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Ionis Pharmaceuticals Inc
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Good morning, and welcome to the Ionis Pharmaceuticals Second Quarter 2022 Financial Results Conference Call. As a reminder, this call is being recorded.
At this time, I would like to turn the call over to Julie Tepper [ph], Investor Relations, to lead off the call. Please begin.
Thank you, Betsy. 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 a reconciliation of GAAP to non-GAAP financials. We believe non-GAAP financial results better represent the economics of our business and how we manage our business. We have also posted slides on our website that accompany today's call.
With me this morning are Brett Monia, Chief Executive Officer; Doug Hougen, Chief Financial Officer; and Richard Geary, Executive Vice President of Development. And joining us for the Q&A portion of the call are Eric Swayze, Executive Vice President of Research; Eugene Schneider, Chief Clinical Development Officer; and Onaiza Cadoret, Chief Global Product Strategy and Operations Officer.
I would like to draw your attention to slide three, which contains our forward-looking statements. 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.
With that, I'll turn the call over to Brett.
Thanks, Julie. Good morning, everyone, and thanks for joining us today. In the first half of this year, we moved significantly closer to delivering an abundance of transformational medicines to the market. The first half was highlighted by the positive results from the Phase III NEURO-TTRansform study of eplontersen in patients with TTR polyneuropathy.
Eplontersen met the co-primary and key secondary endpoints in NEURO-TTRansform, demonstrating a highly statistically significant and clinically meaningful improvements in neuropathy impairment and in quality of life. Based on these positive results, we're well on our way towards filing an NDA later this year.
And at the same time, we and our partner, AstraZeneca, are advancing our global go-to-market preparations to launch eplontersen for the treatment of ATTR polyneuropathy. We're also continuing to advance our ongoing CARDIO-TTRansform Phase III study, which we expect will enable us to move into this much larger market for patients with ATTR cardiomyopathy. We and AstraZeneca are quite confident that eplontersen is well positioned to successfully compete in this space.
We're also pleased that tofersen is now under priority review with the FDA for the treatment of SOD-1 ALS. If approved, tofersen could become the first disease-modifying therapy for a genetic cause of ALS. For the PDUFA date of January 25, 2023, toferson has the potential to be our next product on the market with eplontersen following shortly behind.
Additionally, we continue to advance our late-stage pipeline, including completing enrollment in two of our Phase III studies. We have now fully enrolled the BALANCE study of olezarsen in patients with familial cargomycrodemia syndrome, or FCS, making this study our next potential Phase III data readout planned for next year.
And Novartis also achieved full enrollment of more than 8,000 patients in the Lp(a) HORIZON cardiovascular outcome study of pelacarsen further solidifying our first-mover advantage for this important medicine.
Beyond the positive data we reported from our late-stage pipeline, we also reported positive data from six of our mid-stage programs so far this year. Based on positive Phase II study results, our partners are planning to advance two new medicines into Phase III studies next year. As a result, we expect to expand our rich Phase III pipeline to at least eight medicines across 10 different indications.
In addition to advancing our pipeline, we're also making excellent progress in advancing our go-to-market activities for our near-term product opportunities at inotersen, olezarsen and donidalorsen. With the potential to add two new medicines to our commercial portfolio next year, along with the steady cadence of Phase III data readouts in the near and midterm, we're looking forward to bringing numerous transformational medicines to the market. All of this, positions us well to maximize value for patients and value for shareholders.
With that, I'll turn the call over to Beth to review our second quarter financial results. Then Richard will discuss our recent key data readouts, pipeline updates and will preview upcoming catalysts for the rest of the year. After Richard, I'll wrap up our prepared remarks, before taking your questions. Now, over to Beth.
Thank you, Brett. In addition to achieving key pipeline milestones, we delivered strong financial results, earning revenues of $134 million and $276 million for the second quarter and first half of this year, respectively. Our revenues increased in the quarter and year-to-date over the same period last year, driven by revenue from numerous diverse sources, with just over half from our marketed products and the balance from our partnered programs. We continue to invest in advancing our rich late-stage pipeline and in our commercial readiness activity.
Our operating expenses and net loss for the quarter and year-to-date reflect these important investments. Notably, we maintained our cash and investments essentially flat from Q1 to Q2 at $2 billion. SPINRAZA's global sales were $431 million for the second quarter and $904 million year-to-date. As a result, we earned $60 million and $113 million in royalty revenue for the corresponding periods.
In the US, SPINRAZA sales stabilized on a year-to-date basis compared to last year. Additionally, we remain encouraged that in the US, discontinuations decreased during the quarter, a positive trend we have seen consistently for several quarters. We anticipate SPINRAZA could return to growth as the dynamics seen in the US play out across other geographies.
Additionally, Biogen is executing on a robust life cycle management program that we and Biogen believe further supports SPINRAZA's return to growth. The RESPOND and ASCEND studies are evaluating SPINRAZA's potential to benefit patients who were previously treated with competitive products. As open-label studies Respond and ASCEND can provide Biogen with the continuous stream of data supporting SPINRAZA's market leader position.
The DEVOTE study, which is in the randomization phase, is evaluating the potential of higher dose SPINRAZA to provide even greater efficacy. If the data are positive, they could support filing for approval. All three of these studies are progressing well. In addition, the future of our SMA franchise, includes the follow-on medicine ION306. Based on preclinical data, ION306 may offer the potential to substantially extend dosing intervals.
