Good morning my name is Mary. And I will be your conference operator today. At this time, I would like to welcome everyone to the Intellia Therapeutics’ Third Quarter 2018 Earnings and Corporate Developments Conference Call. Today’s conference is being recorded. [Operator Instructions] Thank you Ms. Lindsey Trickett, you may begin your conference.

Good morning and thank you for joining us today for Intellia’s conference call to discuss our third quarter 2018 earnings and corporate development. I’m Lindsey Trickett, Intellia’s Head of Investor Relations. For those of you on the phone, there is a presentation available for download at intelliatx.com, in the events and presentation section, so that you can follow along with us today. Before we get started, on Slide 2, you’ll find our forward-looking statements disclaimer. I would like to remind every that during our presentation and Q&A we may make certain forward-looking statements. And as you refer to our SEC filing 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. Moving to Slide 3, joining me on today's call from Intellia are John Leonard, President and Chief Executive Officer; Andrew Schiermeier, Executive Vice President of Corporate Strategy and Development and Interim Head of Research; Glenn Goddard, our newly announced Executive Vice President and CFO; and John Hayes, our Controller. Our primary speakers for today will be John Leonard and John Hayes. But we will all be available for questions during the Q&A. Moving to Slide 4. We’ll start the call with an update on our leadership team and update on the in vivo and ex vivo progress we are making in R&D and a review of our financials. On Side 5, I’d like to introduce you to two new members of the leadership team, of Intellia. Glenn Goddard, recently joined us as our Chief Financial Officer and Dr. Jesse Goodman recently joined our Board of Directors. We’d like to extend a warm welcome to Glenn and Jesse from the entire Intellia team. Now I’ll turn it over to John Leonard for R&D update.

Thanks Linsy. And thank you all for joining us today. I’m John Leonard, Intellia’s CEO. I’ll start today with Slide 7, serving as reminder of our long-term strategy. We’re building a full spectrum of genome editing company with balanced efforts across both our in vivo and ex vivo pipelines. We’re building modular platforms to create long-term value and that will achieve our mission to develop curative genome editing treatments that can positively transform the lives of patients living with severe life-threatening diseases. Note that with our in vivo approach, we first emphasize lipid nanoparticle or LNP based delivery to liver with the most basis edit a knockout. That work also serves as the basis for more complex edits such as gene insertion required to address other conditions and diseases of the liver. While the liver is the first tissue that we are pursuing with our LNP platform, our scientists are additionally working in parallel to apply LNP delivery to other tissue types. The right side of this slide depicts how we are taking a similar stepwise approach to ex vivo engineered cell therapy. We’ve chosen a T cell receptor based approach and targeted an important epitope of the Wilms’ Tumor 1 or WT1 antigen that plays a significant role in the blood-based cancer, acute myeloid leukemia. Moving beyond the limitation, so I come with autologous cell therapy is the key to success. And fundamental to our approach is building an allogeneic T-cell platform that goes beyond major histocompatibility complex one and two knockouts. This work promises to address the manufacturing limitations that typify autologous approaches and can service the basis for broad T-cell platform for Intellia. Another aspect of our approach is enhancing T-cells’ ability to intra solid tumors, which may rely on additional edits aimed at overcoming a solid…

Thank you, John. And hello everyone. I'm John Hayes, Intellia’s Controller. As you can see on Slide 20, Intellia is in a very strong financial position today. Our cash and cash equivalence as of September 30, 2018 were $293.2 million, compared to $340.7 million as of December 31, 2017. The decrease was primarily driven by cash expenditures from operating expenses of $78.1 million, which was offset in part by $16.6 million we received in funding from our collaborators. $10.1 million related to employee equity issuances, and $3.8 million of investment income. Our collaboration revenue was $7.4 million for the third quarter of 2018, compared to $7.3 million during the same quarter of 2017. As a reminder, our collaboration revenue is related to our partnership agreements with Novartis and Regeneron. Our R&A expenses increased to $23.2 million for the quarter. As we continue to expand both our in vivo and ex vivo platform development and progress our pipeline programs. Our G&A expenses increased $8.3 million for the quarter, which was largely related to increased personnel related expenses and other administrative expenses to support our growing research and development operations. Today, we are also reiterating our previous guidance, that we expect our current cash balance to fund our current operating plan through mid-2020. With that, I'll turn the call back over to Lindsay.

Thanks John. And thanks everyone for your participation today. We look forward to continuing to share our progress in the upcoming months. With that, I'll turn it over to the operator to manage the call lines of questions.

Thank you. [Operator Instructions] We can take our first question Maury Raycroft from Jefferies. Please go ahead.

