Precision BioSciences, Inc. (DTIL) Earnings Call Transcript & Summary

Good afternoon, and welcome again to the 40th Annual JPMorgan Healthcare Conference. I'm Eric Joseph, senior biotech analyst with the firm. Our next presenting company is Precision BioSciences, and it's my pleasure to welcome company's CEO, Michael Amoroso, to talk to us a little bit about the company. There is a Q&A session after the presentation. So feel free to click the icon and I'll work those in where appropriate. With that, Michael, thanks for sharing some of your time with us this week.

Thank you for having me, Eric. Thank you. So it's my pleasure to be with the investors and the community today. Good afternoon, everybody, at 2022 40th JPMorgan Healthcare Conference. It really is my privilege to be here on behalf of the Precisioners. As you can see on Slide 2, our forward-looking statements. You can access and review our SEC documents and filings for any additional risks to today's forward-looking statements in our presentation. Today's agenda, I will talk to you about the identity of Precision BioSciences, a gene editing company, and our platform and foundation, the ARCUS, premier gene editing platform. And then I'll take you through our ex vivo and in vivo applications of ARCUS. So our ex vivo being our allo CAR T program and our in vivo being across therapeutic areas, which we'll talk to you about. Moving quickly to the clinic, which we expect 3 INDs/CTAs over the next 3 years. First, before we talk about our path in 2022, I think I'd be remiss if we didn't talk about the pillars that have set us up the success in 2021. 2021 was a very strong year for the Precision team. It's my privilege to join them. I think the year was highlighted initially in January of last year where we closed one of the largest gene editing deals in the world with Eli Lilly. Tremendous effort by the team for up to 6 in vivo gene targets. And then, on the other book end of the year in December, we just left ASH in Atlanta. It was great to see everybody. And what we saw there was the full review and presentation by Dr. Alan List of our Phase Ib PBCAR0191 data. That was our first in-market CAR T, first-in-class CAR T. Also in 2021, very important, running 2 programs in parallel, 19B, another CD19 approach, which we call our best-in-class approach. That has the objective of displacing autologous CAR T, that reached the clinic this year. And we've just completed in December cohort 1 of our dose-escalating trial. On the in vivo front, amazing work by the team working on our first wholly owned and our first-to-market PCSK9 in vivo program. The team has partnered with Jim Wilson and iECURE to make sure that we can expedite the PCSK9 program to market even faster. So iECURE will partner with Jim, our experts, and they will do our Phase I work. So wonderful efforts by the team to get us to patients faster, get us into the clinic. Also this year, very important for Precision BioSciences. We fortified the management team. The next phase of the life cycle is a lot -- we'll talk a lot about operational excellence and executing this year. We were able to hire Alex Kelly full time, our CFO, this year. Alan List -- Dr. Alan List from the Moffitt Cancer Institution. He is our CMO and myself was able to join the team this year. So important year for our management team and our employees. And then finally, in December of this year as we continue to [Audio Gap] on the team, but not on the call with us today. loose connection here. Give me 1 moment here to get the slides back in front of you? Sorry, we had some technical difficulties. Our ARCUS platform, very important. ARCUS is a highly differentiated gene editing platform. It comes from the homing endonuclease. What that means is this is existed in nature for thousands of years. ARCUS is small. It has very on-target editing, high rates of on-target editing. It exists in its cellular form, inactive except when the enzymology is dialed up to make its cut, and then it turns completely inactive. We call that Precision. We're very safe and specific. We think this is really important, ex vivo and in vivo editing as we want to minimize off-target editing. We talk about the versatility of ARCUS and that's twofold. When we talk about versatility, ARCUS is small, about 364 amino acids. And what that means is we can deliver ARCUS to different tissues of the body, not only in an LNP, for example, viral delivery through an AAV or also through an LNP. ARCUS can also perform not just knockouts but complex editing. It was designed, frankly, for gene insertion and gene repair. We think these are major advantages that will prove therapeutically. Now moving forward into our application of ARCUS, our ex vivo portfolio, allo CAR T. Give me 1 moment. I think we're having a technical challenge again. [Technical Difficulty] Sorry about that. I think everyone should be able to see their slides again now. So just moving from ARCUS, our platform into our ex vivo application, allo CAR T. We know today since the advent of auto- CAR T in 2017, that we were able to take relapsed/refractory large cell lymphoma patients, leukemia patients and offer cure to some, about 3.5 out of 10. We know the greatest challenge is 1 out of 5 of these patients who are intended for an auto-CAR T are never receiving their product. Unfortunately, they meet their demise while it takes time to manufacture that product. Our goal at Precision is to make sure we have a therapeutic index as good, if not better, than an auto-CAR T off the shelf. Our process uses host donor cells, and we obviously use ARCUS as our single gene edit to knock in the CAR to the TRAC locus and out the TCR. Here, you see our pipeline for our allo CAR T portfolio. Our first-in-class product, PBCAR0191, in the clinic, 19B, which we also refer to as our stealth program. 