Q4 2024 Allogene Therapeutics Inc Earnings Call
Thank you for watching!
[inaudible]
Speaker Change: Hello, thank you for standing by and welcome to Allogene Therapeutics' fourth quarter in full year 2024 conference call. After the speaker's presentation, there will be a question and answer session. Thank you very much.
Speaker Change: These may include statements regarding the success and timing of our ongoing and planned clinical trials data presentation regulatory filings future research and development efforts manufacturing capability, the safety and efficacy of our product candidates commercial market forecast and financial guidance among other things.
Speaker Change: These 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 released and latest SEC disclosure documents. Your question not to place undue reliance on these forward looking statements and Allergan disclaims any obligation to update these statements I'll now turn.
Speaker Change: On the call over to David.
David: Thank you and welcome everyone.
Speaker Change: Or it could be speaking with you today.
At the start of 2024, we set forth a bold strategy.
Speaker Change: Some viewed as really works on Powerpoint with a distant horizon.
Speaker Change: A year later, we stand on the brink of a transformative year.
Speaker Change: <unk>.
Speaker Change: Pioneering allogeneic car T therapy was never expect it to be easy.
Speaker Change: It demands vision rigorous science.
Speaker Change: Relentless persistence and operational excellence.
Speaker Change: Today, all three of our key programs are approaching critical milestones, marking the tangible progress about dedication.
Speaker Change: We enter 2025 stronger than ever.
Differentiated pipeline and a clear path to shaping the future of allogeneic car T.
Speaker Change: Our programs in large b cell lymphoma.
Speaker Change: Auto immune disease, and renal cell carcinoma are breaking new ground reinforcing our commitment to making off the shelf cell therapy, a new standard of care.
Speaker Change: Our pivotal phase III <unk> III trial.
Speaker Change: MSL in first line consolidation large b cell lymphoma is widely considered to be groundbreaking.
Immensely proud of the innovation behind this trial.
Speaker Change: Enthusiasm from both community cancer centers, and leading academic institutions has been truly energizing.
Speaker Change: And momentum continues to build with 40 sites now activated.
Speaker Change: We anticipate reaching a critical milestone with the lymphoid depletion selection.
And futility analysis around mid 2025.
Speaker Change: This interim analysis will provide essential insight into whether our approach is on track to meet its objectives.
Speaker Change: Providing a clear signal of progress when we select our lymphoid depletion regimen.
Speaker Change: Oncology 2024 also marks our expansion into autoimmune disease with allo three to nine.
Speaker Change: First of its kind CD 19, CV 70, dual targeting allogeneic car T product candidate <unk>.
Speaker Change: A word by our propriety technology.
Earlier this year, we secured FDA clearance for our phase one resolution basket trial in rheumatology.
Speaker Change: An important step towards delivering a scalable off the shelf car T access to the vast number of patients who stand to benefit.
The IMD clearance for our <unk> commenced allergan as a true innovator in the autoimmune disease space.
Speaker Change: We did not follow the crowd, we deliberately took the time to ensure our approach was differentiated.
Speaker Change: Developing both an investigational product and trial, specifically to address the unique challenges of autoimmune disease.
Our great. Two nine is designed to induce lasting remissions by targeting both T cell and activate T cells.
Speaker Change: An equally important design feature is incorporation.
Our <unk> technology, which has the potential to reduce or even eliminate the need for lymphoid depletion.
Speaker Change: Successful.
This breakthrough could fundamentally change our car T therapies deployed in auto immune diseases.
With a resolution trial slated to launch in mid 2025 and proof of concept data expected by year end.
Speaker Change: We believe our three to nine represents a new frontier in allogeneic cell therapy that will showcase the power of our platform to redefine treatment paradigms beyond oncology.
Speaker Change: In solid tumors <unk> is emerging as a promising and potentially groundbreaking asset in renal cell carcinoma.
Speaker Change: The phase one data, we presented last year underscores the potential of allogeneic car T therapy to drive meaningful responses in solid tumors, an area where cell therapies have historically faced immense challenges.
Speaker Change: With our regenerative medicine advanced therapy designation outlook rebound six has the potential to redefine treatment of advanced renal cell carcinoma.
Speaker Change: Bringing a much needed innovation to patients with limited options and.
Speaker Change: In mid 2025, we plan to share an update from our phase <unk> cohort focusing on durability.
Speaker Change: A key factor in improving long term patient outcome.
Speaker Change: From a broader perspective, the momentum across our program highlights the potential of allogeneic car T therapy to disrupt multiple disease areas.
We aim to not just compete with autologous therapies, we are demonstrating that allogeneic approaches can surpass them in accessibility and scalability.
Both pivot in 2020 full coupled with our relentless execution of firms that we have the right team.
Speaker Change: <unk> and strategy to make 2025, a breakthrough year for Allergan.
Speaker Change: One that define the future of allogeneic car T therapy.
