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

Well, good morning, everyone, and welcome to another great session here at the 2021 Jefferies Global Healthcare Conference. I'm really excited to have my first fireside chat with Allogene Therapeutics. With us here, we have the Co-Founder, President and CEO, David Chang. Now importantly, he just came off a really important data, preempting that ASCO conference what was important data. So maybe we could just take a step back, David, and maybe just talk about the development of 501A as an allogeneic CD19 CAR T and what was so impressive about this data in your mind that should get people excited that you just presented.

First of all, Mike, thank you very much for hosting Allogene. It's been a little while since you and I were in the firechat, so it's a real pleasure to be together again. So given the time consideration, I'm going to be very quick on some of the responses about the CD19 data that we have presented. So we presented 2 sets of data: one coming from study node as ALPHA, which involves ALLO-501; and the second one coming from ALPHA2, which is ALLO-501A. So these are 2 constructs. The first one is a proof-of-concept construct. The second one is the one that we intend to take it into the pivotal study. So going to the data, 501, we presented the initial data at ASCO in 2020. So what we presented a few days ago was really a long-term follow-up as well as involving more patients than what we initially presented in 2020. So altogether, it included 42 patients, of whom 41 received the cell infusion within 5 days of enrollment. So that is a relatively sort of demonstrating the allogeneic off-the-shelf therapy, really delivers the speed to treatment and also being able to treat everybody who is enrolled, which distinguishes it from the autologous, where up to 30% of the patients can miss the treatment while they are waiting for the manufacturing to complete. What we have shown, first of all, going back to 2020, we have shown the initial objective response rate as well as complete remission rate look very much like what we -- people are used to seeing in the autologous cell therapy. In 2020, we could not really answer the question around the durability because the follow-up was short. So now that we have treated more patients, I think what we have seen were, one, it is safe. The initial absence of graft-versus-host disease lived out in much larger patient numbers. And overall, the newer toxicity as well as cytokine release syndrome were on par, actually numerically at a lower rate than what has been reported in the autologous CAR T pivotal studies. So we are pretty happy about the safety aspect. Our programs sometimes gets cited for potential safety concerns around the infection, and we have monitored the viral reactivation on a weekly basis. So we follow these patients very closely. So certainly, there was some viral reactivation, but overall, Grade 3 infection, which are the infections that raises concern and can potentially alter the treatment course. The incidents remained at -- on par with what had been seen with autologous CAR T therapy. So we're pretty happy about that aspect. Now the efficacy, the most pleasing part of our data that when we look at the 6-month CR rate as the benchmark within the DLBCL population, that was 36%. So how does it compare to what autologous cell therapy is shown, that ranges between 28% to 40%. So numerically, we are right in the smack probably on the upper end of the boundary. So in many ways, I think the data, we're very pleased with the data, and I think it exceeded a lot of people's expectation leading up to our release of the data.

Okay. And so you had, for specifics, different ways to interpret it, but essentially at 36% 6-month CR rate, right? That's the number, right, and that is in line with the bookends of other autologous forms. Is there any reason to believe that, that durability would be different? Like what are the things you think about scientifically as to why that would or not? Because persistency, right, might be one. But how do you think about what should investors think about to weigh that?

I mean, I think the initial depth of response and the persistence, I mean, that really factors -- that leads up to the 6-month CR rate. So I think by the time that you get to the 6-month CR, I think that is really telling what would happen afterwards. And frankly, we also looked at had there been -- were there any progression after 6 months, and we have very few people who are progressing after 6 months. So this is really living up to very similar to what had been seen in the autologous CAR T therapy setting in terms of the follow-up force and attrition of the patients because of progression as time lapses. So in many ways, our follow-up allowed us to talk about 6-month CR as a benchmark, but I think this data is really -- it's a very strong and a very compelling set of data.

Now there's 2 other, I think, components to this rather than just focusing on 36% CR rate and whether that holds, how does that move over time. You presented something, I think, that was important. I think this goes back to the idea of allogeneic, which is, a, I think you hit on it, which is the ability to treat nearly all patients. So perhaps remain intent to treat, is that rate different? Maybe make a comment about that. So on intent to treat, which is how a doctor might think about it, is that rate different if you were to look at that? And number two, retreatment and consolidation, make a comment about that. Because would that also change the rate over time to...

Correct. So in terms of the patients who are enrolled being able to receive the cells in a timely manner, and out of 42 patients in ALPHA study, we only missed 1 patient. This is a patient who had a rapidly progressing disease, which sometimes allow these patients who come on to our site head, and the person had unrelated progression that complicated the patient status to receive the cells. So I think here, the standard of -- at which how the measure -- drug benefit is measured is with the intent to treat. In the cell therapy space for the last 3 years, much of the attention has been given to the modified intent to treat. So this is not everybody who's enrolled. Essentially, you're looking at the benefits in only those patients who receive the cells, which are a lot different. So it leaves out people who may had rapidly progressive disease, who were unable to receive the cells. So they are not counted towards the efficacy or the safety. So...

