Ionis Pharmaceuticals at Barclays Conference: Strategic Growth and Partnerships

On Wednesday, 12 March 2025, Ionis Pharmaceuticals (NASDAQ: IONS) presented at the Barclays 27th Annual Global Healthcare Conference. The discussion, led by CFO Beth Hogan, showcased the company’s transition into a fully integrated commercial stage entity. While highlighting the promising launches and strategic partnerships, the company also addressed challenges in its clinical trials and market competition.

Key Takeaways

• Ionis Pharmaceuticals is transitioning into a commercial stage company with recent and upcoming drug launches.
• The company secured a $280 million upfront payment from a partnership with Ono Pharmaceuticals.
• Ongoing Phase III trials for olezarsen aim to demonstrate significant triglyceride lowering.
• WAYNEUWA has shown strong growth in the polyneuropathy market, with future expansion plans.
• Donidalorsen targets a significant share of the $1.8 billion HAE market.

Financial Results

• Ono Partnership:

- $280 million upfront payment for sapoblersin partnership.

- Potential $660 million in milestones and mid-teens royalties.

• 2024 Financials:

- Ended the year with $2.3 billion in cash reserves.

• WAYNEUWA Performance:

- Nearly doubled revenues in the polyneuropathy market from Q3 to Q4.

- Captured over 50% of the $37 million revenue growth in the US polyneuropathy sector.

Operational Updates

• Tringolza Launch:

- Successful US launch for treating Familial Chylomicronemia Syndrome (FCS).

• Upcoming Launches:

- Anticipating launches of Donidalorsen, olezarsen, and Vilganersen within 1.5 years.

• Partnered Pipeline:

- Expecting launches of pelicarcin, aplontirsen, bepiroversen, and cefaxacin within three years.

• Clinical Trials:

- Phase III studies for olezarsen (CORE, CORE2, ESSENCE) expected to conclude in 2025.

- Donidalorsen under review in the US and Europe for HAE treatment.

Future Outlook

• Key Product Launches:

- Focused on launching Donidalorsen, olezarsen, and Vilganersen soon.

- Partnered launches in cardiovascular, liver, and renal diseases are on the horizon.

• Clinical Trial Readouts:

- Olecarsen Phase III data anticipated later this year.

- WAYNEUWA’s Cardio Transform data expected in 2026 for ATTR cardiomyopathy.

• Expansion Strategy:

- Building a pipeline focused on neurology and cardiology.

- Leveraging strategic partnerships for partnered assets.

Q&A Highlights

• Ono Deal Rationale:

- Partnership allows focus on neurology and cardiology, Ionis’ competitive strengths.

• Olezarsen Safety:

- Expected to maintain a clean safety profile, similar to other drugs.

• Donidalorsen Label:

- Anticipates inclusion of both Q4 and Q8 week dosing regimens.

• WAYNEUWA Growth:

- Expected continued growth in the polyneuropathy market.

For more detailed insights, please refer to the full transcript below.

Full transcript - Barclays 27th Annual Global Healthcare Conference:

Gina Wen, SMICCAD biotech analyst, Barclays: Good afternoon, everyone. My name is Gina Wen. I’m a SMICCAD biotech analyst at the Barclays. Welcome to Barclays twenty seventh Global Healthcare Conference. Always live in Miami.

I know this year become a little more crowded. It is my great pleasure to introduce our next presenting company, Ionis Pharmaceuticals. With me on the stage is Beth Hogan, EVP and Chief Financial Officer. Thank you, Beth. So maybe quick question or do you want to give a very quick overview before we dive into the questions?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Sure. Happy to. Thank you for having us, Gina. We’re glad to be here. I think this what I would have people sort of focus on for Ionis is this is a really exciting time for the company.

We have spent the last several years transitioning into a fully integrated commercial stage company. And we’re there today with the approval and launch of Tringolza for a rare disease population of with FCS, which is basically very severe high triglycerides. That’s our first independent launch in The U. S. It’s going very well.

In the next year and a half, we anticipate having three more independent launches, starting with next step, our Donny de Lorsen for HAE, severe high triglycerides as well coming with olefarsen next year, assuming positive Phase three data later this year. And then Vilganersen, which is a rare CNS disease and that data is expected later this year with a potential approval next year and launch as well. So lots of excitement at the company as we have built a very integrated commercial organization and we’re launching our medicines. And in addition though our partnered pipeline continues to be very rich and delivering as well. So we’re looking forward to four key launches from partnered programs in the next three years.

