly.

And that highlight what the car T therapy can do and there are a lot of questions about is the car T therapy gonna be exists.

For the relapsed refractory setting or tenant move out for the early on line I think Zuma 7 study.

That's a clear example of that the car T therapy can be more effective and work better in the earlier lines of therapy, and we see that as an opportunity for the allogeneic to Basel the level of set by the autologous car T therapy.

Having been involved and both autologous and allogeneic car T therapy.

As I've said in the prepared statement, what we are seeing in the allogeneic car T therapy coming out of the 501 and 501 data is.

Rafael Amado: That's it for me. Thank you. And

So many consistency.

Operator: Yeah, so the consolidation, Kelsey, just started relatively recently, so there may be, there will be patients, but there may not be long follow-up. There will be more follow-up on the higher doses, which we've already noted that were more effective than the lower doses, so we treated in DL3 and DL4, and so we will have more patients on those, as well as longer follow-up, and you know, gastroesthetics are growing well, but we will need, you know, to have sufficient patients and sufficient follow-up, and so we believe that that will probably be 2022 type data release, just like 605, so, you know, most likely will be much more mature data with the higher doses on 715 that we will present towards the end of the year.

And what we saw in the autologous car T. I mean thats 1 of the reason that we are very.

I guess somewhat bullish and confident about the future of allo 500, running and the future for Allo 501 will not stop in the relapsed refractory setting, we will definitely and advanced that to other indications, especially in the early and line as for opt out has earlier alluded to.

Thank you. Our next question comes from the line of Dane Leon from Raymond James Your line is now for them.

Hi, Thank you for taking the questions congrats on all of the progress.

And looking forward to some of the updates later this year.

1 question for me just wanted to.

Focus on.

The primary inbound that we get.

In terms of your dataset and.

And aggressive B cell lymphoma, right now and Thats really focused on understanding the infection risk profile.

I guess, maybe a multipart question here sorry.

Operator: Thank you. Our next question comes from the line of Jason Gerberry from Bank of America. Your line is now open.

1 could you just remind everyone how the length of depletion works for the consolidation.

Operator: Hey, guys. Thanks for taking my questions. Another BCMA question, just heading into ASH. Do you, you know, obviously, as you guys have mentioned, autologous is at a high bar.

On <unk>.

And then that you are now using debt we should see more data on later this year and then 2 maybe comment on your expectations for infection rates.

For that consolidation regimen.

Relative to maybe what we saw reported around <unk>.

David D. Chang: Your data last year at ASH were immature for the 480 million cell dose. So I'm just curious, do you think you might be at a point at ASH to determine whether or not single dose is the right path forward or whether you need to shift the focus to gamma secretase or turbo CARB programs or dose consolidation? Just sort of curious if you feel like the data might be mature enough for single dose to make that pivot or prioritization. Thanks. Hey Jason,

And the 90 milligram of our 6 for 7 which seemed to be a bit higher than the 60 milligram dose.

The.

And then lastly, how that could play into discussions with FDA about clinical trial design. If you do go forward with the consolidation dose or not what they would want to see in terms of maybe patient numbers to understand that infection risk.

Relative to other salvage line therapies for those patients. Thank you.

David D. Chang: Thanks for a great question. I mean, I think you're asking all the right questions. I mean, certainly, from the beginning, you know, we set up the DCMA program slightly different than the way that we set up the CD19 program. I mean, yes, there are different levers that, you know, we can test, including higher cell doses and more stronger lymphoid depletion, leveraging what we have, specifically our 647. And consolidation, and all these are parameters that we tested in the CD19 program, and we have a lot of knowledge about how to best utilize different levers to optimize the benefits of ALICE-715.

Thanks for the question and this is.

On a complex question on the.

That's true to do it justice.

So just the start with the consolidation we give.

Dosing density that is the same and the 90 milligrams.

<unk> been seen with the single dose and Doug.

And we gave 60 milligrams and 3.

Doses.

Upon the first infusion and then on the second infusion which is.

Don after the day 28 gig 30 milligram. So the total dose intensity of the same but it is split into 2 doses.

We've been incredibly.

And we the Tolerability of both the initial and the consolidation infusion and what we hear on what we see is the.

Particularly with consolidation of patients defined as the there's been really no.

Plus the effects.

And the Tolerability has been quite good down to the point, where considering whether this could be done on us on outpatient.

David D. Chang: Also, you know, we have taken a somewhat unusual step of concurrently developing the next generation, ALICE-605, that utilizes therbocard technology. So in terms of, you know, the question about when we will know about what to do with our different BCMA approaches that we are making, we have to take all the different information that we are generating and all the ongoing trials are enrolling patients, and we are in a pretty good position, I believe, that sometime in 2022, there will be a convergence of data that will help us to map out the path for the BCMA program.

