Arrowhead Pharmaceuticals is a biotechnology company that develops RNA interference-based therapies to silence disease-causing genes, with a focus on liver, cardiometabolic, pulmonary and CNS indications.
To start, how would you characterise the current level of interest in RNA and RNAi, particularly in light of the recent wave of big pharma M&A in the space and Arrowhead’s own deal with Novartis?
Interest in RNA generally, and RNAi more specifically, has been growing over the last decade. Within the industry, companies are looking for technologies that work and allow them to treat diseases that couldn't be treated before. As RNAi and broader RNA technologies have matured, they have become real, validated and scalable modalities. RNA interference, in particular, is now well accepted as hyper-specific.
Healthcare has long wanted to move towards precision medicine. The problem with small molecules is that they go everywhere and do many things; you hope one of those effects is the pathway you care about, but they also do a thousand other things. RNAi, and to a lesser extent other RNA technologies, essentially do one thing, and the evidence for that has been accumulating for years. So I don't think this year is dramatically different; it's part of a continuing trend that has been good for our company and, more importantly, for the medical community.
This year is nevertheless particularly important for you at Arrowhead, with the FDA having just approved your plozasiran. What are the implications of this clearance?
Plozasiran was designed to silence ApoC3. The biology has been clear for some time: if you decrease expression of this protein, you can reduce circulating triglycerides, one of the key fats in the system. Everyone knows about LDL, the so-called bad cholesterol, but other lipids and lipoproteins also matter, and ApoC3 and triglycerides are among them. In our phase three studies, we saw drastic reductions in triglyceride levels and a well-tolerated drug, which is particularly important for patients suffering pancreatitis driven by very high triglycerides, an area where there has historically been no effective treatment.
The initial population we will address is patients with familial chylomicronemia syndrome, who live with extremely high triglycerides and a very severe low-fat diet—down to the equivalent of about 12 almonds of fat per day—and recurrent, painful, sometimes ICU-level pancreatitis. For them, having a treatment is a major change. For us, it’s also a graduation from a pure R&D organisation to a commercial one, which is why we are in this business: to bring important drugs to patients. At the same time, we don’t want to lose our core R&D DNA. We expect to have around 20 drug candidates in clinical studies by year-end, giving us many chances to help patients across different diseases.
How prepared are you to commercialise, and what are the main execution risks you’re focused on over the next year?
We're ready. We've been building our commercial team for over a year, and we've had medical affairs teams in the field for 18 months to two years, educating physicians who treat these patients. The organisation is excited to bring this drug to people who need it. From an internal standpoint, the infrastructure and teams are largely in place.
The biggest risk—and opportunity—is finding patients. We believe there are many undiagnosed individuals, which makes sense when there has been no available treatment; physicians are less likely to diagnose a condition they can't do anything about. Now that we have a therapy, education becomes critical. We need to help clinicians recognise that these patients are out there, that they are suffering, and that a new option exists.
Our job is to bring those patients out of the dark and onto effective therapy.
You mentioned multiple therapies entering clinical trials shortly, with programmes in lung, cardiometabolic disease and CNS. Where do you see the next major breakthrough coming from, and how broad is the potential of your platform?
Our strategy has been that if we can treat a disease, we should go after it, even though that’s unusual for a company of our size because capital is limited and it is expensive to tackle disparate indications. We’ve always believed that if some programmes are not core or we can’t take them forward ourselves, we can partner them. We’ve been successful in finding strong partners—Novartis, Sarepta, GSK, Amgen, Takeda and others—who allow us to keep our foot on the gas in discovery while still finding “homes” for programmes we don’t progress in-house. At the same time, we intend to maintain a substantial set of drugs that we will bring to patients ourselves.
The coming year is important for proof of concept. In obesity, we should learn whether our first two candidates are doing what they’re supposed to do. They’re interesting because they’re not designed to suppress appetite, but to increase fat metabolism. In animal models, treated animals eat the same amount as controls but lose weight, specifically visceral fat rather than muscle. If that translates to humans, there are many places these drugs could fit into obesity care. We also expect readouts on our new brain shuttle, where animal data suggest we can deliver these molecules into the brain—a potentially transformational step the field has been chasing for decades. By summer 2026 we should know if it works, and we already have an Alzheimer’s drug heading into patients, plus a Parkinson’s partnership with Novartis and other neurodegenerative targets behind that. In cardiometabolic disease, a new candidate designed to lower both LDL and triglycerides in one molecule will start treating patients soon; if successful, it could help around 20 million Americans with mixed hyperlipidemia. Additional Phase 3 studies for plozasiran in broader populations should also begin to read out in the summer.
Focusing on Novartis specifically, what does this partnership represent for Arrowhead’s strategy? How do you determine which programmes to retain in-house versus out-license, and should we expect additional partnerships of this kind in the near term?
Partnerships are a core part of our business model, even if we don’t expect another major one in the next few months. Drug development is expensive, and we can’t rely entirely on capital markets to fund everything. So we will continue to need partners in the near to mid-term. Deciding what to keep and what to partner is dynamic; our capabilities and ambitions evolve over time. Our aim is to assemble a group of medicines that we commercialise ourselves, with enough shared ground to support a cohesive commercial and late-stage development organisation.
Today, we’re most focused on cardiometabolic disease, broadly including cardiovascular conditions and obesity. We also want to see how CNS develops around the brain shuttle, and we may choose to build serious expertise there. The same is true for lung: depending on upcoming data, we might either own that space or partner it. Novartis is an excellent partner for us in neurodegeneration: they have deep expertise and a strong interest in Parkinson’s, and they are well placed to take that potentially powerful medicine through clinical studies and, we hope, to patients. For us, that is one less drug to develop internally, and we believe it sits in the right hands.
