So I'm going to cover a little bit more on the cost base. The first thing I'd like to say is that we've made good progress on the previous program that had announced a billion dollars of cost savings. That -- those billion dollars have been secured and have been -- that program is complete. But over the last several months, I have been getting a better understanding of how the company operates, working with our senior leaders and thinking about how we operate at all levels of the company. We kicked in early at a global regional and affiliate level. And as we said before, we do have a higher cost base than the average company in our category. And so we've initiated an additional program to align our operations and cost base with the expected revenue while leaving enough money for the upcoming launches.

And we internally refer to this program as fit-for-growth. And really what we're trying to do is balance the opportunity for profitable growth by investing in our product launches and the R&D projects that we deem priority with an attempt to try to reduce that cost base and get that back to something that looks a little bit more in line with our competitors. Now that's not just a simple job of taking out costs. What we're really trying to do is redesign the company. We have these two launches. They're going to have different geographic points of focus at the start. We won't have Zuranolone for few years outside of the US. Zuranolone is clearly a top priority in the short-term in the US. And outside the US, we're going to be certainly focused on the LEQEMBI launch in the first instance.

So one of the things we want to do is make sure that we don't lose what is good in the company and what has been working. We also have to remember that we are still a leader in multiple sclerosis. There are lot of patients who depend upon our products and we have to make sure that the physicians who treat those patients have adequate information. So there is a balancing act as we tried to shift our resources behind the growth opportunities while still supporting our historic MS business. And so we're taking a -- essentially a bottoms-up and a methodical approach to this. This could have a much different approach to our operating model. We've been 45 years in multiple sclerosis with a limited product profile. Yes, we had at one point some products in hemophilia and obviously we have SPINRAZA.

And as a result, we had an awful lot of centralized cost. Right now, we're looking at how do we get a lot more of our resource and our attention closer to the customer. So it's a redesign effort and it's meant to be durable. So, we do recognize that there is an opportunity to reduce cost, but we really are looking at something more transformational that really sets the company up for growth. We'll be able to say more about that in Q2. Another priority is really managing the base business. There's two dynamics in the company. We are a leader in MS, but that business is increasingly affected by competition. And we have growth opportunities with LEQEMBI and Zuranolone. So on the base business, the idea is how do we manage that business as profitably as we can.

We did receive a favourable decision from the Court of Justice of the European Union related to TECFIDERA regulatory data and marketing protection, which was an important reinforcement of intellectual property and exclusivity rights. We believe this provides us marketing protection until at least February of next year. And we are looking to enforce that protection, but it will take a little time for the market to settle. And separately, we also continue to enforce our 2028 patent for TECFIDERA in the EU. We're also looking to aim to -- we're looking to maximize the profitability of the MS franchise. Up until now, the goal has been to defend revenue at all cost. I think now we want to take a little bit more of a nuanced approach of looking at where the opportunities in MS, where do we have intellectual property, where do we have still sales promotion sensitivity and tried to align our resources with that and perhaps look at other means of promoting products that are a little less expensive.

We do believe that SPINRAZA can return to growth and we are seeing stabilization up there in the marketplace, gene therapy has not for everyone. And the oral therapy has its limits and there are still quite a few patients that suffer from SMA that don't benefit from any treatment. And as we announced at the previous quarter, we do have a formal process underway to evaluate strategic options for our biosimilars business. This is a very good business and I think especially with the launch of biosimilars for Humira, we are seeing an opportunity for the healthcare system to make important economies that help fund innovation and we need to think about who is the -- and how is the best way to manage this business and who might be the best owner of that business.

On external growth, we're looking at external growth really from two perspectives. One is how do we balance the company a little bit more on its pipeline. It has been very neuroscience focused. But as I've argued in the past, I think with MS, which is basically an autoimmune disease, I think we could migrate into immunology. With SPINRAZA, I think, we have an experience in rare diseases and that will be reinforced with Tofersen. And, of course, we're in neuropsychiatry with Zuranolone. So these offer opportunities to think about how do we build out some of those franchises. Yeah, there is, no, I did describe this dynamic of the MS franchise declining slightly and new growth coming and we may look at external growth as a way of making sure that that transition is as smooth as possible from a results point of view.

