Biogen Inc (BIIB) 2017 Q1 法說會逐字稿

Good morning.

My name is Dan, and I will be your conference operator today.

At this time, I would like to welcome everyone to the Biogen First Quarter 2017 Financial Results and Business Update.

(Operator Instructions) Thank you.

I would now like to turn the conference over to Mr. Matt Calistri, Senior Director, Investor Relations.

You may begin your conference.

Thanks, Dan.

Thank you, and welcome to Biogen's First Quarter 2017 Earnings Conference Call.

Before we begin, I encourage everyone to go to the Investor's 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 result better represent the ongoing economics of our business, and reflect, how we manage the business internally.

We've 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'm joined by our Chief Executive Officer, Michel Vounatsos; Dr. Michael Ehlers, EVP of Research and Development; 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 Michel.

Good morning, everyone, and thank you for joining us today.

I am especially pleased to welcome you to this call as the CEO of Biogen.

Before I turn to the details of the quarter, I would like to share some initial thoughts on how Biogen is positioned today, and where we see the company progressing.

We do have a differentiated expertise in neuroscience and expect this to remain our core moving forward.

We intend to maximize the potential of our R&D assets and bolster our pipeline through both internal and external opportunities.

We are focused on flawless commercial execution in our priority geographies across MS, SMA and biosimilars.

We are aligning the organization around these goals, including, building our senior management team, where we want our actions to speak louder than our words.

As you will see throughout the rest of the call, I think we are already off to a great start.

Q1 was a very good quarter financially and also a quarter with exciting events.

For the first quarter of 2017, Biogen generated revenues of $2.8 billion, a 3% increase from the same period a year ago.

On an apples-to-apples basis, when we exclude all hemophilia revenues from both periods, we grew revenues 8% from the same period a year ago.

GAAP earnings was $3.46 a share, a 22% decrease from the same period a year ago, driven by the charge we took related to our settlement and license agreement with Forward Pharma, which Paul will discuss later.

Non-GAAP EPS was $5.20, a 9% increase versus the same period a year ago.

Excluding hemophilia, non-GAAP EPS growth would have been even higher.

I am pleased with our results and achievement this quarter.

Let me highlight what we think are the key takeaways for the quarter.

First, financial performance.

We saw continued stability in our MS franchise this quarter with a 38% global market share.

MS revenues grew 3% year-over-year.

We continued to add patients globally with a 2% increase versus last quarter and a 5% increase versus prior year.

Biogen remains the global leader amongst the oral, high efficacy and interferon MS therapies.

Our SPINRAZA launch is off to a promising start, with the first quarter revenue of $47 million.

I am very proud of what our team has already accomplished, but we are still in the early days of the launch and have much more to achieve.

We will not be satisfied until all of the patients and families that seek this treatment are able to receive therapy.

This will take some time and tremendous effort from many, such as the dedicated medical teams that treat SMA, the passionate families, the remarkable advocates that rally for these patients and our team of committed Biogen professionals, all of whom have been working seemingly nonstop to secure access and building the point of care.

Our biosimilars business continued its strong trajectory and grew revenues 25% quarter-over-quarter.

Next, I want to walk -- I want to talk about nonfinancial achievement during the quarter.

First, we recently enhanced our pipeline with the announcement of the license agreement with Bristol-Myers Squibb for a Phase II anti-tau asset, which we expect to close this quarter.

We believe this transaction positions Biogen to be at the forefront of Alzheimer's research in terms of both, mechanisms of ACTION and time to market.

I am really proud to see us deliver on this deal, and we are just getting started.

And with that said, I also want to add that we are working to add more assets to our pipeline.

Second, we are very pleased with the favorable outcome of the IPR proceeding and the interference.

We believe these rulings underscore the strength of our patent portfolio for TECFIDERA.

Additionally, we believe this will give us an ability to defend against potential challenges from MMF prodrugs that deliver a similar dose of MMF.

Third, we are progressing and prioritizing our pipeline and Mike will be giving you an update.

But before I turn it over to Mike, let me provide you with more details on our commercial performance.

Starting with MS. First, we believe underlying demand for TECFIDERA remains stable in the U.S. with continued growth overseas.

We remained focused on maximizing TECFIDERA's growth potential, and we believe we are ready and well equipped to compete in an increasingly crowded market.

Second, we are very pleased with the increased demand seen for TYSABRI this quarter, in both the U.S. and overseas.

Our research indicates a consistently positive benefit-risk profile in the eyes of prescribers, and we believe physician confidence in patients management may be increasing, especially in light of updated label in Europe.

We continue to launch ZINBRYTA in the U.S. and in an increasing number of international markets.

We believe ZINBRYTA fulfills an important unmet need for patients transitioning from one of the platform or orals to a high-efficacy agent.

Overall, we maintain our global market share in MS. We are committed to resourcing and focusing the Biogen team on maintaining our position as the market leader and growing the business even with the and entrance of new competition.

Moving on to biosimilars.

BENEPALI is now available in 16 countries, with market share growing steadily particularly in Germany, the U.K. and Sweden.

