My name is Erica and I will be your conference facilitator today for Amgen’s Fourth Quarter 2020 Financial Results Conference Call. All lines have been placed on mute to prevent any background noise. There will be a question and answer session at the conclusion of the last speaker’s prepared remarks.

[Operator Instruction] I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin..

Okay. Thank you, Erica. Good afternoon, everybody. Welcome to our call to review our Q4 and full year financial results for 2020. I would say, the strong execution, despite the pandemic and pipeline advancement are two themes that were pervasive. So, let’s get after it.

We'll stick to an efficient format of limited prepared comments or one question rule, as Erica pointed out, and the overall duration of the call to one hour. Slides have been posted. Just a quick reminder that we use non-GAAP financial measures in our presentation, and some of the statements would be forward-looking.

Our SEC filings identify factors that could cause our actual results to different materially. So, with that, I would like to turn the call over to our Chairman and CEO, Bob Bradway.

Bob?.

Thank you, Arvind, and thank all of you for joining our call. I’ll start today by discussing Amgen’s performance in 2020, and then provide some perspective on our priorities for 2021. By any measure 2020 was a very successful year for us.

Despite the disruption of COVID-19, we delivered strong sales and earnings, driven by volume growth of 15% of our products. We advanced our innovative pipeline, most notably sotorasib and tezepelumab, both of which have received breakthrough therapy designation from the FDA.

We successfully integrated Otezla, strengthening our decades-long leadership in inflammation with a $2 billion plus product that we believe has runway for further global growth. We grew our sales outside the U.S.

to more than $6 billion, delivering on long-term goals by expanding our presence in China and Japan, the successful transactions in both markets. We did all this while staying focused on the health and safety of our 24,000 employees around the world. And to all of them, I want to say thank you for a job well done.

As we look to 2021, we're embracing three realities. First, COVID-19 is leading to some lasting changes in how we do business. For example, we expect to continue leveraging digital capabilities, call on customers and run clinical trials around the world with improved speed, efficiency, effectiveness.

Second, we expect ongoing pressure on drug prices across the industry. We are fortunate to have products like Repatha, Prolia, Aimovig that meet the needs of millions of patients and can grow through increased penetration of the appropriate patient populations. Our industry-leading portfolio of biosimilars is also well-positioned for future.

Third is capital continues to flow into our sector. We've entered a time of intense competition where speed of execution is paramount. We've built a track record featuring quality and speed. We’ve shown that with innovative first-in-class medicines like Repatha, the first approved PCSK9 inhibitor, and Aimovig, the first approved CGRP inhibitor.

We showed it also with biosimilars, like MVASI and KANJINTI, the first approved biosimilars to Avastin and Herceptin, here in the U.S. And we're doing it right now with sotorasib, the first KRAS G12C inhibitor to be filed for approval just 28 months after we dosed our first patient.

We expect to do it again later in the year when tezepelumab as the first TSLP inhibitor. We are excited about our pipeline and plan on increasing our R&D investment in 2021. Dave will speak in a moment about some of our promising mid-stage pipeline candidates.

But since this is the time of year when I'd like to address our long-term investments, I want to focus for a moment on a couple of areas central to our early research strategy. These are areas where we are building differentiated capabilities.

First, in human genetics, where we have industry-leading capabilities, we are adding to our database approximately 1 million subjects from the U.S. and the UK, or whom we will have extensive phenotypic and genotypic information. This will augment the data we already have on in excess of 1.5 million individuals.

In addition, we're pioneering the use of large-scale proteomics to measure the relative levels of some 5,000 different proteins in the blood. We're excited about the insights we generate from this genomic proteomic work and expect to benefit in the selection of new drug targets and clinical trial design.

There's growing interest in our industry in the area of targeted protein degradation. We believe the opportunity is broader than that, and our efforts are not just limited to degrading proteins. We're looking at degrading other biologic molecules as well.

We're designing molecules to have multi-specific activity through a principle we call induced proximity. The idea is to use this platform to dramatically expand the universe of druggable targets. It's still early days in the field, but I wanted to flag it as an area where we want to emerge through time as an industry leader.

All of our work is taking place at a time when more is expected of companies than ever before. Amgen is advancing an ambitious ESG agenda that includes providing medicines at no cost to low-income patients and funding world-class STEM education programs.

With respect to the environment, we're committed to achieving carbon neutrality by 2027, along with a 40% reduction in water use and the 75% reduction in waste. In summary, our success in 2020 gives me great confidence in our ability to deliver in 2021 and beyond.

The world needs more innovation, not less, and we've proven ourselves ready, willing and able to provide it. I look forward to your questions a little later on in the call. Right now, let me turn over to Dave Reese, our Head of R&D. .

Thanks, Bob. Good afternoon, everyone. I'll begin today with sotorasib, our first-in-class KRAS G12C inhibitor. To-date, more than 700 patients have been treated across five continents. We are accelerating this groundbreaking program into new indications and earlier lines of therapy.

A few days ago, we presented the first pivotal data for KRAS G12C inhibitor at the World Conference on Lung Cancer, where we reported on 126 patients with second line plus non-small cell lung cancer. Sotorasib drove rapid, deep, and durable responses across a broad range of mutational profiles in subgroups with poor prognoses.

In a centrally adjudicated intent-to-treat analysis, the objective response rate was 37%, including three complete remissions, progression-free survival was 6.8 months and duration of response was 10 months. Importantly, sotorasib demonstrated a very tolerable and differentiated clinical profile.

And based on these data, we completed regulatory submissions in the United States and EU in December. More recently, we submitted files in Canada, the UK, Brazil, and Australia with additional global submissions anticipated in the coming weeks and months, and launch preparations are well-advanced.

The Phase 3 non-small cell lung cancer monotherapy study versus docetaxel continues to advance nicely as do our 10 combination cohorts and Phase 2 colorectal study with data expected from these latter two, beginning in the first half of this year.

We will initiate a Phase 2 study in first line non-small cell lung cancer in the second quarter, where we will investigate sotorasib monotherapy in patients most likely to benefit, based on tumor profiling. For example, those tumors harboring STK11 mutations.

