Ionis Pharmaceuticals Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 9, 2023

There are 16 speakers on the call.

Operator

Good morning, and welcome to Ionis' Second Quarter 2023 Financial Results Conference Call. As a reminder, this call is being recorded. At this time, I would like to turn the call over to Wade Wach, Senior Vice President of Investor Relations to lead off the call. Please begin.

Speaker 1

Thank you, MJ. Before we begin, I encourage everyone to go to the Investors section of the Ionis website to view the press release and related financial tables we will be discussing today, including the reconciliation of GAAP to non GAAP financials. We believe non GAAP financial results better The economics of our business and how we manage our business. We have also posted slides on our website that accompany today's call.

Speaker 2

With me

Speaker 1

on the call this morning are Brett Monia, our Chief Executive Officer Richard Geary, Chief Development Officer and Beth Haugen, our Chief Financial Officer. Eric Swayze, Executive Vice President of Research Eugene Schneider, Chief Clinical Development Officer and Onaza Katare, Chief Global Product I'd like to draw your attention to slide 3, which contains our forward looking statement. During this call, we will be making forward looking language statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors contained in our SEC filings for additional detail.

Speaker 1

With that, I'll turn the call over to Brett.

Speaker 3

Thanks, Wade. Good morning, everybody, and thanks for joining us today. We achieved a great deal in the first half of twenty twenty three as we continued to focused on our most important strategic priorities. We advanced our pipeline in many important ways. We made great progress Building our commercial capabilities.

Speaker 3

We are writing the next chapter for Ionis as we transform Ionis into a highly successful, Fully integrated biopharma focusing on delivering an abundance of new medicines to patients. Launch preparations For our 3 near term commercial opportunities, heblontirsen, olsarsen and Donadelorsen are right on track. Eblantersen is currently under regulatory review for ATTR polyneuropathy in the U. S. And we're on track to submit additional filings outside the U.

Speaker 3

S. Before the end of the year. We and AstraZeneca share the goal of bringing eplontericine to ATTR patients globally, who today have limited treatment options. We're also pleased with the longer term week 85 data for eponterstin from the Phase 3 Neuro Transform study that we reported last month. These longer term data showed continued improvements from baseline out to 19 months highlighting Eponcirsen's durable efficacy and contributing further to its overall attractive profile.

Speaker 3

And in a few minutes, Richard will dive deeper into the importance of these data. And just last week, we reported that our landmark cardiotransformed study of eponterosin in patients with ATTR cardiomyopathy completed full enrollment Our next major late stage milestone is the top line readout of the olefarsen Phase 3 BALANCE study in FCS in the second half of this year. We expect olezarsen in FCS to be the 1st independent commercial launch for Ionis and we're well prepared.

Speaker 2

In parallel,

Speaker 3

we're advancing our olezarsen Phase 3 pivotal studies in the much larger patient population, severe We also completed enrollment in the Phase 3 OASIS HAE study of Don Delorsen earlier this year. This important milestone keeps us on track for data in the first half of next year. We continue to be encouraged by the efficacy data Don Delorson has generated to date. We recently announced 2 year open label extension data that showed And sustained protection against HAE attacks in line with what we previously reported from our randomized Phase 2 study and our open label extension study at 1 year. I also want to highlight the continued success we've achieved developing medicines for patients with neurological SPINRAZA continues to be the global market leader for the treatment of all types of SMA.

Speaker 3

And just recently SPINRAZA's proven strong efficacy was reinforced Further with highly encouraging new data from the ongoing RESPONSE study in SMA patients who had a suboptimal response to gene therapy. And with the recent approval of CalSati in the U. S, we now have 2 breakthrough commercial medicines on the market to treat 2 severe Neurodegenerative diseases. The FDA's accelerated approval of CalSati brings hope and a breakthrough treatment to people with SOD1 ALS And their families. And CalSati's approval further validates our capabilities to treat intractable neurological diseases.

Speaker 3

Today, we have 12 medicines in clinical development for neurological diseases, including treatments for other forms of ALS, Dementias, neurodevelopmental diseases and much more. Our industry leading neurology research team is also making remarkable achievements to further Our leadership in neurology therapeutics. With a track record of driving innovation, we are focused and making great progress in advancing new cutting edge medicines into development to address severe neurological diseases for patients in need. Additionally, for the Q2 in a row, our robust late stage Phase 3 pipeline has expanded. Roche recently initiated Phase 3 development of Ionis FTLRx and IgA nephropathy increasing our late stage Phase 3 pipeline 8 drugs being developed for 10 separate indications.

Speaker 3

Our robust late stage pipeline sets us up for a steady cadence Phase 3 data readouts over the next few years, positioning Ionis to deliver many new important transformational products to the market for years to come. And just last week, we were pleased to announce our expanded collaboration with Novartis, demonstrating their confidence in Ionis' capabilities to create a next generation compound, targeting LP as a potential follow on to pelacarsen utilizing our latest cutting edge technologies. As a reminder, pelacarsen is in an ongoing Phase 3 cardiovascular outcome study called LP Horizon, which is fully enrolled with more than 8,000 patients. The Horizon study is progressing well with data and a potential filing plan for 2025. We also recently expanded our cardiovascular franchise when we advanced our first cardiac muscle LICA, 1st cardiac muscle like a drug into preclinical development.

