Ionis at RBC Conference: Strategic Growth and Innovation

On Wednesday, 21 May 2025, Ionis Pharmaceuticals (NASDAQ:IONS) participated in the 2025 RBC Capital Markets Global Healthcare Conference, showcasing its strategic advancements and challenges. CEO Brett Monia emphasized the company’s recent drug approvals and commercial launches, while also addressing competitive pressures and financial forecasts.

Key Takeaways

• Ionis highlighted the successful launch of Tringolza, achieving over $6 million in net revenue in Q1.
• The company is optimistic about the upcoming approval of Donidalorsen for hereditary angioedema.
• Ionis aims for positive cash flow soon, backed by a robust pipeline and strategic collaborations.
• The ESSENCE study showed significant triglyceride reductions, bolstering Ionis’s competitive position.
• Ionis maintains strong confidence in Wainua for TTR polyneuropathy despite temporary revenue dips.

Financial Results

• Tringolza Q1 Revenue: Over $6 million, surpassing expectations.
• Operating Loss Guidance: Mid to high single-digit percentage for the year.
• Cash Position: $1.9 billion at year-end.
• Revenue Guidance: Increased by 20% from the original forecast.
• Net Loss Guidance: Expected to be under $300 million.

Operational Updates

• Tringolza Launch: First independent commercial launch, targeting familial chylomicronemia syndrome (FCS). Cardiologists write about half of the prescriptions.
• ESSENCE Phase 3 Study: Demonstrated over 60% triglyceride reductions at the commercial dose for severe hypertriglyceridemia.
• Wainua for TTR Polyneuropathy: Despite temporary revenue declines due to Medicare Part D redesign, patient demand remains strong.
• Donidalorsen for Hereditary Angioedema: PDUFA date set for August 21, with European approval anticipated early next year.

Future Outlook

• Wholly Owned Pipeline: Expected to generate multibillion-dollar revenue potential.
• Partnered Pipeline: Four Phase 3 readouts and commercial launches anticipated over the next year.
• Revenue Growth: Substantial and sustained growth anticipated.
• Cash Flow: Aiming for positive cash flow in the near term.
• TTR Cardiomyopathy Phase 3 Readout: Expected in the second half of next year.

Q&A Highlights

• Tringolza Competition (Arrowhead): Ionis focuses on Tringolza’s efficacy, safety, and convenience, leveraging its first-mover advantage.
• TTR Polyneuropathy (Wainua): AstraZeneca projects over $5 billion in peak revenue, with strong belief in Wainua’s market position.
• TTR Cardiomyopathy Competitive Landscape: Confident in positioning Wainua as monotherapy or in combination.
• Hereditary Angioedema (Donidalorsen): Confident in approval and launch, citing significant advantages over existing treatments.

For further details, readers are encouraged to review the full transcript below.

Full transcript - 2025 RBC Capital Markets Global Healthcare Conference:

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Right. Great. Thanks, everybody. Luca Aysi, senior biotech analyst here at RBC Capital Market, and today is our great privilege to have Ionis as part of our twenty twenty five global health care conference. Representing the company, have Brett Monia, chief executive officer.

Brett, thanks so much for joining us. How are you doing today?

Brett Monia, Chief Executive Officer, Ionis: I’m doing great, Luca. It’s a pleasure to be here. Thank you for for for the invitation.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Absolutely. Absolutely. Look. We have a long list of questions here, but maybe before we go to the individual programs, Brad, it would be great if you can give us some opening remarks, maybe just talk about, like, some of the progress that the organization has made over the last few months, and maybe most importantly, what’s ahead here for Ionis.

Brett Monia, Chief Executive Officer, Ionis: Yeah. Happy to, Luca. Thank you. We’re really, really pleased. We couldn’t be more pleased with the remarkable progress we’ve been making at Ionis over the over the last few months, really over the last year year or two.