Finally, we recently cleared the safety hurdle at the full sotorasib dose in our MEK inhibitor combination study and have completed enrollment in an expansion cohort.

In inflammation, along with our partner, AstraZeneca, we look forward to presenting the results from the Phase 3 NAVIGATOR study at the American Academy of Allergy Asthma and Immunology Virtual Annual Meeting, also known as AAAAI, at the end of February.

You may have seen the abstract posting yesterday, with results from the primary and key secondary endpoints data that in our view, provide a compelling rationale for the potential utility of tezepelumab in a broad population of patients with severe uncontrolled asthma, including those with low eosinophil counts where we have breakthrough therapy designation in the United States.

We are working closely with AstraZeneca on our U.S. and EU filing packages, which we expect to submit in the first half.

Turning to our BiTE platform, we are particularly excited about the rapid progress we are making with two solid tumor programs, AMG 160, targeting prostate-specific membrane antigen, or PSMA, for castrate-resistant prostate cancer; and AMG 757, targeting DLL3 for small cell lung cancer.

AMG 160 is currently in dose expansion, and we expect to advance AMG 757 into dose expansion in the coming months. We are quite pleased with the clinical profiles we are seeing with both of these molecules. And, as you will see in our press release, we also continue to actively prioritize our oncology portfolio.

In migraine, Aimovig continues to demonstrate important benefits for patients as our colleagues at Novartis announced positive Phase 4 results, showing superior efficacy and safety of Aimovig over topiramate in the migraine prevention setting.

Finally, our biosimilars portfolio continues to advance, and we have completed enrollment in our Phase 3 study of ABP 959, our biosimilar SOLIRIS. In closing, I'd like to thank our staff for their ongoing efforts to deliver our portfolio for patients.

Murdo?.

Thanks, Dave. 2020 product sales grew 9% year-over-year, driven by 15% volume growth, with roughly equal growth rates in the U.S. and internationally. Starting with our innovative portfolio, Prolia grew year-over-year, despite significant impacts from the pandemic. And EVENITY sales increased 85% year-over-year, driven by strong volume growth.

Repatha is now annualizing at over $1 billion in revenues with 67% year-over-year volume growth. In the first full year since acquisition, we've seamlessly integrated Otezla, growing total prescriptions by 13% year-over-year. And finally, our biosimilars portfolio totaled $1.7 billion in sales. Moving to fourth quarter performance.

Product sales grew 8% year-over-year, driven by 13% volume growth. In our bone franchise, we remained focused on ensuring patient continuity. By year-end, osteoporosis diagnoses reached approximately 80% of pre-COVID levels, leading to a positive trend in new patient starts, entering 2021.

In Q4, Prolia's repeat patient numbers were lower than historical trends, as a result of the echo effect of COVID disruption in Q2. EVENITY sales grew quarter-over-quarter.

We believe EVENITY's unique bone building profile will continue to drive growth in our franchise as physicians appreciate its benefit risk profile for treating their high-risk post fracture patients. In cardiovascular, Repatha remains the global PCSK9 leader. Net sales in Q4 were $253 million, driven by sequential volume growth and stable U.S.

net price. As we enter 2021, we expect continued momentum for this brand globally, driven by growth from international markets, improved U.S. PBM formulary position and relatively stable net price in the U.S.

Moving on to Aimovig, which is the market leader in the highly competitive CGRP class, volumes grew 21% year-over-year in the fourth quarter, but remained flat quarter-over-quarter as the pandemic negatively impacted new patient starts. Next to Parsabiv. Q4 sales declined 8% quarter-over-quarter in the U.S.

as some customers decreased utilization, while others built inventory in advance of the January reimbursement change. With Parsabiv’s inclusion in the end-stage renal disease bundle, we expect sales to decline by approximately 40% to 50% in 2021 as U.S. dialysis centers update their treatment protocols to accommodate generic forms of cinacalcet.

We also expect sales in Q1 to be the lowest of the year as customers deplete $40 million of inventory build in the second half of 2020. For patients on hemodialysis, Parsabiv is the only IV-administered calcimimetic that lowers and maintains key secondary hyperthyroidism lab values.

Also, Parsabiv offers providers control over calcimimetic delivery and the opportunity to reduce patient pill burden. Transitioning to our inflammation portfolio, Otezla sales were $617 million in Q4, driven by a 13% year-over-year increase in total U.S. prescriptions.

We see attractive future growth opportunities through global launches, and our planned submission for the mild to moderate psoriasis indication in the U.S. in the coming weeks. With Enbrel, fourth quarter sales declined 5% year-over-year.

Volumes declined from gradual share loss, coupled with slower growth in the rheumatology segment, which we attribute in part to the pandemic. For 2020, net price declined in the low single digits, and we expect volume and net price trends to persist in 2021.

Enbrel has an established record of safety and efficacy, and we will continue to invest in innovative solutions to enhance the patient experience. Switching to biosimilars. Q4 sales were $541 million, driven by volume growth, which was partially offset by declines in net selling price.

We are leading in biosimilar share in Europe for AMGEVITA and in the U.S. for MVASI and KANJINTI, with a respective 48% and 41% average share in Q4. We recently launched our fifth biosimilar, RIABNI, a biosimilar to Rituxan.

For 2021, we expect biosimilar volume growth to be partially offset by a decline in net selling prices due to increased competition. In oncology, Neulasta Onpro remains the preferred long-acting GCSF with 54% share of volume in the quarter.

Onpro continues to demonstrate the value of innovation, allowing patients to receive their GCSF treatment without having to return to their doctor's office or other sites of care for administration. Overall, Neulasta sales decreased 19% year-over-year, driven by declines in volume and net selling price.

And the most recent published average selling price for Neulasta in the U.S. declined 28% year-over-year. Going forward, we expect the price and volume trends to persist as biosimilar competition increases. Looking ahead, we're excited about new opportunities across our business.

Internationally, we recently received national reimbursement drug listing for Prolia, which will accelerate growth in China. In Japan, we're preparing for the launch of Aimovig, and we're planning for the launch of our biosimilar brands across multiple markets in 2021.

