Amgen Inc. (AMGN) Earnings Call Transcript & Summary

Welcome to the Amgen Business Review broadcast from the Amgen campus in Thousand Oaks, California.

Hello, everyone, and thank you for joining us. We'll be talking to you mostly today about the future of our business, and in particular, what we expect to deliver through 2030. As we think about what's next, we're encouraged by our past accomplishments and we're ready and looking forward to delivering on the future for patients and shareholders. As the industry's response to the pandemic has shown, this is an extraordinary time for biotechnology. Science and technology are converging in ways that are accelerating the cadence of innovation in our field. And though our industry is not without its challenges, we believe the fundamentals remain very attractive, global companies that are able to innovate at speed, and we expect to be 1 of those companies. We've been a leader in biotechnology for the past 40 years, and we think we're well positioned to maintain that leadership for decades to come. And our goal today is to share with you the reasons why we're excited about the future. And as we talk to you today, our comments will be governed by these elements of our safe harbor statement. Now here's what we'll cover. I'll provide an overview of our business through 2030. Peter Griffith will then review our 2021 financial results and provide guidance for 2022 and guidance through the end of the decade, including our perspectives on capital allocation. Murdo Gordon and Susan Sweeney will review our key growth products and the reasons why they're confident in the outlook for our brands through 2030. Dave Reese will discuss the dozen or so potential first-in-class medicines that are advancing through our late- and mid-stage pipeline, medicines that have the potential to help many patients and accelerate growth in 2025 and beyond. Dave will then be joined by 2 additional leaders from our R&D organization, Ray Deshaies and Alan Russell to discuss the capabilities we've recently added to our research organization, positioning us for long-term success in the discovery field. While the bulk of our time today will be focused on the future, I thought it might be instructive to take a few minutes to reflect on the past. Let me remind you what we said we were going to do in the past. First, if you look back over the past decade, we said we were going to launch a wave of new innovative medicines, and that's what we did. Since 2012, we've launched 10 novel medicines directed at cancer, heart disease, osteoporosis and other serious illnesses, building a broad base for our business. We said we would roughly double the number of countries in which we do business around the world. And we did that too, creating a global platform for our innovation without diluting returns or drawing on significant shareholder capital to do it. We said we would leverage our installed capabilities and build an industry-leading biosimilars business that would be accretive to earnings and shareholder value and we've done that, launching 5 biosimilars around the world on time and on budget that collectively generated $2 billion or more than $2 billion of revenues last year. And we have 6 more molecules to come. We said we would launch our ecologically and economically efficient manufacturing of the future, and we've done that, too, in Singapore and soon in Rhode Island as well, enabling us to uphold our record of serving every patient every time even during a pandemic that has wreaked havoc on global supply chains. We said we would do all this: Launch new products, expand into new countries, invest in manufacturing and still increase our operating margins, and we did that too. From 38% in 2012, we now consistently deliver industry-leading operating margins north of 50%, driven by productivity efforts that are embedded in every aspect of our business. As for capital allocation, we said we would look to strengthen our company through business development, and that's what we've done. Over the past decade, we've invested more than $30 billion in nearly 3 dozen significant deals, including 3 already announced this year. We said we would return capital to shareholders, and we've done that, returning some $75 billion to shareholders since 2012 through our share repurchases and a dividend that has risen sixfold since inception. Finally, a decade ago, we were often asked if we could grow through patent expiration. We thought we could. And as you know, we did. Revenues grew by 5% per year, EPS grew by 2.5-fold and shareholder value more than tripled. And even if the past is not prolonged, I hope that quick look back has given you a sense that when we talk about what we're planning to do next, we're building on a foundation of solid execution. And looking back, I hope you can also see an important fundamental of our business, which is that we are heavily weighted to biologics, and we have skill in managing them throughout the whole of their life cycle, a capability which we expect to serve us well in the future as it has in the past. Cash flows from biologic products don't disappear overnight following the loss of exclusivity as is the case with small molecules. A decade ago, about 40% of our revenues, largely biologic, were exposed to loss of exclusivity. Those biologic products today still account for about 10% of our revenues. So if you're measuring our business for quarterly performance, the slow erosion is a drag. But if you're measuring our business for long-term cash flows, those residual biologic margins are clearly an asset to be managed thoughtfully. And those residual biologic margins enabled us a decade ago to invest in efforts like our international expansion, our biosimilars development, new manufacturing technologies, and there's no question that we will reap the benefit of those investments over the coming decade. And though we don't have any biologic patent expiries still for several years, we'll approach them in the future as we did in the past and seek to repeat our success. Now let's look forward. similar to what we achieved over the past decade, when we look at the products and opportunities that we have in hand and take into account the likely competition and industry pressures that we see, we believe we can deliver mid-single-digit revenue growth and more than double our EPS through the end of the decade. Now this is an organic outlook. So any growth from business development would be additive to these numbers. How will we do it? Well, that will be the focus of our presentations today. We don't think we're taking a great leap of faith in giving this outlook. We think we're banking on our ability to execute against known opportunities. Our future doesn't hinge on one product or one clinical trial or in one country. Amgen has a broad portfolio of 25 products across 3 major therapeutic categories. Many of these products have the momentum of their established efficacy and safety profiles, and are clearly poised for continued growth. We do business now in 100 countries around the world, and many of these are also poised for considerable growth during the decade. Our pipeline is robust at all stages, and our balance sheet is strategically strong. And we think we have the pieces in place that we need to succeed, and no single piece will disproportionately tell the tale. It's our job now to execute across the board. And while the success factors for Amgen moving forward may be familiar, we recognize that the world that we live in has changed, and we've worked hard to anticipate many of these changes, trying to stay ahead of the curve. I'll just give you 2 examples. First, we all know there's intense price pressure on prescription drugs, and the impact of the pandemic on economies around the world will only increase this. So irrespective of what may or may not come out of Washington, the direction of travel is clear. Prices will continue to come down, and our business is built around that assumption. So how have we positioned ourselves to succeed in this environment? Well, we focused on being first and best in having first and best-in-class medicines, medicines that deliver significant benefits in areas of high unmet need and that demonstrate clear value to patients and the health care system. We've also positioned our portfolio to feature medicines that can grow through volume, not just through price increases. Our fully-integrated biosimilars business saves money for the health care system, thereby freeing up funds for our innovative offerings. Second, we recognize there's tremendous life cycle compression in our industry. Growing competition, narrowing landscapes for intellectual property and technological leapfrogging all have the same effect: fewer years to earn a return on innovation, and that puts a premium on speed. And so we've taken steps to significantly reduce our cycle times across the business. And especially in R&D, where on average, we've been able to eliminate 3 years out of the life cycle of the development of a new medicine. With LUMAKRAS, we delivered one of the fastest cycle times in industry history. So while many companies are pursuing their own KRAS inhibitors, LUMAKRAS remains the only one approved anywhere in the world. Nearly 40 countries now and still counting. And LUMAKRAS is far from our only first. We have a history of them. Prolia and XGEVA, they were the first antibodies against rank ligand and bone health. Repatha was the first PCSK9 inhibitor for