Ionis Pharmaceuticals Inc at TD Cowen Genetic Medicines & RNA Summit Transcript

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

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : So we have as normal lots to talk about. So I think just to give the audience a little bit of a bird's eye view, we're going to start with renewal both for PN and then TTR cardiomyopathy. I will go to Angelman next, and then to HAE, probably move to Factor B, ahead of GA Phase 2 data that's expected -- we're expecting in Q4, and then Olezarsen, ahead of the sHTG data next year. And we'll probably ask LPL a little late question as well. And if you have any questions, either e-mail us directly at yourown.org or at tdsecurities.com, that's the new e-mail address or you can go ahead and just put that into the website right there, and I can see the questions and take them up for you. So let's start with the first renewal for TTR-PN, how is the launch? This is still a market that sort of early in its infancy, (inaudible) obviously launched not too far ahead of you. WAINUA is differentiated in terms of auto-injector, one thing which is pretty easy. What kind of feedback are you hearing so far, both from clinicians and payers as well?

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : Are all patients, is it exclusively self-administered or some of them inevitably have to come into the clinic.

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : And when you're thinking about the level of diagnosis so far in PN, kind of where is the market in terms of just the maturation of PN as an indication?

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : Okay. Let's shift over to TTR cardiomyopathy. Alnylam was expected to release the HELIOS-B data scuttled by the Wall Street, which is obviously scuttle by, it's as early as next week. And if it's not in June then it certainly they set July. When there's a lot of questions as to whether that's going to hit in the overall ITT, or whether it's going to hit more on the mono side, just given the previous (inaudible) data, and the APOLLO study, which is obviously a shorter study showed more efficacy on the combo side. When you're thinking and there's a lot of discussion these days about whether a cardiomyopathy TTR is more wild type driven, and it's really whether it's a question of sort of homeostasis and maybe ubiquitin related protein degradation, and within the cells have modifiables to fibrils and whether through the mutant that's driving the cardiomyopathy or it's really wild-type enhancing at a silencer or stabilizer. What do we know about the biology for TTR cardiomyopathy? What's the pathology driven by?

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : And then what's your view, I know again, it's probably unfair to ask you this a little bit, I'm sure you have a view relating to the (inaudible) data and why the combo looked better than the mono, again, short endpoint, much smaller study, obviously, but the stabilizers did show sort of a more rapid effect.

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : And when you're looking forward to your data, the primary is a composite. Do you have a view as to whether you can show a survival benefit as well, just given that you moved a lot of the study, you know, after over a rolling sort of early on in the US, you then so cap the US sites and you moved to the UK and South America, where patients are going to be sort of newly onset. Is there more of a chance to show survival benefit and where those patients newly onset by (inaudible) are they newly (inaudible) and kind of earlier stage in their disease. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 20, 2024 / 7:30PM, IONS.OQ - Ionis Pharmaceuticals Inc at TD Cowen Genetic Medicines & RNA Summit

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : And just remind us, that study does not cap what percentage combo would there would be with the tafamidis, right?

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : Okay. And again, for the audience, if you have questions, feel free to either e-mail that or put them up as well. And so it sounds like the patients are going to be on combo, one would imagine they were onto tafamidis and they're rolling on (inaudible) on top of it. In that study, is it possible to start with WAINUA and then roll on tafamidis or at that point, it's too late because you're going to count as a -- chances are when they're adding that patient and the patient's progress because of an event? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 20, 2024 / 7:30PM, IONS.OQ - Ionis Pharmaceuticals Inc at TD Cowen Genetic Medicines & RNA Summit

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : And then maybe finally on that program (inaudible) is talking a lot about their relative risk reduction and a survival benefit tafamidis showed roughly sort of a 30% survival advancements or a benefit. Do you -- is there a (inaudible) as mono that you think a silencer needs to hit or the rates very different these days than they were, you know, back in the days?

