Ionis Pharmaceuticals, Inc. (IONS) Earnings Call Transcript & Summary

Well, good morning, everybody, and thank you for joining us for our 2nd RNA Summit. I'm Yaron Werber, on the biotech team here at TD Cowen, and it's a great pleasure to moderate the next session with Ionis Pharmaceuticals with Brett Monia, who is the Chief Executive Officer. Brett, good morning. Right and early on your side. Thanks for joining us.

Good morning, Yaron. it's a pleasure to be here.

So lots to talk about. I want to kick off with eplontersen, especially on the heels of the 85 week data was literally which just got presented showing a nice sustainability now we've seen from 35 weeks to 66 weeks, and now to 85 weeks on TTR reduction and clinical outcomes as well. The PDUFA is coming up in December for TTR polyneuropathy. Can you talk a little bit about the launch prep and how you'll split up the responsibility also with AstraZeneca?

Sure. Happy to, Yaron. These are very exciting times at Ionis. We are making great progress across all the key functional areas of the organization including our commercial products, our development pipeline in our technology. And certainly, eplontersen is a key component to the excitement we're having at Ionis today; excitement that we think is going to bring tremendous value to all stakeholders at Ionis for years to come. Absolutely, we announced some very exciting new data today, our week 85 or 19 month data for long-term treatment of eplontersen in patients with hereditary TTR polyneuropathy. This exciting data builds on our very positive week 66 data that we presented at the AAN earlier this year. The week 85 data today shows that patients continue to improve in their neurological disease endpoints for both mNIS+7 and Norfolk Quality of Life continue to improve with continued treatment. And with a very attractive safety and tolerability profile. Before jumping into eplontersen and getting into the details there, we certainly are prepared to launch assuming approval late this year. But before getting to that, Yaron, maybe I could just touch on and provide a brief summary of where we are today at a higher level at Ionis. We have 3 near-term commercial opportunities today, eplontersen being one of those, which is in development for 2 indications, the neuropathy indication that we just talked about briefly as well as the broad cardiomyopathy indication, and things are going very well in both of those Phase III studies. Eplontersen is being codeveloped and co-commercialized with our partner, AstraZeneca, and we are prepared for launching eplontersen in the neuropathy indication soon after approval, as I mentioned earlier. Our other near-term commercial opportunity is olezarsen, which is being -- also being developed for 2 indications, a rare indication, FCS, as well as for a much larger indication, severe hypertriglyceridemia, sHTG. Olezarsen has now completed enrollment in the FCS trial and the sHTG study is going well. And olezarsen is expected to be our first independent commercial launch for those 2 indications. Our other near-term commercial opportunity is donidalorsen, a prophylactic treatment for hereditary angioedema. We completed enrollment in the HAE Phase III study called OASIS earlier this year. We're looking forward to data readout from that study early next year with assuming a positive outcome of another independent launch potentially late next year. The rest of our Phase III pipeline is also going extremely well, going -- hitting on all aspects, making great progress across the board. And we're very pleased that we recently expanded the Phase III pipeline this year with 8 drugs now in Phase III development across 10 disease indications, all of which have the potential to be first-in-class to the market for various areas where there's a very large unmet need and potentially best-in-class through many of those drugs. SPINRAZA continues to be the market leader, the global market leader in spinal muscular atrophy. It continues to perform very well despite emerging competition. And we and our partner, Biogen, expect SPINRAZA to potentially return to growth over the next couple of years and QALSODY, now a real breakthrough for the ALS community. QALSODY is now our second drug from our platform now on the market for severe neurodegenerative disease right alongside SPINRAZA and QALSODY is now launched, and we can talk more about that. And then on the technology side, we're making great advancements across all aspects of our platform, including additional chemistry, drug delivery and in her areas as well. And this, of course -- these advancements will expand our drug discovery capabilities and maintain our leadership position in the RNA space. Now back to your question about eplontersen. Everything is in place for the launch of eplontersen, assuming approval with a PDUFA date for the polyneuropathy indication on December 22 of this year. Everything is on track. Our U.S. brand strategy is now in place to ensure for a successful and robust launch soon after approval. Our tactical plans are in place. Our infrastructure is in place with AstraZeneca. This includes medical affairs team that's already in the field, preparing for the upcoming launch of eplontersen and polyneuropathy. Market access work is well underway and essentially complete. And we're really putting the final touches on our launch plans as we prepare to go to the market. The -- our role in the launch -- in the commercialization of eplontersen for polyneuropathy is quite extensive. We have a leading role in patient services as well as in medical affairs as well as in the global brand strategy as we launch in the U.S. market. And AstraZeneca will take on the responsibility for some of those aspects, but in collaboration with us, but also, they will be responsible for the field force, the commercial field force in the U.S., and they have ex-U.S., they have -- they will be -- they will need commercialization for eplontersen as well. So we're ready to launch eplontersen. We think we have a great drug. The week 85 data builds on our confidence. It really shows that this drug is very competitive. It has a great profile. And also has a profile that's very differentiated from current treatments that are on the market today as well as emerging treatments. And we can talk more about how this is different -- how we see eplontersen differentiating, and as you wish you get, Yaron.

And by the way, for the audience, if you have any questions, feel free to e-mail me directly or go ahead and chime them in to the Wall Street Webcasting portal and I can read them anonymously on your behalf. Brett, maybe a follow-on question maybe a little technical question. Is eplontersen going to be commercialized by AstraZeneca? Or is it going to be within -- it's going to be within the Alexion sort of business unit? And do they need to hire an additional sales force? It's obviously neuro focused right now, but is it within the broader sales force or it's going to be its own sort of carve out?