We estimate, there are now 40,000 patients on BENEPALI across Europe and growing.

Now on to, SPINRAZA.

The initial underlying demand has been robust.

We noticed a solid progress in terms of both infrastructure and insurance coverage.

Infrastructure.

In the U.S., as of last week, there were 88 sites across 36 states that have administered SPINRAZA and 203 sites that have submitted start forms.

These numbers have been increasing every week.

Some leading centers are already dosing more than 10 patients, but most sites have only dosed 1 or 2 patients so far.

From a coverage and reimbursement perspective, there are now over 165 plans that have an approved individual use of SPINRAZA, 100 commercial plans and 65 Medicaid plans.

Broadly speaking, of all the commercially insured lives across the U.S., not just the ones covered by the 100 plans, I mentioned, we estimate 75% have a plan with an established policy regarding SPINRAZA and half of those have a policy with broad access.

The 65 Medicaid plans, I mentioned, span 35 states and approximately 20 of those Medicaid plans have a formal policy in place, with about half of the covered life under these policies, having a broad access.

To-date, the majority of the dosed patients are type 1 and we continue to see approval for type 2 and type 3. For plans without a policy, or with a restrictive type 1 policy, often patients still are still able to get approval through an appeal process or medical necessity request.

We will be presenting CHERISH data later today at AAN, which includes control data for patients, most likely to develop type 2 and type 3 SMA.

The FDA has already granted a broad label for all SMA patients and it is our hope, this new data will convince the payers, who have developed narrow medical policies to offer broader access to patients.

In the U.S., it continues to be our goal that no patient will forgo treatment because of financial limitation or an insurance denial.

To-date, roughly 25% of units dispensed have been provided through the free drug program.

There is plenty of attention on the launch of SPINRAZA in the U.S., but we cannot forget about the demand outside of the U.S. Our expanded access program outside of the U.S. now has 353 type 1 patients across 20 countries, of which 306 of those patients are in Europe.

And last week, the CHMP in the EU adopted a positive opinion for SPINRAZA, recommending a broad indication.

We are preparing for potential EU markets approval in the coming months.

We are also getting ready for potential approvals in Japan and Canada this year, and anticipate filing in at least 10 additional countries throughout 2017.

It is still early in the SPINRAZA launch and we have a lot more work to do to get patients who need on therapy.

So, all in all, a rich quarter with solid financial performance, stable leadership in MS, a promising launch of SPINRAZA, a steadily growing biosimilar business, progress in business development and 2 important patent victories.

I now turn it over to Mike for an update on our progress in R&D, the true engine of value creation for the company.

Thank you, Michel, and good morning, everyone.

Let me start with some broad comments on the evolution of Biogen R&D.

I am extremely excited about how we're becoming more entrepreneurial.

Our approach is to blend strong science with a medical mindset and an entrepreneurial emphasis on innovation.

We will be agnostic to whether we find innovation internally or externally.

The goal is to continue our tradition of applying our deep scientific expertise as we aim to discover and develop the very best medicines for patients.

We are laser-focused on neuroscience and value-creating adjacencies.

I believe this makes abundant sense and positions Biogen uniquely in this breaking area to leverage our leadership in multiple sclerosis, to capture broad opportunities in neuroscience.

There is arguably no bigger area of unmet medical need than diseases of the nervous system, and I believe Biogen has a tremendous competitive advantage to be the leader in this space.

The genetics of neurological disorders has exploded, yielding critical insight to the new therapeutics, and we can now measure and monitor disease states of the brain with unprecedented precision.

We believe the SPINRAZA experience provides a glimpse of the future for targeting severe neurological disease, and we aim to capitalize on this changing paradigm.

I'm now going to walk you through the significant progress we made this quarter, advancing, prioritize and building out our pipeline.

Like the amyloid pathway, we believe tau pathology is central to Alzheimer's disease and other neurodegenerative disorders.

Similar to our investments in Abeta antibodies and BACE inhibition, our commitment to tau is strong.

Earlier this month, we expanded our portfolio beyond BIIB076 and our preclinical anti-tau antisense oligonucleotide with Ionis by entering into licensing agreement with Bristol-Myers Squibb, for an advanced tau asset, BMS-986168, as Michel mentioned.

This new antibody is aimed at lowering tau and slowing progressive diseases, such as Alzheimer's disease and progressive supranuclear palsy, or PSP, a rare and devastating condition that affects movement, speech, vision and cognitive function.

PSP is currently an untreated orphan indication with a tremendous need for an effective therapy.

BMS-986168 has shown compelling clinical data, robust lowering of tau and cerebral spinal fluid and an appropriate benefit-risk profile on a Phase I study.

We plan to rapidly initiate Phase II studies in both Alzheimer's disease and PSP.

This licensing agreement reflects one of the most significant external additions to the Biogen pipeline in many years and highlights our heightened activity to seamlessly integrate business development with internal R&D.

We expect more pipeline augmentation in the coming months.

We also advanced BIIB076 into Phase I trial this quarter.

BIIB076 is a human recombinant monoclonal antibody targeting tau that was developed using Neurimmune's reverse translational medicine platform.

