Ionis Pharmaceuticals Inc at Citi Global Healthcare Conference Summary

The following is excerpted from the question-and-answer section of the transcript.

Question: David Lebowitz - Citigroup Inc. - Analyst : Now you have a PDUFA date coming up later this month for olezarsen for the treatment of FCS. Could you tell us about the drug, the disease and your expectations?

Question: David Lebowitz - Citigroup Inc. - Analyst : This is an ultra-rare disease, approximately an estimated 3,000 patients. What's the diagnostic journey for these patients to actually get to the point where people know they have FCS? And obviously, that will change with the drug available in the market. But how long does it take until people actually identify it in the first place?

Question: David Lebowitz - Citigroup Inc. - Analyst : Now obviously, it's an ultra-rare disease, can be very expensive. What requirements do you think -- first of all, what will the label -- could the label look like? And what requirements could the payers place on the drug to prevent these severe hypertriglyceride patients from being put on drug right now and keeping it isolated towards FCS? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 03, 2024 / 1:45PM, IONS.OQ - Ionis Pharmaceuticals Inc at Citi Global Healthcare Conference

Question: David Lebowitz - Citigroup Inc. - Analyst : With data for severe hypertriglyceridemia coming in the second half of next year, what would we expect to see? What can we extrapolate from what we've seen in FCS? And how should we set our expectations?

Question: David Lebowitz - Citigroup Inc. - Analyst : Do you think that the acute pancreatitis data needs to be on label and the initial approval to be for doctors to be willing to use the therapy? Is that something we can expect to see in the top line release?

Question: David Lebowitz - Citigroup Inc. - Analyst : Now let's jump over to HAE. Could you tell us about donidalorsen? That's at the FDA, I believe a PDUFA date in August. Tell us about the drug. It's a very different market than FCS. And what are your initial thoughts now of the drug's profile and how it might fit into this market?

Question: David Lebowitz - Citigroup Inc. - Analyst : Now the Switch study is -- obviously, it's not a double-blind study. It's different than the primary pivotal trial. But it essentially provides an instruction manual for doctors looking to switch. Is that something that can end up on label? How ultimately do you feel it will be used?

Question: David Lebowitz - Citigroup Inc. - Analyst : And I guess as far as overall expectations, given it is more crowded, how should we view the -- what the potential initial revenue might be and where it ultimately might sit within the market? And frankly, given of the therapies out there, prospective therapies, who do you believe is the biggest challenge?

Question: David Lebowitz - Citigroup Inc. - Analyst : So we go through next to 582 in Angelman. You recently announced a Phase 3 trial design. The primary endpoint of the trial is expressive communication. How did you come to that as your primary endpoint as opposed to the Bayley-4 overall? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 03, 2024 / 1:45PM, IONS.OQ - Ionis Pharmaceuticals Inc at Citi Global Healthcare Conference

Question: David Lebowitz - Citigroup Inc. - Analyst : You were using a placebo-controlled and a competing pivotal trial is using a sham control. Could you elaborate on the differences between the two? And how could it affect each study and what they eventually show?

Question: David Lebowitz - Citigroup Inc. - Analyst : Now let's jump to WAINUA. WAINUA was launched in polyneuropathy, ATTR polyneuropathy. And tell us about how that launch is going? How the drug is being used in naive patients versus switches from other commercial options out there and what you think is driving that?

Question: David Lebowitz - Citigroup Inc. - Analyst : Now we jump over the cardiomyopathy side of things. There's WAINUA's profile itself, its trial. Then there's the dynamic of TTR silencers versus stabilizers. How do you think that things ultimately will shake out between the two different mechanisms or mode of action themselves, the silencers versus stabilizers? And how do you think WAINUA will ultimately fit in?

Question: David Lebowitz - Citigroup Inc. - Analyst : So next year, there will be pivotal data from another cardiovascular program, pelacarsen Lp(a). How should we frame our expectations for what we'll see there? It's an outcomes trial, so the results will be fairly definitive in what it achieves. What should we expect to see? And what are Novartis is your partner, Novartis (technical difficulty) plans in that area? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 03, 2024 / 1:45PM, IONS.OQ - Ionis Pharmaceuticals Inc at Citi Global Healthcare Conference

Question: David Lebowitz - Citigroup Inc. - Analyst : Thank you for that. Now how easy is it going to be to actually show an outcomes benefit just given we don't necessarily have a lot of direct data to show how the lowering of Lp(a) ultimately contributes to cardiac benefit? It just seems to be generally accepted that it might, but we don't really have any definitive evidence.

Question: David Lebowitz - Citigroup Inc. - Analyst : Thank you for that. And to wind things up, obviously, the technology antisense, Ionis is a pioneer in that area. It's ahead in the chemistry that's evolved over the years as a way to deliver greater payload and essentially overall lower volumes and with less frequent administrations to reduce tolerability issues that were more apparent early on. What's the next step? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. DECEMBER 03, 2024 / 1:45PM, IONS.OQ - Ionis Pharmaceuticals Inc at Citi Global Healthcare Conference

Question: David Lebowitz - Citigroup Inc. - Analyst : Got it. Thank you very much for your time.