high cholesterol. Aimovig was the first CGRP inhibitor for migraine. BLINCYTO, the first approved bispecific T-cell engager for cancer. And of course, Tezspire, the first approved TSLP inhibitor for severe asthma. And to succeed in our industry, you're going to have to be fast, and we're confident that we are that. And we're confident that there are many more firsts still to come at precisely the time when being first matters most. While the world has certainly challenged or changed rather, in ways that are challenging, other changes represent extraordinary opportunities. Take demographics. The world is growing older, right? That's the future that is certain. There are already 700 million people worldwide over the age of 65, coping with diseases of the aging process like cancer, heart disease and osteoporosis. And these individuals consume 3x as much health care as those under the age of 65. By 2030, another 150 million people will have joined the over 65 Club. So if you do the math, there will be huge demand for what we do through 2030 and beyond. Innovation is another. There's never been a better moment for innovating than now. The protein folding problem, for example, was considered to be one of the grandest challenges in biology for 50 years, and the solution to the problem was reported on July 22 last year. There is no question this will increase the speed and success of biologics discovery. Closer to home with LUMAKRAS, we achieved something that had eluded cancer researchers for more than 40 years, offering new hope to patients with KRAS G12C-mutated cancers. And it's not a coincidence that we're seeing these decades old challenges being solved at this particular moment in time. As I said at the outset, we're entering an extraordinary new era in biotechnology, a moment where both the need for innovation and our ability to innovate are expanding exponentially. And that's good news for Amgen; we intend to ride this wave of opportunity and not watch it pass us by. You see our strategy here, and we've made some adjustments to it over time, but the fundamentals remain in place, and we'll guide our focus to 2030. At the heart of our strategy are innovative medicines that make a significant difference for patients around the world suffering from serious diseases. If you look at our portfolio and all the firsts I just mentioned, for example, or you look at the pipeline that Dave Reese is going to review with you. Every molecule that we speak to you about today from the pipeline is a potential first-in-class medicine. And the world needs more innovation, and we're bringing it. At a time of extraordinary scientific progress, we recognize that great ideas are happening everywhere, not just at Amgen. And we want the best innovation we can get our hands on, whether internally or externally generated. Historically, roughly half of Amgen's revenues have come from products discovered internally, while the other half has come from products that we've acquired or licensed. And we'll continue to be active deal makers moving forward in our stated areas of interest, and I would note that any growth or repeat that any growth coming from external sources will be additive to the financial outlook we're sharing with you today. And it's not lost on us that the recent decline in valuations for many biotech assets could create more compelling opportunities for us, and we have the financial strength and the flexibility to consider a wide range of possibilities. So where are we looking to innovate? You can expect us to remain focused in inflammation, oncology and general medicine. These are categories where innovative medicines have already demonstrated tremendous value to patients and the health care system. To give just one example, the death rate for cancer in the United States peaked in 1991 and has been steadily declining ever since, falling by more than a quarter. And fully half of this decline is attributed to the growing number of innovative cancer medicines that have become available to patients. But despite this progress, there are still categories or these are still categories where we see millions of patients in need. We know the pandemic has overshadowed other health concerns for the past 2 years, and that's understandable. But the pandemic will eventually recede, and when it does, we expect society to turn its attention to solving some of the massive health challenges that we know haven't gone away, and we're ready. You'll hear more shortly about that from Murdo, Susan and Dave Reese, who will share with you their perspectives on the growth opportunities that we see in each of our focus areas through the end of the decade. Another key element of our strategy is to capitalize on the investments we made to expand our geographic presence. We're especially excited about our growth prospects in the Asia Pacific region where, for many years, we did business largely through partners. In Japan, for example, we only took full ownership of our business in 2020. And our portfolio of products there is particularly well-suited to the needs of what is the world's oldest population. In China, our oncology collaboration with BeiGene is going very well, even as we continue to independently grow our general medicines business through products like Repatha and Prolia. Overall, we expect sales outside the U.S. to account for roughly 35% of our total sales by 2030, up from less than 30% today. Now I'd like to spend a moment on Discovery Research, our engine for growth beyond 2030. We've been actively building differentiated research capabilities in 3 particular areas that are rapidly emerging in our industry. These are Human Data, Multi-Specific Drugs and Generative Biology. We've been active internally and externally in these areas, and we think they'll each play a prominent role in our future, so we thought it was appropriate today to share some of the thinking behind our strategy with you. Our established leadership in human genetics is paving the way for us to build a competitive advantage in personalized medicine and the broader use of human data for target discovery and drug development. With our multi-specific drug capabilities, we're no longer willing to accept that 85% of the targets in humans are undruggable. Already 2/3 of our pre-clinical molecules are multi-specifics. With our decades of leadership in large molecules, we're already quickly capitalizing on machine learning and automation in the new field of generative biology, and you'll hear more about all of these areas from Dave, Ray and Allen shortly. Underpinning and enabling everything we do is our commitment to being a responsible corporate citizen. The past few years have certainly raised the bar in terms of what's expected for corporations, and that's a welcome development here at Amgen. We've long embraced our responsibility to be a good corporate citizen. And let me just give you a few examples. More than 30 years ago, we created the Amgen Foundation to inspire the next generation of scientists. This year, the Foundation Science Education programs will reach nearly 24 million students worldwide. More than 20 years ago, we created the Amgen Safety Net Foundation to help patients in financial need gain access to our medicines at no cost, including $6 billion worth of medicines in just the past 5 years. 15 years ago, we began implementing a series of projects to reduce our impact on the environment. Now, we're aiming even higher, with plans to achieve carbon neutrality by 2027. We're grateful for the recognitions we've achieved from a number of external organizations, and we're eager to do more. We'll be publishing our next environmental, social and governance report in April, and ESG is an element of our corporate goals for 2022 as it was last year. As I wrap up, I hope you've gotten a clear sense from me that I'm excited about Amgen's future and the value I think we can create for patients and shareholders, and I think you'll see that excitement is shared by the rest of the team too. Our people believe in Amgen's mission to serve patients, and they understand the role they play in advancing that mission. They've executed exceptionally well under very challenging circumstances these past 2 years. The commitment they've shown to patients to our business and to each other during these difficult times has been nothing short of extraordinary, and I'm very grateful to all of them. You know, of the thousands of companies that were founded during the Biotech revolution of the 1980s, only 2 of note remain independent to this day, and one of them is Amgen. And that's not by chance, we wake up every morning knowing that in our business, we innovate or we disappear. And we've had great people delivering great innovation throughout our history, and I'm convinced that we have the right people, and we have the right focus to remain a leader through the end of this decade and beyond. Now I'll turn things over to Peter Griffith in a moment. But before I do, let me just say that we understand we earn the right to compete over the long term by delivering in the near term. We delivered our targets in 2021. And clearly, 2022 is a year that will still be -- where we'll still be affected by the pandemic and by pricing pressures from competitive products. But we see this as a year that will set the stage for the long-term growth that I've just described. The fundamentals of our growth story are in place, as Peter will describe to you in some detail. Now let's turn to Peter.

