My name is Jason, and I will be your conference facilitator today for Amgen's Third Quarter 2022 Financial Results Conference Call. [Operator Instructions] I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin..

Okay. Thank you, Jason. Good afternoon, everybody, and welcome to our Q3 call. So we continued with our execution during the quarter with a focus on driving volume growth for our key products and advancing our innovative pipeline. Leading the discussion today will be our Chairman and CEO, Bob Bradway.

We have posted some slides for your reference and my customary reminder that we'll be making some forward-looking statements and use non-GAAP financial measures to describe our performance. So with that, I would like to turn the call over to Bob..

Okay. Thank you, all of you, for joining our call. In the face of both macroeconomic and industry-specific challenges, Amgen remains laser-focused on delivering for patients and shareholders. Benefit of that focus was evident in the third quarter with volumes up a healthy 8% and 16% outside the United States.

These results reflect the strong underlying demand for our medicines and the value they bring to patients even in challenging economic times like those prevailing at the moment. Revenues for the quarter were down 1%, reflecting a 5% net price decline consistent with what we communicated earlier in the year and a 2% impact from foreign exchange.

All told, 11 of our products generated record sales in the quarter, and non-GAAP earnings per share increased 15% with free cash flows reaching $2.8 billion for the quarter. Looking forward, we remain focused on several growth drivers. With the recent closing of the ChemoCentryx acquisition, we're excited to have TAVNEOS in our portfolio.

TAVNEOS is the first new treatment for ANCA-associated vasculitis in more than 10 years, and we're confident that we can leverage our decades of experience in inflammation and nephrology to bring this innovative medicine to many more patients moving forward. Two recently launched products, TEZSPIRE and LUMAKRAS, are off to solid starts.

TEZSPIRE is performing well in asthma, and we have studies underway for several other indications for that product as well. LUMAKRAS is performing well globally with patients, payers and prescribers recognizing the importance of this innovation.

With combination studies underway, we're exploring the many different ways this product may benefit patients through time. We have a number of key products led by Repatha, Otezla, Prolia and EVENITY that we know can benefit millions more patients globally than they do today.

And let's not lose sight of the fact that these 4 products collectively generated $2 billion in third quarter sales with volume growth of 17%.

We've built an industry-leading biosimilars business, having now launched five products in markets around the world, and we're months away from being the first company to launch a biosimilar to HUMIRA in the U.S. AMGEVITA is already the most prescribed HUMIRA biosimilar in Europe, giving us confidence as we prepare to enter the U.S. market.

Looking forward, our next wave of biosimilars to STELARA, SOLIRIS and EYLEA are well positioned with our having now successfully completed Phase III trials for all three of these molecules. We have many potential new medicines advancing through our innovative pipeline, including Olpasiran, tarlatamab, rocatinlimab, bemarituzumab and AMG 133.

These five molecules and several others that you'll hear about shortly from Dave Reese are vintage Amgen, which is first-in-class medicines that make a big difference for patients suffering from serious diseases for which there remains a real need for new and better treatments.

Finally, we have a highly engaged and committed workforce, and I want to thank them, as always, for their great work. With that, let me turn over to our CFO, Peter Griffith..

first, our recent acquisition at ChemoCentryx is a clear example of investing in the best innovation, in this case, external for patients; second, investing in our business through capital expenditures, including advancing construction on our new environmentally friendly facilities in Ohio and North Carolina; third, returning capital to shareholders through growing dividends, including $1.94 per share in the quarter, representing a 10% increase from Q3 2021; and fourth, opportunistic share repurchases.

The final settlement of the accelerated share repurchase, ASR program, occurred in the third quarter, and we have repurchased about $6.3 billion of shares year-to-date. Turning to the outlook for the business for 2022. We're pleased with our execution through the third quarter.

For the full year, we now expect to absorb about $560 million in FX headwinds against product sales based on recent FX rates, of which we absorbed nearly $400 million through the third quarter. And this is net of our hedging activities, reflecting our strong execution through the third quarter.

And despite challenging foreign exchange dynamics, we're updating our 2022 revenue guidance range to $26.0 billion to $26.3 billion. We are updating our non-GAAP EPS range to $17.25 to $17.85.

This range encompasses both FX headwinds of approximately 3% or $0.45 for the full year based on recent FX rates and costs associated with our acquisition of ChemoCentryx incurred between closing and year-end. I'll share a few additional points to consider for the remainder of 2022 with a particular focus on how these trends are likely to impact Q4.