The overall and the infection risk I mean, if you look at the USPI of.

And the 3 products that are approved and the autologous setting very.

Very clear that it is similar to the infection growth that we see with.

The <unk>.

The green juice between 19% of the mid 20% in terms of grade III.

Infection rates and Thats really what we see so we do not believe that way that we're using on our 6% and is leading to a higher range of infection.

And.

It's really.

Really of common feature which is really.

Highlighted.

Hi.

On the guidelines of how to treat these patients and how the Brooklyn Lockton.

And it is possible debt.

Split dosing may lead to even lower rates, but this is something that we really have to wait and see and even with the single dose the rates being higher than what we've seen year come on the thing and.

Day, and if I can just add onto that.

And as a clinician and if somebody would spin and both in the current case study.

And understand some of the concerns that are being raised by of.

About the infection rate.

Operator: Hi guys, thanks for taking the question. I'll follow up on the last question actually. Just curious, for L715, in terms of combining with nergazistat, I'm wondering if you're considering giving multiple doses. If it may be beneficial to dose initially in combination with 715 and 647, please contact, And then maybe after that, give another dose or two. Just curious if that's something that you're considering. Hi John. This is Rafael.

Now we have treated over 100 patients across different programs with our allogeneic car T. Allo car T..5 of 1 <unk> and 71, 5 and I think at this point then of clinical data speaks for itself in terms of the infection rates and we are seeing and.

And I have to say that in the 100 patients that we have treated.

Some of the consensus being raised I mean, the day that doesn't really indicate that the infection rate is any higher than what has been reported in the autonomous car T therapy.

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

He knows the debt.

And this is kind of the night of finance on for Ben.

Rafael Amado: Yeah, good question. I mean, we haven't gone into how we're dosing neurogastrostats, you know, for competitive reasons, obviously, but I can tell you that we don't just give one dose. And, you know, our intent is to try to maximize the benefit of BCMA expression that neurogastrostats can afford. So we will be testing the potential, and it may take the form of several doses. And this is something that is currently under exploration. So stay tuned for the results.

Thank you for for the questions for.

And suddenly it cause tumor program without a lot of PD 1.6 on her.

How should we think of.

And the expansion of the data on what time points can we expect the recent bucket by tissue biopsy data.

So, we and Q1 and 6 follow on Silicon and the same way that we're doing and the rest of our programs, which is pretty closely early on and then obviously we did on it.

For us.

Time goes on but we continue to follow until.

We seek to see cell expansion.

1 out of premature and we haven't obviously share of any data with your 1.6 yes.

Operator: Thank you. Our next question comes from the line of Mark Breidenbach from Oppenheimer.

But we've seen some expansion of our cell persistence of all the way out the 6 months and beyond.

Operator: Back from Oppenheimer, your line is now open. Hey guys, thanks for taking my question. Just a quick one from me.

And there is 1 feature of 206.

And we've mentioned in the past, which you said it is expressed on activated T cells. So we believe that.

Rafael Amado: I know the main focus of the upcoming pivotal trial will be on large B-cell lymphomas, but I'm wondering if you have plans to continue development of 501A in follicular lymphoma, or is that off the table? Yes, Marc. I mean, this is something that we are crafting right now, which is a comprehensive program that includes a suite of studies across various lines of therapy, as well as pathologies. As you know, there are second-line results that have come up, and we are thinking about follow-on trials that would address that need with the Allogeneic 501A therapy.

And the allo reactive T cells.

May Express CD 70, and may be susceptible to actually on so killed by the allogeneic car bearing sales.

And it is possible that the.

Assistance and actually be even superior and this is something that we are.

Looking out and taken a look very closely so.

In terms of the tissue, we definitely want to see what's happening in the tissue, particularly the migration of the card market itself for the tissue.

And we do biopsies very early on.

And entry into the study and then within the first 10 day.

And we look for the car.

Preference will look obviously for the 70 <unk>.

PD, 1 PDL, 1 and other markers.

On to tell us what's happening with the tumor microenvironment.

Rafael Amado: And likewise, to follow on with follicular lymphoma and potentially other histologies. So right now, we are very focused on the third-line histology and in discussions and preparations to get that study started, but there will be a lot of activity around 501A to really form a comprehensive program.

And so far.

The data on our premature but we.

We're accumulating this result, and it will be part of what will be presented with the dawn of mature.

So stay tuned.

Thank you. Our next question comes from the line of Zika and the warning from true at your line is now open.