19B is also in the clinic, and that is an attempt that are best-in-class, and we'll show you more about the objectives of our clinical development at Precision in a moment. We have our BCMA CAR T 269A in combination with SpringWorks GSI in multiple myeloma. And this year, we will also move through our partnership with Tiziana. We've got an exclusive partnership with the only fully human anti-CD3, and we will continue to move toward updating our IND and our CD19 programs so we can partner with foralumab and combine the foralumab if needed. This slide here shows how we're approaching development of Precision in our CAR T markets. PBCAR0191, where we just showed the data at ASH is what we call our first in class. That means this might not be applicable to all patients in the relapsed/refractory setting. But what we did is we took all comers to see where those biological signals were strongest. And we will talk about that a little bit in the presentation, I'll highlight some of the data. On the best-in-class line, you see that the attempt here means single gene edit, single dose for us. 19B is our first attempt or our stealth program. And we can also go further into this year. We'll update our IND to make sure we have the ability to combine with foralumab, any of our CD19 programs. We also have other vectors or CARs in R&D right now that we haven't disclosed yet. The goal there is we will not stop until we're able to be as good, if not better, than an auto CAR T. We want 1 single gene edit and 1 single dosing. Now we move into PBCAR0191 and highlight some of the data from the ASH presentation. 0191 was taken into the clinic with enhanced lymphodepletion. What enhanced lymphodepletion is it builds upon the lymphodepletion regimens of standard. It is an extra day of Fludarabine 30 milligrams per meter squared and a doubling of the cyclophosphamide dose with Cytoxan dose to 1,000 milligram per meter squared. The reason we decided to go with an enhanced lymphodepletion regimen was to allow the CARs to hit a high level of peak expansion and to have a duration in order to evade immune rejection and work getting the cancer at bay in these patients. There was a dose-dependent response that we saw with PBCAR0191 in enhanced lymphodepletion. This highlights why we selected the enhanced lymphodepletion arm to move forward with. You see versus standard lymphodepletion at the same dose. There was a 21-fold mean peak expansion and the area under the curve improved by 47x. Very, very important is to increase that peak sooner and make sure that the CAR Ts are sticking around past day 28, so that we can evade immune rejection and fight this patient's cancer. The result, in this trial, we took all comers. The median lines of therapy in lymphoma patients were 6. What you see here is in ORR 73% that was in line with what auto-CAR T does in the third line plus. You also see a best response of 59% also in line with auto-CAR T. We did allow CAR T experienced -- auto-CAR T experienced patients who had relapsed in the trial. And what you can clearly see here is these patients did as well as the CAR T naive patients. Overall, the heterogeneous population did not have the durability we would want for a best-in-class to displace auto-CAR T. But we were very encouraged by the post-autologous treatment with PBCAR0191 in eLD. We believe we might have found the right patient population, the right CAR and the right tailored lymphodepletion regimen, and I'll tell you more about that. What you see here on the swimmers plot is 6 subjects who were post auto-CAR T. The top line represents the duration of response with their auto CD19 CAR T before enrolling on PBCAR0191 trial. We call this a remission inversion, very uncommon in the cancer space. You'll notice the first 3 subjects had a longer response on PBCAR0191 with enhanced lymphodepletion than they did on their prior auto CAR T. This is 3 out of 5 evaluable patients. Subject F obviously has not reached the period yet to be able to be evaluated as their auto CAR T response was up to 2 years. So you see this data is very encouraging to us. We're excited about this data. This is a patient population that's growing and has dire need if and when they fail an auto CAR T. The questions are coming in, why, why would it work better in this population? Why is that possible? And I think consistent and potentially better. What you see here in the pink line is somebody who had been treated with CAR T and auto-CAR T and relapsed on the left-hand graph. And on the blue line, you see someone who was CAR T Naive. You will see clearly that PBCAR expansion peaks sooner, starts at day 3 and higher than in the CAR T Naive treated patients. The graph on your right hand might help explain the Y behind that. The Y axis plots CARs -- I'm sorry plots your CD3 -- host CD3 T cells that would be used to reject the allo CAR T. And you'll see that the nadir is much deeper on the CAR T relapsed patients. These patients are myelosuppressed and therefore, their immune system is not coming and rejecting. It's allowing PBCAR0191 to do its job and stay around longer. So we are excited about this data, and we think this might be a nice biologic tailoring of a patient type in PBCAR0191. Our steps going forward, the post auto-CAR T population is a growing population. In fact, on the back of ZUMA-7, which now shows that auto-CAR T will displace auto transplant as second line standard of care. This population will be a larger population in the years to come than today's auto-CAR T population. There is no FDA therapeutics approved for patients who have relapsed post-CD19 auto-CAR T. PBCAR0191 with eLD is a regimen we will continue to take forward here in H1. And we will look to replicate what we've seen from the ASH data. We will look to give you updates at the midpoint of this year. Moving forward now for our best-in-class approach, our second program in the clinic, our stealth cell or CD19B. Reminder, when we say best-in-class, the bar is very high for our clinicians and our development folks here at Precision. We're looking for a single gene edited CAR. We believe