Ionis Pharmaceuticals' (IONS) CEO Stan Crooke on Q2 2016 Results - Earnings Call Transcript

| About: Ionis Pharmaceuticals, (IONS)

Ionis Pharmaceuticals, Inc. (NASDAQ:IONS)

Q2 2016 Earnings Conference Call

August 09, 2016, 11:30 ET


Stan Crooke - Chairman & CEO

Wade Walke - VP, Corporate Communications & IR

Beth Hougen - CFO

Lynne Parshall - COO


Jim Birchenough - Wells Fargo Securities

Eric Schmidt - Cowen and Company

Stephen Willey - Stifel Nicolaus

Yale Jen - Laidlaw & Company

Salveen Richter - Goldman Sachs

Varun Kumar - Leerink Partners

David Lebowitz - Morgan Stanley


Welcome to the Ionis Pharmaceuticals Second Quarter Financial Results Conference Call. [Operator Instructions]. I would now like to turn the conference over to Dr. Stan Crooke, Ionis Chairman and CEO. Dr. Crooke, please begin.

Stan Crooke

Good morning and thanks everyone for joining us on today's call to discuss our second quarter financial results and business highlights. On the call today Beth will walk you through the financial results. Lynne will provide more color on the positive step forward that we recently announced with nusinersen and the plans to file regulatory dossiers around the world this year. And then I'll wrap up the call with an update of the status of our other phase 3 drugs and the progress we're making in the technology.

I'll start with the most recent news about nusinersen. As we announced last week, the Phase 3 ENDEAR study met the prespecified primary endpoint for the interim analysis. Infants treated with nusinersen achieved motor milestones substantially greater than infants who did not receive nusinersen. The difference was highly statistically significant. Data from all other endpoints we reviewed were all strongly in favor of the treated infants.

Nusinersen's safety profile continued to be consistent with the attractive safety profile that we've observed in the open label studies. We're therefore bringing the ENDEAR study to an immediate conclusion, a decision which our data safety monitoring board supported and transitioning all patients to an open label study. This means all patients, including control patients, will now be treated with nusinersen. We're certainly very pleased that all patients in the control arm of the study will now have the opportunity to receive nusinersen. Working with us, Biogen will now file marketing applications in the U.S. and EU in the coming months, with filings in other countries to follow shortly.

Importantly, Biogen plans to open a global expanded access program for patients with the infantile-onset SMA this fall. We're also pleased that we continue to have highly constructive interactions with the FDA on an ongoing basis. With nusinersen we believe have a drug that has the potential to dramatically improve patients' lives and fundamentally change the course of infantile-onset SMA. We're pleased that we're accelerating the time when nusinersen could be approved and we know that every day matters to these patients and their families. As you'll see from Beth's report, we remain a strong financial position and on track to meet our 2016 financial guidance.

After the financials and Lynne's comments, I'll finish up with some highlights from our current -- most recent R&D Day, including the status of our other phase 3 programs, our investigations on platelets and our progress in advancing our antisense technologies. Joining me on today's call are Lynne Parshall, Chief Operating Officer; Beth Hougen, Chief Financial Officer; Sarah Boyce, Chief Business Officer; and Wade Walke, Vice President of Corporate Communications and Investor Relations.

Now, Wade, would you please read our forward-looking language statement?

Wade Walke

Thanks, Stan. A reminder to everyone that this conference includes forward-looking statements regarding the financial outlook for Ionis, Ionis's business, the business of Akcea Therapeutics and the therapeutic and commercial potential Ionis's technologies and products in development. Any statement describing Ionis's goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of nusinersen, IONIS-TTR RX and volanesorsen is a forward-looking statement and should be considered an at-risk statement.

Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and the endeavor of building a business around such drugs. Ionis's forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis's forward-looking statements reflect the good faith judgment of its management, these statements are based on known facts and factors currently known by Ionis.

As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis's programs are described in additional detail in Ionis's annual report on Form 10-K for the year ended December 31, 2015 and its most recent quarterly report on Form 10-Q which are on file with the SEC. Copies of these and other documents are available from the Company.

And now I'd like to turn the call over to Beth.

