Q4 2020 Biogen Inc Earnings Call

[music].

Okay.

Operator: And ladies and gentlemen, please stand by. Good morning.

And ladies and gentlemen, please standby.

Good morning, My name is Jack and I will be your conference operator today at this time I would like to welcome everyone to the Biogen fourth quarter and full year earnings call and financial update all lines have been placed on mute to prevent any background noise.

Operator: My name is Jake, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen fourth quarter and full year earnings call and financial news. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. 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.

After the Speakers' remarks, there'll be a question and answer session.

Like the asking the question during this time simply press star one on your telephone keypad.

Please limit yourself to one question to allow other participants time for questions.

Operator: If you require any further follow-up, you may press Star 1 again to rejoin the queue. Thank you. I would now like to turn the conference over to Mr. Mike Hanke, Director of Investor Relations. Mr. Hanke, you may begin your presentation. Thank you, Jake.

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

Thank you I would now like to turn the conference over to Mr. Mike Hickey Director Investor Relations. Mr. Hanky, you may begin your conference.

Thank you Jake good.

Mike Hanke: Good morning, and welcome to Biogen's fourth quarter 2020 earnings call. Before we begin, I encourage everyone to go to the investor section of biogen.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 will discuss today. Our GAAP financials are provided in 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. We have also posted slides on our website that follow the discussions related to this call. I would like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs.

And welcome to Biogen fourth quarter of 2020 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 will discuss today are.

GAAP financials are provided in 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. We've also posted slides on our website that follow the discussions related to this call.

I would like to point out that we will be making forward looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and our actual results may differ materially.

Chuck Triano: These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. On today's call, I am joined by our Chief Executive Officer, Michelle Vounatsos, Dr. Al Sandrock, EVP, Research and Development, and our CFO, Mike McDonnell. I will now turn the call over to Michelle.

Encourage you to consult the risk factors discussed in our SEC filings for additional detail.

On today's call I'm joined by our Chief Executive Officer, Michel <unk>, Dr. Al Sandrock, EVP research and development and our CFO, Mike Mcdonnell I will now turn the call over to Michel.

Michelle Vounatsos: Thank you for watching, everyone, and thank you for joining us. I would like to start by thanking Joe Marra for his excellent contribution to Biogen during the past 14 years, and also congratulations on his well-deserved promotion. At the same time, I am delighted to have Mike Encke stepping into the role.

Good morning, everyone and thank you for joining us I would like to start by thanking Joe Mara for his excellent contribution to Biogen during the past 14 years and also congratulation for his well deserved promotion on.

At the same time I am delighted to have Mike and key stepping into the role.

Michelle Vounatsos: As we announced last week, the FDA has extended the review timeline for aducanumab in the U.S. to June 7th. We are committed to working with the FDA as it completes its review of the aducanumab application, and we continue to stand behind our clinical data. We believe our results support approval. Now, let me now review the year.

As we have announced last week. The FDA has extended the review time line to educate you might have in the U S to June seven we are committed to working with the FDA as it completes its review of the educating them on the application and we continue to stand behind our clinical data.

We believe our results support approval.

Let me now review of the year.

Michelle Vounatsos: 2020 was a year of uncertainties due to COVID-19 for both society at large and also for our industry, and I am proud of what the Biogen team delivered. For the full year 2020, Biogen generated $13.4 billion in revenue, representing a 6% decrease year-over-year as we are experiencing the erosion of tax-federal revenue in the U.S. due to the impact of generic entry. Full year 2020 non-GAAP earnings were $33.70 a share, a slight increase versus full year 2019. Now, let me review our progress against our strategic priorities. First, full-year MS revenues, including all previous royalties, were $8.7 billion, a decrease of 6% versus the prior year. Excluding Tetridera in the U.S., our global MS revenue remained relatively stable for both Q4 and the full year versus 2019.

2020 was a year of.

Certainties due to COVID-19 for both society at large and also for our.

Our industry.

I am proud of what the Biogen team delivered.

For the full year 2020, Biogen generated $13 $4 billion on the revenue representing a 6% decrease year over year as we are experiencing the erosion of the exit of our revenue in the U S. Due to the impact of generic entry.

Full year 2020, non-GAAP earnings were 33, the allowance of <unk> 70, a share a slight increase versus full year 2019.

Now, let me review, our progress against our strategic priorities.

First full year of MS revenues, including our previous royalties were $8 7 billion, the announced a decrease of 6% versus the prior year, excluding debt there on in the U S. Our global and that sort of a new remained relatively stable for both Q4 and the full year versus 2019.

<unk>.

Michelle Vounatsos: Despite the challenges of launching a new product during COVID-19, we were pleased to see strong improvement in trends for Vimerity, which has become the number two MS product and the number one oral in terms of new prescriptions in the U.S. We believe these results demonstrate our ability to maintain leadership and execute well despite increased competition, the erosion of federal revenue in the U.S., and COVID-19. Second, Spinoza generated full-year global revenues of $2.1 billion, a 2% decrease versus the prior year. Q4 global revenues were stable versus Q3.

Despite the challenges of launching a new product during COVID-19, we were pleased to see strong improvement in trends for humanity, which has become the number two <unk> product and the number one overall in terms of new prescriptions in the U S.

We believe these results demonstrate our ability to maintain leadership and execute well despite increased competition the erosion of the exit of our revenue in the U S and COVID-19.

Second the spinners that generated full year of global revenues of $2 1 billion.

A 2% decrease versus the prior year Q4 global revenues was stable versus Q3.

Michelle Vounatsos: While Spinraza is facing increased competition in the U.S., which has been exacerbated by the impact of COVID-19, this has been offset by continued growth outside the U.S. We remain committed to further exploring the potential to enhance outcomes for patients with Spinraza. This includes the DEVOTE study testing a higher dose, as well as the recent initiation of the RESPONSE study, evaluating Spinraza in patients with a sub There are important questions that remain unanswered about the other approved treatment options, and we are committed to generating relevant data to further inform treatment choices. We believe that Spinraza will remain a foundation of care in the treatment of SMA.

Whilst <unk> 50 increased competition in the U S, which has been exacerbated by the impact of COVID-19. This was offset by continued growth outside the U S.

We remain committed to further exploring the potential to enhance outcomes for patients. We spin of Ahs on this includes the devote study testing of higher dose as well as the recent initiation of the response study evaluating <unk> in patients with the sub optimal clinical response.

To gene therapy.

The important questions that remain on answered on the other approved treatment options and we are committed to generating 11 data to further inform treatment choices.

I believe that's been run out we remain a foundation of care in the treatment of SMA.

Michelle Vounatsos: Third, Biosimilars delivered solid performance despite continued COVID-19 impact, with revenues of $796 million for 2020, which represents 8% growth year-over-year. We estimate that the use of our biosimilars generated approximately 2.4 billion euros of savings to the European health care systems in 2020, which should help expand access and create headroom for new innovation. We also made important progress towards potential geographic expansion and future growth for our biosimilars business with the filing of SB 11, referencing Lucentis in the U.S., where over the next five years, biosimilars are expected to generate over $100 billion in savings.

Third Biosimilar ounce delivered solid performance. Despite the continued COVID-19 impact with the revenues of 796 million the allowance for 2020, which represents 8% growth year over year.

We estimate that the use of a biosimilar generated approximately $2 4 billion euros of savings to the European Health care systems in 2020, which should help expand access and create headroom for new innovation.

We also made important progress towards potential geographic expansion and future growth for our Biosimilars business with the filing of <unk> 11, and enhancing lucentis in the U S where over the next five years biosimilars the expected to generate.

Over $100 billion in savings.

Michelle Vounatsos: Fourth, 2020 was a very productive year for our R&D organization. Last year, we submitted regulatory filings for Educandumab in the U.S., EU, and Japan. We remain ready to launch Educandumab in the U.S. if and when it is approved. Our teams have evaluated the availability of specialists, infusion capacity, the ability to confirm the pathology of amyloid beta, and MRI capacity. And for midwifery approval processes, we believe there are several hundred sites in the U.S. that are ready to start treating patients should the education roadmap be approved.

Gross 2020 was a very positive year for our R&D organization last year, we submitted a regulatory filing flood you can imagine the in the U S EU and Japan.

We remain ready to launch as you can imagine the U S. If and when it is approved.

Our teams have evaluated the availability of the specialist inefficient capacity the ability to confirm the pathology of immediate EBITDA.

<unk> capacity.

Formulary approval processes, we believe that several of 100 sites in the U S that are ready to start treating patients should educating might be approved.

Michelle Vounatsos: Beyond Addy Canimab, we addressed or advanced 12 new clinical programs last year across MS, ALS, Parkinson's disease, depression, and biosimilars, including four in phase three. Importantly, we entered new strategic collaborations with SAGE and Benally, providing access to potential first-in-class therapies for serious neurological disorders such as depression and Parkinson's disease. Our collaboration with SAGE has important late-stage diversification through phase 3 programs in both major depressive disorders and postpartum depression, with critical readouts expected this year. An asset in depression would offer multiple synergies across Biogen's existing portfolio. Overall, in 2021, we expect eight mid- to late-stage data readouts, including four programs in Phase 3.

Beyond that you can imagine we addressed or advanced 12, new clinical programs last year across MFS.

S Parkinson's disease Depression, and Biosimilar, Inc.

Including four.

In the phase III.

Importantly, we entered the new strategic collaboration with safe, each and Ben Natalie providing access to potential first in class of therapies for serious neurological disorders, such as depression and Parkinson's disease.

Our collaboration with sales.

The important late stage diversification through phase III programs in both major depressive disorders, and postpartum depression with critical Readouts expected this year.

And the asset in depression would offer multiple synergies across the biogen existing portfolio.

Overhaul in 2021, we expect.

Eight mid to late stage data data readouts, including four programs in phase III.

Michelle Vounatsos: Fifth, our cash flow generation continues to provide us with significant flexibility to allocate capital. During 2020, we returned approximately $6.7 billion of capital to shareholders and allocated roughly $3 billion for business development to enhance our pipeline. In summary, 2020 was a very productive year for the company, as we executed on our strategy. Despite the challenges from COVID-19 and taxidera generics, we maintained global leadership across our core businesses in MS, SMA, and biosimilars. And we have made significant progress towards building a multi-franchise portfolio. As Mike will outline with our guidance, we believe 2021 will be a reset year for the company financially on both the top and bottom lines. But we believe we can grow the company over the long term. 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.

Fifth our cash flow generation continues to provide us with significant flexibility to allocate the capital during 2020, we return of approximately $6 7 billion.

Of capital to shareholders and allocated roughly $3 billion for business development to enhance our pipeline.

In summary, 2020 was a very productive year for the company as we have executed on our strategy.

Despite the challenges from COVID-19 in tech feeder of generics, we have maintained global leadership across our core businesses in Ms SMA and Biosimilars and we have made significant progress towards building a multi franchise portfolio.

