Q1 2021 Biogen Inc Earnings Call

The your conference operator today.

Operator: At this time, I would like to welcome everyone to the Biogen third quarter earnings call and financial update. All lines have been placed on mute to prevent any background noise.

At this time I would like to welcome everyone to the Biogen quarter today's call and financial updates.

All lines have been placed on mute to prevent any background noise.

And the speaker's remarks, there will be a question answer session if you'd like to ask a question. During this time simply press star one on your telephone keypad.

Operator: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star 1 on your telephone keypad. Please limit yourself to one question to allow other participants time for questions. If you require any further follow-up questions, you may press star 1 again to rejoin the queue. Thank you. I would now like to turn the conference over to Mr. Mike Henke, Director of Investor Relations. Mr. Henke, you may begin your conference.

Please limit yourself to one question to a lot of other participants time for questions.

If you require any further follow up questions you May press star one again to rejoin the queue.

Thank you I would.

And I would like to turn the conference over to Mr. Mike Turnkey director of Investor Relations. Mr. Humphrey You May begin your conference.

Good morning, and welcome to Biogen is first quarter 2021 earnings call before we begin I encourage everyone to go to the investors section of Biogen Dot com to find the earnings release and related financial tables, including our GAAP financial measures and the reconciliation of the GAAP to non-GAAP financial measures that we'll discuss today.

Mike Henke: Good morning, and welcome to Biogen's first quarter 2021 earnings 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 our GAAP financial measures and 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, and Table 4 includes the reconciliation of our GAAP to non-GAAP financial results because we believe non-GAAP financial results better represent the

Our GAAP financials are provided in the tables, one and two and table. Four includes the 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.

Mike Henke: We present 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.

Mike Henke: We have also posted slides on our website.

Operator: This concludes today's conference. Thank you for joining us.

And I would like to point out that we will be making forward looking statements, which are based on our current expectations and beliefs.

Mike Henke: I would like to point out that we will be making forward-looking statements that 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 details. On today's call, I am joined by our Chief Executive Officer, Michelle Vunatsos, Dr. Al Sandrock, Head of Research and Development, and our CFO, Mike McDonnell. As a reminder, during the Q&A portion of the call, we kindly ask that you limit yourself to one question. I will now turn the call over to Michelle.

These statements are subject to certain risks and uncertainties and our actual results may differ materially and.

And 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 Bernard says, Dr. Al Sandrock head of research and development and our CFO Mike Mcdonnell.

As a reminder, during the Q&A portion of the call. We kindly ask that you limit yourself to one question and I'll now turn the call over to Michel.

Good morning, everyone and thank you for joining us we the strong focus on operational execution, we have continued to serve patients and advance our strategic priorities.

Michelle Vunatsos: Good morning everyone, and thank you for joining us. With a strong focus on operations and execution, we have continued to serve patients and advance our strategic priorities. While we know that 2021 will be a financial reset year for the company, we are pleased with our operational performance during Q1, with first quarter total revenues of $2.7 billion and first quarter non-GAAP EPS of $5.34. These results were driven by solid performance across MS, SMA, and biosimilars. Together, we continue to implement strong cost management.

While we know that 2021 will be a financial we secured for the company. We are pleased with the operational performance. During Q1 with first quarter total revenues of $2 7 billion doors and first quarter non-GAAP EPS of $5.34. These.

These results were driven by solid performance across the M S SMA and Biosimilars and together with continued strong cost management.

We are ready to launch and you can imagine the U S should we receive it doesn't mean that the re approval and we anticipate and FDA decision by the June seven and spud due for the eight <unk>.

Michelle Vunatsos: We are ready to launch aducanumab in the U.S. should we receive regulatory approval, and we anticipate an FDA decision by June 7th, per DUFA date. If approved, aducanumab will be the first therapy to meaningfully change the cause of Alzheimer's disease and will represent a significant growth and value creation opportunity. Our cross-functional team in the U.S. has been working for months in preparation for the potential launch of Adukan UMAB. We have identified and evaluated key sites of care that have the necessary infrastructure for Alzheimer's patients.

And if approved and you can imagine it will be the first therapy to meaningfully change the cost of funds out of Ms disease, and will represent a significant growth and value creation opportunity.

Oh of cross functional team and the U S has been working for months and preparation for the potential launch of educating them up.

We have identified and evaluated Keith sites of care that have the necessary infrastructure for Alzheimers patients, we believe that and more than 600 of the sites will be ready to treat patients shortly after a potential approval.

Michelle Vunatsos: We believe that more than 600 of these sites will be ready to treat patients shortly after a potential approval. Our team is currently working to evaluate the capacity at these and other sites to absorb an influx of Alzheimer's patients. Together with SI, we were pleased to support Us Against Alzheimer's in the development of BrainGuide, a platform which is powered by Amazon Web Services. BrainGuide aims to increase brain health awareness and empower people to take action based on responses to a memory questionnaire.

Our team is currently working to evaluate the capacity of these and all the sites to absorb and interest of Alzheimer's patients.

Together, we decided we were pleased to support us against Alzheimer's in the development of brain guide it platform, which is powered by Amazon Web services brand guide aims to increase the brain health wellness and empower people to take action based upon responses to.

And memory questionnaire, and we hope that brain guide along with all the collaboration with Apple aiming to identify biomarkers of cooking and keep health will enable people to see cash sooner in order to maximize the benefits of treatment.

Michelle Vunatsos: We hope that BrainGuide, along with our collaboration with Apple, aiming to identify digital biomarkers of cognitive health, will enable people to seek care sooner in order to maximize the benefits of treatment. We are also working to ensure an equitable launch to facilitate broad access to aducanumab should it be approved, including underserved populations, a critical issue that has been highlighted by the COVID-19 pandemic. I am pleased to announce that outside the U.S., we recently submitted additional regulatory filings in Brazil, Canada, Switzerland, and Australia, adding to our earlier submissions in Europe and Japan. Turning to our progress towards our strategic priorities, first Q1 overall MS revenue, including Ocrevis royalties, was $1.7 billion.

We are also working to ensure and equitable logs to facilitate the broad access to educate the market should it be approved including underserved population a critical issue that has been highlighted by the COVID-19 pandemic.

I am pleased to announce that outside the U S. We recently submitted additional regulatory filings in Brazil.

And at the Switzerland, and Australia, adding flow earlier submissions in Europe and Japan.

Turning to our progress towards our strategy priorities first Q1 overhaul and mis revenue, including arquebus royalties was $1 $7 billion, putting aside the entry of defeat the exit of a generic and the U S. Our brother of M. S business 14th of demonstrates the resilience and progress it.

Michelle Vunatsos: Putting aside the entry of Tefidera Generic in the U.S., our broader MS business continues to demonstrate resilience and progress. Excluding Tefidera in the U.S., the number of patients on our MS products worldwide increased by approximately 5% versus the prior year. Importantly, in the current COVID-19 environment, we believe our MS products are well positioned versus the competition based on our current treatment guidelines. We were very pleased to see strong revenue growth from Umerity, which is now the number one oral MS product in terms of new prescriptions in the U.S. We believe this performance is a testament to a strong product profile and our team's ability to execute well, validating our plan announced mid-last year to accelerate the launch of Umerity.

Excluding to exceed the range of the U S. The number of patients on our M. S products worldwide increased approximately 5% versus the prior year and importantly in the current COVID-19 environment. We believe our MH products are well positioned versus the competition based on our current treatment guidelines.

Yeah.

We were very pleased to see strong revenue growth for the memory T, which is now the number one or all of M. S product in terms of new prescription and the U S. We believe this performance is a testament to our strong product profile and our team's ability to execute well validating our plan and launched mid last year.

And to accelerate the launch of humility.

We are also excited that the actually there are recently received regulatory approval in China.

Michelle Vunatsos: We are also excited that Tecfidera recently received regulatory approval in China. Furthermore, we continue to advance new approaches to help address the remaining unmet medical need in MS. This quarter, we launch an intramuscular formulation of plaguity in both the U.S. and EU, which we believe offers an improved tolerability profile, and we obtain approval for subcutaneous administration of disability in the EU, with the first expected launch in Germany, while we await a regulatory decision in the U.S. We also continue to advance the potential use of extended interval dosing for Tysabri, with important data expected in the middle of this year.

Furthermore, we continue to advance new approaches to help address the remaining unmet medical need in the Miss this quarter, we launch and E. Commerce Qunar formulation of grade we see in both of the U S and EU, which we believe offers and improved total liability profile and we obtained approval for subcutaneous administered.

And of Tysabri in the U. We the first expected launch in Germany, while we await regulatory decision in the U S. We also continue to advance the potential use of extended interval dosing for Tysabri, we the important data expected in the middle of this year.

So you can see.

Second spin of Ahs that generated first quarter of global revenues of 521 million daus and while it's been the wise ice fishing competition and the U S, which has been exacerbated by the impacts of COVID-19, we were encouraged to see that speed of Rosa the discontinuation decrease of Hershey's Q4 of last year.

Michelle Vunatsos: Second, Spinraza generated first-quarter global revenues of $521 million. While Spinraza is facing competition in the U.S., which has been exacerbated by the impacts of COVID-19, we were encouraged to see that discontinuations decreased versus Q4 of last year. Outside the U.S., Spinraza continues to perform very well, with 13% revenue growth versus Q1 of last year. Overall, Spinraza remains the market-leading treatment for SMA, and we believe it will remain a foundation of care.

Outside the U S. Spin of Raza continues to perform very well with 13% with the new growth versus the one of last Europe or the whole screen Raza remains of the market leading treatment for SMA and we believe it will remain a foundation of care.

Third our Biosimilars business delivered revenue of 200 and fives of millions of lives. We are pleased with this performance as the continuing impact of the COVID-19 pandemic How's the resulted in a slowdown in new treatment starts and reduce clinic capacity for immunology patients in Europe.

Michelle Vunatsos: Third, our biosimilars business delivered revenue of $205 million. We are pleased with this performance as the continuing impact of the COVID-19 pandemic has resulted in a slowdown in new treatment starts and reduced clinic capacity for immunology patients in Europe. We aim to continue to grow our biosimilars business and create additional financial headroom for innovation by launching new products. To that end, we recently announced a collaboration with Bioterra Solutions to develop and commercialize BAT-1806, a proposed biosimilar referencing Actimera currently in phase 3 development.

