Q4 2023 Allogene Therapeutics Inc Earnings Call
Thank you for standing by and welcome to allergy and Therapeutics fourth quarter and full year 2023 conference call.
This time, all participants are in a listen only mode. After the speaker presentation. There will be a question and answer session to ask a question. During the session you will need to press star one on your telephone to remove yourself from the queue. You May Press Star. One again, please be aware that today's conference call is being reported.
Now I'd like to turn the call over to Christine Casciano, Chief Corporate Affairs and brand strategy Officer Ms. Casiano. Please go ahead.
Thank you operator and welcome to also join this call.
After the market closed today <unk> issued a press release that provides a business update and financial results for the fourth quarter and full year 2023.
This release and today's webcast are both available on our website.
Following our prepared remarks, we will host a Q&A session. We ask you to limit your questions to one per person. If we will keep this call to an hour and do our best to get through as many questions as possible joining.
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.
During today's call, we will be making certain forward looking statements. These may include statements regarding the success and timing of our ongoing and planned clinical trials data presentations regulatory filings future research and development efforts manufacturing capabilities, the safety and efficacy of our product candidates in 2024 five.
<unk> guidance among other things. These forward looking statements are based on current information assumptions and expectations that are subject to change a description of potential risks can be found in our 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 call over to David.
Thank you Christine and thank you for all who have joined our call today.
Rather than looking back which is the norm for this type of call I would like to take the opportunity to look ahead.
We have recently returned from an Investor conference in Boston, and well beyond thrilled to fill out the renewed enthusiasm for biotech and even more so a resurgence in cell therapy.
I would argue that this is also true for allergy in a second.
Seemingly shared by many of our investors following the pivot we announced at the beginning of 2024.
Innovative offer three trial, which is designed to embed MSL as part of a curative first line regimen for patients with large b cell lymphoma, specifically.
Specifically, creating a car T that could meet the unique needs of patients with autoimmune disease, and possibly reduce reliance on NIM for depletion. Our development approach focuses on the distinctive attributes of an off the shelf alternative and creates an advantage.
<unk> car T programs.
We are no longer developing car T using an outdated playbook.
Now that we have established.
Liability.
Our allogeneic platform our product can be developed using a fresh approach created for what we do both in design of our trial.
And design of our cost structure to meet the current and future needs of patients and dramatically expand opportunity.
<unk>, three which based on feedback from investors and doctors is perhaps one of the greatest example of the roll on Allogeneic car T can play in this resurgence futsal therapy. This is the first pivotal trial, but frontline consolidation in large b cell lymphoma with the goal.
<unk> of improving cure rates.
There was significant insight gathering work and discussion with the FDA in 2023 to inform and finalize offer III.
When we reveal the trial in January delegates acknowledgment almost right away that this groundbreaking trial creates the potential to leapfrog all out of car T and embed <unk> in first line treatment.
Equally important.
Is the innovative concept of treating minimal residual disease or <unk>.
D together with the benefit of drug in a vial could open the door to make allogeneic car T available in community based cancer centers, where most early line patients are treated.
The more we have talked about offer III the deeper understanding this trial design is something truly unique.
Rare opportunity in oncology to do a randomized trial against observation.
And the prospect of becoming new standard of care in the first line setting.
Based on the addressable market in the U S. The revenue potential could be upwards of $3 billion and could easily double when expanded ex U S.
This type of opportunity only presents itself when you center on patients and their endeavor to be curative.
Our second most asked program by Investor App to offer three is our <unk> hundred nine in autoimmune disease or AIB.
<unk> for car T and AIB is palpable. However, we have chosen not to rush into the already crowded undifferentiated.
Undifferentiated approach the future results that could mean, an uphill battle in trial enrollment or worse at commercialization.
Instead, we are applying our deep and hard earned experience to specifically design, our viewer targeting car T to Plano for autoimmune disease.
Our design is centered on both scalability and reducing or eliminating lift for depletion, which we believe is absolutely critical for rapid clinical development and future commercial success.
We expect to be in clinic with our three to nine in a phase one trial in early 2025.
Our next to call program also lean into attribute of Allogeneic car T.
Our new offer two cohort for <unk> cel in chronic lymphocytic leukemia, or CML aims to address a growing unmet need among patients whose disease are not controlled by D teekay and or Bcl two inhibitors.
<unk> refractory CLO in the second and third line setting represents a commercially attractive opportunity with revenue potential in the $3 billion range in the U S.
We believe an allogeneic car T product is particularly well suited to overcome and limitation of autologous car T.
<unk> T cell fitness is a non barrier to efficacy.
New approvals could reopen the door of interest in CLO, and we look to charge through it with our program.
Our ongoing <unk> trial tackle this one of the hardest industry challenges, but one we are willing to undertake solid tumors.