As Mike will outline with our guidance, we believe 2021 will be a reset year for the company financially on both the top and bottom lines, but we believe we can grow the company over the long term.

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.

Geoffrey Christopher Meacham: Thank you, Michelle, and good morning, everyone. I'd like to begin by thanking my colleagues in R&D for their dedication to discovering and developing innovative, potentially life-changing therapies for patients in need. As a result of their hard work, 2020 was a year of milestones for Biogen. We made significant progress toward building a multi-franchise portfolio with 10 programs, now in either phase 3 or 5, across a number of key therapeutic areas. We are proud that after more than a decade of work aimed at introducing the first treatments that treat the underlying pathophysiology of Alzheimer's, we have completed regulatory filings for aducanumab in multiple geographies.

Yes.

Thank you Michel and good morning, everyone.

I'd like to begin by thanking my colleagues on R&D for their dedication to discovering and developing innovative potentially life changing therapies for patients in need.

As a result of their hard work each one of you was the year of milestones for Biogen we.

We made significant progress towards building a multi franchise portfolio by 10 program now on either phase three of our file across a number of key therapeutic areas.

We are proud that after more than a decade of work aimed at introducing the first treatments that treat the underlying pathophysiology of Alzheimer's disease, we have completed regulatory filings of edge of Canyon map and multiple geographies.

Geoffrey Christopher Meacham: We hope that these filings will pave the way to the introduction of the first therapy that may slow the inevitable clinical decline in patients around the world suffering from Alzheimer's disease. Moreover, our collaboration partners at ACI have initiated the AHEAD-345 trial, designed to evaluate whether VAN-2401 may be of benefit in people with the early pathology of Alzheimer's, even before they are aware of cognitive impairment. Finally, we bolstered our early and late stage pipeline through both internal development and collaborations with leading neuroscience companies, including Denali, Sage, and Sangamo. Let me now turn to the progress we made in the fourth quarter, starting with Alzheimer's disease and dementia.

We hope the beads filings will pave the way to the introduction of the first therapy that may slow the inevitable clinical decline on patients around the world suffering from Alzheimer's disease.

Moreover, our collaboration partners that day site initiated the ahead 345 trial designed to evaluate whether it band two 401 may be of benefit and people with the early pathology of Alzheimers disease, even before they are aware of cognitive impairment.

Finally, we bolstered our early and late stage pipeline through both internal development and collaborations with leading neuroscience company, including Denali Sage and Sangamo.

Let me now turn to the progress we made in the fourth quarter, starting with all timers disease and dementia.

Geoffrey Christopher Meacham: The clinical trials of aducanumab were the first to show, in randomized, double-blind, placebo-controlled studies, that an antibody that targets aggregated forms of amyloid results in the robust removal of amyloid plaque and reduces clinical decline in Alzheimer's disease. Recently, Eli Lilly released results from the Phase 2 trial of Donanimab, another anti-amyloid antibody for Alzheimer's. These top-line results indicate that bananamab is now the third molecule, after azucanumab and BAN2401, to show that antibodies that target the amyloid plaque and produce a robust effect on amyloid plaque reduction also produce a clinical benefit. These Phase II results seen with Thunanimab were comparable to what was demonstrated by aducanumab in its Phase III trials in terms of amyloid plaque reduction as measured in We plan to present further details on these data at the upcoming ADPD meeting in March.

The clinical trials of the Badger <unk> were the first to show and randomized double blind placebo controlled studies than an antibody that targets aggregated forms of amyloid result in the robust removal of amyloid plaque and reduce clinical decline in Alzheimer's disease.

Recently, Eli Lilly released results from the Phase II trial of Donana Mab, another anti amyloid antibody for all farmers can feed.

These top line results indicate that banana Mab is now the third molecule after accurate <unk> and Ben through 401 to show the antibody that targets the amyloid plaque and produce the robust effect on amyloid plaque reduction also produced a clinical benefit.

These phase II results in banana Mab were comparable to what was demonstrated by as you can imagine its phase III trials in terms of amyloid plaque reduction as measured in central Florida, as well as clinical effect as measured on the composite scale of Adas cog and activities of daily living.

We plan to present further details on the data at the upcoming ADP the meeting in March.

Geoffrey Christopher Meacham: These data continue to strengthen our belief that antibodies that target the forms of A-beta concentrated in the amyloid plaque may produce therapeutic benefits, thus distinguishing these molecules from earlier anti-amyloid antibodies. Thus, we are optimistic about the potential for BAN 2401 that is currently being evaluated in the Clarity Phase 3 trial. The target enrollment, for clarity, has recently been increased by approximately 200 patients to mitigate COVID-19-related dosing challenges in consultation with the FDA. Nevertheless, the anticipated readout timing of Q3 2022 remains unchanged.

These data continue to strengthen our belief that antibodies that target for forms of a beta of concentrated in the amyloid plaque may produce therapeutic benefits. Thus distinguishing these molecules from earlier anti amyloid antibodies.

Thus, we are optimistic about the potential for <unk> hundred one that is currently being evaluated in the clarity phase III trial.

The target enrollment for clarity has recently been increased by approximately 200 patients the mitigate COVID-19 related dosing challenges in consultation with the FDA. Nevertheless, the.

The anticipated readout timing of Q3 2022 remains unchanged.

Geoffrey Christopher Meacham: In addition to anti-amyloid therapies, we continue to pursue a number of approaches targeting tau, which, when misfolded, is the principal constituent of neurofibrillary tangles, another hallmark of Alzheimer's pathology. We expect data from the Phase 2 study of Gosaranumab, our anti-tau antibody, which aims to prevent the spread of tau in the brain, in the first half of this year. We also have BIV-80, a tau-targeted antisense oligonucleotide that aims to reduce the production of all forms of tau. In collaboration with Ionis, we recently learned that in a Phase 1b multiple ascending dose study in mild Alzheimer's disease patients, BIV-80 treatment was generally well tolerated and resulted in a dose and time-dependent reduction from baseline in CSF, total tau We plan to present additional details at an upcoming scientific meeting.

In addition to anti amyloid therapies, we continue to pursue a number of approaches targeting Tau, which when the Misfolded is the principal constituent of neuro Fibrillary tangle, another hallmark of Alzheimer's pathology.

We expect data from the phase III study of <unk>, the random App, our anti Tau antibody the aims to prevent the spread of Tau in the brain and the first half of this year.

We also have the ability of power.

Of the targeted antisense oligonucleotide that aims to reduce the production of all forms of Tau Inc.

In collaboration with <unk>, we recently learned that the phase <unk> multiple ascending dose study in mild Alzheimer's disease patients.

The bid 80 treatment was generally well tolerated and resulted in a dose and time dependent reduction from baseline in CSF total Tau and phosphates out with durability of effect.

We plan to present additional detail at an upcoming scientific meeting.

Geoffrey Christopher Meacham: We are currently finalizing plans to advance BID-80 into a Phase II study in Alzheimer's disease. In summary, across amyloid and tau, as well as other targets in the preclinical stage, we are advancing an industry-leading pipeline that seeks to alter the course of Alzheimer's disease. Turning to MS, we have made significant progress in bolstering our existing MS franchise.

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

In summary across amyloid and Tau as well as are the targets in the preclinical stage, we are advancing on an industry, leading pipeline that seeks to alter the course of Alzheimers disease.

Turning to <unk>, we have made significant progress in bolstering our existing Ms franchise.

Geoffrey Christopher Meacham: This includes the approval of intramuscular plagiarity in the United States and the European Union, a positive CHMP opinion for subcutaneous disabery, and the submission of a marketing authorization application for boomerity in the EU. Additionally, we expect a readout for the NOVA study evaluating the efficacy of extended interval dosing of Tysabri by midyear. We recently added BID-107, an antibody that targets alpha-4 integrins, to our MS pipeline. The clinical utility of targeting alpha-4 integrin has been proven with Tysabri, a highly efficacious treatment for relapsing MS. Fib 107 is a new molecular entity that has demonstrated higher binding affinity, reduced Fc effector function, and a predictable pharmacological effect in preclinical studies. Our intent is to integrate all of our learnings from Tysabri, including extended interval dosing so as to optimize safety, the dosing regimen, and patient convenience while maintaining the high efficacy of Tysabri.

This includes the approval of intramuscular <unk> in the United States and the European Union.

Positive CHF.

The <unk> opinion for subcutaneous Tysabri and the submission of the marketing authorization application for <unk> in the EU.

Additionally, we expect the readout for the Nova study evaluating the efficacy of extended interval dosing of Tysabri by mid year.

We recently added bid 107, an antibody that targets Alpha <unk> integral to our Ms pipeline.

The clinical utility of targeting outperformed integrant, that's been true with Tysabri of highly efficacious treatment for relapsing Ms.

The 107 is the new molecular entity that has demonstrated higher binding affinity reduced the FC effector function and a predictable pharmacological effects in preclinical studies.

Our intent is to integrate all of our learnings from tysabri, including extended interval dosing. So at the optimized safety the dog.

Dosing regimen and patient convenience, while maintaining the high efficacy of Tysabri.

Geoffrey Christopher Meacham: In neuromuscular disorders, we aim to continue enhancing the therapeutic benefit of Spinraza and recently announced that we dosed the first patient in the response study, which will evaluate the effect of Spinraza in patients who have had a suboptimal clinical response to gene therapy. We also continue to enroll patients in the DEVOTE study, which is evaluating whether higher doses of Spinraza can provide greater efficacy than the currently approved dose. In ALS, we recently enrolled the last patient in the Phase 3 trial evaluating BID-54 in SOD1 ALS, and we look forward to the readout in the second half of this year. In movement disorders, we were disappointed to learn that the Phase 2 study of BID-54 in Parkinson's disease did not meet the primary or secondary MQT criteria.

In neuromuscular disorders, we aim to continue enhancing the therapeutic benefit of spin rather and recently announced the dose we dosed. The first patient in the response study, which will evaluate the effect of spin Raza and patients who've had a suboptimal clinical response the gene therapy.

We also continue to enroll patients in the devote study, which is the evaluating where the higher doses of <unk> can provide greater efficacy than the currently approved dose.

In the recently enrolled the last patient in the phase III trial evaluating to a person and so do you on AOS and we look forward to the readout in the second half of this year.

The movement disorders, we were disappointed to learn that the phase II study of <unk> 54 in Parkinson's disease did not meet the primary or secondary endpoint.

Geoffrey Christopher Meacham: Based on our Phase 1 data in CSF samples with VIV-54, we believe we have tested doses in the Phase 2 trial that were sufficient to engage extracellular alpha-synuclein in the central nervous system. As a result, we have decided to discontinue development of BIP-54 and plan to present detailed studies at a future scientific meeting. Nevertheless, we believe that this study provides a high-quality clinical data set that can be used to inform our future efforts in Parkinson's disease. Denali recently announced completion of the Phase 1B study for BIV-122, otherwise known as DNL-151, a small molecule inhibitor of LRRK2, which met target and pathway engagement goals.