Sorry, we aim to continue to grow our biosimilars business and create additional financial headroom for innovation by launching new products do that and we recently announced the collaboration with the biotech have solution to develop and commercialize b a T 18 zero six.

A proposal by you'll see me lives with the wrenching Actemra currently in Phase III development Biogen will have the rights to commercialize the a T 18 of seats globally in countries outside of China, which will expand our global Biosimilars footprint.

Michelle Vunatsos: Biogen will have the right to commercialize BAT-1806 globally in countries outside of China, which will expand our global biosimilars footprint. Fourth, this quarter, we continue to meaningfully progress on our pipeline. We reported phase two data in essential tremor, and we expect seven additional meetings to late stage readout this year.

Fourth of this quarter, we continued to meaningfully progress on all of the pipeline, we reported the phase two data and essential tremor and we expect seven additional mid to late stage Readouts This year.

Gene therapy represents a key area of focus for Biogen as we continue to pursue multiple modalities to this and we recently announced our plan to build a new state of the art gene therapy manufacturing facility I thought the RTP sites in North Carolina.

Michelle Vunatsos: Gene therapy represents a key area of focus for Biogen as we continue to pursue multiple modalities. To this end, we recently announced our plan to build a new state-of-the-art gene therapy manufacturing facility at our RTP site in North Carolina. Fifth, our cash flow generation remains strong and continues to provide us with significant flexibility to allocate capital. In Q1, we generated approximately $769 million in cash flow from operations and $676 million in free cash flow.

Fifth our cash flow generation remains strong and continues to provide us with significant flexibility to allocate the capital in Q1, we generated approximately $769 million and cash flow from operations and 676 million in free cash flow.

As we have demonstrated in the past we are committed to maximizing returns for our shareholders. As we aim to bring you know that Keith therapies to patients.

Michelle Vunatsos: As we have demonstrated in the past, we are committed to maximizing returns for our shareholders as we aim to bring innovative therapies to patients. I will now turn the call over to Al for a more detailed update on our recent progress in R&D.

I'll now turn the call over to idle for a more detailed update on our recent progress and are ready.

Thank you Michel and good morning, everyone.

Geoffrey Christopher Meacham: Thank you, Michelle, and good morning, everyone. As always, I'd like to start by thanking the Biogen team for their hard work as we continue to advance our R&D program. We achieved a number of key milestones this quarter, and we look forward to seven additional readouts anticipated this year, including pivotal trials in major depressive disorder, postpartum depression, ALS, and choroid oremia. Let me now turn to the advances we made across our pipeline in the first quarter.

As always I'd like to start by thanking the Biogen team for their hard work as we continue to advance our R&D programs.

We achieved the number of key milestones this quarter and we look forward to seven additional readouts anticipated this year, including pivotal trials and major depressive disorder, postpartum depression, AOS and choroid or EMEA.

Let me now turn to the advances we made across our pipeline and the first quarter.

Starting with Alzheimer's disease as Michel mentioned this quarter of resubmitted additional regulatory filings for edge of Canyon, Mab, and Brazil, Switzerland, Canada, and Australia, together with our prior filings and the U S. EU and Japan, we have now submitted filings and seven key geographies and continue to engage with.

Geoffrey Christopher Meacham: Starting with Alzheimer's disease, as Michelle mentioned, this quarter we submitted additional regulatory filings for aducanumab in Brazil, Switzerland, Canada, and Australia. Together with our prior filings in the U.S., E.U., and Japan, we have now submitted filings in seven key geographies and continue to engage with regulators as they review the aducanumab data. Turning to Leucanumab, or BAN2401, our collaboration partner, ACI, has recently enrolled the last patient in the Phase III Clarity Study in early Alzheimer's disease. We look forward to the readout in Q3 of next year.

As they review the edge of Canyon mass data.

Turning to the Cana mab or a bit band 2401.

Our collaboration partner Eisai has recently enrolled the last patient and the phase III clarity study and early Alzheimer's disease.

We look forward to the readout in Q3 of next year.

Additionally, we plan to present at the detailed results from the Phase <unk> study of <unk> 80, and mild Alzheimers disease at the upcoming AIC meeting later this year.

Geoffrey Christopher Meacham: Additionally, we plan to present detailed results from the Phase 1B study of BIP-80 in mild Alzheimer's disease at the upcoming AAIC meeting later this year. BIP-80 is a Tau-targeted antisense oligonucleotide that aims to reduce the production of all forms of Tau, both intracellular and extracellular. The Phase 1B study demonstrated that BIV-80 was generally well-tolerated and resulted in a dose- and time-dependent reduction from baseline in CSF total Tau and phospho Tau, with durability of effect.

The 80 of the Tau targeted antisense oligonucleotide that aims to reduce the production of all forms of Tau, both intracellular and extra cellular and the phase <unk> study demonstrated that <unk> 80 was generally well tolerated and resulted in a dose and time dependent reduction from baseline and CSF total Tau.

And phosphate Tao with durability of effect.

We are currently finalizing plans to advance the baby into a phase II study in Alzheimer's disease.

Geoffrey Christopher Meacham: We are currently finalizing plans to advance VIB-80 into a Phase II study in Alzheimer's disease. Moving to MS, we are presenting new data across our portfolio at the AA meeting this week. An updated analysis of data from the Touch Prescribing Program of Tysabri showed an 88% reduction in the risk of PML when used with extended interval dosing, or EID, as compared with standard interval dosing. This supports previous findings that showed that EID is associated with a lower incidence of PMS.

Moving to MFS, and we are presenting new data across our portfolio at the Ada meeting this week.

And updated analysis of data from the touch prescribing program of Tysabri showed an 88% reduction and the risk of P&L when used with extended interval dosing or E D as compared with standard of interval dosing.

This supports the previous findings that showed that E. D is associated with the lower incidence of here now.

We continue to generate the state of the art real world data through M. S pads.

Geoffrey Christopher Meacham: We continue to generate state-of-the-art, real-world data through MS-PATH. Through MS-PATH, Biogen is collaborating with 10 leading MS centers in the U.S. and Europe to generate standardized quantitative data from a diverse MS patient population as they are seen in the clinic. More than 17,000 patients have been enrolled in MS-PASS to date, and we aim to use quantitative measurements across a range of key clinical dimensions. High-Position MRI Measurements of MS Disease Activity, and patient-reported data using a validated quality of life instrument.

And the EMS past Biogen is collaborating with 10, leading Ms centers and the U S and Europe to generate standardized quantitative data from a diverse M. S patient population as they are being seen in the clinic.

More than 17000 patients have been enrolled and M. S has to date and we aim to use quantitative measurements of across a range of key clinical dimensions hi.

Hi position MRI measurements of the M S disease activity.

Patient reported data using a validated quality of life instrument led.

Blood Biomarkers, such as neuro filament and electronic health records to obtain a more holistic view of that mass and gain insights on how currently approved drugs are affecting real world outcomes.

Geoffrey Christopher Meacham: Blood biomarkers such as neurofilament and electronic health records to obtain a more holistic view of MS and gain insights on how currently approved drugs are affecting real world outcomes. Moreover, with the use of modern analytical methods such as machine learning, we hope to make new discoveries about the key subtypes and stages of MS, as well as its pathogenesis.

Moreover, with the use of modern analytical methods such as machine learning, we hope to make new discoveries about the key subtypes and stages of MFS as well as its pathogenesis.

At the a and meeting we were showing data from the EMS past that show that extended interval dosing of Tysabri may maintain comparable efficacy to standard interval dosing as assessed by the rate of new or newly enlarging T. Two lesions on MRI scans quantified by advanced image analysis software.

Geoffrey Christopher Meacham: At the AAN meeting, we are showing data from the MS PADS that show that extended interval dosing of Tysabri may maintain comparable efficacy to standard interval dosing as assessed by the rate of new or newly enlarging T2 lesions on MRI scans, quantified by advanced image analysis software which we developed in collaboration with Siemens. A prospective study of the efficacy of extended interval dosing is being assessed in the ongoing NOVA study, from which we expect top-line results around mid-year.

Which we developed in collaboration with Siemens <unk>.

The prospective study of the efficacy of extended interval dosing is being assessed and the ongoing Nova study from which we expect top line results around mid year.

And also being presented at a a and another study leveraging data collected using EMS pads and demonstrated the tysabri can lead to clinically meaningful improvements and aspects of mental and social health as assessed by the neuro qual, a validated and the instrument that that evaluates physical and mental and social.

Geoffrey Christopher Meacham: Also being presented at AAN, another study leveraging data collected using MS pads demonstrated that Tysabri can lead to clinically meaningful improvements in aspects of mental and social health as assessed by the NeuroQOL, a validated instrument that evaluates the physical, mental, and social effects reported by patients with neurological disorders. For 11 of the 12 domains tested, the adjusted rate of improvement was greater for patients treated with Tysabri than for those treated with Ocrevus.

All of the effects reported by patients with neurological disorders for 11 of the 12 domains tested the adjusted rate of improvement was greater for patients treated with Tysabri then for those treated with oak grievous.

Also being presented at AAN is the first real world analysis of the merit of treated patients.

Geoffrey Christopher Meacham: Also being presented at AAN is the first real-world analysis of Umerity-treated patients. The retrospective study of 160 patients found that overall persistence was high, with 88% of individuals remaining on Bumarity at 8 months, and that treatment discontinuation due to GI adverse events was low at 3.8%. These results follow the recent publication of EVOLVE-MS-2, a Phase 3, 5-week, randomized, multi-sensor study that assessed the GI tolerability of Bumarity and Tecfidera using self-administered questionnaires.

The retrospective study of 160 patients found that overall persistence was high with 88% of individuals the remaining on humanity at eight months and that treatment discontinuation due to Gi adverse events was low at three 8%.

These results follow of recent publication of evolve Ms. Two phase III five week randomized multi center study that assessed the Gi tolerability of the merits and tech Vadera using self administered questionnaires. The study demonstrated that the only nine 5% of the Meredith treated patients.

Geoffrey Christopher Meacham: The study demonstrated that only 9.5% of Bumarity-treated patients indicated that GI symptoms interfered quite a bit, or very much, with regular activities, as compared to We believe that the differentiated tolerability profile of bumeridae will lead to improved adherence to therapy.

<unk> indicated the Gi symptoms interfered quite of bit or extremely with the regular activities as compared to almost 29% of tech vadera patients. We believe that the differentiated tolerability profile of humanity will lead to improved adherence to therapy.

