Biogen Inc. (BIIB) Q1 2019 Earnings Report, Transcript and Summary

Good morning. My name is Jessa, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen First Quarter 2019 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] Please limit yourself to one question to allow other participants time for questions. [Operator Instructions] Thank you. I would now like to turn the conference over to Mr. Matt Calistri, Vice President, Investor Relations. You may begin, sir.

Thank you and welcome to Biogen's first quarter 2019 earnings conference call. Before we begin, I encourage everyone to go to the Investors section of biogen.com to find the earnings release and related financial tables, including a reconciliation of the GAAP to non-GAAP financial measures that we will 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 reflects how we manage the business internally. We’ve also posted slides on our website that follow the discussions related to this call. I would like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and our actual results may differ materially. I encourage you to consult the Risk Factors discussed in our SEC filings for additional detail. On today's call, I am joined by our Chief Executive Officer, Michel Vounatsos; Dr. Michael Ehlers, EVP of Research and Development; and our CFO, Jeff Capello. We will also be joined for the Q&A portion of the call by our Chief Medical Officer, Dr. Al Sandrock. Now, I’ll turn the call over to Michel.

Good morning, everyone, and thank you for joining us. First let me start with some financial highlights. Biogen started 2019 with first quarter revenues of $3.5 billion, an increase of approximately 11% compared to the same period a year ago. First quarter 2019 GAAP earnings were $7.15 per share, an increase of 29% versus the same period a year ago. First quarter 2019 non-GAAP earnings were $6.98 per share, a 15% increase versus the same period a year ago. These results were driven by solid execution of our strategy to maximize the resilience in MS, progress in our dual launch of SPINRAZA, expand our anti-TNF biosimilar success in Europe, create a leaner and simpler operating model and prioritize our capital allocation efforts with the goal of maximizing shareholder returns. Let me expand on capital allocation. We remain focused on investing in areas with the highest potential benefit for patients and return for our shareholders. In addition to investing in our organic pipeline collaborations and acquired programs, we have made strategic investments in our operations, our biosimilars joint venture, our next-generation manufacturing facility that we are building in Solothurn, Switzerland. We have also taken measures to unlock capital that can be redeployed for higher return such as our agreement to sell our Hillerød, Denmark manufacturing operations to FUJIFILM for up to $890 million. In addition, we have allocated capital with the proposed acquisition of Nightstar Therapeutics. Following the discontinuation of aducanumab, we viewed repurchasing our own share as an area with high potential return and announce a $5 billion share repurchase program. So far in 2019 Biogen has repurchased approximately 4.5 million shares for approximately $1.1 billion and our previously announced 2018 share repurchase program. We have $1 billion remaining under that program, plus $5 billion from our new repurchase program announced in March. We are committed to maximizing the value of our investments and to allocating capital and resources towards the areas we believe to be of the highest potential return something that demands a thoughtful approach over both the short and the long-term. Capital allocation includes the investment we have made in our pipeline. Over the past two years we have added 13 clinical programs and most recently announced our plan to acquire Nightstar Therapeutics. When we articulated our strategy almost two years ago, we identified four core and four emerging growth areas, as we widen our lens to diversify. We have made meaningful progress towards this diversification and have entered into new therapeutic areas, while building depth in our core growth area of neuromuscular diseases and movement disorders and potentially accelerating our entry into ophthalmology. In addition, we continue to advance other assets and pursue therapeutic adjacencies with scientific promise. Today we have 23 programs in clinical development, including BIIB098, which has been filed with the FDA. And we expect 10 mid to late-stage clinical readouts by the end of 2020. In addition two [ph] more mid to late stage clinical assets assuming completion of the Nightstar acquisition. Let me now address three critically important topics. First, the discontinuation of aducanumab and its short-term implications TECFIDERA IP challenges and the outlook for SPINRAZA. First I will address the discontinuation of aducanumab. We are in the business of discovering and developing breakthrough treatments to meet unmet medical needs. The unfortunate reality is that the pursuit of this objective is not always successful. The results for aducanumab are a terrible disappointment for the patients and families desperately hoping for a scientific breakthrough. Our scientists, researchers, medical professionals and as humans we share this disappointment. We followed the science and the outcome was not as we hoped, but we followed the science. I am incredibly proud of everyone at Biogen involved in this journey. We believe that the learning from the aducanumab trials will better position us to potentially attack this terrible disease successfully in the future. Importantly, for our remaining programs focused on targeting beta-amyloid BAN2401 and Elenbecestat, we are analyzing the results from the Phase 3 studies of aducanumab and the Phase 2 study of BAN2401. The learnings from these data will inform our view of the development of BAN2401 and. Elenbecestat. We plan to continue to advance our tau programs in Alzheimer's disease. BIIB092, BIIB076 and 080BIIB080. Beyond the disappointment of aducanumab this outcome takes nothing away from everything else we have accomplished. What we aim to deliver in terms of operational performance over the near term, what we believe we can accomplish in the future with the rest of our pipeline. Biogen is the world's leading neuroscience focused biopharmaceutical company. We intend and expect to remain the leader in the discovery, development and treatment of neurological diseases, while we will also continue to progress our very interesting compounds in lupus and idiopathic pulmonary fibrosis or IPF. We will continue working towards our goal of a multi-franchise portfolio, by growing our pipeline and executing on our strategy. In the short-term, we remain focused on solid quarter-over-quarter execution, financial discipline and our high return capital allocation priorities. And we will continue to pursue opportunities to improve business performance, explore indication expansions, look for ways to accelerate time-to-market for our clinical programs, optimize our clinical resources and manufacturing capacity. Biogen has key competitive advantages. We have deep scientific and clinical development expertise in neuroscience, global commercial expertise including market access, as evidenced by a leading MS, SMA and European entity NS biosimilars commercial portfolio, world-class biologic manufacturing capabilities; and last but not least, a highly talented and energized team, fully committed to realizing the value of the investment we have made in our organic pipeline, collaborations and acquired R&D with the goal of delivering the highest return to our shareholders. As we have communicated in the past, our strategy is long-term-leadership in neuroscience. That is still our reality today. Now, I will address TECFIDERA intellectual property. First, we appreciate that there are many questions regarding our U.S. intellectual property for TECFIDERA, which is being challenged in an inter partes review or IPR in the patent Office and a litigation in District Court. Let me remind you that our 514 patent which covers TECFIDERA and expires in 2028 has been very carefully scrutinized by the U. S. Patent Office multiple times. There was already an IPR before the PTAB where we prevailed, and we were also successful in an interference proceeding. We continue to believe we have valid patents. Nonetheless, we are appropriately preparing for all possible outcomes. Importantly, ahead of the outcome of the IPR and District Court and the Litigations, we shall have the opportunity to launch VUMERITY, a novel oral fumarate disease modifying treatment that has the potential to be another important choice for MS patients. The FDA has accepted the NDA filing of VUMERITY and we expect a regulatory decision in the fourth quarter of this year. VUMERITY has a composition of matter patent with a base expiration date in 2033. It is a priority that we appropriately maximize the potential of VUMERITY. Finally, I will address the outlook for SPINRAZA. Many of you are focused on the potential of upcoming competition for SPINRAZA. While we welcome the options for patients, we continue to believe that SPINRAZA will remain the standard of care in SMA for years to come. There are approximately 7,500 patients on SPINRAZA worldwide, including the EAP and clinical trials with over 7,000 patients having real world experience in the post-marketing setting. We have clinical data following patients for up to six years. The efficacy and safety profile of SPINRAZA in the post-marketing setting has been viewed very positively by patients and physicians. And we believe the NURTURE study of pre-symptomatic infants demonstrates the remarkable efficacy profile of SPINRAZA. Overall, we expect SPINRAZA to continue to grow, as we aim to reach a global patient population that we believe is larger than what we initially estimated. The Biogen team is standing up proud, while taking the current situation very seriously. As always, we are committed to working for patients with unmet medical needs and maximizing shareholder value creation by investing in the areas that we believe have the highest potential return. I will now turn the call over to Mike for a more detailed update on our recent progress in R& D.

