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On Tuesday, 27 May 2025, Allogene Therapeutics (NASDAQ:ALLO) participated in TD Cowen’s 6th Annual Oncology Innovation Summit, offering a strategic overview of its pipeline and market opportunities. CEO David Chang highlighted both the promise and challenges of Allogene’s allogeneic CAR T-cell therapies, particularly in community-based cancer centers.
Key Takeaways
- Allogene’s ALLO-316 shows promise in renal cell carcinoma with a 33% response rate.
- ALPHA3 trial faces delays due to staffing and patient flow issues, impacting timelines.
- ALLO-329’s dual-targeting mechanism is a novel approach for autoimmune disorders.
- Market potential for ALPHA3’s target population is estimated at $5 billion globally.
- Allogene is optimistic about FDA’s evidence-based regulatory approach.
Operational Updates
ALLO-316:
- Data from the Phase 1b expansion cohort will be presented at ASCO, involving 20 patients.
- The study tested various cell doses and lymphodepletion strategies.
- Preliminary results showed a 33% response rate in patients with CD70 expression.
ALPHA3 Trial:
- Interim analysis and lymphodepletion decision delayed to February due to staffing issues.
- Over 250 patients consented for MRD testing; expansion to Canada aims to accelerate randomization.
ALLO-329:
- Phase 1 study in rheumatology to be activated soon, with proof-of-concept data expected by February.
Future Outlook
ALLO-316:
- Discussions with FDA on the registrational path, considering single-arm or randomized studies.
ALPHA3 Trial:
- Plan to randomize 36 patients for futility analysis.
- Focus on sharing meaningful interim analysis insights with investors.
ALLO-329:
- Proof-of-concept data for autoimmune disorders targeted for February.
Q&A Highlights
ALLO-316:
- Inquiries about ASCO data presentation, patient numbers, and follow-up times.
ALPHA3 Trial:
- Questions on the impact of FDA’s Dr. Prasad on trial progress and significance of futility analysis.
ALLO-329:
- Discussion on Phase I study and target autoimmune diseases.
Readers are encouraged to refer to the full transcript for more detailed insights.
Full transcript - TD Cowen’s 6th Annual Oncology Innovation Summit:
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Great. Well, good afternoon, everyone. Tyler Van Buren here, senior biotech analyst at TD Cowen. Thank you very much for attending TD Cowen’s sixth Annual Oncology Innovation Summit. For our next session, very excited to have a q and a discussion with Allogene.
And from Allogene, it’s my pleasure to introduce, the David Chang, cofounder, president, and CEO. David, thanks very much for joining me.
David Chang, Cofounder, President, and CEO, Allogene: Well, Tyler, thank you very much for having Allogene in your health care conference. This is very exciting time for us, and glad to be here.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Great. So before I get started with the questions, for those of you in the audience, feel free to email me questions at tyler.vanburen@tdsecurities.com or cowen dot com. Once again, that’s first dot last. So maybe we’ll start with, 316 given the upcoming update and from the dose expansion. And you recently presented data in November of last year from the dose escalation.
So maybe you could provide a quick review of that data and why you selected dose level two for expansion and what we should expect from the upcoming presentation.
David Chang, Cofounder, President, and CEO, Allogene: Yeah. We are very excited to update three one six, data. This is a anti CD 70 directed allogeneic CAR T program that we have been studying in renal cell carcinoma patients. So, we will be presenting in the ASCO, which is just in a matter of next few days, the data coming from the phase one b expansion cohort. But, going to that, we have presented the three one six data in the past.
The phase one study essentially looked at different cell doses anywhere between 40,000,000 cells, per dose to, you know, 20,000,000 cells. In addition, we also explored different lymphodepletion. This is coming from the fact that c d 70 has intrinsic dagger activity, and therefore, the cells were expanding much differently than the allogeneic CAR T programs that did not have the dagger technology built into it. So with that, we decided to explore more than FCA, which is what we have been using in other programs. And another thing that we did is given that we are going after c d seventy expressing renal cell cancer, that makes a perfect sense.
