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Edited Transcript of NTLA earnings conference call or presentation 31-Oct-19 12:00pm GMT

Q3 2019 Intellia Therapeutics Inc Earnings Call

CAMBRIDGE Nov 20, 2019 (Thomson StreetEvents) -- Edited Transcript of Intellia Therapeutics Inc earnings conference call or presentation Thursday, October 31, 2019 at 12:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Glenn G. Goddard

Intellia Therapeutics, Inc. - Executive VP & CFO

* John M. Leonard

Intellia Therapeutics, Inc. - President, CEO & Director

* Laura Sepp-Lorenzino

Intellia Therapeutics, Inc. - Executive VP & Chief Scientific Officer

* Lina Li

Intellia Therapeutics, Inc. - Associate Director of IR

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Conference Call Participants

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* Amanda Louise Murphy

BTIG, LLC, Research Division - MD & Senior Biotechnology Equity Analyst

* David Matthew Nierengarten

Wedbush Securities Inc., Research Division - MD & Head of Healthcare of Equity Research

* Huidong Wang

Barclays Bank PLC, Research Division - Research Analyst

* Madhu Sudhan Kumar

Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst

* Maurice Thomas Raycroft

Jefferies LLC, Research Division - Equity Analyst

* Rick Stephen Bienkowski

SVB Leerink LLC, Research Division - Associate

* Silvan Can Tuerkcan

Oppenheimer & Co. Inc., Research Division - Associate

* Steven James Seedhouse

Raymond James & Associates, Inc., Research Division - Research Analyst

* Tashdid Hasan

ROTH Capital Partners - Analyst

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Presentation

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Operator [1]

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Good morning. My name is Derek, and I will be your conference operator today, and welcome to the Intellia Therapeutics Third Quarter 2019 Financial Results Conference Call. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

At this time, I will turn it over to Lina Li, Associate Director of Investor Relations at Intellia. Please proceed.

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Lina Li, Intellia Therapeutics, Inc. - Associate Director of IR [2]

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Thank you, operator. Good morning, and thank you all for joining us today to discuss Intellia's third quarter 2019 operational highlights and financial results. Earlier this morning, we issued a press release outlining our progress this quarter and the topics we plan to discuss on today's call. This release can be found on the Investors section of our website at www.intelliatx.com. This call is being broadcast live, and a replay will also be archived on our website.

Before we get started, I would like to remind you that during this call, we may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. All information in this presentation is current as of today, and Intellia undertakes no duty to update this information unless required by law. Joining me on today's call from Intellia are Dr. John Leonard, our President and Chief Executive Officer; Dr. Laura Sepp-Lorenzino, our Executive Vice President and Chief Scientific Officer; and Glenn Goddard, our Executive Vice President and Chief Financial Officer.

Following their prepared remarks, we will be open for Q&A, for which Andrew Schiermeier, our Executive Vice President and Chief Operating Officer; and José Rivera, our Executive Vice President and General Counsel, will also be joining. For today's call, John will begin by discussing the company's highlights, Laura will provide an update on our R&D progress, and Glenn will review our financial results from the third quarter of 2019.

With that, let me turn the call over to our CEO. John?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [3]

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Thanks, Lina, and welcome, everyone, to our third quarter earnings call. At Intellia, we're pursuing a full spectrum strategy to rapidly develop a diverse pipeline, including programs that apply genome editing in vivo where we deliver CRISPR/Cas9 components as a therapy and ex vivo, where we use CRISPR/Cas9 as a tool to create engineered cell-based therapies.

We continue to believe our modular approach and innovative science position us well to translate genome editing into new medicines that address critical areas of unmet medical need. To date, we've generated a robust set of preclinical data supporting our potential to cure genetic diseases with a single administration. And we're especially excited about the progress of our ex vivo approach, which we believe can capture the full promise of novel engineered cell therapies for the treatment of cancer and autoimmune disease. On the in vivo side, with our systemic lipid nanoparticle or LNP-based delivery system, we believe we have unlocked treatment of genetic diseases that have their origin in the liver. We've demonstrated we can selectively knock out disease-causing genes, and we can also precisely insert genes to produce normal human proteins for therapeutic purposes.