The co-commercialization and co-development relationship with AstraZeneca is with AstraZeneca proper. We're really not working directly with the Alexion Group today. And what was the other part of your question? I'm sorry, Yaron.

And is it within -- are they hiring? Are you jointly hiring a new sales force?

They are -- AstraZeneca is taking advantage of existing manpower and expertise in both neurology as well as in cardiovascular disease, but they're also doing hiring also for the commercial field force. Yaron, you went on mute.

Thank you. I'm typing away. So going to mute intermittently. So we're expecting data obviously soon from BridgeBio, literally it could be any day from their Phase III study. And next year, we're going to get the data from Helios-B. As you're thinking about what you know so far about accumulation of events and you've now powered your study to about 1,500 patients or so. We're expecting the data in 2025 from CARDIO-TTRansform. The other companies obviously are running smaller studies, about 560 and let's say, 640 or so, respectively, BridgeBio and Ionis -- and I'm sorry Alnylam. As you're thinking about the bar for success and the need to have ample sample size, can you talk about both given what you know now?

Sure. Happy to. So TTR cardiomyopathy is a disease that has a prevalence estimated to be about 300,000 to 500,000 patients worldwide. So very significant unmet medical need for these patients suffering from TTR amyloid buildup in their heart, causing heart failure. There's 2 components to this indication. There's the hereditary component of the disease, which makes up a minor fraction of the disease. These are patients with mutations in the TTR gene that promote TTR buildup in the heart and cause heart failure as well as the wild-type indication, which is the much much broader indication. Our trial design, we think, is the -- well, it's absolutely the most comprehensive trial ever conducted or in patients with TTR cardiomyopathy, including contemporary studies that are ongoing today. And we believe that this represents a very significant differentiating -- differentiator for our program and very significant advantage as well for our eplontersen cardiomyopathy program. The demographics in this disease are dynamic and they're changing and evolving rapidly since the approval of tafamidis due to better, more effective, noninvasive diagnosis techniques such as technetium pyrophosphate imaging. Patients are diagnosed more easily today and due to better disease awareness, thanks to tafamidis, patients are also being diagnosed more earlier in their disease because of better disease awareness. This shifting landscape fits very nicely into the design of our study. As you mentioned, it's a very large study. It's the largest study ever conducted with 1,400 patients expected to complete enrollment very soon in our CARDIO-TTRansform study. And very importantly, we will have a very good balanced -- relatively even balance of patients that are not on stabilizer as well as patients on stabilizer. What that means is that our CARDIO-TTRansform study is positioned to provide the richest data set in this rapidly evolving patient population data which we'll be able to have -- we're going to have strong results in patients that are naive to stabilizer as well as eplontersen on top of stabilizers. In addition, the size of our study will allow us to -- is allowing us to add a large percentage of patients that have hereditary TTR cardiomyopathy. So we're going to have the, we think, richest data set in that subpopulation as well. Furthermore, we have several profile-enhancing studies in progress, imaging studies that will further add the evidence, we think, for eplontersen to provide data that patients, physicians and payers are going to be seeking and selecting what is the best drug for patients with TTR cardiomyopathy and all of that is playing out very well. This is really, Yaron, a landmark study in TTR cardiomyopathy. And we believe the size of the study as well as the dynamics of the patient population is really going to be a very key differentiator for this program and has gone to provide data, which all stakeholders are going to be looking for in this very large and competitive market. In addition, we're very excited by the fact that we have a very convenient approach for patients to administer this drug. Eplontersen for both indications, neuropathy as well as cardiomyopathy, is formulated as a simple auto-injector in which patients can administer the drug themselves at home using a subcutaneous low-volume injection. And based on all the market research we've done over the last several years, along with our partner, AstraZeneca, we're confident that this represents a very significant advantage from a differentiation standpoint as upon -- at the time eplontersen reaches the market. So we're very well positioned in this landscape -- for this rapidly evolving landscape and this very large market opportunity and the eplontersen program continues to perform very well.

So a couple of quick questions. In CARDIO-TTRansform, can you just remind us what percentage of patients do you think are going to be on stabilizers concomitantly? And is it fixed and stratified?

Sure. It is not fixed, but we have the ability to pull various levers to settle on to finish the study with the balance of naive patients and patients on stabilizers that we want to have, which is about equal. We expect to finish the study with about equal amounts of patients on stabilizer versus patients not on stabilizer. And yes, it is stratified for this outcome so that we can look at subpopulations of patients either on stabilizer with eplontersen or not on stabilizer.

And are you targeting a certain percent having hereditary cardiomyopathy?

Not a specific percent. We're trying to get as many patients into the study with hereditary TTR cardiomyopathies as we can. As you know, Yaron, these patients progress very rapidly in the unmet need there compared to wild type and the unmet need for these patients is even greater than wild type. And we want to have, again, a very rich data set that we can speak to for this population as well. So we don't have a specific percentage, but we're very pleased with the enrollment we're getting in our study with the hereditary population.

Okay. And is it stratified also across [ two arms ] ?

It is not stratified for hereditary versus wild type.

Okay. Okay. So I'm getting a few questions from the audience. What percentage of the market do you think ultimately you can capture or ASOs can capture, ASOs or RNAi's between PN and CM?