Q3 2021 Biogen Inc Earnings Call

Shelby: Good morning. My name is Shelby, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen third quarter earnings call and Financial Update. All lines have been placed on mute to prevent any background noise.

Good morning My name.

Shelby and I will be your conference operator today at this time I would like to welcome everyone to the Biogen third quarter earnings call.

And financial update all lines have been placed on mute to prevent any background noise.

Shelby: After the speaker's remarks, there will be a question and answer session. If you'd like to ask a question during this time, simply press star 1 on your telephone keypad. Please limit yourself to one question to allow all participants time for questions.

MS Sugar the Speakers' remarks, there'll be a question and answer session. If you'd like to ask a question. During this time simply press star one on your telephone keypad. Please limit yourself to one question to allow all participants time for questions. If you require any further follow ups you May press star one again to rejoin the queue. Thank you I would like to now.

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

This conference over to Mr. Mike <unk> Investor Relations. Mr. <unk> you may begin.

Mike Hinke: Good morning, and welcome to Biogen's third quarter 2021 earnings. Before we begin, I encourage everyone to go to the Investors section of Biogen.com to find the earnings release and related financial tables, including our GAAP financial measures and a reconciliation of the GAAP to non-GAAP financial measures that we will discuss today. Our GAAP financials are provided in Tables 1 and 2, and Table 4 includes a reconciliation of our GAAP to non-GAAP financial results. We believe non-GAAP financial results better represent the ongoing economics of our business and reflect how we manage the business internally.

Good morning, and welcome to Biogen's third 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 include.

<unk>, 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 we.

We believe non-GAAP financial results better represent the ongoing economics.

<unk> of our business and reflect how we manage the business internally.

Mike Hinke: 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 that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.

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.

These statements are subject to certain risks and uncertainties.

And our actual results may differ materially.

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

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

Today, we will be discussing adding him I do home is indicated for the treatment of Alzheimer's disease treatment with that new home 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.

Mike Hinke: This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with aduheim. Continued approval for this indication may be contingent upon verification of clinical benefits in a confirmatory trial or trial. Amihelm 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. AdduHelm 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 plaque observed in patients treated.

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

And can cause serious side effects, including amyloid related imaging abnormalities or ARIA.

<unk> is a common side effect that does not usually cause any symptoms.

Treated with it can be serious.

I do home can cause serious allergic reactions.

The most common side effects include ARIA headache and fault.

Mike Hinke: 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 Vunazzo; Dr. Al Sandrock, Head of Research and Development; and our CFO, Mike McDonald. We will also be joined for the Q&A portion of our call by Alisha Alaimo, President of our U.S. organization, and Toby Ferguson, Head of Neuromuscular Development. 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.

Please see full prescribing information and patient medication guide at <unk> Dot com.

On today's call I am joined by our Chief Executive Officer Michel.

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Dr Al Sandrock 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 and Toby Ferguson head of neuromuscular development.

As a reminder, during the Q&A.

Sheldon of the call we kindly ask that you limit yourself to one question.

I will now turn the call over to Michele.

Michelle Vunazzo: Good morning everyone, and thank you for joining us. We continue to view 2021 as a transformational year for our company. We are satisfied with our 2021 pipeline accomplishments and the continued operational performance of the company. However, we are obviously disappointed with the delayed uptake of AdreHelm in the U.S. We had solid financial results for the third quarter, with total revenue of $2.8 billion and non-capital EPS of $4.77. Biogen has continued to execute well and demonstrate resilience across MS, SMA, and biosimilars despite competition. Mike will provide more details on our financial results, and I will focus primarily on I.V. Helmet.

Good morning, everyone and thank you for joining US we continue to view 2021 as a transformational year for our company. We are satisfied we dealt with 2021 pipeline accomplishments and.

Hey portion of <unk> operational performance of the company. However, we are obviously disappointed with the delayed uptake of <unk> in the U S.

We had solid financial results for the third quarter, we thought had revenue of $2 8 billion and non-GAAP EPS of $4 <unk>.

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Biogen has continued to execute well and demonstrate resilience across Ms SMA and Biosimilars. Despite competition, Mike will provide more details on our financial results and I will focus primarily on Ivy Hill.

Michelle Vunazzo: We continue to believe in Aduhelm's long-term potential, and this quarter, we continue to progress the launch in the U.S. in anticipation of the reimbursement decision for Medicare patients. We are working through the three near-term challenges we have previously described with a core focus on enabling patient access. Importantly, we have made steady progress on key metrics, but the health care system remains a major bottleneck. In particular, the lack of clarity on reimbursement has delayed patient access to the first treatment, to address the underlying pathology of Alzheimer's disease, which is reasonably likely to predict clinical benefits.

And we continue to believe in that you had in the long term potential and this quarter. We continued to progress the launch in the U S. In anticipation of the reimbursement decision for Medicare patients. We are working through the three near term challenges. We have previously described with.

Our focus on enabling patients access <unk>.

Importantly, we have made steady progress on key metrics for the healthcare system remains a major bottleneck in particular, the lack of clarity on reimbursement has delayed patient access to the <unk>.

The treatment.

To address an underlying pathology of Atlas disease, which is reasonably likely to predict clinical benefit.

Michelle Vunazzo: We look forward to the upcoming Medicare National Coverage Determination expected by next April, which would clarify Medicare reimbursement for the entire class of antibodies directed against amyloid. The NCD is a rigorous process involving a number of consultations, and we understand this is required for this new class of drugs for Alzheimer's. However, keep in mind, this will delay access for many patients by approximately 300 days from approval.

We look forward to the upcoming mid Medicare National coverage determination expected by next April which would clarify Medicare reimbursed.

First men for the entire class of antibodies directed against amyloid. The NCD is a rigorous process involving a number of consultation and we understand this is required for this new class of drugs for zimmers. However, keep in mind this will delay.

But access for many patients by approximately 300 days from approval.

Michelle Vunazzo: Biogen is acting with urgency across the three strategic priorities as we work to support access for patients. First, we are working to improve the community's understanding of our clinical data. As a reminder, the Phase 3 eMERGE study met its pre-specified primary and secondary endpoints, showing a significant reduction in clinical decline. Patients who receive high doses at the helm experience significant benefits on measures of cognition and function, including activities of daily living.

Biogen is acting with urgency across the three strategic priorities as we work to support access for patients.

First we are working to improve.

Prove the community's understanding of our clinical data.

As a reminder, this phase III emerge study met its prespecified primary and secondary endpoints showing a significant reduction clinical decline.

Patients who receive high dose that you had them experience significant benefits.

On measures of cognition and function, including activities of daily living.

Michelle Vunazzo: Although the other Phase III study engaged did not meet its primary endpoint, analysis for both studies demonstrated that higher exposures to adrenaline were associated with greater reduction in clinical decline. We have submitted these Phase III results to a top-tier journal with a manuscript now under peer review, in addition to all the publications on our data. And we will continue to generate additional data.

Although the other phase III study engage he did not meet its primary endpoint analysis for both studies demonstrated that high your exposure to what the Hell were associated with greater reduction in clinical decline.

We have submitted these phase III results to a top tier journal, we the manuscript now under peer review.

<unk> two older publication on our data.

And we will continue to generate the additional data we launched <unk> a D. The first real world observational phase four study.

Michelle Vunazzo: We launched iCARE-AD, the first real-world observational phase 4 study in Alzheimer's disease designed to evaluate the safety and effectiveness of algae helm in clinical practice. We have submitted a draft protocol to the FDA for the required phase 4 confirmatory study. We have fully resourced this study with the goal of completing it ahead of schedule.

Zheimer disease designed to evaluate the safety and effectiveness of had you held them in clinical practice.

We have submitted a draft protocol to the FDA for the required phase four confirmatory study.

We have fully resource this study with the goal of complete.

<unk> ahead of schedule.

Michelle Vunazzo: In addition to presenting your held data at this year's AIC meeting, the embarked baseline data have been accepted for presentation at next month's CITAD meeting, which will provide important information regarding the impact of a gap in treatment. Furthermore, we also plan to present important new plasma phosphorylated tau data from Emerge and Engage that highlight the downstream effect of aducanumab as soon as possible. Overall, the approval of AdjuHelm was supported by a significant data set from eight studies with more than 3,000 patients, and we look forward to continuing to generate additional data to support the clinical profile of AdjuHelm. Our second priority is to appropriately support the development of the necessary infrastructure.

In addition to presenting at your health data additions AIC meeting.

<unk> baseline data have been accepted for presentation at next month's Seatac meeting, which will provide important information regarding the impact of.

The gap in treatment.

Furthermore, we also plan to present important new plasma phosphor related Tau data from emerge and engage that highlight the downstream effect of agitated mab as soon as possible.

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<unk> was supported by a significant data set from eight studies with more than 3000 patients and we look forward to continuing to generate additional data to support the clinical profile of <unk>.

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Our second priority is to appropriately support development of the necessary.

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Michelle Vunazzo: At launch, we established a program with LabCorp and Mayo Clinic Laboratories for amyloid beta-CSF testing. Throughout the quarter, we saw a continuous increase in the number of patients utilizing this program. We also continue to advocate for reimbursement of amyloid PET imaging. Furthermore, we are continuing to see additional sites come online, with approximately 120 sites now treating patients with AdjuHelm and many more sites in progress. And third, to clarify reimbursement, as we wait for the NCD decision for this class of antibodies, we have obtained the permanent adjuvant J-code, becoming active in January of next year, and we hope this will help simplify the coding process for healthcare providers.

At launch we established a program with Labcorp and Mayo clinic laboratories for amyloid beta CSF testing throughout the quarter, we saw a continuous increase in the number of patients utilizing this program. We also continue to advocate for reimbursement.

<unk> of amyloid pet imaging.

Furthermore, we are continuing to see additional sites come online with approximately 120 sites now treating patients with <unk>.

Many more sites in progress.

And third to clarify reimbursement as we wait the NCD decision for this class of antibodies. We have obtained the permanent agile held J code, becoming active in January of next year and hope this will help simplify the cutting process for health care providers.

Michelle Vunazzo: Looking forward, in addition to presenting and publishing the data that I have previously mentioned, the most significant near-term milestone will be the outcome of the NCD for antibodies directed against amyloids. We expect a draft decision in January, followed by a final decision in April of 2022.

Looking forward in addition to presenting and publishing the data that I previously mentioned the most significant near term milestone will be the outcome of the NCD for antibodies directed against amyloid.

We expect a draft decision in January following by a final decision in April of 2020.

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Geoffrey Christopher Meacham: In Alzheimer's, more broadly, our partner, SI, recently initiated the FDA rolling submission for Canima BLA under the accelerated approval pathway following the receipt of breakthrough therapy designation in the U.S. With the anti-amyloid antibodies that are either approved or in late-stage development, Biogen and Essai have the opportunity to provide patients with two out of the four potential options, with the first FDA-approved therapy to address an underlying pathology of The Potential to Bring Le Canemabre to Market, Promising Tau Pipeline Programs such as BIP-80, And with the benefit of digital technologies, we believe Biogen is well positioned to remain a long-term leader in Alzheimer's disease.

