Q4 2021 Biogen Inc Earnings Call

Madison: Good morning, my name is Madison, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen fourth-quarter earnings call and financial update. All lines have been placed on mute to prevent any background noise.

Good morning, My name is Madison and I will be your conference operator today at this time I would like to welcome everyone to the Biogen fourth quarter earnings call and financial update all lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this time.

Madison: 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.

Simply press Star one on your telephone keypad.

Please limit yourself to one question to allow other participants time for questions. If you require any further follow ups you May press star one again to rejoin the queue.

Madison: If you require any further follow-ups, you may press star 1 again to rejoin the queue. Thank you. I would now like to turn the conference over to Mr. Michael Henke, Head of Investor Relations. Mr. Henke, you may begin.

I would now like to turn the conference over to Mr. Michael <unk> head of Investor Relations. Mr. Hanky, you may begin your conference.

Michael Henke: Good morning, and welcome to Biogen's fourth quarter 2021 earnings. 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 a reconciliation of the GAAP to non-GAAP financial measures that we will discuss today. Our GAAP financials are provided in Tables 1 and 2, and Table 4 includes a reconciliation of our GAAP to non-GAAP financial results.

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

Our GAAP financials are provided in tables, one and two and table four includes a reconciliation of our GAAP to non-GAAP financial results.

Michael Henke: We believe non-gap 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... 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.

We believe non-GAAP financial results better represent the ongoing economics of our business and reflect how we manage the business internally.

We have also posted slides on our website that follow the discussions related to this call.

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

Michael Henke: I encourage you to consult the risk factors discussed in our SEC filings for additional details. Today, we will be discussing Aduhelm. Adieu Helm is indicated for the treatment of Alzheimer's. Treatment with Adieu Helm should be initiated in patients with mild cognitive impairment or mild dementia, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than those studied.

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

Today, we will be discussing how do M. <unk> is indicated for the treatment of Alzheimer's disease treatment without new homes should be initiated in patients with mild cognitive impairment or mild dementia stage of disease. The population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier.

Or later stages of the disease then were studied.

Michael Henke: This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with aduhev. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial or trial. Aduhelm can cause serious side effects, including amyloid-related imaging abnormalities, or ARIA. ARIA is a common side effect that does not usually cause any symptoms but can be serious. Aduhelm can cause serious allergic reactions. The most common side effects include aria, headache, and fall.

This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with Andrew Hill.

<unk> approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial or trials.

I do home can cause serious side effects, including amyloid related imaging abnormalities or ARIA or.

ARIA is a common side effect that does not usually cause any symptoms, but can be serious I do home can cause serious allergic reactions. The most common side effects include ARIA headache in fall.

Michael Henke: Please see full prescribing information and patient medication guide at aduhelm.com. On today's call, I am joined by our Chief Executive Officer, Michelle Vounantzos, Dr. Priya Singhal, Interim Head of Research and Development, and our CFO, Mike McDonnell. We will also be joined for the Q&A portion of our call by Alisha Alaimo, president of our U.S. organization. As a reminder, during the Q&A portion of the call, we kindly ask that you limit yourself to one question. I will now turn the call over to Michelle. Good morning, everyone, and thank you for joining us.

Please see full prescribing information and patient medication guide I do home Dot com.

On today's call I am joined by our Chief Executive Officer, Michel <unk>, Dr. Pressing call interim head of research and development and our CFO Mike Mcdonnell.

We will also be joined for the Q&A portion of our call by Alisha Alaimo President of our U S organization.

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

Good morning, everyone and thank you for joining us I will start by briefly reviewing our financial performance and Mike will provide more details.

Michelle Vounantzos: I will start by briefly reviewing our financial performance, and Mike will provide more details. For the fourth quarter, Biogen generated approximately $2.7 billion in revenue, representing a decrease of 4% year-over-year, as we continued to experience the erosion of federal revenue in the U.S. due to the impact of generic entry. Fourth quarter 2021 non-GAAP earnings were $3.39 a share.

For the fourth quarter Biogen generated approximately $2 7 billion velocity in revenue, representing a decrease of 4% year over year as we continued to experience the erosion of victory there about revenue in the U S. Due to the impact of generic entry.

Fourth quarter 2021, non-GAAP earnings were $3 39, a share.

Michelle Vounantzos: We believe this performance reinforces Biogen's ability to execute well. However, given a number of challenges we have faced recently, we announced that we would implement cost reduction measures, which are expected to yield approximately $500 million in annualized savings. Mike will provide additional details.

We believe this performance reinforces biogen's ability to execute well however, given a number of challenges. We have faced recently, we announced that we will implement cost reduction measures, which I expected to yield approximately $500 million in annualized savings and Mike will provide.

Additionally themselves.

Michelle Vounantzos: Let me now say a few words regarding the proposed National Coverage Determination, or NCD, for the class of monoclonal antibodies directed against amyloid for the treatment of Alzheimer's disease. As currently written, the proposed NCD calls for coverage with Evidence Development, or ECED, which will provide reimbursement only for Medicare beneficiaries enrolled in an approved randomized controlled trial. In reaching this proposed recommendation, the Center for Medicare and Medicaid Services, or CMS, highlighted three key areas of focus for this class of therapies, all of which have implications for adrenal. First, CMS believes there are gaps in the data on the clinical benefit of the therapy. Second,

Let me now say a few words regarding the proposed national coverage determination or NCD for the class of monoclonal antibodies directed against Emilio each for the treatment of Alzheimer's disease.

As currently written the proposed NCD calls for coverage with evidence development or C D, which will provide reimbursement for.

For Medicare beneficiaries enrolled in an approved randomized controlled trial.

In reaching this proposal recommendation the center for Medicare and Medicaid services or CMS.

Michelle Vounantzos: CMS believes more information is needed about the potential risks of removing amyloid, principally aria. Additionally, CMS would like additional data to be generated on the underrepresented communities in which Alzheimer's disease is more prevalent. These are also areas of focus for Biogen, with many important initiatives already underway. We are committed to constructive engagement with CMS to address their concerns, and we agree with CMS that additional data may be helpful to continue to characterize the benefit-risk profile for this class of therapies.

Highlighted three key areas of focus for this class of therapies, all of which have implications for us.

First CMS believes that gaps in the data on the clinical benefits of these therapies second CMS believes more information as needed about the potential risks of removing amyloid principally ARIA.

And third CMS would like additional data to be generated on the underrepresented communities in which alzheimers disease is more prevalent.

These are also areas of focus for Biogen, we have many important initiatives already underway.

We are committed to two constructive engagement with CMS to address their concerns and we agree with CMS that additional data may be helpful to continue to characterize the benefit risk profile for this class of therapies.

Michelle Vounantzos: Now that Aduhelm is approved by the FDA, we believe the most helpful data generation can really only be generated from greater drug utilization in real-world practice. We also agree with CMS that the final NCD decision should not lead to a duplication of ongoing activities. As currently postured, however, we believe the proposed CD requirements will be prohibitive for patients and are overly burdensome.

Now that <unk> held these approved by the FDA. We believe the most helpful data generation can really only be generated from greater drug utilization in real world practice.

We also agree with CMS that the final NCD decision should not lead to a duplication of ongoing activities.

As currently posture. However, we believe the proposed requirements will be poised for patients.

Overly burdensome.

Michelle Vounantzos: Costly to companies, and duplicative of the data that will be generated from ongoing trials and the FDA's existing required post-marketing requirements. We believe the best way to address the concerns of CMS is to supplement the data from the adieu helm phase 3 studies, which generated data from over 3000 patients, by taking a multi-pronged approach, leveraging the phase 4 inflammatory study and vision. Our Embark Redosing Study, which has enrolled approximately 1,700 patients, the ongoing Eye Care Aggie Registry, the ongoing phase 3 studies of all the antibodies in the class, and all the ongoing and anticipated real-world data generation efforts.

Costly to companies and duplicative of the data that will be generated from ongoing trials and the FDA is existing retry post marketing requirements.

We believe the best way to address the concerns of CMS is to Superman the data from the phase III studies, we generated data with 3000 patients by taking a multi pronged approach leveraging the phase four confirmatory study in vision.

I will embark re dosing study, which has enrolled approximately 8700 patients.

The ongoing I can't AE registry.

The ongoing phase III studies of older antibodies in the class and all the ongoing energy debated real world data generation efforts.

Michelle Vounantzos: We believe this extensive data generation opportunity will adequately address any open questions regarding the clinical efficacy and safety of amyloid beta-lowering therapies. On this note, we expect to begin patient screening for the ENVISION study in May of this year, with a primary completion date anticipated approximately four years later. This is expected to be a global placebo-controlled trial aiming to enroll 1,500 patients with MCI due to Alzheimer's disease or mild Alzheimer's disease with confirmation of amyloid beta pathology. The planned primary end point will be CDR sum of boxes at 18 months, with a planned long-term extension for up to 48 months.

We believe this extensive data generation opportunity will adequately address any open questions regarding the clinical efficacy and safety of amyloid beta lowering therapies on this note we expect to begin patient screening for the envision study in may of this year.

We the primary completion date anticipated approximately four years. Later this is expected to be a global or a placebo controlled trial aiming to enroll 500 patients with mci due to us that means disease or mild Alzheimer's disease with confirmation of amyloid beta pathology.

The planned endpoint will be <unk> some of the boxes at 18 months with the plan long term extension for up to 48 months.

Michelle Vounantzos: We believe this study, combined with the other studies I mentioned, should address the questions raised by CMS. Therefore, we will continue to advocate for an NCD that provides rapid and equitable patient access by providing coverage only for the patients identified as most appropriate for treatment in our FDA-approved label, which generally aligns to our Phase III clinical trial population. Thank you. We also believe this multi-pronged approach will allow for more equal access in all communities. We have concerns that the restrictions of the proposed CED would unfairly exclude access for patients in underserved communities and geographically remote areas.

We believe this study combined with the August studies, I mentioned should address the questions raised by CMS.

Therefore, we will call she's new to advocate for an N C. Either provides rugby and equitable patient access by providing coverage only for the patients identified as the most appropriate for treatment you know FDA approved label, we generally aligns to our phase III clinical trial population.

[noise] sorry, we also believe this multipronged approach will allow for more equal access in all communities.

We have concerns that the restrictions of the proposed C. D will unfairly exclude access for patients you know the surf communities and Youll geographically remote areas. In contrast, we expect both envision and I kept a registry which she.

Michelle Vounantzos: In contrast, we expect both Envision and our iCARE-AD registry, which seeks to enroll up to 6,000 participants, to obtain more representative data from those communities by aiming to enroll 16% to 18% of US participants from Black and Hispanic populations. In summary, we will advocate for a final CD that strikes a better balance between patient access to an FDA-approved therapy today and the desire for additional data that can only be gathered over time and with higher levels of drug utilization in the real world.

<unk> two <unk> up to 6000 participant to obtain more represent that chi data from those communities by aiming to enroll 16% to 18% of U S participants from black and he's spending population.

