Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference Call. Throughout today's recorded presentation, all participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. I will now hand the conference over to Vince Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead, Vince.

Thank you. Good afternoon, and thank you for joining us today to discuss Arrowhead's results for its fiscal 2024 year-ended September 30, 2024. With us today from management are President and CEO, Dr. Chris Anzalone, who will provide an overview of the quarter; Dr. Bruce Given, Interim Chief Medical Scientist, who will provide an update on our cardiometabolic pipeline; Andy Davis, Senior Vice President and Head of Global Cardiometabolic Franchise, who will provide an update on commercialization activities; Dr. James Hamilton, Chief of Discovery and Translational Medicine, who will discuss our earlier-stage development programs; and Ken Myszkowski, Chief Financial Officer, who will give a review of the financials. We will then open the call to questions. Before we begin, I would like to remind you that comments made during today's call contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical fact are forward-looking statements and are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed in any forward-looking statements. For further details concerning these risks and uncertainties, please refer to our SEC filings, including our most recent annual report on Form 10-K and our quarterly reports on Form 10-Q. I'd now like to turn the call over to Chris Anzalone, President and CEO of the company. Chris?

Thanks, Vince. Good afternoon, everyone, and thank you for joining us today. Over the years, we've built platforms capable of addressing liver, lung, adipose, CNS, skeletal muscle, cardiomyocyte and soon other cell types to bring RNAi therapeutics where a multitude of diseases are. Any one of these would represent an important advance in human health, but together, we believe they have a revolutionary potential. I don't think it's hyperbole to say that we've created a machine that spits out high-quality drug candidates if you just feed it money and gene targets. Importantly, those drug candidates can be produced quickly relative to other methodologies and given the modality and increasingly validated nature of the platforms, we have an expectation that most will do what they are designed to do. We've always had a conviction that building and constantly expanding this machine is critical to our dual-mandate of serving as many patients as possible and creating long-term durable value. In the early to mid-stages of building a company around such a machine, we require partnerships to develop and commercialize non-core assets and provide capital for us to develop and commercialize our wholly-owned assets while also reinvesting in the machine to expand its reach and capacity. When this is done well and in a timely fashion, it creates balance for us. Of late, we have become out of balance. The partnership we announced today with Sarepta is transformational because it returns balance to our business model, helps to focus our investment thesis without constricting upside potential and puts us on a fairly straight path to profitability. Let's take a closer look at the deal. Arrowhead and Sarepta entered into a licensing and collaboration agreement that includes select programs utilizing multiple TRiM delivery systems targeting various tissue and cell types. Under the agreement, Arrowhead…

Thank you, Chris, and good afternoon, everyone. It has been a remarkable year for plozasiran. We've had a series of high-impact presentations at major international academic meetings accompanied by four simultaneous publications and highly selective, high-impact medical journals. We also initiated our Phase-2 program in severe hypertriglyceridemia or SHTG this summer and culminating with our new drug application or NDA, submission to the U.S.-FDA earlier this month. I'll review some of those highlights over the next few minutes. First, it was a great pleasure to submit our NDA for plozasiran in the orphan condition of familial chylomicronemia syndrome or FCS to the FDA. That started the clock for their validation process, which is expected to take up to 60 days. If the FDA determines that the filing is complete and accepts it for review, they will inform us at that time of the PDUFA date by which a decision on approval may be made. Because the FDA has granted plozasiran breakthrough therapy designation, we are hopeful for priority review, but that determination will be made solely at the discretion of the FDA. Our database for the pivotal PALISADE study in subjects with genetically confirmed or clinically diagnosed FCS was only locked on May 16 this year. So this was an excellent performance by the Arrowhead team, especially given that this was the organization's first NDA. We look forward to hearing the FDA's filing decision. If we take a step back to assess the results that have been generated with plozasiran over the last year at medical meetings and in publications, a clear picture emerges. As data from the Phase-2 trials were presented and published in JAMA Cardiology and The New England Journal of Medicine in the first half of the year, we saw in the MUIR study of patients with…