Speaker Change: I would like to now hand, the call over to that to provide further details on our clinical programs.
David: David we take great pride in our clinical progress across our R&D organization and the company as a whole.
David: All three of our cutting edge programs demonstrate significant promise reinforcing the strength of our science and execution.
We are energized by the momentum in our pivotal <unk> trial in first line consolidation <unk> the upcoming launch of the resolution basket trial with Allo 329 in rheumatology.
David: And the compelling data emerging from Allo 306 in advanced renal cell carcinoma.
David: Let's start with the foundation of our programs. The field has question for years, whether an allogeneic car T could deliver durable responses with multiple patients with relapsed refractory <unk> and ongoing complete remissions beyond four years.
David: Now have proof that our products can achieve that.
The journal of clinical oncology as recent publication of our phase one Alpha Alpha two trial results in relapsed refractory large b cell lymphoma marks a defining moment for the field.
These findings represent the most comprehensive allogeneic car T dataset to date. The study showed efficacy comparable to approved autologous car Ts with an overall response rate of 58% and a complete response rate of 42% across the study increasing to 67% and 58% respectively with the pivotal study regimen.
David: Importantly treatment delivered exceptional durability with a median duration of response of $23 one months and median overall survival not reached in patients who attained CR.
David: We also observed a potentially best in class safety profile with no cases of graft versus host disease immune effector cell associated neurotoxicity syndrome or high grade cytokine release syndrome. The median time to treatment was just two days significantly shorter than the weeks long wait times acquired for autologous car T.
Moreover, these results provide compelling evidence supporting the use of car T therapy in patients with low disease burden.
David: A growing body of research indicates that earlier intervention with car T. When the disease burden is minimal can lead to improved safety and efficacy outcomes. In this study reinforces that premise among.
David: Among patients with baseline tumor burden of less than 1000 millimeters squared or normal LDH levels, a key biomarker of low disease activity.
David: The complete response rates were 100% and 82% respectively.
David: These findings strongly supports MSL as a breakthrough therapeutic option for patients with minimal residual disease, which is the population studied in alpha three the first randomized trial evaluating car T. As first line consolidation therapy for <unk> positive patients.
David: With <unk>, 100% CR rate in patients with low, but still radiographic evidence of disease burden in these earlier trials.
David: Three presents an unprecedented opportunity to both predict relapse and intervene before it occurs.
David: If successful Alpha III stands to up and the standard of care in first line L. Bcl potentially marking the first significant advance the treatment paradigm in the last 25 years.
David: Since the trials launch in June we have made steady progress today, we have successfully activated 40 of the planned approximately 50 sites with roughly a 50 50 split between community cancer centers and academia and we're progressing towards the first key milestone in Alpha three trial <unk> depletion regimen selection anticipated around mid 2025.
David: Beyond signaling progress in accrual the Olympia Depletions selection step is paired with a futility analysis and thus our decision to proceed will be a critical indicator that the trial is on track to meet its objectives based on early data.
David: Moreover, this milestone will help map the registrational path forward further solidifying our confidence in <unk> potential to redefine the standard of care.
David: Due to the seamless pivotal design. These early patients results count towards the pivotal analysis, and therefore, we will not be releasing detailed efficacy or safety outcomes to protect trial integrity.
David: Beyond LD selection, we plan to conduct an interim analysis, which will be overseen by the independent data safety monitoring board in the first half of 2026.
David: The primary analysis data readout is expected around year end 2026, with a potential BLA submission in 2027.
Speaker Change: None of this would be possible without the great partnership of foresight diagnostics and Theyre ultra sensitive Cte DNA based clarity assay powered by phase seek.
Speaker Change: For this reason, we expanded our strategic collaboration with foresight to support the development of their MRV assay as a companion diagnostic in the EU, UK, Canada, and Australia to support <unk> clinical development of <unk>.
Speaker Change: Shifting gears to autoimmune diseases in January 2025, the FDA cleared the IND for the phase one resolution basket trial, a first of its kind study evaluating allo 329, and systemic lupus erythematosus lupus nephritis, idiopathic inflammatory myopathy and systemic sclerosis.
Speaker Change: This true basket design brings significant operational efficiencies, allowing enrollment access to a broad patient pool with a single IRB approval. This is one of several differentiating factors that may prove advantageous in this competitive space.
The strategy behind Allo 329 stems from two key observations first autologous car T data suggest that short term car T. Persistence is sufficient to reset the immune system and auto immune diseases contrasting with the months to even years long persistence needed in oncology.
Speaker Change: Since b cell depletion loss around 100 days in autologous studies Allogeneic car Ts natural two to four months persistence makes it uniquely suited for autoimmune therapy.
Second data from our phase one allo 300, <unk> six program and kidney cancer demonstrated that our dagger technology intrinsically enhances cell expansion and persistence, allowing us to significantly reduce the intensity of lymphoid accretion without sacrificing efficacy.