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : Okay, terrific. Okay. Let's move to Angelman and because that program alone we can speak about for 20, 30 minutes. We're waiting for the HALOS Phase 1/2a data with ION582, that's going to be the upcoming Angelman meeting in late July in Ohio. It's the Angelman Syndrome Foundation meeting. And I think you've said in your press release that about 60% or 70% of patients had a benefit relative to natural history across several of the parameters that it was consistent across scale, so to speak, and it was clinically meaningful. I think you've also made some comments that you'll be moving toward a Phase 3, we'll talk about it with the regulatory agencies and you'll most likely pick a (inaudible) sub domain is one of the primary endpoints. And for the audience, I think (inaudible) they're going to take the (inaudible) for cognitive scale. You're didn't say you wouldn't comment cognitive is potentially one of them, there's one other scale potentially as well, which could be hyper activity, but you've (inaudible) you've commented on as well. When you're thinking about the (inaudible) data, the biggest pushback from investors has been one is the lower extremity -- lower extremity weakness, let's put that aside. The other one was because there wasn't a placebo -- constant questions that we're getting about how clinically meaningful is that data and how likely is it to predict success in the future Phase 3 that is going to be placebo adjusted, obviously. You know, I think in some ways, if I remember correctly, you and your team view the (inaudible) data is also kind of being confirmatory a little bit for an antisense oligo approach and your data will further build on that. So can you comment on all of that?

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : And when you're thinking about the secondary endpoints. I think this is where you diverge of maybe potentially a bit from (inaudible) I think they've talked about using a multiple domain responder index. They talked about using some of the validated sort of traditional endpoints, but also some of the Angelman syndrome assessment, (inaudible) are not yet -- are not validated historically and those endpoints that might resonate with you or would you look at CGI, would you looked at the [Vineland] and sort of both kinds of other domains of the (inaudible) et cetera.

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : And would you talk to FDA and EMA or usually talk to FDA first, and so the EMA follows.

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : Yeah. Okay. Then you would start the study -- do you normally start the study before you get EMA alignment or how does that work?

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : Okay. Let's move next and I'm thinking on things that are the way we're kind of progressing based on things that I think are going to be important for the stock and where things are, there's a little debate. So I'm going to next to Factor B LRx, which is now the Phase 2 geographic atrophy study that's ongoing. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 20, 2024 / 7:30PM, IONS.OQ - Ionis Pharmaceuticals Inc at TD Cowen Genetic Medicines & RNA Summit I think we're expecting the data and it's a big 330 patient golden study. There's a Part A that was 30 patients with three doses respectively (inaudible) and two doses were then chosen for the protocol, moved into the randomized Part B and that's 300 patients, so two doses against placebo. And again, the data we're expecting in Q4 in the company's second half in geographic atrophy and the primary endpoint is it is a 12 months and different division based endpoints as well obviously, safety. And the second prior data you've shown about a 75%, maybe even 80% reduction in Factor B (inaudible) subcu, I believe, Q4 weeks. The first question we always get is Factor B -- so Roche to Factor D antibody, which was intravitreal and that failed in Phase 3. Again it's an antibody intravitreal injection. And the people are still unsettled as to whether Factor B is a good target for geographic atrophy. Can you talk about that and some of the genetics data that you have?

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : And just maybe final question. Just remind us at the time that you did the deal with Roche, the IgA nephropathy -- so Roche ultimately licensed the program, Ionis, we are already running the Phase 2 GA study (inaudible) conducted study. And then Roche, when they license the program, they went into Phase 2 IgA (inaudible) and then they move to Phase 3. Just remind us chronologically how things happened.

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : All right, terrific Brett. As always, I think we're just a little bit over. Great to see you. Thanks so much for the time, and we'll continue to stay in close touch.

Question: Yaron Werber - TD Securities (USA) LLC - Analyst : Thanks, everybody, for joining us. And I think it's the last session for today, and then we have a full day tomorrow as well, starting at 9:00 AM with a (inaudible) panel. Thanks so much.