We expect FX headwinds to reduce product sales in Q4 by about $165 million. The U.S. government has agreed to purchase $290 million of Nplate. We will recognize about $200 million of those sales in Q4 with the remainder in 2023.

We have completed the previously discussed divestiture of Gensenta, our generics business, in Turkey and will no longer recognize product sales and operating expenses from that business effective November 2, 2022. Sales of that business annualized at approximately $90 million.

We now expect full year other revenue for 2022 between $1.5 billion to $1.6 billion versus our prior guidance of $1.4 billion to $1.6 billion. When comparing against our recast 2021 results, we continue to expect full year non-GAAP operating expenses to reflect a low double-digit decrease year-over-year.

We continue to expect 2022 non-GAAP operating margin as a percentage of product sales to be roughly 50%. We continue to expect non-GAAP cost of sales in the range of 15.5% to 16.5% as a percentage of product sales.

We now expect non-GAAP R&D expenses in 2022 to decrease 5% to 8% year-over-year compared to our recast 2021 non-GAAP R&D expenses, which include the $400 million upfront payment we discussed above. We expect non-GAAP SG&A spend to be roughly flat year-over-year as a percentage of product sales.

We expect OI&E to be in the range of $1.6 billion to $1.7 billion with fourth quarter results closer to the first and second quarter results. For the full year, we now anticipate a non-GAAP tax rate range of 13.5% to 14.5%, down from our prior guidance of 14.0% to 15.0%.

As you consider your modeling for 2023, recall that tax law changes enacted by Puerto Rico in June of 2022 that replaced the Puerto Rico excise tax, the PRET, in favor of an income tax will increase our 2023 income tax expense while reducing by roughly an equivalent amount of cost of goods sold.

Note, however, there will be a onetime residual negative impact in 2023 related to the amount of the PRET currently capitalized in inventory that will be charged to cost of goods sold without a corresponding tax benefit.

This charge is slightly larger than the benefit previously recognized with the implementation of the PRET in 2011, which was discussed in our 2011 Form 10-K. Summing up, since the business review in February, much has changed at the macro level with the strengthening of the U.S.

dollar, persistently high inflation, higher interest rates and the passing of the Inflation Reduction Act. Despite these headwinds, we have executed well in 2022. As we plan for 2023, we anticipate that these headwinds will continue. We're adapting our operating plans and expect to successfully execute against them.

Like previous years, we expect to provide 2023 guidance on our Q4 earnings call in January. Our confidence in the long-term growth of Amgen remains strong. I thank our millions of patients for their courage and my 25,000 colleagues for their mission-driven work on behalf of those patients every day. This concludes the financial update.

I'll turn it over to Murdo..

Thanks, Peter. We saw strong volume growth in the third quarter with an 8% increase year-on-year. We delivered record quarterly sales for 11 products, including EVENITY, TEZSPIRE, AMGEVITA, Vectibix, KYPROLIS, Nplate and BLINCYTO; and double-digit volume growth for several additional products, including Repatha and LUMAKRAS.

Excluding the impact of foreign exchange, third quarter global product sales grew 1% as our volume increases were offset by a 5% decline in net selling price, consistent with our prior estimates. Including the 2% negative foreign exchange impact, product sales declined 1% year-over-year.

I'll start now with our general medicine business, which includes Prolia, EVENITY, Repatha and Aimovig. Overall revenue for this portfolio grew 14% year-over-year driven by 20% volume growth. In bone health, Prolia sales grew 7% year-over-year driven by 8% volume growth.

EVENITY, which complements Prolia in our bone portfolio, had record sales of $201 million for the quarter driven by 45% volume growth in the U.S. and 30% volume growth outside of the U.S. Repatha sales increased 14% year-over-year driven by 52% volume growth, which was partially offset by lower net selling price.

In the U.S., we generated 32% volume growth aided by broad adoption of Repatha by cardiologists and increasing adoption by primary care providers. We also saw declining net selling prices in the U.S. as we offered higher rebates to support broad Medicare Part D and commercial patient access. Looking ahead to 2023, we expect less year-over-year U.S.

price erosion than we saw in 2022. Outside the U.S., sales of Repatha grew 26% driven by 73% volume growth. Net price declines outside the U.S. were primarily a result of Repatha's inclusion on China's National Reimbursement Drug List as of January 1, 2022.

Overall, we remain focused on addressing leading cause of morbidity and mortality by bringing Repatha to patients in need all around the world. Moving to our inflammation portfolio. Otezla sales increased 3% year-over-year for the quarter. Otezla saw 9% volume growth, partially offset by lower inventory and unfavorable foreign exchange impact.