The study is designed to evaluate safety, tolerability and pharmacokinetics in both healthy volunteers and Alzheimer's disease patients.

We continue to advance assets targeting the beta amyloid pathway, which we believe plays a particularly important role early in the disease course.

Phase III enrollment for aducanumab is going well and we expect both ENGAGE and EMERGE will be 50% enrolled by mid-May.

We anticipate studies to be fully enrolled by mid-2018.

And we are honored, that just last week, aducanumab received SAKIGAKE designation by the Ministry of Health, Labor and Welfare in Japan.

Under the SAKIGAKE system, the target review period for designated products may be reduced from the standard review period of 12 months to as short as 6 months.

Our collaboration partner, Eisai, is progressing a Phase II study of BAN2401, a humanized anti -- Abeta antibody, which exhibits a strong binding preference for protofibrils.

We expect data from this trial by the end of the year.

Also, under our collaboration, Eisai has recently initiated the second Phase III study of elenbecestat, an oral BACE inhibitor.

Now moving to multiple sclerosis.

This week, at the 69th Annual Meeting of the American Academy of Neurology or AAN in Boston, we will be presenting over 50 presentations and posters from our portfolio of treatments in investigational therapies.

Specifically with MS, new data includes real-world evidence that supports TECFIDERA's efficacy profile, and we believe underscores the importance of early treatment.

Results showed TECFIDERA significantly reduced the risk of relapse by 30% compared to teriflunomide, in newly diagnosed patients and those previously treated with the prior disease-modifying therapy.

TECFIDERA also demonstrated comparable efficacy to fingolimod.

New data from ENDORSE, a long-term extension study, also affirmed the well-characterized long-term safety profile of TECFIDERA use for up to 9 years.

New data from the TYSABRI observational program or TOP shows treatment-naive patients who began taking TYSABRI within 1 year of symptom onset, had a significantly greater likelihood of disability improvement than those who initiated treatment later in the course of their disease.

Importantly, data also showed patients who continue TYSABRI treatment experienced better clinical outcomes than those who switched to another therapy.

Also in MS, as part of our ongoing portfolio prioritization effort, we have decided not to advance BIIB061 an oral remyelinating agent into a Phase II MS study and instead have chosen to prioritize opicinumab or anti-LINGO.

No new data on BIIB061 has driven this position.

We expect to initiate a Phase IIb study for opicinumab in the fourth quarter.

After much diligence, we believe the feasibility of running studies for both BIIB061 and opicinumab in similar patient populations would ultimately slow down development for both compounds.

We have more robust data and a greater clinical understanding of opicinumab and have thus chosen to prioritize this program.

We are exploring other indications for BIIB061 where remyelination and repair are important.

Also, as Michel noted earlier, we will present significant data on SPINRAZA at AAN this week.

We believe the overall findings continue to support the robust efficacy and benefit-risk profile of SPINRAZA, a suite of remarkable data made possible through our close collaboration with Ionis.

Specifically, later today, we will present the end-of-study CHERISH results, which we believe further demonstrate the meaningful impact SPINRAZA can have in individuals with later-onset SMA.

CHERISH was a Phase III study, designed to assess the efficacy and safety of SPINRAZA in individuals most likely to develop type 2 or type 3 SMA.

The end-of-study analysis demonstrated a statistically significant and clinically meaningful improvement in motor function as assessed by the treatment difference of 4.9 points in the mean change from baseline to month 15, and the Hammersmith functional motor skill expanded.

From baseline to month 15, individuals who receive SPINRAZA, achieved a 3.9 point mean improvement, while individuals who were not on treatment experienced a mean decline of 1 point.

Data from the other end points analyzed, including upper limb motor function and attainment of new motor milestones were consistently in favor of children who received treatment.

No patients discontinued the study due to adverse events and our results demonstrated a favorable benefit-risk profile.

This Thursday, we will present new interim data from the Phase II NURTURE study, evaluating SPINRAZA for the treatment of infants under 6 weeks old, with genetically diagnosed and presymptomatic SMA at initiation of treatment.

At the time of the interim analysis, 20 infants were enrolled for a median of 317 days, and all infants in the study were alive and none required respiratory intervention.

Additionally, most infants achieved motor milestone and growth parameter gains, generally consistent with normal development, such as head control, independent sitting, standing and walking independently.

These results are dramatically different from the known course of SMA infants with Type 1 SMA, where motor milestone achievement of any sort is absent.

In this study, no infants have discontinued or withdrawn from the study due to adverse events and no new safety concerns have been identified.

These results are encouraging and we believe continue to highlight the need for newborn screening.

Importantly, as we look to expand our presence in SMA, we are also excited about the potential for gene therapy as a complementary mechanism.

Through our collaboration with University of Pennsylvania, we plan to advance our SMA gene therapy program into the clinic by the first half of next year.

We're also working to advance BIIB074 for neuropathic pain.

We recently completed the top line data analysis of the exploratory Phase IIa study in erythromelalgia, a disease characterized by Nav 1.7 mutations.

In this study, of the 7 patients analyzed, no statistically significant treatment effect was observed for the primary or secondary endpoints and the variability and responses was notable.