On the ex vivo side, we focus on engineering lymphocytes that retain normal cell physiology while targeting various hematopoietic and solid tissue cancers. Our approach to engineering lymphocytes is designed to overcome limitations of most currently available cell-based therapies.

In the third quarter and more recently, we've continued to progress our lead programs for transthyretin amyloidosis and acute myeloid leukemia and successfully executed on our objectives as we prepare to enter the clinic. And just last week, we presented data at the 2019 European Society for Gene & Cell Therapy Annual Meeting or ESGCT. These results included the first demonstration of a consecutive in vivo gene editing approach to address alpha-1 antitrypsin deficiency. This novel editing strategy provides further validation of our modular approach and, importantly, offers yet another proof point for the advantages of our proprietary nonviral delivery system for systemic administration of CRISPR/Cas9.

I'll now hand it over to Laura to review our R&D progress in detail. Laura?

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Laura Sepp-Lorenzino, Intellia Therapeutics, Inc. - Executive VP & Chief Scientific Officer [4]

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Thanks, John, and good morning. Indeed, this is an exciting time for us as we continue to validate our novel therapeutic modality and progress of our initial programs to the clinic. I would like to first talk about our in vivo pipeline, starting with NTLA-2001, our development candidate for the treatment of transthyretin amyloidosis or ATTR. As you know, ATTR is a progressive and fatal disease that results from the production of misfolded TTR protein in the liver and the deposition of insoluble TTR protein fibrils in multiple organs, leading to diverse disease manifestations, including peripheral neuropathy and cardiomyopathy.

Over 120 genetic mutations are known to manifest as hereditary ATTR, which affects approximately 50,000 patients worldwide. Furthermore, in the absence of a genetic mutation, ATTR can also develop spontaneously, known as wild-type ATTR, which affects an estimated 200,000 to 500,000 patients across the globe.

With NTLA-2001, our goal is to treat patients with ATTR regardless of whether they have either the hereditary or wild-type form of the disease because we will be knocking out the underlying disease-causing TTR gene. Over the past few years, our peers have made tremendous strides in serving patients with ATTR. They have validated the target and shown that reducing expression of TTR protein is an effective way to achieve clinical benefit. We hope to build on those results as both fundamental to the promise of gene editing with CRISPR/Cas9, and true to our mission, we believe that the potential to provide a onetime potentially curative treatment meets unaddressed need for patients and represents a key differentiating factor of our approach.

Today, we have demonstrated this potential in studies with our lead LNP formulation targeting the TTR gene in nonhuman primate. Following a single administration, we achieved an average reduction of greater than 95% of circulating TTR in nonhuman primate, which is expected to be clinically efficacious. As part of the ongoing durability study, we have demonstrated 10 months of durable liver editing with sustained reduction of circulating TTR protein. We're very pleased with these results and continue to advance our IND-enabling studies.

We also announced today that we have commenced clinical scale manufacturing for our Phase I materials and, importantly, we remain on track to submit an IND application for NTLA-2001 in mid-2020, which we expect to be the first systemically delivered CRISPR/Cas9 therapy in the clinic. As a reminder, for this program, we have a 50-50 co-development and co-commercialization agreement with Regeneron with Intellia as the lead party.

Let's now turn to our targeted insertion efforts in the liver. As discussed on prior calls, we demonstrated the first CRISPR/Cas9-mediated targeted transgene insertion in the liver of nonhuman primates using Factor IX inserted into the albumin locus. As a reminder, Factor IX encodes the blood clotting protein that is missing or defective in hemophilia B patients. This study used our proprietary hybrid delivery vehicle, which combines our CRISPR LNP delivery system with an AAV vector encoding the Factor IX gene. In a nice demonstration of the modularity of our platform, the CRISPR LNP delivery system is the same as the one used in our ATTR program, with the sole change being the guide RNA. We believe our targeted insertion approach provides key advantages over traditional gene therapy in both safety and efficacy. Targeted insertion should reduce the risk of mutagenesis due to random integration of retroviral vectors. In addition, targeted insertion should provide durable efficacy with single course of treatment and potentially cure the disease.