We earned R&D revenue of $56 million in the second quarter and $126 million year-to-date, both of which increased compared to the same period last year. We generated R&D revenue from several different partners for advancing numerous programs, demonstrating a key element of our financial strength. We earned $57 million in the first half of this year for from Biogen for advancing neurological disease programs under our strategic collaboration. We also earned $37 million from AstraZeneca for their portion of F1 tofersen development cost, and $22 million Roche for advancing Ionis FB-L in development.
In line with our goal to invest in our pipeline and commercial capabilities, our non-GAAP operating expenses increased in the second quarter and year-to-date compared to last year. The increase was driven by higher R&D expenses from advancing the six Phase III studies we are currently conducting, with eplontersen comprising our largest investment. Our R&D expenses also included increased spending for CMC and medical affairs activities to support our near-term opportunities.
SG&A expenses decreased year-over-year for both periods. This was largely due to the substantial savings from the Akcea integration and Sobi transaction last year. We are redeploying some of those savings as we invest in our go-to-market preparation for eplontersen, olazorsen and donidalorsen.
Our results for the first half of this year keep us on track to meet our 2022 financial guidance. As we look forward to the rest of the year, we anticipate our Q3 revenues to be similar to Q2. In fact, we have already earned nearly $45 million from Roche and Biogen this quarter.
As our Phase III studies continue to progress, we expect our R&D expenses to increase between 25% and 30% this year compared to last year, consistent with our guidance. We project our SG&A expenses to be in line with last year, even while we increased our investments in preparing to bring our near-term opportunities to the market.
With $2 billion in cash and investments at the end of June, together with the revenue and cash we generate from numerous diverse sources, we continue to have a strong financial foundation. By investing in our strategic priorities, including advancing our goal to deliver a steady stream of new medicines to the market, we are poised to deliver significant future growth.
With that, I'll turn the call over to Richard.
Well, thank you, Beth. Our mid and late-stage pipeline continues to perform extremely well with eight positive data readouts so far this year. These achievements position us to add to our commercial products and expand our rich Phase III pipeline in the near-term. And over the next few minutes, I will review the key highlights from these recent pipeline achievements and then preview the key catalysts we expect in the second half of this year.
The most important event in the first half of this year was the positive data from the Phase III NEURO-TTRansform study of eplontersen in patients with ATTR polyneuropathy. As we reported in the prespecified interim analysis of 35 weeks of treatment eplontersen met its co-primary endpoints of serum TTR concentration in mNIS+7 as well as the key secondary endpoints, Norfolk quality of life. Eplontersen demonstrated highly statistically significant and clinically meaningful changes from baseline in each of these endpoints as compared to historical placebo.
Importantly, a substantial number of eplontersen treated patients showed improvement in neuropathy impairment and quality of life in the study.
We're looking forward to presenting data from the interim analysis at the International Symposium on Amyloidosis or ISA in September. With these data in hand, we and AstraZeneca are finalizing the NDA and planning to file for regulatory approval for TTR polyneuropathy in the US later this year.
Additionally, our CARDIO-TTRansform study, the largest and longest study to-date for patients with ATTR cardiomyopathy also continues to progress well. Our broad olezarsen development program remains the lead medicine targeting APOCIII in clinical development to treat patients at risk for effects of triglyceride-driven disease. We recently achieved full enrollment in the BALANCE FCS study, which is on track for data next year, making this our next planned Phase 3 data readout.
Our core sHTG or severe hypertriglyceridemia study for the much larger indication with more than three million patients in the US alone remains on track for data in 2024. Additionally, we expect to initiate a second confirmatory pivotal study of olezarsen called CORE 2 later this year, also projected to read out in 2024.
Our donidalorsen OASIS Phase 3 program in patients with hereditary angioedema, also continues to progress well and remains on track for data in 2024. We recently initiated OASIS+ study that includes a switch cohort for HAE patients, previously treated with other prophylactic therapies. Coming up later this year, we plan to report new longer-term data from the Phase 2 open-label extension study in HAE patients treated for one year to demonstrate long-term durable efficacy.
With the differentiated efficacy, safety, dosing and administration pro, we believe donidalorsen has the potential to be a best-in-class treatment in the attractive and growing HAE market. We are also very pleased that the NDA for tofersen is now under priority review with the FDA. This expedited review underscores the significant unmet need of patients with SOD1-ALS, and it also emphasizes the tremendous value tofersen could deliver to patients, as potentially the first disease-modifying treatment approved for a genetic cause of ALS.
The filing includes new integrated data from the Phase 3 VALOR study and ongoing OLE study, which shows tofersen significantly slow decline across multiple measures of ALS disease progression and importantly, led to robust and sustained reductions in neurofilament, a marker for neuro generation.
With the January 25, 2023, PDUFA date, tofersen is on track to be our next product to enter the market. Additionally, we believe these new encouraging data also support the promise of our leading neurology pipeline with 11 medicines in development today to treat rare and broad neurological diseases.
Our leading cardiovascular franchise comprised of medicines in development to treat major cardiovascular risk factors, also continues to progress nicely. Importantly, the safety and tolerability seen across our LICA pipeline enables us to address these fraud indications. An excellent example of this is pelacarsen.
