Biogen Inc. (BIIB) Q4 2014 Earnings Report, Transcript and Summary

Good afternoon. My name is Courtney and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Idec Fourth Quarter and Year End 2014 Earnings Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker’s remarks, there will be a question-and-answer session. [Operator Instructions] Thank you. Carlo Tanzi, Director or Investor Relations, you may begin your conference.

Thank you, and welcome to Biogen Idec’s fourth quarter and full year 2014 earnings conference call. Before we begin, I encourage everyone to go to the Investors section of biogenidec.com to find the press release and related financial tables, including a reconciliation of the non-GAAP financial measures that we’ll discuss today. Our GAAP financials are provided in tables one and two. Table three 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 our SEC filings for additional detail. On today’s call, I’m joined by our Chief Executive Officer, Dr. George Scangos; Dr. Doug Williams EVP of Research and Development Tony Kingsley, EVP of Global Commercial Operations; and our CFO, Paul Clancy. Now I’ll turn the call over to George.

Thanks Carlo. Good afternoon everyone thank you for joining us today. Sorry we had to move the call at the last minute, but as you can imagine things were little chaotic yesterday morning in Boston. I think we have optimally positioned it between the blizzard and the [indiscernible] discussions that will start [indiscernible]. So you guys have something to fill your, the void. 2014, I think, was a very successful year for Biogen Idec, we brought several new therapies to the market, we had encouraging data from some of the compounds in our pipeline and importantly we delivered 40% revenue growth and 54% non-GAAP EPS growth compared to 2013. In 2014 we launched four new products in two distinct therapeutic areas, which I think is a real accomplishment for a company of our size. TECFIDERA is in its second year on the market in the U.S. In 2014 we successfully launched TECFIDERA in the EU and are continuing to expand preference across the globe. TECFIDERA is now the most prescribed MS therapy in Germany and the most prescribed oral therapy in U.S. with more than a 135,000 people having been treated worldwide. As you all know from the IMS data, TECFIDERA did experience moderating growth in Q4, which we believe is due to a variety of factors that Tony will discuss in more detail. However, we believe that TECFIDERA will continue to grow in the U.S. and it will grow substantially in international markets, so that we anticipate that 2015 will be another year of meaningful growth for TECFIDERA and for our portfolio of MS products in general. PLEGRIDY was approved for the treatment of relapsing MS and launched in both the U.S. and EU in the second half of 2014. Although we are early in the launch, PLEGRIDY appears to be gaining rapid adoption. PLEGRIDY is an important part of our strategy to maintain our leadership position in the interferon segment of the MS market. We also obtained approval and subsequently launched our hemophilia products in the U.S. in 2014. ALPROLIX for hemophilia B and ELOCTATE for hemophilia A. ALPROLIX and ELOCTATE represent the first meaningful innovations in the treatment of hemophilia in many years, and reflect our mission to help bring new therapies to patients who are underserved. In our pipeline, we advanced several potential therapeutic options across a broad set of disease areas, along with our collaboration partner AbbVie, we reported positive results from the Phase 3 trial of ZINBRYTA for relapsing forms of MS, and expect to file for marketing authorization in the first half of the year. We believe ZINBRYTA has the potential to become another important treatment option to serve the diverse needs of MS patients. Our collaboration partner ISIS advanced the spinal muscular atrophy program SMNrx to Phase 3 in both infant and childhood forms of the disease. In December, we announced positive top line results from our Phase 1b trail of BIIB037 in patients with Alzheimer’s disease, this data are early but we believe they’re compelling and we are aggressively working to advance this program into Phase 3. Earlier this month we announced Phase 2 results for our anti-LINGO antibody in acute optic neuritis. We believe that the data strongly suggest that our anti-LINGO antibody induced remyelination, and we’re now focused on the data from the MS trial which we expect to have in early 2016. Throughout 2014 we also continued to build our research and development capabilities, by hiring a number of highly accomplished researchers from both academia and industry, and I believe that we now have truly world-class capabilities across the breadth of R&D. That has been a goal for a number of years and is rewarding to have made such a significant progress this year. In 2000 - excuse me in 2014, we increased the number of promising assets in our pipeline through strategic acquisitions and collaborations with a number of partners including Sangamo, Eisai and most recently Convergence and San Raffaele Hospital. We also made significant progress and advancing our internally developed candidates into the clinic, including the BIIB061 and oral compound in Phase 1 development with the objective of enhancing remyelination. Additionally, Phase 1 studies are ongoing for several novel formulations of dimethyl fumarate, the active ingredient of TECFIDERA, with the goal of achieving once-a-day dosing and potentially reducing side effects. We’ve not yet analyzed the data from these trials, but our hope is to move one or more of these formulations forward towards approval. Our bio-similar joint venture Samsung Bioepis continues to make important progress toward our objective of becoming a leader in the development of bio-similar pharmaceuticals. The EMEA recently accepted our application for approval of a bio-similar version of etanercept and we believe that we’re making excellent progress on other bio-similar molecules as well. Through this JV, we intend to develop high quality bio-similar pharmaceutical, by utilizing our world-class protein engineering and biologics manufacturing capability. It’s our belief that bio-similars will become increasingly important in the role of healthcare. And we believe that we’re well positioned to contribute to this evolution. So all in all, it was a very busy and a very good year. And with that, I’ll now pass the call along to Doug.

