Good morning, welcome to the Intellia Therapeutics second quarter 2021 financial results conference call. My name is Jason, and I will be your conference operator today. As a reminder, all participants are currently in listen-only mode. If anyone requires operator assistance during the conference, please press star zero on your telephone keypad. Following formal remarks, we will open the call up for questions. This conference is being recorded at the company's request and will be available on the company's website following the end of the call. I will now turn the conference over to Ian Karp, Senior Vice President of Investor Relations and Corporate Communications at Intellia. Please proceed. Thank you operator, and good morning, everyone. Welcome to Intellia's second quarter 2021 earnings call. Earlier this morning, Intellia issued a press release outlining the company's progress this quarter, as well as topics for discussion on today's call. This release can be found on the Investors and Media section of Intellia's website at intelliatx.com. This call is being broadcast live, and a replay will be archived on the company's website. At this time, I would like to take a minute to remind listeners that during the call, Intellia management may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for 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. Joining me on the call today are Dr. John Leonard, Chief Executive Officer, Dr. David Lebwohl, Chief Medical Officer, Dr. Laura Sepp-Lorenzino, Chief Scientific Officer, and Glenn Goddard, Chief Financial Officer. On today's call, John will lead with the company's second quarter and recent business highlights, followed by David, who will provide an update on clinical efforts surrounding NTLA-2001. Lara will recap the company's R&D progress, followed by Glenn, who will review Intellia's financial results for the quarter. John will make some closing remarks, and we'll open up the call for Q&A. With that, let me turn the call over to our CEO. John? Thank you, Ian, and thank you all for joining us today. The past few months have been incredibly exciting for both Intellia, as well as for patients battling diseases that may be addressable with our genome editing therapies. Most notably, in June, we became the first company to report clinical data for a systemically delivered CRISPR-based therapy in patients. This milestone represents a significant advance in our mission to develop curative genome editing treatments. At Intellia, we've set out to build the broadest and deepest toolbox to fully realize the promise of revolutionary CRISPR-based medicines. To that end, our platform deploys differentiated modular solutions across in vivo and ex vivo therapeutic applications of our Nobel Prize-winning technology. For genetic disease, we're leveraging a 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 is designed to produce a homogeneous, robust cell product that epitomizes a patient's natural immune system to eliminate cancer cells. Across these efforts, we've made significant progress advancing our full spectrum strategy since last quarter's call. Our landmark data presented in June highlighted the interim clinical data from the first 2 cohorts of 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 in the cohort led to a mean serum TTR reduction of 87% at day 28, with a maximum 96% reduction. Notably, these results exceed the current standard of care for ATTR amyloidosis patients with polyneuropathy. 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. We view this as a profoundly important outcome for patients, for Intellia, and for medicine. These positive results not only support NTLA-2001's therapeutic potential as a one-time treatment for ATTR amyloidosis, but also offer proof of concept for our non-viral delivery platform. It gives us added confidence to pursue other targets to treat diseases that originate in the liver via reproducible development path. More broadly, we believe these results open a new era in medicine in which curing genetic disease may be within reach. Shortly, David will elaborate more detail on the landmark data and next steps for this program. Beyond the NTLA-2001 readout, NTLA-2002, our in vivo knockout candidate for hereditary angioedema, or HAE, and NTLA-5001, our lead engineered TCR T-cell therapy for acute myeloid leukemia, or AML, continue marching towards the clinic. In June, we shared that we submitted our first CTA for NTLA-2002 to regulatory authorities, and we're pleased to announce this morning that we have submitted our first CTA for NTLA-5001 as well. Pending regulatory authorization, both first-in-human trials are on track to begin by the end of this year. In addition, together with Cellex Cell Professionals and Blackstone Life Sciences, we launched a new universal CAR T company. This new company combines Intellia's allogeneic cell engineering platform with a clinically validated universal CAR T construct from GEMoaB. Additionally, this company, which aims to develop differentiated immuno-oncology and autoimmune therapies, is resourced with up to a $250 million financing commitment from Blackstone. In exchange for a license to our technology, Intellia will receive a significant equity stake of this new company, along with 2 options to co-develop and co-commercialize 2 allogeneic universal CAR T candidates in the U.S. and key European countries. Collaborations like this one are a key instrument of our broader corporate strategy to enable us to realize the full scope and potential of our technology for patients. They can extend the reach of our technology beyond our core areas of strategic focus while retaining rights across a diverse ex vivo landscape. This collaboration brings the additional benefit