My name is Julianne, and I'll be your conference facilitator today for Amgen's Fourth Quarter 2023 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 Instructions] I would now like to introduce Justin Claeys, Vice President of Investor Relations. Mr. Claeys, you may now begin.

Thank you, Julianne. Good afternoon, and welcome to our fourth quarter 2023 earnings call. Bob Bradway will lead the call and be followed by a broader review of our performance by Murdo Gordon, Vikram Karnani, Jay Bradner, I am pleased to welcome and he is joining us for the first time on our quarterly earnings call, and Peter Griffith, Dave Reese, will also be available during the Q&A session. Given the timing of these Horizon Therapeutics acquisition close, the results as shown in our press release and slides include contribution from the Horizon business from October 6 onwards. For the avoidance of doubt, this will also be the basis for our filed financial results. To supplement this information, Vikram will also provide sales information for these products for the full fourth quarter, including the first week of October as further context in his remarks. Through the course of our discussion today, we'll use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement, and please note that actual results can vary materially. With that, over to you, Bob.

Okay. Thank you, Justin, and let me thank all of you for joining our call. 2023 was another year of performance and progress for Amgen, further positioning us to deliver attractive growth through the end of the decade and beyond. Last year, we delivered double-digit volume growth in all four quarters with balanced growth across products and geographies. 18 [ph] of our medicines generated record annual sales, including Repatha, Prolia EVENITY, TEZSPIRE, BLINCYTO, KRYSTEXXA and UPLIZNA. The acquisition of Horizon, which is completed on October 6, gives us a significant new rare disease business that now stands as a fourth pillar of growth alongside our leading general medicine, oncology and inflammation businesses. The medicines we acquired are all very early in their life cycles and by leveraging Amgen's world-class biologics manufacturing, decades of experience in inflammation and our extensive global presence, we believe these products have the potential to reach many more patients around the world. Last year, we also advanced the deepest and most diverse pipeline in our history with promising molecules at all stages of development across our four pillars of growth. We anticipate well over a dozen significant pipeline milestones this year. I'll touch on a few. In General Medicine, we'll generate Phase II data this year for our lead obesity molecule, MariTide, and we're excited, of course, to learn more about this asset. We're also advancing a number of early-stage assets in this space. In Oncology, we have a June 12 PDUFA date for the FDA to complete its priority review of Tarlatamab as a third-line treatment for small cell lung cancer. Tarlatamab is the first bispecific T cell engager shown to be effective in addressing a major solid tumor. In this case, one for which there has been no new treatment in decades and which…

Thanks, Bob, and I'm very pleased with our performance in 2023. Execution was strong across the business, resulting in record sales in the year for 18 brands and robust volume growth across the four pillars of our business. Full year product sales increased 9% year-over-year. Volume growth was 15% with strength across our regions. U.S. volume growth was 14% and volume growth in our Europe, Latin America, Middle East and Canada region was 10%. Asia Pacific continues to be our fastest-growing region with 41% volume growth. These results include $954 million of sales from the legacy Horizon portfolio from the period of October 6 through December 31. I'll start with our General Medicine business, which includes Repatha, Prolia EVENITY and Aimovig. Overall revenue for these four products grew 15% year-over-year in the fourth quarter and 17% for the full year, driven by 18% and 20% volume growth, respectively. Repatha sales increased 25% year-over-year in the fourth quarter with volume growth of 35%, partially offset by lower net selling price. Outside of the U.S., we saw 25% volume growth with strength across our regions. In the U.S., volume growth of 48% was driven by a 66% increase in the number of new patients starting treatment. We saw a decline in net selling price in the U.S., primarily driven by new formulary coverage. We expect this additional coverage to lead to strong volume growth, which will more than offset declining net selling price. In addition, some payers have recently removed prior authorization for some patients, which will further ease their access to Repatha. We remain committed to the urgent need to educate physicians and patients on the importance of LDL-C lowering to reduce the risk of cardiovascular events. In the U.S., we activated more than 20,000 new prescribing physicians in 2023 in…