In summary, we will advocate for a final LCD that strikes a better balance between patient access for an FDA approved therapy today and their desire for additional data that can only be got it overtime and with higher levels of drug utilization.

In the real World.

Michelle Vounantzos: We look forward to discussing this consideration with CMS and working towards a final decision that is in the best interest of patients. Beyond NCD Last quarter, we presented additional data from the adrenaline phase three clinical trial, showing the effect on downstream tau Alzheimer's biology and the correlation between plasma P-tau reduction and less cognitive and functional decline. In addition, we published the phase three ARIA findings in JAMA Neurology. As we look forward, we aim to expand both within and beyond neuroscience, with a focus on four pillars to drive growth and value creation. First,

We look forward to discussing these consideration with CNS and working towards a final decision that is in the best interest of patients.

Beyond the NCD last quarter, we presented additional data from the adjuvant phase III clinical trial, showing the effect on downstream Alzheimers biology, and the correlation between plus my Pizza is action and less cognitive and functional decline. In addition, we published the phase <unk>.

Our Ria findings in Jama neurology.

As we look forward, we aim to expand both within and beyond neuroscience with a focus on four pillars to drive growth and value creation first.

Michelle Vounantzos: We intend as a company to build on our strong foundation in neuroscience, where we currently have 26 programs in clinical development. Second, we have what we believe to be two compelling phase three programs in lupus. This is a therapeutic area with a different risk profile, and we are continuing to evaluate additional opportunities in specialized immunology. Over the last several years, we have also built a very successful new business with our biosimilars.

We intent as a company to build on our strong foundation in neuroscience, where we currently have 26 programs in clinical development.

Second.

We have what we believe to be two compelling phase III programs in rupees.

This is a topic area with a different risk profile and we are continuing to evaluate additional opportunities in specialized immunology.

Third.

Over this over the last several years, we have also built a very successful new business without whereby you'll see me loss we.

Michelle Vounantzos: We recently announced an agreement to sell our stake in the Samsung BioEPS joint venture to Samsung Biologics, with Biogen remaining in our current role as the commercialization partner for the Samsung BioEPS anti-TNF portfolio and ophthalmology program. We currently anticipate that this transaction will close in mid-2022. Once closed, going forward, we will have an expanded ability to pursue the biosimilars business on our own as we aim to bring more biosimilar products to more patients in more geographies. Mike will provide more details.

We recently announced an agreement to sell our stake in the Samsung by the way P joint venture to Samsung Biology's with Biogen remaining in our current role as the commercialization partner for the Samsung by OE piece anti TNF portfolio and ophthalmology programs.

We are currently anticipate we currently anticipate that this transaction will close in mid 2022 .

Once closed going forward, we will have an expanded ability to pursue the biosimilars business on our own as we aim to bring more biosimilar product to more patients in more geographies, Mike will provide more details.

Michelle Vounantzos: And lastly, we are also focused on accelerating our efforts in digital health to support our commercial and pipeline programs while also creating opportunities for potential digital therapeutics. To this point, we have built a dedicated digital health portfolio, which includes the recently announced new collaboration with Terrapanacea with the aim of leveraging our significant database, but also machine learning and artificial intelligence to develop digital health solutions that may improve patient care, accelerate drug development, and further the understanding of underlying pathology.

And lastly, we are also focused on accelerating our efforts in digital health to support our commercial and pipeline programs. While also creating opportunities for potential did you start the optics to this point, we have built a dedicated digital health portfolio, which includes the recently announced.

New collaboration with the Hopper and S. Yeah with yen of leveraging our significant database, but also machine learning artificial intelligence to develop digital health solution that may improve patient care.

Accelerating drug development and further the understanding of underlying pathologies.

Michelle Vounantzos: Our progress across these four pillars provides us with the potential for two future waves of growth as we launch in new geographical areas and build new franchises. We are now at the center of the world.

Our progress across these four pillars provides us with the potential for two future waves of growth as we launch in new therapeutic areas and build new franchises.

Michelle Vounantzos: We are now in the center of the world, first in the next few years. We believe we have significant potential. In Alzheimer's disease and depression, two large therapeutic areas with significant and unmet needs. For Alzheimer's disease, we have a deep pipeline of clinical and preclinical assets, leveraging multiple modalities and targets, including both amyloid and Tau.

First over the next few years, we believe we have a significant potential.

In Alzheimers disease, and depression to large therapeutic area with significant unmet needs.

And as I missed disease, we have a deep pipeline of clinical and preclinical assets, leveraging multiple modalities and targets, including both amyloid and Tau without your help allocate them up Biogen in SA has two out of the full potential anti amyloid antibodies hobbies.

Michelle Vounantzos: With aduhelm and lecanumab, Biogen and SI have two out of the four potential anti-amyloid antibody therapies that are either approved or in late stage development. In depression, we are collaborating with such therapeutics on the run, which we believe have the potential to provide a valuable new option for patients suffering from major depressive disorder and post-traumatic stress disorder. We believe our second future wave of growth anticipated in the mid to late 2020s will be driven by a number of diverse Parkinson's disease and lupus programs, with some of these programs already in phase three.

That are either approved or in late stage development in depression, we are collaborating with <unk> on January <unk>.

Which we believe has the potential to provide a valuable new option for patients suffering from major depressive disorder and postpartum depression.

We believe our second future waves of growth anticipated in the mid to late 2000, Twenty's will be driven by a number of diverse therapeutic areas, including stroke parkinsons disease and lupus. We some of these programs already in phase III.

Michelle Vounantzos: These anticipated future waves of growth will be supported by our diversified pipeline, which today includes 32 clinical programs, 10 of which are in phase 3 of 5. Additionally, outside of our core business, we are pleased to have recently exercised an option for mosin etuzumab, a late-stage investigational bispecific antibody targeting CD20 and CD3 in development by Genentech for oncology and potentially other indications. Exercise of this option will provide Biogen with a profit share while Genentech will lead strategy and implementation with an expected FDA filing in the near future. This builds on Biogen and Genentech's long history of productive collaboration which began with Fetuximab. Our focus in 2022 will remain on execution and agility as we expect a number of important milestones.

These anticipated future waves of growth will be supported by our diversified pipeline, which today includes 32 clinical programs 10 of which are in phase III or filed.

Additionally.

Outside of our core business. We are pleased to have recently exercised an option for most of you need to zoom up late stage investigational Bispecific antibody targeting CD 20, and she did three in development by Genentech for oncology and potentially all the indication exercise of these.

Option, we provide biogen will be the probably chair, while Gentex will lead strategy and implementation. We then expected FDA filing in the near future. This builds on Biogen and Gentex long history of productive collaboration which began with Citrix you Bob.

Yeah.

Our focus in 2022 will remain on execution and agility as we expect a number of important milestones.

Michelle Vounantzos: This includes the continued launch of ADUELM in the U.S., the launch of Umeriti in the EU, and our expected entry into the U.S. biosimilars market with BioViz. We expect five data readouts, three of which are in phase three, and the completion of three regulatory filings in Alzheimer's disease, depression, and biosimilars. Before I turn the call over to Priya for an update on our progress in R&D, I want to first say how impressed I am by what I have seen from Priya, both as a head of safety and regulatory science and, most recently, as our acting head of R&D. Her ability to lead, her strategic thinking, and her subject matter expertise give me the utmost confidence in her ability to advance our pipeline while we work to name a permanent successor Please go ahead, Priya.

This includes the continued launch of the U S. The launch of humanity in D U N or expected entry into the U S biosimilars market with babies.

We expect five data readouts three of which are in phase III.

And the completion of three regulatory filings in Alzheimer's disease depression in Biosimilars.

Before I turn the call over to pry out pre asked for an update on our progress in R&D.

I want to first say, how impressed I am by what I've seen from pre op books, as our head of safety and regulatory science and most recently as our acting head of R&D.

Her ability to lead the strategic thinking and her subject matter expertise gives me the utmost confidence in her ability to advance our pipeline, while we work to name a permanent successor. Please go ahead.

Priya Singhal: Thank you, Michelle, and good morning, everyone. First, I want to say what an honor it is to serve as acting head of R&D at Biogen. Biogen has a track record of developing life-changing therapies in MS and SMA. With a deep and diverse R&D pipeline, Biogen aims to bring impactful medicines to patients suffering from neurological and immunological diseases characterized by significant unmet needs. As this is my first earnings call within this role, I would like to review a few areas that I'm especially excited about. First, we believe that Biogen has a unique opportunity to lead in Alzheimer's disease.

Thank you Michelle and good morning, everyone.

First I wanted to say what an honor it is to serve as acting head of R&D at Biogen.

Biogen has a track record in developing life, changing therapies and L S and SME.

With a deep and diverse R&D pipeline Biogen aims to bring impactful medicines to patients suffering from neurological and immunological diseases characterized by significant unmet need.

Priya Singhal: Not only because we are advancing an industry-leading Alzheimer's pipeline but also because of the proactive focus we have placed on continued data generation for aducanumab. This includes Envision, the planned post-marketing phase 4 study, the ongoing Embark Redosing Study, and obtaining real-world data through the iCare AD registry.

As this is my first earnings call within this role I would like to review a few areas that I'm, especially excited about.

First we believe that Biogen has a unique opportunity to lead in Alzheimer's disease.

Not only because we are advancing an industry, leading Alzheimer's pipeline, but also because of the proactive focus we have placed on continued data generation. So how do you can you map.

This includes envision the planned post marketing phase four study.

The ongoing embark re dosing study.

And obtaining real world data to the ICANN registry.

Priya Singhal: We believe data from patients treated with aducanumab in real world settings with greater drug utilization is the best way to complement the extensive clinical data generated on aducanumab to date, in addition to the ongoing and planned clinical trials. We also continue to gain potential insights from the aducanumab phase 3 clinical data regarding Alzheimer's disease biology and the treatment effect of aducanumab on this particular point. Biogen recently presented additional data from the Engage and Emerge Phase 3 trials at the annual CTAD meeting last November.

We believe data from patients treated with Eddie can you map in the real world settings with greater drug utilization.

The best way to complement the extensive clinical data generated on AD you can't even lab to date. In addition to the ongoing and planned clinical trials.

We also continue to gain potential insights somebody and you can't you might phase three clinical data.

Adding Alzheimer's disease biology, and the treatment effect of that you can't do that.

Okay.

On this particular point.

Biogen recently presented additional data from the engage and emerge phase III trials I'd.

That'd be and you'll see that meeting last November .

Priya Singhal: Important analysis of this data showed that in addition to reducing amyloid plaques in the brain, aducanumab treatment also resulted in changes in downstream tau Alzheimer's disease biology, specifically Soluble Phospho-Tau or P-Tau as seen in both C-S-F and Plasma.

The important analysis of this data showed that in addition to reducing amyloid plaques in the brain and you can't you might treatment also resulted in changes in downstream Dow Alzheimer's disease biology, specifically soluble possible Chow offbeat, though I've seen in both CSS and plan.

Uh huh.

