Ionis Pharmaceuticals Inc at Stifel Healthcare Conference Transcript

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

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Yeah. So I asked you just now offline, I said, what topic could we start with. And you said Angelman is pretty cool. So to that point, do you want to just level set and give an update there on where you are with the design of the Phase 3 program, why you're excited? And then I can ask a follow-up or two.

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Do you want to talk a little bit more about specific endpoint subscale selections? What was the conversation like inside Ionis? What else were you considering? How did you end up where you did? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 18, 2024 / 3:50PM, IONS.OQ - Ionis Pharmaceuticals Inc at Stifel Healthcare Conference

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : It's true across subscales.

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay. Great. And I think for all neurology drugs going from an open-label study to placebo control, there's a question around placebo effect. This was a question with SPINRAZA historically. How do you get comfortable with that around not just that the efficacy signal you're seeing so far is real, but also how conservative you want to be with powering?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay. Makes sense. And competitively, how should we try to stack up yours versus Ultragenyx's?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Yes. Okay, makes sense. Let's cover olezarsen for a bit now. Maybe just walk us through what you're doing on the commercial side, and then we can talk about the broader indication expansion.

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : How would you define success in the initial rare population launch? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 18, 2024 / 3:50PM, IONS.OQ - Ionis Pharmaceuticals Inc at Stifel Healthcare Conference

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Do you have a guess at what the diagnosis rate might be right now?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Yes, okay. And have you guys thought about what metrics you might share to help investors understand the launch?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay. As it relates to indication expansion, I mean, I think it feels self-evident that this drug works. What would you say is the biggest risk to the pivotal study?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : So is that like -- what defines those clinicians? Are they just of this specific view that triglycerides are of greater importance versus other doctors who are just focused on other biomarkers?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : That alone, that clinician --

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : The believers market.

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : As it relates to the Phase 3 study, how should we think about the probability of you showing something robust enough where you can have a claim around pancreatitis attack reduction? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 18, 2024 / 3:50PM, IONS.OQ - Ionis Pharmaceuticals Inc at Stifel Healthcare Conference

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : What are you going to see?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Yes, okay. Timing of that data?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay. And then in the meantime, the other question you get over and over with every program because you're in a bunch of hot areas is competition as it relates to the Arrowhead program. How are you weighing the way olezarsen stacks up?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Yes, okay. And what kind of sales force do you think you need to really monetize not just the believers, but also the broader prescriber community?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay. And when you talk about the incremental physician who you still really need to sell on the value of aggressively treating triglycerides, with that physician, are you competing in terms of share of voice with like LDL therapies, GLP-1s? Is that kind of a group where you're trying to fight the battle of just sort of the metabolic milieu of where this fits in?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : So what's different about that clinician that's not sold then?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay, great. Anything else to add there?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay. All right. Let's talk about TTR. Do you want to maybe set the stage and talk a little bit about the eplontersen launch and how it's going relative to your expectations?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay, great. In the meantime, what did you learn from Alnylam's outcomes data when it was presented at ESC? And specifically, I mean, I think the surprise, but somewhat surprise was just the time it took really to show real meaningful separation. How do you kind of incorporate that into the thinking around your trial and probability of success?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Makes sense. I mean, Alnylam definitely benefited from extending the study to 36 months and then having an endpoint be 36 to 42. Any concern that you're ending at 33 months? Or do you feel like that's outweighed by the bigger sample?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Yeah. Do you still have the opportunity to extend the study at this point?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : That's 33 months, right?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Right, that's what I thought. So I didn't think you could extend it. So what could you change at this point, if anything?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Right, to incorporate that into the --

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Yes, okay. Makes sense. Where should we go next?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Okay. Sounds great.

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : What does the early adopter pool of this drug look like?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Makes sense. Okay. Maybe to kind of round things out, do you want to talk about some of your other pipeline efforts in other tissues, including your cardiac program?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Yes, okay. Great. Maybe lastly, the other big readout we're waiting for next year is Lp(a). That one is super interesting; maybe set that up for us. And in some sense, that outcome study is kind of proof-of-concept study for the target. How are you thinking about the probability of success?

Question: Paul Matteis - Stifel Nicolaus and Company, Incorporated - Analyst : Makes sense. All right. Thank you, Brett. Appreciate it.