Q3 2024 Allogene Therapeutics Inc Earnings Call
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Unknown Executive: Thank you for standing by, and welcome to Allogene Therapeutics Third Quarter 2024 Conference Call.
Speaker Change: Hello, Thank you for standing by and welcome to Allergan Therapeutics third quarter 2024 conference call.
Unknown Executive: After this speaker's presentation, there will be a question and answer session. To ask a question during this session, you'll need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again.
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Unknown Executive: Please be aware that today's conference call is being recorded.
Speaker Change: Please be aware that today's conference call is being recorded I would now like to turn the call over to Christine Cristiano Chief Corporate Affairs and brand strategy Officer Ms. Christina. Please go ahead.
Christine Cassiano: I would now like to turn the call over to Christine Cassiano, Chief Corporate Affairs and Brand Strategy Officer. Ms. Cassiano, please go ahead. Thank you, operator, and welcome to all who have joined this call.
Christine Cristiano: Thank you operator and welcome to all for joining this call.
Christine Cassiano: After the market closed today, Allogene issued a press release that provides a business update and financial results for the third quarter of 2024. This press release and today's webcast are available on our website.
Christine Cristiano: After the market close today Allergan issued a press release that provides a business update and financial results for the third quarter of 2024. This press release and today's webcast are available on our website.
Christine Cassiano: Following our prepared remarks, we will host a Q&A. We recognize that historically questions have been multifaceted, but note that we will endeavor to keep this call to underwriting.
Christine Cristiano: Following our prepared remarks, we will host a Q&A session. We recognize that historically questions has been multifaceted, but note that we will endeavor to keep this call to under one hour.
Christine Cassiano: Joining me today are Dr. David Chang, President and Chief Executive Officer, Dr. Zachary Roberts, Executive Vice President of Research and Development and Chief Medical Officer, and Geoff Parker, Chief Financial Officer.
Speaker Change: Joining me today are Dr. David Chang, President and Chief Executive Officer, Dr. Zachary Roberts Executive Vice President of research and development and Chief Medical Officer, and Geoff Parker, Our Chief Financial Officer.
Christine Cassiano: During today's call, we will be making certain forward-looking These may include statements regarding the success and timing of our ongoing and planned clinical trials, data presentations, regulatory filings, future research and development efforts, manufacturing capabilities, the safety and efficacy of our product candidates, commercial market forecast, and financial guidance, among other things. All of 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 press release and latest SEC disclosure document. You are cautioned not to place undue reliance on these forward-looking statements, and Allogene disclaims any obligation to update them.
Speaker Change: During today's call, we will be making certain forward looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials data presentations regulatory filings future research and development efforts.
Speaker Change: Factoring capabilities, the safety and efficacy of our product candidates commercial market forecast and financial guidance among other things.
Speaker Change: Forward looking statements are based on current information assumptions and expectations that are subject to change and description of potential risks can be found in our press release and latest SEC disclosure documents you are cautioned not to place undue reliance on these forward looking statements and Allergan disclaims any obligation to update these statements I'll now turn the.
David Chang: I'll now turn the call over to David. Thank you, Christine, and welcome to those on the call today. Today I am excited to share our recent progress and upcoming milestones as we continue our mission to redefine cell therapy for both cancer and autoimmune diseases. In the third quarter, our groundbreaking achievements include, one, inherent malign We continue to activate sites and advance the pivotal Phase 2 Alpha 3 trial of SEMICEL for large B-cell lymphoma. This trial marks a significant step forward as stem cell could become the first CAR-T therapy integrated into the first line therapy. With its focus on patients at high risk for relapse and the ability to potentially predict who those patients might be, This trial could transform first-line treatment and set a new standard for patient outcomes.
David Chang: Call over to David.
Thank you Christine and welcome to tell us on the call today.
David Chang: I'm excited to share our recent progress and upcoming milestones as we continue our mission to redefine cell therapy for cancer and autoimmune disease.
David Chang: In the third quarter, our groundbreaking achievements include.
David Chang: One in heme malignancy, we continue to activate sites and advance the pivotal phase III <unk> III trial MSL for large b cell lymphoma. This trial marks a significant step forward as <unk> could become the first car T therapy integrated into the first line treatment.
David Chang: It's focused on patient as high risk for relapse and the ability to potentially predict.
David Chang: Those patients might be this trial could transform personalized treatment and set a new standard for patient outcomes.
David Chang: Thalassemur, ALO316 is showing unprecedented efficacy in thalassemurs through the Phase 1 Traverse Trial for renal cell carcinoma, achieving a confirmed response rate of 33% and best overall response rate of 50% in heavily pretreated patients with high CD70 expression. We define high CD70 expression as tumor proportion score greater than 50%, which represents the majority of patients. This breakthrough led to the ARMED designation from the FDA, positioning ALO316 as a promising treatment for advanced renal flood carcinoma. Our pipeline innovation extends into autoimmune diseases with Allo329, the first dual CD19-CD70 card designed to target CD19-positive B cells and CD70-positive T cells, both key drivers of autoimmune dysfunction.
David Chang: Solid tumor <unk> six is showing unprecedented efficacy in solid tumors through the baselines for breast trial for renal cell carcinoma, achieving a confirmed response rate of 33% and best overall response rate of 50% in heavily pre treated patients with high <unk>.
David Chang: 70 expression.
David Chang: We define high <unk> 70 expression as tumor proportional score of greater than 50%, which represents the majority of the patients.
David Chang: This breakthrough led to the RMS designation from the FDA positioning outlook realized six as a promising treatment for advanced renal cell carcinoma.
David Chang: Pipeline.
David Chang: Pipeline innovation extends into autoimmune diseases with our 2829. The first your CD 19, CD 70 car designed to target CD 19 positive b cells as CD 70, <unk> positive T cells, both key drivers autoimmune dysfunction.
David Chang: By addressing both B-cells and activated T-cells, we are tackling a broader spectrum of autoimmune mechanisms. which could significantly enhance therapeutic outcomes and expand the range of autoimmune diseases we can address. But what really differentiates R0329 is our proprietary Dagger technology. This technology, now clinically validated via the L0316 program, could enable L0329 to overcome one of the biggest anticipated barriers for cardiotherapy in autoimmune disorders, lympho-depletion. We believe this unique feature of L0329 will allow us to reduce or eliminate the need for lympho-depleting chemotherapy, which we believe is a significant barrier to advance cardi-beyond severe cases of autoimmune disorders.
By addressing both T cell and activating T cells, we are tackling a broader spectrum of autoimmune mechanisms, which could significantly enhance therapeutic outcomes and expand the range of autoimmune diseases, we can address.
David Chang: What really differentiates our trait to nine is a proprietary CAGR technology.
David Chang: This technology now clinically validated <unk> six program could enable our suite Tonight to overcome one of the biggest anticipated barrier for car T therapy in autoimmune disorders lymphoid depletion. We believe this unique feature of allo three to nine will allow us to reduce or eliminate.
David Chang: The need for lymphoid depleting chemotherapy, which we believe is a significant barrier to advance cocky here severe cases of autoimmune disorders.
David Chang: Beyond its technical strength, Allo329 is designed as an off-the-shelf and once-and-done solution, which differentiates Allo329 from autologous CAR T or by specific T-cell engagers and allow us to potentially reach these larger patient populations more efficiently. We anticipate an IAMD filing in first quarter 2025 with PREFA concept data by year-end 2025. A sneak peek at the potential of our 3 to 9 infrequent clinical models will be presented at the American College of Rheumatology Convergence on November 18, 2024. Looking ahead to 2025, these developments reflect a potential paradigm shift, highlighting the Allocardi platform's unique ability to address diverse patient This journey is not without challenge, as each trial brings its own level of complexity in a highly competitive field.
David Chang: Beyond his technical strengths. Our 2829 is designed as an off the shelf and once enhanced solution, which differentiates allo 329 from autonomous car T or bi specific T cell engages and allow us to potentially reach these large patient population more efficiently.
David Chang: We anticipate an IND filing in first quarter 2025 with proof of concept data by year end 2025.
David Chang: Sneak peek at the potential of our three Tonight in preclinical models will be presented at the American College of Rheumatology convergence on November 18th 2000 Twenty's Paul.
David Chang: Looking ahead to 2025 CES develop end reflects a potential paradigm shift highlighting the allo car T platform unique ability to address diverse patient needs. This journey is not without challenge as each trial brings its own level of complexity in a highly competitive.
David Chang: It's for this reason we crafted each program with a long-term vision in mind. As Wayne Gretzky famously said, skate to where puck is going to be, not where it hasn't been. That's precisely our approach. By pursuing what we believe are best-in-class therapies with differentiated development approaches to maximize the key attributes of LRKT, we are confident that this strategy of anticipating future needs will yield remarkable outcomes. Each of these programs has the potential to revolutionize the application of cardiac therapy in treating disease and shaping the future of medical practice.
David Chang: At field.
David Chang: It's for this reason we crafted each program with a long term vision in mind.
David Chang: As Wayne Gretzky famously said skate to air pocket is going to be not where it has been that's precisely our approach by pursuing what we believe are best in class therapies with differentiated developed and approaches to maximize the key attributes of Allo car T.
David Chang: We are confident that this strategy of anticipating future needs will yield remarkable outcomes.
David Chang: Each of these programs has the potential to revolutionize the application of car T therapy in treating disease and shaping the future medical practice.
Zachary Roberts: Now, I would like to handle the call over to Zach to discuss the status of Alpha 3 trial and provide a deeper dive into the latest data from our LL316 program. Thank you, David. This quarter, Allogene has made substantial progress, moving us closer to potentially redefining treatment options. Including both oncology and autoimmune diseases through our innovative AlloCart Looking ahead to 2025, we're energized by the advancements in our pivotal SEMICEL trial, the upcoming IND submission for ALLO329, and the promising data for ALLO316 in advanced renal cell carcinoma, recognized by the FDA as a potential...
Speaker Change: Now I would like to handle the call over to Zach to discuss the status of <unk> III trial and provide a deeper dive into the latest data from our three <unk> six program.
Zach: Thank you David this quarter allergy interest made substantial progress moving us closer to potentially redefining treatment options in both oncology and autoimmune diseases through our innovative allo car T platform.
Speaker Change: Looking ahead to 2025, we are energized by the advancements in our pivotal <unk> trial, the upcoming IND submission for our <unk> nine and the promising data for Allo 316 in advanced renal cell carcinoma recognized by the FDA as a potential breakthrough.