It is c d seventy directed CAR. We also wanted to look at the impact of c d seventy expression on both safety and efficacy. So after we have more or less completed various different doses and lymphodepletion, we settled on 80,000,000 cells with a standard lymphodepletion that only has fludarabine and cyclophosphamide, and that’s essentially the, you know, the phase one b expansion cohort. Previously, last November at SITC meeting, we presented the preliminary data that’s based on eight patients. Out of those eight patients, six patient had c d 70 expression at the target range, which is, yes, they have to express c d 70 and also tumor proportion score.
So this is percentage of tumors that express c d 70 had to be, fifty percent or higher. Within that patient population, which, represents the majority of renal cell cancer patients, we were seeing a confirmed response rate of thirty three percent. And at the time, the durability was somewhat limited, but both patients who responded had ongoing responses at month four and second patients beyond month six. So the expectation, you know, at the ASCO present, you know, upcoming ASCO is we will have more patients. Obviously, with that, we’ll get much more, accuracy in estimating the response rate.
And with a longer follow-up, we will be able to say more about the durability of responses among the responders.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. Great. That’s very helpful. Are you able to say how many more patients there will be and what the approximate amount of follow-up time will be?
David Chang, Cofounder, President, and CEO, Allogene: Yes. So, we were targeting, about 20 patients in the phase one b cohort. That’s approximately number of patients who have been, enrolled. And, the last patients in the phase one b cohort, was treated earlier this year. So, you know, the data cut, you know, based on, you know, when it is, you know, expect that everybody would have had at least, three plus month more follow-up, and certainly some patients will have much longer follow-up.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. That’s great. And, what response rate and durability, do you all believe you need to observe, from allo three one six to warrant further pivotal development in this indication?
David Chang, Cofounder, President, and CEO, Allogene: So that’s it’s really, that question has to be answered in the context of the patient population. In the study, you know, we enrolled heavily pretreated patients with a median number of prior treatment in, of of full prior treatment. So, with that, you know, we can you know, with that as a caveat. I mean, generally, in solid tumor, the way we think about this is we like to see responses in about one third of the patients. And also with respect to the durability, responses that goes on in a six month or longer, that’s, sort of the minimum target profile product profile that we’re looking for.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. And just standard of care, what would you expect to see from standard of care in these patients?
David Chang, Cofounder, President, and CEO, Allogene: Yeah. So that is, you know, for the, you know, the similar patient population, you know, that information is really not there. I mean, because, you know, the patients that we are treating, not only, they had to have at least one, tyrosine kinase inhibitor and checkpoint inhibitor to go on the study. But when we look at the patient population, you’re talking about patients who have had two prior checkpoint inhibitors and also a majority of them had two or more tyrosine kinase inhibitors and growing number of patients also having treated with inhibitor. So, you know, new treatment in that patient population, you know, there is really limited information.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay.
David Chang, Cofounder, President, and CEO, Allogene: So in some ways, we rely on, you know, what the investigators are telling us, especially given, the lack of information here. But, you know, the investigators consistently tell us that, you know, seeing any kind of responses in the patients that you are treating would be quite remarkable. And if it’s a durable response, I mean, that, you know, could be very interesting treatment options. So, also, another way to think about is renal cell cancer. I mean, essentially, there’s about, you know, four different class of medicines that are used.
The checkpoint inhibitor, tyrosine kinase inhibitors, the, you know, the metabolic pathway and then, the hip two alpha inhibitors. So here, you know, c d seventy targeted therapy as a cell therapy would be a new modality, which could give a lot of options to patients.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. So as we think about a pivotal trial for three one six, maybe we’re getting ahead of ourselves here ahead of seeing the data. But just Mhmm. Maybe briefly, so you have in mind what a pivotal trial might look like, and would that be, you know, sponsored by Allogene, or would you look to potentially partner, allo three one six?
David Chang, Cofounder, President, and CEO, Allogene: Yeah. We are trying to find, you know, what, would be the appropriate next step, you know, for us, you know, presenting the data, getting the responses from, we have a, know, sort of reactions from most KOLs, but, getting the, reactions from the analysts and investors. And, also, another thing that we have in plan is taking the phase one data to the FDA to have a discussion around the next step. Obviously, you know, when the unmet need is high, I mean, there is a single arm registration or path that could be available. And, you know, that also you know, success of such program will be very much dependent on, you know, how you can find that controls, which can be generated from the real world data.