Before turning to 2021, let me also reiterate Amgen's strong record of accomplishment and execution, and that we are extremely excited about the future value we believe we can deliver for patients, shareholders and staff. Since 2012, we have realized revenue and non-GAAP EPS growth of 5% and 11%, respectively. We are well positioned to deliver long-term growth. From now through 2030, we expect mid-single-digit revenue and high single-digit to low double-digit non-GAAP EPS growth respectively. Recall in 2014, we committed to margin improvement, and we have since consistently delivered on a 50% non-GAAP operating margin with focused efforts in productivity and efficiency, including our next-generation manufacturing capability that saves time, space and money, that adds flexibility, and that contributes significantly to meeting the environmental goals that are part of our ESG efforts. From 2021, cost of sales was about 1.3 percentage points lower by moving to this technology versus utilizing the traditional fed batch manufacturing approach. Process improvement, simplification and digitalization are indisputably important to deliver results for patients, shareholders and staff. With revenue growth, efficiency and a strong biologics portfolio, we have driven stable and consistent cash flows, enabling both internal and external innovation as well as attractive shareholder payouts. Free cash flow was $85 billion from 2012 to 2021, growing from $5.2 billion in 2012 to $8.4 billion in 2021. We expect our cash flows to continue to be strong through 2030. We had a shareholder payout ratio of well over 70% over the 2012 to 2021 period, comprising about $28 billion of dividends and $48 billion of share repurchases. Recall that the higher level of share repurchases in 2018 and 2019 were primarily a function of United States tax reform. When we normalize the payout ratio in this period, it was roughly 70%. Let's turn now to our full year 2021 financial results. You've had the opportunity to review the press release, so I will focus on the fiscal year highlights. Total revenue grew 2% on a year-over-year basis. Within that, product sales were flat with strong volume growth of 7%, offset by decreases in net selling prices of 7%. Foreign exchange had a negative 1% impact on growth, which was more than offset by about $400 million of favorable changes to estimated sales deductions. Volume growth continued to be negatively impacted by the cumulative effect of COVID on diagnosis and treatment rates since the onset of the pandemic. Total revenue benefited from about $400 million in other revenue from our partnership with Lilly in manufacturing COVID-19 antibodies. Strong expense discipline resulted in a 51% operating margin while we continue to invest in both internal and external innovation. In addition to the $3.2 billion in upfront payments we paid for external innovation that we excluded from our non-GAAP results, we did layer in about $300 million in our non-GAAP operating expenses related to the acquisitions of Five Prime, Teneobio and Rodeo Therapeutics, as well as the licensing transactions with Kyowa Kirin, Generate Bio and Arrakis. Full year non-GAAP EPS grew 6% year-over-year to a record $17.10. We generated $8.4 billion in free cash flow for the year. Total dividend payments in 2021 were about $4 billion as we grew the dividend by 10% from 2020, and we grew at an additional 10% from Q4 2021 to Q1 2022. Total share repurchases were about $5 billion in 2021. With our strategy established and our execution during COVID strong, we are confident about the long-term growth prospects for the company. Let's turn to our long-term outlook. We prepared many years ago for the evolving pricing environment, particularly that related to the United States. And as a result, we increased our focus on embedding productivity initiatives across the company. In addition to increasing our focus on innovative products that also drive volume growth. As anticipated, we and the industry have experienced net selling price pressure since 2018, and expect to continue to operate in a declining net price environment going forward. Recall net selling prices had risen for the previous 4 decades, but we saw the pricing pressure coming and have adjusted while keeping our fundamentals intact. Our long-range plan projects meaningful volume growth that will more than offset projected price declines and will result in strong revenue growth. In a declining price environment, we have also accelerated digitalization, automation and process simplification efforts, which are keys to success in declining price industries. And finally, speed is required to make sure revenue growth leads expense growth. We are working faster and faster. You've heard about our LUMAKRAS development program from first in human to FDA filing in 28 months. In manufacturing, we made our first COVID antibody shipment to Lilly about 6 months after signing the agreement. And commercially, the first Tezspire patient obtained their medicine within 3 days of approval. As Bob stated, we expect mid-single-digit revenue growth and high single-digit to low double-digit EPS growth from 2022 to 2030. Between our marketed products, upcoming biosimilar launches, innovative and longer-range biosimilar pipeline, and with sales from new products more than offsetting the impact of future competition for denosumab, Otezla and ENBREL, we are confident in our long-term growth through the end of the decade. We plan our quality of execution high and achieve -- we will achieve an operating margin as a percent of sales of roughly 50% despite a declining net price environment. We project a payout ratio of greater than 60% of non-GAAP net income on average through 2030. I'll come back and provide more details on our long-range guidance after reviewing our 2022 guidance. For 2022, we are expecting revenue of $25.4 billion to $26.5 billion, an EPS of $17 to $18. The revenue range is a bit wider than recent history, and the top end of it is predicated on the possibility of additional COVID antibody manufacturing revenue, which I'll discuss later in my remarks. On a portfolio basis, we expect net selling prices to decline in the mid- to high single digits, driven primarily by Neulasta and our biosimilar portfolio. So let me start with Neulasta, which continues to be the most preferred long-acting filgrastim product for patients and physicians. Neulasta exited Q4 2021 with 61% U.S. volume share, and the Onpro kit still represents nearly half of the volume of the total long-acting filgrastim segment. However, we expect the declining pricing trends for Neulasta to continue into 2022. Average selling price in the U.S. declined 32% in 2021 versus 2020, following a 15% decline from 2019. Given our projection of this continuing trend, we expect 2022 worldwide Neulasta sales to be between $900 million and $1 billion. Regarding biosimilars, we see that portfolio growing to more than double by 2030. However, with no new significant biosimilar launches in 2022, we expect biosimilars to decline in 2022 before returning to growth on 2023 on the U.S. launch of AMJEVITA in January of next year. ENBREL is our largest brand. With its strong track record of safety and efficacy, it has a very important role for rheumatology and dermatology patients and providers. We note that the pace of volume decline for Enbrel has been slowing over the last 3 quarters. In fact, in Q4 '21, we delivered 2% sequential volume growth. Recall that ENBREL benefited from about $250 million of accounting adjustments in 2022 that may not repeat in 2022 -- excuse me, of accounting adjustments in 2021 that may not repeat in 2020. Foreign exchange had an adverse impact on our fourth quarter 2021 sales. And based on current rates, is expected to create a roughly $200 million year-over-year headwind to product sales in 2022. Recall, however, that we have an effective hedging program that partially mitigates the foreign exchange impact on our net income on a full year basis. In total, our 2022 non-GAAP EPS guidance includes a negative impact from foreign exchange of approximately 1%. Switching to our view on the effects of COVID generally and the recent Omicron surge, we continue to anticipate some uncertainty and quarter-to-quarter variability in revenue and earnings in the first half of 2022. I previously mentioned that we had about $400 million of other revenue from our Lilly partnership. COVID-related manufacturing partnership opportunities remain dynamic, and we look to utilize our world-class manufacturing capabilities to help in the fight against the pandemic. Therefore, we are guiding to a range of $1.4 billion to $1.7 billion for other revenue in 2022. We expect non-GAAP cost of sales as a percent of product sales will be in the range of 15.5% to 16.5%. Non-GAAP research and development is expected to increase between 3% and 5% year-over-year as we continue to invest in internal innovation across all the stages of R&D. Non-GAAP SG&A will be roughly flat to 2021, with productivity gains fueling investment in launches and geographic expansion. Within SG&A, we are continuously reallocating capital away from our lower opportunity brands to the highest opportunity growth brands, including Repatha and Otezla. All of this results in our non-GAAP operating margin guidance of approximately 50%. For other income and expense, we had about a $285 million benefit from our share of BeiGene due to a combination of first, a gain from dilution of our ownership stake when they raised capital on the Shanghai Star Exchange in December; and second, their recognition of a large upfront license payment from a partner that we recorded in the second quarter of 2021. For 2022, we are guiding other income and expense to a range of $1.4 billion to $1.6 billion of expense. Expect a non-GAAP tax rate in the range of 13% to 14%. And we expect capital expenditures of approximately $950 million, primarily increasing due to construction around our new facilities in Ohio and North Carolina, in which we also will further strengthen our leadership in environmental imperatives. So just to wrap up on 2022. Recall that the first quarter is historically our lowest revenue quarter due primarily to the effect of insurance reverifications, co-pays and deductibles for patients, which is most pronounced for Otezla and ENBREL. Thus, we expect to see their historical patterns of lower sales in the first quarter. And in addition, we expect to see the effects from the Omicron surge also impact our first quarter results. So overall, we expect total revenues in the first to be approximately flat when compared to the first quarter of 2021. Let us now come back to long-term guidance. We expect to generate strong financial results through the end of the decade, and we see accelerating growth in 2023. We expect this accelerating in growth to come from the U.S. launch of AMJEVITA, from continuing post-launch momentum for Tezspire and LUMAKRAS and in addition to continued growth from key brands including Repatha, Otezla, Prolia and EVENITY. And let me remind you that we expect our biosimilar sales to more than double from 2021 levels by 2030, and that our biosimilars are not dilutive to our overall