Thank you, Michel. And good morning, everyone. Diseases of the nervous system are the leading cause of disability and the second leading cause of death worldwide. The burden and unmet medical need in neurological diseases continues to grow. We remain committed to developing effective, differentiated medicines for these devastating diseases and we believe that are our focus on and asymmetric capabilities in neuroscience position us to lead in this critical area of medicine. Before I review recent progress within our pipeline in greater detail, let me first elaborate on Michel's comments and discuss the recent news on aducanumab. Last month we and Eisai announced our decision to discontinue ENGAGE and EMERGE, the Phase 3 studies designed to evaluate the efficacy and safety of aducanumab in patients with mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease dementia. The decision to stop these trials was based on a futility analysis conducted by an independent data monitoring committee. The pre-specified futility criteria were defined as less than 20% conditional power to meet the primary endpoints of both studies. The recommendation to stop these studies was not based on safety concerns. Further analysis of these data has demonstrated that treatment with aducanumab resulted in a dose and time-dependent reduction in cerebral amyloid deposition, as assessed by amyloid PET imaging. We are actively analyzing the complete data set to fully understand the behavior of aducanumab across doses and cohorts in these two trials. As part of the decision to discontinue ENGAGE and EMERGE, the EVOLVE Phase 2 safety study and the long-term extension of the PRIME Phase 1b study of aducanumab have also been discontinued. We have also decided not to initiate a Phase 3 secondary prevention study to evaluate whether early use of aducanumab can prevent or delay the clinical onset of Alzheimer's disease at this time. We appreciate that these results raise questions about the precise role of aggregated forms of beta amyloid in this patient population. We continue to analyze the data from ENGAGE and EMERGE to inform our view of BAN2401 and Elenbecestat, our programs being developed in collaboration with Eisai. While disappointing for patients, families and the Alzheimer's community, we believe that the data collected from ENGAGE and EMERGE are extensive and that a full analysis will inform future efforts. Data from these studies will be presented at future medical meetings to advance the field's understanding of the neurobiology of Alzheimer's disease and help guide ongoing research. As a leader in neuroscience, we remain committed to our goal of developing novel therapies for the treatment of Alzheimer's disease. We believe the Phase 3 results for aducanumab have limited read through to our portfolio of tau-directed therapeutics. Accordingly, we are continuing to advance BIIB092 or gosuranemab, an anti-tau antibody in Phase 2. BIIB076, a distinct anti-tau antibody in Phase 1 and BIIB080, an antiantisense oligonucleotide targeting tau currently in Phase 1 being developed in collaboration with Ionis. Importantly, two years ago together with Michel we articulated our goal of becoming the leader in neuroscience by building and diversifying our portfolio beyond Alzheimer's disease. Since then, we have made meaningful progress toward that goal by adding considerable depth across our core and emerging growth areas. Specifically, we have added 13 clinical programs since the beginning of 2017, including two that have achieved proof-of-concept and three that have achieved proof-of-biology. These include programs in multiple sclerosis Alzheimer's disease, progressive supranuclear, palsy, ALS, stroke, epilepsy, cognitive impairment associated with schizophrenia and neuropathic pain. And with our planned acquisition of Nightstar Therapeutics we have the potential to add two mid to late-stage assets for inherited retinal disease. Today and not including Nightstar, we have 23 programs in clinical development, including six programs in Phase 1, 13 programs in Phase 2 and three programs in Phase 3, as well as BIIB098 which has been filed with the FDA. This represents a substantial expansion and diversification of our clinical portfolio with many important and promising drug candidates each with significant potential to address some of the most debilitating diseases of our time. Turning to our proposed acquisition of Nightstar Therapeutics. We are extremely excited about the opportunity to join forces with this talented team of drug developers and together address serious genetic causes of blindness for which there have been no treatment options. This acquisition would accelerate our entry into ophthalmology, with the potential to deliver first-in-class adeno-associated virus based gene therapies to patients suffering from severe retinal diseases. Retinal degeneration shares many characteristics with the generative diseases of the central nervous system. And we therefore see positive synergy din pursuing treatments for inherited rental diseases that leverage our scientific and clinical capabilities. Nightstar's lead drug candidate NSR REP1 targets choroideremia, a rare degenerative disease that inevitably leads to blindness for which there are no current therapies. In Phase 1/2 trials treatment with NSR REP1 via targeted subretinal injection was associated with a higher rate of maintained vision, and in a subset of patients, a meaningful improvement in visual acuity, suggesting that NSR-REP1 has the potential to significantly alter the course of this disease. Based on compelling proof-of-concept data in the Phase 1/2 studies, Nightstar initiated the Phase 3 STAR trial. We expect enrollment in this trial to complete in the first half of this year with Phase 3 data expected in the second half of 2020. Of note, NSR-REP1 has received regenerative medicine advanced therapy for RMAT designation from the FDA, which confers all the benefits of both fast track and breakthrough therapy designation. Nightstar's second clinical stage asset is NSR RPGR for X-linked retinitis pigmentosa or XLRP. Like NSR REP1, NSR RPGR is an AAV based gene therapy delivered by targeted subretinal injection. Data from ea Phase 1/2 dose escalation study showed promising signals of early efficacy, including increases in central retinal sensitivity as measured by microperimetry. A Phase 2/3 dose expansion study of NSR RPGR is currently enrolling and assuming the transaction closes we would plan to add a Phase 3 study to support registration. In addition, Nightstar is advancing preclinical programs that include gene therapies targeting Stargardt disease, the most common form of inherited juvenile macular dystrophy, Best vitelliform macular dystrophy and additional programs targeting other genetic forms of retinitis pigmentosa. These diseases which inevitably lead to ability blindness and the associated severe disability are amongst the large group of inherited retinal diseases which have been estimated to afflict up to 200,000 patients in the U.S. alone, many of which may be amenable to similar gene therapy solutions. Subject to final approvals, we look forward to coming together with the remarkable scientific and clinical team at Nightstar with he goal of bringing breakthrough therapies to patients to slow or halt blindness across a range of inherited retinal diseases. Turning to our progress in neuromuscular disorders. Last