Thanks, Murdo. I am glad to share an update on our rare disease business now that we are 4 months past due close. We are now fully operating as part of Amgen with integration activities ongoing. As Bob has mentioned before, we are excited to be Amgen's fourth pillar of long-term growth. I wanted to make sure you're aware that we are not reporting the full quarter in press release and slides, which reflects sales from October 6 onwards and totaled $954 million. This excludes $41 million of sales that occurred in the first week of October prior to deal close. For the full quarter, our rare disease brands from Horizon delivered product sales of $995 million, representing 6% year-over-year sales growth. Throughout the remainder of my remarks, I will reference full quarter product sales. TEPEZZA, and IGF-1R monoclonal antibody for patients with thyroid eye disease generated $467 million of sales during the entire fourth quarter, representing 3% quarter-over-quarter growth. This is the third quarter in a row of quarter-over-quarter growth for TEPEZZA with the growth largely driven by the U.S. We saw a number of positive leading indicators, including a record number of unique TEPEZZA prescribers, total patient enrollment forms and patient starts in 2023. Additionally, thanks to our efforts, we've been able to generate favorable medical policy changes for greater than 50% of U.S. covered lives, and we expect to continue this momentum throughout 2024. We continue to see approximately 100,000 patients with moderate to severe disease in the U.S. who could benefit from TEPEZZA with the majority of these patients in low clinical activity score settings. Given positive leading indicators and high unmet need, we see a long-term growth opportunity for TEPEZZA in the U.S., while also recognizing there is some time lag between our execution efforts…

Thank you, Vikram, and good afternoon, everyone. I'd like to take a minute to convey how thrilled I am to join the Amgen R&D organization and its leadership team. The creativity of our discovery research, expert and expedited clinical development, most authoritative biomanufacturing organization in the industry, all were well known to me before joining. But now on staff at Amgen, I appreciate the strong sense of service, the patients facing serious illness, the like-minded commitment, growing the impact of our medicines and our business and the shared conviction in this remarkable portfolio of potential first-in-class and best-in-class medicines. In 2023, we executed with speed across our clinical pipeline, achieving excellent enrollment in key programs and setting up 2024 as the year with significant data readouts across the portfolio for medicines with the potential to transform patient care. Key highlights in 2023 included the delivery of promising data from four key oncology assets and the attainment of three breakthrough therapy designations in oncology. We initiated pivotal Phase III studies for Tarlatamab in small cell lung cancer, LUMAKRAS in non-small cell lung cancer and colorectal cancer, along with dazodalibep in Sjögren's syndrome. In General Medicine, as previously disclosed, top line 52-week data from the 592 patient MariTide Phase II study is expected by late 2024. Leveraging the durability of weight loss observed in Phase I and rapid enrollment enjoyed in Phase II, we recently added a part 2 to this study, which explores durable weight loss beyond 52 weeks. Our planning for a comprehensive Phase III program across multiple indications remains on track. Lastly, you may have seen that yesterday, Nature Metabolism published manuscript from Amgen R&D that provides the integration of MariTide preclinical and Phase I data. Beyond MariTide, our obesity strategy encompasses several assets with AMG 786 in Phase…

Thank you, Jay. We're pleased with our strong execution and performance in the fourth quarter and for the full year 2023. In the fourth quarter, total revenue of $8.2 billion grew 20% year-over-year and non-GAAP EPS of $4.71 grew 15% year-over-year. For the full year, we delivered total revenue of $28.2 billion, 7% growth year-over-year and non-GAAP EPS of $18.65, 5% growth year-over-year. As a reminder, both Q4 and the full year results include Horizon's results beginning October 6 when the acquisition closed. So our financial results will exclude approximately 1 week of Horizon's results from our fourth quarter results. I'll review the details of our fourth quarter and full year financial results before discussing our outlook for 2024. The financial results are shown on Slides 54 to 56 of the slide deck. Turning to our fourth quarter's total revenue of $8.2 billion. We saw product sales increased 20% year-over-year, driven by volume growth of 23%, offset by net selling price decline of 3%. Excluding the impact of Horizon, product sales increased 5% year-over-year driven by volume growth of 9%. Full year total revenues of $28.2 billion grew 7% year-over-year. Product sales increased 9% year-over-year, driven by 15% volume growth. Other revenues decreased 16% year-over-year, primarily due to lower profit and cost sharing from our COVID-19 collaboration with Lilly in 2022. Strong expense discipline resulted in a 50% non-GAAP operating margin as a percentage of product sales for the full year 2023. While we continue to focus on both internal and external innovation, investing $4.7 billion in our pipeline and $27.8 billion in our acquisition of Horizon. With product sales volume growth at 23% in Q4 and 15% for the full year, we still efficiently manage the operating expenses of the business. Q4 non-GAAP operating expenses increasing 18% year-over-year, while…

