Arrowhead Pharmaceuticals, Inc. (ARWR) Earnings Call Transcript & Summary

Hi, everyone. Thanks for joining us at the first day of the Goldman Sachs Global Healthcare Conference here in sunny beautiful Southern California. I don't want to judge Chris, but he came all this way, and it's raining and cold. We're required to make certain disclosures in public appearances about Goldman Sachs' relationships with companies that we discuss. The disclosures relate to investment banking relationships, compensation received or 1% or more ownership. We're prepared to read aloud disclosures for any issuer during the sessions upon your request. However, these disclosures are available in our most recent reports available to U.S. clients on our firm's portal. In addition, updates to those disclosures are available by ticker on the firm's public website at www.gs.com/research/hedge.html. Goldman Sachs agrees to host this conference on the basis that no third-party speaker will provide confidential or material nonpublic information. In addition, by attending this conference, you provide Goldman Sachs the right to record and redistribute the conference information. The views of third-party speakers do not necessarily reflect those of Goldman Sachs. So it's really great to be joined by Chris Anzalone here from Arrowhead Pharmaceuticals.

Let's just dive right in. So let's turn to a high-level overview. Please remind us where you are with Arrowhead's RNAi platform.

Sure. So thanks again for having us. It's really a pleasure to be here. We are building a broad-based RNAi company. We have 12 clinical programs right now, 7 are wholly owned, 5 are partnered. And our model is to exploit our ability to move quickly into the clinic and build a broad and large platform and to finance that, at least in part, through partnering. I think, we've done a good job about being disciplined in that partnering because I think the way that we're going to create a lot of value quickly is through our wholly owned assets. So again, of our 12 programs, 7 are wholly owned, 5 are partnered. I think we'll push another 3 or so new clinical candidates into studies -- into clinical studies this year. And we are in a number of different cell types; of course, hepatocytes. So we've got a number of drug candidates that target hepatocytes. We have new data in our pulmonary platform; suggests that we can address pulmonary epithelial cells. We are addressing skeletal muscle cells. We've got one program ARO-DUX4 that's ready for CTA and another that I think will be CTA towards the end of the year. And we have a new initiative into CNS. I think we'll be in the clinic with that, with CNS over the next couple of months. And then of course, adipose, we just talked about at our Analyst Day. So we are in a number of different areas. Our thinking is that, to extract proper value from RNAi, we need to go where disease is and get outside the liver.

Excellent. So you've actually done a great segue to discuss on the R&D Day. So I think we're going to start with a discussion of what you all are seeing in the lung. Can you give us an overview of your approach there and how you've been able to get RNAi systemically into lung tissue?

Sure. So we've been at this for quite some time. Our drug candidates are inhaled, although we also have a couple of programs where we are testing subQ injections. But right now, at least the data that we've seen so far, has been via inhalation, via nebulizer. These are targeted RNAi constructs, just like they are for hepatocytes. Of course, we use different targeting ligands, but the concept is the same. They are structurally simple molecules of an RNAi backbone that's clinically modified and then conjugated to a targeting ligand. We can get knockdown with RNAi molecules that are not targeted. But we get substantially better knockdown with targeted constructs. We have made great strides in increasing our potency over the last couple of years that I think has enabled us to get good knockdown. We've seen as much as 95% knockdown after a single dose, in fact, in our pulmonary program.

Maybe kind of focusing in on that notion of potency, how do you think about how the current wave of RNAi drugs you have in the clinic, in the lung, so RAGE and MUC5AC, what have your learnings been from the kind of earlier-generation approaches, particularly when you think about like the nonclinical tox signals and how you feel comfortable on the forward?

