Biogen Inc (BIIB) 2016 Q3 法說會逐字稿

Good morning. My name is Dan, I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen third-quarter 2016 financial results and business update.

(Operator Instructions)

I would now like to turn the conference over to Matthew Calistri, Senior Director of Investor Relations. You may begin your conference.

Thank you, Dan. Welcome everyone to Biogen's third-quarter 2016 earnings conference call. Before we begin, I encourage everyone to go to the Investor section of Biogen.com to find the press release and related financial tables, including a reconciliation of the GAAP to non-GAAP financial measures that we'll discuss today. Our GAAP financials are provided in Tables 1 and 2, Table 3 includes a reconciliation of our GAAP to non-GAAP financial results. We believe non-GAAP financial results better represent the ongoing economics of our business and reflect how we manage the business internally.

We have also posted slides on our website that follow the discussions related to this call. I would like to point out that we will be making forward-looking statements, which 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 discussed in our SEC filings for additional detail.

On today's call, I am joined by: our Chief Executive Officer, Dr. George Scangos; Dr. Michael Ehlers, EVP of Research and Development; our Chief Commercial Officer, Michel Vounatsos; and our CFO, Paul Clancy. We'll also be joined for the Q&A portion of the call by our Chief Medical Officer, Dr. Al Sandrock. Now, I'll turn the call over to George.

Okay, thanks, Matt. Good morning, everyone. Thanks for joining us today. I'm happy to say, Biogen delivered another solid quarter, complete with strong financial performance and significant advancements in the pipeline. Through the third quarter of 2016, Biogen generated a record $3 billion in revenues, 6% increase from the same period a year ago. Our GAAP earnings were $4.71 per share, a 13% increase versus Q3 last year. Non-GAAP earnings were $5.19 per share, a 16% increase.

I'll come back to the financials in a minute, but first, I'd like to highlight some of the important third-quarter pipeline progress. One of the most exciting milestones this quarter was the positive interim analysis of nusinersen in the ENDEAR study. Recognizing the tremendous need in the SMA community, we moved quickly to establish the expanded access program and completed the NDA filing with the FDA in less than two months. The fastest filing time in Biogen's 38-year history.

We continue to be grateful to the patients, families, investigators and employees who have worked tirelessly to bring this program to this point. We've also filed with the EMA, where nusinersen has received accelerated assessment status. If approved, nusinersen would be the first treatment for patients with spinal muscular atrophy, a leading genetic cause of death in infants.

We were honored when one of our key pipeline programs was featured on the cover of Nature. Specifically, the results of our preclinical research and Phase 1b study of Aducanumab. This rare distinction was a first for Biogen research and one that I think further highlights the important work that we are doing in the area of Alzheimer's disease. We also announced that Aducanumab was going to Fast Track designation by the FDA.

Our commercial business continued to deliver solid results this quarter. We furthered our leadership in MS through the launch of ZINBRYTA in collaboration with AbbVie. We continued to grow the number of patients benefiting from our full portfolio of MS products. Our third-quarter hemophilia revenues grew to $217 million. We made further progress with the spin-off of our hemophilia business into a separate independent publicly traded company known as Bioverativ, with the initial filing of the Form 10 in August. We continue to expect to complete that transaction in early 2017.

In Europe, we doubled our biosimilars revenues over the prior quarter, as BENEPALI continues to launch in markets across the continent and pick up share at a rate previously unseen for a biosimilar anti-TNF. We launched FLIXABI, our biosimilar of infliximab. We continue to believe work in biosimilars is an important growth opportunity for Biogen. So we've seen great progress in both our pipeline and our commercial portfolio during the quarter.

As you will hear shortly from Mike and Michel, our entire executive leadership team is focused on driving commercial performance, prioritizing our assets, advancing our clinical programs and reshaping our pipeline. Our 7,000 employees globally remain committed to delivering therapies that we believe can make a positive difference in the lives of patients. I will now turn the call over to Mike, so that he can give you a thorough update on our pipeline.

Thank you, George. Good morning, everyone. Let me provide some highlights from this quarter, starting with multiple sclerosis. Last month at ECTRIMS, we presented clinical findings from our broad portfolio of MS therapies, as well as top-line results for opicinumab, or anti-LINGO, a potential neural reparative therapy for people with relapsing forms of multiple sclerosis. We presented real-world data and clinical evidence showing that TECFIDERA consistently demonstrates strong efficacy by reducing MS disease activity in patients that have had up to nine years of treatment.

These data also affirmed TECFIDERA's well-characterized safety profile. Importantly, we believe these findings provide additional support for the early use of TECFIDERA to improve patient outcomes. Data were also presented for ZINBRYTA, our newly launched once-monthly, self-administered, subcutaneous treatment option for relapsing forms of MS. A new post hoc analysis from the pivotal DECIDE study showed that a significantly greater number of people treated with ZINBRYTA showed no evidence of disease activity compared to those taking intramuscular interferon.

