Allogene Therapeutics at TD Cowen Conference: CAR T Therapy Expansion

On Wednesday, March 5, 2025, Allogene Therapeutics (NASDAQ: ALLO) presented at the TD Cowen 45th Annual Healthcare Conference. The company highlighted its strategic advancements in allogeneic CAR T therapy, underscoring both promising developments and ongoing challenges. Key discussions revolved around expanding therapy access and upcoming clinical milestones.

Key Takeaways

• Allogene is advancing allogeneic CAR T therapy for hematologic malignancies, solid tumors, and autoimmune diseases.
• The ALPHA-3 study aims to improve outcomes for lymphoma patients by intervening early.
• Allogene reported a strong cash position of $403 million, funding operations through 2026.
• Key data readouts and trials are planned for 2025, marking a pivotal year for the company.

Financial Results

• Cash Position: Allogene reported a cash reserve of $403 million.
• Cash Runway: The company expects these reserves to support operations until the second half of 2026.

Operational Updates

• ALPHA-3 Trial Enrollment: Between 30 and 40 sites, including community and academic centers, are active in the trial.
• Lymphodepletion Selection: A decision on lymphodepletion for Semacel is anticipated in mid-2025.
• ALLO329 IND Clearance: The IND for ALLO329 has been cleared, with a Phase 1 study expected to begin in mid-2025.
• ALLO316 Phase 1b Cohort: Enrollment continues, with data updates expected by mid-2025 for approximately 20 patients.

Future Outlook

• Semacel (ALPHA-3 Study):

- Mid-2025: Interim analysis for lymphodepletion and futility.

- First half of 2026: Event-free survival analysis.

- Year-end 2026: Primary analysis, potentially leading to a BLA submission in 2027.

• ALLO329:

- Mid-2025: Start of Phase 1 study.

- Year-end 2025: Initial proof-of-concept based on biomarker data.

• ALLO316:

- Mid-2025: Phase 1 update in renal cell carcinoma.

Q&A Highlights

• ALPHA-3 Trial Design: Aims to enroll patients with low disease burden, potentially improving efficacy.
• Lymphodepletion Decision: Based on MRD conversion rates and safety data.
• Autoimmune Program (ALLO329): Success indicators include B cell depletion and CAR T cell dynamics.
• ALLO316 Prioritization: Focus on demonstrating durable responses in renal cell carcinoma.
• Unappreciated Aspect: Allogene believes the market underestimates the potential of allogeneic CAR T therapy.

For more detailed insights, refer to the full conference call transcript provided below.

Full transcript - TD Cowen 45th Annual Healthcare Conference:

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Great. Well, good morning, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining TD Cowen’s forty fifth Annual Healthcare Conference for next session. Very excited to have a hybrid presentation and Q and A fireside chat discussion with Allogene.

And it’s my pleasure to introduce the David Chang, Co Founder, President and CEO of Allogene. David, it’s a privilege to have you here. Thank you for joining us. I’ll pass it over to you to start the presentation.

David Chang, Co-Founder, President and CEO, Allogene: Tyler, thank you for that kind introduction, I would say. And thank you very much. I know that this is coming towards end of the call meeting, and I appreciate your attention to what Allergan is doing. I’m President and Co founder of Allergan, and we have been working on advancing allogeneic CAR T therapy. What the allogeneic CAR T therapy brings is really an opportunity to expand this potential life saving therapy across heme malignancies and now going beyond heme malignancies into cellular tumor as well as in autoimmune indications.

We have three clinical programs at various different stages. The lead program is Semacel, which is in potential pivotal registrational study in frontline consolidation setting in large B cell lymphoma. This is a very unique and differentiated approach that we are advancing SemaCell into what we believe is ideal setting to use the allogeneic CAR T therapy. Another program that we have been working on for a couple of years is ALLO-three sixteen in cellular tumor. We recently presented a data supporting its continued advancement, especially highlighting at the recent SITC meeting the response that we have seen with ALLO-three sixteen in patients with advanced renal cell carcinoma.