And I'm pleased to say that we have appointed Adam Keeney as our Head of Corporate Development. Adam has over 20 years of experience, not just in business development, but also in R&D and strategy across both large pharma and he was the CEO of a Biotech. So I think he's got some entrepreneurial spirit that will be very welcomed at Biogen. We do see LEQEMBI and Zuranolone as major contributors to revenue, but we want to continue to think about business development to support the growth trajectory and diversified as I said. So if I could have the next slide please. So we really got an unprecedented opportunity. We have today a PDUFA date for Tofersen. We have a PDUFA date on July for LEQEMBI and a PDUFA date in August for Zuranolone. I can't think of another major biopharmaceutical company that has that many new significant products to launch.

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That's a huge opportunity. But as I said earlier, we have to think about capabilities on that. These are going to be different areas. Obviously, LEQEMBI is little closer to home, since it's still in neurologist, but there's an awful lot of market building we will have to be done there. And, of course, Zuranolone takes us into a much different area and a much different position franchise. But we're making our milestones. We received accelerated approval in the US back in January. We filed for traditional approval in the US on the same day and within the EU, Japan and Eisai initiated regulatory filing in China. Filing all of those dossiers in that kind of timeframe is really quite significant and I have to congratulate our colleagues at Eisai for this effort.

These filings have received priority review in the US, Japan and China. And, of course, a major milestone in that Veterans Health Administration has decided to reimburse LEQEMBI. Now, LEQEMBI is going to be the first anti-amyloid antibody to receive traditional approval globally hopefully in July. As we said, this is not a straightforward launch, it's a complex diagnosis involving PET scans, lumbar puncture for amyloid confirmation, specialists who are already busy, MRI imaging, bi-weekly infusion. And we know that capacity could be an issue initially. CMS reimbursement will be the next major milestone, which we expect to have an answer on once the product has received full approval as expected following the PDUFA date in July. More importantly though, we are looking at how do we right now alleviate those bottlenecks.

Yes, CMS is there, but both companies are already thinking about what we can do to make this easier for patients and actually reduce cost. Eisai and Biogen are pursuing maintenance dosing in the subcu formulation. Blood-based diagnostics, as I've said in the past, are really going to be a game-changer in this space. And we believe that over time, capacity is going to expand to meet the need. For reimbursement, this is a big question, the Veterans' Association is certainly helpful. I would just point out that compared to the situation that ADUHELM faced, we are getting a lot more support from Congress. The American Association of Neurologist has written in support. And I know that a number of patient advocacy groups are active and ensuring that patients have access to this important therapy.

So Eisai is responsible under the contract for engaging with CMS and we would hope to see broad coverage coming out of the CMS decision. Now I'd like to talk about Zuranolone just for a few minutes. I mean, Zuranolone is still I think an underestimated asset in our portfolio. Unfortunately, a lot of people suffered from depression, so it is a large market. There are clearly a number of older medicines that are available. The main problem with those are the side effects of those medicines and the length of time it takes for them to work. And Zuranolone works potentially in three days and it's going to be a different type of launch because we're talking about a treatment that works in two weeks. The only analogue I can find that is in a way similar was Zithromax.

So we do know that there is going to be some need for education, physicians are used to treating on a chronic basis. As we launch even, we're going to have to think about different metrics. One of the things in the launch that you look for is when the NRxs switched to TRxs. Well, we're not going to see that. They are not going to be TRxs with the product. So I think there are these changes in physician behaviour. This is a paradigm shift and paradigm shift is not always a good thing in pharmaceutical marketing as we know. However, what really drives us, this is a product that really makes a difference for patients. This is a product that, well, it's efficacious, it works fast. And think about the freedom of knowing that after two weeks that you can stop taking Zuranolone.