No new safety signals were observed.

We are planning to initiate another Phase II study in small fiber neuropathy towards the end of this year as we continue to explore multiple potential indications for this asset.

We have previously seen compelling efficacy signals for BIIB074 in the Phase II studies of both trigeminal neuralgia and painful lumbo-sacral radiculopathy or PLSR.

Results for trigeminal neuralgia were recently published in Lancet Neurology.

We continue to enroll the Phase IIb PSLR study with data expected next year.

For trigeminal neuralgia, we now intend to initiate the Phase III studies simultaneously in the U.S. and Europe.

As a result, we now expect patient enrollment to begin in 2018.

Lastly, in our effort to develop new therapies for neurologic diseases, we believe there is opportunity in stroke.

We expect the follow-on Phase IIb dose-ranging study for natalizumab and acute ischemic stroke ACTION 2 to be fully enrolled this year and hope to show the results shortly thereafter.

We're making good progress advancing our early clinical pipeline with 13 programs in Phase I or Phase II development.

I look forward to sharing updates on these programs as they progress.

Overall, I'm very excited about our pipeline.

Well good is never good enough, we'd like to see more later-stage candidates.

We aim to continue prioritizing the most promising assets, while looking externally to expand our pipeline.

With that, I will now pass the call to Paul.

Thanks, Mike.

Our GAAP diluted earnings per share were $3.46 in the first quarter.

GAAP EPS was negatively impacted by $1.22 related to the settlement and license agreement with Forward Pharma in the U.S. PTO ruling in favor of Biogen in the interference proceedings.

Our non-GAAP diluted earnings per share were $5.20 in the first quarter, an increase of 9% versus prior year.

Total revenue for Q1 increased 3% year-over-year to approximately $2.8 billion.

Excluding hemophilia revenues from both periods, total revenue grew 8%.

Global first quarter TECFIDERA revenues were $958 million.

This included revenues of $751 million in the U.S., an increase of 1% versus Q1 last year; and $207 million outside the U.S, an increase of 3% versus Q1 last year.

On a sequential basis, U.S. TECFIDERA revenues were negatively impacted by approximately $50 million to $60 million due to lower levels of inventory at the specialty pharmacies.

Interferon revenues, including both AVONEX and PLEGRIDY, were $648 million during the first quarter, a decrease of 3% versus Q1 last year.

This included $465 million in the U.S. and $184 million in sales outside the U.S.

TYSABRI worldwide revenues were $545 million this quarter, an increase of 14% versus Q1 last year.

This included $306 million in the U.S. and $239 million outside the U.S.

Outside the U.S., Q1 TYSABRI revenue benefited by approximately $45 million due to reaching an agreement with the price and reimbursement committee of the Italian National Medicines Agency related to prior periods.

SPINRAZA revenues for Q1, its first full quarter in the market was strong, as we reported $47 million.

SPINRAZA U.S. revenue was $46 million.

This represents very strong underlying demand combined with some natural inventory build as the launch ramps.

We estimate that less than $10 million of the SPINRAZA revenue was due to inventory that was built up in the channel in the U.S. We also had $1 million in sales outside the U.S. related to named patient sales.

Hemophilia revenues for the subperiod prior to the spinoff of Bioverativ were $74 million.

Our biosimilar business generated $66 million in revenue this quarter.

Anti-CD20 revenues were $341 million for Q1.

In total, other revenues were $90 million.

Now turning to the expense lines on the P&L.

Both Q1 GAAP and non-GAAP cost of goods sold were $385 million or 14% of revenue.

Q1 GAAP R&D expense was $423 million or 15% of revenue.

Q1 non-GAAP R&D was $421 million, also 15% of revenue, a decrease on a sequential basis as we had no meaningful milestone payments or BD activity in Q1 and as the Phase III studies for SPINRAZA wound down.

Q1 GAAP SG&A expense was $499 million or 18% of revenue.

Q1 non-GAAP SG&A was $483 million or 17% of revenue.

Both GAAP and non-GAAP other net expense was $38 million in Q1.

In Q1, our GAAP tax rate was approximately 24% and our non-GAAP tax rate was approximately 23%, which includes some modest favorability from discrete tax items related to Q1.

Our weighted average diluted share count was approximately 216 million for Q1.

During the quarter, we repurchased approximately 2 million shares of the company's common stock for a total value of $584 million.

And since March 31, we've purchased an additional, approximately 2 million shares for a total value of $543 million.

We ended the quarter with approximately $5.7 billion in cash and marketable securities, with approximately 24% of this in the United States.

As we go forward, we'll be closely watching the launch of OCREVUS.

Overall, we anticipate a negative impact to our portfolio that'll be partially offset by the royalties that we receive.

In conjunction with the recently announced agreement to exclusively license the BMS anti-tau molecule, we expect to make an upfront payment of $300 million to Bristol-Myers Squibb in the second quarter.

In the near-term, $60 million payment to the former stockholders of iPierian, these will impact both our GAAP and non-GAAP R&D expense assuming deal closure.

