Q2 2021 Biogen Inc Earnings Call

Mhm.

Yes.

Uh huh.

Okay.

Yes.

[music].

Okay.

Yeah.

Good morning, My name is Kim and I would be your conference operator today at this time I would like to welcome everyone to the Biogen second quarter earnings call on financial update.

Kean: Good morning. My name is Kean, and I will be your conference operator today. At this time, I would like to welcome everyone to the Biogen Second Quarter earnings call and financial update. All lines have been placed on Muse to prevent any background noise.

All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this time simply press star 1 on your telephone keypad.

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

Please limit yourself to 1 question to allow other participants time for questions.

If you require any further follow up you May press star 1 again to rejoin the queue.

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

Yes.

Mike Henke: Good morning, and welcome to Biogen's second quarter 2021 earnings call. Before we begin, I would encourage everyone to go to the investor section of Biogen.com to find the earnings release and related financial tables, including our gap financial measures and a reconciliation of the gap to non-gap financial measures that we will discuss today. Our gap financials are provided in tables one and two, and table four includes a reconciliation of our gap to non-gap financial results. We believe non-gap financial results better represent the ongoing economics of our business and reflect how we manage the business internally.

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

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

Mike Henke: We have also posted slides on our website that follow the discussions related to this call. I would like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.

I would like to point out that we will be making forward looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors discussed in our SEC filings for additional detail.

Mike Henke: I encourage you to consult the risk factors discussed in our SEC filings for additional details. On today's call, I am joined by our chief executive officer, Michelle Vounsos, 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 Sherfi Gwendo, head of Global Product Strategy and Commercialization, and Alicia Alimo, president of our U.S. organization. As a reminder, during the Q&A portion of the call, we kindly ask that you limit yourself to one question. I will now turn the call over to Michelle.

On today's call I am joined by our Chief Executive Officer, Michel <unk>, 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 Sherfey Guido head of global product strategy, and commercialization and Alicia <unk> President of our U S organization.

As a reminder, during the Q&A portion of the call. We kindly ask that you limit yourself to 1 question I will now turn the call over to Michel.

Good morning, everyone and thank you for joining US we have completed the first half of a transformative year for Biogen with progress across our neuroscience portfolio.

Michelle Vounsos: Good morning, everyone, and thank you for joining us. We have completed the first half of a transformative year for biogen, with progress across our neuroscience portfolio. However, I would like to start by addressing the confusion and criticism surrounding the recent approval of Hadjelm. We are cognizant of the key issues raised by the community and are working to provide additional clarity through the following goals, exploring all options to maximize patient access, including for the underserved population and those more at risk due to ethnicity, and educating on the updated labor language, which I will discuss.

However, I would like to start by addressing the confusion and criticism surrounding the recent approval of <unk>.

We are cognizant of the key issues raised by the community and are working to provide additional clarity to the following goals.

Exploring all options to maximize patient access, including for the underserved population and those more at risk due to ethnicity.

Educating on the updated label language, which I will discuss.

Michelle Vounsos: Publishing I will face three results in a peer-reviewed journal and disseminating additional data to inform clinical practice, including the management of the area, expediting the execution of the phase four confirmatory study, and leveraging the unique data generation opportunity we have with Embark, the longest and most comprehensive longitudinal study for an Alzheimer's disease therapy. Biogen stands behind our clinical data from eight studies with more than 3,000 patients that supported accelerated approval. As the FDA's current chief stated publicly earlier this month, Agihelm was approved on very solid grounds and represented the right thing to do for the patient.

Publishing our phase III results in a peer reviewed journal and disseminating additional data to inform clinical practice, including the management of ARIA.

But I think the execution of the phase 4 confirmatory study.

And leveraging the unique data generation opportunity, we have we to embark the longest and most comprehensive longitudinal study on it.

Diluted <unk> therapies.

Biogen stands behind our clinical data from 8 studies with more than 3000 patients that supported accelerated approval.

Yes.

Yes current chief stated publicly earlier this month <unk> was approved Apple quickly on us.

Very solid grounds and represented the right thing to do for the patients.

I want to be clear that biogen stands behind the integrity of the review process.

Michelle Vounsos: I want to be clear that biogen stands behind the integrity of the review process; respectful dialogue between the industry and regulators is standard and essential to advance the understanding of the therapeutic data driving innovation, as demonstrated more recently by the COVID-19 vaccine development programs of last year. We believe the accelerated approval pathway has transformed the treatment of oncology and now has the potential to transform the treatment of Alzheimer's disease. We appreciate the concerns about the price and are committed to ensuring sustainability of the system and maximizing access for patients without access.

Respectful dialogue between the industry and regulators is standout and essential to advance the understanding of the therapeutic data driving innovation as demonstrated more recently by the COVID-19 vaccine development programs of last year.

We believe the accelerated approval pathway has transformed the treatment of oncology.

And now has the potential to transform the treatment of Alzheimer's disease.

We appreciate the concerns about the price.

And are committed to ensure sustainability of the system and maximizing access for patients.

Without access.

Every day that passes we estimate that approximately 1000 Americans move from the early stage of Alzheimer's to moderate or severe dementia, and therefore may no longer be a <unk> session of treatment with <unk>.

Michelle Vounsos: Every day that passes, we estimate that approximately 1,000 Americans move from the early stage of Alzheimer's to moderate or severe dementia and therefore may no longer be appropriate for any session of treatment with Adjelm. This is why we are working with a sense of urgency to engage with the community, with payers, with CMS, and with policymakers to discuss potential innovative approaches with the goal of ensuring that price does not represent access issues for patients. With that said, I would like to focus on the fundamentals.

This is why we are working with a sense of urgency to engage with the community with bayer's with CMS and with policymakers to discuss potential innovative approaches with a goal of ensuring the price does not represent access issues for patients.

With that said I would like to focus on the fundamentals.

Another quarter with solid underlying financial performance that exceeded our expectation the accelerated approval of IGN for people suffering from Alzheimer's disease.

Michelle Vounsos: Another quarter with solid underlying financial performance that exceeded our expectations, the accelerated approval of ADUL for people suffering from Alzheimer's disease, and key redouts across our diversified portfolio. First, the accelerated approval of Hadriel represents the first new therapy for Alzheimer's disease in almost 20 years. Biogen has a deep history of building new markets and delivering innovative and impactful therapies to patients in need. We pioneered and currently maintain the market-leading portfolio of therapies for MS. We delivered the first approved and market-leading therapy for SMA.

Key readouts across our diversified portfolio.

First the accelerated approval of hydrogel and represents the first new therapy for Alzheimer's disease in almost 20 years.

Biogen has a deep history of building, new markets and delivering innovative and impactful therapies to patients in need we pioneered and current team maintain the market leading portfolio of therapies for MFS.

We delivered the first approved and market leading therapy for SMA.

Now.

Michelle Vounsos: Now, with Agihelm, we have the first approved therapy to address a defining pathology of Alzheimer's disease, which we believe represents a significant value creation opportunity for years to come. To lead us in successfully executing on our long-term leadership strategy, I am pleased to announce that Rashid Isar will be head of our newly created Alzheimer's Disease and dementia business unit and will join the Executive Committee of Biogen. Rashid is currently in charge of biogen's intercontinental region and our biosimilar business unit.

We have the first approved therapy to address a defining that total G of Alzheimer's disease, which we believe represents a significant value creation opportunity.

For years to come.

To lead us in successfully exiting executing on our long term leadership strategy I am pleased to announce that Rashid is or will be heard.

Our newly created on Zama disease, and dementia business, you need and will join the executive Committee of Biogen.