Beth Hougen

Thank you, Wade. We maintained our strong financial position by ending the second quarter with more than $660 million in cash which does not include the $85 million we've generated so far this quarter from the license of nusinersen and our first development candidate under our Janssen collaboration. To date in 2016, we have generated more than $145 million in payments from our partners, including approximately $95 million from Biogen. In the second quarter Kastle acquired KYNAMRO from us for which we received a $15 million upfront payment. Under our agreement with Kastle, we can earn up to a total of $95 million.

Beginning next year, we're entitled to royalties in the mid to low teens on sales of KYNAMRO. We also received a 10% equity stake in Kastle which provides us with the opportunity to share even more in Kastle's success with KYNAMRO. We finished the first half of 2016 with a pro forma net operating loss of $64 million. Our financial results for the first half of this year were in line with our expectations and we remain on track to meet our financial guidance of a pro forma net operating loss in the low $60 million range and a year-end cash balance in excess of $600 million. In the first half of this year we earned $75 million of revenue, including more than $15 million in milestone payments, majority of which were related to nusinersen and the $15 million from Kastle.

We have projected 2016 revenue of more than $240 million. As we've said, we expect revenue to be significantly higher in the second half of this year. And in fact, we're well on our way to achieving our second-half projections as we have already earned $85 million from license fees. We also have numerous opportunities to earn revenue from milestone payments over the rest of the year. Our ability to generate substantial revenue from milestone payments and license fees is the natural result of our large advancing pipeline and our partnering successes because of the sources and timing of our revenue, as it does every year, we expect our revenue and our pro forma net operating loss to fluctuate on a quarterly basis.

And this year is a good example of this because much of our planned revenue for the year is in the second half. Our pro forma operating expenses for the first half of the year were $139 million and as anticipated, increased compared to same period last year. The increase in our operating expenses was due in large part to the five phase 3 studies we're currently conducting. In addition, Akcea has continued to prepare for the launch of volanesorsen. As these activities continue, we expect our expenses in the second half of this year to be modestly higher compared to the first half.

In closing, we're extremely pleased about the potential for accelerating the timeline for getting nusinersen to patients and the opportunity to add commercial revenue from nusinersen and KYNAMRO to our financial results next year, with the promise of commercial revenue from volanesorsen and IONIS-TTR RX to follow. The progression in nusinersen, along with all of our other achievements to date, has positioned us for continued financial strength.

And now I'll turn the call over to Lynne.

Lynne Parshall

Thanks, Beth. As you can imagine, we're very excited about the recent positive news from the nusinersen program. The results confirms what we saw during the phase 2 open label studies, in which we saw infants achieving milestones that SMA infants would not normally achieve, like rolling, sitting, standing and walking. I want to thank the SMA community for their support and trust in us and I want to especially thank the parents of infants who participated in our trials. We received many wonderful commentaries from the patients' parents and advocacy groups and we thank you all for your kind words. I also want to thank the extraordinary physicians who care for these infants.

We at Biogen are very focused on making sure this drug makes it as quickly as possible to regulatory review in the U.S. and Europe. To achieve that, we believe we're submitting a regulatory package that has strong potential to achieve marketing authorization as rapidly as possible. This is the first time a potential treatment for infantile-onset SMA has demonstrated a substantial clinical benefit in a controlled clinical study. We're pleased that this provides hope and encouragement to patients and their families. We keenly feel the urgency to bring nusinersen to patients with SMA as rapidly as possible. As Stan said, Biogen intends to file marketing applications for nusinersen with regulatory authorities in the U.S. and the EU in the next few months, with filings in other countries following soon after.

We believe our regulatory dossiers will provide a strong data package. Importantly, the interim analysis endpoints were designed in consultation with the FDA, with the intention of identifying the most rapid path to filing and potential approval. Because we believed there was a good chance the interim analysis would be positive, we and Biogen have already substantially completed most of the NDA and MEA dossiers and we plan to use our fast-track status with this program to submit sections of the NDA for review as they are completed which should help shorten the review timeline. Biogen's planned expanded access program is another example of out joint commitment to making nusinersen available to patients.