Okay. Thank you. Let's open the line, and we'll take questions from our callers. And Julian, why don't you remind them of the procedures so we can get through these questions here efficiently for everyone.

Thank you [Operator Instructions] Our first question comes from Michael Yee from Jefferies. Please go ahead. Your line is open.

Hey, guys. Good afternoon, and thanks for good results and good guidance. We had a question on obesity. On 133, of course, you had the publication yesterday I feel like it was the most scrutinized Phase 1 publication. But maybe you could just talk to - maybe Jay could talk to your interpretation of some of the markers, for example, lipids, A1C, blood pressure and all that kind of thing. And maybe talk about your confidence about the profile versus competitors? Thank you so much.

Yes. Thanks a lot, Michael. We really appreciate the consideration the Phase 1 paper is receiving from the community. It's exciting to report these data. For those who haven't seen it, this was a randomized, double-blind, placebo-controlled study, 49 patients, looking at safety, PK, PD, single ascending dose, 7 cohorts, multiple ascending dose 3 cohorts, 3 monthly doses, patients with obesity being migrated than 30. And we were quite pleased with the outcome. Looking at the 420-milligram dose as an example, which was the highest dose study, 14.5% weight loss at only day 85. And moreover, quite durable coming off of that medicine out to 150 days, all with relatively mild gastrointestinal side effects. And so to answer your last question first, we find the Phase I data, which we're pleased to share with the community to be quite supportive of our ongoing work to develop this medicine to the greatest possible benefit of patients suffering from obesity. Now you've asked questions around some of the measurements on this study, lipid, blood pressure and A1C. And I would just caution that this is a Phase I trial, the numbers are very small, that the duration of treatment is rather short. But even with all of those caveats, while hard to draw conclusions from such small numbers, especially labile measurements like blood pressure and lipids, all are directionally favorable. And so we have - we take no concern whatsoever from those measurements on the study.

Okay. Thank you. Those are the questions. Yeah.

Thank you, Michael. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead. Your line open.

Good afternoon. Thanks for taking my question. Another one here on the obesity program. So post the published Phase I data, how are you thinking about differentiation on GI tolerability? Is the dose range being evaluated in the Phase II study similar to that in the Phase I? Thank you.

Yes. Thanks for the question. I'll take this one as well. As you may or may not know, the Phase II study, which is ongoing at present and going very well, explores 11 dosing cohorts with relevant placebo controls. And through that study, we'll have a chance to gain an experience with a longer exposure to MariTide dosed in different ways. We've recently added a part 2 to this study that will allow us to explore even more durable weight loss beyond 52 weeks enabled by just very rapid enrollment. And these four dosing cohorts will go on to test dose level and even less frequent dosing schedules than monthly. And so these Phase II data, even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into Phase III clinical investigation.

Yes. The only thing I would add is we're starting from a basis of a monthly dosing cadence and schedule. And so the additional dosing cohorts would look at potential dosing schedule beyond monthly. And the data are pretty clear in the market right now that the GI toxicity or GI side effects are generally related to the day of dosing of the GLP-1s, which are dosed weekly. We see some of that same GI side effect profile in kind of the first dose part of the dose titration. But there's an opportunity here to potentially spread the dosing intervals out further and further improve tolerability in our program. And as Jay clearly described, we've got all of the different aspects of that being studied in the Phase II program.

Thanks, Julianne. We'll go to the next question.

Thank you, Salveen. Our next question comes from Jay Olson from Oppenheimer. Please go ahead. Your line is open.