Thank you, Bruce. Just over one week ago, our team was at the American Heart Association Scientific Sessions 2024 or AHA, where we announced new results from the Phase-3 PALISADE study and the open-label extension from the Phase-2 MUIR and SHASTA-2 studies of investigational plozasiran. And the feedback we collected on site from both physicians and patient societies continues to be very encouraging. We hear lots of enthusiasm about the differentiating attributes of plozasiran, which generally fall into five value pillars that you've heard me speak about before. First, the reduction in triglycerides has been both deep and durable. In PALISADE, as Bruce mentioned, plozasiran reduced triglycerides by around 80% from baseline as early as month one and maintained this reduction with limited variation throughout the full 12-month treatment period. Second, and for really the first time, patients and their doctors see real hope of achieving triglyceride levels below guideline-directed risk thresholds associated with acute pancreatitis, such as 880 and even 500 milligrams per deciliter. Around half of the patients at the 25-milligram dose in PALISADE maintain TGs below 500 milligrams per deciliter, with approximately 75% achieving levels below 880 milligrams per deciliter. To support physician education on guideline-directed risk thresholds, we announced on FCS Awareness Day earlier this month, the launch of a new disease awareness campaign called We'll Get There Soon. A key focus of our messaging is to educate the physician community about expert guidelines from several professional medical societies, which recommend maintaining triglyceride levels below 500 milligrams per deciliter to reduce the risk of acute pancreatitis. Third, the triglyceride reductions in PALISADE were generally consistent in patients with genetically confirmed and clinically diagnosed FCS. As I mentioned at the outset, new results from PALISADE were presented in an oral presentation at AHA and simultaneously published in…

Thank you, Andy. With our sharpened focus on the cardiometabolic therapeutic area, I'd like to discuss our two new programs for obesity and metabolic disease. Clearly, there have been advancements in the obesity space of late. This has created excitement in the field and we believe our programs ARO-INHBE and ARO-ALK7 have attractive profiles and may fill gaps in the current standard of care. We held a webinar in August on the obesity and metabolic space as part of our summer series of R&D webinars. We covered the biology of these targets, our preclinical data and our clinical plans. That presentation is still available as an archive on the website. As a high-level refresher, activation of the INHBE, ALK7 pathway instructs adipocytes to store fat. In an environment of nutrient excess, this pathway can become dysfunctional and overactive. Both targets are supported by human genetics where loss-of-function carriers have favorable body composition and metabolic characteristics compared to non-carriers. ARO-INHBE is a GalNAc-siRNA conjugate intended to silence hepatic INHBE expression. INHBE mRNA codes for Activin E protein, which is one of the ligands binding the ALK7 on the adipocyte's surface. It's the expression of ALK7 mRNA that is targeted with ARO-ALK7, which uses Arrowhead's novel adipocyte siRNA delivery platform. ARO-INHBE and ARO-ALK7 achieved 22% and 50% reduction in fat mass respectively versus saline controls in a mouse diet-induced obesity model. Importantly, this is achieved with the preservation of lean mass. In the same mouse model when studied in combination with incretin therapy, inhibition of the INHBE ALK7 pathway can potentiate weight loss with lower doses of incretin therapy while simultaneously preserving lean mass. Again, for those interested, I refer you to our August Obesity and Metabolic R&D webinar for more preclinical data details. Turning to the clinical studies planned for these molecules, both Phase-1 studies will evaluate single- and multiple-ascending doses as a monotherapy in obese patients as well as multiple doses in obese patients with or without type-2 diabetes in combination with incretin therapy. ARO-INHBE dosing should initiate very soon and dosing with ARO-ALK7 should initiate in 2025. We look forward to providing updates on these studies throughout 2025. I will now turn the call over to Ken Myszkowski.

Thank you, James, and good afternoon, everyone. As we reported today, our net loss for fiscal 2024 was $599.5 million or $5 per share based on $119.8 million fully diluted weighted average shares outstanding. This compares with a net loss of $205.3 million or $1.92 per share based on $106.8 million fully diluted weighted average shares outstanding for 2023. Revenue in 2024 was $3.6 million as there were no new partnership or license agreements executed during the year and no major milestones from previous license agreements were triggered during 2024. Revenue in 2023 was $240.7 million, revenue in 2023 primarily relates to our collaboration agreements with Takeda, GSK and Amgen. Total operating expenses for fiscal 2024 were $604.6 million compared to $445.7 million for 2023, an increase of $158.9 million. In 2024, operating expenses, excluding noncash stock compensation charges and depreciation and amortization, a better indicator of cash spend were $512.1 million compared to $355.1 million in 2023, an increase of $157 million. The key drivers of this change were increased research and development costs, primarily candidate costs, which is driven by clinical costs, manufacturing costs and toxicology costs. In particular, during the third fiscal quarter, we kicked off certain large Phase-3 clinical trials for our drug candidate, plozasiran, to address further indications beyond FCS, namely severe hypertriglyceridemia or SHTG. Net cash used in operating activities during fiscal 2024 was $462.9 million, compared with net cash used in operating activities of $153.9 million in 2023. The increase in cash used in operating activities is driven primarily by higher research and development expenses as well as lower revenue versus the prior year. Our footprint expansion is complete with only minor final payments to be made over the next few months totaling $8 million. We expect very little capital expenditures in fiscal…