Our 316 in renal cell carcinoma, leverages, our <unk> technology to optimize car T cell expansion and persistence to maximize the potential of an hour car T.
In the second quarter, we plan to publish what we believe to be fundamental discovery. The algorithm that may mitigate the treatment associated hyper inflammatory response without compromising the car T function needed to eradicate tumor.
More comprehensive update from the <unk> trial is planned for year end 2024.
Now I'd like to turn the call over to Zach to address some of the more commonly asked questions about our programs.
Thank you David as I'm sure you can tell we are all very excited about our new strategy and thrilled that investors and investigators alike share that enthusiasm.
With cielo, because that gets a little less attention than alpha three although it has the potential to pack a powerful punch.
Ironic that complete remissions in relapse refractory CLO ignited the car T field, many years ago, but that excitement Wayne for the Berry limitations, we stated.
New approvals could offer a much needed alternative for these patients, but there remains a growing need for effective treatment post <unk> and Bcl two inhibitor therapies recent.
Recent autologous CD 19 car T data has been a positive step for patients with relapse refractory CLO, but there is still room for improvement.
Durable responses in relapsed refractory CLO is likely hindered by an unfortunate reality that T cell dysfunction and high circulating tumor burden makes manufacturing of highly active T cell it's difficult.
There is strong scientific rationale to believe that an allo car T products derived from healthy donor cells could create a clinically meaningful advance for these late stage patients with a onetime dose and simpler administration and logistics.
New phase one alpha two cohort will include 12 patients treated with <unk>. This study driven by investigator enthusiasm is now enrolling patients and we plan to have initial data at the end of this year.
I'll now talk about Allo 329 in autoimmune disease, our next intend to advance.
We believe the approach we are taking to reduce or even eliminate the need for a standard length of depletion will be critical to meet the unique requirements for these patients.
The risk tolerance of these patients is very different than those with cancer in large part because of the patient demographics wide availability of effective therapies and rheumatologist general lack of experience with chemotherapy leukapheresis procedures and cell therapies.
Our wholly owned next generation site specific integration based dual targeting CD 19, CD 70, Allo car T is designed to reduce or eliminate the need for standard chemotherapy, while targeting CD 19 positive b cells, and CD 70 positive activated T cells, both of which play a role in autoimmune disorders.
We have invested in this highly differentiated dual targeting approach to set us apart from the pack and position us for long term success.
All current car T programs in AI are targeting CD 19, and therefore solely addressing the b cell component.
We believe that introducing CD 70 will allow the elimination of both pathogenic b and T cells that underlying autoimmunity, thereby potentially increasing effectiveness in diseases with direct or indirect T cell involvement, possibly allowing us to extend beyond indications in which strip CD 19 targeting has demonstrated clinical benefit.
Of course, the ability to manufacture hundreds of off the shelf car T doses from a single healthy donor leukapheresis could provide.
An additional competitive advantage during clinical trial execution and with much more readily meet the potentially enormous commercial demand.
Initiation of this phase one trial with Allo <unk> nine is expected in early 2025, we are very excited to have partnered with Arbor biotechnologies for use of their proprietary CRISPR gene editing technology to support our overarching next generation Allo car T platform and autoimmune disease.
Finally, I am, particularly proud of and excited by our history.
No mistake. This was a year of hard work, but bringing this novel trial to life with the broader allergen team, our advisory boards and potential investigators those comprised of academic kols and community oncologists alike, and securing the support of the FDA is already one of the highlights of my career.
The elegant design of this innovative trial and the Aha that comes with it is likely why we get asked why hasn't anyone tried this before it's simply was a possible until now.
To run the study like Alpha <unk> III, we needed two things to come together, a highly accurate Mardi assay and a onetime powerful treatment that could be administered immediately.
We believe we now have the right combination the design of the Alpha three first line consolidation trial builds upon the results demonstrated in the phase one alpha to trial and Leverages. The investigational cutting edge diagnostic test developed by <unk> diagnostics to identify patients who have minimal residual disease at the completion of frontline chemo.
<unk> therapy for treatment with <unk>.
Approximately one third of <unk> patients, who initially respond to R. Chop will relapse. Unfortunately until recently there has been no way to know which patients would go on to never experience of disease recurrence.
And which would have their cancer relapse.
The standard of care after frontline treatment has for decades been to simply watch and wait for this disease to relapse Alpha.
Alpha III takes advantage of stem cell as a one time off the shelf treatment that can be administered immediately upon discovery of MRV. Following six cycles of R. Chop.
<unk> it to become the standard <unk> cycle of frontline treatment available to all eligible patients with MRV.
After three build on the growing understanding that the administration of car T therapies to patients with low disease burden.
<unk>, both safety and efficacy outcomes.