Additional new interim data from the long-term extension study EXTEND show that treatment with ZINBRYTA had long-term benefits in the proportion of patients who remained relapse free, as well as those who did not experience 24-week confirmed disability progression. For opicinumab, we presented top-line results from the Phase 2 SYNERGY study in MS, in which opicinumab missed the primary endpoint. However, we believe the robust design of the study has allowed us to identify an appropriate patient population and dose to move forward with development.

Within the 10 mg/kg dosing arm of the study, we identified a treatment effect in patients whose MRI scans had specific features suggesting evidence of reduced myelination and intact axons at study entry. This subset represented approximately one-quarter of all patients in the SYNERGY study. Based on these data, we hypothesize that patients with similar features may have the potential to benefit from treatment with opicinumab. We're in the final stages of designing the next study and look forward to providing an update in the coming months.

Turning to another late stage asset, we made significant progress advancing nusinersen this quarter. As George highlighted, in August, Biogen and Ionis announced that we met the pre-specified primary endpoint upon interim analysis of ENDEAR. In the analysis, patients with infantile onset SMA or SMA consistent with Type I, who were treated with nusinersen demonstrated a highly statistically significant and clinically meaningful improvement in the achievement of motor milestones, as measured by the Hammersmith Infant Neurological Examination. The responder analysis looked at achievement of tangible milestones like kicking, head control, rolling, sitting, crawling, standing and walking.

We believe the results provide a real demonstration of the value nusinersen could bring for patients and their families. Data from the other endpoints analyzed were also consistently in favor of the treated infants. The ENDEAR study remains ongoing and will be stopped once enrolled patients complete their next office visit. But it is anticipated to happen for all patients before the end of the year. Once this occurs, we will be able to provide more detailed efficacy data, including an analysis on survival.

During the quarter, we also successfully completed the rolling submission of a new drug application to the FDA for nusinersen. The US filing was submitted less than two months after the positive interim analysis of the ENDEAR trial, a significant accomplishment for the Company in recognition of the urgent need in this community.

We've apply for priority review, which if granted, will shorten the review period for nusinersen following the Agency's acceptance of the filing. Earlier this month, we also filed the marketing authorization application to the European Medicines Agency. The EMA's committee for medicinal products for human use has granted nusinersen accelerated assessment status, which also can reduce the standard review time. We look forward to working with both agencies over the coming months to bring this treatment to patients as quickly as possible.

For nusinersen, our regulatory submissions are comprised of results from the pre-specified interim analysis of ENDEAR, as well as all other clinical and preclinical data currently available, including open-label data in both Types 2 and 3 SMA patients. We're seeking a broad label for the treatment of SMA in our current filing applications in the US and the EU. Our other randomized placebo-controlled Phase 3 study, CHERISH, in children with later onset SMA consistent with Type 2, was fully enrolled in March this year and remains on track for completion in the first half of 2017.

Earlier this month, we presented additional data for nusinersen at the 2016 World Muscle Society Congress in Granada, Spain. The presentations including safety results from the interim analysis of the Phase 3 ENDEAR study, which demonstrated a favorable safety profile. Analysis of the ongoing Phase 2 open-label study, NURTURE, demonstrated a positive effect in genetically diagnosed and pre-symptomatic SMA infants.

In the NURTURE interim analysis, all 13 infants have demonstrated increases in mean Hammersmith Infant Neurological Exam scores over time. No infants have discontinued, withdrawn from the study or reached the primary endpoint of death or respiratory intervention in patients who have been enrolled for a minimum of 64 days and up to 13 months.

A recent analysis of data from the CS2 and CS12 open-label studies in patients with later onset SMA, which included both Type 2 and Type 3 patients, was also presented at World Muscle. The data showed that children with SMA treated with nusinersen exhibited improvements on several measures of motor function for up to nearly 3 years. These results are in contrast to the stable or slow decline in scores typically observed in patients with later onset SMA over time. We continue to be encouraged by the consistently positive results for nusinersen, which we believe support is benefit in SMA.

Now turning to Alzheimer's disease. During the quarter, a number of exciting developments occurred for our lead candidate Aducanumab. As George mentioned, results from preclinical research in the Phase 1b study of Aducanumab were published in Nature, a significant achievement for the program and recognition of Biogen's high-caliber science. Aducanumab was granted Fast Track designation by the FDA, an important step in bringing this potential therapy to patients as quickly as possible.

In a recently completed interim analysis from the Phase 1b study, which included the titration cohort, Arms 8 and 9 and a portion of the long-term extension study, efficacy and safety were consistent with results previously reported and support the design of the ongoing Phase 3 ENGAGE and EMERGE studies. The data from both the titration cohort and a portion of the long-term extension study of PRIME have been accepted to the 9th Clinical Trials of Alzheimer's Disease meeting in San Diego. We look forward to sharing additional safety and efficacy data with you in December.

We're also making important progress across our pipeline. We continue to shape our R&D engine for the future. Last year, we announced an agreement to license amiselimod, an oral sphingosine 1-phospate receptor modulator from Mitsubishi Tanabe. Since announcing the license agreement, we assessed the compound for a number of autoimmune indications, with a particular interest in inflammatory bowel disease. As we prioritize our strategic objectives and the IBD landscape continues to evolve, we've decided to discontinue our current development plan for amiselimod.