Hey, thank you so much for taking a question, and congrats on the progress. Another question on 133. Talk about whether or not that we see later this year will include patients from two of the study? And do you think it's possible that 133 could be dosed twice every 2 or 3 months? And also, if you could just comment on the rollover rate of patients from Part 1 to Part 2? Thank you.

Jay, could you catch all that some of what Jay asked was broken up at the beginning...

The third part was a little bit broken up of your question. I heard a better explanation of part two frequency of dosing. And then I did not hear your third part.

If you just comment on the rate of patients rolling over from Part 1 to Part 2? Thanks.

Okay. Yes. Thank you for the question, Jay. Let me give a little bit of context on this Part 2 study that I think will help answer them. In part 2, the intent is to really look at durable weight loss beyond 52 weeks. And so by durable weight loss, patients eligible for Part 2, which begins at the end of 52 weeks, will be responding to this medicine. And then they'll be rerandomized to four cohorts that will test dose level. And again, this even less frequent dosing schedule. We have not disclosed the granularity on the dosing schedule. This is a competitive environment. But we're afforded this chance because the ADC, the antibody core of MariTide, like so many immunoglobulin therapeutics allows for the opportunity to use it much less frequently. The rate of patients rolling over to Part 2 will be established as the Phase II study continues to progress this year.

Thank you, Julianne. Next question.

Thank you, Jay. Our next question comes from Chris Schott from JPMorgan. Please go ahead. Your line is open.

Great. Thanks very much. Just maybe to pivot over to TEPEZZA [ph] for a question. Can you just talk a little bit about the dynamics for 2024? It seems like the products come back to growth. But I'm just trying to get a sense of now that Amgen owns the asset and has more kind of time with it. What are your top priorities? And how do you think about continuing to kind of grow the new patient base here? Thank you.

Sure, Chris. Maybe we'll take it in a couple of parts. But Vikram, share your thoughts first.

Yes. Thank you for the question. I think if you focus a little bit on what are the underlying factors that are driving TEPEZZA growth, we saw a record number of unique TEPEZZA prescribers. We saw an increase in patient enrollment forms and patient starts. In addition, we've made pretty significant progress on payer coverage, as we've seen our covered lives have now increased to greater than 50% of U.S. covered lives. And that's important, educating some of those stakeholders on the new clinical data updated indication, it continues to drive uptake across the full spectrum of TED patients. And finally, what holds all of this together is a really robust patient service model that supports patient access. I think we continue to make progress and execute towards each one of these important leading indicators. And we shouldn't forget that we - there is still low penetration of the approximately 100,000 patients that can be eligible for this medicine in the U.S. alone. Now, just one last point here is that as we've noted before, there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers. As we said before, it can take up to 90 days once a patient is identified for therapy for that patient to actually get on therapy. But we're pretty happy with all of our leading indicators and the execution that we have seen coming out of last year.

And Chris, the only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well, and I think he characterized that well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of TED patients. So all in all, I feel excited about the rare disease pillar that we've established and the role that TEPEZZA will play in that.

All right. Next question, Julianne?

Thank you, Chris. Our next question comes from Evan Seigerman from BMO Capital Markets. Please go ahead. Your line is open.

Hi, guys. Thank you so much for taking my question. I wanted to touch on TEZSPIRE specifically in COPD. How are you planning to differentiate given the pretty competitive data we saw from Dupixent [ph] And how should investors be looking at this data from an efficacy bar? Are there nuances in this trial that need to be clarified that might make it harder to do an apples-to-apples comparison?

Yes, and thanks for the question. Murdo, why don't I start and then you add on. So it's a great and timely question. The Phase II COPD study of TEZSPIRE, we expect data in the first half of this year. This was a big study, 337 patients, moderate to severe COPD. They're having exacerbations despite being on triple therapy. And so reflective of the current unmet need inadequacy of therapy for patients with COPD. This is a slightly broader population than Dupi that we're studying here. We're totally on track for the readout. We quite like the mechanism here. You must know that TSLP [j works as a signaling factor upstream and by blocking it with our unique biotherapeutic, we block TSLP IL-25, IL-33 signaling. TSLP so many cell types modulating this airway Type 2 response. By hitting TSLP upstream, we think we can really have an impact on the disease biology. We see TSLP-elevated in the serum patients in bronchial mucosa [PH] and bronchoalveolar lavage fluid. It's released by airway epithelium. There's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature. And by looking at the broader population than they did with Dupi, we have a chance to really figure out who the responder is. Murdo?

