Welcome to the next session of the Guggenheim Oncology Conference. My name is Kelsey Goodwin. I'm one of the research analysts here at Guggenheim. Next, we have Allogene. I'm here with the CFO, Erick Schmidt. Let's kick it off with some big picture questions, if you don't mind. Allo is one of the front runners in the off-the-shelf cell therapy field. Maybe just remind us, what are the key advantages offered by allogeneic cell therapies relative to other therapies and kind of what you've seen so far in the clinic? Kelsey, thank you very much for having us here. Appreciate the opportunity to present the story. Thanks to all of you in the room for coming as well. Why Allogene? Why, why, you know, why do we exist? How do we fit into the armamentarium? Obviously, these days, there are a lot of great innovative therapies coming to the market for heme malignancies. Maybe not quite as many coming to the market for solid tumors. We absolutely believe that AlloCAR T-cells, allogeneic, off-the-shelf, on-demand deliverable CAR T-cells really fit a unique niche here. One that cannot be filled by either the existing autologous products or some of the future programs such as the bispecific therapies that are being developed. In particular, we think that only an allo product can really provide the best of both worlds in that high-end spectrum of efficacy. All these products seem like they're bringing great benefit to patients. Certainly, the autologous products have that one-and-done ability to create potentially a curative effect. The bispecifics, of course, have the ability to be used off the shelf on demand in scalable fashion. Only an allo CAR T-cell can do both. Only an allo CAR T-cell, we believe, provides that one-and-done, time-limited therapy that can put patients into long-term remissions, as well as being able to be dosed within days in a scalable fashion with guaranteed delivery. That's kind of that niche best of both worlds that we're trying to fill with our programs. Great. Investor debates have largely centered around cell persistence and durability of response in this space, and Allogene utilizes a CD52 knockout plus an anti-CD52 antibody as their strategy to overcome this. I guess how is this method differentiated from competitors, and what have kind of been the clinical learnings to date? I mean, I think the method that we've used, and we've deployed this method now for five plus years and going, I mean, it was started even before Allogene was formed at Pfizer based on the knowledge that fludarabine lymphodepletion alone would not suffice, would not be sufficient to create a window of CAR T-cell expansion persistence that could enable durability. Right now, you know, five years later with 100+ patients of clinical studies, we've been really gratified to see that the platform is working, and it's worked in myeloma, it's worked in lymphoma, and increasingly it looks to be working in solid tumors as well. It seems very differentiated, honestly, from the other datasets that we've seen in the allogeneic space. By enabling a longer window of CAR T-cell persistent expansion using this anti-CD52 antibody, we've been able to get durability that approaches that of the autologous CAR T-cells in myeloma and probably matches or exceeds the durability that we've been able to see thus far in CD19 disease. We think the proof of concept is heavily supporting this platform, and we still believe we're the only ones that have been able to show that benefit with an off-the-shelf product. Right now, you know, we're all in on this approach. Great. You recently initiated two pivotal trials for your CD19 program. Maybe just remind us of the trial designs and how we should think about the timelines? We are the first company to kick off a potentially pivotal phase II program. This is in CD19 disease, specifically third line, relapsed refractory large B-cell lymphoma. We have started one study called the ALPHA2 trial, which is a single-arm study, very comparable to some of the autologous pivotal studies that have come before us. Response rate would be an overall response endpoint. It's going to enroll about 100 or so patients, and that trial kicked off late last year. That study is enrolling right now with the goal of achieving complete enrollment in the first half of next year. The other study is called the EXPAND study. This is a companion study that is designed to show the benefit, to prove the benefit of the ALLO-647 lymphodepleting antibody to the cell therapy and that's a 70-patient study. We've been operationalizing that study, and we'll kick off enrollment shortly in that trial, and we're hopeful also that we can complete enrollment in that study in the first half of next year. That study deploys a PFS endpoint, which should enable a fairly efficient trial design and a fairly rapid readout as well as we'd expect a pretty large difference in progression-free survival between the control and active arms. Great. How should we think about the regulatory efficacy bar for ALPHA2? Yeah, I mean, honestly, in ALPHA2, the regulatory bar is probably somewhat modest. You know, the CAR T-cells that have been approved with full approval based on single-arm studies have packed a very large punch, so, you know, complete response rates in that 40- 50%-ish range. The FDA has viewed that as certainly definitive proof of efficacy for those therapies that have come before us. We're hoping to be in the same range, and in many ways, the bar for us is a commercial bar. Can we be competitive with those existing therapies? We think we can. There have been more recent approvals with very much more modest response rates, I would say, in the, you know, teens to even 20% range. You know, we'll have to see how the FDA views our product. I certainly don't wanna speak for the agency, but we believe that, based on the phase I experience, we'll surmount the efficacy bar from a regulatory basis quite easily. Great. For