As we mentioned last quarter, we generated encouraging Phase 1 data on BIIB059 or anti-BDCA2 for lupus. The anti-BDCA2 Phase 1 study included both healthy volunteers and a cohort of 12 lupus subjects. We anticipate presenting these data at ACR next month, including results from the lupus cohort. A Phase 2 study evaluating the efficacy and safety of BIIB059 is underway with the first subject dose this month.

We're also working to advance BIIB074, a novel investigational state dependent subtype selective sodium channel blocker for neuropathic pain. We have initiated an open to enrollment of Phase 2b trial for lumbosacral radiculopathy, also known as sciatica. We're also close to completing enrollment in a small exploratory Phase 2a study in erythromelalgia. We're working toward initiating a Phase 3 study in trigeminal neuralgia in 2017.

BG00011 or STX-100 for Idiopathic Pulmonary Fibrosis is enrolling its final cohort in a Phase 2a study. We expect to present the data after the trial completes in the second half of next year. BG00011 blocks alpha-v-beta-6 integrin, which is selectively up-regulated in epithelial cells and fibrotic conditions, such as IPF and is known to be a key mediator of TGF-beta activation. We believe early safety and biomarker results from this study evaluating BG00011 and IPF patients are encouraging.

In summary, we continue to make strong progress across our pipeline. We're working aggressively to optimize and reshape our R&D activities, focusing resources to rapidly advance assets that present the greatest opportunity and address unmet need. With that, I will now pass the call to Michel.

Thank you, Mike. This is a solid quarter for our MS business. Our portfolio of MS therapies delivered revenues of $2.3 billion, an increase of 3% versus Q3 last year and 2% versus Q2. Excluding the impact of foreign exchange, MS revenues increased 5% versus Q3 last year and 2.5% versus Q2. Biogen maintained its global leading market share of 38% and remains the leader for both newly diagnosed and switch patients representing the dominant portion of the MS market. As I communicated during our last call, the commercial organization is now focusing on four key opportunities: portfolio strategy, commercial excellence, medical leadership, trust and value.

Since the beginning of Q3, we are now in execution mode, especially for MS in the US. With portfolio strategy, we have progressed and now identified our prioritized growth opportunities for now and 2017. It is all about making hard choices, driving consistency in resource allocation and following through with tactical plans and execution. With commercial excellence in the US, we have piloted and defined a specific engagement model with key MS centers. The rollout is expected to be completed by year end. Additionally, we are currently enhancing our sophistication in multi-channel marketing with a strong focus on digital execution capabilities.

We need to meet our customers where they are, defined by the customer journey, to provide a seamless and differentiated Biogen engagement experience, whether through direct, digital or other media. These are important steps, not only to improve performance in the short term, but also towards the creation of the new go-to-market model that is more effective and at a lower cost. In terms of medical leadership, during the third quarter, our R&D colleagues have identified several key opportunities as to how to improve MS care today.

We believe we have the opportunity to bring to use regular and quantitative measurement of disease progression, including cognition and imaging. In addition, we just launched our MS Paths initiative that we believe will create a standardized high-quality data repository from a very diverse real world patient population in the US and EU. We believe this will open new and differentiated engagement opportunities with major MS clinical centers in the US and in Europe.

Finally, trust and value. We are developing, beyond the pill, solution that we believe will meet customer's day to day needs in living with or treating MS. We are working on establishing the leading ecosystem for patients and providers to improve patient outcomes. We believe that Biogen is the only Company that has the position and commitment to MS to be able to provide this level of support in a trustworthy and valuable way.

Across these four priorities areas, we have well-defined plans and as I said, since early Q3, we are now in execution mode. Delivering on those well means enhancing the phenomenal capability of the commercial operation at Biogen. These priorities are intended to not only drive performance for our in line products, but also to prepare the organization for current and future product launches.

Turning to MS performance. In the US, the overall MS market has experienced a 2% decline in commercial patients versus Q3 last year. While in Europe, the market continues to grow with a 7% increase in patients versus Q3 last year. For TECFIDERA, global market share has increased by approximately 1 point to 15% versus Q3 last year. In the US, we have a stable TECFIDERA performance. TECFIDERA continues to capture roughly half of all patients starting on an oral, with a current oral share of 51%.

Overall patient share remains relatively stable at 20% since the beginning of the year. This is a clear leadership position for all three metrics. In Europe, there are approximately 65,000 patients on TECFIDERA, an increase of approximately 30% versus Q3 last year and approximately 4% versus Q2. TECFIDERA is now the most prescribed MS therapy in Germany, France, the UK and Italy, with more of the key launch market continuing to drive patient growth.

We do aspire to restore growth to the more mature markets. We are very pleased to see early indicators that TECFIDERA gained share this quarter in France, following two quarters of flat performance. Over the past year, TECFIDERA has seen steady incremental share gains globally, as it continues to add patients driven by increased share in the US as well as in the emerging markets. As we continue to see a shift towards increased use of high-efficacy therapies, we believe TYSABRI is benefiting from growing first line in the US.