Hi, guys. Thanks for taking my question.

Operator: Thank you. Our next question comes from the line of Ren Benjamin from JMP Securities.

Just kind of following back up on allo stem up 5 to kind of see.

The precise inhibitor.

Operator: Thank you. Hey, good afternoon, guys.

So you did mention that you might see the state and in early 2022 and I just wanted to I just want to check if that early part of it is still in place here.

Operator: Thanks for taking the questions- That's just one for me. When we go to Aloe 316, can you just remind us why RCC as opposed to, let's say, any other solid tumors? When I think about RCC, I always think about it in combination with checkpoints. We're curious as to where you guys are.

And if not could you maybe give a little bit more granularity as to when and then related for that I guess, the first response rates and margins.

The level of volume will be similar levels of etc. What other measurements of data can we expect in the first look.

David D. Chang: Development of evaluating these allogeneic cell therapies in combination with checkpoints, whether it's with RCC or any of the other indications is in the 500. Great question. As you're pointing out, with our Allo 316 targeting CD70, there are several different development opportunities. CD70 as a target, it is very attractive in both heme as well as bowel tumor indications, certainly renal cell carcinoma, and I'll go into why we chose renal cell carcinoma, as well as other types of tumors, bowel tumors, and also there is a lot of interest, and we are certainly getting a lot So we have, you know, many different options to consider.

Of this combination that will help support the rationale.

For putting these 2 together thank you very much.

Yeah, and we haven't.

Debt exactly when the data will be shown on I mean, we said it was the 2022 and I think.

We will make the decision once we consider that we have a meaningful data set.

So stay tune.

All I can say.

Running these 2 excellent team inside of accrual is not.

Not being a problem and.

The execution continues.

No.

And actually on a very brisk pace.

So hopefully we will accumulate data as soon as possible and be able to share with you.

Yes, I mean, obviously, we're looking at the CMA expression and the approximate sales we're looking at cellular the CMA and we're looking at MRV, we're looking of persistence.

We're looking.

Something that's important and just feel also which is the extra medullary disease and the ability to.

Prevent relapses on side of the bone marrow.

But perhaps the most important.

The factor is the mechanistic.

David D. Chang: In the end, from the corporate perspective, we wanted to advance the allogeneic carcino to the bowel tumor, you know, which is the reason that we chose renal cell as the first indication. And as part of your question, I mean, is there an opportunity to combine CAR-T therapy with a checkpoint inhibitor? I mean, that's definitely, you know, a topic that has been explored in other CAR-T settings as well. We will be considering that once we sort of generate the safety and efficacy data from the single agent treatment of LO316. And also, at the same time, as we get more proof of concept from 316, stay tuned. We will be advancing that program into other indications as well.

On a recent forgiven neovasc the stat, which is the we actually see a meaningful increase from the CMA and that result in.

Better and other activity of the car Ts.

On a set of 1.5 and the.

And that's where we're focused on but we're doing all of the right Biomarkers for and you mentioned.

Yeah.

Thank you our next question.

Comes from the line of Carl Pizza per tell from B Riley Securities. Your line is now for them.

Yes, hi, and thanks for taking the question and maybe 1 for David on a Raphael.

And the study for renal cell, obviously safety the priority first but at what dose level should you should we expect.

And do you see some signals of clinical activity based on your preclinical PK PD modeling.

Operator: Thank you. Our next question comes from the line of Raju Prasad from William Blair. Your line is now open.

And then can you remind us if the length of depleting doses that you're using and renal cell are essentially the same as what you use and your liquid tumor trials. Thanks.

Operator: Thanks for taking the question. I wanted to get your thoughts on, you know, the Zuma 7 trial and its transformative results as it relates to how the LBCL landscape might change by the time, you know, AL501 goes through its pivotal trial. Just curious to kind of hear the thoughts on, you know, CAR T's moving into earlier lines of therapy, given the CAR T naive. Thank you. Raju, you know, thanks for that question.

Yes, let me take total sell the question.

And from the preclinical and clinical.

<unk> learned that in the car T field.

It is not as predictable so income for what is to see and clinics I mean, it really has to be done and carefully planned clinical study, which is currently being done so.

Stay tuned I mean, it could happen and the first dose level for it could happen and the second the plan and dose is the 3 dose levels in the in the $3.6 study.

David D. Chang: You know, I personally was involved in the Zuma 7 study, and I have to say that I was really thrilled when the, you know, the preliminary data came out, and certainly that highlights what CAR-T therapy can do. There are a lot of questions about whether CAR-T therapy is going to be just for the relapsed refractory setting, or can it move back to the earlier line?

The second question.

1 of the administration of.

