Arrowhead Research Corporation H.C. Wainwright 28th Annual Global Investment Conference
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Hello everyone. Good morning, and welcome back to H.C. Wainwright's 28th Annual Global Investment Conference. I'm Patrick Trucchio, a senior healthcare analyst at H.C. Wainwright. It's my pleasure to welcome our next speakers, CEO Chris Anzalone and CMO and head of R&D, James Hamilton at Arrowhead Pharmaceuticals. Arrowhead's a commercial stage pharmaceutical company developing RNA interference or RNAi therapeutics with broad pipeline across cardiometabolic indications and CNS. Arrowhead's REDEMPLO plozasiran was approved by the U.S. FDA in 2025 as an adjunctive dye to treat triglycerides in adults with familial chylomicronemia syndrome, or FCS. At the end of August, Arrowhead presented the full 12-month results of the pivotal phase III SHASTA-3 and SHASTA-4 trials in severe hypertriglyceridemia, or SHTG, in a hotline late-breaking signed session with the European Society of Cardiology Congress and plans to file supplemental NDA by year-end in SHTG using a priority review voucher.
It's a huge year for Arrowhead. Pleasure to have you with us. Just first, it's been a transformational last few months, FCS launch, two positive pivotal trials, priority review voucher. For those who are new to the Arrowhead story, can you give us an overview of the RNAi platform, why subcutaneous RNAi to the liver became such a robust franchise?
Sure. First, thanks very much for having us. It's a pleasure to be here. We have been banging our head against the RNAi wall now for over 15 years. As you point out, the first tissue that we could address is the liver, hepatocytes. But we decided early on that in order to extract proper value from this technology and to treat as many patients as we could, we needed to get outside the liver. As early as 2010 or so, we started working on technologies to get us outside the liver. Where we are now is we've got a broad platform that enables us to get into several different cell types, five of which are represented in clinical candidates right now.
We've said publicly that we think we can get into a new cell type every 18 to 24 months, and we believe we'll continue to do that. While the first leg of our journey was in the liver, it was certainly not the last. I think we'll talk about CNS today as well as probably some other cell types. Our goal all along was to build a very broad-based company, which was a new thing. It's a different thing for a small biotech company to do. We were not focused on one or two areas. We were focused on a large number of them. Things were hard for quite some time, but it feels like over the last 18 or so months, we have finally broken out.
We have become a commercial company, and we now have something like 21 or 22 individual drug candidates in clinical studies.
REDEMPLO is launched in FCS. Maybe before we get into more specifics on that program, maybe you can just talk about the launch. How is it going? Where is payer policy landing? How are things proceeding? Sure.
First, just to be clear, plozasiran or REDEMPLO is an APOC3 inhibitor, and it was developed to silence APOC3 and therefore lower triglycerides. We view this as a two-step drug, if you will, from a commercial standpoint. Step one is to be approved in a narrow indication, FCS, familial chylomicronemia syndrome. It is an ultra-orphan indication. However, there are a class of patients that we have discovered that we call clinical or clinically defined FCS that make this a bit of a larger population. We have been focusing a lot on that population. Our goal then was to expand the label and treat severe hypertriglyceridemia, and that is about a 3.5 million person market in the U.S. So we launched an FCS a bit ago, and the launch has been good.
It has taken us a bit of time, a couple of quarters to get contracting worked out with payers, but we are there now. We are able to serve both, as I mentioned, genetic FCS as well as clinical FCS. There could be as many as 15,000 or 20,000 or so clinical FCS patients. We have also been ramping up our sales force. When we first launched, it was a very narrow sales force, about 20 or so sales reps. But as we were into the market, we realized that there really were more of these clinical FCS patients than we had first anticipated. We have begun to ramp this. We ramped pretty aggressively over the summertime. We will have another phase of growth in January, February timeframe, and that will enable us to prepare ourselves for SHTG launch sometime in the second quarter, we believe, of 2027.
Recently presented full SHASTA-3 and SHASTA-4 12-month data set at ESC. Can you summarize this data set and why it's meaningful?
Sure. James? Sure. I can take that one.
The top line data for SHASTA-3 and 4, first and foremost, we were achieving about 80% reduction from baseline in triglycerides, and this was all in a severe hypertriglyceridemic population, so triglycerides greater than 500 at baseline. That reduction in triglycerides translated into a statistically significant improvement in the rates of acute pancreatitis, which is the major problem those patients have. There's maybe some other issues around cardiovascular disease, but the life-threatening pancreatitis that can be recurrent in that population is the key clinical event that's driven by triglycerides. The reduction in triglycerides correlated with a reduction in acute pancreatitis. Depending on the population, the risk reduction was 78% to greater than 80%.
All of this was matched with really a pretty clean safety profile. We didn't see any evidence of thrombocytopenia or hypersensitivity reactions. Our liver safety profile was really pretty quiet. The transaminase elevations in the active arms looked similar to those in the placebo arms. Then something that we've been asked about quite a bit over the last year or so was liver fat or hepatic steatosis. We measured liver fat with MRI in the study and saw no clinically meaningful or statistically significant increase in liver fat versus placebo. All around, we were really pleased with the data on both the efficacy, the pharmacodynamic side, and the safety side.
Severe hypertriglyceridemia is a far broader population than FCS. Can you talk about the data that you've generated so far and how we should think about the meaningfulness of pancreatitis risk reduction, triglyceride reduction, and how this sort of translates across these different patient populations?
Sure. James? Yeah. In the SHTG population?
Again, I think that the It's a spectrum, right? SHTG, FCS is the worst form of SHTG, and there's some overlap in these clinical FCS patients with just SHTG patients. Of course, the rates of pancreatitis increase as the triglyceride rates or levels get higher. We view those patients with triglycerides above 880 and a history of pancreatitis as the highest risk population. In fact, in that subset, in the SHASTA-3 and SHASTA-4 pooled data, the risk reduction was 100%. There were no events on active in that population. That's probably the population that is most amenable, at least earliest, to treatment, and where the most medical need is. That being said, we also saw events in patients with triglycerides just greater than 500, but with a history of pancreatitis.
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