Speaker 3

This muscle targeting drug is our first to enter development utilizing our in license by cycled technology. This achievement further highlights the potential for us to expand our drug discovery capabilities for cardiovascular and neuromuscular And importantly, we remain on track to accomplish our other key strategic goals across the business, including achieving our and with that, I'll turn the call over to Richard to discuss our recent pipeline progress and preview upcoming key events. Next, Beth will review our Q2 and first half financial results. And then I'll wrap things up before taking your questions. Richard?

Speaker 4

Thank you, Brett. Well, as Brett just mentioned, we've made important pipeline progress in the first half of this year, bringing us even closer to our goal to deliver an abundance of new medicines to patients and to the market. We believe that the positive data we have reported to date from the NEURO T TRANSFORM study demonstrate eplentercen's potential to provide substantial benefit For patients with ATTR polyneuropathy, the recent 85 week data further strengthened our confidence in eplontercen's competitive profile. Through 85 weeks, saplentirsen continued to demonstrate a sustained and substantial reduction in serum TTR concentration pace Compared to baseline, as you can see from both the MNIST plus 7 and NORFA quality of life graphs, The changes from baseline through 85 weeks of treatment are very encouraging. Importantly, a substantial number of patients treated with eplentirsen Continue to demonstrate improvement in neuropathy impairment and quality of life through the 85 weeks of treatment.

Speaker 4

These data further add to the totality of data supporting eplontersen's differentiated profile. We plan to report the full data set at a medical conference later this year. Eflantirsen is currently under review in the U. S. With additional filings We and AstraZeneca recently expanded our agreement to include Latin America, further underscoring our and AstraZeneca's commitment to bringing eplentersin to patients around the world.

Speaker 4

Positive efficacy and safety results we've seen from NeuroT Transform study also support our confidence in eplentirsen For ATTR cardiomyopathy. Notably, we recently completed enrollment in our Phase 3 CARDIO T TRANFORM study. With more than 1400 patients, this is the largest study ever conducted in this indication. We designed the study to demonstrate benefit on cardiovascular comes in a broad set of patients. Now that enrollment is complete in Cardio T Transform.

Speaker 4

We expect to report data as early in the first half of twenty twenty five. As with most outcome trials, our timelines are based on a variety of factors, including event rates and the evolving clinical landscape. Following up on turcine, Olasarsen is the next drug we expect to bring to the market and is the first we will commercialize ourselves. We are developing oasarsen Two indications, FCS and SHTG. And while FCS is a rare indication and SHTG represents a much broader population, Both indications are characterized by severely elevated triglycerides, which can lead to fatal pancreatitis and atherosclerosis, and both are poorly managed by the current standard of care.

Speaker 4

We remain on track to report data from the Phase 3 BALANCE Our development program to support the broader SHTG indication is also Progressing well. With over 3,000,000 patients in the U. S. With severe hypertriglyceridemia and first mover advantage, We believe olosarsen represents a blockbuster opportunity for Ionis. Following closely behind olosarsen is our next wholly owned And Donnie Doloresen, 3 patients with hereditary angioedema.

Speaker 4

We recently completed enrollment in the Phase 3 OASIS HAE JE study for Donnie Doloresen keeping us on track for data in the first half of next year. In June, we reported top line 2 year results on the Phase 2 open label extension study of divaloresen showing an overall sustained mean reduction We plan to present these data at a medical conference later this year. Based on the totality of the data generated to date, Dizlorsen continues to demonstrate sustained protection in preventing potentially fatal HAE attacks. As a result, we are confident in divaloresis' competitive profile, providing us with a meaningful commercial opportunity. Our industry leading neurology franchise continues to deliver groundbreaking medicines.

Speaker 4

In April, the FDA approved KAL SADI For patients with SOD1 ALS, making it the first approved treatment to target the genetic cause of ALS. In addition, we have 12 medicines in clinical development to treat neurological diseases, including 2 in Phase 3 studies And 8 in Phase 2, one of our highest priorities is to expand our wholly owned franchises in neurology and cardiology. We currently have several wholly owned medicines that are moving quickly to the clinic. Our world class neurology research team is working to turn great science into great medicines that we plan to develop and commercialize ourselves. As a result, we expect A steady cadence of new clinical study starts over the next several years, ensuring our neurology franchise continues to lead in innovation and positioning us to deliver a growing number of new medicines to patients and the market for years to come.

Speaker 4

Now, I would like to briefly touch on the recent positive interim results from the RESPOND study of SPINRAZA. RESPOND is an ongoing 2 year Phase 4 open label study evaluating SPINRAZA in SMA infants And toddlers with suboptimal response to gene therapy. Results from the interim analysis showed that most patients Approved in measures of motor function with SPINRAZA treatment. SPINRAZA also continued to demonstrate a favorable safety profile on these patients previously treated with gene therapy. These data add to the extensive body of evidence demonstrating SPINRAZA's benefit for SMA patient In addition to respond, Biogen is conducting the ASCEND and DEVOAT studies that together aim to address remaining unmet need and inform treatment Our late stage pipeline expanded for the 2nd consecutive quarter With the start of a pivotal program for Ionis FBLRx in patients with IgA nephropathy.

Speaker 4

We now have 8 drugs in late stage development advancing in a total of 10 separate indications. GSK recently presented new data for viperavirsen In chronic HBV patients, our other medicine that started a robust Phase 3 development program earlier this year. The data presented at EASL showed that the paraberson treatment resulted in a durable response in responders from the BCLR Phase 2b study. GSK plans to present new data later this year from the BeTogether study, which is evaluating the firmercin in combination with pegylated interferon. In totality, we have had an eventful first half with many important positive data events in In the second half of this year, we remain on track for a number of key additional events, including US eflontercin approval and regulatory filings outside the U.