In Alzheimer's more broadly our partner <unk> recently initiated the FDA rolling submission for the Panama BLA under the accelerated approval pathway. Following the receipt of breakthrough therapy designation in the U S.

Of the anti amyloid antibodies.

Are either approved or in late stage development Biogen in ASI have the opportunity to provide patients with two out of the full potential options.

With the first FDA approved therapy to address an underlying pathology of Alzheimer's disease.

The potential to bring la <unk>.

Missing our pipeline programs such as <unk>.

And with the benefit of digital technologies, we believe Biogen is well positioned to remain long term leader in Alzheimers disease.

Geoffrey Christopher Meacham: Moving beyond Alzheimer's disease, together with our partners at SAGE, we continue to make progress towards bringing a potential number of therapeutic options to patients suffering from depression. We recently obtained positive data from a Phase II study in Japan, representing the third positive placebo-controlled study for uranolone in MDD. In addition, we announce our plans to initiate a filing in the U.S. Lastly, we recently reported data from the VALOR Phase 3 study of Topherson in ALS.

Moving beyond Alzheimer's disease, together with our partners at Sage, we continue to make progress towards bringing a potential novel therapeutic options to patients suffering from depression. We recently obtained positive data from our phase II study in Japan, representing the third.

Positive placebo controlled study for <unk> hundred one in NPD.

In addition, we announced our plans to initiate a filing in the U S.

Lastly, we recently reported data from the <unk> Phase III study of <unk> in ALS.

Geoffrey Christopher Meacham: Although the VALOR study did not meet the primary endpoint, signs of reduced disease progression across multiple endpoints were observed. We are encouraged by the totality of the evidence and are engaged with regulators on next steps. Following discussion with investigators, bioethicists, and having listened to the voice of patient advocacy groups, we intend to expand the Early Access Program to the broader population of individuals living with SOD1 ALS. We believe these recent developments represent a significant step forward in our goal of transforming Biogen from what was once an MS company to one that is built upon a multi-franchise portfolio across a broad spectrum of neuroscience therapeutic areas. I would now like to turn the call over to Al for a more detailed update on our progress in R&D.

Yes.

Although the vital study did not meet.

Meet the primary endpoint signs of reduced disease progression across multiple endpoints were observed.

We are encouraged by the totality of the evidence and engage with regulators on next steps.

Following discussion with investigators bioethicists and having listened to the voice.

Patient advocacy groups, we intend to expand the early access program to the broader population of individuals living with SRT one <unk>.

We believe these recent developments represent a significant step forward in our goal of transforming transforming biogen.

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<unk> and EMS company to one that is built upon a multi franchise portfolio.

<unk>, a broad spectrum of neuroscience therapeutic areas.

I would now like to turn the call over to al for a more detailed update on our progress in R&D.

Geoffrey Christopher Meacham: Thank you, Michelle, and good morning, everyone. As always, I'd like to start by thanking the Biogen team for their hard work as we continue to advance our R&D program. In addition to key readouts in major depressive disorder and ALS, we hosted an R&D Investor Day to tell you about our pipeline programs, research capabilities, and expertise. I encourage you to take a look at these presentations on our website.

Thank you Michelle and good morning, everyone.

As always.

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

In addition to key Readouts in major depressive disorder, and AOS, we hosted an R&D investor day to tell you about our pipeline programs research capabilities and expertise.

I encourage.

Encourage you to take a look at these presentations on our website.

Geoffrey Christopher Meacham: Let me now start with Alzheimer's disease, beginning with aducanumab. At the R&D Day presentation earlier this month, I underscored the importance of determining the relationship between drug-to-biology as well as biology-to-disease during the drug development process. In late June, FDA made data from the Drug Approval Package of Adjuhalam publicly available.

Let me now start with all Simers disease, beginning with <unk>.

At the R&D day presentation earlier this month I underscored the importance of determining the relationship between drug to biology, as well as biology to disease during the drug.

Doug development process.

In late June FDA made data from the drug approval package of agile helm publicly available but.

Geoffrey Christopher Meacham: The clinical pharmacology review included in the approval package addresses some of these key relationships, as shown in the next two slides. This first slide shows the relationship between the amyloid plaque burden, as measured by the observed SUVR score, versus drug exposure, as measured by the predicted cumulative AUC, both at week 78, taking into account all of the data from both phase 3 trials of aducanumab. The relationship between exposure to azucanumab and amyloid plaque reduction is consistent across the two studies and shows that amyloid plaque burden decreases as cumulative drug exposure increases.

Our clinical pharmacology. We review included in the approval package addresses some of these key relationships as shown in the next two slides.

This first slide shows the relationship.

ZIP between the amyloid plaque burden as measured by the observed SUV, our score versus drug exposure as measured by the predicted cumulative AUC. Both at week 78, taking into account all of the data from both phase III trials of agile can you map.

The relationship between exposure to <unk>.

When you're Mad and amyloid plaque reduction is consistent across the two studies and showed that amyloid plaque burden decreases as the cumulative drug exposure increases.

Geoffrey Christopher Meacham: The next slide shows another figure from the same document, which plots the relationship between the reduction in amyloid plaque burden, as measured by SUVR, and the preservation of clinical function, as measured by the CDR sum of boxes across multiple dose levels of several anti-A-beta antibodies. Studies 301 and 302 are referred to as Study 2 and Study 1, respectively, in the Adjuhelm label.

The next slide shows another figure from the same document which plots the relationship between the reduction in amyloid plaque.

Burden as measured by <unk> and the preservation of clinical function as measured by the CVR sum of boxes across multiple dose levels of several anti a beta antibodies.

That is 301 and 302 are referred to as study two and study one respectively.

<unk> home label.

Geoffrey Christopher Meacham: When viewed together, these data from six different anti-amyloid antibodies show that there is an association between amyloid plaque reduction and a reduction in clinical decline, and that greater degrees of amyloid plaque reduction are needed for a reduction in clinical decline. At the annual AAIC meeting in July, we presented additional data from the eMERGE, ENGAGE, and PRIME trials, which showed that aducanumab treatment led to a reduction in amyloid plaques as well as downstream biomarkers of Alzheimer's disease pathophysiology, and that this also led to a slowing of clinical decline.

When viewed together these data from six different anti amyloid antibodies show that there is an association between amyloid plaque reduction and a reduction in clinical decline.

And that greater degrees of amyloid plaque reduction are needed for a reduction in clinical.

In the line.

At the annual AIC meeting in July we presented additional data from the emerge engage and prime trials, which showed that <unk> treatment led to a reduction in amyloid plaques as well as downstream biomarkers of all Simers disease pathophysiology and that this also led to a.

Slowing of clinical decline.

Geoffrey Christopher Meacham: We are looking forward to presenting more data from our aducanumab trials, including the baseline data from the EMBARQ study at the upcoming CTAD meeting next month in Boston. We're also looking forward to presenting, at the earliest possible opportunity at a scientific venue, new data on plasma P181 tau, reflecting the downstream biological and clinical effects of aducanumab, which I believe will be of great interest to scientists and clinicians. By way of reminder, amyloid plaques containing A-beta protein and neurofibrillary tangles containing phosphorylated tau are the defining pathophysiologic features of Alzheimer's disease.

We are looking forward to presenting more data from our <unk> trials, including the baseline data from the embark study at the upcoming <unk> meeting next month in Boston.

We're also looking forward to presenting at the earliest possible opportunity at a scientific venue.

<unk> new data on plasma <unk>, 181, Tao, reflecting the downstream biological and clinical effects of <unk>, which I believe will be of great interest to scientists and clinicians.

By way of reminder, amyloid plaques containing a beta protein and neuro February tangles containing.

<unk> phosphorylated Tau are the defining pathophysiological features of all Simers disease.

Geoffrey Christopher Meacham: Finally, I'm happy to say that we are on track to soon publish the Phase 3 aducanumab trial results in a major peer-reviewed journal. This quarter, we also submitted a draft protocol for the required Phase 4 confirmatory trial of aducanumab to the FDA. As I have said before, we have fully resourced the study and aim to complete it ahead of schedule.

Finally, I am happy to say that we are on track to soon published the phase III <unk> trial results in a major peer reviewed journal.

This quarter, we also submitted a draft protocol.

Call for the required phase four confirmatory trial of <unk> to the FDA.

As I have said before we have fully resource to study and aim to completed ahead of schedule.

Geoffrey Christopher Meacham: The key goal of the confirmatory study is to ensure that we enroll appropriate numbers of Alzheimer's disease patients from underrepresented populations. It is estimated that by 2030, nearly 40% of all Americans living with Alzheimer's disease will be African American or Latinx, and therefore, having sufficient participation of these communities is especially important to reflect the diversity of the disease in the real world. Through the Phase 4 confirmatory study, as well as iCARE-AD, we aim to provide further evidence of the clinical benefits and risks associated with aducanumab treatment.

The key goal of the confirmatory study is to ensure that we enroll appropriate numbers of all simers disease patients.

<unk> from underrepresented populations.

It is estimated that by 2030, nearly 40% of all Americans living with all Samaras disease will be African American Latinx, and therefore, having sufficient participation of these communities is especially important to reflect the diversity of the disease.

Disease in the real World.

Through the phase four confirmatory study as well as eyecare.

We aim to provide further evidence of the clinical benefits and risks associated with <unk> treatment.

Geoffrey Christopher Meacham: Outside of the United States, we are under regulatory review in multiple geographies, including the EU, where we are actively preparing for a scientific advisory group meeting as part of the CHMP review process. Turning to licanumab, we are looking forward to when we can potentially provide two anti-amyloid antibody options for Alzheimer's disease patients. As previously announced, our collaboration partner EJSAI recently initiated a rolling submission of the Leucanomab data to the FDA for potential accelerated approval. We expect this submission to be complete sometime in 2022.

Outside of the United States, we are under regulatory review in multiple geographies, including.

Including the EU, where we are actively preparing for a scientific advisory group meeting as part of the <unk> review process.

Turning to <unk>, we are looking forward to when we can potentially provide two anti amyloid antibody options for all simers disease patients.

As previously.

Previously announced our collaboration partner <unk> recently.

<unk> initiated a rolling submission of the <unk> data to the FDA for a potential accelerated approval. We expect this submission to be complete sometime in 2022.

Geoffrey Christopher Meacham: Moving to MS, we presented new data at the annual ECTRIMS meeting last week, including primary results from the NOVA Phase 3B study evaluating the efficacy of Tysabri extended interval dosing versus the approved every four weeks. A real-world claims-based analysis of relapse and hospitalization rates in MS patients treated with natalizumab versus ocrelizumab. A new analysis of the Evolv MS2 data focusing on the impact of dose titration on the GI tolerability of Umerity relative to Tecfidera, and data from the MS Path showing that 100% of people with MS treated with natalizumab, interferons, or fumarates achieved an antibody response following COVID-19 vaccination as compared to 40% of MS patients treated with anti-CD20 or S With respect to the introduction of Bumerity in the EU, we were happy to learn of its approval in Switzerland, as well as the positive CHMP opinion, and look forward to the final EMA decision.