Finally, our team is ready to launch sotorasib upon approval, and we're excited to establish it as a foundational therapy for patients with advanced lung cancer.

And we're also preparing for the launch of tezepelumab with our partner, AstraZeneca, and are enthusiastic about the prospect of having a therapy that can help treat the 2.5 million people in the world living with severe uncontrolled asthma.

Overall, I'm pleased with our Q4 and full year performance, and look forward to Amgen serving more patients in 2021. Now, I'll turn it over to Peter..

Thank you, Murdo. Good afternoon and good evening, everyone. We are pleased with our strong execution and performance in the fourth quarter and for the full year 2020. In Q4, we delivered 7% revenue and 5% non-GAAP EPS year-over-year growth. For the full year, we delivered 9% revenue and 12% non-GAAP EPS year-over-year growth.

As Murdo mentioned, both Q4 and the full year benefited from volume-driven sales growth of 13% and 15%, respectively.

Non-GAAP operating expenses increased 9% year-over-year in the fourth quarter as spend accelerated to advance our innovative pipeline, drive volume growth for much of our portfolio around the globe and prepare for future launches, particularly for sotorasib and tezepelumab.

Operating expense grew 7% for the full year, including a full year of Otezla-related activities and expenses. Free cash flow for the fourth quarter and the full year was $2.0 billion and $9.9 billion, respectively. Now, turning to the outlook for business for 2021 on page 37.

We look forward to investing in innovation in 2021 and in launching new products. We will also continue to execute on our volume-driven growth strategy.

Due to COVID, we also anticipate some uncertainty and quarter-to-quarter variability in revenue and earnings throughout 2021, with potential recovery later in the year, contingent upon the speed and effectiveness of global vaccination.

Our 2021 revenue guidance is $25.8 billion to $26.6 billion, and our non-GAAP earnings per share guidance is $16 to $17 per share. GAAP earnings per share guidance is $12.12 per share to $13.17 per share. Now, let me mention several key assumptions embedded in our guidance.

First, our revenue range reflects volume growth from Prolia, Otezla Repatha, EVENITY, Aimovig, and our biosimilars portfolio, and importantly, our innovative oncology portfolio. At the same time, we expect continued competition against our filgrastim and ESA franchises, as well as accelerating erosion in U.S. Parsabiv sales, as Murdo highlighted.

We experienced a 6% decline in net selling prices globally in 2020. For 2021, we again expect mid-single-digit price declines. A couple of points to recall when considering Q1 of 2021.

Historically, the first quarter represents the lowest product sales quarter of the year, with planned changes, insurance reverifications and higher co-pay expenses as U.S. patients work through deductibles, especially for products, including Enbrel, Otezla and Aimovig.

Additionally, I want to remind everyone that in Q1 2020, Enbrel benefited from approximately $115 of favorable changes to estimated sales deductions, and the entire portfolio saw roughly $100 million in inventory build due to COVID.

So, as a proportion of our full year sales, we expect Q1 2021 to be a slightly lower percentage than the 24% it was in Q1 2020. We expect other revenue to be in the range of approximately $1.4 billion to $1.5 billion for the full year 2021.

This includes revenues from COVID-19 antibody manufacturing and profit share agreement with Lilly, under which we expect to begin shipping in the second quarter.

We expect 2021 total non-GAAP operating expenses to grow at a rate similar to the 7% 2020 non-GAAP operating expense growth, as we continue to invest in innovation, launches of new products and digitization efforts. We have created an industry-leading cost structure and expect an operating margin of roughly 50% in 2021.

Cost of sales as a percent of product sales will increase to a range of 16% to 17% due to an evolving product mix, and higher royalties and profit share payments. Additionally, cost of sales will increase in connection with our manufacturing agreement with Lilly.

As I mentioned previously, the revenues and profit share will be included in other revenue. Research and development expenses will increase as our pipeline advances with year-over-year increases in early and late-stage investments. And SG&A will decline, primarily due to changes in our commercial model including an increased focus on digital efforts.

Now, let me take a moment to explain an update we are making to our non-GAAP policy. Effective January 2021, our non-GAAP results will no longer include fair value adjustments to equity investments. These adjustments to equity investments have historically been recorded in other income and expenses and were positive in our 2020 non-GAAP results.

This change will not apply to our strategic investment in BeiGene, which is included in our non-GAAP results and is accounted for under the equity method of accounting. The press release contains the pro forma 2020 results by quarter under our updated policy.

We will also now use updated adjusted 2020 amounts that conform to this policy for comparison purposes going forward. Under our updated non-GAAP policy that I just explained, here is our guidance for other income and expense. We anticipate non-GAAP other income expense in the range of $1.3 billion to $1.5 billion of expense.

This 2021 guidance reflects incorporation of four quarters of BeiGene's results versus three quarters in 2020, which are recorded on a one quarter lag.

Recall that we only use the limited publicly available consensus estimates for BeiGene in connection with our guidance and thus may experience additional variability depending on BeiGene's actual results.

Our basis in BeiGene as of December 31, 2020, was approximately $2.9 billion, and this long-term investment is valued at approximately $6 billion today based upon the current U.S. market price.

Our non-GAAP tax rate guidance is 13% to 14%, and we expect capital expenditures of approximately $900 million this year, including investments in additional manufacturing and other capacity to support our volume-driven growth strategy as well as an environmental sustainability initiatives that will enable our global operations to achieve carbon neutrality by 2027 and also in our digitization efforts to continue to scale up and integrate data and analytics in everything we do at Amgen.

And finally, our capital allocation hierarchy remains unchanged. After both internal and external innovation and then investing in our capital expenditures, we remain committed to returning capital to shareholders in the form of growing dividends, including the 10% increase in the first quarter of 2021 to $1.76 per share.

We anticipate opportunistic share repurchases in the range of $3 billion to $4 billion, subject to our Board's authorization.

So, in summary, we deliver for patients every patient every time, and for our investors in a challenging year that included the greatest public health crisis in 100 years, and the greatest economic disruption since the great depression. And we are confident in the outlook for Amgen's success in 2021 and beyond. This concludes the financial update.