Novartis recently completed enrollment in the Lp(a) HORIZON cardiovascular outcome study, enrolling more than 8,000 patients. pelacarsen has the potential to be the first medicine on the market to address cardiovascular risk, driven by elevated LP(a).
Elevated LP(a) cannot be adequately addressed with currently available treatments nor with lifestyle changes such as diet and exercise. As a result, with over 8 million people estimated to be affected worldwide who also have cardiovascular disease, pelacarsen represents a multibillion dollar opportunity. pelacarsen is on track for data and a potential regulatory filing in 2025.
We also recently reported several positive mid-stage data readouts, including from our Factor XI program, our HBV program and for IONIS-FB-LRx in IgA nephropathy. As a result of these positive data readouts, our Phase III pipeline is poised to expand to at least eight medicines addressing 10 indications.
Today, we anticipate a steady cadence of Phase III data readouts and have started this year, expands to 2023, 2024, and 2025, and as we expand our Phase III pipeline, we'll be extending the steady flow of Phase III data readouts beyond 2025.
We are looking forward to building on the substantial positive pipeline progress we have delivered so far this year with additional key data readouts and program updates. In addition to Eplontersen, our second half highlights include Phase IIb data from IONIS-AGT-LRx, our medicine for treatment-resistant hypertension, OLE data from donidalorsen intended to demonstrate long-term durability in HAE patients, and monotherapy data from Syndelirsen, our medicine to treat acromegaly.
With that, I'll turn the call back over to Brett to close this portion of the call.
Thank you, Richard. As you've heard this morning, it's been a great year so far for Ionis. We made great progress in advancing our key priority is to grow our commercial pipeline and deliver abundant new transformational medicines to the market.
We're looking forward to potentially adding eplontersen and tofersen to our commercial portfolio as early as next year. We continue to make excellent progress in advancing our other near-term opportunities, our olezarsen and donidalorsen and with multiple positive mid-stage data readouts, we're well-positioned to expand our Phase III pipeline to these eight medicines across 10 indications.
In addition to all of our pipeline advances, we've been making excellent progress in expanding and diversifying our technology as well. Specifically, we are focused on advancing new chemistries, including expanding our LICA platform beyond liver. Look forward to providing updates on these exciting advances in the future.
The second half of this year, we expect to continue our positive momentum by delivering additional key milestones highlighted by the NDA filing for eplontersen. And importantly, we have the resources needed to continue executing on our priorities to drive substantial growth and value for all stakeholders.
With that, I'll now open the call up for questions. Operator, can we start the question session?
We will now begin the question-and-answer session. [Operator Instructions] The first question today comes from Yanan Zhu with Wells Fargo. Please go ahead.
Great. Thanks for taking our questions and congratulations on a very productive quarter. So on Eplontersen in TTR polyneuropathy, what do you hope to show at the upcoming presentation at the ISA meeting? And as we try to compare the data with existing data from approved TTR silencers, what should we focus on to get a sense of the competitiveness of Eplontersen? Would it be the change in mNIS+7 from baseline, Norfolk QoL or proportion of patients with improvement? Any color would be helpful. Thank you.
Sure, Yanan, thank you for the question. We couldn't be more pleased as we try to drive the message in our prepared remarks, more pleased with the overall package for Eplontersen. The efficacy, safety, tolerability, target engagement there really is -- we couldn't have hope for more. And as we also said in our prepared remarks earlier, we're well on our way to submitting the NDA for potential approval and preparing for launch next year for Eplontersen for TTR polyneuropathy.
We're very much looking forward to sharing results from our 35-week interim analysis data in polyneuropathy ISA, and we're looking forward to sharing a lot of the results at ISA. We're certainly going to be looking forward to sharing the safety and tolerability profile. They're rich and there is a really exciting target engagement for TTR lowering as well as efficacy data and so on at the meeting.
As you know, the primary endpoint in -- it was a co-primary endpoint in the – at week 35. We also have a key secondary endpoint. Primary endpoints were mNIS+7 as well as TTR lowering. And the key secondary endpoint was Norfolk QoL-DN. So in addition to safety and tolerability, we're looking forward to sharing some of the efficacy results as well. And as for comparison, TTR amyloidosis is a big indication.
And I think the comparison will be important to be looking at in the primary and the secondary endpoints as well as the exploratory endpoints for neuropathy. But beyond that, it's really the cardiomyopathy data that I think is going to be incredibly important for Eplontersen. We're running the most robust, the richest, the largest and longest trial ever done for TTR cardiomyopathy and really believe that, that is going to be a key differentiator for this very large market. So stay tuned for that -- and stay tuned for the presentation of ISA.
Got it. If I have a very quick follow-up on cardiomyopathy, and that is, could you share your thoughts on the probably top-line data and whether that changes your thinking around the powering of your cardiomyopathy study, including the recent upsizing of the study size? Thank you.
Thanks, Yanan. Good follow-up. You know, we've been in this field for many years now, nearly a decade, I think you keep developing therapies for TTR amyloidosis. And we couldn't be more pleased that that there is new encouraging data that shows that silencers could very effective in the broad cardiomyopathy disease indication. And we couldn't be more pleased and happy with the trial design for our cardio transform study. As I mentioned, it's very robust.
