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

Good morning, everyone. Thanks for joining us. I'm Salveen Richter, biotechnology analyst at Goldman Sachs, and we're pleased to have Arrowhead Pharmaceuticals with us this morning. And from the company, we have Chris Anzalone, CEO; as well as Vince Anzalone, Vice President. With that, I'll turn it over to you, Chris.

To start here, as you look to 2020, you're looking to move into extra hepatic tissues. And I think we saw your data sets last year and this year as well as you look at liver directed, but can you help us understand, as you go outside of liver-directed tissues, what are the key aspects of your technology and data to date that lend confidence to be able to achieve this?

Yes. Thanks very much, Salveen, and thanks very much for having us. It's really a pleasure to be here today. It's a good question. So look, this is a big year for us. We've been talking about extra hepatic delivery now for many years. We always view this as a big, as a big move for the field and certainly a big move for our company to bring RNAi outside the liver. We think that in order for RNAi to really live up to its potential, we need to go -- we need to go to where disease is, and it's not always in liver. So as I mentioned, this is a big year for us. We filed an IND for our first solid tumor-targeted program in December. This is HIF-2 alpha. We expect to begin dosing that this month. We filed a CTA for our first lung-directed program recently, and we expected to begin dosing that over the next month or so. And then I think next year, we've guided that we expect to be in skeletal muscle sometime in the first half of the year. So there's a lot going on here, and we view each of these, the solid tumor-directed set of programs, the lung-directed set of programs and the muscle-directed set of programs, we view each one of those as franchises for us that will allow us to address a number of different disease areas. So again, big play. We -- when we look to what makes us feel confident about it, we've seen -- we've been studying these for years now. We've got good animal models. For instance, the first lung-directed program, ARO-ENaC against cystic fibrosis, we've got a ton of data in rodent models, in sheep models and nonhuman primate models. And so we go into the clinic cautiously optimistic that we have something that's going to work. Same thing with our other programs. So we rely on the animal data, of course. But we also look -- we rely on the theoretical expectations. We've got a ton of experience with these direct conjugates. With oligos conjugated directly to a targeting ligand. And we know that, that's pretty inert. It doesn't become toxic unless and until you stick on toxic molecules onto that structure. So we feel cautiously optimistic about our safety profile, about our activity. RNAi is an increasingly validated process. So that all makes us feel good. And then -- and now it's just time to go into humans. I think that what -- I think, importantly, what has gotten us here is that we've spent an awful lot of time developing some technologies, algorithms, rules, et cetera, that allow us to design innately potent triggers. And so I think that's really what got us into extrahepatic spaces. We have technologies that will allow us to predict sequences that may be potent in vivo but are not potent in vitro. And we know that, that's going to be critical as we address extra hepatic spaces because we know we'll get advantage in these small amount of material into these non-hepatocytes. And so we've got to squeeze all the potency we can out of them. And we've been able to do that, so...

And then on the first quarter EPS call, you did provide more details on the clinical development plan for your cardiovascular programs here. Can you just speak to whether there's any update here with regard to what your overall strategy is?

