Intellia Therapeutics, Inc. (NTLA) Earnings Call Transcript & Summary

Good afternoon, everyone, and thank you for joining us today. My name is Michael Peters, and I'm an analyst in JPMorgan's Healthcare Investment Banking Group. In this session, we're delighted to introduce Intellia Therapeutics, a leading stage genome editing company, leveraging CRISPR-based technologies. If you have any questions throughout the presentation, please submit them by clicking the blue button at the bottom of your screen, and we'll address them at the end of the prepared remarks. With that, I'm pleased to introduce you to John Leonard, CEO of Intellia.

Thank you. Good afternoon. I'm John Leonard, President and CEO of Intellia Therapeutics, and I'm pleased to be starting off the year presenting at the JPMorgan 40th Annual Healthcare Conference. As we enter 2022, it's apparent that genome editing holds the power to revolutionize medicine by treating disease in ways that were inconceivable prior to the Nobel Prize-winning discovery of CRISPR/Cas9. And today, I'm happy to say that this revolution is well underway, and Intellia continues to make meaningful progress towards bringing CRISPR-based medicines to patients across a host of life-threatening diseases. 2021 was a landmark year for Intellia as we presented the first-ever clinical data showing it's possible to precisely edit a disease-causing gene within the body through a systemically delivered CRISPR-based therapy. This was an important milestone for patients, for Intellia and for medicine. It was no coincidence, so we were first. Rigor, intentionality and innovation have been at the heart of our team's work from the start, and we're focused on expanding our technology platform with unsurpassed genome editing tools and capabilities to harness the full potential of these modalities for patients. It's my pleasure today to highlight our plans to extend our leadership position and further leverage the power of genome editing in the years to come. I'd like to take a minute to remind everyone that during this webcast, I may make certain forward-looking statements and ask that you refer to Slide 2 of this presentation and to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law. Moving to Slide 3. At Intellia, we're building a full-spectrum genome editing company by deploying the industry's broadest and deepest toolbox of genome editing capabilities in order to fully realize the promise of CRISPR-based medicines. Treating and potentially curing a broad range of severe diseases will require multiple approaches. We designed a platform to deliver differentiated modular solutions across in vivo and ex vivo therapeutic applications so we continue to break new ground for patients with life-threatening diseases. For genetic diseases, we're leveraging our proprietary lipid nanoparticle or LNP-based delivery system to selectively inactivate disease-causing genes or precisely insert genes to produce desired proteins. Our ex vivo approach leverages our differentiated cell-engineering platform to produce a homogeneous, robust cell product to fight cancer or address autoimmune diseases. Our genome editing technology platform allows us to continue to develop novel approaches for the treatment of genetic diseases, cancer and autoimmune conditions. On Slide 4, you'll see the foundation of our platform, namely our extensive genome editing toolbox. With proprietary CRISPR/Cas9-based technology at the core of our platform, we're also adding new capabilities to expand our current solutions for addressing a multitude of life-threatening diseases. These additions include our own base editor as well as additional CRISPR enzymes which provide us with the capabilities to achieve any editing strategy, including single nucleotide modifications. These are examples of how broadly we are moving our platform forward. Importantly, we believe that the targeted and efficient delivery of CRISPR-based genome editing tools is a critical component of realizing the full potential of future transformative medicines, both in the in vivo and ex vivo settings. Moving to Slide 5. The landmark clinical data we presented in June for a systemically delivered CRISPR-based therapy in patients marked just the beginning of our next phase of innovation. The positive interim results for NTLA-2001 was the first demonstration of CRISPR-based therapy to edit genes inside the human body, this case, targeting the liver. It supports the potential of NTLA-2001 to be the first onetime treatment for transthyretin amyloidosis, capable of improving patient health outcomes by achieving deeper TTR reductions as compared to current standards of care. Further, these data support our belief that, with our modular genome editing technology, we may be able to target any genetic disease originating in the liver with future CRISPR-based medicines. With clinical proof of concept for our LNP delivery platform now in hand, we have already advanced NTLA-2002, our second in vivo candidate, for the