And lastly, we recently announced IND clearance of ALLO329, which is specifically designed with autoimmune indications in mind. This is a dual CD19 CD70 CAR. And now let me go into each of these programs more in detail. So the ALPHA3 study of SemaCell in the frontline consolidation setting is a really unique study. Let me first walk through the clinical setting here.

Patients who are newly diagnosed with large B cell lymphoma undergo what is known as a Rituxan based chemo immunotherapy. It is a highly effective therapy where majority of the patients after six cycles of R CHOP, continue to stay in remission. However, there is about one third of patients who do not respond or who progress soon after completing the R CHOP despite initially achieving a good response. During this period, patients are followed with uncertainty until the disease progresses. What we are trying to do with ALPHA-three study is identify those patients who are at risk of having a disease relapse and intervening before the recurrence manifest symptomatically.

What we believe is essential for this kind of study is right product, that is Semacel and right patient population, being able to identify those patients who are likely to relapse and doing it at the right time before disease relapse occurs. Let me go into each of these components a little bit more in detail. We recently published Phase one data of SemaCell in the JCO, really demonstrating that as allogeneic CAR CD19 CAR T, Semacel brings the efficacy that is comparable to a total of CD19 CAR. Along with that, we also demonstrate the durability of the response in patients who receive Semacel as well as our manageable safety profile. So going more into the details, this is the highlights of the JCO paper, starting with the response rate that we have reported with SemaCell in the relapse and recurrent setting, large B cell lymphoma setting.

Response rate of sixty seven percent, fifty eight percent of CR and CR rate that is maintained through a six month at forty two percent. And also we reported the durability of the response in patients who achieved the response to be 23, which is getting to the range of what the autologous CD19 CAR T has shown. Safety profile as numerically shown appears to be comparable or in some categories better than autologous CAR T therapies as they have reported in their pivotal study Kymriah, Yescarta and Brienzy, each of which carries approval in the relapse recurrent setting. Now more details on the durability. On the right is the sorioplata patients who have achieved the complete remission.

And a majority of the complete responses continue on. The longest follow-up we have at this point is several patients who have passed forty eight month follow-up time period. And this type of durability is quite reminiscent of what has been seen with AUTOS CD19 CAR in relapse and recurrent setting in patients. Another important aspect of the study was looking at the sort of the subgroup analysis, specifically patients with a low volume disease where we have seen six out of six complete remission. And this is highly relevant as we think about the ALPHA-three study and I’ll come back to this point in couple slides later.

Next, how to identify the patient? This has been a somewhat challenging issue. The existing radiological method does not properly identify those patients who are at risk. What we are doing is working together with our diagnostic partner, Foresight Diagnostics, and using their CLARITY assay to identify MRD in patients after completion of the frontline R CHOP regimen. What’s shown here on the right side is a Kaplan Meier progression free survival curve that shows, the outcome of patients who are MRD negative, shown in the blue line, and outcome of patients who are MRD positive.

It’s a clear separation of Kaplan Meier curve. Patients who are MRD negative continues to enjoy remission, whereas patients who are MRD positive at the end of six cycles of our CHOP have a disease recurrence, majority of them and at relatively quickly with a median time to disease recurrence of probably less than six months. In all, MRD positivity at the end of frontline R CHOP denotes about 12 fold increase in the risk of recurrence in patients. Another important point is the relevance of disease volume and outcome of patients treated with CAR T therapy. What’s shown on the left is a probability of curve, both in terms of achieving response and experiencing adverse event relative to the disease volume.

Patients with low disease volume are more likely to experience durable complete remission, whereas patient with a high volume are more likely to experience more severe adverse events. As I’ve shown in couple of slides before, what we have seen, like other CAR T has shown, is that SemaCell works very well in patients with low volume disease. And this is exactly the indication that we are going after in the frontline consolidation setting. When you look at the disease volume extrapolated by the MRD status, this is done by our partner Foresight Diagnostics. Being able to identify patients who are only MRD positive versus waiting for these patients to have manifestation of the recurrence radiologically, that gives an opportunity to intervene when the disease volume is 200 fold lower than in otherwise patients who will be presenting for the second line treatment after disease recurrence.