And that includes pelicarcin for LP driven cardiovascular disease, aplontirsen for ATTR cardiomyopathy, bepiroversen for HBV and cefaxacin for IgA nephropathy. So lots of excitement around the company as we bring our own drugs to the market and as we add partnered medicines to SPINRAZA, Kalsati and WAYNEUWA that’s on the market for polyneuropathy right now.

Gina Wen, SMICCAD biotech analyst, Barclays: That’s great. I think before even going to the other programs, I do wanted to ask you about the UNO deal that you just announced yesterday. So maybe give us a little bit more color regarding the deals and why this is done. And I know some investor views are very favorable in terms of upfront payment and the milestone. And so maybe walk us through maybe a little bit high level on the owner deal.

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Yes, happy to. Glad that we could be here to talk a little bit about that transaction. For those of you, just to give you a sense, we partnered our saplersin in, which is a TEMPUR6 inhibitor for polycythemia vera. We partnered that with Ono Pharmaceuticals and announced that transaction aftermarket closed yesterday. The upfront payment is, as Gina mentioned, was $280,000,000 There’s six sixty million dollars worth of development regulatory and commercial milestones, as well as royalties in the mid teens.

This is a patient population that’s in need of new therapies. The existing therapy is really not doing these patients real justice frankly. And so we’re excited that we were able to partner this. And for two reasons, one is that we’re really focused in neurology and cardiology. We believe that that’s where our competitive advantages.

We’ve seen that particularly in neurology with SPINRAZA and with Calsati, with WAYNEUWA for polyneuropathy. And we’re going to continue to build that wholly owned pipeline. And we’re also very deeply in the cardiology space and we’ll continue to build that wholly owned pipeline as well. So with sapoblersin being in the hemonc space, it really made more sense for us to partner that for real to really maximize the potential of that drug. There’s I think one hundred thousand patients in The United States in need of that therapy and that’s just U.

S. Only. So there’s a tremendous market opportunity and we believe that saproblurcine can be very competitive. We’re running an open label Phase two study right now. We ran a very competitive space in that it’s partnering transaction.

And that those competitors who were in the partnering transaction discussions with us did have the ability to see some of those data. So they have a sense of how sapoblersin is performing in that patient population. And I think that speaks to the very attractive economics that we were able to command for this drug. It’s also very important for Ionis to add that $280,000,000 to our balance sheet. We have a healthy balance sheet today.

We ended 2024 with $2,300,000,000 in cash. And this just adds to that healthy balance sheet and gives us more firepower to really focus on our wholly owned pipeline, particularly as we look at revenue growth for our existing products, WAYENUHA, TRINGOLZA. And as we look ready to begin bringing donidolorsen and olezarsen to market in the next very short while. So a lot going on at the company and this gives us additional fire power to be able to execute on all of those plans.

Gina Wen, SMICCAD biotech analyst, Barclays: So the milestone $660,000,000 is the mainly the back end loaded or do you have a multiple development regulatory sales?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: There are development and regulatory, so we can anticipate seeing some of those milestones in the nearer term. Ona will be fully responsible for operationalizing and financing the Phase three program. It’ll be on their expense books, if you will, on their P and L. So that helps a lot. And then we’ll learn those additional milestones as they advance through Phase III development and through regulatory process to the market.

Gina Wen, SMICCAD biotech analyst, Barclays: Okay. And the mid teen royalty, that’s just fixed?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: It’s a fixed. Yes, exactly.

Gina Wen, SMICCAD biotech analyst, Barclays: Good. Going back to your Trangosa launch preparation, I think the investor are more excited about the SHTG opportunity there. And you will have two studies, so data expected second half this year. So maybe give us a little bit thoughts on the study design of the expectation there and what endpoint would matter most for the commercial perspective?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Right. So to your point, olezarsen, which is Tringolza for FCS is in the Phase III program right now for severe high triglyceride. So those are patients who have triglyceride levels that are 500 mgs per deciliter and up. And many of these patients have triglyceride levels that are eight eighty mgs per deciliter and higher. And the higher you go, particularly from eight eighty and above, the greater the risk of acute pancreatitis.

