Biogen Inc. (BIIB) Q3 2015 Earnings Report, Transcript and Summary

Good morning. My name is Chris, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Third Quarter 2015 Financial Results and Business Update. All lines have been placed on mute to prevent any background noise. After the speakers’ remarks, there will be a question-and-answer session. [Operator Instructions] Thank you. Ben Strain, Investor Relations, you may begin your conference.

Thank you, and welcome to Biogen’s third quarter 2015 earnings conference call. Before we begin, I encourage everyone to go to the Investors section of biogen.com to find the press release and related financial tables, including a reconciliation of the GAAP to non-GAAP financial measures that we’ll discuss today. Our GAAP financials are provided in Tables 1 and 2. Table 3 includes a reconciliation of our GAAP to non-GAAP financial results. We believe non-GAAP financial results better represent the ongoing economics of our business and reflect how we manage the business internally. We have also posted slides on our website that follow the discussions related to this call. I would like to point out that we will be making forward-looking statements which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult our SEC filings for additional detail. On today’s call, I’m joined by our Chief Executive Officer, Dr. George Scangos; Dr. Alf Sandrock, our Chief Medical Officer; and our CFO, Paul Clancy. I’ll now turn the call over to George.

Okay. Thank you, Ben, and good morning, everyone, and thanks for joining us today. Third quarter was marked by significant progress across several key areas. We delivered a 11% revenue growth and 18% non-GAAP EPS growth, as we continue to see modification growth across the portfolio. We have several important developments in our pipeline. We initiated enrollment for our Phase 3 clinical program for aducanumab and Alzheimer’s disease. We announced Phase 3 results for TYSABRI and secondary progressive MS, which I will cover in more detail later in the call. And we continue to strengthen our pipeline by announcing an agreement to exclusively license MT-1303 for Mitsubishi Tanabe. On the commercial front, we remain committed to improving our commercial trajectory with a particular emphasis on TECFIDERA. Our market research continues to indicate that prescribers believe TECFIDERA has a very strong benefit risk profile. However, patient growth in the U.S. and Germany remains challenging, and we’re actively working to improve this dynamic. We’ve increased sales costs for TECFIDERA, as we continue to educate physicians on TECFIDERA’s strong efficacy and favorable safety profile and its label and monitoring requirements. We’ve also increased our direct-to-consumer marketing in the U.S., including a recently launched television campaign that some of you may have seen. We also made significant progress on capital allocation. Through yesterday, we’ve returned approximately $3.9 billion to our shareholders through the repurchase of our common stock. Importantly, Biogen still retains strategic flexibility to support both continued business development and potentially larger scale acquisitions. We remain focused on strengthening and expanding our early stage pipeline through tuck-in acquisitions and collaborations. The strategy that has produced assets, such as TECFIDERA, ELOCTATE, ALPROLIX, aducanumab, Isis-SMNRx and Raxatrigine. We’re actively looking for late-stage and commercial assets, which have the potential to add both strategic value and near-term revenue growth, while maintaining financial discipline. Today, we also announced the corporate restructuring that we believe will best position the company to achieve our strategic priorities. This decision to reduce our workforce was extremely difficult and we’re very thankful for the hard work and contributions of our talented colleagues and friends. As part of our effort to focus on key commercial initiatives and high potential pipeline candidate, we’ve also made a decision to discontinue several pipeline program that includes TECFIDERA in secondary progressive MS, as well as certain programs in immunology and fibrosis research, including anti-TWEAK. Importantly, we plan to reinvest the savings from this restructuring into key commercial initiatives and a number of prioritized programs across our emerging mid- and late-stage pipeline, including commercial initiatives aimed at increasing sales and marketing therapies, including new direct-to-consumer marketing programs for TECFIDERA, the advancement of aducanumab, BAN2401, and E 2609 for Alzheimer’s disease, Anti-LINGO for multiple sclerosis, Isis-SMNRx for spinal muscular atrophy, our recently acquired asset from Convergence, Raxatrigine for Trigeminal Neuralgia and other pain indications, and MT-1303 for inflammatory bowel disease and other autoimmune diseases. And with that, I’ll turn the call over to Al for an update on R&D.