operating margin. This growth reflects layering in 6 new products on top of our existing 5. So while individual products may peak quickly and even turn down, in the aggregate, the portfolio will grow to a profile similar to one super blockbuster, yet with a lower risk profile versus just one innovative asset. Overall, our product portfolio is attractive given its diversity, both geographically and therapeutically as well as its durability. Our portfolio effectively transitions through loss of exclusivities and competition and doesn't hinge on a single product. This revenue profile, combined with our efficient operating model, is projected to deliver high single-digit to low double-digit EPS growth with an approximately 50% operating margin that effectively prioritizes investing in innovation wherever the best innovation is found, internal or external. The sales will increase with the mix of products and also due to royalties and profit share of payments. We expect our manufacturing cost per unit to decrease over the period. Research and development expense will increase to greater than $6 billion by 2030, of which we expect to allocate approximately $1 billion of the $6 billion or about 15% of our R&D budget to our research engine, which will fuel growth from 2030 and beyond. SG&A expense through 2030 will continue to benefit from our ongoing productivity efforts and digitalization, which will result in it being flat to declining as a percentage of product sales. Our commercial group continues to dynamically reallocate resources towards the brands with the greatest potential to serve patients and generate after-tax cash flows for our shareholders, and we are not including any potential tax reform in our estimates through 2030. So now let's turn to our capital allocation hierarchy. Our capital allocation hierarchy remains unchanged and uninterrupted. It starts with internal and external innovation, focused on our core therapeutic areas wherever the best innovation for patients is found. Our internal innovation starts with research and development investments, which we expect to grow through 2030. Our external innovation sits right alongside internal innovation. We have a strong track record of value-generating deals across the commercialization spectrum and ones where we are confident that we will deliver returns to our shareholders, not just the shareholders of the sellers. And then our capital allocation goes to capital expenditures, primarily to maintain our industry-leading protein engineering and manufacturing capabilities. Our next-generation drug substance plant in Rhode Island was licensed in January, right on schedule and on budget, and meets our high level of standards for sustainability. We evaluate each of our projects for the impact on our ESG goals and work to assure that lines up with our commitment to be a leader in our industry on ESG achievements. And I just want to note that we expect to return to our historical levels of capital expenditures after we complete our Ohio and North Carolina facilities. And after capital expenditures, we return capital to shareholders through growing dividends and then through opportunistic share repurchases. The foundation of our capital allocation hierarchy is an efficient capital structure that results in an optimal weighted average cost of capital. We seek the best innovation, whether it's internally or externally generated. We've been active this year. We've been active in years past. As Bob mentioned, we've completed over $30 billion in deals over the last decade. These deals span the commercialization spectrum, from platform and technology-related deals that Ray and Alan will speak of shortly, to deals for marketed products like Otezla and in every stage in between. We patiently evaluate external opportunities that clear our hurdle rate and are consistent with our core therapeutic areas. And although the plan we are presenting today is based on programs at hand, it's organic, we do expect external innovation to continue to contribute to our portfolio and pipeline going forward. And let me also note that we have not assumed any additional COVID antibody revenue beyond 2022. And if COVID becomes endemic and continues to mutate, we will assess whether there is a role for our world-class antibody manufacturing capabilities going forward. We will continue to return capital to shareholders at attractive levels. In 2021, we paid dividends of $1.76 per share per quarter, which resulted in about $4 billion and repurchased approximately $5 billion in stock. We've grown the dividend meaningfully each year since we started it in 2011. We plan for continued dividend growth over the long term. We're planning to buy back up to $6 billion in the first quarter. And over the balance of the decade, we plan on a competitive payout ratio and expect to return greater than 60% of our non-GAAP net income to our shareholders on average through a combination of dividends and share repurchases each year. Let me wrap up here before turning it over to Murdo and Susan. We're excited and confident in our future. We covered what we set out to cover with you this morning. We said what we would do and what we've accomplished. We reviewed 2021, which was highlighted by the early approvals of LUMAKRAS and Tezspire along with 7 important transactions to get external innovation for patients. We shared our excitement around the rest of the decade and our long-term financial outlook. We gave you our outlook for 2022 and our confidence in accelerating growth into 2023. We expect mid-single-digit compound annual revenue growth through the end of the decade, along with high single-digit to low double-digit growth in EPS. We are confident in our high quality of execution, and we'll continue to create capacity for investment in both internal and external innovation for patients. And finally, we are excited to continue to deliver long-term value to patients, shareholders and staff. Murdo?

Thanks, Peter. Over the next 30 minutes or so, Susan and I will share our excitement about how we will capitalize on our growth opportunities now through 2030. For over 4 decades, Amgen has discovered and commercialized innovative first-in-class medicines, transforming the natural course of many diseases and positively impacting the lives of millions of people. Over the last decade, we've accelerated our ability to help even more patients across more disease areas. By launching 10 products since 2012, we have grown to 25 marketed brands and $26 billion in revenue in 2021. We've also delivered substantial value to health care systems around the world by launching 5 biosimilar products since 2018, generating over $2 billion in revenues in 2021. This fully integrated biosimilar portfolio is supported by our outstanding development and manufacturing operations capabilities, and they ensure that we have first wave launches and resilient supply for patients globally. Amgen now operates in approximately 100 countries, doubling the geographic footprint we had in 2012, and revenues in our Asia Pacific region surpassed $1 billion and will drive strong long-term revenue growth for the company. This portfolio transformation and global expansion required significant effort in order to allocate our resources to the highest growth opportunities in disease areas of significant unmet need that address tens of millions of patients worldwide. While managing our legacy portfolio and slowing the erosion from recent biosimilar competition, we've been looking ahead at the key opportunities we have for growth, and have been building differentiated capabilities that Amgen needs to compete. We invested in several critical areas to advance the way in which diseases like psoriasis, severe asthma, cancer, osteoporosis and heart disease are treated. Given the increasing prevalence and burden of these conditions, it's imperative that in addition to improving screening and diagnosis efforts, we need to accelerate the adoption of novel treatments that can reduce morbidity and mortality and improve patient outcomes. As a leader in biotherapeutic innovation, we see it as our mission to serve as many patients as we can who are battling these diseases. We're focused on building our portfolio and critical capabilities to enable this mission, and these include our global reach in more than 100 countries, our broad and diverse portfolio of innovative and biosimilar products across 6 therapeutic areas. We've designed a global, locally-deployed digital customer engagement model, and it will allow us to reach customers despite COVID challenges. These digital capabilities, along with our advanced customer data and analytics, also helps us optimize investment and predict customer response to field and remote engagement. We significantly optimized our media spend, improving overall investment return. We've established very sophisticated value and access capabilities, particularly for growth in launch products, and this has allowed us to have access established in closer proximity to regulatory approval. And this was the case recently with LUMAKRAS in the United Kingdom. We've also simplified and enhanced our patient reimbursement support on both innovative and biosimilar products, and this ensures a lower abandonment and much improved persistency. So when combined, these capabilities increase our competitiveness and our agility to meet and anticipate the needs of customers and patients, and that supports mid-single-digit revenue growth over the decade. This growth will largely be driven by our innovative in-line portfolio, recently approved launch brands and soon-to-be launched biosimilar products. This means much of our future growth is secured. It has regulatory approval. It's reimbursed, and is now in the hands of our highly effective medical and commercial teams to execute and drive demand by increasing physician adoption and supporting care. So we're very pleased despite the COVID pandemic challenges with the early launch progress of 2 first-in-class products, LUMAKRAS and Tezspire. And our biosimilar portfolio growth accelerates with the launch in early 2023 of AMJEVITA, our biosimilar to HUMIRA, in the U.S. And we're currently the adalimumab market leader with AMJEVITA in Europe, and have launched this product in more than 55 countries around the world. The U.S. AMJEVITA launch will be complemented by subsequent launches of biosimilars to STELARA, EYLEA and SOLIRIS. Lastly, we expect additional launches in the decade from our deep R&D pipeline in inflammation, oncology, general medicine along with additional biosimilar product development. So given the challenges we face in the market today and the broad set of growth opportunities we have, it's essential that global brand strategies are clear and that we build global capabilities followed by outstanding local execution. Now, Susan Sweeney leads the global marketing access and customer capabilities organization at Amgen. She has over a decade of experience in the inflammation therapeutic area and has launched multiple brands across our therapeutic areas, including inflammatory diseases. So it's great to have Susan with us today, and she'll cover our inflammation portfolio in more detail. Susan?