So I think that is going to be an enormous opportunity. And I'll just finish with Tofersen on this, it is not a big product obviously, about 300 patients. But it's classic Biogen. There is a -- we have a long history in ALS, lot of setbacks. But the organization has an ability to learn and adapt and Biogen was able to partner with the scientific community to help characterize neurofilament as a biomarker in neuromuscular disorders. This is a huge deal because neurofilament will be relevant to a lot of researchers who are looking at ALS. So I think we've got some ground-breaking science here. And this is where Biogen has had the resilience to go after a lot of significant unmet need that -- has resolved things in a way that not everybody has been able to do.

Next slide, if I could. We've got a number of milestones coming, as you can see here on the slide. By our Q2 call, we would expect to be in a different place with LEQEMBI. We should hopefully have the PDUFA date behind us successfully. Hopefully, we've received a traditional approval and broader CMS coverage in the US. And, of course, we'll be communicating more about our fit-for-growth cost optimization program. By the end of this year, hopefully we've got the first ex-US approval of LEQEMBI in Japan and hopefully we'll have received the approval for Zuranolone in both MDD and PPD as well as having completed a three-month DEA scheduling period and initiated the launch. And if I look further ahead by the end of -- by the time -- this time next year, I think we have an opportunity to build a global footprint of LEQEMBI with approvals in Europe and China.

And, of course, we'll take the next steps on evolving the treatment paradigm with Alzheimer's disease with an expected regulatory filing of LEQEMBI maintenance dosing. We would also expect regulatory filings for subcutaneous dosing, which could facilitate at-home administration. So in conclusion, through a combination of ground breaking of sign, high-potential near-term commercial opportunities and diligent capital allocation. I think Biogen is going to be well-positioned for the sustainable long-term growth. I'd like to now turn it over to Priya for an update on our progress in R&D.

Priya Singhal: Thank you, Chris. Last quarter, we made important progress advancing key pipeline programs. As Chris just pointed out, we now have the opportunity to deliver three potential new drug launches across four indications this year, all in areas of high unmet need, including Alzheimer's disease, major depressive disorder, postpartum depression and SOD1-ALS. We also continue to evaluate potential opportunities for geographic and indication expansion for Zuranolone as we work with our collaborator Sage to prepare for a potential US launch later this year. I will share key highlights from the quarter across broader efforts in Alzheimer's disease, the Tofersen program in SOD1-ALS and the progress that we're making to rebalance the risk profile and improved productivity of the R&D pipeline.

I will now share highlights of additional analysis Eisai recently presented or published, consistent with both companies' commitment to transparency. First, regarding activities of daily living. New analysis of ADCS-MCI-ADL presented at AD/PD last month, showed that all individual items of this scale favoured LEQEMBI at 18 months as compared to placebo. This includes items like ability to make a meal or keeping appointment. This result also measures Clarity AD study outcome on the CDR sum of boxes where LEQEMBI treatment slowed decline across all six individual domains at 18 months versus placebo. Additionally, results from Clarity AD showed that at 18 months, LEQEMBI treatment resulted in a 50% less decline from baseline on scales designed to assess quality-of-life and reduced care partner burden as compared to placebo.

In addition was also presented an updated analysis of ARIA from the CLARITY AD study to evaluate ARIA incidents in LEQEMBI-treated participants on antiplatelet or anticoagulant drugs as compared to LEQEMBI-treated participants that were not on either. The results were encouraging and showed that ARIA incidents were similar in the two groups. In addition to the data presented at AD/PD, newly published analysis from LEQEMBI Phase II study reinforce the finding that while plaques level begin to return slowly after treatment discontinuation, other biomarkers of AD biology such as Plasma Abeta42/40 ratio re-accumulate quickly. We believe these findings further support the potential benefit of continued treatment with LEQEMBI after plaques have been removed.