of a concurrent manufacturing agreement with Cellex, which Laura will expand on a bit later. Finally, before passing the call on, I'd like to extend a warm welcome to two new members of our leadership team, James Basta, Executive Vice President and General Counsel, and Ian Karp, Senior Vice President of Investor Relations and Corporate Communications. We're thrilled to have them join Intellia, and I have no doubt their expertise and support will prove to be of great value as our company continues to mature. I'll now hand over the call to our Chief Medical Officer, David Lebwohl, who will recap our NTLA-2001 data and provide a more in-depth update on our progress in the clinic. David? Thank you, John. I'll start with a bit of background on ATTR amyloidosis and our approach with 2001. ATTR amyloidosis is a rare, progressive, and fatal disease caused by the buildup of TTR proteins in multiple organs. People living with the disease can have either the hereditary or wild type form, resulting in a diverse range of disease manifestations, the most frequent being polyneuropathy and cardiomyopathy. Our lead candidate, 2001, is the first systemically delivered CRISPR-based therapy dosed in a patient and a potentially curative treatment for ATTR amyloidosis. 2001 applies our in vivo LNP delivery technology to knock out the TTR gene in the liver, which is a source of circulating TTR protein, therefore permanently reducing amyloid deposition after a single dose. Although the current standard of care has achieved meaningful therapeutic impact with roughly 80% knockdown of serum TTR, there remains unmet medical need in this population. As Dr. Gilmore shared at our June investor event, beyond the benefits of a one-time treatment as demonstrated in ATTR amyloidosis, as well as other types of amyloidosis, greater TTR knockdown is anticipated to improve clinical outcomes. We therefore believe a single-dose therapy that most importantly produces greater and durable TTR reduction will offer a significant benefit to patients and value to our healthcare system over the current standard of care. The 2021 Peripheral Nerve Society's annual meeting and concurrently published in "The New England Journal of Medicine," we shared positive interim data from a Phase I study evaluating 2001 in patients living with hereditary ATTR amyloidosis with polyneuropathy that support this hypothesis. Data representing six patients from the first 2 dose cohorts of part 1 of the study, the single ascending dose portion, were highly encouraging, showing that 2001 induced a dose-dependent reduction in serum TTR. In our second dose level, 0.3 milligrams per kilogram, we achieved an average TTR reduction of 87% at day 28, reaching a maximum TTR reduction of 96%. 2001 was generally well-tolerated at both doses, with adverse events all being grade 1 and mostly unrelated to the treatment. Altogether, the data suggest that we can achieve targeted in vivo editing for the desired pharmacological effect, supporting 2001 as a first-in-class single-dose treatment for ATTR amyloidosis, validating our LNP technology and unlocking treatment of diseases that originate in the liver. In terms of next steps for this program, we are continuing enrollment in the dose escalation portion of the Phase I study. We plan to provide additional data from part one of the study at a scientific or medical conference later this year, including additional durability data beyond 28 days from the initial cohort. For cohort 3, each subject will receive a single dose of 2001 at 1 milligram per kilogram. For cohort 4, we have flexibility in the protocol to proceed to a higher dose or explore an intermediate dose. Once we identify the recommended dose, we plan to initiate part 2 of the trial, a single dose expansion cohort. In this portion of the study, 8 patients will be administered the recommended dose identified in part 1 with the objective to further characterize the activity of 2001, including an initial assessment on clinical measures of neuropathy and neurologic function. We expect to advance into part 2 of the study later this year. In addition, we plan to engage with regulators, including the FDA, to move into later-phase clinical trials in which we aim to include both patients with polyneuropathy and cardiomyopathy. While we recognize these are interim phase I results with much more to learn, observations so far are quite meaningful, offering support that substantially de-risks our in vivo efforts. We look forward to keeping you updated on our progress. With that, I'll now turn over the call to our Chief Scientific Officer, Lara Sepp-Lorenzino, to provide updates on our two additional development candidates, 20-02 and 50-01, and across our R&D efforts. Thanks, David. Given the modularity of our platform, we're equally excited about what the interim clinical data imply for our efforts beyond NTLA-2001. Now that we have demonstrated we can deliver to hepatocytes in humans, we believe this accelerates the development of additional in vivo programs and increases their probability of technical success. This applies to several programs, and especially to our in vivo knockout programs, such as NTLA-2002, our wholly owned candidate in development for HAE. NTLA-2002 leverages the same LNP delivery system as NTLA-2001, but targets the KLKB1 gene in the liver to permanently reduce plasma kallikrein protein and thereby its activity, a key mediator of the disease. This approach is expected to provide continuous suppression of kallikrein activity and eliminate HAE attacks. In June, alongside results from NTLA-2001, we announced the submission of our first clinical trial application to the New Zealand Medicines and Medical Devices Safety Authority to initiate a first-in-human