Okay. This is Arrowhead. The analysts at the back of the room and also at the front desk. What a year. Congratulations.
Thank you.
We sit up here every year.
Yeah. Thank you.
What a year for Arrowhead with the approval of your first drug, Plozasiran. Massive opportunities too. This is what we were just starting to talk about beyond FCS and severe hypertriglyceridemia, but also a lot of other really cool things going on in cardiometabolic. Lots of good partnerships. Chris Anzalone is the Chairman and President of Arrowhead. So maybe start off by describing this market opportunity in FCS and how you anticipate competing with us.
Sure. First, thank you very much for having us. It's a pleasure to be here all the time. I guess the more appropriate question is, how is Tryngolza going to compete with us? I'll get to that in a second. So look, the FCS opportunity here is important for us for a couple of reasons. Reason one is these patients need medicine. We think that between genetic FCS patients and phenotypic FCS patients, and the latter are those patients with trigs above 880, history of pancreatitis, but without the common genetic mutations associated with FCS. But their symptoms are the same as genetic FCS. Anyway, between those two groups, we think there may be close to 10,000 or so patients who just desperately need this medicine because they suffer from a repeated bout of pancreatitis that can be fatal.
With every pancreatitis event, subsequent events are more likely, and they can be more severe. And we have something that can really treat that. Our FCS phase III data were compelling. We saw an 80% reduction from baseline of triglycerides. We saw a numerical risk reduction in pancreatitis. It was well tolerated. And so it's important to get this medicine to those patients. The second reason that FCS is important is it gets us into the market, and we know that the broader economic opportunity here is with SHTG. These are patients with triglycerides above 500. The sooner we can get to market and the sooner we can start working with physicians to educate them on the need to lower triglycerides in these patients, the better off we are. And so both of those together mean that this launch is important to us. We are in the field now.
And so we think this is an important year for this field.
Now, one of the things that I thought was very interesting and got a lot of questions on was the relative pricing, because I believe Tryngolza, a whack of around $595,000 per year per patient. You guys went at a much lower price, but I've really talked about this being your price for Redemplo. Tell us a little bit about what went into this.
Sure, so let's be clear on what this is not. This is not a price war. We view the long-term market opportunity as being driven by the severe hypertriglyceridemia market, and rather than starting at a high rate and then lowering it once we're approved for FCS, we just came out of the gate with this. That's important for us for a couple of reasons. One, it gives us time to work with payers to show them the value of Redemplo in the severe hypertriglyceridemia market. Second, it gives them time to budget for it. There are two ways you can address the SHTG market, I think. A hard way and an easier way. The harder way is you price this lower and you go for the entire 3.5 million-person market of patients with triglycerides above 500.
Look, 500 is severely elevated triglycerides, and those patients do need to get their triglycerides down. But we saw the very high risk population of above 800 or 880 as a better way to at least start this market, right? Go after these folks where we can make a very clear and powerful value proposition that there is a very good chance that these patients are going to have pancreatitis in the near term, many of them in the first year. And so we are pricing it for that. I think that the health economics work there. We know the pancreatitis is expensive. It often requires multi-day stays in the hospital. It can be well over $60,000 for a single event. And so the health economics work in a compelling manner. But also, again, there's a human component here. And these patients have lost productivity.
They've got recurrent bouts of abdominal pain. They have brain fog and such, and so there is a clear human cost as well, and both of those together, to us, make it compelling. $60,000 just felt like the right number for that population. Now, eventually, over time, I think that we will start to treat patients in the 700 range, 600 range, eventually 500 range, but out of the gate, the compelling value proposition is in those high-risk patients.
Absolutely. Again, we should get phase III data from your trials next year and subsequently expansion. And again, huge opportunity, more than enough for you and profile you. Now, just recently filed for a really interesting program, the PCSK9 ApoC3 dimer, if I'm not mistaken. So this is your first dual dimer targeting these two targets. Tell us about this candidate and kind of where this fits into your goal of treating. Could you also have Zodasiran or, I mean.
Zodasiran.
Yes. Zodasiran, thank you for homozygous HoFH. So really, how are you thinking about treating the continuum of cardiovascular lipid disease?
That's a great question. Yeah. And that's the right way to think about this. We have this continuum of diseases from high LDL on one end of the spectrum to high triglycerides on the other end of the spectrum. And then in the middle is elevated LDL and triglycerides, the so-called mixed hyperlipidemia population. We think there's about 20 million people in the United States with elevated LDL and elevated triglycerides. We know that elevated LDL is a substantial risk factor in cardiovascular disease. We know that. And we know that if you can lower LDL through a PCSK9 inhibitor, certainly a statin, that you can decrease cardiovascular risk. You don't take it all away, though. There is substantial residual risk, at least in this 20 million population, that we think is largely coming from remnant cholesterol.