Yes. Thanks. We're really excited about this program. So if you look at -- so those 2 programs are against the targets APOC3 and ANGPTL3. The candidates or ARO-APOC3 and ARO-ANG3. So I'll take a step back. We presented data in healthy volunteers at the American Heart Association meeting in November in back-to-back oral presentations. And the data were good. Safety profile was good. Knockdown was good. We then -- about a few months ago, I guess, we released some data in patients. And those data were stunning. For ANG3, we saw around 80% reduction in triglycerides. We saw around 40% reduction in LDL. And mind you, this is reductions in LDL on top of statins on top of PCSK9 inhibitors. So we think that was -- that it's quite important. And then on APOC3, we saw about a 95% reduction in triglycerides, again, just stunning. Compare that to fish oil. Vascepa, I think, was showing between 18% and maybe 30% reduction in triglycerides. And we just -- we're just in a different universe there. So with those, then we seek some clear overlaps. And so then the question, to your point, is how do you develop those and what patient populations will you seek to address. And I view ANG3 as our broader market drug. What we're thinking about there are those patients who are not meeting LDL goal but also have elevated triglycerides. We think there's maybe 10 to 15 million of those in the U.S. alone, and there's just no good treatment for them. This is not designed to be -- to -- or place PCSK9 inhibitors, for instance. It is designed to address a different patient population, again, those who still have elevated LDL and elevated triglycerides. And we think it's a really powerful construct for that, again, given our data. On the APOC3 side, we view that more as our pure-play hypertriglyceridemia drug, at least initially. What we're thinking there is to go after those patients with severe hypertriglyceridemia and history of pancreatitis. We think there's maybe 30,000 of those in the U.S. alone, and they have really limited treatment options. Really, the only thing that they're treated with right now is a very severe diet. And as I said, we've seen reductions around 95% of circulating triglycerides. And so with these patients, with trigs in the thousands, that's going to be meaningful to them and I think really should go a long way to decreasing that -- those bouts of pancreatitis, which are very painful, which require hospital -- hospitalization often and can be fatal about 10% of the time. So that would be the initial market, I think. I think that's a pretty straightforward, reasonably rapid regulatory pathway. I think we can be in a pivotal study in the first half of next year for that. And then we can -- that drug has an awful lot of optionality. We can then do a follow-on study, for instance, to look at those patients with trigs over 500, if you will. We know that once triglycerides breach 500, there are severe health outcomes. We think there's maybe 600,000 or 700,000 of those patients in the U.S. alone. And then who knows? You could always then do the broader study, do an outcome study for secondary prevention of cardiovascular disease, something like that. So that's our idea right now. Look, I think that given that our initial focus with APOC3 is going to be smaller markets, I believe that we can or we are hopeful that we can be in a pivotal study for the first half of next year. We'll have discussions with the FDA shortly, and we'll see if that's going to work. For ANG3, I think that because it's a broader market, we'll probably have to do a larger Phase IIb study. So it's my expectation that we'll be in that Phase IIb first half of next year as well.

Great, Chris. And then you've -- we've also seen you partner here with Amgen for Lp(a), J&J for HBV. Can you just discuss your strategy here as it relates to business development, what you're thinking about keeping and taking through to commercial versus where you may be looking to partner and what those inflection points going to be here?

Sure. Yes. So I've said it before. We've got a bit of an embarrassment of riches. We've become really good and really fast at going from idea to the clinic, and so we'll have a pipeline of, pretty soon, 10 clinical programs right now, 2 of which are partnered, but 8 could be wholly owned. And I think we double that to 20 in the next 3 or 4 years. It's just stunning. A company our size really has -- does not have the ability to commercialize all 10 or 20 or 30 eventually of these, and so we have to partner if, in fact, we want to get these to the patients who need them. So partnering is an ongoing strategy for us just out of necessity. But second, it allows us the access to non-dilutive capital such that we can hold on to some, hopefully, reasonably large number of our own candidates to commercialize them. I think that it is that sort of positioning that allows us to think of ourselves as a very large company in a not-so-distant time frame because we will be commercializing our own drugs. And then to your point, the question is, okay, so what do you hold on to and what do you not hold on to. And that's a bit of a dynamic question because what I would hold on, what I would feel like I need a partner today, I may not need a partner 4 years from now because we'll be a larger company because we'll have access to additional capital, et cetera. But at least right now, the way we look at it is that on the cardiometabolic side, we think that ANG3 and APOC3 are really important potential drugs. And we are committed to -- at least right now, we're committed to bringing at least one of those commercialization. It may make sense to partner one of them, but certainly, we'd like to hold on to at least one of those. If you look beyond that with, say, CF, that's a market that we could handle. And frankly, I see a big opportunity for us in pulmonary. We announced at our last conference call that we'll have our second lung candidate at CTA by the very end of this year. I think we'll have 1 or 2 more in the clinic next year. So it could make sense for us to build up a sales force in pulmonology. So we're thinking about holding on to those at least for right now. Then if you look at oncology, we'll probably need some help on that at some point. If you look at AAT, we can hold on to that. I think that's a market that we really should address ourselves. If you look at NASH, look, we -- we're on -- we're a bit on the fence on that right now. That's a difficult space. And so that may make some sense for us to partner at least strategically at some point. But I think the global take-home message here is that: a, we've got the ability to partner some of these programs to finance our own internal programs; b, we don't have a gun to our head. We've got plenty of capital right now. And so we can be really opportunistic as it relates to which one of these programs we partner and when we partner.