Rashid is currently in charge of Biogen and definitely hotel region, and our Biosimilars business unit. He has experience across multiple geographies and global position will service well as you work to maximize our potential impact on the lives of people living with this devastating disease.

Michelle Vounsos: His experience across multiple geographies and global position will serve him well as he works to maximize our potential impact on the lives of people living with his devastating disease. We have seen strong indications of very high initial patient interest in Adyhelm, as well as increased referrals from PCPs to specialists. However, it will take some time for sites to get up and running.

We have seen strong indications of very high initial patient interest in that you held as well as increased referrals from pcp's to specialist.

However, it will take some time for sites to get up and running while some large centers have said they will refrain for now for administering agenda to patients. Many of those sites are moving forward with the internal processes, such as pharmacy, and therapeutics or PMT Committee review.

Michelle Vounsos: While some large centers have said they will reframe for now to administer Aguilm to patients, many other sites are moving forward with internal processes such as Pharmacy and Therapeutics or P&T committee review, with some accelerating faster than we had originally planned. Of the 900 sites estimated to be ready shortly after approval, we estimate that approximately 325, or 35%, have completed a PNT review with a positive outcome or indicated that they won't require a PNT review. We have also seen some sites leverage external infusion centers if they face internal resistance or are awaiting clarity on their facilities' internal processes.

With some accelerating faster than we had originally planned.

Of the 900 sites, approximately which we expect it to be ready shortly after approval, we estimate that approximately 325 or 35% have completed PMT review with a positive outcome or indicated that they won't recur.

On a PNT review.

We have also seen some sites leverage external infusion centers each day.

<unk> internal resistance or awaiting clarity on their facilities internal process.

We continue to believe that consistent with our clinical trials. Most special lease will require confirmation of amyloid beta pathology, either via pet or CSS, which is also taking time to schedule and coordinate.

Michelle Vounsos: We continue to believe that, consistent with our clinical trials, most specialists will require a confirmation of amyloid beta pathology, either via PET or CSF, which is also taking time to schedule and coordinate. In terms of reimbursement, it is still early days, and I'm pleased to say that we have seen the first examples of Medicare Advantage plans approving pre-authorization. We welcome the recent opening by CMS of a national coverage determination analysis by CMS for monoclon antibodies targeting amyloid beta, including Adyhelm.

In terms of reimbursement it is still the early days and I am pleased to say that we have seen the first examples of Medicare advantage plans are proving preauthorization.

We welcome the recent opening of a national coverage determination on Az's by CMS for monoclonal antibodies targeting amyloid beta including <unk>. We believe this process will provide additional clarity on coverage for Medicare beneficiaries and drive consistency of access across the country.

Michelle Vounsos: We believe this process will provide additional clarity on coverage for Medicare beneficiaries and drive consistency of access across the country. We expect that regional Medicare administrative contractors and Medicare Advantage plans will provide coverage for Adjelm while the NCD analysis is underway.

We expect that original Medicare administrative contractors and Medicare advantage plans will provide coverage for <unk>, while the NCD analysis is underway.

We believe that CMS has switched decision to initiate the NCD analyses is a testament to the large unmet need in Alzheimer's disease, and the urgency to clarify access for patients.

Michelle Vounsos: We believe that CMS's swift decision to initiate the NCD analysis is a testament to the large unmet need in Alzheimer's disease and the urgency to clarify access for patients. We obtained new labor language for Adyhelm in July to clarify that treatment should be initiated in patients with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's dementia. This is the population studied in our clinical trials and where we generated clinical evidence as stated in Section 14 of the Adjelm label.

We obtain new label language for agile held in July to clarify that treatment should be initiated in patients with Michael <unk> impairment due to Alzheimer's disease or mild Alzheimer's dementia.

This is the population studied in our clinical trials and where we generated clinical evidence as stated in section 14 of the agile head on label.

This updated language aligns with our consistent expectation that <unk> will be prescribed mainly by specialties for patients in the early stage of Alzheimer's disease, and this update has been well received by the community, including prescribers payers and policymakers.

Michelle Vounsos: This updated language aligns with our consistent expectation that Adjelm will be prescribed mainly by specialists for patients in the early stage of Alzheimer's disease. And this update has been well received by the community, including prescribers, payers, and policy makers. Outside the US, we continue to engage with regulators regarding the ongoing review in Europe, Japan, and other markets, while also continuing to submit new regulatory filings around the world. In addition, we are pursuing early access mechanisms wherever possible, including an early access program and a charge-managed access program.

Outside the US we continue to engage with regulators regarding the ongoing review in Europe, Japan and other markets. While also continuing to submit new regulatory filing around the world.

In addition, we are pursuing early access mechanisms wherever possible, including an early access program and a charge manage access program.

We recognize that building a new market for Alzheimer's disease is an unprecedented undertaking and that this is just the beginning of our journey as we aim to make us home and potentially <unk> accessible to patients around the world.

Michelle Vounsos: We recognize that building a new market for Alzheimer's disease is an unprecedented undertaking and that this is just the beginning of our journey as we aim to make adieu and, potentially, lecanum accessible to patients around the world. We believe our teams are well equipped to successfully execute on a well-defined strategy aimed at long-term leadership for biogen in Alzheimer's disease. Second, this quarter, our pipeline delivered meaningful mid-to-late stage results in key areas, including depression, stroke, and biosimilars.

We believe our teams are well equipped to successfully execute on a well defined strategy aimed at long term leadership for Biogen in Alzheimer's disease.

Second this quarter, our pipeline delivered meaningful mid to late stage results in key areas, including depression stroke and Biosimilars.

The positive water for phase III trial for <unk> hundred on in major depressive disorder is a significant milestone towards bringing a differentiated potential treatment option to the 17 million patients suffering from depression in the U S alone.

Michelle Vounsos: The positive waterfall phase three trial of zuranolone in major depressive disorder is a significant milestone towards bringing a differentiated potential treatment option to the 17 million patients suffering from depression in the U.S. alone. The observed rapid onset of benefit in as soon as three days, In addition to a differentiated tolerability profile and two-week dosing regimen, I would believe that if approved, ziranolone would be a multi We were also excited to see positive data from the phase 2A trial of TMA 07 in acute ischemic stroke. Stroke is the second leading cause of death worldwide, and those who survive may suffer irreversible damage to the brain. We are highly encouraged by the results of the trial, and we immediately moved forward with executing the option to acquire CMS 07.

The observed rapid onset of benefit in as soon as free days. In addition to a differentiated tolerability profile and 2 week dosing regimen underscore our belief that if approved zero handle on would be a multibillion dollar product.

We were also excited to see positive data from the phase Iia trial of TMA zero 7 in acute ischemic stroke stroke is the second leading cause of death worldwide and those will survive may suffer irreversible damage of the brain. We are highly encouraged by the results of the trial.

And we immediately moved forward with executing the option to acquire Tms zero 7.

Should both as Johan alone <unk> be approved Biogen will be in a leadership position in offering novel therapies for Alzheimer's disease. The number 1 novel degenerative disease Depression, 1 of the most common mental health disorder and stroke, a leading cause.

Michelle Vounsos: Should both Zeranolone and TMS-07 be approved, biogen will be in a leadership position in offering novel therapies for Alzheimer's disease, the number one neurodegenerative disease, Depression, one of the most common mental health disorders, and a leading cause of neurologic disability. In addition to these withouts, we had a positive phase three without for our biosimilar referencing actamera. With these positive results in hand, we begin to prepare for a regulatory filing.