These amounts exceed the $100 million we earmark for business development expense in our previously announced 2017 full year financial guidance.

We plan to update our annual financial guidance on the second quarter earnings call.

I'll turn the call over to Michel for his closing comments.

Thank you, Paul.

I would like to say that 2017 is off to a strong start for Biogen, but we have much more to do.

We are refocusing the organization, and I'm building my management team.

We are all energized and are working to develop the strategy and priorities for both short-term and long-term shareholder value creation.

We plan to update you on our progress when we report our second quarter earnings in July.

But we do not wait with obvious actions to be taken to support Biogen in terms of R&D, BD and commercial.

Our actions will speak for themselves.

For July, we hope to provide you with clarity on our priorities and plan.

I aim to communicate a clear picture of the Biogen of tomorrow, a company that can meaningfully improve patient's life in the increasingly important field of neuroscience through new innovative therapies, and create long-term sustainable value for our company and our shareholders.

And I believe strongly that this is the new Biogen, a clear leader in a well-defined and fast-growing space.

We do tackle big challenges.

We are laser-focused on execution, and we aim to deliver strong results.

In closing, I'd like to thank our employees around the world, who are dedicated to making the positive impact on patients lives and all of the physicians, caregivers and participants in our clinical development programs.

The past and future achievements could not be realized without their passion and commitment.

With that, we'll open the call for questions.

(Operator Instructions) Your first question comes from the line of Eric Schmidt with Cowen and Company.

Congrats on the fine launch for SPINRAZA and the overall quality of the Q1 results as well.

My question is on SPINRAZA.

I guess, we've gone in the last 3 months from thinking the launch will be gradual to today calling it robust.

So what's going better than you expected?

Is it access to reimbursement or your ability to work through the logistical issues at the centers, or greater urgency to treat, greater demand?

Please comment.

So a couple of months ago and since the beginning actually, this is Michel, we did identify 2 bottlenecks.

And #1 was infrastructure due to the intrathecal therapy injection modalities that were not performed into the SMA known in our neuromuscular centers, and in addition the insurance coverage.

Those 2 bottlenecks remain and they will be also relevant for the other markets where we're going to launch SPINRAZA, hopefully, soon.

Having said that, motivated families, patients, parents, advocacy groups, a professional team at Biogen, dedicated providers, the leadership of the hospital and their providers were able to accommodate not as a linear fashion, some bigger centers with a certain pattern, smaller centers eventually with more speed and flexibility.

One size does not fit all, but all in all, this is where we stand today.

Your next question comes from the line of Geoffrey Porges with Leerink Partners.

And share my congratulations on SPINRAZA.

Could you give us a little more detail on the MS business, particularly the contribution of price and volume in the U.S. for the brands there.

And comment on price.

Previously, you'd said that you anticipate taking 1 price increase a year.

Is that still the company's view and something that we should continue to plan for the balance of the year?

So in the U.S., that remains our largest and stable market for which we remain fully dedicated to continue to improve the picture.

First of all, on the market dynamic, if you recall, well, I did mention in 2016, we saw a slight contraction of the market in terms of commercial goods versus the prior period.

Well, we did see that sustain during Q1 versus Q4 of 2016.

Probably and by a few percentage, nothing dramatic, one of the reasons might well be that there was a bit of warehousing due to OCREVUS.

I don't know by facts, but this might be a reason.

All in all, the assumption within the company is that the market will return to low single digit market growth for the remainder of 2017.

For Biogen business, it's a very strong defense of our performance.

And actually, I am pleased by the momentum I see in a slightly declining market of our NTRx and TRx shares and you can have a look into those.

I think that TECFIDERA defended very well.

TYSABRI rebounded.

Overall, Biogen is holding very strong, and we continue to see a slight erosion of the interferons, as expected.

So all in all, I will say a good performance that I want to see improved.

Capture rate is holding very well, slightly improving.

Discontinuation due to TEC GI did not really improve and I'm not satisfied by that, but I do not give up.

So we're working hard to improve on this figure.

But all in all, I will say it's very solid engagement, while the team has the plate full of tactical plans in order to be ready for an increased competition while we speak.

And then Geoff, this is Paul.

Just second part of your question, we understand it's an important question but -- and I know I've commented in the past but, we're not going to comment on any kind of perspective of forward pricing in the MS market.

If I may, just a small comment on this important dynamic that we see in the marketplace, is that Biogen has the opportunity to benefit from a complete portfolio in MS. And we are working very hard.

And if we want to change the landscape, we need to move away and try to progress on the value-based and innovative type of contracting.

It's difficult, the team is making some progress.

But today, I have nothing to report, except that some progress and some discussions with different [events].

So we are working on this dimension.

And your next question comes from the line of Geoff Meacham with Barclays.

And also I want to give my congrats on the quarter.

Michel, you talked about filling up the pipeline more and with the launch of anti-tau, are you comfortable with the number of assets or mechanisms that you have in the Alzheimer's portfolio?

And is it reasonable to assure -- to assume that biz dev may be neurology focused?

Or is it likely that you guys will look more broadly at the orphan space, just given that SPINRAZA launch?