I will now turn the call back over to Bob..

Okay. Thank you, Peter. And Erica, let me invite you to remind our callers of our process for Q&A, and let's begin the question session..

[Operator Instructions] Your first question in queue is from Alethia Young with Cantor Fitzgerald..

Hey, guys. Thanks for taking my questions. Congrats on a solid guidance and great quarter.

I just wanted maybe if you guys could talk a little bit about, obviously, the KRAS program and the combinations, and maybe perhaps kind of -- I know it is probably early Phase 1 studies, but what you're kind of looking to glean from some of these different combinations? I know you get asked a lot about this, but just kind of as we're getting closer and closer, like how you think about unpacking that with different indications? Thanks..

Hi, Alethia, and thanks for the question. Yes, we do get this one quite a bit about the combinations. What I will say is there's no generic answer here. It's going to depend on line of therapy end indication, non-small cell lung cancer, of course, colorectal cancer and then some of the other indications beyond that.

Typically, you're looking for a 15%, 20%, 30% increment on any given endpoint beyond standard of care, but also looking at the totality of the data. I think in many of these settings, in particular, progression-free survival and ultimately, overall survival.

So, given the safety profile we've demonstrated to date, those are the sort of efficacy metrics that we'll probably take a look at..

Your next question is from Michael Yee with Jefferies..

I bet you're going to get a lot of combo KRAS questions, so I'm just going to ask as well. The MEK expansion cohort, David, I thought it's really exciting that you've actually completed enrollment. And I know, I guess, that was mentioned at the conference as well. That could be potentially pivotal.

Can you talk about whether you would actually be able to announce data on that at some point this year? It's pivotal, do you want the whole thing to be done before you report out on it? Could you have piecemeal data? And then, maybe make a comment on the SHIP2 combo as well?.

Yes. Thanks, Mike. No, we are very pleased with rapidity of enrollment in the MEK safety cohort. As we noted, we've moved beyond that to the expansion cohort. It's quite possible we'll have data from that over the course of this year. It will depend on just as the data come in and as we see those results.

And again, it's too early to speculate on whether this could be pivotal or not. As I've mentioned, the master protocol from which these data are derived is essentially designed, so that any given arm can be blown up into a pretty rigorous Phase 2 trial.

And depending on indication and line of therapy, of course, we would make any sort of decisions regarding regulatory intent in that context. So, more to come as those data unfold, but we're quite happy with what we're seeing in terms of enrollment..

And SHIP2?.

On SHIP2, it's moving along. I think biologically, that is a very interesting combination. And again, potentially more to come over the course of the year on that combination as well..

Your next question is from Terence Flynn with Goldman Sachs..

Maybe just a two-part from me. Maybe for Peter. I was just wondering as you look out the sustainability of that 50% operating margin, how you think about some of the puts and takes? And then, any visibility into your biosimilar franchise, the margins there? I know, that's a question we get frequently. And then, again, a higher level, and maybe for Bob.

You mentioned protein degradation is an interesting platform on the forward that you guys are spending a lot of time building out.

Do you expect to do that all internally, or is that an area where you could also look externally for opportunities?.

Thank you. Great question on the operating margin. As you know, we don't go out on a long-term basis on that. But, you also know that we intend to continue to be a top-performing biopharma firm, when you look at any number of financial metrics and importantly, operating margin.

I do want to make sure that I mention and confirm, we will remain flexible and adaptable as attractive internal and/or external investment opportunities arise. We have the underlying objective to grow our volumes and after tax cash flow. So, that's really important to us. We are committed to lean on our permanent productivity commitment.

As I mentioned, we're investing in and working on digitization and automation. So, we'll continue to exercise all that muscle to make sure that we do remain an outperforming biopharma firm and operating margin. On the biosimilars, that's a fair question. We continue to see biosimilars as an extremely strong allocation of capital for us.

The margins continue to be very competitive. And we're very confident in terms of allocating capital to that category, and we'll continue to do that. And we think we've got some strong expertise there. I like to quote Murdo, who says that we've played a lot of defense in biosimilars.

And now, as we're on offense, we're able to have a high quality of execution level. So, good questions in that, and I'll flip it over to -- I think, to Bob..

Terence, thanks for the question. As I said in my remarks, rather than calling it targeted protein degradation, we're describing it as our induced proximity platform. The intention there, as I said, is just to be clear that we think the technology that we're building can be used, not just to degrade proteins but other molecules as well.

So, we're excited about it. This is -- as I said, again, in my remarks, long-term research strategy. And Dave, his team and I spent a lot of time with each other, trying to think about how to position for the long term. And in this area, will be both internal and external.

I'd remind you that we acquired new evolution now two years ago for the purpose of helping to build out this set of capabilities. And I would imagine we'll continue to look, as I said, both internally and externally. Dave, feel free to jump in and add your thoughts..

Yes. I think that covers it pretty well, Bob. I would say that we view this multi-specificity in drugs as part of the future. Many of you know that 80% to 85% of the currently desirable targets are currently undruggable. We think this is going to be a very important technology and making many of those targets tractable.

And as Bob mentioned, we are investing for the long haul, and we expect that to be a combination of both internal and external innovation..

Our next question is from Matthew Harrison with Morgan Stanley..

Dave, I was wondering if you could just comment a little bit more on the BiTE program and some of the, I guess, safety issues that have happened? And just what's your confidence in those programs, especially as it seems to relate to some of these extended half-life programs?.

Yes. Thanks, Matt. Thank you for this question. I would say, overall, I feel very bullish on the BiTE program. As we mentioned, AMG 160 and AMG 757 are advancing quite rapidly. Cytokine release syndrome is clearly the single challenge that sits before the entire field. And we're making adjustments in the 701 program to handle that.

I'm quite confident that we can come up with a clinically important profile for that molecule. There are many BCMA molecules in development. And of course, we'll shape our investments according to whether we can really fulfill an unmet medical need.

I would say, in closing that I'm quite optimistic about the half-life extended BiTE platform, the -- a few of the positives such as AMG 673 for acute myelogenous leukemia were done on purpose because we selected the first generation molecule, which we are investigating in a minimal residual disease, setting where that technology is well suited.