So we're working with Regeneron to identify next steps for the hemophilia B program and have been simultaneously exploring the insertion of other transgenes to support the expansion of our in vivo pipeline. As part of these efforts, and again, highlighting the modularity of our approach, we have exchanged only the DNA template for the gene of interest in the hybrid LNP-AAV delivery system. Building on our insertion work with Factor IX and alpha-1 antitrypsin, we have now generated in vivo protein expression for 2 additional genes of interest and are evaluating several more. These results are highly encouraging, and we look forward to presenting this innovative science at upcoming scientific meetings.

As John previewed, we reported at the 2019 ESGCT Annual Meeting, the first demonstration of a consecutive in vivo gene knockout and insertion in a mouse model of alpha-1 antitrypsin deficiency or AATD. This disease requires both a reduction in the level of the disease-causing protein and restoration of the wild-type protein to ameliorate the disease. The consecutive edits led to a greater than 98% reduction of the disease-causing protein and sustained restoration of the missing protein to therapeutically relevant circulating protein levels throughout the study. We believe this presents a compelling and differentiated therapeutic approach for AATD, as it addresses both the liver and lung manifestations of the disease. Moreover, this is another example of our leadership in systemic genome editing to treating genetic diseases. We will be moving forward with our consecutive editing strategy for AATD in higher animal species.

Moving on to our engineered cell therapy pipeline. We're designing engineered cells to create a range of hematological and solid tumors. As we discussed on prior calls, we have 4 work streams towards this end, so our focus today will be on our wholly owned T cell receptor or TCR replacement approach. Initially, we're utilizing this approach to target Wilms' Tumor 1 for acute myeloid leukemia and then potentially a variety of additional liquid and solid tumors. As a reminder, our proprietary and highly efficient TCR-based approach knocks out the endogenous TCRs by eliminating the alpha and beta chains and simultaneously inserts the therapeutic TCR in locus. Notably, the therapeutic TCR we precisely insert is a naturally occurring TCR that can be found in healthy donors. This approach should enable us to preserve normal T cell physiology, enhance and stabilize expression of the inserted therapeutic TCRs and reduce the risk of graft versus host disease that could result from mispairing between the endogenous and inserted TCRs.

In contrast to CAR-Ts, TCRs expand the range of addressable tumor types because they can recognize a broad set of tumor antigens, where CAR-Ts typically recognize only surface protein. In addition, we believe our TCR-directed engineered cell therapy approach offers meaningful efficacy and safety advantages over currently available engineers of therapy treatment.

As you know, acute myeloid leukemia or AML is a cancer of the blood and bone marrow with significant unmet medical needs. Generally, outcomes for the majority of AML patients remain poor and the 5-year overall survival rate is less than 30%. By directing TCRs or the Wilms' Tumor 1 antigen, which is overexpressed in the majority of AML patients, we believe it provides tremendous opportunity to develop a broadly applicable treatment for AML regardless of mutational background of a patient's leukemia. As discussed on our last quarter's call, we're currently conducting functional testing in patient-derived xenograft models of multiple lead WT1-TCR candidates that recognize the primary WT1 epitope of interest in AML with high affinity. Data from these ongoing studies will inform the nomination of our development candidate, which we remain on track to achieve by year-end.

In parallel to ongoing studies, we're advancing GMP manufacturing-related development activities in support of a Phase I clinical trial. We believe our AML program will lay the foundation to pursue a broader rate of cancers, including solid tumors. As WT1 is highly expressed across many liquid and solid tumor types, there is significant opportunity to target a number of subsequent tumor types with the same TCR, and we've begun to generate promising in vitro activity in solid tumor cell line. We expect this work will unlock new immuno-oncology opportunities to further expand our pipeline.