Based on our phase one data in CSF samples with the 54, we believe we have tested doses in the phase II trial that were sufficient to engage extracellular alpha in the.

The central nervous system.

As the result, we have decided to the discontinued development of the 54 and plan to present detailed studies at a future scientific study results at a future scientific meeting.

Nevertheless, we believe that the study provides the high quality clinical dataset that can be used to inform our future efforts in Parkinson's disease.

The <unk> recently announced completion of the Phase <unk> study for <unk> 122, otherwise known as the <unk> five one a small molecule inhibitor of <unk>, which met the target and pathway engagement goals we.

Geoffrey Christopher Meacham: We expect to initiate late-stage clinical development in Parkinson's disease patients by the end of this year. In stroke, TMS completed enrollment in the Phase 2 trial of TMS007 in acute ischemic stroke in Q4 of 2020, and we are excited about the upcoming readout expected in the first half of this year. TMS007 is a small molecule modulator of plasminogen and is hypothesized to facilitate thrombolysis selectively at the site of the clot, while simultaneously exerting an anti-inflammatory effect to help reduce the risk of additional tissue damage. We believe the targeted mechanism of action of TMS007 may result in significant advantages over recombinant tissue-class antigen activator, or TPA, which currently remains the standard of care This includes potentially extending the therapeutic window to 12 hours or beyond, up from the 3 or 4.5 hour window of TPA, and reducing the risk of adverse bleeding events.

We expect to initiate late stage clinical development in Parkinson's disease patients by the end of this year.

And stroke CMS completed.

Completed enrollment for the phase II trial of Pms 007, and the acute ischemic stroke in Q4 of 2020, and we are excited about the upcoming readout expected in the first half of this year CMS.

CMS there there are seven of the small molecule modulator of plasminogen is hypothesized to facilitate thrombolysis selectively at the site of the club while simultaneously exerting an anti inflammatory effect to help reduce the risk of additional tissue damage.

We believe the targeted mechanism of action of Tms Zero-zero seven May result in significant advantages over recombinant tissue plasminogen activator or Tpa, which currently remains the standard of care for ischemic stroke.

<unk> includes potentially extending the therapeutic window to 12 hours of our beyond up from the three or four and a half hour window of PPA and reduce the risk of adverse bleeding events for.

Geoffrey Christopher Meacham: For these reasons, we believe TMF-007 represents a potential best-in-class thrombolytic agent. We continue to enroll patients in the Phase III trial of BID-93 for the treatment of cerebral edema caused by large hemispheric infarction despite the challenges posed by the COVID-19 pandemic. Finally, we have had a very productive quarter on the business development front, executing a number of collaborations that provide access to innovative potential first-in-class therapy. Significantly accelerating our expansion into neuropsychiatry, we entered into a collaboration with SAGE, a leader in psychiatry. Major Depressive Disorder, or MDD, and Postpartum Depression, or PPD, are highly prevalent disorders, and we believe that SAGE's lead asset, Duranolone, has the potential to be a first-in-class oral therapy for both. We look forward to multiple Phase 3, upcoming Phase 3 readouts for Zaranolone this year, including Waterfall for the episodic treatment of MBD, Coral for rapid response therapy when co-initiated with standard antidepressant therapy in MBD, and Skylark in PPD.

For these reasons, we believe <unk> represents a potential best in class Thrombolytic agent.

We continue to enroll patients in the phase III trial of <unk> 93 for the treatment of cerebral edema caused by large hemispheric infarction. Despite the challenges posed by the COVID-19 pandemic.

Finally, we've had a very productive quarter on the business development front executing a number of collaborations that provide access to innovative potential first in class of therapies.

Significantly accelerating our expansion into neuropsychiatry, we entered into a collaboration with Sage the leader in psychiatry.

The major depressive disorder, or mbd, and postpartum depression, or PPD are highly prevalent disorders, and we believe that the sages lead asset and ran alone has the potential to be of first in class oral therapy for boat.

We look forward to multiple phase III upcoming phase III readouts towards around alone. This year, which includes waterfall, where the episodic treatment of mbd coral for rapid response therapy, when COVID-19 initiated with the standard anti depressant therapy in MPD and Skylark in PPD.

Geoffrey Christopher Meacham: Beyond Zoran alone, we will also collaborate on stage three to four, currently in development for a central tremor, with a readout of the phase two study expected in early 2021. Furthering our commitment to ophthalmology, we entered into a collaboration with Bigeneron with the goal of developing gene therapies to treat inherited retinal disease. With this collaboration, we aim to use Bigeneron's proprietary AAV capsids to efficiently transduce retinal cells via intravitreal injections, which could potentially be performed in the clinic and offer efficacy via significantly enhanced retinal area coverage as compared to subretinal injections through surgery. More recently, we entered into a collaboration with Atalanta Therapeutics, based on technology that comes from the RNA Therapeutics Institute at the University of Massachusetts, started by Nobel Laureate Dr. Craig Mello.

Beyond the <unk> alone. We will also collaborate on stage three to four currently in development for essential tremor with the readout of the Phase III study expected in early 2021.

Furthering our commitment in ophthalmology, we entered into a collaboration with Biogen are on with the goal of developing of gene therapies to treat inherited retinal diseases.

With this collaboration we aim to use by general <unk> proprietary AAV capsid sufficiently transduce retinal cells via intra vitriol injections, which could potentially be performed in the clinic and offer efficacy EPS significantly enhanced.

The retinal area of coverage as compared to sub retinal injection through surgery.

More recently, we entered into a collaboration with Atlanta Therapeutics based on technology that comes from the RNA Therapeutics Institute at the University of Massachusetts started by Nobel Laureate, Dr. Craig Mello.

Geoffrey Christopher Meacham: As part of this collaboration, Atalanta will utilize its proprietary branched siRNA platform to develop potential treatments for multiple CNS targets, including HDT for the treatment of Huntington's disease. This collaboration with Atalanta, combined with our recent collaborations with Sangamo, Scribe, Digeneron, and the Massachusetts Eye and Ear Infirmary, as well as our long-term collaboration with Ionis, extends our ASO and RNAi capabilities and complements our ongoing efforts in gene therapy, including the development of our gene therapy assets for inherited retinal disorders. Additionally, we created a gene therapy accelerator unit to focus on solving the key technological challenges in the field with the goal of bringing more gene therapies to market. In 2020, Biogen R&D assembled and progressed a cutting-edge neuroscience pipeline employing state-of-the-art therapeutic modalities against genetically well-validated drug targets.

As part of this collaboration Atlanta will utilize the proprietary branch <unk> RNA platform to develop potential treatments for multiple CNS targets, including H D. T for the treatment of Huntington's disease.

This collaboration with Atlanta combined with our recent collaboration with Sangamo scribe Biogen are on and the Massachusetts eye and ear on the primary as well as our long term collaboration with ion and extend our ASO and RNA add capabilities and complement our ongoing efforts in gene therapy.

Including the development of our gene therapy assets for inherited retinal disorders.

Additionally, we created of gene therapy accelerator unit the focus on solving the key technological challenges in the field with the goal of bringing to market margin therapies that may transform the lives of patients.

In 2020, Biogen R&D assembled and progressed the cutting edge neuroscience pipeline employing state of the art therapeutic modalities against genetically well validated drug targets.

Geoffrey Christopher Meacham: As a result, we believe we are well positioned for growth in a transformative year with eight clinical trial readouts anticipated, including four pivotal programs. We remain optimistic about the opportunities ahead of us, and we believe we are entering a promising time for neurotherapeutics and their ability to meaningfully impact the lives of patients, including potentially bringing the first therapy to change the course of Alzheimer's disease. I will now pass the call over to Mike.

As a result, we believe we are well positioned for growth and a transformative year with eight clinical trial readouts anticipated, including four pivotal program.

We remain optimistic on the opportunities ahead of us and we believe we are entering of promising time for neuro therapeutics and their ability to meaningfully impact the lives of patients, including potentially bringing the first therapy. The change the course of Alzheimer's disease.

I will now pass the call over to Mike.

Michael R. McDonnell: Thank you, Al, and good morning, everyone. Biogen had another solid quarter despite the challenges from COVID-19 and taxidermy US generics, as we continue to execute well and maintain global leadership 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 also share with you our guidance for 2021. Total revenue for the fourth quarter of $2.9 billion, and total revenue for the full year of $13.4 billion, declined 6% versus the prior year at both actual and constant currency.

Thank you al and good morning, everyone Biogen had another solid quarter. Despite the challenges from COVID-19 in tech the dairy U S. Generics as we continued to execute well and maintain global leadership across our core businesses.

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 of our financial performance for the quarter and also share with you our guidance for 2021.

Total revenue for the fourth quarter of $2 9 billion declined 22% versus the prior year of both actual and constant currency.

Total revenue for the full year of $13 4 billion declined 6% versus the prior year at both actual and constant currency.

Michael R. McDonnell: If the client was...

This decline was mostly driven by tech the Dara generic entry in the U S.

Michael R. McDonnell: This decline was mostly driven by Tecfidera generic entry in the U.S. Total MS revenue for the fourth quarter, including Ocrevus royalties of $1.8 billion, decreased 24% versus the prior year at both actual and constant current exchange rates. Total MS revenue for the full year, including Okurvus royalties of $8.7 billion, decreased 6% versus the prior year at actual currency and 5% at constant currency. This decline was also driven by the entrance of multiple generic versions of Tecadera in the U.S. Excluding U.S. tech federa, total MS revenue, including OKRAVIS royalties, was relatively flat both in the fourth quarter and the full year versus the prior year. Demonstrating the resilience of our MS business in a competitive market.

Total mis revenue for the fourth quarter, including <unk> royalties of $1 8 billion decreased 24% versus the prior year of both actual and constant currency.

The total EMS revenue for the full year, including O'connor of as royalties of $8 7 billion decreased 6% versus the prior year at actual currency and 5% at constant currency.

This decline was also driven by the entrants of multiple generics of <unk> in the U S. Excluding U S Tech Vadera total EMS revenue, including <unk> royalties was relatively flat both in the fourth quarter and the full year versus the prior year demonstrating.

Demonstrating the resilience of our Ms business and a competitive market.

Sure.

Global <unk> revenue for the fourth quarter of $608 million declined 48% versus the prior year and revenue for the full year of $3 8 billion declined 13%.

Michael R. McDonnell: Global TechFedera revenue for the fourth quarter of $608 million declined 48% versus the prior year, and revenue for the full year of $3.8 billion declined 13%. Outside of the U.S., fourth quarter Tecadera revenue of $288 million increased 1% versus the prior year, and full year revenue of $1.2 billion increased 3% with continued patient growth. During the quarter, we saw continued improvement in the Bumerity trend.

Outside of the U S fourth quarter of <unk> revenue of $288 million increased 1% versus the prior year.

Full year revenue of $1 2 billion.

The increased 3% with continued patient growth.

During the quarter, we saw continued improvement in the <unk> trends.