So and that is a potentially fatal, very painful, very debilitating symptom of having very, very high triglycerides. So olecarsen is in Phase three development for that very broad patient population. We’re actually running two pivotal studies. We’re also running a supportive safety study. So three Phase three studies, all three of which will read out here this year.

The ESSENCE study is the supportive safety study. That’s about fourteen hundred patients and the primary endpoint is triglyceride lowering. It’s not in our commercial patient population. So those are patients in the ESSENCE study who have triglyceride levels in the 150 to five hundred mgs per deciliter range. And the reason for picking that range of TG levels is because it’s a patient population that’s very, very large and we were able to enroll the study fairly quickly, which was important for us.

It’s just the safety study. That data will be available mid this year and we’ll probably be putting out a top line press release. And we’re looking forward to that coming first. In the second half of this year, we’ll be reporting the core and core two, which are the pivotal and the confirmatory pivotal studies in the commercial patient population. So those are patients who have triglyceride levels that are 500 mgs per deciliter or higher.

And they have in some cases, some of these patients will have a history of acute pancreatitis as well. So we’re looking forward to presenting the data and reporting the data for CORE and CORE2. We’ll report that data out at the same time. The studies are concluding about the same time. So that works out very well.

And we’ll be able to report data independently for each of the studies and also pooled. And that’s going to be very important, particularly as we think about acute pancreatitis, which while it’s not a pivotal endpoint, it’s a very important secondary endpoint for these two studies. We believe that the ability to show at least some trends in acute pancreatitis attack reductions is going to be meaningful for physicians as they look to treat their patients with severe high triglycerides. As a reminder for folks, we did see a very substantial reduction of eighty eight percent in acute pancreatitis attacks, excuse me, in our Phase three balance study in the FCS patient population. And we believe that that gives us even greater confidence that we’ll be able to see at least trends in the core and core two studies for acute pancreatitis.

So that’ll be very important for us to see.

Gina Wen, SMICCAD biotech analyst, Barclays: Okay. And the full triglyceride reduction. So, what is the threshold you were thinking in order to hit this step?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: So in the SCS Phase three study, we had triglyceride lowering of about, call it, 59% placebo adjusted. And that’s really important. You want to ensure that you’re looking at placebo adjusted when you look at these statistics. So consider that 59%. Now the interesting thing with SCS is these patients have very, very high triglyceride levels.

I think baseline in our Phase three study was somewhere in the sort of two thousand three hundred mgs to two thousand five hundred mgs per deciliter range. So very, very high triglyceride levels. So being able to get them down sixty percent almost is very, very important and very meaningful for these patients. Interestingly enough, they only have one mechanism for clearing triglycerides. So that effectively reduces the ability to bring down your triglycerides, whereas the severe high triglyceride patients actually have two mechanisms for clearing TGs.

And so that gives us confidence that we should see at least the same level of tg lowering in our Phase three studies in severe high triglyceride patients as what we saw in the FCS study and potentially higher. And that’ll be very meaningful for these patients as well.

Gina Wen, SMICCAD biotech analyst, Barclays: Great. For the acute pancreatitis, as you say, hopefully, we’ll show maybe similar level. Like, are you look when the study was a power, do you think that you were hoping based on the powering, do you think that you could have a chance to hit us back?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: So we didn’t power the Phase three studies for acute pancreatitis. Frankly, we didn’t power the FCS Phase three study for acute pancreatitis either. And we’re able to see a very significant reduction in that patient population. So even though it’s not powered for that, we do anticipate given the success that we had with FCS that we’ll be able to see similar success in the severe high triglyceride patient population and in these Phase three studies. So we’re looking forward to those data.

And as I said, even trends are going to be very, very important, because what we know with severe high triglycerides is that the higher your triglycerides, the greater the risk of acute pancreatitis. And we also know that if you’ve had one attack of AP that you’re at a much greater risk of a subsequent attacks. And that’s these attacks could be fatal. They put patients in the hospital for days on end. And that’s and it’s there they always feel their disease.

They’ve got severe abdominal pain. They’ll be in the ER for pain, fairly frequently. And so true burden on their lives and on the healthcare system. So we think that even with trends, it will be very important for the commercial opportunity for this drug. Now commercially, we see olelarsen for severe high triglycerides as a potential blockbuster opportunity.