Sure. It's a great question. So our first pulmonary program was ARO-ENaC. It was targeting cystic fibrosis. We found, I guess 2 years ago now, yes, I guess 2 years ago, that -- we were in the clinic and we were seeing good tolerability. But then, in a chronic tox program, we saw some local lung inflammation, not at all doses but at some of the higher doses. And so we diluted that. And we decided that we needed to crank down the potency on all future programs. What we are able to figure out, given that some of those doses were -- led to inflammation and some did not, we found this sort of ceiling, if you will, that over the course of about 6 months, that ceiling was around 100 mg per kg. And we didn't think it was target specific. We didn't think it was ENaC specific, but just -- we didn't think it was oligo specific, it was just the amount of stuff, if you will, that gave us this macrophage overload. And so that's our bogey, that we want to stay below 100 mg per kg over a 6-month time frame. What we've seen in ARO-RAGE is, I believe, we'll be dosing every couple of months or so, and we have data at our second-highest dose, which gives us -- which is just under 1 mg per kg. And so we are well below that 100 mg per kg over 6 months. We're probably more like 3 mg per kg over 6 months for ARO-RAGE. And so we think we're well beneath that threshold. Now we don't have chronic tox data yet. But given what we have learned with ARO-ENaC, we think we should be clear.

Okay. So maybe moving over to the data you all saw at the R&D Day, can you walk through some of the data you presented both in the top line a few months ago but also at the R&D Day for ARO-RAGE in healthy volunteers?

Sure. So as you say, we have data in -- we have some data so far in healthy volunteers. ARO-RAGE is an interesting target because we believe that we can look at activity in circulation as well as with BAL, bronchoalveolar lavage, fluid. What we first disclosed was circulating data. And after a couple of doses in circulation, we saw 80% knockdown, as high as 90%, but a mean knockdown around 80%. And that was very encouraging. I don't think anyone has shown anywhere near data like that. And so we thought we are on the board. And that was with the second-highest dose. Again, that's after 2 doses. We then have had additional data at a higher dose. We have BAL's data after only a single dose, and we saw 90% knockdown within the lung; again, a mean of 90%, as high as 95% knockdown. So that tells us a few things. One, I think we are on the board. We're getting good knockdown. It's well tolerated so far. We think it's a good target as well as our other targets that we're going after. Second thing that I think we're seeing is, at least for RAGE, I think there is better local knockdown than is represented in circulation. I think there are extra pulmonary sources of RAGE. And so what we care about for this drug is how much knockdown you get in the lung. And so whatever you see in circulation may be a slight underestimate of how much knockdown you're seeing in the lung. And so we didn't see anything that is anything but encouraging for us. We expect ARO-MUC5AC and ARO-MMP7 to follow as we see data from those programs. But I think it's a great first step for us for that whole franchise.

I think I want to follow up on something you mentioned, that you have extra pulmonary sources of RAGE. So certainly, we would see among the more skeptical individuals we talked to around the RAGE program is, well, every 20 years, RAGE comes up as a target for your favorite disease. For a while, it was for the CNS and Alzheimer's; for a while, it was in cardiovascular disease and the genetics of -- of genetic variance of RAGE. So what gives you comfort that depletion of RAGE, specifically in the lung, can provide benefit in lung conditions without affecting kind of other pathologies?

Right. So we -- look, the -- it's an interesting anti-inflammatory pathway because it's proximal. We think that we can knock down RAGE, that we can get good, broad anti-inflammatory activity. There is no reason to expect that we should see on-target tox. I think the challenge -- the reason it's been undruggable is that it's been very difficult to silent, to knock down, and I think we've shown that.

All right. So to that end, at again a more simplistic level that we run into the RNAi conundrum, what do you believe is the degree of RAGE silencing that will translate to clinical benefit and the lead indication of asthma and other kind of lung pathologies?

The short answer is I do not know. If we were seeing knockdown at 50% or 60%, I think that's a real question, is that going to be enough to see disease-modifying effects. But I think the fact that we're seeing 90-plus percent knockdown in the lung gives us confidence that whatever that number is, that I think we are there. We'll have -- of course, we'll have data in health -- I'm sorry, in patients through this year and then into next year. And so we'll have a much better understanding of disease-modifying effects. But again, just given the degree of knockdown, we are -- we have good confidence that we can see disease-modifying effects.

So following up on what you just mentioned, can you remind us where the next developmental stage is, steps, for ARO-RAGE in asthma?