Michael R. McDonnell: Umerity revenue was $39 million in the fourth quarter. Diasabri fourth quarter global revenue of $475 million was relatively flat versus the prior year, and full year revenue of $1.9 billion grew 3% for the full year. We were pleased to see continued global patient growth throughout the year and 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. Moving now to SMA

<unk> revenue was $39 million in the fourth quarter.

Tysabri fourth quarter global revenue of $475 million was relatively flat versus the prior year.

And full year revenue of $1 9 billion grew 3% for the full year.

We were pleased to see continued global patient growth throughout the year and believe Tysabri is well positioned to play an increasingly important role in the treatment of EMS as we progressed several important initiatives, including subcutaneous administration and extended interval dosing.

Moving now of SMA global fourth quarter of spin Rozzer revenue of $498 million decreased 8% versus the prior year at actual currency and 10% at constant currency.

Michael R. McDonnell: Global fourth-quarter Spinraza revenue of $498 million decreased 8% versus the prior year at actual currency and 10% at constant currency. In the U.S., Finraza revenue decreased by 34% versus the prior year as we see an impact from competition which is exacerbated by COVID-19. Outside the U.S., PENRASA revenue grew 13% versus the prior year, with strong growth in emerging markets, partially offset by the maturation of larger European markets.

In the U S. It's been Rozzer revenue decreased by 34% versus the prior year as we.

See an impact from competition, which is exacerbated by COVID-19 outs.

Outside the U S and raise the revenue grew 13% versus the prior year with strong growth in emerging markets, partially offset by the maturation of larger European markets.

Michael R. McDonnell: For the full year, global Spinraza revenue of $2.1 billion decreased 2% versus the prior year at actual currency and 1% at constant currency. Full year U.S. Benraza revenue decreased 16%, and full year revenue outside the U.S. grew 9%. Although new competition and COVID-19 have had an impact on Spinraza, as you heard from Michelle and Al, we believe Spinraza has a very strong efficacy and safety profile and will continue to be a foundation of care.

For the full year global spin Rozzer revenue of $2 1 billion decreased 2% versus the prior year at actual currency and 1% at constant currency.

Full year U S. Ben Rozzer revenue decreased 16% and full year revenue outside.

Outside the U S grew 9%, although new competition and COVID-19 have had an impact on spin rozzer.

As you heard from Michel and out we believe <unk> has a very strong efficacy and safety profile and we will continue to be a foundation of care.

Michael R. McDonnell: Moving to our biosimilars business, fourth-quarter revenue of $197 million was flat versus the prior year at actual currency and declined 4% at constant currency. Full-year revenue of $796 million grew 8% versus the prior year at actual currency and grew 6% at constant currency. However, 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. Despite the continued impact of COVID-19, we continue to be the leading anti-TNF biosimilar provider in Europe, and Benopoly continues to be the number one prescribed eutanercept product across Europe.

Moving to our Biosimilars business fourth quarter revenue of $197 million was flat versus the prior year at actual currency and declined 4% of constant currency flow.

Full year revenue of $796 million grew 8% versus the prior year at actual currency and grew 6% of constant currency.

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

The continued impact of COVID-19, we continue to be the leading <unk>.

Anti TNF biosimilar provider in Europe, and Ben of Poly continues to be the number one prescribed etanercept product across Europe we.

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 developed by our Samsung BioEffice JB and other biosimilar products. Total anti-CD20 revenue in the fourth quarter of $419 million decreased 30% versus the prior year with relatively flat Okravis royalties and a 45% decrease in revenue from Rituximab. Total anti-CD20 revenue for the full year of $2 billion decreased 14% versus the prior year, with a 23% increase in Ocrevus royalties and a 29% decrease in revenue from Rituxan. The decrease in Rituxan revenue is due to the impacts of COVID-19 and accelerating erosion from biosimilars.

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, the followed by our Samsung <unk> JV and other biosimilar products.

Total anti CD 20 revenue in the fourth quarter of $419 million decreased 30% versus the prior year with relatively flat <unk> royalties and a 45% decrease in revenue from Rituxan.

Total anti CD 20 revenue for the full year of $2 billion decreased 14% versus the prior year with a 23% increase in the <unk> royalties and a 29% decrease in revenue from Rituxan. The decrease in Rituxan revenues is due to the impacts of COVID-19, and accelerating erosion from Biosimilars.

Michael R. McDonnell: Turning now to gross margin. Fourth quarter gross margin was 83% of revenue versus 88% in the fourth quarter of 2019. The decrease was due to the declines in Tecfideri and Rituxan, both of which are high-margin products, as well as higher costs related to our corporate partner revenue due to product. Gross margin for the full year 2020 was 87% versus 86% in 2019. Moving now to expenses.

Turning now to gross margin fourth quarter gross margin was 83% of revenue versus 88% in the fourth quarter of 2019 the.

The decrease was due to the declines in tech the Dara and Rituxan, both of which are high margin products as well as higher costs related to our corporate partner revenue gain of product mix.

Gross margin for the full year 2020 was 87% versus 86% in 2019.

Moving now to expenses Q4 of non-GAAP R&D expense was $642 million and includes $68 million related to external collaboration agreements with scribe at Atlanta and by general on.

Michael R. McDonnell: Q4 non-GAAP R&D expense was $642 million and included $68 million related to external collaboration agreements with Scribe, Atalanta, and Generon. Full year non-GAAP R&D expense was $2.1 billion. Q4 non-GAAP SG&A was $793 million, including approximately $100 million related to launch preparations for Adjacatum. Full year non-GAF SG&A was $2.5 billion, including approximately $250 million related to AgEconomy. In Q4 of this year, our effective non-GAAP tax rate was approximately 16%, flat versus the fourth quarter of 2019. Our full year effective non-GAAP tax rate was approximately 18% versus approximately 16% in 2019.

Full year non-GAAP R&D expense was $2 1 billion.

Q4 of non-GAAP, SG&A was $793 million, including approximately $100 million related to launch preparations for edge of Canada.

Full year, non-GAAP, SG&A was $2 5 billion, including approximately $250 million related to edge of Canada.

In Q4 of this year, our effective non-GAAP tax rate was approximately 16% flat versus the fourth quarter of 2019.

Our full year effective non-GAAP tax rate was approximately 18% versus approximately 16% in 2019.

Michael R. McDonnell: During the fourth quarter, we repurchased 1.6 million shares of the company's common stock for a total value of $400 million. Throughout 2020, we will repurchase 22.4 million shares for a total value of $6.7 billion. As of December 31, 2020, there was $4.6 billion remaining under the Share Repurchase Program, which was authorized in October of 2020. Our weighted average diluted share count was approximately 154 million shares for the fourth quarter and 161 million shares for the full year. NIME GAAP diluted earnings per share in the fourth quarter were $4.58.

During the fourth quarter, we repurchased one 6 million shares of the company's common stock for a total value of $400 million throughout 2020, we repurchased $22 4 million shares for a total value of $6 7 billion.

As of December 31, 2020, there was $4 $6 billion remaining under the share repurchase program, which was authorized in October of 2020.

Our weighted average diluted share count was approximately 154 million shares for the fourth quarter and 161 million shares for the full year.

Non-GAAP diluted earnings per share in the fourth quarter was $4 58.

Michael R. McDonnell: Full-year non-GAAP diluted earnings per share was $33.70, a 13 cent increase versus the prior year and above our most recent guidance range. In 2020, we generated approximately $4.2 billion in net cash flow from operations. Capital expenditures for the full year were $425 million, and free cash flow was approximately $3.8 billion. We ended the year with $3.4 billion in cash and marketable securities. $7.4 billion in debt, resulting in $4 billion in net debt. Additionally, our $1 billion revolving credit facility was undrawn as of the end of the year.

Full year non-GAAP diluted earnings per share was $33 70.

The 13th increase versus the prior year and above our most recent guidance range.

In 2020, we generated approximately $4 $2 billion of net cash flow from operations cash.

Capital expenditures for the full year were $425 million in free cash flow was approximately $3 8 billion.

We ended the year with $3 $4 billion on cash and marketable securities and 747.

Seven $4 billion in that.

The resulting in $4 billion on net debt. Additionally, our 1 billion.

Dollar revolving credit facility was undrawn as of the end of the year.

Let me now turn to our full year guidance for 2021, we expect full year 2021 revenue to be between.

Michael R. McDonnell: Let me now turn to our full-year guidance for 2021. We expect full-year 2021 revenue to be between $10.45 billion and $10.75 billion, non-GAAP diluted EPS to be between $17.00 and $18.50 per share, and capital expenditures to be between $375 million and $425 million. It is important to note that this guidance is based on a number of critical assumptions which are currently uncertain. Changes in these assumptions could materially impact our results.

10, four of 5 billion and $10 $75 billion.

Non-GAAP diluted EPS to be between $17 and $18 50 per share and capital expenditures to be between $375 million and $425 million.

It is important to note that this guidance is based on a number of critical assumptions, which they're currently uncertain changes in these assumptions could materially impact our results.

Our guidance assumes <unk> will be approved in the U S. By June seven although uncertainty remains on the Fda's decision. If <unk> 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.

Michael R. McDonnell: Our guidance assumes aducanumab will be approved in the U.S. by June 7, although uncertainty remains on the FDA's decision. If adjukatumab is approved in the U.S., we would expect an immediate launch. However, dose titration will result in less revenue for patients in the initial months of treatment.

As a result, we would expect only modest revenue for <unk> in 2021 ramping thereafter post commercialization, we would book 100% of net revenue in the U S and <unk> profit share of 45% would be booked in a separate line item, which is not part of R&D or DNA.

Michael R. McDonnell: As a result, we would expect only modest revenue for Aducanumab in 2021, with revenue ramping thereafter. Post-commercialization, we would book 100% of net revenue in the U.S. An A-size profit share of 45% would be booked in a separate line item, which is not part of R&D or SG&A. In addition, while the erosion of our U.S. taxidermy business to date has been slower than anticipated, If we are unsuccessful in our legal appeals, we expect a sharp decline during the first half of 2021. This is our guidance assumption. We also expect significant erosion of retoxin in the U.S.

G&A.

In addition, while the erosion of our U S Tech Vadera business to date has been slower than anticipated.

If we are unsuccessful on our legal appeals, we expect the sharp decline during the first half of 2021 and this is our guidance assumption.

We also expect significant erosion of Rituxan in the U S. Along with tech the Dara, we expect that the reduction in revenue from these high margin products will put pressure on our gross margin percentage of.

Also as a reminder, in Q2 of 2020, we recorded $330 million in revenues related to the onetime license of certain manufacturing related intellectual property, which was at 100% gross margin.

We expect non-GAAP R&D expenses will be between $2 $35 billion of two four of $5 billion.