In Europe, we are also encouraged by the recent update extending the indication for TYSABRI and allowing physicians to better optimize risk management based on JC virus antibody index values. Following the EU label approval, we have also received similar label updates in Japan, Canada and Switzerland. Our interferon therapies continue to play an important role amongst the injectable portion of the market. We believe PLEGRIDY is helping to slow the decline of our interferons, though it does not completely compensate for the loss of our next patients.

In collaboration with AbbVie, we launched ZINBRYTA in August in the US and Germany. We just recently obtained approval in Australia. We believe the launch of ZINBRYTA comes to the right time as we see a trend towards increased use of high efficacy products with both current therapies and future entrants. While early in the launch, we are encouraged by the level of physician and patient interest in the strong product profile.

In the US for example, over half of our targeted physicians have completed enrollment on our rents program, enabling them to begin prescribing. These are early data, but we see indications that we are capturing many switching patients who otherwise might not have chosen a Biogen product. So it appears that our positioning and execution is working. Looking forward, we expect to receive reimbursement for ZINBRYTA in all the major European markets within the next 12 to 18 months.

So over all, we had a solid performance this quarter across our MS business, despite a recent slowdown in the overall MS commercial market in the US. We are also very excited about the continued progress of our biosimilar business. BENEPALI is now available in 13 countries. In most markets we are seeing a conversion rate superior to the first infliximab biosimilar launch in Europe, with up to 60% to 80% conversion in markets such as Norway or Denmark. With BENEPALI, we believe we are able to compete beyond price. We're seeing a strong preference for the BENEPALI auto injector versus that of the originator. With our research indicating that 86% of the nurses prefer our device.

We recently also launched our infliximab biosimilar, FLIXABI, which is now available in Germany, the UK and the Netherlands with three additional countries anticipated in Q4. We believe our ability to potentially be the first Company to offer all three major anti-TNFs in Europe could put us in a position of strength in the market. We believe biosimilars are an important growth opportunity for Biogen as we work to optimize our engagement with stakeholders across the healthcare system.

In summary, we had a very productive quarter across our MS business in terms of performance. We are encouraged with our new product launches, and we see clear progress as we work hard to elevate our commercial execution capabilities to new levels and as we improve our go-to-market model. Also, we are particularly excited about the potential to soon launch nusinersen for SMA. With approximately 20,000 patients across the US, Europe and Japan, and no available treatments today, we believe nusinersen represent a significant opportunity for both Biogen and more importantly for the patients who today have no treatment option. With that, I turn the call over to Paul.

Thanks, Michel. In the third quarter, our GAAP diluted earnings per share were $4.71, a 13% increase versus Q3 last year, while our non-GAAP diluted earnings per share were $5.19, an increase of 16%. Total revenue for Q3 grew 6% versus Q3 last year to approximately $3 billion. Global third-quarter TECFIDERA revenues were $1.034 billion, an increase of 10% versus Q3 last year. This included revenues of $845 million in the US, an increase of 12% versus Q3 last year and $189 million outside the US, an increase of 3% versus Q3 last year. In the US, we believe TECFIDERA benefited by approximately $40 million to $50 million versus Q2 due to inventory build in the channel.

Outside the US, Q3 TECFIDERA decreased by $17 million versus Q2, largely driven by parallel trade dynamics. Versus Q3 last year, foreign exchange and hedge impact weakened TECFIDERA revenues by approximately $17 million. Interferon revenues including both AVONEX and PLEGRIDY were $708 million during the third quarter, a decrease of 10% versus Q3 last year. This included $506 million in the US and $203 million in sales outside the US. In the US, we believe there was a drawdown of AVONEX inventory in the wholesale channel resulting in approximately $10 million versus Q2. Outside the US, foreign exchange and hedge impact weakened interferon revenue by approximately $20 million versus Q3 last year. TYSABRI worldwide revenues were $515 million this quarter, an increase of 7% versus Q3 last year. This included $301 million in the US and $214 million outside the US.

Outside the US, TYSABRI revenue benefited by $20 million due to a favorable adjustment to our discounts and allowances. Foreign exchange and the hedge impact weakened TYSABRI revenue by approximate $16 million versus Q3 last year. Our hemophilia products continue to perform well this quarter. ELOCTATE revenues for the quarter were $132 million, an increase of 46% versus Q3 last year. This includes $110 million in the US and $22 million outside the US. ALPROLIX revenues in Q3 were $85 million, an increase of 30% versus Q3 last year, including $67 million in the US and $19 million outside the US. Our biosimilar business generated $31 million in revenues this quarter, driven primarily by BENEPALI.

Turning to our anti-CD20 revenues, which include our profit share for Rituxan and Gazyva in the United States, as well as our profit share and royalties on sales of rituximab outside the US. We recorded $318 million for Q3, a decrease from Q2 driven by a reduction in inventory from the second quarter. Total other revenues, which include revenues from collaboration relationships, royalties and contract manufacturing were $99 million in the third quarter. The increase versus Q2 was related to contract manufacturing for a strategic partner, slightly offset by a $13 million loss in our AbbVie collaboration profit share.

