Ionis Pharmaceuticals Inc at Guggenheim Global Healthcare Conference Transcript

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

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : All right. So like you said, multiple positive Phase 3 readouts, a lot has gone right for the company. But somehow, the stock has underperformed. So what changes in '25? And how do you fix it?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : Got it. So traditionally an antisense oligonucleotide company, but I believe you've made substantial strides on the siRNA side. When can we see the first iterative advances moving away -- not moving away, but adding siRNA to the platform?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : So let me make sure I got that right. CNS penetrant medicines delivered either intrathecally -- sorry, intrathecally, but subcutaneously or intravenously and not intrathecally? 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 13, 2024 / 3:30PM, IONS.OQ - Ionis Pharmaceuticals Inc at Guggenheim Global Healthcare Conference

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : Got it. So olezarsen PDUFA date is approaching. No showstoppers on CMC or anything?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : And how are you thinking about positioning olezarsen first in FCS and then in the broader sHTG segment and differentiate versus competition, let's say, you'll have a competitive threat in FCS within a year?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : So let's talk about FCS first. It's a relatively rare disease. Given the severity of the underlying condition, do you think the patients are already identified and housed at specialized lipid treatment centers and the uptake should be relatively quickly? 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 13, 2024 / 3:30PM, IONS.OQ - Ionis Pharmaceuticals Inc at Guggenheim Global Healthcare Conference

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : Got it. And you mentioned sHTG in the broader segment. This could be a blockbuster drug, but somehow the Street has still not bought into it, right? Because otherwise, you should have been trading at a very different level. So what's that disconnect between what the company thinks from its market research versus the perception on the Street?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : Just to finish up on olezarsen. From a label perspective, what are you expecting for FCS, either from a genetic testing perspective or the breadth of the label? And do you think you'll get the pancreatitis on the label as well? 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 13, 2024 / 3:30PM, IONS.OQ - Ionis Pharmaceuticals Inc at Guggenheim Global Healthcare Conference

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : Got it. So let's switch to doni. That will be a second launch probably in the second half of 2025. How are you positioned to launch that in a relatively competitive market?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : And do you think the switch data are going to be reflected in the label to make it easier post-launch, especially laying out how you transition away from whatever therapy you're on to doni?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : And if I understand it correctly, there is a life-cycle management product for doni which is probably more of an siRNA backbone?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : Awesome. So switching to pelacarsen. There was the big HORIZON Lp(a) study readout middle of '25 or approximately. How are you feeling about the study based on your discussions with partner Novartis? 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 13, 2024 / 3:30PM, IONS.OQ - Ionis Pharmaceuticals Inc at Guggenheim Global Healthcare Conference

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : So given the scope of the indication, I believe you're also working with Novartis on a follow-on potential in siRNA molecule. How quickly does that program come to maturity if the HORIZON Lp(a) study is successful? And from a positioning perspective, is that going more in the frontline preventative setting? Or would you again start in an ACVD population?

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : Got it. Let's touch upon the Angelman program because you just had the regulatory agreement, which looks to be very different from your competitor's program. Maybe touch upon that one and just think about positioning how quickly you can move that study. Currently, stated to start early next year.

Question: Debjit Chattopadhyay - Guggenheim Partners, LLC - Analyst : Unfortunately, the gatekeepers are telling us you're talking too long. So Brett, I wish I could touch on a couple of other things, but I can't. Thank you so much, and I appreciate your time today.