study for NTLA-2002. We're submitting additional applications for this program and expect to enroll the first patient by year-end. The first-in-human study will evaluate NTLA-2002 for safety, tolerability, and activity, including levels of kallikrein knockout in patients with HAE. On the basis of our preclinical data and clinical results from NTLA-2001, we expect to determine the recommended dose with a very limited number of dosing cohorts. Now turning to our ex vivo efforts. Here we're using CRISPR-Cas9 as a tool to create engineered cell therapies. Similar to our efforts in vivo, our proprietary approach to cell engineering serves as a foundation to our modular platform. This approach allows us to mix and match cell types, targeting modality, and the edits necessary for eliciting the desired pharmacology. Regardless of therapeutic format, we expect to achieve highly efficient sequential editing, high yields, optimal cell performance, and scalable manufacturing. Our lead program, NTLA-5001, is a potential best-in-class engineered T-cell therapy designed to treat all genetic subtypes of AML. This investigational candidate is an autologous T-cell receptor, or TCR, T-cell therapy targeting the Wilms' tumor 1 antigen and restricted to the HLA-A*02:01 allele. Importantly, WT1 is overexpressed in more than 90% of AML patients, regardless of mutation subtype, and HLA-A*02:01 is one of the most common serotypes. Furthermore, NTLA-5001 utilizes our proprietary cell engineering process to replace patients' endogenous TCRs with a WT1-targeting TCR, creating a homogeneous cell product with high intrinsic potency and improved safety by eliminating TCR mispairing. By utilizing our sequential editing process, the resulting cell product has the desired attributes of high viability, robust levels of expansion, desirable memory phenotype, increased functional activity, and reduced translocations. Despite recent therapeutic advances delivering improved response rates in subsets of AML, long-term outcomes continue to be poor, with overall 5-year survival below 30%. With our proprietary cell engineering process and the prevalence of WT1, we believe NTLA-51 will be a highly active and well-tolerated agent to improve outcomes for AML patients. As John mentioned today, we're excited to share that we have submitted our first CTA to the United Kingdom's Medicines and Healthcare products Regulatory Agency for a phase I study of NTLA-51 in the U.K. This first-in-human trial will evaluate the safety and activity of NTLA-51 in patients with persistent or recurrent AML who have previously received first-line therapies. We expect to be screening patients for this phase I study by year-end. Beyond NTLA-5001, we plan to share more information on our allogeneic solution later this year. We believe our approach is differentiated from others currently in the clinic that typically address only graft versus host rejection. We have focused on creating allogeneic cells that not only avoid graft-versus-host disease, but also persist by avoiding elimination by host T cells and NK cells. This approach should avoid the aggressive lymph depletion and the induced profound immunodeficiency currently employed to address a significant challenge in adoptive cell therapy. In June, concurrent to launching a new universal CAR T-cell therapy company, we entered into a preferred partnership agreement with Cellex. This agreement provides Intellia access to dedicated GMP manufacturing capacity and high-quality donor cells for our allogeneic programs. Our access to both will be of great value in supporting and accelerating the development of our wholly owned ex vivo programs. All the R&D progress, along with demonstrations earlier this year, such as preclinical data introducing our proprietary base editor and our first demonstration of in vivo editing outside the liver, reflects both the breadth of our technology's reach and our steadfast commitment to drive our pipeline forward through continued platform innovation. To that end, we plan to present additional in vivo and ex vivo updates at scientific conferences later this year. We remain on track to nominate at least 1 new development candidate this year, and we continue to work towards nominating the company's first allogeneic development candidate by the first half of 2022. With that, I would like to hand over the call to our CFO, Glenn Goddard, who will provide an overview of our second quarter financial results. Thank you, Laura, and good morning. Our cash equivalents, and marketable securities were $551.3 million as of June 30, 2021, compared to $597.4 million as of December 31, 2020. The decrease was driven by cash used to fund operations of approximately $115.1 million, which was offset in part by $45.3 million of net proceeds from the company's at-the-market agreement, $20.5 million in proceeds from employee-based stock plans, and $3.2 million of funding from cost-sharing agreements with Regeneron. Following the disclosure of our NTLA-2001 clinical data, we completed a successful follow-on offering in July, raising $648.1 million in net proceeds, putting Intellia in a strong position to aggressively advance and expand our pipeline. Our collaboration revenue decreased by $9.7 million to $6.6 million during the second quarter of 2021, compared to $16.3 million during the second quarter of 2020. The decrease was driven by $8.4 million of revenue recognized for a one-time catch-up adjustment related to the amendment and expansion of our 2016 Regeneron collaboration agreement in Q2 of last year. Our R&D expenses increased by $21.1 million to $58.9 million during the second quarter of 2021, compared to $37.8 million during the second quarter of 2020. This increase was driven by a $10 