We’ve enjoyed several very important drug approvals during that that period of time and and subsequent launches, including our first independent commercial launch, Trungolza, for FCS. The pipeline has just continued to deliver mid stage as well as late stage pipeline, several very important phase three readouts, positive readouts, including just this week, the ESSENCE phase three study was that we announced on Monday was was was very strong. In in addition, this you know, in addition to the these near term launches and and the pipeline progress, we also have done a great job with our partners. Our partners are on track for several important phase three readouts over the next few months, over the next year or so, with subsequent launches as well. In addition to our first independent launch, Trangolza, which really represents a really strategic achievement for the company, it represents our evolution to become a fully integrated commercial stage biotech company.

Trangolsa indicated for familial chylomicronemia syndrome, the first and only FDA approved medicine medicine for this severe devastating disease. Right behind Trangolsa is Donna DeLorsen of prophylactic treatment for hereditary angioedema. We’re expecting approval in the second half of this year, and that represents, as I mentioned, our second independent commercial launch. Our wholly owned pipeline and anticipated launches are are projected to be offer a multibillion dollar revenue potential from our wholly owned pipeline. And and then I already touched on our our partner pipeline with four anticipated phase three readouts and commercial launches over the next year or so, which which really is and combined with our wholly owned pipeline sets us up for substantial and sustained revenue growth and and our goal to achieve positive cash flow in the near term.

So, know, the pipeline is delivering, the launches are delivering, and and we’re really excited about the progress we’re making.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Sure. Sure. Sure. No. That’s actually super helpful.

Maybe entering Gold’s out, let’s talk about launch a little bit. Obviously, when we look at the q ’1, ’6 million dollar for the quarter, I a good mix of NutraBrand versus patients coming from the EAP. What can you tell us about April and May? How are things going? Do you see an inflection there and accelerations in scripts?

Like, any context on what you have seen since the quarter? Yeah.

Brett Monia, Chief Executive Officer, Ionis: As I mentioned, Trungolza is our first represents our first independent commercial launch for Ionis for familial chylomicronemia syndrome, FCS. We’re very encouraged by the q one results for Trungolza were in excess of $6,000,000 in the first quarter in net revenue, which really exceeded expectations, all expectations out there today or at the time. We’re really pleased with the mix of prescribers, cardiologists, about half of prescribers are cardiologists. We also have a good representation of endocrinologists. And and what’s really important is that we’re seeing scripts being written not only for genetically confirmed FCS, but a substantial number of scripts being written for clinically the clinically determined FCS.

Access has gone very strong, has been very strong, and things are looking very encouraging going forward too. Over the last couple of months, we’re encouraged by what we’re seeing. It’s, you know, it is early days in the launch. The success we’ve had so far is really a product of really hard work and execution. We we do you know, we did a lot of work prior to the approval of Trangolza in December.

You know, we we we did we we we did we essentially converted all of our patients in our US open label extension and expanded access program to commercial product now. There’s also there were no treatments available for FCS the US, so there were a lot of patients already identified. We were able to do a good job of getting those patients onto Tringolza. And and we we’ve also done a good job of of pre identifying potential patients that had SCS. So we’ve been doing a pretty good job of converting those newly identified patients to Trigos as well.

That’s the work where the work is gonna have to be going forward. Most of these patients, the vast majority of these are not identified to date, so we need to continue to identify these patients to continue the momentum we built in the first quarter. But things are going well. We’re very encouraged.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Got it. Got it. That’s very helpful. Maybe let’s talk about competition for a minute Obviously, Arrowhead, there’s their PDUFA date upcoming.

What are your thoughts on that molecule? The molecule maybe is those a little bit less frequently than your molecule. They’re making argument that maybe the acute pancreatitis benefit could be reflected in the indication sections of the label instead of the clinical sections of the label. Will any of that matters? How how are you thinking about the impact of a competitor getting into the mix as well?

Brett Monia, Chief Executive Officer, Ionis: Well, you know, Luca, we’re we’re laser focused on our program. We’ve our our our the profile of Trangolza for FCS is second to none with respect to efficacy, pristine safety, and the convenience of of once per month self administration using a simple painless low volume auto injector. It doesn’t get much more convenient than than that. You know, as I mentioned, the launch is off to a very good start, and and that’s because of the profile and all the work that we’ve done, and also taking advantage, real, really, really important advantage of being first to market by quite an extended period of time. You know, we were the first to validate this mechanism, a p c three targeting in FCS.