Now what we are doing in the ARFA-three study is depicted in this diagram. We will be randomizing approximately two forty patients, essentially comparing what is considered to be a standard of care, which is watch and wait, essentially translating to having patients to come back to the clinic every three to six months for blood test and radiographic imaging studies. And we’ll be comparing that to a single infusion of SemaCell. Initially, there will be a run-in phase where we will be comparing two different types of lymphodepletion, FC, which is a standard lymphodepletion that has been used with Autonomous CAR T and FCA, which is the lymphodepletion that we have been studying with a somers cell in the relapse recurrent setting. Mid-two thousand this year, we expect to carry out the first interim analysis.

We’ll be looking at the futility as well as looking at the MRD conversion rate to make a determination of the lymphodepletion. After that point, randomization will continue as a one to one with a selected lymphodepletion versus observation. Primary endpoint of this study is event free survival with a key secondary endpoints of progression free survival and overall survival. In addition to the mid-twenty twenty five in a first interim analysis, we expect second interim analysis in the first half of twenty twenty six. This is an interim analysis is statistically powered and we’ll be looking at the event free survival measures to see whether the statistical boundary has been crossed.

Regardless of what happens in the second interim analysis, we expect to have the primary EFS analysis towards the year end 2026 that could potentially lead to a BLA submission in 2027. Now let me move to the second program, ALLO329. This is a dual CD19 CD70 card that is specifically designed for autoimmune indications in mind. With the goal of overcoming rejection, as well as addressing the underlying mechanism of autoimmune disorders by with the ability to deplete not only the B cells, but also CD7D positive activated T cells. Essentially, the ultimate goal is resetting the immune system, while preserving the underlying in a patient’s immune defense mechanism and maintaining the patient in remission for longer duration.

We recently announced the clearance of the IND. We expect to start the Phase one study middle of this year with a goal of providing initial proof of concept based on biomarker data towards the year end. Now let me detail about why going with a CD19, CD70 as a dual CAR approach. Otago CD19 CAR T has shown that depleting B cells with a CD19 CAR can provide effective way to reset the immune system. That’s the data coming initially from Georg Shet in Germany as well as have been confirmed by others other companies.

Another thing that we know from the CD70, which is extrapolation that we have made from the studies that we are doing with ALLO three sixteen, which is a CD70 only CAR T program, is that having a CD70 allows allogeneic CAR T cells to expand and persist much longer. This is an intrinsic ability of CD19 CAR to deplete the patient’s whole cells that leads to the rejection of allogeneic CAR T cells. So in this diagram, I would say what the CD19 can be done can do in clinics and what the CD70 CAR can do to protect allogeneic CAR T cells, we have clinical evidence coming from our CD19 program and our CD70 programs. What is also tantalizing about being able to deplete CD70 positive cells is the role of CD70 in immune response. CD70 positive autoreactive T cells have been attributed as an underlying pathophysiological mechanism leading to autoimmune disorders.

Also CD70 positive dendritic cells or antigen presenting cells that have been reported to be upregulated in patients with autoimmune disorders. So we believe being able to deplete the CD70 positive immune cells would lead to a much better reset of the immune system, potentially leading to much longer duration of the remission that one can achieve with a chimeric antigen receptor that is directed only against CD19. We recently presented the IND enabling data of ALLO329. And in this study, we made a direct comparison of what ALLO329 can do versus CD19 only CAR. What can be shown in the left upper panel is that both products can deplete the B cells effectively.

And also when you look at the cell expansion, both products seem to have expanded a little bit better. If anything, ALLO329 expands much better in one of the experiments. What is also tantalizing is when you look at the auto antibodies, ALLO329 is a lot more effective in reducing the titer of autoimmune antibodies in this experimental model. And lastly, when you look at the persistence of CAR T cells, not only in the circulating blood, but in tissue, ALLO-three 29 persists much longer in tissue, namely in the spleen, which is shown on the right lower panel. The potential of autoimmune indications that can be addressed with CAR T programs is listed here.

It ranges from rheumatologic indications to neurology, nephrology, hematology and potentially, GI indications. Initial study that we will be in the initial study, we will be focusing on patients with lupus, systemic sclerosis as well as inflammatory myositis. And this will be proceeding as a basket study. And from the beginning, we will be studying both reduced lymphodepletion, which utilizes cyclophosphamide alone with atofludarabine. And in parallel, we will be investigating without lymphodepletion whether ALLO-three twenty nine can lead to the B cell depletion and reset of the immune system.