million one-time payment related to the amendment of our 2014 Novartis agreement, as well as employee-related expenses due to the continued expansion of our development organization. Our G&A expenses increased by $5.2 million to $16.7 million during the second quarter of 2021, compared to $11.5 million during the second quarter of 2020. This increase was mainly due to employee-related expenses, including stock-based compensation of $2.1 million. Finally, we expect our current cash balance to fund our operating plans beyond the next 24 months, as Intellia is well positioned to drive long-term growth and execute on our upcoming milestones. Now I will turn the call back over to John for closing remarks. Thank you, Glenn. As you can see, we've made significant progress executing against the ambitious goals and strategic priorities set forth at the beginning of this year. Our presentation of proof-of-concept clinical data from the first-ever study of a systemically administered CRISPR genome editing therapy in humans was clearly a highlight. Not only is this data important for the ATTR amyloidosis community, but it helps us advance our growing full-spectrum pipeline. Moreover, this milestone represents just one key step in unlocking the full therapeutic potential of our CRISPR platform. Following the positive interim data from our Phase I study of NTLA-2001, we look forward to sharing additional interim results and to initiating Part II of the study, a single-dose expansion cohort, later this year. We've continued to progress our pipeline with CTA submissions for our second in vivo candidate, NTLA-2002, and our lead ex vivo candidate, NTLA-5001, and we anticipate initiating both first-in-human trials by the end of this year. With validation of our CRISPR-Cas9 platform, we remain on track to nominate at least one new development candidate by the end of the year. Additionally, we plan to share preclinical data on our allogeneic solution this year and expect to nominate the company's first allogeneic development candidate by the first half of next year. Across our R&D efforts, we look forward to sharing additional in vivo and ex vivo updates at upcoming scientific and medical conferences. We're eager to carry this momentum forward as our recent progress offers a springboard from which to advance our long-term vision for Intellia. Operator, you may now open the call for questions. Thank you. We will now begin the question and answer session. Our first question comes from Maury Raycroft from Jefferies. Please go ahead. Hi. Good morning, everyone. Congrats on the progress, and thanks for taking my questions. To start off, I was wondering if you can talk more about when you aim to engage with FDA about next step trials. Would that be after the 8-patient expansion data, or can you have those meetings sooner? For the 8-patient expansion, any new thoughts on how many mixed patients will be included in that, and if you will assess for cardiovascular measures and biomarkers like NT-proBNP? Thanks, Maury. Good morning. Nice to hear from you. Maybe I'll turn to David. David, can you just tell us a little bit about your plans for progressing the work? Thank you, John. Thank you, Maury. With the data that we have from the phase I so far, we're seeing that we've achieved a 87% reduction in TTR. This result is, as you know, is better than with available therapy. In the trial, we think we are getting close to where we need to be with dosing. We will be reporting on that before the end of the year. We are, at the same time, planning on the next studies. At this time, we don't think we need any particular additional data to be able to engage with regulators, both the FDA and other regulators around the world, about our next plans. In terms of the expansion, what is in the trial is patients with polyneuropathy. If you look in clinicaltrials.gov, we talk about some of the measures. There are measures of cardiac function because, as you know, many of these patients do as well have cardiac involvement, but they don't have heart failure. Their main involvement is neuropathy. Got it. That's all helpful. It sounds like you could potentially engage with regulators sooner than later to get some additional feedback on what next step trials could look like. That is a reasonable assumption. Okay. Follow-up question just on cohort 4, what are gating factors to determine if you decide to assess an intermediate dose at dose level in that cohort, and what could that dose look like? Yeah, we're going to look at the data from cohort 3. We mentioned cohort 4, but it's not required within the study. If we think we've had the right dose to go forward based on the first 3 doses, we can do that. We also do have the flexibility to go to either an intermediate dose that's higher or lower than that 1 milligram per kilogram. We'll be looking at all the data that comes in from the third cohort, and then decide what to do after that. Okay. Makes sense. Thanks for taking my questions, and I'll hop back in the queue. Thanks. The next question comes from Salveen Richter from Goldman Sachs. Please go ahead. Hi. Thank you so much for taking our question. This is Sonia on for Salveen. We just had two questions. The first is on NTLA-2001. How should we think about the upcoming data for cohorts 3 and 4? Just if you could help us frame expectations there. The second one is on the trial design for WT1 AML, and just if you could remind us what that is again, that would be helpful. Thank you. I think I'll turn to David again. David, just say a little bit about our expectations for the end of the year and I know it's early for WT1 trial designs, but maybe you can just speak to where we are in the regulatory process just to remind our listeners. Okay. No, thank