These insights shaped allo three to nine which includes the dagger technology and is intended to enable reduction or even elimination of lump for depletion a major differentiator and autoimmune treatment.
Speaker Change: The resolution trial will immediately test the requirement for lyft for depletion in parallel cell dose escalation pathways and one we will use a single infusion of cyclophosphamide at a dose used in rheumatology and in the other car T only arm with no lymphoid depletion relying entirely on the dagger effect.
Speaker Change: The trial is set to launch mid year with proof of concept data expected around year end.
Speaker Change: Extensive preclinical validation published data and an optimized designed allo <unk> is positioned to be the most rigorously designed allogeneic car T program for autoimmune disease to date beyond rheumatology, it's potential extends to nephrology neurology hematology and even inflammatory bowel disease paving the way for a new era of car T.
Speaker Change: <unk> and immune driven conditions.
Speaker Change: Last quarter I highlighted allo 316, and it's remarkable potential following data that showcased encouraging responses from a single infusion with an impressive 50% best overall response rate and a 33% confirmed response rate and heavily pretreated metastatic kidney cancer patients, whose tumors expressed high levels of CD 70.
Speaker Change: Given that update I'll keep it brief today with just a reminder of the next steps for this promising program.
Speaker Change: We have completed enrollment in the phase <unk> expansion cohort, which is assessing safety efficacy and durability of allo 316 at dose level, two or 80 million car T cells. Following standard lymphoid depletion with Fludarabine and cyclophosphamide.
Speaker Change: As we continue to evaluate outcomes, we will determine the best path forward, including the potential to pursue a strategic partnership.
Speaker Change: We expect to share data from this cohort in mid 2025.
I'll now turn the call over to Jeff.
Thank you Zach I'll focus my remarks on our financials and our financial position is strong and we continue to operate with capital discipline, ensuring we are well positioned to advance our pipeline and pursue our strategic objectives.
Speaker Change: As of December 31, 2024, we had $373 1 million in cash cash equivalents and investments with our cash runway extending into the second half of 2026.
Speaker Change: Research and development expenses for Q4, 2024, or $45 million, including $5 6 million in noncash stock based compensation expense.
Speaker Change: The full year of 2020 for R&D expenses totaled $192 3 million <unk>.
Speaker Change: Including $24 million in non cash stock based compensation.
Speaker Change: General and administrative expenses for Q4, 2024 were $15 5 million <unk>.
Speaker Change: Including $7 3 million in noncash stock based compensation.
For the full year, G&A expenses were $65 $2 million, including $31 3 million in noncash stock based compensation.
Speaker Change: Net loss for Q4, 2024 was $59 9 million or 28 per share, including $12 9 million in noncash stock based compensation.
Speaker Change: For the full year net loss was $257 6 million or.
Speaker Change: Or $1 32 per share, including $51 7 million in noncash stock based compensation and $15 7 million in noncash impairment of long lived asset expense.
Turning to guidance for 2025, we expect a cash burn of approximately $170 million. We expect full year 2025, GAAP operating expenses to be approximately $250 million, which includes an estimated noncash stock based compensation expense of approximately $50 million. This.
<unk> excludes any impact from potential business development activities, we will now open the call for questions.
Speaker Change: Thank you as a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw your question. Please press star one again.
Speaker Change: One moment for questions.
Okay.
Speaker Change: Our first question comes from Tyler Van Buren with TD Cowen You May proceed.
Speaker Change: Hey, guys, thanks, very much and congratulations on all the progress.
My question was just sort of following up on the recent <unk>.
Speaker Change: Oh publication that you highlighted and thinking about the read through as to the ongoing Alpha III trial.
Speaker Change: 100 patients with low disease burden and the publication compared to those being enrolled in alpha three as we think about the high complete response rate holding up and offer III.
Tyler: Hi, Tyler.
Speaker Change: Excellent question.
Speaker Change: I think one thing that we highlighted in our ACO paper and this is in fact something that we have been saying for some time based on what has been seen in autonomous car T therapies.
When you look across patients who have been treated with car T. I think this extends not just CV 19, but with out there.
Speaker Change: CMA or other.
Speaker Change: <unk> targeted car T in heme malignancies.
Speaker Change: There is a very strong correlation.
Speaker Change: Likelihood of response.
Speaker Change: As well as likely experiencing.
Speaker Change: Adverse events serious adverse events have been actually it's an inverse relationship in the latter case when the disease volume goes down the likelihood of response is much higher.
Speaker Change: At the same time, the probability of having a serious adverse event ghost town that hasnt been seen numerous times and there are many publications on that.
C J C. Okay Kurt.
We had was showing that essentially the same all its true for the allogeneic car T. Now probably not that surprising and I think thats really bodes well for what we are doing not only in.
Speaker Change: And to offer brief study, but also as we think forward into the autoimmune program with our <unk> Tonight.