Michael R. McDonnell: Along with Tecfidera, we expect that the reduction in revenue from these high-margin products will put pressure on our gross margin percentage. Also, as a reminder, in Q2 of 2020, we recorded $330 million in revenues related to the one-time license of certain manufacturing-related intellectual property, which was at 100% gross margin. We expect non-GAAP R&D expenses will be between $2.35 billion and $2.45 billion. We remain committed to our long-term growth through continued investment in our pipeline, which has now grown to a total of 33 programs across 10 therapeutic areas, including 10 programs which are in Phase 3 or filed. Importantly, we expect our pipeline to generate eight important mid- to late-stage readouts this year, including four in Phase 3. Additionally, we expect non-GAAP SG&A expenses will be between $2.6 billion and $2.7 billion.

We remain committed to our long term growth through continued investment in our pipeline, which has now grown to a total of 33 programs across 10 therapeutic areas, including 10 programs, which are in phase III or filed importantly, we expect our pipeline to generate eight important mid to late stage Readouts. This year.

Including four in phase III.

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

This estimate includes an approximate 600 million dollar of investment in support of the potential launch of edge of Canada.

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.

In addition, it is important to note that we have allocated a significant portion of our manufacturing capacity to edge Academy.

Which could impact 2021 result of AD you can map is not approved.

We expect our non-GAAP tax rate for 2021 to be between 16, and 17% and we assume we will utilize a portion of the remaining share repurchase authorization of $4 6 billion throughout the year. Although this will depend on a variety of factors, including our business development activity.

Michael R. McDonnell: This estimate includes an approximate $600 million investment in support of the potential launch of Aducanumax. 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. In addition, it is important to note that we have allocated a significant portion of our manufacturing capacity to aducanumab, which could impact 2021 results if AgiCataMap is not approved. We expect our non-gas tax rate for 2021 to be between 16 and 17%, and we assume we will utilize a portion of the remaining share repurchase authorization of $4.6 billion throughout the year, although this will depend on a variety of factors, including Foreign exchange rates as of December 31, 2020 are assumed to remain in effect for the year, net of hedging activities, and we have not included any impact from potential tax or health care reform or any impact from potential acquisitions or large business development transactions. Going forward, we plan to update our full-year financial guidance each quarter. I'll now turn the call back over to Michel for his closing comments.

Foreign exchange rates as of December 31, 2020 are assumed to remain in effect for the year net of hedging activities and we have not included any impact from potential tax of healthcare reform or any impact from potential acquisitions or large business development transactions.

Going forward, we plan to update our full year financial guidance items each quarter.

I'll now turn the call back over to Michel for his closing comments. Thank you, Mike Biogen demonstrate it resilience and strong execution in 2020 positioning us well to manage the impact of the <unk>.

The red generics and to make 2021, a transformative year for the company as we continue executing on our strategy to build the multi franchise portfolio.

We are advancing an industry leading pipeline for the.

On this disease.

We are waiting an important decision on that you can imagine the U S now expected by.

The early June.

As I described our belief in the therapeutic approach of targeting amyloid plaques has never been stronger we believe.

That's all the data supports the approval of <unk> and we are optimistic about about <unk> 24, one in phase III.

We are also pursuing.

<unk> complementary approaches targeting Tau pathology with three clinical assets targeting either extracellular Tau, we then antibody or in Castilla, we the asos.

Michelle Vounatsos: Thank you, Mike. Biogen demonstrated resilience and strong execution in 2020, positioning us well to manage the impact of TechFedera generics and to make 2021 a transformative year for the company as we continue executing on our strategy to build a multi-franchise portfolio. We are advancing an industry-leading pipeline for Alzheimer's disease, and we are awaiting an important decision on aducanumab in the U.S., now expected by early June. As Al described, our belief in the therapeutic approach of targeting amyloid plaques has never been stronger. We believe that our data supports the approval of Educandumab, and we are optimistic about band 24-1 in phase 3. We are also pursuing complementary approaches targeting Tau pathology with three clinical assets targeting either extracellular Tau with an antibody or intracellular Tau with an ASO.

We begin 2021 with an expanded and diversified pipeline and we anticipate eight mid to late stage III notes by the end of this year. These include four pivotal and full phase II readouts across the number of the hub to kick array as characterized by significant unmet medical need.

Such as stroke.

And the new phase III programs in <unk> and PPD would stage.

We also expect significant milestones across our core business the share in the Miss we are launching income misconduct clearly key and we are planning for the potential launch of subcutaneous tysabri as well as important data on extended interval dosing in the middle of the year.

As we build for the medium to long term.

Aim to scale, our digital capabilities to fill the need the needs of patients.

As part of our vision to lead the <unk>. We are excited to be collaborating with Apple to develop potential digital biomarkers that may aid in diagnosing and monitoring disease progression at the earliest stage of cognitive decline.

Michelle Vounatsos: We begin 2021 with an expanded and diversified pipeline, and we anticipate eight mid to late stage readouts by the end of this year. These include four pivotal and four phase two readouts across a number of therapeutic areas characterized by significant and medical need, such as ALS, stroke, and the new phase 3 programs in MDD and PPD with SAGE. We also expect significant milestones across our core business this year. In MS, we are launching intramuscular plaguity, and we are planning for the potential launch of subcutaneous disabery as well as important data on extended interval dosing in the middle of the year. As we build for the medium to long term, we aim to scale our digital capabilities to further meet the needs of patients. As part of our vision to lead in Alzheimer's disease, we are excited to be collaborating with Apple to develop potential digital biomarkers that may aid in diagnosing and monitoring disease progression at the earlier stage of cognitive decline.

I want to hit the right our commitment to maximizing returns of shareholders and bringing the T therapies to patients over the long term. These demands that we continue to allocate capital efficiently effectively and appropriately as we have demonstrated in the past we will always strive to have an optimal capital.

As well as aiming for superior returns from the investments we make.

Lastly, I would like to reflect on biogen to longstanding commitment to corporate interests from <unk> dedication to patients and the broader society is not only do you needed to developing novel therapeutics for patients suffering from serious diseases that extends much further.

Michelle Vounatsos: I want to reiterate our commitment to maximizing returns to our shareholders and bringing innovative therapies to patients over the long term. This demands that we continue to allocate capital efficiently, effectively, and appropriately. As we have demonstrated in the past, we will always strive to have an optimal capital structure as well as aim for superior returns from the investments we make.

At Biogen, we take a holistic view of health and strive to improve the broader society of reserve now more than ever we continue to invest in climate and health.

Access and equity as well as diversity and inclusion.

In closing I would like to thank our employees around the world who have demonstrated their dedication to making a positive impact on patients' lives and all of the physicians caregivers and participants in our clinical development programs, our past and future achievements could not be realized without the passion and commitment we will.

Michelle Vounatsos: 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 take a holistic view of health and strive to improve the broader society we serve. Now, more than ever, we continue to invest in climate and health. Access and Equity as well as Diversity and Inclusion. In closing, I would like to thank our employees around the world who have demonstrated their dedication to making a positive impact on patients' lives and all of the physicians, caregivers, and participants in our clinical development programs. Our past and future achievements could not be realized without passion and commitment. We will now open the call for questions.

We'll now open the call for questions.

Yeah.

And ladies and gentlemen, if you would like to ask a question. Please press star one on your telephone keypad. As a reminder, please limit yourself to one question. If you require any further follow up you May press star one again to rejoin the queue.

Your first question comes from the line of Matthew Harrison with Morgan Stanley.

And Matthew you may be muted. Please on mute your line.

Oh, sorry about that this is Mac score on the line for Matthew Harrison Kia.

Elaborate on the design of the response study how do you define sub optimal response to gene therapy, and what are your expectations around how long it will take to enroll the study. Thank you.

Thank you for the question.

Ben I will answer it demonstrates the basically our commitment to best inform clinical practice based on the new modalities that we have for the good day for the benefit of patients. Each of those also our mindset in terms of having skin Raza is the foundation of care in SMA treatment iron.

Operator: And ladies and gentlemen, 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, you may press star 1 again to rejoin the queue. Your first question comes from the line of Matthew Harrison with Morgan Stanley.

Yes.

Response study and will enroll about 60 patients.

Based on physician determination that the.

Responses suboptimal based for example on chop intend scores.

And in the future. We may also be advocating for other measurements of suboptimal response, but yes. It will be a two year study and we will look to see whether a motor milestones based on.

Operator: And Matthew, you may be muted. Please unmute your line. Oh, sorry about that. This is Max Gore on the line for Matthew Harrison.

Michelle Vounatsos: Can you elaborate on the design of the response study? How do you define suboptimal response to gene therapy? And what are your expectations around how long it will take to enroll the study?

Scales, such as the Hammersmith score of our improved by adding <unk>.

I will now move to our next question, we'll hear from Terence Flynn with Goldman Sachs.

Michelle Vounatsos: Thank you for the question. I will answer it demonstrates basically our commitment to best inform clinical practice based on the new modalities that we have for the good and for the benefit of patients. It shows also our mindset in terms of having Spinraza as a foundation of care in SMA treatment.

Great. Good morning, Thanks for taking the questions I just had a two part one I was just wondering if you can Michel maybe provide any perspective on the decision here to include the <unk> approval on your guidance and then anything you can share at this point regarding your pricing strategy broadly I know, you're probably not going to give specifics, but can you just talk high level do you see.

Geoffrey Christopher Meacham: Yes, the response study will enroll about 60 patients. It's based on physician determination that the response is suboptimal based, for example, on CHOP and TEN scores. And in the future, we may also be advocating for other measurements of suboptimal response. But yeah, it'll be a two-year study, and we'll look to see whether motor milestones based on scales such as the Hammersmith score are improved by adding

See this more as the specialty price drag versus the primary care biologic and any early read from payers. Thank you.

I think the guidance, it's the basically the best reflection on how we see the business moving forward. Even if these assumptions that we decided on that may not represent.

Operator: We'll now move to our next question, and we'll hear from Terence Flynn with Goldman Sachs.

On the ADT moving forward to achieve basically the business in which we are the disease. The best belief that we have while we speak.

Michelle Vounatsos: Great. Good morning. Thanks for taking the questions. I just had a two-part one. I was just wondering if you could, Michelle, maybe provide any perspective on the decision here to include Atacanamab approval in your guidance and then anything you can share at this point regarding your pricing strategy broadly. I know you're probably not going to give specifics, but can you just talk at a high level? Do you see this more as a specialty price drug versus a primary care biologic and any early read from payers? Thank you.

Concerning price.

We are getting we are getting there.

We had very large engagements with many stakeholders and basically the two main dimensions. The first one is the.

On the clinical meaningfulness and potentially in terms of cognitive functions, but also functional aspects on the activity of the leading this is one side of the equation. The second one each of the cost of Alzheimers Society, which is nowadays more than 550.

Michelle Vounatsos: Providing guidance is basically the best reflection on how we see the business moving forward. Even if these are assumptions that we decide on, that may not represent the reality moving forward, which is basically the business in which we are. But this is the best belief that we have while we speak.

The BD in a year in the U S.

The cost for caring for patients.