Thanks, George. We had important clinical study readouts and good progress advancing a new generation of mid- and late-stage clinical program. This morning, we reported top line results from the Phase 3 ASCEND study for TYSABRI and secondary progressive MS. The objective of the ASCEND was to determine whether TYSABRI had an impact on slowing disability progression unrelated to relapses in patients with SPMS. Most patients that enrolled in ASCEND had non-relapsing SPMS and had EDSS scores of 6.0 to 6.5. ASCEND did not achieve its primary or secondary endpoint, and we do not intend to file for label expansion. We are disappointed in these results, as SPMS is a serious condition with no effective therapies. ASCEND study results did demonstrate that TYSABRI had a robust impact on relapses and MRI measures of disease, consistent with its known clinical profile in relapsing MS. Study results also indicated that TYSABRI had a statistically significant effect on upper limb function measured by the 9-Hole Peg Test, which was a component of the composite primary endpoint. Full study results will be reported at our future medical meeting. Moving onto our other MS development programs, at the ECTRIMS Meeting earlier this month, we represented an additional analysis for renew, a Phase 2 study that evaluated Anti-LINGO in patients with acute optic neuritis, the top line results of which we reported earlier this year. About half the patients in renew underwent multifocal visual evoked potential testing, a method that allows us to record electrical responses produced in the occipital cortex upon stimulation of small segments within the retina. First, we found that Anti-LINGO had an effect on the recovery of the multifocal VEP amplitude recorded by stimulating the eye that was affected by the optic neuritis. Interestingly, we also found that Anti-LINGO treatment preserved the multifocal VEP amplitude, recorded by stimulating the opposite eye, which was seem to be deteriorating in the placebo group, likely due to lesions developing in the visual system, as a result of some of these patients being in the early stages of MS. We believe that these results further support our previously reported findings and provide evidence that Anti-LINGO may have neuroprotective properties. We continue to expect top line results from the Phase 2 synergy study in MS in mid-2016. Turning to ZINBRYTA, The New England Journal of Medicine has just published the results of the ZINBRYTA Phase 3 DECIDE study. In DECIDE, ZINBRYTA demonstrated a compelling 45% improvement in annualized relapse rate compared to interferon therapy. If approved, we believe ZINBRYTA could be an important new therapeutic option for relapsing MS patients. At ECTRIMS, Roche presented positive Phase 3 results in both relapsing and primary progressive MS for ocrelizumab, a product in which we have a business interest. Results from two Phase 3 studies in relapsing MS showed a 46% and 47% reduction in annualized relapse rate compared to interferon therapy. Ocrelizumab also demonstrated a significant role in the treatment of primary progressive MS, a serious neurodegenerative condition for which there are no approved therapies. If approved, it would be wonderful to be able offer these patients a meaningful new therapy. Turning to our hemophilia therapies, ELOCTA, which is the approved European trade name for ELOCTATE, obtained a positive recommendation from the CHMP, as a therapy for hemophilia A. If approved in the EU, ELOCTA would be commercialized there by our collaborators Sobi. At the 2015 National Hemophilia Foundation Meeting, new ALPROLIX data showed a beneficial long-term safety and efficacy profile in patients with hemophilia B. Favorable long-term clinical results for ELOCTATE treatment of patients with hemophilia A were also recently published. Moving to the aducanumab Phase 3 program for patients with early Alzheimer’s disease, we have initiated clinical sites in both the emerged and engaged studies and the first study subjects have now been enrolled. We are pleased to have received FDA agreement on a special protocol assessment on the aducanumab Phase 3 study protocols. We have previously reported that ARIA or amyloid-related imaging abnormality was the most significant adverse event observed in the aducanumab Phase 1B study. All patients currently enrolling into Phase 3 studies of aducanumab are undergoing dose titrations in an effort to mitigate the risk of ARIA. Preliminary data from the Phase 1B study suggests that dose titrations does seem to reduce the incidence of ARIA, although these findings will need to be confirmed with further study. We continue to obtain additional clinical data from the Phase 1B study, and we anticipate discussing these results at a scientific meeting in the second-half of next year. We have made progress in expanding our development pipeline by acquiring rights to MT-1303, a Phase 3 ready program with potential and multiple autoimmune diseases. At the recent ECTRIMS Meeting, Mitsubishi Tanabe presented compelling results from a 415 patient Phase 2 study in MS. Results demonstrated that MT-1303 did not cause a decrease in heart rate with administration of the first dose, even without dose titration. This characteristic of the molecule may serve to eventually differentiated from other S1P modulators. We anticipate deal completion in the fourth quarter and we intend to initiate Phase 3 studies in inflammatory bowel disease as soon as possible next year. We continue to evaluate potential further development in MS. Progress has also been made with several early-stage programs BIIB061 and oral treatment being developed as a potential reparative therapy for MS has successfully completed Phase 1 studies. We recently initiated a Phase 1 study for BIIB054, a monoclonal antibody targeting α-synuclein, which is being developed as a potential disease modifying therapy for Parkinson’s disease. The target of BIB-54 α-synuclein is a major component of Lewy bodies, a pathologic hallmark of Parkinson’s disease. R&D continues to make good progress advancing the next wave of therapies and development candidates. Next year, we anticipate the approval of ZINBRYTA for relapsing MS. We also intend to initiate a number of clinical studies, including a Phase 3 study of MT-1303 in IBD, a Phase 3 study for Raxatrigine for trigeminal neuralgia, as well as a Phase 2 study BIIB61 in MS. We’re also looking forward to several upcoming clinical readouts, including Phase 3 results for SMNRx in spinal muscular atrophy, Phase 2 results for Anti-LINGO in MS, and interim phase 2 results for BAN2401 and E2609, both for Alzheimer’s disease. We look forward to a deeper discussion of these pipeline programs and other initiatives that are upcoming R&D Investor Day on November 3. I’ll now pass the call to Paul.