Speaker 4

S. As well as Phase 3 data for olsarsen and FCS, our next potential medicine to launch after Epon Kearson. We will keep you updated on our progress on these events and more throughout the rest of the year. And with that, I'll turn the call over to Beth.

Speaker 5

Thank you, Richard. In the Q2, we continued to make progress on our goal to Further strengthen our financial foundation in support of our strategic priorities. Our financial results for the 2nd quarter reflect our ability to generate meaningful revenue to fund investments in key growth opportunities across our business. We earned revenues of $188,000,000 $319,000,000 for the Q2 and first half of this year, respectively. Our revenues increased 40% for the quarter and 16% year to date over the same period last year, driven by significant partner payments.

Speaker 5

As anticipated, our operating expenses and operating loss for the Q2 and first half of this year increased over the same periods last year as we advanced our commercial readiness activities and our pipeline, especially our late stage programs. We remain well capitalized with $2,400,000,000 in cash and investments at the end of June, enabling us to continue deploying our financial resources to bring transformational medicines to the market. In the Q2, we opportunistically refinanced our 2024 convertible notes and were able to accomplish all our objectives. We retained our cash to continue making key value driving investments in our pipeline. We extended the maturity of our 2024 notes to 2028, while maintaining a low coupon.

Speaker 5

And importantly, we We retired approximately 80% of the 2024 convertible notes. And as a result, our cash balance at the end of June included approximately $115,000,000 we have earmarked to address the remaining 2024 notes. SPINRAZA's global sales were $437,000,000 for the 2nd quarter and $880,000,000 year to date. As a result, we earned $61,000,000 $111,000,000 in royalty revenue for the SPINRAZA's global sales were essentially flat compared to the same periods last year, reflecting SPINRAZA's resilience against emerging competition in the U. S.

Speaker 5

And abroad. By working to expand existing markets, while also generating important efficacy data from SPINRAZA's robust life cycle management program. Biogen is making good progress on their goal of returning SPINRAZA to consistent growth. We earned R and D revenue of $110,000,000 in the Q2 and $173,000,000 year to date, both of which increased substantially compared to the same period last year. Our significant R and D revenue reflects the value Ionis' technology is creating as numerous partner programs advance.

Speaker 5

Notable payments earned in the Q2 included $40,000,000 from AstraZeneca for eplontersen, which included development cost sharing payments and the $20,000,000 license fee for Latin America rights, dollars 20,000,000 also from AstraZeneca for advancing ION 839 into a Phase 2b study for NASH and a $16,000,000 milestone payment from Biogen for Calsati U. S. Approval. As planned and aligned with our goal to invest for revenue growth, our non GAAP operating expenses increased in the second quarter and year to date compared to last year. As most of our ongoing Phase 3 studies are either fully enrolled For approaching full enrollment, as you would expect, our clinical study costs increased, which resulted in higher R and D expenses.

Speaker 5

Additionally, as we prepare to launch aplantirsen, olsarsen and Danitelorsen, our SG and A expenses also increased modestly Our results for the first half of this year keep us on track to meet our 2023 financial guidance, including our Looking ahead with many partnered programs advancing, we continue to have numerous opportunities to earn additional R and We anticipate revenue in the second half will be weighted towards the back end of the year. For example, we are Back to recognize additional amortization revenue from our recently expanded collaboration with Novartis. We project operating expenses to continue to gradually increase over the course of this year. Consistent with our guidance, which includes expenses related to our capital intensive Phase 3 studies. We estimate our full year R and D expenses will increase between 20% 25% year over year, excluding the metagenome upfront payment from last year.

Speaker 5

We also continue to project our full year SG and A expenses to increase approximately $35,000,000 year over year as we prepare to bring eflontersen, oluzarsen and Danita lorsen to the market. For example, as we move closer to launching eplontersen, assuming an approval in late December, our SG and A expenses will include our share of the cost Poised to launch several medicines. As a result, we are in a period of investment. We project our operating expenses to grow modestly. And importantly, substantial base of R and D revenues to contribute meaningfully to our overall revenue as our partners continue to advance numerous programs.

Speaker 5

And with 3 near term commercial opportunities that have a combined multibillion dollar peak sales potential And a steady cadence of medicines poised to follow closely behind, we are well positioned to drive substantial revenue growth and long term value for shareholders. And with that, I'll turn the call back over to Brett.

Speaker 3

Thanks, Beth. Looking forward to the rest of this year, we're laser focused Advancing our key priorities with additional important regulatory and late stage pipeline events planned for the second half. We're well on our way to achieving our goal of delivering an abundance of new medicines to patients. We now have 2 breakthrough medicines to treat devastating neurological diseases on the market. And with the December PDUFA date, we could also add emploncirsen to our commercial portfolio late this year.

Speaker 3

We're on track with our go to market activities for each of our near term commercial opportunities. Our first planned launch of eponterseen with AstraZeneca in patients with ATTR Polyneuropathy is quickly approaching with our independent launches for olezarsen and Donadilarsen following closely behind. With our rich late stage pipeline, we're well positioned to bring additional medicines to patients for many years to come. We also continue to make innovative technological advancements to enhance our leadership position in RNA Therapeutics, positioning us to add to our steady cadence of new Transformational medicines well into the future and our strong financial foundation enables us to invest in areas with the greatest potential to drive increasing value. Look forward to sharing our progress as we advance our priorities.

