Q4 2022 Intellia Therapeutics Inc Earnings Call
Speaker 1: We shared additional positive results from the ongoing Phase 1-2 clinical study at the American College of Allergy, Asthma, and Immunology 2022 Annual Scientific Meeting this past November . The data presented demonstrated that a single dose of 2002 led to robust reductions in plasma calor crime and HAE attack rates. For the 25 milligram and 75 milligram cohorts, these deep reductions in plasma calor crime were sustained in all patients through data cutoff, which ranged from week 16 to week 32. Importantly, all patients dosed in these two cohorts who completed the pre-specified 16-week observation period have maintained an attack-free status as of the data cutoff date. Patients in the 50 milligram cohort have not yet completed the primary 16-week observation period before the presentation cutoff date, and so we look forward to presenting attack rate data on this cohort later this year. At all three dose levels, 2002 was generally well tolerated, and the majority of adverse events were mild in severity. The most frequent adverse events were infusion-related reactions, which were mostly Grade 1 and Grade 2. The results were not yet resolved within one day. No dose-limbing toxicities, no serious adverse events, no adverse events of Grade 3 or higher, and no clinically significant laboratory abnormalities were observed. We believe these data speak to 2002's potential to address the significant disease burden
Speaker 1: faced by people living with HAE by permanently preventing the debilitating swelling attacks with a single dose. We look forward to presenting additional data from the Phase 1 portion of the study in 2023, including longer-term safety, and more.
Speaker 1: durability and the TACRAT data across all three cohorts. As John mentioned, it's been a very productive first two months of the year, especially for the 2002 program. In January until he was awarded the Innovation Passport in the United Kingdom for 2002, which provides entry to UK's innovative licensing and access pathway.
Speaker 1: We're pleased to receive the iLAP designation, which aims to accelerate time to market and facilitate patient access to innovative medicine.
Speaker 1: Today, we announced that Intellia has initiated patient screening in the phase two portion of the study in New Zealand.
Speaker 1: The phase two portion, a randomized placebo controlled expansion study, is evaluating two doses, 25 milligrams and 50 milligrams.
Speaker 1: We anticipate expanding country and site participation in the coming months.
Speaker 1: To support inclusion of patients in the United States, Antelia recently submitted an IND application to the FDA, and we look forward to providing you with an update on the status of that application's review.
Speaker 1: As 2001 and 2002 continue to progress, we believe we are moving closer to setting a new standard of care for people living with these serious diseases.
Speaker 1: I'll now hand over the call to Lara, our CSO, who will provide updates on our R&D efforts and platform advancements.
Speaker 2: Thank you, David. We're entering the next stage of growth at Intellia as we advance new platform capabilities to the clinic, such as in vivo gene insertion, our allogeneic technology and base editing.
Speaker 2: For targeted individual gene insertion, we're progressing both wholly owned and partner programs leveraging our modular insertion platform.
Speaker 2: This includes NTLH31, our wholly owned candidate for the treatment of AADD-associated lung disease, for which we plan to submit an IND or IND-equivalent application in the second half of this year. In parallel, we're advancing IND-enabling activities for NTLH23, our third in vivo knockout candidate as it treatments for NTLH23.
Speaker 2: and those shared with partners utilizing our proprietary allogeneic platform.
Speaker 2: These platform capabilities demonstrate the already broad opportunity of our robust research engine, but there is still more on top potential and so we're further pushing the boundaries of what therapeutic gene editing can do. We have made rapid and significant headway with the development of our proprietary DNA60 Morrison Review.
Speaker 2: platform capability, offering massive potential to target diseases beyond those currently being exploring our pipeline.
Speaker 2: And now hand over the call to Glenn, our CFO , who will provide an overview of our fourth quarter and full year 2022 financial results.
Speaker 1: Thank you, Laura. Good morning, everyone. Intellia continues to maintain a strong balance sheet that allows us to execute on our pipeline and platform. S ya
Speaker 1: Our cash, cash equivalents and marketable securities were $1.3 billion as of December 31, 2022, compared to $1.1 billion as of December 31, 2021.
Speaker 1: The increase was driven by $337.9 million from our December follow-on offering.
Speaker 1: $227.9 million of net proceeds from the company's at the market program.
Speaker 1: and $17.2 million in proceeds from an employee-based stock plan.
Speaker 1: The increase was offset in part by cash used to fund operations of approximately $372.8 million and the acquisition of Rewrite Therapeutics for $45 million.