<unk> phase one safety profile with low rates of Crs and I can already permitted use in the outpatient setting and relapsed refractory patients and may further improve in patients with no radiological evidence of disease.
What's incredibly exciting is that the outcome of this pivotal trial could allow <unk> to be embedded in the frontline setting where autologous therapies are far less feasible.
Consolidated in response with an <unk> positive results post R. Chop requires immediate and definitive action to prevent an impending relapse.
A onetime treatment with <unk> could happen roughly two to three days post MRV positive test results.
As we have seen autologous car Ts have had difficulty penetrating community cancer centers and accessing earlier line patients.
Use of stem cell wont rely on the same complex logistics that have hindered car T adoption, nor will there be a reliance on referrals as the intent is for car T to be available in these community cancer centers.
In allogeneic likes MSL is what these doctors have been waiting for as entry to the modality in their centers.
We believe these differentiated attributes of <unk> cannot be reproduced by autologous car T bi specifics or any other treatment modality.
Startup activities for Alpha three had been initiated the study will randomize approximately 230 patients who are already positive at the end of frontline therapy to either consolidation with MSL or the current standard of care, which is observation.
The design with the primary endpoint of event free survival will initially include two of them for depletion arms, one with standard Fludarabine and Cyclophosphamide, plus allo 647, and one without allo 647.
The trial start is planned for mid 2024 and will be conducted in a wide array of cancer treatment centers, including community cancer centers, where most earlier line patients seek care.
The outcome of this pivotal trial could allow <unk> to potentially improved cure rates and become the only treatment approved for frontline consolidation.
With the potential to significantly reduce the need for car T. In later lines.
We look forward to answering any additional questions you have on our pipeline during the Q&A I'll now hand, the call over to Jeff.
Thank you Zack I'd like to Echo David's comments made at the beginning of this call. It's been a very exciting few months speaking with current and prospective investors. The enthusiasm expressed for our strategy has been greatly appreciated and inspirational for our team such broad and unanimous enthusiasm is something that is <unk>.
<unk> in my career.
We look forward to having ample opportunity to continue to share our vision and program updates throughout the year, especially on Alpha III traverse our CLI trial and allo three to nine our car T 2.0 for autoimmune disease.
Our vision is bold and we recognize the cash runway is critical we are pleased that the changes we've made following our announcement in early January have focused the strategy and extended our runway into 2026, but acknowledged that extending that runway must remain a focus.
Rest assured that while we actively manage costs. We will also be actively pursuing opportunities to build our cash reserves.
We do however have a strong cash balance ending 2023 with $448 7 million in cash cash equivalents and investments and we have no debt.
As we look ahead to our full year 2024, we expect a cash burn of approximately $190 million.
We expect our full year 2024, GAAP operating expenses to be approximately $280 million.
Which includes estimated noncash stock based compensation expense of approximately $60 million.
From a longer term perspective, we continue to forecast that our cash runway will support our operations into 2026.
This guidance excludes any impact from potential business development activities.
Full year 2023 research and development expenses were $242 9 million.
Which included $31 $9 million in expenses associated with noncash stock based compensation.
For the full year 2023 General and administration expenses were $71 7 million, which included $34 million of noncash stock based compensation expense.
For the full year of 2023, our net loss was $327 3 million or $2 <unk> per share include.
Including noncash stock based compensation expense of $66 million and $13 2 million in noncash impairment of long lived asset expense.
With that we will now open the call for your questions.
Thank you as a reminder to ask a question you will need to press star one on your telephone.
To remove yourself from the question queue. Please press star one again.
You will be limited to one question before returning to the queue. Please standby, while we compile the Q&A roster.
Our first question.
It comes from the line of Tyler Van Buren of kidney Cowen Your question. Please Tyler.
Oh, Great Hey, guys. Congrats on all the progress during the quarter.
So I wanted to first ask you about your autoimmune approach this time around.
Personally have been fascinated by the Doctor technology ever since it was unveiled at the November 'twenty, two R&D day, where we saw responses in renal cell without allo 600, 700, a full FCA regimen, so I'm glad to see that technology being deployed the allo 329 for autoimmune disease, however, removing liquid depletion altogether and AIG it takes it.
Another big step further so why do you think this is feasible in autoimmune and how would you intend to test that in the early innings of clinical trials.
And.
Maybe for a second question or half a question forgive me.
Could you just briefly talk about the potential impact from a bio secure bill in Wuxi to our jeans business.
Hi, Tyler sitting here. Thanks for your question and say and I like how you're sort of squeezing that have questions. After the first one.
On the outlook three to nine I mean.
This is a product from the design to how we are manufacturing, it's really built on being able to differentiate our <unk> prom from out there.
Car T product sets going into the <unk> indications and this is already getting in.
In a crowded space I mean, the key differentiation as Zach had commented during the during the <unk>.
<unk> remarks is really pitfalls.