Let me take and is more than half of million.

The age of 18.

75% of the patients are in nursing homes and disclose more than the 100000, the announced a year.

Michelle Vounatsos: Concerning price, you know, we are getting there. We had very large engagements with many stakeholders. And basically, there are two main dimensions. The first one is the clinical meaningfulness, and potentially, in terms of cognitive functions, but also functional aspects, on the activity of daily living. This is one side of the equation. The second one is the cost of Alzheimer's to society, which is currently more than 550 billion a year in the US. The cost of caring for patients, if I'm not mistaken, is more than half a million dollars. By the age of 80, 75% of patients are in nursing homes, and this costs more than $100,000 a year. These are the main elements that we consider in our wide engagement. On the important topic of price, we are getting there, as I said, but it is too early to give more specifics.

And the <unk>.

These are the main element that we consider in our wide the engagement.

On the important topic of price, we're getting the as I said the too early to give more specifics.

We will now move of our next question, we will hear from Marc Goodman with VEB Leerink. Please go ahead.

Yes, good morning on.

Andrew.

Just on.

I was trying to understand given the close working relationship with the FDA and how.

How long of what's been going on and how much data they have already gotten it's hard for us to understand.

What else the could possibly move what they don't know so I was wondering if there was.

Total type of color you could just give us on that what's going on.

Data from the embark study of that they were asking for.

Just a little more clarity around the situation would be helpful. And then just secondly, just on the SG&A of 600 normal on that you're committed to.

Can you just talk about how the Google of spend is kind of thing is that on launch moving with all of that of you on the second half of the year or is half of that in the first half of year just trying to understand.

Operator: We will now move to our next question. We will hear from Marc Goodman. V.B. Lurien, Yes, good morning on ADU.

Yes, Adam.

Is not approved in the middle of the year, how much of that spend is actually going to take place. Thank you.

Thanks for the greater the question I will take the first part of it is already the second part on the SG&A and al will come back on the data aspect of the important data aspect.

Michelle Vounatsos: I mean, just we're all trying to understand given your close working relationship with the FDA and how long it's been going on and how much data they have already gotten. It's hard for us to understand what else they could possibly need, what they don't know. So I was wondering if there was any type of color you could just give us on that.

So concerning the SG&A.

Basically we have only one opportunity to potentially launch when such an important product.

So we basically resource to deliver a major launch for what could be the first product to able to deliver meaningful clinical and functional value to patients affected by the disease and these are potentially 10 million patients in the U S.

Geoffrey Christopher Meacham: Was there any data from the Embark study that they were asking for? Just any more clarity on the situation would be helpful. And then, just secondly, just on the SGMA of 600 million that you're committed to, can you just talk about how the gating of spend is going to be? Is that on launch, meaning it's all going to be in the second half of the year? Or is half of that in the first half of the year? Just trying to understand if ADU is not approved in the middle of the year, how much of that spending is actually going to take place. Thank you.

<unk> multi billion opportunity for the.

<unk>, we sold two wind.

The.

Yes, we've been saying all along that we're under review.

And as a normal course during the review process there are information requests from FDA.

More recently, we had one that required the submission of additional analyses and clinical data.

Geoffrey Christopher Meacham: Thanks for the great question. I will take the first part, sorry, the second part on SG&A, and I will come back on the data aspect, the important data aspect. So concerning ESG and A. Basically, we have only one opportunity to potentially launch such an important product well. So we basically have the resources to deliver a major launch for what could be the first product able to deliver meaningful clinical and functional value to patients affected by the disease, and these are potentially 10 million patients in the US. Thank you very much.

And that led to a major amendment, which led to the Paducah delay.

On that I don't want to provide too much more detail on to the specifics.

So Mike will provide a bit more color on the part of your second question on the sequence, yes. So.

Mark Good morning, I think it's.

A couple of points of note.

Obviously, we'll get the spend as best we can in the event that we don't receive approval.

You should not expect that we would be able to mitigate 100% of those costs, but we would be able to mitigate a meaningful portion of and obviously, we would maximize the amount that we would mitigate the other point that I would just remind on is that in the.

Michael R. McDonnell: Yeah, we've been saying all along that we're under review. And as a normal course during the review process, there are information requests from FDA. More recently, we had one that required the submission of additional analyses and clinical data. And that led to a major amendment, which led to the DUFA delay.

The U S substantially all of the costs that we incur for edge Academy are subject to our agreement with ESI, which in the U S is reimbursable at the rate of 45% and so when you look at the guidance that we gave the $600 million. That's in SG&A, there is about $200 million.

Geoffrey Christopher Meacham: On that, I don't want to provide too much more detail.

Michael R. McDonnell: So Mike will provide a bit more color on the second part of your second question about the sequence.

Michael R. McDonnell: Yeah, so... Marc, good morning. I think there are a couple of points of note. Obviously, we'll gate the spend as best we can in the event that we don't receive approval. You should not expect that we would be able to mitigate 100% of those costs, but we would be able to mitigate a meaningful portion, and obviously, we would maximize the amount that we would mitigate. The other point that I would just remind you is that, in the U.S., substantially all of the costs that we incur for aducanumab are subject to our agreement with ACI, which in the U.S. is reimbursable at the rate of 45%. And so when you look at the guidance that we gave, the $600 million that's in SG&A, there are about $200 million that would be reimbursable out of that that would come through on a different line in our P&L on our collaboration sharing line.

On.

That would be reimbursable out of that that would come through on the different line in our P&L on our collaborations.

Collaborations sharing line and the reason why that ratio was a little bit different than you would expect is because of the accounting is complex and the differs a bit pre and post launch some of the ASI reimbursements are actually netted in that $600 million and on the rest.

Come through the collaboration line, but at the end of the day economically it is up 45% reimbursement schedule that's important to remember.

We will now move to our next caller in the queue, we'll hear from Nomura <unk> with Evercore go ahead. Please.

Hi, Thanks, so much for taking my question Paul.

I was just looking to understand how you're thinking through the emerging data from embarked re dosing study.

And I guess, what I'm wondering is when you look at for example, the first interim 24 week efficacy results do you overlay that with the last data point on a patient by patient basis coming off of phase III or are you comparing the curve on that first 24 weeks versus the curve in the first 24 weeks of the American engage phase III I guess, the challenge with that would be.

Michael R. McDonnell: And the reason why that ratio is a little bit different than you would expect is because the accounting is complex, and it differs a bit pre and post launch. Some of the ASI reimbursements are actually netted into that $600 million, and the rest come through that collaboration line. But at the end of the day, economically, it is a 45% reimbursement schedule that's important to remember.

At the initial two phase threes were dose titrated on the first 24 weeks I'm just curious how youre thinking about that thank you.

Hi, Mara Thank you Yep.

Well, we're still enrolling embark.

Part way through enrollment Youre right that the first presented at the recent meeting the first analysis of the six months of our fleet.

But.

Operator: We'll now move to our next caller in the queue. We'll hear from Umer Raffat with Evercore.

And some of those issues that you just pointed out of a good or issues that will need to be addressed in the analytical plan.

Geoffrey Christopher Meacham: Go ahead, please. Hi, thanks so much for taking my question. Hal, I was just looking to understand how you were thinking through the emerging data from the Embark Redosing Study. And I guess what I'm wondering is, when you look at, for example, the first interim 24-week efficacy results, do you overlay that with the last data point on a patient-by-patient basis coming off of Phase 3? Or are you comparing the curve in that first 24 weeks versus the curve in the first 24 weeks of the Emerge and Engage Phase 3s? I guess the challenge with that would be that the initial two Phase 3s were dose titrating in the first 24 weeks. I'm just curious how you're thinking about that.

But yes, we are still enrolling patients it's an important study and we.

We should be hopefully completing enrollment soon.

Soon in the first half or so of this year.

We will now move onto our next question, we'll hear from core CASM of with J P. Morgan.

Great. Thanks, Thanks for taking the question. Good morning, guys I guess I'll just a follow up on the Embarq question is are you taking looks at this where if the FDA needed or was the requesting information you'd be able to provide it to them and then I just wanted to ask if you can kind of frame. This pending phase III readout for your anti Tau antibody pair of 92.

That's coming up here in the first half kind of remind us of the trial design, what youre, hoping to show here. Thank you.

Geoffrey Christopher Meacham: I am Maria. Thank you. Yep. Well, we're still enrolling in BARC. We're partway through enrollment. You're right that the first analysis, as presented at the recent meeting, is at six months, roughly. But some of those issues that you just pointed out are good ones, and they will need to be addressed in the analysis plan. But, yeah, we're still enrolling patients. It's an important study, and we should hopefully be completing enrollment soon in the first half or so of this year.

Yes, Thanks Corey.

Yes, so we will.

The endeavor to provide the FDA whatever they ask for and the information request and the federal.

Requires.

At trials that are still enrolling or are still ongoing and we will do so.

In terms of bit of 92.

What we're looking for is an effect on all timers progression.

In this.

Largely early stage patients with.

Operator: We'll now move on to our next question, and we'll hear from Corey Kazimov with J.P. Morgan.

Mid 92 is the.

Has shown in phase one trials to have a substantial decrease in extracellular tau.

Operator: Great. Thanks. Thanks for taking the question. Good morning, guys. I guess I'll just follow up on the embark question: are you taking a look at this where the FDA needed or was

And so.

The hypothesis is that we're going to block the spread of Tau from south of the cell.

The type of pocket size of that there is the prime like spread of cow in Alzheimers disease. So we're going to see over the course of about one year, whether or not we effect the progression of Alzheimer's disease using.

Operator: https://www.youtube.com

Operator: I just wanted to ask if you could kind of frame this.

The typical clinical outcome measures.

Operator: Unknown executive, Ami Fadia, Adam Keeney, and Chris Schott, Biogen Inc.

Now moving onto our next caller on the queue Evan <unk> Credit Suisse. Please go ahead.

Operator: Anti-Tau Antibody BIP-92

Hi, all thank you so much for taking the question. So I am referencing of comment you made earlier al talking about 2021, being the reset year, particularly agile Kenya of out of the picture auto revenue and earnings grow in 2022 and beyond I'm really trying to understand if your outlook and kind of your comments, mainly predicated on the edge can you map there are other significant.

Operator: Thank you.

Geoffrey Christopher Meacham: Yeah, thanks, Corey. Yeah, so we will endeavor to provide FDA whatever they ask for in their information request. And if that requires looking at trials that are still enrolling or are still ongoing, we will do so. In terms of BID 92, what we're looking for is an effect on Alzheimer's progression in this largely early stage patient. BID 92 is, you know, has been shown in phase one trials to have a substantial decrease in extracellular tau. And so, and the hypothesis is that we're going to block the spread of tau from cell to cell. It's hypothesized that there is a prime-like spread of tau in Alzheimer's disease. So we're going to see over the course of about one year whether or not we affect the progression of Alzheimer's disease using the typical clinical outcome measures.