We're going to be able to generate data in several different important patient subpopulations, including ebontersen compared to naive as well as on top of tafamidis and so on. It's a very rich – we're expecting a very rich, robust data set in the cardiomyopathy study, and it's a cardiovascular outcome trial.
So – and we think the outcome data is absolutely essential key to driving uptake into this very attractive market. And there's no data that we've seen that is changing our assumptions that, our trial design is the right design. And it's a study that, we're – that's enrolling very well now, and we're looking forward to bringing it to its conclusion, as planned. We're also looking forward to additional data that has come out from APOLLO-B in the future, which we shed additional light on things. But we're – right now, we're not planning to change our trial design in any way based on any new data that has come out today.
Great. Thanks for all the color.
The next question comes from Paul Matteis with Stifel. Please go ahead.
Hey. This is Kathy on for Paul. Thanks so much for taking our question. I had a quick question on the tofersen recent NDA filing acceptance. I guess, would you consider filing any of your other neuro or ALS programs, with NFL as a surrogate endpoint. So I guess, in other words, do you see any read-through on this acceptance on to any of your other neuro programs? Thanks so much.
Sure. I'm going to ask Richard to take a stab at that one, Kathy?
Yeah. Of course, the tofersen package is an important one. And there are many learning's from that program. One of those is that functional endpoints don't change as rapidly as some of the biomarkers. And of course, we get engagement with the target. We can see that in a very short period of time. Following that, we saw the neurofilament decrease, very strong, very robust. And seeing it again, with the placebo patients going on to Tofersen, kind of brings that whole thing home that you're actually having on impact on neurodegeneration through this potential biomarker.
Will we be looking at the potential of filing on biomarker alone? I think biomarker alone is probably not the play but rather, looking at the biomarker is a very good early surrogate for what can happen as we play it out. So for us, we have a robust design for our study. We have interim analysis built in that doesn't force us to be static in the way that we look at the end points. So, we'll be able to see when we're having good movement in functional as well as, of course, neurofilament is part of the design.
Okay. Great. Thank you.
The next question comes from Jessica Fye with JPMorgan. Please go ahaed.
Hey, guys. Good morning. Thanks for taking my question. Maybe sticking with TTR and following up on the APOLLO-B question, recognizing all the details are not yet. Can you just remind me whether you plan to take an interim in cardio transform? And maybe talk about whether or how you see the APOLLO-B results affecting that decision if it is sort of up to you to whether to take an interim?
And then second, I think you mentioned planning additional studies for eplontersen. Can you talk in a little bit more detail about what those might include? Thank you.
Sure, Jess. Eugene, can you take that?
Yes, sure. Good question. Well, I'll start in the order of your questions related to the early look option for cardio transform. We certainly have that option, and we plan to be very judicious in taking that option when the timing is right. But it is within our protocol to have an option for an early look into the primary endpoint, and we are using primary endpoint for that, which is CV mortality and morbidity.
So it's important to, again, distinguish that from the current readout in APOLLO-B, which really was more of an early look at the functional changes. So having said that, we are looking forward to seeing the full results from the APOLLO-B, of course, as everyone else, it is important to look at magnitude of these differences from placebo to understand their clinical significance, not just distal significance.
And on the additional eplontersen trials you alluded to?
Yes. That continues to be an area of active work and discussion with our partners, and we're not really prepared to start disclosing all of the life cycle management activities, and I kind of use that term broadly for this group of studies. But there are important clinical questions that need to be answered. And we believe that we will have a profile that is highly differentiated from competitors. So stay tuned.
Yes, Jess, just stay tuned. We're working, as Eugene said, on several set of studies, life cycle management, imaging studies, et cetera, with our partner, and those will be hitting clinical trials like in the future is. So we will talk more about it at that time.
Great. Thank you.
The next question comes from Do Kim with Piper Sandler. Please go ahead.
Great. Thank you for taking my question. First, as you think about and look at the data for NEURO-TTRansform, are there aspects to that or just the drug profile in general that physicians will find compelling to switch from the recently launched -- announced fitusiran, or do you think you'll be competing for just newly diagnosed patients?
I'd like ask Onaiza to maybe address that question. Onaiza, can you take that?
Yes. Hi, Do. So I think it's really important to know that with polyneuropathy and the mixed phenotype patients, this is fairly a large market with the first generation silencers, we've only put really a marginal dent in getting these patients diagnosed and treated. So as a result, there is really still continues to be about good 40,000 patients in this population that I think both drugs will have access to. So we do expect to get a lot of new patients on. We have a very compelling product profile. Richard went through it in his prepared remarks, that we have a product profile with the great improvements of mNIS+7 plus Norfolk Quality of Life, which are actually really clinically meaningful important considerations for physicians that packaged in with our go-to-market strategy with AstraZeneca and trying to identify, diagnose and treat these patients as rapidly as possible in all types of settings because they do present in a variety of different settings, not just in the neurologist office. We will be able to kind of access that broad peculation very quickly. So yes, we're expecting to go in and find these patients readily and get them diagnosed and treated on eplontersen.