Thanks, George. Biogen Idec has a strong and increasingly diverse pipeline. I’d like to discuss several of our ongoing programs and the progress we are anticipating during the upcoming year. Our Phase 3 study of TYSABRI and secondary progress of MS known as ASCEND, is fully enrolled. There’s no effective therapies available today for this progressive and debilitating form of MS. ASCEND is a two-year placebo-controlled study in 890 patients that will determine whether or not TYSABRI has an impact on disability progression as measured by a novel composite end point. The study is being conducted under a special protocol assessment with the FDA and we expect the data from ASCEND in the second half of 2015. We’re also conducting ACTION, which is a Phase 2 study evaluating TYSABRI in acute ischemic stroke. In this study, we are examining if blocking the lymphocytic infiltration, known to occur in the brain following stroke, can reduce the extent of injury. ACTION is a placebo-controlled study in a 160 patients where brain imaging is used to measure the change in infarct volume compared to Baseline. ACTION is fully enrolled and we expect data later this year. We previously discussed our positive top-line interim Phase 1b results for BIIB037 in Alzheimer’s disease. Additional BIIB037 study data will be presented at the upcoming ADPD meeting in March, the Phase 1b, BIIB037 study remains ongoing and our current plan is to initiate our Phase 3 program later this year. We also recently announced Phase 2 data from the anti-LINGO RENEW study in acute optic neuritis. We hope to present full data for menu at the upcoming American Academy of Neurology Meeting in April. The second ongoing Phase 2 study evaluating Anti-LINGO in MS patients is fully enrolled and we anticipate obtaining results in 2016 as previously disclosed. We continue to develop Neublastin as a novel biologic therapy for neuropathic pain. Our Phase 2 study in patients with painful lumbar radiculopathy will evaluate whether or not Neublastin has an impact on pain intensity scores. The study is now fully enrolled and results are anticipated in the second half of this year. Enrollment on our STX-100 Phase 2a study in idiopathic pulmonary fibrosis continues, and the study is currently enrolling the fourth and potentially final patient cohort. Through our collaboration with Eisai, we’ve obtained co-development and co-commercialization rights to two Alzheimer’s disease candidates, BAN2401, an anti-amyloid BETA monoclonal antibody and E2609 a small molecule BACE inhibitor. BAN2401 is enrolling patients in Phase 2 and Eisai has initiated a Phase 2 study with E2609 in patients with Prodromal AD and mild cognitive impairment due to Alzheimer’s disease. We’ve also made progress in strengthening our pipeline through business development. And earlier this month we announced our agreement to acquire Convergence, a leader in the development of therapeutics for neuropathic pain. Convergence’s lead program CNV1014802 is a small molecule inhibitor of the Nav 1.7 sodium channel, that’s being developed for trigeminal neuralgia. Following completion of the acquisition, we expect to work expeditiously to advance CNV1014802 into registrational clinical programs. This morning, we announce the collaboration with San Raffaele Hospital in Milan, Italy, to develop gene therapy for both hemophilia A and hemophilia B. Our collaborators at San Raffaele are leaders in the use of Lentiviral Based gene therapy approaches. While this technology remains in early research, we believe gene therapy has the potential to provide lifelong benefits to patients with hemophilia. We look forward to continuing to drive R&D progress during the year. I’ll now pass the call to Tony.

Thanks Doug. We launched four new products in 2014, and I’m proud of the execution of the commercial organization. In 2014, we continue to grow our global MS market share, fueled by the continued rollout of TECFIDERA worldwide, improving performance from TYSABRI and continued strength for our interferon business, including the recent launch of PLEGRIDY. Over the past six months, our data suggested our portfolio has consistently captured roughly half of all newly diagnosis patients and switch patients in the U.S. TECFIDERA continue to demonstrate strong performance, which we believe is a testament towards attractive product profile combining strong efficacy, favorable safety, and tolerability and the convenience of overall administration. We believe TECFIDERA is on track to become the most prescribed therapy for MS worldwide. In the U.S. we saw continued growth through the fourth quarter with its market share near 20%. As you may have seen through IMS, we observed moderating new starts for TECFIDERA in the fourth quarter. We believe several factors have impacted the recent performance of TECFIDERA including a decline in the overall market switch rate. The U.S. label update in December and the recent launch of PLEGRIDY, which is capturing some interferon switches that otherwise, may have gone to TECFIDERA. Importantly, we have not noticed a meaningful change in TECFIDERA discontinuation rates. We are actively engaging physicians to ensure proper education on the label update and we believe in the continued growth potential of the product in the U.S. Out side of the U.S. we’re continuing to see strong uptick in multiple launch markets matching or exceeding the pace that we’ve seen in the U.S. In November, we launched TECFIDERA with full reimbursement in the UK and as of January, we secured reimbursement in both Italy and Spain. We continue to expect to achieve full reimbursement across the other major European markets by the end of the year. We believe that PLEGRIDY may become the interferon of choice based on its combination of efficacy of favorable safety profile and every two-week dosing with a convenient sub-Q autoinjector. To-date roughly half of PLEGRIDY prescriptions have come from AVONEX switches. The other half have come from other therapies and from newly diagnosed patients, which we believe is a positive message about the therapy’s broad appeal. The rollout of PLEGRIDY is expected to continue across Europe in 2015 with launches in most of the major markets anticipated by the end of the year. TYSABRI continues to perform well as the therapy enjoyed its third consecutive quarter of positive net new patient adds, even as the oral therapies have continued to gain share. We believe that this performance is due to the high level of efficacy that TYSABRI provides to patients. Turning to our hemophilia products, we continue to believe that reduced infusion frequency is the largest unmet need for the hemophilia community and that ALPROLIX and ELOCTATE meaningfully address this burden. We are encouraged by the strong up tick of ALPROLIX in the U.S. We believe its value proposition to patients has been relatively straightforward, as the majority of patients starting on ALPROLIX have been choosing the once weekly prophylactic dosing schedule. ALPROLIX ended the year with its market share in the low teens with over 60% of hemophilia treatment centers prescribing the products. The U.S. launch of ELOCTATE has been preceding the plan ending the year with share in the mid-single digits with over 60% of hemophilia treatment centers prescribing after two quarters on the market. As we expected the hemophilia A market, has been more competitive than hemophilia B. Acquiring additional patients will require sustained educational and promotional efforts, but we believe we have the ability to execute on this strategy. I will now pass the call to Paul.