month, we dosed the first patient in the Phase 3 VALOR study of BIIB067 or tofersen, an antisense oligonucleotide for ALS with mutations in superoxide dismutase 1 or SOD1. BIIB067 selectively targets the mRNA for SOD1 to reduce the levels of toxic mutentmutant SOD1 protein that is thought to be the causative agent in this autosomal dominant genetic form of ALS. VALOR is a continuation of the Phase 1/2 single and multiple ascending dose study of BIIB067 for which we have previously communicated proof-of-biology and proof-of-concept. VALOR is enrolling to assess the efficacy and safety of BIIB067 versus placebo. And the primary endpoint of this study is an analysis based on the ALS functional rating scale revised score. In parallel, we are in active discussions with regulators as we collaborate to further define the scope of the clinical data package required to support the registration of BIIB067. Very limited treatment options for this devastating genetic form of ALS, we believe the data from the VALOR study have the potential to support a rapid path to patients. Moreover, given that BIIB067 engages RNase H mechanisms to degrade endogenous mRNAs and hence decrease levels of the target, we believe that these data have positive implications for additional antisense oligonucleotides that we are advancing in our pipeline together with Ionis, that similarly utilizes RNase H-dependent mRNA degradation. Including BIIB078 which targets C9orf72 for ALS, BIIB080, which targets tau for Alzheimer's disease and other tauopathies and up to two new antisense oligonucleotides that could enter the clinic this year. Further, we believe these data exemplify the depth we are building in neuromuscular disorders, including ALS and highlight the interconnectivity across our pipeline. We plan to present data from the single and multiple ascending dose portions of the Phase 1/2 study of BIIB067 in the emerging science session at the American Academy of Neurology annual meeting next month. And you'll hear more specifically about our ALS pipeline at an R&D investor webcast on June 5th. Moving to SMA. At the 2019 Muscular Dystrophy Association Clinical and Scientific Conference earlier this month, we presented an encore presentation of data from the NURTURE study of SPINRAZA in pre-symptomatic infants with SMA. highlighting the unprecedented efficacy profile of SPINRAZA, these data show patients on average achieving motor milestones consistent or nearly consistent with normal development. Specifically, as of May last year of the 25 infants treated with SPINRAZA in this study, 100% were alive, none required tracheostomy or permanent ventilation, 100% were able to sit without support and 88% were able to walk either with assistance or independently. We believe that SPINRAZA's efficacy profile, including data on patients treated for up to six years combined with real world safety and efficacy experience in over 7,000 patients supports SPINRAZA as the standard of care in SMA. Even after the potential introduction of alternative modalities with significantly less data and outstanding questions regarding long-term safety and efficacy. Within movement disorders, we are making strong progress advancing our assets for progressive supranuclear palsy or PSP and Parkinson's disease. We look forward to the final readout for the Phase 2 study of BIIB092 and PSP in the second half of this year. BIIB092 is a monoclonal antibody targeting extracellular tau, with the aim of reducing the spread of tau pathology in the brain. And we are making strong progress with recruitment in the Phase 2 study of BIIB054, a monoclonal antibody targeting extracellular synuclein for Parkinson's disease. We now expect to receive data on the primary outcome measure from the one-year placebo-controlled period of this study in the second half of 2020. As Michel mentioned, we remain steadfast in our commitment to neuroscience, while we continue to explore therapeutic adjacencies where we have existing assets and/or expertise. Importantly, we continue to progress our clinical programs in lupus and idiopathic pulmonary fibrosis. Specifically, we are advancing BIIB059, a humanized monoclonal antibody that binds BDCA2, a C-type lectin that inhibits type-1 interferon signaling in plasmacytoid dendritic cells. We are currently evaluating BIIB059 in a Phase 2 study in cutaneous lupus erythematosus or CLE and systemic lupus erythematosus or SLE with data expected by the end of this year. Moreover, we expect to work with our collaboration partner UCB to agree on the details of a potential global Phase 3 program for dapirolizumab pegol, an anti-CD40 ligand PEGylated FAB in SLE. A previous Phase 2b study of dapirolizumab pegol in SLE demonstrated consistent and potentially meaningful improvements for the majority of clinical endpoints in patients treated with dapirolizumab pegol compared with placebo. Although the primary endpoint of this Phase 2b study to demonstrate a dose response at 24 weeks on the British Isles lupus assessment group based composite lupus assessment was not met at p=0. 07. We believe the totality of the Phase 2b data supported proof-of-concept. In addition, biomarker data demonstrated strong evidence of proof-of-biology. Dapirolizumab pegol was well tolerated and demonstrated an acceptable safety profile. We believe that the Phase 2b data together with a post-hoc analysis that indicated a notable response in a refined population support a decision to advance to Phase 3. Together with UCB we intend to present these findings at a future scientific forum. So what do we expect from Biogen R&D going forward? Four key priorities. Focus on clinical trial execution and optimizing our resources with up to 10 mid to late-stage readouts by the end of 2020, diversification, including potential indication expansions, continued progress advancing our pipeline including ways to accelerate time to market, and balancing the risk of our pipeline including a continued pursuit of late-stage opportunities. On this last point, let me elaborate on how we think about balancing risk across our pipeline. Biogen is, always has been and will remain a science-driven company, dedicated to converting differentiated biology into breakthrough medicines. That is the promise of innovation spawned from creative ideas and risks at the forefront. It is the incubator of future SPINRAZAs and solutions for patients and families that change medicine. As we advance our portfolio, we will continue to mitigate risk by seeking later-stage assets, taking advantage of our unique capabilities in developing antisense oligonucleotides and gene therapy to target causal genetic drivers of disease such as SOD1 and C9orf72 in familial ALS. Leveraging our depth of expertise in MS and SMA to expand our footprint in neuroimmunology and neuromuscular disorders and deploying rigorous experimental medicine methods, including biomarkers of target engagement and disease activity to derisk early-stage clinical programs. As we diversify and balance risk within our pipeline, we will also thoughtfully consider therapeutic adjacencies that synergize with our core and emerging growth areas and where we have existing assets or expertise. Backed by a significantly expanded portfolio of clinical stage assets, we remain focused on our goal of developing transformative medicines for patients living with devastating neurological diseases. I will now pass the call to Jeff.