Alternative is a randomized controlled study, you know, which is a gold standard of how we conduct clinical study in, you know, any therapeutic area. So there are various different options. And what we are trying to do is, you know, we know that, three one six is an active program, and we know that it works. What is the registrational path and how to find a way to support the program to the next stage.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. That’s clear. Now let’s move to CMA cell and alpha three with CMA cell falling under receiver oversight. Can you walk us through the alpha three trial design and just any implications that there might be with doctor Prasad’s recent appointment and, some of his historical comments if you think as an a read through to the alpha three trial.
David Chang, Cofounder, President, and CEO, Allogene: Yeah. So let me first comment because there has been so much speculations and misconception about what may happen to FDA. So truth of matter is nobody really knows. We just have to wait. But I have to say all the initial indication, you know, coming from the FDA with the new, you know, leadership makes me feel very confident that, you know, FDA is an institution.
It’s never about a single individuals. And as an institution, you know, which is the best, you know, in the world in terms of regulating drug development. So far, nothing has made me, change my view on how FDA will embrace evidence based approach and continue to support the drug development across various different indications. So, you know, with that, now let’s go to the as your question about the alpha three design. Foremost, this is a randomized control study.
We are comparing a single infusion of SemiCell against standard care, which is watch and wait, you know, observation. So that’s a one, you know, very important that’s a gold standard with which we anybody would be, you know, conducting the clinical study. Second, patient population is pretty well defined. Essentially, we are treating patients, not everybody who undergoes the frontline treatment, but identifying those patients who are at high risk of having a disease recurrence using the state of the art MRD assay. So I think that’s also, in many ways, in a very efficient way to conduct any kind of clinical study, and that’s always viewed very positively in in the in the regulatory bodies as well as, by the clinicians.
And then third is the, the endpoint that we are using. We are using event free survival as a primary endpoint, and that is the most appropriate endpoint in this setting. And it also has a precedent, you know, as endpoint that has been used with, autologous CAR T therapies in the second line large B cell lymphoma setting. So when I think about the study design, patient population, as well as endpoints, we I’m pretty confident that, you know, alpha three study itself meets all the requirement, necessary requirement to, you know, generate, high quality data, that will be very evidence based and, could support the registration, pending the outcome.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. Wonderful. And, so, again, following up on alpha three on the recent earnings call, you offered updated timelines. Maybe you could walk through some of these changes and what caused, the slight delay in timelines.
David Chang, Cofounder, President, and CEO, Allogene: Yeah. So, you know, last earnings call, we pushed out the first milestone event, the futility interim analysis, where we also intended to make the determination of the lymphodepletion from the the mid two thousand twenty five to the February. So just on the lymphodepletion, you know, in the initial phase of the study, we are testing two different lymphodepletion. And based on the initial data, we always had made plans to eliminate one of the lymphodepletion arms and proceed as one to one randomization till the completion of the study. So, the reason for the delay is really, operational issues, you know, coming from one, delay at the time it took, for most of the sites in The United States where most, you know, we have the activated sites for them to, you know, get the necessary staffing to support the study.
And this is something that I had never experienced in the past. Usually, when all the regulatory work is done, you know, sites are more or less, you know, all ready to start screening the patients more than once. And, you know, as we, you know, activated most site, it became a general finding. Then most sites now go through the second stage of finding the right, study coordinator to support the study, and that took additional time that we had not expected. The second is really the patient flow issue, and that is unique to the clinical study that we are doing.
In our study, we identify the patients anytime during their frontline R CHOP, treatment. So when we identify the patient, we consent them for the MRD testing. And when they get to the MRD window, which would be at the completion of our CHOP, that’s when we can collect the samples and do the MRD testing. And those who are MRD positive, then they can randomize the second time to go on to the, the the, you know, alpha three study. So this is what we call as a patient flow from initial patient identification to actually patient going onto the alpha three study can take as much as four to five month.