Zachary Roberts: While we won't have an update on the Alpha-3 First-Line Consolidation Trial for SEMICEL until mid-2025, when we finalize our go-forward lymphoclepsia. I want to recognize our accept They are navigating a highly complex landscape to bring trial sites online. Since its launch in June, the trial has successfully activated 27 of the planned 50 sites, with approximately 60% of those at community centers. Although the proportion will shift as more academic sites are activated, this early emphasis on community-based centers is essential to ensuring broad access. If any CAR T therapy can make meaningful inroads into community settings, we believe it will be an allogeneic product.
Speaker Change: While we won't have an update on the Alpha III first line consolidation trial for <unk> until mid 2025, when we finalize our go forward lymphoid depletion regimen.
Speaker Change: I want to recognize our exceptional clinical team. They are navigating a highly complex landscape to bring trial sites online amid intense competition and I'm incredibly proud of their accomplishments to date.
Speaker Change: Since its launch in June the trial has successfully activated 27 of the planned 50 sites with approximately 60% of those at community centers, although the proportion will shift as more academic sites are activated. This early emphasis on community based centers is essential to assuring broad accessibility.
Speaker Change: Any car T therapy can make meaningful inroads into community settings, we believe it will be an allogeneic product like ours.
Zachary Roberts: Beyond the LD selection in mid-2025, we continue to anticipate primary event-free survival data by the end of 2026.
Speaker Change: Beyond the LD selection in mid 2025, we continue to anticipate primary event free survival data by the end of 2026 with potential for a biologics license application submission in 2027.
Zachary Roberts: I'd like to now turn your attention to ALLO 316 and the data we released. We are excited to share groundbreaking Phase 1 data on Allo316, our first AlloCAR-T product candidate. This data showcases the encouraging responses found in heavily pre-treated... and underscores the potential for ALLO316 to become a pivotal, off-the-shelf CAR-T therapy. Single infusion of Allyl-316 demonstrated an impressive 50% best overall response. 33% confirmed. patients with metastatic kidney cancer with high CD70 target expression, defined as a tumor proportion score, or TPS, above 50%. Importantly, the majority of patients with advanced or metastatic RCC have CD70 TPS scores at or above.
Speaker Change: I'd like to now turn your attention to our 316 and the data we released this morning.
Speaker Change: We are excited to share groundbreaking phase one data on our 316, our first allo car T product candidate for the treatment of advanced renal cell carcinoma or RCC.
Speaker Change: This data showcases the encouraging responses found in heavily pretreated patients and underscores the potential for <unk> to become a pivotal off the shelf car T therapy for solid tumors.
Speaker Change: Let's dive into the details.
Speaker Change: I'll first start with response rates a single infusion of <unk> demonstrated an impressive 50% best overall response rate and a 33% confirmed response rate in patients with metastatic kidney cancer with high <unk> 70 target expression defined as a tumor proportion score our TPS above 50%.
Speaker Change: Accordingly, the majority of patients with advanced or metastatic RCC have CD 70, TPS scores at or above this level.
Zachary Roberts: Given the number of previous therapies...
Speaker Change: Given the number of previous therapies. These patients have been on most of which were in combination I can't overstate how meaningful. This data is a single infusion that generates responses in patients with advanced disease and also yields what we would call a treatment break.
Zachary Roberts: been on, most of which were in combination, I can't overstate how meaningful this Single Infusion that Generates Responses in Patients with Advanced And also yields what we would call a treatment break. This is part of the reason we believe our investigators are eager to investigate. Just as exciting as the response. first is the dose cohorts where we are seeing... The rates I just mentioned, 50% overall and 33% confirmed responses, occurred in our selected Phase 1b expansion doses. This dose cohort featured a standard fludarabine and cyclophosphamide-based lymphotopoietin. We believe the unprecedented anti-tumor activity of this allogeneic CAR in a solid-tumor setting is attributable in part to our proprietary CD70 dagger technology.
Speaker Change: This is part of the reason we believe our investigators are eager to enroll patients in this trial.
Speaker Change: Just as exciting is the response rates, we've seen in reverse as the dose cohorts, where we're seeing them the rates I just mentioned, 50% overall and 33% confirmed responses occurred in our selected phase <unk> expansion dose cohort.
Speaker Change: This dose cohort feature to standard Fludarabine and cyclophosphamide based when for depletion regimen. We believe the unprecedented antitumor activity of this allogeneic car in a solid tumor setting is attributable in part to our proprietary <unk> technology.
Zachary Roberts: With this technology and our deepening understanding of its intrinsic ability to selectively deplete activated... We have seen robust expansion and sustained activity of allo even with standards, flu side, lymphidoplete chemotherapy. This highlights the potential of the CD70 CAR as a next-generation allogeneic platform capable of producing meaningful clinical responses in solid tumors. In the case of Allo 329, which incorporates...
Speaker Change: With this technology and our deepening understanding of its intrinsic ability to selectively deplete activated CD 70 positive allo reactive host T cells, we have seen robust expansion at sustained activity from our 316, even with standards flu side Lymphopenia chemotherapy regimens.
Speaker Change: This highlights the potential of the <unk> 70 car as a next generation allogeneic platform capable of producing meaningful clinical responses in solid tumors and in the case of our <unk>, nine which incorporate podagra technology and autoimmune disorders as well.
Zachary Roberts: Autoimmune Disorders.
Zachary Roberts: Lastly, and something that has been. With the addition of another 20 patients enrolled since the last data update, we have gained significant experience handling the potent activity of ALLEL316 and have established a safety profile that could enable continued progress in a challenging http://TheBusinessProfessor.com Through our newly implemented diagnostic and management algorithm, we have been able to effectively recognize and treat immune effector cell associated HLH-like syndrome known as IECHS. Much like what was done in the early days of CAR-T development. wrestled with CRS and neuro... Developing and proactively utilizing tools to mitigate risk creates a pathway to maximizing potential.
Speaker Change: Lastly in something that has been much discussed with the addition of another 20 patients enrolled since the last data update we have gained significant experience handling the potent activity of our <unk> six and have established a safety profile that could enable continued progress in a challenging field like car T therapy for solid tumors.
Speaker Change: Through our newly implemented diagnostic and management algorithm, we have been able to effectively recognize and treat immune effector cell associated HLA <unk> syndrome noticed IEC Hs.
Speaker Change: Much like what was done in the early days of car T development that the industry wrestled with Crs and neurotoxicity, developing and proactively utilizing tools to mitigate risk creates a pathway to maximizing potential efficacy and improving patient outcomes.
Zachary Roberts: The strength of our data has led to RMAT designation for ALLEL316, signifying the FDA's acknowledgment of ALLEL316. for Advanced. While we don't typically comment on FDA interactions, the speed with which this designation Allo 316 may have for patients. The data will be featured in an oral presentation at the International Kidney Cancer Symposium, or IHCS. On November 8th, followed by a poster presentation. Society for Immunotherapy of Cancer. Both present. Continue to actively evaluate Allo 316's safety. This will help define the optimal dose for Phase II trials, setting the stage for development for our CAR-T. We are deeply encouraged by these results and the opportunity to offer hope to patients in need of new options.
Speaker Change: The strength of our data has led to our mat designation for Halo 301, six signifying the fda's acknowledgment of allergy about six as a potential treatment for advanced RCC.
Speaker Change: While we don't typically comment on FDA interactions the speed with which this designation was received reflects the promising impact our <unk> may have for patients with advanced or metastatic RCC.
Speaker Change: The data will be featured in an oral presentation at the international kidney cancer Symposium our Ics.
Speaker Change: On November eight followed by a poster presentation at the society for immunotherapy of cancer or <unk> annual meeting on November 9th.
Speaker Change: Both presentations will be accessible on our website.
Speaker Change: We continue to actively evaluate allo 360, <unk> safety and efficacy in the phase <unk> expansion cohort. This will help to find the optimal dose for phase II trials setting the stage for development for our car T technology in solid tumors.
Speaker Change: We are deeply encouraged by these results and the opportunity to offer hope to patients in need of new options for managing their disease. Today's data is a testament to the potential of <unk> 316, and ultimately <unk> commitment to advancing the field of car T cell therapy, we look forward to providing further updates as we move into the next stages of development across all of <unk>.
Zachary Roberts: Today's data is a testament to the potential of HALO 316 and, ultimately, Allogene's commitment to advancing... We look forward to providing further...
David Chang: All right. Thank you, Zach. As I noted last quarter, Allogene is in an enviable position. We control the only clinically validated allogeneic CD19 CAR-T product in a pivotal trial, positioned to transform how and where CAR-Ts are used in heme malignancy. We control the only allogeneic RT that has shown real potential in solid tumors. And we control the only CD19-CD70 dual-car that has been specifically designed to treat autoimmune disease.
Jeff: Programs I'll now turn the call over to Jeff.
Speaker Change: Okay.
Jeff: Thank you Zack as I noted last quarter allergy is in an enviable position, we control the only clinically validated allogeneic CD 19 car T product in a pivotal trial positioned to transform how and where car Ts are used in heme malignancies.
Jeff: We control the only allogeneic car T that has shown real potential in solid tumors.
Jeff: And we control the only CD 19, CD 70 dual car that has been specifically designed to treat autoimmune disease.
David Chang: To continue with David's hockey analogy, these three shots on goal all have the potential to be transformative.
Jeff: To continue with David's hockey analogy. These three shots on goal all have the potential to be transformative let.
Geoff Parker: Let me now turn to our financial highlights. Our cash balance as of the end of Q3 2024 was $403.4 million in cash, cash equivalents, and investments, and our cash runway continues to extend into the second half of 2026. Q3 2024 research and development expenses were $44.7 million, which includes $5.6 million in expenses associated with non-cash stock-based compensation. General and administrative expenses in Q3 were $16.3 million, which includes $7.8 million of non-cash, stock-based compensation expense.
Speaker Change: Let me now turn to our financial highlights.
Speaker Change: Our cash balance as of the end of Q3, 2024 was $403 $4 million in cash cash equivalents and investments and our cash runway continues to extend into the second half of 2026.
Speaker Change: Q3, 2020 for research and development expenses were $44 7 million, which includes $5 6 million in expenses associated with noncash stock based compensation.
Speaker Change: General and administrative expenses in Q3, or $16 3 million, which includes $7 8 million of noncash stock based compensation expense.
Geoff Parker: For Q3 2024, our net loss was $66.3 million, or $0.32 per share, including non-cash stock-based compensation expense of $13.4 million and $10.7 million in non-cash impairment of long-lived asset expense.