Speaker 3

And with that, We'll now open it up for questions. Operator?

Operator

Thank you. We will now begin the question and answer session. Today's first question comes from Myles Minter with William Blair. Please go ahead.

Speaker 6

Hey, thanks for taking the questions. Congrats on the quarter. First one is on ologzarsen. And I know that your Stands in the severe hypertrophyroglyceridemia trials is that you wouldn't need to conduct an outcome study or not looking to. There's been some language put out there from one of the peer companies developing in the space as well that they would be doing an outcome study.

Speaker 6

Has that language sort of changed your viewpoint on the need to conduct an outcome study in that population? Thanks.

Speaker 3

Thanks, Myles. Absolutely not. We're focused on patients with severely elevated triglycerides either genetically Caused FCS for severely elevated triglycerides where there's no known genetic cause of disease. These are patients that suffer From severe metabolic diseases, particularly acute pancreatitis that can evolve to chronic pancreatitis, All kinds of other morbidities. There is also a cardiovascular component to severely elevated triglycerides, but our focus is on Getting patients out of harm's way in the that are suffering from severely elevated triglycerides.

Speaker 3

We've done a lot of research. We're preparing the market and we're ready to be preparing for launching all of us are some press CS and SHDG and I'd like to just maybe I'll ask Sonaeza to expand on Miles' question.

Speaker 7

Sure. Hi, Miles. Yes, As we've spoken before, we see a great unmet need for severely elevated triglycerides in the marketplace over 500. This is a market where we have over 3,500,000 patients. The standard of care is just Not sufficient to actually meet the goals that these patients are required to meet or the medical guidelines, which is to Get them below 500 or as close to 500 as possible to get them out of harm's way for the risks Brett just highlighted particularly acute pancreatitis risk.

Speaker 7

So we have we're really looking forward to getting the market for that both for the rare disease genetically defined as FCS. We expect to see the balanced data by the end of the year and, then looking forward to launching into that and then ultimately into the severe hypertriglyceridemia space.

Speaker 6

Okay. Cool. And second question is just on the week 85 data for epontercin in polyneuropathy. I do also understand that there was vitamin A deficiency related ocular events that were discovered in that trial. Obviously, with TCR reduction that you get VITA deficiency and you can supplement that.

Speaker 6

But my question is, If you submitted that data to the FDA just for safety purposes only, I don't think you've submitted it with the efficacy data, but Will they see that safety data? Thanks.

Speaker 8

Eugene? Yes. Thanks for your question, Myles. So we Submitted all of the comprehensive safety information, including the information that was routine with the day 120 update as part of the NDA. So all of the safety data that was available at the time as well as the updates related To the day 120 update were submitted to the FDA and are under review.

Speaker 8

And everything is

Speaker 3

on track, right, Richard? Everything is on track. Absolutely.

Speaker 6

Beautiful. Thanks for the questions.

Operator

The next question comes from Debjit Chattopadhyay with Guggenheim Securities. Please go ahead.

Speaker 9

Hi, team. This is Robert on for Debjit. Thanks for taking our question. How does Ionis and AZN plan to compete against siRNA options in the ATTR PN market? And does AZN's presence potentially allow aponteracin to be first approval to any significant global markets.

Speaker 9

Thank you.

Speaker 3

Thanks, Robert. And Nezhi would you

Speaker 7

like to? Yes, sure, Robert. We're very excited with the data that we're seeing. The week 85 data was very encouraging. We saw duration of effect Sustained TTR suppression for TTR and then obviously halting disease progression And seeing improvement in a substantial number of patients in both MNIST plus 7 and Norfolk quality of life.

Speaker 7

So we've got a really great efficacy data Package, we have, from all of the research we've done, the more preferred administration profile, which is self administration at home, Allows patients to be empowered in taking control of their disease and taking the medication wherever they are with them and not relying on Going into the HCP's office, the efficacy combined with this self administration profile gives us a really strong way to enter the marketplace. As I've said before, this is a market where we still have 40,000 patients And less than 20% of those patients have been either identified, diagnosed and treated For polyneuropathy, including mixed phenotype. So our ability to get to where these patients are, Identify them and get to the offices outside of the centers of excellence where they're presenting is going to be really important. And those are some of the strategies we're Working on with AstraZeneca. And then as to your question whether we will be first in many global markets, yes, That is the goal we are planning to file in different markets outside of the U.

Speaker 7

S. In the second half of the year, particularly Europe. But as you know, we're also looking at expanding into markets such as Eastern Europe, Russia, China, Japan. And again, these are places where AstraZeneca's global scale will bring the ability to really penetrate and get these patients in care when there is needed.

Speaker 3

And as you know, Robert, we're very pleased that AstraZeneca also enthusiastically Licensed Latin America rights to for epontercin for both of course for all indications neuropathy as well as cardiomyopathy It demonstrates their enthusiasm for Flonterusen, our partnership and their enthusiasm for the data that has been generated to date.

Speaker 9

Thanks, Tim.

Operator

The next question comes from Kostas Biliouis with BMO. Please go ahead.

Speaker 2

Thanks for taking our question. One on pelacarsen follow on molecule that you recently announced. Can you discuss the potential technologies that you could leverage there to improve the efficacy and the dosing frequency of the 1st generation molecule and approximately how many years did you expect this follow on molecule to enter the clinic after to enter The market is shorty after from Acastas. Thank you.