I think you've covered all the bases. I would just add this, Evan, that with the unique and differentiated mechanism, as Jay described, we hope we can treat a broader population of patients than perhaps the currently available therapies. And we also recognize that there are patients who are refractory to those currently available therapies, and we would obviously want to understand if they would be responders to TEZSPIRE. I think we've got strong commercial capabilities, including with our partners at AstraZeneca and are well positioned to take a product like this into the market if we're successful in Phase III.

Okay. All right. Thank you, Julian. Next question?

Thank you, Evan. Our next question comes from Umer Raffat from Evercore ISI. Please go ahead. Your line is open.

Hi, guys. Thanks for taking my question. I wanted to touch up on AMG 133 as well, two parts question. First, on the discontinuations at the high dose, we know five out of eight did not finish the full duration of the study, but there was a second arm also of this high dose 420-milligram with 10 patients, which was not reported. This was the one with digital tools. Could you speak to the discontinuation rate in that arm? So this a 420 done separately, which is not part of paper? And secondly, I know there's a case of liver enzyme elevation of the 280-meg dose, but this patient also had COVID. Could you perhaps speak to the timing of liver enzyme elevation relative to the COVID episode? Thank you very much.

Yes. Thanks, Umer. I won't be able to provide patient level insights to the Phase I study at this time, but I do appreciate your question and your interest in the report. I'll speak to the dropouts of the Phase 1 at the 420-milligram dose, which was four out of the eight patients. First, it's notable to say that the high-dose cohort in the multiple ascending dose receiving the three doses of 420 experienced real weight loss, real benefit of 14.5% after these three monthly doses. This was the group that proved actually quite durable out to day 150. Four subjects decline to participate in this clinical study setting largely from logistical reasons. The AEs and other characteristics were comparable to all the other patients in the study. Now the second question around the digital group, I don't have insight into that. Dave, do you...

No. I mean we can get back to you on that. I don't know that we reported that - those data and the discontinuation rate.

Julianne, next question.

Thank you, Umer. Our next question comes from Colin Bristow from UBS. Please go ahead. Your line is open.

Good afternoon and thanks for taking the questions. Maybe a couple more on MariTide. First, could you provide some insight into the dosing? I mean, obviously, these are pretty large doses. And if we look at like Repatha for 20 milligrams takes over 5 minutes by infusion or 3 infective injections. So I was wondering if you could give any insight there. And then in terms of the relative affinity for gip versus GLIP [ph] MariTide seams to have preferentially favor GLIP much more than competitor molecules. And so do you think the ultimate clinical profile is more closely going to resemble that of a long-acting glip-1 versus competitive git GLIPS [ph]? Thanks.

Yes. Thanks, Colin. I appreciate the deep consideration of the molecule, especially. I'd start by saying, I don't regard these doses as high. I'm new here, but 420 milligrams for biotherapeutic that's an antibody drug conjugate with a peptide antibody ratio 2:1 seems well in scope for a modern biotherapeutic product. I don't need to tell this community paying so close - such close attention to Amgen that this is a very sophisticated biotherapeutics organization. And on the manufacturing side, just every patient, every time. And we have all the capabilities necessary to deliver this medicine at whichever of these three or other dose and schedule we arrived at. So no concerns there for me whatsoever. Regarding the balance of the pharmacology, you do invoke a difference between our medicine and medicines developed by pure pharmaceutical companies. Namely mechanistically the core antibody of MariTide inhibits the GIP receptor, whereas these other peptide medicines agonize it. We feel very secure in our choice to inhibit that receptor supported by just the finest level of experimental data available experiments of nature that genome-wide association studies in very large populations have pointed to a need, an opportunity to inhibit the gift receptor to deliver lower BMI as observed with variance in that receptor and downstream signaling pathways that correlate with reduced body mass index in large populations. As to the balance, which you asked, between inhibition of GIP receptor and agonism of GLP-1, these are very difficult measurements to make in humans, but our modeling suggests that with the therapeutic doses and exposures that we observe that we're achieving both.