Thanks, Tony. Our GAAP diluted earnings per share were $3.74 in the fourth quarter and $12.37 for the full year. Non-GAAP diluted earnings per share in the fourth quarter were $4.09 and $13.83 for the full year. Total revenue for the fourth quarter grew 34% to approximately $2.6 billion and grew 40% for the full year to $9.7 billion. Global fourth quarter TECFIDERA revenue was $916 million. We recorded revenues of $743 million in the U.S. and $173 million outside the U.S. TECFIDERA U.S. sales included 14 shipping weeks in the fourth quarter, this added approximately $50 million to U.S. sales. Foreign exchange offset by hedging weakened TECFIDERA revenue by approximately $7 million for the quarter, versus the prior quarter. Our estimate is that we ended the quarter with approximately 2.5 weeks of inventory in the U.S. wholesale channel, a similar level to last quarter. For the full year world wide TECFIDERA revenues were $2.9 billion consisting of $2.4 billion in the U.S. and $483 million in sales outside the U.S. Interferon revenues including both AVONEX and PLEGRIDY were $777 million during the fourth quarter, which includes $528 million in the U.S. and $249 million in sales outside the U.S. For the full year worldwide interferon revenue grew 2% to $3.1 billion consisting of $2 billion in the U.S. and $1.1 billion in sales outside the U.S. AVONEX U.S. sales included 14 shipping weeks in the fourth quarter, which added approximately $35 million of the U.S. sales. Foreign exchange offset by hedging weakened Q4 interferon revenue by approximately $9 million versus prior quarter. TYSABRI worldwide revenue was $484 million in the fourth quarter these results were comprised of $266 million in the U.S. and $218 million internationally. TYSABRI U.S. sales included 13 shipping weeks in the fourth quarter versus 14 shipping weeks in Q3. Foreign exchange offset by hedging weakened TYSABRI revenue by approximately $9 million for Q4 versus Q3. For the full year, worldwide TYSABRI revenue was approximately $2 billion of which U.S. revenue was $1 billion and $934 million internationally. Moving to hemophilia, ALPROLIX revenue in Q4 was $40 million and $76 million since being launched in May. ELOCTATE revenue in Q4 was $37 million and $58 million since being launched in July. Turning to our anti-CD20 unconsolidated joint business, which includes RITUXAN and GAZYVA U.S. profit share, as well as the profit share on royalties on sales of rituximab outside the U.S. We recorded $305 million for Q4 and $1.2 billion for the full year. Royalties were $31 million for Q4, compared to $67 million in the prior quarter. Our royalty revenues from Angiomax ended on December 15 with the patent expiration. For the full year royalty revenues were $177 million. Now, turning to the expense lines on non-GAAP P&L. Q4 non-GAAP cost of goods sold were $297 million or 11% of revenue. For the full year non-GAAP COGS were $1.2 billion or 12% of revenues. Q4 non-GAAP R&D expense was $409 million or 19% of revenue, which includes approximately $50 million in milestones and other payments related primarily to our JV with Samsung Bioepis and our recent collaboration with Google [x] Life Sciences. For the full year non-GAAP R&D expense was $1.9 billion or 19% of revenue, an increase of 31% over 2013. Q4 non-GAAP SG&A expense was $573 million or 22% of revenue and the full year non-GAAP SG&A expense was $2.2 billion or 23% of revenue, an increase of 30% over 2013. Our Q4 non-GAAP tax rate was approximately 24% for the fourth quarter, as we benefited form the reinstated R&D tax credit. Our full year tax rate was approximately 25%. During the quarter, we made a $200 million CVR payment to the former shareholders of Fumapharm. And in Q4 as part of our ongoing share stabilization plan, we repurchased 1.7 million shares for total of approximately $527 million. Our weighted average diluted shares at the end of the year were $237 million and we ended the year with approximately $3.3 billion in cash and marketable securities, split approximately fifty-fifty between the U.S. and ex-U.S. This brings us to our non-GAAP diluted earnings per share, which again were $4.09 for the fourth quarter and $13.83 for the full year, representing a 54% year-over-year increase. Let me turn to our full year 2015 guidance. In 2015, we plan to provide annual guidance and one update per year during our second quarter earnings. This modest change is intended to synchronize with our internal planning processes and ensure continued focus on the long-term. Now starting with revenues, we expect revenue growth between 14% and 16%. Before I provide color on the products I’d like to highlight three factors. First, our plan assumes exchange rates at the recent spot rate. Second, as a reminder, we expect a year-over-year decrease in royalty revenue of approximately $130 million as the royalties on ANGIOMAX sales have expired. And third, our plan assumes our one year free [ph] pricing in Germany for TECFIDERA will end this March and move to a lower price. Now, let me characterize how we’re thinking about each of our products. Our plan assumes TECFIDERA will represent the largest contributor to our overall revenue growth. In Europe, our plan assumes TECFIDERA will have full reimbursement in the majority of the EU market. For TYSABRI we believe the therapy will continue on a positive patient growth trajectory. We continue to be in discussions with IEPA to resolve the outstanding periods yet a settlement is not included in our 2015 guidance. We believe we’re well positioned with PLEGRIDY within the interferon and combined with AVONEX our plan assumes, we’ll continue to gain share within this declining segment. For our MS therapies our plan assumes a constant number of shipping weeks of 13 for each of the four quarters in 2015. We believe ALPROLIX and ELOCTATE will continue to grow at a strong pace, as we continue to focus on expanding the depth and breadth of the therapies. Our 2015 plan assumes revenues related to RITUXAN and GAZYVA will grow modestly. R&D expense is expected to be between 19% and 20% of sales, which includes approximately $250 million year mark for business development activity at similar level of spend when compared to 2014. SG&A expense is expected to be approximately 20% to 21% of revenue, as we are now through the commercial ramp of both TECFIDERA and hemophilia therapies we anticipate over 200 basis point improvement in SG&A year-over-year. We anticipate non-GAAP EPS results between $16.60 and $17 and GAAP EPS to be between $15.45 and $15.85. From a cash perspective, we expect to pay over $1 billion in CVR payments to Fumapharm related to the sales of TECFIDERA. And we anticipate capital expenditures of approximately $400 million to $450 million, an increase over 2014 as we invest in our manufacturing capabilities and IT infrastructure. I’ll now turn the call over to George for his closing comments.