Speaker Change: For Q3 2024, our net loss was $66 3 million or <unk> 32 per share.
Speaker Change: Including noncash stock based compensation expense of $13 4 million and $10 7 million in noncash impairment of long lived asset expense.
Geoff Parker: For 2024, we continue to expect a cash burn of approximately $200 million. We continue to expect full-year 2024 GAAP operating expenses to be approximately $300 million, which includes estimated non-cash stock-based compensation expense of approximately $60 million. This guidance excludes any impact from potential business development activities.
Speaker Change: For 2024, we continue to expect a cash burn of approximately $200 million.
Speaker Change: We continue to expect full year 2024, GAAP operating expenses to be approximately $300 million, which includes estimated noncash stock based compensation expense of approximately $60 million.
Speaker Change: This guidance excludes any impact from potential business development activities.
Unknown Executive: We'll now open the call for questions. Thank you. At this time, we'll conduct a question and answer session.
Speaker Change: We will now open the call for questions.
Speaker Change: Thank you at this time, we will conduct a question and answer session.
Unknown Executive: As a reminder to ask a question, you'll need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.
Speaker Change: To ask a question you will need to press star one of your telephone and we appear to be in.
Speaker Change: To withdraw your question. Please press star one again, please standby will compile the Q&A roster.
Tyler Van Buren: Our first question comes from Tyler Van Buren of TD Cowen. Your line is now open.
Speaker Change: Our first question comes from the line of colored Baron of TD Cowen. Your line is now open.
Tyler Van Buren: Hey, guys. Good afternoon, and congratulations on all the progress. I have a couple for you. The first one is just on the RCC data, the 30% confirmed response rate in these late-line patients is, of course, pretty impressive.
Speaker Change: Hey, guys good afternoon, and congratulations on all the progress.
Speaker Change: A couple for you the first one is just.
Speaker Change: On the RCC data, 30% confirmed response rate in these late line patients of course.
Tyler Van Buren: So, can you give us insight into when you might be done with the expansion cohort and be able to start at pivotal for potential approval? And then the second is just regarding the read-throughs of the 316 data to your 329 autoimmune program. I agree that these data with Just Fc is impressive as we think about reducing or removing lymphodepletion, but can you discuss your confidence and safety in autoimmune specifically and why the 316 data might not be the best read-through?
Speaker Change: Impressive. So can you give us insight into when you might be done with the expansion cohort and be able to start a pivotal for potential approval and then the second is just regarding the read throughs of the 316 data to your 309 autoimmune program.
Speaker Change: I agree that big data with just FCA is impressive, but as we think about reducing or removing them up with depletion, but can you discuss your confidence and safety and autoimmune specifically and why the 316 data might not be the best.
Speaker Change: Read through.
David Chang: Tyler, this is Dave Chang. Thanks for very insightful questions.
Tyler: Tyler This is state, saying thanks for your very insightful questions. The first one in terms of the status.
Zachary Roberts: The first one, in terms of the status of ongoing traverse study, let me turn it over to Zach to answer the questions that you had.
Speaker Change: Ongoing Trucker study, let me turn it over to Zach too.
Zach: To answer the questions that you had.
Zachary Roberts: Thanks, David, and thanks, Tyler. Great questions. So the first one, how many patients do we expect to enroll into this expansion cohort? So we're aiming for approximately 20. We think that that will give us the sort of adequate number of patients to really ascertain response rate as well as durability, which, of course, we'll have to wait for some of that information to come in into next year.
Zach: Thanks, David and thanks, Tyler great questions.
Speaker Change: So the first one.
Speaker Change: How many patients do we expect to enroll into this expansion cohort. So we're aiming for approximately 20%. We think that that will give us the sort of adequate number of patients to really ascertain response rate as well as durability, which of course will have to wait for that some of that information.
Speaker Change: To come come in into next year. So we expect to be able to give program update next year.
Zachary Roberts: So we expect to be able to give a program update next year. As for the second question on 329, so, you know, we continue to be quite encouraged by the dagger effect in the 316 program, and, you know, we have some additional data in the poster that will kind of illustrate that even further, and, you know, with additional patients having been treated, we have more and more confidence that this is real, and, in fact, we have selected a Phase 1b expansion lymphodepletion regimen that does not include ALLO647. So we've already been able to demonstrate efficacy with a reduced, substantially reduced lymphodepletion regimen.
Speaker Change: As for the second question on Us on 329 so.
Speaker Change: We continue to be quite encouraged by the dagger effects.
Speaker Change: <unk> hundred six program.
Speaker Change: We have some additional data in the in the <unk>.
Speaker Change: <unk> started that will kind of illustrate that even further.
Speaker Change: Additional patients having been treated this.
Speaker Change: More and more confidence that this is real and in fact, we have selected.
Speaker Change: The phase <unk> expansion lymphoid depletion regimen that does not include <unk>.
Speaker Change: Our 647, so we've already been able to demonstrate efficacy.
Speaker Change: With a reduced substantially reduce some sort of depletion regimen. So we have pretty high confidence actually that that will carry forward into the <unk> nine program.
Zachary Roberts: So we have pretty high confidence, actually, that that will carry forward into the 329 program. We don't intend to use 647 in the autoimmune setting.
Speaker Change: We don't intend to use 647 in the autoimmune setting.
Zachary Roberts: We'll be dealing with chemotherapy alone, and we, while we haven't disclosed exactly the plan to really pressure test the ability to reduce or eliminate lymph node depletion, that is definitely one of the key objectives of the early phase of that study. And then finally, just a comment quickly on the safety piece. So, you know, we know that patients with advanced malignancies are fundamentally different from an inflammatory milieu from patients with autoimmune disease. And secondly, you know, it's pretty obvious from the existing data that the duration of CAR T persistence and functional activity, namely the duration of, say, B-cell aplasia as a biomarker of CAR T cell activity, we know that that is substantially lower in the autoimmune setting than it is in somebody who's got, you know, a very, very bulky tumors, as many of the patients in the 316 program did.
Speaker Change: We'll be dealing with chemotherapy alone.
Speaker Change: While we havent disclosed exactly the plan to to really pressure test the ability to reduce or eliminate LIFO depletion that is definitely one of the key objectives of the year.
Speaker Change: Phase of that study.
Speaker Change: And then finally just to comment quickly on the safety piece.
Speaker Change: We know that.
Patients with advanced malignancies are fundamentally different from an inflammatory milieu from patients with autoimmune disease and secondly.
Speaker Change: It's pretty obvious from the existing data that.
Speaker Change: The duration of car T persistence.
Speaker Change: And functional activity, namely the duration.
Speaker Change: Duration of safety sell aplasia as a biomarker of car T cell activity, we know that that is substantially lower in the autoimmune setting than it is in somebody who's got a <unk>.
Very bulky tumors as many of the patients and that would be one six program did so overall, we think that the.
David Chang: So overall, you know, we think that the intensity of the therapy that will be required in an autoimmune patient will be comparatively lower. That said, you know, we have built a lot of experience dealing with the toxicity associated with ALO 316, you know, through management of infections, the details around IECHS. We have a really good handle on how to diagnose and manage these. So we think that, you know, number one, lower intensity therapy in AID. Number two, you know, we will be absolutely ready for any talks that does crop up. And Tyler, let me just add, I mean, I think over the years, we have learned that, you know, the patient population and indications and the tumor burdens or the target burden, you know, greatly influences, you know, safety as well as efficacy.
Speaker Change: The intensity of the therapy that will be required in an autoimmune patient will be comparatively lower that said, we have built a lot of experience dealing with the toxicity associated with.
Speaker Change: With our 316.
Speaker Change: Through management of infections, the details around IU CHS, we have a really good handle on how to diagnose and manage these so we think that.
Speaker Change: Number one lower intensity therapy in AIB number two we will be absolutely ready for any talks that does crop up.
Speaker Change: And Tyler let me just add I mean, I think over the years, we have learned that.
Speaker Change: Patient populations and indications and tumor burdens.
Speaker Change: Target burden.
Speaker Change: Lee influences safety as well as efficacy. So yes, we know a lot from our experience in <unk> six and also through the course of <unk>.
David Chang: So, yes, you know, we know, you know, a lot from, you know, our experience in 3.1.6 and also through the course of developing 3.1.6, we learned to manage the adverse event a lot better.
<unk> 316, we learned to manage to add a lot better.
David Chang: And to your specific question about, you know, the read-through into the autoimmune program, you know, my view is that this is something that we have to clinically, you know, you know, test. I don't think there is a much read-through that you can make because of the indication target burden are so different, you know, between advanced kidney cancer versus autoimmune disease.
Speaker Change: And to your specific question about the read through into the autoimmune program.
Speaker Change: My view is that this is something that we have to clinically.
Speaker Change: First I don't think there is a much read through that you can make.
Speaker Change: Because the indication target burden is so different between advanced kidney cancer versus autoimmune disease.
Unknown Executive: Thank you.
Unknown Executive: One moment for our next question.
Speaker Change: Thanks.
Speaker Change: Thank you our next question.
Brian Chang: Our next question comes from the line of Brian Chang of J.P. Morgan. Your line is now open.
Speaker Change: Okay.
Speaker Change: Question comes from the line of Brian Cheng of Jpmorgan. Your line is now open.
Shauna: Hi, thanks for taking our question. This is Shauna for Brian. Could you give us a better sense of the Grade 5 events that you reported in the data today? Were there any confounding effects that led to those cases?
Hi, Thanks for taking our question. This is Sean on for Brian could you give us a better sense of that.
Speaker Change: Great five events that you reported in the data today or is there any confounding effects that led to those cases.
Shauna: And on the ICHS case, could you walk through how the management algorithm is implemented? How easy will it be for doctors to monitor potential ICHS cases?
Speaker Change: On the ICA chest case could you just walk through how the management algorithm has implemented how easy will it be for doctors to monitor potential IHS events.
David Chang: Yeah, Sean, thanks for those, you know, great questions. I mean, you know, we disclose all the you know, adverse event findings from the 316. And especially in oncology in, you know, in a patients with advanced metastatic disease. In my experience, there is never a simple, you know, adverse event, it's very much confounded by the underlying disease. And also a lot of times in phase one, the doses that we use, as well as different lymphodepletion that we have tested. So I can simply say that every case of the adverse events that we see in the 316, especially the grade five events that you mentioned, are very confounded.
Speaker Change: Yes.
