In this company presentation, Derek Hicks, newly appointed Chief Business Officer of Intellia Therapeutics, delivers a high‑level overview of the company’s mission, modular CRISPR‑based genome‑editing platform, and its broad pipeline of in‑vivo and ex‑vivo therapeutics. He explains the foundational technologies—including a lipid‑nanoparticle delivery system and novel editing tools acquired from Rewrite—highlighting their applicability across diverse disease areas. Hicks walks through the lead in‑vivo programs: NTLA‑2001 for transthyretin (TTR) amyloidosis, presenting Phase 1/2 data showing dose‑dependent serum TTR reductions of 87‑93% and sustained knock‑down over 12 months, supporting a potential one‑and‑done curative approach; and NTLA‑2002 for hereditary angioedema, showing 65‑92% reduction in C1‑inhibitor activity and marked decreases in attack frequency in early patients. He then outlines the ex‑vivo pipeline, including a pivot of the WT1 TCR asset from autologous to allogeneic, collaborations with Novartis on sickle‑cell disease, and the spin‑out Adencell focused on universal CAR‑T. Throughout, Hicks emphasizes strategic partnerships (Regeneron, SparingVision, Kyverna, Novartis) that leverage Intellia’s toolbox for ophthalmology, autoimmune disease, and immuno‑oncology. The talk concludes with a reaffirmation of Intellia’s vision to develop curative genome‑editing treatments and an invitation to engage further at the conference.
Chapters
All right, good morning everyone. Thank you all for joining this company presentation. Again, my name is Derek Hicks. I'm Chief— oh, okay, thank you. I'm Chief Business Officer at Intelia. I just joined in December and, you know, really excited to be here to talk about our company and our platform. What I'm going to do is walk through a very high-level overview of our company, our pipeline, recent clinical data, and finally I'll talk a little bit about our strategic partnerships. So, you know, everything at Intellia really starts with our mission, which is to transform the lives of people with severe diseases by developing curative genome editing treatments. And how do we do that? We have a full spectrum strategy And we have a robust R&D engine to develop in vivo and ex vivo therapies for diseases with unmet needs. The foundation of that is having modular solutions. And those solutions focus on building differentiated technologies with a broad applicability that can be applied to future candidates. And some of those technologies include our lipid nanoparticle platform, for example. In addition, we've built novel tools, and we have an array of editing tools and delivery modalities for therapeutic applications. And some of those tools came from a recent acquisition that we did with a company called Rewrite back in February of 2022. One of the things that really drew me to Intellia is the fact that we do have this world-class genome editing toolbox, which we can apply in various ways. And we're very excited about that toolbox, and we look forward to continuing to build on it. Our goal at the end of the day is to build an unsurpassed genome editing pipeline, and we believe that we are doing that at Intellia. So many of you may know that we announced some pretty exciting data back in 2021. That data was for our TTR asset. You can see some of the periodicals and some of the quotes from the data release back in 2021. You can also see, you know, a journal article that was written by our colleagues. Again, very exciting data that just shows the potential of CRISPR gene editing in humans. And this is also something for us to get excited about in terms of new treatments for patients. As I mentioned previously, we have the ability to apply our toolbox to in vivo therapies as well as ex vivo therapies. We apply novel tools for both applications. In the case of in vivo, CRISPR is a therapy where we fix the target gene. In the case of ex vivo, we create the therapy. And in some of the areas for ex vivo, we're focused on areas such as immuno-oncology and also autoimmune diseases. And we'll talk about that a little bit more in terms of not only what we're doing internally, but also for some of our partnerships. So here's our pipeline. We have a lot going on in Telya, as you can tell by this chart as well as the next one. You'll see that we have a very broad pipeline fueled by a broad, robust research engine. If you look at the second column from the right, you'll see our different approaches in terms of gene editing, everything from knockout to insertion, as well as different approaches that we're using with our partner Regeneron. You can again see that we have programs that are partnered. The way that we do this is we do it through partnerships. So one of our partners, I actually think I just saw her earlier, SparingVision, is working on some ophthalmology programs where we're essentially giving some of the tools for them to do development in IRD as well as other ophthalmologic diseases. And also here you can see that our ex vivo pipeline is fairly broad as well too. The panel here was just talking about allo earlier. We recently pivoted our auto WT1 TCR asset from an autologous to an allo approach. We believe our proprietary differentiated cell engineering platform can solve many of the known challenges faced by autologous and current allogeneic approaches. We also believe that we have the best allogeneic platform best-in-class allogeneic platform. In addition, again, this is a very broad platform, so you can see we also work with partners such as Novartis for a sickle cell asset. And also last year we spun out our assets into a new co called Adencell, where they're focused on allo-universal CAR-T. Let's go through some of our clinical assets. First of all, I'll talk about our lead asset, NTLA-2001 for TTR amyloidosis. I think many of you are probably familiar with this condition, but it's essentially caused by accumulation of misfolded TTR protein, which affects various organs in the body. The current treatments, chronic dosing is indeed required. Our approach, as you saw on the previous slide, is a knockout approach. You'll see from some of