that's important for safety. A single dose and a therapeutic index that's as good, if not better, than auto-CAR T. The stealth cell, as a reminder, is an addition to PBCAR0191, which knocks in the CAR and out the TCR, the TRAC locus, but elements 2 and 3 are unique and additional for CD19B or stealth cell. With 1 single gene edit, our scientists have been able to knock down B2M with an shRNA, not completely out. We think that's very important, knock down the B2M, which will help to evade T-cell rejection. And at the same time, we knock in one of the main elements of ARCUS, we insert and knock in the HLA-E transgene to help evade NK cell rejection. Thus far this year, the study has initiated. The first dose level was 2.7 x 10 to the 8 million cells. The first 3 patients have been treated. We're currently enrolling at multiple sites, and we expect to give you a clinical update at the midpoint of the year as well as this is a population where 6 months durability will be very important, and we could expect to probably see that later durability period towards the end of the year, end of '22. Next, I'm going to transition to the ARCUS application in our in vivo programs. Here, you see our in vivo pipeline. The first 3 programs, PCSK9, PH1 and HBV are fully and wholly owned. The programs 4 through 6 you see starting with DMD are through our partnership with Eli Lilly. Right now, PCSK9, I'm going to give you a little update on the first 2 programs, PCSK9 with familial hypercholesterolemia and PH1. FH is a common genetic disease. Unfortunately, patients are not able to clear LDL out of their blood and the homozygous form is the most serious which can lead to mortality by the age of 30. While this data is preclinical, you'll realize why we're so excited about PCSK9 and why this is our first wholly owned program moving into the clinic. Our goal here is to use a single treatment, provide a knockout of the PCSK9 gene, which will enable and allow LDL serum levels to be decreased. What I will show you is what I'm aware of the longest data, 3-year nonhuman primate data, where with a single dose of AAV delivering ARCUS, we were able to knock out PCSK9 down to 60% to 82% reductions. As a result, the direct correlation, serum LDL levels were reduced by up to 62%. This is 1 single treatment. And we've been able to see up to 3 years that this knockout, this gene correction has held its index here when it comes to reducing LDL in the serum. For our program 2, PH1. PH1 is a rare genetic disease. 40% of patients are diagnosed at end-stage renal that affects adults and children and it combines liver/kidney transplants often required. PH1 is 1 out of 3 in every million patients. And unfortunately, these patients have a challenge with an accumulation of calcium oxalate, leading to painful kidney stones that ultimately leads to end-stage renal disease. Our attempt here with ARCUS is to upstream from where the mutation occurs and knock out the HA01 gene. What I will show you again through our nonhuman primate data is up to 98% reduction with a single gene edit, knocking out HA01. Conversely, it's not as easy to measure calcium oxalate. So you'll see we measure the Serum Glycolate levels here. And what you'll see is one single gene edit, 1 dose was able to have a Serum Glycolate increase that tells us that calcium oxalate is not accumulating. And you'll see the yellow line here is repeat dosing. That's what the siRNAs out in the market would potentially do the levels of reduction for serum in the 60th percentile. You'll see with ARCUS in a single corrective gene edit, we're able to increase the Serum Glycolate levels higher than that. So this is exciting and encouraging data for us. Last, I'll talk about our partnership with Eli Lilly, up to 6 programs. First of those programs has been identified in DMD, Duchenne muscular dystrophy. The next 2 programs have not been identified, but we have identified what tissues we'd be targeting, the liver and CNS. We, at Precision BioSciences, will do all the work on the pre-IND state, up to delivering the IND and Lilly from there will lead the clinical development. This is 1 of the largest partnerships in the history of gene editing, and we're very proud of this partnership and our working relationship with Lilly has been exceptional. Finally, what do we expect from us in 2022? On the application of ARCUS in our ex vivo programs. Our first in market or first-to-market -- first-in-class PBCAR0191 will continue in the post autologous CD19 CAR T failure patients. We expect to provide you an update by H1 of this year. 19B continues in the clinic at multiple sites. This is our first shot on goal for best-in-class. Again, I'll remind you to displace auto-CAR T is the goal. We expect to give you an update on 19B, our stealth cell at the midpoint of this year and also at the end of the year. Our BCMA program, 269A, is in combination with nirogacestat, the GSI from SpringWorks. We also expect to be able to give the market an update by the midpoint of this year. That is in the clinic as we speak. And then finally, we will update our INDs for the CD19 programs to make sure we have all the toxicology work needed to be able to deliver and dose if we decide in combination with foralumab in 2023. So we look to update the IND for our CD19 programs in '22. Finally, on our in vivo programs. Very important pioneer year for Precision BioSciences. Our first IND/CTA will be delivered on PCSK9 with the partnership with Jim Wilson and iECURE in 2022. From there, we will move fast to market. '23 and '24, respectively, we will deliver INDs for PH1 and HBV. That will be our first 3 wholly owned organic programs. Also this year, we plan with our partner, Eli Lilly, to pick a final clinical candidate selection for DMD, and we will give you updates on timing once we do so. I thank you for your time today. I'm going to ask and invite Alex Kelly, our CFO; Derek Jantz, our CFO; and Alan List, our CMO, to join us. Thank you.