Priya Singhal: In this analysis, we evaluated over 7,000 plasma samples from more than 1,800 subjects from the eMERGE and ENGAGE phase 3 trials to investigate the effect of adecanumab treatment on plasma beta-181. The results showed a time and dose-dependent reduction in PETA 181 over 78 weeks with adi canumap treatment in both phase three trials. The reduction in plasma Ptau 181 from baseline to week 78 in this analysis was significantly correlated with change in amyloid PET over the same time period and was also significantly associated with less clinical decline across all primary and secondary outcome measures assessing cognition and function in both studies. These findings are consistent with the hypothesis that aggregated forms of amyloid may mediate soluble tau phosphorylation.

In this analysis be evaluated over 7000 plasma samples from more than 1800 subjects from the emerge and engage phase III trials to investigate the effect of Eddy County map treatment on plasma beat a 181.

The results showed eight time and dose dependent reduction in beta 181 over 78 weeks with Eddy County map treatment in both phase III trials.

The reduction in plasma beat a 181 from baseline to week 78, and this analysis was significantly correlated with change in amyloid pet over the same time period and was also significantly associated with less clinical decline across all primary and secondary outcome measures assessing cognition.

<unk> and function in both studies.

These findings are consistent with the hypothesis that aggregated forms of amyloid may immediate soluble downforce correlation.

Priya Singhal: With regard to our AD pipeline, we are excited about Leucanomab, our other anti-amyloid antibody in Alzheimer's disease that is being developed in collaboration with Eastside. In phase 2, Leucanumab did not utilize a titration period and demonstrated rapid and robust reduction of amyloid plaques. [inaudible] and showed an ARIA incidence of around 10%. We look forward to the Phase 3 readout expected in the second half of this year. Beyond our programs targeting amyloid, we are also pursuing a multi-modality approach focused on other targets in Alzheimer's. First, we have BIP-80, which is an ASO that we believe facilitates tau mRNA degradation and has demonstrated both a time- and dose-dependent reduction of CSF-phospho and total tau in phase 1.

With regard to our 80 pipeline, we are excited about mccann them at our other anti amyloid antibody in Alzheimer's disease that is being developed in collaboration with ESI.

In phase two.

And Mccanna Mab did not utilize it titration period.

Demonstrated rapid and robust reduction of amyloid blocks and showed an ARIA incidence of around 10%.

We look forward to the phase III readout expected in the second half of this year.

Beyond our program programs targeting amyloid. We are also pursuing a multi modality approach focused on other targets.

Ms <unk>.

First we have built a T which is in air so that we believe facilitates tau mrna degradation and has demonstrated both a time and dose dependent reduction of CSF thoughtful and total tau in phase one.

Priya Singhal: We anticipate starting the Phase 2 study of Bib A.T. by mid-year. Second, we are also planning for the near-term initiation of a phase one study for Bib 113, a small molecule inhibitor of Ogliknacase or ODA, an enzyme believed to catalyze the removal of Ogliknac post-translational modification of tau protein. Evidence suggests that ooglycnylation of tau attenuates aggregation.

We anticipate starting the phase two study of baby D by midyear.

Second we are also planning for the near term initiation of a phase one study. So big 113 is small molecule inhibitor of oblique Nutcase R. O G and enzyme believed to catalyze the removal of all glickman post translational modification of Talcott.

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Evidence suggests that all click emulation opt out attenuates aggregation.

Priya Singhal: By inhibiting OGA, we aim to increase the O-glucanylation of Tau to potentially inhibit Tau aggregation and thereby slow clinical decline. Having developed the first FDA-approved therapy to address a defining pathology of Alzheimer's, we believe that Biogen is uniquely positioned with the right expertise, experience, and access to modalities to lead in Alzheimer's disease.

By inhibiting Oh Gee, we aim to increase the oblique emulation opt out to potentially inhibit tau aggregation and thereby slow clinical decline.

Having developed the first FDA approved therapy to address a defining pathology of Alzheimer's we believe that Biogen is uniquely positioned with the right expertise experience and access to modalities to lead in Alzheimer's disease.

Priya Singhal: This is a complex disease requiring a multi-faceted approach and continued investment. As we work to build on the scientific learnings of AdduHelm and develop the next wave of potential Alzheimer's therapies, I would now like to talk about depression. I believe that Zuran Alon, with a novel mechanism of action, may provide an important new treatment option for patients suffering from major depressive disorder and postpartum depression.

This is a complex disease, requiring a multifaceted approach and continued investment as.

As we work to build on the scientific learnings of AD you have and develop the next wave of potential Alzheimer's therapies.

I would now like to talk about depression.

I believe that you ran alone with a novel mechanism of action may provide an important new treatment option for patients suffering from major depressive disorder and postpartum depression.

Priya Singhal: The reported clinical data generated to date from multiple clinical trials showed the following. First, in earlier studies, an improvement in depressive symptoms was observed as early as day three. Second, Zuranalone has displayed a consistent safety and tolerability profile with no observed evidence of weight gain, sexual dysfunction, euphoria, or increased suicidal ideation.

The reported clinical data generated to date from multiple clinical trials showed the following.

First in earlier studies and improvement in depressive symptoms has been observed as early as day three.

Second Standalone has displayed a consistent safety and tolerability profile with no observed evidence of weight gain sexual dysfunction euphoria or increased suicidal ideation.

Priya Singhal: Third, the Shoreline Phase 3 Open Label Study showed that approximately 80% of patients who responded to the initial course of 50 milligrams of ranalone needed at most one additional treatment total during their time in the one year study. For example, in the waterfall phase three study, Zorana Lone reduced depressive symptoms in patients suffering from MDD, both wide and without elevated anxiety. Fifth, Zoranolone has shown improvements in depressive symptoms in postpartum depression.

Uh huh.

Third the shoreline phase III open label study show that approximately 80% of patients who responded to the initial costs of 50 milligrams of the ran alone needed at most one additional treatment solta during their time in the one year study.

Pork in the waterfall phase III study is around alone reduced depressive symptoms in patients suffering from M. D D, both with and without elevated anxiety.

Fist Joanne alone has shown improvements in depressive symptoms in postpartum depression.

Priya Singhal: Paul Zuranalon, we look forward to two phase three readouts this year: the Coral Study in MDD and the Skylark Study in PPC. The next area I would like to highlight is Stroh. Last year, we were excited by the results from the phase two study of bib 131, formerly known as PMS 007, in acute ischemic stroke. Administration of the current standard of care, pharmacological thrombolytic, TPA, is limited to a short therapeutic window within four and a half hours following the acute onset of stroke symptoms.

First around alone we look forward to phase three readouts this year.

The Cornell study in M D D and the Skylark study in PPD.

The next area I would like to highlight is so.

Last year, we were excited by the results from the Phase two study of <unk> 131, formerly known S. P. M. S 007 in acute ischemic stroke.

Administration of the current standard of care pharmacological Thrombolytic P. P. E is limited to a short therapeutic window within four and a half hours following the acute onset of stroke symptoms.

Priya Singhal: This short time window is meant to mitigate the risk of intra-cranial hemorrhage, which is the most concerning adverse event associated with TBA, in the face of a study of bit 131. Acute stroke patients were randomized to receive bit 131 or placebo, out to 12 hours from their last known normal. The primary objective of the study was safety, and of the 52 patients who received the 131, none experienced symptomatic intraabdominal hemorrhage compared to one out of the 38 patients who received the CEPA.

This short time window is meant to mitigate the risk of intracranial hemorrhage, which is the most concerning adverse event associated with D. A.

In the Phase Iia study of <unk> 131.

Huge stroke patients were randomized to receive 131 or placebo out to 12 us from the last known normally.

The primary objective of the study.

Safety and all of the 52 patients who received the 131 non expedient symptomatic intracranial hemorrhage compared to one out of the 38 patients who received placebo.

Priya Singhal: This was despite an extended treatment window where patients on average received BIV-131 at 9.5 hours after the onset of acute stroke symptoms. Additionally, BIB 131 showed a statistically significant improvement versus placebo on the Modified Rankin Scale, or MRS, a Registrational Endpoint of Functional Independence. Furthermore, the rate of recanalization or improvement of vessel blood flow in patients who had a visible vessel occlusion was approximately 58% at 24 hours in those who had received BIP-131 as compared to 27% of patients who received placebo.

This was despite an extended treatment window, where patients on average received 131 at nine five hours after the onset of acute stroke symptoms.

Additionally, the 131 showed a statistically significant improvement versus placebo on the modified Rankin scale or mris, a registrational endpoint of functional independence.

Furthermore, the REIT, a recapitalization or improvement of vessel blood flow in patients who had a visible vessel occlusion was approximately 58% at 24 hours in those who had received 131 as compared to 27% of patients who received placebo.

Priya Singhal: We believe Biv 131 may have the potential to be a best in class from the LITIC for the treatment of acute iscremic stroke by extending the treatment time window out to 24 hours with an appropriate efficacy and safety profile. We are currently evaluating the next steps in the development of BIP 131. In addition to bib-131, we also continue to advance a Phase III study for bib-93 in large hemispheric infarction based upon the effects observed on mortality and cerebral edema in the Phase II study.

We believe the 131 may have the potential to be a best in class thrombolytic for the treatment of acute ischemic stroke by extending the time treatment time window out to 24 hours with an appropriate efficacy and safety profile.

We are currently evaluating the next steps in the development for Bip 131.

In addition to 131, we also continued to advance a phase III study with 93 in large hemispheric infarction based upon the effects observed on mortality and cerebral edema in the phase two study.

Priya Singhal: I would now like to turn my attention to specialized immunology. We currently have two phase three assets in SLE, including Daperna Los Mab, the goal in collaboration with UCB, and BIP 59, our anti-BDC-A2 antibody developed in-house at Adbiogen. These two assets represent potential first-in-class molecules in SLE. Bip 59 also has the potential to be a first-in-class biologic in cutaneous loopless erudomatosis or CLE. CLE is a skin-based autoimmune disease that can be associated with severe scarring and dispigmentation.

I would now like to turn my attention to specialize immunology.

We currently have two phase three assets in Italy, including Deputy lose a mab the goal in collaboration with UCB and Bib 59, our anti B D. C. Two antibody developed in house at Biogen.

These two assets represent potential first in class molecules in SLE.

That 59 also has the potential to be a first in class biologic in cutaneous lupus erythematosus or cle.

Yeah, Lisa skin based auto immune disease that can be associated with severe scarring and this pigmentation.

Priya Singhal: In the face-to-lilac study, the CLE part of the study also met its primary end point by demonstrating a dose response of BIP 59 on the percent change from baseline in the classy A score, its standardized scale measuring CLE disease activity at week 16 in individuals with CLE. Furthermore, a higher Classy 50 response rate, or number of individuals with a 50% greater improvement from baseline in the Classy A score, was observed in patients who received BIP 59 at week 60. Based upon these results, we are currently planning to initiate a pivotal study for BIP-59 in CLE this year. Next, I will touch upon each other.