One this is a deal or CD 19, CD 70 car and what that allows the.
Our <unk> to do is not just depleting the pathogenic T cells. It can also depletes CV 70 positive activated T cells, which we believe play a pretty significant role in the autoimmune disease itself.
The other part is back to this concept of lymphoid depletion.
Able to deplete the activated T cells.
We believe allo three to nine or CD 70 day of containing products.
To work well.
Even as an allogeneic car T product without being dependent on having to use a CD 52 antibody.
One.
Starting point for US is a lymphoid depletion is very much on par with lateral colorless CD 19 car T. Players are growing but we think that we can go even further west CD 70 dagger can do is.
Through growing App <unk> T cells.
And is.
The expansion is much greater and also it has potential to start tapering.
Tapering off while eliminating the components of lymphoid depletion EDA fludarabine or cyclophosphamide.
Cyclophosphamide and it's not just the laboratory concept, we actually have clinical data coming from our CD 70, or our <unk> six program from the <unk> study. So I think this is going to be a very interesting proposition that we believe is critical in that net debt to conduct this study rapidly.
The Audi <unk> indications, but also for the future commercial success and that sort of leads to the third point.
Our three to nine which is really the scalability not only his analogy in AG. We also believe in the autoimmune indications.
The duration of the persistence.
I don't think we need a long duration of car T. Persistence. This is really depleting the pathogenic lymphocytes deep enough. So you can reset the immune system. So when we think about this for the indication that we are going we believe that.
The construct illustrate to nine can be effective at very low cell dose. So we are very excited and as we have said. This is one of the top priority programs that we have for 2020 full and our intent is to accelerate the timeline.
Much as we can currently we expect our <unk> 809 phase one two study to start in 2025 potential data readout phase one data readout at least the early portions by the end of 2025.
So second question I'm going to give a very brief response I mean, what's going on with <unk> and we will see an allergen it doesn't impact allergen at all.
And that also leads to something that we have been talking about for some time.
We always have believed and that manufacturing is core to our business.
That reason from early days, we built a fully integrated CMC manufacturing team that covers not just process and analytic assay development, but the supply chain and manufacturing.
And that's really why we.
<unk> invested in building a fully dedicated allogeneic car T manufacturing facility, which we call <unk> and that will be a very differentiated and distinctive advantage as we try to expand the use of car T. Not only in <unk>, but also in AIB.
We believe the scalability is the key.
Okay.
Thank you.
Our next question.
Comes from the line of solving Richter of Goldman Sachs. Your question. Please.
Good afternoon. Thanks for taking my question with regard to your auto immune disease program.
<unk> <unk> technology here could you speak to the strategy here with regard to bringing in the Arbor CRISPR based gene editing technology and just how you think about.
You know indication preference starting out just maybe help us understand about that profile you are looking for and then how youre going to go after specific diseases within the basket here.
Okay.
Thanks, Avi and this is a great question. So what we what we wanted to do with the Arbor partnership is really create new opportunities for us that would allow us to internalize that the that technology sort of independently and move away from the talent technology.
And and so.
Christopher based.
Platform that Arbor brings will allow us to have some flexibility in introducing site specific integration, which we also believe will improve the overall product profile and safety profile of this for this unique patient population.
So really it is a tool to allow us to go.
Fast and in new directions with product design as far as the clinical trial goes as we get a little bit closer to the launch of that program will be eager to share more details.
I'm willing to sort of say and speculate at this point that we will be looking carefully over the data that matures in the coming months from the field and learning what we can learn about <unk>.
Inroads being made into other indications of course.
Lupus is is the indication in which the clearest clinical proof of concept exists and so we will be carefully paying attention to that.
The design of the study again will we will get into that as we get a little bit closer but.
Weighted to Tyler's question before we are very much looking at how far we can push this lymphoid depletion reduction as we can including potentially testing.
No lymphoid depletion at all so.
Stay tuned for more details on the clinical development plan as we get a little bit closer to the launch of the program in early 2025.
Okay.
Thank you. Our next question comes from the line of Brian Cheng of J P. Morgan. Your line is open up Brian.
Hey, guys. Thanks for taking my questions today.
Curious if you can walk through your latest thinking around the phase one for our 3% to nine.
Specifically, how many doses do you plan to execute or you doing dose escalation in autoimmune patients and if so which indication should we expect in the Sir IPO player. It now already in indications like <unk> and myasthenia gravis. Thank you.
Hey, Brian.
I'll take that question.
Great question.
What I can say is stay tuned.
In comms.
Steps of dose escalation that left for completion I believe those are details that given our teams track history in conducting the clinical studies that can execute those pretty well I'm more likely not to think about the objective set the phase one study with three to nine I mean, the three things that we have called out that differentiation coming.