Thank you, Paul. Okay in closing, we had a very productive year. We gained regulatory data protection for TECFIDERA in the EU and subsequently launched in Europe. We launched PLEGRIDY in the U.S. and Europe and ELOCTATE and ALPROLIX in the U.S., as well as some other countries. We had a good year commercially and financially and we received positive results in some of the important compounds in our pipeline. We started out 2015 with the agreement to acquire Convergence and the collaboration with San Raffaele Hospital. And we expect to complete additional business development transactions during the year. We also expect to see pipeline readouts for several compounds. In addition to the presentations of the data for BIIB037 Anti-LINGO antibody expected in March and April and the completion of the TYSABRI SPMS trial. We expect to see mid stage data for Neublastin in neuropathic pain and TYSABRI in stroke. So this will be another busy year with meaningful milestones, with aggressive goals and all aspects of the business and we’ll continue to do our best to achieve them. So in closing and as always I’d like to thank our employees for a dedicated to making positive impact on patient lives, and the patients and physicians who are involved in our clinical development programs. The achievements we’ve made together could not have been realized without their passion and commitment. I thank you all for joining us this afternoon. And operator, we’ll now open up the call for questions.

[Operator Instructions] Your first question comes from the line of Eric Schmidt with Cowen. Your line is open.

Thanks for taking my question and congrats on a great 2014. Maybe for Paul on the ex-U.S. TECFIDERA trajectory, it sounds like the drug is now number one in Germany and that you’re quite optimistic for a lot of growth ex-U.S. in 2015, yet we think the numbers came in a little bit below consensus, you flagged this $7 million FX hit. But was there anything else on TECFIDERA that credit maybe a little bit of a weaker ex-U.S. sales number?

No, nothing meaningful ex-U.S., I mean we’re actually very happy with how things are moving along ex-U.S. as you had noted. Our challenge to our organization is that every country that we get reimbursement and we do better than the [prior] [ph] we actually were able to better in terms of launch curve at time equal to zero in Germany than the United States, and we hope to do it as we kind of go to every other country, that’s obviously an aspiration more than anything else, so nothing too meaningful in terms of the trends to point out.

Your next question comes from the line of Geoffrey Porges with Bernstein. Your line is open.

Thanks very much and congratulations on the results. I appreciate the detailed guidance. I just want to ask about BIIB037 still getting questions about that, and you provided some useful color, first out of the year, but could you just talk a little bit about specifically where you’re going with the dose and I am thinking about the Phase 3 trials and discussions that you’re having, when might you have those discussions with the FDA and when might be have a physician to sort of talk about what the trials look like, the scope and that sort of thing?