And just add to answer that -- thanks, Onaiza. And just add to that though, of course, polyneuropathy is just a start. And as you know, cardiomyopathy is where the big population for the big opportunity and the biggest unmet medical need is today. And there, we think we have several key differentiators eplontersen. One is the study design that we've already emphasized. We think the amount of data, the quality of the data, the details of all the data we're going to generate for that study is going to be very differentiating.
Also, the fact that we have a global powerhouse in the cardiovascular space in AstraZeneca to maximize delivery of eplontersen for many patients as possible globally is another key advantage for – for eplontersen in addition to the really exciting neuropathy data that we've generated in NEURO-TTRansform.
Great color, Brettt. Very strong clinical data package that's being generated here. And I want to remind everybody that we do – we are powered with the longest acting and the largest study to be able to make sure that these data are available in our label, so we can provide that to all types of physicians in a very promotionally sensitive and what is turning out to be a competitive market.
Perfect. Thanks for taking my questions.
The next question comes from Gena Wang with Barclays. Please go ahead.
Thank you for taking my questions. Maybe I would just ask regarding your HBV program with your partner, GSK. Any additional color you can provide regarding the second half of this year, the data update? And then also quickly on the HAE program, Phase 2 OLE data, if you can give a little bit more color on the type of data you'll be sharing.
Eric, do you want to take the HBV question for Gena?
Yes, sure. Thanks, Brad. Gena, as I'm sure you're aware, GSK presented some nice data at EASL on the 24-week end of treatment time point for Bepirovirsen and showed -- but I think it's really remarkable data in 28% and 29% of patients either non-therapy or oncotherapy nucleosides showing going below the limit of detection in the antigens.
And this has been – it's really been unprecedented in monotherapy to see that level of decline in this patient population. So we think the data is very encouraging. And as does GSK’s, they've announced their intention to do a Phase 3 program, in the near future. And really the keys for that will be, seeing if that's sustained in the continued B-Clear data and also in the B-Share study, which is an open-label extension with those patients. So that will be the key bits of information for that program going forward.
Yes. And I think the buzz phrase is functional cures, right? Functional cures with the durability that GSK plans to present second half -- additional data second half this year, is to really nail down whether or not we're achieving functional cures in these patients.
As far as HAE, yes, we're looking forward to presenting the open-label extension data. These will be patients, now treated for a year, with donidalorsen. As you recall, Gena, the efficacy was remarkable in Phase 2. I mean, unprecedented reductions in HAE attacks, as well as greater than 90% of the patients were completely attack-free during that period.
The objective for the presentation for the second half of the year is to show that those effects are durable. And that's what we're planning to present in the second half of this year, is the durability of the remarkable efficacy that we showed in Phase 2. In addition, there will be some data for monthly and bimonthly dosing, because patients were eligible for -- to do either in the open-label extension. So you'll see some of that as well, and how well the bimonthly holds up with the monthly and so on.
Thank you very much.
The next question comes from I-Eh Jen with Laidlaw & Co. Please go ahead.
Hello. Good afternoon and thanks for taking the questions. Besides the GSK, I understand that Roche also will move their program into Phase 3, the FB program. Could you elaborate a little bit more about that? And I have another follow-up.
Yes, l-Eh. That's of our -- we have 4 Phase IIb studies -- I'm sorry, five Phase IIb studies reading out this year. We already have put out 3D positives, PCSK9 Factor B, that you just referred to in IgA nephropathy and our – that’s a medicine program, Factor XI and more coming. The results in patients with IgA nephropathy were really compelling. It looks like some of the best efficacy that's been disclosed in -- by targeting Factor B with our LICA medicine FB-LRx. Based on the data, Roche is really excited about moving it into Phase 3 development, as we announced next year. In addition, that same drug is in a larger trial in patients with geographic atrophy, dry AMD. That study continues to enroll today and is progressing well.
Okay. Great. That's very helpful. Maybe one more question on your preclinical data. You're talking about you will have a muscle LICA program, I guess, early study to come, readout to come this half? And any elaboration on that side?
Thanks, I-Eh Jen. Eric?
Yes. We're planning on getting a muscle LICA program into preclinical development. We don't have any more elaboration on that right now. But certainly, our happy with the multiple technologies we've moved forward into targeting the muscle, including some of the things we've talked about, like the Bicycle collaboration with Bicycle Therapeutics, using fairly small Bicyclic peptides to engage the transferrin receptor and target them to muscle. And so we have multiple programs progressing, that's one of them and look forward to getting them started in development across multiple therapeutic areas in the not-too-distant future.
Okay, great. Thanks a lot and congrats.
The next question comes from Salveen Richter with Goldman Sachs. Please go ahead.
Hi, thanks for taking our question. This is Sonya on for Salveen. Are this about the upcoming hypertension data, how are you thinking about potential efficacy bars there? And then on the program in Angelman, can you help us kind of gauge the differentiation from other potentially disease-modifying therapies in this space? And I guess provide us maybe with an update on when we could see data from this program? Thank you.
Sure. Rich, do you want to talk through the AGT program and what we're expecting from the Phase IIb data?
Sure. So for AGT, like we have a Phase IIb in resistant hypertension that will read out in the second half of this year. And in addition to that, we have a study in heart failure -- safety study in or failure that will read out either late this year or early next year.
In the endpoints...
In the heart failure...
In the hypertension study, the Phase IIb study.