Lastly, let me talk a little bit about ALLO three sixteen. This is a renal cell cancer program that we recently updated the clinical data. CD70 is an antigen that is upregulated immune cells as I’ve just talked about. But it is also significantly upregulated in the majority of the patients with a clear cell renal cell carcinoma. What we have been shown in the three sixteen study is ALLO-three sixteen, which is directed against CD70 antigen, is highly effective in demonstrated meaningful antitumor activity in CD70 positive renal cell carcinoma.

So going a little bit more in the details, in the Phase one study, we tested different lymphodepletion as well as different cell dose. To come to a conclusion that the ideal cell dose and lymphodepletion is cell dose of 80,000,000 and lymphodepletion then consists of standard flu side lymphodepletion, which is highlighted in the orange box on the left side. What we have seen in this in a subset of patient is that the response rate in the high tuba positive score, so these are the patients who express high levels of CD70, can be as high as fifty percent and confirmed response rate being as high as thirty three percent. This is based on relatively small number of patients. And what we are doing is continuing to enroll additional patients into this Phase 1b cohort.

And we expect to update the data based on approximately 20 patients by mid-twenty twenty five. Lastly, let me conclude by sort of highlighting where we stand as a company. The last reported cash position at Allergan is $4.00 $3,000,000 which will give us a cash runway into the second half of twenty twenty six. We have three active programs in hematologic malignancies, solid tumor and soon to be in autoimmune indications. Key readout data readout is listed here, SemaCell lymphodepletion selection mid-twenty twenty five ALLO329 clinical profile concept based on the biomarker data towards the year end 2025 and also ALLO316 Phase one update in renal cell carcinoma mid-twenty twenty five.

Each of the indication that we are pursuing, frontline consolidation, autoimmune indications and renal cell carcinoma comes with total market opportunities that is highly attractive. So with that, let me conclude my presentation and thank you for your attention.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Great. Thank you very much for that presentation, David. We’re going to kick off Q and A, but I’m also or we are also joined here by Zach Roberts, Executive Vice President, Head of R and D and Chief Medical Officer at Allogene. So we had a panel this morning where Simicel showed quite favorably. It was picked as a favorite among the allogeneic therapies in development.

Not surprised just like both you were pioneering at KITE. You guys are pioneering a new approach here in frontline lymphoma. So I want to ask a couple of follow ups on that JCO publication that you reviewed. Obviously, this doc had a pretty significant reaction as people cut on to that. So, you know, six out of six responses in patients with low disease burden is obviously great, right?

One hundred percent. But as you think about the low volume of disease burden in those patients and compare that to what you’re enrolling in ALPHA three in the frontline post R CHOP. Can you elaborate on what the difference in disease burden is or if it’s very similar to what you’re enrolling and how that may translate to probability of success?

Zach Roberts, Executive Vice President, Head of R and D and Chief Medical Officer, Allogene: Thanks, Tyler, and thanks for the invitation to participate in the Q and A here. So great question. And, you know, ALPHA-three is different from the ALPHA and ALPHA-two programs that were presented in the JCO paper. In that all patients are going to be coming into the trial with very, very low disease burden. So by design, this study will have really the lowest disease burden that’s ever been studied in a prospective clinical trial ever.

So we’re already sort of putting ourselves in a great position because these patients really have very few cancer cells left in their body relatively speaking. So what was so exciting to us about that subgroup analysis that David presented was that even in patients who still have visible disease radiographically, but have a low disease burden, that’s where we saw the greatest concentration of efficacy. So by extrapolation, when you’re treating patients with even less disease that’s only molecularly detectable by this MRD test, we strongly believe that the efficacy may even improve further over what we’re able to show in the relapsed refractory setting.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: That’s great. And, can you talk more about how enrollment is progressing in the ALPHA three trial? How many sites are active? And what’s been the reception by KOLs and physicians in the academic and community settings?