In the phase two lilac study the cle part of the study also met its primary endpoint by demonstrating a dose response of bib 59 on the percent change from baseline in the class C. H score it standardize scale measuring tape cle disease activity.

At week 16 in individuals with Sealy.

Furthermore, a higher classy 50 response rates or number of individuals with a 50% or greater improvement from baseline in the classic a score was observed in patients who received bib 59 at week 16.

Based upon these results. We are currently planning to also initiate a pivotal study for <unk> 59 in cle this year.

Next I will touch upon a L S.

Priya Singhal: ALS has been a key focus area for Biogen for many years, and we remain encouraged by the data from the Phase III Valor study of the person, where despite missing the primary endpoint of a statistically significant change from baseline to week 28 in the ALSFRS, we believe there are trends favoring the person across multiple secondary and exploratory measures of biological and clinical activity. We are continuing to collect data in the Valor Open Label Extension, and we are actively recruiting for the ATLAS pre-symptomatic study. Many SORD1 ALS patients have received access to Tufersen through the Global Expanded Access Program, which is available in countries where local regulations permit it and where we hope to secure long-term access.

L. S has been a very key focus area for Biogen for many years.

And we remain encouraged by the data from the Phase III Valor study of the person.

Where despite missing the primary endpoint of a statistically significant change from baseline to week 28 in the L. S. FRS, we believe that our trends favoring to person across multiple secondary and exploratory measures of biological and clinical activity.

We are continuing to collect data in the valor open label extension and we are actively recruiting for the Atlas pre symptomatic study.

Many sod one L. S patients have received access to fasten through the global expanded access program, which is available in countries, where local regulations permitted and where we hope to secure long term access.

Priya Singhal: In addition, we are engaged with regulators to determine the next steps for the program. Aside from the areas I've highlighted, Bajin continues to grow and diversify the R&D pipeline, which now includes 32 clinical programs. New additions include the exercise of the option with IONUS on bib 115 and investigational ASO with the potential for extended dosing intervals in SMA, as well as the recent initiation of a phase 1 study in Angelman's in Rome, a rare genetic neurodevelopmental disorder that affects the nervous system and causes severe physical and learning disabilities with symptoms beginning in the infant at the end of the day.

Although we are engaged with regulators to determine the next steps for the program.

Aside from the areas that I've highlighted biogen continues to grow and diversify the R&D pipeline, which now includes 32 clinical programs.

New additions include the exercise of the option with I honest on Big 115, an investigational air so with the potential for extended dosing intervals in SME as well as the recent initiation of a phase one study in Angelman syndrome, a rare genetic neuro development.

INTL disorder that affects the nervous system and causes severe physical and learning disabilities with symptoms beginning in infancy.

Priya Singhal: Importantly, I believe that 2022 will be a significant year for Biogen's pipeline, given the number of important readouts expected, including licanumab phase 3 in Alzheimer's disease, and key readouts in neuropsychiatry for both Zoranolone in depression and BIP-104 in schizophrenia and BIP-78 in ALS.

Importantly, I believe that 2022 will be a significant deal for biogen's pipeline given the number of important readouts expected.

Including the <unk> phase III in Alzheimer's disease.

Key readouts in neuropsychiatry for boat Saran alone in depression, and they've won afford in schizophrenia and <unk> 78 in a L. S.

Priya Singhal: In closing, I believe Biogen has assembled an extensive pipeline of programs informed by genetics, a deep understanding of disease biology, specialized modality expertise, and digitalization. Therefore, I believe Biogen is uniquely positioned to shape the future of therapeutics in neurology and specialized immunology and make a difference in patients and their caregivers' lives. I will now pass the call over to Mike. Thank you, Priya, and good morning, everyone.

In closing I believe Biogen has assembled an extensive pipeline of programs.

Informed by genetics, a deep understanding of disease biology.

Specialized modality expertise and digitalization.

Therefore, I believe biogen is uniquely positioned to shape the future of therapeutics in neurology and specialized immunology and make a difference in patients and their caregivers lives.

I will now pass the call over to Mike.

Mike Mcdonnell: Thank you for joining us. I'll focus my commentary on the fourth quarter results along with some discussion regarding the full year 2021. Total revenue for the fourth quarter of $2.7 billion declined 4% versus the prior year at both actual and constant currency. Total revenue for the full year of $11 billion declined 18% versus the prior year at actual currency and 19% at constant currency. This decline was mostly driven by Tecfidera generic entry in the United States. Non-GAAP diluted earnings per share in the fourth quarter were $3.39.

Thank you Perry and good morning, everyone. Thank you for joining us I'll focus my commentary on fourth quarter results along with some discussion regarding the full year 2021.

Total revenue for the fourth quarter of $2 $7 billion declined 4% versus the prior year at both actual and constant currency total revenue revenue for the full year of $11 billion declined 18% versus the prior year at actual currency and 19% at constant currency. This decline was mostly driven by tech vadera generic entry in the United.

States non.

non-GAAP diluted earnings per share in the fourth quarter was $3.39 full year non-GAAP diluted earnings per share was $19.22.

Mike Mcdonnell: Full year non-GAAP diluted earnings per share was $19.22. Total MS revenue, inclusive of Okravis royalties, in the fourth quarter was $1.8 billion. Global Tech Federer revenue in the fourth quarter was $486 million, and US revenue was $161 million. Outside of the US, Techvedera revenue of $326 million increased by 13% versus the prior year, with 7% growth in underlying patients. Bumerity's fourth quarter global revenue was 125 million dollars as compared to 39 million in the fourth quarter of 2020.

Total M S revenue inclusive of Volcker as royalties in the fourth quarter was $1 $8 billion global Tech for their revenue in the fourth quarter was $486 million U S revenue was $161 million.

Outside of the U S <unk> revenue of $326 million increased by 13% versus the prior year with.

With 7% growth in underlying patients.

Well Meredith fourth quarter global revenue was $125 million as compared to $39 million in the fourth quarter of 2020.

Mike Mcdonnell: We expect Lumerity to continue to grow both in the U.S. and outside the U.S. To Sabri, fourth-quarter global revenue of $513 million increased 8% versus the prior year, benefiting from positive channel dynamics in the U.S., and we were pleased to see continued global patient growth. Moving to SMA, global fourth-quarter Spinraza revenue of $441 million decreased 12% versus the prior year.

We expect we're married to continue to grow both in the U S and outside the U S.

To Sabri fourth quarter global revenue of $513 million increased 8% versus the prior year benefiting from positive channel dynamics in the U S. And we were pleased to see continued global patient growth.

Moving to SMA global fourth quarter, its been Rozzer revenue of $441 million decreased 12% versus the prior year.

Mike Mcdonnell: In the U.S., Spinraza revenue of $150 million decreased by 6% versus the prior year, as we saw continued impact from competition. However, we were encouraged to see the discontinuations moderated somewhat versus Q3 of this year. U.S. Spinraza revenue increased 7% versus the prior quarter, inclusive of some favorable pricing and channel dynamics. Outside the U.S., Benraza revenue of $291 million decreased 14% versus the prior year due to competition and pricing pressure.

In the U S. It's been raws are revenue of $150 million decreased by 6% versus the prior year. As we saw continued impact from competition. However, we were encouraged to see the discontinuation is moderated somewhat versus Q3 of this year.

<unk> been Rozzer revenue increased 7% versus the prior quarter inclusive of some favorable pricing and channel dynamics outside the U S been rozzer revenue up $291 million decreased 14% versus the prior year due to competition and pricing pressure. We continue to believe it's been rozzer can return to growth over the medium.

Mike Mcdonnell: We continue to believe that Benraza can return to growth over the medium to long term. Total Agihelm revenue for the fourth quarter was $1 million. Moving to our biosimilars business, fourth-quarter revenue of $221 million increased 12% versus the prior year, with increased volume partially offset by pricing pressure. Our Q4 biosimilars revenue benefited from a one-time price adjustment of approximately $10 million. Last week, we announced that we have entered into an agreement to sell our equity stake in our biosimilar joint venture, Samsung BioEpis, to Samsung Biologics for an aggregate consideration of up to $2.3 billion.

To long term.

Okay.

Total <unk> revenue for the fourth quarter was $1 million moving to our Biosimilars business fourth quarter revenue of $221 million increased 12% versus the prior year with increased volume, partially offset by pricing pressure. Our Q4 Biosimilars revenue benefited from a onetime price adjustment of approximately.

$10 million.

Last week, we announced that we have entered into an agreement to sell our equity stake in our Biosimilar joint venture Samsung bio weapons to Samsung biologics for aggregate consideration of up to $2 $3 billion. We believe this represents an attractive financial return given that our cumulative investment in the joint venture.

Mike Mcdonnell: We believe this represents an attractive financial return given that our cumulative investment in the joint venture was $727 million. It's important to note that we will continue to record revenue and cost associated with the commercialization of Benapoli, Imraldi, and Flix Abbey, with economics that will be substantially unchanged from what you have seen previously.

It was $727 million, it's important to note that we will continue to record revenue and costs associated with the commercialization of poly and royalty and flicks RB with economics that will be substantially unchanged from what you have seen previously. So we are pleased with this transaction because we not only maintain the commercialization rights that we have.

Mike Mcdonnell: So we are pleased with this transaction because we will not only maintain the commercialization rights that we have, but we will also have an expanded ability to pursue additional biosimilars products on our own going forward. Closing of this transaction is currently anticipated in mid-2022, contingent on the effectiveness of a securities registration statement filed by Samsung Biologics and satisfaction of certain regulatory and other customary closing conditions. Total anti-CD20 revenue in the fourth quarter of $414 million decreased 1% versus the prior year, and Rituxan revenue of $153 million decreased 29% versus the prior year due to the impacts of COVID-19 and continued erosion from biosimilar competition. Okravis royalty revenue of $261 million increased 29% versus the prior year.

But we will also have an expanded ability to pursue additional biosimilars products on our own going forward.

Okay.

Closing of this transaction is currently anticipated in mid 2022 contingent on the effectiveness of our securities registration statement filed by Samsung Biologics and satisfaction of certain regulatory and other customary closing conditions.

Total anti CD 20 revenue in the fourth quarter of $414 million decreased 1% versus the prior year Rituxan revenue of $153 million decreased 29% versus the prior year due to the impacts of COVID-19, and continued erosion from Biosimilar competition.

OCA this royalty revenue of $261 million increased 29% versus the prior year.

Mike Mcdonnell: As a reminder, the effective royalty rate for Okravis royalties resets each calendar year. Fourth quarter gross margin was 76% of revenue, down from 83% in Q4 of 2020. The reduction in gross margin versus the prior year was primarily due to a $164 million charge for Agilent inventory and purchase commitments in excess of forecasted demand.

As a reminder, the effective royalty rate for <unk> royalties reset each calendar year.

Fourth quarter gross margin was 76% of revenue down from 83% in Q4 of 2020 the reduction in gross margin versus prior year was primarily due to a $164 million charge for Ajay home inventory and purchase commitments in excess of forecasted demand.