Moving to MFS, we presented new data at the annual.

<unk> meeting last week, including primary results from the Novo Phase III <unk> study evaluating the efficacy of Tysabri extended interval dosing versus the approved every four week dosing.

A real world claims based analysis of relapse and hospitalization rates and Ms patients.

Treated with <unk> versus OCA realism app.

A new analysis of the evolve Ms. Two data focusing on the impact of dose titration on the Gi tolerability of <unk> relative to Tech Vadera.

And data from the EMS paths, showing that 100% of people with MFS treated.

With Natalie <unk> Mab Interferons <unk> achieved an antibody response, following COVID-19 vaccination as compared to 40% of Ms patients treated with anti CD 20, or <unk> therapies.

With respect to the introduction of <unk> in the EU, we were happy.

Part of the approval in Switzerland, as well as the positive <unk> opinion and look forward to the final EMA decision.

Geoffrey Christopher Meacham: In neuropsychiatry, we were excited to see the results of the phase two study of ziranolone in major depressive disorder recently completed by Shionogi. The Phase II trial was similar in design to the other studies evaluating xeranilone and MDD and compared 20 and 30 mg doses of xeranilone to placebo in Japanese patients with MDD. The results of this study further support the safety and efficacy profile of zaranolone in that it demonstrated rapid onset and significant reductions in the HAMD17 score at day 3, day 8, and day 15.

In Neuropsychiatry, we were excited to see the results of the phase III study of <unk> alone in major depressive disorder recently completed by Shionogi.

The phase.

Two of our trial was similar in design to the other studies evaluating <unk> alone and MDT and compared 20% and 30 milligram doses of <unk> alone to placebo in Japanese patients with Mds.

The results of this study further support the safety and efficacy profile of <unk> alone in that it demonstrated rapid.

<unk> <unk> <unk> and significant reductions in the Ham D 17 score at day, three day, eight and day 15.

Geoffrey Christopher Meacham: Additionally, while not statistically significant, we see separation from placebo for both the 20 and 30 milligrams of round on treatment arms out to day 57. All adverse events in the study were mild to moderate and consistent with the known safety profile of xeranolone.

Additionally, while not statistically significant we see separation from placebo for both the 20% and 30 milligrams around on treatment arms out to day 57.

All adverse events in this study were mild to moderate and consistent with the known safety profile Libs and ran alone.

Geoffrey Christopher Meacham: The Chianoghi study is now the third double-blind placebo-controlled trial evaluating granulone in MDD where the primary endpoint of the change in the HAMD score at day 15 was met. These results in MDD are in addition to the efficacy of zaranolone in PPD as observed in the Robyn study. Given the consistent results observed across the Zoranolone trials, Biogen and Sage have announced plans to submit an NDA to the FDA in the second half of 2022. The planned initial submission package will be used to seek approval of Zoranolone for the treatment of major depressive disorder, and an additional filing for postpartum depression is anticipated in the first half of 2023.

<unk> study is now the third double blind placebo controlled trial evaluating <unk> alone and rent.

MDT, where the primary endpoint of the change in the Ham D score at.

<unk> was met.

These results in MPD are in addition to the efficacy of <unk> alone in PPD as observed in the Robin study.

Given the <unk>.

Given the consistent results observed across the us around alone trials, Biogen and Sage have announced plans to submit an NDA to.

The SBA in the second half of 2022.

The planned initial submission package will be used to seek approval hubs around alone for the treatment of major depressive disorder.

And an additional filing for postpartum depression is anticipated in the first half of 2023.

Geoffrey Christopher Meacham: Additionally, the CORAL study, designed to evaluate zaranolone as an acute rapid response therapy when co-initiated with standard antidepressant therapy, is now fully enrolled with top-line data expected in early 2022. Moving to neuromuscular disorders, earlier this week, we announced results from the Pivotal Phase 3 study evaluating to a person in people with SOD1 mediated ALS. The Phase III, or VALOR, study utilized a study enrichment approach to stratify participants into faster and slower-progressing cohorts.

Additionally.

<unk> oral study designed to evaluate <unk> alone as an acute as an acute rapid response therapy, one co initiated with standard anti depressant therapy is now fully enrolled with topline data expected in early 2022.

Moving to neuromuscular disorders earlier this week, we announced.

<unk> results from the pivotal phase III study evaluating to a person and people with <unk> mediated ALS.

Phase III or valor study utilize the study enrichment approach to stratify participants into faster and slower progressing cohorts.

Geoffrey Christopher Meacham: We were disappointed to learn that the study did not meet the primary endpoint of a statistically significant change from baseline to week 28 on the ALS functional rating scale in the faster-progressing population. Nevertheless, we did observe encouraging trends favoring the person across multiple secondary and exploratory measures of biological and clinical activity, including assessments of motor function, respiratory function, muscle strength, and quality of life. Moreover, a pre-specified integration of data from the Phase 3 study and its ongoing open-label extension study reinforced these findings and showed that early-to-person initiation led to a slower decline across these measures.

We were disappointed to learn that.

The study did not meet the primary endpoint of a statistically significant change from baseline to week 28 in the ALS functional rating scale in the faster progressing population.

Unless we did observe encouraging trends favoring to first in across multiple secondary and explore.

Exploratory measures of biological and clinical activity, including assessments of motor function respiratory function muscle strength and quality of life.

Moreover, a pre specified integration of data from the phase III study and it's ongoing open label extension study reinforce these.

These findings and showed that early to person initiation led to a slower decline across these measures.

Geoffrey Christopher Meacham: Beyond the clinical measures, we observed reductions in CSF-SOD1 as compared to placebo, suggesting target engagement was achieved. Moreover, on the key secondary endpoint of a change in plasma neurofilament light, a potential marker of neuronal degeneration, we observed reductions of 67% in the faster-progressing patients and 48% in the slower-progressing patients with Tiferson treatment relative to placebo.

Beyond the clinical measures, we observed reductions in CSF <unk>, one as compared to placebo, suggesting target engagement was achieved Moreover.

Moreover, on the key secondary endpoint.

A change in plasma neuro filament light a potential marker of neuro neuronal regeneration, we observed reductions of 67% and the faster progressing patients and 40%, 48% in the slower progressing patients with <unk> and treatment relative to placebo.

Geoffrey Christopher Meacham: To our knowledge, this represents the greatest reductions in plasma neurofilament levels ever observed in an ALS clinical trial. Most adverse events in the Phase III study were mild to moderate in severity, and many were consistent with ALS disease progression or lumbar puncture-related events. Serious adverse events, including transverse myelitis, were seen in some patients receiving to first.

To our knowledge.

This represents the greatest reductions in plasma narrow if government levels ever observed in an ALS clinical trial.

Most adverse events in the phase III study were mild to moderate in severity and many were consistent with ALS disease progression or lumbar puncture related events.

<unk>.

Serious adverse events, including transverse myelitis were seen in some patients receiving to person.

Geoffrey Christopher Meacham: Based on the results of the Phase 3 study, we are actively engaging regulators, the medical community, patient advocacy groups, and other key stakeholders around the world to determine the next steps for Tufersan. Additionally, following discussions with key medical experts and ethicists, we plan to provide early access to Tufersan to all eligible SOD1 ALS patients through an expanded access program. Given the possible importance of early treatment of SOD1-ALS, we continue to enroll patients in the ATLAS study, a Phase III trial of tefersin initiated in clinically pre-symptomatic SOD1 mutation carriers.

Based on the results of the Phase III study, we are actively engaging regulators the medical community patient advocacy groups and other key stakeholders around the world to determine next steps for Jefferson.

Additionally, following discussions with key medical experts and ethicists, we plan to provide early access up to person to all eligible <unk> ALS patients through an expanded access program.

Given the possible importance of early treatment of <unk> AOS, we cannot.

And due to enroll patients in the Atlas study, a phase III trial up to first and initiated and clinically pre symptomatic.

<unk> one mutation carriers.

Geoffrey Christopher Meacham: Our hope is that treating patients earlier in the disease may provide the best opportunity to slow or even delay the onset of this terrible disease. Also, in neuromuscular disorders, this quarter, we announced our plans to initiate ASCEND, a phase 3b study that aims to evaluate whether treatment with an investigational higher dose of nusinersen has the potential to improve clinical outcomes in patients previously treated with Rizdaplam. Our SPINRASA data indicate that exposure remains similar as patients age and grow.

Our hope is that treating patients earlier in the disease may provide the best opportunity to slow or even delay the onset of this terrible disease.

Also in neuromuscular disorders. This quarter, we announced our plans to initiate the <unk> phase III <unk> study, which aims to evaluate whether treatment with an investigational higher dose of NUCYNTA Ericsson has the potential to improve clinical outcomes and in patients previously treated with risk the plan.

Our spin spin rozzer data indicate that exposure remains similar as patients age and grow. We're also advancing the ongoing devote study evaluating the safety and efficacy of higher exposures of spin rozzer as our preclinical studies indicate that we ought to be able to safely increase its dose.

Michael R. McDonnell: We're also advancing the ongoing DEVOTE study, evaluating the safety and efficacy of higher exposures of SPINRASA, as our preclinical studies indicate that we ought to be able to safely increase its dose. Through the DEVOTE and ASCEND studies, we hope to be able to further inform SMA treatment and address the remaining unmet needs of patients. In summary, as I described during our recent R&D Investor Day, we believe the science is breakthrough and that this is exactly the right time to be pioneers in neuroscience.

With.

With the devote and assent studies, we hope to be able to further inform SMA treatment and address the remaining unmet needs of patients.

In summary, as I described during our recent R&D Investor Day, We believe the science is breaking and that this is exactly the right time to be pioneers in neuroscience.

Michael R. McDonnell: By leveraging a deep understanding of human genetics and disease biology, we are working to usher in the future of neurotherapeutics, where we identify the right patients and treat them early, perhaps even before the onset of symptoms, to meaningfully delay or even prevent disease progression. I will now turn the call over to Mike. Thank you, Al.

By leveraging a deep understanding of human genetics and disease biology, we are working to usher in the future of narrow therapeutics, where we identify the right patients and treat early perhaps even before the onset of symptoms to meaningfully delay or even prevent disease progression.

I will now turn the call over to Mike.

Well, we're very pleased with our third quarter results as we continued to execute well as we move forward. We remain fully focused on our core business, including the launch of <unk> in the United States total.

Michael R. McDonnell: We are very pleased with our third-quarter results as we continue to execute well. As we move forward, we remain fully focused on our core business, including the launch of AgiHelm in the United States. Total revenue for the third quarter of $2.8 billion declined 18% versus the prior year at both actual and constant currency and reflects the impact of Tecfidera generics. Total MS revenue for the third quarter was $1.8 billion. 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30, Looking at some of the individual products within MS.

Total revenue for the third quarter of $2 $8 billion declined 18% versus the prior year at both actual and constant currency.