Thanks, Mike. Good morning, everyone. I'll now review our financial performance for the first quarter of 2019 starting with revenues. As Michel mentioned earlier, we had a strong Q1 2019 from a revenue perspective. Total revenues for the first quarter grew 11% year-over-year to approximately $3.5 billion. Overall, our MS business delivered revenues of $2.1 billion in Q1 2019, including OCREVUS royalties of approximately $112 million. MS revenues in Q1 2019 decreased 2% versus the prior year without OCREVUS royalties and were stable including OCREVUS royalties. U.S. MS revenues in Q1 2019 were impacted by a decrease in channel inventory of approximately $170 million compared to a decrease of approximately $140 million in Q1 2018 and an increase of approximately $105 million in Q4 2018. Global first quarter TECFIDERA revenues increased 1% versus the prior year, driven by revenue growth outside the U.S. U.S. TECFIDERA revenues were impacted by a decrease in channel inventory of approximately $110 million in the first quarter of 2019 compared to a decrease of approximately $80 million in Q1 2018 and an increase of approximately $60 million in Q4 2018. We were pleased to see an increased share of both new and total prescriptions for TECFIDERA in the U.S. With our share of new prescriptions exceeding our share of total prescriptions for the first time in almost two years. Outside the U.S., TECFIDERA performed very well in Q1 2019 with continued double-digit volume increases across most large European markets and Japan versus the prior year, somewhat offset by pricing pressure in several European countries. Q1 interferon revenues including both AVONEX and PLEGRIDY decreased 9% versus Q1 2018 due to the shift from the injectable platforms to oral or high efficacy therapies. Within the U.S., AVONEX and PLEGRIDY were impacted by a decrease in channel inventory of approximately $45 million compared to a decrease of approximately $60 million in Q1 2018 and an increase of approximately $35 million in Q4 2018. TYSABRI worldwide revenues were stable versus the first quarter of 2018. Within the U.S., TYSABRI revenues were impacted by a decrease in channel inventory of approximately $15 million compared to relatively stable inventory levels in Q1 2018 and an increase of approximately $10 million in Q4 2018. TYSABRI's underlying performance improved in the U.S. with an increased share of both new and total prescriptions. Outside the U.S., TYSABRI revenues increased 1% versus the prior year. Overall despite the headwinds from channel Dynamics, we were pleased with the continued resilience of our MS business in the first quarter and are focused on maintaining the resilience of this franchise in light of new competition entering the market. Let me now move on to SPINRAZA. Global first quarter SPINRAZA revenues increased 42% versus the prior year and increased 10% versus the fourth quarter of 2018. In the U. S. revenues increased 19% versus Q1 2018 driven by continued patient growth. Compared to the fourth quarter 2018, U.S. revenues decreased 5% which we believe was driven in part by seasonality. Outside the U.S., revenues increased 26% versus Q4, driven by continued new country launches and increased penetration across all major geographies, as well as a positive pricing adjustment in France following the receipt of former reimbursement and timing of shipments across several international markets. The number of patients on therapy in the U.S. increased 5% as compared to the end of the fourth quarter of 2018 and discontinuations remained relatively low. In the U.S., we continue to make strong progress with adults. In the first quarter approximately 50% of new starts were adults, increasing the total number of adult patients on SPINRAZA to over 1000, an increase of approximately 8% versus the fourth quarter of 2018. We saw continued increase in the revenue contribution from maintenance doses this quarter. In the U.S. approximately 75% of SPINRAZA units in the first quarter were attributed to maintenance doses, as compared to approximately 65% in the fourth quarter. In the first quarter approximately 10% of U. S. SPINRAZA units were dispensed through our free drug program, a decrease from approximately 15% in Q4. Outside the U.S., the number of commercial SPINRAZA patients increased approximately 24% versus the prior quarter. And there are approximately 210 patients active in the expanded access program. We recorded revenues from over 40 international markets in the first quarter. During the past quarter, SPINRAZA was approved in Argentina, Colombia, Taiwan and China where SPINRAZA is now available for self-paying patients. We also secured broad reimbursement in France and South Korea and our named patient sales program in Turkey where we estimate there are approximately 1500 estimated [ph] patients, was expanded to cover type 1, 2 and 3 patients. As Michel mentioned, we believe the global opportunity for SPINRAZA is significant and even greater than we initially anticipated. We now estimate there are over 45,000 individuals with SMA in the markets where Biogen has a direct presence. For example, we now estimate that there are approximately 10,000 SMA patients in Latin America, approximately 15 to 25,000 SMA patients in China and approximately 3,600 SMA patients in the rest of Asia Pacific. These estimates were not factored into our original estimate of 20,000 SMA patients. SPINRAZA has now become our second-largest product, as we continue to execute well on growing our treated patient base. Let me now move on to our biosimilars business. Revenues this quarter increased 37% versus the prior year and 12% versus the prior quarter. BENEPALI has been strengthening its leadership position in countries such as Germany, the UK, Denmark and Norway, shipping again more than 1 million doses in the quarter. In the first quarter FLIXABI exceeded 100,000 doses for the first time in a quarter. For its first full quarter in the market, IMRALDI, which references HUMIRA exceeded 200,000 doses with sales in 18 different countries. In general, the rate of HUMIRA biosimilar adoption has been steeper than for the previous two anti-TNFs. And our data indicate that IMRALDI is the market-leading HUMIRA biosimilar in Europe. As an example, in Germany the largest anti-TNF market in Europe we estimate that HUMIRA biosimilars have already captured approximately 35% market share with IMRALDI capturing about 40% of that share. Overall, our success outside the U. S. with MS, biosimilars and SPINRAZA has led to meaningful geographic expansion and diversification of revenues. Specifically the proportion of our product revenues coming from outside the U.S. increased from 39% a year ago to 44% in the first quarter of 2019. Total anti-CD20 revenues in the first quarter increased 17% versus the prior year, primarily driven by OCREVUS royalties. Q1 was a particularly strong quarter for RITUXAN due in part to channel dynamics and pricing adjustments. As a reminder, our royalty rate on sales of OCREVUS resets at the beginning of every calendar year. Total other revenues in the first quarter increased 78% versus the prior year, driven primarily by the sale of approximately $200 million of inventory associated with the Bioverativ spinoff, somewhat offset by a decline in our other corporate partner revenues. As noted in our Q4 2018 earnings call, this sale of inventory represents most of the remaining hemophilia inventory that we’ve been hold to Bioverativ. Let me now turn to gross margin performance. Q1 2019 gross margin was 83%, negatively impacted by the sale of Bioverativ inventory which carried a very low gross margin. Q1 GAAP and non-GAAP R& D expense were both 16% of revenue. Q1 R&D expense includes approximately $39 million related to our agreement with Skyhawk and approximately $45 million in trial closeout costs for aducanumab. Q1 GAAP and non-GAAP SG&A were both 16% of revenue. For the balance of the year we expect a reduction in operating expenses of approximately $125 million related to aducanumab with ea net savings of approximately $80 million for the full year 2019. In Q1 we booked a GAAP loss of $116 million associated with our agreement with FUJIFILM related to the proposed sale of our manufacturing operations in Denmark. We expect to receive up to $890 million in cash related to this transaction subject to certain working capital adjustments and other contractual terms. Q1 GAAP other income was $357 million, including $376 million in net gains on investments. This includes a $321 million increase in the fair value of our equity investment in Ionis that we made last year in conjunction with our expanded strategic collaboration. We continue to believe that this deal is a great example of how we aim to create long-term shareholder value through a strategic capital allocation. In Q1 non-GAAP other expense was $19 million. In Q1 our GAAP tax rate was approximately 23%, negatively impacted by approximately 400 basis points due to the proposed sale of our manufacturing operations in Denmark. In Q1 our non-GAAP tax rate was approximately 18% which declined from approximately 21% in Q1 2018 due to the remaining benefit of the U.S. corporate tax reform. We repurchased approximately 2.4 million shares in Q1 at an average price of $268 for a total value of approximately $656 million. And so far in April we repurchased an additional 2.1 million shares at an average price of $236 for a total value of approximately $492 million. As Michel mentioned, in the first quarter of 2019 our Board authorized a new $5 billion share repurchase program. This is in addition to the approximately $1 billion remaining under the share repurchase program authorized in August 2018. which now brings us to our diluted earnings per share. In the first quarter we booked GAAP EPS of $7.15, an increase of 29% versus the prior year and non-GAAP earnings per share of $6. 98 percent - excuse me $6.98 per share, a 15% increase versus the prior year. We generated approximately $1.5 billion in net cash flows from operations in Q1. We ended the quarter with approximately $5.3 billion in cash and marketable securities and $5.9 billion in debt. I'll now turn the call back over to Michel for his closing comments.