Speaker 3

Sure, Acastas. Thanks. Very excited that Novartis Came to us with a proposal to work on with them a follow on Strategy follow on program for palacarson. Let me just say right from the outset that palacarson the palacarson pastry program is going well, Very well, on track, and is on track for data readout and potential filing in 2025. The fact that Novartis came to us really demonstrates their enthusiasm, their added enthusiasm, for this There's opportunity for LTH cardiovascular disease.

Speaker 3

They expect to be Assuming approval for pelicarcinib first to the market, and to have a substantial global reach. And the follow on program is to extend that The purpose is to reach more and more patients with a follow on program. Novartis recognizes our Expanded and vast capabilities in RNA targeted therapeutics and we're bringing our full arsenal to the table and they appreciate that and that's why They partnered with us on this. That includes all the great work that our research organization has been doing over the last few years in expanding our medicinal chemistry capabilities, including MSPA backbone that we've talked a lot about in the past, and other chemistries, As well as our rapidly emerging capabilities in RNAi technology and combinations of both, we can utilize chemistries We utilize an ASO technology as well as for RNAi platforms. It's tough to beat the efficacy that pelacarson has demonstrated in Phase 2 Costas, I mean with 98%, 99% of patients with CVD due to high we were able to get their Lp levels down below the threshold associated with CBD.

Speaker 3

So really we want to maintain that efficacy. We want to reproduce that efficacy in a potential follow-up molecule, but what we're really focused on is less frequent dosing. We're very confident in our ability to deliver a molecule with semi annual dosing, maybe annual dosing, utilizing a mixture of our And that is the focus with Novartis. And we're going to be working hand in hand with them to bring the best molecules forward to follow on It does follow on to Tyler Carson.

Operator

The next question comes from Mike Ohl. Please go ahead.

Speaker 3

Sorry, Carlos. Did you join that one?

Speaker 2

Sorry, no, I was going to ask approximately how many years behind is the Follow-up related to compared to pelacascen?

Speaker 3

Yes. We haven't stated, discussed that publicly, Kastas, what the timelines are. And obviously, the molecule we're still in research phase. So it would be a little risky to actually speculate about that right now.

Speaker 2

Very helpful. Thank you.

Operator

The next question comes from Mike Ulz with Morgan Stanley. Please go ahead.

Speaker 10

Hey, guys. Thanks for taking the question. Just on eplentirsen and cardiomyopathy, Maybe you can comment on the recent BRIDGE data and sort of how that impacts your thinking in terms of the cardio Transform study? And then maybe secondly to that, is there potential for you to maybe stop the Study earlier or is the thinking still to go through sort of the full results there? Thanks.

Speaker 3

Sure, Mike. So, BRIDGE Biodata, obviously, good for patients to have another Potential option for TTR cardiomyopathy, to state the obvious, we need a lot more data. We need to see more data. We're looking forward to seeing more detailed data in I think they're planning to present later this year. The demographics of the study supports our trial design.

Speaker 3

It further reinforces our trial design. It gives us even greater confidence in Our expanded trial design in which we're going to have we have now as we have completed enrollment, a very good balance between tafamidis Patients who have oncursor on top of tafamidis as well as naive patients, so it supports that. SIVA mortality, Overall mortality is very important in this population and maybe I'll ask Onasa to just really expand as On the importance of this from a physician standpoint, from a payer perspective?

Speaker 7

So as you know in, at Blanterson, Michael, that we love the breadth of our trial. We believe we're going to it's a landmark It's going to generate the significant amount of data to really go in and arm the physicians with the Data that they need to actually treat these patients. This means anything from knee class 1, 2 and 3, so mild to severe, Hereditary and wild type naive to silencer therapy naive to cardiomyopathy therapies and TTR as well as on top of standard of care tafamidis as well. We really love our endpoints. We have done a fair amount of work in recent times To really understand the difference in terms of how physicians view all cause mortality versus cardiovascular death And that is actually a more meaningful cardiovascular endpoint along with the richness of cardiovascular hospital And then some of our secondary endpoints, obviously, in 6 minute walk and other measures that are going to be at play.

Speaker 7

But The endpoint is just actually really meaningful. So all in all, we are really excited Our data set, our trial design and looking forward to seeing the output of that in the coming times.

Speaker 3

And Michael, we there's no plans to change our There's no changes to our plans for when the study will complete based on any new emerging data that has come out recently. We love our trial design. There are several factors that will impact when we read the study out. The first of course was to complete enrollment. We've now achieved that and we've achieved it very successfully.

Speaker 3

We have the demographics in the study that we intended to have To achieve that actually have the greatest data set when the study reads out, we'll also be looking at changing Competitive landscape new data as it emerges that could potentially affect the time we read the study out. We don't think the BRIDGE BIO data is going to impact that, But there may be other data that comes out. And thirdly, our blinded event rates will be very important for us to continue to monitor And we decide when the study should be complete, but there's no change in the currently there's no change in the timing of when that study is Our Cardio Transform study is due to readout.

Speaker 7

Let me just address one other question, which was on the payer reimbursement that I missed. Just to make sure that we've done a fair amount of testing with payers on the trial design. And again, if We show the cardiovascular risk reduction on top of Tafamidis. There is clinical meaningfulness in that for physicians and they are not going to be Kind of standing in the way in terms of reimbursing a combo product here. Again, the data will bear out and they're very favorable in making sure these patients We're highly at risk.

Speaker 7

It's a terminal disease or getting the best medication and care possible. So We're really pleased to see them thinking about the disease and the patients this way and thinking about the landscape of reimbursement as either mono or combo in this space.