Speaker Change: Specifically about your question.
Speaker Change: In terms of estimating that disease by them.
Speaker Change: Compared to patient who is starting the frontline study I'm sorry second line study there is some information that we have done together with <unk> diagnostics.
Speaker Change: Positivity is about 204 less disease volume than patients who are presenting with disease for the start of the second line treatment.
Speaker Change: Your particular question about how that compares.
Speaker Change: With low volume.
Speaker Change: Deb.
The two character two categories alone.
<unk> volume that we have published JCR LDH or tumor measurement.
Speaker Change: More or less six extrapolate to the same degree.
Lower disease volume as we have previously reported together with fore sight in the second line setting versus mrna positive.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Michael Yee with Jefferies. You May proceed.
Michael Yee: Hey, good afternoon.
Michael Yee: Congrats on all the progress as we are thinking about the mid 'twenty five.
Futility and.
Michael Yee: And look for depletion decision.
I wanted to get your affirmation that you believe that $6 seven is extremely likely to not be needed and that should be the general wall Street expectation I believe that would be a positive for a number of reasons.
Michael Yee: And then as we get to the first half of 2006, which would be around the corner.
I would say that there is an interim D. SMB efficacy analysis what is the.
The criteria.
Michael Yee: There are events or is there are very high P value bar on that what are you expecting or what should we expect that that interim.
Michael Yee: Yes.
Mike: Hi, Mike.
Mike: Before your questions to exact.
Can you take those two questions.
Michael Yee: Of course, thanks, Thanks, Mike for the great questions. So.
Michael Yee: Our opinion on the lift for depletion selection as is.
Michael Yee: Sort of agnostic I think you raise a fair point that.
Michael Yee: They're not meeting 647 bring some attractive.
Attribute like it will be simpler for us we're registering one entity instead of two.
It certainly would be cheaper for us to do it that way.
Michael Yee: However, we see.
Requiring 647 is actually potentially beneficial as well because that's part of our proprietary regimen. So it would help kind of protect our our status here as the as the only therapy that is optional debt in this particular clinical setting so.
Michael Yee: We have designed this clinical trial to give us a solid answer to that question is 647 needed in this unique clinical trial or is it not and I think we can we can work with either independently.
Michael Yee: Independently, both both has upside for us.
And.
Michael Yee: The sorry, Michael you repeat the second question I forgotten.
Speaker Change: Yeah, Yeah, right around the corner.
Sandy: Alright in 12 months or so as the interim by Sandy.
Sandy: The criteria is it a high bar because you don't want to spend alpha there.
But obviously investors have had great discussions with you about how the drug is clearly going to be working here you can definitely have a chance of hitting their thank you. Yes. So yes, so we havent disclosed.
Sandy: A lot of the specifics around the nature of that analysis.
Sandy: Some of the specifics that you're requesting except to say that it is a.
Sandy: A formal efficacy test, where we will be testing the hypothesis with the primary endpoint of event free survival.
We'll be some minimal alpha spend so it is quite possible just given the way. This study is designed that we could end up with a.
A statistically significant finding there.
Sandy: And of course allow us to initiate conversations with the FDA.
Begin to kind of move more briskly across the other elements that need to fall in place to launch the.
Sandy: Program.
In the coming months after that so we're looking forward to that that analysis.
Sandy: And in either case, whether it meets statistical significance or it doesn't.
Sandy: We look towards that as a very significant.
Sandy: Milestone in the delivery of this program.
Sandy: Thank you.
Sandy: Thank you.
Our next question comes from Salve in Richter with Goldman Sachs. You May proceed.
Mark: Hey, this is mark on for solving thanks for taking my question.
Speaker Change: Alastair you denied and the trial starting soon in autoimmune disease.
Speaker Change: What data are you looking to show by year end demonstrate proof of concept and maybe more importantly.
Speaker Change: Since there are many CD 19 players and also allogeneic players showing data. This year. How do you think your approach is differentiated and could your year end data support that differentiation.
Speaker Change: Hi, Mark This is Dave Chang, let me take that question. So three to nine we have cleared the IND and we expect to initiate the clinical study mid 2025, and we have been guiding towards profit.
Speaker Change: <unk> concept data twice a year and the number of pesos that we expect to treat in 2025 and that because this is a dose escalation phase one study will be somewhat limited, but it'll be handful and what we're looking for is biomarker based proof of concept.
Speaker Change: One.
Speaker Change: <unk> allogeneic.
Speaker Change: Our 329 today expand well I think those are.
Speaker Change: Very importantly, inflammation and second do we achieved b cell depletion, while also allowing some of the b cell recovery to occur. These.
Some of the important information that will lead to the proof of concept and also in some of the patients that we treat we expect them to have auto antibodies and the measurement of auto antibodies before and after the treatment.
That could also give a lot of insight into what the program is doing.