Thanks, Al. Our GAAP diluted earnings per share were $4.15 in the third quarter. Our non-GAAP diluted earnings per share were $4.48. Total revenue for Q3 grew a 11% year-over-year to approximately $2.8 billion. Foreign exchange offset by hedging weakened total revenue by approximately $63 million year-over-year. Global third quarter TECFIDERA revenue was $937 million, an increase of 19% versus Q3 of last year, and an increase of 6% versus the prior quarter. Foreign exchange impact offset by hedging weakened TECFIDERA revenue by approximately $12 million year-over-year. This quarter’s TECFIDERA revenues consisted of $754 million in the U.S. and $183 million outside the U.S. Compared to the second quarter of 2015, U.S. TECFIDERA revenue increased 5%, partially due to an increase in inventory at specialty pharmacies, while U.S. revenue also benefited from a price increase in the quarter, this was partially offset by an increase in managed care and government rebates. In Europe, TECFIDERA had strong sequential patient growth this quarter, driven by newly launched markets, including the U.K., Italy, and Spain. Interferon revenues, including both AVONEX and PLEGRIDY increased 5% year-over-year to $785 million in the third quarter. Foreign exchange impact offset by hedging weakened Interferon revenue by approximately $23 million year-over-year. Interferon revenues were comprised of $538 million in the U.S. and $247 million in sales outside the U.S. On a sequential basis, we believe the 18% increase in U.S. Interferon revenue benefited from a wholesaler inventory rebalancing coming off of the inventory drawdown in Q2, which contributed approximately $40 million. Outside the U.S., AVONEX revenue benefited by approximately $16 million from the timing of shipments in Brazil and a clinical trial order in our rest of world business. TYSABRI continue to add patients this quarter with worldwide revenues of $480 million. These results were comprised of $284 million in the U.S., and $196 million internationally. Foreign exchange impact offset by hedging weakened TYSABRI revenue by approximately $23 million year-over-year. Turning to our hemophilia business, ALPROLIX revenue in Q3 was $66 million and ELOCTATE was $91 million. In the U.S. after a period of rapid uptake for our ALPROLIX with elevated switching in the market, we saw the switch rates start to moderate is roughly half of the moderate and severe hemophilia B patients, treated prophylactically have switched to ALPROLIX. ELOCTATE has continued to grow in the U.S., and we saw increased breadth and depth of prescribing. Approximately 20% of moderate and severe prophylactic patients with hemophilia A have switched to ELOCTATE. Our U.S. profit share for RITUXAN and GAZYVA, as well as our profit-share and royalties on sales of Rituximab outside the U.S. were $337 million. Now, turning to the expense lines in the non-GAAP P&L Q3 cost of goods sold were $310 million, or 11% of revenue. Q3 R&D expense was $520 million, or 19% of revenues. This includes $48 million in upfront and milestone expense related to our recently closed collaboration with AGTC. We made a $60 million milestone payment to Neurimmune this quarter triggered by dosing of the first patient in, in the Phase 3 trials for aducanumab. This payment was an expense and presented within the non-controlling interest line in the P&L. Q3 SG&A expense was $478 million, or 17% of revenue, as we continue to make steps in containing SG&A expenses. Our non-GAAP tax rate was approximately 24% for Q3. This brings us to our non-GAAP diluted earnings per share, which were 448 for the third quarter, an increase of 18% over Q3 2014. While there are number of puts and takes in the quarter, we delivered a very solid quarter with solid results from the United States Interferon business, continued European rollout of TECFIDERA, continued progress in the hemophilia franchise, and meaningful cost control absorbing the AGTC in Neurimmune payments. Let me turn to discuss our progress on returning capital to shareholders. Recall, our Board had authorized the $5 billion share repurchase program in May of this year. Due to lower share price, we put in place a more robust share repurchase plan in late July, effectively expediting the program. Through September 30, we’ve repurchased approximately 9.7 million shares of our common stock for a cost of approximately $3 billion. And since the end of the quarter, we have purchased an additional 3.2 million shares for approximately $900 million. Our current expectation is to complete the 5 billion share repurchase plan by the end of the year. In conjunction with funding our share repurchase program, we borrowed $6 billion of senior unsecured notes in mid-September. This included maturities of 5, 7, 10 and 30 years. We ended the quarter with approximately $7.8 billion in cash and marketable securities split approximately 60/40 between the U.S. and ex-U.S. Let me now provide additional detail on the corporate restructuring. The restructuring includes the termination of a number of pipeline programs in a 11% reduction in workforce. The reduction was the result of a number of actions, including the consolidation and elimination of certain overlapping groups across the organization in analytical and operational support and in marketing. Resizing portions of the company, where we felt there was excess capacity, including in our manufacturing operation. Resizing our ex-U.S. commercial operation and reductions driven by our de-emphasis of certain activities in immunology and fibrosis research in the termination of certain development programs. We plan to complete the majority of the reduction of the global workforce by the end of 2015. The restructuring is expected to reduce the current annual run rate of operating expenses by approximately $250 million. We expect to incur charge in the range of approximately $85 million to $95 million, primarily in the fourth quarter related to the restructuring. Additionally, we’re currently in the middle of our financial planning for 2016, and aim toward additional savings in non-labor expenses, with the objective of reducing lower priority fees and services expense. Conversely, on the investment side, as we move into 2016, we’re excited and plan to invest behind in emerging, mid- and late-stage pipeline, invest in TECFIDERA DTC, and we’ll potentially invest at risk behind prelaunch activities related to the potential commercialization of SMNRx. While we outline our specific 2016 financial guidance in late January, we currently expect upward pressure in R&D and aim for leverage in SG&A. We aim to achieve lower overall expense growth in the top line for 2016. The restructuring will yield risk savings to enhance our operating results for 2016 and beyond, while also providing financial flexibility, as we embark on a number of meaningful pipeline opportunities. Given the restructuring change in capital structure and share repurchase activity this quarter, we’re updating our full-year 2015 guidance. Let me start with revenues. We now expect revenue growth between 8% and 9%, a modest increase versus prior guidance, reflecting the revenue strength seen this quarter. This guidance assumes modest patient growth in the U.S. for our MS products as a whole for the balance of the year. The revenue outlook also assumes a sequential decrease in Q4, due to the assumption of stable U.S. channel inventory levels for the balance of year in MS, and a reduction in U.S. wholesaler inventory levels for RITUXAN. Non-GAAP full-year R&D expense is expected to be between 19% and 20% of revenue, unchanged from prior guidance. Assuming deal closure, we will book in approximately $60 million expense to R&D in the fourth quarter, relating to our agreement with Mitsubishi Tanabe. Non-GAAP full-year SG&A expense is expected to be approximately 19% to 20% of revenue, a decrease from prior guidance. We do expect to invest in TECFIDERA TV in Q4. We anticipate booking a GAAP charge of approximately $85 million to $95 million, primarily in Q4 related to the restructuring. In conjunction with our recently completed bond offering, we now anticipate additional interest expense of approximately $60 million per quarter. We expect to end the year with approximately $219 million fully diluted shares, and have a full-year weighted average diluted share count of approximately 231 million shares. We anticipate non-GAAP full-year earnings per share results between $16.20 and $16.50. This represents an increase of 17% to 19% year-over-year, and GAAP earnings per share, we expect to be between $14.65 and $14.95. The increase versus prior guidance is due to stronger than anticipated revenues in Q3, taking costs out of the business in the share repurchase activity. I’ll turn the call over to George for his closing comments.