Great. Well, thanks. Hopefully, I'm still on. Thanks for that presentation over to you, Michael. By way of questions, maybe we can just start out with PBCAR0191 and the opportunity that you're laying out here in the post auto-CAR T setting. You kind of laid out some of the market opportunity seen here. I think it might be kind of helpful to get a little more context in terms of the kind of -- type of -- in that forecast, the type of penetration, I guess, the auto-CAR T has in DLBCL. And the extent that you anticipate competitors in this space as well given that the sort of the similar ability to leverage immune -- the more immunosuppressive environment that patients experience in the post auto-CAR T setting?

Yes. I'll take the first part of that, and I'm going to ask Alan to speak about the immunosuppression in these patients and the need in these patients and why we think 0191 might be a really nice tailored match for these patients. About the size of the market and the competitive landscape. Unfortunately, there's not -- it's not competitive enough. Patients with late-line large cell lymphoma don't have enough options. Today, auto-CAR T was approved in 17 in third-line plus, third-line plus large B-cell lymphoma. We only cure a 3.5 out of every 10 patients. That means 6.5 out of every 10 have -- need another option. We have a landscape where there's some -- advent of some monoclonal antibodies, some of the ADCs and that's great, having options for patients is terrific. None of that I'm aware that are potentially curative. So there is really a high unmet need here. When you look at the third line setting, I'll comment, Eric, on your question about the size of the market. When you look at the third line auto-CAR T, large cell lymphoma market today, in the United States as a proxy, that's about 8,500 patients, okay? When you think about the fact that [indiscernible] just showed data where we'll be moving to second line and displacing auto transplant. That population is more like 16,000, 17,000 doubling of patients. So we don't know what the cure rate will be yet in second line, but you can imagine the number of patients who may relapse off of an auto-CAR T is growing exponentially, and there'll be a tremendous need for a therapy to potentially offer cures or long-term outcomes in this population. Alan, could you talk about the biologic -- biology of these patients. Why they might be a great fit.

