Ionis Pharmaceuticals Inc at Bank of America Global Healthcare Conference (Virtual) Transcript

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

Question: Jason Gerberry - Bank of America - Analyst : Great, great. Well look, the Company has been a leader in the RNAi space -- or the RNA interfering space for quite some time. And maybe -- you had a lot of interesting success with Spinraza, and I'm curious if you can talk a little bit about what you see as some of the next key inflection points in the story, what excites you most about what's going on in the pipeline in terms of potentially ASOs with important derisking data coming up here in the next 12 to 18 months that have blockbuster revenue potential.

Question: Jason Gerberry - Bank of America - Analyst : Well, great. And maybe can you just talk strategically how you guys are thinking about that go-to-market commercial integration ambition and the -- Sobi is now commercializing Tegsedi and your thoughts on what sort of programs you want to prioritize to bring to market yourselves? Has that lens at all shifted or changed in the last six to nine months, or is focus still the same in terms of the assets you want to focus on and commercialize yourself?

Question: Jason Gerberry - Bank of America - Analyst : Got it. So, for something like PKK -- may fall outside the therapeutic scope, but you could still potentially be opportunistic on opportunities because they might still be more narrow in the commercial intensity of bringing those to market. It still may fit with what you want to do as a company. Is that fair to say?

Question: Jason Gerberry - Bank of America - Analyst : Okay. Now, as a biotech company, you get the benefit of the economics on Spinraza which help subsidize a lot of your investment into future product opportunities. So, one of the questions that I had for you just in terms of what you are seeing real time in the SMA market with the competitive dynamics -- I think there was some recent interesting commentary from you guys around some anecdotal feedback that perhaps some patients might be coming off [terprizaplom] and coming back to Spinraza. There are COVID dynamics that are probably playing into how many patients maybe have gone on to Spinraza in the last 12 months or so, or maybe even longer. So, can you talk about potential tailwinds to the business, if there are tailwinds to the business, and how you guys are just thinking about what you can comfortably rely on potentially for the next couple of years in terms of Spinraza economics?

Question: Jason Gerberry - Bank of America - Analyst : Can you remind us the cadence of dataflow here from all these studies looking at Spinraza and either patients who previously are on Risdi or gene therapy and some of the other programs?

Question: Jason Gerberry - Bank of America - Analyst : Okay, that's fine. You mentioned three pillars at the start, developing as many ASOs or high quality ASOs -- going to be a commercially integrated entity at some point, and then expanding the reach, which I assume is other delivery formats, aerosol, oral ASOs, moving beyond just liver and CNS targeting antisense. So, we've seen some interesting data on animals. I get the sense with aerosol, and perhaps with oral ASO, there's still some work to do tweaking those formats to be brought into humans. Can you talk a little bit about where the Company sits in terms of moving into some of these newer frontiers?

Question: Jason Gerberry - Bank of America - Analyst : Okay, great. Well, maybe we'll go to some program specific questions in the pipeline. And starting with Tofersen and the agent for patients with SOD1 mutation, just sort of a general question. So, we'll get topline data in the fall. Can you talk a little bit about the format of the data that we'll get? I realize your partner presumably is calling the shots, but what can you say? Will it be a medical meeting, will it be just a topline press release where we get detailed data? Just curious how you could frame the nature of the update that we'd get in the fall.

Question: Jason Gerberry - Bank of America - Analyst : Okay. The next question is something that comes up a lot. It came up in Huntington's, comes up in cardiomyopathy as well. How do you guys know or derive comfort, what is the right level of SOD1 knockdown necessary to drive therapeutic benefit?

Question: Jason Gerberry - Bank of America - Analyst : Got it, okay. And can you just talk about some of the changed variables going from your successful Phase 2 to now this pivotal study with Tofersen in SOD1 mutation? I believe that the endpoint duration is one of the main differences, but can you just remind the listeners what are some of those differences in what you saw in prior support of Phase 2 testing?

Question: Jason Gerberry - Bank of America - Analyst : Okay. Well, looking forward to the data in the fall. Maybe we can shift gears to ANG3 and APOCIII. Two assets that are striving to accomplish similar objectives in terms of lowering triglyceride levels. And so, how do you see those two assets fitting together? On the one hand, expensive to do these large outcome trials, so I can understand the rationale for bringing Pfizer on board as a logical partner in the cardiovascular space. You guys have APOCIII, you got the asset rights back. Do you intend to just focus maybe on more narrow applications where you wouldn't be investing in the same larger outcome trials as perhaps Pfizer might be with ANG3? Just maybe help us think through how these two assets can coexist.

Question: Jason Gerberry - Bank of America - Analyst : That is 300,000 or 3 million?

Question: Jason Gerberry - Bank of America - Analyst : I thought I heard thousand. I was like that doesn't sound very big.

Question: Jason Gerberry - Bank of America - Analyst : Yes, and that's definitely feedback we hear from investors is that the cardiovascular portfolio is maybe one of the more underappreciated aspects of the story. So, as we think about TTR LICA, I guess TEGSEDI has lagged its closest competitor in the polyneuropathy space. The markets are moving to less frequently dosed versions of these silencers. And as we think about what we'll learn next year with the polyneuropathy study, I imagine you can validate TTR LICA can improve upon the safety of first generation. Ultimately the read across, I would assume, to cardiomyopathy is still low just because the key question there is what is the outcomes benefit. And you're not going to really glean much in terms of cardiomyopathy outcomes from a polyneuropathy study. So, I guess the main things to look for next year would just be, I assume, competitive positioning relative to Alnylam and just the ability to improve upon the safety profile of TEGSEDI. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 15, 2021 / 2:55PM, IONS.OQ - Ionis Pharmaceuticals Inc at Bank of America Global Healthcare Conference (Virtual)

Question: Jason Gerberry - Bank of America - Analyst : What's the confidence level internally that you can get rid of the [REMS] associated with TEGSEDI. If there is a drawback at-home dosing is positive, but then there is heightened monitoring with platelets. And I guess that would be the safety shortcomings that you would want to solve for with the LICA and ultimately less oligonucleotide being dosed to the patient.

Question: Jason Gerberry - Bank of America - Analyst : Got it. And then obviously the bigger opportunity ultimately is cardiomyopathy. And can you talk about how you guys went about designing your outcomes trial where effectively, I think maybe differentiated from your competitors, you'll have a head-to-head look with a comparative arm that presumably most patients will be on a stabilizer? So, can you talk about the data you'll generate, how that could differentiate your TTR LICA in the marketplace? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 15, 2021 / 2:55PM, IONS.OQ - Ionis Pharmaceuticals Inc at Bank of America Global Healthcare Conference (Virtual)

Question: Jason Gerberry - Bank of America - Analyst : Got it. Well, we've got roughly two minutes left. Maybe just a couple -- a quick one on HAE and your PKK program. And how are you viewing the market evolving with new oral agents coming into the marketplace? There is a view out there that perhaps the existing injectables have reduced the attack rates to very, very, very low attack rates. So, as you embark upon a Phase 3, I don't believe you are considering a head-to-head trial versus the market-leading injectable. So, how do you see the value proposition emerging with PKK?

Question: Jason Gerberry - Bank of America - Analyst : All right, well, great. I appreciate the time and your insights, Beth, and best of luck. Looking forward to the ALS data in the fall.