Speaker Change: In terms <unk>.
Speaker Change: Differentiation of our treats benign to many other programs that are currently in the autoimmune space I think the key is that while this is an allogeneic program and two this has ability to not only deplete the b cells, but also activated T cells, which contributes to the overall pathogenesis.
Speaker Change: Autoimmune disorders, how the latter would translate I think.
Speaker Change: We will have to see the clinical data, but possibilities of being able to address the T cells can allow us to go to indications that.
Speaker Change: CD 19, T cell targeting therapies may not necessarily be sufficient and another potential benefit of targeting T cells is that.
Speaker Change: The remission could be much longer because you are eliminating that just decile start also T cells.
Speaker Change: Thank you.
Speaker Change: Thank you.
Brian Chin: Our next question comes from Brian Chin with Jpmorgan you May proceed.
Brian Chin: Hey, guys. Thanks for taking my question this afternoon.
Speaker Change: David I am just curious if you can provide a little bit more comment around your latest thinking around incorporating potentially either milder lymphoid depleting agent or even.
Speaker Change: Completely removing the standard size.
Speaker Change: <unk> that youre using any color on timeline and and what it's really the fastest and the best way to kind of sort that out. Thank you.
Speaker Change: Yes.
Brian Chin: Brian excellent question. These are the things that we hope to address in the phase one study.
In the planned study first of all.
Brian Chin: The lymphoid depletion that we will be depleted deploying is a milder LIFO depletion we have.
<unk> taken out fluids Arabic so.
Brian Chin: One cohort will be treated with cyclophosphamide alone as a lymphoid depletion.
Brian Chin: And a second one.
Brian Chin: We have also clarified in when we announced.
Brian Chin: The clearance of IMD is that in parallel there'll be a second cohort, where we will be testing without any lymphoid depletion. So.
Now little bit to your question as well to the previous question about Mark.
Brian Chin: Mark is really.
Brian Chin: The phase one study already is built in to address the key questions about three to nine weather.
Brian Chin: You kind of achieved our objectives with milder winter.
Brian Chin: Which will be a fantastic news or even without any other input depletion, which will be phenomenal for this program.
Brian Chin: Thank you.
Our next question comes from Sami Corwin with William Blair You May proceed.
Sami Corwin: Hey, congrats on the progress this quarter. Thanks for taking my question.
Just curious any greater difference.
Speaker Change: Survival powered shell and then I noticed in your 10-K that said that both treatment arms look better than the control of the futility analysis.
They don't look any different than each other that additional patients could be enrolled and analyze so I guess, what kind of difference in looking to see between the two treatment arms and if they do look similar or would you foresee is it lumpier depletion arm without <unk>. Thank you.
Sami Corwin: Yes, Sami I mean, the question about the powering up there yet.
Speaker Change: III study at the <unk>.
Sami Corwin: Primary endpoints event free survival.
We haven't gone into that that's the thing that specifics about the powering of the study other than to say.
Sami Corwin: The targeted.
Sami Corwin: Targeted about 110 patients in each arm for comparison. This study is very well powered and this also goes back to the earlier question around from Mike about.
What could be possible at the interim analysis, which will happen early 2026, yes.
Spending somehow.
Sami Corwin: And obviously, we believe that there is.
Some possibility, which may be not so small that.
The statistical boundary May have crossed at the time and frankly, if you look at what has happened with our car T studies in.
Sami Corwin: In the second line study.
Sami Corwin: Whether it's the <unk> study the sample size number of patients that were treated in the second line study, which was comparing car T with active treatment.
Around 262.
Sami Corwin: Some mid three hundreds not so dissimilar so that those studies obviously.
Sami Corwin: Sure the statistical significance in the in the midyear. So I think that is probably some good reference to think about how offer <unk> III study may have been powered and.
Second question about.
Sami Corwin: What we have disclosed in the 10-K, we have provided a little more guidance about how many number of patient number of patients that we'll be looking at as.
Sami Corwin: As we start looking at the.
Futility as well as selecting for depletion.
Obviously, if we don't see any difference.
Sami Corwin: There are the possibility that we may want to have some more patients to see what are the differences more significant or not.
Sami Corwin: Another possibility is that.
At the time.
Sami Corwin: Doing about 36 patient data that may provide a sufficient information for us to make the lymphoid depletion we will get there and then this will be unmatched data driven so probably it's best that we wait till that time client rather than speculating too much.
Sami Corwin: Got it thank you.
Sami Corwin: Thank you.
Sami Corwin: Our next question comes from Jack Allen with Baird You May proceed.
Jack Allen: Awesome. Thank you so much for taking the questions and congrats on progress.
Jack Allen: I wanted to ask about the futility analysis as well.
Should we be thinking about the futility analysis as it relates to a comparison is that or is that a comparison against the control arm here or is it against some sort of hurdle rate and then on what metrics will you be looking at.