Neurologic disability.

In addition to these readouts, we had the positive phase III readout for our Biosimilar referencing actemra with these positive results in hand, we begin to prepare for a regulatory filing.

As with any company engaging and breakthrough science, we also had setbacks in some programs, including our anti Tau antibody in Alzheimers disease, and our gene therapy programs in ophthalmology.

Michelle Vounsos: As with any company engaging in breakthrough science, we also had setbacks in some programs, including our anti-tow antibody in Alzheimer's disease and our gene therapy programs in ophthalmology. Third, we reported a solid quarter as we continue to execute well across our core business of MS, SMA, and biosimilals, and we are pleased to be raising our revenue guidance for the year, which Mike will discuss. Q2 overall MS revenue, including Okrevis royalties, was $1.8 billion. Putting aside the entry of Tech Federal Generics in the U.S., our broader MS business continued to demonstrate resilience, with a 5% increase in patients worldwide. These performances underscore our ability to execute well.

Third we reported a solid quarter as we continued to execute well across our core business of Ms. SMA and Biosimilars and we are pleased to be raising our revenue guidance for the year, which Mike will discuss.

Q2, overall, EMS revenue, including <unk> royalties was $1.8 billion.

Putting aside the entry of <unk> generics in the us our broader MSP business continued to demonstrate resilience with a 5% increase in patients worldwide. These performance underscore our ability to execute well.

We were very pleased to see continued revenue growth for Humira.

Michelle Vounsos: We were very pleased to see continued revenue growth for Vumerity, which remains the number one oral MS product in terms of new prescriptions in the U.S. We believe this performance is a testament to Vumerity's strong product profile. Given the progress of the Vumerity launch to date, in addition to the planned XUS launchers, we believe Vumerity can reach over a billion dollars in annual sales over time. We also continue to invest in new potential treatments to address the remaining unmet medical needs for MS patients.

<unk> remains the number 1 oral Ms product in terms of new prescriptions in the US. We believe this performance is a testament to <unk> strong product profile given the progress of the <unk> launch to date. In addition to planned ex U S launches. We believed we marry Keith can reach over $1 billion in <unk>.

<unk> sales over time.

We also continue to invest in new potential treatment to address the remaining unmet medical needs in <unk>.

MF patients last week, we announced the license and collaboration agreement with <unk> for <unk> with unique and innovative CNS penetrant phase II <unk> inhibitor for the potential treatment of all forms of MFS. This transaction is subject to customary closing conditions.

Michelle Vounsos: Last week, we announced a license and collaboration agreement with Inocare for Orila Brutinip, an innovative CNS penetrant phase 2 BTK inhibitor for the potential treatment of all forms of MS. This transaction is subject to customary closing conditions.

Next spin Raza generated second quarter global revenues of 500 million.

Michelle Vounsos: Next, Spinraza generated second-quarter global revenues of $500 million. While Spinraza is facing competition in the US, which has been exacerbated by the impact of the COVID-19 pandemic, we were encouraged to see that SpinRaza's discontinuation rates continue to decrease versus Q1 of this year. Total revenue in the US was flat versus the pre-quarter, and Spinraza continued to perform very well outside the US with 23% revenue growth versus Q2 of last year. SpinRaza remains the market-leading treatment for SMA, and we stand behind its proven efficacy and well-established safety profiles across all types of SMA.

<unk> is facing competition in the US which has been exacerbated by the impact of COVID-19 pandemic. We were encouraged to see that spin rather us discontinuation continued to decrease versus Q1 of this year.

Total revenue in the US was flat versus the prior quarter and <unk> continued to perform very well outside the us with 23% revenue growth versus Q2 of last year.

<unk> remains the market, leading treatment for SMA, and we stand behind spin raws us proven efficacy and well established safety profiles across all types of SMA.

In fact, our market research indicates so thats been raised us perceived efficacy among adult has improved over the past year and exceeds the efficacy perception for therapeutic alternatives, including recently plan.

Michelle Vounsos: In fact, our market research indicates that Spinraza's perceived efficacy among adults has improved over the past pasture and exceeds the efficacy perception for therapeutic alternatives, including RISD plan. Although we face near-term competitive pressure in SMA, we believe SpinRaza can continue to grow over the medium to long term, both in the U.S. and globally, driven by overall market growth, the efficacy and safety profile in all age groups, continued data generation, particularly in older patients, and further geographic expansion.

Although we face near term competitive pressure in SMA, we believe spin rise that can continue to grow over the medium to long term both in the us and globally driven by overall market growth.

Efficacy and safety profile in all age groups continued data generation, particularly in older patients and further geographic expansion.

Our biosimilars business delivered revenue of $2.2 million allows us this quarter, while we remain focused on executing against our currently marketed therapies. We also look to expand our portfolio, including our recent collaboration with bio terror and a positive <unk> opinion for our buyers.

Michelle Vounsos: Our biosimilar business delivered revenue of $2 million this quarter. While we remain focused on executing against our currently market therapies, we also look to expand our portfolio, including our recent collaboration with bioterra and a positive CHMP opinion for our biosimilar reference Lucentis. Fourth, we still have two key phase three studies without anticipated in the remainder of 2021. This includes the phase three study for Tofercennes, potentially the first genetically targeted therapy for ALS, as well as an additional phase three study for Zuranolone in major depressive disorder.

Referencing lucentis.

So we still have 2 key phase III readouts anticipated in the remainder of 2021 day.

This includes the phase III study photo FSN potentially the first genetically targeted therapy for a less as well as an additional phase III for <unk> handle on in major depressive disorder.

Given the incredible unmet medical need in AOS and encouraging results from the prior to Hudson Trail. We recently initiated an individual compassionate use program to provide <unk> to the most rapidly progressing patient suffering from <unk> 1 AOS.

Michelle Vounsos: Given the incredible unmet medical need in ALS and encouraging results from the prior ToferCEN trial, we recently initiated an individual compassionate use program to provide ToferCEN to the most rapidly progressing patients suffering from SOD1 ALS. Taken together, these 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-franchised portfolio across a broad spectrum of neuroscience therapeutic areas. I would like now to turn the call over to all for a more detailed update on our progress in R&D. Thank you, Michelle.

Taken together these developments represent a significant step forward.

Our goal of transforming Biogen from what was once an EMS company to 1 that is built upon a multi franchise portfolio across.

Across a broad spectrum of neuroscience therapeutic areas I would like now to turn the call over to us for a more detailed update on our progress in R&D.

Unknown Executive: I'd like to start by saying a few words about aducanumab. The accelerated approval of Aducanumab has generated discussions reflecting a broad range of opinions, including about its efficacy, the FDA's selection of the accelerated approval path, and the regulatory process in general. Since June 7th, the FDA has made several clarifying statements on these topics. As always, we defer to the FDA as the lead voice on such matters. They are the independent regulatory body charged with weighing the data expertly and dispassionately in order to make critical decisions that have the potential to impact millions of people.

Thank you Michelle I'd.

I'd like to start by saying a few words about edge of Canyon Mab.

The accelerated approval of <unk> has generated discussion, reflecting a broad range of opinion, Inc.

<unk> about its efficacy the FDA selection of the accelerated approval path and the regulatory process in general.

Excuse me since June 7 the FDA has made several clarifying statements on these topics.

As always we defer to the FDA as the lead voice on such matters.

Are the independent regulatory body charged with weighing the data expertly and dispassionately in order to make critical decisions that have the potential to impact millions of people.