Thanks for the question.

I'll get started and, obviously, Mike, will comment more thoroughly.

First, I would like to say that I'm very pleased that Biogen was able to pull it in a very competitive setting.

Anti-tau is an important mechanism that complements well the other programs we have with the same target.

But also, the Abeta assets that we have with aducanumab at the forefront and the BACE inhibitor that we have partnered.

So this positions Biogen, I will say, pretty well in AD and Mike will complement.

We'll continue to work hard, and we are doing that in order to improve the footprint of our phase early-stage, which is a sweet spot on where we can add much value with the development.

Biogen -- At Biogen, neuroscience is the mission in life and this is where we can add most of the value with meaningful development because we have great people, great team and the partners see that.

So before we move beyond, we look in the neuro space.

And in the neuro space, we look first at MS, SMA and neurology.

Mike?

Yes, thanks, Geoff, for the question.

On the tau side, I'd say that we're very excited now to have this more advanced tau antibody in the portfolio.

As I'd mentioned, we've got an earlier second antibody, BIIB076, and our collaboration with Ionis, an antisense oligonucleotide against tau, which we are looking to advance in the clinic in the coming months.

So we are quite excited about that.

Michel said it well we're really concentrated in neuro as an area.

I'd say when we look across the opportunity landscape externally, we really try to focus on things that are in the early clinical asset space that's kind of our core, where we believe that we can identify things with a bit of asymmetric knowledge and apply some asymmetric capabilities to that.

We don't exclude other areas, but that's just where we are concentrated.

So if we see a good opportunity that's a little bit later in a more adjacent area or even some that's earlier, we're quite open to it.

On the question around more orphan diseases or other things, I think that the experience with SPINRAZA highlights to us the real potential advantage of intrathecal ASOs as a modality.

We've got an early Phase I ongoing study in SOD1 mutant ALS, it's just another example of that.

So we see great opportunity in that intersection between neuroscience and certain orphan diseases.

And your next question comes from the line of Umer Raffat with Evercore.

I thought I'd ask you how to understand SPINRAZA numbers some more.

So Paul, thank you.

You mentioned there was about less than $10 million worth of inventory of the $46 million in U.S. So that would imply $36 million in sales or perhaps something like 360 infusions.

So I guess what I'm trying to understand is, if there were 30 centers enrolled as of early March and 88 centers as of April 21, that implies most of the patients have probably not had more than 3 infusions.

So is it unreasonable if I were to say, 360 divided by 3, perhaps about 120 patients on therapy as of Q1.

And I'm partially doing that to understand if there's a spillover into 2Q or not.

And may be one -- just a quick one on R&D.

I just wanted to understand the significance of the midway enrolled on aducanumab Phase III.

Is it -- does the protocol enable an interim analysis of sorts on week 52 or week 76 for the first 1,300 patients?

This is Paul.

Let me kind of do a couple of things.

One is the inventory I know was important for every -- on SPINRAZA was important, but it literally is a triangulation of data.

So I wouldn't -- it's not as precise as our knowledge of kind of the inventory on TECFIDERA in the specialty pharmacy channel.

But it is our best estimate at this time that it's something in the less than $10 million range.

And while we have a closed system on SPINRAZA, sometimes the patient let data lags and we're estimating things along the way.

No doubt as we move through Q1, the patients began to ramp and the dosing schedule as you point out, the loading dose schedule does likely have some level of spillover effect.

But I think that's kind of small dynamics and broadly what we're trying to do is get patient access and get through the infusion capacity constraints, get through the access constraints, get as many patients across all the different types of SMN patients on therapy.

And Umer, this is Al on the aducanumab question.

We have a policy here that we're not talking about interim analysis.

I'm afraid, I can't answer that question.

And your next question comes from the line of Ronny Gal with Bernstein.

I'm going to stick with nusinersen.

First, do you have any better feel right now for how long the effect of nusinersen is?

Given that we're kind of done with the question early launch, the question now is how long can you actually keep those patients alive?

And therefore, what should we model for those products -- accumulation of patients long-term?

And second, you've mentioned that you're about to take your gene therapy into the clinic.

I guess, the question is where is -- what is differentiation of your program versus the existing gene therapy, which is already in the clinic?

What are you doing better than they that will allow you to differentiate it versus their product?

Okay, Ron, this is Mike.

I'll start with that a little bit.

On the question of SPINRAZA durability, I guess what we can say is that we started the first patient dose just about 5 years ago.

And from what we have seen for that, there's been essentially sustained effects with those patients to date.

There's a lot that's not known here.

Obviously, this is not kind of ongoing clinical experiment.

Many of these patients are being rolled over into an open-label kind of observation period for this.

So the fact is that we just -- we don't know what, ultimately, the durability would be.

But everything that we've seen is a durable effect of continued dosing of SPINRAZA.

So I'd say on the gene therapy side of this, so there are a lot of things.

One is we're very encouraged by the gene therapy data that is out there of what AveXis has publicly reported.

We are quite bullish, in general, on the modality of AAV-based gene therapy.