And Colin, this is Murdo. I would just add that from a patient experience perspective, we've learned a lot from other biologics. And Amgen has a world-class process development, manufacturing and device team, and we've done a lot of work on this one, and we anticipate a very positive and simple patient experience on at least a monthly dosing schedule. And we've learned a lot from Repatha specifically, and there's more to follow on Repatha from that, but we continue to work to improve patient experience with our biologic injectables.

Just as we go to the next question, let me observe that we're almost up to the hour that we actually all to set aside, but I know we still have quite a few questions in the queue. So we'll try to get one question for a caller here and get through. We'll stay through the queue of calls or questions rather that's still waiting for us, but I know some of you may have to drop. So let's move forward, Justin.

Julianne. Next question please.

Thank you, Collin. Our next question comes from Yaron Werber from TD Cowen. Please go ahead. Your line is open. Q – Unidentified Analyst: All right. Great, thanks. This is Brendan on for Yaron. Thanks for taking the question. Just a quick one from us. Actually, based on the data you've seen so far and maybe some feedback from physicians that you've heard, this is on UPLIZNA. Where do you kind of see UPLIZNA fitting into maybe the MG treatment paradigm given all the competition there, but maybe more to the point, how you're thinking about expansion opportunities given all the different autoimmune indications you could potentially pursue? Just trying to kind of understand how you see longer-term growth there?

First, why don't we ask Vikram, just to address the performance of the product right now in NMOSD. And then a combination of Jay and Dave can talk about the other activities or other potential applications.

Yes. Thanks for the question. Yes, UPLIZNA is actually growing quite nicely and quite well in NMOSD. As you know, it is now the fastest-growing biologic in NMOSD. We continue to execute across a variety of fronts. I mean, we're - we see this product nicely positioned versus as it's appropriate for NMOSD patients and within the competitive environment that we operate in. We've continued to make significant progress over the last 18 months or so, maybe even longer of continuing to drive more growth with newer prescribers and even depth with existing prescribers. So the product continues to do well. And I think we hope to continue to deliver good execution on this medicine in NMOSD. Maybe, Jay, you want to talk about the second question?

Yes. No, I'm happy to. As you may know, on a hematologist, I think CD19 is a terrific target. It's expressed really on all B cells and spares plasma cells. And therefore, considering indication expansion, as you've asked, there's a large number of diseases that could potentially be approached with UPLIZNA to the real benefit of patients with unmet need, far beyond the application of the prevailing CD20s that target just a subset of B cells. This is not lost on our team, and we're working through indication expansion priorities presently.

Julian, let’s got the next question.

Thank you. Our next question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Great. Thank you very much for taking my question. I have a question regarding the subcutaneous delivery of TEPEZZA. You do have a plan to initiate a Phase III study. Can you talk a little bit about which technology you are using? Is this with the pre-existing Halozyme technology? Or are you using something else for this development? Thank you.

Sorry, I had trouble understanding your question.

The question is what technology we're using for the subcutaneous injectable form of TEPEZZA?

Maybe I'll jump in. Mohit, we're not commenting at this point on the provider. We just said that we're going forward with the subcu.

Okay, Julian, we’ll go to next question.

Thank you, Mohit. Our next question comes from Geoff Meacham from Bank of America. Please go ahead. Your line is open

Hey, guys. Thanks for the question. Another one on 133. When you think about the Phase III program, I just wanted to know what sort of informs the next indications you're going to go after? Is it unmet need? Is it the potential for differentiation on 133 and the timing of that, do you think that you'd want to have the Phase II data in hand? Or is this something that you could roll out sort of that risk? Thank you.