Now turning to the expense lines on the P&L. Q3 GAAP cost of goods sold was $417 million or 14% of revenue. Non-GAAP COGS was $396 million or 13% of revenue. The increase versus Q2 was primarily attributable to a mid single-digit royalty on US sales of both AVONEX and PLEGRIDY. Q3 GAAP and non-GAAP R&D expense was $529 million or 18% of revenue. Both GAAP and non-GAAP R&D expense included a $75 million payment to Ionis related to the exercise of our opt in right to develop in commercialized nusinersen globally.

I would like to note that our collaboration partner Eisai has stated their goal to start a Phase 3 trial for E2609. A $50 million milestone payment is expected to be triggered once the first patient is dosed in the E2609 Phase 3 trial. There's a potential chance they could dose the first patient by the end of this year. The $50 million milestone was not considered in our midyear 2016 R&D guidance. Q3 GAAP, SG&A expense was $463 million. Q3 non-GAAP SG&A expense was $461 million or 16% of revenue. Other net expense was $58 million in Q3, which includes $66 million in interest expense primarily related to our 2015 bond offering.

In Q3 both our GAAP and non-GAAP tax rates were approximately 25%. Our weighted average diluted share count was approximately 219 million for Q3, which brings us to our diluted earnings per share, which were $4.71 on a GAAP basis and $5.19 on a non-GAAP basis. We ended the quarter with $7.4 billion in cash and marketable securities, with approximately 40% of this in the United States. During the quarter, we repurchased 1.1 million shares of the Company's common stock for a total value of $349 million. So as often we had a number of puts and takes in the quarter; nevertheless, a very solid financial quarter. I will turn the call over to George for his closing comments.

Okay, thank you, Paul. I am very pleased with what we've accomplished this quarter. We delivered solid commercial performance, strong financial results and important advances in the pipeline. I am particularly excited about the direction we're heading as we finish 2016 and look forward to 2017 and beyond. As I've said, I believe we're at the beginning of a transformative era in neuro-degeneration, which could result in a new era for Biogen as well. We're already starting to see the types of discoveries that can be expected as science advances and innovative trial designs you have previously unseen results and insights.

We believe the early data for Aducanumab went to additional opportunities to invest in novel science to address Alzheimer's disease and other neuro-degenerative diseases. The insights we've gained from the SYNERGY trial are teaching us more about remylenation. We're enthusiastic about moving Opicinumab forward. The encouraging results we're seeing from nusinersen point to the possibility that there can be entirely new mechanisms and modalities for treating the many daunting diseases of the central nervous system. I'm proud to have led Biogen for more than six years now. It's gratifying to me to be in the possession to turn a high-performing organization over to a successor.

Our Board's search for a new CEO is progressing. We don't have a formal update on timing yet, but as you would expect, the opportunity to lead Biogen is generating plenty of interest. In the meantime, I am working closely with our management team as we strive to realize our goals for 2016 and kick off the busy and productive 2017. We are fortunate to have a great leadership team and a passionate group of employees who come to work every day to make a positive impact on patient's lives. I thank all of them for their hard work and dedication. Thanks to all of you for joining us this morning. We'll now open up the call for questions.

(Operator Instructions)

Eric Schmidt, Cowen and Company.

Congrats on a solid quarter. I was hoping you could talk a little bit more about the parallel trade issue associated with TECFIDERA? Is that something new? Is there anything you can do about it? Is it going to get worse in the future? Thanks.

Thanks, Eric. This is Paul. I'll try to take a crack at it. We didn't point it out last quarter, so in fairness, looking at the numbers this quarter we kind of noticed it in looking backwards. It effectively happens when a low-priced country gets extra purchasing patents and it ends up in a more higher price company. Across all of our products, we look hard at this. We tried to -- to the extent we can manage it. I don't expect it -- we haven't across the whole time in multiple sclerosis for 10 or 15 years seen this to be a big issue. But we will continue to try to manage it. I don't expect it to be a meaningful issue as we go forward over the next bunch of quarters. It could bounce around every now and then though. Thanks for the question.

Geoff Meacham, Barclays.

Congrats on the quarter. Thanks for the question. Just on the remylenation side for Mike or Al, so what are the puts and takes of finding a population for anti-LINGO versus expanding the program for BIIB061? I'm just curious if you could use lessons from SYNERGY to optimize 061 development? Or if you have to prioritize one over the other? Thank you.

Yes. Geoff, this is Mike. That's a good question. So, what I'd comment on the SYNERGY results is, we've been using that data to really look at the potential for an identified population. We think we found that. We think this is really going to inform our development of BIIB061, we're thinking about that very closely. There is reason to believe that the same population may be something we can investigate similarly with BIIB061. We think it will inform the development. That's going to be part of the plans for how we would develop opicinumab as well.

Yes, maybe I can add to that. This is Al. The subpopulation that we identified has really good biological plausibility, in other words, these are patients who have evidence of impact axons. They have evidence of demylenation. This make sense to us that the drugs -- both of these drugs would work better in this population. That's why we're encouraged by these results.