Mike Mcdonnell: Moving now to expenses on the balance sheet, Q4 non-GAAP R&D expense was $700 million, which included a $60 million opt-in payment to Ionis for BIB 115 and a cost of approximately $50 million for the exercise of our option with Genentech for the bispecific antibody mentioned earlier. We will share in the operating profits and losses for this program in the low to mid 30% range in the United States. Non-Gap S.GNA was $785 million, including approximately $155 million related adjunct.

Moving now to expenses in the balance sheet Q4, non-GAAP R&D expense was $700 million, which includes a $60 million opt in payment to I honest for bid 115, and a cost of approximately $50 million for the exercise of our option with genentech for the bi specific antibody mentioned earlier.

We will share any operating profits and losses for this program in the low to mid 30% range in the United States.

non-GAAP SG&A was $785 million, including approximately $155 million related to agile.

Mike Mcdonnell: A size reimbursement of US SG&A costs of approximately $45 million is reflected in the collaboration. Fourth quarter collaboration profit sharing reduced our net operating expense by $67 million, which includes reimbursement of approximately $140 million from ASI related to Agilent Home commercialization, partially offset by $75 million of net profit sharing expense related to our collaboration with Samsung Bioweapons. During Q4 of this year, our effective non-gap tax rate was approximately 17%

<unk> reimbursement of U S. S. G&A costs of approximately $45 million is reflected in the collaboration profit sharing line.

Fourth quarter collaboration profit sharing reduce our net operating expense by $67 million, which includes reimbursement of approximately $140 million from ACI related to add your home commercialization, partially offset by 75 million of net profit sharing expense related to our collaboration with Samsung Bioweapon.

Yeah.

During Q4 of this year, our effective non-GAAP tax rate was approximately 17%.

Mike Mcdonnell: During 2021, we repurchased approximately 6 million shares of our common stock for a total value of $1.8 billion. However, no shares were repurchased in the fourth quarter of 2021. As of December 31, 2021, there was $2.8 billion remaining under the Share Repurchase Program, which was authorized in October of 2020. Our weighted average diluted share count was approximately 147 million shares for the fourth quarter. In 2021, we generated approximately $3.6 billion in cash flow from operations.

During 2021, we repurchased approximately 6 million shares of our common stock for a total value of $1 $8 billion no shares were repurchased in the fourth quarter of 2021 as of December 31, 2021, there was $2 $8 billion remaining under the share repurchase program, which was authorized in October of 2020.

Our weighted average diluted share count was approximately 147 million shares for the fourth quarter.

In 2020 , one we generated approximately $3 $6 billion in cash flow from operations capital expenditures were $258 million and free cash flow was approximately $3 $4 billion. We ended the year with $7 $3 billion in debt $4 $7 billion in cash and marketable securities of $2 six.

Mike Mcdonnell: Capital expenditures were $258 million, and free cash flow was approximately $3.4 billion. We ended the year with $7.3 billion in debt, $4.7 billion in cash and marketable securities, and $2.6 billion in net debt. In addition, our $1 billion revolving credit facility was undrawn as of the end of the year.

Billion dollars in net debt.

In addition, our $1 billion revolving credit facility was undrawn as of the end of the year overall, we remain in a very strong financial position with significant cash and financial capacity to grow the business over the long term.

Mike Mcdonnell: Overall, we remain in a very strong financial position with significant cash and financial capacity to grow the business over the long term. Let me now turn to our full year guidance for 2022. We expect full-year 2022 revenue to be between $9.7 billion and $10 billion. This financial guidance assumes minimal Agihelm revenue in 2022, continued declines in Rituxan revenue due to biosimilar competition, as well as continued erosion of Tecfidera revenue in the U.S. due to generic entry.

Yeah.

Mike Mcdonnell: This guidance also assumes the potential entry of Tecfidera generics in the EU as early as the first half of 2022, as the outcome of the ongoing challenges to Tecfidera market protection is difficult to predict. We expect the decreased revenue from these high-margin products to reduce our gross margin percentage as compared to 2021. We expect full year 2022 non-GAAP diluted PFC between $14.25 and $16.

Let me now turn to our full year guidance for 2022.

We expect full year 2022 revenue to be between $9 7 billion and $10 billion.

This financial guidance assumes minimal age at home revenue in 2022 continued declines in Rituxan revenue due to Biosimilar competition as well as continued erosion of tepid air revenue in the U S due to generic entry.

This guidance also assumes the potential entry of <unk> generics in the EU as early as the first half of 2022 as the outcome of the ongoing challenges detect vadera market protection is difficult to predict we expect the decreased revenue from these high margin products to reduce our gross margin percentage as compared to 12.

'twenty one we expect full year 2022, non-GAAP diluted EPS to be between $14.25 and $16.

Mike Mcdonnell: Our guidance assumptions are highly dependent on the final national coverage determination, which is currently uncertain. If the final NCD, which is expected in April, is not broader than the draft NCD, our anticipated results and guidance may be impacted. This guidance assumes that we will not have any write-offs of AgiHelm inventory in 2022, which is valued at approximately $225 million as of the end of 2021. This guidance also assumes reasonable levels of utilization of our manufacturing capacity dedicated to our Alzheimer's disease program. If our manufacturing capacity is underutilized, we will incur incremental period costs which are not reflected in our guidance.

Our guidance assumptions are highly dependent on the final national coverage determination, which is currently uncertain.

The final NCD, which is expected in April is not broader than the draft NCD, our anticipated results and guidance may be impacted.

This guidance assumes that we will not have any write offs of agile home inventory in 2022, which is valued at approximately $225 million as of the end of 2021 .

<unk> also assumes reasonable levels of utilization of our manufacturing capacity dedicated to our alzheimers disease programs, if our manufacturing capacities underutilized, we will incur incremental period costs, which are not reflected in our guidance.

Mike Mcdonnell: We expect non-GAAP R&D expenses to be between $2.2 billion and $2.3 billion and our non-GAAP SG&A expense to be between $2.5 billion and $2.6 billion. This non-GAAP SG&A expense estimate includes approximately $400 million in support of the launch of AgiHelm, of which approximately $145 million would be reimbursable by ASI and reflected in the collaboration profit-sharing launch. These R&D and SG&A expense estimates reflect the implementation of previously disclosed cost reduction measures, which are expected to yield approximately $500 million in annualized savings, of which approximately $350 million is expected to be realized in 2022.

We expect non-GAAP R&D expense to be between $2 2 billion and $2 $3 billion and our non-GAAP SG&A expense to be between $2 5 billion and $2 $6 billion. This non-GAAP SG&A expense estimate includes approximately $400 million in support of the launch of ads at home of which approximately.

$145 million would be reimbursable by ASI and reflected in the collaboration profit sharing line.

These R&D and SG&A expense estimates reflect the implementation of previously disclosed cost reduction measures, which are expected to yield approximately $500 million in annualized savings of which approximately $350 million is expected to be realized in 2022.

Mike Mcdonnell: These savings are expected to be achieved through various initiatives, which may include downsizing of our global Alzheimer's infrastructure, the savings from which would be shared with ASI, and operating efficiency gains across SG&A and R&D. Additionally, these savings are expected to be offset by approximately $200 million in additional investments in our pipeline and strategic initiatives. In the event of a final NCD that is not broader than the draft NCD, we anticipate taking further cost reduction measures, which are not reflected in our guidance, to further align our cost base with our revenue base.

These savings are expected to be achieved through various initiatives, which may include downsizing of our global Alzheimers infrastructure savings from which would be shared with ASI and operating efficiency gains across SG&A and R&D.

These savings are expected to be offset by approximately $200 million and additional investments in our pipeline and strategic initiatives.

In the event of a final NCD that is not broader than the draft NCD. We anticipate taking further cost reduction measures, which are not reflected in our guidance to further align our cost base with our revenue base.

Mike Mcdonnell: Some of the savings from these further cost-reduction measures would be shared with ASI. We expect our non-GAAP tax rate for 2022 to be between 15.5% and 16.5%, and we assume that we will utilize a portion of the remaining share repurchase authorization of $2.8 billion throughout the year, although this will depend on a variety of factors, including our business development activities. Foreign exchange rates as of December 31st, 2021 are assumed to remain in effect for the year net of hedging activities. We have not included any impact from potential Aduhelm is now the first FDA-approved treatment targeting the defining pathology of Alzheimer's disease.

Some of the savings from these further cost reduction measures would be shared with ACI.

We expect our non-GAAP tax rate for 2022 to be between 15, 5% and 16, 5% and we assume that we will utilize a portion of the remaining share repurchase authorization of $2 $8 billion throughout the year. Although this will depend on a variety of factors, including our business development activities.

<unk>.

Foreign exchange rates as of December 31, 2021 are assumed to remain in effect for the year net of hedging activities. We have not included any impact from potential acquisitions or large business development transactions as both are hard to predict or any impact of potential tax or health care reform.

I'll now turn the call back over to Michel for his closing remarks. Thank you Mike in summary, 2021 was an eventful year for Biogen.

How did your helm. He's now the first FDA approved treatments targeting a defining pathology of Alzheimer's disease, but as we all know this is a complex disease, which will require continued investment in research over the years to come.

Michelle Vounantzos: But, as we all know, this is a complex disease that will require continued investment in research over the years to come. Aduhelm is an important first step, and we remain focused on advancing our leading portfolio with the goal of further addressing the remaining unmet needs for patients. We hope that over time, we'll be able to bring additional impactful treatment options, which will build on the scientific learnings from Aduhelm, similar to the waves of innovation we have seen in oncology.

Could you help me as an important first step and we remain focused on advancing our leading portfolio with the goal of further addressing the remaining unmet needs for patients.

We hope that over time, we'll be able to bring additional impact with treatment options, which will build on the scientific learnings from agile held similar to the waves of innovation, we have seen in oncology.

Michelle Vounantzos: Before I conclude, let me touch on Biogen's strong commitment to corporate responsibility. Climate, health, and equity are deeply interrelated challenges that demand bold action. And that's why we are working to advance a healthier, more sustainable, and equitable world.

Before I conclude let me touch on Biogen strong commitment to corporate responsibility climate has an equity a deeply integrated challenges that demand bolt action and that's why we are working to advance a healthier more sustainable and equitable world.

Michelle Vounantzos: Through our signature initiative, Healthy Climate, Healthy Lives, and all our efforts, our goal is to create new ways of doing business that positively impact the way we live and the way we deliver for patients. We are proud that our leadership actions and transparency in this area have been recognized recently by the Dow Jones Sustainability World Index, Corporate Nights Global 100, and Just 100. Through this work, we aim to create shared value by meeting the needs of our patients, employees, the environment, and the communities we serve.

<unk> seen that your initiative healthy climate healthy lives and all of the efforts. Our goal is to create new ways of doing business that positively impact the way, we live and the way we did even for patients. We are proud that our leadership actions and transparency in this area.