Unknown Executive: But I thought it would be helpful to add our perspective on several of these topics, including our interactions with the agency. We are proud of the work our dedicated team has done to develop aducanumab and the hope it brings to patients with Alzheimer's disease. We are equally proud of the professionalism both our team and the FDA demonstrated during a very lengthy process. We therefore welcome a formal review into the interactions between FDA and Biogen on the path to the approval of aducanumap.

I thought it would be helpful to add our perspective about several of these topics, including our interactions with the agency.

We are proud of the work our dedicated team has done to develop <unk> and the hope it brings to patients with Alzheimer's disease.

We are equally proud of the professionalism of our team and the FDA demonstrated during a very lengthy process.

Unknown Executive: A better understanding of the facts is good for everyone involved to ensure confidence in both the therapy and the process by which it was approved. We will cooperate fully with the review, even as we prioritize the issues that affect us. I want to emphasize that it is normal and appropriate for scientists and clinicians to discuss the data from experiments in clinical trials, debate, and disagree on the interpretation of the data.

We therefore welcome a formal review into the interactions between FDA and Biogen on the path to the approval of <unk>.

A better understanding of the facts is good for everyone involved to ensure confidence in both the therapy and the process by which it was approved.

Unknown Executive: That is how science advances, and we welcome these discussions. However, I would like to correct some of the misinformation we have seen recently. First, several people have stated that all anti-ameloid antibodies clear amyloid from the brain. This is factually incorrect.

We will cooperate fully with the review even as we prioritize the issues that affect patients.

I want to underscore that it is normal on appropriate for scientists and clinicians to discuss the data from experiments in clinical trials.

Day and to disagree on the interpretation of the data.

Unknown Executive: First-generation anti-ameloid antibodies such as Bathynozomab and Solenozumab are not specific for aggregated forms of A-Beta or target soluble monomeric A-Beta, and Krenesimab, being an IgG4, is deficient in effector function. As a result, these antibodies do not clear amyloid from the brain. This slide shows the amyloid PET imaging results from the peer-reviewed literature of these first-generation antibodies. Crenazimab and Solonizumab had no significant difference from placebo in amyloid plaque burden. Bapapineuzamab did show a significant difference from placebo in phase three trials, but this was largely driven by an unexplained increase in amyloid plaque burden in these placebo-treated patients in the mild to moderate stage of Alzheimer's disease.

That is our science advances and we welcome these discussions.

However, I would like to correct some of the misinformation we have seen recently.

First several people have stated that all anti amyloid antibodies clear amyloid from the brain.

This is factually incorrect.

First generation anti amyloid antibodies, such as <unk> and solid news on that are not specific for aggregated forms of day beta or targets soluble monomeric, a beta and for <unk> being on <unk> 4 is deficient in the effector function.

As a result, these antibodies do not clear amyloid from the brain.

This slide shows the amyloid pet imaging results from the peer reviewed literature of these first generation antibodies.

Unknown Executive: We believe this increase in amyloid plaque in placebo patients must have been a spurious result, as we now know that plaque buildup reaches a maximum by the time patients have mild cognitive impairment. In short, there is no evidence that the first generation antibodies against A-Beta actually removed amyloid plaque. There is no basis for using the failure of these antibodies as a reason not to approve canyamab as your canyamab. We have also seen statements that all of Ed Ducanamaz's results are post hoc, that is also factually incorrect.

Current as the Mab in solar Newsom had no significant difference from placebo on amyloid plaque burden.

<unk> did show a significant difference from placebo on the phase III trials, but this was largely driven by an unexplained increase in amyloid plaque burden.

And these placebo treated patients in the mild to moderate stage of Alzheimers disease.

We believe this increase in amyloid plaque in placebo patients must have been a spurious result, as we now know the plaque buildup reaches a maximum by the time that patients have mild cognitive impairment.

Unknown Executive: The primary and secondary endpoints had been pre-specified in the phase three trial protocols and statistical analysis plans before the first patient was enrolled in the trials. The aducanumab label shows the results on these pre-specified endpoints based on data that had already been collected at the sites by the time the trials were prematurely terminated on March 21, 2019. Additionally, some have contended that Aria led to unblinding.

In short there is no evidence that the first generation antibodies against a beta actually removed amyloid plaque.

There is no basis for using the failure of these antibodies as a reason not to approve <unk>.

We are also seeing statements that all of <unk> results our post hoc.

That is also factually incorrect.

The primary and secondary endpoints had been pre specified in the phase III trial protocol and statistical analysis plans before the first patient was enrolled into the trial.

Unknown Executive: We took great care to ensure that the neurologists who assessed the clinical outcome measures did not know about the occurrence of ARIA. One way in which we assured ourselves that unblinded, unblinding did not affect the results was to examine the clinical outcomes after ARIA was seen. If Aria had affected blinding, the results after Aria might be expected to change. This slide shows that the results excluding data that have been obtained after ARIA events were the same as the overall results.

The <unk> label shows the results on these pre specified endpoints based on data that had already been collected at the sites by the time the trials will prematurely terminated on March 21.2019.

Separately, some have contended that ARIA led to unblinded.

We took great care to ensure that the neurologists, who assess the clinical outcome measures did not know about the occurrence of ARIA.

Unknown Executive: Thus, we are confident that unblinding due to ARIA did not affect the results of the phase three trials of aducanumab. And finally, while some people have opined that the approval of aducanumab would inhibit the development of other drugs for Alzheimer's disease, this statement is contradicted by precedent. Prime example of this is the history of drug approvals for HIV AIDS, non-Hodgkins lymphoma, and multiple sclerosis, to name just a few. In neurology, the first medicine ever approved for MS was in 1993 when Beta Interferon received accelerated approval in the United States.

1 way in which we ensured ourselves that unblinded on blinding did not affect the results with to examine the clinical outcomes. After Oreo was seen with <unk>.

<unk> had an effective blinding the result, after ARIA might be expected to change.

This slide shows that the results excluding data that had been obtained after Oreo events were the same as the overall results.

We are confident that on blinding due to ARIA did not affect the results of the phase III trials of <unk>.

And finally, some people have opined that the approval of agile Canyon Mab would inhibit the development of other drug for all farmers disease.

Unknown Executive: Within the next several years, two other types of beta interferon were approved after controlled clinical trials showed that they slowed the progression of disability. Today, there are more than 20 drugs approved for the treatment of MS, all of which reduce the risk of relapse or slow the progression of disability or both.

This statement is contradicted by precedent.

Prime example, where the history of drug approvals for HIV AIDS non Hodgkin's lymphoma, and multiple sclerosis to name just a few.

In neurology, the first medicine ever approved for MFS was 1993, when beta interferon received accelerated approval in the United States.

Unknown Executive: All new molecular entities were approved based on randomized controlled clinical trials that have continued to be conducted to this day, nearly 30 years after the accelerated approval of beta interferon. We believe a similar situation is just starting to unfold with Alzheimer's disease. Over the coming years, data will become available from phase three trials of several second-generation anti-ameloid antibodies, which are capable of effectively removing amyloid plaque. And we will also have the results of the post-marketing trial of aducanumab. These data should address any residual uncertainty surrounding the efficacy of this class.

Within the next several years to other types of beta interferon will approved after controlled clinical trial showed that they slowed the progression of this ability.

Today, there are more than 20 drugs approved for the treatment of MFS, all of which reduce the risk of relapse or slow the progression of disability or both.

All new molecular entities were approved based on randomized controlled clinical trials that continue to be conducted to this day nearly 30 years after the accelerated approval of beta interferon.

We believe a similar situation is just starting to unfold with Alzheimers disease.