Thank you, Jeff. The Biogen team is taking the current situation very seriously and dedicating every effort to maximize shareholder value creation. I am inspired by the reaction of the team. And we now have the opportunity and the obligation to rebound. We remain focused on growing our core business in MS, SMA and biosimilars, while addressing the short-term priorities already discussed, including the TECFIDERA IP challenge and preparing for the expected launch of VUMERITY by the end of the year. As always, we will invest in the areas we believe have the highest potential return for shareholders. Between now and the end of 2020, we expect continued progress as we aim to build a multi-franchise portfolio, including data readouts in MS, PSP, lupus, epilepsy, Parkinson's disease, ALS, pain, cognitive impairment associated with schizophrenia and stroke. Potential regulatory approval in the U.S. for VUMERITY in MS and up to 10 new assets advancing into the clinic. Finally I want to reiterate our commitment to maximizing returns to our shareholders and bringing innovative therapies to patients over the long term. This demands that we continue to allocate capital efficiently effectively and appropriately. As we have demonstrated in the past, we will always strive to have an optimal capital structure, as well as aim for superior returns from the investments we make. I will end by stating explicitly that everyone at Biogen is highly committed to making a positive impact on patients life by remaining at the forefront of discovering and developing breakthrough treatments, while always being dedicated to maximizing the long-term returns on behalf of our owners. With that, we will open the call for questions.