Speaker Change: Thanks for those great questions.
Speaker Change: We disclose all the adverse events findings from the 316.
Speaker Change: And especially in oncology.
Speaker Change: In patients with advanced metastatic disease in my experience there is never a simple adversity that it's very much confounded by the underlying disease and also a lot of times in phase one.
Speaker Change: Doses that we use as well as deployment for depletion that we have tested so I can simply say that every case of the adverse events that we see in.
Speaker Change: In the 316, especially the great events that you mentioned, Barry compounded and ill ask Jack to answer the second question.
Zachary Roberts: And I will ask Zach to answer the second question.
Zachary Roberts: Yes, thanks Shauna and David. So, as far as management of IECHS, the algorithm that we've developed and is detailed in the upcoming SITC materials is pretty clear. It's very analogous, in fact, to the algorithms that were developed in the early days for CRS and ICANN. It's sort of a two-step process. You monitor signs and symptoms and lab values carefully, and if you are convinced that there is an inflammatory process ongoing based on the diagnostic criteria, which are very, very clear, then you institute first-line therapy, and then you escalate quickly if you don't see a very rapid response to that first-line therapy.
Jack: Yes, Thanks, Sean.
David Chang: David So as far as management.
David Chang: CHS.
David Chang: The algorithm that we've developed and we will and as detailed in the upcoming 60 materials is pretty clear, it's very analogous in fact too.
David Chang: The.
David Chang: The algorithms that were developed in the early days for Crs and I can so theres sort of a two step process.
David Chang: Monitor signs and symptoms and lab values carefully and there is if you are convinced that there is.
David Chang: Inflammatory process ongoing based on the diagnostic criteria, which are very very clear.
David Chang: And then you Institute first line therapy.
David Chang: And then you escalate quickly if you don't see it.
David Chang: Rapid.
David Chang: Our response to that first line therapy.
Zachary Roberts: So, thank you. You know, this is a tried and true methodology for managing CAR T related toxin. This one is just a slightly different flavor, given that it's IECHS. So it should be pretty clear and pretty easy to implement. And in fact, it has been easy to implement.
David Chang: This is a tried and true methodology for managing car T related toxic just want is just a slightly different flavor. Given then it's IHS. So it should be pretty clear and pretty easy to implement and in fact, it has been easy to implement in the study.
Zachary Roberts: when we meet again. And, Sean, I would also add, you know, this entity, IECHS, now that it's more widely recognized and, you know, based on the publications over the last couple years, there's a much better understanding. And, in fact, as people, you know, better understand this entity, it is being recognized as, you know, a spectrum of, you know, cytokine release syndrome, but, you know, time course is a little bit different.
David Chang: When we needed it.
Speaker Change: And Sean I would also add this entity CHS now that it's more widely recognized and based on the publications over the last couple of years. There is a much better understanding and in fact as people better understand this and it.
David Chang: It is being recognized as.
David Chang: Spectrum.
David Chang: Cytokine release syndrome, but no time course is a little bit different and I think all of these nuanced understanding is making the management.
Zachary Roberts: And I think all these nuanced understanding is making the management of this hyperinflammatory events a lot easier. Thank you, David.
David Chang: Now this hyper inflammatory events a lot easier.
Unknown Executive: Thank you.
David Chang: Great. Thank you David Thank you.
Unknown Executive: Thank you one moment for our next question.
Speaker Change: Thank you one moment for our next question.
Michael Yee: Our next question comes from the line of Michael Yee of Jeffries.
Speaker Change: Our next question comes from the line of Michael Yee of Jefferies. Your line is now open.
Michael Yee: Your line is now open. Hey, guys. Thanks for the updates.
Speaker Change: Yes.
Speaker Change: Hey, guys. Thanks for the updates.
Michael Yee: We had two questions. One was on your first line lymphoma study. I know it's early, but maybe just comment a little bit about what you're seeing out there in terms of the screening rate for MRD positivity, how are things in terms of execution going, and how are you thinking about the pace of enrollment as you are getting that underway?
Speaker Change: Two questions one was on your first line.
Speaker Change: Lymphoma study I know, it's early but maybe just comment a little bit about.
Speaker Change: What youre seeing out there in terms of the screening rate for MRV positivity, how are things in terms of execution going and how are you thinking about the pace of enrollment.
Michael Yee: And then the second question is back to autoimmune. Obviously, that has been a big focus point for a lot of different companies, and actually, we're seeing a lot of dynamics around CAR T versus T cell engagers, and now a battle around that. Maybe just comment about how you see CAR T there versus T cell engagers and talk a little bit about your perspective there, given what we're seeing out there.
Speaker Change: As you are getting that underway.
Speaker Change: And then the second question is.
Speaker Change: Ottawa, obviously, there has been a.
Speaker Change: Big focus point for a lot of different companies and actually we're seeing a lot of dynamics around car T versus T cell engagement and our battle around that maybe just comment about how you see car T. There versus T cell engaging <unk> talk a little bit about.
Speaker Change: About your perspective, they are given.
David Chang: Thank you. Mike, nice to hear from you. Always fantastic questions.
Speaker Change: What we're seeing out there. Thank you.
Speaker Change: Mike Nice to hear from you always a fantastic questions I'm going to reverse the order I'm going to talk about the AIB in different modality, that's going into and I'll ask Zack to get back to the.
David Chang: I'm going to reverse the order. I'm going to talk about the AID and different modality that's going into, and I'll ask Zach to get back to the frontline study. We can think how to manage these diseases in a totally different way. B cell depletion, which is really underlying mechanism behind what I use using T cell engager or CAR T. That is being targeted, and people are realizing that this can bring a substantial so-called drug-free and disease-free interval to patients. When I think about autoimmune indications, I mean, this is, you know, there are so many different diseases and, you know, so many opportunities.
Speaker Change: Frontline study.
Speaker Change: Yes.
Speaker Change: I think what we all have to recognize is that.
Speaker Change: Through the experience.
Speaker Change: Palace car T over last two to three years.
Speaker Change: People are sort of looking at the auto immune disease as well as other diseases that.
Speaker Change: Caused by although we active b cell so antibody productions.
Speaker Change: We can think how to manage these diseases in a totally different way.
Speaker Change: B cell depletion, which is really underlying mechanism behind what I use using T cell engagement or car T.
Speaker Change: That is being target in <unk>.
Speaker Change: People are realizing that this can bring a substantial.
Speaker Change: <unk> core dropped three.
Speaker Change: And disease free interval to patients when.
Speaker Change: When I think about auto immune indications I mean this is.
Speaker Change: There is so many different diseases and so many opportunities.
David Chang: With respect to the modality, the way we view about different modalities, there are more than one modalities that can coexist. And even within, you know, one particular modality, I think there can be multiple successful stories. And if you look at the history of, you know, autoimmune, you know, drug development, that's exactly the case. So, you know, I just want to emphasize the opportunities, the great opportunities that there is. You know, obviously, even in that context, you know, our team thinks about, you know, how is, you know, different modalities different, and everything comes with a different twist.
Speaker Change: With respect to the modality the way we deal about different modality and there are more than one modalities that can coexist.
Speaker Change: And even within one particular modality I think there can be multiple successful stories and if you look at the history up.
Speaker Change: Audra immune.
Speaker Change: Drug development, that's exactly the case, so I just want to emphasize to opportunities to create opportunities that there is.
Speaker Change: Obviously, even in that context, our team thinks about how is different modalities different and everything comes with a different twist, but for the allogeneic car T.
David Chang: But, you know, for the Allogene CAR-T, I mean, one is, this is off the shelf, you know, the convenience and all those things, you know, factor in. And also, CAR-T, you know, usually is being viewed as a, you know, once and done, you know, one time treatment. I think these are very attractive propositions, you know, to the physicians who are managing autoimmune disorders.
Speaker Change: One is.
Speaker Change: This is off the shelf.
Speaker Change: <unk> and all those things factor in and also car T. Usually view is being viewed as.
Speaker Change: <unk> done one time treatment I think these are very attractive proposition.
Speaker Change: The physicians, who are managing those immune disorders and lastly, the focus of our outlook by two nine development program is really address one of the sort.
David Chang: And lastly, you know, the focus of our, our 329 development program is really address one of the sort of perceived challenges of, you know, CAR-T, which is the lympho-depleting chemotherapy. The way that the 329 is designed is to really address this head on, you know, the built-in dagger technology that's coming from the CD70 portion of our dual CAR-T. And, you know, like anything else, we are really, you know, you know, accelerating this, you know, program and, you know, some of the key questions that you are asking. As the data matures, data emerges, I think we will know a lot better.
Speaker Change: Perceived challenges.
Speaker Change: Car T, which is the lift for the plan and chemotherapy.
Speaker Change: Laid at the 3% to 90 is designed is to really address this head on.
Speaker Change: Built in dagger technology, that's coming from the CD 70, a portion of our deal of car T and like anything else we are.
Speaker Change: Really accelerating this program.
Speaker Change: Program and some of the key questions that youre asking as that data matures data emerges I think we will know a lot better, but we feel very excited about <unk> and <unk>.
Zachary Roberts: But, you know, we feel very excited about our L0329 and the potential benefits that it can bring to the patients with autoimmune disorders.
Speaker Change: Potential benefits that it can bring to the patients with autoimmune disorders.
Zachary Roberts: Zach, on the first question. Yep. Thanks, Mike, for the question. So, what I can say is that the, the enthusiasm and the engagement from our clinical trial sites has really been through the roof. I, I am, you know, on a daily basis extremely excited by the, the, the pace at which we are able to onboard sites, the activity of the sites that have been onboarded. I would say in these early days of the trial, there, there, you know, things are sort of unfolding in a standard way. And, and especially as the, as we pointed out in the prepared remarks and in the press release, you know, the earliest sites to activate here have been predominantly community sites.
Speaker Change: <unk> on the first question.
Speaker Change: Yes, Thanks, Mike for the question so what I can say is that.
Speaker Change: The enthusiasm and the engagement from our clinical trial sites has really been through the roof.
Speaker Change: And on a daily basis extremely excited by the.
Speaker Change: The pace at which we're able to onboard sites the activity of the sites that have been on boarded.
Speaker Change: I would say in these early days of the trial there things are sort of unfolding in a standard way and especially as the as we pointed out in the prepared remarks and in the press release.
Speaker Change: The earliest sites to activate here has been predominantly community sites and <unk>.