The impact of <unk> generics.

Total MFS revenue for the third quarter was $1 8 billion.

Inclusive of <unk> royalties.

At some of the individual products within MFS.

Michael R. McDonnell: Global Tecfidera revenue for the third quarter was $499 million. In the U.S., third quarter revenue of $179 million was flat versus the prior quarter, with lower volume offset by a decrease in discounts and allowance. We expect Tecfidera revenue in the U.S. to decline going forward.

Global <unk> revenue for the third quarter was $499 million in the U S third quarter revenue of.

<unk> recruited $79 million was flat versus the prior quarter with lower volume offset by a decrease in discounts and allowances. We expect <unk> revenue in the U S to decline going forward outside of the U S third quarter <unk> revenue of $319 million increased by 13%.

Michael R. McDonnell: Outside of the U.S., third-quarter Tecfidera revenue of $319 million increased by 13% versus the prior year with 7% underlying patient growth. We were pleased with the continued ramp-up in Pomerity revenue from $91 million in the second quarter to $121 million in the third quarter. We are also pleased that Bumerity received a positive CHMP opinion in the EU, as well as full regulatory approval in Switzerland.

One how does the prior year with 7% underlying patient growth.

We were pleased with the continued ramp in primarily revenue from $91 million in the second quarter to $121 million in the third quarter we.

We are also pleased that <unk> received a positive <unk> opinion in the EU.

Versus as well as full regulatory approval in Switzerland.

Michael R. McDonnell: Tysabri third-quarter global revenue of $523 million increased 1% versus the prior year, notwithstanding some negative channel dynamics in the United States. We are pleased to see 7% growth in global Tysabri patients, and we believe Tysabri remains well positioned to play an increasingly important role in the treatment of MS with initiatives including subcutaneous administration and extended interval dosing. We are also encouraged by the new data on COVID vaccinations that Al mentioned.

Tysabri third quarter global revenue of $523 million increased 1% versus the prior year, notwithstanding some negative channel dynamics in the United States. We were pleased to see 7% growth in global Tysabri patients and we believe tysabri.

It remains well positioned to play an increasingly important role in the treatment of Ms with initiatives, including subcutaneous administration and extended interval dosing. We are also encouraged by the new data on Covid vaccinations that al mentioned.

Michael R. McDonnell: Moving to SMA, global third-quarter Spinraza revenue of $444 million decreased by 10% versus the prior year. In the U.S., Spinraza revenue of $140 million decreased by 23% versus the prior year as we see continued impact from competition. However, we were encouraged to see that discontinuations decreased versus the second quarter of this year.

Moving to SMA global third quarter spin Rozzer.

Sabra of $444 million decreased by 10% versus the prior year.

In the U S <unk> revenue of $140 million decreased by 23% versus the prior year as we see continued impact from competition. However, we were encouraged to see that discontinuation decreased versus the second quarter.

Revenue here.

Michael R. McDonnell: Outside the US, Spinraza revenue decreased 2% versus the prior year due to competition and pricing pressure in Europe, partially offset by growth in regions outside of Europe. As a reminder, Q1 and Q2 2021 Spinraza revenue outside the US benefited from accelerated shipment. With overall market growth, continued data generation, the efficacy and safety profile in all age groups, and further geographic expansion, we continue to believe that Spinraza can return to growth over the medium to long term. Total Agihelm revenue for the third quarter was $300,000 as we saw wholesalers gradually draw down inventory purchased in Q2. For the three main reasons Michelle discussed, uptake has been delayed.

Outside the U S. It's been Rozzer revenue decreased 2% versus the prior year due to competition and pricing pressure in Europe, partially offset by growth in regions outside of Europe. As a reminder, Q1 and Q2 2020 once been rozzer revenue outside the U S benefited from accelerated shipments.

With overall market growth continued data generation, the efficacy and safety profile in all age groups and further geographic expansion. We continue to believe that's been Roger can return to growth over the medium to long term.

Total <unk> revenue for the third quarter was $300000 as we saw wholesalers gradually.

Of this draw down inventory purchased in Q2 for.

For the three main reasons Michel discussed uptake has been delayed.

Michael R. McDonnell: I would refer you to this slide as well as slides in the appendix for details on the accounting for ASCI and Neuroimmune, which differs depending on geography. Moving on to our biosimilars business, third-quarter revenue of $203 million decreased by 2% versus the prior year, as we continue to be negatively impacted by pricing pressure as well as the COVID-19 pandemic. We are excited that BioViz was approved in the U.S., E.U., and U.K. and believe that we have the opportunity to continue to grow our biosimilars business by commercializing new products and entering new geographies such as the U.S. Total anti-CD20 revenue in the third quarter of $415 million decreased 26% versus the prior year.

I would refer you to this slide as well as slides in the appendix for details on the accounting with Eisai in neuro immune which differs depending on geography.

Moving on to our Biosimilars.

<unk> third quarter revenue of $203 million decreased by 2% versus the prior year as we continued to be negatively impacted by pricing pressure as well as the COVID-19 pandemic.

We are excited that <unk> was approved in the U S EU and UK and believe that we have the opportunity to continue.

To grow our biosimilars business by commercializing new products and entering new geographies such as the U S.

Total anti CD 20 revenue in the third quarter of $415 million decreased 26% versus the prior year.

Michael R. McDonnell: This decline was primarily driven by the decline in rituxan revenue as we see continued impact from biosimilars, a trend that we expect going forward. However, total other revenue in the third quarter of $158 million increased 26% versus the prior year. Other revenue in the quarter benefited from the timing of shipments related to contract manufacturing. Third quarter gross margin was 82% of revenue, down slightly from 83% in the prior quarter and down from 87% in Q3 of 2020. The reduction in gross margin versus the prior year was primarily due to the declines in Tecfidera and Rituxan, both of which are high-margin products. We expect continued downward pressure on gross margins going forward.

This decline was primarily driven by the decline in Rituxan revenue as.

Business continued impact from Biosimilars, a trend that we expect going forward.

Total other revenue in the third quarter of $158 million increased 26% versus the prior year.

Revenue in the quarter benefited from the timing of shipments related to contract manufacturing.

We seek our gross margin was 82% of revenue down slightly from 83% in the prior quarter and down from 87% in Q3 of 2020.

The reduction in gross margin versus the prior year was primarily due to the declines in <unk> and Rituxan both of which are high margin products. We expect continued downward.

Pressure on gross margins going forward.

Michael R. McDonnell: Moving now to expenses on the balance sheet, third quarter non-GAAP R&D expense was $702 million, which included a $125 million upfront payment related to our collaboration with InnoCare. Non-GAAP SG&A was $651 million, including approximately $135 million related to Agilent. Note that beginning in the second quarter, ASI's reimbursement of U.S. SG&A costs is reflected in the collaboration profit sharing. Third quarter collaboration profit sharing was a net expense of $21 million, which includes a reimbursement of $51 million from ASI related to the commercialization of Agilent in the US. Our effective non-GAAP tax rate for the quarter was approximately 14% versus approximately 19% in the third quarter of last year.

Moving now to expenses in the balance sheet third quarter non-GAAP R&D expense was $702 million, which included a $125 million upfront payment related to our collaboration with Endo care non-GAAP SG&A was $651 million.

Third quoting approximately $135 million related to agile.

Note that beginning in the second quarter ASI is reimbursement of U S. SG&A costs as reflected in the collaboration profit sharing line.

Third quarter collaboration profit sharing was a net expense of 21.

And <unk>, which includes the reimbursement of $51 million from Eisai related to the commercialization of <unk> in the U S.

Our effective non-GAAP tax rate for the quarter was approximately 14% versus approximately 19%.

In the third quarter of last year.

Michael R. McDonnell: Third quarter non-gap loss attributable to non-controlling interest was $11 million. As a reminder, Adjaheim royalties and commercial launch milestones paid to Neuromun will be reflected in this line. A-size reimbursement for these items will be reflected in collaboration profit sharing.

1 million third quarter non-GAAP loss attributable to Noncontrolling interest was $11 million as a reminder, <unk> royalties and commercial launch milestones paid to near immune will be reflected in this line.

<unk> reimbursement for these items will be reflected in collaboration profit sharing.

Michael R. McDonnell: During the quarter, we repurchased 2.2 million shares of the company's common stock for $750 million. As of September 30, 2021, there was $2.8 billion remaining under the Share Repurchase Program authorized in October of 2020. Our weighted average diluted share count was approximately 149 million shares for the quarter. Non-GAAP diluted earnings per share in the third quarter were $4.77. In the third quarter, we generated approximately $805 million in cash flow from operations.

During the quarter, we repurchased two 2 million shares of the company's common stock for $750 million.

As of September 32021, there was $2 8 billion remaining under the share repurchase program authorized in October of 2020.

Our weighted average diluted share count was approximately.

149 million shares.

For the quarter.

Non-GAAP diluted earnings per share in the third quarter was $4 77.

In the third quarter, we generated approximately $805 million in cash flow from operations.

Michael R. McDonnell: CapEx was $42 million, and free cash flow was approximately $763 million. We ended the quarter with $7.3 billion in debt, in cash and marketable securities, and $3.3 billion in net debt. In addition, our $1 billion revolving credit facility was undrawn as of the end of Q3.

Capex was.

<unk> <unk> $42 million in free cash flow was approximately $763 million.

We ended the quarter was $7 3 billion in debt.

$3 9 billion in cash and marketable securities.

At $3 3 billion in net debt.

In addition, our.

$2 billion revolving credit facility was undrawn as of the end of Q3.

Michael R. McDonnell: Overall, we remain in a very strong financial position with significant cash and financial capacity to grow the business over the long term. And now I turn to our updated full-year guidance for 2021. We are increasing our full year 2021 revenue guidance from our previous range of $10.65 billion to $10.85 billion to a new range of $10.8 billion to $10.9 billion, primarily as a result of stronger Microsof performance. We are increasing our non-GAAP diluted EPS guidance, from our previous range of $17.50 to $19.00, to a new range of $18.85 to $19.35, primarily driven by the revenue upside I just mentioned.

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 updated full year guidance for 2021.

We are increasing.

Our one of our full year of 2021 revenue guidance from our previous range of 10, six 5 billion to $10 85 billion to a new range of $10 8 billion to $10 9 billion, primarily as a result of stronger EMS performance.

We are increasing our non-GAAP diluted.

Leasing EPS guidance from.

From a previous range of $17 50 to $19.

To a new range of $18 85 to.

To $19 35.

Primarily driven by the revenue upside I just mentioned.

Michael R. McDonnell: We are lowering our capital expenditure guidance from a previous range of $375 million to $425 million to a new range of $250 million to $300 million, primarily as a result of delayed spend on certain projects, including some which have been impacted by COVID-19. Our guidance assumes minimal Agilent revenue in 2021. We continue to expect revenue to start ramping in 2022 and beyond, particularly after the NCD decision in April, assuming a positive outcome. We expect continued declines in both Tecfidera and Rituxan in the U.S., and that the decreased revenue from these high-margin products will put pressure on our gross margin percentage.