Unknown Executive: In the meantime, the main serious risk associated with Aducanumab is ARIA. Based on data from phase three trials, ARIA, which is an amyloid-related imaging abnormality, occurred in 41 of patients who took percent of patients who took aducanumab, 10 milligrams per kilogram, and 10% of patients who took placebo. Of the patients taking aducanumab that experienced ARIA, 24% experienced clinical symptoms. In other words, about 10% of patients treated with the approved dose of aducanumab experienced symptomaticaria, and serious symptoms were reported in 0.3% of patients. Alzheimer's disease is 100% fatal, and before death, it robs people of themselves.

Over the coming years data will become available from phase III trials of several second generation anti amyloid antibodies, which are capable of effectively removing amyloid plaque and we also have we will have the results of the post marketing trial of accurate Canyon Mab.

These data should address any residual uncertainty surrounding the efficacy of this class.

In the meantime, the main serious risks associated with AD you can you map us ARIA.

Based on data from the phase III trials, ARIA, which is an amyloid related imaging abnormality occurred 41 patients.

<unk> of patients who took <unk> 10.

Milligrams per kilogram.

10% of patients who took placebo.

Of the patients taking agile canyon bad debt experienced ARIA.

4% experience clinical symptoms.

Unknown Executive: Should these additional clinical studies confirm that this class of drugs is effective in slowing clinical decline, as Michelle mentioned, patients who lack access to aducanumab may no longer be appropriate for treatment. We have been discussing the adjutantamad data for many months now. Educanamad was approved for use in the United States on June 7th, and the data are summarized clearly in the label. Our hope is for doctors to discuss the benefits and risks of taking aducanumab with their patients and caregivers based on rational analysis and accurate information.

Other words about 10% of patients treated with the approved dose of <unk> experienced symptomatic ARIA.

Serious symptoms, we reported and 0.3% of patients.

All timers disease is 100% fatal.

And before that Robert people of themselves.

Should these additional clinical studies confirm that this class of drugs is effective in slowing clinical decline as Michel mentioned mention patients who lack access to Azure Calumet may no longer be appropriate for treatment.

Unknown Executive: We are doing what we can to provide that information to the prescribing community in a number of ways. First, we will continue to present at scientific forums and publish analyses from our phase three trials of aducanumab, with a focus on publishing the primary manuscript and disseminating additional data to inform clinical practice, including the management of ARIA. This includes four presentations planned for the AAIC conference next week. Second, we are moving with a sense of urgency to finalize the design of the aducanumab post-marketing confirmatory phase four controlled study intended to verify the clinical benefit of aducanumab in Alzheimer's disease. We are still working through the details and are actively engaged with regulators.

We have been discussing the <unk> data for many months now.

<unk> was approved for use in the United States on June 7.

The data are summarized clearly in the label.

Our hope is for doctors to discuss the benefits and risks of taking agile can you map with their patients and caregivers based on rational analysis and accurate information we.

We're doing what we can to provide that information to the prescribing community and a number of ways.

First we will continue to present at scientific forums and publish analyses from our phase III trials of <unk> with a focus on publishing the primary manuscript and disseminating additional data to inform clinical practice, including the management of ARIA. This.

Unknown Executive: Our goal is to execute the study as expeditiously as possible and well ahead of the post-marketing commitment of approximately nine years. Third, we have a unique data generation opportunity with the Embark Long-Term Extension Study. Just this month, we enrolled our last patient in the trial, bringing the total enrollment in the study up to roughly 1,700 Alzheimer's disease patients. The two-year embark study will include patients previously treated with aducanumab for approximately 6.5 years, thereby generating important long-term safety and efficacy data for aducanumab.

This includes 4 presentations planned for the AIC Conference next week.

Second we are moving with a sense of urgency to finalize the design of the agile <unk> post marketing confirmatory phase 4 controlled study intended to verify the clinical benefit of <unk> in Alzheimers disease.

We're still working through the details and are actively engaged with regulators.

Our goal is to execute this study as expeditiously as possible and well ahead of the post marketing commitment of approximately 9 years.

Unknown Executive: We plan to present the embark baseline data at an upcoming medical meeting, which should yield important insights on the effects of treatment interruption, the longer-term impact of reducing amyloid plaques, and the potential benefits of continued treatment. Lastly, we plan to initiate a real-world observational study in Alzheimer's disease called I-Care ADUS in order to collect real-world long-term effectiveness and safety data on aducanumab. We are also evaluating additional formulations of aducanumab with the goal of increasing patient confidence.

Third we have a unique data generation opportunity with Embarq with the Embarq long term extension study.

Just this month, we enrolled our last patient in the trial, bringing the total enrollment in the study up to roughly 1700, all farmers disease patients.

The 2 year embark study will include patients previously treated with Azure can you map for APA.

Approximately 6.5 years, thereby generating important long term safety and efficacy data for <unk>.

We plan to present, the Embarq baseline data at an upcoming medical meeting, which should which should yield important insights on the effects of treatment interruption the longer term impact of reducing amyloid plaques and the potential benefits of continued treatment.

Unknown Executive: Last month, we initiated a phase one study to evaluate the bioavailability of a subcutaneous formulation of aducanumab and continue to engage with regulators on the appropriate development strategy. Finally, we continue to advance our innovative pipeline of potential Alzheimer's disease treatments. This includes Lachanamab, our other anti-ameloid antibody that we are collaborating on with ASI. Canomab was recently awarded breakthrough therapy designation by the FDA, and we are working with A-Side to engage with the FDA and pursue the optimum regulatory pathways.

Lastly, we plan to initiate a real world observational study in Alzheimer's disease called Eyecare AWS in order to collect real world long term effectiveness and safety data on <unk>.

We are also evaluating additional formulations of agile can you map with the goal of increasing patient confidence.

Last month, we initiated a phase 1 study to evaluate bioavailability bio availability of a subcutaneous formulation of <unk> and continue to engage with regulators on the appropriate development strategy.

Unknown Executive: We also look forward to the readout of the Clarity Phase 3 study of Lacanamab, expected next year. In addition to our anti-ameloid approaches, we are also targeting tau, the primary component of neurofibrillary tangles, another pathological hallmark of Alzheimer's. Although we were disappointed to learn that the phase two study of Goceranamab in early Alzheimer's disease did not meet the primary or secondary endpoints, we do not believe these results diminish the relevance of TOW as a potential therapeutic target in Alzheimer's disease.

Finally, we continue to advance our innovative pipeline of potential all farmers disease treatments. This includes lacana mab or other anti amyloid antibody that we're collaborating on with ACI.

<unk> was recently awarded breakthrough therapy designation by the FDA and we are working with eisai to engage with the FDA and pursue the optimum regulatory pathway.

We also look forward to the readout of the clarity phase III study of Mccanna Mab expected next year.

In addition to our anti amyloid approaches we are also targeting Tau the primary component of neuro Fibrillary tangles, another pathological hallmarks of Alzheimer's disease.

Although we were disappointed to learn that the phase III study of <unk> in early Alzheimer's disease did not meet the primary or secondary endpoints. We do not believe these results diminish the relevance of Paul as a potential therapeutic target in Alzheimers disease, whereas we have discontinued the bid 92 program we're continuing.

Unknown Executive: Whereas we have discontinued the BIB 92 program, we are continuing the development of BB80, our antisense oliglucleotide, which aims to reduce the production of all forms of tau, both intra-cellular and extracellular. Results of the Phase 1 trial will be presented at AAC next week. In addition to Alzheimer's disease, this quarter we continue to progress a broad neuroscience pipeline with positive data readouts in depression and First, in neuropsychiatry, in collaboration with SAGE, we were excited to learn that the Phase 3 Waterfall Study, evaluating a 50 milligram dose of Xeranolone for major depressive disorder, achieved its primary endpoint.