you, John. What we'll be reporting before the end of the year is additional data from the dose escalation portion of the trial. What you know from our report so far is that we will have data from patients receiving 1 milligram per kilogram. We've also said that we'll be talking more about the durability in the cohort in the existing patients in the trial. Of course, we'll bring forward as much information as we can from the trial and let people know where we are with that. Looking at NTLA-5001, we have announced that we've made our first CTA submission or regulatory submission, that is. With that, we will be talking about the trial design after we are really getting started with the trial, after we have our first approval to move forward in the trial. The next question comes from Gena Wang from Barclays. Please go ahead. Hi. This is Sheldon on for Gena. Thank you for taking our question. We have two, one on twenty one. For the second half update. Could you narrow it down a little bit for us, whether it's third quarter or fourth quarter, and could you update us also on the enrollment progress? Yeah. This is John. Thanks, Sheldon. We're really not going to be able to give more specificity other than we'll give you an update by the end of the year. We will apply the principles that we've been applying throughout the study to date. We want those updates to be interpretable, meaningful, and consistent, and that's been what's been guiding us throughout the work. It's certainly our expectation to share more information, but as we did with the first go-around, we'll give people advanced notice on where we're going to do that and how we're going to do that. Stay tuned for that. We're not going to catch anybody by surprise. Right. Very helpful. My second question is on HAE. When you share the data, how should we think about the gating factors about when you will be able to share? Is it like to achieve certain follow-up or to achieve certain knockdown level? Yeah, I think that's premature. At this time, I understand what's behind the question. We've begun the regulatory process as we laid out. We're excited about moving that forward very, very expeditiously. As Lara commented, we think we're in a very good position to benefit from the work that's been done with NTLA-5001. That will find its way into the clinical program. Once we've cleared on the regulatory side, we'll talk about the specifics of the program and the protocol. At that point, we can start to think ahead about what we'll share and when we'll share it. I think, as you know, in these first-in-human studies, it's all very much a function of the protocol design and the rate of progression of enrollment that dictates what you can talk about. Stay tuned, again. I think you should just expect that we'll do it in a fashion that's quite similar to what we did with 2001. That's very helpful. Thank you. The next question comes from Joon Lee from Truist Securities. Please go ahead. Hi. Thanks for taking our questions and for the update. For the patients in the cohort 1, if you look at the data, they didn't look like they plateaued. Have you collected more data beyond day 28? If so, do you see a further knockdown in TTR? Related to that, when will you be able to share some clinical updates, which could be particularly interesting given the completely different PK/PD profile compared to ASO? I have a follow-up. I'll take that. As David said in his comments, we'll provide more information as the study progresses, and we've committed to doing that before the end of this year. We presented the data that we had. It's an ongoing study, and what we try to do is present information that we think is meaningful. Generally speaking, we expect the TTR effects to settle out by day 28. Subsequent work and data collection, I think, will corroborate that, at least based on pre-clinical work. With an upcoming update, we'll share the information that we have. Stay tuned. It's an ongoing process. With respect to the clinical information, that's something that we'll collect more robustly in the stage 2 of the study, although there's some descriptive work in this phase I, which, as you know, will speak to the particular doses that the patients have received. As we shared with our update a few weeks ago, cohort one, we think, has very, very meaningful knockdown, but I don't think presents the drug with the maximal effect that one would hope to see from a clinical point of view. That better, more robust description really is going to come in stage two. Got it. Then as you advance NTLA-2001 towards commercialization, can you discuss your freedom to operate in the U.S. specifically to commercialize that in the U.S. unencumbered, or do you foresee a need to negotiate with another company or pay a royalty? Is that something James Basta will be tackling? Thank you. I think we're in a really good position to commercialize the product, and at this point, anything to share specifically with respect to dealings with other companies. Thank you. The next question comes from Luca Issi from RBC Capital Markets. Please go ahead. Oh, great. Thanks so much for taking my question. Congrats on all the progress here. I have a philosophical question on durability. I know gene therapy is an imperfect comp, but we have seen the FDA asking for at least 2 years' durability before considering approval, at least for liver, and you need to look at the BioMarin data in hemophilia A as a comp. Conceptually, do you anticipate the FDA to ask shorter timeline for gene editing, given its permanent nature? Maybe do you expect them to ask even longer timeline, given we don't really understand the long-term consequences of potential off-target effects? Thanks so much. That is not only philosophical, but