Sure. So we are in asthma patients right now. We will be -- we'll be looking at a variety of parameters over this year and probably into next year. I expect that we will have patient data this year. I don't know if we will have enough to disclose those data because -- we're not going to disclose data unless we have a story there. My hope is that -- or my expectation is that we'll have data sometime towards the end of the year into the first part of next year, at least to show activity in healthy volunteers. Disease-modifying effects may not be quite around that time, but we'll see.

Okay. So maybe getting more granular on that front, so we understand that the asthma patients in the Phase I multiple ascending dose, they include patients who have detectable fractional, I would say, nitric oxide or FeNO. So do you think they could be assessed in parallel with RAGE suppression? And do you know from the existing Phase I MAD that there are patients for whom FeNO changes would be measurable?

Yes. So we don't know that for patients who have been dosed so far. But we have changed our protocol, we've amended our protocol, to bring in high-FeNO patients. And so we will -- we don't have those patients in yet. Now some of our patients may, just by luck, be high. But we are actively interrogating that patient population this year. And so we will be dosing those patients this year. Will we have data by the end of the year? I don't know. It's possible, but certainly into early next year, I think we'll have those data.

But the -- there will be a reasonable expectation that at higher doses of the MAD, you would be trying to enrich for patients who have a high FeNO...

We absolutely will be doing that.

Okay. So stepping back again, how do you think about the use case for a drug like ARO-RAGE in the asthma treatment lens?

Sure. Look, I think it's going to be an interesting compound for severe asthma, for all of types of severe asthma, both eosinophilic and non-eosinophilic. It also may be an interesting drug against COPD. We are thinking now that RAGE is more of our asthma drug and ARO-MUC5AC is more of a COPD drug, but I think there's good crossover for both of those.

Okay. So to that end, how do you think about where a drug like ARO-RAGE could be used versus the kind of variously well-entrenched biologics in eosinophilic asthma, and what it would take to show activity in neutrophilic asthma, which is obviously kind of the great white whale in asthma?

Yes. And I can't answer that. We'll have to wait to see what our data look like.

Okay. I guess, kind of stepping back, what do you think people are missing about the lung RNAi branch?

Well, look, I think there is skepticism around it. And I think that was reasonable. No one has succeeded. Well, first, a few people have succeeded with inhaled drugs broadly. Second, nobody has succeeded with RNAi in the lungs. And so I think there is a big -- there's a wait-and-see attitude. And also it's understandable because ARO-ENaC, again, we were seeing some local lung inflammation in chronic toxicities. So I get that. I think we just crossed a big bridge though, the fact that we are seeing good deep knockdown with ARO-RAGE at relatively low doses with good durability. As I said, I think that's going to be dosed once every 2 months, maybe less frequent than that. I think that puts us well within the range that we expected, had to -- have to be into to have a well-tolerated drug. And so I think that all the data so far has been encouraging to a data point. And so I think people are waiting to see what the health of -- sorry, what the patient data look like. But, we're still in early times here. We had our R&D Day, what, a week or 2 ago. We had some top line data maybe a month before that. And so the market still is trying to digest what those data are going to mean. But look, I think we're bullish on that. I think that this whole pulmonary franchise is just that. I think it's a franchise. ARO-RAGE, I think is going to be done by drug. I think ARO-MUC5AC and ARO-MMP7 are also going to be done by drugs. But this is a target-rich environment. And I think that the long-term real value of the ARO-RAGE data so far is that it suggests that we have a true franchise. And we think that the lungs are a target-rich environment where we don't see 2 or 3 or 4 drugs, we see 9, 10, 11 drugs, gives us an awful lot of ammunition to treat various lung diseases.

So maybe to that end, and kind of coming back to the discussion at the beginning of the RNAi platform, how do you think about the idea of if you start to see efficacy signals with ARO-RAGE, then like this becomes like a major focus of the company to march this thing forward as the Arrowhead drug as compared to -- and you mentioned maybe this is a platform, how much you could try to like partner this and other assets. So like how do you think about where that is today? And when do you think you'll feel more comfortable saying, okay, we can make a choice here about what ARO-RAGE is going to be to us versus what it could be to a potential business development partner?