Hi. Good morning everyone and welcome to Glenn and Jesse and congrats on the progress. The first question is for the Hybrid LNP-AAV approach. I am just wondering how you envision incorporating that into the development plans and would you bridge the technology into your initial ATTR program or is it designed for specific applications or disease indications?

Thanks for the question Maury, it's John. The hybrid approach is focused on repairs and insertion and our expectation is that the TTR program is best addressed by the knockout, so I don't see that hybrid approach really having applicability for that, but as you can imagine there's a long list of potential insertion targets to pursue. So we're excited about what we've shown with the two targets that we discussed today and we think that there's lots of places where we can take it in vivo and I want to make sure that you recognize that the approach of insertion in the [indiscernible], whether it's with the hybrid approach or not, has applicability to the ex vivo side as well. So we think this is a very significant move forward along our strategic plan.

Got it. Okay. And then for the bar graph figure on slide 8 just to clarify, so that's the same dose for each of the time points, and then I am wondering if you can specify whether the change that you've made over time is more heavily weighted towards the LNP the guide or the Cas9 and I guess what requires the most optimization there?

Yes, I wouldn't know how to score it more heavily one way or the other. We've been coming down a systematic path, looking at the various components, whether it's the lipid aspects of the LNP and that’s the constituents and how you put them together or the individual cargo elements contained within the LNP. So each of those have been tested and are the result of many, many experiments. So shown on the red are elements that address each of those individual aspects. The doses are the same doses, [indiscernible] a low and a high that we did way back in October. And those doses are shown in red graph here. Clearly we're getting a lot more out of dose and we did a year ago.

Okay. And last question is just on the IND timeline and if you can provide more granularity on what you're thinking first half of 2020 or second half?

Our approach now is under promise and over deliver Maury and there are very quick ways to get to an IND and there s longer ways and what our objective right now is to have the best performing LNP and with that guidance that we're putting out a very comfortable that we will get the work done on time.

Got It. Okay. Thanks again and thanks for taking the questions.

Thank you.

We will now take our next question from Gena Wang from Barclays. Please go ahead.

Thank you for taking my questions that I wanted to first, congratulations on a lots of the progress on the R&D part, I know actually for the investors I think, one pushback is always when the company can enter – I know that a, quite some other competitors already in clinic or ready to go into clinical development this year. So just wondering, I follow Maury’s question regarding the R&D filing. So can you just walk us through the steps you need to do a before R&D filing for the TTR program?

Yeah, Thanks Gena, it's John again. It’s interesting when you say competitors, I'm not sure, I know how you think about it. I'll tell you how I think about it, we take the view that we want to have a format that is the best possible agents that we can bring forward for any particular condition that we're going after, and I don't measure progress by first IND date. I measure progress by the best medicine that we can bring to patients and that's the approach here. So I don't want it to escape people's attention that the progress we've made here is broadly applicable across our pipeline and I think it enhances a, the product profile of probably virtually everything that we're working on. And secondly, I think deals with optimizations that we might had to play out for some of those individual targets. But, to the heart of your question in terms of what we need to do, as I said in my remarks, we want to extend the data here and that's done in very short order. We know exactly what we need to do in terms of building out the data set and some of the approaches deciding on what we choose to do here, given that there's a variety of ways to bring this all together. Some of the steps can be done very, very quickly it's really just a matter of swapping in versus swapping out and then going back to directly to PAC studies. That's why I'm comfortable in saying that in 2020, I fully expect to have an IND, I just don't want to tell you which month, but it's my objective to make that happen as quickly as possible.

Okay. That's very helpful; and I do want you to comment, if vivo approach is certainly much, much more challenging than the ex vivo approaches and certainly acknowledge the data you've provided at the EDGCT certainly a lots of progress? My next question is regarding the insertion approach. We know that’s similar concept with other technology is already in Phase 1 clinical trials. So of course I do see this as a much improved version, just wondering if you have any thoughts, what will be the next step you need to do a before you will be able to enter clinical development.

Yes Well, one of the programs we're doing in collaboration with Regeneron, so that's a discussion to have with them, but I think both parties when they look at that data are very enthusiastic, so we will progress that as quickly as we can.. I think Gena, the first order of business is to make sure that the work that we're showing here that we portrayed on Slide 8 is absolutely applicable to the insertion program as well. We will do that, that's part of this confirmatory work and with that, when it becomes a matter of capacity to a certain extent, I mean, we want to move very quickly, because we're a small organization, but believe me, we will put pedal to the metal as quickly as we can, when we believe we have a product that's going to be absolutely compelling in the market, but it goes back to the question you asked, it's about competition, which I view as irrespective of platform, irrespective of the modality. In the end, doctors and patients don't care about the particular treatment, they care about the results and we're trying to design a platform here and an approach that will be better than the choices that doctors and patients have. That's the objective.