And so when we were first developing Zodasiran and now Plozasiran, we saw this as a three-step drug, right? Step one is FCS, step two is SHTG, step three is to do a cardiovascular outcomes trial and show an improvement in outcomes, and then treat the broad population. As we were moving down the development road for Zodasiran and now Plozasiran, we continued to work on our dimer technology. And it's finally ready for prime time. It's taken us years to optimize this. It's not a simple approach. We think we have what is the world's first RNAi dimer or bispecific. And the idea here is compelling, right? It's designed to inhibit PCSK9 and ApoC3, therefore lower LDL and remnant cholesterol triglycerides. And in animal studies, it was quite active. We know how our GalNAc work. We expect this to be well tolerated.
We expect it to be around quarterly dosing. And so I think the middle of next year or so, we'll see how it translates. And if we do see a lowering in LDL cholesterol and we do see a lowering of triglycerides, we have a drug. And I think we'll know that in the next six or so months and a very compelling drug. Just by virtue of lowering LDL, that should give us a positive cardiovascular outcomes trial endpoint. But then you layer on top of that whatever risk reduction you get from remnant cholesterol. It should be even better.
I mean, sticking with this theme of massive market opportunities and building on your cardiometabolic pipeline, you guys are conducting phase I/II studies of ARO-INHBE and ARO-ALK7 for obesity. Maybe you can tell us sort of the differences between these two programs because it's a really compelling pathway here for weight loss. Tell us what you're working on there and maybe when we could get some data.
Sure. Yeah. That's a really exciting couple of programs also. Again, broadly, as you can see, we are building out expertise and infrastructure in cardiometabolic with Plozasiran, with you mentioned Zodasiran, which we are in phase three studies for HoFH with the dimer and now with obesity. So INHBE and ALK7 are essentially hitting two ends of the same pathway, this activin E pathway. The idea here is that the liver produces this INHBE and therefore activin E, which then binds to adipose. The receptor there is ALK7, and it essentially tells the body to store fat. There has been good genetic data to suggest that people who are lacking INHBE or ALK7 don't have a negative phenotype, but have better metabolic attributes than the general population. And so our animal studies were compelling in both candidates. We saw weight loss in rat studies.
It's hard to do weight loss studies in non-human primates, but we did show good knockdown of INHBE and ALK7 in primates to the tune of better than 80%. So we know we're active in primates. And the idea here is to, again, if this translates from animals to humans, we would expect people to not necessarily decrease their food intake because it doesn't affect appetite, but just increase lipolysis. And so what we saw in the animals is they ate the same amount of chow as the control animal, but lost weight. And importantly, the quality of that weight loss was good. It was primarily, actually exclusively, I guess, visceral fat. And that's the metabolically active fat. And so not only is that what we want to lose from a cosmetic standpoint, but from a metabolic standpoint, we think it's quite important.
And so we're doing studies, SAD and MAD studies as monotherapy, as well as MAD studies as combination with a low dose of Tirzepatide. We think that's the idea for both of these is not to put the GLP-1s out of business, but we see a lot of white space around how those drugs, those are largely good drugs, how those are acting, right? Could we enable someone to lose higher quality weight with a lower dose of a GLP-1? That'll be interesting to see. Could we use this as a maintenance therapy? The world is pretty good at helping people lose weight. It's not very good at helping people keep that weight off. And it could be that INHBE or ALK7 could address that part as well.
And so we'll have our first small-ish slug of data in the first part of January, and then probably a fuller data set sometime in the first half of 2026. The biggest lag there is ALK7. We started that, gosh, I guess almost two quarters later than INHBE. And also that MAD, the doses are separated by three months. And so it just takes time.
Yeah. Yeah. That's going to be a really exciting readout. Does it make sense? Are you targeting ADA for that, or would this be more of like a company presentation for the more substantive data rollout?
I don't really answer that. It could be a combination of those things.
Yeah. Awesome. So I'm going to ask one more question about your proprietary pipeline. You guys also just filed a CTA for ARO-MAPT. This is another really big opportunity. Again, here starting to move into the CNS delivery. Tell us about this target and really how you're delivering to the CNS.
Yeah. We're really excited about that as well. And that's another one that I think should start to read out in the middle of next year. So it's a well-validated target. We know that in Alzheimer's patients, as well as in various other patients with tauopathies, that there are these tau tangles within cells. It's not easy for an antibody to address this, right? Because it's intracellular. Now, we know that some of those tangles will be exported and then be taken up by other cells, but the real problem here is intracellular. And so this is, from our perspective, tailor-made for RNAi. And we have an approach that is a TRiM shuttle that enables us to administer with a simple subcutaneous injection.
