Good morning, and welcome to Ionis' conference call to discuss its collaboration with Metagenomi. Should you need any assistance during today's call, please signal a conference specialist by pressing the star key followed by zero. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Jennifer Capuzelo, Investor Relations, to lead off the call. Please begin.
Thank you, Joe. Hello, and thank you for joining us this morning for our discussion about our collaboration with Metagenomi. Before we begin, I encourage everyone to review the press release Ionis issued this morning, which outlines the details of this agreement. We have also posted slides on our website that accompany today's call. Joining me on today's call are Brett Monia, Chief Executive Officer, Frank Bennett, Chief Scientific Officer, and Eric Swayze, Executive Vice President of Research. Joining us for the Q&A portion of the call are Joseph Baroldi, Chief Business Officer, and Beth Hougen, Chief Financial Officer. During this call, we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.
I encourage you to consult the risk factors contained in our SEC filings for additional details. With that, I'll turn the call over to Brett.
Thanks, Jennifer. Good morning, everyone, and thanks for joining us today as we discuss this important new step we're taking at Ionis to advance and expand the reach of our technology. Ionis was founded over 30 years ago to deliver innovative new medicines for diseases with great medical needs. We pioneered the RNA-targeted therapeutics industry, leading the way with our antisense platform. Today, we're making unprecedented advancements in oligo RNA-targeted therapeutics and building on our first 30 years of success to broaden the scope of our technology and move closer to achieving my vision for Ionis to be the leader in precision genetic medicines. When I assumed the role of CEO in 2020, I laid out the three strategic objectives that I believe were essential to drive substantial value for Ionis and all stakeholders, and these are them.
First, to build our commercial pipeline and capabilities to launch Ionis medicines. Second, to expand and diversify our technology and thereby extend and solidify our leadership in genetic-based medicines. Third, to deliver a sustained, steady cadence of new transformational medicines to the market. We've made excellent progress against all these objectives. Our portfolio of marketed products is expected to grow and grow substantially over the next few years, starting with the potential delivery of two new medicines, eplontersen and tofersen, to the market next year. Our rich late-stage pipeline is also positioned to deliver even more, a steady cadence of pivotal data and new drugs to the market, not just next year, but for many years to come. Second, we're making great progress in expanding our capabilities in RNA-targeted therapeutics.
For example, we recently advanced new programs into IND-enabling studies targeting muscle and using our MsPA backbone chemistry as well. Our muscle-targeting delivery uses LICA technology similar to what we use in the liver today. Our MsPA backbone chemistry was designed to improve efficacy and durability for both systemic and local delivery, such as in the CNS. At Ionis, we have and will continue to exploit the full potential of RNA as a target for human therapeutics. Now we're expanding our scope to DNA to exploit its full potential as a target for human therapeutics. Today, we announced a new collaboration with Metagenomi to focus on next-generation DNA editing.
This collaboration represents our most significant step to date to advance and expand our technological capabilities to become the leader in precision genetic medicines, enabling us to tackle more diseases and reach more patients with significant unmet needs. As Frank will discuss in a moment, our decision to expand into gene editing followed a lengthy process involving thorough interrogation of emerging innovative therapeutic platforms. This process culminated in a clear conclusion that gene editing was the technology most complementary and synergistic to our existing RNA-targeting therapeutics platform, with significant potential to extend the reach of our current capabilities. During this process, it also became clear that to accelerate our path to bring optimized gene editing strategies to the clinic, it would be important to partner with an established and highly experienced leader in the field. Metagenomi is one of the industry leaders in next-generation gene editing.
That, together with their leadership team, who shares our vision for the future of gene editing, makes them the ideal partner for Ionis. I'll now hand the call over to Frank, who will go into more detail about the process we followed that brought us to today's announcement, who will also talk in more detail about Metagenomi's gene editing capabilities, the powerful synergies we expect to achieve between our platforms, and how we plan to leverage the expertise of both companies to accelerate the delivery of the next wave of genetic medicines to patients. Eric will then discuss how the Ionis and Metagenomi teams will work together and touch on the internal team we're building to support the collaboration. He'll also discuss more about the capabilities Ionis will bring to this collaboration.