Speaker 1: Our collaboration revenue increased by $0.7 million.
Speaker 1: to $13.6 million during the fourth quarter of 2022.
Speaker 3: compared to $12.9 million during the fourth quarter of 2021.
Speaker 3: Our R&D expenses increased by $28.9 million to $100 million during the fourth quarter of 2022 compared to $71.2 million during the fourth quarter of 2021.
Speaker 3: This increase was mainly driven by the advancement of our LEAD programs.
Speaker 3: personnel growth to support these programs.
Speaker 3: Our GNA expenses increased by $1.5 million to $23.6 million during the fourth quarter of 2022 and paired to $22.1 million during the fourth quarter of 2021.
Speaker 3: This increase was primarily related to employee-related expenses.
Speaker 3: Finally, we expect our cash balance to fund our operating plans beyond the next 24 months. With that, I will now turn the call back over to John for closing remarks.
Speaker 3: Thank you, Glenn. As you can see, we're making steady progress towards executing against our strategic priorities, which are focused on late-stage development of our CRISPR-based therapies, while continuing to innovate and bring forth new platform capabilities.
Speaker 3: This year, we look forward to advancing the Phase 2 portion of the NTLA-20-02 study and expect to add US clinical sites.
Speaker 3: We're also focused on preparing for the initiation of a global pivotal trial of MTLA-2001 for patients with a cardiomyopathy manifestation of ATTR amyloidosis.
Speaker 3: For both programs, we plan to provide further updates in the coming months.
Speaker 3: As we continue to deliver on the promise of gene editing, we maintain our broader vision for Intellia by rapidly expanding the reach of our platform to accelerate the impact on patients.
Speaker 3: With that, we would be happy to answer any questions.
Speaker 3: Operator, you may now open the call for Q&A.
Speaker 3: We will now begin the question and answer session.
Speaker 3: To ask a question, you may press star then 1 on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys.
Speaker 4: If at any time your question has been addressed and you would like to withdraw your question, please press star then 2.
Speaker 4: Please limit yourself to one question.
Speaker 4: At this time, we will pause momentarily to assemble our roster.
Speaker 4: The first question comes from Maury Raycroft with Jefferies.
Speaker 4: from Maury Raycroft with Jeffries. Please
Speaker 5: Hi, good morning. Congrats on the progress, and thanks for taking my question. I was going to ask about the HAE IND...
Speaker 5: I'm wondering if you're commenting any more on what exactly FDA requested to be in the IND and what you included in the IND for the Phase 2, and do you expect a typical IND acceptance timeline for that program? Hi, my name is face.
Speaker 3: Maury, good morning. Thanks for your question. It's a pretty standard application and aligns with some of the comments we've made in prior communications of what the FDA is looking for. I think where this IND may differ from other INDs is that...
Speaker 3: We're pretty far along from a clinical point of view and we were able to supply clinical information from the ongoing study done outside the United States. So we were of course careful to provide a very, very careful and complete update of that information. Otherwise, I'd say it's pretty standard stuff.
Speaker 5: Okay, and maybe one follow-up, just if you could talk a little bit more about the Phase II design and types of patients and how you can leverage the data for potential streamlined pivotal study in HAE.
Speaker 3: So David, do you want to address that?
Speaker 1: Yeah, so the phase two is shown it publicly, it's in our slides, but basically it's three arms. There'll be an arm at 25 milligrams, an arm at 50 milligrams, and a placebo arm. And the size is 10, 10, and five patients. And the idea here is to select the dose for the pivotal study. We have obviously some very good information already from the phase one being...
Speaker 1: Really excellent results at all three doses.
Speaker 1: 50 and 70 looked very much the same in terms of pharmacokinetics, so we did choose the lower dose.
Speaker 1: possibly being a safer dose. And the 25 milligram dose as well is quite good, but did look a little different in terms of pharmacokinetics.
Speaker 1: So that's really the trial. It will be informing our phase three, which we are already thinking about the design and getting ready for. It will contribute to the eventual BLA by additional information about patients. So that's the main use of the trial.
Speaker 5: Okay, thanks for taking my questions. I'll hop back in the queue.
Speaker 4: The next question comes from Greg Harrison with Bank of America. Please go ahead.
Speaker 4: Hey, good morning. Thanks for taking the question. I wanted to ask how you're thinking about the future of the curative sickle cell landscape now that some competitor is a discontinued investment in the space. What do you think will be the next step beyond the CRISPR vertex approach and how do you win there?