We've seen in animal studies that we get good knockdown across various targets, frankly, but also from ARO-MAPT, good knockdown across various brain regions, deep brain regions as well. We love the idea of treating Alzheimer's patients, but also these smaller tauopathies. That may be an interesting way to get to market relatively quickly with the smaller tauopathies as we're doing the longer and more expensive Alzheimer's studies. The first step here is to know if we are seeing translation from animals to humans. I think we'll start to see that in the summertime. We'll be looking at tau knockdown in the CSF. I think if we see that, and people always ask us about a bar, what's success there.
I think if we can show anything above 50% knockdown in the CSF, that's a big win for us because ARO-MAPT, I think, could become a very exciting Alzheimer's and tauopathy drug, but also is the first substantial step in clinically validating that whole platform. If we can knock down tau, we can knock down any gene target in the brain. With Sarepta, we have a Huntington's target that will be in the clinic shortly. With Novartis, we have alpha-synuclein against Parkinson's that will be in the clinic shortly as well. And we are developing a number of additional targets.
Some questions brought up Sarepta because this has been a very interesting collaboration. I mean, I was actually at this conference last year that you guys announced it, I think. And it was just a massive deal, $800 and some upfront, $10 billion in potential milestones. How has that partnership evolved? They've been facing some setbacks with Elevidys. Now, the confirmatory ESSENCE trial for Amondys and Vyondys did not succeed. Walk us through sort of what are the main components and why did Sarepta make sense to Arrowhead?
Sure. So last year made a lot of sense for us to do that deal because anybody in this room last year would have, I think, agreed that what we're good at is building a pipeline. We had a huge pipeline then. We have a huge pipeline now. We've got 20 individual drug candidates in clinical studies by the end of this year. And most of those drugs we think are going to work. This technology is well validated. We've been in the clinic with enough patients that we have a good expectation that these drugs should work. The question was our balance sheet. And that was a good question. We needed to bring in a substantial amount of capital. And we did that. And frankly, one fell swoop with Sarepta. And we just triggered, in fact, a $200 million milestone payment a week or so ago.
And so we expect to get that shortly. And then we should get another $50 million in, I think, February of 2026. So it was very important to us from a capital standpoint. But also, you know what? It's important to us to get these drugs that are not core to our business into the hands of folks who will develop these and commercialize them. And so the cornerstone of that partnership were DM1 and DUX4, the two skeletal muscle programs. And Sarepta knows how to develop those, knows how to commercialize those. And so we view that as really strong hands for these drugs that we're excited about and we think are going to be important drugs. So look, so this partnership, I know they've had their challenges over this last year or so, but the partnership has gone well. We expect that to continue.
We are still operating those studies, the DM1 and DUX4 studies, until the phase I is finished, in which case they will take them over, but they control data flow, and I think they said publicly that they expect to have some kind of data in the first quarter, I think, certainly for DM1, and I'm not sure if they said about DUX4.
Excellent. Looking forward to that. I'm going to pause to see if there's any questions from the audience. One thing that's really struck me, we just wrote this big RNA report in which Arrowhead featured prominently with the new approval. One thing that really came out is just how much Novartis is investing in this space. They've got Leqvio. They've done some deals with some Chinese companies developing siRNA. They just paid you guys $200 million for a preclinical Parkinson's disease drug. Tell us a little bit about that partnership and sort of what Novartis means to you guys in this space.
Sure. That was a very important partnership for us. As you mentioned, it was $200 million upfront and then milestone payments to around $2 billion or so, commercial and regulatory. And then royalties, I think, to low double digits. It's a good deal for us financially, but also they are a strong partner in this space. As I mentioned, our dual goal of our partnership is to bring in capital, but also to make sure that these potentially important drugs are in the hands of folks that can bring them to the patients who need them. And Novartis clearly can do that. And they've shown a real interest in this alpha-synuclein Parkinson's space. And so we look forward to working with them.
Great. So last question that I have, you guys ended your fiscal year, which is a September year-end, with cash of $782 million, but subsequently brought in the $200 million you mentioned from Sarepta, another $200 million upfront from Novartis. So that's well over a billion, probably close to $1.2 billion in cash. How long does this fund you guys? What does it really enable you to accomplish?
Yeah. So it enables us to go full speed ahead in our core programs. This is the dimer. This is the right now two obesity programs. There will be more. It is Plozasiran. It is the Zodasiran. It is the burgeoning CNS platform. It allows us to fully fund these and move quickly. We have cash between our current cash and our existing deals, expected milestones to get into 2028. This does not get us profitability, but we can kind of see it from here, and my expectation is that we will do some more business development deals over the next few- years, and our goal here was to build a business that was not entirely reliant on the capital markets because you can't control that, and I think we built that here.
It doesn't mean that we will never raise money again, but it means that we can be a bit more a master of our own destiny.
That's great. Well, Chris, congratulations. It's really been awesome to see the progress you guys are making and a lot of fun too. And I know you're just getting started. Please join us later too. We're going to do an RNA panel downstairs in the big room at 2:00 P.M., in which Chris will be participating as well. So thank you very much.
And thank you too.