Hey, thank you, Paul. This year has been a challenging month for those of us here at Biogen. But I believe that we have a solid business and R&D pipeline with exceptional potential, a thoughtful capital allocation strategy, a well-controlled expense base, and a capable group of people, who can execute against our goals. If we put aside quarterly revenue variations due to fluctuations in inventory levels, FX, or other factors, on a unit basis, we’ve seen moderate but steady growth in the underlying business. Our pipeline has matured, and I believe that pipeline is more exciting and more promising than it was a year ago. Additional data for aducanumab and Anti-LINGO increased our optimism about both of those compounds. We believe that MT-1303 has real potential in ulcerative colitis and Crohn’s disease. Raxatrigine had promising data in a controlled Phase 2 trial and will move to Phase 3 trial in trigeminal neuralgia in a Phase 2B trial in sciatica. SMNRx data from the open label Phase 2 trial are encouraging, and we’re looking forward to the Phase 3 data late next year or early 2017. Additionally, our research has become truly world-class, and were looking forward to giving you a deeper view of what we’re doing at R&D Day on November 3. In Q3, we began the execution of a thoughtful capital allocation strategy. We issued $6 billion of senior unsecured notes, which allowed us to take advantage of our lowered stock price to return approximately $4 billion to investors through stock buy backs with an additional $1 billion to go. We have been able to reduce our share count substantially, while leaving adequate financial flexibility for strategic acquisitions of compounds and our companies. We continue to consider opportunities within our core areas of expertise, both large and small, and as always, we’ll do so, while being financially disciplined. The restructuring that we announced today was an extremely difficult position, and all of us feel deeply for the affected employees. These people are our friends and colleagues and they’ve played a big role in the successes that Biogen has had up until now. They’re good people, good employees, and it truly saddens us to have to take this action. On behalf of the senior leadership team, I want to express our sincere appreciation for the work that everyone at Biogen has done. Although this action is extremely difficult, it’s a necessary step in order for us to fulfill our goals as a company. I believe that our mid- and late-stage pipeline is larger and higher quality than it has ever been, aducanumab, SMNRx, Raxatrigine, and MT-1303 either are or soon will be in Phase 3, and we’re hopeful that LINGO will join them next year. These programs will require substantial investments and we believe that restructuring will allow us to aggressively conduct these programs, while maintaining healthy earnings growth. Next year, we expect to have meaningful clinical data from SMNRx, Anti-LINGO, BAN2401, our base inhibitor E2609, and we hope to gain approval for ZINBRYTA and for two of our bio-similar molecules. So our pipeline has both near-term and longer-term potential to add value to patients and the company. And we need to be able to adequately fund these exciting programs. The restructuring helps us to do so. Before I conclude, I want to take a moment to acknowledge Tony Kingsley’s contributions to Biogen. Tony joined Biogen over five years ago and was instrumental in leading the successful introduction of several important new therapies that help serve patients around the world. I want to publicly thank Tony for all that he has done and wish him all the best in his next endeavor. Tony built an extremely capable team, and I believe that we have the people and programs in place to maximize the potential of our commercial portfolio. In the interim, leadership of this group will be assumed by John Cox, EVP of Pharmaceutical Operations and Technology. John has been with Biogen for over 12 years, has a good understanding of all aspects of our business, and I believe that we will – he will effectively lead this group. So as we move forward, we’re starting from a good base and we’ll focus on five key goals. One, maximize the potential of our commercial portfolio; two, aggressively advance our mid- and late-stage clinical programs to get them gone on or ahead of schedule; three, continue our emphasis on world-class science and medicine; four, carefully control our costs; and five, pursue nonorganic growth opportunities. We’re energized by the potential that we have to transform the lives of patients around the world, and by doing so to do right by our shareholders. I can’t promise you success in everything that we do, but I can promise you our commitment and dedication. And with that, we’ll now open up the call for questions.