The lymphoid depletion, but the solid tumor versus heme malignancies.

The different reasons.

Apologize for not answering the question we are trying to remain relatively silent on the lymphoma depletion strategy that we are making so just wait for the data presentation and as we've said in the prepared statement. We expect 316 data presentation to occur in 2000.

David D. Chang: I think the Zuma 7 study, you know, sets a clear example that CAR-T therapy can be more effective and work better in the earlier lines of therapy, and we see that as an opportunity, you know, for the allogeneic to follow what was set by the autologous CAR-T therapy. You know, having been involved in both autologous and allogeneic CAR-T therapy, as I said in the prepared statement, what we are seeing in allogeneic CAR-T therapy coming out of the 501 and 501A data is, you know, so many similarities with what we saw in the autologous CAR-T.

On to next year.

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

Thank you and it's an exciting time for allergy and as we look ahead to 2 and near term events that begin the journey towards commercialization the Pla.

<unk> initiation of our first pivotal trial and taking control of our manufacturing with sales force 1 first word class.

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With that thank you for joining us today and for taking part of our journey to define the future of allogeneic cell therapy.

David D. Chang: I mean, that's one of the reasons that we are very, you know, I guess I'm not foolish and confident about the future of LL501A, and, you know, the future for LL501A will not stop in the relapsed refractory setting. We will definitely advance that to other indications, especially in the earlier lines, as Rafael has earlier alluded to.

Operator, you may now disconnect.

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

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Yes.

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Operator: Thank you. Our next question comes from the line of Dane Leon from Raymond James.

Operator: Your line is now open. Hi. Thanks.

Operator: Thank you for taking the questions. Congratulations on all the progress. I'm looking forward to some of the updates later this year.

Rafael Amado: One question for me, I just wanted to focus on the primary inbound that we get in terms of your data set in aggressive B-cell lymphoma right now, and that's really focused on understanding the infection risk profile. I guess this might be a multi-part question here, sorry. One, can you just remind everyone how the lymphodepletion works for the consolidation regimen that you're now using that we should see more data on later this year? And then, two, maybe comment on your expectations for infection rates for that consolidation regimen relative to maybe what we saw reported around ASCO between the 90-milligram dose of ALIS-647, which seemed to be a bit higher than the 60-milligram dose.

Rafael Amado: And then, lastly, how that could play into discussions with FDA about clinical trial design if you do go forward with the consolidation dose or not, what they would want to see in terms of maybe patient numbers to understand that infection risk potentially relative to other salvage line therapies for those patients. Thank you.

Rafael Amado: Thanks for the question, and this is a complex question, and I'll do my best to do it justice. So just to start with consolidation, we give dose intensity that is the same as the 90 milligrams that you've seen with a single dose, in that we give 60 milligrams in three doses upon the first infusion, and then on the second infusion, which is done after day 28, we give 30 milligrams. So the total dose intensity is the same, but it's split into two doses.

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Rafael Amado: We've been incredibly pleased with the tolerability of both the initial and the consolidation infusion. What we hear and what we see is that, particularly with consolidation, patients do find there's been really no class effects, and tolerability has been quite good to the point that we're considering whether this could be done as an outpatient. The overall infection risk, I mean, if you look at the USPI of the three products that are approved in the autologous setting, it's very clear that it is similar to the infection risk that we see, which is, you know, in the 20. It ranges between, you know, 19% to the mid-20% in terms of grade 3 plus infection rates. And that's really what we see.

David D. Chang: So we do not believe that the way that we're using LL647 is leading to a higher rate of infection. And it's really a common feature which is really highlighted by, you know, the guidelines on how to treat these patients and how to prophylact them. And it is possible that, you know, the split dosing may lead to even lower rates, but this is something that we really have to wait and see.

Operator: But even with the single dose, the rates have not been higher than what we've seen in your follow-up. And, Dane, if I can just add on to that, you know, as a clinician and as somebody who's been involved in the CAR-T study, I can understand some of the concerns that are being raised about the infection rate. But now, you know, we have treated over 100 patients across different programs with our Allogene CAR-T, our CAR-T 501, 501A, and 715.

Operator: And I think at this point, you know, the clinical data speaks for itself in terms of the infection rate that we are seeing. And I have to say that in the 100 patients that we have treated, despite some of the concerns that are being raised, the data doesn't really indicate that the infection rate is any higher than what has been reported in those CAR-T therapies.

Operator: Thank you. Our next question comes from the line of Ben Burnett from Stiefel.

Operator: Your line is now open. Hello, good afternoon. This is Catalina Ibanez on behalf of BEM. Thank you for the questions. For your sublete tumor program with Arlo 316, how should we think of cell expansion data, and what time points can we expect to be supported by tissue biopsy data?