It it was really considered to be a bad idea back in the day when we were we were considering this possibility because of the lack of the lipoprotein lipase pathway, which APOC three works through in part. We proved that, and we’ve built a reputation out there as as an innovative leader in triglyceride management. The launch is off to a great start. Our market access has gone extremely well. And, you know, first mover advantage is is is really is really a key advantage.

And then, you know, you double down on the much larger indications of your hypertriglyceridemia, which we’re one and a half to two years ahead of any competition with a great looking drug. And as I mentioned earlier, we already have positive phase three data this week that we announced from the ESSENCE study to support that. So we’re pleased with the profile, second to none, laser focus on execution, and first mover advantage we think is is really going to serve us very well.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Got it. Got it. It’s actually very helpful. Maybe you if you wanna talk briefly about the ESSENCE data given that this is, you know, fresh off the press, if you will. So maybe if you wanna recap the data, that’d helpful.

And then maybe two related to it, how are you thinking about acute pancreatitis and, you know, the possibility of showing a benefit in acute pancreatitis for severe hypertriglyceridemia? What do you need to hit stat sig or not in in your secondary endpoint there? What are maybe the implications for payers and commercial adoption? And maybe related to it, any comments on the blinded event rate? I’m assuming you are seeing blinded event rate for acute pancreatitis.

So I know multifaceted questions, but any thoughts there? Much appreciated.

Brett Monia, Chief Executive Officer, Ionis: Yeah. And and and thanks for that because I I I realized when you mentioned AP that I didn’t answer your question about acute pancreatitis and FCS. We actually showed substantial significant reductions in acute pancreatitis in our FCS phase three balanced study, which is in our label. So we think that that, of course, is also serving us very well in the Tregoza launch for FCS. The the ESSENCE phase three study that we read out early earlier this week, with top line data is a safety supportive study in patients with cardiovascular disease and mildly elevated triglycerides.

It’s a supportive study because of the very large patient highly prevalent patient population for patients with severe hypertriglyceridemia, SHCG, millions of people in The United States alone. So you’re it requires by the FDA a a minimum safety database to for safety exposure for for patients to support an approval. The safety aspects of the study was was pristine, very successful, but what was what was also remarkable truly remarkable was the substantial reductions in triglycerides that we saw in the study. At the projected commercial dose for SHTG, we saw greater than 60% reductions in triglycerides, and that’s on top of standard of care. All almost all these patients in this study were on everything you can take, fibrates, fish oils, statins, to lower their triglyceride levels.

And on top of that, we were actually achieved greater than 60% reductions in triglyceride, and the vast majority of the patients were normalized to to normal triglyceride levels. So that was that’s very exciting. It’s a big step forward to our phase three readout in SHTG core and core two that we expect in the third quarter of this year. So very, very pleased. Couldn’t be more pleased with the results of the ESSENCE study.

Of course, those patients do not have acute pancreatitis events because their triglycerides aren’t high enough. That’s what we are trying to prevent in the SHTG population and in core and core two phase three studies. You know, we’ve done extensive market research. We recently had a panel of HCPs that have been managing people with SHTG for forever. All these patients are essentially on treatment today, so they they’ve been managing them managing them for decades, but they can’t get even close to their triglyceride goals in this study.

So they’re already convinced that what we need is a new mechanism, an APOC three driven mechanism to substantially lower triglycerides in these patients, and that’s what we need to show for rapid and significant uptake in the HCP community for people with SHCG, substantial triglyceride reductions on the order of what we’ve seen in FCS and in ESSENCE study. That alone will do it. With respect to acute pancreatitis, as I mentioned, we already have that in the label because this is a supplemental NDA. We have that in the FCS portion of the labels, and that’ll that’ll serve us very well. You know, f c AP events, the rate of AP is is lower.

It’s quite a bit lower in SHTG than it is in FCS, and that’s because it’s directly related to the magnitude of triglycerides in this study. With that said, it’s all about how many events you accumulate in the study. It’s not about the rate. Correct? Right?