treatment of hereditary angioedema into the clinic. Moving forward, our results give us confidence to pursue even more diseases that originate in the liver, following this reproducible development path and a modular approach, where the LNP formulation remains virtually identical except for the last 20 or so nucleotides of the guide RNA. And as you'll see later, we believe these groundbreaking data have opened the door to a new era of medicine, in which curing a broad range of genetic diseases may be within our reach. In addition to presenting our first clinical data last year, our team accomplished a number of other key milestones in 2021, reinforcing our leadership position and bringing us closer to impacting the lives of patients with CRISPR-based medicines. A number of these achievements are highlighted on Slide 6. Specifically, we dosed the first patient with NTLA-2002, our second in vivo clinical candidate, in an ongoing first-in-human study in patients with HAE. Next, we nominated not 1, but 2 development candidates, leveraging our targeted insertion platform. We initiated patient screening for our first wholly owned ex vivo clinical trial to evaluate NTLA-5001 for acute myeloid leukemia. And finally, we presented several noteworthy research and platform advancements, such as preclinical proof-of-concept for in vivo editing of bone marrow, base editing with our proprietary cytosine deaminase and engineering [ stem ] cells capable of evading immune attack utilizing our allogeneic technology. We accomplished a tremendous amount in 2021 and intend to build upon those achievements in 2022 as we continue to advance our in vivo and ex vivo pipeline. Now a look ahead to upcoming catalysts across our platform and programs can be seen on Slide 7. First, we look forward to sharing an interim update from our Phase I study of NTLA-2001 later this quarter with additional details to follow. We plan to complete enrollment of both the polyneuropathy and cardiomyopathy arms of the Phase I study this year. Beyond our lead program, we continue to advance first-in-human studies of NTLA-2002 and NTLA-5001. For NTLA-2002, we expect to present interim data in the second half of the year. Finally, we expect to nominate multiple new development candidates this year and to share more data on our research and platform advancements at upcoming scientific conferences. As a brief reminder, our technology platform allows us to develop investigational therapies in both the in vivo setting, that is where CRISPR is a therapy; or in the ex vivo setting, where we use CRISPR technology to engineer cells which then become the therapy. As we move to Slide 8, I'll start with a highlight of our in vivo approach. There are some clear strategic advantages of this approach when using our CRISPR/Cas9 technology in the in vivo setting to develop therapies for genetic diseases. First, this approach allows us to bring forth potentially curative therapies for genetic diseases where there is unmet need and limited treatment options for patients. We believe a single dose CRISPR-based therapy could have tremendous advantages for both patients as well as the broader health care system. Next, systemic nonviral delivery of CRISPR/Cas9 using our LNP technology provides transient expression of both the delivery vehicle, that is the LNP, as well as the CRISPR/Cas9 RNA cargo within the LNP. This transient expression confers a number of potential advantages. Next, our technology allows for the permanent gain of function with targeted gene insertion when developing treatments for diseases where the patient is missing a critical protein. And finally, our platform is capable of delivering CRISPR/Cas9 machinery to multiple tissue types for various therapeutic applications. Our most advanced in vivo program, which I mentioned earlier, is NTLA-2001 for transthyretin amyloidosis. So let's now move to Slide 9, where I will highlight the interim clinical data we recently presented. Our landmark data presented last year highlighted the interim clinical data from the first 2 cohorts of the disease -- sorry, or the dose escalation portion of our ongoing Phase I trial for NTLA-2001. These data indicate an encouraging safety profile and dose-dependent protein knockdown response. In the second dose level, treatment with NTLA-2001 in the 3 patients led to a mean serum TTR reduction of 87% at day 28 with a maximum 96% reduction. Notably, these interim results exceeded the current standard of care for ATTR amyloidosis patients with polyneuropathy. As shown on Slide 10, at both dose levels, NTLA-2001 was generally well tolerated by the 6 patients included in the interim analysis with no serious adverse events by day 28. In terms of next steps, we plan to present interim data from all 4 cohorts from Part 1 of the polyneuropathy arm in Q1 this year at a company-hosted event. We expect to share a comprehensive data set from Part 1, which will include safety and serum TTR knockdown for cohorts 3 and 4 as well as extended observation