Rafael Amado: So, we in 2.1.6 follow cell expansion the same way that we do in the rest of our programs, which is, you know, pretty closely early on, and then obviously, we spread it out as, you know, time goes on, but we continue to follow until we, you know, cease to see cell expansion. The data is premature, and we haven't, obviously, you know, shared any data with 2.1.6 yet, but we've seen cell expansion or cell persistence all the way up to six months and beyond.

Rafael Amado: There is one feature of 3.1.6 that, you know, we've mentioned in the past, which is that it is expressed in activated T cells. So, we believe that alloreactive T cells may express CD70 and may be susceptible to cell kill by the allogeneic CAR-bearing cells. So, it is possible that the persistence may actually be even superior, and this is something that we are looking at and taking a look at very closely.

Rafael Amado: So, in terms of the tissue, we definitely want to see what's happening in the tissue, particularly migration of CAR-positive cells into the tissue, and we do biopsies very early on at entry into the study and then, you know, within the first 10 days. We look for CAR presence. We look, obviously, for CD70, PV1, PV01, and, you know, other markers to tell us what's happening with the tumor microenvironment. So far, the data are premature, but we are accumulating these results, and they will be part of what will be presented when the data mature. So stay tuned.

Operator: Thank you. Our next question comes from the line of Asthika Goonewardene from Truist. Your line is now open.

Operator: Hi guys. Thanks for taking the time to answer my questions. I just want to follow back up on LO-SELMA-5-plus-Zika-MSC-precision inhibitor. Guys, previously, you did mention that you might see this data in early 2022, and I just want to check if that early part is still in place here. And if not, could you maybe give a little bit more granularity as to when? And then related to that, I guess besides response rates, MRD levels, soluble BCMA levels, et cetera, what other measurements and data can we expect in this first look at this combination that will help support the rationale for putting these two together? Thank you very much.

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Rafael Amado: Yeah, I mean, we haven't said exactly when the data will be shown. I mean, we said it would be 2022. And I think, you know, we will make the decision once we consider that we have a meaningful data set. So stay tuned. All I can say, you know, running this excellent team, is that accrual has not been a problem.

Rafael Amado: And, you know, the execution continues, you know, actually, you know, at a very slow pace. So hopefully, we'll accumulate data as soon as possible and be able to share it with you. Yeah, I mean, obviously, we're looking at BCMA expression in the plasma cells, we're looking at soluble BCMA, we're looking at MRD, we're looking at persistence, and we're looking at something that's important in this field also, which is extramedullary disease and the ability to prevent relapses outside of the bone marrow.

Rafael Amado: But perhaps the most important factor is the mechanistic reasons for giving neurogastrostat, which is, you know, do we actually see a meaningful increase in BCMA and does that result in a better enhanced activity of the CAR-Ts out of 715? And, you know, that's what we're focused on, but we're doing all the right biomarkers that you mentioned.

Operator: Thank you. Our next question comes from the line of Kalpit Patel from B. Reilly Securities. Your line is now open.

Operator: Hi, thanks for taking the question. Maybe one for David or Rafael?

David D. Chang: In the study for renal cell, obviously, safety is a priority first, but at what dose level should we expect to see some signals of clinical activity based on your preclinical PK-PD modeling? And then can you remind us if the lymphodepleting doses that you're using in renal cell are essentially the same as what you use in your liquid tumor trials? Thanks.

David D. Chang: Let me take the dose-cell-dose question, you know, from the preclinical to the clinical, you know. We all learned that in the CAR T field, it is not as predictable, so in terms of what we expect to see in clinics, I mean, you know, it really has to be done in carefully planned clinical studies, which are currently being done. So stay tuned, I mean, you know, it could happen at the first dose level, or it could happen at the second; the planned dose is three dose levels in the 316 study.

David D. Chang: The second question. The lymphoid depletion for the thalassomer versus heme malignancies, you know, for different reasons, you know, I apologize for not answering the question, you know, we are trying to remain roughly silent on the lymphoid depletion strategy that we are making, so just wait for the data presentation, and as we said in the pre-care statement, we expect the 316 data presentation to occur in 2022,

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

David D. Chang: Thank you. It's an exciting time for Allogene as we look ahead to two near-term events that begin the journey towards commercialization, the planned initiation of our first pivotal trial and taking control of our manufacturing with CellForge1, our first world-class facility. With that, thank you for joining us today and for taking part in our journey to define the future of allogeneic cell therapy. Operator, you may now disconnect. Thank you. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program, and you may now log off and disconnect.

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