We do believe that there's a prospect for differentiation in terms of tissue tropism, serotype, delivery route, dosage, viral load, manufacturing and so forth.

So we think there's ample room for differentiation and time will tell.

The other thing we would say is we believe that there can be a future out there where these are used in combination in certain settings that will depend very much on the stage and type of SMA.

And your next question comes from the line of Cory Kasimov with JPMorgan.

Just curious, what are the qualifications for the free drug program for SPINRAZA?

And do you anticipate 25% of units flowing through now will kind of remain a steady state going forward?

Ron, this is Paul.

Thanks for the question.

It's kind of tied up in if there's denial, effectively.

There's, obviously, also some normal, as you would expect, income for people that can't afford it.

With respect to the kind of free goods, I think that it's an estimate that we won't know until we get much further -- and I would guess it wobbles quarter-to-quarter.

I mean, it even wobbled within the quarter, so I think it wobbles around a little bit quarter-to-quarter as well.

And your next question comes from the line of Ying Huang with Bank of America Merrill Lynch.

Firstly, maybe Mike, can you comment on what's the difference between BIIB076, your anti-tau antibody that just entered Phase I, and then the anti-tau antibody licensed from Bristol-Myers, what really caused the decision to license that compound?

And then secondly, maybe, I think Michel, you commented on roughly half of the Medicaid plans now cover SPINRAZA.

Can you provide any color on what's the percentage of commercial plans that cover SPINRAZA now?

Okay, Ying.

So I'll start with that.

Thanks for the question.

I mean, a few things the reason we like -- I mentioned about how we just -- in general, to tau is -- intersecting taus is a very important future of neurodegenerative disease, including Alzheimer's disease.

I said 3 or 4 core things.

One, it was a more advanced clinical-stage asset that was of an interest.

Two, it's really quite clear that it had a very potent antibody here where they generated a very compelling biomarker data in terms of robust lowering of CSF tau, there had been more clinical experience and a known kind of benefit-risk profile that have been seen in many patients to date as you would expect from a more advanced clinical asset.

And then, it also gave us this kind of accelerated opportunity in progressive supranuclear palsy as another very exciting indication for us.

Ying, this is Paul.

Let me kind of try to tackle the second part of your question in terms of coverage on SPINRAZA in the commercial plans.

Our estimate is that about 75% of lives -- plans that cover the lives across the United States have coverage in approved SPINRAZA.

Of that, about half of those have a narrow call it, type 1 type, coverage and about half of those have broad coverage.

Importantly, as Mike pointed out, we'll be presenting data tonight that will hopefully start to get a more broad coverage as well.

Your next question comes from the line of Joshua Schimmer with Piper Jaffray.

Can you please estimate the size of the SPINRAZA patient backlog?

And do you believe you can address infrastructure bottleneck issues so that it's no longer getting stopped by the end of the year?

And then for Europe, how are you handling this so it doesn't slow launch there too?

Yes, Josh, actually, we'd prefer not to.

We obviously have internal data on start forms, and we have a sense for that.

But we prefer not to, because I just don't know the accuracy of it all at this point in time.

With respect to Europe, we effectively have been putting prelaunch efforts in place on a country-by-country basis, prioritizing, obviously, those countries that we expect to get reimbursements earlier as opposed to later.

So tremendous amount of energy in Germany, energy in the Nordics, energy actually also in U.K. for some relatively unique circumstances.

And I think it's going to be a very similar dynamic with respect to trying to accommodate and get through the infusion capacity.

If I may add very briefly.

I am monitoring very closely the ability of the organization to implement and to execute, being for SPINRAZA and I think that the data to date speaks for itself, and we continue to do the same in Europe with the individual regulators to follow-up following the CHMP endorsement with a broad label and including reimbursement.

So we'll get started, hopefully, we believe this summer with Germany and Scandinavia with an access condition.

And we have an early access program with more than 300 patients.

And gradually, the countries we come with market access condition one after the other.

And it's all about execution from the Biogen team, execution on SMA, execution on biosimilar and execution, obviously, on MS. I just want to reiterate that for TECFIDERA, we are working very hard.

TECFIDERA is now the market -- it's growing share 17 out of 21 markets in Europe, okay.

Germany is growing share 6 months in a row.

We have hit in France the highest ever share for TECFIDERA.

So it's all about the ability for the team to implement well with what we have in the bag in the portfolio today, in a very focused manner and a right way.

And your next question comes from the line of Salim Syed with Mizuho Securities.

Just 2 questions.

Paul, I think that both of these are for you.

You mentioned OCREVUS having a negative impact.

Can you just go into a little bit more color there and what products in particular do you see OCREVUS impacting?

Is it mostly TYSABRI or do you think it's TECFIDERA?

And then second, just on SMid- cap valuations.

It sounds like now you guys are approaching M&A a little bit more aggressively.

Paul, can you maybe comment on what your thoughts are on SMid-cap valuation at this levels?

Yes, let me take the second one first.

I mean, no commenting on that one.

So yes, I mean, I have points of view on it.

But I mean, we obviously don't talk about it.

It's kind of like one step away from talking about names.

Look, OCREVUS, we've done a lot of work on it.