It's been recognized recently by the Dow Jones Sustainability World Index Corporate Knights Global 100, and just 100 through this work we aim to create shareholder value by meeting the needs of our patients employees the environment and the communities we serve.

Michelle Vounantzos: In closing, I would like to reiterate that we are committed to engaging with CMS and other stakeholders with the hope of finding an appropriate path forward for the patients in access of Adjahelm. We will now open the call to questions. Thank you. If you would like to ask a question, please press star 1 on your telephone. As a reminder, please limit yourself to one question. If you require any further follow-ups, you may press star 1 again to rejoin.

In closing I would like to reiterate that we are committed to engaging with CMS and other stakeholders with the hope of finding an appropriate path forward for the patients and in excess of your help we will now open the call for questions.

Thank you if you would like to ask a question. Please press star one on your telephone keypad.

Winder, please limit yourself to one question. Thank.

If you require any further follow ups you May press star one again through join the queue.

Robyn Karnauskas: Your first question comes from the line of Robyn Karnauskas with Truist Security. You know, given the recent deal that you did with Samsung, you now have more cash. Could you just talk a little bit about your thoughts on how you might want to utilize that cash? And, you know, was there a near-term acquisition or things that you're looking at, or is it just something that gives you optionality? exile. Thanks for the question.

Your first question comes from the line of Robyn <unk> with <unk> Securities.

Yeah.

Okay.

Given the recent deal that you did with thinking about you know Samsung you now have more cash could you just talk a little bit about your thoughts on how you might want to utilize that cash and you know is that it.

Was there a near term.

Mm mm acquisition or things that you're looking at or is it just something that gives you optionality.

Michelle Vounantzos: As you know, we have a strong balance sheet, and we are constantly looking at how we can deliver long-term shareholder value. So we are actively working on some business development opportunities to enrich our pipeline and complement our portfolio in line with our strategy. And we will look at the deals based on their own merits, and we are working on that. And I'll just add to that, Robyn, I mean, as we said in our prepared remarks, we're pleased with the transaction. This represents a very attractive return relative to the capital that we invested.

Thanks for the question.

As you know we have a strong balance sheet and we are continuously looking at how we can deliver long term shareholder value.

So we are actively working on some new business development opportunities to to enrich our pipeline complement our portfolio in line with our strategy.

And we will look at the deals based on their own their own merit and we are working on that.

And I'll just add to that Robert I mean, as we said in our prepared remarks, we were pleased with the transaction that represents.

A very attractive return relative to the capital that we invested and are the first priority will be to get the transaction closed as you saw in the release around the deal.

Mike Mcdonnell: And the first priority will be to get the transaction closed. As you saw in the release around the deal, the proceeds will come in gradually over time. And so the first priority would be to get the transaction closed.

The proceeds will come in gradually over time and so the first priority would be to get the the transaction closed and we will continue to explore all of our options around BD deals of all sizes.

Mike Mcdonnell: And we'll continue to explore all of our options around BD, deals of all sizes, and we will continue our share buyback program as well. And the pipeline remains robust.

And we will continue our our share buyback program as well and the pipeline remains robust we look at a lot of opportunities and you know we have an extremely healthy balance sheet as Michel said Ah and this will only make it healthier.

Michelle Vounantzos: We look at a lot of opportunities, and we have an extremely healthy balance sheet, as Michelle said, and this will only make it healthier. And Robyn, if I may, an important consideration is now whether we can create more value with our biosimilar portfolio. More products, more geographies.

And Robin if I may is an important consideration is that if we can create more value without biosimilars as well.

Audio.

More products more geographies.

Michael Yee: Okay, we'll go ahead and take our next question from Michael Yee. Thank you. Good morning.

Okay. We'll go ahead and take our next question from Michael Yee with Jefferies.

Michelle Vounantzos: I guess my question is in regards to Adahelm and what you are actively doing to try and change the NCD decision. And again, to reiterate, if it's not changed dramatically, you guys would look to cut further expenses. So can you talk about what that would entail and under what scenario that might change?

Thank you good morning.

I guess my question is in regards to out of home or what you are actively doing to try and change the NCD decision and again to reiterate if it's not changed dramatically.

You guys would look to cut further cut expenses. So can you talk about what that would entail and under what scenario that might change for example, bandwidth positive maybe just outline the thoughts and the roadmap for <unk> in 2022. Thank you.

Michelle Vounantzos: For example, if the ban was positive, maybe just outline the thoughts and the roadmap for Adahelm in 2022. Thank you. Thank you, Mike.

Thank you Mike I will get started and then my colleagues will come in.

Michelle Vounantzos: I will get started, and then my colleagues will come in. First of all, we take into account with a lot of caution all the areas of focus that CMS has communicated. And based on those, we look at all the initiatives on the way in order to scientifically fulfill the question they have: being on the benefits-risk, being on area, being on disparity.

First of all we take into account with a lot of cushion or the areas of focus that our CMS has communicated and based on those we look at all the initiatives on the way you know the two scientifically fulfill the question they have being on the business is risk being on ARIA.

<unk> been on disparity and we have a lot going on.

Michelle Vounantzos: And we have a lot going on from interventional studies, embarking on, and envisioning on top of phase three. Now is the time, together with CMS, to engage in a broad real-world evidence set of initiatives already on the way, like our Care AD, but we are contemplating even more. That could be a disease registry and more. So we are engaging with CMS constructively, demonstrating empathy, you know, to try to find a path forward that will be best for patients. Alisha?

From Interventional studies, and Bakken envision on top of the phase III.

And now the time together with CMS to engage into a broad a.

Real World evidence set of initiatives already underway like Ikea a D. But we are contemplating even more that could be a disease registry and more so we are engaging with.

With CMS constructively, demonstrating empathy you know to try to find a path forward that would be the best for patients.

Alisha Alaimo: Yes, thank you, Michelle, and hello, Michael. Thank you for the question. In regards to what we've been doing as an organization during the past three weeks, we have met with CMS to share our perspective and answer any of the questions that they have. And you will see that we will be submitting our in-depth comments in the coming days, obviously during this comment period. In parallel, we've also been educating physicians and policymakers and advocates about what this would actually mean for patients. I think a lot of people, as you've seen, have been quite confused by the draft NCD and what a CED actually means to them.

Alicia Yes, thank you Michelle and Hello, Michael Thank you for the question in regards to what we've been doing as an organization. During the past three weeks, we have met with CMS to share our perspective and answer any other questions that they have and you will see that we will be submitting our in depth comments in the coming days obviously during.

This comment period in parallel we've also been educating physicians and policymakers and advocates about what this would actually mean for patients I think a lot of people as you've seen have been quite confused by the draft NCD and what a C E D actually means to them and as you've likely seen many stakeholders have had similar concerns so we.

Alisha Alaimo: And as you've likely seen, many stakeholders have had similar concerns. So we've seen patients, patient advocates, HCPs, other manufacturers, and industry groups like Bio and Pharma also sharing their perspectives quite publicly. And there is one week remaining for the open comment period, and we are very much looking forward to this final decision in April so the community has more clarity. Where you may have seen over, I think as of today, there are around 26, 2700 public comments submitted to CMS, and again, with still one week remaining.

<unk> seen patients patient advocates hcp's other manufacturers and industry groups like bio and pharma also sharing their perspectives quite publicly and there is one week remaining for the open comment period and we are very much looking forward to this final decision in April so that the community has more clarity and that brings me now to the comment period, where you.

You may have seen over and I think as of today. It's around 26 2700 public comments submitted to CMS and again was still one week remaining I think it's important for everyone to remember and to keep in mind that CMS indicated on their website that the most helpful comments are ones that site published clinical evidence and when you actually separate them.

Alisha Alaimo: I think it's important for everyone to remember and keep in mind that CMS indicates on their website that the most helpful comments are ones that cite published clinical evidence. And when you actually separate the comments out from the dementia specialists, you will see that many of them are against this draft NCD. In prior comment periods, we have seen that.

Comments out from the dementia specialists, you will see that many of them are against this draft NCD with prior comment periods. We have seen that in the final days you tend to see more letters that are heavily researched and referenced and as I've said before you will see ours being posted in the coming days. So we do remain engaged actively.

Alisha Alaimo: In the final days, you tend to see more letters that are heavily researched and referenced, and as I've said before, you will see ours being posted in the coming days. So we do remain engaged actively with all stakeholders. We do remain engaged, obviously, still with CMS, and we are looking forward to the final decision in April. And so, Mike, in your question on the cost measures, as we said in our prepared remarks, our guidance does assume that the final NCD would allow for meaningful patient access over time. That does not translate into material revenue in 2022, but it would create, you know, more open access than what we saw in the draft.

With all stakeholders, we do remain engaged obviously still with CMS and we are looking forward to the final decision in April .

And so Mike and your question on the cost measures you know as we said in our prepared remarks.

You know our our guidance does assume.

That the final NCD would allow for meaningful patient access over time that does not translate into material revenue in 2022, but it would create a you know.

More open access and what we saw in the draft should that not be the case, we are doing scenario planning now.

Mike Mcdonnell: Should that not be the case, we are doing scenario planning now on the cost measures. You know, we mentioned our plan for a 500 million dollar cost measure, of which we estimate we will get 350 million dollars in 2022, which is assumed in our guidance. And we will invest about 200 million of that in a variety of different initiatives, including product launches. And in the event that we have a much more restrictive NCD, we will need to look at the elements of that.

On the cost measures, we mentioned our plan of a $500 million.

Cost measure of which Ah, we estimate we will get $350 million in 'twenty.

22, which is assumed in our guidance and we will invest about $200 million of that in a variety of different initiatives, including product launches and are in the event that we have a much more restrictive M. C. D. We will need to look at the elements of that we certainly will be flexible and looking at allocating resources between age of home and Mccann a mab we mentioned in our.

Mike Mcdonnell: We certainly will be flexible in looking at allocating resources between AgiHelm and Leucanomab. We mentioned in our SG&A that it's assumed that we have a 400 million dollar AgiHelm support estimate, and we obviously would take a hard look at that as well. Other costs we could take out in order to offset any potential impacts on, you know, inventory, potential write-downs, and excess capacity charges, which are not reflected in our guidance.

SG&A, it's assumed that we have a $400 million Ajay home support.

Estimate and we obviously would take a hard look at that as one of the other costs, we could take out in order to offset any potential impacts on <unk>.

Inventory potential write downs and excess capacity charges, which are not reflected in our guidance.

Michelle Vounantzos: And Mike, as a closing comment, if I may, as a company, we are fully committed to delivering on this data, being the international study, being the real-world ones, and we believe that this extensive data generation will adequately address any open question raised by CMS. And we'll go ahead and take our next question from Matthew Harrison with more. Good morning.

And Mike as a closing comment if I may as a company. We are fully committed to deliver on these data being the interventional study being the real world ones and we believe that these extensive data generation will adequate adequately address any open questions raised by CMS.

Okay.

And we'll go ahead and take our next question from Matthew Harrison with Morgan Stanley .