Right. Well, first, so I -- we get that question a lot, what is the Arrowhead drug. And I don't like that question. I don't think we have to make that designation. What we're building here is a broad-based company. Look, we're a 3-point -- whatever we are today, $3.8 billion, $3.9 billion market cap company. We're a small company. But I think that we have technology that is well validated. We have the ability to bring it to a number of different cell types and, therefore, diseases. And so we're building a broad pipeline. And I think we can pull that off. With respect to pulmonary, we like that space. We like the idea of building out commercial infrastructure for pulmonary. There are around 16,000 pulmonologists in the U.S. And as I said, we see a number of good drugs there. And so it makes sense for us to really -- to build out infrastructure there, and I expect we'll do that. Which is not to say we will never partner in the pulmonary space, that's also not true, because there are so many good targets. I expect that we will target -- we will partner there. But I do expect that if we -- when we're here 5 years from now, we'll be talking about a pretty broad pipeline of wholly owned pulmonary assets.

That's very interesting. I'll tell you, you can put me in the bucket of at least prior lung RNAi skeptics. So we'll be watching that space very carefully. So maybe, shifting gears over to kind of another topic that came up in the R&D Day, which is the development of the adipose tissue as a target. So obviously, very early stages, but can you give us some insight about how we should be able to get specificity and how should we think about kind of target and disease space that you're looking to pursue?

Right. So it's very early days, of course. But just to level set here, here's what we're seeing. With a single dose -- after a single dose of this platform, we've not talked about yet what exactly the targeting ligand is and such, but the structure there is the same as all of our conjugates. It's a very structurally simple set of molecules, right? It's an RNAi sequence that's chemically modified, conjugated to a targeting ligand. What we're seeing there is deep knockdown, 90-plus percent knockdown, the last many months. We don't even know how long yet. We've gone out a bit beyond 6 months, and we're still seeing a very flat knockdown of these gene targets. And so I would expect this to be at worst a twice-a-year injection, a subQ injection, and maybe even less frequent than that. And so that is interesting. So that's point one. Point two is, what are you going to do with this, what disease areas to go after? And there's a number of cardiometabolic targets we can go after. Obesity also clearly -- and it's funny. If I were talking to you about a possible obesity program or set of programs 5 years ago, you wouldn't let me talk about it because it's a stupid thing to talk about. The fact that we are now seeing some real strides in that space have made it safe to go into obesity. And I think we can play there. So within metabolic disease, within obesity, I think there's a number of areas we can go in with adipose.

Okay. So maybe shifting gears over to the CNS. So you mentioned that your lead indication is SOD1-mutant ALS. Obviously, Biogen and Ionis have an approved drug in the U.S. in Qalsody. And sort of about 1.5 hours ago, Mylan was talking about a SOD1 program as well. How do you think about competitive positioning in a crowded space with very few patients?

Sure. So first, let's -- that's our first CNS program. I wouldn't call it our lead CNS program, but it's our first. It's a good first program. And the reason is because there's a clear regulatory pathway. We've been first in a number of areas, and there are certain benefits to being first, but there are also certain liabilities. And the fact that we are not first here is helpful to us because we have a clear regulatory pathway that we can follow, and it involves biomarkers. And so we can see early on what kind of knockdown we're getting and what kind of durability we're getting. This won't be a very large clinical program. And so we think we can get to approval relatively quickly, and we'll know how the platform is working. So it's a great benefit to us as a learning tool to see how this platform is behaving. But now, beyond that, this -- we expect this to be a good drug. And these are patients who need -- who desperately need new therapy. We expect our drug candidate, ARO-SOD1, to be -- to lead to deeper knockdown than tofersen and at least given our animal data. And we expect to have a longer durability as well. Is it once every 3 months? Is it once every 6 months injection? We don't know yet, but I think it's going to be less frequent than tofersen. And so I think that we will have a competitive advantage there. I think we do have something to offer to those patients.