From being able to go after B cell and T cell that's more of a biologic clinical question that needs to be addressed through.
Conduct studies and going after different indication, but also as we have called out one of the important question that we want to answer is whether we can administer outlook reached two nine would reduce or with no input depletion and has the same.
Type of immune resetting phenomenon I think that will be really the focus of how we designed the phase one study and of course the.
Trying to get that answer as quickly as possible I mean that led to that at least in a couple of different study designs, but all these things are being discussed right now.
Thank you.
Alright, please standby our next question.
Comes from the line of micro G of Jefferies. Your question. Please Michael.
Hi, This is Mac on for Michael.
Was wondering pushing away from the autoimmune focus.
Thinking about the first line study for Alpha three how do you ensure that this.
You'll be able to enroll the study and I guess, what gives you confidence in your ability to enroll the study in a timely fashion and I guess as a corollary.
When would we be able to expect some some initial data from.
From these patients thank you.
Hey, Matt this is <unk>. Thanks.
Thanks for the question so.
As far as the first part of your question why are we confident that this study.
We will be able to be enrolled quickly.
In a word enthusiasm I think.
The what we have seen so far as we have reached out to investigators across the treatment spectrum from.
Academic Kols, who have been part of the car T story for 10 15 years, all the way to community oncology practices that have a large volume of patients, but have not yet made the jump into car T.
The response to the study has been uniform and it's been extremely positive and we are seeing levels of engagement from investigators clearing obstacles to open the program as quickly as they can we've seen that left and right. So there is a there is a palpable level of enthusiasm around this call.
<unk> really driven by the possibility of curing patients after frontline and preventing a relapsed from ever occurring this is a very novel and innovative approach to <unk>.
Studies in <unk> and people are really excited to be part of that.
As far as data goes.
As we get a little bit closer to the start of the study in midyear of this year I think we'll be in a position to provide a little more clarity on when enrollment is going to complete and when data will be available on what we have said and I'll reiterate here is that.
The study is designed to have an interim analysis that is currently slated for middle of next year. When we will examine <unk> conversion from positive to negative everybody that comes into the study will be MRV positive. So we're looking for evidence of clearance of MRV as well as safety and translational outcomes.
And we will use that interim analysis to select the lymphoid depletion arm that will be carried forward for the rest of the accrual period. So as we pass through that gate.
We'll make a modification to the study design and that will be plainly visible too to all who are paying attention and we will not however be able to share.
Granular detail from that analysis because this study is pivotal from the very first patient that's enrolled and so all of these patients starting again middle of this year, we will count towards the overall.
And thats required for the pivotal study so.
Lest we jeopardize trial and checkup integrity by sharing those results.
We'll not be sharing data update at middle of next year and.
And Brian I would add.
I like the question about your focus on enrolling the pace and execution of the study, which I think is the key.
When you look at what we are doing alpha three I mean, thats still on all the data that we have generated from the opportunity in relapsed refractory large b cell lymphoma, setting and we share that data.
Paul with all of you and this is really on par with autologous car T therapy, which I don't think any of the other allogeneic car T companies can say that yet.
And from the technical perspective, we believe that this highly de risked I mean after all this is comparing against observation.
And wait so we feel pretty good about that execution is the key and frankly I think.
Study start and enrolment I think that is a pretty significant derisking information about the offer III study. So stay tuned I mean, our teams working really hard to make sure that we execute this study as quickly as possible.
Thank you.
Our next question comes from the line of Jack Allen of Baird. Please go ahead Jack.
Alright, Thanks for taking my question and congratulations on the progress.
I'm kind of thing Dan is the last question I wanted to ask about that interim analysis by middle of 2025.
And then it sounds like you may not be planning to outwardly share the results, but any context, you can provide around the number of patients who are looking to have that dataset.
Is there an internal bar you are thinking about that you are within our reach as it relates to progression in the study forward past that interim analysis. Thanks, so much.
Hey, Jack Thanks for the question.
So we haven't gone into detail about how many patients are going to be included in that analysis.
I'll say that it's sort of.
Maybe unhelpful not too many not too few we want to have enough statistical power to make a good a good call and with respect to the second part of your question. How are we going is there an internal bar that we're going to be looking for so there's really two parts to this right. We want to make sure that we are improving upon.
The standard of care, which is watch and wait and we think as David pointed out that we've largely derisked that question through our experience in phase one we know that <unk> is an active therapy. So.
So we think that we will be able to clear that bar, but of course, we'll be paying attention to it and then of course, we have an additional set of criteria that we'll be using to make the selection of FCA versus FC. So.
This is a very well thought out prospectively designed analysis that.
That we think is going to lead us to the right answer.
Thank you.
Our next question.
Comes from the line of John Newman of Canaccord Genuity. Your line is open Jive.
Hi, guys. Thanks, a lot for taking the question and thanks for the update.