across all 4 cohorts. Additionally, we expect to initiate Part 2, a single-dose expansion cohort to further characterize NTLA-2001 later this quarter. While it has long been our plan to develop NTLA-2001 for all forms of ATTR amyloidosis, we've recently accelerated the evaluation of NTLA-2001 in patients whose primary clinical manifestation is cardiomyopathy, which represents a larger opportunity in terms of patient numbers, level of unmet need and commercial potential. Based on the strength of our interim data, we expanded our Phase I study to include patients with cardiomyopathy, as shown on Slide 11. This incorporates what would have been a separate study. And as a result, we believe we will generate key data in this patient population faster. We're excited to share that late last month, we dosed the first patient in the cardiomyopathy arm of this study. Beyond NTLA-2001, we've made substantial progress across several in vivo therapeutic candidates targeting the liver, such as NTLA-2002. Based on what we've seen with NTLA-2001, we're confident we will have an increased probability of technical success as we advance 2002 and additional in vivo development candidates given the modularity of our platform. As we move to Slide 12, I will highlight our ex vivo approach, which uses CRISPR to produce engineered cells targeted against cancer and autoimmune diseases. Intellia's CRISPR-based platform offers a number of potential advantages with broad applicability across immuno-oncology and autoimmune diseases. We believe our proprietary technology has the potential to result in the development of more effective and safer cell therapies using both TCR and CAR constructs. Our lead ex vivo program, NTLA-5001, is a potential best-in-class autologous engineered T cell therapy for acute myeloid leukemia that leverages our TCR-based approach. With this approach, we target intracellular antigens not accessible by CAR-Ts, specifically the Wilms' Tumor 1 intracellular antigen with NTLA-5001, which is over-expressed in more than 90% of AML patients regardless of mutation subtype. During the fourth quarter of last year, we initiated screening patients for the Phase I/IIa study shown on Slide 13 and expect to dose our first patient in the coming weeks. This first-in-human study will be evaluating NTLA-5001 for safety, tolerability, cell kinetics and antitumor activity in adults who have detectable AML after having received standard first-line therapy. Moving to Slide 14. One noteworthy point of differentiation for NTLA-5001 is that it leverages our proprietary LNP-based cell engineering platform. We employ a distinctly different approach to cell engineering that we believe has the potential to set the standard for adoptive cell therapy. We've shared preclinical data featuring the benefits of our LNP-based sequential CRISPR cell engineering platform, which avoids the use of electroporation. Although commonly used, electroporation is several limitations that affect the attributes of the final cell product. For example, beyond the well-recognized cytotoxicity of the procedure, electroporation also introduces random DNA breaks which contribute to genotoxicity. if multiple edits are required, these edits, if introduced simultaneously, further contribute to on- and off-target translocations and structural variance. By utilizing our proprietary LNP-based delivery technology, we can achieve highly efficient sequential editing, knockouts and insertions of cells for ex vivo application. Importantly, as presented for T cells, our approach yields a cell product that maintains cell viability and expansion rates comparable to untreated cells. We believe our approach will translate to meaningful advantages in terms of safety, cell kinetics, persistence and ultimately efficacy for ex vivo therapies. Before we conclude, let me put this all together to illustrate the impact of our full spectrum approach. We've generated an unsurpassed pipeline of clinical and research-stage in vivo and ex vivo programs, as shown on Slide 15. With the clinical proof of concept for our LNP platform, we're accelerating the progression of our in vivo candidates, both knockouts and insertions. We've already dosed the first patient with NTLA-2002 for patients with hereditary angioedema. And we expect to advance additional development candidates this year. Our first ex vivo program, leveraging our differentiated LNP-based cell engineering platform, has entered clinical development and is being studied in patients with AML, a disease with substantial unmet need and poor clinical outcomes. As we look more broadly into the future, moving to Slide 16, we will build on our leadership position in the genome editing revolution. We've developed a robust pipeline. With our expanding toolbox, we can apply the tools necessary for a broad range of genome editing therapeutic applications. In closing, I'd like to thank you for your attention, and I look forward to keeping you informed of our progress throughout the year. Thank you.