Speaker 10

Got it. Thank you.

Operator

The next question comes from Yanan Zhu with Wells Fargo. Please Go

Speaker 2

ahead. Hi.

Speaker 11

Thanks for taking our questions. So I was wondering if you could share your thoughts on Some recent development in Angelman syndrome field where Roche decided not to move their ASO program into the next stage of And wondering if you could share any update from your Angelman syndrome clinical study That is ongoing. And any thoughts around The program or the product candidates' efficacy and safety profile. And also if you could also talk about your ataxin2 program and its ongoing study, that will be great. I The data are expected around the same time as Angelman syndrome program.

Speaker 11

Thanks.

Speaker 8

Sure. Happy to, Yan, and

Speaker 3

thanks for the question. So the Angelman's program, the IONIS Biogen Angelman's program is going very well. We're operationalizing the Phase onetwo study and we're continuing to enroll patients in the study. We are and with Biogen are planning to have data around mid year, next year from Angelman's program. And as I said, it's going very well so far.

Speaker 3

We haven't disclosed our we really don't have any insights Into the reasoning behind why Roche ended their study, they obviously have said that it wasn't a safety issue. They They didn't meet their minimum target product profile or minimum criteria, I assume on efficacy. We really don't We're not disclosing anything we may think on this. We're really focused on our program. So expect a readout from that study next year.

Speaker 3

We may be able to provide an update on the status of the program late this year. There's a We have a standing invitation to an Angelman's meeting called FAST in which we always have a podium slot and I'm sure we'll be present this year too. But We're not necessarily expecting data, new data at the meeting, but we haven't decided what we're going to present at that meeting yet. As far as ataxin-two, this of course is another one of our ALS drugs. This drug is particularly exciting because it's targeting a sporadic ALS, so no known genetic cause of ALS.

Speaker 3

That is enrolling. This is a study in which we're Examining 4 dose cohorts, with the highest dose cohort having expanded to add more patients To have the most robust data set to inform on a potential Phase 3 study, if study is successful. That, as you mentioned, is also due to readout around the same time next year, around midyear, next year. And All indications are that it's going well.

Speaker 11

Great. Thanks for all the answers.

Operator

The next question comes from David Lebowitz with Citi. Please go ahead.

Speaker 12

My question, given the HAE data is coming up earlier next year, could you assuming the Phase 2 data is replicated, could you tell us What your efforts will look like for launching the therapy and then trying to convince physicians to move to a new modality?

Speaker 8

David, it's Aneta.

Speaker 7

Hi, David. Yes, no, we're very excited about our preparations for dalodilorcel launch And waiting for the Phase 3 data next year. We are thinking about the market in a variety of As you know, this is going to be pretty much a switch market. So we do actually have a switch study that's going alongside our Phase 3s, which will be very informative and give Confidence for physicians to switch. Patients, the confidence piece is going to come from the ability to make sure there are no breakthrough TAC

Speaker 5

is in the process of

Speaker 7

the switch and given our rapid onset, we believe we will be able to demonstrate that. On the patient side, I think you can see the switching behavior already in the marketplace with Orla Deo, kind of, inciting more switches from Cyra, which is the standard of care. So we see that patients are willing to try new treatments and they want, they want 0 attack rates, And they want more convenience and we offer both with our profile as well. So the team is very active in understanding and kind of what will drive some of the switching behavior and their go to market strategies alongside of that.

Speaker 12

Thank you for that. And one additional question. Moving towards potential eflonterosin launch, do you have any thoughts on how Market growth has shifted since the subcu was launched by Alnylam and how that might Apply to eponterosin and how you're thinking about the launch going forward?

Speaker 7

Yes. Taking a look at how Utra's uptake is going on in the marketplace. I mean, they've got a good start. And it's just important to note that They're working through a lot of on patro switches right now, right? So we're really trying to understand how much market growth There is.

Speaker 7

As I said, this continues to be an under penetrated marketplace, lots of patients that are still not identified, diagnosed or treated. And I think Alnylam is doing their job of getting most of their patients on to their next generation silencer. And we have a lot of work to get new patients to just silencer therapy overall in this marketplace. So we expect it to Grow readily. This is when you have a couple of players in the marketplace.

Speaker 7

It's always a good thing for patients. They're looking forward to getting in, in January and Starting the work. And as I said earlier, we have a very exciting product profile, efficacy as well as the self administration profile, which we believe will

Operator

The next question comes from Allison Bradshaw with Piper Sandler. Please go ahead.

Speaker 13

Hi, good morning and thank you for taking the question. Just one for me on the Phase 2 GOLDEN trial in GA. Just curious, is there any update on your view of the geographic atrophy space and Potential opportunity for a therapy targeting complement Factor B, just given some of the recent safety and regulatory updates in the GA space in recent weeks. Could you just frame what you're looking for in the Phase 2 readout next year, to warrant further investment in that space? Thanks.

Speaker 3

Thanks, Allison. Yes, we're and our partner Roche are very enthusiastic about our GA study, our Factor B LRx geographic atrophy study Golden. We're pleased that There's a benchmark to get drugs approved for GA. This sets this helps set a path forward for all drugs that are being developed for GA including ours. We like our drug.

Speaker 3

We like our profile. So far, the Golden study is Quite a large study, around 300 patients, 2 dose cohorts, dosing groups, in which Patients are going to be treated for about 15 months. So it's a good study and what we're looking for is the primary changes in geographic atrophy area So it's an efficacy study, a proof of concept study and that study is due to readout next year. We like this, so we like the target. Factor B in the alternative pathway, we think is the right target for GA.