Geoffrey Porges, Leerink Partners.

I just want to throw a few questions in on nusinersen. First, what would be the earliest that you would be in the position to actually launch the product if the FDA acted with the speed that they have acted on some other recent applications for higher [indications]? Secondly, could you give us a sense of the number of patients continuing from the trials on an open-label basis? Also the number of patients in the expanded access program? When you would expect those to be converted to the commercial patients?

Then lastly, you mentioned the 20,000 patients with SMA in North America, Europe and Japan, but what proportion of those do you consider to be really addressable with the label that you are filing for? Is that the population under 10? Or infant onset? Or is that just all -- the different forms of SMA? Thanks. Sorry, for the multi-part question.

Okay, Geoffrey, this is Mike. I'm going to start and then we're going to tag team that -- the multi-part question here. Hopefully, we will remember each of the parts.

We may need all members of the management team to address this (laughter).

Chime in. So first of all, on the filing, I do want to emphasize that we have submitted the file. We've applied for priority review. We haven't heard back on a determination of that. That will obviously dictate when we will get approval for that in the US. Similarly, the accelerated assessment application we have in Europe, again, that would potentially reduce the review time. But we are expecting that filing to be validated in the coming weeks. So there's some timing dependence on regulator acceptance of this priority review and accelerated assessment.

With that, I'm going to let Michel talk about the launch based on that. But let me address a couple of the other things you mentioned. Our extended access program is active. We've got patients who are receiving drug. This is obviously country by country specific in how they are administering it. It's an ongoing work in progress. That program will really be relevant during this period, while we are filed, but before we've got approval. We anticipate that is going to be a small number of patients that we can get in the relevant countries based on the criteria establish in our expanded access program.

On the incidence and prevalence and the label, what we would say is, this is 20,000 patients prevalence today in the US, Europe and Japan. SMA as a whole has an incident of about 13,000 patients a year across those roughly. The data that we have submitted were from the interim analysis of ENDEAR. These were Type I patients. We've included data across all of our studies as well as preclinical data. We are going to seek a broad label for the treatment of SMA. That obviously will be something under review. Based on that, that will determine the overall size of the patient population, which I'll also let Michel comment on when I turn it over to him.

My final comment on that would be that we expect that if successful and launched, that these prevalence numbers will increase over time to the extent that we have an impact on survival in these populations. So the label, there's a lot of open questions. We'll have to wait and see, and that is going to determine what the ultimate upside is. So Michel, maybe, I will turn it over to you on the (multiple speakers) --

Yes. Thank you, Mike. So basically the label is a question mark. The timeline is also a question mark. I had the opportunity to regulate the US operation in terms of launch readiness, and I can tell you that I'm very pleased to lead the team that is getting together, high qualified, highly committed team in order to best serve the unmet medical needs together with hopefully, a good product, that'd be the good label and approved on time. So launch readiness is there. Basically the label will determine which proportion of the current prevalence we can address at launch. So, for that, we have to wait a little bit. 20,000 patients in terms of prevalence in the geography that we have qualified, but there are many more beyond. We're also looking into that.

(Operator Instructions)

Ronny Gal, Bernstein.

So just first quickly a clarification, on the anti-LINGO, is this another Phase 2 or are you actually starting a pivotal program with that? Then my question is really on market access for multiple sclerosis in 2017. Now that those contracts have been written, can you give us a directional view at your formulary access versus 2016 and the pricing that you were able to -- the pricing environment for your products during that year?

Okay, Ron, thanks for the question. This is Mike. Then I'll probably let Al comment as well on the opicinumab anti-LINGO. We're very much in the design of Phase with this, looking at the potential of a trial. We're looking at timing. We're looking at cost. We're looking at feasibility. We don't have an answer today, but we think in the coming weeks we will have a determination about whether we conduct a Phase 2b trial or whether we look to go straight into Phase 3.

I don't have any further comment.

So, concerning the formulary access in the US, we do not comment on the way 2017 will look like. Nor on the gross to net. What I can tell you is that the organization is committed to continue to generate profitable growth. For that, we go after the cost structure. (inaudible) how we supply and how we procure our business. As I explained earlier, we are working on our go-to-market model. We don't believe the reach and frequency model that prevailed in the past is sustainable. We are basically step-by-step building a new go-to-market model. So we're working on that.

Brian Abrahams, Jefferies.

I guess a question for Mike. I was hoping you could clarify what you guys have meant by -- on the Aducanumab titration data, what you've meant by efficacy results that are consistent with results previously reported? Are you referring to imaging or cognition? Then on the safety side, when you talk about safety looking consistent with what's previously been reported and supporting the design of the Phase 3, does that suggest that the ARIA is consistent with what you're seeing? Or does it support the idea of titration potentially reducing the risk of ARIA in certain populations? Thanks.