Yes. Thanks for the question, Geoff, really appreciate it. As you know, obesity is a major public health crisis, maybe 40% of Americans with a BMI over 30 massively costly. So a huge burden to the global third-party payers and societies. The obesity-related disease list is quite long and expanding from cardiovascular disease and heart failure, type 2 diabetes, obstructive sleep apnea, NASH and AFLD kidney disease. These are chronic conditions that really demand medicines that can deliver durable and chronic weight loss. And so we think we have a really strong offering for these obesity-related diseases rising in our Phase II program, as you know. And obesity has a strong genetic component and we locked on to gipper [ph] inhibition based on genetic insights. So the opportunity space is quite large. You asked the question what indications and perhaps even in what sequence. And when we have all the requisite data, we'll remark in due course. But we intend all indications where this dual mechanism can improve public health. And we are actively planning and on track for an expansive Phase III program.

And in terms of - Dave, you want to add the regulatory piece?

Yes, I think -- Geoff, this is Dave Reese. I would just add that we're planning a very expansive Phase III program. So you can expect to see multiple indications move forward in parallel. And as Jay indicated, as we start to see data, we will begin launching those trials, and we'll discuss them. And then in addition, as you're aware, regulatory authorities around the world require a certain body of safety data before Phase III launches. And so of course, we will be compliant with that. But our goal is to launch Phase III as quickly as possible once we have the requisite data set and regulatory approval.

Great. All right. Julian, we'll go to the next question, please.

Thank you, Geoff. Our next question comes from David Risinger from Leerink Partners. Please go ahead. Your line is open.

Yes. Thanks very much. So I have another question on AMG 133, please. Could you add some more color on your expectations for the impact on blood pressure and lipids in Phase II, specifically whether you anticipate tirzepatide-like efficacy on those metrics? Thanks very much.

Yes. Thanks, David. I mean we're making all these measurements, and I'm not going to try to forecast the outcome of that pharmacology at this time. As you've seen in our Phase I program, the medicines very well tolerated, delivering durable weight loss and benefit without significant excursion of some of those measurements. I just think it's too early to try to answer your question, and we'll have all that data at the end of the first part of Phase II towards the end of this calendar year.

And the best extrapolation that you can have is from the preclinical data that were just published, I urge you to take a look at that.

Okay. Julian, we’ll go to next question, please.

Thank you, David. Our next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead. Your line is open. Q – Unidentified Analyst: It's Ege [ph] on for Michael. Thanks for taking our question. A quick one on [indiscernible] Can you talk about your plan of data disclosure this year and your current thinking on the potential registration path? How do you think about the positioning of this agent relative to some of the other emerging agents based on different mechanisms such as ADC or AR degradors in prostate cancer? Thank you.

Yes. Thanks for this outstanding question, Michael. And Zalaritamag [ph] is a very interesting and exciting molecule for those on the call. This is a steep on CD3 bispecific. We have been studying this in advance castrate-resistant prostate cancer. We have expanded a cohort in the Phase I monotherapy. We're opening to reduce monitoring as well as - as you invoke the existing and novel androgen receptor modulators integrators, we're exploring combinations with novel agents in that domain as well. The priorities for the program right now are to establish reduced monitoring. This will be important to reach just all the patients who can benefit. We're looking at the feasibility of reduced monitoring. We have a great experience with these T-cell engaging bispecifics as well as the plausibility of outpatient therapy. The approach to the regulatory path will present in due course. There'll be no surprises there. The path to bring medicines to patients with castrate-resistant prostate cancer alone and ultimately, in combination is well worn, thankfully, and we know how to deliver there. You asked about differentiation in other medicines. These are often apples to oranges comparisons. We have looked at that, of course, and we really like the offering of Zalaritamag. The patients treated on our study had quite advanced disease, even more advanced disease than the demographics of the patients as reported on other mechanism medicines such as radio ligand therapies.. And the response rates we're seeing are really clinically meaningful to patients. And that gives us great encouragement to develop the medicine more ambitiously in the next few years.

Jay, in terms of the data sharing, do you want to share...

For data availability - as Jay mentioned, we're nearly complete in terms of dose expansion enrollment. So as those data roll forward over the course of the year, we'll provide guidance as to when we might have the next look at that data. But that's probably the next meaningful set of data we'll get a look at either later this year or early into next year.

Julianne, next question, please.

Thank you, Michael. Our next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.