Thanks so much, John, for that overview of Intellia's genome editing platform, clinical programs and key milestones the company expects in 2022. We're now going to move to the Q&A portion of today's presentation, and we're also going to be joined by Intellia's Chief Scientific Officer, Dr. Laura Sepp-Lorenzino; Chief Medical Officer, Dr. David Lebwohl; and Chief Financial Officer, Glenn Goddard. We've been compiling questions received from the JPMorgan portal as well as questions we received during this week from the investment community. So let's start with a few of the big picture strategy questions we've been getting. And this first one I'll direct towards you, John. How should investors think about Intellia's current and future genome editing capabilities? And where should we expect Intellia to focus its technology investments and priorities over the next 1 to 3 years?

Well, as I mentioned in the comments, the goal is to be a full spectrum genome editing company. And that's not limited just to in vivo and ex vivo genome editing, which we talked about in the comments, but they have a platform that is unsurpassed in terms of what it's able to accomplish. Ultimately, we want to be, and I think we're very close to being, in a position where we can introduce essentially any edit that is therapeutically relevant. So we think about applying those edits in the in vivo and ex vivo setting. The clinical work validates that work. And what we're really excited about is having answered the question about being able to knock out a gene specifically, we're advancing programs to ask whether or not we can knock in a gene successfully and have it produce normal levels of human proteins. Behind that, from a technology point of view, as we think about where we want to go, we're always interested in expanding our delivery capabilities. We've produced preclinical data we've shared elsewhere that shows we're moving into the bone marrow, which is exciting as a way to avoid bone marrow transplantation, which I think is a limitation for current therapies. But we're also looking for ways to continue to expand the range of edit types and apply them across a range of targets. Specifically when you think about the ex vivo setting, which we consider to be rewiring cells, we'd like to be in a position where we're unlimited by any number of edits so we can make any change that we want to pursue. We announced our base editing approach earlier last year, and I would expect to see continued evolution of the technology platform.

And John, a follow-up question that we just saw on the website. Can you comment, where might you use a base editor versus other technologies? Or how do you think about kind of which tools to use for specific types of edits?

Yes, it's important to think about it along the lines of what you just said, which is there are specific tools for specific settings. Our view of a base editor is that it's best deployed in areas where you want to multiplex in the setting of doing multiple edits. So we see that best suited in the ex vivo setting. I think we're less enthusiastic about its immediate utility in the in vivo setting because of some of the limitations that come with the stochastic edits. But from an ex vivo point of view, we think it certainly has a role.

Great. And this next question, I think, is going to be maybe a combination of John and you, Laura. So maybe first, John, can you give us a sense of what indications or targets may be coming next for our drug development candidates? And how you think about balancing the portfolio in terms of in vivo or ex vivo? Knockouts, insertions, et cetera? And sort of a follow-up question to that is -- and maybe this is the one for Laura, is where does the allogeneic platform sort of fit into this framework of different types of programs in the pipeline?

So let's save the allo for Laura since her group has done some wonderful science there. Yes. I mean we think about the indications we pursue at a couple of levels. One is the merits of the product itself and the medical need that we're going after. And the examples we've already talked about, I think, are good examples of where gene editing can really make a difference for amyloidosis and HAE. But we also think about expanding the perimeter of demonstrating what the technology can show. So just as we've answered the knock-out question, we think, the knock-in question is particularly interesting and advancing alpha-1 antitrypsin, or in collaboration with Regeneron, the hemophilia B program, I think, will go a long ways to answering what's possible there. We're very, very excited about, if we're successful, what that can do for patients. And on the ex vivo side, we definitely want to have a presence. We've built out some really, I think, fundamentally important editing capabilities. And you'll see that we're going to, as we said, announce our own proprietary development candidate for an ex vivo therapy with our allogeneic platform. And maybe, Laura, you can say a few words about some of the attributes of that platform and why we're excited.