Yes. Brian, thank you for that. By the way, these are all things which we will have a lot more to talk about at CTAD in San Diego in December. So let me comment on that. So when we say consistent with, we're referring to both imaging and functional endpoints in cognition. As you know, we've looked at before is the CDR- sum of boxes, and the MMSE, as well as amyloid PET. On the titration side and safety side, again, we will have a lot more details on this. But what I would say is, what we're seeing is consistent with what we had hypothesized around for the safety basis of Aducanumab. In other words, it is within the range of what we have seen and reported before with the Phase 1b study.

Michael Yee, RBC Capital Markets.

A follow-up on the Alzheimer's prior question. I just wanted to understand the context of the efficacy comments in particular, given that I think there are still some questions around the placebo arm. I think that you're still using partly the pooled placebo from before. So I just wanted to understand the caveats and how confident you are versus that arm? Then just a quick follow-up is, you did mention that line about MT-1303, so I just wanted to understand what happened there? Is that a commercial competition thing? Or what happened in that decision? Thanks so much.

Hi, Michael, this is Al Sandrock. The additional cohorts included some additional placebo patients. So we will show the data from the additional placebo patients as well as the placebo patients from prior cohorts. That will be shown at CTAD. The efficacy is on PET imaging as well as on the clinical cognitive assessments that we looked at previously, MMSE and CDR- sum of boxes. That will all be shown at CTAD.

So, Michael, this is Mike. I will comment on the amiselimod. This was really -- as we looked at how the landscape was evolving, both in terms of a regulatory competitive landscape, changing features there and the corresponding fit with our strategic priorities about where we could best allocate resources, based on our own expertise and competency, we just determined that this was -- that it wasn't as good of a fit as other things, which we could allocate our resources towards.

Ying Huang, Bank of America Merrill Lynch.

Just quickly, we're all anxiously waiting for the top line from solanezumab Phase 3 in December. Can you frame us, what could the read-through be for the Phase 3 program for Aducanumab? Then secondly, what's your view on the recent data from AveXis June 30 in SMA? What that could mean for nusinersen in your commercial opportunity? Thank you.

Okay, thanks for the question. I will take a stab at this and see if anyone wants to open up. First of all, I don't think we will speculate on the potential results of Lilly's solanezumab trial based on that. There are scenarios that one can envision that we are certainly taking into consideration. We very much look forward to seeing their data. A couple things I would point out on this is, although both are A-beta antibodies -- these are actually fundamentally quite different mechanisms of action. So whereas we think if there were positive results out of the solanezumab trial this would give great credence to the amyloid hypothesis of Alzheimer's disease, and I think bode well for the potential results of Aducanumab.

However, because these are fundamentally different mechanisms, we are going at is that it is far more difficult to interpret a negative result if solanezumab would find -- as we would be able to see it. We believe it will be much more difficult to make a conclusion about a negative result on solanezumab vis-a-vis the potential results of Aducanumab. On AveXis, I think, what we would comment is, look, we welcome innovative therapies for SMA. We think it's a very serious, very important disease area. We are highly committed to this disease area and to the patients and families.

We think that gene therapy as an overall approach is a viable one in spinal muscular atrophy. In fact, we're quite excited about our own internal program that we have in our collaboration with UPenn in that regard as well. So we look forward to seeing how the combination of nusinersen potentially being launched and the next-generation therapeutics that we are certainly working on will play out over time. We see great prospect for the treatment of spinal muscular atrophy.

The only thing I would add on the Alzheimer's is the population is a little different. In solanezumab, they are studying the mild patients, which makes sense, because that is where they saw some evidence of efficacy in Expedition 2. Whereas in the case of Aducanumab, we're study prodromal in the early mild patients. Then agree with everything Mike said about the differences in the antibodies.

Matthew Harrison, Morgan Stanley.

I just wanted to go back to SMA for a second again. Just trying to better understand your comments around a broad label. I guess, what data supports a label outside of SMA-1 patients? What's the rationale that you might be able to achieve a label outside of SMA-1 patients ahead of the randomized study data? Thanks.

Okay, Matthew, thanks for the question. I mean I guess I would first start by saying, we really are not going to comment on the data prospects for our label. But what I will say is that we have ongoing studies in Type 2 patients, where we are looking at the potential efficacy of nusinersen. As you know, also, we have an ongoing trial, as I mentioned, in pre-symptomatic genetically diagnosed infants. So, all of that data is data that we look to include in our filing application. From that, the extent of the label that we achieve, that will be based on the agency's review of the totality of the data and the evidence. We will present evidence based on those populations in our effort to seek a broad label. What that data is we'll be able to present at the appropriate time. Many of these studies have not completed.

John Scotti, Evercore ISI.

So on the CEO search, could you just elaborate a bit more, I'm not sure what exactly, but I know this is a big topic for investors right now. On timing, is it unreasonable to hear something by year end? Then exactly, what is the profile of the person you are looking for? Is it someone from industry, out of industry, et cetera? Then on the MS market, Michel, I had a quick question. So, you said that in the US, the volumes are declining year over year. Do you see this trend continuing? If so, is it fair to say that any growth from TEC, which stable patient share? Then, I guess, also perhaps the entire MS market as a whole, would come from price going forward? Or do you see volumes inflecting at some point? If so, what would be the catalyst? Thank you.