Speaker 3

We think systemic approaches to the complement pathway, particularly Factor D is the right approach for treating GA. And we think that the overall safety profile and tolerability profile that we're going to have with Factor B LRx is going to be a very significant advantage Virta versus, IVT drugs, which are administered directly to the eye and have side effects As a consequence to that, we expect Factor B LRx to have an excellent safety profile much like the rest of our LICA platform that has So that's that it's in Phase 2 and we're seeking to achieve Proof of concept for next year, if the data is strong, or if the data supports, I should say, Roche is preparing to go to Phase 3, And they're equally enthusiastic for the program as we are.

Operator

The next question comes from Paul Matteis with Stifel. Please go ahead.

Speaker 10

Thanks so much for taking my questions and congrats on all the progress. I wanted to ask about olexarsen in light of How much the cardiometabolic space has really changed since you initiated the pivotal program? Just specifically looking back at the Phase To baseline characteristics, I think most patients in the study had Type 2 diabetes. Most patients had This recent Wegovy data and more broadly the take off of these weight loss drugs on the market for Olazarsen and I guess What percent of patients with trigs above 500 would you say demographically wouldn't actually qualify for one of those drugs on label? Thanks so much.

Speaker 7

Nathan, you want to take it? Yes. Hi, Paul. Yes, it's been on it's a lot of good data for the GLP recently as well. So a couple of important things to note.

Speaker 7

First of all, they're not going to be indicated, right, for And if you looked at some of their TG, just their TG lowering data, it's very much in line with what current standard of So they're not getting to the really high levels of TG lowering that APOC3 target can actually deliver here. So that's kind of the first thing. If physicians do use it off label, it's a very important reminder and I think most of the endocrinologists know this that the GLP ones are Have a warning in their label for not being used in patients with risk or a history of acute pancreatitis. And as you know, in the 500 plus severely elevated triglycerides where olexarsen is being studied, we have many, many patients who are at risk for AP. So we do think both the magnitude of triglyceride reduction along With the risk for these patients who were over 500 for AEP, we do not expect that to be a direct or indirect competitor.

Speaker 10

Okay. Thanks for the thoughtful reply.

Operator

The next question It comes from Yaron Werber with Cowen. Please go ahead.

Speaker 9

Great. Thanks for taking my question. Just on SPINRAZA, The RESPONSE study, the interim results are definitely encouraging. Can you give us a sense, are these potentially label enabling? Like How do you think about it just given your broad label?

Speaker 9

Do you have a need sort of label enabling or is this just for standard of

Speaker 8

the care sort of

Speaker 9

change? And then secondly, just in terms of some of the ATAXIN II program and the Acton 3 programs, I know you touched a little bit on ALS. You also have a FOS program for ALS. Just maybe give us a little bit of a sense what's the next Data timing and what do you expect from the data? I know the FAST ALS is a pivotal in 2025, but maybe the other 2.

Speaker 9

Thank you.

Speaker 4

Thanks, Yaron. So,

Speaker 3

it's our understanding that Ascend or Respond, Responding to the data you're talking about, very encouraging data. Patients that haven't done That well on gene therapy moved on to SPINRAZA and really showing really good strong signs of doing very well, improving Muscle strength, neuromuscular function. Not surprisingly, there's been a lot of anecdotal data out there Over the years that this is the case, but it's very helpful to that Biogen actually do a study, just demonstrate that the study is ongoing. It's our understanding that these studies in patients that perform sub optimally on keto gene therapy or on And RISD, that lenodemphastimraza would be more for publication purposes and those sorts of things and which are Certainly in line with promotion. It's the DEVOT study that has the potential to actually expand label.

Speaker 3

The DEVOTE study is a randomized controlled Phase 3 study looking at higher doses of And we demonstrated even greater efficacy in SMA patients of all kinds. So that's my understanding.

Operator

The next question comes from Luca Ezey with RBC Capital. Please go.

Speaker 3

Can I just jump in? Eric just reminded me, I didn't answer the ATAXAN-two question, Yaron. So the ATAXAN-two Is enrolling 4 dose cohorts. The top dose is an expanded cohort to have more patients in the dose that has the potential To beat a dose that goes to Phase 3, that data is due to readout midyear next year ATAXA2 for non genetic ALS. Sorry.

Operator

The next question comes from Luca Easi with RBC Capital Markets. Please go ahead.

Speaker 14

Great. Thanks so much for taking my question. Congrats on the progress. Maybe I'll help Q and A, if I may, following up with a prior Brett, you may have already alluded to it, but I want to make sure. Was the pharmacokinase license to next generation molecule informed in any sort by the blinded event trade they're seeing in the cardiovascular come troughs, the Carson or is this just truly life cycle management?

Speaker 14

Question to maybe Eugene, if I may, on TTR cardiomyopathy, wondering if you can comment on what statistical methodology are you using for the Phase 3 for Gil method, which is similar to Alnylam and maybe why did you choose one versus the other? And then lastly, maybe on AGT, What was your reaction to Alnylam's Roche deal and how you're thinking about BT for your molecule? Thank you.

Speaker 3

Sure, Luca. For turning it over to Eugene, I'll take 2 of those and then you can talk about the statistical plan for Cardio Transform, so LP's entirely lifecycle management, the pelacarson Phase 3 study is going very well, On track for data in 2025 with a potential filing in 2025 has nothing to do with any particular data from the study except to Say that the study is going very well. So that lends even greater confidence by Novartis To pursue lifecycle management, we're focused Luca on our own programs, really don't have a reaction to any There's an AGT space or anywhere else in partnering strategies. We our plans haven't changed. We are planning to share new AGT data in the second half of this year at a medical meeting.