This was done in close concert with our investigators. Many of these choices were part of our strategy. We anticipated making these choices as part of prudent shaping of our portfolio going forward. So, overall, I feel quite good about where we are and how that platform is evolving..

Your next question is from Yaron Werber with Cowen..

David, I have a question for you, if you don't mind, and a quick follow-up. On sotorasib, can you give us a sense? Obviously, it's encouraging that the MEK combo, you're able to get the full dose of sotorasib. Any comments on KEYTRUDA, SHIP2 or Erbitux? And then, on tezepelumab, the late-breaker looks really good.

The data in the steroid refractory was surprising. And I’m not sure if it’s potentially trial design differences from the other biologics, just given how robust the response is otherwise.

Would you consider repeating that study with a more similar trial design to the other ones?.

Yes. Thanks for the questions. In regards to the combinations, the ones you mentioned are all actively in dose escalation, looking at either different doses or in some cases, even scheduling, depending on the agents. This is standard Phase 1b oncology drug development. I feel good about how quickly we're moving.

And we'll provide guidance as we expect those data to emerge. With tezepelumab, as you mentioned, the abstract is out now. We feel the data are very strong. We feel we're competitive. With the best in the high eosinophil population and in many ways, standalone in the low eosinophil population, the steroid-sparing study.

As you alluded, we think there were potentially trial design issues. And we're going through that with our investigators, anticipate presenting those data a little later this spring. And we're discussing with our partners, whether a differently designed follow-on study would be appropriate.

I would point out that that trial was not necessary for filing, and we are moving ahead with all deliberate speed, as we announced with global submissions of tezepelumab, based on the current data..

Your next question is from Geoff Meacham with Bank of America..

Peter, I may have missed this, but looking to 2021 revenue guidance, can you speak at a higher level, what contribution, if any, you assume from sotorasib and tezepelumab for this year? And are there any COVID headwinds still factored in when you look at product sales, or do you assume 2021 as a more normalized demand curve all year?.

Thanks for the question, Geoff, and I'll invite Murdo here in just a moment to jump in on soto and teze. And look, we expect continued COVID impact throughout 2021 and revenue potential recovery in the latter part of the year contingent on the vaccination rollout, as I mentioned. So, we'll be closely monitoring that, as you can imagine.

And with respect to soto and teze, let me turn that over to Murdo. And look, it's a very exciting time for us. And we've invested a lot of money getting preparing the launches for those and so forth.

So, Murdo?.

Thanks, Peter, and thanks for the question, Geoff. Obviously, we're quite excited about sotorasib. And I want to complement Dave and his team how fast they've moved in developing this product and also just the number of regulatory submissions they've been able to affect in a very compressed time frame.

So, we are optimistic and hopeful that we'll get a fairly quick review in multiple markets around the world. And so, we would expect sotorasib to contribute to revenue. We don't give product-specific guidance, but this is a very large population of high unmet medical need.

There's not a lot of choice for these advanced non-small cell lung cancer patients. So, we do anticipate that there'll be a potential market with a high need there. The one caution that I'll put out is just the actual percentage of advanced non-small cell lung cancer patients that have a KRAS G12C status result in their file and their medical record.

Right now, we ascertain that to be at about 50%. So, we've got work to do to grow that number. And obviously, we've seen, with other targeted therapies, when you have an actionable mutation, the testing rate rises fairly rapidly. So, we would expect upon approval to be able to do that.

But nonetheless, we think sotorasib will be a meaningful contribution to at least revenue in the U.S. And then teze, we'll see what the regulatory authorities do with the filing, obviously, given that we had breakthrough designation.

And obviously, given the pan-eosinophilic results that we've seen, and now you guys can see the breakdown in that in the abstract. We think this is an important medicine to get to market very quickly.

The last question you asked about COVID in fact, Geoff, was just -- I think, we actually anticipate COVID will have a fairly significant impact on the market, through the better part of the year, beyond the midpoint of the year. I hope we're wrong and I hope that vaccination programs will improve.

But right now, we think that COVID will be with us for the majority of 2021..

Your next question is from Evan Seigerman with Credit Suisse..

So, I want to ask one on business development and capital allocation priorities. So, it seems like there's a growing need for more mid-stage assets, noting several pipeline pauses reported in this quarter.

With 80% of free cash flows going to dividends and repurchases, how do you think about bringing in larger scale assets? And would you lever up beyond your current leverage levels, if there was an attractive opportunity?.

Evan, I think, we've been pretty consistent in saying that our focus is on investing in the business. So, as we said in our prepared remarks, we're planning to increase our investment in R&D this year. So, committing internally to continue to allocate capital to R&D opportunities. We'll continue to look externally.

We'll look at small and larger opportunities, like licensing and business development. They're very active in the areas where we have demonstrated expertise therapeutically. And that's what our focus very likely entail opportunities that sit well with the areas that we have demonstrated expertise in.

In terms of the balance sheet, rather than engage in hypothetical, we maintain a strong balance sheet so that we have strategic flexibility. And we'll consider individual opportunities as they arise..

Your next question is from Dane Leone with Raymond James..

Congratulations on the update and outlook for 2021. So, the question for me, it focuses a bit on tezepelumab, but is a little bit different than what's been discussed previously. Allergy and asthma specifically, in this case, would be a new vertical for Amgen.

How are you thinking about building out that vertical around expected commercial launch of tezepelumab, but also thinking about other indications or assets behind that internally or externally that you could point to, to make it more of a broader vertical going forward. In that same vein, maybe touch a little bit more on oncology.

Obviously, in the solid tumor space, it hasn't been an area that you've been heavily invested in historically, but obviously, it was sotorasib approval coming in the first half this year. You're kind of resting on the BiTE program behind that.

Are there other assets outside the BiTE program that you could highlight internally that might expand your presence there, and/or should we be thinking about something more differentiated that you might do externally around the solid tumor space?.

There is a lot there, Dan, in your question. Murdo and I will just double team you. But, very quickly, let me remind you what we pointed out when we entered into a partnership with AstraZeneca in particular, around the respiratory opportunity, which was that just as you point out, is a new area for us.