I'll then close with a few more remarks before opening it up for calls or questions. Over to you, Frank.
Thanks, Brett, and good morning to everyone. I'd like to echo Brett's enthusiasm for today's announcement. This partnership represents the culmination of an extensive effort to determine the most promising emerging technology that best fits with Ionis' strategic objectives. When exploring technologies, we focused on platforms with broad applications that could, in the short term, build on our current capabilities within our therapeutic franchises. In parallel, for the longer term, our aim is to utilize Ionis' vast experience in nucleic acid drug delivery through medicinal chemistry and routes of delivery to broaden the applications of the technology. We chose gene editing for a number of reasons. Gene editing utilizes specific RNA-guided nucleases known as Cas enzymes to precisely and permanently modify a DNA sequence. Because of this, gene editing holds the promise of treatments that could provide long-term, potentially permanent therapeutic benefits.
Gene editing is a highly complementary and synergistic with RNA-targeting therapeutics. Both platforms rely on the same nucleic acid hybridization principles to precisely target nucleases to either RNA, in the case of RNase H and siRNA drugs, or to DNA in the case of CRISPR-Cas systems. This creates a tremendous opportunity to leverage our expertise in nucleic acids with the goal to enhance gene editing's ability to treat diseases for which there are limited treatment options. Equally important to finding the right technology to expand our capabilities was finding the right partner. There were three key criteria we used in our evaluation. First, we looked for a deeply experienced team with the ability to execute on our near-term and longer-term goals. Secondly, we looked for differentiated capabilities that would enable the teams to explore solutions to solve some of the current challenges in gene editing.
Third, we looked for a team who shared our vision to discover and deliver transformative therapies with a sense of urgency for patients in need, while ensuring that new technologies are advancing to patients responsibly. Metagenomi meets these criteria. By combining their broad, versatile, and highly differentiated platform of fit-for-purpose gene editing tools with our nucleic acid expertise, we have a unique potential to substantially advance the field of precision genetic medicine to deliver therapies to more patients with unmet medical needs. For example, as Eric will discuss in a moment, by utilizing our proprietary capabilities in oligonucleotide medicinal chemistry, we have the potential to further optimize the activity and specificity of RNA-guided nucleases. We'll apply our advancements in gene editing to expand existing therapeutic franchises at Ionis and create new ones.
I'm excited about the opportunity this collaboration creates to deliver potentially transformative therapies to patients in need. Now I'll turn the call over to Eric to walk through how we plan to work with Metagenomi.
Thank you, Frank. I believe our collaboration with Metagenomi represents an important milestone in Ionis' path to advance and expand our technology, with the goal to deliver next-generation therapies to patients. Our teams are very excited about this partnership and the promise it holds to move gene editing modalities forward into Ionis' development pipeline. In the near term, we plan to prioritize validated liver targets that are amenable to permanent knockdown and have well-characterized clinical safety and tolerability profiles. This includes developing follow-on programs for some of the near-term commercial opportunities currently in our pipeline. Strategy to focus initially on liver targets allows us to accelerate discovery and development of gene editing therapies by capitalizing on multiple well-validated approaches that are known to effectively deliver gene editing drugs to the liver. Furthermore, it provides us with additional life cycle management opportunity for medicines currently in our pipeline.
Today, we already have life cycle management and follow-on activities underway for all of our near-term opportunities. These projects, aimed at extending the reach of our current pipeline programs, take full advantage of all the technology advancements we are making, including new ASO backbone chemistries, new LICA, and siRNA strategies. Today, we are adding DNA editing as well. In parallel, for the longer term, we will utilize Ionis' vast experience in nucleic acid medicinal chemistry, delivery strategies, and routes of administration to address novel targets. Gene editing drugs utilize RNA to guide the nuclease to specific regions on DNA. This enables us to apply our nucleic acid-mediated medicinal chemistry technology with the goal to make better gene editing drugs. These efforts could potentially improve potency, therapeutic index, and importantly, DNA targeting selectivity.