Once patients from the ENDEAR and EMBRACE have transitioned to the open label studies, Biogen plans to open the global expanded access program initially at existing clinical trial sites and then more broadly. Biogen has also been making significant progress in preparing for the commercial launch of nusinersen. Pre-commercial activities are ready well underway so that Biogen will be ready to launch nusinersen rapidly once the drug is approved. Based on what we know about Biogen and their plans, we have no doubt that they will be able to maximize the therapeutic and commercial potential of nusinersen. In considering the commercial potential of nusinersen, it's important to remember that about 60% of patients with SMA are born with the most severe type I form of the disease.

However, because type I infants have a life expectancy of less than two years, the prevalence of SMA type I is only about 12% of all patients. If, as we believe we've observed in our open label studies, nusinersen can increase survival in these infants, you could see the size of the total market increase. As Biogen has exercised its option to license nusinersen, we will be transitioning all development activities to Biogen and they will be responsible for all development, regulatory and commercialization activities and costs. We will continue to collect data from infants in the ENDEAR study through their next office visit which will formally be their last study visit. Over the next several months, we'll be working with Biogen to transition patients in the ENDEAR study to the open label of SHINE study.

Biogen will also be transitioning all patients in the EMBRACE study to an open label study. All patients in these open label studies will be treated with nusinersen. Full data from the ENDEAR study will be presented in an upcoming medical congress. As you will understand, while the study is still ongoing, we cannot unblind our colleagues who are finishing up the study, so the full product data presentation will need to wait until after the study is completed. Biogen is continuing the NURTURE study, an open label study in pre-symptomatic newborn infants who are genetically diagnosed. This is an important study, as we believe that earlier diagnosis and treatment may confer an even greater benefit to patients.

Ultimately we hope this study will support Biogen's efforts to encourage newborn and prenatal screening for SMA. We're also continuing the CHERISH phase 3 study in patients with childhood-onset SMA. As we did with the ENDEAR study, we and Biogen are continuing to work with regulatory authorities to identify the quickest path forward to make nusinersen available for patients with childhood-onset SMA. The other clinical trials, including all the ongoing open label studies are also continuing as planned. It's been very rewarding working closely with Biogen on all aspects of our strategic collaboration and especially with the nusinersen program. We believe that Biogen is the right partner to successfully commercialize nusinersen.

They understand the unique needs of the SMA community and the impact this disease has on patients and their families. Importantly, Biogen has the global commercial infrastructure and expertise needed to successfully launch and commercialize nusinersen. Their 40-year history of pioneering advances in drugs for patients with high unmet need and specifically for patients with neurological diseases around the globe, shows that they have the resources and the commitment to bring nusinersen to patients who desperately need this drug.

And now I'd like to turn the call back over to Stan for closing remarks.

Stan Crooke

Thanks, Lynne. I think it's obvious from this call and from previous calls that we've had, that all of us have for some time felt a profound urgency to bring nusinersen to the patients in the SMA community as rapidly as possible. So the recent development and advance preparations we and Biogen have made on both regulatory and commercial fronts bring us closer than ever to having this important new medicine to the patients who desperately need it. For that, we're very excited and very grateful. Nusinersen is a prime example of the power of antisense technology. It is the solution to the core problem, the lack of SMN protein. By specifically correcting the missplicing of the SMN2 pre-mRNA which results in increased SMN protein production.

This is a mechanism that is only accessible to antisense technology and I'm sure you recall the data that we've reported from clinical trials that indeed prove that the drug is working via the mechanism it's designed to work by. It's also a great example of the efficiency of antisense technology. We were able to move rapidly in the course of only half a dozen years of so, from understanding the cause of the disease, to discovering a drug candidate, to where we're today. This program also highlights our ability to address traditionally undrugable targets that work in many tissues by many routes of administration. Nusinersen is just the first in a large neurological disease pipeline that has grown to more than 25 programs in just six years.

We have demonstrated that our CNS drugs distribute broadly in the CNS. They are well-tolerated and are working the way we designed them to work. Today, in addition to SMA, we're developing drugs that address neurological and neuromuscular diseases in both rare and broad patient populations such as TTR amyloid polyneuropathy, myotonic dystrophy, ALS, Huntington's Disease, Parkinson's Disease, spinal cerebellar ataxias and others. The rapid expansion of our neurological disease franchise is a product, again, of the efficiency and productivity of antisense technology, as practiced at Ionis. Of course, beyond nusinersen we have much more to come from a broad pipeline of first-in-class, best-in-class drugs in development.