With that, I would like to turn the call over to Glenn, who will go through the third quarter's financial statement.

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Glenn G. Goddard, Intellia Therapeutics, Inc. - Executive VP & CFO [5]

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Thank you, Laura, and hello, everyone. Intellia remains in a strong financial position as we advanced multiple programs forward into development. Our cash, cash equivalents and marketable securities as of September 30, 2019, were approximately $295.8 million compared to $314.1 million as of December 31, 2018. The decrease was mainly due to cash used to fund operations of approximately $91 million, which was offset in part by $54.1 million of net equity proceeds raised from the company's at-the-market agreement, $8 million of funding received under the Novartis collaboration, $7.3 million of ATTR development cost reimbursements made by Regeneron and $2.8 million in proceeds from employee-based stock plans.

Our collaboration revenue was $10.6 million for the third quarter of 2019 compared to $7.4 million for the same period in 2018. As a reminder, our collaboration revenue is related to our partnership agreements with Novartis and Regeneron. Also, Regeneron funds approximately 50% of the development costs for our ATTR program. Our R&D expenses were $27.5 million for the third quarter of 2019 compared to $23.2 million for the same period in 2018. This increase mainly relates to the progress of our lead programs and our in vivo and engineered cell therapy platform efforts.

Our G&A expenses were $8.4 million for the third quarter compared to $8.3 million for the same period in 2018. This increase was mainly due to employee-related expenses. So finally, today, we are reconfirming that we expect our cash balances to fund our current operating plans through at least the next 24 months.

And now I'll turn the call back over to John to briefly summarize our upcoming milestones and corporate update.

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [6]

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Thanks, Glenn and Laura. In summary, we are extremely pleased with the achievements we've made so far in 2019. We continue to demonstrate our leadership in systemic genome editing with a potential first LNP CRISPR program in IND-enabling tox studies and several breakthroughs in editing approaches. In addition, we've seen our TCR-directed engineering cell therapy efforts move forward at a rapid pace. Looking ahead to the balance of the year, our team remains focused on advancing our lead programs for the treatment of ATTR and AML. We remain on track to nominate our development candidate for AML by year-end. And for our ATTR program, we're on track to submit an IND application for NTLA-2001 by mid-2020. We believe there is incredible opportunity ahead as we leverage our CRISPR-based platform and prioritize next programs to build a robust pipeline of in vivo and engineered cell therapy programs. We look forward to sharing plans for pipeline expansion in 2020, and I'm confident that we have the team and expertise in place to accomplish our mission.

With that, I'd like to thank you all for tuning in today. We'll now open up the line to any questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) And your first question comes from the line of Gena Wang with Barclays.

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Huidong Wang, Barclays Bank PLC, Research Division - Research Analyst [2]

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Congrats on all the progress, I'm really glad to hear the IND moving forward. So regarding the WT1-TCR program, just wondering what additional data we will see before you file for IND?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [3]

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Thanks, Gena. It's John. As we've said, we're working towards our development candidate. And there's a few finishing touches between now and the end of the year. We think we'll be in a position to share that data in an upcoming scientific conference in 2020 sometime, and we'll tell you when and where that will be when we're ready to go.

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Huidong Wang, Barclays Bank PLC, Research Division - Research Analyst [4]

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Okay. That's fair. And also, just wondering, given current, like, newly emerged technology, wanted to hear your thoughts on, I think, maybe last week, the Nature publication on the prime editing? And how do you see the field evolve over time?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [5]

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Well, all of these technologies are based off of CRISPR/Cas9, which is the core of the work that we do here. We haven't seen any format come out that makes us feel that we're using the wrong work -- or doing the wrong work or using the wrong technology. I think there's interesting data, but there's a long, long way to go before any of that will be ready for patient work. So we'll follow the field closely as it evolves and continue on with our own programs.