[Operator Instructions] The first question is from Mark Schoenebaum with Evercore ISI. Your line is open.

Once again thanks for all the transparency that has been the hallmark of Paul’s tenure as CFO, and George as CFO, and your IR team has done a great job too. I had some questions on the pipeline for Al, if I may. Al, when will we actually see data from the some of the titration doses on the antibodies, most importantly the titration to the 10 milligram data please? And number two, you’ve talked about this before, but I think, it’s time that we all start talking about again and just want to get your take. The optic neuritis data that you looked at is kind of you had to really squint to see activity. And so Wall Street expectations right now are extremely low for LINGO and MS. I mean, do you view LINGO and MS as a low probability trial, or is this one that you have a higher degree of confidence in? Thank you.

So, thanks, Mark. On the first question, we expect to show results in the second-half of the year. We actually have two places – oh, next year, yes. The – there’s two places where we’re doing titration. One is that we – when we put people from placebo in the prime study, in our Phase 1B study over into the long-term extension that was the titration phase. And second, in cohorts eight to nine in the prime study, titration was built into the – into that study. So there are these two studies essentially to analyze and it’s going to take us a little time of time particularly to get to the 10 milligram, which is what you’re interested in, and will be the second-half of next year. In terms of the Anti-LINGO, I mean, look, it’s high risk. I mean, nobody has ever even attempted really that I know to repair the central nervous system, and it’s a tall order. On the other hand, we think we have proof of biology based on the optic neuritis study. We believe that the results portend that we’re getting the biology we want. The key question for me is, is that biology going to lead to a clinically meaningful effect? And that’s what we’re hoping to see in the MS trial.

The next question is from Matthew Harrison with Morgan Stanley. Your line is open.

Great, thanks. Definitely a lot of questions to ask, maybe just another one for Al. Maybe just specifically on SPMS. Could you – it’s unclear to me from the press release, it sounded like what you were trying to say was, you saw some impact in patients that had active lesions and you saw no impact in patients that didn’t. Can you maybe just confirm if that was what you were trying to say, and if there was any numerical trend outside of patients without active lesions?

Well, I mean, what we are saying is that, it’s true that there was a minority of patients, that were still relapsing in the trial, and that’s why we were able to show a robust effect on relapse rate. Those are what I would call active from the inflammatory point of view. And that – there clearly was – we saw what we had seen in the past an inflammatory disease with TYSABRI. In the non-inflammatory group, which was, I think, the majority of patients, we think, we see something in the upper extremity. However, we did not see an effect on the other two components of the primary endpoint, which was the EDSS and the Timed 25-Foot Walk. And so we were disappointed in the fact that, we didn’t see an effect on ambulation. And so I think that’s the reason why the primary endpoint was negative. I would say that upper extremity function is important in patients, particularly if their ambulation is starting to get lost. So that’s why we’re going to present these results next year at the Scientific Meeting.

The next question is from Geoff Meacham with Barclays. Your line is open.

Morning, guys. Thanks for all the detail today and congrats on the quarter. Switch gears to ask a couple of questions on commercial for TECFIDERA and then DTC campaign. What population MS patients do you get or do you expect to get that you couldn’t reach previously? And maybe can you speak to the breadth and length of time that you’ll be doing the PCR reach just thinking from a cost perspective? Thanks.

Yes, thanks, Geoff. This is Paul, I’ll take a crack at that – at that question. We essentially started in the first week and some of you may have seen the TV campaign, I think, the current thinking now is, we’ll look hard at measuring this thing along the way. But I think the current thinking now is well into 2016. And our planning that we’re doing now is to effectively have it ongoing throughout the majority of 2016. I think the overall objective isn’t that similar to the – what we saw early on in the launch is that, TECFIDERA when it came early on the launch, expanded the market, activated new patients, many of them that had gotten injection fatigue on the sidelines. And I think the thinking here is to activate those patients, activating a whole set of patients through patient awareness, which we do have some data that actually suggests that, it’s a relatively low level of patient awareness, sorry, said another way, at least, that there’s a big opportunity in driving patient awareness. And we also have data that suggests that when a patient comes to a doctor, particularly in the United States with a preferred therapy that is often the therapy that the patient goes on. So that’s kind of a bit of a core thesis, and we look forward to kind of moving forward with it.

The next question is from Ying Huang with Bank of America. Your line is open.

Good morning. Thanks for taking my question. First one I have a housekeeping question. Can you spell out the TECFIDERA U.S. inventory impact exactly? And then also maybe for Al, what’s your consideration behind the decision to proceed for MS indication for MT-1303? Is that conditional on the readout from LINGO, or the other programs in MS programs. And lastly, can you update on the timing for the antibody BAN2401 and also the base emitter E2609 in second-half? Thank you.

All right. I think, I’ll take the first of your four questions, Ying. So that’s a pretty easy one. What our best estimate on the essentially the tailwind we had on TECFIDERA inventory in SPP this quarter was about $10 million to $15 million. Al?