Thank you, Murdo. Amgen Inflammation has been serving patients with autoimmune diseases for more than 20 years. Our diverse portfolio of innovative and biosimilar medicines and highly efficient operating model enables strong execution and growth. We have broad coverage across the main areas of autoimmune disease including gastroenterology, dermatology, rheumatology and respiratory. One in 10 patients who receive a systemic therapy by a rheumatologist or a dermatologist in the U.S. is prescribed an Amgen product. Our nimble medical sales and access teams of more than 2,000 people globally gives us a strong share of voice across all 4 of our core specialties. Ensuring patients and physicians get access to our products is critical, with the consolidation and vertical integration of payers and PBMs and increased competition, barriers, prescribers' experience related to treatment choice and patient affordability continue to be a challenge. With our well-established presence, integrated biosimilar and innovative brands, we are in a position of strength to sustain and gain access. When we launch a new product, whether it's a biosimilar like AMJEVITA, an innovative therapy like Tezspire or an expanded indication as in the case for Otezla, we can quickly leverage our experience and portfolio to speed access uptake. We serve millions of patients. We have proven success in the -- as the #1 market leader in dermatology in the U.S., #2 market leader in rheumatology in the U.S., and have the #1 adalimumab biosimilar AMJEVITA in Europe. We expect to continue to achieve leading shares through effective launch of future biosimilars and by capitalizing on the strength of our partnership with AstraZeneca for Tezspire. In development, we have a robust inflammation pipeline and are expecting launches in these disease areas over this decade. Dave Reese will discuss more about those potential products in detail. I've spent my career as a marketer working on many brands. Having a unique product like Otezla is a privilege because of its benefit for patients with psoriasis. Psoriasis is a visible and burdensome disease, the effects of which go well beyond the skin. Even mild disease can be unsightly, uncomfortable and difficult to treat with topicals. For a complicated disease, the first and only oral systemic treatment for patients with mild, moderate and severe psoriasis is now available with Otezla. Otezla is the oral standard of care and is well positioned for growth. It is differentiated from both current and future competitors. It has been in the market for almost 8 years, and over 700,000 patients have been treated. As we've seen with the JAK class safety is important for patients and physicians. Otezla's safety profile is well known by the health care community. The convenience of oral dosing and no requirements for pre-screening or lab test is a benefit for starting patients on therapy. By leveraging our vast inflammation portfolio and negotiations with PBMs in the U.S., we have over 90% first-line coverage, and now we've secured broad access to our expanded label without a step change in that price. Otezla has been broadly studied. It currently has 3 indications, and we are pursuing additional expansion of use into genital psoriasis, palmoplantar pustulosis, pediatric psoriasis and once-daily treatment. With this strong profile, access position and best-in-class team, we are well prepared for future competition. The psoriasis market is crowded. There are now 14 systemic brands to treat moderate to severe psoriasis. Otezla has maintained a leadership in this very competitive market. As you can see from the graph on the left, there has been consistent growth in the use of systemic therapies to treat psoriasis. This growth trend has been steady, except for a slowing of new patient growth at the beginning of the pandemic. New patients initiating therapy for the first time flattened in 2020, but got back on track in '21 as it progressed. And we should see, with the return of patients to their dermatologists, continued growth. As you can see from the graph on the right, we are and have been the #1 therapy for patients initiating their first systemic. Because we are the only oral systemic, our growth is dependent on new patients seeking treatment. For Otezla, the pandemic initially had a disproportionate impact, with less patients being able to visit their dermatologists. Now that the market is growing again, we will not only expect to keep our leading share position but also expect to see an improvement in our growth rate. The expansion of our label in the U.S. provides an option for more patients and is a catalyst for growth. In '21, Otezla grew 8% on a volume basis offset by pricing pressures. We believe, had it not been for the pandemic impacting the new to systemic therapy market in '20, there was a high likelihood that the volume growth in '21 would have been notably higher. The expansion of our label to all forms of psoriasis is off to a good start. Physician awareness is increasing. We're hearing stories from our field team of physicians prescribing Otezla to milder patients. We are also seeing an inflection in our dermatology new patient share. As we look to '22 and beyond, we feel confident in our ability to deliver low double-digit average annual sales growth until U.S. loss of exclusivity. Another major expansion in our inflammation franchise is the launch of Tezspire for patients with uncontrolled severe asthma. Launching Tezspire, a new mechanism that could help more patients, is something everyone at Amgen is proud of. We've seen tremendous anticipation and support from the asthma community and physicians for a new medicine that has the potential to treat severe patients regardless of their asthma type. 1 million people in the U.S. and 2.5 million people globally live with severe asthma that is uncontrolled or biologic eligible. Serious exacerbations require 1.6 million emergency room visits and 180,000 hospitalizations per year, and that's just in the U.S. alone. And the number of Americans with asthma is anticipated to grow 10% by 2039. We feel we can change the way this disease is treated. There are many physicians who want a simpler approach given the complexity of the biomarker testing and phenotyping. Tezspire can be that simple approach. We were very pleased by the FDA's earlier approval of Tezspire, and have been working to make the drug available to patients as quickly as possible. Tezspire is the first and only biologic for severe asthma to be approved without phenotypic or biomarker limitations. It has the opportunity to change the treatment paradigm. For a complex condition, Tezspire can streamline physician choice and access for more patients. In terms of where Tezspire will ultimately be used, there is a significant market opportunity given that 85% of eligible people with severe asthma are not currently receiving a biologic. With the introduction of Tezspire in the U.S., the biologic eligible patient population expanded by approximately 20%. Over time, we expect the U.S. biologic penetration to continue to increase. The Tezspire launch is very early, but we feel well off to a strong start. In conversations with our teams and physicians, Tezspire is being received extremely well, and there's a lot of excitement. Patients' initiations are starting. As a new mechanism, educating physicians is important. Through our field medical teams and disease education, we have high [ unaided ] awareness of TSLP, the mechanism for Tezspire. There have been almost 2,000 samples distributed since launch and over 1,000 patients enrolled in Tezspire Together our patient support program. We submitted the application for coverage and medical benefit. The early approval and early launch allowed us to pursue a permanent reimbursement [ J code ]. Just a few weeks into launch, physician intent to prescribe is high, with 80% interested in prescribing Tezspire. Our winning position in severe asthma biologics comes from the strength of our partnership with AstraZeneca. Pairing their strong legacy in respiratory and pulmonology with our unmatched leadership in inflammation and our world-class commercial teams, we are confident in our opportunity and ability to deliver. Lastly, we have a broad life cycle plan and are pursuing a number of indications that Dave Reese will review. As we round out this discussion on inflammation, we'll shift our focus to the U.S. launch of AMJEVITA, which is fully integrated into the inflammation portfolio. The model, integrated innovative products and biosimilars positions us to address areas of greatest importance to payers, providers and patients when a new biosimilar is introduced. When we talk to stakeholders about what's most important consideration for biosimilars, they have different needs. Proven safety and efficacy is table stakes for all, and a reliable product supply is often assumed but is critical. For providers, ongoing support from the manufacturers needed to support the switch to biosimilars and even when -- with a biosimilar, continued education is needed. Patients require efficacy, safety and supply, but also have special needs for support. Patient support on device usage and co-pay assistance are required to ensure continuity of care. AMJEVITA's launch will meet the needs of our customers. Our unique integrated biosimilar and innovative product portfolio and experience in growing AMJEVITA to the #1 biologic for adalimumab in Europe sets us up for success. AMJEVITA has treated more than 250,000 patients worldwide and safety and efficacy is well understood, thanks to our large real-world evidence data set. This track record of efficacy and safety is important for all customer types. Amgen has a world-class supply chain, and as one of the first biologic manufacturers, a deep and long history in ensuring that we serve every patient every time. Our integrated medical field and access teams will launch AMJEVITA and provide the same support our customers have become accustomed to. We are a company with a rich history and development of devices and support for patients. We will leverage our current patient support systems to ensure seamless transitions with co-pays and other support services. We are well positioned for a successful launch of AMJEVITA. As Peter said, we will grow our biosimilar revenues beyond AMJEVITA bearing 6 additional sequential product launches throughout the decade, which fuel the steady growth. Given that biosimilar life cycles are somewhat compressed, having a sequential set of biosimilars to launch allows us to sustain growth over time. We expect overall biosimilar revenues to be more than 2x '21 revenues by 2030. We have a very strong inflammation portfolio currently serving millions of patients. Our first-in-class inflammation product line has produced a leading market position and the unique integration of biosimilars and innovative business will continue to drive impact over the next decade. I'll turn the discussion back to Murdo to talk about our exciting oncology portfolio.