Sure. Thanks, Michael. I think there was an interesting signal when we first looked at these 6 patients, 3 of the 5 that Michael just showed you that are evaluable for response compared to the response duration of the auto-CAR, it had a longer response to 019. And those remission inversions are rare in Oncology, and that was our signal. Certainly, when you look at the data on who are the patients that relapse from autologous CD19-directed CARs. Those are the ones that had poor product T cell function. In other words, their fitness was poor, which is no surprise. These patients have had a lot of chemotherapy. Those effects persist. It reduces the number of naive cells, I can expand. It causes metabolic problems from DNA, injury to the mitochondria. So they fail because they had poor immune integrity and a poor product. And as you saw from Michael's slide presentation, these patients indeed have deeper CD3 nadirs, longer and delayed recovery. And with that, in parallel then, is a greater peak and a greater AUC. In other words, earlier expansion, later -- later decline. In fact, it was 3.2-fold higher in patients who had received a prior autologous-CAR T product and failed compared to CAR T Naive. So we think it fits perfectly and gives us a biologic rationale for an allogeneic CAR to be moving into the space.

Thank you, Alan. Eric, you're on mute. We can't hear you.

Thank you. Sorry about that. So you're seeing a promising signal you want to expand this patient population looking towards an update or providing an update later in the first half of this year. How many patients do you think would give you confidence in confirming the signal and pursuing the post auto-CAR T setting as part of perhaps ultimately a pivotal development strategy. And then as looking toward that, I guess, can you just comment on how enrollment has been progressing and any headwinds as a result of the resurgent COVID pandemic?

Alan, would you take those questions, please?

Sure. Yes. I think, obviously, we want to have a sufficient and to be confident in the data that we see. So we think another 6 to 12 patients to add those, natural experience that we've already had, will be sufficient for us to confirm the signal and feel confident that we want to have a dialogue with the FDA about the strategy. This is an unmet need, Eric. I don't think this would require a randomized trial. And I think it's going to be very similar to what you saw with your initial approvals of the autologous-CAR T cells back in 2017. And that is just Phase II data. We're already looking to expand the number of centers that are involved with this. But we think we're easily going to have the next 6 to 7 and perhaps more enrolled by the end of the first quarter. That will allow us to get an idea of response rates and by -- certainly by midyear, we'll have an idea about the durability.