And then how do you see yourselves as different? Or maybe it is similar to Alnylam and Dicerna. Like where are the points of differentiation here?

Yes. So I think the most glaring differentiated point -- those glaring point of differentiation is our ability to get outside the liver. As I mentioned, we've been talking about this for quite some time, for years, maybe a decade. And we've been working on it for that long. We finally, I think, wrestled it to the ground, where I think we're clear leaders in extrahepatic, and so as I said, by the end of this year, I think that we'll be in hepatocytes. We'll be in lung. We'll be in solid tumors. Next year, we'll be in muscle cells. And it's possible that the next year, we could also be in a fit cell type -- a sick cell type in addition to hepatocytes. And so that's a big one for us. Now science is a wonderful thing, and people will catch up, but I think that we've got such a lead in these that by the time competitors can address these other cell types, we will have already gone through the well-validated targets, and they'll have to ask themselves, do they want to compete in those targets being, I don't know, fill-in-the-blank number of years behind or do they want to go after less validated targets and that's something they'll have to ask themselves. And so I think that's a big advantage that we've got a big differentiator. A more esoteric way, I think we've got a -- I think we are different in our ability to design these very potent triggers, as we talked about earlier. I don't think that our competitors have the same kind of algorithms and rules, and that's important. It's important as it relates to hepatocytes because it allows us to be very stringent on our bioinformatics to make sure we screen out any potential cross reactivity with other genes. It allows us to screen out any sequences that could have homology to known microRNAs. But it becomes critical when we're talking about extrahepatic because, as I mentioned, you really need to have those very potent sequences. So that feels to me like our big differentiator. Having said all that, look, Dicerna and Alnylam are good companies. And I think there's -- I think there are plenty of patients in need that 3 companies can serve. And so I think it's good for the world that there are 3 companies that are pretty good at RNA interference.

And then you are working on a therapy against COVID-19, and you have a program against other coronaviruses as well. Where do you stand with these programs right now?

Yes. So they're still pretty early. But I'll remind folks that what we have is a clinic-ready lung delivery franchise. With ARO-ENaC and now with follow-ons. And so we come into this pretty good, I think, at delivering to the lung. I think that's going to be important as it relates to COVID. And also, remember that this will be administered via inhalation just like ARO-ENaC and just like follow-on constructs. So we are cautiously optimistic that we've got a platform that we can use here. We are now in the process of designing these various constructs. We can go after host factors, for instance, the receptors that are the front door of the virus. We can also go after the conserved regions within coronaviruses to knock down the virus itself, and we're exploring all those options. Our thinking here is that I think that we could have something that is helpful for COVID-19, but more broadly, I think we have something that could be helpful for the third and fourth and fifth coronavirus outbreak that I think is probably going to be with us. If you look at MERS and SARS and now COVID-19, I think all of that suggests that we are -- we live in a world now where we have to expect every several years some kind of coronavirus outbreak. Now hopefully, none of them are going to be as severe as we're seeing right now with COVID-19, but we see that as the future. We wanted to be out in front of that. And I think we've got a reasonable chance to create something that we -- that could be used across coronaviruses. And so we're ready for the next one and the next one after that.