We felt that we could deliver more for our shareholders and more for patients by collaborating with a group that had demonstrated an expertise in respiratory medicine. And so, we chose to partner with AstraZeneca, and we're pleased with that collaboration and look forward to taking the molecule to market with them.

And I would just point out that we came to this through our commitment to anti-inflammation and have decades of experience in the biology of information that we've been able to capitalize on with this program and hopefully others over time. But Murdo, jump in and in particular, share your thoughts also on the solid tumor question..

Yes, sure. Thanks, Bob. We are building out our teams as we speak. And Amgen will help commercialize tezepelumab in the Americas region. So, U.S. and Canada, we will be focused on allergists, while AstraZeneca will play a broader role beyond just allergists, including the respiratory specialties.

So, this is -- as you mentioned, it's a new area, but it's not that different from what we've done, as Bob mentioned, in other inflammatory disease processes. The other thing that's worth mentioning is we'll be taking a leading role in establishing access for tezepelumab with payers.

And again, our extensive biologics contracting experience in Part D and the government programs will help us secure broad access for tezepelumab for a broad range of patients. As you saw, we have a nice product profile here that will benefit a lot of patients regardless of their eosinophilic status.

And then, Dave Reese's team is obviously building out medical capabilities for the same customer-facing group. So, we're excited about it. It's a focused effort. The beauty of focusing on allergists is they're very productive prescribers, but they're a relatively small audience size. So, we'll be quite focused on addressing that.

When it comes to kind of how we're looking at our oncology portfolio, we've got a very strong base right now in oncology between our hematology business, our solid tumor therapeutics that we have now our overall biosimilar portfolio and our supportive care. Basically one in five oncology patients today receives an Amgen therapy.

And so, bringing sotorasib into that mix and then the potential of AMG 160 and 757 and 701, I think, is a fairly action-packed next few years in oncology that we can build on the current strength that we have, and we're excited about that.

I'm always asking Dave Reese to deliver more, and I know his team have a lot of other earlier assets to put into the clinic. I'll turn it over to Dave for additional comments..

Exactly. We've got a couple of gastric cancer BiTEs, of course, also a solid tumor indication. And we've got some other molecules in late preclinical. We're just entering the clinic that will target solid tumor indications. More on those, as we're ready to speak about them going along. So, I think it's going to be quite a broad portfolio..

Your next question is from Robyn Karnauskas with Truist Securities..

So, I have a question for Murdo. I was just looking at the MVASI strength and the KANJINTI decline, and the Neulasta price decline was significant.

Putting all these trends together, can you just help us think now what you think of how to model the tail for biosimilars? And if there's differences between some of your oncology drugs like the strength of MVASI is really impressive versus the decline of Neulasta, just give a sense of how we should think about that and help us model that.

Thank you..

Thanks for the question, Robyn. And as we look at 2021, I would say that the majority of our growth will come from additional international launches of our biosimilar portfolio. And obviously, some additional revenue from AVSOLA and RIABNI, two relatively recent biosimilar launches in the U.S.

Specifically, if you think about MVASI and KANJINTI, they are a little bit different. And the differences are twofold. There's more than that ballistic to the two major ones. Bevacizumab as a molecule is actually growing, whereas trastuzumab as a molecule is flat to declining.

So, one thing that we're seeing in MVASI is actually the number of cycles of bevacizumab overall is growing. And so, even holding share in that molecule actually holds up quite well. We also have less competition. That's the other factor. So there's less competition for now in the bevacizumab molecule, whereas with trastuzumab, we have more competitors.

And so, I think going forward, you would see competitive dynamics shaping those two brands a little bit differently..

Your next question is from Mohit Bansal with Citigroup..

Congrats on all the progress. Maybe one question on EVENITY. It seems like you have been able to grow this product, not just U.S., globally as well. And this has been a difficult market historically.

So, could you please help us characterize the growth in terms of whether you are taking share from existing anabolics or you're expanding the market? And then, do you expect any challenge when the [Technical Difficulty] comes to market of this product..

Yes. I was picking up a little bit of static. So, I think the question's on EVENITY. The first part of the question I understood was how are we sourcing our EVENITY growth? Is it from existing anabolic patients, or are we expanding and treating new patients? I didn't catch the second part of the question, but let me address the first part.

Overall, we're pleased with how EVENITY has evolved. We've got nice evolution in our Japan business. In Japan, it's obviously -- we've been in the market a little bit longer. So, one thing that we're seeing with EVENITY is patients are on the product for a 12-month duration of treatment. And so, you have to replenish those new patients.

You do have to source those new patients. And so, I think the team in Japan is quite experienced now at sourcing new patients and not necessarily where we got our early growth was from which was switching from other anabolics.

And there are -- unfortunately, there are a lot of aging patients in these markets where osteoporosis goes unchecked and patients suffer fractures and these high-risk patients need a solid bone builder, like EVENITY to be able to improve their clinical outcomes.

So, I think in Japan, we're sourcing now more de novo growth than we were perhaps 6 to 12 months ago. Whereas in the U.S., it's much more of a mix of de novo and switch. The other thing that's helping us in the U.S. is, of course, having both Prolia and EVENITY for the customer.

A lot of the time when a patient will come in and have a fracture despite their Prolia treatment, they're a really good candidate for EVENITY. So, we're often getting patients on both treatments. And sometimes after the 12 months of EVENITY treatment are up, they'll roll back on to Prolia.

So, it's a nice franchise to have and have both an anti-resort and a bone-building agent for our customers. So, I think, the future growth looks very good. Obviously, our partners at UCB are just getting going in Europe as they establish reimbursement for the product.

But, I'm quite excited about what EVENITY could become for bone building for these very high-risk post-fracture patients..

Your next question is from Umer Raffat with Evercore ISI..

Murdo, you recently mentioned 25,000 as the target population for KRAS. And that sounded rather irony, at least for U.S. So, I was curious, A, whether that was for U.S.-only or worldwide? And B, if you were assuming a -- around 14% prevalence rate for G12C and whether you are doing this analysis only for this math? Thank you so much..