Jack Allen: To evaluate futility it would be I'm already converted and response rates or any early survival data. Thanks, so much.
Jack Allen: Okay.
Yes.
Let me yes.
Jack Allen: Yes, let me just take this question we get asked about the futility question there isn't anything unique about the futility analysis that we are doing this is a very standard thing that many.
These phase III studies, sometimes even phase II studies, we will be doing what gets looked at in the futility analysis really the totality of the data.
Jack Allen: You can look at the safety, obviously, we want the safety to be tracking close trial expectation based on what we have seen in the offer III study.
Jack Allen: There is a significant imbalance in the safety.
Jack Allen: Between the observation control arm versus two treatment arms.
Jack Allen: And then the <unk>.
One is that the setup the signs of efficacy and here, we will be relying primarily on the <unk> conversion rate. So every patients who get enrolled in the offer three study stocks with MRV positive both the control as well as.
Two three.
Treatment using different LIFO depletion.
Jack Allen: The expectation is M R&D conversion.
We'll be heavily.
Jack Allen: Creating more.
Not any more in the in the treatment arm compared to the observation so that will be the essentially the utility that we will be looking for that app stores and the ones that utility has been cross we'll be looking at the two treatment arms to LIFO depletion Ams to see which one is better.
Speaker Change: Alright, thanks, so much for coming.
Jack Allen: Thank you.
Speaker Change: Our next question comes from Byron them in with Piper Sandler You May proceed.
Speaker Change: Yeah, Hi, guys. Thanks for taking my question.
Speaker Change: I think for the Alpha three your prior guide a state of the patient enrollment would complete by first half of 2026. So I just wanted to see if you are continuing to track towards that timeline.
Speaker Change: And then I guess second question is I think you mentioned that the split in the trial.
Speaker Change: 50, 50 between community versus academic in terms of sites.
How about the patients but is that 50 50 as well.
In terms of the overall file in our guidance.
Now focusing more on the data readout, which has not changed and obviously your particular question Ron.
Speaker Change: <unk> completion, I think we are more or less tracking around that time, and obviously as we progress with the study we'll provide more information.
Speaker Change: Respect to your second question.
Speaker Change: Okay.
Speaker Change: Can you just repeat the second question distributions.
Yes.
In terms of the trial split the site split is 50 50 across the 40 sites that you've activated between community and academic yes, yes, yes, I wanted to understand if the patient, but similar as well.
Speaker Change: Yes, let me pass that question to <unk>.
Speaker Change: To provide more details on the.
Speaker Change: The site distribution across community versus academic centers, yes, thanks, David and thanks for the question.
Yes, you are correct that its about 50 50 split right now.
With about four four fits of the sites activated community versus academic.
Speaker Change: As far as the patients coming in what I can say is that we haven't seen.
Speaker Change: A heavy skew in one direction or the other I can't say, it's exactly 50 50, but what I can say is that we are seeing.
Speaker Change: Robust activity in both the community centers as well as the academic centers.
Speaker Change: Great. Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question comes from John Newman with Canaccord Genuity you May proceed.
John Newman: Hi, guys. Thanks for taking my question just wondered on the initial data for 302 nine at year end 25, just curious if.
How much follow up do you might have if you would be able to.
John Newman: Look at one month or maybe three.
John Newman: And then also given the mechanism of vaccine for three to nine.
John Newman: Is there a way that you can look at not just the b cell depletion, but also potentially depletion of the active T cells.
John Newman: John Great question, it's something that we constantly talk about internally, let me pass off to exact to ask the questions about.
John Newman: The length of follow up that we may have and what else, we're going to be looking at in the biomarker analysis.
Speaker Change: Yes, so thanks John.
So we Havent said exactly how much follow up we expect to have them, we have said that.
Speaker Change: With the trial starting middle of this year.
Speaker Change: And as obviously moving as quickly as we can we should have a handful of patients treated hopefully by the end of the year and a little bit of a follow up I mean, what we've guided towards in terms of proof of concept as David pointed out earlier, the biomarker data, so b cell depletion as well as expansion of the car T cell.
Speaker Change: We will have some early safety results too. So we can gather that information in relative short order in a clinical trial.
Speaker Change: We won't really have.
Speaker Change: Significant read on durable efficacy of course by the end of this year.
Speaker Change: Diving into your second question on the on the specific analyses that we plan to conduct.
Speaker Change: So obviously b cells as is.
As a must have.
Speaker Change: The T cells as we've shown in the 306 program is going to be an area of focus as well and what I think we've elegantly shown.
Speaker Change: Such as in the 50 data just a few months ago is that we can really parse out the CD 70 positive versus the <unk> 70 negative cells in the patients and really that is what has given us the foundation to net has validated the dagger effect in patients. So we will be doing very similar analyses and <unk>.
Speaker Change: And seeing whether we are seeing that evidence of a strong bagger effect in these patients.