Maybe a final question here before we jump into the pipeline. But what do you see on tap in terms of catalysts and events over the next 12 months?

Yes. That's a good question. So we are -- because we have so many programs at various stages, but from early to mid- to later-stage clinical development, I think that we're always in a situation where we are -- where we've got regular catalysts, whether it's 2020 or '21 or '22, I think we're always going to have regular catalysts. And so this year, it feels like, in no particular order, we expect to have data from the 6-month biopsy of our AAT open-label study. I think that's important. No one has ever looked at what happens within the liver if you reduce production of the monomer. And so we'll see that. We expect deproduction of the monomer. We'll see what it -- if you see any reduction in the polymer, they'll be interesting. And we'll have those biopsies, I believe, in August. And so I expect to release that sometime this year. We'll have a full data set for both APOC3 and ANG3. ANG3 is fully enrolled. APOC3 is nearly fully enrolled. We've already been accepted at 2 different conferences for each of those drug candidates. We'll see what the medical conference world looks like this year. But hopefully, we can present there, if not -- or at those 2 places. If not, then we'll find other ways to release data. And then if you look at the bucket of HSD, our NASH drug or candidate, HIF-2 alpha, our solid tumor drug and ENaC or CF drug, if you look at all 3 of those, we're a little bit up in the air about whether or not we'll have releasable data this year. It's just too early to tell because they're a bit too early in enrollment. At the very least, I think that we will have internal proof of concept for all 3 of those. And we'll just have to see if we have enough data that would allow us to submit abstracts, et cetera. We've got -- we have a history of presenting some early data at smaller conferences to give people a flavor of data that are coming out. And so we'd certainly like to do that if time permits and if conferences permit.

So with regard to the AAT program, I think there was some impact from COVID-19 on new patient screening and enrollment. Can you just remind us of the status of that right now?

Sure. Yes. So that was -- we had a voluntary pause in enrollment of new patients. Now importantly -- and that's just because out of an abundance of caution, we wanted to limit folks' travel. We want to limit people's contact with health care facilities, who already might have some impaired pulmonary function. So we paused enrollment of new patients. We did not pause seeing patients that were already enrolled. And as I -- I don't believe that we saw any misses of appointments. And so that continued. That was -- that's helpful. We have restarted now enrolling for both the open-label study and SEQUOIA, the Phase II/III study. And so we're back on track there. It's a bit slow, as you can imagine, given the current environment, but we're back on track. And we're working with all of the sites to get -- to bring in new patients.

And then with regard to the 6-month liver biopsy data that we're going to see in the fall here, what would constitute a clinical success in terms of percentage of monomer reduction? And what are you looking to observe here? And how would we interpret the histological data? Is there a grading scale or something else that we can look at?

Yes, it's a good point. So the agreed-upon approval end point with the FDA is an improvement in a 10-point histologic rating scale that we're developing in conjunction with the FDA. Now we don't expect any changes in that scale after just 6 months. And frankly, it's really just 5 months of drug exposure really because it takes about a month or so to start to see knockdown. And so we just think that's substantially too little time to have those kind of changes. And so we'll look at that, but we certainly don't expect it. And so when you think about changes, you could see. So there will be changes in monomer, changes in polymer, histologic changes and maybe changes in the inflammation markers. And so again, the histologic changes, we don't expect to see. Monomer, of course, we expect to see. What we saw in our Phase I/II study was deep deproduction in circulating monomer down below the level of quantitation for most folks. And so we would expect near complete suppression of monomer production. That's going to be interesting. As I mentioned, no one's ever looked at this. So I think it's important data. Then you look at polymer. Polymer is a bit of a black box here. Nobody knows how it's metabolized. Can it be metabolized on its own or do you rely on turnover of hepatocytes to remove it from the liver? We don't know. So I'm not expecting much, if any, reduction to polymer after just 6 months. The 1-year time point will be more interesting, I think, as it relates to polymer. But well look. We'll see. And then finally, inflammation markers. It will be interesting to take a look at those to see if those change at all. That's a bit of an unknown because, generally, early in liver disease associated with AAT, it's not terribly inflammatory. You don't see, for instance, changes in transaminases until later stage in the disease. And so it could be that we don't see any changes in inflammation markers, but we'll take a look.