Thanks, Susan. Amgen has been pursuing breakthroughs for cancer patients for over 40 years now. We have a deep, diverse portfolio and pipeline of cutting-edge therapeutic approaches that aim to improve patient outcomes. Now in the United States, 1 in 5 cancer patients receives an Amgen medicine. This legacy and incumbent strength in the market builds an extremely strong global foundation to help more patients and generate growth. Our diverse portfolio of promoted oncology brands generated $5.7 billion in sales in 2021, and has grown 8% from 2018 to 2021. This growth was driven by XGEVA and Kyprolis, as well as LUMAKRAS, Nplate, Vectibix, BLINCYTO and IMLYGIC, which will deliver durable growth throughout the decade. Our strong presence in oncology has been further augmented by the addition of our biosimilar products in MVASI and KANJINTI, which generated $1.7 billion in sales last year. It's expected that biosimilar competition will lead to declining price and revenue trends on these 2 biosimilar products. In addition to legacy and incumbent strength, 2021 was exciting for us. We grew our portfolio of innovative oncology therapies in '21 with the launch of LUMAKRAS, the first KRAS G12C inhibitor for advanced non-small cell lung cancer patients with the KRAS G12C mutation. While this is one of the most prevalent biomarkers in lung cancer, treatment has remained elusive for these patients, but now they have hope, and we're really excited to be able to bring that to them. After 40 years of attempting to intervene in this driver mutation pathway, Amgen research and development teams moved at record pace to bring this transformative treatment option to patients. We're exploring the potential safety and efficacy of LUMAKRAS across a number of tumor types and lines of therapy. Lung cancer is, of course, the largest tumor type, and it's estimated that approximately 75,000 patients with advanced metastatic non-small cell lung cancer worldwide have KRAS G12C mutation, with 27,000 of these patients progressing to second line. Beyond lung cancer, we're also exploring the efficacy of Sotorasib in monotherapy and in combination in colorectal and pancreatic cancer. Our extensive and well-established customer presence in academic cancer centers and community oncology practices is supporting a strong launch of LUMAKRAS, with over 1,000 physicians having prescribed the medicine so far. We generated $45 million in sales in Q4 with the majority coming from the U.S. We now have approvals in more than 35 countries including United States, the U.K., Canada, EU and Japan. We continue to drive biomarker testing efforts to ensure that every non-small cell lung cancer patient is tested for their KRAS G12C status. And we're pleased that in the U.S., the majority of testing labs are now listing KRAS G12C as an actionable mutation, and this helps to prompt oncologists to provide a LUMAKRAS as an option for their patients. So let me transition now to our general medicines portfolio, which consists of products that have the ability to impact large populations that are highly underserved. We'll start first with osteoporosis, where we have the potential to positively impact the lives of millions of patients. Osteoporosis is a growing, significantly under-diagnosed and under-treated disease. It affects more than 200 million people worldwide. The Bone Health and Osteoporosis Foundation estimates that osteoporotic fractures will increase by 68% by the year 2040, with associated Medicare costs exceeding $95 billion in the U.S. So in summary, fractures related to osteoporosis are common. They're costly, and thanks to innovative medicines like Prolia and EVENITY, preventable. Having 2 potential ways of intervening in this disease has never been more important. Prolia and EVENITY really are stronger together. For post-menopausal patients with osteoporosis, treatment with Prolia over several years can significantly reduce the risk of fracture. And if a patient has a fracture, that increases the risk of another osteoporosis-related fracture by 86%. For these high-risk patients, EVENITY offers an opportunity to rapidly build bone strength and reduce spine fracture risk in 12 months. For well over a decade, Amgen has partnered with governments, payers, health care systems, advocates, providers, and patients to improve the quality of care for women and men with osteoporosis. Many of these partnerships have created strategies that are extremely effective. Governments providing funding for increased screening and diagnosis, fracture liaison services within health care systems to provide better fracture care and prevention treatment. And of course, physician education to ensure appropriate therapy is initiated pre- and post-fracture. As a result, care is improving, and our bone health business is growing, but there are many more patients who still need help, and we at Amgen are committed to working alongside the many stakeholders that can change the course of this disease and help prevent more unnecessary fractures. Given the large patient population and growing interest in providing better care, we expect continued growth in Prolia through our anticipated LOE. As Peter mentioned, the more gradual biosimilar erosion curve that occurs post-LOE will allow us to continue to invest in bone health and to grow EVENITY in the low double digits on average from '21 through 2030. Now turning to cardiovascular disease, aligning stakeholders to improve quality of care has never been more important. It remains the world's #1 killer, responsible for 1 out of 3 deaths globally. 85% of cardiovascular deaths are due to heart attacks and strokes, and are on the rise. Many risk factors like LDL-C are modifiable, however, only 2 out of 10 patients treated with conventional statin therapy are at their LDL-C goal. So cholesterol is one of the most important modifiable risk factors to help prevent heart disease and stroke. And despite overwhelming evidence that aggressively lowering LDL-C can reduce cardiovascular event risk, there are many barriers to accessing high-quality cardiovascular care. And this means millions of patients around the world do not receive the care they need. Now with Repatha, Amgen was the first company to demonstrate that by inhibiting PCSK9 receptors in combination with statins, more patients can get to goal, and you can further reduce cardiovascular risk in a population of CVD patients regardless of their baseline LDL-C levels. So since then, we've accelerated growth by securing broad access and reimbursement at an affordable out-of-pocket cost for commercial and Medicare patients. And we continue to work with payers and pharmacy benefit managers to make it easier for health care professionals to complete prior authorizations and ensure that a prescription written is a prescription filled. Many patients, despite being on lipid-lowering therapy, have coronary events, and they end up in an acute care setting. Today, many health care systems overlook the importance of aggressive lipid management in these high-risk ASCVD patients. So we've deployed a team of cardiovascular account managers to work with integrated health delivery systems to build standardized care pathways and quality programs to ensure more cardiovascular patients receive a lipid panel and the subsequent treatment to get to goal and lower the risk of a cardiovascular event. To date, over 120 health systems around the United States have established programs that are now more likely to discharge CVD patients on [indiscernible] lipid therapy, including Repatha. We're now the PCSK9 class leader globally, and we've treated more than 1 million patients with convenient, self-administered Repatha. Most recently, we were able to have Repatha listed on the National Reimbursement Drug List in China, ensuring that this truly global brand can help many, many more patients around the world in 2022 and beyond. We continue to invest in new data with hundreds of investigator-sponsored trials, and we also intend to expand our use through additional randomized trials with our Vesalius study that Dave Reese will expand on. We're proud to be actively helping cardiovascular patients and changing the course of this disease that takes so many lives. We remain focused on ensuring that every high-risk ASCVD patient has given a choice to lower their risk by having access to Repatha. These actions have unlocked many of the barriers to Repatha growth, and we anticipate the Repatha will become a multibillion-dollar franchise growing through the end of the decade. So this is truly an exciting time for Amgen. Our mission to serve patients has never been more clear. Amgen medicines have impacted tens of millions of patients over the last 4 decades. The potential for our integrated portfolio of innovative and biosimilar products will help transform the lives of even more patients across more disease areas around the world over the next decade. We have in hand where we need to be successful. We have the components of growth to deliver for patients and shareholders, and we have a team of resilient, dedicated professionals around the world who are driving execution to achieve this growth. So just in summary, Repatha will become a multibillion-dollar franchise growing through 2030. Annual Otezla, low double-digit growth for our average until the U.S. LOE. 2030 biosimilars revenue to more than double our 2021 revenue. Annual EVENITY sales, growth in the low double digits on average from 2021 to '30. Of course, ensure we deliver launch excellence for LUMAKRAS, Tezspire and our new biosimilars. And we're layering in the plans to prepare many additional pipeline launches later in the decade. So to review that extensive pipeline, I'll have over to our Head of Research and Development, Dave Reese.