Furthermore, we plan to take advantage of the unique opportunity this collaboration provides to combine Metagenomi's ability to customize their platform of gene editing tools with our oligonucleotide medicinal chemistry expertise. In doing this, we plan to simultaneously modify both the guide RNA and the nuclease with the goal of improving the overall performance of the resulting optimized gene editing system. We also plan to leverage this work to enable gene editing mechanisms beyond DNA cutting that will allow more versatility in the diseases we can tackle. Finally, we will apply our expertise in the delivery of oligonucleotides to enable efficient and effective delivery of gene editing drugs outside the liver. This includes our know-how and routes of delivery, formulation, and our growing suite of tissue-targeting LICA technology.
We feel these delivery capabilities will be amenable to the delivery of gene editing drugs, just as they have facilitated the delivery of oligonucleotides such as ASOs and siRNAs. To accomplish these goals, we are building an internal team focused exclusively on expanding and advancing our technology into the gene editing space. This team will work directly with Metagenomi to advance our collaboration technology and especially to identify great gene editing drugs for the targets we are jointly working on. Our aim with all of this work is to broaden the reach of gene editing to address more diseases and to reach more patients in need. We're excited about the opportunities ahead, and we look forward to sharing updates on our progress as we advance these programs and unlock the true potential of our combined technology. With that, I'll turn the call back over to Brett for some final remarks.
Thanks, Eric. As I mentioned at the beginning of the call, in the three years since I introduced my vision for Ionis, we've made great progress against the key strategic objectives I believe represent our path to drive substantial value for Ionis and its stakeholders. This collaboration with Metagenomi represents one of the most important steps we've taken to date. We're excited to be moving forward with an industry leader who shares our focus on transforming technology into medicines for patients. Metagenomi houses one of the world's largest metagenomics databases, as well as an unparalleled library of novel and diverse nucleases, which enables us to explore DNA editing anywhere in the human genome with high efficiency and precision. They've advanced the field of gene editing substantially, and we're pleased to be partnering with them.
Today, we're closer to becoming a multimodality, multi-platform company, a major milestone in our evolution in becoming the leader in precision genetic medicines. I'll now open the call up for questions. Operator, if we can set up the questions.
We will now begin the question-and-answer session. To ask a question, you may press star, then one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then two. At this time, we will pause just momentarily to assemble our roster. Our first question here will come from Yanan Zhu with Wells Fargo. Please go ahead.
Hi, thanks for taking my question, and congrats on this partnership. Two questions from us. Could you expand on the differentiation of Metagenomi's technology compared with other players that are mining the metagenome for novel gene- editing tools? Secondarily, would your first target be competing with some of the targets that are being pursued in the clinic by others? Also, generally, how do you expect to differentiate your product candidates with the traditional one, the ones being pursued with the traditional gene editing approach? Thank you.
Thanks, Yanan. Two excellent questions. You know, I think I'll take the first one. Then I'll ask Frank to talk a little bit about how Metagenomi differentiates from other editing companies as well as Metagenomics companies investing in Metagenomics. The targets that we're gonna explore initially in drug discovery, as Eric mentioned, are going to be liver targets, and they'll certainly be targets that will compete with you know, other programs that are out there by other companies pursuing targets in the liver for rare or broad indications. They will also compete with some of our programs internally.
I mean, not really from a competitive standpoint so much, but more of a life cycle follow-on strategy if these editing drugs actually perform in a manner such that they're worthy of a follow-on program. What do they bring to the table? Well, I think we're all familiar with the fact that DNA editing has the potential to be, you know, dosed once or very infrequently and potentially provide a cure for a disease. You know, that's the angle. That's the angle that DNA editing offers. That's the advantage.
What we're gonna focus on is to ensure that we have the most specific, the best specificity, avoid off-target effects, really manage the profile for these drugs so that they're optimal, and highly advanced before we'll move them into development. That's the strategy. I mean, we will certainly work in competitive areas as well as in others. We will also work on some novel targets too, eventually, but we'll start with some competitive programs, probably. Frank, would you talk a little bit about how Metagenomi differentiates?