Thank you [Operator Instructions] Your first question comes from the line of Ying Huang from Bank of America. Merrill Lynch. Please go ahead.

Hi. Good morning. Thank you very much for taking my question. I want to ask one about your strategy on business development and M&A. In the wake of discontinuation of aducanumab Phase 3, does management team feel more urgency to acquire more assets that are either commercial or near commercial? And along those lines does the Board of directors also feel the same urgency to conduct more M&A and transactions? Thank you?

Thanks for the question. And as we communicated, we plan to deploy our capital to areas of highest returns for the shareholders. And we do believe that at the current stock price level buying back shares is very important. We took aggressive steps to diversify our portfolio in the past. But in the context of our current cash flow generation and the profile of our balance sheet we can do both buying back and also conduct some BD, M&A activities.

Your next question comes from the line of Robyn Karnauskas from Citigroup. Please go ahead.

Hi guys, thanks for taking my question. I think you acknowledging all the concerns that investors had including TECFIDERA and SMA. I guess my key question is while you acknowledge that aducanumab failures some of the reasons why we are so concerned. Let's start with SMA. What gives you the confidence that if the oral product maintains its efficacy in more studies that it won't erode SPINRAZA? And maybe specifically, you -- could you clarify maybe what percentage of patients might be low-hanging fruit for that product? Maybe they are not as compliant as their older patients and not as fit that are currently on SPINRAZA? Thank you.

So, Robyn this is Michael. I'll start with that. I think it's still -- look, it's still pretty early days with the data that we know from RITUXAN has been relatively small numbers of patients in the 20s or 30s, but infants and later onset, they clearly generated some encouraging data on this in terms of efficacy. I think some of the open things that the field is looking to understand about this is the overall benefit risk profile, the degree of efficacy, the extent to which that there is manageable therapeutic index on this. These are all parts of that program and data that are still to really emerge. The way we kind of think about is that particularly through the NURTURE study, the data that we generated from SPINRAZA really sets the bar for the degree of efficacy that's really going to define standard-of-care. So we think that's an important feature here. And we have such an extensive safety database on thousands of patients and patient years. So, again, I think that kind of sets the bar for what safety should look like. Much of this is going to have to play out over time. Right now we are very, very confident in SPINRAZA's profile in terms of safety and efficacy and we'll have to see how the RITUXAN data set reads out at this time.

Your next question comes from the line of Geoff Meacham from Barclays. Please go ahead.

Hey guys. Thanks for the question and for all the perspective on aducanumab. Just had another one on SMA, in the US, can you add a little bit more detail for the new start trends? And you think there is a warehouse effect in 1Q ahead of an expected of excess launch? And then related to that I mean obviously you guys have learned a lot from the SMA launch in the orphan space, do you view this as a strategic asset? And by that do I mean, do you look at the orphan space as a broader area for BD or is the emphasis still from a BD perspective neuroscience focused? Thank you.

Yes. Hi, Geoff. It's Jeff. Thanks for the question. So, as a reminder we grew 18% year-over-year in the U.S. in SMA, so pretty strong growth year-over-year. We did have a bit of a slowdown sequentially which I think you are asking about. Couple of things to remember. Our estimated epidemiology in the U.S. is still 9,000 patients. We're only 30% penetrated to-date. And in the adult class, which is the largest class, 65% of the patients, we're only 18% penetrated. So we continue to do a good job executing. We did a very good job this quarter continuing to grow that adult class. We also had a drop in the free drug percentage from 15% to 10% as more insurance coverage picks up the product which is just a testament to the strength of the product and we had very low discontinuations. Having said that, we did see a slight decrease in the number of new patient starts. We actually saw the same dynamic happen when you look at the fourth quarter of 2017 to the first quarter of 2018. And we think part of that is due to the fact of seasonality both with regard to new patient starts and maintenance doses. In fact, if we look at our maintenance doses, we did see less compliance in the first quarter, which we attribute to weather and the cold and flu season. So this is not that the similar from what we saw in terms of the dynamics shifting from the fourth quarter of 2017 to the first quarter of 2018. So we think we continue to have lots of opportunity to grow this business in the U.S. And, of course, outside the U.S. we had a terrific quarter.

Concerning the second part of your question. Thank you for asking. Based -- following aducanumab setback, we gathered the team and we certainly worked hard to maintain the focus on the operations and the progress from all sites of the company. And again I'm impressed by the reaction of the team. If we step back and we look at our - and reach portfolio that is materially improved compared with what it was 28 months ago. The core of our focus remains and we remain neuroscience. Having said that, we also look very carefully at the progress we are making in lupus with the two compounds that Mike spoke about and also idiopathic pulmonary fibrosis. So this may point out adjacencies potentially in immuno, you speak about rare disease. It's too early for the organization to state that clearly. We need to regroup as a team and we got doing that while we speak share and line with the Board and then come back to you.

And Geoff I might add something to that too. I think you raised a very good point about. Our SPINRAZA experience, I think has been highly informative to us and in growing our capabilities in and around rare diseases broadly speaking. I think when you look at the ability to deploy innovative development plans when you look at the extent of regulator engagements and accelerated paths. When you look at the collaborative relationship that we've exercised in patient efficacy and patient support groups that have supported that and then you look at opportunity space in disease like SMA, which ends up being much larger than I think anyone had anticipated at outset. These points to the adjacencies Michel was just talking about, which were programs we have in our portfolio BIIB067, 078, 092 and the proposed Nightstar acquisitions, all will provide positive synergy and give us another lens to look at an additional external opportunities.

Just to conclude on this question and adding to what Mike is saying. It's all about adding value and highest return for the shareholders and finding synergies with the core capabilities of Biogen the way others will not be able to deliver.

Your next question comes from the line of Michael Yee from Jefferies. Please go ahead.

Hi, thanks. Good morning. I appreciate the comment as well, Michel. I guess, a question for Michel following on big picture strategy and the disappointment post Alzheimer's. Maybe you could talk about whether there is any change or pivot on two fronts? One is the change in investment of capital in the Alzheimer's including BAN2401 or what or how we should think about spending in Alzheimer's? And number two, whether or not there can be anything you can do about realizing immediate shareholder value post Alzheimer's given where the stock price is at and how to think about where you are now? Thanks so much.

Thanks for the great question, Michael. So if you sit back and you recall what we said repetitively. The plan A was always to prepare Biogen for growth even without aducanumab. So as I said, the focus will remain on neuroscience based on the portfolio we have, but also on the adjacencies of all the programs we are developing for now and we'll come back with more. If you look at what we have done, we have materially improved our pipeline. We have materially diversified our pipeline. We are basically positioning the company for the future. We have improved the operational performance and also the efficiency of our operations. And we believe we have the ability to go further. This is where the capital also had been. We believe we invested the capital over the highest return opportunity. We have an IP challenge that we need to solve and we are working on that. And we do recognize our responsibility to shareholders to maximize the return over the long term, specifically on Alzheimer's disease. It has to be science driven. We have tons of data points that we are still not yet finalizing to review and to digest. So we have to wait for the team and a team statistician and clinicians to look at the data, so that we can best indicate, educate the course forward for the beta-amyloid hypothesis and for BAN2401 and elenbecestat. And as I said concerning the capital allocation and the share repurchase, I think, we've been pretty clear that at this level we believe that this is an area with very high return opportunity for shareholders. But again, in the context of the pristine balance sheet that we have, we can do more.