Drivers that we should be thinking about and referencing thank you.

Yes, thanks, very much for the question and.

As we said in the prepared remarks.

We do believe that we have the ability to grow the company over the longer term obviously.

<unk> is the catalyst, but we've also got a lot of other very interesting opportunities. We've got 33 programs, including 10 in phase III as we talked about eight.

Operator: Now moving on to our next caller in the queue, Evan Seigerman, Credit Suisse, please go ahead. Hi everyone, thank you so much for taking the question. So I'm referencing a comment you made earlier, Al, talking about 2021 being a reset year, but taking Adukandia out of the picture, how do you think

Readouts in 2021, including four in phase III.

I would point you to our ex.

The <unk> products, which are expanding in a lot of the international markets Biosimilars I would say the same.

The pipeline is very rich I think sage is of Great addition, and we have others. So obviously <unk> is the catalyst, but we do believe that we have the ability to grow the company for the longer term based on what we have on the pipeline on the other pieces that I just mentioned.

Operator: Transcribed by https://otter.ai

Michael R. McDonnell: I'm really trying to understand if your outlook and the kind of your comments, mainly predicated on Educanumab, there are other significant drivers that we should be thinking about in reference.

So we expect the menu readouts. This year. So that's why I quantified the use of being transformative even if that is the financial reset transformative in terms of the data readout, which is somehow unprecedented.

Michelle Vounatsos: Thank you.

Michael R. McDonnell: Mike? Yeah, thanks very much for the question. And, you know, as we've said in the prepared remarks, we do believe that we have the ability to grow the company over the longer term. Obviously, aducanumab is the catalyst, but we've also got a lot of other, you know, very interesting opportunities. We've got 33 programs, including 10 in Phase 3, as we talked about. I would point you to our existing products, which are expanding in a lot of international markets. Biosimilars, I would say the same. The pipeline is very rich. I think Sage is a great addition, and we have others. So obviously, aducanumab is the catalyst, but we do believe that we have the ability to grow the company for the longer term based on what we have in the pipeline and the other

And for the for the company with full phase III and full phase twos and in terms of the largest potential based on epidemiology ECS certainly mgd NPT PPD. So we've <unk> the late stage the had positive readouts in the Ronda.

Studies in PPD, and NPD and we are hopeful.

Beyond maybe.

Maybe just go ahead, Damian and Elas in the phase III that the.

Beyond the beyond the advertising that we have the pipeline progressing very well and the core business is solid as the resilience.

And do we cant come back financially we are sitting on cash and we can continue to complement the pipeline. So the plenty of reasons to believe.

Michelle Vounatsos: So we expect many readouts this year, so that's why I qualified the U.S. as transformative. Even if there is a financial reset, transformative in terms of data readout, which is somehow unprecedented for the company with four phase three and four phase twos. And in terms of the largest potential based on epidemiology, it's certainly MDD and PPD.

We'll now move to our next caller, Michael Yee with Jefferies. Please go ahead.

Okay.

Hi, good morning, Thanks for the question.

I just wanted to ask a follow up to his comments around the Lilly.

Whether you believe that.

That data.

Growing confidence on the scientific community and possibly the regulators kind of very interesting design, but they also use of different endpoint and obviously schwab people over the placebo maybe you could just follow on out of some of those comments and how youre thinking about that as it relates to even keep on the Alzheimer's community.

Michelle Vounatsos: So for which, you know, they are late stage. They have positive readouts in randomized studies in PPD and MDD, and we are hopeful. And beyond, of course, there is coronary myeloma and ALS in phase three.

Operator: But beyond ADHEC-ANIMAB, we have this pipeline progressing very well, and the core business is solid and resilient. And we count on that. So, financially, we are sitting on cash, and we can continue to complement this pipeline. So there are plenty of reasons to believe.

Pretty outspoken on EBITDA.

Yes, I think it's helping to support the amyloid hypothesis.

And supports the concept of targeting amyloid.

The in Alzheimer's disease in the early stages early began working on this antibody. We started publishing on this back in 2012, when they found that to remove preexisting plaque they had to go after.

Operator: We will now move to our next caller, Michael Yee, with Geoffrey Meacham. Hi. Good morning.

Geoffrey Christopher Meacham: Thanks for the question. I just wanted to ask Al as a follow-up to his comments about Lilly, whether you believe that that data is reassuring confidence for the scientific community and possibly the regulators. They have a very interesting design, but they also use a different endpoint. And obviously, it's brought people over to Placebo. So maybe you could just follow on, Al, with some of those comments and how you're thinking about that as it relates to people in the Alzheimer's community who are pretty outspoken about eBeta.

We had to use an antibody that would get into the that we'd get to the plaque and MH showed in animals that the.

The pilot Glu specific antibody.

<unk> that and they now have confirmed that you get the same thing in humans by amyloid pet imaging and I think it's great to see that they also seem to show an effect on clinical decline they use the composite measure of Adas cog and.

<unk>.

All of.

Of which is which I think they did because it's somewhat small study.

I think it's like a couple of hundred patients two of 300 patients.

Geoffrey Christopher Meacham: Yeah, I think it's helping to support the amyloid hypothesis and supports the concept of targeting amyloid in Alzheimer's disease in the early stages. You know, Lilly began working on this antibody, and they started publishing on it back in 2012. When they found that to remove pre-existing plaque, they had to go after it, and they had to use an antibody that would get into the plaque and get to the plaque. And they showed in animals that the pyroglue-specific antibody achieved that. And they now have confirmed that you get the same thing in humans by amyloid PET imaging, and I think it's great to see that they also seem to show an effect on clinical decline. They used the composite measure of ADAS-CoG and IADL, which is, which I think they did because it's a somewhat small study. I think it's like a couple of hundred patients, two or three hundred patients.

And.

So the head the use of more sensitive endpoints.

But it is composed of endpoints that.

That we all recognize on the Alzheimers steel that would be important endpoint for the measurement of business. So I think that I think could add to the body of evidence that suggests the targeting amyloid with the right antibody the depth of the plaque and removes clock is the right approach.

I will now take our next question from Paul Matteis with Stifel.

Hey, great. Thanks, so much for taking the questions I was wondering if you could talk about where you are in refining some of the kind of key real world elements for the usability of out of Cana map, specifically I think in study.

Six of the MRI and the first year is that something you expect to be the case in the real world of this is approved and if so what can you do on your end to actually make this more usable BR.

Beyond just kind of a small number of core academic centers that have these intrinsic capabilities. Thanks a lot.

Al.

Operator: And so they had to use a more sensitive endpoint. But it is composed of endpoints that we all recognize in the Alzheimer's field as being important endpoints for the measurement of disease. So I think it adds to the body of evidence that suggests that targeting amyloid with the right antibody that gets to the plaque and removes plaque is the right approach.

Yes so.

MRI is useful for monitoring ARIA.

And we do expect that there'll be MRI monitoring requirement of one.

Japan is approved if it's approved.

But the quantity and the timing.

Require further discussions with regulators around the world.

Geoffrey Christopher Meacham: We'll now take our next question from Paul Matteis with Schiefel.

Yes concerning the launch sequence, we are obviously, starting with the most important high volume centers the.

Operator: Thanks a lot.

Geoffrey Christopher Meacham: Yeah, so, you know, MRI is useful for monitoring arias. And we do expect that there'll be MRI monitoring requirements. Once that you can, there's proof that it's approved. But the quantity and the timing will require further discussions with regulators around the world.

The debt getting ready to treat and as mentioned earlier these of hundreds.

And the Mdc's substantial.

Stern shown keep in mind the division of immediately beta Kofi mentioned, most probably that will have to be to be done and obviously over time, we will expand it.

Michelle Vounatsos: Yeah, concerning the launch sequence, we are obviously starting with the most important, high volume centers that are getting ready to treat. And as mentioned earlier, these are hundreds, and this is already substantial. Keep in mind that there is an amyloid beta confirmation that will probably have to be done. And obviously, over time, we will expand down the pyramid to larger targets.

Down the pyramid to larger targets.

Our next question will come from Phil Nadeau with Cowen and company.

Good morning, Thanks for taking my question, one on financials and spin spin raws as U S trends. It looks like there was about a 34% decline in Q4 'twenty versus Q4 19.

Operator: Our next question will come from Phil Nadeau with Cowaning Morning, thanks for taking my question. One on financials. In Spinraza's US trends, it looks like there was about a 34% decline in Q4 20 versus Q4 19. You referenced COVID and then also competition in those trends. Curious if you could quantify the impact of COVID and so how much will rebound once the pandemic subsides versus competition and the patients that might be lost more permanently.

You referenced Covid and then also competition in those trends I'm curious if you could quantify the impact of Covid and so how much will rebound once dependent kind of subsides versus competition.

Of the patients that might be lost more permanently.

Thank you for the question and we are watching this trend very carefully.

And I will start up and then Mike will add the first of all we are pleased with the one with $2 1 billion.

Overall revenue for spin of Ahs that in 2020, despite COVID-19.

Michelle Vounatsos: Thank you for the question. And we are watching this trend very carefully. I will start, and then Mike will add.

In the rest of the majority of the impact to east Covid as per the inputs from the team patients as GAAP to go to the centers so they delayed the dosing.

Michelle Vounatsos: First of all, we are pleased with 2.1 billion overall revenue for Spinraza in 2020, despite COVID. So in the U.S., the majority of the impact is COVID, as per the input from the team. Patients are scared to go to the centers, so they delay the dosing. Some sites are being closed or have limited capacity or staffing in order to dose the patient. And last but not least, COVID is accelerating some switches to alternative treatment that exists. We've seen the peak of switch in September, and then we've seen a decline of those, and we've also, very encouragingly for us, some patients deciding to return to Spinraza for reasons of efficacy, perceived efficacy, or side effects. And last but not least, following the spike of launch, we've seen a rebound in demand for Spinraza towards the end of the year.

Some sites are being closed or limited capacity of staffing in order to dose the patients.

Okay.

In the last but not least because these accelerating some switches to alternative treatment.

That's the that's exists we've seen the peak of switch in September and then we've seen a decline of those and we've seen also very encouragingly for us some patients deciding to return to spin Reza for reasons of efficacy perceived efficacy of four <unk>.

<unk> of side effects.

And last but not least following the of spike of launch.

We've seen a rebound in demand for <unk>.

The towards the end of the year.

Michael R. McDonnell: Bye. Yes, I have not a lot to add to that. I would say that, you know, we would describe it as, you know, in the US competition, which is exacerbated by COVID; we are still growing outside of the US. Obviously, in a pandemic, that makes the idea of an oral vaccine more attractive, because you can avoid coming to a healthcare facility. So the idea that somebody would switch from, you know, an injection to an oral becomes more prominent in our current environment, and conversely, it's a little less likely that somebody would switch off of an oral to an injection in that situation. So, you know, the impact that you saw in the fourth quarter in the US, we would attribute it all to, you know, competition exacerbated by COVID.

Yes.