And and in addition to our established treatments, we aim to leverage our Ms pipeline and to address the remaining unmet need and MFS. This includes our oral the myelination program did 61, our oral b TK inhibitor of bid and 91 as well as our next generation anti BLA for antibody that seeks to build on the success of.

Geoffrey Christopher Meacham: In addition to our established treatments, we aim to leverage our MS pipeline to address the remaining unmet needs in MS. This includes our oral remyelination program, BIB61, our oral BTK inhibitor, BIB91, as well as our next-generation anti-VLA4 antibody that seeks to build on the success of Tysabri in the high-efficacy space. Turning to neuromuscular disorders, we are presenting an update on the ongoing DEVOTE study testing a higher dose of Spinraza at the AAN meeting this week.

Tysabri and the high efficacy space.

Turning to neuromuscular disorders, we are presenting an update on the ongoing devote study testing of higher dose of spin rozzer at the a maybe a a and meeting this week day.

Ada from the patients enrolled and the part a open label safety evaluation cohort followed for up to approximately five months were consistent with the well characterized safety profile of the currently approved 12 milligram dose of spin Rozzer the.

Geoffrey Christopher Meacham: Data from the patients enrolled in the Part A Open Label Safety Evaluation Cohort, followed for up to approximately five months, were consistent with the well-characterized safety profile of the currently approved 12 mg dose of Spinraza. The emerging safety profile of the higher dose supports its continued development as we evaluate the potential for greater efficacy. We also added an additional cohort to the Phase I study of BIP-78, our C9-ORF ASO for ALS.

The emerging safety profile of the higher dose supports its continued development as we evaluate the potential for greater efficacy.

We also added and additional cohort to the phase one study of <unk> 78, our C&I and or ASO for a L. S. Safety data has been supportive of escalating the dose enabling us to conduct a more complete evaluation of the therapeutic index and the phase one study containing the additional cohort.

Geoffrey Christopher Meacham: Safety data has been supportive of escalating the dose, enabling us to conduct a more complete evaluation of the therapeutic index. The Phase I study, containing the additional cohort, is now expected to read out in the first half of next year.

And is now expected to read out and the first half of next year.

And neuropsychiatry last month's Sage Therapeutics released and interim analysis of the ongoing open label Phase III shoreline natural history net naturalistic study of Saar and alone and major depressive disorder. The data showed that in the completed 30 milligrams and ran alone and cohort approximately 70.

Geoffrey Christopher Meacham: In neuropsychiatry, last month Sage Therapeutics released an interim analysis of the ongoing open-label Phase III Shoreline naturalistic study of xeronalone in major depressive disorder. The data showed that in the completed 30 mg xeronalone cohort, approximately 70% of participants with a positive response to an initial two-week treatment required at most one additional xeronalone treatment during the one-year study. Shoreline also showed that following the two-week treatment, more than 70 percent of patients in the 30-milligram cohort and 80 percent of patients in the 50-milligram cohort achieved a positive response as evaluated by the 17-item Hamilton Rating Scale for Depression.

Percentage of participants with a positive response to and an initial two week treatment required at most one additional day ran alone treatment during the one year study.

Your line and also showed that following the two week treatment more than 70% of patients and the 30 milligram cohort and 80% of patients and the 50 milligram cohort achieved a positive response as evaluated by the 17 item Hamilton rating scale for depression.

And both of the $30 and 50 milligram cohorts Saran alone demonstrated and an adverse event profile consistent with previously reported data.

Geoffrey Christopher Meacham: In both the 30 and 50 mg cohorts, xeranilone demonstrated an adverse event profile consistent with previously reported data. Adverse events, including somnolence, dizziness, and sedation, were observed to be more frequent in the 50 mg cohort but were similar in severity to events seen with the 30 mg treatment of xeranilone.

Adverse events, including Somnolence, dizziness, and sedation were observed to be more frequent and the 50 milligram cohort, but were similar and severity of two events seen with the 30 milligram treatment of the ran alone.

We believe these data further supports the potential therapeutic effect observed and alone and we look forward to the readout of the waterfall study and ran alone and major depressive disorder anticipated later this quarter.

Geoffrey Christopher Meacham: We believe these data further support the potential therapeutic effect of xeranilone, and we look forward to the readout of the waterfall study of xeranilone in major depressive disorder, anticipated later this quarter. Next, I would like to turn to movement disorders. In collaboration with SAGE, we recently announced that SAGE-324, also known as BIB-124, met the primary endpoint of a statistically significant reduction from baseline compared to placebo in the upper limb tremor score on pre-specified components of the Essential Tremor Rating Assessment Scale, or TETRIS, at day 29. This corresponded to a 36% reduction from baseline in upper limb tremor amplitude in patients BID 124 also demonstrated a safety profile consistent with previously reported data.

Next I would like to turn to movement disorders, and collaboration with Sage, We recently announced that stage three to four also known as the 124 met the primary endpoint of a statistically significant reduction from baseline compared to placebo and the upper limb tremor score on pre specified.

<unk> of the essential tremor rating assessment scale or Tetris at day 29. This.

This corresponded to a 36% reduction from baseline and upper limb tremor amplitude and patients receiving <unk> 124, compared to 21% reduction with placebo bid.

And 124 also demonstrated the safety profile consistent with previously reported data.

This trial was designed to test the higher the high end of the dose range established and phase one studies 60 milligrams and an effort to determine whether or not proof of concept could be established and essential tremor did $1 24, clearly shows efficacy and essential tremor, but at this dose the incidence of <unk>.

Geoffrey Christopher Meacham: This trial was designed to test the high end of the dose range established in Phase 1 studies, 60 mg, in an effort to determine whether or not proof of concept could be established for essential tremor. B.I.B.1.24 clearly shows efficacy in essential tremor, but at this dose, the incidence of somnolence was 68%, with 62% of patients going to a lower dose and 38% of patients discontinuing treatment. We are working closely with SAGE to plan the next steps for the development of BID 124.

<unk> was 68% the 62% of patients going to a lower dose and 38% of patients discontinuing treatment.

We're working closely with stage with Sage to plan next steps for the development of the 124.

The unmet need and tremor essential tremor is significant there.

Geoffrey Christopher Meacham: The unmet need in tremor, essential tremor, is significant. There have been no new drugs approved for essential tremor in more than five decades. The drugs currently used to treat essential tremor have tolerability issues of their own, which limits their use in clinical practice. We believe more can be done to help patients with this common movement disorder that interferes with activities of daily living and hampers social engagement. In Parkinson's disease, the Phase 1 and Phase 1b studies of BID-122, a small molecule Allerp2 inhibitor, are now complete, and the safety and biomarker goals were achieved, which we believe support continued development of BID-122.

Ben No new drugs approved for essential tremor and more than five decades. The drugs currently used to treat the central tremor have tolerability issues of their own which limits their use in clinical practice.

We believe more can be done to help patients with this most common and movement disorder that interferes with the activities of daily living and hampered social engagement.

And Parkinson's disease, the phase, one and phase <unk> studies of bid $1 22, a small molecule <unk> two inhibitor are now complete and the safety and biomarker goals were achieved which we believe support continued development of <unk> 122.

As previously announced with our collaboration partner Denali, we expect to initiate late stage clinical development and Parkinson's disease patients by the end of this year.

Our R&D organization delivered a number of important milestones and the first quarter of the year. We believe there is much to be excited about with seven additional readouts expected by the end of the year, including pivotal Readouts and major depressive disorder Postpartum depression.

Geoffrey Christopher Meacham: As previously announced with our collaboration partner Denali, we expect to initiate late-stage clinical development in Parkinson's disease patients by the end of this year. Our R&D organization delivered a number of important milestones in the first quarter of this year. We believe there is much to be excited about with seven additional readouts expected by the end of the year, including pivotal readouts in major depressive disorder, postpartum depression, ALS, and choroideremia. I will now pass the call over to Mike.

S and choroid arrhythmia.

And now I'll pass the call over to Mike.

Thank you al.

<unk> had another solid quarter. Despite the challenges from tech Vadera of U S generics and COVID-19, as we continued to execute well across our core businesses.

We remain in a very strong financial position with significant cash and financial capacity continue to continue to grow the business over the long term.

I will now review, our financial performance for the quarter and share with you and update to our full year guidance for 2020 one.

Michael R. McDonnell: Biogen had another solid quarter despite the challenges from Tecfidera US generics and COVID-19 as we continue to execute well across our core business. We remain in a very strong financial position with significant cash and financial capacity to continue to grow the business over the long term. I will now review our financial performance for the quarter and share with you an update to our full year guidance for 2021.

Total revenue for the first quarter.

Of $2 7 billion declined 24% versus the prior year at actual currency and 25% of constant currency.

This decline was mostly driven by the continued impact of tech the Dara generics and the United States.

Total <unk> revenue for the first quarter, including our previous royalties of $1 $7 billion decreased 26% versus the prior year at both actual and constant currency.

Michael R. McDonnell: Total revenue for the first quarter of $2.7 billion declined 24% versus the prior year at actual currency and 25% at constant currency. This decline was mostly driven by the continued impact of Tecfidera generics in the United States. Total MS revenue for the first quarter, including Ocrevus royalties of $1.7 billion, decreased 26% versus the prior year at both actual and constant currency. This decline was also driven by the continued impact of generic Tecfidera in the U.S. Excluding U.S. tech federa, total MS revenue, including Ocrevus royalties, was relatively flat, demonstrating the resilience of our MS business in a competitive market.

This decline was also driven by the continued impact of tech the error of generics and the U S. Excluding.

Excluding U S Tech Vadera of total EMS revenue, including our previous royalties were relatively flat demonstrating the resilience of our Ms business and a competitive market.

The global Tepid Air revenue for the first quarter of $479 million declined 56% versus the prior year outside of the U S. First quarter of Tech Vadera revenue of $317 million declined 2% versus the prior year.

Normalizing for accelerated shipments due to COVID-19 of approximately $28 million and Q1 of 2020 revenue outside the U S increased 7% with continued patient growth.

Yeah.

During the quarter, we saw continued improvement in Humira of the trends, primarily revenue was $74 million and the first quarter and is now the number one.

S oral product in terms of new prescription share in the U S.