Of course, so the endpoints in the hypertension study are systolic blood pressure decrease compared to placebo. And this is powered two different dose groups and powered against the control to show a significant decrease.
And Eric, could you address the differentiation in Angelman?
Yes sure. I’d like to talk about Angelman little bit. So as I am sure you’re aware – certainly all the programs I am aware of that are disease-modifying are using the same general mechanism of trying to target this antisense transcript that regulates the carbon [ph] gene and then upregulates the gene that's deficient in Angelman syndrome. Our drug certainly does that. And for differentiation, we hope it's the best molecule in the space.
And we spent a lot of time trying to identify the best molecule. We think we're pretty good at finding optimal drugs for CNS delivery and engagement of their targets. And we're advancing our program. And our program is a first-in-human study. So, the primary endpoint is safety, of course, but we're always looking for target engagement, and we'll be monitoring other clinical endpoints as well to try and see how the drug behaves. And I don't believe Biogen has given timing on when that readout will come out. But we're – our goal is to advance the program as fast as we can to try and get a drug out for patients. So that's what we're trying to do.
Thank you.
The next question comes from Luca Issi with RBC. Please go ahead.
Great. Thanks so much for taking my question. Congrats on the quarter. Maybe on TTR cardiomyopathy. I know you have not seen the Phase 3 from Alnylam APOLLO-B. Is there a scenario where you elevate 6 minutes-walk test from a secondary endpoint to a primary endpoint in your Phase 3, so you can actually get to market faster? Again, I think they hit on 6-minute, trial that is three times smaller than yours. So I would think you may have a good shot at hitting the stat there, so wondering if that is an option.
And then maybe circling back on AGT, it looks like you have a lead compound and a backup compound. Wondering, if you can remind us what's the difference between the two? And why does it make sense to continue to invest in both, instead of just pivoting to the next-gen? Thanks so much.
Yeah. Eugene, could you address the 6-minute walk?
Yeah. Sure.
For revolution and …
So for cardio transform, we are looking at 6-minute walk. However, it is our secondary endpoint, not primary. For the main reason being that the current standard of care already has mortality data and significant benefit on mortality and cardiovascular events, which we believe is really the most meaningful and expected outcome for this indication, certainly in terms of demonstrating value to physicians as well as payers importantly.
So while in theory, you could potentially get to the market or at least through regulatory gate faster. What we're really playing here as a long game. As Brett indicated, we are assembling the most definitive data set for this indication that will be useful for physicians and patients in when this drug is on the market, not trying to kind of find a shortcut to approval. We feel that playing the long game here is critical for us to have the best-in-class therapy here.
Onaiza, do you want to expand on that from a commercial perspective on value a 6-minute walk endpoint would be versus the outcome data?
Yeah. I think we've obviously been preparing for our cardiomyopathy clinical data package and really working closely with the development team as what Eugene described. And looking out there in the marketplace across a robust set of physicians the most important element that physicians are going to want and it depends on the type of patients that they're going to have in their office is that, what is the cardiovascular risk reduction on top of standard of care tafamidis and/or if I don't have a patient on tafamidis. And I'd like to see the total cardiovascular risk reduction for a patient who's naive therapy.
We believe that generating both types of data, the most robust clinical data package that we will need to demonstrate our best-in-class profile. In addition, I think payers will also require that, particularly as you're thinking about adding on therapies. This is a very sick population, and these patients are at risk for terminal death at the end of the day, we do not believe this is a place where physicians will be switching.
And as a result, we're going to have to demonstrate the best value proposition and clinical utility on top of standard of care for payers for reimbursement as well. So we believe we're well positioned across the broadest set of data, the broader set of demographics. And we're really striving for label-enabling data to ensure that we're very competitive --
Thanks, Onaiza. Luca, regarding AGT hypertension, so as Richard pointed out, we have two studies in progress with our lead molecule Gen-2 chemistry with LICA, the Phase 2b, refractory hypertension readout end of this year -- by the end of this year. And then our heart failure study is progressing nicely.
In addition, we initiated development of another molecule, a Gen 2.5 chemistry, LICA targeting AGT. And really there, we're focusing on really just comparing and profiling 2.5 versus 2. We expect greater potency. We also probably expect greater durability, and that's what we're going to be looking for. That study is now in Phase II in hypertension. And we're going to look at all the data.
We're going to look at the hypertension data with the 2.0. We're going to look at the heart failure data, and we're going to look at the 2.5 data next year. And develop our strategy or implement our strategy accordingly based on data-driven decisions. So further -- as far as further investments go, we made our investments, and we're going to look at which is the molecule we want to invest further in and we'll make that decision next year.
Super helpful. Thanks a lot guys.
The next question comes from Myles Minter with William Blair. Please go ahead.
Hi. Thanks for taking the question. The first one is just a clarification question for you, Brett. You said that the IgAN data for the factor B inhibitor was the best you've seen thus far. Was that targeting just factor B, or is that relevant to the complement space more broadly?
And the second question is on the GOLDEN study in geographic atrophy in clinicaltrials.gov has that ending in October 2022. I'm just wondering whether we expect top-line data disclosure in the second half because it's not in your press release. Thanks for that.