Building on their prior work, Eisai published a new analysis of the long-term health outcomes associated with LEQEMBI treatment. Updated analysis incorporated data from the Phase III CLARITY AD study, replacing the prior modeling that used Phase IIb study results. The analysis of the Phase III data, consistent with the analysis of the prior Phase IIb study results, showed that LEQEMBI resulted in a delay of approximately two to three years in meantime to progression to mild, moderate and severe AD dementia versus standard of care alone. We believe these results build upon and reinforce the significant body of evidence that has been generated on LEQEMBI. Biogen is committed to building on a deep expertise and experience in Alzheimer's disease by advancing an industry-leading Alzheimer's pipeline that is diversified across therapeutic modalities and molecular targets.

This includes focusing on tau. Intracellular neurofibrillary tangle, which represent a pathological hallmark of Alzheimer's are composed of hyperphosphorylated tau protein. Unlike amyloid plaques, which are observed to build up in the brain years before the onset of cognitive symptoms, tau tangles are more closely related to the neuronal cell loss and onset of clinical symptoms. To address our pathology, we are advancing BIIB080, an antisense oligonucleotide targeting tau mRNA aiming to reduce all forms of tau protein. Importantly, this is a very different approach than utilizing a tau-directed antibody which is hypothesized to target only extracellular tau. We were encouraged by the early results of this ASO-based approach as evidenced by the BIIB080 Phase Ib data in Alzheimer's disease which were presented last month at AD/PD and also published in Nature Medicine, which went live online yesterday.

Phase Ib data shown here on the slide. BIIB080 was generally well tolerated. Majority of adverse events were mild or moderate in severity. Of which the most common were headache, back pain and post-lumbar puncture syndrome. We observed a time and dose-dependent reduction in CSF total and phospho-tau across the multiple ascending dose and long-term extension periods. Total tau continued to decline 16 weeks following the last dose in the MAD portion of the study, both in the high dose Q4 weekly and the Q12 weekly dose and we saw a 50% reduction from base lines. We observed an effect on neurofibrillary tangle, as visualized, via tau PET as early as 25 weeks across all brain regions assessed. Reduction in tau burden in all treatment groups at the end of the open-label extension at 100 weeks.

The BIIB080 study is the first to demonstrate this magnitude of tau PET reduction across brain regions. Encouraged by these early results, we continue to enroll the Phase II CELIA study of BIIB080 in early Alzheimer's disease, where we are exploring different dosing regimens, including every 12 weeks and every 24 week dosing. Last month, an advisory committee by the FDA met to review the Tofersen data in SOD1-ALS. The advisory committee unanimously agreed that reduction in plasma neurofilament light is reasonably likely to predict clinical benefit of Tofersen for the treatment of SOD1-ALS. And they also reached a consensus that the benefit-risk profile was favourable. As Chris mentioned, Biogen has spent years collaborating with the scientific community to characterize neurofilament as a marker of axonal injury and neurodegeneration and we view the outcome of the advisory committee as a significant advancement for the field.

We believe these developments also inform our other programs in ALS, including BIIB105, an antisense oligonucleotide targeting ataxin-2 which may have therapeutic potential in the broader ALS population. BIIB105 aims to reduce ataxin-2 protein levels, which we hypothesized will reduce toxic TDP-43 clusters that are observed in nearly all people living with ALS. Preclinical experiments confirm that reduction of ataxin-2 levels modified survival and function in a mouse model of TDP-43 ALS. The Phase I/II study of BIIB105 in ALS is expected to read out early next year. We continue to advance our R&D prioritization efforts with the goals of optimizing the value that our pipeline can deliver. This includes investing in areas where we have a strong conviction in the disease biology.

We continue to invest in further data generation for LEQEMBI and Zuranolone and remain focused on executing key clinical studies, including BIIB080 and BIIB105 as well as for litifilimab in lupus. We also made the decision to opt in to Denali Antibody Transport Vehicle A-beta program. With the ATV A-beta, we aim to safely increase exposure of A-beta antibody in the brain. This may enable improved plaque clearance and/or lower incidence of ARIA. We are also deprioritizing programs based upon our integrated view of development, regulatory and on commercialization challenges. Recent updates include that we decided to terminate involvement in the development of BIIB093 programs in large hemispheric infarction and brain contusion due to operational challenges and strategic considerations.