Yeah. You know, in our analysis of different gene editing companies, it was pretty clear that Metagenomi had the largest suite of enzymes that they've identified. They've done an extensive bioinformatic analysis, both public as well as their own proprietary data, to identify novel Cas enzymes. They've then, you know, characterized a large number of those enzymes for both their specificities, their cutting characteristics, as well as the sequence by which they're binding to DNA. What they've created is a suite of very versatile enzymes that they can really tailor an enzyme for a specific gene or a specific location on the chromosome that I think was really unique to Metagenomi.
I just didn't see that diversity and that versatility by other companies that we've looked at. Not to say that the other companies don't have good products, it's just we felt that Metagenomi had the most diverse and versatile portfolio of enzymes.
Great. Thanks for all the color and congrats again.
Thanks, Yanan.
Our next question will come from Jessica Fye with JP Morgan. Please go ahead.
Hey, good morning. This is JL for Jess. Can you elaborate on how Ionis chemistry can be utilized in combination with the Cas enzyme you just mentioned from Metagenomi? Further, is there any color you can share with us regarding extrahepatic targeting, especially in the combination with Metagenomi's platform? Is it going to be through AAV, lipid nanoparticles or anything else? How can you leverage your existing experience with extrahepatic targeting for these purposes? Thank you very much.
Thanks for the question. Eric, you wanna address how we hope to apply medicinal chemistry to the editing platform, and Frank, maybe take over on how you see us tackling extrahepatic targets.
Yeah, sure, Brett. I mean, first on the medicinal chemistry, so I think as many of you know, we have a long history and extensive investment in understanding the medicinal chemistry of oligonucleotides for our ASO drugs and more recently for siRNAs. We think it will be amenable to gene editing technologies as well. We published a paper several years ago on using some of these chemistries in a Cas9 system where we saw some improved benefits. What I think is a really cool concept is to customize both the enzyme system and the oligonucleotide system. There's two components of the gene editing system, so they work optimally together. I think that provides an opportunity and the hope of really making a truly great and high-performing system that we hope could potentially give us the selectivity and the efficacy that we want for these targets.
Frank. Delivery?
Yeah. Yep, as far as the Delivery is concerned, we're looking at a fairly broad portfolio of delivery technologies that could be applied to open up other tissues, other than liver. You know, at this point, AAV or other viral vectors aren't at the top of the list. They add another layer of complexity to the problem. We're trying to look for simpler solutions today.
Thanks, Frank. Other questions?
Our next question will come from Gary Nachman with BMO. Please go ahead.
Hi, good morning, and congrats on the deal. A couple. First, when can we start to hear about the first targets that you're pursuing in the liver? I'm curious how long that discovery process might take from where Metagenomi is right now with the enzymes they've already identified. Talk more specifically about some of your products where you can have follow-on programs and do life cycle management with the gene editing. How versatile the Metagenomi toolbox is to span different therapeutic areas that you guys have been looking at. Thank you.
Thanks, Gary. With respect to timing, Our objective is to move fast. In fact, drug discovery activities for liver targets are already underway. We are working on targets that are both novel as well as targets we have a lot of experience with. We look forward to sharing updates on those targets as soon as we can, as soon as we feel comfortable that we've made some good progress. Stay tuned for that. As far as versatility, I don't know, Frank, maybe you could talk a little bit about, you know, the versatility that Metagenomi brings to the table that allows us to that'll weigh in on the targets we focus on.
Yeah. You know, as I said, they have a spectrum of Cas enzymes that are both Cas9, which is one enzyme family, as well as Cas12 enzyme family. They have a diversity of sizes, so those sizes can impact how well they formulate with you know, lipid nanoparticle formulations. If we ever chose to go to AAV, they have enzyme systems that could very easily fit within the AAV vector. Number one, they sort of bring that diversity. As I also highlighted, there's a DNA sequence that's the enzyme recognizes. It's a 2-3 nucleotide sequence called a PAM sequence, and each enzyme has sort of a unique sequence specificity there.
One of the nice things about the Metagenomi library of nucleases is that they can pretty much target anywhere on the genome with an enzyme. You know, they have an enzyme that would target one three-letter code and another enzyme that targets a different three-letter code. They creates a lot of versatility in where they can target on the genome. Finally, you know, we have a lot to learn about on-target as well as off-target effects. You know, different enzymes will have different specificities. Really what we're trying to do together is find the safest drug to bring forward to patients going forward.