<unk> the development of <unk>, our antisense oligonucleotide, which aims to reduce the production of all forms of Tau, both intra and extra cellular.

Results of the Phase 1 trial will be presented at AIC next week.

In addition to all timers disease. This quarter, we continued to progress a broad neuroscience pipeline with positive data Readouts and depression and stroke both areas in need of innovation.

First in neuropsychiatry and collaboration with Sage, we were excited to learn that the phase III waterfall study evaluating a 50 milligram dose of us around on a major depressive disorder achieved its primary endpoint.

Unknown Executive: Despite the pronounced placebo effect observed in the waterfall study, two weeks of Xeranolone treatment resulted in a statistically significant reduction in depressive symptoms at day 15, as measured by the Ham D-17 scale versus placebo. Suranolone treatment also resulted in a rapid onset of action showing treatment effects at days 3, 8, and 12. The safety profile was similar to that seen previously, and most treatment-emergent adverse events were mild to moderate in severity, and we observed no signal of increased suicidal ideation or behavior or withdrawal symptoms.

Despite the pronounced placebo effect observed in the waterfall study 2 weeks of the Randall on treatment resulted in a statistically significant reduction in depressive symptoms at day 15 as measured by the Ham D 17 scale versus placebo.

It's around on on treatment also resulted in a rapid onset of action showing treatment effects at day, 3.8 and 12.

Unknown Executive: We continue to believe that Xeranolone, with its rapid treatment response, durable treatment effects after a two-week dosing period, and differentiated tolerability, has the potential to transform treatment for people suffering from depression. We are now working with Sage to determine the optimum filing path. The waterfall study is also part of the robust development program for Xeranalone, which also includes the ongoing shoreline, Horal, and Skylark Studies; we expect to report top-line data from coral and shoreline in 2021.

Safety profile was similar to that seen previously and that most treatment emergent adverse events were mild to moderate in severity and we observed no signal of increased suicidal ideation or behavior or withdrawal symptoms.

We continue to believe us around alone with its rapid treatment response durable treatment effects. After a 2 week dosing period and differentiated tolerability has the potential to transform treatment for people suffering from depression.

We are now working with sage to determine the optimum filing path.

The waterfall study is also is part of the robust development program for us around alone, which also includes the ongoing shoreline coral and Skylark studies, we expect to report topline data from coral and shoreline. In 2021, we are working with sage to evaluate enrollment rates for the skyler.

Unknown Executive: We are working with Sage to evaluate enrollment rates for the Skylark study and will provide updates when that work is completed. We have also obtained positive data from the Phase 2A study of TMS 007 in acute ischemic stroke. Current standard of care in the treatment of ischemic stroke calls for the use of thromboitic agents within three to four and a half hours of symptom onset. However, the approved agents also carry the risk of intracranial hemorrhage, or ICH, which increases with time.

<unk> study and we will provide updates when that work is completed.

We also obtained positive data from the Phase Iia study of Tms zero, there are 7 in acute ischemic stroke.

Current standard of care in the treatment of ischemic stroke calls for the use of thrombolytic agents within 3 to 4 and a half hours of symptom onset.

Unknown Executive: During the Phase 2A study of TMS 007, now referred to as BIV 131, patients were dosed 4.5 to 12 hours after the onset of stroke symptoms, with an average of 9.5 hours. There was no symptomatic ICH in the Bib 131 group.

The approved agents also carry the risk of intracranial hemorrhage, or IC, H, which increases with time.

During the phase Iia study of <unk> 7 now referred to US bid 131 patients were dosed for 5 to 12 hours. After the onset of stroke symptoms with an average of 9.5 hours.

There was no symptomatic IC H in the bid 131 group when compared to placebo bid on.

Unknown Executive: When compared to placebo, Bib 131 increased the rate of recanalization of occluded intracranial arteries, as visualized by MRI angiography, in patients with large vessel strokes. Moreover, more patients regained the ability to function independently, as measured by the modified Rankin scale at day 90 compared to placebo. We are encouraged by the results of this study and are hopeful that Bib 131 could have the potential to be a next-generation thrombolytic drug that safely extends the treatment window after stroke onset. We plan to advance Bid 131 into the late stages of development as soon as possible.

31 increase the rate of recapitalization of included intracranial arteries as visualized by MRI on geography in patients with large vessel strokes. Moreover, more patients regain their ability to function independently as measured by the modified Rankin scale at day 90 compared to placebo.

We're encouraged by the results of this study and are hopeful that bid 131 could have the potential to be a next generation thrombolytic drug safety extend the treatment window after stroke onset.

We plan to events did 131 into the late stages of development as soon as possible.

We also bolstered our MS pipeline through a proposed license and collaboration agreement with <unk> care for phase 2 oral small molecule <unk> inhibitor for the potential treatment of Ms.

Unknown Executive: We also bolstered our MS pipeline through a proposed license and collaboration agreement within a care for a phase two oral small molecule BTK inhibitor for the potential treatment of MS. Orelibrutiniv, a covalent BTK inhibitor with high selectivity and demonstrated CNS penetrants, is currently being studied in a global placebo-controlled phase two study in relapsing remitting MS. The ability of Orelibbrutinib to cross the blood-brain barrier, combined with its high kinase selectivity, differentiates it from other BTK inhibitors currently in development for MS.

Oral <unk> <unk>.

Hey, covalent PTK inhibitor with high selectivity and demonstrated CNS Penetrant is currently being studied in a global placebo controlled phase II study in relapsing Remitting Ms.

The ability of <unk> to cross the blood brain barrier combined with its high kinase selectivity differentiates it from other <unk> inhibitors currently in development for MFS.

Looking towards the remainder of the year. We also have 2 pivotal readouts remaining in ALS and depression.

Unknown Executive: Looking toward the remainder of the year, we also have two pivotal readouts remaining in ALS and depression. Earlier this month, we completed the one-year placebo-controlled treatment period of the phase three study of Toferes in S-O-D-1 ALS, and we expect the readout by this fall. We have also recently enrolled the first participant in Atlas, a phase three trial of Fersen initiated in clinically pre-symptomatic SOD1 mutation carriers. Our hope is that treating people earlier in the disease may provide the best opportunity to slow or even delay the onset of this terrible disease.

Earlier this month, we completed the 1 year placebo controlled treatment period of the phase III study of <unk> and so do you on ALS and we expect a readout by this fall.

We also recently enrolled the first participant and Atlas a phase III trial of <unk> initiated and clinically pre symptomatic <unk>.

<unk> carriers.

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

In summary, this quarter, our R&D organization made significant progress advancing our pipeline.

Unknown Executive: In summary, this quarter, our R&D organization made significant progress advancing our pipeline. In addition to the accelerated approval of Aducanumab, we completed five mid-to-late stage readouts in several key therapeutic areas characterized by high unmet needs, including depression and stroke. The field of neuroscience is rapidly advancing, and with the investments we have made in prioritizing genetically validated targets, deploying biomarkers in early stage clinical programs, and building our human and technological capabilities, we believe we are well positioned to take advantage of the many opportunities offered by this exciting area of science for the benefit of patients. I will now pass the call over to Mike.

<unk> for the accelerated approval of <unk>, we completed 5 mid to late stage Readouts in several key therapeutic areas characterized by high unmet need including depression and stroke.