Again, we do think a new entrant that has an interesting profile for patients and physicians will get a place in the marketplace and inevitably, as we have plus or minus 40% share across our existing portfolio of products, there'll be an impact on that.

We think that OCREVUS plays in the high-efficacy segment.

And as a result, the likelihood is that it impacts TYSABRI vis-à-vis the products in our portfolio more than others as well.

There's a chance TECFIDERA -- it impacts TECFIDERA as well.

We think that the platform therapies, inclusive of AVONEX and PLEGRIDY, are the least impacted.

All of that is obviously a total forecast, and we're going to be monitoring it very closely as we move forward.

And look, this is not a surprise, right?

So I think that I would characterize it in similar to way Michel has characterized it is that the best thing that we can do is just simply continue to really put forward the strength of our own products.

And when we have a great, great suite of products across a bunch of different segments and patient needs in the marketplace.

And then certainly, in the United States, we're heartened that we're somewhat hedged from the royalties that are gained from OCREVUS.

If I can just briefly add to what Paul rightly said.

Towards the higher end of the spectrum, I reinforce that at least at the beginning, patients with high level of HCV positivity that have to be switched and this is a good thing.

And obviously, the PPMS, for which we get a benefit.

So this is what we see.

This is very early days.

The label is in line with what we did assume.

We are monitoring very closely, but we are monitoring more our assets than the competition.

And your next question comes from the line of Alethia Young with Crédit Suisse.

Congratulations on the SPINRAZA launch.

Just one around S1P class in general.

I know Celgene

has a drug, ozanimod, and you talked about potentially going forward to partnership.

But what do you think makes for a differentiated S1P1 in general.

I know, you had experience with Mitsubishi as well?

So I might -- I'll start with that just to say that, it's -- I don't know that we're going to really comment that much around...

I think it's a good question for Celgene.

Yes, exactly.

I think that's right.

Yes.

Your next question comes from the line of Terence Flynn with Goldman Sachs.

I was just wondering on SPINRAZA, if you can give us any color on the percentage of new starts versus rollover patients.

And then, I noticed there was an uptick in cost of goods this quarter.

Paul, is there anything notably there?

Or is that going to trend down over the rest of the year?

Terence, thanks for the question.

This is Paul.

Let me try to take both of them.

I think what you're referring to on SPINRAZA is with respect to rollover patients, so those that were in the trial or in our EAP program.

And on both dimensions, it was a very small number.

Actually, the trial patients are continuing on in a trial.

The EAP patients because that -- if you recall, it was approved in such a short period of time from filing.

We actually in the United States had well below 100 patients on EAP and only a handful of them actually have moved into commercial patients.

So the vast majority of the sales for Q1 on SPINRAZA are due to in effect de novo new patient.

Cost of goods sold is a bit of function of a number of things.

The biosimilar business, which is growing quite strong comes with a high cost of goods sold.

We have had -- the AVONEX business, actually, has additional royalty that started in the second half of 2016.

And when we compare to the first half of 2016, we kind of have unfavorable comps.

So I think that's indicative probably of what we're going to see over the next number of quarters.

And our final question comes from the line of Matthew Harrison with Morgan Stanley.

I just wanted to try and sort of group together sort of all the comments you've made on SPINRAZA and just try and understand sort of a broader question, which is, obviously, there are some of these dynamics that you've talked about, including insurance and infusion, which is sort of limiting some of the uptake that you've obviously worked through that with patients.

And I guess what I'm trying to understand is, how should we think about if there was a bolus in this quarter and the new start rate should decline?

Or if you still think that the dynamic you talked about around insurance and infusions are still holding back a substantial portion of patients in that a new start rate should continue to increase as we think about maybe the next quarter or through the rest of the year.

Matt, thanks for the question, it's Paul.

I mean, quite frankly it's hard to really tell on that the kinetics of this.

And we've said it all along, it's hard to tell.

We are very pleased with Q1.

I personally would expect it continues to ramp, if you look at the number of patients in the United States.

I mean, so if you just look at the number of patients and the number of centers that still haven't that were still working through plans, I would.

The kinetics of it -- and also we always have to keep in mind the kinetics of kind of the cohort of patients going through loading dose and moving to maintenance dose and so on and so forth.

I think we'll see some level of -- we'll all be interpreting the data as we go quarter-by-quarter.

But broadly speaking, I think what this really pulls out is the tremendous value of the drug and the tremendous unmet need in the patient population.

And, if I may just add and conclude.

The 2 bottlenecks that we did identify at the outset remain.

Each battle everyday, and we are not yet where we want to be.

Some of the largest plans or the largest facilities in terms of infrastructure are still not dosing the way the patients deserve and the way the families and the advocacy group expect.

So there is still a way to go, but it's unlocking and progressing week after week.

I think the key elements that, first of all, the country deserves, the patient deserves is newborn screening.

The day we have that, we can really change the treatment and the evolution of SMA.

And if you look at the NURTURE data, the results speak for themselves.

Thank you all for your attention today.

Thank you to everyone.

This will conclude today's conference call.

You may now disconnect.