Just curious if you could comment a little bit more regarding the potential targets in autoimmune disease. So obviously your approach is dual targeting.
Other companies out there are also looking at 2019, but some are looking at <unk> 20.
And we have additional companies with the CMA car Ts that are sort of considering.
Treatment of autoimmune disease, namely lupus.
Can you say what.
Which targets could be better.
Why obviously differ.
Different targets sort of crop up at different times during the life cycle.
T cells, but just curious as to your thinking on that thank you.
Yes, so in terms of the John Great question.
Frankly, I think this is a topic that we are sort of looking into but.
Ultimately I believe that when you look at.
Touch any of these targets that you have mentioned CD 19 seats on E&P CMA.
If you look at the coverage of <unk> expression, that's probably most growth and probably a better suited at their targets, but this is something that we also have to buy from.
The clinical data as different players pastis different targets.
The other question around the indications that we are interested in.
We can start to think about this from generating early proof of concept of not requiring a lift for depletion.
That is the primary objective and actually that is.
Indications, where the proof of concept has been established with the seasonality of <unk> would be very good and also lukas that progresses.
Commercially very attractive indication that swaps. So Lucas is definitely in the play I know its getting crowded, but remember our outlook <unk> nine has a very distinct and differentiated approach. So if we can differentiate from others. I think we have a good we will have a good traction even in the crowded field.
But also being able to go after us.
Create a T cell south potentially opens the.
Cohort two other auto immune diseases, we're going out to <unk> alone may not be sufficient and multiple sclerosis is a class sub disease. This one.
To immune diseases that affect the nervous system I think that's also part and so.
Frankly.
Yes.
We have to be focused and we have to go after certain indications, but right now I don't think we have to decide and we have enough time to finalize that decision in next three to formats. So stay tuned.
Hi.
Thank you.
Our next question.
Comes from the line of Sami Corwin of William Blair.
Justin please.
Hi, This is Caleb one for Sami Corwin, thanks for taking the question.
So given the number of car T cell companies pursuing autoimmune disease indications how are you.
Got to have a competing for patients in future trials would you be more focused on enrolling patients in new York or ex U S or a combination of both.
I think that's a relatively.
Simple to me I mean, when you think about that.
Multiple different companies, taking different assets into those indications, yes. It is true.
But when you think about in a number of the pair of patients that are out there.
Yeah.
What.
The current clinical studies are covering us.
Not even a tip of an iceberg I mean, youre probably talking about <unk>.
Fewer than 100 patients out of two.
<unk> hundred thousand potential patient population that we can go after.
So our view is we are.
Less concerned about that as long as we maintain the differentiation and frankly, if you can get rid of the liquid depletion I think opportunities to do a quick.
Our development program.
<unk> becomes a more real and.
Something that we can easily do very quickly.
Thank you our next question.
Come from the line of Kelsey Goodwin of Guggenheim. Please go ahead Chelsea.
Oh, Hey, good afternoon, and thanks for taking my question mine is on CLO.
Do you think about the ICL placement for car T given kind of the agent.
Patient population and the durability of that we see with BT came from BC. Okay. Okay. Thank you.
The question was around the durability that we can expect.
Martha the positioning and what kind of patients would would you want to get on this given kind of the age.
Diagnosis and how how durable the responses are with the inhibitors that are already approved.
Yes, okay. Thank you so well as a reminder, the.
That study will enroll patients that have.
Okay inhibitors and Bcl two now there is non covalent bcl.
TK inhibitor <unk>.
<unk> that's been approved.
That has shown that in a similar patient population there is some benefit too.
To that to that drug however, similar.
Similar to the established.
Modalities. This is non curative and so what we what we have seen from the autologous experience in CD 19 for cielo as that.
Some patients.
Significant fraction of these patients can actually have very meaningful durable complete remissions that go on for months or even years and so and in a patient population that has failed. These prior therapies. So.
Number one I think that the modality is.
Is promising in this patient population number two I'll point out that just looking at our experience from from <unk> is that our toxicity profile.
Is is wholly consistent with a somewhat more frail population with very low rates of high grade Crs.
<unk>.
And inconsistent with outpatient dosing, which we do have experience with so.
While we are getting our feet wet with this phase one study and getting ready to share data later on this year, we will be paying very close attention to how that toxicity profile plays out in this patient population as well as being able to meet or even exceed the bar that has been established by the by the autologous players.
Hi.
Thank you.
Our next question comes from the line of Reni Benjamin of JMP Securities. Please go ahead Randy.
Thanks, guys. Thanks for taking the questions and congrats on the on the progress.
Maybe just continuing with the.
A lot of questions around CLO, what would you consider to be kind of a go no go you know results that you would like to see by the end of this year.
I know, there's only going to be about 12 patients worth of data.