So, on 1303 and MS, there’s a number of option for that, and we’re looking at all of them. And well, first, we have to wait for this deal to close. But in the meantime, we’re considering a number of options. In terms of the other Alzheimer’s program BAN and the base inhibitor, I think the best thing to do, we’d ask a sigh actually what their timelines are. My understanding is that sometime next year, we’ll see some data from the base inhibitor. And in terms of the BAN, I mean, there’s sort of interim analysis that are based on events or numbers of people randomized I believe. So that’s my understanding. But I think we could see something next year as well.

The next question is from Eric Schmidt with Cowen & Company. Your line is open.

Thanks for taking my question. It sounds like you guys spoke a little bit more about SMNRx on this call than in the past. I think I actually heard Paul say something about commercial preparation or potential, of course, preparation next year. Has your optimism around the program changed? And is there a chance for filing prior to the Phase 3 data?

Well, we’ve been fairly optimistic – I’ve been fairly optimistic for quite sometime, and with every passing day, as we look at the open label of the data from the Phase 1 studies, my optimism remains. And but I still think that we’re going to need data from the Phase 3 program. I mean, these are the definitive controlled clinical trials, and I would not want to raise any expectations that we could do anything without looking at that data.

And then, Eric, this is Paul, just to kind of, the other part of your question was commercial preparedness. We would characterize this, as I mentioned that, this would be at risk commercial prelaunch activity, and it’s a specialty market. So I think it’s in a manageable amount of money, but we would likely look towards doing that sometime in 2016.

The next question is from Terence Flynn with Goldman Sachs. Your line is open.

Hi. Thanks for taking the questions. Maybe just two from me. Paul, you gave us some of the drivers for next year spend and recognized you don’t want to give guidance at this point, because you’re in the midst of planning. But net-net, as you think about just OpEx, can you comment directionally if we should think about it up or down versus this year? And then the second question I had relates to ocrelizumab, now that we’ve seen the full Phase 3 data. Al, just wondering if you can frame for us, how you think about this as a competitive threat to either TECFIDERA and/or TYSABRI? Thanks.

Yes, Terence, it’s hard for me, I think, we’re obviously right in the middle of planning. So we did want to provide some context, given we’ve got all these moving pieces coming out of the restructuring right now. But I think it goes back to it likely is operating expenses that are up. It is likely a very manageable number up. I don’t want to give a specific number until we really get kind of to the end of year call and the 2016 guidance call. But the restructuring provides real benefits in the magnitude what we announced today of $250 million. We’re going to – we’re working now, that is very much about head count reduction in some of the program decisions. We’re working now to – during our planning process to look at fees and services, what we call external expenses as well and put it under similar type of lens. And then we’re very happy that we simultaneously on the flipside of all these great opportunities is the mid- and late-stage pipeline starts to mature. So I think we’re attacking the efficiencies and working towards investing wisely towards driving sustainable growth for the future. And what we’re trying to do is essentially make that all work as George had mentioned towards getting some earnings leverage as well.

On ocrelizumab, first of all, I think, Roche did a very nice job of the Phase 3 program in both relapsing MS and PPMS. I do think, I believe it will if approved will be a major contribution from MS patients,, which is good. The – on the efficacy side, it did lineup with our expectations. It’s pretty similar in many ways to what’s already been shown in the Phase 2 program for not only ocrelizumab, but RITUXAN. And so it’s in line with our expectations. As with any program, there’s always some safety issues. And we’ll see how the label shapes up in terms of the benefit risk, and then that will determine, how it relates to other products in the market.

The next question is from Matt Roden with UBS. Your line is open.

Great. Thanks very much for taking the question, and congrats on a nice bounce back quarter here. So one of the biggest questions I’ve gotten in the last quarter or couple of months here has been industry-wide just on drug pricing and the contribution of pricing and volumes to growth. And obviously, this has been industry-wide, but you guys have been included as part of that discussion. So, George, or Paul, can you just add some perspective to this debate from your point of view, it seems like industry isn’t really stepping up and telling their side of the story. And then more specifically, if you can comment on how you expect the net pricing environment to evolve in MS. How you see the relative contributions of pricing and volumes on a forward-looking business? Thanks.

Okay. This is George. I can take the first part of that question. Look, obviously, there has been a lot of rhetoric about drug pricing recently, part of that is the presidential campaign. I don’t expect that rhetoric to go away anytime soon. I think the industry is preparing a thoughtful presentation of a different perspective on drug prices, and the value that we bring to patients [indiscernible]. And – look, I mean, that’s what everybody says, but it’s true. In the end, things are going to be priced according to the value that they bring to patients. And if I – we – I believe that if we bring forward innovative drugs that make a difference in the lives of patients that those will continue to get attractive pricing. And that’s why we’re working on the kinds of drugs that we’re working aducanumab and SMNRx and LINGO for MS. Those potentially can make a magnitude of difference that will continue to justify good reimbursement even in a tough pricing environment. So I think that’s how we’re thinking about it generally. In terms of gross to net, I’ll let Paul take that part of the question.