Hi, Geoff, this is Doug. Thanks for the question. There is not a lot of additional color that I can provide to you vis-à-vis the final study design going into Phase 3. As you can imagine, we’re in the process of having discussions with regulators. In fact, we’ve been having them for some time as we’ve been seeing the data emerge from the study. I think it’s safe to say that our intent going forward will be to try to design a study that most faithfully reproduces the type of patient that we treated in the Phase 1b study, as well as looking at similar endpoints, as you know from a cognition perspective we achieve statistical significance on the CDR sum of boxes, which is a registrational endpoint. The base inhibitor for AstraZeneca and Lilly is actually using that as a Phase 3 endpoint in prodromal and mild patients. So I think you can anticipate a Phase 3 program that will have similar patients entering the study, screened in a similar fashion upfront and the final study design we will talk about at the time we start enrolling patients, that’s our usual practice. I don’t see any reason to break profile for this particular molecule. With respect to the choice of dose, as you know the study is still underway, we still have a couple of cohorts that remain blinded and until we see that data, we won’t be able finalize the exact dosing regimen except reiterating, what Al said at J.P. Morgan, which is we believe we have a dosing window that we can work with from both a safety perspective, but more importantly from what looks like a treatment effect perspective, as well. So a lot more information at the ADPD meeting about the results that we’ve been able to look at, but the study design issues are very much in process right now. And we’ll let you know what those studies are going to look like at the time we enroll the fist patient.

Your next question comes from the line of Mark Schoenebaum with Evercore ISI. Your line is open.

Hi, thank you very much. Just a follow-up on the Alzheimer’s question, if I may, why did you guys choose not to use ADAS-Cog as a cognitive endpoint. And then the two cognitive endpoints that you did, look at mini mental, or the two endpoints, if you look at mini mental I believe sum of the boxes. Doug, there’s been this debate on WallStreet regarding Lilly as to clinical significance versus statistical significance, I’d love to get your view of what would constitute a clinically significant benefit in the mini-mental and the sum of the boxes. Thanks a lot.

Okay. So we choose not to use ADAS-Cog because I think it’s now the view of the field that that’s probably a better tool to use for patients who are further down the disease spectrum. That CDR is I think now becoming much more accepted as a preferred primary end point for studies that focus on patients with Prodromal and mild disease. That seems to be the pattern that’s emerging. If you look at what the primary end points for studies in those cohorts of patients, actually are using with the Lilly study being just an example of that. The issue of what constitutes clinical significance is one that obviously is something that we’ll be discussing with regulators. Our view based on our decision to go right from Phase 1B to Phase 3 is that we believe we’ve seen a treatment effect that is significant enough and our advisors believe this to be the case to meet the criteria in most people’s minds for clinical significance and not just statistical significance.

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

Hi, thanks for taking the question. Two part one for me. Just in terms of your guidance on the Interferon franchise, Paul, just wondering you mentioned you expect to take share in a declining market, which we’ve heard similar commentary from you guys in the past, but do you actually think that can be a growth franchise for you this year. And then the second part of that is just implications of the entry of Daclizumab and longer-term Ocrelizumab and impact on your injectable franchise? Thank you.

Yes, I think we’ll probably end up tag teaming this one a little bit Terence. I think it’s being growth is probably a little bit of a stretch. So I mean I think the reason we’ve been a little bit cautious on kind of phrasing it up that way is this - obviously an interplay of how fast orals move along which effects Interferon, which so and if orals don’t move along as fast I think the Interferon franchise will hang in there. It’s not unheard of. It’s just - I think it’s early days right now, but over – look, conceptually we do believe there’s something special about PLEGRIDY and that once every two weeks subcu is so much more favorable than any of the other Interferons and potentially COPAXONE as well. So we’ll have to see whether or not that turns into the combination of AVONEX and PLEGRIDY growing. But we’re hoping at a minimum it hangs in there.

Terence, it’s Tony. Let me hit dac first, look we think dac is a very good compound and it certainly as a place in the market. I'm not sure I would think of it - look we don’t have the label yet, so there is some things that we don’t know. It wouldn’t necessarily think of it as an injectable in the sense of the platform therapy as we think of them today in that it has - it appears to have a different efficacy profile, so it may play in some broader segments than the existing platform therapies do. In terms of ocrelizumab again we have to wait and see, there is - we hear interest in the market as I am sure you do from physicians that it looks like it could be an interesting, very much in the high efficacy segment, but we’ll have to wait and see how that product plays out and where it fits versus TYSABRI and some of the other alternatives.

Your next question comes from the line of Ravi Mehrotra with Credit Suisse. Your line is open.

Hi, thanks for taking my question and I apologize up front where we’re going to ask you to do our job one level. On TECFIDERA looking at long-term consensus numbers, I know these numbers are no easy, looks like the average 20-20 estimates around $9 billion implying a global market share of around 40% interested in your view on whether you’re seeing the streak may have got ahead of itself here or if you think that TECFIDERA is likely to get to those levels of market share?

Gosh, Ravi, I mean, we don’t give long-term guidance out there and so I think we’re going to kind of stay at that as it is, and let people come to their same conclusions. We think there’s still a very meaningful growth with TECFIDERA that’s embedded in the guidance for this year, but I wouldn’t want to kind of really comments on the bunch of models over a long period of time.

Your next question comes from the line of Cory Kasimov with J.P. Morgan. Your line is open.

Hi, good afternoon thanks for taking my question. In your prepared remarks, you alluded to the ongoing Phase 1 studies for several novel forms of MMF and, I’m just wondering if there’s anything you can say about how these molecules differ from TECFIDERA and when you maybe in a position to provide some data on that? Thanks.

Let me be clear. We’re not testing formulations of MMF we’re testing formulations of DMF, which is the active ingredient of TECFIDERA. And DMF is DMF, but the formulations are different and look the intent is to get through once-a-day formulation, potentially reduce the GI side effects. So we’ll - we have several formulations in Phase 1 now we have others behind those and we’re hopeful to be able to bring forward one of them to the market.