Your next question comes from the line of Cory Kasimov from JPMorgan. Please go ahead.

Hey. Good morning, guys. And thank you for taking my question. I wanted to follow up on the business development front and ask about the companies buying capacity at this point. At the beginning of the year, I believe, you highlighted having roughly $42 billion in buying capacity through 2023. I'm curious if that has shifted at all post the buyback and other transactions? And can you comment how much capacity you believe you have to do something now as compared to over a four to five-year timeframe? Thanks.

Hi, Cory, it's Jeff. Yeah. So we had mentioned back, I believe, it was at your conference that if you took, the metric was – if you took the cash flows of the company at the end of the third quarter of 2018 and you annualize those, you drop the CVRs and then you look at that over a five-year period that was a certain pool of cash. And then, if you look at the cash on the balance sheet, plus leverage up to 2.5 times, less the leverage we have today, that gave you the $42 billion of potential capacity. Assuming all stayed constant in terms of the business, which obviously is not the plan. The plan is to grow the business and grow those cash flows. So that's where we got the $42 billion. We once again had a very strong quarter cash flow wise. We did $1.5 billion in operating cash flow. And I would point out that this quarter was the final payment of the Fumapharm settlement of $300 million. So we're now beyond that settlement. So if anything, we believe that our cash flow will continue and we'll be in a strong position to leverage those cash flows, as Michel had said, with regard to both buying back stock and being active from a business development perspective. So there will be no lack of capacity.

So we believe that deployment of capital at this level of price level should be on the share buyback. We believe this is a high return for everybody and we believe in the value of our company. At the same time, our team is working very hard on looking for other opportunities with high return.

Your next question comes from the line of Umer Raffat from Evercore. Please go ahead.

Hi. Thanks for taking my question. Michel maybe just in a different direction. In listening to you today, I get a sense that the Alkermes fumarate, VUMERITY is more and more important to your MS strategy perhaps than it has been in the past. Can you speak to that? Am I hearing it correct and also should we reasonably expect a meaningful switch ahead of IPR decision? Thank you.

So from day one and this is the reason why we did the -- we deployed capital and acquired this asset is that it was meaningful and strategically important for the company. We have a $9.1 billion franchise in MS that is pretty resilient to date. And we continue to - we want to continue to invest in that space. We believe that this Alkermes compound can eventually be differentiated. We need to wait for some data readouts. In the context of the IP challenge, certainly this is very important. It would be premature to state on any clear tactical plan or strategy for launch. But while we speak, we are working thoroughly on that. It's not that the organization is without any alternative, but we remain confident on our patents for TECFIDERA.

Your next question comes from the line of Alethia Young from Cantor Fitzgerald. Please go ahead.

Hi, guys. Thanks for taking my question and thank you for all the color this morning. I just wanted to go and maybe discuss the pipeline a little bit. I know you have the one data, which will be in? And I just wanted you to talk a little bit more about the C9ORF72 program and like what confidence you've received from the SOD1 that gives you confidence in knocking down that on HUMIRA as well? Thanks.

So Alethia, it's Mike. So I think one thing we've learned from BIIB67 SOD1 program is a lot about how we can very reliably measure target engagement and a pharmacodynamic effect in terms of looking at the relevant cause of the agent species in CSF like SOD1 in that case. We are deploying a very similar approach with C9ORF72 earlier program. So this is now just an essentially safety trials in this ALS patients. So we will be looking at similar types of things. Target engagement lowering of the toxic species and as well as assessing some of the same types of clinical measures. We do think that the extensive experience we've gained in development over time in ALS has significantly enhanced our ability to conduct and execute these trials efficiently.

Your next question comes from the line of Geoffrey Porges from Leerink. Please go ahead.

Thanks very much. I just wanted to clarify a little bit more on what you're saying about 2401 elenbecestat, and particularly in the context of your expenses going forward. It was a bit surprising that canceling of aducanumab was only about 5% saving to your R&D spend. But if you discontinued 2401 elenbecestat, how much would totally you save from expected R&D? And secondly, could you just talk about the contractual flexibility you have to make that decision or can you only suspend funding for those programs with the agreement of your partner? Thanks.

So, Geoff I'll start with the -- I guess the back half of your question. And we disclosed this clearly in our filing. So, our share of the expenses relative to both BAN2401 elenbecestat was $74 million in 2017, that's just our share and $116 million in 2018. And the amount is not -- creeps up a little bit in 2019, but not dramatically. So that gives you a little bit of sense of kind of the run rate. So, should we decide and our partners decide not to move forward those programs, obviously, that expense would come out. But I think as we mentioned in the prepared comments, as we're going through the aducanumab data and we're still having conversations and we'll make those decisions and deliberations as they play out.

Okay, thanks.

Your next question comes from the line of Carter Gould from UBS. Please go ahead.

Good morning guys and thanks for the color on strategy and capital allocation front. Maybe ask one on sort of near-term pipeline comment about BIIB092. I guess Michael can you give a little bit color on how you think about clinical meaningfulness on the PSPr scale, obviously, an indication for a lot of unmet need, but still some color on that front? And then just how you're thinking potential about read-through to targeting tau across other tauopathies depending on the outcome of this study and PSP?

Yes, great questions Carter. Thank you for that. So, the status of this is that we do anticipate getting days relatively large Phase 2 study data by the end of the year in PSP. The PSP rating scale is kind of the recognized standard across this field on areas of clinical meaningfulness. We've been in active collaborative dialogue with regulators on exactly components of this scale and how to use that for a primary endpoint. But I think we're making really excellent progress on that. I do think that this study is powered in a way with the right endpoint to detect a clinically meaningful effect in these patients. We have to keep in mind that to-date what we really know is that we've got a very target engagement in terms of measuring significant lowering of tau in the CSF. There's a lot of stuff that we still don't know and this is a Phase 2 study. So, you have to keep in mind that this is still a relatively early program where this is largely untested hypothesis and thus it remains a risky program in that regard. But I would say if we're able to show and find that there's a clinically meaningful effect in PSP, I do think that this will have significant positive ramifications or ability to intersect tau across many tauopathies. I would also add and say that we have also very cautiously not just limited ourselves to tau monoclonal antibodies in this regard and that's why we're also enthusiastic about our BIIB080 program at tau antisense oligonucleotide which gives us a very different approach to targeting and lowering tau in tauopathies.