Thanks for the question, Umer. The 25,000 was a U.S. number. We actually estimate the non-small cell lung cancer incidents globally at 120,000 patients. Now, obviously, there's some reduction from first-line to second-line in lung cancer because unfortunately, we lose patients in frontline.

The second line and beyond is obviously our target population at launch. And we assume a 13% incidence of KRAS G12C in the broad non-small cell lung cancer patient population..

Right. So Murdo, if we just go down that track, 13% at 120K.

I was just confused, the 25K?.

Yes. So that's a U.S.-only number for incidence of non-small cell lung cancer that have progressed into second line and beyond..

Your next question is from Kennen MacKay with RBC Capital Markets..

Maybe for Dave, maybe it's the BiTEs that you spoke to previously, but I always love asking this question. Within the early stage Phase 1 or stage 2 pipeline, what are you most excited about in 2021? What's going to be the next sotorasib? Thank you..

Yes, thanks. And I think we are able to just rejoin in time for that question. Again, I think in terms of the early pipeline, AMG 160 and AMG 757, as I highlighted in my prepared remarks, are ones that we're really looking at. 160 has advanced into the expansion cohort.

And if we continue to generate data as we have recently through a larger number of patients. That's a program that we would probably be discussing potential registration paths sooner rather than later. I think, AMG 757 is just one step behind. And that's another one that we're keeping a very close eye on.

And then, in our inflammation portfolio, we've got a variety of Phase 2 assets in autoimmune indications, as we previously indicated, and those programs are ones that I'm quite interested in, as we move forward..

Your next question is from Geoffrey Porges with SVB Leerink..

Murdo, a question about your commercial model. You mentioned in the prepared remarks a couple of times that you were shifting to more of a digital approach. And I'm just wondering, we've heard that there have been significant reductions in your commercial field organizations.

Can you give us a sense of what the magnitude of the efficiency in headcount you're seeing on your average sales force by moving towards digital? And could you talk about how you think that might play out in a post-COVID world? Wouldn't you expect to have to ramp back up once we eliminate social distancing?.

Thanks, Geoffrey, for the question. There were a couple of factors that went into our recent reorganization of our field force. One is just portfolio evolution and creating capacity for the new product launches and then reallocating from the older side of the portfolio.

And depending on which region you're talking about in the world with Amgen, we're in very different stages of development. So, for example, we're placing large investments in field force in Japan and in China, even in Russia and some other markets that are emerging for us as being important growth drivers. And in the U.S.

we're really paying close attention to the forces in the market beyond COVID. We're looking at potential negative net price effects and/or price reform, as Bob mentioned in his opening remarks, as being a bit of a prevailing wind here.

And so, what we're doing is looking at our overall commercial model, and to your point, making it more productive and making it more efficient. So, we're largely on track with that plan. We were able to move very rapidly last year and build out our digital capabilities to an even greater extent than we had historically.

We are seeing customers willing to engage in those channels. And we think some of those engagements will be persistent beyond COVID, quite frankly. And it's that persistency that we're betting on.

What we haven’t done is compromised the ability to have competitive share of voice in our field facing interactions, both on the medical side, both on the commercial side, in front of the customer.

And so, we think we'll continue to be able to compete effectively in the categories we're in, as well as augment that with highly efficient digital channels of communication..

Our next question is from Carter Gould with Barclays..

Congrats on sotorasib data, the impressive execution. I guess, Murdo and Bob, coming back to Otezla, at the time of the acquisition, it seems to have oriented us that the majority of the growth would come from the U.S. And I guess, your comments today seem to be teeing up really, I guess, the global nature of the growth going forward.

I guess, just your level of confidence around Otezla growth in the U.S.

through the mid-2025 timeframe, I guess, given the competition and what have you?.

Maybe I'll just take the first sense or two, and then Murdo, you can augment however you'd like. But, Carter, what I'd say is that when we acquired it, we said we felt we could achieve double-digit growth through the first several years of ownership, and we continue to feel confident in that.

And that's a function of both, potential for increased label range in the U.S. as well as the opportunity to launch in international markets.

But, Murdo, maybe you want to elaborate on the opportunity, the mild to moderate, severe opportunity?.

Yes. Thanks, Bob. We do see some of the international expansion maturing now. We've got a good business for Otezla in Japan. We're pursuing registration in China, and we recently secured reimbursement in Australia. So, we're evolving the global footprint of Otezla beyond where the legacy Celgene efforts had it. So, that is one source of growth.

But, as Bob mentioned, we're also pursuing in the U.S. mild to moderate approval on the basis of the positive data set we have there. And that will allow us to move Otezla into a patient population that really is still an unmet need.

These are patients who have enough skin surface area that they might be seeking an alternative to messy and inconvenient topical agents. And I think Otezla can play a very important role there in helping treat those patients.

We're also in making investments in Otezla by expanding the promotional footprint of the product to include primary care promotion, something that Celgene had not done historically. So, we're doing that both for the moderate to severe patient, but as well for that mild to moderate indication in anticipation of that potential approval.

And the only other thing I would say is, while we are seeing a little bit of softness in psoriasis and broader rheumatology, for the category due to COVID, Otezla being an oral has held up quite well, and the execution has been strong.

I also think that the established safety and efficacy profile of Otezla is highly appreciated, given recent news in the broader rheumatology category of other orals where perhaps that risk-benefit equation is different than it is where it's very strong with Otezla. So, we think we've got a good opportunity for growth.

We also said when we gave that guidance that it assumed a successful competitive program from the TYK2 asset. And of course, that was confirmed today..

Your next question is from Jay Olson with Oppenheimer..

Hi.

Congrats on all the progress and thank you for taking the question? Since you received breakthrough therapy designation for sotorasib in China, could you comment on how fast you could submit a filing and gain regulatory approval? And what percent of Asian non-small cell lung cancer patients have their KRAS G12C mutation, and how large is that commercial opportunity is for sotorasib in China? Thank you..