Your next question comes from the line of Yaron Werber with Citi. Your line is open.

Great, thanks for taking my question. So I have a question of, Tony if you don’t mind sort of two of them. One is we’ve been doing a lot of work on biosimilars and we’re trying to figure out your view of what happens to the ABCR class, when Copaxone goes generic, so what would happen let’s say to the interferon class? And then secondly, you mentioned, there is three different reasons TECFIDERA was weaker, it was - or weaker or slowing down in terms of new patient adds, there was a decline in switching U.S. label change and a PLEGRIDY launch. Of the three, which one was the most important? Thank you.

Good, good, two part of question your own. So let me…

You move into the fact of...

Look, Copaxone, I think we’ve been consistent on that. We think U.S. private payer market, the impact of a generic Copaxone is largely unbranded Copaxone. It’s difficult for payers to see or certainly to convince physicians if there is therapeutic substitutability between [indiscernible] and the interferon. So I think that’s where we are on that. And that’s pretty consistent with what we said in the past. On TECFIDERA, look actually you hardened the piece apart, probably the Paul said, we expect the product to grow, but we would see some moderation in growth next year. I think we what is said that in any case for the first reason, which is the switch rate in the market in the U.S. has come down over the last three or four quarters. We’ve talked about that I think again pretty consistently. When TECFIDERA launched in the U.S., and we’re seeing this repeat outside the U.S. It doubled or tripled the switch rate for proto time and that’s been working its way down over time.

One other thing I’d add to it. We’ve always said in the past that over time, we think IMS the data that you all see is pretty accurate. It’s actually been accurate on a short-term basis as well. So I think you can kind of look at the trends of the IMS scripts kind of in the Q3 and Q4 and you can kind of interpret things, PLEGRIDY launched effectively in the first week of November and you can kind of discern a little bit. I think at the end of the day, you look at and say a lot of these things all happen at the same time.

Your next question comes from the line of Geoff Meacham with Barclays. Your line is open.

Good afternoon guys, thanks for taking the question. I just had one on LINGO. I know you guys, obviously, just got the data this month, but when you look beyond AN, will there be much more data internally or over four year publicly released MS data. I guess I am just trying to get us feel for what you’re ultimately be looking for in Phase III effect size wise. And what you can in fact address this year with regulators before you start a formal pivotal in MS. Thanks.

Hi, Jeff, this is Doug. I think there is not a lot of additional data from the acute optic neuritis study that we’re going to see I think you’ll see the majority of the data as much as we can cram into 115 minute platform presentation or at least I hope it’s a platform presentation at AAN. It’s likely that there will be some additional data cuts that we will sort of trickle out at subsequent medical meetings, but I think you get a clear sense of what we’ve seen in that data where the acute optic neuritis at AAN. The MS study as we talked about in a previous earnings call that study is ongoing, it is fully enrolled now. Our intent is to actually have a small group of us internally, see some of that data at the 12-month time point later this year, which we will use as a basis to begin to have some of those discussions with regulators. So I think that what we’re able to see in that data will teach us a lot about which of the various end points where measuring in that study, actually show the best correlation with remyelination. As you know, this is the first of its kind study where we are assessing the impact of remyelination on patients with MS. And so we’re looking at a variety of end points everything from EDSS to cognition to certainly ambulatory parameters. We have a number of imaging end points built into the study. And from that analysis, we hope to be able to piece out what the most sensitive clinical measures of remyelination are, so that we can go to regulators and start discussing what a Phase 3 end point might actually look like. So as we said in the previous call, there will be a small group of us that will see that data and that will allow us to determine how to have a conversation with regulators. We plan to keep the study blinded through to the full 18-month time point, which means that full data disclosure won't come until sometime in 2016 for the full data set. So that that’s what you can anticipate playing out over the course of the next 12 to 18 months.

Your next question comes from the line of Brian Abrahams with Wells Fargo. Your line is open.

Thanks for taking my question. A question for Tony, you mentioned one of the causes for the TECFIDERA slowdown recently, has been the label change, but interestingly you’re not seeing any increase in discontinuations, which I guess you’d presumably get with more aggressive lymphocyte monitoring. So I'm curious what are you seeing in terms of physician reactions to the PML case that might be slowing uptake? And what sorts of educational initiatives do you think will be needed to help physicians work around this?

Thanks, good question. I think the educational initiatives are underway, which is we have our sales forces out, talking new broad set of physicians, our medical team is providing support where there are request. So I think we are executing it and educating people to the label and what the label says and answering those questions. A part of the impact when you’ve something like this is the time that takes to get, you can get to a small set of physicians quickly, and you tend to get to the KOLs quickly, it’s the time to get to the broader community base. So we think we have the right education in place. We have to keep executing and making sure that that continuously happen. Look the lack of meaningful change that we see or we believe we’re seeing in the discount rate is encouraging because it doesn’t suggest there is such a change in the profile that people are anxious to pull patients off on the country. Look I think naturally in a case like this is people are processing the new label. You’ll see softness in the switch rate for a period of time and that is probably what accounts for.

Your next question comes from the line of Matthew Harrison with Morgan Stanley. Your line is open.

Great, thanks for taking the question. Just on BIIB037, so first can you just clarify, earlier you mentioned, only mentioned CDR Sum of boxes is - significant cognition end point. Was it just that or it was that an MMSc? And then should we expect to see or what should we expect to see in the abstract, will there be any significant data there, or is it mostly a placeholder? Thanks.