Next up, we'll bear other phase 3 drugs. Volanesorsen for patients with severe triglyceride disorders, FCS and IONIS-TTR RX for patients with TTR amyloid polyneuropathy. We expect to have phase 3 data for most of these drugs in the first half of next year. As we did with Biogen for nusinersen, we, GSK and Akcea are well along in preparing regulatory filings so that we will be in a position to file for marketing authorization very soon after we analyze the phase 3 data from these programs, assuming the data are positive. GSK continues to prepare for potential commercial launch of IONIS-TTR RX. And, as Paula outlined for you at our R&D Day last month, the Akcea team is actively preparing for the global commercial launch of volanesorsen.

We believe these drugs also have the potential to deliver therapeutic benefit to patients who have the severe, often fatal, disease with no available or adequate therapies. We look forward to the substantial commercial success that we believe will happen with these two drugs, as we do with nusinersen. We're making excellent progress in understanding the few cases of serious platelet declines observed in the neuro-TTR and APPROACH studies. First, all of our programs are continuing on schedule. None of our studies have been put on hold or slowed down as we have responded effectively to these issues.

Second, our monitoring and management of platelet declines is working. We've had no new cases of serious platelet declines in any of these trials or in any other trial with any of our drugs. And compliance in our studies remains high. As we presented at our R&D Day, we've learned a good bit more about the natural history of platelet declines in both FCS and TTR patients. Based on data from [indiscernible] the world leader in treating FCS patients, we now know that with FCS, the disease itself contributes to serious platelet declines. In TTR patients, the contribution of disease-related variations in platelet declines is less, but we believe both diseases contribute. Based on a substantial database of safety experience with two prima facia drugs, we have concluded, as we showed at R&D Day, that serious platelet declines are not a class affect.

In addition to the major strides were making with our pipeline programs, we're always investing in core antisense research. We've made significant innovations in our technology that have already translated into real value in our pipeline today, substantial increases in potency conferred by our LICA technology. Support weekly, monthly, quarterly or even less frequent dosing is a major advance and broadens the reach of our technology to treat much larger patient populations and expand into new therapeutic areas. The additional potency we achieved with Generation 2.5 technology enhances our ability to engage in difficult-to-teach tissues, once again allowing us to continue to expand the opportunities for antisense drugs.

Today we have eight LICA drugs and four Generation 2.5s in drugs in development and we plan to announce our first Generation 2.5 LICA development candidate by the end of this year or early next year. Combining our Generation 2.5 chemistry with our LICA technology should enable even greater lowering of doses to ultra low doses with the potential, of course, to improve further patient acceptance. At R&D Day we introduced two new antisense mechanisms that allow us to specifically increase protein production. Multiple diseases can be treated by increasing the levels of specific proteins. We're currently working on initial therapeutic targets utilizing these two new antisense mechanisms. This work is resulting in important additions to our strong proprietary position in the RNA field.

In conclusion, we believe we're creating great value. All of us are thrilled to be able to offer hope to the SMA community even earlier than we had planned. To have three first-in-class drugs completing phase 3 studies in such a narrow time frame is an achievement that very few, if any, biotech companies have achieved. And each of these phase 3 programs, we believe, has the potential to bring tremendous value to patients, physicians and shareholders. We're on the verge of transitioning to a Company with revenue stream from commercial drugs.

As we move longer term, we think we have the potential to be a fundamentally new kind of Company with a new technology, with new drugs and broad reach to bring benefit to patients with a wide range of diseases. Our strong financial position today and the potential for commercial revenues starting next year from nusinersen, allows us to continue to advance our pipeline and technology to provide that value, now and into the future.

With that, I'd like to turn the call over for Q&A. Andrea, if you can set us up for Q&A.

Question-and-Answer Session


[Operator Instructions]. Our first comes from Jim Birchenough from Wells Fargo. Please go ahead.

Jim Birchenough

A couple questions. First, on nusinersen, I'm wondering if you could provide any incremental detail on what paths you might have to more rapid approval for type II SMA? And how confident you might be in having a broader label than the type I? And to the except you can't comment on that, the broader platform question as it pertains to platelet effects, the Factor XI program is quite a psychrophile program. Any comment on what you've seen with regards to platelets there? And on the platform, when you talk about the 2.5 and the LICA chemistry, how quickly can you convert this pipeline you have to those advanced chemistry? Thanks.

