Allogene Therapeutics, Inc. (ALLO) Earnings Call Transcript & Summary

Okay. Good morning, everyone, and welcome to B. Riley's Oncology Conference. I'm Kalpit Patel, a research analyst here at B. Riley. And it's my pleasure to introduce our first fireside chat of the day, with Allogene's CFO, Eric Schmidt. If anyone in the audience has any questions for Eric, please feel free to e-mail me at kpatel@brileyfin.com. Eric, it's great to have you join us today. Welcome.

Maybe to start, let's dive right into the data that you've showed at your November R&D showcase. I want to specifically dig into the durability data that you've shown for ALLO-501, 501A. There was a nice slide in there with the swimmers plot that was outlined, which essentially showed how patients performed over a long period of time, the patients who achieved a CR. Can you give us a sense of how closely this durability resemble to the auto CAR T's data that we have seen previously with approved therapies? Would you say that they're essentially mirror images of each other? Or do you think there's still some room for improvement on the durability front?

Kalpit, Andy, thank you for the honor of being the first presentation at this conference. And thanks to B. Riley for hosting. Always great to be able to showcase the Allogene story, including some of the recent data that you just referenced. Just to take a quick step back for those who are a little bit less familiar with our company. Our lead program is ALLO-501A. That's the drug that you were asking about, and it is being directed at large B cell lymphoma. In fact, we are in a pivotal study in third-line LBCL, and we believe we're the first program to progress into a pivotal trial using an allogeneic CAR T therapy. So exciting to be pioneers in this space. And yes, I think what's enabled us or allowed us to achieve that whole position is the data we've shown. Specifically, your question was directed at a slide we showed back at our R&D showcase in November. This is a depiction of the patients who had achieved a complete response on our CD19 therapies as of the ASH meeting in December 2021. And then at the R&D showcase just a year later, approximately a year later, we updated this graph. We have had 14 patients total achieve a CR in this portion of the Phase I studies at that point, and 10 were in CR as of December 2021. And about a year later, we were able to show that 9 of those 10 remained in CR. As you can see, given the swimmer plots progressing out and to the right, we now have patients who are in durable CRs without retreatment or any other need for therapy, single administration in many cases and how many patients out to 18, 24, even 24-plus months. So we think these data are exciting. We think these data are best-in-class, and then we're going to talk about why it is that our allogeneic platform appears to provide this level of durability, where others maybe have fallen a little bit short of the mark. But to your question in particular, do we think this is comparing well with the autologous products? Obviously, it's early days, and our numbers are small, and we require still larger studies and longer-term follow-up. And clearly, that's going to be the goal of the Phase II study, which is ongoing. But as we plot our experience from Phase I, given the optimized regimen that we're taking into Phase II, you can see here in this Kaplan-Meier that on a PFS -- from a PFS standpoint, our curves look quite similar to the autologous products. We do see some patients achieve a response and fall out of response in the early months, say, months 3 through 6. But importantly, for those patients who achieved a CR at 6 months, they tend to be very, very durable. And it's that durability, again, that has sparked all the excitement and optimism for autologous CAR T. The fact that you can give a single one-and-done therapy and put a patient into long-term remission or even potentially a cure. So yes, we think we're very much tracking in line with the approved autologous CAR T therapies that are plotted here. Obviously, again, we have some work to do on execution. And it's the execution of this Phase II study, our lead program for ALLO-501A, that's our #1 priority at Allogene in 2023.

Okay. And Eric, I think to my knowledge, I'm not aware of other allogeneic cell therapy players who have shown longer-term durability like in a respectable sample size. I guess what do you think is contributing to the efficacy profile that you're showing with ALLO-501, 501A? Is it more related to the lymphodepletion regimen? Or do you think it's the power of the alpha-beta T cell that's weighing in more here?

Well, we think both are required to be honest. I mean the trick of getting an allogeneic cell therapy to work is twofold. One, of course, these cells are being sourced from foreign donors, healthy volunteers, and you need to prevent graft-versus-host disease. And I think everyone in the field has essentially figured out that if you're able to knock out or delete the T cell receptor, you have very low risk of GvHD. We've treated over 175 patients in our studies and haven't seen a single case. The other potentially more challenging hurdle that needs to be overcome is the premature rejection of the allogeneic CAR T cells before those CAR T cells can go about and exert their anticancer activity. Remember, these CAR T cells, again, are being sourced from foreign donors, and they will be viewed as foreign material and eradicated by the host immune system unless you do something gene engineering-wise or other to keep that rejection in check. And what we've done is use an antibody called ALLO-647. This is an anti-CD52 antibody. It targets host T cells and depletes host T cells, and it enables our allogeneic CAR T cells to expand and persist free from host T-cell rejection over a period of several months. And this is really the special sauce that I think makes Allogene's platform work very well. And of course, we've now got proof of concept with this strategy in 3 different indications, not just large B cell lymphoma, where we've been discussing, but also our second program in myeloma and our third program in solid tumors, namely CD70 targeting renal cell carcinoma. So long-winded answer to your question, Kalpit, but here, in particular on this slide, on the right-hand panel, we have tested varying doses of ALLO-647. And as you can see, higher medium and lower doses have different results with regard to the probability of response. If you are providing a patient just modest doses of this antibody, they are unlikely to get -- the antibody is unlikely to prevent full rejection of the allogeneic CAR T cells, and you're likely to see lesser expansion and lower probability response. We've gone up to 90 milligrams of the antibody, which is the chosen dose for our Phase II study. And at those higher concentrations, we get a very high-probability response coupled with very good expansion. So it's absolutely -- this platform technology, which is unique and proprietary to us and our partner Cellectis, that we believe is enabling ourselves to work where others have failed. In addition to the data shown here, we also have supporting evidence from clinical trials where, in some cases, folks, including Allogene, have not used any antibody, just chemotherapy and lymphodepletion alone. And again, we really don't see that expansion and that persistence and that likelihood of response.