In the U.S., Otezla remains the leader in bio-naive psoriasis patient share, and we see broader adoption of Otezla among patients with mild-to-moderate psoriasis.

Looking forward, we expect continued strong volume growth given Otezla's established safety profile, strong payer coverage and unique position as the only systemic oral that can treat a broad spectrum of patients with psoriasis regardless of the severity of their disease.

ENBREL sales decreased 14% year-over-year for the third quarter driven by lower net selling price, unfavorable changes to estimated sales deductions and a 3% decline in volume. ENBREL remains an important product for patients due to its long track record of efficacy and safety. I'm very pleased with our strong U.S.

launch of TEZSPIRE, which generated $55 million of sales in the third quarter. Allergists and pulmonologists have prescribed TEZSPIRE across a broad range of patients with severe uncontrolled asthma. We're also seeing initiation in both biologic-naive and previously treated patients.

Physicians acknowledge TEZSPIRE's unique differentiated profile and its broad potential to treat the 2.5 million patients worldwide with severe asthma who are uncontrolled without requiring any phenotypic and biomarker testing. We recently completed our acquisition of ChemoCentryx, which adds TAVNEOS to our portfolio.

TAVNEOS recently launched as a first-in-class treatment for ANCA-associated vasculitis, or AAV. This is a serious systemic autoimmune disease that leads to inflammation and eventual destruction of small blood vessels. This inflammatory disease can lead to permanent organ damage and, in some severe cases, can be life-threatening.

TAVNEOS represents a significant advance in treatment for the 8,000 to 10,000 U.S. patients a year who develop severe active disease or experience major relapses of AAV. AAV is often managed by rheumatologists and nephrologists, where Amgen has a strong market presence and successful track record.

We look forward to applying our deep expertise and inflammation experience to help many more patients manage AAV with TAVNEOS. Moving to our hematology and oncology business. Our 6 innovative products grew 8% year-over-year with 10% volume growth.

For Vectibix and Nplate, strong volume growth in the quarter benefited from timing of shipments to our partners in Japan. Our launch of LUMAKRAS is progressing well with revenues of $75 million in the third quarter.

Quarter-over-quarter sales declined 3% driven by lower net selling price due to a $12 million unfavorable price adjustment resulting from our reimbursement approval in Germany. This was partially offset by 15% volume growth.

In the U.S., LUMAKRAS has been prescribed to over 3,700 patients by over 2,200 clinicians in both academic and community settings. Outside the U.S., LUMAKRAS has now been approved in over 45 countries. We've launched in 30 markets and are rapidly pursuing reimbursement in the remaining markets.

As we've noted before, near term, the market for LUMAKRAS is focused on the 7,000 U.S. and 20,000 ex U.S. patients in the second-line setting. Longer term, we expect LUMAKRAS growth to come from earlier-line therapy and the potential of LUMAKRAS to treat other tumor types. Sales of our oncology biosimilars declined 25% year-over-year.

While our biosimilars for MVASI and KANJINTI both hold leading shares, we expect continued net selling price deterioration and accelerating volume declines driven by increased competition. The most recently published average selling price for MVASI in the U.S. declined 37% year-over-year and for KANJINTI declined 38% year-over-year.

Over time, we expect long-term growth in our biosimilars business to be driven by the addition of new molecules and additional launches. We're preparing ourselves for the upcoming launch of AMGEVITA, our HUMIRA biosimilar, in the U.S. in early 2023, followed by the next wave of biosimilar launches to STELARA, EYLEA and SOLIRIS.

Overall, I'm very pleased with our execution in the quarter. Our international presence and diverse portfolio of products position us well to deliver on the execution of our long-term growth strategy. And with that, I'll turn it over to Dave..

Thanks, Murdo, and good afternoon, everyone. I'd like to start by welcoming our new colleagues from ChemoCentryx. We're excited that you're now part of Amgen. For research and development, the third quarter was one of continued execution where we presented new data on several programs and continued to progress our innovative clinical pipeline.

Beginning with general medicine. This coming weekend at the American Heart Association meeting, we plan to present data from a Phase II study of Olpasiran, a lipoprotein little a targeting small interfering RNA molecule in subjects with elevated Lp little a.

We also plan to present additional data from the Repatha FOURIER and Repatha open-label extension studies highlighting the association between the significant and sustained achievement of low and very low LDL cholesterol levels and lower rates of major cardiovascular events.