How do you how do you plan on kind of dissecting that and I guess, just as a second part of that you.
Just given your experience with the <unk> do you think there might be an opportunity to move sema sell to some type of a consolidation or more of our frontline.
Treatment in.
In combination with drugs that are already out there I remember way back when.
Juno or thinking about combination studies and in.
In a frontline setting and just wanted to know how you guys were thinking about this.
Thanks.
Yes, so as far as the bar for internal decision, making of course, we will watch the data as it rolls in but I'll again point out that the bar is not all that high here and actually Thats one of the things that why we believe that moving into <unk> is exactly the right thing that we should be doing with <unk>.
Micelle, because the data that's before the FDA right now suggests that.
An improvement of 50% or on a sub 20% CR rate.
Is something that is probably well not probably is attractive to the treating physicians and patients who are in this predicament of having failed the approved therapies.
We'll be watching the the Fda's response to that dataset very carefully.
And as our data matures being able to make.
Decision about whether to move that into a phase II.
Registrational study.
As far as the other question goes with respect to consolidation and or combinations.
I do think that that.
That is an attractive avenue to pursue and in fact are our focus in consolidation in large b cell with Alpha III is a testament to our belief that our consolidation strategy or treatment with with with car T cells. When the diseases that are relative nadir is a very interesting proposition.
And can be applied to other indications as well.
Combination is a little bit more of a challenging idea, but it certainly has been floating around and I think theres a strong biological rationale to do that.
And so we'll be looking at that carefully as the program matures as well.
Thank you.
Our next question comes from the line of carpet Patel of B Riley Securities. Please go ahead cockpit.
Yeah, Hey.
For taking the question, maybe just one on allo three to nine.
Can you discuss any thoughts on broader immuno modulator modular jewelry effects beyond <unk>.
Direct cytotoxicity as that has any impact on.
Regulatory T cells.
You have targeting of <unk> 70.
And how it might be the FX influence outcomes for autoimmune disease patients.
Thanks, Carl Good question.
So that is the detailed work on sort of the subsets of T cells is ongoing in the context of our 316 program and so really trying to understand.
Are there certain compartments within that T cell.
Lymphocyte population that are more differentially affected by.
By CD 70 targeting therapy.
So we're doing that work in the context of our ongoing 316 and in fact good strong.
Support for this idea of being able to target activated T cells has now been demonstrated as David mentioned from the translational results from the traverse trial.
So I think what we can take away knowing what we know from our in vitro work and and the clinical trial with CD 70 car is that we do see differential suppression of activated T cells, and we know that those activated T cells.
Ebay conventional or or regulatory.
Or are involved in autoimmune pathogenesis and so.
And there is literature that supports the role of CD 70 in certain autoimmune disorders like lupus and so we think that in addition to the dagger effect, which is one of the key reasons that we are pursuing CD 70, as a dual car with allo three to nine we do think we'll be able to modulate the activate the specific activated subset of those T cells.
And so we'll look at the careful subpopulations as we as we execute the 316 study and of course, we'll be paying close attention to that within three to nine.
Okay.
Thank you our next question.
Come from the line of Luca <unk> of RBC capital. Please go ahead Luca.
Oh, great. Thanks, so much for taking my question and congrats on all the progress is ask can you just expand a little bit more on the interim look in mid 2025, I think when you were running the trial in the third line setting the FDA basically ask you to ship PSS superiority when you actually add two versus nuances due in a.
<unk> randomized trial, however, it looks like the FDA is now okay. We just showing patients converting from Emory deposit Dweomer day negative within the context of the <unk> pivotal trial and actually not a separate trial, which is randomized but feel.
<unk> submitted the FDA has kind of lowered the bar here. Despite youre actually moving in earlier studies, one would that be fair and two if so what drove that change in posture from the regulators any cough there much appreciate it.
So I don't I don't say, thanks Luca for the question I don't think that Theres been a change in the Fda's opinion on what would constitute a contribution of effect data package.
What we have done in the design of Alpha three is condense what was two trials in the third line setting into a single trial in the frontline consolidation setting. So we've really got a in a way of speaking of trial within a trial and the first part of the study that will culminate with the interim analysis.
Next year.
<unk> is designed to generate the contribution of effect that will be that will support the registration of allo six or seven.
Now that said.
The reason that we're running this part of the study the way we're running it in a randomized fashion is because we want to actually address the scientific question of whether Allo 647 is truly required in these patients with no radiographic evidence of disease and so there is still a chance I would say a good chance.
That we select beyond that does not even that does not contain allo 647, so but be that as it may the reason that we have designed it how we have done it as to specifically address the fda's requirement for Coa for 647, So I would not say that there has been a change in regulatory stance there.
Thank you our next question.
Comes from the line of athletic are Gonna Warding off Truest. Please go ahead.