Well, with respect to the statistical significance, we did achieve that with both the CDR Sum of boxes and with the MMSc. So I believe we did clarify that at the JPMorgan meetings in January. And with respect to what’s in the abstract, I haven’t actually seen it myself. So I can’t answer the question. I think there won’t be enough to satisfy you in the abstract anyways. So I think the real answer to the question is going to come out of the presentation itself because there will be a lot more information there than there will be in the abstract.

Your next question comes from the line of Ying Huang with Bank of America Merrill Lynch. Your line is open.

Thanks for taking my question as well. So maybe a housekeeping question for Paul. You mentioned that IMS data in the short term was pretty accurate, but it seems you guys did a better job in several drug in the U.S. for TECFIDERA. So I was wondering can you quantify where it was I guess short. And then can you quantify also the exact inventory level, I know its 2.5 weeks from Q3 to Q4. And then just curious your view also on the outcome is, I guess [indiscernible]. It seems that you guys don’t feel very strong about the MS product. Thanks.

Thanks Huang. Yes, I am not sure what question is on the clarification for MS, I think you’re referring to something outside the U.S. and we’ve really don’t have a clear picture outside the United States. So IMS what I was referring is within the United States and just on a more of a week-to-week basis. We kind of see it as pretty accurate vis-à-vis our data that we have from SPTs going to patients.

Okay.

And I think with respect to the MMF prodrug situation, I think there are certainly two programs that are in the clinic at the moment that we’re aware of that are moving along, still very early. I think George pointed out the distinction between DMF and MMF and we think that’s an important distinction because it’s quite clear from a number of studies that we’ve carried out that the biologic response at least in pre-clinical settings to MMF is distinct from DMF. And so, it remains to be proven that the ability to replicate the safety and efficacy profile that we see with TECFIDERA, which is DMF can in fact be replicated with these MMF prodrugs. So I think that’s - what the hurdle is for those programs moving forward and it’s still far too early I think to access how successful those are going to be.

Your next question comes from the line of Michael Yee with RBC Capital Markets. Your line is open.

Thanks. A follow-up question on BIIB037, there has been recent phase to readouts, I guess most recently with Lilly, and we’ve all seen a 34% improvement and cognition there. It has carvedilol [ph] MMSE. So can you help us to frame that data with why you’re suggest up with your data, but I guess also when we see your presentation, how much information will we get, I know there is more information than - a more follow up beyond just the interim, so help us to understand what we’re seeing there.

Well, I think, with respect to our data, which is what I’ll focus the answer to the question on. I think what you’ll see I think is the actual numbers behind the statements that we made. There is a clear dose and time dependent reduction in beta-amyloid levels that we’ve seen in these patients. There is a dose dependent and statistically significant impact on cognition as measured by two parameters, both CDR sum of boxes as well as the MMSE endpoint. And what you’ll also see I believe is data to support the notion that we put forward that we believe we have a safety window to work with vis-à-vis the area that we have seen with our molecule. That’s also been seen with some of the other anti-beta amyloid antibody. So I think that the data that we’ve seen, the data we’ve talked about at least in verbal form is compelling enough and consistent enough for us to want to move the program as rapidly as we can from Phase 1B into Phase 3. And I think that you’ll hopefully get a clear sense of the treatment effect that we’ve seen and the consistency of the results across the various parameters we measure. It was enough to convince us to make the lead from 1B right into Phase 3.

Your next question comes from the line of Robyn Karnauskas with Deutsche Bank. Your line is open.

Hi guys, thanks for taking my question. I guess I’ll ask a hemophilia question, one really hasn’t come up. So you just talked a little bit about its being competitive in the factory base. Help us to think about like what you’re doing to maybe increase switching and should we just expect even in the steady growth of that product or could there be an acceleration in the back of the year after maybe you change some of the marketing or anything like that? Thanks.

Good. Robyn as Tony said if I look back to before we launched both the products, I think we both said, we couldn’t predict the launch curve that well, but we go with even and steady might be was ALPROLIX got off to a faster start because it’s a very straightforward proposition for physicians. For patients you have a pretty friendly group of patients in the fampridine market and there’s zero competitor responsible. We’ve said that we think the ELOCTATE in fact really is going two plan as we’ve expected to which is you have to take captures and early adaptors, you have to have - those patients have good experience, so that they can - it’s a big market they can activate other people. So we’re continuing to execute on patient education, but a lot of it is calling on the hemophilia treatment centers explaining - the label explaining the data talking to both nurses and physicians. So I think it’s pretty consistent with the way we’ve talked about it historically. It takes a lot of good hard execution, but we like the product profile. We think over time you build that virtue a cycle of - patients have good experience, physicians have good experience and you get increased adoption over time. So I think we’re on a steady march - try to convert that market and I think we have a good product and good ability to do that.

Your next question comes from the line of Matthew Roden with UBS. Your line is open.

Great, thanks very much for taking the question. I hope you guys are all dug out from all the snow.

A little soon...

Yes. So Doug, you mentioned in Alzheimer’s staying faithful to the patient population as you move forward, so that prompted me the wonder whether or not they start seeing improvement in cognition style [ph] was in the Prodromal patients or the early AD patients are both, and also whether or not the statistic was on a intent-to-treat basis. Thank you.