Data from the single- and multiple-dose cohorts of the Phase I study of AMG 133, a multispecific that inhibits the gastric inhibitory polypeptide receptor, or GIPR, and activates the GLP-1 receptor, will be presented at the 20th World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease Hybrid Conference in December.

As a reminder, the unique aspect of AMG 133 is the inhibition of GIPR, an innovative approach that we chose to take based on human genetic data that suggest decreased expression of GIPR leads to lower body mass index and lower weight.

We look forward to discussing the Repatha and Olpasiran data along with an update on AMG 133 at our investor call scheduled for Monday, November 7. Turning to inflammation.

In September, we presented data from the Phase III SPROUT trial, where Otezla treatment resulted in significant improvement in measures of moderate-to-severe plaque psoriasis at week 16 compared to placebo in children's ages 6 to 17.

We also presented data from the Otezla Phase III DISCRETE trial, where 16-week data demonstrated statistically significant improvements in genital psoriasis, including skin, itch and quality of life in patients with moderate-to-severe disease. Based on these results, discussion of the FDA is ongoing for DISCRETE to add clinical data to the U.S.

prescribing information, and discussions with regulatory authorities globally for SPROUT are forthcoming. In September, TEZSPIRE was approved in the European Union and in Japan, and regulatory reviews continue in other jurisdictions.

In oncology, we presented data from tarlatamab, a DLL3-targeting BiTE molecule being studying in patients with small cell lung cancer. These data demonstrated encouraging antitumor activity with notable response durability and survival.

In this setting, tarlatamab delivered a confirmed overall response rate of 23%, a median duration of response of 13 months and a median overall survival of 13.2 months. We continue to enroll patients in a potentially registrational Phase II study in this setting.

We're also investigating tarlatamab in combination with standard of care in first-line small cell lung cancer in combination with AMG 404, a PD-1 inhibitor, in patients with second-line or later small cell lung cancer and in neuroendocrine prostate cancer.

In August, we presented data from our LUMAKRAS checkpoint inhibitor and SHIP2 combination studies. Based on these data, we continue to explore LUMAKRAS in both settings.

In September, we presented data on LUMAKRAS in combination with Vectibix, where this combination demonstrated encouraging efficacy and safety in patients with chemorefractory metastatic colorectal cancer. Phase III trial continues to enroll using this combination.

We also presented data from the global Phase III CodeBreaK 200 confirmatory trial, where LUMAKRAS treatment led to increased progression-free survival and a significantly higher objective response rate in patients with KRAS G12C mutated non-small cell lung cancer compared with docetaxel.

Patient-reported outcomes were also improved with LUMAKRAS versus docetaxel. We've just received initial top line data from a post-marketing requirement study comparing the 960-milligram daily dose of LUMAKRAS with a lower dose of 240 milligrams daily in patients with KRAS G12C-mutated advanced non-small cell lung cancer.

Following discussions with regulators, we are planning to submit data from this study along with CodeBreaK 200 confirmatory Phase III data.

As a reminder, we are investigating multiple potential to pass the first-line treatment of non-small cell lung cancer with LUMAKRAS, potentially segmented by PD-L1 expression levels, where the non-small cell lung cancer population breaks down into roughly 1/3 across PD-L1 high expressers, intermediate or low expressers, and PD-L1-negative expression.

We've seen promising early data in the PD-L1-negative population and are planning to initiate a Phase III study of LUMAKRAS plus chemotherapy in first-line advanced or metastatic non-small cell lung cancer.

Finally, I'm pleased to announce that the primary analysis of a Phase III study evaluating the efficacy and safety of ABP 938, an investigational biosimilar to EYLEA compared with EYLEA, met its primary end point in subjects with neovascular age-related macular degeneration.

With these data and previously announced Phase III data from our biosimilar candidates to SOLIRIS and STELARA, we have completed our goal of delivering positive Phase III data from 3 biosimilars in 2022.

In conclusion, with an innovative portfolio or approximately 3/4 of our clinical stage programs have first-in-class potential and a growing portfolio of biosimilars, we are well positioned to continue to deliver important new medicines for patients and growth for shareholders over the near and long term. I'll now turn it back to Bob..

Okay. Thank you, David. And Jason, why don't we now open the line up for questions. If you would remind our callers of the procedure, we can get started..

[Operator Instructions] Our first question comes from Salveen Richter with Goldman Sachs. Your line is now open..

Good afternoon. Thanks for taking my question.