Zach Roberts, Executive Vice President, Head of R and D and Chief Medical Officer, Allogene: Yes. So I think it’s consistent with the poll that you cited just a moment ago. We have really been warmly welcomed by the investigator community, the KOLs, who, strongly believe that this this is a study that is really going to change practice. It’s a paradigm shifting idea, of bringing CAR T cells to patients at the time when they are most likely to derive benefit from CAR T. So that spirit and support has really been quite strongly reflected as we’ve rolled the study out.

We are on our way, somewhere between thirty and forty sites activated so far. We’re gonna activate approximately 50, in The United States. Initially, we had primarily community centers that were activating, because they tend to have a little bit less red tape than the academic centers. As time has gone on, we’ve seen more academic centers activate. So it’s roughly fiftyfifty at this point community versus academic.

And we’re seeing tremendous enthusiasm for the study. So patients are actively being screened and enrolled. And as we’ve repeated, and David just did, our guidance towards our first major milestone in the program in middle of this year as we announce the selection of the lymphodepletion regimen, at which point we will go from a three way randomization down to a two way randomization in complete enrollment.

David Chang, Co-Founder, President and CEO, Allogene: Let me just add another element of alpha three study is, you know, one of the limitations of the current use of approval TALUS CAR T is, you know, the treatment is right now more or less centered in the academic centers or so called cell therapy centers. Whereas the majority of the large B cell lymphoma, especially the frontline treatment is done in the community based cancer centers. So what we are doing with the study and this is really I believe essential to continue to expand the use of the chimeric antigen receptor therapy is placing the trial where the patients are cared for in the community based cancer centers, not only in the tertiary center. So essentially the outcome if this study is successful I believe would allow the use of allogeneic CAR T, semacil, in the community based cancer centers, which I believe will significantly increase the adoption as well as utilization of the semacel in the frontline consolidation setting.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: As you know, Kite Gilead has been focusing on trying to expand into the community centers, but it’s been slow and it’s early innings. So the uptake that you guys have seen is quite encouraging. As we think about the upcoming lymphodepletion decision this half, obviously, a less intensive lymphodepletion regimen would be great. And the safety that you guys have observed with Cemacel has been encouraging and should get better in patients with lower disease burden. But what will you share with us when you make that decision?

What can we look forward to?

Zach Roberts, Executive Vice President, Head of R and D and Chief Medical Officer, Allogene: So, as we’ve pointed out, this is a seamless design. So from the very beginning of enrollment, all of those patients are counting towards our overall sample size for the clinical trial. So when we do this interim analysis to select the lymphodepletion, at which point we’re gonna be looking at efficacy using a biomarker, and that’s looking specifically at MRD conversion. So everybody who comes into the study is MRD positive to start with. And if they become MRD negative, we know that’s a very strong prognostic indicator of durable disease control.

We’ll also, of course, be looking at efficacy. However, that is going to be an internal analysis because these patients will count towards that overall sample. So we will announce that we have selected a lymphodepletion regimen. We will also be performing a futility analysis at the same time. So if we make that announcement that we’ve seen evidence of activity, we’ve selected a lymphodepletion regimen and the study is on track to complete its goals, that will be the extent of the detail that we share because anything further would jeopardize the trial integrity by giving detailed response rates, for example.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: And I guess just to follow-up, clearly based upon those metrics, including MRD conversion from positive to negative, you’re just looking for if you were to make that decision to go to the less intensive regimen of just Fc instead of FcA, you would look for them to essentially be similar results? Correct. Okay. All right. Okay.

And what are your expectations for what the control arm of observation in this study should do, as we think about the final readout?

Zach Roberts, Executive Vice President, Head of R and D and Chief Medical Officer, Allogene: So our assumption is basically what the Kaplan Meier curve that David showed a moment ago. And the patients who are MRD positive, arguably given what we know about this test and about outcomes in large B cell lymphoma, retaining residual disease at the end of frontline treatment is arguably one of the strongest negative prognostic features that you can have about your disease. And that red curve on the Kilometers curve, which showed a median time to progression of less than six months for patients who retain MRD at the end of frontline. So that is what we’ve used to model the ALPHA-three study. And so we expect these patients to be progressing fairly quickly and that’s really what’s driving the relatively rapid series of milestones in this trial interim analysis first half of next year and then primary analysis by the end of next year.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Great. Let’s move to autoimmune. So you discussed the dual CD19, CD70 mechanism of action very well during the presentation. With the initial Phase I data potentially by the end of this year, what do you think you need to show or what do you hope to show to achieve clinical proof of concept?