Speaker Change: Okay, great. Thank you.
Speaker Change: Thank you.
Our next question comes from et cetera.
Wording with tourists you May proceed.
Hey, guys. Thanks for taking my question and appreciate all the color today.
Speaker Change: I want to follow up John excellent question on the resolution study.
Speaker Change: Great to see that you guys are aimed to explore the links repletion free.
Speaker Change: Strategy as well as here I wanted to ask you guys. How much follow up do you need to answer that question I asked because just from some of these indications they're going after.
Speaker Change: LLS.
Let's see maybe.
A treatment benefit up to six months or even a year do you think youll need to do that to you to all the way up to them to really answer that question of whether or not you can go with unlimited accretion can strategy.
Speaker Change: And then second quick follow up on the Jay Seo publication, all the durable responses for Crs and it also fair to say that all six patients with low disease burden had crs so I'd like to confirm a dose of six patients that are the ones that are still in response on disclaimer at the data cutoff on that paper.
Speaker Change: Thanks.
Speaker Change: Alright, yes take that too.
Speaker Change: Question. So let me take three to nine months Lucent question about whether we need to follow the patients for longer definitely without question. We will be following these patients longer than the initial biomarker data analysis. So the way, we see it as a biomarker, especially <unk>.
Speaker Change: B cell depletion as cell expansion or antibody titer changes I think these are very great telltale signs are on whether the treatment is.
Speaker Change: 390 is behaving as we have expected and obviously as we follow these patients we will get more information about that.
Speaker Change: The clinical outcome, including if some of these patients going to complete remission, how long that may last I mean, those are much longer follow up and that will not be the part of the initial data release that we are projecting year end.
The second question I'll pass off to exact to respond.
Yep. Thanks, Oscar so so the first thing to kind of keep in mind as you pointed out in your question is.
Speaker Change: Most important outcome after any treatment at all whether it's car T cells or anything else that you achieve a complete remission that is obviously the number one thing because if you don't get to a complete remission or chance that durable sure is zero. So that's the first thing to keep in mind, what we showed in our subgroup analysis is that if you had low disease.
Speaker Change: Burden as assessed by either the tumor measurements or by the serum LDH.
Speaker Change: At an extremely high chance of achieving that must have clinical scenario of.
A complete remission.
That said we.
Speaker Change: We want to also tout that the set of cell product itself is a very potent product. Obviously is very active as the ACO paper indicated.
Speaker Change: And we actually had plenty of patients that were.
Speaker Change: Bulky disease that achieved durable crs as well so it was a little bit of mixing and matching.
Speaker Change: Thank you.
Our next question comes from Matthew Biegler with Oppenheimer You May proceed.
Speaker Change: Got it thanks for the question I'll ask another one on regulation, but maybe in a slightly different way, which is hypothetically how much efficacy are you potentially willing to leave on the table to get away with no limbo conditioning I E.
Speaker Change: Limbach conditioning really a game changer or is it just a nice to have in your opinion. Thanks.
Matt: Yes, Matt to your ex slowing the question.
Speaker Change: You're asking things that are highly debated internally.
Speaker Change: I mean, probably the best way that I can setup.
Speaker Change: Describe us.
Speaker Change: Lymphoid depletion.
Speaker Change: Yes.
In a potential barrier.
Speaker Change: Lower and if we can lower the length of depletion, that's a big plus and if you can eliminate that that's really a big big game changer, but frankly.
Speaker Change: Probably the best way to think about as you know.
Speaker Change: When it doesn't it doesn't have the burden of lymphoid depletion it can be used more widely so it really creates.
Speaker Change: Potential to treat not only what do you mean disorders with the <unk>.
Speaker Change: In the high severity, but also moderate.
Severity. So it gives a lot more opportunity to address different patients. So.
Is yes, we would love to have known him for depletion, but I think even just lowering the lymphoid depletion would be a significant win for the 3% to nine program.
I appreciate it.
Speaker Change: Thank you.
Speaker Change: Our next question goes from Luca <unk> with RBC capital markets. You May proceed.
Hey, guys. This is <unk> on for Luka and thanks for taking the question on Alpha three it's our understanding that there is an option for inpatient or outpatient treatment.
Is that decision left up to the investigator and how should we think about the mix of patients who will be treated outpatient versus in patient.
Speaker Change: Any color there much appreciate it thanks.
Yes, so I'm going to ask <unk> to respond to your question Zach, Yes, Thanks, David and Shelby So indeed.
Speaker Change: There is no requirement at all for inpatient either LDR cell administration.
Speaker Change: It is entirely up to the investigator on a case by case basis, I will say that.
Speaker Change: We are seeing.
Speaker Change: As we've seen for a long time in our and our <unk> programs, even in the Alpha and Alpha too. We are seeing a significant number of these patients being treated fully as an outpatient and of course that is the vision.
Speaker Change: Part of the vision for for this product is that it's going to be easily too easy to administer in the in.