Yeah. So thanks, Myles. The data that we've seen in IgA nephropathy to date, physicians -- our factor B LRx very competitively. We believe that based on the data we've generated to date, this has the potential to be the most efficacious approach for IgA nephropathy are not, not just factor B, not just complement anything that has been publicly disclosed to date in this patient population. That's why Roche really tried aggressively pull the trigger to move to Phase III rapidly. So not just factor B, but really everything that has been laid out in the public domain to date.
Regarding the GOLDEN trial, no, we're not planning to have data readout from the dry AMD study this year. We haven't really put a time line on that for when the data will read out, it's a big study, more than 300 patients, I think, with dry AMD. And we're still enrolling the study. So stay tuned, but we really haven't put out when any details on when to expect data for that study.
Okay. Helpful. And just a very, very quick clarification again that IgAN comment includes data from the endothelin receptor antagonist class that's inclusive of everything?
That's inclusive of everything. Yeah. Everything includes everybody.
Thanks guys.
Thanks.
The next question comes from Yaron Werber with Cowen. Please go ahead.
Yes, hi. I have three questions and three different drugs, if you don't mind. Just the first one on eplontersen, can you give us any insight as to when are you thinking an AstraZeneca is thinking about filing with EMA for polyneuropathy?
And then secondly, can you just confirm that you've not done an interim analysis on cardio transform before you expanded to 1,000 patients?
And then just a question also on 306 or BIIB115. I don't know what you could say about it. It sounds like it's going to be extended duration. Is it exactly the same sequence as SPINRAZA, or what's the differentiation there as well? And what's timing to starting Phase I? Thank you.
Thanks. So -- actually, Rich, why don't you talk a little bit about our strategy for the EMA filing for Eplontersen.
So Eplontersen polyneuropathy, of course, we'll file in the US this year. And follow with the week 65 or week 66 data as endpoint data that will be included in the EMA filing. Now that means that the staging will be very close, but it's going to be, yes. So I'm getting a little bit of a signal that there. So we're good. On EMA follows the FDA, and it will include -- ultimately, include the final end point week 65.
We're preparing the European filing now, Yaron. It's just -- it will be in segments. The final full filing will require doing 65 days. As far as the decision we made to expand the sample size and the duration for the cardio transform study, that was entirely based on a few factors.
One was the demographics in the study that we want to make sure that we have the right mix of sicker patients in patients suffering with TTR cardiomyopathy. So the right balance. It wasn't really based at all on event rates or anything like that. It was really based on what the demographics were looking like patients coming into the study. This disease is being diagnosed earlier and earlier, patients have mild or a milder disease when they're getting diagnosed and we're seeing that globally. We're not the only one seeing that.
So that was really the basis for that. There was no look at any data – any interim data at all that factored into that. And as far as the follow on to SMA, very excited about this drug. This drug has the potential based on the wealth of preclinical data it's positioned to be able to extend the dosing interval substantially, maybe once every nine months, every 12 months or so, dosing. We have to prove that in the clinic, but the preclinical data is very strong. Biogen has not put out any details on the timing for the start of the new study. So you have to stay tuned for that. We don't want to get ahead of partners on that one.
Okay. Great. And then if you don't mind, I'm just to throw one quickly for Acromegaly, Cimdelirsen. So it sounds like that's fully enrolled now. Are you -- is the -- it's a monotherapy. I know you can enroll both naive or experience, do you have a sense of what the split is between the two patients? And what are you expecting -- what would you like to see to then move into Phase III? Thank you.
So the study that will read out in the second half of this year, Yaron, is monotherapy. So these aren't patients that are on treatment today. If that's your question, it's a pure monotherapy treatment in patients with Acromegaly. What we are looking for is – substantial movement, reduction in IGF-1 biomarker, approvable biomarker for new treatment for Acromegaly. We are hoping also to get a substantial number of patients in to the normal range of their IGF-1 as well. We have to see, if we can achieve that by really, any IGF-1 lowering that's achieving these patients has been shown to have meaningful impact on quality of life for these patients. That's our objective.
Right. So Brett, what I was asking, do you expect patients to be – this is model therapy, do you expect patients same therapy before with other drugs like some metasite analogs or experienced, or these laser experienced – therapy postsurgical?
Yeah. It's – real the eligibility criteria will define what patients are entering the study. So we – you're right, some patients who have been treated before. And either not tolerated for a number of reasons or did not respond. So we'll obviously look, it's important to categorize safety and efficacy in both of these patients, which is what we intend to do. So it is a monotherapy trial.
Thank you.
The next question comes from Joseph Stringer with Needham & Co. Please go ahead.
Hi. Thanks for taking our question. Just on the muscle LICA preclinical program. I understand based on your initial preclinical data and some of the features of the targeting technology, are there set of indications that you incline to focus on albeit consider best fits, or are you indication agnostic at this point? Thanks for taking our question.
I can tell you, I wouldn’t call indication agnostic, but there is lots of indications, so we are looking at both the neuromuscular space, and because we’ve seen good success – and giving uptick into the cardiomyopathy with this class – target migraine, but also looking at the various cardiovascular indications. So we think it's going to be broadly useful in multiple indications and multiple programs, which is one of the reasons why we are so enthusiastic about our current targeting approach for muscle.