Tysabri first quarter global revenue of $503 million declined 4% versus the prior year as a reminder, and Q1 of 2020 Tysabri revenue benefited by approximately $40 million due to a combination of extra shipping days and the U S and the pricing adjustment and Italy.

Michael R. McDonnell: The global Tecfidera revenue for the first quarter of $479 million declined 56% versus the prior year. Outside of the U.S., first quarter Tecfidera revenue of $317 million declined 2% versus the prior year. Normalizing for accelerated shipments due to COVID-19 of approximately $28 million in Q1 of 2020, revenue outside the U.S. increased 7% with continued patient growth. During the quarter, we saw continued improvement in Bumerity trends.

Normalizing for these dynamics revenue grew 4% year over year as we saw a 5% increase and global Tysabri patients. We continue to believe Tysabri is well positioned to play an increasingly important role in the treatment of MFS as we progress on several important initiatives, including subcutaneous administration.

And extended interval dosing.

Michael R. McDonnell: Bumerity revenue was $74 million in the first quarter and is now the number one MS oral product in terms of new prescription share in the U.S. Tysabri first quarter global revenue of $503 million declined 4% versus the prior year. As a reminder, in Q1 of 2020, Tysabri revenue should benefit by approximately $40 million due to a combination of extra shipping days in the U.S. and a pricing adjustment in Italy. Normalizing for these dynamics, revenue grew 4% year over year, as we saw a 5% increase in global Tysabri patients. We continue to believe Tysabri is well positioned to play an increasingly important role in the treatment of MS as we progress several important initiatives, including subcutaneous administration and extended interval dosing.

Yes.

Moving now to SMA global first quarter of spin Rozzer revenue of $521 million decreased 8% versus the prior year at actual currency and 12% of constant currency. Although we were pleased to see 5% growth and global spend rise of patients versus the prior year in the U S spin rozzer revenue decreased 37%.

The prior year as we continued.

As we continue to see impact from competition exacerbated by the impacts of COVID-19.

Outside the U S. It's been raised the revenue grew 13% versus the prior year, including approximately $40 million due to timing of shipments in Q1 of 2021.

Moving now to our Biosimilars business first quarter revenue of $205 million decreased 6% versus the prior year at actual currency and 13% at constant currency.

Normalizing for accelerated shipments due to COVID-19 of approximately $15 million and Q1 of 2020 revenue was flat year over year.

Michael R. McDonnell: Moving now to SMA, global first-quarter Spinraza revenue of $521 million decreased 8% versus the prior year at actual currency and 12% at constant currency, although we were pleased to see 5% growth in global Spinraza patients versus the prior year. In the U.S., Spinraza revenue decreased 37% versus the prior year as we continued to see the impact of competition exacerbated by the impacts of COVID-19. Outside the U.S., Spinraza revenue grew 13% versus the prior year, including approximately $40 million due to timing of shipments in Q1 of 2021.

Our biosimilars business continues to be negatively impacted by pricing pressure as well as the slowdown in new treatments and reduced the clinic capacity due to COVID-19.

Despite the continued impact of COVID-19, we continue to be the leading anti TNF biosimilar provider in Europe, and Ben of Poly continues to be the number one prescribed etanercept product across Europe.

We believe we have the opportunity to continue to grow and Europe as well as within the U S and other geographies by commercializing new products.

Total anti CD 20 revenue and the first quarter of $389 million decreased 25% versus the prior year Rituxan revenue decreased approximately 50% versus the prior year, partially offset by a 29% increase and a previous royalties.

We expect continued erosion of rituxan due the biosimilars.

Turning now to gross margin first quarter gross margin was 82% of revenue down versus 83% and the prior quarter and down versus 87% and Q1 of 2020.

Michael R. McDonnell: Moving now to our biosimilars business, first quarter revenue of $205 million decreased 6% versus the prior year at actual currency and 13% at constant currency. However, normalizing for accelerated shipments due to COVID-19 of approximately $15 million in Q1 of 2020, revenue was flat year-over-year. Our biosimilars business continues to be negatively impacted by pricing pressure, as well as a slowdown in new treatments and reduced clinic capacity due to COVID-19. However, despite the continued impact of COVID-19, we continue to be the leading anti-TNF biosimilar provider in Europe, and Benapali continues to be the number one prescribed etanercept product across Europe.

The continued reduction in gross margin was primarily due to the declines and tech Vadera and Rituxan both of which are high margin products. We expect to continue to experience downward pressure on gross margins.

Moving to expenses and the balance sheet first quarter non-GAAP R&D expense was $514 million.

First quarter, non-GAAP, SG&A was $595 million, including approximately $75 million related to the launch preparations for edge of Cana Mab net of reimbursement from ASI.

And the first quarter of this year, our effective non-GAAP tax rate was approximately 16% versus approximately 17% and the first quarter of 2020.

During the first quarter, we repurchased two 2 million shares of the company's common stock for $600 million.

Michael R. McDonnell: We believe we have the opportunity to continue to grow in Europe as well as within the U.S. and other geographies by commercializing new products. Total anti-CD20 revenue in the first quarter of $389 million decreased 25% versus the prior year. Rituxan revenue decreased approximately 50% versus the prior year, partially offset by a 29% increase in Ecrevis royalty. We expect continued erosion of rituxan due to biosimilars.

As of March 31st 2021.

There was $4 billion remaining under the share repurchase program authorized in October of 2020, and we expect to utilize a portion of this throughout the remainder of the year.

Our weighted average diluted share count was approximately 152 million shares for the quarter.

Non-GAAP diluted earnings per share and the first quarter was $5 34.

And the first quarter, we generated approximately $769 million and cash flow from operations capital expenditures were $93 million and free cash flow was approximately $676 million. We ended the quarter was $7 3 billion and debt and $3 4 billion and cash and marketable securities Reis.

Michael R. McDonnell: Turning now to gross margin. First quarter gross margin was 82% of revenue, down versus 83% in the prior quarter and down versus 87% in Q1 of 2020. The continued reduction in gross margin was primarily due to the declines in Tecfidera and Rituxan, both of which are high-margin products. We expect to continue to experience downward pressure on gross margins.

<unk> at $3 9 billion and net debt.

In addition, our $1 billion revolving credit facility was undrawn as of the end of the quarter.

Let me now turn to our updated full year guidance for 2020 one are.

Our full year 2021 revenue guidance remains at 10.4 of $5 billion to 10, seven and $5 billion, despite unfavorable currency dynamics, which I will explain in a moment.

Michael R. McDonnell: Moving to expenses and the balance sheet, first quarter non-GAAP R&D expense was $514 million. First quarter non-GAAP SG&A was $595 million, including approximately $75 million related to the launch preparations for Adjucanumab, net of reimbursement from ACI. In the first quarter of this year, our effective non-GAAP tax rate was approximately 16 percent versus approximately 17 percent in the first quarter of 2020. During the first quarter, we repurchased 2.2 million shares of the company's common stock for $600 million. As of March 31st, 2021,

We are increasing our non-GAAP diluted EPS guidance from our previous range of $17 to $18 50.

To a range of between $17 and 52.

The $19.

Our capital expenditure guidance is unchanged at 375 million to $425 million.

And this financial guidance assumes that foreign exchange rates as of March 31, 2021 will remain in effect for the remainder of the year net of hedging activities. It.

It is important to note that we are reaffirming our revenue guidance despite.

And expected currency headwind of approximately $80 million net of hedging activities to our full year of 2021 revenue guidance due primarily to the strengthening of the U S. Dollar from January one of 2021 through March 31 of 2021.

Michael R. McDonnell: There were $4 billion remaining under the share repurchase program authorized in October of 2020, and we expect to utilize a portion of this throughout the remainder of the year. Our weighted average diluted share count was approximately 152 million shares for the quarter. Non-GAAP diluted earnings per share in the first quarter were $5.34. In the first quarter, we generated approximately $769 million in cash flow from operations. Capital expenditures were $93 million, and free cash flow was approximately $676 million.

Our guidance continues to assume that edge of can't imagine will be approved and the U S. By June 7th of 2021, although uncertainty remains on the Fda's decision.

If <unk> is approved and the U S. We would expect and immediate launch however dose titration will result in less revenue per patient and the initial months of treatment and as a result, we would expect only modest revenue for edge of cat and map in 2020 one ramping thereafter.

We continue to expect rapid erosion of our U S Tech vadera of business as well as significant erosion of Rituxan and the U S. We expect that the decreased revenue from these high margin products will put pressure on our gross margin percentage note that our gross margin in Q1, and 2021 was 82% of revenue which reflects this dynamic.

Michael R. McDonnell: We ended the quarter with $7.3 billion in debt and $3.4 billion in cash and marketable securities, resulting in $3.9 billion in net debt. In addition, our $1 billion revolving credit facility was undrawn as of the end of the quarter.

We now expect full year non-GAAP R&D expenses will be between $2 3 billion and $2 $4 billion and.

And non-GAAP SG&A expenses will be between $2 6 billion and $2 7 billion.

Michael R. McDonnell: Let me now turn to our updated full year guidance for 2021. Our full year 2021 revenue guidance remains at $10.45 billion to $10.75 billion, despite unfavorable currency dynamics, which I will explain in a moment. We are increasing our non-GAAP diluted EPS guidance from our previous range of $17 to $18.50 to a range of between $17.50 to $19.00. Our capital expenditure guidance is unchanged at $375 million to $425 million.

This guidance reflects our expectation that both R&D and SG&A will increase beginning in the second quarter due to new collaborations.

Graham Readouts and as you can imagine investments as we prepare for the potential launch.

Our full year SG&A estimate continues to include an approximate 600 million dollar investment and support of the potential launch of edge of Canada.

Of this amount approximately $200 million would be reimbursable by ACI and would be reflected as collaboration profit sharing post commercialization and not part of SG&A.

We expect we will utilize a portion of the remaining share repurchase authorization of $4 billion throughout the year. Although this will depend on a variety of factors, including our business development activities.

Michael R. McDonnell: This financial guidance assumes that foreign exchange rates as of March 31, 2021 will remain in effect for the remainder of the year, net of hedging activities. It is important to note that we are reaffirming our revenue guidance despite an expected currency headwind of approximately $80 million net of hedging activities on our full year 2021 revenue guidance due primarily to the strengthening of the U.S. dollar from January 1st of 2021 through March 31st of 2020.

We have not included any impact from potential tax or health care reform or any impact from potential acquisitions or large business development transactions in our guidance.