On AMG 133 in obesity, could you just help us understand how you'll evaluate the data in the context of existing therapies to make a move forward decision and how you're thinking about differentiation here? Is it just a matter of taking a piece of the market given size? Or do you think there's other aspects here to the program?.

Dave, why don't you take that question?.

Yes. Thanks, Salveen. We know there's a lot of interest in this program. And as we mentioned, we'll be showing the data in full in the first week of December at the hybrid conference. Obesity is a large, very heterogeneous disease. It's a global public health problem.

The things that I would look for in evaluating this molecule going forward will be the dosing; dosing interval; what are the kinetics of weight loss; how rapid is that weight loss; what is sustainability. And then finally, the overall tolerability.

We do plan on using our extensive capabilities in human data to help shape our thinking and guide this development program as we move forward..

Thank you..

Jason, we'll take the next question..

Our next question comes from Matthew Harrison with Morgan Stanley. Your line is now open..

Great. Good afternoon. Thanks for taking the question. I wanted to ask a question now that you've been through - or hopefully been through most of the contracting season for next year.

I think one of the key investor concerns is obviously with biosimilar HUMIRA coming next year, what impact that could have to ENBREL and ENBREL pricing dynamics for next year. So I'm wondering if you can just comment on how to think about the potential impact to ENBREL and its pricing next year? Thanks..

Thank you, Matthew. It's Murdo. We're obviously excited about the opportunity to launch the first biosimilar to HUMIRA. And so we are active in our discussions with payers and PBMs for that.

We are not seeing a massive amount of change to ENBREL's access going forward, and we continue to believe we've got good regard on the payers and PBMs for the efficacy and the safety of ENBREL. And if there were to be a change in ENBREL pricing, it would be for volume gains.

As I mentioned in my opening remarks, we're declining in volumes about 3% year-on-year. Our goal is to maintain that and maybe even improve upon it. But we're not quite finished in the contracting cycle..

Okay.

Next question please?.

Our next question comes from Umer Raffat with Evercore. Your line is now open..

Hi, guys. Thanks for taking my question. I have a two part question on what everybody wants to talk about, which is obesity. So Lilly and Novo, the two lead players in the GLP space, they both have early-stage programs. I'm talking Phase I stage programs on triple agonist, et cetera.

And one thing they always emphasize is that they have certain predefined thresholds for moving any of those programs forward. And those thresholds are off of incremental efficacy beyond the current most competitive products out there.

And my question is, I imagine you're thinking about some of those thresholds too relative to Manjaro, perhaps Carsem, as you think about the progression of your program. And I'm curious if you could speak to that.

And secondly, if you could just clarify for us, the low- and the high-dose data from single ascending dose you showed at your business review early in the year, was that an average of the first three and the highest three of the six cohorts in Phase I? Or was it the first two out of the six cohorts? I wasn't quite sure with the low and the high meant within the single ascending dose.

And I remember, there were 6 different cohorts within single ascending. Thank you very much..

Yes. We'll get back to you on the latter half of that question. I'll remember off the top of my head, Umer, what that is. But we're going to have -- in a month, you'll have the full data set with all of the cohorts broken out. So I think, at that point, it will be very clear.

In terms of thresholds, as I discussed a short while ago, there are many potential avenues to differentiation here. Of course, degree of weight loss is one of them; but also dosing interval; what the kinetics are; importantly, durability; importantly, tolerability, since a fair number of patients transition off of these agents for tolerability.

So those are the sorts of things that we'll be taking a look at as we assess whether we've got a differentiated product and it's worth our scale investment..

Our next question comes from Michael Yee with Jefferies. Your line is now open..

Thank you. I'm going to ask another follow-up on 133. David, last quarter, you said you actually started the Phase II. I actually didn't hear that here.

Can you just talk about the actual status of where you are with 133 and also the fact that I believe it's been disclosed that you dialed back the GLP-1 potency, so we should not be expecting material, diabetes types effects, and this is not what we're looking for or people should be examining or scrutinizing? Thank you..

Yes. No, I don't believe we announced we had started Phase II, Mike, but rather that we're in planning. We do expect to initiating the Phase II trial in the relative near term. And once that gets launched, of course, we'll talk about design and give guidance in terms of expected data availability.

I wouldn't over think the GLP-1 component, and I'm not sure that's on point. I think, again, when we share the data in a month, you'll get a look at that..

Thank you..

Our next question comes from Jay Olson with Oppenheimer. Your line is now open..