Okay, great. Thank you.
Thanks, Gary.
Our next question will come from Gena Wang with Barclays. Please go ahead.
Hi, this is Shawn, and for Gena. Thanks for taking our questions and congrats on the partnership. First, could you clarify that, did I hear correctly that you already chose to go with AAV to deliver the CRISPR enzyme? Secondly, just on the economics, what kind of exclusivity would you have for on these AAV targets? Would they be exclusive on targets or by indication? And what economics would Metagenomi get from these AAV products? Thanks.
I think what you heard from Frank was the opposite before. Frank, just confirm for me, but no, we are not putting AAV delivery as the highest priority for tackling extrahepatic targets. You wanna add anything to that, Frank?
No, I just, you're exactly right. I said, that's definitely not our favorite path forward and, you know, we're not taking it off the table, but right now that's not our priority.
Thanks. With respect to the other part of the question, so we have target exclusivity, all indications for target, you know, for a target that we bring into the collaboration. As far as the economics beyond what's in the press release, the press release is, you know, pretty clear and pretty much as far as we're gonna go on the economics for now. It of course will involve, as we have success and move drugs forward through development, we'll have regulatory and if we reach the market, commercial milestones and some low-end royalties for Metagenomi as well.
Thank you.
Okay.
Yeah. Can I have?
Mm-hmm.
Just to follow up. If AAV is not your highest priority, so what other approaches are your highest priority to consider as the, like, as you mentioned, the simpler solution to deliver the guide and the CRISPR machinery?
Yeah. For liver targets, there are a family of lipid nanoparticle-like structures that would be our focus. For extrahepatic tissue, we're looking very broadly at both LNP as well as non-LNP-type technologies.
Okay. Thank you so much.
Thank you for the questions.
Our next question will come from Joey Stringer with Needham & Company. Please go ahead.
Hi. Good morning. This is Rohit on for Joey. Thanks for taking our questions. Can you just provide some additional color around the timing of this collaboration? Do you have any plans to do more collaborations that are complementary to the pipeline, that are perhaps not gene editing in nature? Thanks.
Thanks for the question. We're focused on this area right now, this collaboration. As you know, as we touched on in the presentation as is in our prepared remarks, we have already made great progress in advancing RNA-targeted therapeutics in many different ways, new backbone chemistry, new LICA for muscle, and so on. You know, we're focused on making this partnership a success, and that's what we're gonna focus on. Of course, we'll continue to evaluate other potential opportunities as they go forward. I wouldn't be looking to see us to expand beyond DNA editing. With that said, we're looking forward to exploring other opportunities within this collaboration and anywhere that pops up for opportunities that extend our capabilities in DNA editing.
We really wanna be a leader in this space as we've been in the RNA-targeted therapeutic space, all along. I forgot the first part of the question. If you could remind me or we could, or someone else can.
Sure, yeah. Can you just provide some additional color around the timing of the collaboration?
I don't know what you mean by timing, so it was announced today and we've been working on this collaboration, as Frank took us through the process earlier, for quite some time. We've been working with quite a number of you know leaders in this space, and we settled on Metagenomi you know over the course of the last year plus through extensive evaluation and diligence. But we kicked it off today, and we're hitting the ground running.
Thank you.
Yep.
Our next question will come from Luca Issi with RBC. Please go ahead.
Well, great. Thanks so much for taking my question, and congrats on the deal. Maybe two quick ones. Brett, can you just expand a little bit more on the strategic rationale behind the deal? Are you primarily playing defense here to protect the late-stage pipeline like HAE and TTR, or are you primarily playing offense and going after new indication? Which one would you pick if you could only choose one? Then maybe on the technology, Eric and Frank, are you planning to explore base editing? I think you mentioned on page nine that you're planning to explore additional mechanism beyond cutting, so would love if you can expand on that. Thanks so much.