Stan Crooke

Why don't I go in reverse order and I'll answer several of them and then I'll ask Lynne to comment on the regulatory process and label. With regard to converting the pipeline to LICA and 2.5 LICA, I think we're already almost finished. If you look at what we've done, we now have eight LICA drugs. In some cases we decided to go ahead and develop the parent like we have done with the volanesorsen and Factor XI RX and then follow with a LICA. In other cases we've actually replaced an existing very good drug with a drug we thought was better, such as we did with APOA LRX.

You can assume that our pipeline will be essentially generation 2-plus LICA or generation 2.5 or 2.5 LICA for all intents and purposes going forward, with the exception of the drugs like TTR RX and Factor XI RX and volanesorsen, that are completing late-stage development. We think we're almost there. You'll remember that we advanced 2.5s cautiously because we wanted to be sure that we had sufficient safety information to know what we were doing, certainly with the data that we have on the antrum receptor. And in muscles in animals and hopefully in man, we think we're getting the performance out of 2.5 that we hoped. From animal data we know that 2.5 and LICA combine and can give us doses that we project to be in the 1 milligram per week range.

So we're moving fast now that we're confident that the technologies work and the drugs are safe. With regard to Factor XI, we have taken a very close look at the ongoing phase 2 trial in patients with renal failure and we've seen no significant serious platelet declines at all. We're confident that Factor XI RX is behaving well. You'll remember that in the phase 2 experience in more in, I think, a little more than 300 patients if I remember correctly, we fully anticoagulated patients before they had total knee surgery and we saw no increase in bleeding of any sort.

Again, that is a great comfort to us as well. Then on nusinersen, I think I would refer you to the last update of the open label study that we gave. Obviously we haven't updated that very recently, but those data gave me a great deal of encouragement. And certainly everything we're hearing from the field and everything else that we see certainly encourages us to believe the benefit that nusinersen is bringing to infants will be seen again or similar, in patients with the older children with the type 2 disease. And Lynne, you want to comment on regulatory and label?

Lynne Parshall

Sure. You'll remember that we have data, as Stan pointed out, from our open label study in children. Those data will be included in our nusinersen filing. We're also having discussions, Biogen is, with regulatory agencies, as we said and our last conference call, to identify ways that we may be able to accelerate CHERISH. We and Biogen are both very committed to making this drug as broadly available as possible, as rapidly as possible. That being said, of course, it's much too early to comment on exactly what the label will be and looking forward to having those dialogues with the regulatory agencies.


Our next comes from Eric Schmidt from Cowen. Please go ahead.

Eric Schmidt

Just another quick one for Lynne on nusinersen. Clarification on the CHERISH trial. You guys at Ionis are continuing to conduct and finish that trial? And Biogen's now picking up the tab on an ongoing basis? Is that how that works?

Lynne Parshall

Yes. We're. They been paying for our work on that study all along and we will finish that study up. We're transitioning a variety of activities to Biogen. We've got a good and detailed transition plan that transitions some things sooner and other things later, to deal with resources and ensure that we're being as effective and efficient as we can in bringing all of this stuff to conclusion.

Eric Schmidt

And if there were to be an interim analysis of the CHERISH trial, much like ENDEAR, I guess that would be a decision that you would make jointly with Biogen and the FDA would have input in that as well?

Lynne Parshall



Our next comes from Stephen Willey from Stifel. Please go ahead.

Stephen Willey

I know that there's been -- it's just a quick question on nusinersen -- I know there's been some prior mention on prior calls regarding some of the work that Biogen's been doing regarding the petitioning of states in an effort to get SMA on the newborn screening panel. Wondering if you can talk about where those efforts currently stand and if you would expect the vast majority of states to be screening at launch. And then I have a follow-up. Thanks.

Lynne Parshall

I think we need to let Biogen comment on that.