You know, especially if someone is identified at the beginning of R CHOP, it takes six cycles, each cycle taking about three weeks. So altogether about, you know, almost twenty weeks before they are eligible to have the MRD testing. And once the MRD test is done, which takes about ten days, it takes another, you know, three to four weeks before a patient undergoes the randomization to the second process. This, is something that we should have built into the study timeline, but, it sort of came to our sort of, you know, realization. Yeah.
You know? You know, you can identify the patients, but it does take some time to actually enroll the patients. Now despite all these sort of you know, at the end, you know, from company perspective, it’s an explanation. You know, nobody likes to push out the timeline. But on the other hand, we are seeing a, you know, very good momentum in this patient flow.
And this is, you know, how we explain that there are more than 250 patients who have consented to undergo MRD testing, since the study has been opened, and majority of those patients coming in last three to four month as the momentum is building. So you can think about this as a wave, you know, initial patient consenting, and that wave will continue to MRD testing and then eventually to the randomization. So that’s why we feel very, optimistic about the fact that, you know, this study, you know, has sufficient momentum. You know? In fact, we have talked about in terms of MRD testing consent.
I mean, we are definitely seeing, you know, what we frequently refer to as a hockey puck effect, and, eventually, they will, show is a randomization. That’s where we are marching towards.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. And just based upon everything that you’ve learned that you just discussed, how are you using this to decrease the time to first randomization with the newer initiated sites?
David Chang, Cofounder, President, and CEO, Allogene: So, you know, that’s is this is really the resource issues. I mean, there’s a very little I mean, we can have the conversation earlier. And another thing that we are doing is, also taking the study, you know, outside The United States. I mean, we initially targeted about 50 sites in The United States. We will definitely increase the number of sites as we open up the sites in Canada, which we expect to, do so in next, you know, you know, few weeks, and then also taking into other territories as well.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. Alright. Okay. So with the futility analysis and lymphodepletion decision now expected in the first half of next year, can you walk us all through the significance of that decision? How many patients will be included in that analysis and what you need to see between the lymphodepletion arm assist?
So select one over the other.
David Chang, Cofounder, President, and CEO, Allogene: Yeah. So the plan is to randomize and treat 36 patients altogether. So there’s, 12 patients per arm and, looking at their, safety and also surrogate for efficacy, you know, which would be the MRD conversion. So everybody who goes on this study, starts with the MRD positivity, and this is using the, clarity test that we are partnering with Foresight Diagnostics. And, the expectation is that people who are randomized to, the control arm will remain MRD positive, whereas, patients who are randomized to either lymphodepletion arm and get treated with semisel will convert to MRD, negativity.
So what we will be you know, how we’ll be making the determination on the lymphodepletion selection will be, influenced by the safety profile that was seen as well as the MRD conversion rate. And, obviously, you know, the higher the MRD conversion, the more confidence it will give us. And between the two arms, if both arms work pretty well, it becomes a little bit tricky decision. But if there are some kind of differences that are very discernible, then it becomes a a very clean decision.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Is it possible you could give us a glimpse into the data or what you’re observing in the first half of next year?
David Chang, Cofounder, President, and CEO, Allogene: That’s a great question. I would say stay tuned. You know, you know, ongoing, you know, potential registration study in a general practice is not to talk about the study result, but, we also have heard from, during our meetings with the investors as well as analysts. If we simply remain silent about what we are seeing, it may not be seen as a meaningful. Whereas internally, we will have such a meaningful information on the entire outcome of the of the alpha three study.
So, we are sort of in, you know, you know, reviewing, you know, what we can say and how much we will say, but the intent is, to make the announcement of, you know, initial interim analysis be meaningful to the investors.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. That’s helpful. We saw the recent alpha two paper, which showed very encouraging efficacy with Simicella patients with low disease burden, which is interesting as we think about the ultimate outcome of ALPHA-three. And you’ve talked about expectations for the control arm. But I guess just as we think about the primary the interim and primary EFS analyses, which you know, how should we think about those both in terms of timing, but also what you would like to see to for alpha three to be successful?
David Chang, Cofounder, President, and CEO, Allogene: Yeah. So, you know, going into the statistical assumptions, which we haven’t gone into too much about how the event free survival, you know you know, rates assume that how soon that will occur, That’s all built into how we drive, you know, the patient, you know, total sample size of the of the alpha three study, you know, which is 240 patients. With 240 patients, I mean, you know, the the statistical, finding has to be, you know, pretty with a low hazard ratio. And also with that, you know, the clinical, you know, findings will be, you know, very meaningful. So the outcome that we are looking for in this study is clinically meaningful event free survival difference between the control and the treatment arm.