Diluted or lowering our capital expenditure guidance from a previous range of $375 million to $425 million to a new range.

Of $250 million to $300 million.

Primarily as a result of delayed spend on certain projects, including some which have been impacted by COVID-19.

Our.

Our guidance assumes minimal <unk> revenue in 2021, we continue to expect revenue to start ramping in 2022 and beyond particularly after the NCD decision in April assuming a positive outcome.

We expect continued declines in both tech Vadera and Rituxan in the U S and that the decreased revenue from these high margin.

<unk> will put pressure on our gross margin percentage.

Michelle Vunazzo: Full year non-GAAP R&D expenses are expected to be between $2.45 billion and $2.55 billion. This range is consistent with our previous guidance. Full year, non-GAAP SG&A expenses are expected to be between $2.6 billion and $2.7 billion. This range is consistent with our previous guidance and includes an approximate $500 million Agilent home investment. Of this amount, approximately $150 million would be reimbursable by ASI and is reflected as collaboration profit sharing effective April 1st and is not part of SG&A.

Full year non-GAAP R&D expenses are expected to be between $2 45 billion and $2 $5 5 billion.

This range is consistent with our previous guidance.

Full year non-GAAP SG&A expenses are expected to be beaten.

<unk>, <unk> 6 billion and $2 7 billion.

This range is consistent with our previous guidance and includes an approximate $500 million agile home investment.

Of this amount approximately $150 million would be reimbursable by Eisai and is reflected as collaboration profit sharing effective April one and not part of SG&A.

Michelle Vunazzo: These AgiHelm investments are slightly less than our previous estimates, and of course, we will continue to actively manage the pace of this spend. This annual SG&A range also assumes a seasonally higher spend in Q4, consistent with previous years. I would refer you to our press release for other important guidance assumptions. In closing, we are very pleased with our financial performance and are very focused on the Agilhelm launch. We remain in a very strong financial position with significant cash, modest leverage, and a business that generates significant free cash flow. We believe these dynamics position us well to continue to grow the business over the long term. I'll now turn the call back over to Michel for his closing comments.

<unk> six.

These <unk> investments are slightly less than our previous estimates and of course, we will continue to actively manage the pace of the spend.

This annual SG&A range also assumes a seasonally higher spend in Q4 consistent with previous years.

I would refer you to our press release for other important guidance assumptions.

In closing we are very pleased with our financial performance and are very focused on the <unk> launch we remain in a very strong financial position with significant cash modest leverage and a business that generates significant free cash flow. We believe these dynamics position us well to continue to grow the business over the long term I'll now turn the call back.

G&A Michel for his closing comments, thank you Mike.

Michelle Vunazzo: Thank you, Mike. Biogen continues to demonstrate resilience and strong execution in the third quarter of the year, providing a solid foundation for the company as we make progress on the Ideahelm launch, ahead of the important data releases and publications in addition to the NCD decision for the class of anti-amyloid antibodies anticipated next April. We believe that the helm represents a significant step in the fight against Alzheimer's disease as the first FDA-approved treatment to address the defining pathology of the disease, which is reasonably likely to predict clinical benefits. We know there are patients suffering right now from the disease. And it is those patients we keep in mind as we work to support access.

Biogen continued to demonstrate resilience and strong execution in the third quarter of the year, providing a solid foundation for the company as we make progress on the edge ahead of launch ahead of the important data releases NPV patients. In addition.

<unk> to the NCD decision for the class of anti amyloid antibodies anticipated next April.

We believe that <unk> had and represents a significant step in the fight against Alzheimer's disease as the first FDA approved treatment to address the defined pathology of the disease, which is reasonably likely to predict clinical.

Back over to Pete.

We know that patients suffering right now from the disease.

And those patients we keep in mind as we work to support access in fact.

Michelle Vunazzo: At the CITAD meeting next month, we'll be presenting an analysis showing that, without access... Every day that passes, we estimate that over a thousand Americans move from mild to moderate Alzheimer's dementia and therefore may no longer be appropriate for initiation of treatment with Adderhell. As many have observed, our current system so far falls short in diagnosing and intervening in the disease. In addition, Alzheimer's disease is a particularly acute issue of inequality as African Americans are up to three times more likely and Latinx individuals are one and a half times more likely to have Alzheimer's disease when compared to others.

At the <unk> meeting next month, we'll be presenting an analysis showing that without access.

Rick.

Buses, we estimate that over 1000 Americans move from mild to moderate Alzheimer's dementia, and therefore may no longer be appropriate for initiation of treatment with as you have them.

As many have observed our currency stem so far.

Dave Schulte in diagnosing and intervening in the in the disease.

In addition, as <unk> is a particularly acute issue of inequality.

African Americans are up to three times more likely and latinx individuals are.

And half times more likely to have Alzheimer's disease, when compared to others.

Michelle Vunazzo: We understand the seriousness of this issue and that inclusion of underrepresented populations in drug development is often low, including in our Alzheimer's clinical trial. We also know that we have work to do and a role to play in correcting this. For that reason, the design of ICARE-AD, our real-world phase four observational study of adjuhelm, aims to include at least 16% of the trials that are expected to enroll black, African-American, and Latinx patients.

We understand the seriousness of this issue and that inclusion of Endo represents population in drug development is often low.

Including Alzheimer's clinical trial, we also know that we have work to do and a role to play in.

One of these.

For that reason the design of Ikea AE, our real world face for observational study of <unk> head and aims to include at least 16% of the trials as expected new enrollment from Black African American and Latinx patients.

Michelle Vunazzo: In closing, I would like to thank our employees around the world who have demonstrated a dedication to making a positive impact on patients' lives. And all of the physicians, caregivers, and participants in our clinical development programs. Our ability to deliver medicines to patients could not be realized without their passion and commitment. We will now open the call to questions.

In closing.

Correct I would like to thank our employees around the world will have demonstrated their dedication to making a positive impact on patients' lives and all of the physicians caregivers and participants in our clinical development programs, our ability to deliver medicines to patients could not be realized without their passion and commitment.

We'll now.

<unk> open the call for questions.

Shelby: If you would like to ask a question, please press star 1 on your telephone keypad. As a reminder, please limit yourself to one question. If you require any further follow-up, you may press star 1 again to rejoin the queue. Your first question comes from the line of Robyn Karnauskas. You guys, thanks for taking my question. I think a lot of us have struggled with some of the headlines coming from doctors about

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

As a reminder, please limit yourself to one question.

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

Your first.

Now all question comes from the line of Robyn <unk>.

Hey, guys. Thanks for taking my question.

Sure.

A lot of us have struggled with some of the headlines coming from doctors about how they do not want to give the drug and I understand that you're highlighting.

With the NCD lack of an NCD decision as the core.

Shelby: Transcribed by https://otter.ai

<unk> lack of reimbursement.

A little bit about how are you going to convince doctors, even if you have a positive NCD decision to give the drug to patients and is that something that.

Robyn Karnauskas: Absolutely. It's Robin.

Michelle Vunazzo: It's actually the first priority that we have is to basically educate the community based on additional data on the current data communicated and additional data that we're going to communicate and publish in the near future. They also expect to see a full publication in a peer-reviewed journal, and sometimes, you know, this is brought forward, but also, the worry is the financial risk in terms of the lack of courage in NCD. So those issues are interrelated. I will ask Alisha to say a bit more.

We're seeing it in the headlines is that something that you are you are dealing with is that a core block.

Block for uptake of the drug.

First absolutely.

It's actually the first priority that we have is to basically educate the community based on additional data on the current data communicated and additional data that's begun a communicate and publish in the near future.

They also expect to see.

It could be issued in the review journal.

And sometimes this is brought forward, but also the worry ease the financial risk in terms of lack of core Rachel NCD. So those issues.

The interrelated I will ask <unk> to say it would be small.

Alisha Alaimo: Thank you, Michelle. And thank you, Robin, for the question. You know, this is actually not an exact science, and what we believe and what we are hearing is that the majority of prescribers actually fall into a combination of two categories. The first is gonna be around the benefit risk profile, which of course, you are reading about and the question refers to. And the second is also what we refer to, which is the hesitancy due to the NCD analysis.

Thank you Michelle and thank you Robyn for the question.

This is actually not an exact science and what we believe and what we're hearing is that the majority of prescribers actually fall into a combination of two categories. The first is going to be around the benefit risk profile.

<unk> course, you are reading about in the question refers to and the second is also that we referred to which is the hesitancy due to the NCD analysis.

Alisha Alaimo: However, there is a meaningful portion of prescribers that are still undecided. So though there are some in the headlines, we do have a very large group that haven't made a decision one way or another. And this is why we have multiple teams working every single day and working very hard to help educate sites and HCPs on our clinical data and on the reimbursement pathways, which you know are very complex. And, you know, Michelle referenced this in his opening statements, but we're working with urgency because the cost of doing nothing is also well understood.

However, there are a meaningful portion of prescribers that are still undecided. So those are some of the headlines that we do have a very large bucket that.

<unk> made a decision one way or another and this is why we have multiple teams working every single day and working very hard to help educate sites in HCP is and our clinical data and on the reimbursement pathways, which you know are very complex and Michel referenced. This also in his opening statements that were working with urgency because the cost.

That heavily nothing is also well understood and Michelle mentioned that we estimate that a thousand patients a day advanced in their alzheimers journey from mild to moderate and they may no longer be appropriate for <unk>. So we are really committed to being a part of this solution and that's what motivates us each and every day and.

Alisha Alaimo: And Michelle mentioned that we estimate that 1,000 patients a day advance in their Alzheimer's journey from mild to moderate AD, and they may no longer be appropriate for Adjahom. So we are really committed to being a part of this solution, and that's what motivates us each and every day. And as soon as we get more data, we will be sure to share it because we understand where the question's coming from. So, thank you. We believe, Robin, that the evidence.

And as we get more data, we will be sure to share it.

Because we understand where the question is coming from so thank you. We believe rubbing that evidence not only coming from ICU, but also potentially from older <unk> products.

Michelle Vunazzo: We believe, Robyn, that evidence, not only coming from ADEW but also potentially from other anti-amyloid products... will represent a significant body of evidence for those who have been initiating and challenging the amyloid hypothesis for years. And we are also very encouraged by the data on Avihelm. We continue to stand very strong behind our data. That's why it was really in the script two or three times. So more to come.

They represent a significant body of evidence.

For those we are initiating and challenging.

<unk> six years and we are also very encouraged by by the data on the.

We continue to stand very strongly behind our data that's why it was really in the script two or three times.

Shelby: Thank you. We'll take our next question from the line of Michael Yee with Jeffreys.

And as soon as more to come.

Thank you we'll take our next question from the line of Michael <unk> with Jefferies.

Michael J. Yee: Hi, good morning, and thank you for the update. Appreciating that you commented that the NCD, of course, is an important milestone, can you comment on your view around what the scenarios would be and what you believe a positive NCD outcome is and how important that reimbursement would be as a part of that positive outcome?