Stan Crooke

Yes, I would simply add that I think the key to all of this is always data. You'll recall in our experience in the infant study, the earlier we treated, the better the chance for the drug to work. And so I think a key study that's in progress that Biogen is conducting is the NURTURE study which is treating -- trying to identify patients and treating then pre-symptomatically. I think there will be data to encourage earlier identification of patients, I hope, when that study is finished. Beyond that, I would say that's a question you should ask Biogen.

Stephen Willey

And then with respect to DNPK, I know that's going to be a data read-out that's been flagged for the back half of this year. As we get close to that, wondering if you could provide a little bit of color around what kind of interim data we should be expecting out of that study? Thanks.

Stan Crooke

Yes. Of course safety. And pharmacology, what we're doing is looking at reduction of the target and then using muscle biopsies. And then changes in splicing that would be predicted to occur if muscle bine were working. You'll see some pharmacology. I don't think the study's long term enough that you should expect to see substantial changes in muscle performance. But our key test is whether we get the molecular effects that we would expect based on biopsies of muscle.

Stephen Willey

And then I believe that there was a high dose that was added to that study fairly recently. Will we be getting some of that pharmacology and biopsy data out of the high-dose cohort as well?

Stan Crooke

You'll get up to 600 milligrams, if I remember correctly, Steve.


Our next comes from Yale Jen from Laidlaw. Please go ahead.

Yale Jen

Again, get back the nusinersen. I understand the neutral study will be conducted by Biogen. But given that the potentially type I patient and earlier will be most vulnerable, would you be able to provide any updates in terms of current progress of that study? And any color on that?

Lynne Parshall

Sure. The NURTURE study is right on track and Biogen will be providing data updates as we go through the year.

Yale Jen

Just one more question here. You have a drug for the FGFR4 for the [Technical Difficulty] data could be reported this quarter. Trying to get a little bit color in terms of what should we anticipate and maybe tell us a little bit more about the rationale as well as mechanism of actions and why this one may work in this indication?

Stan Crooke

Yes, the notion of FGFR4 was fundamentally to increase another factor FG, FG19, I think it is. The idea behind it then was to drive a shift into greater energy utilization in tissues. The only drugs that have been found to be able to do that in the past are, of course, thyroid. And no one has ever figured out how to make a thyroid egg that didn't produce significant tachycardia.

So that's the idea and it was a long shot. It remains an idea that's challenging and there are many challenging aspects to it. One of them is just how do you study it? The results that we'll be showing are from a study done at a single center in which they have metabolic chambers and can actually measure oxygen consumption and energy utilization and a whole bunch of very precise measures.

So what we'll tell you about is whether we saw any signal in that study that's sufficient to warrant going forward with the drug. The signal we need to see is a significant change in the way energy is used and oxygen consumption. That's what we'll be looking at.


Our next comes from Jessica Fye from JPMorgan. Please go ahead.

Unidentified Analyst

This is Ryan on for Jess. I appreciate you taking our questions. Maybe a financial question. With transitioning the new nusinersen program to Biogen, is there a potential that we could see a little bit of lower R&D spending in the second half of this year?

Beth Hougen

As Lynne mentioned, we're going to be executing on the transition plan with Biogen over the course of the next several months. So I would not expect to see a reduction in our R&D spend during the transition period. Probably you'll see that reduction next year, early next year. But just as a reminder, Biogen, as they always have, continues to pay us for the work that we're conducting, to cover all of the costs of that work plus a little bit of extra on top of that.

Stan Crooke

In the next -- between now and the middle of next year -- we'll wrap up phase 3 studies on volanesorsen and IONIS-TTR RX, in addition to our wrapping up right now phase 3 work on nusinersen. Doing multiple phase 3 trials on multiple drugs has certainly been challenging and also costly. So there will be lots of changes next year. We're just beginning to look at next year's numbers now. Certainly, there's a significant change in the workload that we'll be experiencing in terms of phase 3 effort.


Our next comes from Salveen Richter from Goldman Sachs. Please go ahead.

Salveen Richter

I just wanted to confirm with regard to CHERISH, that you do not have an interim analysis planned currently? And then with regard to the Hammersmith motor function endpoint in the study, how do you manage for the heterogeneity of the type II patients in the 2 to 12 year range when you're looking at -- that you're enrolling when you're -- when you're looking at a walking endpoint here? And then just another follow-up, but with regard to the Factor XI data we're seeing by year end, will we only see safety data here? Thanks.