Okay. This is George, maybe I will comment on the CEO search first. Look, I am not going to comment on the specific timing. I can tell you that I think we all believe that the sooner we can get through this and have a new CEO come the better it is for all of us. So it's a very active search. The Board is interviewing a number of candidates. There are, as you would expect, very high quality candidates coming in and being interviewed for a variety of backgrounds actually. We will give you an update on that as soon as we can. But I don't want to comment anymore on the specific timing today.

So concerning the US market -- thanks for the question. What we have seen during the past quarters was basically a slowdown towards a low single-digit market growth in the US. What we have seen during the past months or weeks was a shift in the mix between commercial and [free] that is impacting basically the commercial units' performance. So I don't know if it's an overall market trend, but this is what we have seen internally.

What I can tell you is that TECFIDERA remains the number one priority for the organization. We have a plan, as I alluded last time, we are working based on the portfolio work that we are doing on TEC-GI. Discontinuation that remains at an average of approximately 22%. We have a good opportunity to make some inroads there because basically the scope from 5% to 35%. So there are some centers, some MS centers, where they're going to management with the right engagement and here that different type of engagements that are being practiced in the different centers.

There is no evidence yet. One can speculate that we can see a temporal association between the increase of the eosinophil and the GI [stomatology] but this was not confirmed by clinical trials because of many different confounding factors. So we work on TEC-GI. We see early signs that it's heading towards the right direction, also in Europe, but it's too early to claim any big success here. We are working on the capture list and one balanced the other, that's why we have a stable patient base.

The base of the market is certainly lower than what we have estimated in our assumptions, but it's not an excuse for not increasing share. So we do not give up. We invest. We are committed. I can tell you the team in the US is all up and running. They have piloted a new engagement model with the critical MS centers. I'm very pleased to see the perception improvement. Now we have to continue to execute and free rollout of this new plan will be towards the end of the year or by latest early January.

So we are committed. We don't give up on the large mature market where the share of TEC is relatively stable versus the latest launch markets, where we may continue to make fast inroads like in Italy, Spain or the UK. The good news is that we can turn to positive France. We continue for Germany. We continue for the US. We are committed. Thank you.

Robyn Karnauskas, Citigroup.

So just a follow-up on market trends in MS. So help us understand why do you think -- is there anything going on with the MS market? Why is it shrinking in the US? Are you seeing any people who are trying the orals and then hopping off and not getting back into the MS treatment bucket? Then on PLEGRIDY, the market -- having a certain small percentage of the market, it's interesting, but do you think you can grow that? What are you specifically doing to grow the PLEGRIDY market share? Thank you.

So thanks for the question. It's very difficult to speculate on the future trend of the market. So we have seen a couple points negative for the quarter versus prior year. This was not a situation during the prior quarters. So time will speak. We'll see over time -- but I don't believe that this will be sustained. Again, I spoke about some trends in the marketplace between commercial units being commercialized and all the channels. So we're committed to gain market share in the slower pace of the market in all our mature markets, including in the US.

Chris Raymond, Raymond James.

Just back on to SMA and nusinersen, you guys have talked about your expanded access program and moving that forward. It sounds like there's a desire here to get more patients on. We sort of ran across some social media chatter from parents that seem to be sort of complaining about at least some PI's that were looking to restrict access to this program. I wonder if you could -- it seems to be a little bit at odds with what you guys have talked about. Can you maybe comment on that? Maybe help explain what exactly is going on? Thanks.

Chris, maybe I will start there. The essence is we're not going to comment on specific investigators or specific sites around this. I would say that our expanded access program was really designed to --in cases -- at sites in countries where we were able to, with this severe disease before we are able to successfully launch, hopefully if we get a favorably review to maximize the access that we could based on criteria that were medically established at relevant sites.

A lot of that is determined at the site in the country level, they determine that. We're doing our best to ensure access in a way that makes sense, but that does not jeopardize our filing and the potential approval of this for broad access. Our hope, by the way, is that this period will be short and that we will be able to utilize the priority review and the accelerated review -- the assessment at the EMA to bring this to patients as quickly as possible, so that this EAP program can be as short as possible.

Cory Kasimov, JPMorgan.

I wanted to ask you about your broader bus-dev intentions. Obviously, you had the setback with MT-1303, but as we look forward, can you talk about your strategy here? How much you're able to act on it, if at all, while you have a CEO search ongoing? I guess is this part of the business that we should assume is on hold for the time being, until you get someone in, who can kind of take stock of the overall organization? Or are you still preceding with diligence of other companies as usual? Thanks.

No. You should not assume this is on hold. We all believe this is an important part of what we have to accomplish. We are continuing with diligence on several companies as we speak. That will continue. We will continue to work aggressively to finalize some of these issues. I think the areas in which we are interested are clear. We have a very good R&D team now, who can make the technical assessments. We have a great ability now to make the accurate commercial assessments. So we are full speed ahead.

All right, Dan, that should conclude the call for today. Thank you very much.

Thank you to everyone for attending. This concludes today's conference call. You may now disconnect.