So maybe kind of following from that on a very practical basis, how are you thinking about potential trial design? Is there a notion that it would be at least one switch study? Do you think you can run against the placebo? How are you thinking about that?

It's a little too early to opine on that now. I will say, though, that we do expect to continue to follow Phase I patients out. There will be an extension -- we expect there to be extension as part of that Phase I. And so by the time we are in a pivotal, I think we will have several patients that have been on drug for some period of time. And so I think that will give us some functional changes to [ 2.2 ].

Okay. So maybe moving over to NASH, which is another fascinating -- so you mentioned obesity as a 4-letter word a couple of years ago. NASH was also a 4-letter word, but it's back now. How do you think about the PNPLA3 opportunity in terms of target populations and target patient selection and really, what you need to see in terms of histological and biomarker changes that can really give you confidence you have a drug in that space?

Sure. So obesity is a clear problem. We always anticipate that. It's a clear problem. But it was also clearly hard, which is why we partnered ARO-HSD with GSK. We have great confidence. We continue to have great confidence in that drug candidate. But NASH seems to be a heterogeneous condition and may, at least for some patients, require a cocktail approach. And so that, to us, felt better addressed with a -- by a larger company. And so it made sense to us to partner with ARO-HSD. ARO-PNPLA3 is a little bit different. It is a clear genetic population, and it's not small. The thought is there are probably more than 4 million of those homozygotes in the U.S. alone. And so it is one -- a relatively large population that is clear. If we can knock down PNPLA3, there's a good expectation that we can address NASH in those patients. J&J did a great job on their Phase I and have shown us that after a single dose, we're seeing a 40% reduction in liver fat. And so that's a place that is exciting to us, and we expect to take that program forward.

Okay. Maybe following from that, how should we think about kind of the next study for PNPLA3 in terms of like a real NASH kind of efficacy study?

So I think that's what you'll see. I think that we will take that into a large-ish Phase II study where we'll be doing biopsies and we'll be looking at the traditional NASH end points not just liver fat.

Right. So you mentioned again earlier on that you plan to bring 2 to 3 new programs into the clinic every year. And can you give us a sense of like, on the forward, what are other cells? Yes, we mostly hit the highlights. You mentioned DUX4 in the muscle, but are there other tissues we should be looking at as kind of the next space for Arrowhead?

Yes. So we're not giving much guidance on that right now because we've just pushed into the public space, CNS and adipose. And so we're addressing an awful lot of tissue types: hepatocytes, pulmonary, muscle, adipose and CNS. And so it's 5 cell types gives us access to an awful lot of disease areas. We said publicly that we think we can get into a new cell type every 18 to 24 months. We've just pushed 2 new ones into the public space this year. And so let's focus on those and building those out. We see -- CNS, to us, feels an awful lot like pulmonary in that it is a target-rich environment, and there's a number of just grinding unmet medical needs that I think we can address on the CNS. And also we mentioned at our Analyst Day that we're working on getting path to blood-brain barrier. We're not ready for [ front time ] there yet, but we have some very encouraging data to suggest that this is a place that we should continue to place bets, that we think in the near future we could have something -- we could have an RNAi drug that is systemically delivered that can address CNS. That's a very exciting play for us and allows us to get into a number of different CNS diseases that would be much harder to address via intrathecal injection, for instance, those diseases where we require a knockdown in deep brain regions, which will be much harder to address with intrathecal injection. And again, as we talked about adipose, there's a number of metabolic and obesity areas we can go into there. So I think we have our plate full with those 5 cell types for right now.

Fair enough. So maybe going back to the cardiometabolic conditions. Obviously, you have not yet mentioned ARO-APOC3 and ARO-ANG3, which are well underway. Can you remind us how those programs are progressing? And what's coming next?