Zachary Roberts: And some of them, in fact, some of the more active sites don't have CAR T experience. So, you know, they're, they're requiring a little extra handholding, but there is absolutely no shortage of, of engagement and enthusiasm. And, and even the patients that are, are screening, you know, MRD negative, they're deriving a nice benefit, right? Because they're getting access to something a little bit more prognostic than, than what is out there already. So very, very, very encouraging launch to the trial. Yeah, I would say that, I mean, the study is progressing as planned. There are certain things that we are finding out.
Speaker Change: Some of them in fact, some of the more active sites don't have car T experience. So.
Speaker Change: They're requiring a little extra handholding, but.
Speaker Change: There is absolutely no shortage.
Speaker Change: Of of engagement and enthusiasm and even the patients that are our screening.
Speaker Change: MRV negative they are deriving a nice benefit right, because they're getting access to something a little bit more prognostic them and what is out there already so.
Speaker Change: Very very very encouraging launch to the trial.
Speaker Change: Yes, I would say that I mean, the study is progressing as planned.
Speaker Change: There are certain things that we are finding out.
Zachary Roberts: I mean, compared to pre-COVID days, site activation is a lot more, you know, requires a lot more hands-on approach to get all the documents taken care of and also get the site ready. And that's where, you know, I really recognize our clinical operations team to be, you know, so reactive and handling that very effective. And I'm very proud of, you know, what they have done with the site activation, you know, which is, you know, as Zach had said, you know, going very smoothly. Very good.
Speaker Change: Compared to pre Covid days site activation is a lot more.
Speaker Change: Requires a lot more hands on approach to get all the documents taken care of and also get the site ready and that's where I really recognize our clinical operations team to be.
Speaker Change: So reactive and handling that they're effective and I'm very proud of what they have done with our site activation which is.
Speaker Change: As Zack had said going very smoothly.
Speaker Change: Very good thank you.
Unknown Executive: Thank you.
Unknown Executive: One moment for our next question.
Speaker Change: Thank you Luke for next question.
Salveen Richter: Our next question comes from line of Salveen Richter of Schoolman SAC.
Speaker Change: Our next question comes from the line of <unk> Richter of Goldman Sachs. Your line is now open.
Marc: Your line is now open. Hey, guys. This is Marc on for Salveen. Congrats on the quarter, and thank you for taking our question. I have two quick ones on Allo316 and the data that was released today. It seems that for the FC lymphodepletion without the CD52, that group performed a little bit better than the FCA group that did have the CD52. I realize the Ns are smaller here, but can you speculate as to why there's that difference?
Speaker Change: Hey, guys. This is mark on for Solvay and congrats on the quarter and thank you for taking my question I have two quick ones on Allo 316, and the data that was released today.
Speaker Change: It seems that for the FCA depletion without the CD 50 to that.
Speaker Change: That group performed a little bit better than the CF.
Speaker Change: CA group that did have the CD 52, I realize the <unk> small here, but can you speculate as to why there's that difference and also.
Marc: And also, can you discuss what you are looking for in the Phase 1b expansion cohort data that's planned for 2025? Like, what threshold of data would give you confidence on the forward regulatory path?
Speaker Change: Can you discuss what you are looking for in the phase one expansion cohort data that is planned for 2025 like.
Speaker Change: Like what threshold of data would give you confidence on the <unk> regulatory path.
David Chang: Marc, great to hear from you. Let me just quickly respond to the first question. It's a small number. We are seeing responders both with FCA and FC, but the fact that we are seeing the responses in FC is probably the most interesting finding from our CITSE poster presentation.
Mark: Hey, Mark.
Speaker Change: Great to the airport.
Speaker Change: Let me just quickly respond to the first question. It's a small number we are seeing.
Speaker Change: Responders, both with FCA NFC.
Speaker Change: And the fact that we are seeing the responses NFC is probably the most interesting finding from our <unk>.
Speaker Change: The poster presentation as an allogeneic car T program, we foresee that this program moving forward with a standard poolside baseline for depletion.
Zachary Roberts: As an allogeneic CAR-T program, we foresee that this program moving forward with a standard fluocyte-based lymphodepletion without need for any kind of enhancement in the lymphodepletion. And that's really coming from the underlying dagger biology that's intrinsic from the CD70. And the differences that you're seeing, I think, with the small numbers, I would not read too much into that.
Speaker Change: Need for any kind of enhancement in the linked with depletion and Thats really coming from the underlying Diego biology, Thats intrinsic from the CD 70, and the differences that you're seeing I think with a small numbers I would not read too much into that.
Zachary Roberts: And Zach, do you want to take the second question? Yeah, so I think, you know, as I mentioned a moment ago, you know, we're shooting for 20 patients at this phase 1B regimen and then, you know, sort of awaiting for that durability. So I think, you know, if you just look numerically at where we sit right now from a confirmed response rate, you know, we, I think, are numerically better than the third-line options that are currently approved in this context. So we're pretty happy with that. Of course, you know, it's always nice to see, you know, even more responses.
Speaker Change: Zack do you want to take the second question.
Speaker Change: Yes, so I think as I mentioned, a moment ago, we're shooting for 20 patients at this phase <unk> regimen.
Speaker Change: And then sort of a waiting for that durability. So I think if you just look numerically at where we sit right now from a confirmed response rate. We I think are are numerically better than third line options that are currently approved in this in this context.
Speaker Change: So we're pretty happy with that of course, it's always nice to see even more responses, but the question I think that will just need to wait a little bit longer on is the durability. We've got a couple of nice ongoing remissions out several months in the patients treated with the phase one b regimen. So I think stay tuned for that program.
Zachary Roberts: But, you know, the question I think is that we'll just need to wait a little bit longer on is the durability. We've got a couple of nice ongoing remissions out several months in the patients treated with the phase 1B regimen.
Zachary Roberts: So I think stay tuned for that program update next year.
Speaker Change: Graham update next year.
Unknown Executive: Thank you.
Unknown Executive: One moment for our next question.
Speaker Change: Thank you Robert for next question.
Jack Allen: Our next question comes from the line of Jack Allen of Baird.
Speaker Change: Our next question comes from the line of Jack Cohen of Baird. Your line is now open.
Jack Allen: Your line is now open. All right. Thanks so much for taking the questions. And congratulations to the team on the progress.
Jack Cohen: Alright, thanks, so much for taking the questions and congratulations to the team on the progress I guess the first question I had was I mentioned of the alpha to studying the CLO cohort in your release and maybe I missed it on the call, but is that still planned it ongoing and how should we think about the go forward path. There and then Jack I think you just touched on it quite a bit on the <unk>.
Jack Allen: I guess the first question I had was, I didn't see a mention of the Alpha 2 study in the CLL cohort in your release, and maybe I missed it on the call. But is that still planned and ongoing? And how should we think about the go forward path there? And then Zach, I think you just touched on it quite a bit on the 316 program and the bar for durability. I was hoping you could just elaborate how you think about the existing standard of care and what you're looking to see for durability from 316 and RCC.
Jack Cohen: X program and the bar for durability I was hoping you could just elaborate how you think about the existing standard of care and what Youre looking to see for durability from three six in RCC. Thanks, so much.
David Chang: Thanks so much. Hi, Jack.
Zachary Roberts: Well, I'll take the first question and I'll have, you know, Zach answer the second one. The CLL study is ongoing. And, you know, we are currently in the process of prioritizing, you know, different programs. When I look at the overall pipeline, you know, without a question, the Alpha 3 study in the frontline consolidation is our top priority. And as we have shown, you know, sort of advanced the 329, you know, we are realizing that this could potentially be very important program for allergen and perhaps even for the entire field. So we are spending a lot of time to accelerate as much as we can with a 329 program.
Speaker Change: Hi, Jack.
Speaker Change: Well I'll take the first question and I'll have.
Speaker Change: Yes, Zach answer the second one.
Speaker Change: All studies ongoing.
Speaker Change: And we are currently in the process of prioritizing different programs.
Speaker Change: I look at the overall pipeline.
I had a question.
Speaker Change: <unk> III study in the frontline consolidation is our top priority and as we have Shaw.
Speaker Change: That's a three to nine.
Speaker Change: Realizing that this could potentially be very important program.
Speaker Change: For Allergan and perhaps even for the entire field. So we are spending a lot of time to accelerate as much as we can with a three to nine program and certainly the solid tumor program. It's also giving us sort of pause about what to do so in all of this context, yes CLR studies.
David Chang: And, you know, certainly the thalatoma program, it's also giving us sort of pause about what to do.
David Chang: So in all this context, yeah, the CLL study is ongoing, but, you know, it will be part of the prioritization and we'll be providing a program update in next year.
Speaker Change: Ongoing but.
Speaker Change: It will be part of <unk> will be providing a program update.
Next year.
Zachary Roberts: And then, Jack, just to kind of elaborate a little bit more on efficacy, you know, I'll broaden it a bit to sort of speak generally.
And then Jack just to kind of elaborate a little bit more on efficacy I'll broaden a bit to sort of speak generally, but first I want to point out again.
Zachary Roberts: So, first, I want to point out again that FDA has recognized this program with the RMAT designation as a potential breakthrough for patients in relapsed refractory post-TKI, post-checkpoint blocker. So, if you look at that subset of patients that are in the third line, I think outcomes there, both from a response rate as well as a PFS, are fairly modest. And the other thing I'll point out there is that, you know, that's continuous therapy. So, what we have to offer here is, you know, potentially an equivalent or improved response rate and then a period of treatment-free remission.
Speaker Change: <unk> recognized this program with the army designation as a potential breakthrough for patients relapsed refractory post CGI.
Speaker Change: Post checkpoint blocker. So if you look at that subset of patients that are in the third line I think outcomes there both from a response rate as well as our PFS are fairly modest.
Speaker Change: The other thing I'll point out there is that.
Speaker Change: That's continuous therapy, so what what we have to offer here.
Speaker Change: <unk> is.
Speaker Change: Essentially.
Speaker Change: Equivalent or improved response rate and then a period of treatment free remission and I think that's always been one of the key attributes and attractive points.
Zachary Roberts: And I think that's always been one of the key attributes and attractive points of CAR-T therapy, generally speaking, and it's no different in this context. So, you know, I think we have to take all of that together in mind. And, you know, nobody would be happier than I, well, except for potentially the patients themselves, if we were able to put these patients into very, very durable remissions. And that's, of course, what we're hoping to do. But, you know, we have to wait and see how that shakes out and where, you know, how it lines up to the existing therapies, as I said, you know, with the PFS on the order of a handful of months.