What percent of magnitude is that? YESCARTA now in all benefit, I think it's pretty good. Talk to that.

YESCARTA is pretty good, but it's still about 10%.

10%, okay.

KYMRIAH and BREYANZI saw the other 2, the approved drugs. The numbers can be much higher, I mean, given that I think each sponsor is trying to improve this and the rates seem to be coming down. But I think it's going to stay somewhere between 20%, 25% in the real setting. So if you sort of think about 25% of the patients not receiving the cell product, not receiving the intended treatment, that means a lot in terms of patient-physician relationship promising a treatment to patient and not being able to deliver for various reasons. So that's one. And then the other one is it leads to a lot of so-called selection bias within the study.

Right.

And then if you so take very strict rule of like, okay, so let's forget about modified intent to treat, let's go straight to the intent to treat. Then everybody who did not receive the cells by definition should be considered as a nonresponder. So...

That's about a 10% delta, at least.

Yes.

But what about the self-selection criteria? And these are things, I think, physicians would talk to, is the idea that if you were going to get enrolled in an autologous study, would you, by definition, be healthier. So if you already compare baseline criteria or anything like that, do you feel that, that more people are eligible for your therapy? That's question 1, and how many more? And #2, is that just philosophically have a selection bias because people who go into autologous are perhaps, by definition, healthier? I don't know.

I mean both. I mean the selection by a CR means because in 4 to 6 weeks while you're waiting for the cells, patients who are progressing rapidly or who are not unwell, they select themselves out from receiving the cells. So that's a selection bias. We don't have that. And frankly, by treating everybody, one could argue that our study have treated more worst patients than other studies and the outcome could potentially be worse. And that was one of the concerns that, internally, the development team at Allogene has always raised. But behold, when we saw the data, I mean the data looks just as good as people -- as the dataset that had been analyzed based on the modified intent. So that's what makes our dataset very exciting.

That's right against autologous. So now let me bridge that into how that compares against other therapies and other approaches. So number one, talk about the ability to retreat. And how important is that -- like would you institute that in the pivotal study? I've told you before, I'd like you to run 2 studies, one with retreatment, one with not to give drug. So maybe talk to that because I thought that was an important development, and you did have people get to CR. So number one, talk to that. And number two is we're going to get to how this compares ultimately to other approaches because no other approaches can retreat and have high CRs, too, and jump starts up a lot.

So retreatment becomes a very important consideration So this is something that we tested in the ALPHA1 study initially. So the initial approach to retreatment was waiting for someone after receiving the cells. If the response is bad or if the person progresses after having a short response, that's when we implemented the retreatment. And so a number of patients who were retreated in the ALPHA study are not that many. We had about 4 to 5 patients. But in each of those cases, the retreatment led to a longer duration of response than the first treatment. So that's where we got very excited and sort of moved that concept to the next phase, which is what we call a consolidation. So here from the beginning, the treatment is to receive 2 infusion back to back, separated by 28 days. So the person would receive the standard lymphodepletion. And in our case, that's augmented with ALLO-647 and the first cell infusion. On day 28, unless you have progressive disease, so anybody with stable disease, partial response and complete responses, they will get the second cell infusion. However, we take advantage of our unique proprietary lymphodepletion by lymphodepleting for the second cell infusion with a ALLO-647 antibody alone without any chemotherapy and then give the same cell dose of 120 million cells. That's how the consolidation was done.

So number one is 647 standard antibody in CD73 but not a chemo-based consolidation. So the second dose is easier.

Yes.

Okay.

So before anybody in the autologous or anybody in the CAR T therapy would say, "Can you really safely give 2 back-to-back doses of cell safely?" And in our case, if anything, the second cell infusion was very well tolerated, and there were very few adverse events. And our investigators themselves were saying, "You know what, we should really do this as an outpatient rather than inpatient." So I think that sort of tells you about the safety profile about the second infusion. So one, being able to do consolidated cell infusion without any safety concerns. And the second one, the purpose of consolidation from the beginning was to push the complete response rate as much as possible by giving the second cell infusion. So what we saw was there were a number of patients who had partial responses, the best responses after the first cell infusion, and we were able to push that response to complete responses. So I think that's really telling quite a lot about the potential utility of allogeneic therapy and different levers that we can pull. Re-dosing, which is very convenient. The cell product is already there off the shelf. They can get the cell infusion, taking advantage of that plus the proprietary platform of ALLO-647-based lymphodepletion, we were able to do the consolidation back to back. So the durability of the consolidation, we are following that, and this goes to ALPHA2 study. We treated about 13 patients. Out of those, I think about 9 were evaluable. In the ALPHA2 study, yes, it's relatively early, but so far, we have not had anybody progressing. So 56% CR rate. And everybody at the last follow-up, which was the data presented, they're all in CR. And the longest CR goes to 9 months.