We decided to pause initiation of the Phase IIb study of BIIB131 in acute ischemic stroke as we reassess whether we need to initiate the study. We discontinued BIIB132 in spinocerebellar ataxia type 3. We previously announced that we had refocused our investment in gene therapy and we will continue to look to advance technology associated with the safe delivery of these therapies to the right targets in the body which we believe is one of the most critical scientific and technical challenges that is currently associated with this modality. We also had previously announced that we exited ophthalmology research with goals of reallocating resources to areas where we believe there is a greater probability of success. This will be an ongoing process, involving dynamic scientific prioritization and investment based on an ongoing assessment of probability of success, but we expect to complete our initial substantial review by midyear.

In conclusion, Biogen has had a significant number of accomplishments this past quarter, which we believe highlights the ability of our R&D organization to capitalize and deliver on ground-breaking science in the pursuit of new medicines for patients. With key assets in areas like Alzheimer's disease, depression, ALS and lupus, we believe the Biogen pipeline has the potential to deliver significant growth over the medium and long term. I will now pass the call over to Mike for the financial results.

Michael McDonnell: Thank you, Priya. Good morning, everyone. So I'll provide some highlights of our financial performance for the first quarter and please note that all financial comparisons that you will hear are versus the first quarter of 2022. Total revenue for the first quarter was $2.5 billion and that's a decrease of 3% at actual currency and flat at constant currency. Non-GAAP diluted earnings per share in the first quarter was $3.40, a decrease of 6%. Total MS product revenue was $1.1 billion, a decrease of 19% at actual currency and 17% at constant currency. I'd like to provide a few points here regarding MS during the quarter. In the U.S., we continue to see the impact of TECFIDERA generics declines in the interferons and competition for TYSABRI.

As we noted in our last call, Q1 is typically a seasonally weaker quarter for our MS business in the U.S., and that's driven by higher discounts and allowances and some channel dynamics. And as it relates to channel dynamics, we did see a greater-than-expected decrease in channel inventory which added a few percentage points to the overall global decline. And we believe this is likely related to tighter working capital management in wholesalers and specialty pharmacies, due to the rising interest rate environment. In addition, VUMERITY is being impacted by both pricing pressure and a contraction of the oral segment of the market in the U.S. And as a reminder, in Q1 of last year, VUMERITY did benefit from a favourable Medicaid-related sales adjustment which also impacts the year-over-year comparison.

As far as Europe, as you know, we received a favourable decision relating to the TECFIDERA regulatory data and marketing protection in the EU and that was assumed in our guidance. So we believe that TECFIDERA is entitled to regulatory marketing protection in EU until at least February of 2024 and we are working to enforce this protection. I would add that we did expect it would take some time following the decision for all generic products to be off the market and we are assuming that this exit will accelerate in the near term. Separately, we continue to enforce our patent which expires in 2028. So as we look toward the remainder of the year, we do expect to see a slower rate of decline on a year-over-year basis versus what we saw in Q1. We've taken some actions which aim to improve the underlying revenue trajectory for our MS portfolio in the second half, including for VUMERITY in the U.S., and we're continuing to closely monitor the underlying market dynamics in MS closely.

Moving to SMA. Global SPINRAZA revenue of $443 million was a decrease of 6% in actual currency and 2% at constant currency. In the U.S., SPINRAZA revenue decreased 10% due to fewer new patient starts and some channel dynamics as compared to the first quarter of last year. However, we do continue to see what we believe are signs of stabilization in our patient base. Outside the U.S., revenue for SPINRAZA decreased 4% at actual currency and increased 2% at constant currency with competition more than offset by the timing of shipments in certain markets. Biosimilars revenue was $192 million, and that's a decline of 1% at actual currency and an increase of 4% at constant currency and that's due to volume growth driven by the launch of our BYOOVIZ product partially offset by continued pricing pressure for our anti-TNF products in Europe.