I mean, obviously, Joey, heart failure is a key area where we have a lot of – we have a great pipeline of cardiovascular space, and we are looking for opportunities to expand on that with the muscle like it for the heart. So stay tuned for that. And hopefully, we will have – having more to share by the end of the year. And maybe we have time for one last question before wrapping up. We're little long on time.
The next question comes from Gary Nachman with BMO Capital Markets. Please go ahead.
Great. Thanks for squeezing me in. So on olezarsen, with enrollment completed in FCS, remind us about the duration of the study. So will you have data more likely in the first half or second half of next year, and what's your expectation to be with the data? What you're looking for? And what sort of read-through, if any, might there be for the high trig study, once we see the FCS data? Then I have a couple of follow-ups.
Okay. Richard, go ahead.
Absolutely. So fully enrolled, I think reported that in June. It is a one-year study. So your data readout is going to be midyear. I think what we are looking for obviously, as primary endpoint is triglyceride lowering ad what we’ve seen – what we’ve know from WAYLIVRA which is the same sequence by the way. This is this is the LICA of WAYLIVRA essentially. What we saw in the very high triglyceride patients, FCS patient was actually even a greater response than we saw in some of the lower triglyceride baseline patients. So we expect very robust triglyceride lowering with this APOCII 3 targeted drug. And with it being a LICA safety is going to be pristine, which is going to be a very important component of this package.
And then in secondaries, we're looking for the effects of triglycerides on these patients generally drives abdominal pain issue with their pancreatitis and we are looking for reduction in some of those as well as a quality of life tool that we have developed for these patients. We’ve been in FCS for quite a number of years and we are excited to see how this study rolls out to one of the largest FCS studies that were conducted.
Yeah. And as far as read through SHTG Gary, we expect a very strong read-through our Phase 2 data was actually in milder patients, patients with milder triglyceride elevations, and we were so they're 60% or higher reductions in triglycerides, and that was at 50 milligrams per month. Our Phase 3 study will have 50 and 80 milligrams per month, we're seeing great safety and tolerability in the various Phase 3 studies for involving olezarsen. But with the higher dose, we're expecting even greater TG reduction. So looks like a great drug. And we're leading the way enables you to be a great target for managing patients suffering with TG related diseases. You got a follow up Gary?
Yeah. First on that, so you're starting the second high trig Phase 3 study. So is that going to be the same design and scope as the first one? And I mean, anything you can do to accelerate enrollment for these studies, if you have the resources to do that? Is that a possibility?
It's very similar. CORE 2 is very similar to CORE. This is a broad indication. So it requires 2 Phase 3 studies, a confirmatory study, and that's Phase 3 study. As far as enrollment, we are we're always looking at ways to enhance enrollment. It's a lot of patients in the Phase 3 study for all was olezarsen, Phase 3 studies for olezarsen, so takes time to enroll. A study involving more than 1000 patients across the studies and -- but we're always looking at opportunities to do it. It's less about more resources. It's more about just finding the right size finding the patients. Anything you want to add to that Eugene?
No.
Okay. Yeah. Yeah. And then just one last one Tofersen and PN. So after you file in the US, are you expecting a priority review? And then just maybe a few details on you and AstraZeneca just in terms of the plans for the launch. Any idea yet about sizing of the sales force any initial conversations with payers? If you said this, I missed it, I apologize. But maybe just run through some of the key activities as you prep in for that? Thanks.
Got a review Eugene?
Yeah. So for – as far as US filings concerned for polyneuropathy, we're clearly in discussions with regulators now and things are progressing very well for the NDA filing this year with regard to getting priority review, that’s an FDA decision. That’s multifaceted. There’s nothing. That depends on our approach it really is something that we need to wait once the filing is accepted and FDA decides on that.
Yeah. It wouldn't be appropriate for us to speak for the FDA at this point, Gary. But maybe Onaiza, could talk little bit about how our plans for commercial launch of eplontersen going cocoa with AstraZeneca, SMA roles and responsibilities and so on.
Yeah. I have to say, Gary, it's one of the best cocoa collaboration I’ve been a part of and I’ve been part of many in my career. They are great partner, and our teams are just sizing up really well. We’re taking a lead on medical shares. We have been in this category in amyloidosis and know the investigators and KOLs for over a decade.
It's really one of our core strength that we bring to the go-to-market activity. So we’re in field. We’re getting a lots of great request based on our top line sharing of the Phase 3 data and we hope that ISA will be able to kind of share more the robust profile and other indicator as well for this physicians.
We are also haven’t sized of total sales team yet, which is something we’re working on pretty actively. As a reminder and as I said I think earlier that these patients presented variety of different settings, so you knew, you have the neurologist but as a reminder AstraZeneca is already in with cardiologist with their cardiovascular agent in heart failure at the SGLT2.
So just really trying to seeing through where all these patients’ presents, so we can make sure our promotional efforts are all in a right place. We are also actively preparing peer conversations as well as sizing up our nurse case team on the Ionis side and host of other activities to make sure we’re planning for very robust and fulsome launch.
Okay, great.
Thanks, Gary. And I think that wraps up our Q&A session. I’d like to thank everybody join us today on our call, really great first half of the year for Ionis. We’re looking forward to continuing to share the progress throughout the remainder of the year. And until then, thanks again for joining, and have a great day.
Good bye.
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