Hi, good morning, and thank you for the update.

Appreciating that you commented that the NCD of course is an important.

Some milestone can you comment around.

Your view around what the scenario would be and what you believe a positive trend.

CD outcome.

And how important that reimbursement would be.

Michael J. Yee: as a part of that positive outcome.

Michelle Vunazzo: Thank you, Mike and Michael. And as you know, we have been advocating for pet reimbursement for many months.

Part of that positive outcome. Thank you.

Yes.

Thanks.

Thank you, Mike and Michael and as you know, we advocating for better reimbursement since many months and Alicia will provide more color on the different options.

Michelle Vunazzo: And Alisha will provide more color on the different options. Alisha, in terms of NCD? Yeah.

Alicia in terms of MTBE yet.

Alisha Alaimo: Thank you, Michel. And thank you, Michael, for your question. So it's important to remember, as we've stated, that NCD is not only for Adjahelm, right? It's going to be for the entire class of monoclonal antibodies that target amyloid for the treatment of Alzheimer's disease. Now, we can't actually speculate on the outcome of the NCD analysis, but as you know, we do believe it will be a major milestone, and this will alleviate a lot of the confusion that we're seeing with physicians.

You Michelle and thank you.

Michael for your question. So it's important to remember as we've stated.

<unk> the NCD is not only for <unk>, it's going to be for the entire class of monoclonal antibodies that target amyloid for the treatment of Alzheimer's disease.

Now we can't actually speculate on the outcome of the NCD analysis, but as you know we do believe it will be a major milestone and this will alleviate a lot of confusion that we're seeing.

<unk> with physicians. However, there are five potential outcomes and I think the three of the people that people mostly talk about are most interested in are one being a new coverage decision. The second is it going to be coverage with evidence, which we call <unk> and the other will be coverage with restrictions and if you look at history and you look in the past over the last.

Alisha Alaimo: However, there are five potential outcomes, and I think the three that people mostly talk about and are most interested in are one being a no-coverage decision; the second is going to be coverage with evidence, which we call CED, and the other will be coverage with restrictions. And if you, you know, look at history, and you look in the past, over the last 20 years, there's only been 12 that have gone through this process.

Past 20 years, there's only been 12 that have gone through this process. One was a non coverage one was an off label for CEB and the other 10 were basically covered indication. So even though we can't really comment on it. We are in this rigorous process, we are replying to them anytime that they need additional.

Alisha Alaimo: One was a non-coverage, one was an off-label for a CED, and the other 10 were basically covered indications. So even though we can't really comment on it, we are in this rigorous process. We are replying to them any time that they need additional data, but just remember that all manufacturers are in this process together.

Data, but just remember that all manufacturers are in this process together.

Shelby: Thank you. We'll take our next question from the line of Corey Kazimoff with J.P. Morgan.

Next question. Thank you, we'll take our next question from the line of Cory <unk> with JP Morgan.

Corey Kazimoff: Hey, good morning, guys. Thank you for taking my question. So I get that we're all waiting for the NCD. But at this stage of the launch, is there any consideration at all being given to changing the gross price of Agihelm given how difficult initial traction has been? Or do you think that's not a key impediment in all of this?

Hey, good morning, guys. Thank you for taking my question.

I get that we're all waiting for the N C D. But at this stage of the launch is there any consideration at all being given to changing the gross price of agile home given how difficult. The initial traction has been or do you think that's not a key impediment in all of this.

Michelle Vunazzo: I think that NCD is critical, data dissemination is even more so, and one is interrelated to the other. And when we look at the metrics, strategic metrics, market research, price doesn't come up as the first worry. We have strong rationales. We clearly disagree with the underlying assumption of high-threshold assessment, inappropriate pooling of data, pessimistic assumptions on long-term efficacy, and many more.

I think that the NCD is critical.

Data dissemination, even more and one is interrelated to the other.

And when we look at the metrics strategic can introduce market research.

Price doesn't come up as the first worry we have strong rationale, we clearly disagree with the underlying.

<unk> assumption of ISO assessment.

Appropriate putting of data pessimistic assumptions on long term efficacy and many more and I don't think we are the only one in the industry.

Michelle Vunazzo: And I don't think we are the only one in the industry. Okay, so obviously, we always have the opportunity to fine-tune our pricing. And we keep that as an option. But first, data. And data is interrelated, obviously, with the decision for NCD. And infrastructure is also, in the meantime, progressing. Alisha, do you want to give feedback on the issue of price?

So obviously, we have always the opportunity to fine tune, our pricing and we keep that.

<unk> an option, but first is data and data is interrelated. Obviously, we did decision for NCD and infrastructure is also in the meantime progressing.

Alicia do you want to say a feedback on the issue of price, yes. Thank you Michelle and thank you Cory for the question.

Alisha Alaimo: Yes, thank you, Michelle. And thank you, Corey, for the question. And Michelle's absolutely right. While price is always an important factor for sites and for patients, what I can share with you is that we have not heard that price is the primary driver for any decision not to treat patients. In fact, the headwinds that we're facing are the ones that Michelle has mentioned and that you clearly also read in the press every day, and you probably see when you are reporting with your analyst reports.

As michelle's absolutely right, while price is always an important factor for sites and for patients what I can share with you is that we have not heard that price is the primary driver for any decision not to treat patients in fact, the headwinds that we're facing are the ones Michelle.

Shannon mentioned and that you clearly also read in the press every day and you'll probably see.

When you are reporting with their analyst reports, but as with other therapies. If patients think they might face difficulty affording agile helm, we do have financial assistant programs that are available that can help these patients so if reimbursement or affordability.

Alisha Alaimo: But as with other therapies, if patients think they might face difficulty affording Adjahelm, we do have financial assistance programs that are available that can help these patients. So if reimbursement or affordability are potential concerns, we hope that our programs can provide a potential pathway for them, because we do believe that a lack of financial means should not be a barrier for patients to access Adjahelm.

Shell has an initial concerns we hope that our programs can provide really a potential pathway for them because we do believe that a lack of financial means should not be a barrier.

<unk> patients to access that Jim and importantly, Curry Youll remember that at launch. They won we did give the hand two decision.

Michelle Vunazzo: And importantly, Corey, you will remember that on launch, day one, we did give the hand to decision makers for innovative contracts, for a prize volume, but not limited to, on a voluntary basis in order to secure sustainability. And remember, it's not 6 million patients, even not one to two. It's a portion of those that will be gradually treated. So we did offer that, and decision makers and CMS are aware, but now it's the NCD process. So we step back, and we respect this process. The offer is out there. Next question. Thanks.

<unk>.

For innovative contract for price volume, but not limited to on a voluntary basis in order to secure sustainability and remember, it's not 6 million patients even not to one to two its a portion of those that will be gradually treated so.

<unk> offer that and decision makers and Tim as outerwear, but now it's the NCD process. So we step back and we respect this process.

But the offer is out there.

Next question. Thank you, we'll take our next question from the line of Marc Goodman with SBB.

Shelby: We'll take our next question from the line of Marc Goodman with SVP Learnig.

So we did layer Nick.

Marc Harold Goodman: Good morning, my question is on Serenolone. Moving forward with this product for a two-week treatment course implies a pretty significant cost per pill, and basically, it would be an all-in strategy on a paradigm shift in depression treatment, which seems a little bit risky. I'm just curious about the market research that you've done and the conversations you've had with psychiatrists to know that they have a buy-in and that this is a good strategy and this is going to really be successful. Obviously, the product works. ,,,,,,,,

Hi, Good morning, My question's answer ran alone moving forward with this.

Product is a two week treatment course implies pretty significant kind of cost per pill and basically it would be really an all in strategy on a paradigm shift in depression treatment, which is seems a little.

I'm just curious about the market research that you've done in the.

<unk> had with psychiatrists to know that they have a buy in and that this is a good strategy and this is going to really be successful obviously the product works pretty quickly, which is in and of itself important but the two week treatment course would be very.

Risks different.

Thanks.

Michelle Vunazzo: So what is important is that eventually, we'll be in a position to transform the management of major depressive disorders and postpartum depression. And for the time being, we are driven by scientific readouts and the additional data we get. I must admit that we haven't yet had a discussion on price. Well, I know that the team is starting to build, you know, data and market research evidence in order for us to be ready should the data confirm. But we are pleased with the three, you know, placebo control results going into the same direction.

So what is important is that eventually will be in a position to transform the management of.

Major depressive disorders in postpartum depression and for the time being we are driven by science and Readouts and the additional data we get on this.

But we didn't have yet a discussion on price, while I know that the team starts to build.

Data and market research evidence there for us to be ready should the data confirm but we are pleased with the three.

Placebo controlled results going into the same direction.

Geoffrey Christopher Meacham: Yeah, thanks, Marc. It is a paradigm shift and a different way of thinking for psychiatrists, so there'll be a lot of education necessary, assuming we do get approval. I think that the current standard of care is to use SSRIs or SNRIs. However, it takes weeks, if not more than a month, for them to work. And then patients stay on them chronically, often with side effects, and that's not a great situation. And the reason why people stay on them chronically is that there is a slow onset of action.

Yes.

It is a paradigm shift in a different way of thinking for psychiatrists, so there'll be a lot of education necessary.

Assuming we do get approval.

I think that the current standard of care is to use SSRI or SNRI. It takes weeks, if not more than a month.

Thanks for them to work and then patients stay on them chronically often with side effects and thats not a great situation and the reason why people stay on them chronically is because they are slow.

No onset of action, so having a two week treatment course.

Geoffrey Christopher Meacham: So having a two-week treatment course where you can then take the drug as needed is a very different way of thinking and I think would be attractive to many treating physicians. And the fact that it has a rapid onset allows people to give the two-week treatment and wait for the next as-needed treatment because they know, and they can be reassured that within three days of starting, they will see efficacy in their patients. So it is a different way of thinking, but I think it's very, very exciting.

You can then take the drug as needed as a very different way of.

And I think would be attractive.

Too many treating physicians.

The fact that its rapid onset allows people to two.

Give the two week treatment and wait for the next as needed treatment because they know they can be reassured that within three days of starting basically.

Thank you your efficacy they will see efficacy and their patients.

So it is a different way of thinking, but I think it's a very very exciting.

Shelby: We'll take our next question from the line of Matthew Harrison with Morgan Stanley. Good morning, thanks for taking the question.

Next question.

We will take our next question from the line of Matthew Harrison with Morgan Stanley.

Yes.

Matthew Harrison: Good morning, thanks for taking the question. Al, I was wondering if you could comment on and just remind us about the differences in the BAN2401 Phase 3 study versus the Aduhelm studies. And the context here is, how important do you think a successful Phase 3 study is for BAN2401 next year, especially in terms of changing physician perception around Aduhelm and anti-anabolic drugs? Yeah, I think it's very important, Matthew, because, as has already been stated, doctors are uncertain about the benefit risk.

Good morning, Thanks for taking the question.

They see it or if you could.

Comment.