also speculative. I think, in the spirit of your question, the specifics of what it's going to take for this particular therapy to be approved by regulators is something that will be subjected to ongoing future regulatory studies. I think that, in the case of gene therapy, in terms of how we view it, the particular approach has inherent tendencies to at least be susceptible to waning over time, and that's, I think, as you know, tied to the notion of having an episome that is not integrated into the genetic material of the cell. It's our expectation, and we've certainly shared a lot of preclinical work to support this, that the effects should be, in the case of gene editing, lifelong over the life of the patient, and we have no evidence to the contrary at this point. We'll see what the FDA is looking for, but I think that certain principles that are analogous to gene therapy are likely to be applied, but a lot of that is just looking for the clinical outcomes that come with it and sufficient information to indicate that the assumptions are correct. Great. Thanks so much, John. The next question comes from Mani Foroohar from SVB Leerink. Please go ahead. Good morning. This is Greco on for Manny. Thanks for taking my questions. What is your current thinking around the regulatory path for 2001 in cardiomyopathy and polyneuropathy phenotypes in the context of existing treatment options like stabilizers and silencers in these phenotypes that are becoming standard of care. Are you guys expecting to do non-inferiority studies for one or both phenotypes? I'd say at this time, it's far from a foregone conclusion that in the cardiomyopathy space, in particular, we'll be required to do comparative studies. Obviously, we watch the space carefully to learn whatever we can from the progress of other agents. I don't think that most KOLs would agree that there's a standard of care, and certainly from a knockdown point of view, there's not even an approved product yet for cardiomyopathy. That basis of thinking, I think for regulatory studies for us is probably quite premature. With respect to the polyneuropathy space, that's work that we're thinking through at this point. Where the program stands today is we're especially interested in getting information in the cardiomyopathy patients, and after David selects his optimal biological dose and we collect that information, we'll progress that as efficiently as we can. Awesome. My second question is, so far we've seen NHP data from 3 different programs, I think ATTR, HAE, and AATD, but the tested doses were not disclosed. In terms of knockout efficiency, are you seeing similar knockout across different genes at similar dose levels, or are you seeing some meaningful differences in knockout efficiency depending on the gene of interest? How does this, in combination with 2001 clinical data, inform both the trial design and knockout expectations for 2002 in HAE? Well, one of the benefits of the modular approach is that we use the same lipid shell that contains essentially the same cargo, and by that I mean specifically the mRNA that encodes the Cas9 enzyme, and for that matter, the guide RNA is virtually identical with the exception of the last 20 nucleotides. What we've found is that from a product efficiency point of view in our preclinical models, there's great consistency across all of the different targets that we've pursued. We're excited that the logic that we employed at the very beginning about modularity appears to be holding true, and I think the first real test of that's going to be as we move to 2002, and ideally, hopefully corroborate the results that we've already seen with 2001. Our preclinical studies, which have been a very good guide thus far, have been very helpful in terms of predicting where we go in humans. Thanks. I really appreciate the detail, and thanks again for taking my questions. The next question comes from Jay Olson from Oppenheimer. Please go ahead. Oh, hey. Thank you for taking the questions. Maybe just to follow up on NTLA-2001 in cardiomyopathy, do you think that the greater TTR knockdown can lead to improved clinical benefits in both cardiomyopathy and polyneuropathy? Maybe just a quick question on NTLA-5001 for AML. Since you're planning to do your early clinical work in the U.K., can you remind us sort of the pros and cons of doing that work in the U.K. versus submitting an IND in the U.S.? Thank you. Let me speak to the whole knockdown question. Our central thesis. I think it's a thesis that's broadly held in the amyloidosis field, is that you want to reduce the offending protein to the greatest extent possible. By that I mean to the greatest extent possible. There's clinical evidence, when you look broadly across different proteins that cause different forms of amyloidosis to indicate that that's the case. There's even existing clinical data for the agents that currently exist that suggests that deeper responses lead to better effects. There's no reason that we can think of, and no good reason that we've heard, and we certainly discuss this extensively with people who are experts in the field, to indicate that that's going to be any less true for cardiomyopathy than it is for polyneuropathy. The goal of our program is to achieve those greatest responses and TTR that we possibly can. We believe clinical trials then will bear that out. That is, as I said, the central thesis of the overall program. With respect to 5001 or the TCR program, I would point out that the regulatory submissions are in their early stages, and I would not view this as limited in any way, and certainly not limited to the U.K. However, our experience in the U.K., and we anticipate that will continue this way, has been excellent, with standards