Thanks, Murdo, and good morning, everyone. In the research and development part of our presentations, we'll focus on the near and intermediate pipeline, as well as give you a glimpse of the future. We believe we're in an era of profound transformation driven by technological change, and we'd like to highlight some of the strategic choices that we've made. Everything we do in research and development is innovated by our strategic vision. We want to benefit patients and societies through transformative medicines. We bring that to life for our staff by organizing their activities around 3 strategic priorities: increasing success rates, reducing cycle times and enabling access and use throughout the drug discovery and development continuum. Today, we'll focus on improving success rates and reducing cycle times through my presentations and what you'll hear from Ray and Alan. Now as Bob noted, in research, we really focus on 3 key therapeutic areas: Inflammation, Oncology and General Medicine, in particular, cardiovascular disease. Our goal is to develop first-in-class medicines that produce a large effect size in diseases where there remains residual high unmet medical need. In short, we want to change the practice of medicine. And before I launch into a description of the near-term pipeline, our exciting pipeline, I want to introduce some concepts and themes that you'll hear over the course of the next hour or so. First, we believe it is the era of human data. In the last decade, enormous amounts of human data have accumulated, more are coming every day. We believe those data will power drug discovery and drug development for the decades to come. Now collecting human data isn't the end game, but rather, a means to develop new transformative medicines. Ray will talk about our plans in multi-specificity. We believe multi-specific molecules will be just as important in the coming decades as monoclonal antibodies have been in the past few decades. Alan will then talk about a suite of capabilities we've developed called Biologics Next that enables us to molecularly engineer the right molecule for a target in much reduced cycle times and with a much higher success rate. Well, first, let me start with a view of the portfolio. Here are some of the key molecules that I'll discuss over the course of the day, included here for your reference. I'll start with the inflammation portfolio. All of the molecules that I'll discuss in our inflammation portfolio are first-in-class agents. We organize our activities and inflammation across these 4 broad areas: Dermatologic Diseases; Historical Course, rich experience in psoriasis, now focusing on atopic dermatitis; Respiratory Medicine, in particular, asthma, gastrointestinal disorders, including inflammatory bile disease; and Rheumatology. Of course, we have a long history in rheumatoid arthritis and psoriatic arthritis. Now, we're focused on systemic lupus erythematosus as an additional disease. Let me start with Tezspire, our recently launched drug for severe asthma. Shown on the left here to remind you is Tezspire's mechanism of action. Tezspire inhibits TSLP, an upstream epithelial-derived initiator of the inflammatory cascade that is the pathogenic driver in asthma. As you can see on the right, in the Phase III NAVIGATOR study, regardless of eosinophilic subtype, high eosinophils or low eosinophils, Tezspire had a profound effect on the annualized asthma exacerbation rate. It is the first and only biologic regardless of eosinophilic phenotype to have this sort of effect. I've had a chance to talk to a number of patients and physicians since the launch of the medicine. They couldn't be more thrilled to have this treatment option. I think this drug is going to have a profoundly important role to play in the treatment of asthma in the coming years. Now, asthma may not be the end of the story for Tezspire. We have a rich life cycle management program. There's a Phase III program ongoing in chronic rhinosinusitis with nasal polyps. We're planning Phase III in eosinophilic esophagitis, and we've got ongoing Phase II studies in chronic spontaneous urticaria and COPD. Shown here is a subset analysis from the NAVIGATOR Phase III trial in asthma. These are patients with concomitant chronic rhinosinusitis and nasal polyps. You can see on the left that these patients had a substantial 86% reduction in the asthma exacerbation rate over the course of the study. Importantly, Tezspire also led to a clinically meaningful reduction of 22% in clinical symptoms using one of the common scales employed in this disorder. This gives us confidence in the ongoing Phase III study, and if that is positive, I think we can play a real role here in changing the natural history of the disease in patients where impaired quality of life is quite common. One other molecule that can also, I think, change the natural history of the disease and substantially improved quality of life is AMG 451 that targets the OX40 signaling pathway in atopic dermatitis. Atopic dermatitis is an increasingly recognized disorder, now diagnosed in more than 30 million people around the world. It's commonly called eczema, but this is not just an itchy rash. It is an autoimmune disorder, sometimes a severe autoimmune disorder driven by aberrantly activated T-cells. AMG 451 has a putative dual mechanism of action, inhibiting the OX40 signaling pathway, also partially depleting activated T-cells that are some of the bad actors in this disorder. This latter mechanism may account for the prolonged duration of effect that we've observed in clinical studies to date, and may afford longer dosing intervals as the program progresses. Well, shown on this slide are data that were presented last fall at the EADV conference from a Phase IIb study showing that across dose levels, patients with advanced refractory atopic dermatitis had substantial improvements in skin outcome upon receipt of AMG 451. The placebo group at the bottom in gray, and then black were patients who are treated with placebo for 18 weeks then allowed to transition to AMG 451. And you can see after that transition, a substantial improvement in skin outcomes in that group as well. Based on these data and after very productive discussions with regulatory authorities, we're launching a broad-based Phase III program called Rocket. This is intended to establish safety and efficacy in a broad patient population, those who are naive to biologics, those who have received a prior biologic or JAK inhibitor, patients with a range of ethnicities and patients across various age ranges, including adolescents. In addition, the program will investigate different treatment strategies, monotherapy, combination therapy, as well as different dosing and scheduling regimens. All of this is really designed to investigate the optimal way to improve patient outcomes in this disorder. We expect that this suite of Phase III studies will launch in the middle of 2022. Another first-in-class molecule is Efavaleukin alfa or AMG 592, an interleukin 2 mutein that's being studied in patients with different autoimmune disorders. The fundamental hypothesis here is that in many autoimmune diseases, there is a dysregulation of the balance naturally achieved in the immune system. There's enhanced activity of effector T-cells, those are the ones that cause tissue destruction; cell killing; and a concomitant decrease in activity of T regulatory cells, which are a natural break on the immune system. AMG 592 is designed to increase the number and function of T regulatory cells and restore this immune balance. It's now in Phase IIb studies in systemic lupus erythematosus and just launched trial in ulcerative colitis. I should point out that the lupus trial was included as part of the FDA's complex innovative design pilot program, which is really intended to allow rapid transition from Phase II into potentially registration-enabling trials if promising data are observed in Phase II. We'll provide more guidance as this program proceeds. What gives us confidence in AMG 592? These are data presented a few months ago at the American College of Rheumatology meeting showing that the molecule did what it was intended to do. In a dose-responsive fashion, there was an increase in the number of T regulatory cells. In fact, the expansion of T regulatory cells observed here was very consistent with our pre-clinical modeling. This tells us that we have the right tool in hand to explore the hypothesis that expanding the number and function of T regulatory cells can restore immune balance in autoimmune diseases. Now another aspect of the biology of lupus is that it's not just a B-cell-driven disorder. In fact, there is a complex interplay between the T-cell and B-cell compartments. AMG 570 or rozibafusp alfa is a first-in-class multi-specific that is designed to target a T-cell signaling pathway, the ICOS, ICOS-ligand pathway and B-cell pathway [indiscernible]. As you can see on the next slide, in a Phase I trial, we were able to demonstrate receptor occupancy and inhibition of signaling for both the ICOS pathway as well as the B-cell compartment. Again, this gives us the right tool to explore the hypothesis that lupus is not just a disorder of aberrant B-cell signaling and auto-antibody production, but is both a B-cell and T-cell disorder. Well, let me transition to our oncology portfolio. Of course, Amgen has a long history in supportive care, and we're now making a real transition into therapeutics. Shown here is our portfolio, mostly first-in-class medicines. And today, I want to focus in particular on the solid tumor portfolio: Lung cancer, prostate cancer, and gastrointestinal malignancy programs. Well, let me start with LUMAKRAS. I know, of course, you have intense interest in the LUMAKRAS program. We continue to investigate both monotherapy and combination therapy across a range of malignancies, including non-small cell lung cancer, colorectal cancer, pancreatic cancer and other tumors bearing the G12C mutation. In lung cancer, in the monotherapy program, both the dose comparison and the Phase III head-to-head trials against docetaxel are on track. And based on current event rate monitoring, we expect we'll have data in hand from those studies, top line data in the third quarter of this year. Now as you