Hey, congrats on the quarter and closing the ChemoCentryx deal. You have a lot of volume growth outside the U.S. in the third quarter. And as an example, I think you said Repatha grew 73% ex U.S. with inclusion on China's National Drug Reimbursement List. Can you talk about the pace of product launches outside the U.S.

and volume growth and how do you expect U.S. versus ex U.S. revenue mix to evolve over time? Thank you..

Do you want to - yes, jump in..

Thanks, Jay. I think Repatha is a good example of how now with our broadened international presence, we're able to bring new products and new launches to the market fairly quickly. What we're seeing in China is rapid expansion of Repatha. Recall, we were on the market for just over a year prior to securing national reimbursement drug list.

So we did establish good understanding education, awareness of Repatha. We were promoting it primarily for percutaneous coronary intervention patients or stent patients, where the unmet need was deemed to be highest amongst the private cash pay patient group.

But I think what you're seeing is there's real demand in these markets to help millions of patients who are at very high risk of coronary vascular disease. And so we're continuing to build out our business in Japan and China. We had good volume growth in Europe. And obviously, we also had good volume growth in the U.S.

So we're excited about the evolution of Repatha, and we continue to feel good about how that product will drive volume and revenue growth for us in the future.

With respect to other launches, the other good example that we're seeing is just the LUMAKRAS launch given that we've got approval in roughly 40 markets, we've got reimbursement in roughly 30 markets, and we're pursuing reimbursement in the remaining countries.

Our teams -- our oncology teams around the world doing a very nice job of identifying KRAS G12C second-line patients and making sure that they have LUMAKRAS as a treatment option.

So I'm really pleased that the international presence we've been building for many years now is in full place, is functioning at a high level and delivering strong volume growth. Going forward, we have some partner products where we don't necessarily have the launches in every country where we have our partners to do that.

But wherever Amgen has the global responsibility and rights for products, we're feeling very good about our potential and ability to launch them globally..

And Jay, let me just add, don't forget, we've - in the slides that we shared with you tefan [ph] we have the outside U.S. data available for you on all the different products. You'll see the current contribution from the international business there..

Our next question comes from Geoffrey Meacham with Bank of America. Your line is now open..

Hey, this is Charlie on for Geoff. Thanks for taking the question and congrats on the results. I just have questions regarding the, I guess, the EYLEA as well as STELARA kind of potential launch timing.

I think given you mentioned that you already submitted the STELARA data to the FDA, I'm wondering you're expecting to see the product launch kind of second half of next year and whether you anticipate any pushback from J&J? And I guess similarly kind of for EYLEA, were like launch timing is in the 2024 time frame and if you anticipate kind of any pushback from Regeneron? Thank you..

Thanks for the question, Charlie. We're obviously pleased with the successful data readouts on those products and some that have been filed. We expect to be in the first wave of those biosimilar launches, and we're not disclosing specific launch timing on those products..

Our next question comes from Evan Seigerman with BMO Capital. Your line is now open..

Hi, guys. Thank you so much for taking the question. I'm not going to ask about 133 but rather on LUMAKRAS. So you had mentioned you had data from the dose-reduction trial.

Can you characterize how we should think about the relative efficacy of the lower doses versus the approved dose? And on the pembro combination trial, I noticed in the slides, you talked about a dose expansion with a lower dose lead-in.

Are you also treating in combination with that lower dose?.

Yes. Thanks, Evan. Look, we understand there's a lot of interest in the dose comparison data. We're just getting the top line results to the FDA and other regulatory authorities. So it's premature to share these data prior to their review and the appropriate conversations.

In regards to the combination trial, I believe you're referring to with checkpoint inhibitors, we're doing a lower dose lead-in, as I've mentioned before, and then layering on top of that dosing the checkpoint inhibitors. So they are then given concurrently going forward..

Okay. Thank you..

Our next question comes from Mohit Bansal with Wells Fargo..

Great. Thanks for taking my questions and congrats on the quarter result. So I have a question regarding the 30%-plus year over decline that we have seen with the -- a couple of biosimilars.

Is it on expected lives 3 or 4 years after launch? And how should we think about the other biosimilars you have in your portfolio? How should we think about the long-term pricing dynamic there? Because it was an expectation that the pricing would probably stabilize after a certain point, but it doesn't seem like that in biosimilar..

Thanks for the question, Mohit. I think what's important to remember when you're thinking at least about U.S. biosimilars is products in the buy and bill or medical benefit side will continue to see price declines over time because of the way in which the average selling price calculation works.