Stan Crooke

With Factor XI you will see safety data and I believe that we'll probably report Factor XI reduction. The most important set of questions that we wanted to ask in this study was, in such patients as these, what is the dose that we're going to want to use going forward into broad studies? Because we don't believe that we will need 300 milligrams. So from our perspective, an outcome for the study that we're driving toward is to help us pick a dose. And that dose, I believe, will be meaningfully lower than 300 milligrams.

With regard to the CHERISH study, I'll answer part and then Lynne can answer the rest. Remember that in the open label study we divided patients into those that are ambulatory and those are not. The Hammersmith motor was used in the non-ambulatory patients. And that's what it's designed for. The six minute walk test was used for the ambulatory patients. Lynne, maybe you can take the rest of the questions on that.

Lynne Parshall

Sure. With regard to an interim analysis for CHERISH, what I can say about that is, as we've said, we're exploring all possible opportunities to accelerate that study. Certainly an interim analysis would be one possible way that we could do that. And to amplify on what Stan said about Hammersmith, our open label study included both type II and type III patients. CHERISH includes only type II patients. While we're hopeful that some of those children will get to the point of walking, we have ways of measuring that, that are built into the protocol and the analysis. But we actually have a much narrower group of children in terms of Hammersmith scores than we did in the open label study where we had a broader patient spectrum.

Stan Crooke

One of the things that we learned out of our phase 2 experience was that once there are scalable deformities, the principal problems that these patients have with their disease are really just a mechanical levels of being able to sit straight and walk and so on. A lot of that was built into the study design.


Our next comes from Michael Schmidt from Leerink Partners. Please go ahead.

Varun Kumar

This is Varun Kumar on behalf of Michael Schmidt. Thanks for taking my question. I have a question on the quick timeline update for APOA and HBV programs that uses LICA platform. Can you, specifically for HBV, tell us when should we expect to see first antigen reduction data from the patient?

Stan Crooke

You'll remember at R&D DAy, we showed data from three different LICA programs that confirm that somewhere around 5 milligrams per week would be the ID 50. We've never specifically identified HBV. We've called it, I think, a GSK number, right, Wade?

Wade Walke

We recently revealed that target.

Stan Crooke

Was it HBV that we showed at R&D Day, then?

Wade Walke


Stan Crooke

It was another one. The data are going to be similar.


[Operator Instructions]. Our next comes from David Lebowitz with Morgan Stanley. Please go ahead.

David Lebowitz

Given that the open label phase 2 trial did include SMA3 patients and the CHERISH does not, what is your strategy on eventually potentially adding SMA 3 patients to a label?

Stan Crooke

We think all patients with spinal muscular atrophy should benefit from nusinersen. Those kinds of decisions are now in Biogen's hands fully. Again, we look forward to continuing development of nusinersen long after its initial commercial encounter. Lynne, do you want to add anything?

Lynne Parshall

Yes. I agree with what you said. I would just say Biogen is very committed to making the drug as broadly available to patients with spinal muscular atrophy over time.

David Lebowitz

Are any of the current trials in the works set up to be able to include enough SMA 3 patients for that purpose? Or would have to be a new trial?

Lynne Parshall

Our ongoing Phase 3 study does not include patients who, when they enter the trial, are type III patients.

Stan Crooke

And I think that brings us to the end of the questions. So I want to thank everyone for their attention. To sum up, the next few months are going to be consumed by intense activities to bring nusinersen forward as rapidly as possible for as broad a group of patients as possible. And to finishing up the phase 3 work that we have on IONIS-TTR RX and volanesorsen. As we discussed, the rest of the pipeline is moving forward in a solid way and we look forward to giving you updates about all those things in the coming months.


The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Copyright policy: All transcripts on this site are the copyright of Seeking Alpha. However, we view them as an important resource for bloggers and journalists, and are excited to contribute to the democratization of financial information on the Internet. (Until now investors have had to pay thousands of dollars in subscription fees for transcripts.) So our reproduction policy is as follows: You may quote up to 400 words of any transcript on the condition that you attribute the transcript to Seeking Alpha and either link to the original transcript or to All other use is prohibited.


If you have any additional questions about our online transcripts, please contact us at: Thank you!