Thank you, Ken. As I mentioned, Arrowhead is now extraordinarily well-positioned to build value in the short, medium and long term. We think all the necessary pieces are in place to execute effectively and efficiently. We are funded into 2028 with additional non-dilutive funding expected when existing and potentially new partnerships advance through clinical studies and generate commercial products. We are building out commercial to be ready on day one for our first commercial launch of plozasiran in patients with genetically confirmed or clinically diagnosed FCS. We are eager to receive our PDUFA date from FDA, but our expectation for commercial planning purposes is to be ready to launch in the middle of 2025. Plozasiran, our lead program is also in Phase-3 studies to potentially expand into the large and significantly underserved SHTG population a couple of years after we launch in FCS. If successful, that would provide a potentially large revenue stream. Aside of plozasiran, we have focused our pipeline around a cluster of cardiometabolic programs, providing some mid-term opportunities for commercial launches and multiple long-term opportunities. We also retain select key early-stage programs, providing opportunities to build pipeline value while still managing to limit growth in R&D expense. Lastly, we have a new collaboration partner with extensive clinical, regulatory and commercial expertise to advance and commercialize multiple promising candidates outside of our cardiometabolic commercial focus, so we end fiscal 2024 in a strong position across the board and are now well-positioned to execute on our long-term strategy and bring several important new medicines to patients over the coming years. Thank you for joining us today. And I would now like to open the call to your questions. Operator?

Thank you. [Operator Instructions] Our first question comes from the line of Ellie Merle from UBS. Your line is open.

Hi. This is Jasmine on for Ellie. Thanks so much for taking our question and congratulations on all the progress. So first, just with the deal with Sarepta, including a few FCA programs in Huntington's with the subcu delivery. How are you thinking about the future of Arrowhead CNS franchise from here and particularly where else you'd like to go with the subcu delivery? And then second, just curious on anything you can say about future plans for zodasiran? Thanks.

Sure. So thanks very much for the question. So the subcu CNS platform is one that we're really excited about. As you mentioned, HTT will go to Sarepta. We also have MAPT and alpha-synuclein that we are developing that remain wholly-owned, as I mentioned in the prepared remarks, but those are not really core to our business. And so those are potentially partnerable at some point, we are trying to determine the optimum -- the optimal time to partner those. We see a number of good potential CNS targets in the cardiometabolic space. And so I do expect that we will develop and retain some wholly-owned CNS assets that are -- that will be again core to our cardiometabolic business, so stay tuned on that. I expect that we'll have some updates on that in 2025. Regarding zodasiran, we are trying to figure out our strategy there. At the very least, we see a big opportunity or at least an interesting opportunity in HoFH. And so we have a protocol waiting to go -- waiting to start for a Phase-3 study to support HoFH. And we are also exploring how else we may be able to exploit that asset.

Thank you. One moment for our next question. Our next question comes from the line of Luca Issi from RBC Capital. Your line is open.

Great. Thanks so much for taking my question. Congrats on the progress and obviously in the deal with Sarepta. Maybe two quick one. Bruce, if I may. We've seen Eli Lilly discontinuing their siRNA for APOC3. So wondering what was your reaction to that. And then maybe on the deal, Chris, can you just maybe provide any color on whether that deal with Sarepta was competitive? And then maybe related, lots of moving parts, obviously with the FTC, but any potential risk here in the context of what we saw a year ago between Sanofi and Maze? Any color there much appreciated. Thanks so much, guys.

Sure. Bruce, why don't you take -- might take yours first and then I'll go after that.