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Huidong Wang, Barclays Bank PLC, Research Division - Research Analyst [6]

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And the last question is regarding ATTR program. So the IND is mid-2020. I'm just wondering would that be -- what could be the initial dose? Are you looking for reaching minimum within the therapeutic window? And will you be thinking about single dose or multiple -- double dose?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [7]

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Well, we haven't designed the program finally yet. With respect to Phase I work, obviously, that's discussions that we'll have with regulators. As we've said previously, this is likely to be a single ascending dose, and it will be a balance between the appropriate place to begin from a safety point of view, and then we'll see the rate at which we can escalate into areas that would be expected to be therapeutic.

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Huidong Wang, Barclays Bank PLC, Research Division - Research Analyst [8]

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Would that be a 3 plus 3 trial design?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [9]

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We're not ready to talk about the trial design. There's lots of choices, and we're trying to do one that will enable us to move appropriately in patients as prudently and as quickly as possible.

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Operator [10]

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Your next question comes from the line of Maury Raycroft with Jefferies.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [11]

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Congrats on the progress. First question is just with the starting of your manufacturing of materials for both ATTR and WT1. Can you provide more specifics including anything on the supply chain, contingency plans and capacity? And how this might factor into expenses going forward?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [12]

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Good to hear from you. We're not giving any substantial details in terms of all of the pieces and how they come together. Obviously, this is an important part of moving the program forward, and we pay a lot of attention to it. We think we've put in place a plan certainly for ATTR that will get us well into the clinic so we can establish key data and go forward from that. And as WT1 evolves, we're assembling that supply chain as well. I think we have the benefit of learning from others who have gone before us, and we're applying those lessons. So more to come.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [13]

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Got it. Okay. And then for your WT1-TCR program, I know it's autologous. You alluded to the design in your comments. I guess with gene editing capabilities, you've got a lot of options. Just wondering if there's anything else in the works as far as novel modifications to enhance safety and efficacy with the TCR engineered cells that you're thinking about.

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [14]

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Yes. The first development candidate is, as you point out, autologous. We think that nicely isolates the key variable here, which is the T cell receptor. We presented data on the efficiency, the very, very high efficiency with which we knock out the alpha-1 beta chain and the very high efficiency with which we can introduce the TCR of choice. And we're very, very excited about that. We think that represents a real step forward in terms of this type of work. As we presented elsewhere, there's a series of other things underway to enhance how we can think about allogenicity. That's separate from this particular development candidate, but we're making very good progress there. And when it's appropriate to bring that into this program, we'll do so and share that data.

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Maurice Thomas Raycroft, Jefferies LLC, Research Division - Equity Analyst [15]

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Got it. And then last question just on AATD. The data at ESGCT was interesting. Just wondering if you can provide any more specifics on time lines for that program and for the NHP studies? And then separately, if you can talk more about the efficacy you're seeing with AATD and also with F9. And if those data are consistent based on the dose with what you're using in AATR to affirm that you can switch out guides and hit new liver targets.

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [16]

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So thanks for asking about that exciting data. We think it's another demonstration of the importance of modularity. And yes, the LNP format and the dose are essentially the same going from a model to model system. So we're excited about that. So first and foremost, it's a demonstration of that. That work was done in a mirroring system. There's work to extend that into nonhuman primates. And as that data evolves, we'll be talking about it at future presentations. But it's moving along very, very briskly, and we're excited about it.

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Operator [17]

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Your next question comes from the line of Mani Foroohar with SVB Leerink.

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Rick Stephen Bienkowski, SVB Leerink LLC, Research Division - Associate [18]

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This is Rick dialing in for Mani. Congrats on all the progress and all the great presentations at ESGCT. My first question is about the cell therapy program. Could you maybe discuss some of the next steps once the WT1 candidate is nominated and the anticipated time lines for how long you anticipate that the IND-enabling studies will take to complete?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [19]

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I was waiting for a second question there, but this is the first one. As I said earlier, in the WT1 program, we're in the final stages of selecting our development candidate. I would expect early next year, we'll share more details about what the time line is for progressing that program. So today, it's not the right time to be talking about IND time lines.