know, there are also a number of combination programs in lung cancer that move forward, including combinations with checkpoint inhibitors and SHIP2 molecules. We expect the initial data from those combinations in the middle of this year. There are other combinations under investigation in lung cancer that will potentially afford the opportunity to move into earlier lines of therapy. We expect data across the suite of studies to be available over the course of this year and into 2023. Now in gastrointestinal malignancies with LUMAKRAS, we're moving forward in colorectal cancer and pancreatic cancer. We've previously presented data shown on the left here, demonstrating that combining LUMAKRAS with Vectibix roughly tripled the response rate compared to LUMAKRAS monotherapy alone in colorectal cancers with the G12C mutation. Based on those data, we've launched a Phase III trial that's up and enrolling patients, and I'll provide guidance as time goes on as to when we can expect data availability from that event-driven trial. We've also generated what I think are very intriguing data, encouraging data, pancreatic cancer. A week from today, these data will be presented from a Phase I, II study at the monthly ASCO plenary session, and I'd urge you to tune in to that presentation to really take a look at data we've generated in pancreatic cancer. That program is moving forward. In addition, we have combination programs moving forward in pancreatic cancer and colorectal cancer in addition to those that I've already described. I think there's real promise for LUMAKRAS in both of these indications. Now, another molecule that has real promise is tarlatamab, or AMG 757, that targets DLL3 in small cell lung cancer. Small cell lung cancer is a deadly disease. Survival rates haven't changed much in decades. And in fact, the same drugs are used for induction therapy now that were used when I was a newly-minted fellow stepping on to medical oncology wards nearly 3 decades ago. Checkpoint inhibitors have had a measurable but very modest impact on outcomes, and it's clear new therapies are required. Well, shown here is a waterfall plot that we shared with you at ASCO last year, demonstrating that a number of patients in the ongoing first-in-human study across a range of doses, experienced responses. I'm happy to report that as of today, 3 patients have transitioned to complete remissions and current preliminary estimates of the median duration of response now exceed one year. That's exceptional in patients with second, third line and beyond small cell lung cancer where response rates are often in the single digits and last a matter of weeks or a few months. We're enrolling a potentially registrational Phase II monotherapy study in third-line small cell lung cancer, and we're now investigating both combination therapy and sequential approaches that will allow us, hopefully, to move into earlier lines of therapy in this disease where there's really, I think, the possibility of having a big impact. Now, another disease where we have a chance to make a big impact is gastric cancer with bemarituzumab. Bemarituzumab targets the FGFR2b receptor that's overexpressed in about 30% of gastric cancers. Gastric cancer is a public health burden around the world, particularly in East Asia, but in many other countries as well and treatment standards here also have not changed dramatically in the past decades. Checkpoint inhibitors have a measurable effect in improving outcome, but I think there's a long way to go here. And bemarituzumab, a biomarker-driven program, is one about which we're quite keen. These are data on the left that many of you have seen before from a Phase IIb FIGHT trial, showing an improvement in median overall survival when adding bemarituzumab in first-line disease to standard backbone chemotherapy. Based on these data, we've now launched and are enrolling 2 Phase III trials in the first line. One is a combination with standard backbone chemotherapy, the other is a combination with standard backbone chemotherapy plus a checkpoint inhibitor. This accounts for different standards of care in the treatment of this disease around the world. Now, gastric cancer may not be the only solid tumor where FGFR2b is a driver alteration. In particular, squamous cell carcinoma of the lung, a fraction of those tumors will have overexpression of this receptor. And in the coming weeks, we're launching a signal-seeking trial in that indication in combination with standard chemotherapy. In addition, we'll be launching a basket trial in the second quarter of this year that will allow patients with other solid tumors that have FGFR2b overexpression to enroll to see if we can have an impact between gastric cancer and potentially squamous cell carcinoma alone. Let me move to our prostate cancer program. This is an area I'd also like you to pay close attention. Let me start on the right here with tarlatamab. You just heard about that in small cell lung cancer. Well, it may also have utility in prostate cancer. A fraction of prostate tumors, as they evolve, will dedifferentiate to what's called a neuroendocrine phenotype. When that occurs, they almost uniformly express DLL3, the target of tarlatamab. So we've now got a trial up and running to explore the utility of tarlatamab in neuroendocrine prostate cancer. But the bulk of our efforts is focused around the PSMA and STEAP1 programs. I've talked previously about acapatamab, previously known as AMG 160. We've completed enrollment in a dose expansion cohort and should have informative data by the middle of this year. AMG 340, formerly TNB 585, which came to us from the Teneobio acquisition, is marching through dose escalation. We're seeing promising preliminary data, and we also expect to have informative data by the middle of this year from that program. By the middle of the year then, I think we'll be able to outline for you what the development pathway looks like for acapatamab, AMG-340, one or the other or both. Let me end this segment by talking about AMG 51, which -- excuse me, 509, which targets STEAP1. STEAP1 is widely expressed in advanced prostate cancer. AMG 509 is an XmAb being developed in collaboration with our partners at Xencor. And shown here are preliminary data, a PSA waterfall plot from an ongoing dose escalation trial. As you can see, a substantial fraction of these patients had significant declines in PSA levels, 70%, 80% and in many cases, exceeding 90%. Our investigators are very excited about these data. We're very excited about these data. And this is a program we plan to accelerate. I'll have more to say about this in the coming months. You can expect full data from the first-in-human study to be presented perhaps later this year or early next year at the ASCO GU meeting, but this is one to keep an eye on. Let me finish the pipeline review with an update on a couple of our cardiovascular and obesity medicines. Let me start with Repatha in the Vesalius-CV Phase III study. Vesalius targets patients who are very high risk based on clinical criteria of having an event often in a matter of a year or 2. But they haven't yet had a cardiovascular event, a myocardial infarction or a stroke for example. Vesalius is designed to see if Repatha can prevent those first events from happening. It's also designed in a way that I think we can capture the benefit of this therapy, perhaps even in a year or 2 because these patients are at such high risk. We've completed enrollment in this Phase III trial, over 12,000 patients. And as you see here, we anticipate data roughly in 2025 with a potential label update to follow that. Now as the event rate accrues, we will provide further guidance about when we will have data in hand, but this I think could potentially expand the use of Repatha to a large number of patients and really benefit from aggressive cholesterol-lowering and a chance to change the natural history of atherosclerotic cardiovascular disease. But LDL isn't the only factor that drives atherosclerosis. In fact, LDL probably accounts for 50% or 60% of the cases of atherosclerotic cardiovascular disease. There are other important factors, importantly, lipoprotein(a) or Lp(a), obesity and inflammation, systemic drivers that contribute to atherosclerosis, with programs targeting a couple of these. Let me start with the Lp(a) program. Lp(a) is a lipoprotein, as the name implies, about 20% of patients will have elevated lipoprotein (a) levels. Now this isn't a bell curve, but rather a skewed distribution. Roughly 80% of people will have relatively low and so-called normal levels and then a tail of the population can have elevated levels, sometimes markedly elevated levels. There's overwhelming epidemiologic and genetic evidence that links elevated Lp(a) to atherosclerotic cardiovascular disease. Importantly, lifestyle changes such as alterations in diet or exercise, don't affect Lp(a) levels. The levels appear to be genetically fixed. In addition, currently available medicines have very minor or no effects on Lp(a) levels. So it's clear that new therapies are required. And shown on the left of this slide is the cover from Nature Medicine. This was published just a couple of weeks ago, and it's a paper of ours that documents the pre-clinical and ongoing Phase I data from Olpasiran, a small interfering RNA designed to lower Lp(a) levels. You can see here the mechanism of action, olpasiran and siRNA is designed to affect the production of Lp(a) in a profound fashion in target liver cells. On the right, you see data from an ongoing first-in-human study that actually showed that a single dose of Olpasiran induces profound reductions in Lp(a) on the order of 80% or 90% or more. Importantly, the duration of this effect can be quite long, suggesting that the dosing interval for Olpasiran can be relatively infrequent. We've completed enrollment in a Phase IIb trial. We'll have top line data from that in hand by middle of this year, and we're actively planning the Phase III program so that we can quickly transition into a registrational phase of the Olpasiran development program if the Phase IIb data look good. Well, let me finish the pipeline update by talking about AMG 130, another multispecific that targets 2 key metabolic pathways that control weight and regulate metabolism.