Sure. I, of course, don't know why Lilly made that decision. It's hard to assess from a distance. Plozasiran is an awfully good drug and it may have set the bar too high. That's a possibility. But I really can't determine why Lilly would have made that decision one way or the other. Not very fulfilling for you, I know, but that's about the best I could do.

All right. And thanks for the questions, Luca, so regarding my question, so was the Sarepta deal competitive? Sure. We were talking to other companies about large strategic deals. This one made sense to us. There's, of course, never 100% overlap with respect to what's included in these various strategic deals, but at least philosophically, we were talking to other companies about that. And look that, what -- the potential good news here is that we also have additional assets that I mentioned in the prepared remarks that remain unpartnered that are not core to our business. And so I think we have room to do additional partnerships. Nothing I don't think quite as large as what we're talking about here with Sarepta with an overall deal value greater than $11 billion plus royalties. But I think there are still good deals we can do with other companies around other assets and potentially with discovery components. As I mentioned, we've got an extraordinarily productive discovery team that has capacity to serve us and Sarepta as well as other partners. Regarding the HSR risk, look, who knows, I can't give you much guidance on that other than from our perspective, there does not seem to be overlap there that make us concerned. But of course, that's not our call to make. We'll just have to see when that comes down. We expect to have a ruling 30 days after we file. And so sometime, I believe early January is when we would expect to clear HSR.

Thank you. One moment for our next question. Our next question comes from the line of Andrea Newkirk from Goldman Sachs. Your line is open.

Hi, everyone. Thanks for taking my question and congratulations on the Sarepta deal. And maybe on the back of that and in the context of the debt financing that you announced on the last earnings call, how are you thinking about paying that down? And is there a particular amount that's maybe earmarked in the Sarepta deal that's obligated towards paying off the principal for that facility? And then, Ken, maybe a question for you here, if you could quantify the R&D savings that you expect to realize and over what time period we could think about that? Thanks so much.

Sure. So we will be paying down the debt through Sarepta as well as through other deals as cash comes in, there are formulas for that. And so we do expect that to contribute to paying down the debt over time. Ken?

So we've taken certain costs out of the budget, but the main components or the biggest part of our R&D spend relates to those Phase-3 trials that I mentioned earlier. And we expect those costs to continue over the next two years and then decrease by 2027. And so it would depend on if there's any new large trials by that time. But over the next two years, we'd expect it to remain constant with the guidance and then decrease.

Thank you. One moment for our next question. Our next question comes from the line of Maury Raycroft from Jefferies. Your line is open.

Hi. Thanks for taking my questions and congrats on the deal update today. I wanted to ask about the obesity programs. So for INHBE and ALK7, how important are these strategically to the company at this point? And with obesity studies, you can get insight into efficacy relatively quickly. I'm wondering if you'll run a placebo-controlled Phase-1 and can you commit to getting to data from either of these programs sometime next year?

I'll take the strategic question. These are important to us strategically. Look, these are really interesting targets. Genetically validated. We will be, I believe, the first ones in the clinic with INHBE and I think we'll be the first one in the clinic by a long shot with ALK7. I don't know anybody else who will be in the clinic in the near term with siRNA against adipose. So we like our positioning here. We like the genetic data. We love our animal data. And so these are important for us. To be honest, if we wanted to partner these, we could have, but these are important for us strategically. And so we look forward to run these studies and see what we see. James, do you want to address the Phase-1?

Sure. On the Phase-1 designs, both programs are placebo-controlled in patients with obesity. The main purpose of the study are, of course, to generate an understanding around safety and PK and some early target engagement biomarker data. I mean, we have some exploratory endpoints in there, but these are primarily focused on safety, PK and biomarkers.

Thank you. One moment for our next question. Our next question comes from the line of Jason Gerberry from Bank of America. Your line is open.

Hi. Good afternoon. This is Dina on for Jason. Thanks so much for taking our question. Congrats on the deal announcement and the progress this quarter. The first one we had is more of a broad strokes question. How does the Sarepta agreement change your TRiM discovery engine prioritization by tissue type and targeted number of lead preclinical candidates that you plan to kind of accelerate into the IND stage over the near term? Like, do you plan to kind of separately advance preclinical assets for your own internal verticals or for additional partnerships? And then I just had a follow-up on your zodasiran strategy. Is it may be safe to say that we could see an execution of a CVOT when the company is in a better capital position with cost from the plozasiran studies winding down in 2026 or so? Thank you.