If we see something more than trends in acute pancreatitis, that opportunity could actually grow beyond that $1,000,000,000 range and could actually be a multi billion dollar opportunity. So, we’re very much looking forward to reading these studies out a little bit later this year.

Gina Wen, SMICCAD biotech analyst, Barclays: Okay, good. Quickly on the SM study that you said top line in the mid-twenty five. So, what kind of safety profile you think consider as a good safety profile? And what kind of a measurement could trigger some concern?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Well, our this is a LICA drug, which is our sort of advanced generation chemistries that we’ve been using for our liver targeted drugs. And very much like WAYNEUWA, we’ve seen olelarsen safety profile in FCS. We’ve seen the safety profile for donadolorsen. It’s under review right now. And everything we’ve seen is very clean.

We’ve got very, very strong favorable safety and tolerability profiles. And we would expect to see something very similar in the ESSENCE study as well. So nothing we’re not anticipating anything of concern.

Gina Wen, SMICCAD biotech analyst, Barclays: Okay. Good. Now switch to your donegalartan in HAE, we should also have a drug approval soon. And then so maybe the expectation given the drug profile Q8 weeks and Q4 weeks, do you expect both in the label? And then how do you think that the commercial opportunity would look like?

Yes. So, Donnie de Lorsen, just to

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: sort of level set for folks, Donnie de Lorsen is under review in The U. S. And in Europe for HAE. And we’ve demonstrated very, very favorable data in our Phase three studies. We ran a very interesting Phase three program at large.

So let me maybe take a minute and explain that to you and to the folks. The thing about HAE is if you had asked me several years ago, if this was a market where patients would switch off of their current therapies, I would have said no. I think the general belief was that it was a very sticky market and the market leader was dominating. Since then, however, a new product has come to market, an oral and that product has actually done extremely well and has grown sales year over year. And what that demonstrates to us is that there is a that’s very important for these patients to have strong efficacy, a tolerable drug, one that they can take and also to have convenience.

And we believe that Donadolurosen is actually going to be able to provide all three of those attributes in one drug. There’s not a drug on the market today that offers all three of those attributes in a single drug. And that gets to your question about Q4 week versus Q8 week. Our Phase three study evaluated Donadolorsen on a basically a monthly dosing or a bimonthly dosing schedule. In both of those dosing regimens, we saw substantial reductions in attacks of HAE.

And recently we reported data at the Quad AI Conference in San Diego, right by our home base. And in those data, what we showed was that we reduced attacks by ninety six percent in the four week as well as the eight week dosing cohort. So that says to us that both of those are going to be very attractive for patients. We’ve filed the data for both of those dosing regimens with the FDA and with the EMA and we anticipate getting both of those in our label. And I think that both will be well received commercially.

Our belief is that much like the standard of care injectable that folks will start with the Q4 week, just as they start with the Q2 week on the standard of care injectable. And then if they’re well controlled, they’ll move over to the Q8 week and hopefully be able to stay there. So we think that that dynamic is likely going to play out in the market and having both of those dosing regimens available for patients. I think it’s effectively shifting the entire paradigm of treatment for these patients.

Gina Wen, SMICCAD biotech analyst, Barclays: And regarding the pricing, is it fair to assume that will be largely comparable to the other drugs out there? Roughly 500,000 in

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: The U.

Gina Wen, SMICCAD biotech analyst, Barclays: S? Yes.

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: I think it’s fair to assume parity. We’re still doing all of our payer research as we approach the PDUFA date in the at the August. But parity is I think a reasonable expectation, particularly given the strong clinical profile that we’ve demonstrated in the Phase three study, including the data from a SWITCH study that we think is going to be very important as we bring this product to market.

Gina Wen, SMICCAD biotech analyst, Barclays: Okay. And total market opportunity, I think if we’re using Vaucrust, they did a guide at $1,800,000,000 in The U. S. Do you think that’s similar to your goal or you think it could do better?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Oh, I’d love to we’d love to be in those ranges. We’ve been guiding to about $500,000,000 opportunity. I think the profile that we’ve demonstrated is, as I said, I think it’s very favorable for folks. As we think about this market, it is a competitive market. It is absolutely a switch market in The United States.

About seventy percent, seventy five percent of The U. S. Patient population are on an existing therapy. We know that about twenty percent to twenty five percent of those patients switch between therapies on an annual basis. So our focus is going to be on really addressing those patients who are currently treated with Donnie Doloresen.