Your next question comes from the line of Phil Nadeau from Cowen and Company. Please go ahead.

Good morning. Thanks for taking my question. I did have a follow-up question on the broad strategy of targeting CNS diseases. Very clear that you want to maximize return to shareholders and it seems like based on the indications you're going after that means major unmet needs where these reasonably sized patients populations, but also really increasing the return to shareholders and also risk of success. And as we look at slide 37 and the indications that are going to read out between here and the end of 2020, it kind of strikes me that not all those -- or actually most of those conditions don't have a determined mechanism of the disease or the pathogenic mechanisms not really well understood. So, can you talk a bit more about how you assess the risk of success and failure when you're looking at potential indications to bringing to your portfolio? And whether that has changed at all post the failure of aducanumab?

So, I will get started. Since 41 years that this company is in operation, innovation, scientific excellence was at the forefront and is at the forefront of what we did and what we do and what we will do. And this is coming with some risk. And we know historically that there have having some setbacks. But we also believe that nowadays we are able to mitigate some of them with genetically validated pathways and also biomarkers neuroimaging and other elements capabilities that we are building. Mike will give more color.

Yes, Phil. I think this is a very good question. It's a broad question. I think what we would say is, look, in this area what we see and detect is a significantly changing risk profile in the area. And we see this playing out in a number of dimensions and it's within things we're doing. And if you look broadly at the ecosystem, SMA being sort of the cardinal example of that, but it doesn't stand alone on this. This risk profile in changing. Where you're successful, there's considerable high reward, as we've seen with SPINRAZA. We are very focused on mitigating the risk level of this in our overall portfolio. We do that in a number of ways Michel was talking about. It's partly by seeking later-stage assets where we've got clinical data that points to the progress, and particularly objective clinical data where we can – lead to go after genetic origins of disease. And this has been a big focus of ours with the extended collaboration Ionis in leveraging the antisense oligonucleotide platform. It's taking advantage of some of our other unique capabilities and depth of expertise in MS and SMA. And as we've been doing that and growing the portfolio, we would note that of these things we've added by bringing in or identifying, three of these deals were post proof-of-concept, two of these deals were post proof-of-biology. So that's an intentional strategy to really mitigate the risk across the portfolio. And I think whether you look at what's going on in – with – in Biogen or in the field as a whole, you can look at disease after disease where these traditional views of the risk are breaking down. SMA, migraine, muscular dystrophy, tardive dyskinesia, progressive MS, Huntington's, gene therapy, the inherited retinal diseases, ALS, treatment-resistant depression, Parkinson's, psychosis, postpartum depression, all these areas where before there have been very little prospect. In the very recent past, in the last year or two, including today, we're seeing a significant change in the risk profile in this area.

Your next question comes from the line of Ronny Gal from Bernstein. Please go ahead.

Good morning. And thank you squeezing me in. A couple of, if you don't mind. The first one is, I hear Michael, but there - kind of overall reducing risk and in neurological conditions. But you guys have been pretty positive on your amyloid beta program early on. And I was wondering, if in light of the end results here, if you thought about structural changes about you view trial, how you conduct them, more focus on interim analysis or early futility analysis? Have you kind of thought about how you mitigate the risk that you think you've gone into pretty significantly risky area. Are you looking for ways to kind of, like, ensure that you're not going down the wrong path for too long? And how do you think about in light of the aducanumab failure? And then, if I can throw one more in, should we read from the Nightstar acquisition, anything about your interest in biosimilar VEGF programs?

Ronny these are getting great questions, which I guess has been lot of time to answer. Let me try to give a little bit of a flavor for it. So in terms of how it is that we design and think about trials. Key for us is where we can get early signs with objective types of measurements that we know are connected to disease. So you will see more and more this is what we try to do across the board but you'll see more and more of that. That means in some instances specific types of biomarkers target engagement, the powering of trials in a way where we're looking for big effects and looking for them early, where we can and we know there is a particular standard of care where we can do head-to-head type of comparisons, it's really leveraging existing data sets that are out there across these diseases to define and refine endpoints. These are the things that we're looking to do. I'll tell you what we're not looking to do is to do large extensive trials where the only thing we're relying on subjective endpoints in that regard. So you will see less and less of that and more and more about refined patient populations objective measures that we think will be tied to a meaningful outcome for patients.

Concerning the biosimilars. We do believe in the value creation opportunity offered by the biosimilars also in the U.S. The savings opportunity are up to $250 billion in the next 10 years if we had an effective biosimilars market in the U.S. And we don't speak about that enough. But I believe what is being discussed in terms of rebates -- new rebates or the policy; we'll address this potential gap. We are very pleased with our portfolio. We are very pleased with our performance. We do not intend to stop here.

Your next question and your last question comes from the line of Terence Flynn from Goldman Sachs. Please go ahead.

Hi, thanks for taking the question. Maybe just two for, Jeff to follow-up on question Geoff Porges’s question. Just can you be little bit clear, are you obligated to move forward with BAN2401? If Eisai would like to advance this program or if you don't agree, can you opt out and return rights there? And then on biosimilars pricing dynamics in the EU. Can you give us a sense of what you're seeing right now and then maybe beyond Germany for HUMIRA? Any early read on some of the other countries? Thank you.

So, on the first question, Terry I’m not going to be able to get into a lot of detail. That's a private arrangement between us and our partner. So as I said, we're looking at the data across all the programs and we'll certainly be able to give people an update when we have more clarity. On your second question with regard to the pricing dynamics. I would just say that the pricing dynamics are more or less in line with what we expected with regard to the IMRALDI launch having two anti-TNS already in the market. We're pretty well tuned to the pricing dynamics was very dramatically country-by-country. So we understand the dynamics and the different long-term contracts and how the different countries bid. And we're very encouraged by what's happening in Germany where we really have started out strong. So I would say the pricing is more or less in line with expectations than what we've seen historically.

Well, thank everybody. We're going to end the call now. I'm going to have Michel make some closing comments.

I would like just to reiterate our commitment to patients, all customers, and importantly to our shareholders. I believe Biogen is set to rebound and I fundamentally believe that we will be back.

Thank you. This concludes today's conference call. You may now disconnect.+