And just remind us around the differences in the band 20, 401 phase III study versus the AD Johan studies in the context here is how important do you think a successful phase III study is for band 20, 401 next year, especially in terms of changing physician.

I was one perception around AD <unk> helman and anti inflammatory drugs.

Yes, I think I think it's very important Matthew because.

As has already been stated doctors.

Doctors are uncertain about the benefit risk.

Matthew Harrison: And as Michelle said, the data that comes not only from aducanumab but from all these anti-A beta antibodies that share the characteristic of being able to greatly reduce amyloid burden will be very important. The difference, you know, there are more similarities than differences between aducanumab and lacanumab, both bind to aggregated forms of A beta, and both reduce amyloid plaque burden quite substantially. The differences are that there is no titration needed for lacanumab.

And as Michele said the data that comes.

<unk> can you map, but from all of these anti a beta antibodies that share the characteristic of being able to greatly reduce amyloid burden that will be very important.

The difference there are more similarities and differences between <unk> and <unk>, both bind to <unk>.

Aggregated.

<unk> forms of a beta both reduce amyloid plaque burden quite substantially.

The differences are that Theres, no titration needed for la <unk>.

Geoffrey Christopher Meacham: And the rates of aria at the present time do seem to be low. We'll find out in the phase three study, but they seem to be lower than the rates of aria with aducanumab. And it's given every two weeks. So, and look, the design of the phase three trial for your question is very similar to the design of the aducanumab phase three trials. For example, the primary endpoint is CDR boxes, which is the established clinical efficacy measure for this disease.

And the rates of <unk> at the at the present time do seem to be low we will find out in the phase III study, but they seem to.

Not on work than the rates of ARIA with agile Canyon Mab and it's given every two weeks so so.

The design of the Phase III trial to your question is very similar to the design of the agile Canyon Mab Phase III trials for example, the primary endpoint is <unk>.

<unk> boxes, which.

As the established.

Clinical efficacy measure.

Shelby: Next question. Thank you. We'll take our next question from the line of Geoff Mechon with Bank of America.

For this disease.

Next question. Thank you, we'll take our next question from the line of Geos Macca with.

Geoff Meacham: Morning, guys. It's Jeff.

Okay.

Yes.

Good morning, guys. It's Jeff. Thanks for the question just had another one on Azure.

Geoff Meacham: Thanks for the question. I just had another one on You know, prior to approval, you guys have talked about expanding manufacturing capacity and investing pretty heavily in the commercial aspects of the launch. I guess the question is, has the strategy changed just given the pace of the rollout? I'm just trying to get a sense for whether it's more of a holding pattern, you know, before the April NCD, or are you guys going to remain aggressive on the investments that you're making in the edging unlock?

Prior to approval you guys had talked about expansion of manufacturing capacity and investing pretty heavily in the commercial aspects of the launch I guess the question is has the strategy changed.

When the pace of the rollout I'm, just trying to get a sense for.

Whether it's more of a holding pattern.

Before the April NCD or are you guys going to remain aggressive on the investments that you're making in the edge and how much. Thank you.

Michelle Vunazzo: Thanks for the great question. We stay the course as a company, clearly, because it's as if we were in a delayed pre-launch, in an extended pre-launch period before the launch, and we stay the course. Obviously, we are staging the Spant very closely. Mike and I and the team are scrutinizing the investment requests coming from all around the world, so we want to be extremely vigilant, and we are. But we stay the course because we do believe in our data, we do believe in additional data coming up, and we do believe that the system will adjust, and it's a matter of time. You saw on the slide presented that there is a clear process. We are not far from being there, so we should stay the course.

Thanks for the Great question, we stay the course as a company clearly because each as if we were.

Just get delayed.

<unk> pre launch and an extended prelaunch period before the launch and we stayed the course, obviously we are staging the spent very closely Mike and I and the team are scrutinizing the investment request coming from all around the world. So we want to be extremely vigilant.

And we are but we stay the course, because we do believe in our data we do believe additional data coming up and we do believe that this system will adjust.

And it's a matter of EBITDA offline you saw on the slide presented that there is a clear process, we are not far from being there and so we.

Stay the course.

Michael R. McDonnell: Yeah, Geoff, it's a great question, and I would describe it as a gating process. We continue to believe in the long-term potential of AgiHelm. But at the same time, because of the delays, we're going to gate the spend. So we are still making a meaningful investment to the tune of an estimate of $500 million of SG&A, call it $350 million net of reimbursement in 2021. The CapEx, some of that does tie to facilities to support AgiHelm.

Yes, Jeff it's a great question and I would describe it as a gating process. We continue to believe in the long term potential of agile helm.

And at the same time because of the delays were going to gate. The spend so we are still making a meaningful investment to the tune of an estimate of 500 million.

SG&A call it $3 50 net of reimbursement in 2021.

On the Capex some of that does tie to facilities to support adds an element.

Michael R. McDonnell: And we are gating that. Most of the production in our CapEx guidance ties to timing. And we're also managing a challenged global supply chain right now a little bit. So we're going to be prudent and we're going to gate, but we are going to continue to be ready at the moment in time and invest aggressively, but at the same time being prudent and gated as we go. It's a pre-launch somehow, an extended pre-launch, but

We are gaining that most of the reduction in our capex guidance ties to timing and we're also managing a challenged global supply chain right now a little bit.

<unk>.

So we're going to be prudent and we're going to gate, but we're going to continue to be ready.

At the moment in time and invest.

Aggressively but at the same time being prudent and gating as we go and each of prelaunch somehow.

Michelle Vunazzo: And it's a pre-launch somehow, an extended pre-launch, but we are encouraged by the progress, you know, 120 centers that reference our product in their formulary at your helm, and this is more than double what it was a month ago, Alisha. So there is a lot of progress. And if there are some large institutions that are refusing, they want more data and will be there in a few weeks. So it's a process that is unfortunately taking longer than we expected, but we have to be resilient. And the signal we want to send is that we believe because we know the data and we see the progress.

Extended prelaunch, but two we are encouraged by the progress.

One.

120 <unk>.

The centers that <unk> health and disease.

More than double than a months ago. Alicia. So there is a lot of progress and have some large institutions that denied they want more data and we'll be there EMA.

In a few weeks so it's a.

It's a process of <unk>, Unfortunately, taking longer than we expected, but we have to be resilience and in the seat and I don't want to send is that we believe because we know that data and we see the progress.

So that's the first time.

Next question please.

Our next question from the line of Omar <unk> with Evercore.

Hi, guys. Thanks for taking my questions I have two parts if I may so first Mike and Michelle at very helpful.

Shelby: We'll take our next question from the line of Umer Raffat with Evercore.

Commentary on helping us model out agile them for the balance of 2021.

Umer Raffat: Hi guys, thanks for taking my questions. I have two parts, if I may. So first, Mike and Michelle, very helpful commentary on how

But.

Street still carrying a $1 billion in U S AD your home for 2022, which basically implies north of 75000, new starts on agile Hal next year in U S. Most would argue 75000 new starts for next year is probably.

Umer Raffat: [inaudible]

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

Too high, but I guess since we're trying to level set today is 25000 new starts for next.

Unknown Executive: Today is 25,000 new starts for next year, too high an expectation.

Umer Raffat: And then also, Michelle, I feel like as we're heading into the BAN 24-1 PDUFA, it feels like there wasn't enough street discourse between Biogen management and the street ahead of Agihelm pricing. And I wonder, is it reasonable for the street to expect a BAN 24-1 price point that is more consistent with prior Alzheimer's?

Client expectation and then also Michele I feel like as we're heading into the band 24 wanted to do for us.

It feels like there wasn't enough street discourse between Biogen management in the Street ahead of agile home pricing and I Wonder.

Is it is it is it reasonable for St to expect a band 24, one price point, which is more.

Michelle Vunazzo: Thank you very much. So I'll take the first part of the question, Umer. You know, we're not guiding today for 2022, but I would say a couple of things. You know, we did say that we expected, you know, minimal revenue throughout the rest of 2021. We are still expecting, you know, a revenue ramp in 2022 post-NCD, assuming it's successful, and that would be in April. So that should give you some sense for, you know, the first quarter.

Year to mature Alzheimers, Matt Thank you very much.

Okay.

So I'll take the first part of the question.

We're not guiding today for 2022, but I would say a couple of things.

We did say that we expect minimal revenue throughout the rest.

Rest of 2021.

We are expecting still a revenue ramp in 2022 post NCD, assuming it's successful and that would be in April so.

That should give you some sense for the first quarter were in a bit of a delay until that happens we.

Michael R. McDonnell: We're in a bit of a delay until that happens. We don't have great visibility into patient counts, which is why we don't comment on them publicly. But we did give you, we can say that the sites are continuing to progress. We're at approximately 120 sites now that have infused at least one patient, which is more than double what it was about six weeks ago. And we're going to continue to monitor those metrics, and we'll ramp it up as quickly as we can.

We don't have great visibility to patient counts, which is why we do.

Comment on them publicly but we did give you.

We can we can say that the sites are continuing to progress. We're at approximately 120 sites now that are infused at least one patient which is.

More than double what it was about six weeks ago, and we're going to continue to monitor those metrics and.

We'll.

Ramp as quickly as we can but.

Michael R. McDonnell: But because of all the pieces, you know, that does cause a bit of a delay. And then the other important thing to remember is titration. So to the extent that we get through a successful NCD, there is still patient titration and dosing levels that need to ramp up. And so the revenue ramp is going to be gradual. But the important takeaway is that over the long term, we continue to believe that it's a very meaningful multi-billion dollar number.

It does cause a bit of a delay and then the other important thing to remember is titration. So to the extent that we get through a successful NCD. There is still patient titration dosing levels that need to ramp up.

And so the revenue ramp is going to be gradual but the important takeaway is that over the long term we.

We continue to believe.

That is a very meaningful multibillion dollar opportunity. So we do believe that.

Michelle Vunazzo: So we do believe that the uptake will certainly accelerate once the system has indications of potential coverage in January and then the final decision in April. But I don't expect this uptake to be explosive. At the same time, I don't expect it to be linear.

The uptake, we certainly accelerates once the sistema <unk> indication of a potential coverage in January and then the final decision in April.

But I don't expect that this update.

To be explosive at the same time I don't expect these to be <unk>.

Michelle Vunazzo: We believe there will be an acceleration, non-linear, of the uptake. Because the patient journey is still long, and while we make tremendous progress, and beyond the 120 centers, hundreds are progressing towards listing the product. It's really a gradual process. But we won't say more at this stage about the number of patients, but we'll have the opportunity to come back. And then on the band pricing, that's something obviously we'll determine, you know, at the appropriate time, and something that we'll be thoughtful about. I'm not sure there's a whole lot more we can say about it at this date, but we continue to progress the process there, and we're pleased with the initiation of the rolling submission there.

Now we believe there will be an acceleration normally now of the uptick because the patient journey is still young.

And while we make tremendous progress and beyond the 120 centers hundreds are progressing towards.

Listing the products.