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Rick Stephen Bienkowski, SVB Leerink LLC, Research Division - Associate [20]

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Okay. Got it. I'll shift over to the alpha-1 antitrypsin program then. So just thinking about the competitive landscape for this disease, there are competitive oligonucleotide programs that are specifically going after the alpha-1 liver disease, and they're designing clinical trials with histological endpoints. So I was wondering, are there ongoing animal studies or you're specifically looking at reduction of PiZ protein in the liver or maybe histological improvement? And since these programs are specifically just looking to knock down the PiZ allele, just maybe share some of your thoughts on the importance of knocking out diseased PiZ allele versus restoring expression of the wild-type protein in this disease and what it could mean for competitive positioning for your program.

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [21]

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Yes. Thanks for the question. As you know, alpha-1 antitrypsin deficiency has 2 aspects to it. One is the liver disease, which is best addressed by knocking that protein down. Most of the pathology and morbidity and mortality, frankly, comes from lung disease. And to deal with that, you need to reconstitute normal levels of protein. The work that we did shows that we can address both. And that would be the format that we think is most clinically relevant and one that we would intend to bring forward. So to the extent that we achieve those normal levels as we continue our work of circulating protein, we believe that, that would constitute the best solution for patients and that's the bar we're setting for ourselves.

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Rick Stephen Bienkowski, SVB Leerink LLC, Research Division - Associate [22]

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Okay. As far as the histological endpoints for liver disease, is that something you'll be looking at in your ongoing animal studies?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [23]

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We've already shown in mice that you can have an effect, and that's certainly something that we'll continue to study as we progress the program.

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Operator [24]

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Your next question comes from David Nierengarten with Wedbush Securities.

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David Matthew Nierengarten, Wedbush Securities Inc., Research Division - MD & Head of Healthcare of Equity Research [25]

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I just had one curiosity. You're a little bit different with AML and having an autologous approach. Are there other safety or other preclinical data we should be looking for when we take a look at your efforts versus some of the autologous approaches for AML besides GVHD?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [26]

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Yes. Well, thanks for the question. Our approach with an autologous cell source, we think, is one of the very key aspects of addressing safety and then the precision with which one can introduce the chosen TCR in locus and eliminate the endogenous TCR change that could potentially mispair, we think, constitutes a real step forward for patients with this particular approach. So obviously, we study that in a variety of systems, some of them in vivo. And as we bring our development candidate forward at a future scientific meeting, we'll be in a position to share the results of some of those studies with you. But at this point, we're very excited about the activity that we're seeing, certainly in AML blasts as well as other solid tumors as we study them in vitro systems. And we expect that we'll have some exciting clinical candidates to investigate here next year and shortly thereafter.

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David Matthew Nierengarten, Wedbush Securities Inc., Research Division - MD & Head of Healthcare of Equity Research [27]

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All right. And maybe just a quick check. There's no difference or any reason to think there'd be any difference besides tumor biology or having -- besides solid versus liquid tumor between the candidates for solid and liquid tumors?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [28]

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No.

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Operator [29]

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We'll next go to the line of Amanda Murphy with BTIG Capital.

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Amanda Louise Murphy, BTIG, LLC, Research Division - MD & Senior Biotechnology Equity Analyst [30]

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I just had a question on TTR. Obviously, the Pfizer launch seems to be going pretty well there. I just was curious in terms of what the lessons learned there -- what the lessons learned are in terms of physician education and diagnosis. And it seems like there's a little bit of -- you obviously have a wide range in terms of the market opportunity and a little bit of discussion there. So just curious, your thoughts as that market evolves or how big it actually ultimately is both from a mutant and wild-type perspective?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [31]

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I'm not sure I heard all of the elements of your question, Amanda, but I think you're asking me about the market opportunity and how it's evolving for TTR. We clearly are watching it as it happens. We have some new entrants into that marketplace and, as you know, this is a market that didn't exist previously. So there's a lot of learning that will take place. Typically, in cases like this, we see the early estimates tend to underestimate what's actually out there as doctors learn to recognize the disease. And one might conclude from the early Pfizer data that, in fact, that's happening already. So as we put our program in place, we want to position ourselves so that we'll be able to address both aspects of this, both neuropathy and cardiomyopathy. We're doing it in a way that we can address TTR, whether it's mutated or wild-type. And a lot of work to do lies ahead, but we're very, very excited about the opportunity as we understand it better.