And with that I'll now turn the call back over to Michel for his closing comments. Thank you Mike.

Cogent and continue to demonstrate the resilience and strong execution in the first quarter of the year and we believe and we remain on track to make 2020, one a transformative year for the company.

And this of course starts with the potential approval of educating mob and the U S and the unmet need and cost of society for the damage disease are tremendous and mounting and zymase creates a cost burden of over $600 billion per year in the U S and the costs for carrying for the zama patients can be over half of it.

Michael R. McDonnell: Our guidance continues to assume that aducanumab will be approved in the U.S. by June 7, 2021, although uncertainty remains about the FDA's decision. If aducatumab is approved in the U.S., we would expect an immediate launch. However, dose titration will result in less revenue per patient in the initial months of treatment.

And as.

Zoom is deprived and many patients of the independence by the age of 80, approximately 75% of people with Alzheimer's disease, leaving the nursing home at the.

Michael R. McDonnell: And as a result, we would expect only modest revenue for aducatumab in 2021, ramping thereafter. We continue to expect rapid erosion of our U.S. Tecfidera business as well as significant erosion of Rituxan in the U.S. We expect that the decreased revenue from these high-margin products will put pressure on our gross margin percentage. Note that our gross margin in Q1 2021 was 82% of revenue, which reflects this dynamic. We now expect full-year non-GAAP R&D expenses will be between $2.3 billion and $2.4 billion, and non-GAAP SG&A expenses will be between $2.6 billion and $2.7 billion.

The patient cost of approximately 100000, the lost per year, the potential approval of educating mab would it be and unprecedented milestones for patients their families and society at large.

Beyond educate them up we continue to advance our neuroscience pipeline as we work to create the immunity franchise portfolio.

We look forward to the seven expected mid to late stage Readouts of this year the cross a range of therapeutic areas, such as Alzheimer's disease, a L S ophthalmology depression and stroke, including four in phase III.

I want to hit the rate of our commitment to maximizing returns to our shareholders and bringing innovative therapies to patients over the long term. These demands that we continue to allocate capital efficiently and effectively while maintaining operational discipline and managing costs as we have demonstrated in the past we will always strive.

Michael R. McDonnell: This guidance reflects our expectation that both R&D and SG&A will increase beginning in the second quarter due to new collaborations, program readouts, and AgiCanimab investments as we prepare for the potential launch. Our full year SG&A estimate continues to include an approximate $600 million investment in support of the potential launch of Aducanumab. Of this amount, approximately $200 million would be reimbursable by ASI and would be reflected as collaboration profit sharing post-commercialization and not part of SG&A.

To have an optimal capital structure as well as aim for superior returns from the investments we make.

Lastly, I would like to reflect upon biogen's long standing commitment to corporate responsibility.

The indication to patients and the broader society is and not only do you needed to developing novel therapeutics for patients suffering from serious diseases, but extend much further.

As Biogen, we work with purpose to advance science to address the urgent and long term challenge facing humanity.

Michael R. McDonnell: We expect we will utilize a portion of the remaining share repurchase authorization of $4 billion throughout the year, although this will depend on a variety of factors, including our business development activities. We have not included any impact from potential tax or health care reform or any impact from potential acquisitions or large business development transactions in our guidance. And with that, I'll now turn the call back over to Michel for his closing comments.

Now more than ever we continue to strengthen and environmental social and governance priorities across the company.

To underscore this commitment we have decided to incorporate and ESG metric into our corporate scorecard to help ensure that we accelerate the actions across these critical issues.

In closing I would like to thank our employees around the world who have demonstrated the dedication to making a positive impact on patients' lives and all of the physician caregivers and participants in all the clinical development Paul Toms We added Inc. Through challenging times with COVID-19, and our achievements could not be realize.

Michelle Vunatsos: Thank you, Mike. Biogen continues to demonstrate resilience and strong execution in the first quarter of the year, and we believe we remain on track to make 2021 a transformative year for the company. This, of course, starts with the potential approval of aducanumab in the U.S. The unmet need and cost to society for Alzheimer's disease are tremendous and mounting. Alzheimer's creates a cost burden of over $600 billion per year in the U.S., and the cost of caring for an Alzheimer's patient can be over half a million dollars. Alzheimer's deprives many patients of their independence. By the age of 80, approximately 75% of people with Alzheimer's disease live in a nursing home at a per patient cost of approximately $100,000 per year.

Without the passion and commitment we will now open the call for questions.

Thank you if you'd like to ask the question. Please press star one on your telephone keypad of.

The reminder, please limit yourself to one question.

If you require any further follow up questions you May press star one again to rejoin the queue.

First question comes from Michael Yee of Jefferies. Please go ahead.

Okay.

Hey, guys. Good morning, and thanks for the question of.

It sounds like you remain quite optimistic about a potential approval for <unk> I was just wondering if you could make some comments about the work you've done with FERC sites and player.

And now that it does get approved there's a lot of insured and year round reimbursement income.

Our logistics and MRI monitoring and things of that nature. So could you just maybe comment about the work you've done there and how confident you are that that will be fairly smooth. Thank you.

Michelle Vunatsos: The potential approval of aducanumab will be an unprecedented milestone for patients, their families, and society at large. Beyond aducanumab, we continue to advance our neuroscience pipeline as we work to create a multi-franchise portfolio. We look forward to the seven expected mid- to late-stage readouts this year across a range of therapeutic areas such as Alzheimer's disease, ALS, ophthalmology, depression, and stroke, including four in Phase 3.

Thanks for the question Michael the.

And the focus of the team since many months in the U S.

It was first to identify and assist the the sites of care in terms of the.

And has secured device and processes, because we anticipate that there will be if approved and very large influx of patients. We know that the availability of specialist and diagnoses kept the btt's a bottleneck. So we had to prepare the sides of cash and we are what we have worked all around.

Michelle Vunatsos: I want to reiterate our commitment to maximizing returns to our shareholders and bringing novel therapies to patients over the long term. This demands that we continue to allocate capital efficiently and effectively while maintaining operational discipline and managing costs. As we have demonstrated in the past, we will always strive to have an optimal capital structure as well as aim for super returns from the investment we make.

The country in order to identify those today, we anticipate that approximately 600 ready to treat the but many more are on the works. So this was this work was managed by a cross functional team and obviously, we started with the medical engagement and scientific leadership and we are.

Michelle Vunatsos: Lastly, I would like to reflect upon Biogen's longstanding commitment to corporate responsibility. Our dedication to patients and society is not only limited to developing novel therapeutics for patients suffering from serious diseases but extends much further. At Biogen, we work with purpose to advance science to address the urgent and long-term challenges facing humanity. Now, more than ever, we continue to strengthen environmental, social, and governance priorities across the company. To underscore this commitment, we have decided to incorporate an ESG metric into our corporate scorecard to help ensure that we accelerate actions across these critical issues.

And we the way we want where we are in terms of those sites and the ability to welcome the patients to diagnosed the patients to dose the patients to monitor all of the patients, including the including the fine.

Processes, such as Formula really stink, who is in charge of flat. So the team has done a very thorough work and I am pleased with the progress each time I review of the operation and the U S and the the launch readiness. We are we we of bridging we are passing some new might've storms I am also.

So pleased with the digital capability that sees and overlay of the of reach contact and one is the building.

Towards different stakeholders, not only the physicians, but also the patients and the and patient services.

Michelle Vunatsos: In closing, I would like to thank our employees around the world who have demonstrated a dedication to making a positive impact on patients' lives and all of the physician caregivers and participants in our clinical development programs. We are living through challenging times with COVID-19, and our achievements could not be realized without passion and commitment. We will now open the call to questions.

As you know so far the needed debt and they'll CSF amyloid of reimbursing the U S. TSA fees reimbursed in Europe, not in the U S. But we believe the visa path forwards concerning price I think that we have there Mike we have done the a thorough and.

The engagement with different stakeholders.

Operator: Thank you. If you would like to ask a question, please press star 1 on your telephone keypad. As a reminder, please limit yourself to one question. If you require any further follow-up questions, you may press star 1 again to rejoin the queue. Your first question comes from Michael Yee of Geoffrey's. Please go ahead.

During the the burden of the disease and the clinical meaningfulness that and you can imagine will bring and we have engaged with pharma co economics, including the Isa and many times and orders and in the U S and beyond so I think that the team he's he's ready and I am pleased with the progress and actually the three.

Mountain edition, where we're like a gift for the team because we had never fully ready for such a launch and I missed the also approached.

Michael J. Yee: Hey guys, good morning and thanks for the question. It sounds like you remain quite optimistic about a potential approval for ADU. I was just wondering if you could make some comments about the work you've done with both sites and payers. I know that if this does get approved, there's a lot of uncertainty around pet reimbursement and logistics and MRI monitoring and things of that nature. So could you just maybe comment on the work you've done there and how confident you are that this will be fairly smooth? Thank you.

And I appreciate the collaboration from ESI in diesel launch readiness.

Yeah perfect work forward the right. Thank you.

We'll take our next question from Ronny Gal of Bernstein. Please go ahead.

And good morning, everybody and thanks for taking the call and I just.

One and fix it there could be extended you are successful in and.

The prosecuting the the appeal or getting any of your patents can you discuss how that will impact the market.

Michelle Vunatsos: Thanks for the question, Michael. The focus of the team for many months in the U.S. has been first to identify and assist the sites of care in terms of infrastructure advice and processes, because we anticipate that there will be, if approved, a very large influx of patients. So the team has done very thorough work, and I am pleased with the progress. Each time I review the operation in the U.S. and the launch readiness, we are bridging; we are passing some new milestones.

I know you've got a few settlements and I'm wondering and both products and expand the market, okay and when they have the exited the market you basically of agreements.

And you were able to win the appeal.

Yeah. So ronny it's Mike. Thank you for the question and.

You know as we've said, we do expect to hear something on the appeal and the first half of this year and as we sit here and April 22nd that could really come at any time now.

There are many generics on the market as you know and our legal team has worked extremely hard to.

Try to win this appeal and overturn this decision.

Michelle Vunatsos: I am also pleased with the digital capability that is an overlay of rich contact and awareness building towards different stakeholders, not only physicians but also patients and patient services. As you know, so far, neither PET nor CSF amyloid are reimbursed in the U.S. CSF is reimbursed in Europe, not in the U.S., but we believe there is a path forward.