Thanks, Jay. Yes. We're very pleased to get breakthrough therapy designation in China. As our filing plans move forward with our colleagues at BeiGene, we'll provide guidance about what those time lines might look like. But, it has a little bit different implications in China than it does potentially in the United States.

And then, one thing that we're looking at quite carefully is the epidemiology of G12C mutations. There is a suggestion that it may be a little lower in prevalence in Asian populations, probably because they are mutually exclusive with mutations in EGFR, which are quite high in these populations, up to 40% in China and Japan, for example.

So that will be an important question that we address. We've got active research collaborations now, looking at just that. And Murdo, I don't know if you want to add anything about the commercial side in China..

Yes. I think, we're obviously very excited about what we can do with the product, huge unmet medical need. We're seeing that China is an attractive market for specialty products and the fact that sotorasib is an oral makes it very accessible. So, we'll pursue commercialization of sotorasib in China, and our affiliate is very excited about that..

Your next question is from Colin Bristow with UBS..

Obviously, seeing the abstract data for tezepelumab, the less than 150 group looks pretty impressive. I was just curious what your level of confidence is in getting a broad label in light of the fact that you didn't test it for statistical significance? Is that something you've discussed with the FDA previously? And I'll keep it short..

Yes. Thanks, Colin. This is a question we get frequently. We demonstrated efficacy in -- across a broad range of patients regardless of eosinophil count. I think that's what clinicians will pay attention to. We'll provide guidance as regulatory discussions proceed.

I think, it's too early, of course, prior to submitting to debate what a potential label would look like. But, our view is that overall these are very, very strong data pointing to a differentiated product. And I think this is just going to be a really important medicine for patients with severe uncontrolled asthma..

Your next question is from Ronny Gal with Bernstein..

Just about biosimilars. You spiked my head a little bit talking about increased competition pressure.

Is the anticipation that in 2021 the price decrease in oncology will exit that 10%, 15% decline rate? Is there any reason to expect it? Are the payers coming in and making changes, or is this just an issue of you would cite the market, it's going to be hard to get 100%..

Yes. Ronny, I think you definitely see a diminishing rate of return or gain in terms of volume share. You see that in the shape of our uptake curves for both our oncology biosimilars in the U.S.

I think that the way, of course, these products are used, they're largely used in the community setting, about 80% of the usage of both bevacizumab and trastuzumab in a community oncology setting. And those businesses tend to contract on a network by network basis. And by now, most of those contracts are set in motion.

There's still some incremental opportunity to add to our overall revenue base. But yes, I think the gains on volume will be incremental. And then, price trends, as I mentioned in my scripted remarks, will continue to evolve the way we've seen them..

Your next question is from Michael Schmidt with Guggenheim Securities..

I thought it was interesting to hear about some of the early stage R&D efforts and the comments that were made around the induced proximity platform.

Along those lines, I was wondering if you could provide a little bit more insight into progress that may have been made within your human genetics initiative, and when or how this initiative may translate into new pipeline products? Thanks so much..

Yes. Thanks, Michael. In human genetics, as Bob mentioned and as we previously announced, we have collaborations with Intermountain Health and UK Biobank that will add up to 1 million participants. We think we'll have the largest database on earth as these projects move towards completion.

And we have broadened our focus on human data to include other omic technologies such as transcriptomics and proteomics really in the belief that in the long term, it will be human data such as these that are most important for drug discovery and development.

At the current time, a majority of our non-oncology portfolio assets have genetic support that's either primary or secondary. And we expect over time that, that percentage will simply increase because there's now clear evidence that targets for which there's genetic validation and programs based on them have a higher rate of success. So, more to come.

But we firmly believe that the era of human data is upon us, and we believe our collection of capabilities is almost unique in the industry. And we intend to push that forward. Thanks..

Your next question is from Salim Syed with Mizuho Securities..

Just one from me strategically, high level here, guys.

When you think about Amgen here, is it a correct interpretation to say that the interest in hemonc has gone significantly down and the interest in solid tumors has gone significantly up? And just curious if Kyprolis has anything to do with that, if that's the correct interpretation?.

I don't think it is, Salim, but I invite Dave to....

Yes. So, Salim, yes. Kyprolis, I think, has nothing to do with that. What you're seeing is the natural evolution of a portfolio based on emerging data, and we will expect that to be shaped going forward, based on emerging data, of course. And some of the changes we announced today our strategic choices that we had teed up that we anticipated making.

And we think it's a prudent portfolio management to make those choices. Let me call out the MCL-1 programs in particular, where we have elected to move forward with the IV formulation. Again, we had anticipated we would choose among those molecules.

And given our ability to more precisely control exposures and achieve a therapeutic window, in collaboration with our investigators, we made that decision, and we're moving through dose escalation after reinitiation of that program. So, no specific conscious choices, based on hematology versus solid tumors and more shaping to come as data emerges..

Salim, I would just jump in and say, we had a strong quarter on Kyprolis in the fourth quarter, given the approval of CANDOR and our first full quarter promoting it. And we expect to be able to do a nice job of making hemonc specialists around the world aware of those data in combination with daratumumab.

So, more growth to come on Kyprolis, and it's a good story now..

Your final question is from Tim Anderson with Wolfe Research..

This is Andrew Galler [ph] on for Tim. Thanks for taking my question. Just thinking about sotorasib in Europe.

Given EMA typically has a higher threshold for approval for single arm studies, can you describe your degree of confidence you'll be able to get approved on this 37% response rate in 10-month DOR?.

Yes, sure. Let me take that question. We filed in the EU, obviously, we've got ongoing discussions. We'll provide guidance at the appropriate time. We don't speculate on likely timelines or probabilities in terms of regulatory approvals.

But, I think, it is fair to say that regulators around the world do recognize the large unmet medical need in patients with G12C mutations after first-line therapy, and that certainly will be the focus of discussion going forward..

Well, thank you. Again, apologies for the fact that we went about 12 minutes over tonight, but we did want to get to all of your questions. So, thank you for your interest and your support of the Company. And we look forward to seeing you or being back together with you after the end of the first quarter. Thank you..

Ladies and gentlemen, this concludes Amgen's fourth quarter 2020 financial results conference call. You may now disconnect..