Speaker Change: Car T therapy, generally speaking and it's no different in this context. So I think we have to take all of that together in mind and nobody would be happier than I modeled et cetera potentially patients themselves.
Speaker Change: We were able to put these patients into very very durable remissions and Thats of course, what we're hoping to do.
Speaker Change: And but we have to wait and see how that how that shakes out and where.
Speaker Change: Where how it lines up to the existing therapies as I said with the with the PFS on the order of a handful of months. So the bar is quite low here and we shared that continuously from our our investigators who are constantly looking to put patients on this trial. So you have a lot of support from the investigator community here to continue pushing forward.
Zachary Roberts: So, the bar is quite low here, and we hear that continuously from our investigators who are, you know, constantly, you know, looking to put patients on this trial. So, we have a lot of support from the investigator community here to continue pushing forward, and they're seeing, you know, real benefits to their patients.
Speaker Change: And theyre seeing real benefits to their patients.
Unknown Executive: Thank you.
Biren Amin: One moment for our next question. Our next question comes from Biren Amin of Piper Family. Your line is now open.
Speaker Change: Yeah.
Speaker Change: Thank you for our next question.
Speaker Change: Our next question comes from the line of Brian I mean of Piper Sandler Your line is now open.
Biren Amin: Biren Amin, your line is now open. Hi, guys. Thanks for taking my question.
Speaker Change: Alright, I mean your line is now open.
Speaker Change: Yeah.
Speaker Change: Yeah, Hi, guys. Thanks for taking my questions.
Biren Amin: Zach, for ALLO 316, what kind of a durability do you need to see to give you confidence to go meet with FDA on a pivotal design at the end of 2025?
Speaker Change: Zach for Allo 316, what kind of a durability do you need to see to give you confidence to go meet with FDA on a pivotal design.
Speaker Change: At the end of 2025.
Biren Amin: And then I guess on ALLO 329 with the IMD planned imminently, what type of indications are you expecting to pursue in the Phase 1?
Speaker Change: Then I guess on allo three to nine with the R&D plan.
Speaker Change: And then secondly, what type of indications are you expecting pursuing the phase one thanks.
Zachary Roberts: Thanks. Zach? Yep. Thanks, David. Thanks, Biren. Good question.
Zach Allo: Zach yes.
Speaker Change: Thanks, David Thanks, Barry and good question, so on 31 six.
Zachary Roberts: So, on 316, you know, I'll paraphrase, you know, what I've said so far, which is, you know, I think the bar is low here. We've got two of these patients who are in the confirmed responses in that, in the first group and treated at the, in the Phase 1b regimen, who are in ongoing, nice, deep partial remissions at four and six months. So, they're continuing to deepen over time. We'll have to see how those and the subsequently treated patients develop.
Speaker Change: Paraphrase, what I've said, so far which is I think the bar is low here. We've got two of these patients who are in the confirmed responses in that.
Speaker Change: In the first group and treated at the in the.
Speaker Change: A phase <unk> regimen, who are in ongoing nice deep partial remissions at four and six months. So they are continuing to deepen over time, we'll have to see how those and the subsequently treated patients develop the.
Zachary Roberts: The fact that we have this RMAT designation, which is, you know, just nothing more than a few days old now, is it does give us access to kind of more frequent and in-depth conversations with FDA. So, you know, I think they're, you know, by virtue of having granted this designation, they're enthusiastic about the potential for this therapy, and I think we're just going to have to, you know, wait for that durability data to come in, and then, you know, go and have that conversation with the time.
Speaker Change: The fact that we have this army designation, which is just nothing more than a few days old now and it does give us access to kind of more frequent and in depth conversations with FDA. So I think there.
Speaker Change: By virtue of having granted this designation they're enthusiastic about the potential for this therapy and I think we're just going to have to wait for that durability data to come in and then go in and have that conversation when the time comes.
Zachary Roberts: As far as the second question on indications for 329, the preponderance of the data that's out there right now is in rheumatologic conditions, first and foremost is lupus. We have said all along this year that we're going to be starting our focus there in rheumatology. We haven't yet said exactly which indications we're going to pursue and in what order, but suffice it to say we are watching the data develop in the field. We're very excited about rheumatology. We're watching to see how others are expanding beyond that, but we're going to be taking a path that really follows that proof of concept data.
As far as the second question on indications for <unk> nine.
The preponderance of the data that's out there right now is in rheumatology.
Speaker Change: Conditions first and foremost as lupus.
Speaker Change: We have said all along this year that we're going to be starting our focus there in rheumatology, we haven't yet said exactly which which indications we're going to pursue and in what order but.
Speaker Change: Suffice it to say we are.
Speaker Change: Watching the data develop in the field, we're very excited about rheumatology, we're watching to see how others are expanding beyond that but we're going to be taking.
Speaker Change: Past that really follows that proof of concept data.
Unknown Executive: Thank you.
John Neumann: One moment for our next question. Our next question comes from the line of John Neumann of Kennecourt, Genealogy. Your line is now open.
Speaker Change: Thank you next question.
Speaker Change: Our next question comes from the line of John Newman of Canaccord Genuity. Your line is now open.
John Neumann: Hi guys, great progress. Thank you for taking my question.
John Newman: Hi, guys great progress. Thank you for taking my question.
John Neumann: David, I wondered if you could talk about the importance of breaking pathological B-cell and T-cell response in autoimmune disease. So we've heard a lot and we've seen a lot of folks Seems very important. We've seen a lot of focus on the phenotype of the B cells when they recover, but not very many people have talked about how the T cells are involved. So I'm just curious as to how you think about that with your.
David I'm wondering if you could talk about the importance of braking.
Speaker Change: Pathological b cell and T cell response.
Speaker Change: So we've heard a lot and we've seen a lot of focus on b cell depletion levels, which seems very important we've seen a lot of focus on the phenotype of the T cells when they recover.
But not very many people have talked about how the T cells are in the fall. So I'm just curious as to how you think about that with your products.
David Chang: Hey, John, great question. You know that probably goes you know in a beyond even you know you know my scientific understanding but you know if you go to the you know immunology literature The interaction between different lymphocytes leading to, you know, the B-cell development and B-cell differentiating, you know, differentiation into the antibody-producing cells, I mean, that is complex. And, you know, still, you know, the one of the main contributors of that B-cell, you know, the maturation is the T-cells as well as some other, you know, cells. And by the way, these other sort of lymphocytes that are involved in the enhancing the B-cell response, you know, they also express CD70.
Speaker Change: Hey, John Great question.
Speaker Change: Probably goes.
Speaker Change: In the PS zone, even my scientific understanding but.
Speaker Change: If you go to the immunology of literature.
Speaker Change: The interaction between different lymphocytes, leading to.
Speaker Change: <unk>.
Speaker Change: <unk>, South development and B cell differentiation.
Speaker Change: Differentiation into the antibody producing cells.
Speaker Change: I mean that is complex and.
Speaker Change: Still the one of the main contributor of that piece.
Speaker Change: The maturation.
Speaker Change: Is T cells as well as some other.
Speaker Change: Cells and by the way these other sort of lymphocytes that I'm both in enhancing the B cell response. They also express CD 70, so from our perspective.
David Chang: So from our perspective, yes, you know, when the B-cells get depleted, all the indications are the returning B-cells have a naive phenotype. They will have to undergo, you know, some kind of maturation and to become pathogenic again. And I think by going after, you know, both B-cell and the activated T-cell early on, they can potentially, you know, address the underlying pathology more fully, you know, rather than just going after, you know, a single B-cell component.
Speaker Change: Yes.
Speaker Change: When the <unk> get depleted all the indications are that returning b cells have a naive phenotype.
Speaker Change: They will have to undergo.
Speaker Change: Some kind of maturation and to become pathogenic again, and I think by going after both T cell and activating T cells early on they can potentially address the underlying pathology more fully rather than just going after a single b cell components.
David Chang: That's a, you know, hypothesis. And another thing that's very important to us is, in addition to what CD70 can bring in that equation, is that CD70, you know, has the dagger, you know, biologies, which allows us, you know, to use Allo329, you know, with a minimum lymphodepletion. I mean, we have already shown, you know, in the 316 program, even as an allogeneic, when there is a dagger technology incorporated into it, you know, you don't need any enhancement. I think this is something that we can extrapolate into the autoimmune indications. And that, you know, underlies our plan to reduce or eliminate the lymphodepletion during the initial investigation of Allo329 in patients with autoimmune disorders.
Speaker Change: Hypothesis and another.
Speaker Change: Another thing that's very important to US is in addition to what <unk> 70 can bring in that equation is the Cvs 70 in <unk>.
Speaker Change: Biology's, which allows us.
Speaker Change: He used our <unk> two nine.
Speaker Change: With a minimum level of depletion I mean, we have already shown in the 301 sixth program, even as an allogeneic when there is a dagger technology incorporated into it.
Speaker Change: You don't need any enhancement I think this is something that we can extrapolate into the autoimmune indications.
Speaker Change: That underlies our plan too.
Speaker Change: Reduce or eliminate the lymphoid depletion during the initial investigation, our three to nine in patients with autoimmune disorders.
Unknown Executive: Thank you.
Unknown Executive: One moment for our next question.
Speaker Change: Thank you Robert for next question.
Luca Issi: Our next question comes from the line of Luca Issi of RBC Capital.
Speaker Change: Our next question comes from the line of Luca <unk> of RBC capital. Your line is now open.
Luca Issi: Your line is now open. Oh, great. Thanks so much for taking my question, and congrats on the progress.
Speaker Change: Oh, great. Thanks, so much for taking my question and congrats on the progress maybe.
Zachary Roberts: Maybe, Zach or David, on RCC, do you have any tumor aspirates or renal biopsies here? You know, wondering if you have any evidence suggesting that the cells are actually able to infiltrate the tumor microenvironment here, which I think is something that has been kind of the main historical issue here for CAR T for solid tumors. So, I mean, you called there. Much appreciated.
Speaker Change: Maybe jack or David on RCC.
Speaker Change: Do you have any tumor aspirates or renal biopsies here wondering if you have any evidence, suggesting that the cells are actually able to infiltrate the tumor microenvironment here, which I think is something that has been kind of the main historical issue issue here for car T for solid tumors. So any call. It they're much appreciate it and then maybe just to clarify is it fair.
Zachary Roberts: And then maybe just to clarify, is it fair to assume that all the responses so far are PRs and not CRs?
Speaker Change: If you assume that all of the responses so far.