The field of neuroscience is rapidly advancing and with the investments we have made in prioritizing genetically validated targets deploying biomarkers in early stage clinical programs and building, our human and technological capabilities. We believe we are well positioned to take advantage of the many opportunities offered.

By this exciting area of science for the benefit of patients I will now pass the call over to Mike.

Mike: As Michelle noted, we were very pleased with our second quarter results as we continue to execute well. However, we continue to face competition from Tech Federa generics in the U.S., which has impacted our year-over-year financial performance. However, as we move forward, we remain fully focused on our core business as well as the launch of Adjahelm in the United States.

Thank you al.

As Michel noted we were very pleased with our second quarter results as we continued to execute well we continue to face competition from tech Vadera generics in the us which impacted our year over year financial performance. However, as we move forward, we remain fully focused on our core business as well as the launch of <unk> in the United States.

Mike: Total revenue for the second quarter of $2.8 billion declined 25% versus the prior year at actual currency and 26% at constant currency. This decline reflects the impact of Tech Federer generics in addition to approximately $330 million in revenue that was recorded in Q2 2020 related to the one-time license of certain manufacturing-related intellectual property. We were, however, encouraged to see total revenue increase by 3% versus Q1 of 2021, primarily driven by the MS franchise and Okervis royalty. Total Agihelm revenue for the second quarter was $2 million. I would refer you to our slides and commentary that we gave on our June 8th call for details on the accounting with ASI and neuramune.

Total revenue for the second quarter of $2.8 billion declined 25% versus the prior year at actual currency and 26% at constant currency.

This decline reflects the impact of tech that Eric Generics. In addition to approximately $330 million on revenue that was recorded in Q2.2020 related to the onetime license of certain manufacturing related intellectual property.

We were however, encouraged to see total revenue increased by 3% versus Q1 of 2021, primarily driven by the MS franchise and <unk> royalties.

Total <unk> revenue for the second quarter was $2 million I would refer you to our slides and commentary that we gave on our June 8 call for details on the accounting with ASI and neuro immune.

Mike: Total MS revenue for the second quarter was $1.8 billion, inclusive of Okravis royalties. Now, we look at some of the individual products within MS. Global TechVadera revenue for the second quarter was $488 million. In the U.S., second quarter revenue of $178 million increased versus the prior quarter due to seasonality and shipping dynamics, and we expect TechVadera revenue in the U.S. to continue to decline throughout the year.

Total revenue for the second quarter was $1.8 billion inclusive of <unk> royalties.

Looking now at some of the individual products within MFS.

Global <unk> revenue for the second quarter was $488 million in the US second quarter revenue of $178 million increased versus the prior quarter due to seasonality and shipping dynamics and we expect <unk> in the us to continue to decline throughout the year.

Outside of the US second quarter <unk> revenue of $309 million increased 15% versus the prior year with 6% underlying patient growth.

Mike: Second Quarter Tech Fadera revenue of $309 million increased 15% versus the prior year, with 6% underlying patient growth. We were pleased with the continued ramp in Vumerity revenue from $74 million in the first quarter to $91 million in the second quarter, and as Michelle mentioned, we believe that Vumerity can become a $1 billion annual revenue product over time. Tysabry's second-quarter global revenue of $524 million increased 21% versus the prior year, benefiting from shipping dynamics in both the U.S. and outside the U.S. We were 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 multiple sclerosis.

We were pleased with the continued ramp in primarily revenue from $74 million in the first quarter to $91 million in the second quarter and as Michel mentioned, we believe that <unk> can become a $1 billion annual revenue product.

Over time.

Yes.

Tysabri second quarter global revenue.

$524 million increased 21% versus the prior year benefiting from shipping dynamics in both the us and outside the US we were 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 MFS.

Moving now to SMA global second quarter spin Raza revenue of $500 million increased 1% versus the prior year at actual currency and decreased 3% at constant currency in the U S and <unk> revenue of $149 million decreased by 29% versus the prior year as we see continue.

Mike: Moving now to SMA, Global Second Quarter Spenravenu revenue of $500 million increased 1% versus the prior year at actual currency and decreased 3% at constant currency. In the U.S., Spenraza revenue of $149 million decreased by 29% versus the prior year, as we see continued impact from competition. Outside the U.S., Spinravenu revenue grew 23% versus the prior year, although some of this growth was attributable to accelerated shipments.

Impact from competition.

Outside the us it's been Rozzer revenue grew 23% versus the prior year, although some of this growth was attributable to accelerated shipments.

Moving now to our Biosimilars business second quarter revenue of $202 million increased 18% versus the prior year at actual currency and 9% at constant currency.

Mike: Moving now to our biosimilar business, second-quarter revenue of $202 million increased 18% versus the prior year at actual currency and 9% at constant currency. This growth occurred despite our biosimilar business continuing to be negatively impacted by pricing pressure, as well as a slowdown in new treatments and reduced clinic capacity due to the COVID-19 pandemic. Despite the continued impact of COVID-19, we are now the leading anti-TNF provider in Europe.

This growth occurred despite our biosimilars business continuing to be negatively impacted by pricing pressure as well as a slowdown in new treatments and reduced clinic capacity due to the COVID-19 pandemic. Despite.

Despite the continued impact of COVID-19, we are now the leading anti TNF provider in Europe.

Mike: Total anti-CD20 revenue in the second quarter of $440 million decreased 8% versus the prior year. Retuxin revenue decreased approximately 32% versus the prior year, partially offset by a 23% increase in Okravis Royal Peace. Second quarter gross margin was 83% of revenue, up slightly from 82% in the prior quarter and down from 89% in Q2 2020. The reduction in gross margin versus the prior year was primarily due to the declines in Tecvedra and Retuxin, both of which are high-margin products.

Total anti CD 20 revenue in the second quarter of $440 million decreased 8% versus the prior year Rituxan revenue decreased approximately 32% versus the prior year, partially offset by a 23% increase in <unk> royalties.

Second quarter gross margin was 83% of revenue up slightly from 82% in the prior quarter and down from 89% in Q2.2020.

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.

In addition, Q2.2020 includes approximately $330 million on revenue related to the onetime license of certain manufacturing related intellectual property.

Mike: In addition, Q2 2020 includes approximately $330 million in revenue related to the one-time license of certain manufacturing-related intellectual property, which was at 100% gross margin. Moving now to expenses in the balance sheet. Second quarter non-gap R&D expense was $585 million, which included approximately $50 million of upfront payments related to three business development deals. One with Biothera for biosimilers, a second with capsogen and gene therapy, and a third with Kinko to develop a novel gene therapy manufacturing platform. Second quarter non-gap SGNA was $635 million, including approximately $115 million related to adjuvant. Note that beginning in the second quarter, A-size reimbursement of U.S.S. SG&A costs is reflected in the collaboration profit-sharing line.

Was at 100% gross margin.

Moving now to expenses on the balance sheet second quarter, non-GAAP R&D expense was $585 million, which included approximately $50 million.

Of upfront payments related to 3 business development deals 1 with buyout era for Biosimilars are second with capsid gene in gene therapy, and a third with gingko to develop a novel gene therapy manufacturing platform.

Second quarter, non-GAAP, SG&A was $635 million, including approximately $115 million related to agile home.

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

Mike: Second Quarter Collaboration Profit sharing reduced our net operating expenses by $15 million, which included a reimbursement of $85 million from ASI related to the commercialization of Aegehelm in the U.S. In the second quarter of this year, our effective non-gap tax rate was approximately 16% versus approximately 19% in the second quarter of last year. Second quarter non-gap income attributable to non-controlling interest of $84 million includes a milestone payment of $100 million to Neurimune related to the launch of Adjahelm in the U.S. Note that A-S's 45% share of this milestone payment was recognized in the collaboration profit-sharing line.