Yes, with respect to the study itself again I keep pointing you in the direction of the presentation. I don’t want to disclose any additional information about the study itself beyond what we’ve talked about so far. And again with respect to the design of Phase 3, we’ll be trying to faithfully replicate the population of patients that we treated in the Phase 1b study and the Phase 3. So it will be a Prodromal and mild population of patients. I think you can anticipate that we will do a similar of type of entry screening to what we did in Phase 1b to confirm that the patients actually have the target for the drug as a pre requisite to enrolling them into the study, and beyond that I’ll just stay silent until we present the actual dataset in March.

Your next question comes from the line of Thomas Wei with Jefferies. Your line is open.

Thanks, just a follow-up on BIIB037. Just from whatever work you’ve done or when you look at the overall literature, do you think you believe that the BETA amyloid pieces could lead to improvements in cognition or are really just looking for slowing or stabilization of cognitive decline?

It’s a really good question. I think we don’t actually know the answer to that question. It’s testable, if in fact you have an agent that both removes amyloid and does in fact, show improvements in cognition, at least the rate of the decline versus the control population. And my bias and my guests is that what we’re looking at is something a kin to disease modification with DMT’s and MS, which is a hopefully a major slowing in the decline of these patients overtime. Whether in fact we can treat them and reverse some of the damage that’s been done. I think is an unknown at this point, but obliviously the long-term follow-up studies would be designed to try to answer those sorts of questions over a longer duration of treatment than what we’re likely to do in the Phase 3 program. So I think the hope is there, but at the moment, I think it’s a hope.

Tom, this is George. It’s a question that we also I think is a very important. Look we’ve one year data on patients and it’s a long-term disease. And so we just on have enough data yet to answer that question. I think when you see the data that we present in March we can have a more, let’s say intelligent discussion about that topic. But it’s hard to see anything meaningful in the absence of the data.

Your next question comes from the line of Josh Schimmer with Piper Jaffray. Your line is open.

Thanks for taking the question I'm going to ask the Gene Therapy Consortium, is the hemophilia program going to be first experience of an in vivo, use of antivirus and what gives you confidence in the safety and efficacy of this approach? Thanks.

The question is with respect to the gene therapy. Josh can you just repeat the question, you were breaking up.

Yes, you’re breaking up there.

I’m sorry, so I was just wondering is this the first experience with in vivo introducing antivirus to support purpose of gene therapy and what gives you the confidence that the in vivo approach will be both safe and efficacious.

Yes, Josh, this is Doug. I think the deal we announced today is in fact using lentiviral in a systemic delivery mode. It’s still a very early program, but one that we have looked at and one for which we’re excited to be working with Luigi Naldini, who is one of the leaders in this area. It’s an early program he’s got intriguing data at the moment using a vector system that they have designed, there’s still a number of technical hurdles to overcome with this. But it does direct expression into the liver and one of the advantages with lentiviral vectors is that, number one, you obviate some of the issues that you have with AAV vectors, which involved pre-existing immunity to the vector system itself. And it’s also a very long-term expression that you’re capable of getting with that vector system. So Luigi is one of the pioneers in this area, we think that if we can make this a successful approach that it really is a transformational approach from a gene therapy perspective given how broadly you could treat patients with both factor VIII and factor IX deficiency. So still pre-clinical, but I think very much with transformational type of therapy if we can bring it forward and make it work.

Operator, we’ll take one more question.

Your last question comes from the line of Joseph Schwartz with Leerink Partners. Your line is open.

Thanks very much for fitting me in. You’ve been using some innovative patient screening methodologies in the Phase 1b for BIIB037 such as automating PET amyloid quantification and focusing on certain regions of the brand. I was wondering if you could talk a little bit about these tools in terms of how they could influence who will be eligible for receiving the drug. If it comes to market, are you planning to develop a companion diagnostic to can it be commercialized along side BIIB037?

Well, at the moment what we are using is an agent that is in fact already licensed and available in the market. It’s AV-45 as a screening tool for patients coming into the study. We thought that that was an important way of screening patients upfront to confirm that in particular patients with mild cognitive impairment. There are many reasons why that could happen, amyloid-beta deposition being just one of them. So confirming that the patients actually have the target for our drug upfront, we believe it was an important way of enriching the population of potential responders. And as we carried out the study, I think that was confirmed because our screen failure rate was probably on the order of 30% to 40%, meaning that even though these patients had cognitive impairment, it didn’t actually have BETA amyloid deposition at a level that was detectable with the screening reagents. So they were eliminated from the study, they could arguably never have responded to our drug anyways. So we needed to actually get them out of the study upfront. How this plays out with respect to the eventual labeling of the drug? My guess is that it will become standard practice to actually screen patients with early stages of Alzheimer’s with either AV-45, which is available or something a kin to that and a kin to that, I mean there are CSF levels of a beta that can be looked at as well. Someway of screening patients upfront to confirm that their disease, their cognitive impairment is caused by BETA amyloid deposition, I think, will become part of the treatment paradigm. So whether it’s a bio assay based on CSF or whether it’s an imaging approach like we’ve used, I do believe that that will be an essential part of the treatment paradigm going forward, to confirm that these drugs are being used in the right patients.

Okay. So with that I think we’ll bring the call to an end. So thank you all for your flexibility and being with us this afternoon. And thanks for all your interest and we can all get back to work.

This concludes today’s conference call. You may now disconnect.