Speaker 3

And we've said all along that we think a drug like this for indications like Hypertension and heart failure are best suited with a partner to reach as many patients globally Around the world. And we haven't provided any details on the timing when we're going to Part of the program you're with whom, of course, but stay tuned for that down the road. Eugene, could you talk a little bit about the Lucas question about Our stats plan for Cardio Transform?

Speaker 8

Sure. So if I understood your question, it was related to the analysis of the primary endpoint. Is Is that right? Okay.

Speaker 14

That's correct.

Speaker 12

Yes, that's correct.

Speaker 8

Yes. So as we said, the methodology that we're We're planning to utilize for that analysis is a pretty tried and true, using Anderson Gill method to look at both CV mortality and CV events recurrent events that are listed So again, there's nothing fancy about this method. It's been tried and done in multiple outcome studies.

Operator

The next question is from Yale Jen with Laidlaw and Company. Please go ahead.

Speaker 15

Good afternoon and thanks for taking the questions. The first question is for Blantersen that If you get approved later toward the end of this year in the pulmonary neuropathy, Do you anticipate a drug also be used for treating the mixed type patients? Then I have another follow-up.

Speaker 3

Absolutely, we do provided they have detectable polyneuropathy. Yes, this drug would be suitable for Pure TN patients as well as mixed phenotype patients, hereditary patients.

Speaker 15

Okay. And my another question is for Alain Zazen that in terms of The SHHTG enrollment, can you provide any colors in terms of the status? And do you anticipate Completed enrollment later this year.

Speaker 4

I missed the specific

Speaker 3

How are you doing on SHTG enrollment?

Speaker 4

Enrollment is going very, very well. And Either very late this year or very early next year is kind of the guidance that we've been giving.

Speaker 15

Okay, great. Thanks. Appreciate it.

Speaker 3

I see. I'm having time for one more question.

Operator

The last question today comes from Joseph Stringer with Needham and Company. Please go ahead.

Speaker 7

Hi, thanks for taking our question. Just a quick one on olsarsen Phase 3 SCS re up later this year. Can you just frame expectations on what type of outcome you need to see to be successful commercially? What type of key metrics Should we be looking at beyond the primary endpoint from that would be important from a physician or payer perspective? Thanks.

Speaker 2

You want to take that, Eugene?

Speaker 3

I mean, obviously, the primary endpoint is triglyceride lowering percent triglyceride lowering compared Placebo and that's important and we expect what will really drive this market substantial TG lowering in this patient population. But Eugene, and then Onaje, maybe you talk about the commercial also, what additional endpoints we're looking to see? Sure.

Speaker 8

Happy to. We're obviously going to also look at responder a variety of responder analyses. So looking at proportions of patients that get below particular Clinically meaningful thresholds like 8.80 for instance is the classic 100 500. So again, achieving Those reductions that are thought to be meaningful in terms of their risk For having acute pancreatitis events is something that we're and future prescribers will be very keen to see. Also looking at quality of life measures that again will indicate whether these patients are actually feeling better, they're able to function better and those Again, are included as well.

Speaker 7

Yes. No, that's great. I think we've done obviously Good market understanding on this as well. Just a reminder, this is a rare disease Population for FCS, they really have no tools at their disposal. This is where The first line treatment is restrictive diet and it's just not I mean, they just Can't continue on that level of restrictive diet that they're on for a while.

Speaker 7

So there's just a huge unmet need. I really do think that this is going to be Let's get the product that's efficacious, but also really safe and, easy to use. And I think getting some of the

Speaker 3

Thanks, Joey. Great.

Speaker 2

Thank you for taking

Speaker 3

my questions. Thank you. Thanks everybody for joining us today for today's call. We're well on our way. We're planning to continue on a strong momentum in the second half of this year by delivering across all of our All aspects key aspects of our business commercial pipeline, technology and so on.

Speaker 3

Also, I want to highlight that we're looking forward to providing a comprehensive update All the great progress we're making at Ionis at our Investor Day on October 4. We really hope that many of you can join us in person for that meeting. Hope to see you there. Until then, thanks and have a great day everybody.

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Key Takeaways

  • Ionis is on track to launch eplontersen for ATTR polyneuropathy after a December PDUFA, with positive 85-week data showing durable TTR reduction and full enrollment in the Phase 3 CardioTRANSFORM study for ATTR cardiomyopathy.
  • The Phase 3 BALANCE trial of olezarsen in familial chylomicronemia syndrome (FCS) will read out in H2 2023, positioning it as Ionis’s first independent commercial launch, alongside ongoing pivotal studies in severe hypertriglyceridemia.
  • Enrollment finished in the Phase 3 OASIS HAE study of donadelorsen for hereditary angioedema, with data expected H1 2024 and 2-year extension data confirming sustained attack protection.
  • Ionis now has two marketed neurological drugs—SPINRAZA leading in SMA and KALSADI approved for SOD1 ALS—and is advancing 12 neurology candidates in clinical development.
  • Q2 2023 revenues rose 40% YoY to $188 million, driven by partner payments, while cash and investments total $2.4 billion; operating expenses increased as planned to support late-stage programs, and full-year guidance remains unchanged.
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Earnings Conference Call
Ionis Pharmaceuticals Q2 2023
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