Thank you very much. So Eli Lilly today made a couple of sets of comments about this topic of GIP agonism versus antagonism and they also weighed in on the data you published yesterday. And I'm wondering, in as much as you heard that or read those comments, is there any context to add or anything that's factually incorrect or anything to refute because they covered quite a few points, and they continue to express their view, which is agonism is the best way not antagonism?

Tim, this is Jay. I open it up to anyone else who wants to contribute to this. I don't believe that - yes, that engaging in the dialogue around this is as much to the narrative. Rather, I'd say that the argument for GIP receptor antagonism comes from just the highest level of scientific data, the human experience across populations with 1 million patients studied, among those who have variations in the genes associated with this pathway where that variation is directionally inhibitory, the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Okay. Julianne, next question, please.

Thank you, Tim. Our next question comes from Robyn Karnauskas from Truist Securities. Please go ahead. Your line is open. Q – Unidentified Analyst: Hi. Thanks so much for taking the question. This is Nicole on for Robin. So on Daxdilimab, targeting ILT7 business, can you talk about your level of confidence in this target in light of the competitive landscape? And would you expect to see near term from safety and efficacy?

Sure. Jay and Dave?

Yes. Well, it's very early days with this medicine. There is strong preclinical support from the published literature and our own preclinical work. It's nicely for patients, a very competitive landscape, but this is the earliest phases of clinical investigation. And so we're going to approach this with total aquapoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying.

Yes. I would say the target, as you mentioned, is one that helps control some of the central signaling that drives some of the autoimmune diseases that are being investigated here. And at this point, I think it's all efforts towards generating the clinical data.

Okay. Jullian, next question please.

Thank you, Nicole. Our next question comes from James Shin from Deutsche Bank. Please go ahead. Your line is open

Thanks for taking our question. I have one for Jay. I just kind of want to piggyback on what Tim was alluding to. The GIP antagonism versus agonism, I'm looking at the Nature paper, it looks like 133 420-milligram dose has a slight blip in triglycerides that eventually fades, but it does seem like antagonism is behaving a little differently from the literature for agonism. Is it too early to chalk it up to antagonism versus agonism in your view? Just wanted to get your thoughts there.

The short answer is it's too early to talk it up to antagonism versus agonism. As I said before, and I meant it, that these lipids are labile and indirect biomarker of this pharmacology. This is an early stage study that had 1 or 3 monthly doses of the medicine. And so we are not reading anything into the lipids conclusively from this trial. We are making all these measurements in the active Phase I.

Great. Then I think we have time for one more, Julianne.

Thank you, James. Our last question will come from Carter Gould from Barclays. Please go ahead. Your line is open.

Good evening. Thanks for taking the questions. Maybe just one on 786. Can you walk through exactly what's sort of driving - maybe let me take it back. Maybe first kind of if you could outline sort of how you're setting expectations there? And any color on what's driving the delay there? It seems like it's taking a long time to enroll 72 patients? Thank you.

Sure. No, thank you for your question. For the broader group, AMG 786 is an oral medicine being developed for obesity. It is not an increasing that we've not as yet disclosed this target or pathway. This study is progressing fine. The readout of the Phase I is on track for the first half of 2024. We've completed initial dose escalation cohorts, and we're just collecting and analyzing data, expecting the readout in the first half of this year.

And Julianne, we're going to turn it back to Bob for some closing remarks.

Okay. Thank you all for joining the call. As you heard, we're excited about the opportunities that we see for growing our business across all four of our pillars, general medicine oncology, inflammation in rare disease. Last October, we shared an in-depth look at oncology in connection with the ESMO medical meeting. And we plan to do an introductory review of rare diseases and our rare disease pillar in late February to give you more information about the medicines that we already have on the market as well as some of those that are advancing through our pipeline. So we're encouraged by the questions that we heard on this call about those molecules, and we're excited about them and their prospects. So we'll host a call, which IR will share with you here over the next few days and look forward to having that opportunity. In the meantime, again, thank you for your support, and we look forward to talking to you at the Rare Disease Day at our first quarter results call. Thank you.

This concludes our 2023 Q4 earnings call. You may now disconnect.+