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Amanda Louise Murphy, BTIG, LLC, Research Division - MD & Senior Biotechnology Equity Analyst [32]

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Yes, that was -- I was asking just around the -- what we've learned so far on the Pfizer launch, but that makes sense. And then just another one on the TCR program. And I realize this is early, so I appreciate that this may be too early to ask a question, but obviously, you kind of focused on having a modular approach in general. So going forward, longer term, is the right way to think about expansion of indications really focused on WT1? Or would we also think about maybe target expansion or use of different targets going forward? And is that a 5-year kind of time line? Or is that potentially near term -- nearer term, rather?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [33]

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Right. So modularity is key to all that we're doing here, and that's certainly [poised] on the cell-based side as well. The way I would think about the first step that we're doing with WT1 is to validate the T cell receptor and the particular approach that we're taking. But that's immediately extendable into solid tumors, and we would hope to be in a position that we could pursue that very, very quickly or even shortly thereafter the AML program begins. Ways to expand on that include building out the TCR set and doing that across HLA types and then moving into other particular TCR targets. So we think once you have that basic module in place, there's many, many opportunities to move forward very broadly and very aggressively.

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Amanda Louise Murphy, BTIG, LLC, Research Division - MD & Senior Biotechnology Equity Analyst [34]

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Okay. And just last one on the bidirectional template insertion concept. Just curious how, I don't know if the right word, protected is that? I mean it seems pretty interesting and makes some sense. Is that something that you're pursuing in terms of patent protection, just obviously, again, going back to the modularity concept of insertion approaches?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [35]

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Yes. I'd rather not comment on the particular IP approach that we take. Certainly, as we bring our products forward, we expect to have many layers of protection. It's not just one thing or another. It's the various components as they come together for a particular therapeutic approach. And that's the way that we approach the potential products that we have here at Intellia.

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Operator [36]

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Your next question comes from the line of Steven Seedhouse with Raymond James.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [37]

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I had a question about the AATD strategy and data at ESGCT, where you're knocking out the diseased allele and then sequencing the second editing step to insert wild-type gene at the albumin locus, I think, 3 weeks later. I was just curious what are the pros and cons of sequencing those edits versus just multiplexing them at the same time because the 2 editing steps are targeting different loci. So I guess, theoretically, you could multiplex them.

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [38]

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Well, the first step was to carry out the experiment in a way that would be very, very clear. So we wanted to show that we had achieved the knockout and that we could then sequentially dose the LNPs, which is an important element of the study by itself and get an effect, and we demonstrated that. So that comes back to the very notion of -- the basic notion of redosability with LNPs, and we think we demonstrated that in this particular program. The optimal timing of when to do this is something yet to be worked out. I think that will be dependent on additional studies and data as we accumulate it going forward. But you should take this first experiment as already very, very exciting because it's not been subject to much optimization, but we're able to get very high levels of protein. But as we think about the ways to control that further, there's many ways to enhance the system and make it more efficient. So work that lies ahead, nonhuman primate data, et cetera. Stay tuned.

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Steven James Seedhouse, Raymond James & Associates, Inc., Research Division - Research Analyst [39]

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Okay. Appreciate that. And one short one on the optimization that you alluded to. What is the percent efficiency for wild-type gene insertion at the albumin locus that is getting you already to therapeutic levels of AAT?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [40]

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We haven't presented that data yet. So that will be upcoming work that we do as we pursue various targets. It's early days yet.

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Operator [41]

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Your next question comes from the line of Madhu Kumar with R.W. Baird.