Thanks, Luca. Great questions. So with respect to strategic target strategy, great analogy. I love sports, as you know, and it's both defense and offense. We will protect our prioritized programs with potential to you know, to maximize the value to the company, based on extending life cycle and so on with this strategy. We will be offensive. Novel targets, new spaces within the liver, novel targets in the liver as well as if and when we crack extrahepatic delivery, it'll certainly be novel targets there as well. Frank, you wanna talk a little bit about interest in base editing and beyond?
Again, look, I suspect you understand that the Cas9 insight provides a tremendous amount of opportunity for bringing a number of different effectors, including base editors to specific locations of the DNA to have very selective genome editing. Clearly we're very interested in base editing. It's a little bit less mature and so we may not initially focus on base editing, but it's clearly within our deal structure to be able to work on it with Metagenomi.
Got it. Thanks so much.
Thanks, Luca.
Our next question will come from Jason Gerberry with Bank of America. Please go ahead.
Hi. Good morning. This is Chi on for Jason. Thanks for taking the questions. I have two. I'm curious, for the validated liver targets, can you talk about criteria or threshold pre-clinically you would consider, you know, internally as you evaluate whether you want to continue with an RNA-targeting therapy or switching to a gene editing approach? Second question is, I'm curious if you can expand on the opportunity with extrahepatic targets. Is there a particular tissue or disease area where RNA-targeted therapeutics have had limited success that you think this partnership could add to Ionis' portfolio? Thanks.
Let's see. When we refer to validated liver targets, there's potentially two layers, right? Genetic evidence for the target, and then there's pharmacological evidence for the target, right? Those don't always coincide, so having both is absolutely essential. We have a lot of experience with RNA-targeted therapeutics in validating safety and efficacy for liver targets, for example, as well as CNS targets. That will really be the key. That'll be a piece of key criteria to, you know, for us to get comfortable that a target is worth pursuing. The second part of that is the magnitude of reduction that you get because, you know, it's very possible that the editing approaches we take will bring target levels down to almost undetectable levels.
We're gonna have to be very comfortable that that's safe and that's important because, you know, for reversibility, this approach is generally not expected to be reversible. We're gonna have to be very comfortable with that. That's a key criteria. With respect to switching, we're not switching anything. We are very much aggressively moving all of our pipeline products forward to the market, and we plan to have them to be on the market for a very long period of time that's to maximize the value to Ionis. If we go after a target for DNA editing that's the same target as something that we have on the market, it'll be timed in an appropriate manner to maximize life cycle and also we're gonna need to see that it's really gonna give us an advantage, a differentiation factor.
We're not planning to switch anything. The drugs in our pipeline are gonna be. We're expecting to go to market and have a long life on the market. Frank, you wanna talk a little bit about, you know, issues that we may prioritize for extrahepatic targets?
Yeah. Well, I think it's obvious that we have interest in other tissues outside the liver, just given our experience with, you know, our antisense portfolio. Those obviously are tissues that we're interested in. But we would also be amenable if we, you know, find a solution to a different tissue to be able to mine that tissue with, you know, the gene editing technology as well. The initial focuses are areas that we're working in today, but our clear goal is to really go beyond where we're working today and create new medicines for patients that need them.
Great. Thanks.
Thank you.
Our next question will come from Paul Matteis with Stifel. Please go ahead.
Hey, good morning. This is Katherine on for Paul. Thanks for taking our questions. You mentioned that this collaboration could drive value for certain near-term commercial opportunities. Just wondering if you could expand on that, what programs you're looking at here, and when we might see the benefits there? Thanks.
Yeah. Thanks, Katherine. You know, I really go into more detail than what we've gone into already. I mean, the near-term commercial opportunities are gonna be liver targets, while we tried our best and to validate extrahepatic targets, tackle delivery, for non-hepatic tissues. It's gonna be, we're gonna be focused on liver targets and they're gonna be novel targets, we're gonna be working on as well as some targets we're very familiar with. I really can't say much more than that.
Our next question will come from Shrunatra Mishra with Goldman Sachs. Please go ahead.