A lot to add to that I would say that.

We would describe it as in the U S competition, which is exacerbated by Covid, we are still growing outside of the U S. Obviously.

Pandemic.

That makes the idea of an oral more attractive because you can avoid coming to a health care facility. So.

The idea that somebody with switch from.

On injection to an oral becomes more prominent in our current environment and Conversely, it's a little less likely that somebody would switch off of an oral two.

Two of an injection and that situation so.

On the the impacts that you saw on the fourth quarter in the U S. We would attribute it all to.

Competition exacerbated by Covid, how much is each of each of us a little bit hard to parse out exactly but it is both.

Michael R. McDonnell: How much each of them is a little bit hard to, you know, parse out exactly, but it is both. And I think at the end of the day, the important point is that we continue to really believe in the efficacy of Spinraza and its safety profile. And we do believe it'll continue to become and will remain a very important treatment option, particularly once we get through the pandemic.

And I think at the end of the day of the important point is that we continue to really believe in the efficacy of.

The spin rouser and and the safety profile and we do believe it will continue to become a.

It will remain a very important treatment option.

Particularly once we get through the pandemic.

Michelle Vounatsos: So we remain hopeful for Spinraza. Again, this is a very important asset. As we said many times, it's an efficacy play, and hopefully, with the rates of vaccination, this will be better reflected in drug utilization, rather than a perceived convenience.

So we remain hopeful force penalized.

Again this is a very important asset.

As we said many times, it's an efficacy play and hopefully with the rates of vaccination.

And this will be better reflected the into the drug utilization rather than the perceived convenience at the end of the data centric data remains the part two of SUNFISH remains the <unk>.

Operator: At the end of the day, the SUNFISH data remains. The Part 2 of SUNFISH remains. One out of two patients experience disease progression, and our product remains extremely well documented, with the broadest label, and we continue to invest in innovative research.

One on one.

The two patient experiencing disease progression and the.

Our product remains extremely well documented with the broadest label label and we continue to invest in the in the Nova <unk> research.

Operator: We'll now move to Jay Olson with Oppenheimer. Please go ahead.

Well now move to Jay Olson with Oppenheimer. Please go ahead.

Geoffrey Christopher Meacham: Good morning, and thank you for taking the question. You spoke about the positive read across from Lilly's phase two data for Donanimab. Can you please remind us how the binding profile,

Good morning, and thank you for taking the question you spoke about the positive read across from the lead phase III data for banana, Matt can you. Please remind us how the binding profile of the statutes.

The city and PK profile for <unk> compares to Donana ma'am. Thank you.

Operator: Thank you.

Geoffrey Christopher Meacham: Yes, this is Al. Thus, aducanumab binds to aggregated forms of A, both soluble oligomers, as well as insoluble fibrils. And as such, since both are concentrated in the plaque, aducanumab binds to the plaque. It was actually initially discovered based on a past plaque, amyloid plaque immunoreactivity assay. And by targeting the plaque, it removes amyloid quite efficiently in the brain. Donanumab binds to the pyroglutamated form of A, which is present early in the plaque. It's thought to kind of seed the plaque, if you will, and forms part of the dense core. So in that way, it targets the plaque as well. So different ways of targeting the plaque, essentially. In terms of PK, I don't know too much about the PK of donanumab, but I suspect since it's an antibody, it has roughly similar characteristics to other monoclonal antibodies, roughly a half-life of two weeks, etc.

Jeff. This is al so edge can be met by the aggregated forms of a beta of both soluble oligomers as well as insoluble fibrils.

And as such since both are concentrated in the plaque <unk> binds to the plaque it was actually initially discovered based on all of them.

Pat.

And then on practically immuno reactivity.

Hey.

And by targeting the plaque that remove amyloid quite efficiently in the <unk>.

Brian.

Donana map of binds to the power of agglutinated form of.

Of.

The data, which is president early in the plaque the thought there kind of feed the plant. If you are on it and forms part of the dense core so in that way of targets plaque as well so different ways of targeting the plaque essentially in terms of PK I don't know too much about the PK of Donana, Matt, but I can.

The spec to put the antibody has roughly similar characteristics to other monoclonal antibodies roughly a half life of two weeks of et cetera.

Operator: We will now move to our next question. We will hear from Robyn. Robyn Karnauskas with Trist. Good job.

We'll now move of our next question, we will hear from Robin.

Of course with Chris. Please go ahead.

Operator: Thanks, guys, for taking my question. Another one for you, Al, on Denanamab. So the CSO of Lilly had mentioned that, given the unique clearing mechanism, it could have the potential to provide high levels of flat clearance after limited duration dosing. And I was just curious, as you think about the competitive landscape, assuming Adekanamab's approved, how do you see intermittent dosing as being competitive to Adekanamab? And how do you think the competitive landscape could shape up with that profile? Thanks.

Thanks, guys for taking the question. Another one for you al on day nanometer. So the CFO of well you had mentioned that given the unique clearing mechanism that it could have the potential to provide high levels of Blackberry After limited duration of dosing and I was just curious as you think about the competitive landscape assuming adequate amounts of true.

<unk>.

How how.

Do you see intermittent dosing as being competitive to the out of Canada.

And how do you think the competitive landscape could shape up with that profile.

Geoffrey Christopher Meacham: Yeah, thanks, Robyn. It's going to be interesting. I think it's a large market, and I think it'll accommodate multiple therapeutic options, which hopefully will be available for patients. The concept of intermediate dosing or down dosing, perhaps, after changing the dose after plaque removal, is an interesting one. It's something that can be tested and is being evaluated across multiple drugs, Aducanumab, Bantu-401, as well as Donanimab. side effects after stopping Aducanumab, and then they regain some of these benefits after restarting it in a relatively short period of time. And something similar has been seen with other antibodies, including Bantu-401. That second piece may be something more associated with synaptic function, which may be more associated with the soluble oligomer side of things, and I think that will remain to be learned about in future studies.

Yeah. Thanks, Robin it's going to be interesting I think the large market and I think it'll accommodate multiple therapeutic options, which hopefully will be available for patients.

Of the concept of intermediate dosing or down dosing, perhaps after changing the dose after.

After plaque removal.

Is an interesting one.

Something that can be tested and is being evaluated across multiple drugs. As you can do math, Ben to 401 as well as the anatomy.

I would say that you know.

One thing is the <unk>.

On neuro degeneration with respect with respect the plaque removal, but there may also be other effects more acute effects when you listen to patients. In particular, you may have heard at the FDA Advisory Committee the <unk>.

<unk> seem to have.

Have on toward effects after stopping.

As you can map and then they regain some of these.

The benefits after restarting in a relatively short period of time and Thats the nature and similar something similar has been seen with other.

Antibodies, including Ben to 401 second.

Second piece, maybe something more associated with synaptic function, which may be more associated with good soluble oligomer.

I'd of things and I think that will remain to be learned about in the future study.

Operator: It looks like we have time for one final question. We will now hear from Salim Syed with Mizuho.

It looks like we have time for one final question, we will now hear from Salim Sayed with Mizuho.

Operator: Great. Thanks for all the color guys. Appreciate all the color and anti-CANIMEB as well, specifically. Al, just one for me on the BANIMEB as well.

Great. Thanks for all of the color guys I appreciate all the color on hand of 10 members flow specifically.

All of this one for me on banana Mab as well.

Geoffrey Christopher Meacham: So when I go back to the FDA ADCOMM doc, And this is a line in the quote that says anti-amyloid beta antibodies cannot be considered as a single class. They are distinct at the molecular level, and the differences have an impact on their mechanism of action, including, and then it lists, including binding characteristics, etc. That was a pretty strong point that the FDA had made in the briefing documents, and it seems like now you're saying that... Banana Mab is helping the case, so I'm just curious how all this is getting reconciled. Should people be looking at beta amyloid antibodies as a single class or not?

I go back to the FDA AD com docs and the.

As a line in there and the quote of Ann.

Anti amyloid.

<unk> been of antibodies cannot be considered at the single class. They are distinct at the molecular level on the differences have an impact on their mechanism of action, including and then it lifts, including binding characteristics et cetera.

That was a pretty strong point that the FDA had made in the in the briefing docs and it seems like <unk>.

Now you are saying that.

Banana Mab is helping the case, so I'm just curious how Paul.

This is getting reconciled should people be looking at beta amyloid.

The antibodies of the single class or or not.

No that's a really good question and.

I tried to sort of make that point in my in my prepared comments. This morning, but the first generation of antibodies could not really target the.

And the Lloyd plaque for example, solar news of Mab, which was the Lilly antibody bound to mono soluble monomeric.

Operator: That's a really good question.

Operator: And I tried to sort of make that point in my...

Emily.

A beta.

Geoffrey Christopher Meacham: [inaudible] while they had solanusumab in development Lilly began working on a plaque specific antibody and so I think that's what those FDA documents might have been pointing to that it's not just that you have an anti-amyloid antibody you have to have those that will target the plaque and remove pre-existing amyloid plaque in patients. I think also bapineusumab, bapineusumab is non-selective it's bound to soluble monomeric as well as insoluble aggregated forms of amyloid as well as soluble aggregated and that led to issues with dosing and so I think that's what they meant is perhaps solanusumab and bapineusumab may not have shown clinical efficacy for these kinds of reasons but I think that we should not assume that this next generation of antibodies that target the plaque better We all learned from the early studies right and so I think the nanomab is another example where those that target the plaque and remove amyloid robustly in humans and if you study early stage patients.

And if you read the 2012 paper on the plaque specific antibody. They were concerned that such of antibody will not get to the plant and remove plaque preexisting plat. So even while they had some of the news amount of in development really began working on the plaque specific antibody.

So I think thats, what those SBA documents might've been pointing to that but it's not just that you have an anti amyloid antibodies.

We'll have those that will target the clat and remove the preexisting amyloid plaque in inpatient I think also of back of news of matter of fact, the museum app of non selective the bounds of soluble monomeric as well as <unk>.

Volume ball aggregated forms of amyloid as well as soluble aggregated and that led to issues with dosing.

And so I think thats, what the message is perhaps.

<unk> been Bapineuzumab may not have shown clinical efficacy for these kinds of reasons.

We should not assume that this next generation of antibodies that target the plaque better look we all learned from the early study right.

So I think banana Memphis on another example of where those the target the plaque and remove amyloid robustly in humans.

And if you study early stage patients selected port carefully.

Operator: Okay, so we believe 2021 will be a transformative year for Biogen, and I want to thank you all for your attention during our call. Have a good day.

You will see efficacy.

Okay. Okay, we believe <unk> 'twenty 'twenty, one will be a transformative year for Biogen and I want to thank you all for your attention to our call the.

Good day.

Michelle Vounatsos: And with that, ladies and gentlemen, this will conclude your conference for today. We do thank you for your participation, and you may now disconnect.

And with that ladies and gentlemen, this will conclude your conference for today, we do thank you for your participation and you may now disconnect.

Hum.

[music].