Speaker 3: Yeah, thanks for the question. It's an important one and one that we certainly thought about even from the early stage of the company. I think what we've seen is that
Speaker 3: sickle cell is curable. I mean, that question in our judgment has been answered and I think that's great news for patients. The challenge for those patients, however, is the nature of that cure. The editing, I think, is in hand. It's the application of that editing that...
Speaker 3: where we believe we can make significant progress. So we've been focused really since the outset as we've thought about that disease, doing it in an in vivo setting where one can avoid a bone marrow transplant and the morbidity and occasional mortality that comes with that. That's a more general solution.
Speaker 3: for patients. And in fact, I think it's a very, very broad-based solution, even for patients outside the standard Western markets where most patients with sickle cell reside. So that's where we focused our efforts. From our perspective, based on what we've seen, that space is wide open.
Speaker 3: and we intend to get there first.
Speaker 3: and we intend to get there first. Great, that's helpful. Thanks again for taking the question.
Speaker 4: The next question comes from June Lee with Truist Securities. Please go ahead.
Speaker 6: Hi, good morning. This is Mehdi for June . I will follow up on the previous question and asking what is your strategy now? Is it that you're following the same type of edits for sickle cell?
Speaker 6: And what would be your delivery mechanism? And I have a quick follow up question.
Speaker 3: Well, thanks again. Our strategy hasn't changed for some years now. We've always been focused on the in vivo setting. Just to be clear with respect to the Novartis news, that was an ex vivo only application.
Speaker 3: one that has been followed by them and others in the space. For us, we've always focused on the in vivo setting.
Speaker 3: From an editing point of view, we think there's any number of potential edits that can be successful. And our particular approach is not one that we've disclosed, but what I think we've learned is that the disease is curable. So it's really a matter of delivery.
Speaker 6: and making sure that that's done in a way that is robust and works well for patients. Awesome. And could you please provide some color on your handwriting?
Speaker 6: system any idea is it similar to existing techniques
Speaker 1: out there like PACE and 2MPE or is more similar to homologous recombination, any color in that domain would be appreciated, thank you. Yeah, we're not disclosing the specifics. We think about it in terms of capabilities, which is the resulting gene edit.
Speaker 3: In our case, we're most interested in what the resulting change in the DNA is and the specifics of how you get there. The particular enzyme system is proprietary and one that we've worked with about. We're excited about our ability to introduce the intended changes and do that with great fidelity and great specific...
Speaker 6: Thanks for taking our questions.
Speaker 4: The next question comes from Swatneel Medakar with Piper Sandler. Please go ahead.
Speaker 7: Good morning. Thank you for taking my question. So you had previously mentioned the likelihood of having an interim readout for the pivotal trial in ATTR cardiomyopathy. So I was just wondering like how the new emerging data and the new emerging clinical endpoints that you mentioned in the press release are informing this decision of an interim analysis.
Speaker 3: David, do you want to address that? Just to be clear, we're not talking about sharing interim results of a pivotal trial. Maybe David, you could just clarify what our plans are with data disclosures for the ongoing study. Sorry, I went just in terms of clinical trial design if there will be an interim analysis.
Speaker 1: Okay, yeah. So for the phase three, as you know, we're designing that now. We're not talking about the exact details. But we have said that we think the important end points are cardiovascular events and mortality. And we've seen some of the other trials out there. There's have to be a large trial to study these questions.
Speaker 1: We'll have a big advantage as we start to do our trial and that we may see early results from the other trials which will help inform how we design this trial. But we are considering whether interim analysis would be valuable here. Because we have the best reduction in TTR, we also expect to have the best efficacy in that trial.
Speaker 1: And because of that, the trial could be positive in interim analysis, and we're looking carefully at that possibility.
Speaker 7: Got it and one follow up I had is. So you mentioned that there have been like more than 50 patients dosed across two programms, with some of the patients reaching two year Mark. I was just wondering is there were any relapses in ktr or caligram in any of the patients that that?
Speaker 1: we do expect the effects to be permanent.
Speaker 4: The next question comes from Gina Wang with Barclays. Please go ahead.
Speaker 8: Hi, good morning. This is Harshita on for Gina. Thank you for taking our questions. Can you hear me? Okay?
Speaker 8: We can. Awesome. Thank you. This is a question that I have been asking for a while.
Speaker 8: For NTL8-2002, are you able to disclose how recently you submitted the IND? And how will you communicate to the investor community the outcome? Can we expect a press release?