the EXPAND study, I guess what exactly needs to be shown in that trial? Do you foresee any difficulty enrolling the control arm given, without ALLO-647, you know, the cells are unlikely to- Yeah ... to expand. Kelsey, as I mentioned, that EXPAND study is looking at a progression-free survival endpoint. We have now demonstrated, I think quite fairly conclusively from our phase I experience, that there is a dose-response relationship between use of the antibody and the likelihood of response. Specifically, when we've dosed the antibody suboptimally at lower doses, we see lesser response rates and more rapid progression. When we dose the antibody at higher doses in line with that we're using in the active arm of EXPAND, we see higher response rates and better durability of response. I think at this point in time, it's fairly clear to me at least that the antibody is critical to the use of this therapy. We would expect, in the control arm, fairly rapid progression, and in the active arm, you know, data in line with what we've shown in the phase I study. You know, we have high confidence in the outcome, leave it at that. Okay, great. Maybe building upon, you know, the strength you saw in specific lymphodepletion dose, you had several levers that you were looking at in the phase I trial cell dose, lymphodepletion consolidation, Alloy versus non-Alloy. I guess what was most informative when you were choosing your recommended phase two dose? Yeah, I mean, a good question. I'd say all of the above. We did spend a fair bit of time in phase I, given this is a brand-new moiety. Nobody's ever really developed an allogeneic CAR T-cell product before. We knew that we had several different parameters, levers if you will, that we were trying to optimize, the cell dose, the lymphodepletion regimen, the manufacturing processes that we evaluated. You know, by the way, even those processes that we deemed suboptimal, they still came with a fair bit of efficacy. It's not like, you know, there's any cherry-picking to the data here. At the end of the day, we did optimize each of those components, and we have a go-forward phase two recommended regimen that looks extremely potent, quite safe, probably safer than the autologous products, and certainly can be delivered with scalable efficient manufacturing within, you know, days of need. We think the product profile that we're ending up with is highly differentiated. Great. Maybe kind of building on an earlier question around durability and that being a key area of focus for investors. I guess maybe just remind us what have your clinical learnings been so far? Yeah ALLO-501A shown durability-wise? Yeah, good question. You know, we've shown a lot of information, so I'd certainly refer folks either in the room or online to our R&D showcase presentation from late November of last year where, you know, we produced, I'd say, you know, a very hefty dataset on our CD19 program. The main conclusion here is the durability looks very much in line with the autologous products. I think in particular, what we're seeing from a durability standpoint, matches up with the autologous products in terms of another level of detail too, which is six-month complete response rates. It's known in the autologous world that there are some patients who achieve response and fall out of complete response within, say, month two or three or four after therapy. Once those patients are able to get to a six-month complete response, those responses stay very, very persistent, very durable. Our Kaplan-Meier curves, which we've again shown as of the R&D showcase in late November, look very similar, almost overlapping with what's been shown thus far with the autologous products. We do have a number of patients that are able to achieve a complete response rate, and those patients who achieve a complete response rate at six months have a very, very low rate of falling out of response. Great. How will your commercial scale manufacturing facility, Cell Forge 1, be used for the pivotal studies and potential launch? Are you currently, or I guess will you switch from the CDMO that you're currently using to Cell Forge 1, and what's kind of the process there from a regulatory standpoint? Yeah. Also another good question. For those of you who are less familiar with Allogene, we have a very large, wholly owned facility in Newark, California, called Cell Forge 1, and we intend to use that facility for commercial production and supply. We also have been historically making product at a CDMO, and we've been launching the phase II study, the ALPHA2 study with material produced at the CDMO facility as we work to transition all the process development and other ops tech expertise from the CDMO to our Cell Forge 1 facility. I mean, the good news for us is that both of these supply sites are highly scalable, right? We don't have to make a lot of product to treat the 100 or so patients in our clinical studies or to treat maybe, you know, the several thousand patients that we could treat in the commercial world. That's because a single manufacturing run can produce product for 100 or more patients. We certainly are in the process of transitioning from the CDMO to Cell Forge 1, but in reality, we could complete that transition any point in time and have plenty of material to supply the markets. Great. Just to confirm, would any cell product from Cell Forge 1 be used in the pivotal studies, or will it just be CDMO? You know, we're evaluating all the timelines and exactly that right now. You know, there are ways to transition pre or post-approval or pre or post trial enrollment. That's one of the opportunities that we're trying to optimize as we speak. Great. Okay. Then late last year, Servier, your partner ex U.S., informed you they're no longer planning to commercialize CD19 outside of the U.S., and you might have the opt-in, or you have the opt-in position into the ex-U.S. rights. I guess how are