Yes, I mean, hi, Matt, I think, we don’t have too many different comments than we’ve had in the past in terms of the near-term dynamics. We obviously we’ve talked about how United States and Europe dynamics are slightly different. We see a similar dynamics, as we have in the past, and we’ll continue to be very, very thoughtful on what is a critical judgment.

The next question is from Cory Kasimov, JPMorgan. Your line is open.

Hey, good morning, guys. Thanks for taking the questions. George, you mentioned in your scripted comments that you continue to actively look for late-stage or commercial assets. So when thinking about business development in the context of your existing commercial franchising and clinical pipeline, what do you consider the sweet spot in terms of the size of potential deals? And does the restructuring you announced today in anyway impact your willingness to engage in the M&A? Thanks.

Sure. Look, we are constantly looking for interesting opportunities that are consistent with our strategy that are in our areas of expertise. I would say there is no sweet spot, it’s a question of value of what you get for what you pay. And we’ve been financially disciplined in the past. I think, we brought in some attractive assets MT-1303 and Raxatrigine in the past several months. I think, those are very interesting compounds. We will continue to look for compounds like that that we believe are high-quality compounds with reasonable chances of success and making a difference on the marketplace that we can acquire at – also make sense for us. So we’re looking at some small things, we’re looking at some large things. And there’s not so much question of the size, but as of making solid, strategic, medical, and financial decisions.

The next question is from Brian Abraham with Jefferies. Your line is open.

Hi. Thanks very much for taking my questions. Two questions for 1303 you talked about heart rate changes. Can you just talk about any other elements of the compounds profile that you found most attractive? And what you believe differentiates that drug from the other market and developments S1Ps with respect to sell activity in bio-distribution? And then secondly, what proportion of the use of TYSABRI and your other MS therapy today is in primary progressive MS? Thanks.

On 1303, we were – first of all the – on the efficacy side, we felt that the efficacy was similar to all the – to the other S1P1 modulators, and certainly when you look across the MS trials, and even when you look across, say, psoriasis. The most attractive thing was the fact that Mitsubishi Tanabe with their expertise figured out a way to – it’s not simply taking out the S1P3 activity, because a lot of people have done that. But there are other characteristics of the molecule that needed to have a – we think an interesting effect on the heart rate, which we believe is one of the key issues associated with first dose administration. And so it was that, that was attractive. On TYSABRI, I don’t think TYSABRI is used very much in PPMS. In fact, there are no effective therapies for PPMS. And I think I’m pretty – I don’t think that any of the immunomodulatory therapies are used very much at all and PPMS is my understanding.

The next question is from Chris Raymond with Raymond James. Your line is open.

Thanks, guys. I just have a couple of quick questions here. First on TECFIDERA, thanks for quantifying that inventory impact. But I’m just kind of curious, you guys had a mid-quarter price increase oftentimes that’s – that can be seen as a driver for wholesaler inventory moves. Can you just clarify maybe some of the drivers for the inventory increase? And then on BAN2401, besides identifying a dose, can you talk a little bit about what kind of – what success might look like here, I know this trial could be as few as 350 patients, but as many as 800, I believe. And so, there’s a lot of sort of differences with this trial, you’ve got a different sort of cognition endpoints et cetera. I guess, just basically talk about how we should be success with that? Thanks.

Chris, I’ll start with the TECFIDERA inventory question and whether or not, it was driven by pricing, we don’t believe so. Our best understanding is actually the driver of the increase on inventory in the specialty channels was more driven by some government purchases, that really actually potentially relate to fiscal year for certain government institutions. So that wasn’t – as I noted, it wasn’t a lot $10 million or $15 million, so that’s our best understanding at this point.

On BAN, I think, there’ll be several endpoints. One is that there’ll be – we’ll be looking at amyloid plaque load – amyloid plaque burden, which I think is important. And there is an examination of cognition using a composite endpoint, which includes things like the CDR sum-of-boxes. And the number, my understanding of the interim analysis or these analysis is based on a number of patients randomized. And so – but, again, I think, any detailed questions on that, I would rather that you ask [indiscernible]

The next question is from Joseph Schwartz with Leerink Partners. Your line is open.

Thanks very much. I was wondering if you could talk a little more about aducanumab and particular, it seems like you’re shifting your strategy by targeting even more mild patients, or earlier-stage patients in Phase 3. How should we think about this in terms of the enrollment rate and probability of success in the market opportunity? And are you building in a interim analysis here? Thanks very much.

Yes. Well, we are targeting prodromal and the milder sort of segment of the mild populations based on an EDSS, I mean, sorry, MMSE cut off. And that’s because our belief is that the drug – these drugs will work better in the earlier stages of the disease. And in terms of enrollment, we’re pretty encouraged by what we see in early days. There’s a lot of excitement about our drug, and our enrollment line rates are in line or slightly ahead of what we anticipated. So far it’s still early days on the enrollment, and there’s a lot of competition for similar types of patients, nevertheless, we’re encouraged by what we see and…

And baked on accrual?

Well, I just, yes, I think I answered the phone question.

The next question is from Brian Skorney with Robert Baird. Your line is open.

Hi, guys thanks, for taking my question. I guess I was just wondering if you could provide any commentary on in the U.S. MS market. How are you seeing any impact of generic CapEx on October. Are we seeing this primarily impacting the brand right now, or do you think there’s been any impact on your MS franchise. And just real quick on ocrelizumab. Could you just recall that the thresholds on the economics, that you’re getting from Roche on worldwide sales of this program. Thanks.