Thank you. Just one last technical question regarding the hybrid insertion approach, just wondering if you, how thorough you detected it in terms of other forms of insertions in addition to transgenes like for example, AAV or other components that got inserted into the genome. Yes, Gena, I have to get back to you on that in terms of the extent to which that testing has been done. I can tell you this the transgene is as I said in my remarks introduced at the cut site. It's introduced at the cut site – we've demonstrated insertion with the specificity that we think is highly desirable with the program, AAV insertion is at least protected by the presence of protein, the first place it doesn't occur. The extent that the sequencing results which I think is what you're asking me and we can get back to you separately.

Okay. Thank you very much.

Thank you.

We will now take our next question Martin Auster from Credit Suisse. Please go ahead.

Hi. Thanks for taking my question. I had a follow-up on Slide 9, where you're showing the range of effect and the percent of the TTR knockdown in the year with the new construct. It looks like you've got about between kind of 20% and 80% genome editing rate with I believe that's you said that's all from a single dose. Just curious, are you satisfied with that degree of variability? Are there methods you can employ to kind of work to further narrow that and ensure kind of a higher portion of subjects or achieving the therapeutically relevant range here? Thanks.

Thanks Martin. The red dots here correspond to changes in different complex. So, not every single red dot is identical. So that's one way of approaching the variability, showing data from only a single change, but this is portrayed here to demonstrate that there's multiple levers for us to flow, to get what, in our hands is a substantially different from the effects that we've been talking about up until now. Variability, I think it is inherent to populations in general, but it is something in the next few months that we'd like to attempt to reduce. I don't think we're ever going to get to a point which is true for any drug, where every dot is superimposable on the others, but it's always preferable to have less variability to mark.

Thanks. And then just one follow-up, I think since the – since the markets have gotten a little choppier on October, we've been getting increasing calls from investors in kind of really focusing on balance sheets. You guys are actually in a very strong position now with good capital position, but I'm curious how you're thinking long-term because it is going to be a period of time before you have improved products, in kind of sustainable revenue from product sales, how you're thinking about forming new strategic partnerships, and kind of what areas you kind of consider to be most attractive to license order kind of work with a partner on. Thanks.

Yes, thanks. Thanks for the question. I’d first point out that the situation hasn't changed for us. I mean in terms of the resources that we have and where we think they'll take us, that's really unaffected by this and we feel very confident. We'll be able to complete the work and make the headway that we need to. How its fundamental to our work has been having a broad base, this is this full spectrum notion that we have. As you see here today, we think there's any number of projects that we have that have attraction to a potential partner should we choose to go that route. So rather than doing one thing, some people would like us to do that. I think having a choice of things that we can do very well and differentiate ourselves on is the way to proceed. So whether it's the insertion, whether it be a knockout, whether it' be a modular approach on ex vivo side. If we need partners, I'm confident. We will have many to choose from.

Great. Thanks for the answer. Appreciate it.

We'll take our next question from Joseph Schwartz from Leerink Partners. Please go ahead.

Yes, hi good morning. Thanks for taking the questions. This is Dave on diving for Joe. So couple from me, I guess I'll just dive right in since a lot of the questions have been answered. So if we look at just the TTR program specifically, I was just referring back to Dr. Yong Chang's presentation at ESGCT where in one of the slides he was highlighting, which you've referred to as the previous version, whereas for genome editing with about 34%. But right next to that he was also showing the TTR protein knockdown of roughly 70% by meaning and that was on day 30. So if we look at the updated enhanced version today, you'd say TTR knockdown mean of 78% but up to 96%. So I'm just wondering what exactly changed here or if I'm missing anything? And just as a follow on to that how much of a TTR knockdown is really best for I guess patient outcomes since you highlight that greater than 60% knockdown of therapeutic? And I've got a couple of follow up, thanks.

Yeah, so I don’t have his presentation in front of me. I’d point out a couple of things. First of all, we're showing day 21 affects here with the most recent data. And this is a system that equilibrates over and even longer period of time. So I would expect to have additional data that we'll be able to talk about as time goes on. How much is the right amount? Well, we are of the belief that more is better. And if implicit in your question is there a point where it's too much. I have not seen that data. I have not seen anything that makes that case convincingly. I think that when we look at the other agents that are out there and this is why we've chosen the 60% decrease as our target. When TTR levels fall into that range, patients get better. It's just they do. They don't progress and that's a very good thing. The extent to which products may differentiate themselves within that box is something I think we're going to learn more about. But our thesis is pretty straightforward, which is this is a protein that's doing bad things and having less of it is probably desirable. And the likelihood of not making it I think is not something that we have to worry about at this point with any of the approach that’s already here.