Second quarter collaboration profit sharing reduced our net operating expenses by $15 million, which includes a reimbursement of $85 million from ASI related to the commercialization of <unk> in the us.

In the second quarter of this year.

Our effective non-GAAP tax rate was approximately 16% versus approximately 19% in the second quarter of last year.

Second quarter non-GAAP income attributable to Noncontrolling interest of $84 million includes a milestone payment of $100 million dinner immune related to the launch of <unk> in the US note that ASI is 45% share of this milestone payment was recognized in the collaboration profit sharing.

<unk>.

During the second quarter, we repurchased 1.6 million shares of the company's common stock for $450 million as of June 32021, There was $3.6 billion remaining under the share repurchase program authorized in October of 2020.

Mike: During the second quarter, we repurchased 1.6 million shares of the company's common stock for $450 million. As of June 30, 2021, there was $3.6 billion remaining under the share repurchase program authorized in October of 2020. Our weighted average diluted share count was approximately 150 million shares for the second quarter. Non-Gap diluted EPS in the first quarter was $5.68, which increased from $5.34 in Q1 of 2021. In the second quarter, we generated approximately $1.2 billion in cash flow from operations, capital expenditures were $72 million, and free cash flow was approximately $1.2 billion. We ended the quarter with $7.3 billion in debt. $4 billion in cash in marketable securities, and as a result, $3. Additionally, our $1 billion revolving credit facility was undrawn as of the end of the quarter.

Our weighted average diluted share count was approximately 150 million shares for the second quarter net.

Non-GAAP diluted EPS in the first quarter was $5.68, which increased from $5.34.

In Q1 of 2021.

In the second quarter, we generated approximately $1.2 billion on cash flow from operations capital expenditures were $72 million on free cash flow was approximately $1.2 billion.

We ended the quarter with 7.3 billion and debt free.

$4 billion on cash and marketable securities.

And as a result, $3.3 billion and net debt.

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

Mike: 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 full year 2021 revenue guidance from our previous range of $10.45 billion to $10.75 billion to a new range of $10.65 billion to $10.85 billion, primarily as a result of stronger performance than our MS franchise and higher over this royalties.

Let me now turn to our updated full year guidance for 2021.

We are increasing our full year 2021 revenue guidance from our previous range of $10.45 billion to $10.75 billion to a new range of 10, 6.5 billion to $10.85 billion.

Primarily as a result of stronger performance on our MS franchise and <unk> royalties.

We are maintaining our non-GAAP diluted EPS guidance of $17.50 to $19 notwithstanding the inclusion of the $125 million upfront payment related to our recently announced collaboration with <unk>, which we expect to incur in Q3. This payment was not <unk>.

Mike: We are maintaining our non-gap diluted EPS guidance of $17 and $0.50 to $19, notwithstanding the inclusion of the $125 million upfront payment related to our recently announced collaboration with InnoCare, which we expect to incur in Q3. This payment was not included in our previous guidance.

<unk> in our previous guidance.

Our capex guidance is unchanged at $375 million to $425 million.

Mike: Our CAPX guidance is unchanged at $375 million to $425 million. Our guidance continues to assume modest adjutelm revenue in 2021 due to dosing titration, the need for sites to prepare to diagnose and treat patients, and the time that it will take to secure payer coverage. We continue to expect revenue to start ramping in 2022 and beyond. We expect continued erosion of both Techvedera and retuxin in the U.S. and that the decreased revenue from these high-margin products will put pressure on our gross margin percentage.

Our guidance continues to assume modest agile home revenue in 2021 due to dosing titration the need for sites to prepare to diagnose and treat patients and the time that it will take us secure payer coverage. We continue to expect revenue to start ramping in 2022 and beyond.

We expect continued erosion of both tech Vadera and Rituxan in the us and that the decreased revenue from these high margin products will put pressure on our gross margin percentage note that our gross margin in the second quarter of 2021 was 83% of revenue which reflects this dynamic.

Mike: Note that our gross margin in the second quarter of 2021 was 83% of revenue, which reflects this dynamics. Full-year non-gap R&D expenses are expected to be between $2.45 billion and $2.55 billion. This updated R&D guidance range includes the expected $125 million upfront payment in the third quarter of 2021, which, as I mentioned, was not included in our prior guidance. Full-GAR n-G&A expenses are expected to be between $2.6 billion and $2.7 billion.

Full year non-GAAP R&D expenses are expected to be between $2.45 billion and $2.55 billion.

The updated R&D guidance range includes the expected $125 million upfront payment in the third quarter of 2021, which as I mentioned was not included in our prior guidance.

Full year non-GAAP SG&A expenses are expected to be between $2.6 billion and $2.7 billion.

Mike: This range is consistent with our previous guidance and continues to include an approximate $600 million adjahelm investment. Of this amount, approximately $200 million would be reimbursable by ASI and is reflected as collaboration profit sharing effective April 1st and not part of SG&A. Of course, as the launch progresses, we will actively manage the pace of this spend. This guidance continues to reflect our expectation that both R&D and SGNA will be higher in the second half of the year than they were in the first half due to collaborations such as Inocare, program readouts, and investments in Agio Home.

This range is consistent with our previous guidance and continues to include an approximate $600 million.

<unk> investment of this amount approximately $200 million would be reimbursable by ASI and is reflected as collaboration profit sharing effective April 1 and not part of SG&A.

Of course as the launch progresses, we will actively manage the pace of the spend.

This guidance continues to reflect our expectation that both R&D and SG&A will be higher in the second half of the year than they were in the first half due to collaborations such as <unk> care program Readouts and investments in agile home.

We expect we will utilize a portion of the remaining share repurchase authorization of $3.6 billion throughout the year. Although this will depend on a variety of factors, including our business development activities.

Mike: We expect we will utilize a portion of the remaining share repurchase authorization of $3.6 billion throughout the year, although this will depend on a variety of factors, including our business development activities. Additionally, we assume that foreign exchange rates as of June 30, 2021 will remain in effect for the remainder of the year net of hedging activities. We have not included any impact from potential tax or health care reform or any impact from potential acquisitions or large business development transactions other than Inocare in our guidance.

We assume that foreign exchange rates as of June 32021 will remain in effect for the remainder of the year net of hedging activities.

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

Mike: So in closing, we were very pleased with our financial performance in the quarter. 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. Now, I'll turn the call back over to Michelle for her closing comments. Thank you.

So in closing we were very pleased with our financial performance in the quarter, 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.

And now I'll turn the call back over to Michel for his closing comments. Thank you Mike. It is an exciting time at Biogen.

Michelle: Thank you, Mike. It is an exciting time at Biogen, and it is all about execution for the coming period. Our base, the MSSmi biosimilar business, is performing well, demonstrating resilience despite competition. We have an incredible opportunity together with SI, and we are completely focused on operation execution for the global launch of Ady Helm and, hopefully, soon, Le Canemap. We have positive phase three data for zionanolid Depression, and we are anxiously awaiting data for Toferesen in SOD1 ALS.

And it is all about execution for the coming periods.

Our base Ms SMA and Biosimilars business is performing well demonstrating resiliency spite competition.

We have an incredible opportunity together with ESI.

And we are completely focused on operation execution of for the global launch of <unk> and hopefully soon <unk>.

We have positive phase III data for <unk> hundred on in depression, and we are anxiously awaiting data photos lesson in SD Wan Alice we believe.