The clinical settings, where these patients receive frontline care.
Speaker Change: As for sort of specific characteristics that would lead to a patient being treated inpatient versus outpatient I mean, there is a host of them I won't go into them now but.
Speaker Change: One of the great benefits of the Alpha three study is that all of these patients are going to be in remission. When they received their their <unk> and their olimpico depletion and as David pointed out earlier in the call.
Speaker Change: Patients with low disease burden tend to have better safety outcomes than those with high disease burden. So on balance we would expect a significantly greater fraction of these patients over the duration of the study to be managed as fully as outpatients and that is that as our our expectation.
Speaker Change: And also if I can add color to that response Shelby.
Speaker Change: I think the important thing is that in Alpha <unk> III study, we do not require hospitalization and in that way.
In essence, what that's doing is this trial. It is just like any other trial and whether physician.
Speaker Change: With that information, whether they decide to treat as a fully outpatient.
Speaker Change: Maybe put them into the hospital for a data too.
Speaker Change: That's essentially how the practices and not just in the south talk to you about it.
Speaker Change: Their cancer treatment, so, it's really giving the peso and the physicians to option on how they want to have received <unk>.
Speaker Change: Investigational therapy in the office III study.
Thank you.
Our next question comes from somebody at the <unk> with Citi. You May proceed.
Speaker Change: Hi, good afternoon, and thanks very much for taking the question.
Speaker Change: Sameer autologous car T counterparts have spoken about a push to expand into large community oncology centers that could potentially overlap with your alpha three trial sites. So I'm wondering to what extent are you seeing this infrastructure being built at the community centers you interact with how much of the groundwork do you think could be in place by the time, you potentially launched MSL.
Speaker Change: How are you thinking about your ability to leverage that infrastructure for the launch thanks very much.
Yes.
Samantha excellent question I think.
Speaker Change: Effort.
Speaker Change: Not just by US, but also in the entire car T community to move into the sort of community based cancer centers, I think that thats going to.
Speaker Change: Extend and expand the usage of the car T.
Speaker Change: That's a very important aspect of any product launch in <unk>.
Speaker Change: Alex lifecycle management.
Speaker Change: I think in many ways here is where the allogeneic car T really placed favorably.
Speaker Change: Not having the logistical challenge.
Speaker Change: Just being able to ship the product when the patient needs to treatment and also in our case as we are learning as we improve their manufacturing the scalability of the manufacturing all of these things.
Speaker Change: Playing in our favor so.
Speaker Change: As the effort from the autologous car T companies to expand their use into the community cancer centers, we see that as a positive thing for the for the for the field and we also see that as a positive thing for what we're doing with Alpha III study.
Thank you.
Speaker Change: Our next question comes from Ben Burnett with <unk>.
You May proceed.
Speaker Change: Hi, This is <unk> on for Ben Thank you for taking our questions.
Speaker Change: First on the interim analysis of famous early mid 2025.
Speaker Change: Can you remind us when you are measuring the impact.
Speaker Change: The conversion.
Speaker Change: One month, both Marcel in future.
Speaker Change: And a couple of follow up.
Speaker Change: Yes.
Speaker Change: Yes, we're trying to limit the questions to one Zach do you want to take the question about the timing of Amex test.
Zach: Yes, Thanks, Catalina we have not.
Speaker Change: Disclosed exactly the timing of that.
That draw and as David pointed out earlier of course there'll be other elements that we're assessing to make that limpet depletion decision. In addition to the <unk> conversion.
Speaker Change: Okay understood. Thank you.
Speaker Change: Thank you.
Sure.
Speaker Change: Our next question comes from Laura <unk> with Raymond James You May proceed.
Speaker Change: Hey, guys can you elaborate a bit more on the registrational path for the fore sight MRV test and how it relates to the Registrational path for <unk> and one al lymphoma.
Speaker Change: Hey, Zach do you want to take that question.
Speaker Change: Yes, that'll be an easy one thanks Laura.
The plan has been all along to to have a.
Speaker Change: Concurrent launch of these products at the time of the FDA approval the specifics around the path to registration of the MRV tests, though I would refer you to the four site management.
Speaker Change: But you don't foresee it being an issue at all with forgetting.
Speaker Change: So my follow up is in first line.
No.
Speaker Change: Got it thanks.
Speaker Change: 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: Alright, thank you.
Speaker Change: I just want reiterate allergy and entered 2024 with a bold strategy and today, we stand on the brink of a transformative year.
Speaker Change: With three pioneering programs each approaching critical milestones we are proving that allogeneic car T has the potential to redefine patient care. So thank you for your ongoing belief in Allergan and the field of cell therapy. Operator, you may now disconnect.
Speaker Change: Thank you ladies and gentlemen, thank you for your participation in today's conference.
Speaker Change: Does conclude the program and you may now log off and disconnect.
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