our data that we have today that potentially we have the opportunity for a one-and-done treatment, which is absolutely beautiful and amazing. We also have the potential to halt and reverse the disease. Again, you'll see from this data that we're very excited about the progress we're making and the impact that we could potentially have on patients. So let me talk a little bit about the study. NTLA-2001 is being evaluated in a Phase 1, 2-part cohort study, open-label study, and for patients that not only have PN, polyneuropathy, but also cardiomyopathy. Again, this product is subject to the co-development agreement that we have with Regeneron, where we are the lead. To date, we have over 30 patients that have been dosed across both arms. And so here's the results that we announced in June of— June 24th, 2022, for our polyneuropathy study. So as you can see here, The results, you can see the dose-dependent reductions in serum TTR, particularly at the higher doses. You can see the reductions of 87% to 93% depending on the dose. We're very excited about this data, and we think that it's pretty meaningful and impactful. You can see here that this data just shows a growing body of evidence that this product can be treated for a one-and-done and could have deep sustained reductions in TTR. This slide shows the data over time. You can see the deep, consistent, and sustained reductions, particularly at the higher doses. And when you look at this chart, you can see from 6 to 12 months, you can see that consistent continued reduction, which again is very exciting and has been well received. At the moment, we will likely focus on a 0.7 milligram per kg dose, which will likely be fixed. And that will likely be the dose that we bring into our pivotal study. So this is the data for our cardiomyopathy arm. And again, you can see across these cohorts similar deep reductions in TTR. You can see that across the higher doses. Again, very consistent with the polyneuropathy arm. And on the next slide, you can also see that patients achieved greater than 90% TTR reduction by day 28. And in one case where we have data out to 6 months, you can see the reduction of 93%. Again, we're very excited about this data and very encouraged by the potential of CRISPR treatments for patients. So in summary, you know, you can see here that we've achieved a significant milestone for patients suffering from these genetic diseases. And we do believe that this data further supports early findings from this trial demonstrating the promise of CRISPR in vivo gene therapy and genome editing in humans. Once again, very excited about this and look forward to continued data from, from Intellia. More to come here in terms of our assets. Again, I'll try to walk through this very quickly. So we also have an asset, NTLA-2002, for hereditary angioedema. Again, if you're not familiar with this, this is a disease that's characterized by recurring, severe, and unpredictable swelling in various parts of the body. Right now, the only thing that's available are chronic treatments for this disease. One of the advantages that we have here with ours is, with our treatment, is that it is a one-and-done treatment, and it also has the potential to eliminate significant treatment burden for patients, which is very meaningful. This is also a knockout approach, and this is an example of how we're able to leverage our platform to bring another product to pipe to our pipeline as well as to patients. So I'll talk a little bit about the study. As you can see here, this study is basically— we have a 75-milligram dose as well as a 25-milligram dose. It is very early, but you'll see the data is very exciting. We're currently evaluating this, this dose for patients to evaluate safety and tolerability, as well as changes in calcrine protein and activity levels. We also have some observations of patients and their attack levels, which we'll show on the next couple of slides. So again, it has a fairly consistent trend in terms of the data. What you can see is on a 25-milligram dose, calcinein reduction was at 65%, and at the 75-milligram dose, you see 92%. This reduction was reached by week 8. And you can see going forward, even in the 25-milligram dose, we have reduction through week 16. Once again, very consistent and exciting one-time treatment data. Also here you can see the patients and the number of attacks they had during the screening period. So you can see they range anywhere from 1 attack a month to 7 attacks a month in the 3 patients. And what you can see is during the 16-week observation period after they took NTLA-2002, some patients didn't have any attacks at all, while one had 2 per month. Again, very exciting data. I love that. I love those two words, as you can see. And so here you can also see a similar trend. Two of the three patients remain attack-free, but all patients remain attack-free after week 10. And you can see some of these patients were on prophylaxis, but they were taken off of prophylaxis during the study. So, so far so good in terms of CRISPR treatments. So, in this last slide, excuse me, I just wanted to reiterate our platform and how enthusiastic I am about it, which is a big reason why I joined Intelia. The exciting thing about this platform is it can be deployed in multiple ways, and it's endless in terms of the opportunities that we have. As you can see, we're busy enough with our own platform, but we also work with many partners in terms of giving them our tools and technology to leverage so they can develop their own assets. Again, Sparing Vision in the case of ophthalmology, Kyverna, autoimmune disease, CD19, which is very exciting. And some of you have seen some of the very early data for that. It looks very extremely promising. In the case of immuno-oncology, we're working very closely with Adnocell. And we obviously have partnerships with Novartis as well too. So this just shows that it's endless in terms of the opportunities and the way that we can deploy this technology. So that's my presentation. Thank you very much, everyone, and look forward to interacting with everyone at the conference. Thank you.