Speaker 3: We're not sharing when we submitted the IND. We're giving a broad update today, and so that's part of that process. But we will, of course, share the results of the FDA review when we have that information, just as we promised from the outset here. So stay tuned, and hopefully we'll have some favorites.
Speaker 8: that we can expect data on, that would be great. Thank you so much.
Speaker 3: David, what lies in store?
Speaker 1: Yeah, so what we're looking at, you know, the patients have been longest on the trial where we would possibly have the most information of the patients with polyneuropathy. Some things we've looked at in those patients include the NIS score, the NIS, which is a slightly different from the MNIST plus seven but gives similar information on the neuropathy symptoms. Another thing we're looking at is cardiac amyloid.
Speaker 1: This is present both in polyneuropathy patients and in the CM patients.
Speaker 1: So those are the type of things that we may have enough information on later this year.
Speaker 4: The next question comes from Terrence Flynn with Morgan Stanley . Please go ahead. Thanks.
Speaker 9: Great, thanks so much for taking the questions. I was just wondering if you think broadly about the pipeline. I know you did the rewrite therapeutics deal, but just thinking more broadly, do you think there's a need for any additional business development or do you think you have all the tools you need? You are also Hello,
Speaker 9: at this point, John . And then one kind of second question, which again, not sure if it's applicable or not, but yesterday a CRO announced some supply chain issues with non-human primates. And I was just wondering if that might impact any of your preclinical worker timelines. Thank you.
Speaker 3: Yeah, thanks for the question. Yeah, we read the same news and have inquired. We're not aware today that there's any impact on the work that we're doing.
Speaker 3: And we hope that that doesn't change, but that's the current situation. With respect to BD, we think about it two ways, I guess. You asked about it in terms of tools.
Speaker 3: an important part of our strategy is to have a toolbox that is complete. And we think about that in terms of the capabilities, in terms of those different changes that we want to be able to introduce into DNA.
Speaker 3: We think we've got a great toolbox. We watch what's happening on the outside. We have our own scientific efforts internally.
Speaker 3: you know, look for new capabilities that we think would augment the toolbox. At this point, we're pretty satisfied with the things that we want to do, but of course, we'll keep our eyes open. I think the broader approach to DD for us is just thinking about
Speaker 3: deploying that toolbox, not bringing things into it. What we're seeing is all kinds of wonderful opportunities.
Speaker 3: some of which were advancing ourselves, some of which were advancing with collaborators. And you know in the last 18 months we've had four different collaborators that four different collaborations that we've struck augment the work that we do in our own pipeline. So whether it's ophthalmology with sparing vision, autoimmune disease with kyverna.
Speaker 3: our spin out with Evancell or work in NK cells with LNK, these are really exciting applications of the capabilities already in hand and we expect to do more. And I think if you step back and look at our pipeline in...
Speaker 3: Bear in mind the clinical rights that we have, commercial rights that we have from each of those different collaborations. You see that this is, especially for a company like this size, a wonderful pipeline that's complete with opportunities. So, BDS, toolbox, good.
Speaker 3: with a lot of internal work going to make sure that it remains unsurpassed.
Speaker 4: The next question comes from Luca EC with RBC.
Speaker 10: Please go ahead.
Speaker 11: Oh, great. Thanks for taking our questions and congrats on all the progress. This is Lisa on Felucca. Just one on the Cardiomyopathy Pivotal trial. Just wondering if we should expect two trials here, maybe one with the six-minute walk test as the primary endpoint and another with cardiovascular-based outcomes study.
Speaker 3: And maybe on sickle cell disease, can you expand further on why Novartis decided to discontinue the program? And if there is any clinical data available, will you be in a position to share it? Yeah, I can't speak to Novartis' decision other than they've been going through what appears to be a broad review of their pipeline and their different approaches to it. Thank you.
Speaker 3: I'm sure they looked at the ex vivo space and may have had some of the same realizations that you know we had some years ago. So I think it's apparent where that space will ultimately go. But David, maybe you can ask or answer the question about pivotal trials. How many do you actually want to do?
Speaker 1: We're, you know, we would, again, we're not telling the exact program, but we don't think that dividing those things into two trials is a great idea going forward. So the six-minute walk test, there's been more questions about how valuable it is to understanding how patients are doing, and you've seen that in some of the recent trials in amyloidosis. And so we'll continue to images throughout it, the paper can refer to the
Speaker 1: But again, we think the important endpoints are cardiovascular events and mortality. And that's what the patients are interested in, the doctors are interested in, the payers are interested in. So it's really what we're most interested in. The regulators, of course, are very interested in those factors.