you thinking about the ex-U.S. opportunity and what would you need to see to kind of want to opt into that? That's right. Put this in perspective a little bit. Servier had been our partner on CD19 globally, and we have been jointly developing our CD19 products with Servier. Allogene has historically been responsible for paying 60% of the global development and Servier 40% of the global development. Servier has made the decision to get out of cell therapy. This program was their only pursuit in cell therapy, and for that matter, as we've discussed, they only had the ex-US rights. They informed us of that decision back in September that they would like to exit the field. Allogene has the option to step into their shoes, Servier's shoes, and pick up the ex-U.S. rights to our CD19 product. If we do that, we would, of course, also be picking up their 40% of cost-sharing obligation. We are evaluating that decision as we speak. As you can obviously assume, there are pros and cons to opting in. On the opportunity side, we would gain the ex-U.S. rights. On the other hand of the equation, we would also be responsible for picking up the 40%. Mm-hmm. Got it. Do you have any timelines of when you might opt in or opt out, or is it something that you would maybe wait? Yeah, I think it's under evaluation for sure. It's a little bit of a complex discussion because there are questions about when we would need to opt in and some contractual questions as well. It's something that we're evaluating. Okay. Great. Shifting gears to ALLO-715, your anti-BCMA CAR T. You recently presented updated clinical data also at your showcase. Remind us the clinical learnings to date and how 715 has looked compared to the approved autologous CAR T therapies? BCMA is a very interesting program. You know, on the one hand, we are the first and only company to have proof of concept with an allogeneic off-the-shelf BCMA product. Not only did we present updated data at our showcase and at ASH last year, but you may have also seen the phase I dataset published in Nature Medicine just about 10 days ago. We're very proud of the fact that we have a safe and effective drug that has very high response rates relative to what, you know, historically has been seen in the myeloma space. On the other hand, does not have efficacy that matches up with the I guess the market leader, at least with regard to clinical efficacy, which is CARVYKTI. You know, ABECMA today is the market leader commercially, in part because they have a little bit more supply. We think our dataset does match up very well to that commercial leader in ABECMA. We have an ABECMA-like response rate and an ABECMA-like duration of efficacy in terms of duration response. Again, very, I would say, strong proof of concept for the platform and for ability to deliver a high-end myeloma therapy. On the other hand, it is obvious that it's going to be challenging for this product to match up to CARVYKTI in terms of, you know, where the field might be going should the field be able to figure out all the supply and other constraints that come with working out an autologous therapy. This is something that we're evaluating as we speak, to be honest. We are having FDA discussions and phase 1 discussions on what a potential pivotal study might look like. At the same time, we're also evaluating our next generation product, our ALLO-605, which is, you know, is a TurboCAR formulation of an anti-BCMA-directed therapy, and that TurboCAR provides constitutively active cytokine signaling. It may be that we can get to, you know, better efficacy with that molecule. Certainly pre-clinically, it looks like ALLO-605 could be as efficacious as CARVYKTI. I'd say that, you know, there are a lot of decisions that we need to make around the BCMA program. You know, meanwhile, we also have to resource our CD19 program, which has, I would say, an extraordinarily competitive product profile all in. Certainly, we also need to think about earlier line studies for CD19 and what we can resource and what we can't, given our budget constraints. Got it. I guess how should we think about the build-out of the BCMA franchise kind of in context of what you're saying? Like what is still going on with the UNIVERSAL trial, and will you wait to see 715 versus 605? What do you need to see to kind of make that go forward decision for the program in BCMA? Yeah. I think that there are process optimization, workflows that we'd like to complete in manufacturing. We've talked a little bit about that for ALLO-605 and for that matter, ALLO-715. With CD19, some process manufacturing tweaks, as we briefly touched on with the Alloy process. They had the ability to tune up the efficacy, you know, fairly materially. We'd like to make sure we've got an optimal process on both of these products and see if that creates a even more competitive product profile. We'd also like to complete our FDA discussions and see, you know, what will be required of regulators to move forward here. all the time, you know, kinda monitoring the field and seeing what opportunities are gonna persist for potentially, you know, many years there. We'll come back to you on exactly what might be the next steps for the BCMA program. You know, I'd say it's safe to say that our focus and our prioritization on CD19 is extreme right now, and we wanna make sure that we get that up, that set of pivotal studies off the ground and running at a very rapid pace. Okay, great. for ALLO-715, you opted not to move forward with the GSI combination. I guess can you provide some color on what was seen and why you maybe made that decision? Yeah. That was a decision we made, I think, early last year to not proceed with the 715 plus gamma secretase inhibitor combination. As you know, there had been some theoretical rationale to believe that combining a GSI with 715 or any BCMA product would enhance the efficacy by increasing expression of the target BCMA moiety on