Hi, team. This is Shrunatra on for Salveen Richter. Thank you for taking my question and congratulations on the collaboration. Could you shed some light on the rationale for the, behind the timing of this deal, considering that Ionis is already advancing multiple, it's advancing in multiple tech areas like muscle LICA? What sort of synergies do you see of this particular collaboration with these technologies that you are currently advancing?
Yeah, thank you. I'll touch on the timing. Maybe Eric could talk a little bit about synergies that he sees in our experience in RNA therapeutics with DNA editing. As Frank mentioned, and I touched on in my earlier remarks, there's very common thinking on the vision and strategy between Ionis and Metagenomi. We actually had some commonalities in place already on targets we wanted to prioritize. There was complete agreement on where to focus initially on the first set of targets and therefore we're well on our way. You know, it becomes official today. You know, drug discovery activities are underway.
They've been underway, and we've been preparing for this partnership for some time now. I think, you know, like I said earlier, we've hit the ground running, and we're well along in drug discovery activities. Eric, where do you see the synergies between RNA, what we've done in RNA, with DNA editing?
Yeah, I think there's a couple synergies. One, as I touched on in an earlier question and also in my section is our expertise in nucleic acid chemistry. I mean, gene editing drugs as practiced today in humans have been RNA therapeutics, right? So there's an RNA that makes a Cas protein and there's a guide RNA. And we know RNA. We know how to make it, we know how to modify it, we know how to deliver it into animals, and it's been our core expertise is to make drugs out of nucleic acids. So I think there's great synergy in applying that knowledge to the gene editing problem with the hopes of making the best possible drugs. The other area that we focused in is delivery, and we focused on LICA strategies.
There's some tricks and techniques and methods to get oligonucleotides to go where you want them to go in the body. Obviously you have to get them to the right tissue and cell type to practice the pharmacology you wanna practice in your patient. So I think there's lots of overlap with things we've been doing and things we've done, and it's an exciting time for gene editing space and our team is all fired up to put our knowledge and efforts together with Metagenomi to try and really advance these programs.
Thanks, Eric. I think we have time for one more question.
Our last question today will come from Myles Minter with William Blair. Please go ahead.
Hi. You've got Sarah on for Myles Minter. Congrats on the collaboration. So just two questions from us. First, a clarification. Are the four initial targets restricted to liver targets with the optional second four for extrahepatic targets, or is there some flexibility there? Second, just wanna get your thoughts on securing an IND through the FDA, considering, you know, some clinical holds in this space and other delays preventing the dosing of patients. Thanks.
Thanks, Sarah. The first I could answer is, and Frank, you could maybe touch on a little bit on, you know, challenges with respect to regulatory challenges and how we think Metagenomi sets us up very nicely to overcome some of those challenges, because that's how I see it. Very quickly, Sarah, yeah, we have flexibility on the first sets of targets, the first four targets, liver and non-liver, we have access to. Frank, wanna talk a little bit about, you know, some of the regulatory challenges we see that we think we might be able to. We have advantages too with our partnership with Metagenomi?
Yeah. Well, I think we're learning, you know, what's going on and how the FDA is responding to the various products. There's still a lot we don't know as far as, you know, what is the reason for the holds that, at least as far as I know, hasn't been communicated broadly. It's a little hard to figure out how to fix it without knowing what the problem is in essence. We do have the advantage of sort of you know following some of the other products and so we identify where the sensitivities are with regulatory agencies and being able to navigate so that hopefully we're more successful getting the products through the regulatory agencies based on prior knowledge.
You know, the regulatory white paper that they sent out clearly, you know, suggests that there is a path forward for gene editing technologies, and the regulatory agencies have thought a lot about it and have provided guidance on, you know, how to proceed. We'll pay close attention to that guidance and follow it as best we can to bring the first, you know, few products forward.
Yeah.
Great.
Thanks, Frank. Thanks, Sarah.
Thank you.
All right, we're gonna wrap it up. Today, we're very much closer to becoming a multimodality, multi-platform company at Ionis, which is a major milestone in our evolution in becoming the leader in genetic medicine. We're very excited about this partnership, obviously, and we're looking forward to providing updates as we make progress going forward. Thanks very much everybody for joining and have a great day.