Matthew Harrison: Thanks for taking the question. I was hoping you could just clarify on the tech for the EU contribution to guidance and what we're going to learn this year which may either help us understand it. That revenue, is it a risk this year or if you could continue to expect to see it, and that can be a potential outside tip to your current guidance? Thanks.

Great. Good morning, Thanks for taking the question I was hoping you could just clarify on the temporary EU contribution to guidance and.

What we're going to learn this year, which may either help us understand that.

That revenue is at rest of this year or if you could continue to expect to see it and that could be potential upside to your current guidance.

Yeah.

Mike Mcdonnell: Sure, Matthew, you know, thanks for the question. And, um... We believe there is the potential for generic entry at some point in the first half of 2022. We do believe that we're entitled to market protection, and we're certainly going to do all we can to assert that, but we did reflect in our guidance, as we mentioned in our opening remarks and in our press release, that we do assume that there could be some generic entry somewhere in the first half of 2022.

Sure Matthew.

Thanks for the question and.

You know there is a.

We believe there is the potential for generic entry at some point in the in the first half of 2022, we do believe that we're entitled to market protection, and we're certainly going to.

Do all we can to assert that but we did reflect in our guidance as we mentioned in.

In our opening remarks and in our press release that.

We do assume that there could be some generic entry somewhere in the first half of 2022.

Mike Mcdonnell: So this is Assumption Driven, at the same time as for tech, at the same time as we have already communicated, we are launching the emergency in 20 markets within the EU. And we'll go ahead and take our next question. Umer Raffat with Evercore. Hi guys, thanks for taking my question. I wanted to focus on then 24-01 for a second, and really just two questions there.

So this is our assumption driven at the same time foot thick at the same time as already communicated we are launching boomer routine 20 markets within the EU.

And we'll go ahead and take our next question from Nomura <unk> with Evercore ISI.

Mike Mcdonnell: One, can you help us understand the magnitude of misdialysis in phase three? Because I recall you increased the sample size by 200 patients, and I wonder if that percentage increase versus the original sample size reflects the amount of misdialysis.

Hi, guys. Thanks for taking my question I wanted to focus on down 24 to one for a second.

Really just two questions there one.

Can you help us understand the magnitude of missed visits you know the phase III because I recall you increase the sample size by 200 patients and I wonder if that percentage increase versus the original sample size reflects the amount of Mr. Ofer <unk>.

Secondly, the primary analysis is that I T T or will that.

Screen out rapid progressive or certain subsets of patients based on some of the learnings from agile health. Thank you very much.

Umer Raffat: And secondly, the primary analysis, is that ITT, or will that screen out the rapid progressives or certain subsets of patients based on some of the learning from Agile? Thank you very much, Priya.

Korea.

[laughter].

Priya Singhal: Thank you for the question. So, just stepping back, I just want to reiterate that Clarity AD will read out in Q3 this year, and we remain very excited about that outcome. I cannot really comment on the details of the statistical analysis plan, but what I can tell you is that any learnings that can be incorporated have been incorporated, and that the primary endpoint remains the CDR sum of boxes.

Thank you for the question. So just stepping back I just want to.

I reiterate that clarity E D will readout in.

In Q3, this year and we remain very excited about that outcome I cannot really comment on the details of the statistical analysis plan, but what I can tell you is that any learnings that can be incorporated have been incorporated and that are the primary end.

Priya Singhal: So we look forward to the readout. Thank you. And we'll go ahead and take our next question from Marc Goodman with SBB. Yes, good morning.

Point remains the C D. Our sum of boxes. So we look forward to the readout. Thank you.

And we'll go ahead and take our next question from Marc Goodman with F E D.

Inc.

Marc Goodman: So look, there's two key events, right? We have the CMS decision that we're waiting on. And then, obviously, we have the Leucanomab data in the third quarter. So just kind of wondering your thought process if the first one goes disappointing, do you make the changes?

Yes. Good morning, So look there's two key events right. We have the CMS decision that we're waiting on and then obviously, we have the or kind of a data in the third quarter. So just.

Just kind of wondering your thought process of it.

If the first one goes disappointing do you make the changes or are you waiting for the kind of outdated because you know we're kind of wondering whether youre going to break down.

There's infrastructure before you get that data and how much business development is being impacted by those two decisions. I mean are you looking at these BD opportunities right now regardless of what happens with those events.

Michelle Vounantzos: Or are you waiting for the Leucanomab data? Because, you know, we're kind of wondering whether you're going to break down the Alzheimer's infrastructure before you get that data? And how much business development is being impacted by those two decisions?

Mike Mcdonnell: I mean, are you looking at these BD opportunities right now, regardless of what happens with those events? Thanks. Thanks for the very fair question. As I communicated, we will remain as a team, agile and flexible. And obviously, we will do everything we can to preserve our operating results while delivering on the strategy. We do believe in LECA, but we will take some aggressive steps should the NCD remain in its current form.

Thanks for the very fair question.

Communicated we will remain as a team a jail and flexible and obviously, we will do everything we can to preserve our operating results while delivering on the strategy. We do believe in later, but we will take some aggressive steps should be NCD remain.

On the on the current form.

Mike Mcdonnell: And I think, Marc, I would just add that, you know, the amount of our infrastructure we would allocate to licanumab versus not, etc., that really depends on what the final NCD says. It's across the entire class, and that would really depend on the specifics of how the final NCD reads.

And I think Mark I would just add that you know.

You know how much of our infrastructure, we would allocate to the Cana mab versus not et cetera that really depends on what the final NCD says it's across the entire class and that would really depend on the specifics of how the final NCD reads I would say on BD. We will continue our BD efforts, regardless those are ongoing and they're always on.

Salveen Richter: I would say on BD, we will continue our BD efforts regardless. Those are ongoing, and they're always ongoing. And we'll go ahead and take our next question from Salveen Richter. Good morning.

Okay.

Yeah.

And we'll go ahead and take our next question from Victor <unk> with Goldman Sachs.

Michelle Vounantzos: Thanks for taking my call. In light of the recent opt-in for the Roach compound, does this signal a greater structural move into oncology? And are there any other areas you're looking at as you pursue VD?

Good morning, Thanks for taking my question.

In light of the recent opt in for the Roche compound does this signal a greater structural move into oncology and are there any other areas youre looking at as you pursue BD.

Corey Casimov: No, I mean, it's a continuation of the very good partnership that we have had with Genentech since Retriximab, and we have benefited from a remarkable cash flow contribution that we all appreciate, even now, even if they are biosimilars. So it's a continuation; it's not a shift of strategy. I communicated the four pillars of growth, and we remain focused on those, and we believe that we are set for long-term shoulder value generation by sticking to, staying the course, and delivering on those. And we'll go ahead and take our next question from Corey Casimov with JCPenney. Hey, good morning, guys. Thanks for taking the time to answer the question. I wanted to follow up on the Phase 3 Leucanomab study.

No I mean, it's a continuation of the offer the very good partnerships that we have with Gentex since rituximab and we have benefited from me if a basketball or cash flow contribution that we all appreciate and even now even if they have but you'll see me those so it's a continuation it's noticed.

So strategy I communicated the four pillars of growth and we remain focused on those and we believe that we have set for long term shoulder value generation by sticking by staying the course and delivering on those.

And we'll go ahead and take our next question from Macquarie <unk> with Jpmorgan.

Hey, good morning, guys. Thanks for taking the question I wanted to follow up on the Phase III <unk> study and can you comment on the enrolled patient population in terms of adequate representation for underrepresented communities that may address the CMS concerns you spoke to and just with regards to Mike's comment you just made on N C D and waiting waiting for this data.

Priya Singhal: And can you comment on the enrolled patient population in terms of adequate representation for underrepresented communities that may address the CMS concerns you spoke to? And just with regard to Mike's comment you just made on NCD and waiting for this data, wouldn't it be your expectation that a final NCD could be changed if we have robust, positive Phase 3 results from other Alzheimer's programs later in the year? Thank you. Priya?

Wouldn't it be your expectation that a final NCD could be changed if we have a robust positive phase III results from other Alzheimers programs later on in the year. Thank you.

Yeah.

Priya Singhal: Yes, thank you for the question. I think that Esai will comment on the underrepresented population percentage, but it is actually very robust, and we are very encouraged by the efforts made to include this population in the clarity AD with regard to the outcome of the NCD and how it might impact the Lecana map. I think that that remains to be seen currently. It is a class, you know; the NCD is addressed. We are addressing the entire class, but we believe that there is, you know, hope at the end of the road here. So we look forward to seeing the final outcome in April. Thank you.

Yes. Thank you for the question I think that ESI will comment on the underrepresented population percentage, but it is actually very robust and we are very encouraged by the efforts made to include this population and the clarity a D with regards to the outcome.

Some of the N C D and how it might impact Mccanna map I think that that remains to be seen currently it is a class a you know the.

N C. D is addressing the entire class, but are we believe that that is you know there is hope at the end of the road here. So we look forward to seeing the final outcome in April . Thank you. So I think that we all have to do a better job.

Michelle Vounantzos: So I think that we all have to do a better job, including the other population, unfortunately affected with a high level of incidence for the disease in intervention studies and real world studies. And this is what we are doing. And I think I hope that this will be well received by CMS. And we did communicate that for the envisaged study, we aim to reach from 16 to 18% of the diverse population, the same in the real world with I care AD.

Including Devers population, Unfortunately affected with the high level of incidence of the disease.

Intervention studies and real World Studies and this is what we are what we are doing and I think I hope that this would be a well received by by CMS and we did communicate that for the envision study, we aim to reach from 16% to 18% of diverse population the same in real world with Ikea.

Michelle Vounantzos: So moving forward, we'll get much more data, and the same for the other real world evidence opportunities that we are sharing with CMS. And we'll go ahead and take our next question from Jay Olson with Austin. Oh, hey, thanks for the update and for taking the question. Since a self-administered sub-Q formulation of Aduhelm could fall under the purview of Medicare Part D and therefore lie outside the scope of a potential CED if it's finalized, could you comment on where Biogen stands with regard to the development of sub-Q Aduhelm? I think you did a bioequivalent study a few years ago.

So moving forward, we'll get we'll get much more data and the same for the older real world evidence opportunities that we are we are sharing we did with CMS.

And we'll go ahead and take our next question from Jay Olson with Oppenheimer.

Jay Olson: So is sub-Q something that could be a relatively near-term option? So we will certainly comment on the life cycle management opportunity, and Priya will say a few words. But I just want to outline and come back to the first area of concern communicated in the draft NCD, which is basically benefits, risk, and questioning the hypothesis and the class in terms of mode of action and positive impact on patients. And this is obviously independent from any formulation.

Oh, Hey, thanks for the update and for taking the question.

Since the self administered subcutaneous at home could.

All under the purview of Medicare part D and therefore, my outside the scope of a potential C. E. D. It's finalized could you comment on where Biogen stands with regard to the development of a sub Q auto home I think you did a bio equivalent study a few years ago. So it is so cute something that that could be a relatively near term option.