And then are there any points of differentiation between your program and just the construct itself versus Alnylam's and Dicerna's?

Yes, that's a good question. It's -- we don't know the answer to that because neither of them, I don't think, have presented data. So who knows which is going to be better? I think the biggest difference here -- let's assume that they have good candidates. The biggest difference is just time here. I think that Dicerna is in a single site in Sweden, dosing healthy volunteers. And we are in 2 studies, an open-label study and a potentially pivotal study in 40 or so sites throughout Europe and the United States. And so we've got a several year lead on both Alnylam and Dicerna. My hope is that, that lead actually expands over time because we've been in this field for quite some time. We've been talking to the PIs for many years now. We've just been in this field for a bit. And I think that, that's going to bear fruit for us and allow us to get this to patients reasonably quickly.

And with regard to the APOC3 program here, so I know you've been in discussions with the FDA on study design for the Phase III. Can you just outline your current thinking of what you're going to do here? And would you be using the same population as your Phase I/II?

Yes. It's a great question. So in the Phase I/II, we have various cohorts in different patient strata. And so once all those data -- once that entire data set is released, it will be interesting, right? Because we'll have various types of patients, and we'll see how the drug works in all those patients. So we are speaking with the FDA over the summer to get guidance on our potentially pivotal study. Our thinking now is somewhat in this order. It feels like we have the -- potentially the greatest immediate impact on those severely hypertriglyceridemic patients with a history of pancreatitis, these 30,000 or so folks. People think about FCS and certainly, FCS patients are within that patient population, but there is maybe a hundredfold more patients that have polygenic causes of that hypertriglyceridemia rather than the monogenic cause of FCS. And so we're thinking of them as one larger patient population. So our thinking is that we will address those folks. They don't -- they just don't have any real options right now, and we think that's a pretty straightforward and reasonably rapid regulatory pathway. And then probably the first step outside of that would be to do another study in patients with triglycerides above, say, 500. As I mentioned, Vascepa did that. We think there's 600,000 or 700,000 of those patients in the U.S. There's not good treatment for those folks. And goodness, if we can reduce triglycerides in those folks by 95%, I think there will be a substantial impact in their quality of life. And yet it's still a somewhat manageable patient population. And then we'll see. Over time, as I mentioned, look, I think that ARO-APOC3 could do a heck of a lot for patients with elevated triglycerides but not in the 500 range, say, in the 100 to 200 to 300 range. And that becomes a very large population that is underserved right now. We'll sort of keep that in our back pocket as we generate data in these smaller markets. And we can always expand into that market, I think, in the future.

And then when you look at ANG3, similar type of question here, the opportunity in dyslipidemia is huge. So how do you think about the initial population you target? And then just maybe help us understand the importance of an outcome study in Phase IIb prior to the pivotal study here.

Right. Yes. So the good news about ARO-ANG3, at least our expectation, is that we see severe reductions in triglycerides, 80 or so percent in patients. We see good, severe reductions in LDL on top of statins and PCSK9 inhibitors, which is, again, is not a surprise because we're reducing LDL in a non-LDL receptor mediated fashion. And so we can address some patients who don't respond to statins but also address those patients who are just not meeting goals. So as you say, these mixed dyslipidemia patients with continued elevations of LDL and elevated triglycerides, we think we have something that's really special. We're the only RNAi player here. There's nobody else doing this. The only -- really the only other option here is with antisense, and we think we win on safety and dosing schedule there. So that's all the good news. The bad news is or the challenge is that, that's going to clearly, I think, require an outcome study. That's going to be long to long-ish and expensive. But I think The Medicines Company and Amarin have shown that smaller companies are capable of doing outcome studies and sometimes maybe a bit more quickly and cheaply than big pharma. So I don't think it's off limits to us. It's a hurdle, but I think that it is a hurdle worth addressing because the biology risk here, I think, is quite low. We would expect a continued good safety profile from ANG3 as with all of our hepatocyte-directed drugs and I think that the data are pretty clear that if you can reduce LDL and triglycerides by the amount that we are reducing them that you will see positive effects on outcomes.