To the extent that we are successful obviously that would be very good news on winning the appeal, but there would be of course forward.

From there and so in order to come.

Come up with you know of quantification of potential financial benefits it would be premature and it would be hard to catch.

Calculate immediately it would be the type of situation, where we would get the the good news and we would have to <unk>.

Navigate from there and a number of additional steps that we would have to go through.

Michelle Vunatsos: Concerning price, I think that we are there, Mike. We have done a thorough, you know, engagement with different stakeholders considering the burden of the disease and the clinical meaningfulness that aducanumab will bring. And we have engaged with pharmacoeconomics, including ICER, many times and others in the U.S. and beyond, so I think that the team is ready and I'm pleased with the progress. And actually, the three months' addition was like a gift for the team because we are never fully ready for such a launch. And I must also appreciate the collaboration from SI in this launch readiness.

And to get to Finalization and how the generics that are in the market that would react it is a little bit hard to.

Predict before that would actually happen. So I would say that obviously it would be a very good day and good news and we're working very hard and we believe in our case.

But we would have to sort of evaluate the ruling what it says and we would communicate more in terms of potential benefits as soon as we know what that what that of course look like.

Sure, let me sharpened as just a little bit do you have any settlements that will allow.

The market longer term, even if you win.

Operator: We'll take our next question from Ronnie Gall of Bernstein. Please go ahead.

Yeah, that's not that's not something that we can kind of comment on with specificity Ronnie.

Ronnie Gall: Good morning everybody, and thank you for taking the call. Just one on Texadera.

Thank you again, yeah, and where I and I.

Apologize for that but this is one where.

Michael R. McDonnell: To the extent that you are successful in prosecuting the appeal or getting an initial patent, can you discuss how that will impact the market? I know you've got a few settlements, and I'm wondering if those products are going to stay on the market, or will they have to exit the market if you are able to win the appeal?

Again, we are of great legal team, that's working very hard and overturning the appeal and were very.

And hopefully hear something very soon and we'll communicate more on exactly what it all means we'd have to look at the rolling and the specifics and we have to see the reaction of the generics that are and the market before we really could answer that.

Alright I appreciate it.

Michael R. McDonnell: Yeah, so Ronnie, it's Mike. Thank you for the question. And you know, as we said, we do expect to hear something on the appeal in the first half of this year, and as we sit here on April 22nd, that could really come at any time now. There are many generics on the market, as you know, and our legal team has worked extremely hard to try to win this appeal and overturn this decision.

Alright, thanks for the question.

Goodman of SBB Leerink. Please go ahead.

Yes. Good morning can you give us more color on spin Ross of outside the United States and we can talk about some of the regions with just the the underlying trends and what's going on there.

And then just the sleep Secretary of China can you just help us of your bookings sales is that something that you view of the big opportunity.

Michael R. McDonnell: To the extent that we are successful, obviously, that would be very good news on winning the appeal, but there would be a path forward from there. And so in order to come up with a quantification of potential financial benefits, it would be premature, and it would be hard to calculate immediately. It would be the type of situation where we would get the good news, and we would have to navigate from there a number of additional steps that we would have to go through to get to finalization and how the generics that are in the market now would react.

So thanks for the equation and we are very pleased with the performance of speed and was the ex U S and I'm also pleased with the performance and the U S. Even if and we.

We did the we did face some discontinuation due to the compounded the effect of the Covid and also the perceived the enhancer and modality, we the role of <unk>. The convenience and so there are a lot of learning that the coming from the U S to apply to Europe and ex Europe.

We can see a very strong resilience and call you hope and markets and we can see and the very fast the momentum of growth in the.

Michael R. McDonnell: It's a little bit hard to... (inaudible)

The emerging geographies. So all in all of I am and I am very pleased I think that the moving forward with the pending are improving with the rate of explanation of this.

Michael R. McDonnell: Um, yeah, that's not, that's not something that we can, you know, kind of comment on with specificity, Ronnie. Um, you know, again, yeah, we're

Here are two of these you can see tuition will gradually decrease and and and the the SUNFISH. Two data continues to reinforce the say the disease that basically the product is not that difficult issues for the for the total rose above the age of five.

Operator: Thank you. I appreciate it. Our next question comes from Marc Goodman of SVB Leering. Please go ahead.

Marc Harold Goodman: So thanks for the question. We are very pleased with the performance of Spinraza XUS, and I'm also pleased with the performance in the US, even if, you know, we did face some discontinuation due to the compounded effect of COVID and also the perceived enhanced modality with the oral of ABRIS-D, the convenience. And so there is a lot of learning that is coming from the US to apply to Europe and ex-Europe. We can see very strong resilience in core European markets, and we can see a very fast momentum of growth in emerging geographies.

The the dose limitation because of all the reasons that we all know and and basically is set the limit in terms of efficacy while the weight of the of of the young adult of total young adult increasingly teas and lots of spots of the of the market and where we have faced some switches. So obviously.

The learning from the U S will benefit probably the ex U S in an environment, where we should have and.

Marc Harold Goodman: So obviously, the learning from the US will benefit the US ex-US in an environment where we should have less of the pandemic. I am pleased with the emerging economies where rare diseases were not a priority for so long and are nowadays on the agenda in terms of resource allocation. So very good momentum.

And the less of the 10 day beyond I am pleased with the emerging economies, where rare diseases, where not the priority for so long and nowadays are the you know on the agenda in terms of resource allocation. So very good momentum concerning the feed the raw in the in China, you know, it's the second and.

Michelle Vunatsos: It's the second product approved in China for Biogen, and I am delighted about that. As you know, I was posted there for my previous company for four years with my family, and I fundamentally believe in the long-term potential of this market, which is already number two in the world. So the demand is tremendous, and epidemiology is rapidly merging with similarities to that of the West. So incidence is lower for MS, but there are still more than 100,000 patients. The rate of diagnosis and treatment with DMTs is extremely low.

It's the second product approved in China for Biogen and I am delighted about that as you know I was supposed to be there for my previous company Dream for years with my family and the and I fundamentally believe into the long term potential of this market that he is already the number two in the world.

And so the the demand is tremendous and epidemiology ease the rapidly emerging we the similarities with the one of the of the of the West.

And the incidence is lower for Ms, but there's still more than 100000 patients.

And the rate of diagnosis and the rate of treatment with <unk> is extremely low it's less than 5% of the market. So disabilities are high and the and the ETE gives a great opportunity to establish the exceed era together with the rest of the portfolio with the bit more time hopefully.

Michelle Vunatsos: It's less than 5% of the market, so disabilities are high, and it gives a great opportunity to establish a tech federation together with the rest of the portfolio and hopefully a bit more time. China is an important market for Biogen. We are managing Asia-Pac without Japan from China. We have partnered with a Chinese company on a biosimilar, so it's an investment geography. Obviously, we don't lose the focus on the rest, but good momentum in China. We have a great team, more than 200 people, and it's only the beginning. Thank you for the questions.

<unk>.

China is an important market for Biogen.

We are managing Asia Pac without Japan from China, We have partnered with the Chinese company on the on the Biosimilar and it's so eats and invest geography, obviously, we don't lose the focus on the rest the two good momentum in China, we have a great team more than 200 people and it's the only the beginning thank you for the questions.

Yes.

We'll take our next question is from Yadkin. Thank you Joe.

Operator: We'll take our next question from Yatin Sanuja of Guggenheim Partners. Please go ahead.

Google Home partners. Please go ahead.

Hey, guys. Thank you for taking my question and I have a question on the rental on the can you maybe talk about the expectation from the upcoming of waterfall study.

Yatin Sanuja: Hey guys, thank you for taking the time to join us today.

Geoffrey Christopher Meacham: My question is, can you maybe talk about the expectation from the upcoming waterfall study, the importance of durability, and how should we think about durability beyond the two-week dosing period? Do you need to hitch that segment beyond day 15, and how the powering might be structured?

And the importance of durability and and how should we think about.

You know.

Durability beyond the two week dosing period, do you need to hit Stat Sig.

Beyond day, 15, and how the poverty and might be structured after the primary endpoint. Thank you.

Geoffrey Christopher Meacham: Thank you. Hi, this is Al.

Hi, This is al yeah. So the primary endpoint is the efficacy of day 15 and.

Geoffrey Christopher Meacham: Hi, this is Al. Yeah, so the primary endpoint is efficacy at day 15. And, you know, a key secondary endpoint is durability, if you will, at day 42. And, you know, there are two ways to look at that.

And you know of key secondary endpoint is the is the durability of if you will at the at day 42.

And you know, it's there's two ways to look at that one is does it stay separated from placebo or perhaps more importantly, what changed what happens between day 15 and day 42.

Geoffrey Christopher Meacham: One question is, does it stay separated from placebo? Or perhaps, more importantly, what happens between day 15 and day 42 with regard to the efficacy of the HAMD score in the treated patient? And so I think that if you look at precedent, the latter is probably more important than the former, but I think both will need to be looked at. And then, of course, the key durability comes from the data from Shoreline, which shows that patients who responded to the initial course of treatment need at most one additional treatment. About 70 percent needed at most one additional treatment for an entire year. So I think that both kinds of durability are important.

On the efficacy on the Ham D score and the treated patients.

And and so I think that the if you look at our prior precedents and the latter is probably more important and the former.

But I think both will need to be looked at and then of course, the the key durability comes from the.

Data from shoreline, which shows that the patients.

Patients who responded to the initial of course of treatment need at most one additional treatment about 70% needed and needed at most one additional treatment for an entire year. So I think that are both kinds of durability of our important.

Operator: We'll take our next question from Umer Raffat of Evercore. Please go ahead.

We'll take our next question from Omar.

Also of Evercore. Please go ahead.

Hi, Thanks, so much for taking my question.

Umer Raffat: Hi, thanks so much for taking my question. Michelle and Michael, I would just like to understand the stock repurchase trends better, and I'm specifically looking at over $10 billion worth of repurchases that were done between 4Q19 through 3Q20 versus around a billion that were done in 4Q20 and 1Q21.

Michel Michael I would just like to understand the stock repurchase trends of better and and and I'm specifically looking at over $10 billion worth of repurchases that were done between <unk> 19 through the <unk> 'twenty.

And versus around 1 billion, that's been done and <unk> 20, and <unk> 21, I'm just trying to understand the the drop and magnitude better and I realize we can't necessarily correlate that to one specific thing, but I would just love to understand the thought process there.