So our study is more than 10 times the size of our FCS phase three study, so you would expect that we’ll be able to accumulate acute AP events in in in our patient population that we’re studying. And in fact, yes, we are seeing blinded in a blinded manner adjudicated AP events. Not surprising because our our our our median our mean triglyceride levels in that study we recently published our baseline clinical trial design paper is in the 800 plus range, and we have nearly fifty percent of patients that are approaching 900 triglyceride. So they’re at very high risk for for acute pancreatitis. You know, a a grand slam would be triglyceride lowering in on the order of what we’ve seen in essence and balance, FCS balance study, with with favorable trends in acute pancreatitis reduction.

So we’ll see. We’re looking forward to the data in the third quarter, and we’ll report on our top line our in our top line, the primary endpoint, safety, as well as anything we see in AP.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: But the blinded event trade overall is on track with your originally what you originally planned?

Brett Monia, Chief Executive Officer, Ionis: We made some projections we made some projections on how many accumulated AP events we would like to see, estimated to potentially see, and and we’re in pretty good shape in in in what we’re saying seeing in this study with respect to AP. I also want to make the point that we’re doing everything we can to accumulate as many events as possible. The primary endpoint on triglycerides is at six months, but with six month follow ups, it’s a twelve month study. However, the AP secondary endpoint is at twelve months, and our pooling, both the core phase three study as well as the core two phase three study to be able to accumulate as many events as possible. So we’re doing everything we can to to get the signal we want, but but, again, you know, we’re really focused on the magnitude and and they’re showing substantial reductions in triglycerides, which we think is a real win for this patient population.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Got it. Got it. Super helpful. Maybe let’s move on to TTR polyneuropathy. Again, you know, the your partner, obviously, with AstraZeneca.

I think this quarter was maybe, down a little bit quarter over quarter. Obviously, there were some headwinds from Medicare Part D redesign, which are important considerations here. But, you know, just give us an update on how the launch is going. And then maybe in the context of Alnylam doing 1,300,000,000 in revenues today for TTR polyneuropathy, what do you think this drug can do at peak in polyneuropathy alone? So we

Brett Monia, Chief Executive Officer, Ionis: knew the launch for Weinua for hereditary TTR polyneuropathy is going great. You know, the the revenue was a little bit down because of the IRA redesign, as you mentioned, which kicked in in January, but the patient demand is is very strong. And in fact, the patient numbers in our first quarter exceeded that of our fourth quarter. So it’s all about the redesign. Going forward, we expect growth throughout the year and continuing beyond that up to the expected cardiomyopathy through the cardiomyopathy phase three readout and launch.

So patient demand is is going great. We haven’t carved out polyneuropathy from cardiomyopathy, but I can tell you that our our partner, AstraZeneca, our co development co commercialization partner, has has has stated publicly that they see Waynua not only as the preferred treatment for TTR amyloidosis in the future, but the the commercial revenue that they expect for for whenua is in the $5,000,000,000 plus range. So we we expect whenua will do very well. You know, the the profile is very strong respect to efficacy, pristine safety, and the convenience of the patients to be able to self administer using a simple auto injector. So the way new launch is going very well, and we think that that will project very well for the cardiomyopathy cardio transform phase three readout, which we expect in the second half of next year.

It’s tracking well.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Got it. Got it. Very helpful. Let’s maybe talk about TTR cardiomyopathy for a minute. Maybe just one big picture question.

What’s your take on, you know, the competitive landscape and how that competitive landscape is evolving? Will, like, BridgeBio as well as Alnylam obviously both launch their drugs? Love to pick your brain on how you’re seeing that space evolving. And then maybe part two of the question is remind us why you decided to to go for Medicare part d drugs and not part b. Obviously, part b drugs can be pretty profitable for hospitals, right, when you think about the buy and build dynamic and the 106% that they can make essentially pocket as a as a delta.

So, again, two part question. One, how you’re seeing the competitive landscape evolving, and then two, remind us why you decided to go

Brett Monia, Chief Executive Officer, Ionis: for part d and not part b. Sure. So the unmet need for for better treatments for TTR cardiomyopathy is still is very, very high. You know, the we’re we’re pleased that the first silencer for t targeting TTR for TTR cardiomyopathy is now approved, and and it’s starting it’s in its launch mode. It really derisks our study greatly.