David Chang, Co-Founder, President and CEO, Allogene: Obviously, one thing with the chimeric antigen receptor approach, I mean, especially with the CD19 CAR is the depletion of B cells. And in some autoimmune indications that are known to be associated with autoantibodies, Autodesk CAR T has also shown that along with the depletion of B cells, the antibody titer can go down. I think those are very good indicators. And also as an allogeneic program where we are testing with a different lymphodepletion, we would also like to see the cell expansion. Here, I think this is a very unique situation.

We don’t believe the persistence is required in the autoimmune indication. The CAR T cells needs to go away relatively quickly for the immune reconstitution to occur after depleting B cells and CD 70 positive T cells. So, you know, we just want to see a nice peak of CAR T expansion and following contraction and disappearance. And along with that, recovery of the patient’s endogenous B cells and T cells. But probably the most important thing early on is the expansion, depletion of B cells and possibly reduction of auto antibody titers.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Do you think you’ll have enough data then to decide whether to reduce or potentially remove lymphodepletion?

David Chang, Co-Founder, President and CEO, Allogene: Well, let’s go step by step. We have a very set objectives in this Phase one study and we will be reviewing the data very carefully. The way we view it is, you know, with a cyclophosphamide alone for depletion, that already gives you a lot of opportunity within patients with autoimmune disorders. If you can do this without any depletion, that opportunity expands greatly to patients with a moderate, severity autoimmune disorders, which is essentially all the treated all the patients who gets treated for the autoimmune disorders. So, you know, this is a product that can bring a great opportunity for patients.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Great. And obviously, you’ve incorporated the DAGR technology there, which I continue to be semi infatuated with. I think it’s a super cool technology. I don’t think folks appreciate it and this early data will be exciting to see. But with ALLO three sixteen, again encouraging late stage data in relapsedrefractory renal cell, we’re going to get data later this year.

What are your thoughts on moving that forward in development? How do you prioritize that versus the two programs we just discussed?

David Chang, Co-Founder, President and CEO, Allogene: Yes. First of all, I think we have to recognize that the evidence that the chimeric antigen receptor approach can work in cell tumor is growing. Most of them are coming from, you know, ATLAS CAR T, you know, targeting CLAU1918.2 or GPC3, you know, for hepatocyte carcinoma. What is remarkable about, you know, the Phase one data of three sixteen is as an allogeneic CAR T, this matches up with what the hotel’s CAR T has shown in with different targets in different cell tumors. So this is very exciting.

And as you sort of have asked, this is I think what the DAGR technology is allowing us to do. The second question about, you know, what are you going to do? What is the development plan? Obviously, this is something that we are thinking very carefully about. Renal cell cancer brings a lot of opportunity.

CD70 is also antigen that’s known to be upregulated number of other cancers. So there are different ways to think about it. But first of all, we want to get to the proof of concept that gives us the confidence that you know we will move forward there’s an opportunity go forward. The response rate that we have reported, I think gets us there. What we are waiting for is the durability that is associated with those responses.

That’s why we’re treating more patients and following that longer to look at that important element. Great.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Makes sense. So I believe it’s lunchtime, but to wrap up the conversation, I’d like to ask you what you believe is the most underappreciated aspect of the allogene story by investors right now?

David Chang, Co-Founder, President and CEO, Allogene: Well, that’s a loaded question and I can give you many different reasons. But what I would say is I think we are ever so close to realizing the potential of allogeneic CAR T therapy. And this is happening not only in hematologic indications, but also in solid tumor. And now, yes, we’re moving forward in autoimmune indication. So when we look at 2025, I think this is really the year that we can highlight all the benefits that the allogeneic CAR T therapy can bring across many different indications.

Tyler Van Buren, Senior Biotech Analyst, TD Cowen: Wonderful. David, Zack, thank you very much for your time.

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