Great, thanks for that color. Just two more, one with regards to the TTR program. So with the new enhanced version, you can now use low dose with I guess a much higher efficacy than what you saw with the previous versions of your components. But any way you can disclose what kind of safety profile or AEs you've seen with the previous version when you were using the high dose? And that I'm assuming you've overcome that with the new enhanced version. And my last question is on your LNP AAV hybrid approach. I'm just wondering if you could provide some context or some more granularities on the AAV and LNP doses that you’d use. You’ve mentioned that you can modulate based on the doses of each component. And what kind of effects you see in terms of antibody emergence or T cell responses to the Factor IX? Thank you.

Yeah, I don't think I can be able to address your antibody question today here. In terms of the doses for the hybrid approach, these are doses within the range of what we've already been working at. And the comment I made about being able to modulate, there is a relationship between varying one or the other elements of it and that can set the degree to which the insertion actually takes place. So, it's possible with the Factor IX to achieve super therapeutic levels. And one of the things that I think we want to really understand is how to set that. So it's just right for the patients who need it. And then again I would emphasize that that's work that we're doing in collaboration with Regeneron. So that will clearly have a lot to say about that. But the point I think you should take away is that we're not stretching to make it work. We have a range of different approaches at least in these animal models where it works [indiscernible]. So we're very excited about that. In terms of safety, we've presented data in the past that shows that when LNPs are provided, you can have a brief response with some cytokines and low level LNP elevations. And that profile hasn't really changed with any of the new material that we're working on here.

We will now take our final question from Steven Seedhouse from Raymond James. Please go ahead.

Hi, good morning. Thanks for taking my questions. John, I just had a theoretical question. Just thinking about the relative editing efficiency and variability of those NHP data sets that you're showing on Slide 8 so for indications that you can use just LNPs without the AAV component like ATTR. Do you think it's more desirable once you get into like ATTR? Do you think it's more desirable once you get into the clinic to start at a low dose and enable redosing to titrate to very precise editing levels? Or would it be preferable to try and get to maybe therapeutic editing levels at the first dose, avoiding having to re-dose and maybe accepting more of that variability or higher editing than you might even need for full effect?

Thanks for the question. I don't think that's a theoretical question. Well, I think it's a very practical question, which is when it actually comes to dosing a patient, how should one proceed. I think about this way. You want to have choices, right. You want to have the capacity to do whatever is right for the patient. So, ideally we would like to have the ability to get to where we need to be in a single dose. And this data I think is consistent with that kind of a trajectory. So we're very excited about, but there's a lot of learnings that take place, so the course of this clinical program, which is true for all modalities. And the ability to come back and dose again if one starts from a very low dose is another desirable aspect to have. One of the beauties of TTR and one of the primary reasons we chose it is that effect is readily measured. There is a circulating protein that can be detected and just as we've shown with our animal data here, we get a pretty good idea of where you are. So instead of flying blindly, one can measure the TTR effect. And in theory, back to your word, set this target exactly to a particular TTR level. So that will emerge I think as the program proceeds and as we entered the clinic. Bottom line for patients, you know, if all those plays out the way we think it's headed right now is that whether it's one or a very brief treatment course. Patients will have the ability to be treated and presumably for a very, very long time, perhaps even the rest of their lives have the offending agent of their disease reduced to the point where it's not an issue. So that's what we're working on.

Okay, I appreciate that. Maybe just to follow up, last question. So since you can measure TTR, again thinking ahead to initial clinical trials, are you expecting that you would want to or need to collect liver biopsies and assess gene editing at the DNA level in your initial clinical studies? And also are you anticipating needing or wanting to immunosuppressed patients at least initially in the first ATTR trial? Thank you.

Thank you. Yeah, uh, I don't know why the biopsy would be necessary. It's not fundamental to understanding the therapeutic effect because as I said before the offending agent is the protein. And there's a correlation between the extent of the edit and the level of protein that's achieved. So, you know, not to make light of it, but doing a liver biopsy is almost just spectator support. It's to know as opposed to judge what is the right regimen for the patient because again, it's about getting to the TTR protein levels. And again that's one of the reasons why we chose this particular target. In terms of immunosuppressing patients, that's not been part of our program so far, and if we see reasons to include that, that's fine. We would do that. It's – one of the appeals of this is that given the short treatment course that we would anticipate that shouldn't be an issue for patient as opposed to having potent immune suppression applied every two to three weeks when, you know, regimen is taken lifelong for patients. So if it is necessary and right now we don't see indications that it is. We will certainly explore that. But again, I don't think that that's a major issue for us.

Thanks very much.

Thank you.

The Intellia Therapeutics third quarter 2018 earnings conference call is now concluded. Thank you for attending today's meeting and presentation.