Sure. So ARO-APOC3 has -- is in -- has completed Phase II studies and is in a Phase III study right now. It's fully enrolled against FCS, a very small population. The way that we are looking to develop that drug is sequentially. So we are in this Phase III for FCS. I expect that to be completed around this time next year, and I expect it to be at NDA or thereabouts towards the end of 2024. So I think that's a near-term commercial opportunity. Again, it's a small market but allows us to become commercial, allows us to get the drug into the marketplace and allows us to begin to talk to the market and to providers about this drug. And look, we expect that to work. Our triglycerides lowering has been unbelievable, frankly, with ARO-APOC3. We are bringing these patients with severe hypertriglyceridemia into the normal range where you don't see risk of pancreatitis. And so we think that's a real drug. Now we don't we don't expect to end there. I expect, by the end of this year or early next year, we'll be in a pivotal study against severe hypertriglyceridemia, or SHTG. We think that's a very interesting market. It's a fairly large market, we think, a few 3 million or 4 million patients in the U.S. The regulatory pathway there is clear, simply lowering triglycerides as an approval end point. And we think, that's a year-long study. And so I think we'll be in that pivotal, as I said, at the end of this year or early next year. That will enable us to broaden out that label from FCS to a much larger population in SHTG. We also expect then to start a pivotal study in the much larger population of mixed dyslipidemia. Probably early next year -- probably not at the end of this year, probably early next year. That will be a CBOT. That's going to be a large and expensive study but allows us, I think, to broaden out that label one more time to treat a very large population. And we're very excited about what APOC3 can do for those folks not just in lowering triglycerides but also lowering LDL and increasing HDL and lowering ApoB. It is a powerful cardiometabolic drug because in a world -- in a cardiometabolic -- cardiovascular system that has been only looking at lowering LDL where we know there are other lipid parameters that are increasing cardiovascular risk, we are now addressing those other risk factors. And so we expect to be in that pivotal study shortly, and we think we have a good shot there. With ARO-ANG3, there is clearly some overlap with ARO-APOC3. And so we are now thinking about that drug as an Ho or HeFH drug. We expect to be in a Phase III study for HoFH towards the end of this year, early next year. And then, we're trying to figure out what our strategy is for HeFH going forward.

Okay. So maybe thinking about APOC3 as a kind of a test case for this. What you have is the FCS drug, about $0.5 million price tag. If you think about this as a severe hypertriglyceridemia drug, we're probably talking like $10,000 price tag. If we're talking cardiovascular disease, we're talking like $1,000 to $2,000 price tag. How do you think about that, particularly given we've seen the history of the PCSK9 drugs that there's certainly a consensus, either they're going to [ suffer ] the launch by overpricing too high in the rare indication for -- like, how are you thinking about kind of that progress? And how do you think about kind of the launch of that drug assuming -- you said it's a relatively near-term commercial opportunity?

Sure. Hopefully, particularly for the SHTG market and the MD markets, hopefully, we will learn from the PCSK9 inhibitors. But look, I think that we can have a very open and transparent conversation with payers. As we -- hopefully, as we get approval in FCS, I think we can have a conversation that, look, this is a very narrow population and we don't know if this drug is going to be approved in SHTG or mixed dyslipidemia markets. But should we be lucky enough that these get approved there and we can broaden about the label out, of course, the prices will come down. But until we have approval in those larger markets, it doesn't make sense to us to talk about a relatively cheap drug for a very small population of FCS. And so I don't know if there's good precedent for that sort of approach, but it seems to be very logical approach that is our intention to pursue.

Okay. Maybe following from that, how do you think about the kind of cadence of building out the sales force for FCS and then other indications moving forward given that's the kind of nearest-term opportunity?

Sure. So for FCS and SHTG, we will be building sales forces that will be addressing lipid clinics and cardiologists. And for mixed dyslipidemia, that's when you may broaden out and start looking at primary care physicians. But at least in the near to midterm, we'll be building our infrastructure just for cardiologists and lipid clinics.

Okay. So maybe kind of following from that, as you think about business development for you guys, as you mentioned, you're still going to do a lot of partnering. As you look at kind of what you have on deck today, are there specific programs you think you specifically favor versus disfavor partnering?