Sure. So with respect to the C1 question, look, we have always been interested in asking this triglyceride question in outcomes in our KOLs, feel strongly that plozasiran could be a very powerful ASCVD drug. And so we just need to wait to see a better visibility on capital in order to start that [indiscernible]. Those can be expensive and time-consuming. And so we just want to make sure that we've got the capital in front of us before we start that. With respect to the first question, sorry, what was that again?

About our bandwidth for all the targets.

Bandwidth, yeah, right. So look on discovery, we really can be an and company not an or company. We've got plenty of bandwidth to serve Sarepta and to serve ourselves and frankly, to serve other partners. James, approximately how many nominations can we do over the last couple of years?

I mean, we've done close to double-digit nominations per year. So five to 10 per year is certainly doable and all of the targets will probably not come in all at once from a partner, so.

Right. So if we are in the 5 to 10 nomination range per year, this is a five year collaboration. And so over those five years, we could, goodness, we'll have dozens and dozens of nominations over that time. So we've got plenty of room to have a vigorous discovery campaign with ourselves -- for ourselves as well as for Sarepta as well as for other partners.

Thank you. One moment for our next question. Our next question will come from the line of Patrick Trucchio from H.C. Wainwright. Your line is open.

Thanks. Good afternoon and congrats on the collaboration. I just have a couple of follow-ups on it. Can you tell us how the clinical or preclinical programs are expected to be prioritized within the collaboration with Sarepta? And how much input Arrowhead would expect to have in that process and separately, can you tell us how the collaboration contributes to or accelerates achieving the 2025 strategy?

Sure. So I'll take that one first. I don't know that it affects our 2025 strategy so much because we have one more year for 2025, okay, and I don't know if Sarepta can move fast enough to get us a target and for us to get them something that will enter the clinic during that time. So I don't think it's relevant to 2025 necessarily. Regarding prioritization or regarding how we run those, well, so I think, so the clinical assets will go to them. And we are happy to help them with the transition, but those will ostensibly move to them and they will continue those clinical programs and essentially on day one, again, we're happy to help them, but that will be their purview. The non-clinical assets, we will get those two CTA ready and then they will take those over and assume all the costs and of course, all the burden of running clinical studies with them. Same thing with the discovery bucket. Our job is to get them a CTA-ready package and then they would take those for you in the clinic.

Thank you. One moment for our next question. Our next question comes from the line of Edward Tenthoff from Piper Sandler. Your line is open.

Great. Thank you, and my congrats too on the financing. You guys have been wheeling and dealing. I'd love to see it. When it comes to the $250 million over the five-year period, firstly, is that considered like an R&D funding or is it -- what is sort of the classification of that? And how will that be -- is that just straight line amortized or how would you be recognizing that?

So the $250 payment was just a timing of the payment. The accounting recognition -- revenue recognition for that, we need to assess that and with the rest of the deal, including the upfront payment and what our performance obligations are. So we'll get more information to you on how we will recognize that revenue. And that's simply $50 million a year over five years starting on the one-year anniversary of the closing of the deal.

Thank you. One moment for our next question. Our next question comes from the line of Mayank Mamtani from B. Riley Securities. Your line is open.

Yes. Good afternoon. Thanks for taking my question and congrats on a productive quarter and the deal. Just quickly following up on the plozasiran NDA filing strategy. Could you confirm if the focus there is on the 25 mg dose level? And how do you think of the total patient exposure there to be able to have that broader label that you did evaluate the study for with and without FCS genetic confirmed patients? And I do have a follow-up.

Bruce?

Well, so the filing is only for the 25-milligram dose because it performed really, at least equally to the 50-milligram dose. So as I said, that all the data for the drug and all the indications at 25 milligrams was the right dose. So I think we feel very solid there. The question -- if I understood the second question right, I didn't really hear it very well, but if I understood it correctly we, of course, don't know at this point, how the agency, how the FDA will feel about the question of genetic versus clinical FCS. We did expand to include the clinically diagnosed FCS patients at the suggestion of the agency. So that says something. But ultimately, it -- we would assume that assuming the agency is happy with the NDA in the end, we won't be discussing indications until the very end. I hope I answered your question there, but I'm not 100% sure I did.