Michael R. McDonnell: Unknown Executive, Ami Fadia, Adam Keeney, Chris Schott, Biogen Inc. Umer, it's my fault.

Michael R. McDonnell: Mr. Umer, it's Mike. Thanks for the question. So, a couple of comments. I would say that, you know, we did buy back $600 million in the quarter, and we continue to be very committed to our share repurchase program, and we continue to see our stock as a very accretive investment, and we will continue to buy back stock and utilize a portion of the remaining $4 billion authorization throughout the rest of the year, as we said.

The rumor it's Mike Thanks for the question. So a couple of comments I would say that.

You know, we did buy back $600 million and the quarter and we continue to be very committed to our share repurchase program and we continue to see our stock as a very accretive investment and we will continue to buy back stock and utilize the portion of the remaining $4 billion authorization throughout the rest of the year as we said.

If you look back five years a.

Michael R. McDonnell: You know, if you look back five years, Biogen has repurchased something on the order of 71 million shares for a total value of $20 billion, and I would say that we've certainly availed ourselves of a great opportunity there. And I think that you do have to differentiate levels of cash flow prior to the entry of generics for Tecfidera. Obviously, that was a highly profitable product with a large revenue base in the U.S. that's now eroding pretty rapidly, so we don't have the level of free cash flow that we had prior to that, but with that said, we still do have a meaningful amount of cash, with $3.4 billion on hand at the end of the quarter, and we remain very committed to share repurchases.

Biogen has repurchased something on the order of 71 million shares for a total value of the $20 billion and I would say that we've certainly availed ourselves of of a great opportunity there and I think that.

You do have to differentiate levels of cash flow prior to the entry of generics protect the Dara, obviously that was a highly profitable product with a large revenue base and the U S. That's now eroding pretty rapidly. So we don't have the level of free cash flow that we had prior to that but with that said, we still do have.

A meaningful amount of cash of $3 $4 billion on hand at the end of the quarter and we remain very committed to share repurchases. There is a differential obviously and the level of free cash flow and and we had a lot of excess cash on hand during various periods of time, even more than we have now prior to the generic situation.

Michael R. McDonnell: There is a difference, obviously, in the level of free cash flow, and we had a lot of excess cash on hand during various periods of time, even more than we have now prior to the generic situation.

So within the confines of what we can do we remain very committed $600 million is still a pretty meaningful number and we will continue to evaluate a very robust pipeline of BD opportunities. We will continue to invest and those of you probably saw that.

Michael R. McDonnell: So within the confines of what we can do, we remain very committed. $600 million is still a pretty meaningful number, and we will continue to evaluate a very robust pipeline of BD opportunities. We will continue to invest in those. You probably saw that we announced an investment in a biosimilar opportunity with BioThera that we're excited about, and we will continue to repurchase shares, and we have the wherewithal to do that. So I wouldn't read too much into the volume as being a sign that we're not committed to it because it's something that we continue to see as a very accretive investment.

We announced our investment in the Biosimilar opportunity with bio thorough that works excited about and we will continue to repurchase shares and we have the wherewithal to do that so I wouldn't read too much into the to the volume as being a sign that we're not committed to it because we are something that it's something that we continue to see is of very accretive investment.

Operator: We'll take our next question from Matthew Harrison of Morgan Stanley. Please go ahead.

We'll take our next question from Matthew Harrison of Morgan Stanley. Please go ahead.

Matthew Harrison: Great. Good morning, Al. I was wondering if you could just comment on Cal and, you know, given what we've seen from some of the other studies, what your level of confidence is in this phase two readout that's coming up.

Great. Good morning, and I was wondering if you could just comment on Paul and just given what we see and from some of the other study what your level of confidence is the next phase III readout, that's coming up.

Geoffrey Christopher Meacham: Yeah, hi, Matthew. Well, you're talking about Gosaranumab-BiB-92, which is our antibody that targets essentially extracellular tau, trying to prevent the spread of tau from cell to cell. And you're right. The Roche negative results do make us think that, you know, it's tough to target tau with an antibody. But we remain hopeful.

Yes, Hi, Matthew.

Well, you're talking about ghosts and ran a mab bib 92, which is our antibody that targets essentially extracellular tau of trying to prevent.

<unk> the spread of Tau from cell to cell.

And you're right I mean, the Roche a negative results do make us think that you know that it's tough to target with an antibody, but we remain hopeful we haven't seen the data from our own phase II results yet the large study 650 plus patients testing several doses.

Geoffrey Christopher Meacham: We haven't seen the data from our own phase two results yet. It's a large study, 650-plus patients testing several doses, and we're testing it in the early stages of Alzheimer's. So I think it's a robust study that'll enable a very good go-no-go decision for phase three. I did mention BiB-80 in my prepared comments because it's a different approach to tau. It uses an antisense to decrease the production of tau, and it should affect both the intracellular and extracellular forms of tau.

And we're testing it and the early stages of Alzheimer's. So I think it's a robust study that will enable the very good go no go decision to phase III.

Did mentioned <unk> 80 of my prepared comments, because it's a different approach to Tao, it's using and antisense to decrease the the production of Tau and it should affect both intracellular and extra cellular forms of Tau very different approach.

Geoffrey Christopher Meacham: Very different approach, and we're excited about the results that we found in phase one in terms of dose and time-dependent reduction in tau expression as seen in the CSF, and we're looking forward to sharing those results later this year at a scientific meeting.

And we're excited about the results that we found and phase one in terms of dose and time dependent reduction.

And in Tau expression of as seen in the CSF and we're looking forward to sharing those results later this year the scientific meeting.

Operator: We will take our next question from Brian Abrahams of RBC Capital Markets. Please go ahead.

We will take our next question from Brian Abrahams RBC capital markets. Please go ahead.

Hey, guys. Thanks, so much for taking my question.

Brian Abrahams: Hey guys, thanks so much for taking my question. On aducanumab, can you maybe remind us again of this phase?

And how to kind of map can you maybe remind us again of the phase III monitoring requirements for safety and those studies and and maybe your latest views and what you think would be most appropriate and a real world setting I guess, what preparation centers would need to have for both management and monitoring as well as optimizing the benefit risk on the patients whose.

Brian Abrahams: Phase 3 Monitoring Requirements for Safety

Brian Abrahams: What are your latest views on what you think would be most appropriate in a real world setting? I guess what preparation centers would need to happen?

Brian Abrahams: Patients Centers would need to have for both management and monitoring as well as optimizing benefit risk for the patients who start at you.

Start out too.

Yeah, Hi, Brian the the.

Geoffrey Christopher Meacham: Hi Brian. The main adverse event associated with ADU is ARIA-E, and that's readily monitored by a very standard sequence used for MRI scans. And in the Phase III trial, almost all the monitoring was done within the first year of treatment because the risk of ARIA goes down with time. The longer you treat, the less likely you are to get ARIA-E, and I believe we had six or nine scans in the trial.

The main adverse event associated with AD you are is ARIA E and.

And that's readily monitored by a very of standard sequence used for MRI scans and.

And are in the phase three trial most of the.

Almost all of the monitoring was done and within the first year of treatment because the risk of ARIA goes down with the time as you. The the longer you treat the less likely you are to get them.

E.

And I believe we had the six or nine scam.

Scans in the trial, but we don't think that you'll need that many we were being extra cautious and in.

Geoffrey Christopher Meacham: We don't think that you'll need that many. We were being extra cautious in our Phase III trials. Exactly how many we'll need will obviously depend on our discussions if we get to them or when we get to them in terms of the label, which we don't have yet.

And our phase III trials exactly how many will need will obviously depend on our discussions if we get to them.

Or when we get to them and.

In terms of the of.

The label, which we don't have yet.

I would remind you the most of the.

Geoffrey Christopher Meacham: I would remind you that most of the ARIA-E patients were asymptomatic. I'd say about two-thirds were asymptomatic, and when symptoms were present, they were generally mild, such as headache and confusion. So I think it's a readily dealt with, readily managed adverse event. And I think the sites, because almost all, I mean virtually every center, even private practice clinics have readily access to MRI, and as I said, it's a standard sequence. So I don't think it's going to be a major problem to monitor for ARIA.

ARIA E.

Is it were asymptomatic I'd say about two thirds were asymptomatic and when symptomatic. They were the symptoms were generally mild such as headache and confusion. So so I think it's the readily dealt with and readily managed.

Adverse event and I think the sites because almost all I mean, virtually every center, even a private practice clinics have access readily access to MRI and as I said, it's the standard sequence. So I don't think it's going to be a major problem to monitor for Oreo.

Operator: We'll take our next question from Colin Bristow of UBS. Please go ahead.

We will take our next question from Colin Bristow of UBS. Please go ahead.

Hey, good morning, and congrats on the quarter.

Colin Nigel Bristow: Hey, good morning, and congrats on the quarter. On the EMBARQ trial, I believe you reduced the planned enrollment from 2,400 to 1,800. I was just wondering, could you give us some color on the drivers of this?

The embark trial I believe you've reduced the planned involvement through 'twenty 400, 1800, I was just wondering could you give us some color on the drivers of this was it was it the slower enrollment and your expectation, but most importantly, I wanted if you could give us do you have any data around the enrollment rates.

Geoffrey Christopher Meacham: Was it slower enrollment than your expectations? But most importantly, I wondered if you could give us any data around the enrollment rates from the active adecanamab arms versus placebo arms for the FEDA trial? Thanks.

All of them you know the active out of Canada have arms versus.

Versus placebo arms to the feed of trials.

Thanks.

Geoffrey Christopher Meacham: Thanks for the question. MBARC is enrolling students now. The rate of enrollment is actually as predicted. It's enrollment is on track. But as you noted, the total number of patients to be enrolled was reduced, and the main reason for that was that there were eligibility requirements, medical eligibility requirements, that were not met by many of the patients who were seeking to enroll in MBARC. I'd say, though, that the interest level on the part of patients as well as investigators remains high. And, as I said, enrollment does remain on track. And I don't have data on whether or not there's differential enrollment from the different feeder arms.

Yeah. Thanks for the question embark is enrolling the rate of enrollment is actually as predicted it's enrolling on track and but as you noted the and the the total number of patients to be enrolled was reduced.

And that's the main reason for that was that they were eligibility requirements medical eligibility requirements that.