Yes. No, thank you. Yes, I do believe we have a unique opportunity and a very differentiated opportunity for our allo platform. As we're learning from the clinical experience of others in the field where their own "allo solutions," it's really becoming clear there are significant limitations to the approaches that are being taken. There is the classic knocking out of MHC Class 1 by knocking out beta-2 microglobulin, and then relying on immunosuppression to create an allo activity window for efficacy. The issue is that, as the immune system reconstitutes, natural killer cells are one of the first to appear, and they will recognize the allo cells that are like in the MHC class, and they will effectively eliminate them. And this is -- recent clinical disclosures have really shown a lack of persistence with impact on efficacy. So what we are developing is a proprietary allo approach that was designed upfront to address all immunological requirements for allogenicity. And this is not only preventing [ efforts to those disease ] and rejection by T cells, CD8s or CD4s, but also to prevent this graft rejection by natural killer cells. We have shared some data late last year. We're going to be sharing more about the specifics on how we're doing that. But at ASH, we presented preclinical data, functional data demonstrating resistance against natural killer cells. And we believe that that's going to be really, really important for an effective and persistent response for our allo platform. We -- as John just said, we are on track to nominate our first-ever development candidate in early 2022, but also have used these allo chassis as a catalyst for partnerships. We announced 2, 1 most recently last week with Kyverna for autoimmune disease, and an earlier agreement is a NewCo, [ AvenCell ], that is also looking at a universal CAR-T approach using our approach. And just to reiterate what John was saying, what's important for how we do this is the ability to introduce as many edits, knockouts and insertions in a sequential manner using our LNP technology, avoiding electroporation, avoiding insertion and mutagenesis with lentiviruses and retroviruses. And this allows us to have a high-quality cell therapy with chromosomal integrity and a number of attributes that we believe will translate to efficacy and persistence in the clinic.

Great. And that's a great segue to the next question we've got. And I think maybe this is one for Glenn. We've now seen Intellia announce 3 separate business development transactions over the last 6 months, and Laura just commented on 1 of them. But can you describe how Intellia is thinking about business development in terms of our overall strategy? And should we expect to see more deals in 2022? And if so, what exactly are we looking for?

Great. Thanks for the question. So just important to note, while our core focus remains on advancing therapies within our own research and clinical pipeline. We recognize that our platform can have additional impact when we partner with others that have complementary capabilities. So our recent business transactions with [ AvenCell ], SparingVision and Kyverna reflects our strategy to enable programs outside our key areas of focus and provide valuable future pipeline options that come with significant development and commercial rights. So as we move forward, we will look to continue to look for these sorts of partnering opportunities. I think it's key, as we look to fully leverage our platform to continue, to build options for our pipeline and build value for our shareholders. So we'll continue to, again, look for these sorts of deals. But stay tuned. We're not going to probably comment more on details as to what we're looking for. But we will continue to move forward with this partnering strategy that you've seen over the last 6 months.

Great. Thanks, Glenn. Maybe let's switch gears. And not surprisingly, we're getting a number of questions about NTLA-2001. So let me try to consolidate them in terms of the most frequent questions we're getting about the program. And David, maybe I'll direct these to you because you and your team are leading much of this development work. Why don't we start with -- can you remind investors of what specific 2001 data we expect to see at the Q1 update? And will this include data on cardiomyopathy patients as well as polyneuropathy? Or just the polyneuropathy patients? So maybe you can just kind of detail what you're expecting to share.