of care that are essentially indistinguishable from those that would be expected here in the U.S. From a limitation point of view, we don't see any. Great. Thanks for taking the questions. Sure. The next question comes from Steve Seedhouse from Raymond James. Please go ahead. Hi, this is Ryan Deshon in for Steve Seedhouse. Just wanted to ask, do you guys expect to report mNIS plus 7 data in the ATTR trial by end of year in patients at clinically relevant dose? I have a follow-up question. David, the question is, do you expect any mNIS data from this trial by the end of the year? We are measuring mNIS as part of the Not mNIS plus 7, as part of the early patients. Of course, this is in dose escalation, so there'll be very limited follow-up. If there was sufficient follow-up to be meaningful, we'd present it, but we're not sure we'll have that yet. Okay, thanks for that. Also, have you or do you plan to assess 2001's propensity for chromothripsis ex vivo? Is there a way to monitor this in vivo? This work has been done extensively in the preclinical setting, and that has been characterized and even reported on with respect to any off-target analyses in the New England Journal paper. I would refer you to the supplement where it's far longer than the paper itself. It speaks to how this work is done, the data that's resulting, the testing at concentrations that far exceed those that are expected to be achieved in the clinic. From the standpoint of chromothripsis, I don't think the word even applies, actually. What we're looking for is any evidence of off targets, and what we find is that there are none at the doses and concentrations that we're administering to patients. Okay, thank you very much. The next question comes from Sylvain Turcan from JPMorgan. Please go ahead. Good morning. Thanks for taking my question. I have two questions, please. Just on the NTLA-5001, I know you can't tell us much about the trial, but would there be any reason to believe that there will be major differences from the Fred Hutchinson trial that included pre- and post-transplant patients? Would there be any reason why you would exclude one of them or not? Then I have a follow-up. I want to make sure I understand the question. Are you asking from an outcome point of view, or are you asking about from a design point of view? From a design point of view. Yeah, I'd say it's still a little early to speak specifically about the design of what we're going to be doing with NTLA-5001. I think there are general principles that people broadly apply that you should anticipate in the early studies. But once we get regulatory clearance, we'll go into greater detail as to exactly what we're going to do. We certainly, looking ahead, as you refer to the University of Washington Fred Hutchinson Cancer Center results, we look to that as a helpful guide to set some expectations in terms of what might work, and some of that logic supports our thinking about WT1, but there's differences between our particular approach and the one that they applied. Great, thank you. Maybe if you can speak to the high-level strategy for the new company that you've created with GEMoaB and Blackstone. Do you think these new CAR T cells, will they explore new targets or do you plan to just produce better cells with existing well-established CAR T targets. If you can just speak to that. Thank you. The new co will have its own story to tell as it moves along. It's an independent company which we have a significant ownership position in. We're very excited about that. I'll remind you that we're supplying the allogeneic platform that we have not broadly disclosed. It is available to them, and you should look forward to hearing a little bit more about that as we go forward here. It's our expectation that they'll pursue whatever they think the modality best addresses, and that could apply to existing CAR T targets. With the switchable protein that actually targets these lymphocytes, they're certainly in a position where they could potentially explore other targets that I think that technology uniquely helps them to do. That will be their story to tell as they lay out their plans going forward. Great. Thank you for taking my question. Sure. The next question comes from Jack Allen from Baird. Please go ahead. Hi. Thank you so much for taking the questions. Congratulations on all the progress this quarter. We wanted to ask about your most recent thoughts surrounding the potential for redosing with your LNP platform. How are you thinking about the potential need to redose NTLA-2001? Is this something that's on the radar, or are you very confident that 1 dose is going to be enough to drive meaningful clinical benefit? Our quick follow-up question was, how frequently are you receiving data from the study of NTLA-2001? I know it's a single-arm study, and I'd imagine you're receiving data on some sort of rolling basis. Any color you could provide there would be great as well. Thank you so much. I'll take that. We certainly look very carefully at the data as it comes in. It's an ongoing interaction with the investigation sites. Our development team is in daily contact with them as that study progresses. It's not a blinded study. We have the benefit of getting information and interacting with the investigators as we go. You're going to have to remind me the first question that you asked me. I just lost that. I'm sorry. Oh, redosing. I'm sorry. Yeah, the way we think about redosing is the LNPs certainly enable that. That's by their very nature and one of the reasons that we chose them way back at the very beginning. They're not inherently immunogenic. They do not raise neutralizing antibodies, which means that if we need to redose, we can redose. The redosing approach in