Thank you. One moment for our next question. Our next question comes from the line of Prakhar Agrawal from Cantor. Your line is open.

Hi. Thank you for taking my questions and congrats on the Sarepta deal. Maybe firstly, on the deal, how much of the data did Sarepta see on both DM1 and FSHD programs? Was it mostly limited to the SAT program, SAT cohorts or were you able to see some of the multiple-dose data as well? And the second question is on INHBE. It's an interesting target, preclinical data are very interesting and the genetic evidence is out there. So maybe just broadly, how are you thinking about where this drug fits in the obesity landscape relative to the incretins out there commercially and that are coming out soon? And how does an RNAi therapy differentiate in obesity? Thank you.

Sure. So Sarepta side, we have not moved into MAD cohorts yet. So all we have is very limited, in fact, SAD data, but that's what I saw. Regarding INHBE and ALK7, look, our job here is not necessarily to put GLP-1s out of business. And I think that we have an opportunity to work with GLP-1s as we talked about in the prepared remarks and also in the webinar several months ago. At least in animal studies, we were able to use a sub-therapeutic dose of tirzepatide in combination with either ALK7 or INHBE and show good weight loss, in fact, better quality weight loss than tirzepatide alone that could be possible use. Also maintenance could be a possible use in order to be on a GLP-1 and then lose a substantial amount of weight and then keep it off with INHBE or ALK7. They could also be used as monotherapy, who knows? We'll see what the tolerability looks like. From our perspective, the --- we've -- the -- as you say, the non-clinical data were compelling, the genetic data are compelling and so we really look forward to seeing how this translates into humans.

Thank you. One moment for our next question. Our next question comes from the line of David Lebowitz from Citi. Your line is open.

Thank you very much for taking my question. Given the large partnership with Sarepta, what are your thoughts on additional partnerships going forward? Are you intending to take a pause from that or are you still on the lookout?

I would say somewhere in between those, we are still on the lookout. As I mentioned, we are -- we were, before we did a Sarepta deal, we were in discussions with other companies about large strategic collaborations. Those we are no longer really considering, but there are smaller bite-size collaborations and license agreements that certainly could take place. Look, our hair is not on fire. This is an important deal for us. This gives us a lot of breathing room and gives us frankly what we needed in a number of areas. And so I think we can get the right deal or deals done over time. We don't have to have that tomorrow, but I do expect more deals over some period of time. Certainly, we've got the capacity on the discovery side and we've got the assets, both non-clinical and clinical that are not core to our metabolic -- to our cardiometabolic focus. And so I think there's ample ammunition there for additional deals.

Thank you. One moment for our next question. Our next question comes from the line of Keay Nakae from Chardan. Your line is open.

Hi. Yes. Thank you. Congrats on the deal. Just looking for some further clarification about the plans for lung. I think you said you're still taking RAGE into a Phase 2, maybe first half of next year. But will you look to partner that? And then beyond that, will you look to pursue any other loan targets? Thank you.

Sure. Look, yes, I think that ultimately RAGE should be partnered. And that's going to require large and relatively complicated asthma studies, maybe COPD. With our renewed focus on cardiometabolic, it would make sense for us to find the right partner for that. We don't have to do it tomorrow. But at some point, it would make some sense to partner that. It could be that it makes sense for us to do a bit more work. Some kind of Phase-2 study we'll see in order to increase the value of a partnership. We haven't made those decisions yet, I'm just telling you what's on the table, I guess. Look, we like the pulmonary platform. I think there's an awful lot we can do there, particularly in deep lung targets and so my hope is that we continue to develop that. Again, less for ourselves, longer-term at least, less for ourselves and more for partners, it doesn't mean that we wouldn't initiate some programs, but it would mean that we'd be doing those largely on spec. And my hope is that we can find partners who are interested in helping us develop the right medicines against the right targets in pulmonary.

Thank you. One moment for our next question. Our next question comes from the line of Brendan Smith from TD Cowen. Your line is open.