It’s the largest study by far ever conducted in this patient population. We have a great drug in Weinua, TTR lowering that’s as good if not better than anything we’ve seen out there with excellent safety. And again, this the ability for patients to be able to self administer using an oil injector bodes very well for our readout in the second half of next year. You know, there are no details on the silencer launch to date. We’re looking forward to seeing those, but, you know, Atruvi has done well.

And I think that reflects the fact that patients are unsatisfied. They need better treatment options. I think the estimates on stabilizers, tafamidis, are that fifty percent of patients progress in the first year and the rest of them progress over thirty over three years. So, you know, patients need a new mechanism. I expect all stabilizers that’s going to be true for all stabilizers.

Need a new mechanism, a silencing mechanism we believe in that is going to be the preferred choice for TTR amyloidosis, including cardiomyopathy. And we strongly believe that whenua in the silencer class will be well positioned to serve primary right up front front primary cardiomyopathy, prime the primary indication as a monotherapy. All those progressing patients that I just mentioned that go from stabilizers, they’ll go on to silencers, and then also combination use. And we’re gonna have the best data from our phase three study in combination use as well as in monotherapy. Part d, part b, hey.

We have a lot of experience in part b drugs. Right? You know, our our neurology drugs, SPINRAZA, Kalsadi, our Angelman’s program, they’ll all be in the part b class. So we’re not we believe in in part b drugs. We believe in part d drugs.

It’s really where what is best for patients, what is best for for for, you know, our drugs that we bring forward. You know, there there’s gonna be patients. There’s gonna be HCPs that want to buy and build and and be in that part b drug to make some extra profit maybe from those drugs. But, you know, the fact is is that this is also gonna be driven by it’s a very complex process to to do part to do buy and bill, inventorying drugs, and all of that buying billing staff to support patients that are coming in on a frequent relatively frequent basis to get a treatment that is perfectly cape that they’re perfectly capable of administering themselves at home conveniently. And then once you start getting to very large patient populations, it the the the the challenges are gonna go go even gonna become even greater.

And then when you go from the centers of excellence to the communities, it’s gonna be even greater. So we believe that patients will prefer the convenience of self administration. That’s gonna drive a substantial share of market for part d drugs for TTR amyloidosis, and not to mention the fact that now the out of pocket expenses for in the IRA redesign has greatly gone down for patients. That that has that’s a tailwind for part d drugs. So, you know, it depends on on your view on on on what is going to be preferred by HCPs and patients, but I think there’s going to be plenty of room for a lot of success for part d drugs in in the TTR space going forward.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Sure. And no question. Big market given you should look at the latest of family sales. Maybe just a quick, quick question on CardioTransform. Just walk us through how that trial is going.

Just maybe walk us through, you know, the blinded event rate, what you’re seeing there, maybe the families drop in, are you seeing families drop in kind of on par with your expectations, higher or lower? Just walk us through that part.

Brett Monia, Chief Executive Officer, Ionis: As I mentioned, we’re we believe that we have the the the right trial design for the richest to produce the richest dataset ever in TTR cardiomyopathy based on the sheer size of the study. More than 1,400 patients, more than double the size of any other study that’s ever been conducted to date, which is positioned to give us the richest dataset in subgroups. Of course, it’s been highly derisked based on silencer that’s already read out, as I mentioned. Richest dataset for subgroups such as combination usage, monotherapy. We have imaging studies, large imaging studies that we’re gonna be looking at amyloid burden, cardiac function with and without tafamidis.

So we’re in a very good position to to really produce the the most the most beneficial, we think, the most the richest dataset ever in this in in this space. The the the study is tracking well. The events are tracking as we anticipated they would track. Doing very well on the blinded events, and we’re on track to read out in the second half of next year.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Are you seeing tafa drop in ahead of your like, this is not becoming standard of care. Right?