<unk> had youll process, but we won't say more at this stage, but the number of patients, but we will have the opportunity to come back and then on the band pricing that's something obviously, we'll determine at the appropriate time and.

And something that we'll be thoughtful about im not sure theres a whole lot more we can say about it at this at this stage.

Continue to progress the process, there and where we're pleased with the initiation of the rolling submission there.

Shelby: Thank you. We'll take our next question from the line from Ronnie Gao with Bernstein.

Next question.

Thank you we'll take our next question from the line of Ronny Gal with Bernstein.

Ronnie Gao: Good morning. A question about the Adelhelm versus Le Canamab dynamics. If you're going to look at slide 10 in your presentation, it does look like Le Canamab has at least the same number of seats.

Good morning, a question about the <unk>.

But we can put ourselves lacana dynamics.

If you got to look at slide 10 in your presentation.

Does look like like Canada at least the same benefit as auto <unk> and given this drug will have full people though.

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

Michelle Vunazzo: Alzheimer's. I kind of wonder when you talk about Aldehalme being your growth driver longer term. Are we really saying it's either Aldehalme or Ben-2401? Can you talk a little bit about the comparative dynamics of the two products and could Ben-2401 end up being the major Alzheimer's product that Biogen markets in the future years?

Positive data, presumably positive in the third quarter of next year, it's a safer product.

It is indeed, the product youre, taking into pre symptomatic Alzheimer's I kind of wonder when you talk about <unk> being your growth driver longer term are we really saying, it's Eva I'll do harm or been through four line can you talk a little bit about the comparative dynamics of the two products and could <unk> end up being the major alzheimer products.

And at.

Biogen markets in the future years.

Michelle Vunazzo: So we are delighted to see Le Canemab coming along strong with a rich database after Adjuhelm, more than 600 patients, but it's only phase two. So we need to see phase three, but certainly very positive and reinforcing, and the line modification and signals will have the opportunity and the luxury to have two assets. Importantly, I want to reiterate that we stand by the data for Aduhelm because we know the data, we see the data, we see the new data, and we are very confident in the profile and the benefits and risks of these products for the long run. Now, with LECA, it's an even stronger position, but we need to wait for additional data. Yeah, I agree. You know,

So we are delighted to see <unk> coming along the strong leader.

It reached database after after <unk> had more than 600 patients, but its only phase III. So.

So we need to see the phase III.

To southern the very pleasant, even reinforcing in line model.

<unk> faction and signals will have the opportunity and the luxury to have two assets importantly, I want to hate the rate that we stand by the data for <unk>, because we know the date that we see the data we see the new data.

And and we are very confident in the profile of <unk> III products for the long run now with liquor.

Even a stronger position, but we'll need to wait for additional data.

Geoffrey Christopher Meacham: Yeah, I agree. You know, in my experience, things look really, really good after phase two sometimes. But then phase three, you know, it's a larger study, more sites, more countries. And so I think time will tell. And then, of course, we'll get the label. So I agree with Michelle.

Yes, I agree.

And my experience things look really really good after phase II sometimes.

But then phase III.

The larger study more sites more.

More countries.

And so I think time will tell and then of course, we will get the label So I.

Agree with Michelle.

Okay.

Next question please.

Shelby: Thank you. We'll take our next question from the line of Salim Saad with Nazoom.

Thank you.

We'll take our next question from the line of program with Merck.

Salveen Jaswal Richter: Great. Good morning, guys. And thanks so much for the color and detail.

Great. Good morning, guys and thanks, so much for the color and detail I had one on <unk>.

Salveen Jaswal Richter: I had one on adihelm. So when we look at peak sales for adihelm, the street seems to lead to sell-aside, which seems to be carrying around $9 billion in peak sales for this drug sale. And when I run the math here, it seems like that's more based on a chronic sort of administration and usage of the product. But when we consider things like coverage with evidence and that this product may not be, you know, I think you got to mention as well, in moderate patients, it's no longer appropriate to use the product.

So when we look at peak sales for adding on the street seems to like the sell side seems to be carrying around $9 billion in.

Peak sales for this drug sale.

And when I run the math here it seems like Thats more based on a chronic sort of.

Administration and usage of the product, but when we consider things like coverage with evidence and that this product may not be.

Yeah.

As I mentioned as well and moderate patients it's no longer appropriate to use the product and that this is a significant portion or it could be a significant portion of the Medicare part B wallet should people be really looking at this more you think it is an incidence based model.

Salveen Jaswal Richter: And that this is a significant portion or could be a significant portion of the Medicare Part B wallet. Should people really be looking at this more as an incidence-based model? in a duration of coverage cap coming out of the NCD, potentially.

And the duration of coverage cap coming out of the NCD.

Michelle Vunazzo: I'm not sure people will look solely at the incidents, you know, as if we're doing that for SMA or for HIV. I think I will comment on that.

I think you could potentially.

I'm not sure people, we look solely at the incidence.

As if we're doing that for SMA.

For HIV I think Ali will comment on that.

Geoffrey Christopher Meacham: We continue to stand behind the data, and we believe the long-term prospects are significant in terms of value creation. We believe the competition will enlarge the market, and the epidemiology is so large that there is room for actors, and out of the four, we have two, and it's a global play also. And we are not panicking because it's not because there is a delay in the U.S.; there is a process. The system is not ready. Evidently, we can see that, but it's a long way to go.

We continue to stand behind the data and we believe the long term prospect.

Aspect are significant in terms of value creation.

We believe the competition will enlarge the market and D. P D muesli being sold out there.

<unk> room for for actors and out of the four we have to any two global play also and we are not banking because.

See deeper because they've either he named the U S. Because there is a process.

He is not ready evidently we can see that but it's a long way to go.

Shelby: Yeah, I think underlying your question is the possibility, I think, that you've proposed that you could stop treatment after a certain period. And I refer you to the beautiful data generated by my colleagues at ASI and shown at the AAIC, where they took their Phase II trial patients, and there was a treatment gap, and they looked at them in the follow-on study. And during that treatment gap, even though the amyloid plaque burden remained low in those in which amyloid plaque had been removed by licanumab, during that treatment gap, the A42 to 40 ratio changed slowly over that period, suggesting that there are changes going on biologically related to the amyloid pathway during that gap period.

Yes, I think underlying your question is.

The possibility I think that you propose that you could stop treatment after a certain period of time.

And.

I refer you to the beautiful data generated by my colleagues at <unk> site.

Shown at the AIC.

They took their phase III trial patients and there was a treatment gap and they looked at them and they're in the.

And the follow on study and during that treatment gap, even though the amyloid plaque burden.

<unk>.

Low and those in which amyloid plaque had been removed by law cannot map that during that treatment gap a beta of 42 to 40 ratio changed slowly over that period, suggesting that there are changes going on biologically related to the amyloid pathway during that gap period. So.

Shelby: So I think the jury is still out on whether or not chronic treatment is needed, and I think that remains to be studied, and we look forward to providing more data on that. Okay, we have time for one more question.

I think the jury is still out on whether or not chronic treatment is needed.

And I think that remains to be studied and we look forward to providing more data on that.

Okay. We have time for I think one more question.

Phil Nadeau: We'll take our last question from Phil Nadeau with Cowan & Company.

We'll take our last question from the line of Sharon, Joe with Cowen and company.

Phil Nadeau: Good morning. Thanks for fitting me in. A question on the sites that are activated. You mentioned that 120 sites are currently active. We're curious to know how many you think you could have activated by the NCD decision in April. And also, could you talk a little bit more about the challenges of opening those sites? Are the challenges the exact same as you see with the physicians, or are there additional issues like the logistics around monitoring for the area or giving the infusion?

Hey, good morning, Thanks for fitting me in a question on the sites that are activated you mentioned that 120 sites are currently activated.

Curious to know how many you think you could have actually been activate by the NCD decision in April and also could you talk a little bit more about the.

The challenges in opening those sites are the challenges the exact same as you see with the <unk>.

Or are there additional issues like the logistics around monitoring for hernia or are giving the infusions.

Alisha Alaimo: Yeah, so thank you for the question, Phil. And I think when you take a step back and you look at the activated sites, which you know we're right around 120 or more, and we do have several hundred that are in queue on this journey, right? So we're giving you a number that talks about the activated site, which means one patient has been infused, but it doesn't capture all the sites that are going through these multiple steps.

Alicia.

Yeah. So thank you for the question, Phil and I think when you take a step back and you look at the activated sites, which you know we're right around a 120 or more and we do.

<unk> hundred that are in queue on this journey right. So we're giving you a number that talks about the activated site, which means one patient has been infused what it doesn't capture all of the sites that are going to these multiple steps. The operational challenges are still the same and when you really look at this I mean being first and being a pioneer in the space has.

Alisha Alaimo: The operational challenges are still the same. And when you really look at this, I mean, being first and being a pioneer in this space has been overwhelming for the system and for these sites. They've never had a drug like this before for their patients.

<unk> has been overwhelming for the system and for these sites they've never had a drug like this ever for their patience and writing their protocols having to go through all the steps of finding where will they do an MRI, where you know how well they do the lumbar puncture.

Alisha Alaimo: And writing their protocols, having to go through all the steps of finding where will they do an MRI, where will they do the lumbar puncture, and where will they do their infusions has been taking them some time. You know, I was talking to a couple sites just last week, and they've been trying to do this since June. So it's been taking them several months to get up and running. But when you think about our original strategy, which was focused on the sites where the majority of our patient population had already been diagnosed, you do remember that over 900 sites were ready.

Where they do their infusions has been taking them some time.

Talking to a couple.

Do have just last week and they've been trying to do this since June.

So it's been taking them several months to get up and running but when you think about our original strategy, which was focusing on the sites where the majority of our patient population have already been diagnosed you do remember that over 900 sites. We're ready so we believe that once we of.

Alisha Alaimo: So we believe that once we, of course, get our additional data out, we share our data, and the NCD outcome is finalized, those are going to be the majority of the sites that we will continue to focus on to get them up and running and get patients through the system.

Site for us to get our additional data out we share our data and the NCD outcome is finalized those are going to be the majority of the sites that will that we will continue to focus on to get them up and running and get patients through the system.

Michelle Vunazzo: So thank you so much for attending the call today. Biogen delivered another very strong quarter. The base business is solid. We are making some progress with Aducanimab and Aduhelm despite the short-term challenges we face. So what is key is the outlook and the mid to longer term. We have a path forward for zyranolone, and we are getting prepared to launch the biosimilar of Lucentis in the U.S. in a few months from now. Thank you very much for attending the call. It is an exciting time at Biogen.

Yeah.

So thank you so much for attending the call today Biogen delivered.

We had a very strong quarter again, the base business ease.

Solid.

We're making some progress toward you can imagine flood you haven't despite the short term challenges we face. So what is key is.

The outlook and the mid to longer term, we have a path forward was Johan alone.

Of course, we are getting prepared to launch the biosimilars of Lucentis in the U S. In the two months from now.

Thank you very much for attending the call exciting time at Biogen.

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

Yes.

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

And.

Okay.