And help us understand, when we look at the competitive landscape and the commercial landscape here, the PCSK9s that were approved, notwithstanding good data, had challenges with uptake here. So as you look at this space evolving and those challenges that are faced, where do you see yourselves being positioned and how so?

Yes. So this is a really interesting time for cardiovascular disease. For decades, this has been a story of LDL. For a couple of days, it was a story of HDL until it wasn't. But generally, it's been a story of LDL. And the reason is because that's the only tool we had. We knew that there is potentially a linear relationship between cardiovascular risk and LDL levels. And so if you could bring this down, it's a good thing. And the lower you can bring it down the better. So we focused on that. Statins did a great job. PCSK9s appear to do a great job as well. But the incremental value of just lowering LDL a bit more was maybe less than people expected. That was the challenge with PCSK9 inhibitors, I think. But now we are in this new world where we've got new tools. We've got triglycerides. Now all of a sudden, we've got ways of lowering triglycerides, and there are increasing data to indicate that elevated triglycerides are an important independent risk factor of cardiovascular disease. And now we've got a hammer to knock that down. Same thing with Lp(a), our partnering program with Amgen. We/they are the only RNAi player in the field, and we would expect good data to come out of that. And I think that's another hammer to further reduce cardiovascular disease. And so my point here is that rather than just shaving a bit more LDL off in patients who need it, we are embarking on a new -- into a new space where we can treat these patients more completely, lower triglycerides and continue to lower LDL. And so I think that the magnitude of our effect could be substantial. And I think patients are just waiting for these extra tools.

Great. And then looking at the rest of the pipeline, it does seem like when you talked about NASH earlier, you seem to have taken a step back in your enthusiasm towards targeting that disease area. What does that mean for this program? And what are you looking to glean from the -- this next data set?

Yes, yes, yes. So I don't want to mislead anyone. We think it's a very important challenge. This is a severe unmet medical need, and we think that ARO-HSD is a strong tool against that. The genetic data are clear, right? These heterozygous recessive folks without HSD show a significant protective effect, if you will, against liver disease. So there's a big problem out there. My concern is that it's a complicated disease and certainly multifactorial. And so this, in a lot of ways, may be a bit like hepatitis B, where there are a large -- there's a large patient population who might need a cocktail approach, which is important, but may be better addressed by other companies to try the various permutations. Like I think ARO-HSD could be an important backbone just like ARO-HBV, now JNJ-3989, I think is going to be an important backbone for hepatitis B therapy. So there's that. Second, at least in my mind, there is a lack of clarity on the regulatory pathway for NASH going forward. I don't know where that's going to go. And so all that suggests to me that I think we should be in this space because I think we have some important tools against it. But at some point, it might make sense for us to be aligned with another company with deeper biology experience in the space. And again, what's helpful here is that there's not a gun to our head. We don't need to find that alliance at this point. We're happy to continue to develop ARO-HSD and potentially other targets right now. And as the right partner comes out, we can have those discussions.

Great. And there's a question here from the audience on the cardiovascular programs. The question is what is the key milestone for Amgen APOC3 for large indications in CV disease and what is the partnership outlook for these 2 in terms of rare disease and large population cardiovascular outcome trials.