Alzheimer's disease revenue, which includes revenue from ADUHELM and the LEQEMBI collaboration equated to a headwind of $18 million to revenue. As a reminder, beginning this quarter, our share of LEQEMBI commercial expenses in the U.S. is recorded as a component of revenue, thus the negative number this quarter. And for this line item, we expect this to continue to be negative in 2023 as ramping LEQEMBI commercialization expenses throughout the year are expected to exceed initial revenue. Total anti-CD20 revenue of $399 million was flat. Revenue from OCREVUS royalties increased 12%, which was partially offset by a 25% decline in revenue from our profit share on RITUXAN, and that was driven by biosimilar competition. The anti-CD20 revenue line also included a $10 million operating loss related to LUNSUMIO.

I'd note that our R&D expense for LUNSUMIO is also recorded as a component of the anti-CD20 revenue line. Important to note that starting in the second quarter, our pre-tax profit share percentage on RITUXAN, GAZYVA and LUNSUMIO will decrease from 37.5% to 35% and that sales targets for GAZYVA as part of our contractual agreement with Genentech. Contract manufacturing royalty and other revenue of $319 million benefited from the timing of production of some contract manufacturing batches which includes LEQEMBI. While this line tends to vary from quarter-to-quarter, we do not expect this level of contract manufacturing revenue to continue throughout the remainder of 2023. A couple of details regarding Q1 expenses. For the first quarter, non-GAAP cost of sales was $663 million or 27% of revenue.

This includes $45 million of idle capacity charges which Eisai no longer shares. During Q1, we did see pressure on cost of sales associated with product mix. We saw increased contract manufacturing revenue which has a higher cost of sales including manufacturing revenue for LEQEMBI which is at minimal gross margin. We continue to expect our cost of sales as a percentage of revenue for the remainder of the year to be higher than the 22.4% that we saw for full year of 2022 and that's primarily as a result of product mix and idle capacity charges. First quarter non-GAAP R&D expense was $571 million and that compares to $552 million in the first quarter of last year. Non-GAAP SG&A was $603 million and this compares to $635 million in the first quarter of 2022.

The decrease in non-GAAP SG&A expense was driven primarily by cost savings initiatives which importantly were partially offset by investments to support new product launches and $31 million related to the termination of the co-promotion agreement with Eisai to Biogen's MS products in Japan. We continue to expect operating expenses to be lower in the second half of 2023 than in the first half. And as Chris mentioned, separate from the previously announced $1 billion cost savings initiative, we have initiated our fit-for-growth program in order to align our cost base with expected revenue while also investing in our growth opportunities. And we expect this program to have a modest impact on 2023 expenses and a more meaningful impact in 2024 and beyond and we'll have more to say about this on our second quarter earnings call.

As for our balance sheet, we ended the quarter with $6 billion in cash and marketable securities, $6.3 billion in debt and roughly $300 million in net debt. Subsequent to the end of the quarter, we received approximately $813 million related to the sale of our equity stake in Samsung Bioepis, which is not included in these cash figures. And this payment is the second payment related to this transaction which closed around this time last year and we're expecting a third payment of approximately $438 million in April of 2024. In the first quarter, we generated $455 million in cash flow from operations. CapEx was $67 million. Free cash flow was $389 million. So overall, we remain in a very strong financial position with significant cash and financial capacity to invest in growing the business over time.

Let me now turn to financial guidance for full year 2023. We are reaffirming our full year guidance of a full year 2023 revenue decline in the mid-single-digit percentage range as compared to 2022 reported results and full year 2023 non-GAAP diluted earnings per share of between $15 and $16 and I would refer you to our press release for other important guidance assumptions. So in closing, Biogen continued to make strong progress against our business priorities in the first quarter. We remain focused on three potential launches in 2023 while continuing to be diligent in prioritizing our R&D pipeline, optimizing our operating model and also evaluating external opportunities. We expect that execution of these priorities will position us well for returning Biogen to sustainable growth and creating long-term value for our shareholders.

And with that we will now open the call for questions.

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