Yes. Thanks, [ Ian ]. Yes. So this is an important follow-up to what John showed in the presentation, the first 2 dose levels that were presented in the New England Journal. We will now show really the rest of the dose escalation phase of this trial, 2 additional doses. To remind you, the first 2 doses were 0.1 and 0.3, where we had seen the 87% average reduction. Was already a great result, but we do want to see if we can even do better. And have dose levels of 0.7 milligrams per kilogram and 1 milligram per kilogram that we'll talk about in the first quarter of this year. In addition to talking about the effects and the safety, we'll be looking at the effects on TTR reduction, again. And as part of that, we'll also give follow-up of, now that the patients have been followed for a significant period of time, to show what's happening after the first 28 days. The results will all be coming from the patients with polyneuropathy because these are the patients where we have a significant body of data. But very importantly, we're accelerating the program for cardiomyopathy by having introduced these patients as an amendment into this current Phase I trial. We have also announced that we've started to enroll those patients, but it will be too early to talk about those patients in the first quarter.

Great. And maybe a couple of follow-ups to that, David, that we've gotten. I guess, first is, can you remind investors what was the rationale to dose patients at the 0.7 milligram per kilogram dose in the fourth cohort following 1 mg per kg? And thoughts -- and what are your thoughts in terms of, will that be a single dose, do we think across both polyneuropathy and cardiomyopathy patients? Or do you expect different doses for different kinds of patients?

Yes. What -- the trial was preplanned to go from 0.1 to 0.3 to 1 milligram per kilogram. This is, of course, before we knew anything about the effect in people. I should say the effect in people was certainly even better than what we expected. So we feel that the jump from 0.3 milligrams to 1 milligram is a more than threefold, it was a pretty large jump. We really want to fill in the dose response here. We really want to understand the whole range of doses to get really to the best minimally effective dose and the best dose for the patients. We do think with this, we will have a greater effect on TTR as we already had at the second level than the available agents, and we really want to maximize that effect. And what we expect to see in the patients with cardiomyopathy is a picture very similar to the patients with polyneuropathy. Biologically, for every reason, we think that they should respond in the same way as the patients with polyneuropathy. But of course, as we're going to go forward to pivotal trials in patients with cardiomyopathy, we do want to have data available to support those larger trials coming in the future.

Great. And there seems to be quite a bit of interest in the cardiomyopathy portion of the trial. Let me just ask just a couple of more questions on that, David. Can you remind folks, is this trial for both wild-type and hereditary patients? And at what point would we expect to enroll patients in the U.S.?

The Phase I does include patients, both with the variant, the mutation as well as the patient with wild type. In fact, the group with wild type is, as many people know, is becoming the predominant group that's being diagnosed in these days. Coming to the U.S., we'll be discussing our plan for the pivotal study. We don't feel we need the U.S. to complete the Phase I. So we're in very good shape in terms of the interest that investigators have and patients have in the Phase I outside the U.S. But at the same time, we are getting ready for the U.S. We are thinking about our pivotal trial design. These will be discussed in detail with U.S. health authorities. And we do plan to open an IND in the U.S. as well as broadly with within the globe in order to complete our larger trials.

And then maybe finally, David, I know as a general rule, we tend not to like to comment on other company's data. But can you comment just briefly on how we're thinking about the recent BridgeBio Phase III data in cardiomyopathy and how that might inform our thoughts on future trial design?

I think most importantly, if you think about the fact that the therapy that Bridge was using is very different from what we're doing. It's a stabilizer, what we are doing is reducing the TTR in patients. So this will work very differently. We know already from other types of amyloidosis that reducing protein has a very major effect on benefit to patients. And that's really the -- ultimately, the important factor. The trial itself, there are things we don't understand completely. They have been raised questions about the patients in the placebo arm doing very well, but they might have enrolled patients in general with very early disease. I think all this information will help inform what we do in our advanced trials as well results coming from Alnylam, presumably in the near future, in the same type of setting. And of course, we're going to think importantly about the 6-minute walk test. Is this really the best test to use to assess benefit to patients rather than the better-established end points such as mortality and cardiovascular events? We do feel good in some ways that we're getting information from other trials as we design our trial, and that will help us design the best trial coming up in the coming months.