myeloma cells. We did a fairly rapid and quick experiment of a phase 1 trial enrolling some patients under the combination arm. We were hoping to see potentially, you know, very meaningful enhancements in efficacy. We didn't see that. We've moved on to other strategies. Okay. Makes sense. I wanna save some time for ALLO-316. You presented early clinical data on that at the showcase as well. Maybe walk us through the clinical findings that you presented and how you plan to enroll patients in this trial moving forward based on what you've seen. Yeah. ALLO-316 is an incredibly exciting construct for us. For those, again, who are a little bit less familiar, this is a allogeneic CAR T therapy that targets CD70. CD70 is a molecule that is well expressed and quite frequently expressed on renal cell carcinoma as well as other solid tumors and even some hematologic malignancies. We started our exploration in renal cell carcinoma. These are third line patients who have failed IO therapy as well as TKI therapy. Once, unfortunately patients have failed those two lines, there are very, very few options. In fact, tivozanib, the most recent approval in the third line setting, gained approval on about 18% or so objective response rate. A lot of patients and a lot of unmet medical need here. In our phase 1 study to date, it's still a trial that's ongoing, we had enrolled 17 patients as of our R&D showcase event. Of those 17 patients, 9 had been deemed to have CD70 positive expression. So those would be, you know, in theory the patients who could benefit from a CD70-directed therapy. Three of those 9 saw meaningful tumor shrinkage qualifying as responders, and then there were some stable disease patients as well. At the end of the day, we thought that was a very strong and very exciting clinical signal, albeit one that's still early. At this stage, we're now enrolling patients who exclusively present with CD70 positive disease. We have a diagnostic that can be deployed as a screen in the phase one study clinically and approved by the FDA for that use. We'll be screening only patients for enrollment who have CD70 positive disease. We'd like to try and enrich this pool, get a few more patients and identify the recommended phase two dose and then make a decision. Certainly moving forward in renal cell carcinoma would be a possibility. Certainly it makes strong scientific sense to combine this with IO therapy, provide the activated CAR T cells with the PD-1 inhibitory signal that can enable those cells to be, you know, potent within the realm of the tumor microenvironment. That's very exciting to me personally. Also consider whether we should be doing a basket study in other solid tumors that express CD70 or going into potentially hematologic malignancies like lymphoma or B-cell or T-cell lymphoma that express CD70. A lot of different options for this program. We wanna make sure it gets the resources that it needs and we're intent on doing just that. Great. I guess in the maybe kind of lead indication or what we've seen so far in RCC, how do you guys think about the efficacy benchmark there? I know it's late line. There's not really much else to give the patients. What would you need to see to advance it into pivotal studies? I mentioned tivozanib which was approved with a very low response rate. I think generally speaking when we speak to KOLs in the space, yeah, they would be pleased with a 20%-30% response rate in a study that provided, you know, a meaningful duration of response out to six or so months. That's kinda what we think the benchmark is for proceeding here. Okay, great. Separately you have an ongoing partnership with Notch Therapeutics for iPSC-derived therapies. How do you think about iPSCs versus the donor-derived cells, and when will we hear more about that collaboration? I mean, iPSCs are probably the future. They certainly sound great on paper and we're working with what we believe is the best in the business, Notch Therapeutics, to create an iPSC-generated therapy. Notch is doing something a little bit different from what other players are doing. They are differentiating iPSCs into fully functional T cells. A lot of other companies have stopped at the, you know, the NK cell stage of differentiation. We believe fully functional T cells are needed to drive the true benefit of cell therapy. We don't think that NK cells are going to be as potent or as expansive as CAR T cells. We're working with Notch now for the last couple years to scale up the differentiation process and create a process that's not only GMP compatible but also has the scale to supply large clinical studies and potentially the market. Stay tuned on that. We have not committed to, you know, an IND filing and honestly I think we're still some time away from that. I do think the progress is quite steady and that the team at Notch is still well out ahead of others in the field. Great. Are these alpha-beta T cells? Yes, they are. gamma delta? They're alpha beta. They're alpha, yeah. Okay, great. Great. Okay, with our last 30 seconds, could you maybe just remind us the cash runway and then expected catalyst lineup for the year? In terms of cash, we have not yet reported our Q4 numbers, but we ended Q3 with $636 million in cash. Our guidance for 2022 was to burn a little bit less than $250 million of cash. I think, you know, that we ought to be consistent with that guidance. In terms of the future outlook, we have not given guidance for 2023 in terms of cash burn, but our cash burn will ramp up moderately. We've made the major investments at Allogene in manufacturing. I think we can leverage those investments quite substantially and add just a little bit to our spend through greater clinical development expansion. I believe our cash balance will be quite sufficient to, you know, capitalize us for the next several years. Okay, great. With that we'll wrap up. Thank you, Eric for joining us. Thanks all for joining.