Right. So it's a good question. I think the -- I think that the important milestones for both of those have somewhat been reached by our release of data a few months ago. There just weren't holes in those data. 95% reduction of triglycerides with ARO-APOC3 and better than 80% reduction of trigs and 40% reduction in LDL with ANG3, I think those -- and a good safety profile so far. They just hit the mark. So now we just have to show that those data continue in larger data sets and in other patient populations. We'll show that this year. And so I think this is a very important year to really validate these 2 targets. As I said before, we're the only RNAi player in both of these, and I think we have an awful lot to offer these patients who need these therapies. So that's not a "2 year from now" issue. That's a current issue. That's all great news. Then the question is how do we bring this forward and with whom, and we're a bit agnostic there. Look, I love both these programs. I think they're both powerful for different reasons. And as I said, over time, it might make sense for us to partner one of them. But I'm okay partnering either one of them because I think that we can play in either space, and I think that we have a lot to offer in either space. As I said, we -- I'm not considering partnering both of them at this point because I think there's just too much value. We don't have the bandwidth now or in the near future to push 2 large cardiovascular programs forward at the same time. And so we'll see if we can find a good broad partner for 1 of those 2 at some point.

And on your HBV program here that was partnered with J&J. You did mention recently that you're testing it in additional targets. Could you maybe comment on that? And then how are you thinking about your approach versus others that think that you need a combinatorial approach here to really get a long-term functional cure for CHB?

Yes, that's a great question. So I think that I don't know that you need a combinatorial approach for all patients. My gut would say that there is maybe a large population but certainly a population where ARO-HBV, now JNJ-3989, could be sufficient because it is -- we know that it is reducing everything that, that virus produces. We -- I think that, that will: a, disrupt the life cycle of the virus; but b, enable the immune system to reconstitute itself for some population of patients and control the virus. Now if you're looking to continue to expand that percentage of functional cures, then you may have to go after -- you may have to take a combinatory approach. And one of the reasons that we did the deal with J&J is that I think they are uniquely positioned to interrogate that for a couple of reasons. One, in-house, they've got a variety of compounds that they can combine with our compound, and they're doing that. They're in 2 triple-combo studies as we speak, REEF-1 and REEF-2. We have been we have been thrilled by their performance in executing those studies so far. And so I think there's not a better company in the world that's capable of doing these large multinational complicated studies. So that's reason 1. Reason 2, again, is the fact that they've got in-house compounds to combine with ours. And I -- so I think it's going to be an exciting next few years with respect to hepatitis B, and I think we're going to get it. I think there's going to be -- I think that J&J will find the right recipe to reach functional cures in a large percentage of the population. I think that's an important thing for world health.

And then a second question here from the audience. What are your thoughts on the new dimer approach announced last year with respect to potentially addressing certain NASH targets?

Yes. That's a really important question. We are excited about that dimer approach. It sounds a bit esoteric or inside baseball that, sure, we can knock down one gene now, but guess what, it's also important to knock down 2 genes. But when you look at the biology of some of these diseases, NASH is a great example. There could be benefits to knocking down 2 genes at the same time. And so we continue to push forward with that platform. And part of that is certainly with an eye to NASH. That's for sure. And it just occurred to me that your prior question also had to do with the other targets with J&J, and let me just be clear on that. So that deal was a two-fold deal. One was with HBV, and 1 was 3 additional targets that were not having to do with HBV. And as we mentioned on the conference call recently, we are working with them on all 3 of those targets as we speak. They've been a good collaborative partner for us. And so we are optimistic that those should be good programs.

And then one last question here, Chris. When we look to the CF program, when might you see that data from the Phase I/II study?

Boy, I wish I knew that. I think that internally, at least, we'll see an awful lot of data this year. We haven't started dosing yet. And so it's too early to make any predictions on when we could be fully enrolled. We are -- that's taking place in both New Zealand and Australia. So again, we're confident that we'll at least have data this year. We'll see how much and when we have it. We'd love to present some this year if, in fact, we could enroll quick enough to do that.

Great. Well, with that, thank you so much for joining us. We really appreciate your time, Chris and Vince.

Thank you.

Great. Take care.