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Madhu Sudhan Kumar, Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst [42]

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So our first one is, could you generally walk through the remaining steps for NTLA-2001 between now and the mid-20 IND submission? And then thinking about our clinical program for NTLA-2001, at a kind of broad strokes level, what is the target TTR suppression level you're looking to achieve? Are you looking for an Onpattro level of TTR suppression or something deeper?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [43]

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Thank you, Madhu. We don't give a step-by-step analysis of our work in the IND. There's -- general steps, I think, are broadly understood. Some of this is time-gated work that relates to the tox studies, and we're well into that. There's manufacturing of material, which we -- as we've talked about on the earlier part of the call, we've begun, and all of that stuff is on its way. We expect to hit the target of 90 of mid-2020 next year. And we're all working very diligently to achieve that.

With respect to the targeted suppression levels of TTR, we've learned from those that have come before us that levels below 60% are associated with therapeutic activity, and that's certainly foremost in our mind, but we want to hit the benchmarks that we think will represent a therapeutic advance for patients. So we are striving to achieve higher levels of suppression and would hope to exceed levels of 80% suppression of TTR and certainly demonstrate that we can do that in nonhuman primates. So it's all a question of moving into the human clinical situation and collecting data, but that is our benchmark at this point.

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Operator [44]

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(Operator Instructions) We'll next go to Silvan Tuerkcan with Oppenheimer.

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Silvan Can Tuerkcan, Oppenheimer & Co. Inc., Research Division - Associate [45]

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Congratulations on the impressive AATD data. At ESGCT, you also presented updated data in a mouse model in primary hyperox -- PH. What is your current thinking around the best target gene in between Hao1 and Ldha?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [46]

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So we continue to think about PH1. It's in our discovery group, and we've done a fair amount of research. One aspect that we've learned from that is the modularity of our system, and you should think of some of the data that we presented that way, take the LNP in across all of these different targets in the liver. Whether the PH1 targets alpha-1 antitrypsin or TTR, we've demonstrated that, that same LNP is useful against all of those targets. So part of the data speaks to that.

With respect to the best way to proceed in PH1, we haven't decided, but we've demonstrated that there's more than one way to be successful there. And how we advance that program, and if we advance that program, it's a function of some of the other choices that we've been working on. So stay tuned.

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Silvan Can Tuerkcan, Oppenheimer & Co. Inc., Research Division - Associate [47]

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Great. And with respect to the Novartis collaboration, that's coming to an opt-in decision point in December 2019, is there any update you can give us? Or how you think or what the plans are?

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [48]

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That's for Novartis to decide. And as appropriate, we'll provide updates, but none today.

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Operator [49]

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We'll next go to the line of Tash Hasan with ROTH Capital.

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Tashdid Hasan, ROTH Capital Partners - Analyst [50]

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Going back to data presented at the gene and cell therapy conference, in the mouse model of primary hyperoxaluria, it looks like, well, there's a very good correlation between reduction in oxalate levels and gene editing percentage. However, that seems to break down between 1 milligram and 2 milligram dose. I would like to hear your thoughts on this, if possible.

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John M. Leonard, Intellia Therapeutics, Inc. - President, CEO & Director [51]

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Well, I could go into all of the details of the data other than to say, generally speaking, there's a relationship between the extent of editing and the effect that you achieve. And the extent to which you knock out the gene of interest, that's going to have the attendant physiologic correlate. And that's work we've demonstrated across all the targets as, I think, you should expect. So it's not surprising.

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Operator [52]

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Thank you. And it does appear we have no further questions at this time. I'd like to turn the conference back over to Lina Li for any additional or closing remarks.

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Lina Li, Intellia Therapeutics, Inc. - Associate Director of IR [53]

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Thanks. And thank you all for joining today's call and for your continued interest and support. We look forward to updating you on our progress. Have a great day.

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Operator [54]

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Thank you. And again, that does conclude today's call. We do thank you for your participation. You may now disconnect.