Products on the pharmacy benefit side, so think Medicare Part D products or commercial-insured retail pharmacy products, they are likely to have slower declines in the slope of their net price over time. Now both of those conditions depend on how many competitors for each molecule. So everyone is a little bit different.

But I would hesitate to put a time frame on the class of products. I think you need to look at each one of the molecules. One thing I will say is we've been very clear on where we're going to get growth in our biosimilars portfolio, and that's by launching successive new biosimilars on top of our continuing base of business.

Outside the U.S., biosimilar pricing tends to come down fairly rapidly and then can hold in some of the larger, what we call retail markets. In markets where it's a heavy tender business, prices will continue to decline as long as there are competitors in the market..

Our next question comes from Yaron Werber with Cowen..

I got just a couple maybe. David, the first one on 133, can you comment it's an antibody? Can we assume it's monthly dosing? And then secondly, for 938 against EYLEA, now that there's going to be high-dose EYLEA, the 8 milligrams approved, it's obviously the same underlying drug, just a different formulation.

How does that impact what you need to do to bring in a high-dose 938 to market and how that jives versus the fiscal year '25 potential launch?.

Yes. Let me take the first part on 133. It's -- as I said, it's a multispecific or bifunctional molecule, meaning it's got an antibody component that inhibits the GIPR receptor. And then there's a component that agonizes GLP-1. So as you noted, you can expect antibody-like pharmacokinetics, and we'll be sharing all of that in a month.

But that's what will drive the dosing interval. On 938, let me ask Murdo to comment briefly on that..

Yes. Yaron, we continue to want to be able to have a full complement of competitive biosimilar products that compete effectively with their innovative parent products. And we've, I think, done that very successfully, thanks to the talented team in our formulation and process development organization.

So we feel confident that we'll be able to bring various concentrations across the portfolio as needed. So we're working on that one..

Our next question comes from David Risinger with SVB Securities. Your line is now open..

Great, thanks very much. So my question is on biosimilars timing for 2023, please.

Regarding AMGEVITA, in light of your interchangeability study, which has an estimated completion in January, assuming that succeeds, when in 2023 do you think FDA will add interchangeability to the label? And then is Amgen planning to launch biosimilar STELARA in September at risk if patent litigation remains outstanding?.

Yes. Thanks again for the question. Maybe take the second part first. We haven't made any statements about when we will launch our biosimilar to STELARA, but we're pleased that we've got strong data in hand, and we're pleased that we've got the strength of the Amgen manufacturing network and commercial organization ready to go.

And we'll track that space closely. We expect to be in the first wave of launches on STELARA, EYLEA and SOLIRIS, the next wave of new biosimilar launches. And we expect to be in the market in early Feb in the new year with AMGEVITA. The interchangeability stat is an interesting one. I think over time, that may grow in importance.

But being first with AMGEVITA, we understand it to be of lower priority from payers and PBMs. But we do expect to have interchangeability in a relevant time frame for when the other biosimilar entrants to HUMIRA come into the market..

Next question comes from Robyn Karnauskas with Truist..

Just going to follow up with you on the ENBREL comment ahead of the biosimilar HUMIRA launch. We've heard that ENBREL is often used as a third- or second-line TNF.

And so I was just curious whether -- you've noted that you don't expect further pricing declines, but that part of it is when ENBREL - HUMIRA launches that really you're already having a flow-through HUMIRA get to ENBREL in many cases, and that's why there may not be motivations have to compete on price.

Just sort of clear -- that's a detailed question. Maybe help me understand the dynamics there..

Yes. Robyn, thanks for the opportunity to clarify. I didn't say that we don't expect continued price declines on ENBREL. I said we don't expect the current price declines to be dramatically different going into next year.

So we do expect to continue to concede price on ENBREL as the category is quite competitive, but we don't see the slope of that changing dramatically. And ENBREL is used across a broad range of patient types in rheumatoid arthritis as well as in psoriatic arthritis.

I think what we see is we see a lot of frontline usage still, and we do see some post-TNF frontline usage. So I think that will continue.

Not every patient is going to respond to TNF inhibitor, and many clinicians prefer the well-demonstrated safety and efficacy profile of ENBREL, and we think that will continue despite biosimilar options in the market. So that hopefully clarifies your question..

Our next question comes from Colin Bristow with UBS. Your line is now open..

Hey, good afternoon. Congrats on the quarter. So I'll take another one on 133, if I may. As we think about time line, it took Lilly and Novo around 5 to 6 years to move their lips from sort of Phase I initiation to the market.