the case of NTLA-2001 for the patients participating in our first human study, has been to say to patients that once we determine an optimal biological dose, we will make that available to patients who did not receive that. That's not formally a part of this particular protocol, but that is something that will be made available to patients as the program proceeds. Going forward, as we think about dosing patients in generally, once we have the final format and final dosing, again, it's our expectation, and this is based on the preclinical results that we have, that the likelihood of to require redose, assuming an optimal dose is given in the first place, is remote and probably not necessary. Awesome. Thank you so much for the call. The next question comes from Yanan Zhu from Wells Fargo. Please go ahead. Hi. Thanks for taking my question. I was wondering, for AML patients for the NTLA-5001 program, is there anything that might be different from the T cells from AML patients compared with B-cell lymphoma patients that might affect the ability to grow out and manufacturing CAR Ts from those patients? Thanks. David, do you want to try to address that? Is there any reason that we should be aware of underlying differences in cells based on what we're doing relative to other cell types in other programs? Yeah. Thanks. We don't think that patients with AML have any intrinsic issue, let's say, with their T cells, that they can't be manufactured well. Of course, we'll get more experience in the trial when we go forward, but so far, we have no evidence of that. Got it. A quick follow-up on your transduction method. I think in the past, you mentioned that you have a gentler approach to transfection and manufacturing either the TCR or the CAR T cells. Could you elaborate a little more on that, and what might be the advantage to traditional CAR T manufacturing? Thanks. Yeah, thanks for the question. It's something that we're really proud of, that our scientific team has worked on and developed. We don't share the specifics of how we do that. We think that that is an area of competitive advantage for us for the simple reason that standard out-of-the-box electroporation damages cells. It's certainly an effective way of getting material into cells, and it's widely used. The approach that we've taken does that at least as well, maintains cell viability, allows cells to behave as if they had never been transduced in the first place from a division point of view. We think that's going to translate into dosing advantages for patients. Importantly, when you look at the genetic architecture of those cells, once they've been transduced, it's maintained. There's no inherent damage done to the genetic architecture by our transduction technique, irrespective of the editing itself, which is certainly not the case for standard electroporation. Our approach is that the editing is part of the story. How you do the editing is also critically important, and what you want to do ultimately is have cells that are as normal as possible and advantaged to the greatest extent so that they'll behave well once a patient's dosed. Great. Thanks for taking the questions. The next question comes from Tony Butler from Roth Capital. Please go ahead. John, NTLA-5001, or maybe the first program in cell therapy, I wanted to address what may be a very simplistic question, and that is, back when you and the team sat down to think about what would be your first target, you arrived at AML and WT1, which is great. The question is, was there any specific reason for that particular program that is a blood tumor target versus maybe, say, a solid tumor target? I'm asking not because it's WT1 or because it's AML, but just based upon the way that I perceive you've laid out all the other programs, there may be some learnings you want to take from a particular set of experiments, and this target and this blood tumor may give you the answer to those particular questions. I'm curious if that's correct and if you may share that. Thank you. I think it's an astute observation of how we think about our work. We try very hard to isolate a key variable, get the clearest answer that we can with respect to that variable, and then move on from there. In the case of engineered cells, we believe, as we've presented extensively in other venues, that a T-cell receptor-based approach brings with it tremendous opportunities and moves outside the fairly limited space that CAR T-cells are active in. What we wanted to determine was could we, with our approach, isolate healthy donor TCRs, develop an editing paradigm that introduced those TCRs into cells, and that we could show that they could work. What we tried to do is strip away all of the other potential confounding factors. Solid tumors have some. Liquid tumors tend to be less complex. They have their own complexity for sure, there's other factors that characterize solid tumors that don't apply in liquid tumors. We thought with AML and the high levels of WT1 expression that characterize this, it would be a wonderful test case for the overall thinking. We're excited to see if our preclinical work is on target. As David shared, we're at the point where we're going to find those things out because we're moving to the clinic by the end of this year. I'm grateful for your comments. There are no more questions in the queue. This concludes our question and answer session. I'd like to turn the conference back over to Ian Karp for any closing remarks. Great. Thank you so much, and thank you everyone for joining us today and for your continued interest and support in Intellia. We look forward to updating you on our progress, and we hope everyone has a great day. Bye now. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.