Terrific. Thanks for those insights about the 2001 program. Let's now shift over to 2002 as we're getting some questions about that program in HAE. And I think really the main question we're getting is, what data should we expect to see in the second half of this year for the program in HAE?

Well, this program is, as we've announced, is getting started. Patients are enrolling. What we've said already is that, instead of having 4 dose levels, we plan on 3 dose levels. We're using the safety information from the TTR study to start at a higher dose in this study. As you know, even at our second dose level, we did have a very major effect on protein. So we do expect that given the similarity of the mechanism, these drugs are exactly the same, except for the 20 nucleotides at the 5-prime end of the guide RNA. We do expect to see a major effect on prekallikrein protein and activity. And that we know as well from other types of therapies, that this can have a major effect on the number of events, of angioedema events, that patients experience. So with that, I have to say we don't know exactly what we're going to present in the second half of the year as we never know, we're just doing a trial. However, based on the things I say, you should have an idea that we'll have substantial information, starting with the first dose level coming out of this trial.

Great. And I think our next question, maybe we'll ask Laura to help with this one. And it's about the 5001 program. So that's Intellia's first ex vivo program. And so the question is, why did we choose a TCR approach? And how is this approach to cell therapy different than what some of our competitors are doing? Laura, is that something you can help us with?

Yes, sure. So T cell receptor, or TCR, that's the physiological mode of recognition that T cells use to -- for surveillance and elimination of tumor cells. So our goal is to recapitulate that biology for an adoptive cell therapy, where we can select the T-cell receptors, the TCRs, that have high specificity and ability and activity against a desired tumor antigen. This is difference from CARs, which is another modality we pursue as well as others, but CARs are limited only to target surface antigens, right, which are most often expressed also in normal tissues, leading to on-target, off-tissue toxicity, right, and limiting the efficacy of those therapies. With TCR, we can recognize both surface as well as intracellular tumor antigens. So we have a vast array of targets we can choose from. The other thing that we are pursuing is that the TCRs, we are identifying and selecting them from normal donors. We keep them unchanged. That way, we avoid any concerns for normal tissue toxicity. And then we use CRISPR to completely remove the endogenous TCRs from the T cells, whether they are autologous or allogeneic T cells, and then insert the therapeutic TCR specifically in the track locus. So now that cell only will be displaying 1 TCR. And that leads to a homogeneous cell product with high intrinsic activity. We're very excited about 5001. This is our first autologous TCR therapy for AML. The TCR target Wilms' Tumor 1, which is the #1 tumor antigen as selected by NCI, is -- for AML, is over-expressed in the majority of AML cases, over 90%, independent of subtype, is even expressed in blast, in minimal residual disease. So -- and the peptide we've chosen, we know that's processed and presented by the blasts. And that obviously is important for recognition of the tumor and elimination. For us, there is value, 5001, of course as what it could bring to AML patients, but also a positive result answers one of the categorical questions for us, which is the value of TCRs not only for hematopoietic malignancies but the promise for solid tumors. And marrying that with our cell engineering, ability to introduce, not be limited by the number of edits, we can also introduce immune-enhancing edits that we believe are going to be key for a successful therapy for solid tumors.

Great, Laura. And unfortunately, as I'm looking at the clock, it looks like we're almost about out of time. So maybe before we close the call, maybe I'll hand it back to John. Are there any final comments you'd like to make before we close today?

Thanks, [ Ian ]. Just first of all, thank you to the audience for listening to our comments. I hope this notion of a full spectrum genome editing company is clear. You see the work that we're doing on the in vivo side, general approaches or systemic, that allow us to extend the reach to any number of different tissues; a full range of edits. With respect to the ex vivo side, a novel allogeneic platform and the ability to rewire cells essentially without limit from an editing point of view. And then a platform that is unsurpassed. And that's always going to be an area of focus for us. If there's new modalities, we will have them and we will deploy them in the appropriate way that's most relevant to whatever the genetic target is. So a very exciting year for us ahead, and I'm quite confident we're going to build on the early success that we had just last year.