Brian, thanks for the question, it’s Paul. Let me try to take both those in the – with respect it’s relatively early I think we could say the same thing on the last call, so it’s 90 days more than, it was relatively early last call. But we’re seeing mostly exactly as you had alluded to the impact of a generic comp on comp. So and we’re certainly keeping a very watchful eye on that. Ocrelizumab economics to us are 13.5% to 24% royalty rate it’s a tiered royalty rate on net effectively net sales was a formula for it. We act interesting, we also, which I don’t think we’ve shared in the past we gave 3% royalty on ex-US sales, as well. So as Al, had alluded too in his prepared remarks, and we’ve got a business interest in this. There could be impact on our existing therapies, but we do see this as very interesting financial interest, and certainly in primary progressive MS where there is a tremendous unmet need. There is a real opportunity as well a financial opportunity for us as well.

The next question is from Tom Shrader with Stifel. Your line is open.

Good morning, you didn’t actually answer the interim look question for aducanumab. But I’m a little curious, if this gigantic trial going on with to looks at other drugs. So how do you think about that?

I knew there was a second part of that question. I think we missed the market opportunity as well. So I – we I don’t think it’s great practice to be talking about interim looks and we’re not really planning on anything like that for aducanumab, I think we have a robustly designed trial it’s at the right duration. And so we’ll go right to the end.

The next question is for Michael Yee with RBC Capital Markets. Your line is open.

Thanks, for the question. On commercial question for Paul, on TECFIDERA you had suggested I guess in the last call, that you really thought things were going to be flattish, I didn’t really sort of hear certainly that tone here and thought a bunch of positive things, but maybe like it start to creep up on the volume side. So two-part question one is are you seeing volumes creep up a little bit just trying to understand what’s going on near-term and as to the end of the year. And then second part on one rebating the managed care you mentioned increases in rebating, so just maybe explain a little about what’s going on there as it relates to TECFIDERA volumes and net price. Thanks.

Yes, no thanks, thanks Michael, it’s actually helpful the point of clarification. So we actually are to a large extent what we outlined in the middle of year is, that we’re aspiring for much more. But we outlined on relatively flat patient demand in the United States, that is actually what we witnessed in Q3. We definitely saw continued solid growth in a number of the launch countries in Europe, U.K., Spain, Italy they’ve had very, very good performance. But I’d characterize that that is a launch countries, I think we still absolutely aspire towards much better performance in the United States, there continues to be a lot of big homework in. But until we see that result turnaround we won’t really incorporated in our near-term financial outlook. The action plans, that we have under it is absolutely a priority number one, number in terms of our commercial efforts the action plans we have underway include DTC activity they include enhanced patient support around tolerability, and working that. We’re focused hard on in our own patient services when working with SBP’s of getting patients on therapy, that what we call cycle time. And we’re certainly very focused on increasing sales for details across the world, but certainly in the United States. So we aspire towards, but we haven’t yet actually seen it as George, had noted in his remarks as well.

The next question is from Geoff Meacham with Barclays. Your line is open.

Hi, guys, thanks for taking the follow-up. I guess there’s question for Paul. In the past you guys have given parameters around the level of the old licensing activity. Just want to kind of get a sense, I’m assuming that tuck-in probably means in line with what you guys have done in the past and want to get that perspective from you. And then maybe how you would prioritize capital allocation with the stock where it is now versus buybacks with the stock where it is today versus deal activity. Thanks.

Yes, it’s a yes it’s a tough question I mean look I think we’re going to try to have our P&L in a way set up, that we can not have internal friction to do the classic tuck-in type deals that’s how we’ve done it over the last couple of years within. At this point for the fourth quarter it’s essentially the Mitsubishi Tanabe expense, that we expect assuming HSR Clarence. We’ll try to allow ourselves that the normal type as we go into 2016. In terms of capital allocation, we certainly don’t want to be opaque, but I think this is in the category of it depends. We definitely aim towards all of our decisions on capital allocations is about driving intrinsic value, shareholder value creation. So when we see great opportunities in terms of doing that for returning capital to shareholders through share repurchases we’ll execute against that, we’ve certainly shown that action over the last 60 days. And as George had mentioned, we feel we have an absolute obligation to build the business in a financial disciplined ways with larger deployments, if we can achieve that.

Yes, and this is George. Look, if you look out into next year, we’ll have four compounds in Phase 3, that’s not four Phase 3 trial it’s more than four trials, but it’s for Phase 3 programs. And we’re hopeful if LINGO has data next year that justify moving that forward that will be a fit and we certainly want to leave capacity to move LINGO forward through the Phase 2 data justifying doing so. So I think anything that we would look to in-license that would go immediately into Phase 3, we’d have to cross a pretty high hurdle right. We will, but we’re continuing to look for compounds at all stages I think and at this point with particular emphasis on their earlier pipeline.

There are no further questions at this time. We will turn the call back over to our presenters.

Okay. Well, that was a lot to digest. Thank you all for your attention today, we have a lot going on here. And we’ll keep you posted as we go forward. Thanks.

Ladies and gentlemen, this concludes today’s conference call. You may now disconnect.