Brett Monia, Chief Executive Officer, Ionis: At baseline at baseline, we were well balanced Yeah. Generally well balanced between tafamidis usage and monitor. We’re seeing a slight increase in tafamidis drop in based on approvals in Europe, but we’re not we’re we we don’t we actually think that that’s a tailwind because it it will just strengthen our combination data going forward. And and and most of these patients are are dropping into in with tafamidis at the very tail end of the study. So they’re they’re the benefit they’re gonna receive with tafamidis is probably minimal.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Got it. Got it. Very helpful. I know we are already running out of time, but maybe that’s a couple more questions here, if I may. One on hereditary range of edema.

You already mentioned the PDUFA is upcoming. I guess two part question. One, is there anything that keeps you up at night about that PDUFA? And then two, I mean, this is a question we get from investors all the time. You know, this is a pretty competitive space.

There’s a lot of companies that are either launching or have launched. Just maybe remind us what’s the differentiations of your molecule versus others.

Brett Monia, Chief Executive Officer, Ionis: Yeah. Nothing’s keeping me up at night on on the expected approval for Donavelorsen for prophylaxis of hereditary angioedema. We have a PDUFA date of August 21, and every we are exactly where we should be in the review process with the FDA. And we’re also exactly where we need to be at the European review, which we expect approval next year, early next year. So that’s all going well.

You know, there there are there are drugs out there, of course, for prophylactic prophylaxis of hereditary angioedema. The market leader is TekZero, and then we have Orlodayo, an oral drug. And and there are drugs that are several years behind on the lorisin that are in development. But, you know, what we’re focused on is the market leader right now, which is TekSiro. Seventy percent plus patients in The US are on prophy treatment.

Most of them are on TekSiro. Both prophylactic treatments that are approved today have a large significant amount of unmet need both on efficacy, tolerability, and convenience. Donna Deloresen offers very significant advantages in all three areas. We have we have one of the best HAE attack rate reductions ever seen, probably the best in long term treatment. The convenience of a simple at home auto injector once per month or once every two months, patient can self administer with excellent tolerability, just like Weinua, just like Trigolsen, same platform.

And and we believe that patients are gonna want to switch. It’s gonna be the preferred treatment for many patients for prophylaxis of HAE based on all of this. And our switch data, we actually ran a switch study switching patients from Tekxiro or Lidea or other treatments over to Donadaluirsen, and and we not only showed further improvements in efficacy or further reductions of sixty percent plus on reductions of HAE attacks in in that study, patient preferences were above eighty percent for doneadolorsen. And I could also tell you that patients have stayed on donaldolorsen throughout that study, of course, but also long term, and we’re keeping them on donaldolorsen. So we think Donnie is going to be a preferred treatment.

It’s a switch market. We’re looking forward to the PDUFA in August, and assuming approval, we will launch in in the second half of this year.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Maybe just a super quick follow-up there. How many more sales folks are you expected to hire as you launch on HAE versus your current infrastructure with FCS? And how should we think about the the SG and A increase based on the launch of Yeah.

Brett Monia, Chief Executive Officer, Ionis: The drug? So, essentially, everybody has been hired to prepare in in preparation for the launch. The the the numbers of sales customer facing field team is on the order of what is out there for drugs today for Profeit in the 50 to a hundred person range. And we’ve already factored that into our guidance for the year and which we’ve already up upgraded our last on our q one earnings call. So the impact on SG and A, you know, what we’ve said in our guidance is that we expect operating losses here in the in the mid to high single digits for the year.

So we’re in good shape there. When we upgraded our guidance at our earnings in in in March, we said that we’re gonna we’re in very good shape, $1,900,000,000 of cash at the end of the year, very strong revenue, upgraded 20% versus our original guidance increase in revenue and under $300,000,000 in that loss. So we’re in very good shape there. The team is ready to launch, we’re ready to go, and we’re looking forward to the Donnie launch.

Luca Aysi, Senior Biotech Analyst, RBC Capital Market: Great. Great. Great. I have 300 more question, but no more time. So, Brad, thanks so much for joining us.

Thanks everyone for joining this conversation, and, yeah, we’ll we’ll talk soon. Thanks again.

Brett Monia, Chief Executive Officer, Ionis: Thanks, Lucas.

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