Yeah.

So we will commence its only on the lifecycle management opportunity pre I will say a few words, but I just want to outline and come back to the first area of concern communicated in the draft and she did an NCD, which is basically benefit risk and questioning the hypothesis and the plus.

In terms of motor function and positive impact on the patients and these obviously he's a he's independent from and formulation.

Yeah.

Michelle Vounantzos: Priya. Thank you for the question and thanks, Michelle, for those comments. We will definitely be building on our prior learnings in adjuhelm subcutaneous formulation development. And we are currently engaging with regulators on having a robust plan forward for this development. So that is ongoing. Thank you, and we will take our... Thank you for watching. We're Think of America. Good morning, everyone. This is Jason on for Jeff.

For the question and thanks, Michelle for those comments.

We will definitely be building on our prior learnings are in and you have a subcutaneous formulation development and we are currently engaging with regulators on having a robust plan forward for this development so that is ongoing.

Thank you.

Yeah.

And we will take our next question from Geoff Meacham with Bank of America.

Good morning, everyone. This is Jason on for Jeff. Thanks, So much for taking our questions on the color I wanted to connect the dots a little bit on your earlier comments about capital allocation specifically what are the priorities here and what is going to be the deciding factor is it candidly going to be the.

Priya Singhal: Thanks so much for taking the time. I wanted to connect the dots a little bit on your earlier comments about capital allocations. Specifically, what are the priorities here and what is going to be the deciding factor? It is obviously going to be.

Jason: Final NCD decision in terms of how, Anderson, Matt Adoud, or our activities. Yeah, Jason, thanks for the question. It's Mike speaking.

A final NCD decision in terms of how.

Things are met it out or our activities ongoing thank you.

Mike Mcdonnell: And, you know, just reiterating a bit of what we said before, we are constantly looking at options around BD, deals of all sizes, different opportunities, early stage, late stage across, you know, it runs the gamut, primarily focused on neuroscience, which is our focus. And we will continue to do that. And we will continue to invest in our pipeline. And that is regardless of the outcome in the NCD.

Yeah, Jason Thanks for the questions, Mike speaking and you know just reiterating a bit of what we said before we are constantly looking at options around BD deals of all sizes different opportunities.

Early stage late stage across you know it runs the gamut, primarily focused on neuroscience, which is our focus.

And we will continue to do that and we will continue to invest in our pipeline and that is regardless of the outcome on the on the NCD and it's regardless of the fact that we have now incremental.

Mike Mcdonnell: And it's regardless of the fact that we now have incremental cash if we get the, you know, once the Samsung transaction closes, so I think we have a healthy balance sheet that's unchanged at 4.7 billion of cash and marketable securities at the end of the year, a modest amount of net debt, less than one turn, and we have a billion dollar revolver that's undrawn. So we will continue to actively pursue BD; that strategy is unchanged. And I don't see a significant shift in strategy.

Cash if we get the you know once the Samsung transaction closes. So I think we have a healthy balance sheet, that's unchanged $4 7 billion of cash and marketable securities at the end of the year, a modest amount of net debt.

Less than one turn and we have $1 billion revolver. That's undrawn. So we will continue to actively pursue BD that strategy is unchanged and I don't see a significant shift in strategy.

Brian Abrahams: In terms of, you know, the NCD outcome or the Samsung transaction or anything else, we will continue to explore all of our options around BD actively, and we are doing that. And we will take our next question from Brian Abrahams with RBC Capital Markets. Hey guys, thanks so much for taking my question. On Leucanomab, just a couple of quick follow-ups on that.

In terms of NCD outcome, or Samsung transaction or anything else. We will continue to explore all of our options around BD actively and we are doing that.

And we will take our next question from Brian Abrahams with RBC capital markets.

Hey, guys. Thanks, so much for taking my question on Makena map just a couple of quick follow ups on that just can you give us a sense of any COVID-19 impact to data collection in that study are your plans for accelerated filing for accelerated.

Priya Singhal: Can you give us a sense of any COVID impact on data collection in that study? Are your plans for accelerated filing for accelerated approval still intact in light of the NCD? And any modifications that you might need to make to infrastructure upon success to accommodate for the more frequent dosing versus Adderall?

Salaried and approval still intact in light of the NCD and any modifications that you might need to make to infrastructure upon success to accommodate for the more frequent dosing versus that amount.

Yeah.

Priya Singhal: Thanks. Thank you for the question. So I can say that, like anamab, it is on track to read out as previously communicated. This will be in Q3 of 2022. So at this point, we don't expect any changes to that along with e-size.

Thank you for the question. So I can say that our Lacana mob is on track to read out as previously communicated this will be in Q3 of 2022. So at this point, we don't expect any changes to that along with ESI. So that's number one and second I think that.

There are no other changes to communicate on the outcomes or on the measures that have been included in the study. So is that another question that I'm missing here.

Yeah.

Yeah.

Priya Singhal: So that's number one. And second, I think that there are no real other changes to communicate on the outcomes or on the measures that have been included in the study. So is there another question that I'm missing here? Okay, patient follow-up due to the pandemic. I know it's a global study with a lot of sites.

Okay.

Two follow ups due to the pandemic I know, it's a global study with a lot of sites.

Priya Singhal: Yes, and I think that it's been managed really well. So I don't expect any delays in terms of the readouts. And I think your second question was about accelerated approval. As you know, they have breakthrough designation on this product, and there will be a filing. We are intent on filing the filing. Many components have already been filed.

Yes, and I think that has been managed really well. So I don't expect any delays in terms of the Readouts and I think your second question was about accelerated approval as you know they have breakthrough we had breakthrough designation on this product and there will be a filing we are intent on filing the filing many components have already been <unk>.

Priya Singhal: And once the filing is complete, that will be communicated. I think that the most important thing to remember here is that while it might go in as an accelerated filing, the confirmatory study for Leucanomab is the Clarity AD trial, which will read out this year. So I do expect the Clarity AD confirmatory study to read out during the review period for this program. I hope that helps.

Filed and once the filing is complete that will be communicated I think that the most important thing to remember here is that while it might go in as an accelerated filing the console Mitre study if all kind of map is the clarity E D, which will read out this year. So I do expect the clarity a decline for me.

<unk> study to read out during the review period for this program I hope that clarifies.

Michelle Vounantzos: I just want to outline one small example of how we are working very closely with the SI to find synergies in terms of the capabilities of both organizations and how we can optimize the value for both compounds. I think we have time for one more question, and we will take our leave. Salim Syed from Missou, Great

I just wanted to outline once more that we are working very closely with ESI.

The finding synergies in terms of capabilities of both organization and how we can optimize the value for both compounds.

I think we have time for one more question.

And we will take our last question from Celine <unk> from Mizuho.

Salim Syed: Thanks so much for the question, guys. Michelle, I wanted to address a bit of an elephant in the room, and I asked this question constructively, and I hope you can appreciate that. So, obviously, people talk about misalignment between management and the board at Biogen, and business development is obviously a key focus for you guys, and I appreciate all the commentary that you guys are looking at deals of all sizes, early stage, late stage, but in your view, is there a misalignment here that would make meaningful BD difficult in 2022, or has something changed that we can now expect that to occur? Thanks so much.

Great. Thanks, so much for the question guys.

Michelle I wanted to address it a bit of an elephant in the room and I asked this question constructively and I Hope you can appreciate that.

So I think when people talk about misalignment between.

Management and the board at Biogen and business development is obviously, a key focus for you guys and I appreciate all the commentary.

You guys are looking at deals of all sizes early stage late stage, but in your view is there a miss alignment here that.

It would make it meaningful BD something difficult in 2022 or or has something changed that we can now expect that to occur. Thanks. So much.

Michelle Vounantzos: Thank you, Salim, for giving me the opportunity to answer this question. I will invite you to look at all the BD deals that were done during the past five years versus the previous five years. And I think this will give you an idea about the alignment. But it doesn't mean that it's an easy road.

Thank you sell in for giving me the opportunity to answer the question I will invite you to look at all the BD deals that were performed during the past five years. This is the previous five years and I think this will give you a an idea about the alignment.

But it doesn't mean that it's an easy roads. It means that we are challengers management, we really need to have open discussion between the board and management to secure that we in the best position to allocate capital, but we were able and we continue to be able to work together in order to move forward.

Michelle Vounantzos: It means that we are challenged as management. We really need to have open discussions between the board and management, you know, to ensure that we are in the best position to allocate capital. But we were able, and we continue to be able to work together in order to move forward the organization in the best strategic position, the way we believe we are today compared with the period before. Look at the four pillars of growth.

Organization in the best strategic position the way we believe we are today compared with the period before look at the four pillars of growth look what we're doing with the Biosimilars, we are and reaching the cash flow generation opportunity and even if we are in the unfortunate situation of losing their it takes them out of my hand to treat.

Michelle Vounantzos: Look what we are doing with biosimilars. We are enriching the cash flow generation opportunity. And even if we are in the unfortunate situation of losing the ethics, you might want to take FIDERA and delay the launch by almost a year.

Iraq and the delayed launch by almost two you're eventually if NCD is positive for <unk>. We are still in the multibillion cashflow generation opportunity we work together very closely.

Michelle Vounantzos: Eventually, if NCD is positive for Aduhelm, we are still in the multi-billion cash flow generation opportunity. We work together very closely. So, I would really like to reiterate that we are committed to engaging with CMS and all the other stakeholders with the hope of finding an appropriate path for immediate patient access to Aduhelm.

So thank you all for this for this good engagement and I would like really to Haiti or rigs that we are committed to engaging with CMS and all the other stakeholders with the hope of finding an appropriate path for immediate patient access to how do you think.

Madison: Thank you all for your attention today. This concludes today's call. Thank you all for your participation. You may now disconnect.

<unk> you all for your attention today.

This concludes today's call. Thank you all for your participation you may now disconnect.

Operator: [music] Music playing, E. E. E. E. E. E. E.. ... Music playing, Dr. Justin Trudeau, Dr. Justin Trudeau, Dr. Justin Trudeau, Thank you for watching, please subscribe, like, and turn on the notification bell. [inaudible] Dr. Justin Trudeau, Dr. Justin Trudeau, Dr. Justin Trudeau, , , , , , , , , Thank you for watching! E. E. E. E. E. E. E. Steve Miller, and I'm I'm I'm I'm I'm I'm I'm I'm, Music playing, E. E. E. E. E. E. E. E. E. R.R.

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Yes.

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Operator: Dr.. .. ... Dr. Justin Trudeau, Dr. Justin Trudeau, Dr. Justin Trudeau, , , , , , , , , , Dr. Justin Trudeau, Dr. Justin Trudeau, Dr. Justin Trudeau, Dr. Prima, Dr. Prima, Dr. Prima, Dr. Prima, Nathanael Hickman, and and and and and and and and and and and and and [inaudible] Thank you for watching! E. E. E. E. E. E. E. E. E. Hey, everyone. You.

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Yeah.

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Yeah.

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Yeah.

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