Yes, that's a hard question because it's a dynamic question because partnering acquires a number of things, not the least of which is a counterparty that wants to license one of those drugs. And that changes with time. As we talked about NASH and obesity, those were those were 4-letter words until they weren't. So what we look for is to have some kind of synergy among classes of drugs and some kind of scale among classes of drugs, right? Pulmonary is a great example. I like the idea of building out a sales force to address 16,000 pulmonologists and have them sell not 1 drug but several drugs. That's what we hope to do with our various franchises. We've been very fortunate in our ability to partner in what we have been looking to partner over the last few years. I think over the last 6 years, we brought in almost $1 billion worth of partnering capital. And I think that only grows because those partnerships mature and we are eligible for larger milestones going forward. But also we anticipate continuing to partner programs. Like I said, we got 12 clinical programs now. We've got initiatives right now to have 20 -- 25 clinical programs or drugs at market by the year 2020, and I think we're going to hit that -- I'm sorry reverse that, 20 clinical programs or drugs at market by year 2025. And so that gives us an awful lot of ammunition to continue to partner and bring in undiluted capital.

Okay. I mean, I guess kind of to put a finer point on it, as you think about your balance sheet, like how do you think with a longer-term balance sheet strategy to -- like as they front pursue all of these different things, I mean, like God forbid, the best case scenario, a lot of these things work, like how do you think about kind of pushing all of them forward kind of given that you are a mid-cap biotech company, not a large strategic?

Yes. So what, I think, we have going for us is we're not a 1- or a 2-drug company. And so we've got a number of different sources of capital. We talked about partnering and that will continue to be a big source of capital, and we'll continue to utilize that. Of course, we can raise equity capital. We've done that judiciously. We haven't raised equity capital in 3.5 years, but that certainly is available to us. I think we are entering a point in this company's life history where we can start to tap the debt market. I think there are creative financing opportunities as well. We did a deal towards the end of last year with the Royalty Pharma to monetize royalties associated with our Lp(a) drug with Amgen, olpasiran. But there's also other opportunities to bring in product financing for individual products. I think we can tap that as necessary. So I think we're not going to align in any one of those buckets exclusively, but we're going to spread out our reliance on all those to decrease our cost of capital, and I think that we feel pretty comfortable that we have access to the capital that we need.

Okay. So maybe more practically, how should we think about the catalyst path in the next 12 to 18 months for Arrowhead?

Goodness. In no particular order, we will have patient data from our pulmonary programs. That's a big catalyst, I believe. We will become commercial when the FCS Phase III study is complete and we file an NDA. That's a big catalyst. We'll be getting into CNS shortly. I think -- again, I think it will be in clinic over the next couple of months. That's a catalyst. We will bring our new adipose platform to the clinic sometime next year. That's a catalyst. We talked about today -- we didn't talk about it today but we talked about it at our Analyst Day the possibility of bringing dimers into the clinic. That's a very powerful approach where we can knock down 2 genes with the same construct. My hope is that we can be in the clinic next year with that platform. That's a big catalyst. We will be starting Phase III programs for APOC3 and ANG3 later this year and into next year. That's a big catalyst. We'll have -- we'll continue to have data from our programs such as ARO-C3, such as ARO-PNPLA3, those are catalysts. We are a catalyst-rich company because we have so many things going on. And I think that over the next 12 to 18 months, you'll see a number of things.

Okay. So finally, the question we ask every company at the conference, what is the reason to own Arrowhead stock in the next 12 months?

So we -- RNAi, I think it's a non-controversial statement to say that RNAi is a validated technology. This works. It is scalable. It is generally well tolerated where it's been studied. And there are an awful lot of disease areas that should be addressed, that can be addressed, with RNAi. And there are 2 companies that are good at it, and we are one of those 2 companies. We are also, I think, the only company that is able to bring RNAi to a variety of tissue types, and so it allows us to scale this business very rapidly and to create an awful lot of value in a short period of time. In a lot of these areas, we will be unopposed. And so I think that it is -- I think that our value proposition is reasonably clear.

Okay. Well, thanks so much, Chris, for joining us this morning, and thanks, everyone, for joining us today at the Goldman Sachs Global Healthcare Conference.

Thanks very much.