That were not met by many of the patients who were seeking to enroll in and embark I'd say, though that the interest level on the part of patients as well as the investigators remains high and as I said, the enrolment does remain on track and and <unk>.

And I don't have the data on whether or not the there's a differential of enrollment from the different feeder.

Arms.

Operator: We'll take our next question from Evan Seigerman of Credit Suisse. Please go ahead.

We'll take our next question from Evan Siegel line of Credit Suisse. Please go ahead.

Hi, all thank you for taking my question I just wanted to touch on the recent data read out of stage $3 24, while you have the stats say good result on the primary we did see a very high discontinuation rate and the treatment arm two things can you remind us how you plan to mitigate this and a pivotal trial and what is the acceptable rate of thumb non spore a successful commercial assets and <unk>. Thank you.

Evan Seigerman: Hi all, thank you for taking my question. I just wanted to touch on the recent data readout for stage 324. While you had the STAS-SIG result on the primary, we did see a very high discontinuation rate in the treatment arm.

Evan Seigerman: Can you remind us how you plan to mitigate this in a pivotal trial and what is the acceptable rate of somnolence for a

Evan Seigerman: Assam Noland for a successful commercial asset in ET. Thank you.

And.

Geoffrey Christopher Meacham: Well, you're correct that, as I stated in my comments, the primary endpoint was met, which I think, and I want to congratulate my colleagues at SAGE on that. That's a major result.

Oh well.

The Youre correct that as I stated in my comments the primary endpoint was met which I think.

And I want to congratulate and my colleagues at Sage for that.

And that's a major a result.

The obvious thing to do now since we tested the hide and of the dose range is to see whether we can reduce the dose mitigate some of the adverse events, while maintaining efficacy there may be other maneuvers such as the.

Geoffrey Christopher Meacham: The obvious thing to do now since we tested the high end of the dose range is to see whether we can reduce the dose, mitigate some of the adverse events while maintaining efficacy. There may be other maneuvers, such as changing the dosing algorithm, if you will, perhaps easing up to dose titration. Other approaches would include potentially looking at key subgroups. In terms of what's acceptable, I think that's a very tough... It's something that needs to be answered definitively.

Changing the dosing algorithm, if you will perhaps of.

Easing up to two of dose.

And tight trading.

The other approaches would include of.

In terms of what's acceptable I think that's the that's a very tough.

To answer definitively I think the every patient and looks at the benefit they are receiving from the drug and the tolerability issues. They have to accept with the drug it's probably of day to day decision the patients, making and and this situation. They can see themselves, what's going on with the tremor and and the and perhaps there'll.

Geoffrey Christopher Meacham: I think that every patient looks at the benefit they're receiving from a drug and the tolerability issues they have to accept with the drug. It's probably a day-to-day decision that patients make. And in this situation, they can see themselves what's going on with the tremor. Perhaps there will be several doses one day that will allow patients to choose between doses that optimize for them the benefit versus the risk.

Several doses of one day that will allow patients to choose.

The between doses that optimize for them the benefit versus the risk of.

And I think that the stage of development. The mindset of the team is to try to do better than what we have seen with this initial phase II.

Geoffrey Christopher Meacham: Evan, I think that at this stage of development, the mindset of the team is to try to do better than what we have seen with this initial phase two, 60% or so symptomatology and approximately 30% discontinuation. So it's a fascinating question that you ask. It's all about the benefits-risk, but the mindset is to try to do better.

The 60% of saw symptomatology and the approximately 30% discontinuation so and it's a fascinating question that you asked and it's all about the benefit risk the the mindset and this is try to do better.

Operator: We'll take our next question from Jay Olson of Oppenheimer. Please go ahead.

We'll take our next question from Jay Olson of Oppenheimer. Please go ahead.

Hi, Thanks for taking my question. My question is about your sub Q strategy do you consider sub acute tysabri as a complement to IV tysabri or substitute that will eventually replace IV tysabri and.

Jay Olson: Thanks for taking my question. My question is about your sub-Q strategy. Do you consider sub-Q Tysabri to be a complement to IV Tysabri?

Unknown Executive: Unknown Executive, Ami Fadia, Chris Schott, Biogen Inc., Ami Fadia, Ami Fadia,

And since there was the study of sub Q and you kind of map can you remind us about your plans for a sub Q form of that academy of and how you apply your experience from the third Q tysabri to add kind of Nab.

So thanks for the question and we are very excited by the momentum we see behind the Tysabri high efficacy and the mechanism that cheesy eventually is slightly favored in the current environment.

Unknown Executive: So thanks for the question. We are very excited by the momentum we see behind Tysabri, high efficacy, and a mechanism that is eventually slightly favored in the current environment versus beta cell depletors. You know, the stigma around Tysabri was always the risk of PML, and with the data we generate and the extended interval dose and, hopefully, the data with the NOVA study media readout, we should really shed light on the optimal dose and, mostly, frequency of the treatment. Sub-Q is an opportunity to enlarge the target.

Beta cell Depleters and.

And the you know the the stigma around the around the Tysabri was always the risk of P&L and we the data we generate and the extended the interval dose and.

And hopefully the the data we didn't know that study meet your readout.

Really shed light on the optimal dose and the mostly frequency.

And of the of the treatment sub Q ease and opportunity to enlarge the targets when we look at the at the prescribers landscape for Tysabri, we choose a tremendous success.

Unknown Executive: When we look at the prescriber landscape for Tysabri, which is a tremendous success, it's extremely limited. And is it because of the infusion centers? Is it because of the risk of PML? Probably both. Here, we are combining the opportunity of accessing high efficacy with subcutaneous dosing. So we should be in a position to enlarge the use and the targeting for disabling.

Extremely limited and the easy because of the infusion centers is it because of the risk of PMA and probably both here and we are combining the opportunity of accessing high efficacy. We the subcutaneous dosing. So we should be in a position to enlarge the use and the targeting and.

And for Tysabri.

Operator: We'll take our next question from Geoff Meacham of Bank of America. Please go ahead.

We'll take our next question is from Geoff Meacham of Bank of America. Please go ahead.

Geoff Meacham: Hey guys, good morning, and thanks for the question.

Hey, guys good morning, and thanks for the question.

And on as you I was just I was just curious if you guys have provided any more materials to the regulator I wasn't I wasn't sure of further details from the embark study.

Geoff Meacham: On Agio, I was just curious if you guys have provided...

Geoff Meacham: If you guys have provided any more materials to a regulator, I wasn't sure if further details from the EMBARQ study were a deciding factor. And just real quick on tau, Al, why don't you just get your view of the tau imaging, what Lilly did just to be able to assess Alzheimer's disease severity. Is that something that you think down the road could be implemented in your studies?

Worried getting factor and just real quick on Tao Al I wanted to just get your view of the.

The Tau imaging.

It really did two just to be able to assess alzheimers disease severity is that something that you think down the road could be implemented the and your studies. Thank you.

Hi, Jeff.

We remain on track for the Paducah date of June 7th and obviously, if we had submitted a major additional data that would affect that so but other than that we don't want to comment on what were what were.

Geoffrey Christopher Meacham: We remain on track for the PDUFA date of June 7th, and obviously, if we had submitted major additional data, that would affect that. But other than that, we don't want to comment on what we're submitting, or our interactions with FDA, except to say that we continue to have regular meetings with them, and that, to us, everything is on track for a PDUFA decision by that date.

So submitting our interactions with FDA, except to say that we continue to have regular meetings with them and.

And the.

To us the everything's on track for it could do for decision on by a by the way by the Paducah date in terms of Tau the concept of using Tau imaging essentially to stage patients is a very interesting and novel concept and.

Geoffrey Christopher Meacham: In terms of tau, the concept of using tau imaging essentially to stage patients is a very interesting and novel concept, and they showed that there are certain patients, if you look at amyloid PET as well as tau PET, you could potentially choose patients with the right stage of Alzheimer's disease that would maximally benefit from an amyloid-lowering agent such as Donanimab and potentially Aducanumab and BAN2401. So I think it' I think it's something that we need to look at again with further study, but it's something that could potentially be useful.

And they showed that there are certain.

If you look at the amyloid pet as well as Tau pet you could potentially choose patients with the right stage of Alzheimer's disease that would maximally benefit from and amyloid lowering agents such as the nano mab and potentially as you can even have been Ben to 401. So I think it's a very interesting concept.

I think it's something that we need to look at again and with further study, but it is something that could potentially be useful.

Operator: We'll now take our last question from Samant Kulkarni of CannaCords. Please go ahead.

We will now take our last question from <unk> Kulkarni of Canaccord. Please go ahead.

Good morning, Thanks for taking my question.

Samant Kulkarni: Thank you for taking my question. Given you're so deep in the FDA's review of aducanumab, other than perhaps the stage of Alzheimer's disease in patients, what are your latest thoughts or expectations on any specific limitations and labeling of ADU, perhaps by APOE for carrier status or other more genetic-oriented variables?

And then your so deep and the Fda's review of out of kind of other than perhaps stage of Alzheimer's disease. The patients what are your latest thoughts of expectations on any specific limitations and labeling of baidu, perhaps by equal equal. Okay. Yes that is the other more genetic ODM debatable.

Geoffrey Christopher Meacham: Yeah, I wish I could, you know, I just can't answer those types of questions. We're still in the middle of our review process, and I'm sensitive to the fact that we're under review. So, one day soon, I hope to be able to discuss all that with you.

Yeah, I wish I could you know I just can't answer those types of questions. We're still in the middle of a review process and I'm sensitive to the fact that we're under review so one.

And one day soon and I hope to be able to discuss all of that with you.

I want to thank you all for joining the Biogen call today, and we remained focus on flawless execution and our operation in order to deliver on our guidance. We are also focused on the velocity of our pipe and in the short run we are very excited with the important readouts and obviously with.

Michelle Vunatsos: I want to thank you all for joining the Biogen call today. We remain focused on flawless execution and our operation in order to deliver on our guidance. We are also focused on the velocity of our pipeline. And in the short run, we are very excited about the important readouts and, obviously, a critically important regulatory decision for aducanumab. Have a good day.

The critically important regulatory decision for educating them and have a good day.

Yes.

Operator: Thank you. That now concludes the call. Thank you for your participation. You may now disconnect.

Thank you that now concludes the call. Thank you participation you may now disconnect.

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Okay.

And.

Yeah.

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Okay.