Ionis Pharmaceuticals Inc at Needham Virtual Healthcare Conference Summary

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

Question: Joey Stringer - Needham & Co. LLC - Analyst : <_ALACRA_META_ABSTRACT>Well, we'll start off with Olezarsen, your program for FCS and SHTG. I guess let's focus on SHTG for now. Your Phase 3 program consists of three separate trials, CORE, CORE2 are the pivotal ones, and you've got a supportive safety study at Essence. For CORE and CORE2 data coming second half of this year, it will be a big readout for you guys. And the Essence data are coming middle of this year. So with that backdrop, I want to focus on SHTG. It's the much larger indication relative to SCS, but what have you learned about the SCS launch so far? How's it been playing out, and how's it helping set the commercial stage for SHTG? Eric Swayze - Ionis Pharmaceuticals Inc - Executive Vice President, Chief Global Product Strategy Officer Thanks for the question, Joey. I think, if you don't mind, before we start talking about SHTG -- and I love people talking about SHTG. We think it's a great space for us to be in, but I kind of want to back up just a little bit and set the stage for Ionis as a whole and kind of where we're heading. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. APRIL 07, 2025 / 7:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at Needham Virtual Healthcare Conference

Question: Joey Stringer - Needham & Co. LLC - Analyst : Now on the clinical side of things, CORE and CORE2, primary endpoint is percent change in fasting trigs, but can you talk about the importance from both the clinical and commercial perspective, the key secondary endpoints, in particular the acute pancreatitis? How big of a deal is AP for patients and payers?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Do you have to hit the primary endpoint in both CORE and CORE2 for regulatory approval? How do you think regulators will view a successful outcome?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Got it. And from a statistical analysis plan for the two CORE Phase 3 trials, what's the -- can you walk us through that on the primary trig endpoint and the AP secondary endpoint? You touched on it a little bit before.

Question: Joey Stringer - Needham & Co. LLC - Analyst : And sorry I've missed this before, but are the patients stratified between CORE and CORE2.1 trig levels?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Okay, got it. What are your updated thoughts on pricing strategy for the larger SHTG indication? What are reasonable costs to think about on price?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Yes. The SHTG market, do you think that's a winner-take-all market, or what product profile will ultimately win majority market share?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Got it. And speaking of WAINUA, obviously approved in December of 2023, had posted solid $42 million in fourth-quarter '24 sales. Can you talk about some of the launch metrics and how these are trending in the drug's first full-year launch?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Yes, and switching to cardiomyopathy, big-picture question on the market. How big do you think the total market is in cardiomyopathy, just given what we know about tafamidis sales and some Pfizer commentary that the drug only has 20% market penetration?

Question: Joey Stringer - Needham & Co. LLC - Analyst : The cardiomyopathy space, it's competitive. Obviously, there are two approved oral drugs, stabilizers, silencer recently approved. So I guess, big picture, how do you view this market or how do you see this market playing out given the competitive dynamics around those three competitors? Also, thinking about the potential for defamitous LOE in 2028 and any other factors that we should consider that plays into your long-term outlook.

Question: Joey Stringer - Needham & Co. LLC - Analyst : Yes, and you guys mentioned that they're [reflectors] in the Phase 3 cardiomyopathy trial. Can you just briefly outline trial design there and highlight some of the key design elements that you think gives you confidence that you have the right approach here, number one, and the results set you up for long-term success in this space?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Got it. Great. Well, helpful discussion on WAINUA and the TCR space. Want to switch to Donidalorsen for HAE. Obviously, PDUFA coming up in August of this year. Starting off with a market size question, there are multiple prophylactic therapies that are approved, TAKHZYRO, ORLADEYO, HAEGARDA. Can you outline what the current prophylactic market size is in terms of number of patients and sales?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Now HAE is a rare disease that kind of sits outside of Ionis' current commercial focus on CV metabolic and CNS programs. So what gives you the confidence that you can execute commercially in this indication? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. APRIL 07, 2025 / 7:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at Needham Virtual Healthcare Conference

Question: Joey Stringer - Needham & Co. LLC - Analyst : Great. The pelacarsen program partnered with Novartis, can you briefly walk us through the economics to Ionis?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Great. That's very helpful, Wade. Novartis, they announced in late January that the top-line data for the Phase 3 CV outcomes trial for pelacarsen, it was shifted from second half of 2025 to the first half of 2026 based on blind event rates. So I guess, how should we view the potential impact to that shift on the trial outcome?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Anything else weighed on the stats plan for the Phase 3? You touched on it a little bit, but my understanding, the trial is looking at CD risk reduction on the primary endpoint for both 70-plus and then the 90-plus mg per deciliter. Can you explain the significance of each of these analyses? And I guess, how will these be -- how do you think these will be viewed by regulators? And what would this mean from a commercial opportunity perspective?

Question: Joey Stringer - Needham & Co. LLC - Analyst : Got it. Lastly, I want to briefly touch on Angelman syndrome. 582, the program there, can you briefly outline the unmet need here and what is the commercial opportunity in Angelman syndrome?

Question: Joey Stringer - Needham & Co. LLC - Analyst : What do you think differentiates Ionis's approach and program in Angelman relative to some of the competitors out there?

Question: Joey Stringer - Needham & Co. LLC - Analyst : No, we are up on time, so it was good timing there. But thank you, Wade, Kyle, and Eric for participating. It was a very helpful discussion.