That’ll be our primary focus. And as I said, we ran a prospective switch study, which no one else had ever done in this space. And the data from that switch study told us a few things. One, it told us that while these patients believe they were well controlled on their existing therapy, when we moved them over to Donnie de Lurcen, they saw an incremental sixty four percent reduction in attacks on Donnie Doloresen. That’s a significant improvement in attack rate reduction for these patients.

We also spoke to these individuals and surveyed them when they finish the SWITCH study and asked them their preference. And more than eighty percent of the patients who switched over to dinadoloresin in the study indicated a preference for dinadoloresin and remain on the on dinadoloresin today. Interestingly, ninety percent of the patients who were on the oral actually preferred Donadulersen and about seventy percent, seventy five percent of the patients who were on the standard of care injectable preferred Donadulersen. So very strong preference data that we’re going to be able to use in the market as we come forward after hopefully approval in August.

Gina Wen, SMICCAD biotech analyst, Barclays: That’s great. With the remaining a few minutes, I do wanted to ask you have too many pipelines.

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: It’s a high quality problem.

Gina Wen, SMICCAD biotech analyst, Barclays: Right. Weinear and also the Angioma program, right. So weinear, we did see you had pretty good growth in the polymers, obviously, last quarter, quarter over quarter is a pretty high growth. And how do you see in the 2025, the polyneuropathy, the market, like how much growth do you think you expect to see the trajectory wise? And I think we know that Alnylam was $41,220,000,000 in the polyneuropathy market.

And where do you see where you go because you just recently received approval, right? So maybe like

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: where do you see the opportunity here? And also the ATTR cardiomyopathy,

Gina Wen, SMICCAD biotech analyst, Barclays: ATTR cardiomyopathy, the much bigger market opportunity there?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Yes. We knew it is as Jan mentioned, we knew it was approved a year or so ago now for ATTR polyneuropathy. And our co we have a co commercialization agreement with AstraZeneca. They lead the field efforts with WAYNEUWA. And we launched WAYNEUWA just a little bit more than a year ago now as we sit here in mid March.

WAYNEUWA has demonstrated very favorable metrics in the early days of its launch. We saw last year accelerating sequential growth. So in other words, quarter over quarter growth that was growing each quarter. And in the fourth quarter over the third quarter, we nearly doubled revenues in the polyneuropathy space. And I think very interestingly, if you look at the growth in polyneuropathy across the three drugs that are in that space, there was a $37,000,000 increase in revenues between Q3 and Q4.

In The U. S. Market, which is the only place we knew it was approved last year, we knew it captured more than 50% of that growth quarter over quarter. And so you can see that we’re really gaining ground in the polyneuropathy space on the existing therapies. So we believe that that will continue this year.

We’re excited by the dynamics that we’re seeing in the launch and the metrics that we’re seeing, all are pointing very favorably to WAYNEUWA. And we anticipate that with positive data in the Cardio Transform study in cardiomyopathy in the second half of twenty twenty six that we’ll be able to continue delivering WAYNEUWA to these patients. And we and AstraZeneca believe that we knew it could be a $5 plus billion revenue opportunity in ATTR broadly across both indications. And we also believe that it could be the silencer of choice for these patients.

Gina Wen, SMICCAD biotech analyst, Barclays: Beth, just quickly, I just hear you saying second half twenty twenty six?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Second half of ’20 ’20

Gina Wen, SMICCAD biotech analyst, Barclays: ’6. So is that because monitoring the blinded events that make it a little bit differently?

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: So it’s a one hundred and forty week study and we’ve decided to take that study all the way out to its full one hundred and forty weeks after seeing the Helios B data last year. We and AstraZeneca made the decision that taking the study to its natural conclusion gave it the greatest opportunity, gave the drug the greatest opportunity to demonstrate differentiating data. And that we felt was very important as we go into this very, very large and growing market.

Gina Wen, SMICCAD biotech analyst, Barclays: Okay, good. I know we are running out of time. I will ask other pipelines of the difference.

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Okay, good. Looking forward to it.

Gina Wen, SMICCAD biotech analyst, Barclays: Yes. Thank you so much.

Beth Hogan, EVP and Chief Financial Officer, Ionis Pharmaceuticals: Thank you. Appreciate it.

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