Okay. Okay. That makes sense. And one of the most frequently asked questions or discussion points is actually surrounding this antibody and combining it with Flu/Cy and showing the benefit in a randomized study, your EXPAND study. Can you walk us through maybe the powering of the EXPAND study? What are your assumptions there? And what range of benefit in terms of PFS improvement you expect to see there in that arm with ALLO-647?

Yes, great question, Kalpit. So just again, to refresh those who I know might be a little bit less familiar with our story, we have undertaken 2 potentially pivotal Phase II studies to support the approval of ALLO-501A, that's the cell therapy, as well as the concomitant therapy ALLO-647. The ALPHA study is a more traditional cell therapy study, very similar in design to trials that were used to support the approvals of the autologous cell therapies. It's a single-arm study. It's 100 patients. And in that study, we're looking at the potential for ALLO-501A coupled with ALLO-647 to induce deep and durable responses. Your question pertains to the EXPAND study, which is shown on the lower part of this graph. EXPAND is designed to support the registration of ALLO-647. In other words, it's designed to demonstrate its benefit or the addition of ALLO-647 to our cell therapy, and it is designed as a randomized study. Half the patients will get lymphodepletion with Flu/Cy alone, and the other half will get lymphodepletion with Flu/Cy plus ALLO-647. In this case, because it's randomized, we're unable to use a primary -- sorry, a progression-free survival endpoint, PFS endpoint. That helps us keep the sample size low as PFS comes with greater statistical power than might say, an overall response rate endpoint. And as you can see, we've targeted 70 patients for this trial, so a fairly modest sample size. We haven't discussed the powering, but because we expect the control arm, that arm that does not include ALLO-647, to perform very poorly, we can get away with a small sample size and good statistical power. So this is a trial we have tremendous confidence in based on the slide I showed previously. That dose-dependent relationship between the antibody and likelihood of response provides us with just a lot of confidence that the EXPAND study will prove positive.

Okay. And let's assume for a second that you successfully cleared that EXPAND study, should we expect the regulators to ask for similar randomized studies for other indications or follow-on indications like multiple myeloma or even renal cell?

Yes, that's a good question. We would hope that demonstrating the benefit of the antibody once and for all, in addition to all of the PK/PD data we've shown and some of the anecdotal experience that we and others have in the space without the antibody, we'd hope that, at some point in time, there's going to be a preponderance of data that support this antibody and that maybe in the future, we won't have to do studies like this as we seek to register our other products. And here's a quick snapshot of our pipeline. As you know, we're looking at BCMA as our next -- sorry, BCMA-directed anti-myeloma therapy as our next potential indication as well as renal cell carcinoma in solid tumors. So we'll just have to have discussions with the regulators as we go through these various other opportunities and see at what point in time, hopefully, they'll let us get away without further demonstration of this effect in a randomized study.

Okay. And maybe switching to the ALPHA2 trial. Have you previously guided the time lines for enrollment? I'm just trying to get a sense of how enrollment could be for a pivotal trial, and it should be similar to what we have seen with axi-cel studies back in the day, also keeping in mind how competitive it might be to get patients on a trial.

Yes. I mean certainly, we're -- it's early days, and we'll have to see how quickly we can execute. Again, this enrollment in this -- in our EXPAND study is our #1 corporate priority for 2023. So we're going to do everything we can to accelerate our time lines. We have guided to completion enrollment in both studies by the first half of 2024. So it gives us ballpark 18 months to finish enrollment. In terms of the potential competitive threat from autologous therapies, the unfortunate truth is that the autologous therapies have penetrated, unfortunately, a very small minority of the available patient pool. If you look across all indications for all of the various approved autologous therapies, only about 10% of the patients who might be treatable on label are actually getting these drugs. It's a little bit higher in the third-line LBCL indication, where YESCARTA and other agents have been approved for now over 5 years. We estimate the penetration in that indication in autologous CD19 therapies is ballpark 30%. So there's still a majority of patients who are not able to get therapy. And again, we don't think that's going to be a major hindrance to enrollment.

Okay. Okay. And maybe help us understand what you see as the efficacy bar for the ALPHA2 trial. Has the FDA set maybe a lower bound for a response rate for you to secure approval?