Is there any reason at all for us to think that there's any sort of abbreviated path here that you could explore? And just with those sort of aforementioned time lines in mind and the fact that this efficacy bar that we see now could be raised by what are the competitor assets is ahead of you, does this raise the bar for progression to Phase II from your side?.

Yes. Thanks for the question. The -- I think -- let me start with, again, the disease itself, obesity, which is a very heterogeneous disease. Obviously, it's one of the major public health problems globally right now. Our belief is that there are a number of diseases tucked within the label of obesity.

Some patients have primarily cardiovascular manifestations; others, type 2 diabetes; others, mechanical problems. And so as I noted, we will be using our human data capabilities to further understand and potentially segment these populations to determine if there can be a particular benefit in subsegments of patients.

And then I would just remind you of the things that we'll look for in this program as we go forward to see whether we have a differentiated molecule or not, dosing; again, the kinetics, in particular, pidity [ph] and sustainability of weight loss; and then overall tolerability.

Those are the things that we'll be looking at as we take a look at Phase II data and determine as the field unfolds where we go from there..

Our next question comes from Carter Gould with Barclays. Your line is now open..

Great. Thanks for taking the question.

Sorry to beat a dead horse here, but to follow up on the prior question, how important is it that you also pursue diabetes alongside an obesity indication? Or do you feel like you could just go after obesity and that might be able to suffice and work out commercially?.

Yes. Thanks, Carter. That's a question we'll address it as we go forward. But I don't feel that it's essential that this be a diabetes medication. As I said, this is -- obesity powers a large number of diseases, and we're going to guide our development to where we think we get the most effect size..

Our next question comes from Michael Schmidt with Guggenheim..

This is Ted on for Michael. We have [won] LUMAKRAS coming out of World conference with updated data on different combinations you presented, I mean, PD-1 and SHIP2.

How do you think these different combo regimens can be positioned to develop each other? Do you have any updated view? And would you prioritize one over the other with data so far?.

Yes. No, in terms of the combination, SHIP2 checkpoint inhibitor combinations, we're enrolling Phase II trial now with the SHIP2 combination that will guide our development. That's a combination that could potentially be applied regardless of PD-L1 expression levels.

And then as I mentioned, we are exploring in the PD-L1-positive population a low-dose run-in of LUMAKRAS then followed by layering on of the checkpoint inhibitor. And as those trials enroll, I'll provide guidance in terms of when we have data readouts. And those data will determine how we think about the first-line population.

Finally, let me remind everyone again that in the PD-L1-negative population, we're going to be looking at a chemotherapy plus LUMAKRAS combination..

Jason, I see one more participant in the queue. So let's take one last question, after which Bob will make some closing comments..

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

I wanted to ask a two part biosimilar question related just to the U.S. market, and that's what you think uptake will be like in 2 disease areas that are a little different than most.

So in the rare disease space, where you'll have a biosimilar SOLIRIS and then in the eye space with your biosimilar EYLEA, how do you think those will compare to disease areas where we already have precedents, such as in oncology? I know the ice pace is buy and bill. I think rare diseases is not buy and both, but if you could compare those, please..

Yes. Thanks, Tim, for the question. As I mentioned before, you do have to look at each product slightly individually in the circumstances that would generate or drive uptick.

If we go back to the oncology biosimilars, we had an assumption at the beginning of those products that patients may not get switched on the maintenance phase of their treatment, so mid-cycle or mid-course of treatment.

And what we saw, at least in the buy-and-bill space, for both MVASI and KANJINTI that -- was that oncologists were comfortable with the quality of the Amgen biosimilars and by the fact that they had access to our medical teams and our salespeople who are out there calling on them to help them understand the data behind our biosimilars.

And so we did see mid-course of treatment switching to our biosimilars. So I think the threshold for what we thought would be a hesitancy on the part of the subscriber was different. And I think that we're looking closely at both SOLIRIS prescribers and EYLEA prescribers.

And we've done some in-market research with both customer types, and we feel good about our opportunity to create value for the health care system by offering biosimilar alternatives to those 2 branded products. And we feel good about our chances of having a decent uptake on both..

Okay. Well, again, let me thank all of you for joining our call. We appreciate your interest in Amgen. And let me just end by saying that we remain focused on ending the year strong and positioning ourselves for a good '23 and beyond.

We look forward to having a chance to engage with you again here in a few short weeks or Monday and then in a few short weeks thereafter, at various conferences. So thank you and we'll look forward to seeing you soon..

Thanks, everybody..

This concludes our 2022 Q3 earnings call. You may now disconnect..