Hi, This is <unk> thanks for taking the question.
Following up on CLO license, all his generated an 18% CR rate Hum.
Efficacy of allogeneic car T compared to autologous since yellow and particularly considering the potentially superior T cell fitness.
And also what data would you like to see.
When evaluating the efficacy of our car T. In this context.
Thanks, Corrina, so I think I like the way you asked that question because I think it really speaks to our primary motivator for US opening. This trial and then is that we believe that the underlying T cell fitness coming from a healthy donor derived product is going to be superior to the T cell fitness.
That is derived from a patient.
Leukapheresis because cielo is a notoriously immunosuppressive malignancy.
Number one number two often those T cells are are surrounded by a very high circulating leukemic burden, which makes isolation of those cells for manufacturing all the more difficult we Dodge both of those those problems starting with healthy donor material.
So we think that there is a chance that we will actually have a meaningful improvement over what has been shown by autologous but of course, that's why we're running the experiment.
I've sort of addressed what we think.
The target is here of course to 18% CR rate that's been established as potentially register a bowl, we'll see what happens with the.
The decision by the FDA, there, but we think that given the comparability that we believe we have shown in large b cell against autologous products.
That we should at least be able to meet that.
Thank you our next question.
Come from the line of Laura Prendergast of Raymond James Your question. Please Laura.
Hey, guys. Thanks for taking the question I was curious.
I'm already testing yeah as expected it becomes more broadly is how do you expect that having any issue isn't rolling off our three especially since some patients will be randomized to the control arm with no therapy.
How do you think about this and if you look at that and if you're a carrier competition and lesser setting given the projects are already testing.
Thanks, Laura so so we don't we are not worried in the least about the patients who are going to be randomized observation that is the current standard of care and that means that these patients. There is no data anywhere let alone an approved agent to direct the physicians.
To offer another line of therapy to patients who are in the observation arm. So we don't think that there in fact, we know for a fact based on the work that we've done already in during the study startup that there that there is wide agreement that this is the most appropriate management for these patients which is the current standard of care observation.
These patients will be monitored very closely in the context of a clinical trial, probably as closely if not more so than they would be.
Were they not participating in a clinical trial, that's the nature of clinical investigation and this is going to be part of why we think patients will be willing to sign up for this study.
And as far as competition goes.
There is a good chance that at some point, we will see some company in the development of of agents for patients with MRV only disease.
We do think that we have a unique product profile with <unk>.
Onetime administration, so there's no need to for a long period of treatment or maintenance therapy. This is a as we said kind of a seven cycle of treatment that these patients can get and just go home and move on and number two.
These patients can progress very quickly after they complete frontline therapy and they have <unk> disease, So being able to act definitively in very rapidly and I'll remind you that we initiated treatment within two to three days after patients are enrolled in our third line study. So we know that we can we can affect this treatment extremely quickly. So we think we have a built in.
Advantage with our modality and that's on top of the.
The strong lead advantage that we have having.
Launch this study before any of our competitors.
Okay.
Thank you. Our next question comes from the line of William Pickering of Bernstein. Please go ahead William.
Hi, Thank you for taking my question and your Alpha three trial, you've talked about including community centers could you speak to the level of.
Interest that Youre getting from these centers do you expect it to be a large or small percent of total sites in these centers need to already be fact accredited to participate. Thank you.
So.
I will say that the the reception that we've gotten from these community practices has been.
Very very positive and very there's a high level of engagement and enthusiasm.
Many of them are moving extremely quickly to be ready to open the study.
There's even a little bit of friendly competition amongst some of them to really be the first to open so.
We've been very encouraged by the by the reception that we've gotten.
Uh huh.
As far as the percentage goes it's going to be that we're going to we're definitely going to have some.
Academic centers because they are as excited about this concept as the as the community oncologists, so theres going to be a.
A continuum.
We don't exactly know yet we havent completed the full selection of the entire panel.
Programs, but I will say that there will be a substantial.
Percentage of patients coming from these community practices in the overall study.
Okay.
Thank you.
Thank you I would now like to turn the conference back to David Chang for closing remarks, Sir.
Alright. Thank you for joining me on our call today and your continued support we are more excited than ever about the potential for Allergan.
And the opportunity to fulfill the promise of allogeneic car T for patients with cancer and now extending that promise to patients with autoimmune disease with our car T to know our three to nine.
<unk>, who has been involved in developing cell therapies in particular excited about what's happening in the field today.
Thinking differently and putting in a basin at the forefront that is exactly what is needed to appeal. This new resurgence in cell therapy.
Look forward to providing updates to our exciting programs throughout the year with that goodbye.
Yeah.
This concludes today's conference call. Thank you for participating you may now disconnect.
Okay.
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Okay.
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Yeah.
Mhm.
Hum.
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Okay.
Okay.