Speaker 10: Great, thanks for taking our questions. The next question comes from Yanan Zhu with Wells Fargo. Please go ahead. Stay tuned.
Speaker 10: Hi, thanks for taking my question. On the HAE program, I was wondering what's the reason or rationale for having this placebo arm in this Phase II study?
Speaker 10: Also, in terms of the goal of the treatment for this one-time treatment approach,
Speaker 10: Do you think a complete cure is kind of the expected outcome for this type of approach? Or there could be a different kind of outcome and still appropriate for this approach? Thanks.
Speaker 3: David, what role does placebo play and what's the aspiration?
Speaker 1: Sure. So the placebo, having placebo-controlled trials are the gold standard in randomized trials. Of course, you don't expect them to benefit in the placebo arm, but of course you've also seen there can be a strong placebo effect in many trials. And that's the risk of not having that arm to compare. It's not a comparative trial, it's a phase two, but it's a reference arm to see that.
Speaker 1: to cross over and get the active drug once their evaluation is completed. And of course, we do this because of the contribution they are making to our study and their desire to get this type of therapy as part of their potential cure, going to the second part of this. This idea of a functional cure is what – the idea that you could get to zero attacks in patients with this single treatment.
Speaker 1: And whether we can achieve that is, you know, it's too early to say. We're very encouraged by the early results. We are getting deeper reductions in calicrime than is achieved with the best agents that are out there. So it is possible that this will also lead to better efficacy.
Speaker 1: And again, this aspiration to have a functional cure or to patients to have no attacks after receiving our drug.
Speaker 10: Great, thanks. If I could have a quick follow up on the cardiac amyloid you mentioned that might be a readout for the 2001 program. Just wondering, it's the expectation that the cardiac amyloid will be resolving or...
Speaker 10: is the expectation that it is just stabilizing and no more additional amyloid addition. Thanks.
Speaker 1: This isn't been well established. Of course, there aren't therapies that get to the very low levels of TTR that we're able to achieve. But the idea we have, and we hear from the key investigators in this area, is that if you do get to low enough TTR levels, you will be rate of amyloid deposition into organs.
Speaker 1: will be so reduced that the equilibrium will be the other way. In other words, the removal of amyloid from the heart greater than the addition of amyloid due to the small amount of TTR that would be in the blood at that point.
Speaker 1: So that's what we're hoping to. The idea then is a possible reversal of the heart disease by getting rid of that amyloid and that is our aspiration for that trial.
Speaker 10: Great. Thank you for taking the questions. The next question comes from Salveen Richter with Goldman Sachs. Please go ahead.
Speaker 12: Hi, this is Shrinathra on for Sarveen. Thank you so much for the update. Could you provide some color on the nature of discussions that you're having with regulators regarding the global pivot and study for NTI-LA-201 in both ETTR, CM and PN, and also regarding NTI-LA-202 help.
Speaker 12: are you regarding the IND acceptance, and do you have any timelines in mind about when we get this information?
Speaker 3: Maybe, David, you can address how we think about the pivotal and when we'll be in a position to share information. I just, with respect to the IND, I would say it this way. We've had a variety of interactions with various regulators, including the FDA, in the run-up to this.
Speaker 3: We believe that we're addressing the questions that they wanted us to address. It's not just the list of those questions, but it's the extent of the data that we've tried to provide that actually goes to making sure that...
Speaker 3: We're not just checking boxes, but we're really answering questions and helping them to evaluate the product. Additionally, as I said at the outset,
Speaker 3: We've supplied clinical information, which I think is unique with respect to some of the other INDs that have played out over the last few years in this space. We think that's a helpful bit of information for the FDA to consider as they do their evaluation.
Speaker 3: So we look forward to the outcome. Obviously it's subject to their review, but we think we've done a good job of robustly supplying information. As we've said with respect to timelines when we have the information in terms of the outcome of that review, we will share it and everybody will know it the same.
Speaker 3: time. David, you just want to say a few words about how we approach the pivotal and when we'll be in a position to share that information.
Speaker 1: So this is what John said about all aspects of our, say, the IND submission. Another piece of that are clinical discussions that have gone on both in the pre-IND setting with regulators around the world, in Europe . And with that, we have...