Speaker Change: And not CR.
Speaker Change: Thanks, so much.
Zachary Roberts: Zach, do you want to take that question? Sure.
Jack Cohen: Jack you want to take that question sure look as always great questions.
Zachary Roberts: Luca, as always, great questions. So the first one, the answer is yes. We have actually quite a number of tumor aspirates and biopsies that we have collected within the first couple of weeks after infusion. And we do have a figure in the poster that really lays that out. In fact, there's a dozen contemporaneous biopsies and peripheral blood samples. And in that figure, it's quite convincing, actually, that the ability of Allo316 to get into the tumor bed itself is quite robust. And we see, essentially, in almost all of those 12 biopsies, equivalent CAR transgene in the tumor aspirate is in the peripheral blood drawn at the same time.
Jack Cohen: So the first one the answer is yes, we have actually quite a number of tumor aspirants in biopsies.
Jack Cohen: That we have collected within the first couple of weeks after infusion.
Jack Cohen: And we do have a figure in the poster that really lays that out in fact theres a dozen.
Jack Cohen: Contemporaneous biopsies and peripheral blood samples and in that figure. It is quite convincing actually that the ability of <unk> to get into the tumor bed itself is quite robust and we see essentially almost all of those 12 biopsies equivalent car Trans gene.
Jack Cohen: In the Bakken in the tumor aspect is in the peripheral blood drawn at the same time, so we find that to be extremely encouraging in terms of getting to where the cells need to be.
Zachary Roberts: So we find that to be extremely encouraging in terms of getting to where the cells need to be.
Jack Cohen: The source decide a path apology.
Zachary Roberts: Regarding your second question about PRs and CRs, we did have one complete metabolic remission in a patient who had an antecedent confirmed PR, so it was a PR that deepened to a complete remission. Unfortunately, that patient contracted COVID and expired from that infection, so sort of an extremely unfortunate situation to die from an infection when you're in remission, but that patient was in a complete remission in addition to the other ongoing and deepening PRs. Thank you.
Jack Cohen: Regarding your second question about Prs and Crs.
Jack Cohen: We did have one complete metabolic permission in a patient who had an antecedent confirmed PR. So it was a PR.
Jack Cohen: That deep into a complete remission and.
Jack Cohen: Unfortunately that patients contracted COVID-19, an expired from that infection. So.
Jack Cohen: Sort of an extremely unfortunate situation to die.
Jack Cohen: From a from a.
Jack Cohen: And infection. When you are in remission, but that patient wasn't a complete remission. In addition to the other ongoing and deepening Trs.
Unknown Executive: One moment for our next question.
Speaker Change: Thank you for our next question.
Samantha Semenkow: Our next question comes from the line of Samantha Semenkow of CD, your line is now open. Hi, good afternoon. Thanks for taking the question. I just wanted to follow up with some of the prior questions on the safety data for Allo 316 and completely understanding that the underlying disease burden is a confounder here.
Our next question comes from the line of Cementos <unk> with Citi. Your line is now open.
Speaker Change: Hi, good afternoon. Thanks for taking the question I just wanted to follow up on some of the prior questions on the safety data for Allo 316, and completely understanding that the underlying disease burden is a can founder here, but is there any rationale that targeting CD 70 in the context of the dagger technology could also be.
Samantha Semenkow: But is there any rationale that targeting CD70 in the context of the Dagger technology could also be contributing to the grade 5 events and just overall safety profile? And what are your thoughts on how that could translate into your autoimmune program, particularly in the context of how you're thinking about choosing a dose for that program?
Speaker Change: Contributing to the grade by grade five events and just overall safety profile and how what are your thoughts on.
How that could translate into your autoimmune program, particularly in the context of how youre thinking about choosing a dose for that program. Thank you.
David Chang: Thank you.
David Chang: Hi, Samantha, let me take the question. We are looking, you know, like in any drug development, all the safety findings, you know, very carefully, but, you know, especially in the 316 study, I do believe the poster will go online, you know, like pretty soon, so, you know, it will be more detailed. I mean, these are very heavily pretreated patients, really, you know, running out of options, and usually in that kind of situation, you know, they are pretty, you know, sick patients, and so, you know, yes, you know, these events did occur, but, you know, trying to read through that to what may happen in autoimmune, you know, patients with autoimmune disorder, you know, I don't think, you know, there is much that we can read through, and the second question is, does this have to do with the DAGGER technology?
Speaker Change: So Matt let me take that question.
Speaker Change: Got it.
Speaker Change: We are looking like.
Speaker Change: Like in any drug development, all the safety findings seen a very carefully but.
Speaker Change: Specially in the 301 six studies I.
Speaker Change: I do believe the poster will go online.
Speaker Change: Pretty soon so it will be more detail on these are very heavily pretreated patients.
Speaker Change: Really running out of options and usually in that kind of situations.
Speaker Change: They are pretty sick.
Speaker Change: Sick patients and so.
Speaker Change: Yes.
Speaker Change: These events did occur, but trying to read through that to what may happen in autoimmune patients with autoimmune disorder.
Speaker Change: There is a much that we can read through and the second question is does this have to do with a dagger technology.
David Chang: DAGGER technology, you know, what does, you know, what it does is really, you know, enhance the pharmacodynamic effect of CAR-T, so, you know, yes, to some extent, but at the end, you know, this is really how you develop the, you know, any, you know, is the ABCs of drug development, you know, we are dealing with active drugs, which is always a good place to start, and then we have to find the right cell dose, and for the CAR-T, right lip for depletion, that balances out the efficacy and the safety, so, like anything else, as I said before, these are the things that will be part of the phase one study, you know, as we, you know, advance the Aller-329 program.
Speaker Change: Diego technology, what does.
Speaker Change: What it does is really enhanced pharmacodynamic effect of car T. So yes to some extent, but at the end. This is really how you developed.
Speaker Change: Any any.
Speaker Change: Is the abcs of drug development.
Speaker Change: We are dealing with active drugs, which is always a good place to start and then we have to find the right cell dose.
Speaker Change: And for the car T right look for depletion.
Speaker Change: Balances out the efficacy and the safety so.
Speaker Change: Like anything else as I've said before these are the things that will be part of the phase one study as we.
Speaker Change: Our bands to outlook with two nine program.
Unknown Executive: Thank you.
Unknown Executive: One moment for our next question.
Speaker Change: Thank you Luke for next question.
Okay.
Matthew Biegler: Our next question comes from the line of Matthew Biegler of Outcall. Your line is now open. Great, thanks. Hi, everyone. Just one from us.
Speaker Change: Our next question comes from the line of Matthew Blair of Alco. Your line is now open.
Speaker Change: Great. Thanks, Hi, Ron just one from US can you talk about patient retention efforts in alpha three.
Matthew Biegler: Can you talk about patient retention efforts in alpha-3, because the question we often get is why a patient randomized to watch and wait would choose to stay in the trial versus maybe some form of like off-label consolidation treatment. I don't even know if that exists, but can you just kind of comment on that theory that we're hearing?
Speaker Change: Because the question, we often get is why a patient randomized to watch and wait would choose to stay in the trial versus maybe some form of like off label consolidation treatment I don't even know if that exists but can you just kind of comment on that theory that we're hearing thanks.
David Chang: Thanks.
David Chang: Hi, Matt. Yeah, it's very so, you know, let me let me take that question. Give Zach a little bit of break. The standard care in, you know, in a large B-cell lymphoma after they complete the treatment is watch and wait. And, you know, watch and wait, meaning that they undergo periodic radiographic scans to see what's happening to the disease. And, you know, it occurs at a different interval, as you know, after the completion of the, you know, the archery. In terms of that particular question about patient retention, I mean, The patients who are enrolled in our study, they'll be getting the best standard care that is available to them.
Speaker Change: Hi, Matt.
Speaker Change: Yes, So let me let me take that question gets a little bit of a break.
Speaker Change: The standard of care in.
Speaker Change: In our large b cell lymphoma. After they complete the treatment is watch and wait.
Watch and wait meaning that they undergo periodic.
Speaker Change: Radiographic scans to see what's happening to the disease and it occurs at a different interval at after the completion of the.
Speaker Change: Oxide treatment.
Speaker Change: In terms of that particular question about patient retention.
Speaker Change: The patients who are enrolled in our study they'll be getting the best standard of care that is available to them.
David Chang: And in our discussions with the investigator, they feel that that is very sufficient, you know, for them to carry out the conversation with the patient and retain the patients on the study. And obviously in this setting, you know, when patient progresses, you know, they can go on to any of the available treatment. But when the patient progresses, I mean, they already had the primary event, you know, the primary endpoint of the Alpha 3 study is, you know, event-free survival. So, you know, when somebody, you know, starts the next treatment, I mean, that is an event in the event-free survival analysis.
Speaker Change: And in our discussions with investigators they feel that that is very sufficient for them to carry out the conversation with the patient and retained the patients on the study and obviously in this setting when peso progresses.
Speaker Change: They can go on to any of the available treatment by when the patient progresses I mean, they already had the primary event.
Speaker Change: The primary endpoint of the Alpha three study is.
Speaker Change: Event free survival, so when somebody starts.
<unk> treatment that is sudden event and the event free survival analysis.
Unknown Executive: Thank you.
Sammy Corwin: One moment for our next question. Our next question comes from the line of Sammy Corwin of William Blair. Your line is now open. Hi, thanks for taking our question.
Speaker Change: Thank you Gordon for next question.
Gordon: Our next question comes from the line of Sami <unk> of William Blair. Your line is now open.
Speaker Change: Hi, Thanks for taking our question, which is <unk> first annual Sameer.
Brooke: This is Brooke on for Sammy. So we are wondering, going off on Alpha-3 again, how has physician interest been with the Alpha-3 trial and what feedback have you received on what aspects of potential use of SemaCell in the first line is most valuable? Like, is it community use, affordability, time to treat or something else?
Speaker Change: I was wondering going off on all shopping again.
Speaker Change: Has the physician interest bandwidth that olfactory trial and what feedback have you received on what aspects of potential use of <unk> in the first line is most valuable.
Speaker Change: Community with the portability time to training or something else.
Brooke: Great questions. Zach, you want to take that? Sure. Thanks, Brooke. So, you know, overall, the enthusiasm is extremely high. Honestly, you know, having been part of the, you know, the team at KITE that really led to the approval of YesCarta, I mean, I lived and breathed third-line LBCL for several years. I can say that the level of enthusiasm for Alpha 3 has been as high, if not higher, than those early days of the Zuma 1 trial. So, I think physicians broadly recognize that if Alpha 3 is successful, that this will usher in a new era of LBCL management and kind of fundamentally change the paradigm.