Hi, guys. Thanks for taking the questions. Another big congrats from me on the deal. I guess piggybacking really on that last question, just on the pulmonary vertical, have you feel that inbound at this point or are you in any active discussions about potentially partnering that platform more broadly? I guess, obviously Arrowhead is kind of the lead there, but to your point, there seems to be a lot of optionality for that kind of across-the-board. So just wondering where you guys are -- where you're headed on that a little bit more broadly? And then can you just maybe confirm for plozasiran if kind of now this renewed focus on cardiometabolic, does this mean that a commercialization partner is just kind of off the table altogether now and you think you should be able to fully commercialize it across the different segments on your own or is that still maybe something you consider like post SHTG data before the CVOT readout? Thanks.

Yes. So we would certainly consider ex-US partners or partner or partners. Within the U.S., we really see ourselves building out our commercial infrastructure largely around plozasiran and then and then using that infrastructure to commercialize other cardiometabolic assets as well. But sure, we would certainly consider some ex-U.S. partnership if the right one came around. Back -- again back to lung, we have spoken with folks about lung, as you can imagine. I don't know -- I don't have any guidance on when we may get a pulmonary deal done. As I mentioned, my -- the Sarepta deal is important for us and it allows us to have some breathing room here. And so I don't expect a pulmonary partnership in the very, very near-term, but it's certainly something that we have spoken with other companies about and we will continue to do that.

Thank you. One moment for our next question. Our next question comes from the line of Mani Foroohar from Leerink. Your line is open.

Guys, you have Ryan on for Mani. I'll add my congrats on the deal and thanks for taking our questions. So maybe first, just a follow-up on a prior question around paying down debt through the BD cash flow from Sarepta and other agreements. So does that mean you plan to utilize this new cash to cover the interest expense on the debt or are you planning to actively pay down the principal and the latter to what degree and on what time horizon should we expect that? And then real quick, maybe just circling back to the $300 million near-term milestone for DM1 enrollment. Any specifics you guys can provide on the $100 million and $200 million milestones and how those are achieved?

Yeah. And so I can't get too granular on that but I can tell you that has to do, as you mentioned, with the DM1 program and it just has to do with when a certain number of patients have been dosed within some of the early cohorts. We are on track, I believe to reach that over the first three or so quarters of 2025. Look, that can change as those studies go on, but at least right now, that's -- that is our hope, that's our expectation. Regarding the debt, we'll be paying down both interest and principal over time as cash comes in through Sarepta as well as through other partnerships.

Thank you. One moment for our next question. Our next question comes from the line of William Pickering as an analyst for Bernstein. Your line is open.

Hi. Thank you for taking my question and congrats on the deal. You made some reference to cardiomyocyte targets during the prepared remarks, and I was wondering if you could expand on what sorts of indications you're interested in here, whether it's rare, higher prevalence? Is there a clear demarcation between the cardio targets that you want to pursue independently versus what Sarepta has dips on? Thank you.

Yeah. So I can't give you too much guidance. I can't give you any guidance, frankly on what targets we are considering within cardiomyocytes. That's still pretty early. Our non-clinical data have been compelling. And so we view that as a platform that we can start to really consider bringing into the clinic. I can tell you Sarepta has not given us any targets yet within cardiomyocytes. I don't know if they have any, in particular, they're thinking about right now. They just have the ability to designate some targets within cardiomyocytes as well as skeletal muscle and CNS. So I don't know where they're going to go or when they're going to do that. We have some ideas on targets and so my expectation would be that probably sometime in 2025, you might hear a bit more about that.

Thank you. One moment for our next question. Our next question will be a follow-up from Mayank Mamtani from B. Riley. Your line is open.

Hi. Thanks for taking my follow-up. Could you also touch on how your TFR ligand-based targeted approach is different than maybe the other main shuttle approaches being looked at? And what attributes you feel allow you to optimally target, I believe MAPT, there's a couple of approaches being looked at there. And thanks for taking my follow-up.

Yeah. Sure. So we haven't disclosed a lot of details on that. I would refer you to the webinar that we gave a few months ago, what month was that?

October.

October, where we covered the CNS platforms and talked a little bit more about that specific platform and how it differentiates itself.

And I think structurally all we said it was TFR targeted, but we didn't describe the structure any more specifically than that.

Thank you. And as there are no further questions at this time, I would now like to turn it back over to Chris Anzalone for closing remarks.

Thanks very much everyone for joining us today. This has been an important day for us with this Sarepta deal, we are excited about what that's done for us as a company. We're excited about working with Sarepta. So thanks for joining on the call today, and I wish you all a happy Thanksgiving.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.