Ionis Pharmaceuticals Inc at JPMorgan NAPA Valley Forum (Virtual) Transcript

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

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : So maybe we can get right into it. Since Brett became CEO last year, the company has evolved its strategy and is now planning to commercialize some of its wholly owned medicines independently. So what's Ionis' strategy on which drugs it's going to commercialize? And do you still plan to partner some programs? And how will you decide?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Great. So maybe related to that, how do the acquisition of Akcea accelerate your commercial strategy? And what particular insights, if any, have you gained from having that team back [in-house]?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : What about the Sobi agreement? What was the rationale there? And how does that benefit Ionis?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. And maybe just to cover a recent topical question and, I guess, recognizing you can't really speculate too much what will happen without the data, but can you just hit at a high level the different potential outcomes [at least since] there are different outcomes following Roche's further analysis of tominersen data? 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 29, 2021 / 8:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at JPMorgan NAPA Valley Forum (Virtual)

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Got it. Maybe I'll take this chance to just remind folks, if you want to ask a question over the portal, you can hit that blue Ask a Question button that will send it to me and I can ask Beth. Before we turn to the questions on the portal though, how are you thinking about the timing to refile the WAYLIVRA NDA with the FDA? And what other countries are you targeting in the near term?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Great. So we've got our first question on the portal. It's topical. What are the next steps for HAE? When can you start Phase III? In the Phase II, did you test schedules other than once monthly?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Got it. Another question here from the portal. To the extent that you see ongoing value in the HTT lowering approach in Huntington's, are you tied to Roche? Is there a way to move forward independently with a follow-on candidate?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Got it. Okay. Maybe switching back to my questions. What -- I guess, more broadly on the pipeline, what gives you the confidence that you can meet your goal of 12 or more medicines on the market in 2026?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : So I guess -- so related to that, can you walk us through the key pipeline catalysts for this year?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Great. And I guess what's the (inaudible), if there is one, from the tominersen update to your other neuro products? Specifically wondering if biodistribution were at play here, what risk could that suggest? 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 29, 2021 / 8:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at JPMorgan NAPA Valley Forum (Virtual)

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Got it. You mentioned the 12% Phase III data coming in the back half of this year as kind of one of the key updates. What are your expectations for that Phase III readout? And what do you see is the efficacy bar in this setting?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Another question from the portal here, going back to Huntington's. Can you confirm that Ionis has delivered more Huntington's compounds to Roche? When they license a target, does that include all versions of the technology, LICA 2.0, 2.5, et cetera?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Great. So maybe shifting back to ALS, how quickly could Biogen file an NDA for tofersen in SOD1-ALS? 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 29, 2021 / 8:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at JPMorgan NAPA Valley Forum (Virtual)

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Great. And for the Phase III ATLAS trial set to start this year in increased symptomatic patients with the SOD1 mutation, how long do you plan to evaluate those patients before you can assess for clinical benefit?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Got it. Can you give us an idea of the totality of the data we can expect to see for IONIS-ENaC-2.5Rx coming at ATS. What potential meaning does this have for other aerosol formulations in the pipeline?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : And maybe coming back to one of the first drugs that we talked about, PKK-LRx in HAE. How should we think about development plans from here, assuming this data gives you confidence to move forward?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Maybe just against the backdrop of a landscape that has multiple efficacious agents on the injectable side, a new oral entrant as well in HAE, how does Ionis kind of position a product like this or differentiate it within the HAE landscape relative to those other kind of effective injectables?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : So you've talked about sort of cardio and neuro as products that you want to keep. This is a rare disease product, but feels like it doesn't necessarily fall into those buckets. So how do you think about this product and potential partnering?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Great. What about the C9 Rx program in C9 ALS? Can you remind us of the Phase I/II study design there and frame what would be considered a clinically meaningful benefit?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Makes sense. Maybe shifting to cardiovascular, what do you see as the key advantages of AGT-LRx's mechanism in heart failure?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : So how should we think about the timing for other Phase II data for that product in addition to the hypertension data coming this year? And how do you envision potentially progressing that asset into pivotal studies with multiple indications potentially available?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : How should we think about timing for the ongoing SPINRAZA studies? And how do you see the potential for these trials to impact SPINRAZA's market position relative to Evrysdi and Zolgensma.

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Got it. Okay. We have a couple more questions in from the portal. So first, as we think about Ionis's partnership strategy going forward, should we think about continued one-off partnerships with leaders in their respective therapeutic areas? Or how does management and the Board think about a broader partnership with a strategic player as a way to more rapidly advance a group of assets?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Makes sense. Another one from an investor here. The company has made amazing progress in antisense technology. It's a commercial biotech company, and there are only a few of those, but the stock is at the same level as it was in January 2014. Do you have any thoughts as to why investors don't appreciate these achievements?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Okay. Great. So just one minute left, so I'll leave with the final question we're asking all the management teams today. What's your favorite Napa Valley wine?

Question: Jessica Macomber Fye - JPMorgan Chase & Co, Research Division - Analyst : Wise response. Thanks, Beth, and thanks, everyone, for tuning in to listen.