Great question, Zach you want to take that sure. Thanks.
Zach Allo: Thanks Brook.
Zach Allo: So overall the enthusiasm is extremely high honestly, having been part of.
Zach Allo: The team at kite that really led to the approval of yes, Carter I lived and breathed.
Zach Allo: Third line <unk> for several years I can say that the level of enthusiasm for alpha three.
<unk> been as high if not higher than those early days in the Zuma one trial, so I think physicians broadly recognize that.
Zach Allo: Alpha <unk> is successful this will usher in a new era of <unk> management and kind of fund really fundamentally changed the paradigm.
Zachary Roberts: As far as, you know, why they think that, which is the second part of your question, I think it's all those features that you mentioned.
Zach Allo: As far as why they think that which is the second part of your question I think it's all of those features that you mentioned I think.
Zachary Roberts: I think, you know, first is, you know, being able to implement a new and novel and highly accurate prognostic tool in this MRD test. Being able to respond immediately to the result. That is something that is paradigm shifting unto itself. And to be able to do that with an off-the-shelf therapy that, you know, literally that, you know, within days of receiving the MRD positive result, you can initiate lymphodepletion and then deliver a potentially curative dose of CAR T cells. And to do that in community settings that have been on the sidelines of the CAR T revolution from the beginning.
Zach Allo: First is being able to implement.
Zach Allo: Our new and novel and highly accurate prognostic tool in this MRV test being able to respond immediately to the result that is something that is.
Zach Allo: Paradigm shifting unto itself and to be able to do that with an off the shelf therapy that literally.
Zach Allo: Within days of receiving the MRV positive result, you can initiate them for depletion and then deliver a potentially curative dose of car T cells and to do that in community settings that have been on the sidelines of the car T Revolution from the beginning so we see we see enthusiast.
Zachary Roberts: So, you know, we see enthusiasm coming from sites, community sites that don't have a lot of CAR T experience or any CAR T experience because it's giving them access to this. We see enthusiasm from academic sites because they see how this could fundamentally alter the future of frontline LBCL management. So it's really kind of a grab bag of really exciting topics that we're hearing lots of positive feedback.
And coming from sites community sites that don't have a lot of car T experience or any car T experience, because it's giving them access to this we see enthusiasm from academic sites because they see how this could fundamentally alter the future of frontline <unk> management. So it's really kind of a grab bag of a really exciting topics.
Zach Allo: That we are hearing lots of positive feedback from.
Unknown Executive: Thank you.
Unknown Executive: One moment for our next question.
Speaker Change: Thank you one moment for our next question.
William Pickering: Our next question comes from the line of William Pickering of Bernstein.
Our next question comes from the line of premium Pickering with Bernstein. Your line is now open.
Zachary Roberts: Your line is now open. Hi, thank you for taking my question, and congrats on the progress this quarter. I had a safety question about LO316. It looks like you had multiple DLTs at the dose level 2 that you're using in the expansion cohort, including one of the grade 5 AEs. So could you just speak to how you see the acceptability of this safety profile if it's more or less unchanged once you have data in the full 20 patients you're targeting for the cohort?
Speaker Change: Yes.
Speaker Change: Alright. Thank you for taking my question and congrats on the progress this quarter.
Speaker Change: I had a question about allo 316, it looks like you add multiple DLT or dose level, two that youre using in the expansion cohort, including one of the.
Great Fine Aes. So could you just speak to how you see the acceptability of this safety profile, if it's more or less unchanged. Once you have data in the fall 20 patients you're targeting for the cohort. Thank you.
Zachary Roberts: Zach, you wanna take that question? Sure. So I'll point out that the DLTs were in, it was the same cell dose, it was 80 million, but it was in patients who had received FCA conditioning, so the inclusion of allo-647.
Speaker Change: Zack do you want to take that question sure.
Zach Allo: I'll point out that the DLT is we're in it.
Speaker Change: It was the same cell doses 80 million, but it was in patients who had received FCA conditioning. So the inclusion of allo 647. So.
Zachary Roberts: So we had reached the DLT limit in that cohort, so we did not advance dosing any further in the FCA arms beyond dose level two. So because the overall treatment intensity is lower in the FC only arm, right, with the elimination of one of the three-part lymphodepletion, we did not encounter DLTs in that cohort, and the efficacy seemed to be the best in the subsets that we were evaluating in a dose exploration phase, so that's why that was selected. Yeah, and we never take any kind of safety findings lightly, but the two DLTs, there have been two DLTs as our press release indicated.
Speaker Change: Those we had reached the.
Speaker Change: DLT.
Speaker Change: <unk>.
Speaker Change: Limit in that cohort. So we did not advance dosing any further in the FCA arms beyond.
Speaker Change: Dose level two so because the overall treatment intensity is lower in the FC only arm the elimination of one of the three part.
Speaker Change: Lymphoid accretion that the.
Speaker Change: We did not encounter DLP is in that cohort.
Speaker Change: The efficacy.
Speaker Change: Seem to be the best in the subset that we were evaluating in that dose exploration phase. So that's why that was selected.
Speaker Change: And we never take any kind of safety findings slightly but.
Speaker Change: Two a DLT is that David <unk> as our press release.
Zachary Roberts: One was a DLT that we had previously disclosed back in 2023 when we presented at AACR, and that was in a patient who had previous exposure to checkpoint inhibitor before going on to another study and autoimmune hepatitis. So again, it's somewhat confounded DLT, but it is a DLT from the protocol perspective, and the second one is the one that is described as a cardiogenic shock in this data communication.
Speaker Change: Indicated.
Speaker Change: One was a DLT that we had previously disclosed back in 2023, when we presented.
Speaker Change: At ACR and that was in <unk>.
Speaker Change: Patients, who had previous exposure to checkpoint inhibitor before going on to on a at a study in autoimmune hepatitis. So again is somewhat compounded DLT, but it is a DLC from the protocol perspective, and the second one is the one that is described as a cardiogenic shock.
Speaker Change: And this data communication.
Unknown Executive: Thank you.
Unknown Executive: One moment for our next question.
Speaker Change: Thank you Margaret for next question.
Laura Prendergast: Our next question comes from the line of Laura Prendergast of Raymond James.
Speaker Change: Our next question comes from the line of Laura <unk> of Raymond James.
Laura Prendergast: Your line is now open. Hey guys, congrats on the progress. I was generally just curious, the rate of enrollment in these autoimmune indication studies for cell therapy has been pretty slow.
Speaker Change: Your line is now open.
Speaker Change: Hey, guys congrats on the progress.
Speaker Change #100: Generally just curious the rate of enrollment than these autoimmune indication.
David Chang: As you think about 326 entering phase one, how are you guys planning on maneuvering these headwinds? You know, Laura, I mean, you know, great question. I mean, that's, you know, a topic that we are following pretty closely as other companies present about the enrollment status. But the general sense I get is, you know, you know, like six, you know, nine months ago, you know, everything in enrollment seemed to be pretty slow. But definitely the enrollment into the autoimmune studies are picking up. And this is very typical. I mean, you're dealing with the investigators who have, that have not had any CAR T experience, you know, in the beginning.
Speaker Change #100: For cell therapy has been pretty slow as you think about breaches. That's entering phase one how are you guys planning on maneuvering you had one.
Speaker Change #100: Laura.
Speaker Change #101: A great question I mean thats.
Speaker Change #101: Topic that we are following pretty closely as the Companys presents about the enrollment status.
But the general sense I get is.
Speaker Change #101: <unk>.
Speaker Change #101: Slide six nine months ago every scene enrolment seem to be pretty slow, but definitely the enrolment into the Ot immune studies are picking up and this is very typical I mean, you're dealing with the investigators who that have not had any car T experience in the beginning I mean, we.
David Chang: I mean, we certainly learned that when we were involved in CD19 CAR T in the, during the ESCADA development. But once they get somewhat familiar with, you know, the CAR T, things will speed up. And I think that's exactly what we are seeing. And in our case, not only, you know, we are, you know, going into an area where, you know, physicians are getting some familiarity with the CAR T, but we are also going in with the Allogene CAR T, which really takes away a lot of logistic complexity of administering the CAR T. So we are very hopeful that as we move into the autoimmune, we will be able to execute studies smoothly.
Speaker Change #101: Certainly learned that when we were involved in CD 19 car T. In the during the ESCADA development, but once they get somewhat familiar with.
Speaker Change #101: The car T things to speed up and I think thats exactly what we are seeing and in our case.
Not only.
Speaker Change #101: We are going into an area where.
Speaker Change #101: Physicians are getting some familiarity with the car T. But we're also going in with the allogeneic car T, which really it takes away a lot of logistic.
Speaker Change #101: Complexity of administering the car T. So we're very hopeful that as we move into the Ot immune.
Speaker Change #101: We'll be able to execute study smoothly.
Unknown Executive: Thank you.
David Chang: That concludes our question and answer session. I would like to turn the conference back over to management for any additional comments. Yeah, I just want to end by saying that our commitment remains clear to be to bring transformative off the shelf therapies to patients with difficult to treat cancer or autoimmune diseases. With each new milestones, we move closer to realizing the potential of our CAR-T products in ways that could reshape treatment landscape across oncology and autoimmune diseases.
Speaker Change #102: Thank you that concludes our question and answer session I would like to turn the conference back over to management for any additional comments.
Speaker Change #103: Yes, I just want to end by saying that our commitment remains clear to be to bring transformative off the shelf therapies to patients with difficult to treat cancer for autoimmune diseases.
Speaker Change #103: With each new milestones, we move closer to realizing the potential of our car T products in ways that could reshape treatment landscape across oncology and autoimmune diseases and with that thank you very much for joining us on this journey and operator you may now disconnect.
Unknown Executive: And with that, thank you very much for joining us on this journey.
Unknown Executive: And operator, you may now disconnect. Thank you for your participation in today's conference. This does conclude the program.
Speaker Change #104: Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Unknown Executive: You may now disconnect.
Unknown Executive: Thank you for watching!
Speaker Change #104: Okay.
Speaker Change #104: [music].
Speaker Change #104: Okay.
Speaker Change #104: Okay.
Speaker Change #104: Yes.
Speaker Change #104: [music].
Speaker Change #104: Okay.
Okay.
Speaker Change #104: [music].