Okay. That makes a lot of sense. Okay. And with PBCAR19B, you talked a little bit about the incremental edits and modifications to allow for immune evasion or allo evasion with that candidate. I'm just curious to know, as you sort of look at the -- to the extent measurable, are you able to look at the consistency with which the edits kind of take place, right, looking almost on an individual cell level, the consistency in beta-2M down regulation and HLA-E overexpression?

Derek, would you take that, please?

Yes, absolutely. And importantly, it's edit, singular. It's only 1 edit. Don't make me get on my soapbox, Eric. Yes, we do everything we can with a single edit. And 1 of the advantages of doing that other than avoiding chromosome translocations is all of the parts of the stealth cell are at a single vector and that entire vector gets integrated permanently into the genome at the same spot in every cell. So what we see is pretty extreme uniformity in terms of cell-to-cell expression of the CAR, cell-to-cell knockdown of beta-2 microglobulin and cell-to-cell expression of the HLA-E transgene because it's -- in fact, every cell or just about every cell in our CAR T formulation is genetically identical to every other cell. So they all behave more or less the same way. One of the big advantages of this approach, and we really put a lot of energy into figuring out how to do all of this with a single gene edit.

Thank you, Derek.

Okay. So I guess as -- well, just curious -- well, I suppose I kind of know answer to the question, right, which is what clinical markers you'd be looking to as evidence of allo evasion, right? And I guess that would in part be evidenced in the kinetics [indiscernible] cell expansion in that durability. Is that kind of a fair going assumption. As we think about updates on the program in normal in the middle of the year, can you just kind of speak to patient numbers and follow-up, I guess, that we could be looking toward?

Eric, just to clarify for the team, and I'll ask Derek or Alan in a moment. You're talking 19B now, stealth cell, correct?

Correct. 19B. Yes.

Yes, Alan so could you talk a little bit about what -- how many patients could be up to -- at the midpoint of the year, maybe some of the early data we would have and what we would wait for probably to later in the year?

Sure. There were some things built in to the protocol by the FDA requiring at least in the first dose, a 28-day safety monitoring. We did that for the first 3 patients, and we've now completed that. So moving up to other dose levels. We have a delay of only 14 days with the first patient at an end dose level. We can quickly accrue thereafter. So my expectation is we may have 6 to 10 additional patients by midyear, at least enrolled. What really matters here is not just kinetics and response, it's the durability if we're going to compete with auto-CAR. We think we could actually complete accrual by the end of the year. And I think by ASH, I think we'll at least our first glimpse at durability to have some confidence in it.

Okay. Great. Great. Maybe just pivoting a little bit to the in vivo editing portfolio. I know you're furthest along with PCSK9, we now have multiple products and approaches approved currently. What would be differentiated with this approach is the potential to have durable down regulation of the target and an LDL with a single treatment. I'm curious to get a sense of how you think -- well, really, the overall -- the required tolerability profile, I think, in order to be -- to get meaningful traction with this approach. And is there a sort of higher unmet need low-hanging fruit population that you think this might be kind of better suited to when looking within the heterozygous FH population.

Derek, why don't you maybe -- I think Eric is exactly what it is. I think it's easy to think that this problem solved for all, but this is a heterogeneous group with FH. Derek, why don't you talk about the path we're starting in and there's some tremendous unmet need in the subset of patients.

Yes, you're absolutely right, Eric. And that's -- safety here is paramount. Obviously, we -- this is going to be our first foray into in vivo editing in the clinic. So safety is first and foremost on our minds. To that end, we are really focusing on the -- the segment of the familial hypercholesterolemia patient population that, on the one hand, has the most severe disease and therefore, the most severe unmet need. But the population who can respond to PCSK9 targeted therapies. There is a subset of the most severely affected homozygous FH population that have no LDL receptor function and therefore, do not respond to PCSK9 targeted therapies at all. So we would unfortunately not expect this approach to be effective in that particular population. But for everyone else that has some level of LDL receptor function, our approach should be very effective. So we are initially focusing on the most severely affected population. And then once safety is established, have the ability obviously to expand from there.