And, also, as a, you know, secondary endpoint, we are looking at, you know, in a slightly different, endpoint of progression free survival as well as overall survival. But, study is not powered for overall survival nor the expectation in our discussions with FDA, a survival demonstration will be required for this study.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. That’s helpful. And maybe to to round out the discussion here for alpha three, how big do you believe the post R CHOP MRD positive patient population is in terms of market size?
David Chang, Cofounder, President, and CEO, Allogene: We believe that this is probably the largest indication that one can come up within the large B cell lymphoma. So there are two things. The number of patients, our expectation around how many patients will be MRD positive is somewhere around one out of five to, you know, one out of four. That’s the rough range. I mean, that already gives a much larger patient number.
Another important thing about alpha three study is, we are trying to overcome current barriers of CAR T penetration in the large B cell lymphoma by taking the study directly into the community based cancer centers where the majority of the patients are cared for. So what we are trying to create is take the treatment to the, initial place where patients do not have to be referred. And what’s enabling us to do that is the fact that we are allogeneic. You know, we can provide drug, you know, bile when the patient is ready. There’s no complicated logistics that’s associated, with, CAR T delivery.
So all these things have gotten a lot of, attractions from the community based cancer centers. And with that, we are hoping that we can get a sizable, you know you know, we can create sizable commercial opportunity. Current estimate, you know, for the market opportunity, globally, is, is around, you know, $5,000,000,000 a year.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Okay. Sizable indeed. So this is an oncology summit, but and I know we’re about up on time here, but just wanna get to allo three two seven quickly in autoimmune given the importance, to the allogene story. The CD19, CD70 dual targeting mechanism is really unique. So maybe you could just talk a little bit about the Phase I study and what you kind of want to see here as well as the autoimmune diseases and indications you all are most interested in.
David Chang, Cofounder, President, and CEO, Allogene: Yeah. So allo three two nine is the dual targeting. It’s a target c d 19 and c d 70 for the purpose of really addressing the underlying defect in autoimmunity. Autoimmune disorders are never AP cell disorders. In addition to B cells where, for some reason, because of c d nineteen CAR T data coming up, everybody thinks if you eliminate T cells, you know, you will take care of the autoimmune disorders.
But, what supports the B cell maturation activation? You know, T cells and antigen presenting cells, which c d 70 can address. And in addition, there are autoimmune disorders such as type one diabetes that are purely driven by T cells as we currently understand the underlying biology. So l three two nine has a potential to go after T cell driven autoimmune disorders. So this is the, you know, three two nine program that we are taking initially into the rheumatology indication.
So patient population that we’ll be studying, lupus patients, systemic sclerosis, as well as inflammatory myositis patients as a basket study. The intent of the study is, leveraging the uniqueness of the, three to nine, start testing low or lymphodepletion, which can you know, if we can achieve that, they can, you know, open up the market opportunity for what we are doing with the autoimmune programs with the CAR T. So in this basket study, we will be studying the lymphodepletion with cyclophosphamide alone. So we already are taking out the fludarabine. And then another arm that we will be studying concurrently is one arm that has no lymphodepletion altogether.
So this is a dose escalation study. We expect to activate this study shortly, and our goal is to generate a proof of concept data come you know, by the February. Very exciting program, and it’s a great opportunity for the autoimmune disorders where one time treatment can potentially provide durable, you know, drug free disease control. So, you know, we are very excited about it.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Great. Really looking forward to seeing the initial three to nine data. With that, we are well over time here. So I think we’ll go ahead and wrap up. But, David, thank you very much for the time and the great discussion, and thanks to everyone for logging in.
David Chang, Cofounder, President, and CEO, Allogene: And, Tyler, as always, thank you very much for hosting us, and great to be talking about allogeneic cell therapy now. We are so close to actually getting to the finish line about making the allogeneic CAR T available for patients.
Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Indeed. Have a great day, everyone. Alright.
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