Ionis Pharmaceuticals Inc at William Blair Growth Stock Conference (Virtual) Transcript

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

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : Yes, it certainly is. And maybe before we dive in individually to some commercial-stage assets and then into those pipeline assets, we can talk a little bit about the technology as a whole and sort of where you sit in the landscape. So there was actually a question in from a listener about sort of the differences with your single stranded antisense oligonucleotide technology versus other double-stranded siRNA therapies that are out there? And maybe a broader question about like how these RNA-targeted therapeutics sort of fit into the treatment landscape with all these gene therapies and gene editors sort of being developed as well? Where does Ionis sit in all amongst that burgeoning landscape?

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : That's very helpful. And maybe we can dive more into SPINRAZA because that's no scratch of a therapy for a devastating disease, it's become standard of care, and it does generate over $2 billion annually. We did see some tapering of prescribing, I think, during the COVID-19 pandemic. And now that we're seeing sort of a return to normal, hopefully and more hospitalization rates increasing and patients coming back for their procedures. Are we seeing recovery for SPINRAZA prescribing? And do we expect sort of a return to normal as long as this pandemic continues to subside?

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : Yes. That's interesting. Maybe we'll keep the commercial metrics to Biogen. But both companies, I believe, have been messaging as of first quarter that around about 11,000 patients, may be greater than that are currently on therapy. I think the market estimates are about 60,000 patients, so SMA patients worldwide. So I guess, what's the low-hanging fruit here? Where can growth come from? What patients are currently on SPINRAZA versus what patients aren't on SPINRAZA? And I guess, why are they not taking SPINRAZA currently? 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 01, 2021 / 3:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at William Blair Growth Stock Conference (Virtual)

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : Makes sense. And that's certainly what we're seeing currently. Maybe on the DEVOTE and the RESPOND studies. You did mention them and sort of looking to demonstrate either increase dosing, more efficacy or providing greater benefit over Zolgensma, the gene therapy. Is there any update on how those trials are enrolling? When we might see data from those trials? And sort of how those trials could potentially inform on prescribing SPINRAZA down the road?

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : Yes. And then just in terms of like the outcome here, I guess, like do we envisage a scenario where you kind of mentioned it's already happening, like people get gene therapy and then they get SPINRAZA add-on therapy, that would technically be off-label, I guess, currently. So is that how these trials are going to inform usage going forward, get that in a label per se and unlock those patients that are on gene therapy? Or is there another way we should be thinking about the readouts of these trials?

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : That's fair enough. There'll be exciting data sets for sure. Maybe we can switch to TEGSEDI and WAYLIVRA, and it's a little bit of a devil's advocate question here. But I know investors, they were looking at the Akcea acquisition, and it made sense to bring in this commercial part of the business as you continue to develop wholly-owned assets, and you're expected to do this yourself. We have seen the out-licensing in Europe to Sobi for the commercial rights of those products. I think PTC is doing in Latin America, and we've seen a sales force reduction after the Akcea acquisition. So without being too commercially focused, I guess my overarching question is, is Ionis still committed to the TTR amyloidosis community? And I guess, how do you envisage the developments that are going on in the company to sort of influence that marketplace going forward?

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : That makes sense. Maybe on the TTR amyloidosis population. You obviously mentioned that increasing the -- or decreasing the frequency between doses is obviously beneficial from a compliance standpoint. But I guess how many patients are currently on therapy in the hereditary inherited 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 01, 2021 / 3:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at William Blair Growth Stock Conference (Virtual) population. And I guess, what are the unmet needs outside of just compliance and encouraging usability of this product that your next-generation LICA products could address?

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : Yes. Completely agreed. I have to ask, you're definitely not the only player with a knockdown agent in the space here. I think a competitor just filed a vutrisiran product with the regulators. I guess how do you see this competitive landscape evolving over time? And where the Ionis products would fit into that?

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : Great. We've only got 3 minutes, so I do want to hit some pipeline questions. You mentioned the wholly owned neuro pipeline as a growth pillar for the company, and you really are advanced and leading the field in that space. We talk about Lafora disease, Alexander disease, ALS linked to FUS mutations. How should we be thinking about these disease opportunities and the efficacy of your platform, maybe relative to something like SPINRAZA that we know has been incredibly successful? 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 01, 2021 / 3:00PM, IONS.OQ - Ionis Pharmaceuticals Inc at William Blair Growth Stock Conference (Virtual)

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : And then you mentioned 12 more therapies potentially commercialized by 2026. It's a bold statement and vision for the company. I mean if you had to pick 3 and maybe just based on just scientific interest on this one. What are the most exciting? You mentioned an asset for hereditary angioedema straight up. I'd imagine that might be one of them, maybe some neuro stuff? What are you looking forward to the most here?

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : Beautiful. Well, that's incredibly helpful. And a lot of exciting things going on in the company, as usual. So Eric, really appreciate your time and stepping in last minute, and I'm sure we'll chat again very soon. And hopefully, in person next time.

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : Damn right. Damn right.