Again, I'm muted. So I guess, maybe just -- can you just talk through kind of gating steps to the IND filing anticipated within this year? And just coming back to the point of safety being paramount from your IND enabling activity, is there any -- a little bit of a preview that you could offer in terms of the type of preconditioning regimens that might be -- that might a company delivery of this approach -- delivery of this therapy.

Derek, why don't we let you walk us through kind of some of the steps of IND?

Yes. So we've shared that we expect to file the CTA at some point this year. So you could reasonably expect that we are in the pretty late stages of the IND-enabling work at this point. So it's sort of standard gene therapy development stuff, manufacturing and regulatory and GLP tox studies. Working very much in our favor for this program is we have a pretty large group of nonhuman primates that were first treated way back in 2017 with AAV vectors encoding an ARCUS nuclease to knock out PCSK9. And we have been following those animals since 2017. So we actually do have a very nice data set of long-term nonhuman primate safety and efficacy data that we can rely on in making our regulatory filings.

Okay. But I want to get to ahead of my skis here with the ongoing -- with remaining, sorry, the balance of the in vivo platform, but I guess, for looking that PH1, the coming up I guess, any more granular guidance you might provide in terms of where that is in preclinical development and when we -- when within 2023, we could think about an IND filing and sort of clinical trials there.

Yes, sure. Derek?

Yes, sure. Sort of similar to PCSK9, we have very good proof-of-concept data already generated in the PH1 program, Michael shared some of that data. So at this point, it is, I would say, somewhat routine drug development as drug development for gene therapies goes. The big difference, though, between the PH1 program and the PCSK9 program is PCSK9, we're going to be using AAV for delivery. For PH1, we're using lipid nanoparticle for delivery. So they are -- while they are both ARCUS-based drugs being delivered to the liver, the drug itself is actually completely different. One is a lipid nanoparticle of mRNA and one is an AAV vector. So from manufacturing, from GLP tox perspective, they are very, very different drugs. So this was done intentionally because 1 of the nice things about ARCUS is because it is so small, we can use a variety of different delivery modalities to deliver to different tissues. So we wanted to pick 1 AAV program to move into the clinic quickly and one lipid nanoparticle-based program to move into the clinic quickly to see how ARCUS works with those 2 very different delivery modalities and establish proof of concept with it. So PH1 is also moving very quickly.

Okay. Okay. And just final [ port ] on both of those programs. Can you just speak to sort of the -- how you're sourcing both the AAV vector and LNP as well? And I guess what -- to the extent there is any additional sort of manufacturing work or build-out that needs to be done heading into the start of clinical development for both programs.

Derek, [indiscernible] back to you.

So in the case of the PCSK9 program, this is where it's very nice to be working with Jim Wilson because AAV manufacturing is kind of 1 of the things that he's built his career on. So the team at Penn and the team at iECURE is working with us to get the AAV vector manufactured for that program. And in fact, the iECURE Group is actually responsible for running the Phase I trial for PCSK9. In the case of the LNP for PH1 program, we've shared that we've in-licensed lipid nanoparticles from Acuitas. So they're responsible for providing the LNP, and we make the mRNA ourselves. So we have our own in-house mRNA platform that we use to produce the ARCUS encoding mRNA and then we use the Acuitas lipid nanoparticle for delivery.

Eric, the only thing I would add to that is we are making a lot of our own cell therapy products today, and we are scaling appropriately with the staggering and we just have these programs tagged in for a reason. We plan on having our manufacturing in-house and that's an important control of the supply chain that we think is necessary in these programs. So to Derek's point, we're very prescriptive of where we're starting, when we're scaling and having the appropriate people in the appropriate space [indiscernible].

Okay. Great. Great. Well, gentlemen, thanks so much for your time this afternoon. Really appreciate it. And thanks, everybody, for tuning into the session.

Thank you, Eric. Thank you, Derek.