Ionis Pharmaceuticals Inc at Barclays Global Healthcare Conference Summary

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

Question: Huidong Wang - Barclays Bank - Analyst : That's great. I think that before even going to the other programs, I do want to ask you about the Ona deal that you just announced yesterday. So maybe give us a little bit more color regarding the deals and why this is done. And I know some investor views are very favorable in terms of upfront payment and the milestone. And so maybe walk us through maybe a little bit high level on the Ono deal.

Question: Huidong Wang - Barclays Bank - Analyst : So the milestone $660 million is mainly the back-end loaded? Or you do have multiple development regulatory sales?

Question: Huidong Wang - Barclays Bank - Analyst : Okay. And the mid-teen royalty, that's just fixed?

Question: Huidong Wang - Barclays Bank - Analyst : So I go back to your TRYNGOLZA launch preparation, the investors are more excited about the sHTG opportunity there. And you will have two studies, so data expected second half this year. So maybe give us a little bit thoughts on the study design of the expectation there and what endpoint will matter most for the commercial perspective.

Question: Huidong Wang - Barclays Bank - Analyst : Okay. And the full triglyceride reduction. So what is the threshold you were thinking in order to hit the 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. MARCH 12, 2025 / 5:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at Barclays Global Healthcare Conference

Question: Huidong Wang - Barclays Bank - Analyst : Great. And for the acute pancreatitis, so you say you hopefully will show maybe similar level. Like you look -- when the study was a power, do you think that you were hoping, based on the powering do you think that they could have a chance to hit a step?

Question: Huidong Wang - Barclays Bank - Analyst : Okay. Good. Quickly on the ESSENCE study that you said top line mid-'25. So what kind of safety profile you think consider as a good safety profile? And what kind of a measurement could trigger some concern? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 12, 2025 / 5:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at Barclays Global Healthcare Conference

Question: Huidong Wang - Barclays Bank - Analyst : Okay. Good. Now I'll switch to your donidalorsen in HAE, which should also have a drug approval soon. And then so maybe the given the drug profile Q8 weeks and the Q4 weeks, do you expect both in the label? And then how do you think that the commercial opportunity would look like?

Question: Huidong Wang - Barclays Bank - Analyst : And regarding the pricing, is it fair to assume that will be largely comparable to the other drugs out there, roughly $0.5 million per year? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 12, 2025 / 5:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at Barclays Global Healthcare Conference

Question: Huidong Wang - Barclays Bank - Analyst : And total market opportunity, if we're using BioCryst, they did guided $1 billion and $800 million in the US. Do you think that similar to your goal? Or you think it will do better?

Question: Huidong Wang - Barclays Bank - Analyst : That's great. the remaining few minutes, I do wanted to ask, you have too many pipelines.

Question: Huidong Wang - Barclays Bank - Analyst : WAINUA and also the Angelman program, right? So we did see you have pretty good growth in the polyneuropathy last quarter, quarter-over-quarter, it's a pretty high growth. And how do you see in the 2025 the polyneuropathy, the market, like how much growth do you think you expect to see the trajectory wise? And I think that we know that Alnylam reported $1.22 billion in the REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 12, 2025 / 5:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at Barclays Global Healthcare Conference polyneuropaty market. And where do you see -- where you go, because the drug just recently received approval right? So maybe like where do you see the opportunity here? And also the ATTR cardiomyopathy, a much bigger market opportunity?

Question: Huidong Wang - Barclays Bank - Analyst : So Beth, just quickly, I just hear you saying second half '26.

Question: Huidong Wang - Barclays Bank - Analyst : So is that because monitoring the blinded events that make it a little bit delayed?

Question: Huidong Wang - Barclays Bank - Analyst : Okay. Good. I know we are running out of time, I will ask other pipelines have a difference. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 12, 2025 / 5:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at Barclays Global Healthcare Conference

Question: Huidong Wang - Barclays Bank - Analyst : Yeah. Thank you so much.