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spk20: I would now like to introduce Justin Claes, Vice President of Investor Relations. Mr. Claes, you may now begin.
spk14: 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 Myrto Gordon, Vikram Karnani, Jay Bradner, who I'm pleased to welcome and 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 the Horizon Therapeutics Acquisition Close, the results as shown in our press release and slides include contribution from the Horizon business from October 6th 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 is in his remarks. Through the course of our discussion today, we will 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.
spk04: 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 of our medicines generated record annual sales, including Rapatha, Prolia, Avenidae, Aspire, Linsido, Crisstexa, and Uplizno. The acquisition of Horizon, which was completed on October 6th, 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 and 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 two 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 12th PDUFA date for the FDA to complete its priority review of Tarlatumab as a third line treatment for small cell lung cancer. Tarlatumab is the first bispecific T cell engager shown to be effective in addressing a major solid tumor. In this case, one for which there's been no new treatment in decades and which today has a five-year survival rate of just 3%. We're studying Tarlatumab in earlier lines of treatment and hope over the fullness of time to be able to serve the tens of thousands of patients diagnosed with small cell lung cancer each year in the US and major markets around the world. We've done this very successfully now with our first bite, Blincyto, which has steadily moved into earlier lines of treatment for acute lymphoblastic leukemia, and we'll take the same approach with yet another promising bite, that being xaluridomig in prostate cancer. In inflammation, we'll have phase three data from Rocatinlumab and atopic dermatitis from the first of what are now eight trials in the ROCCAT program. And in rare disease, we'll have phase three data from Uplizna and Myasthenia Gravis, an IgG4-related disease. At a time when a rapidly aging global population needs more innovation, Amgen is delivering, both with the medicines we have on the market today and with the promising new medicines that are advancing in our pipeline. We're also excited by the rapid convergence of biotech and tech, which is enabling us to innovate more quickly and confidently. We've been preparing for this hinge moment for more than a decade and recently named Dave Reiss as our first ever Chief Technology Officer to ensure that we're capitalizing on technologies like generative artificial intelligence, not just in R&D, but across the entire company. Succeeding Dave as Amgen's head of R&D is Jay Bradner. Jay is a physician scientist and a seasoned R&D leader, having served for many years as president of the Novartis Institutes for Biomedical Research. Jay previously also served as a faculty member at Harvard Medical School and prior to joining Amgen was a practicing oncologist at the Dana-Farber Cancer Institute. We're delighted to have Jay on board and excited by the work that he, Dave, and the rest of our team will do together to accelerate innovation at Amgen for the good of patients and for the long-term growth of our business. With that, I want to thank our 27,000 employees around the world for their many contributions to our success and let me now ask Murdo to talk about our commercial performance in 2023.
spk03: Thanks, Bob. 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. US 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 6th through December 31st. I'll start with our general medicine business which includes Rapatha, Prolia, Evenity, and Amovig. 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. Rapatha 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 US we saw 25% volume growth with strength across our regions. In the US 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 US 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 pairs have recently removed prior authorization for some patients which will further ease their access to Rapatha. We remain committed to the urgent need to educate physicians and patients on the importance of LDLC lowering to reduce the risk of cardiovascular events. In the US we activated more than 20,000 new prescribing physicians in 2023 in both the primary care and cardiology settings. And while we're pleased with this progress we'll continue to work tirelessly for the many, many more patients around the world who can benefit from Rapatha. Transitioning to bone health, the vanity had record sales of $318 million for the quarter driven by 39% volume growth. Osteoporosis disproportionately impacts postmenopausal women and the diagnosis and treatment rates for these patients are low. In the US only 6% of very high risk patients with osteoporosis are treated with a bone builder creating an urgent need for treatment with an effective therapy. Venity is an important therapy to address this unmet need as it is the only bone builder that works with the body's natural ability to increase bone formation and also decrease bone resorption. We see strong growth potential for vanity and will continue to apply our proven experience in bone health to ensure it reaches all the patients who need it. Prolia sales grew 12% year over year to a record $1.1 billion for the fourth quarter. Volume growth of 10% was supported by real world evidence reaffirming prolia superiority in reducing fracture risk when compared to lendronate in treatment-naive patients with postmenopausal osteoporosis at a high risk of fracture. Moving to our oncology business which includes Blincyto, Lumicraz, Vectabix, Kiproas, Endplate, and Xjiva. Sales of these 6 innovative products grew 5% year over year for the fourth quarter with 3% volume growth. Full year sales grew 12% year over year driven by 12% volume growth. Blincyto sales grew 47% year over year to a record $241 million for the fourth quarter. Volume growth of 55% was supported by broad prescribing to patients with acute lymphoblastic leukemia in frontline consolidation treatment. Long term we see significant growth potential for Blincyto from utilization earlier in the frontline as part of induction treatment. Lumicraz sales increased 8% year over year for the fourth quarter. We see future growth opportunities for Lumicraz coming from launches in new markets and additional indications. Vectabix sales increased 5% and Kiproas sales grew 8% year over year for the fourth quarter both driven by volume growth. Endplace sales decreased 18% year over year for the fourth quarter driven by volume decline related to timing of orders placed by the U.S. government partially offset by volume growth across our regions. Full year sales increased 13% primarily driven by volume growth including U.S. government orders. Excluding U.S. government orders, endplace sales grew 23% year over year for the fourth quarter and 8% for the full year. Transitioning to our inflammation business, Tesla sales increased 2% year over year for the fourth quarter driven by favorable changes to estimated sales deductions and 3% volume growth partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4% driven by lower net selling price and lower inventory levels partially offset by 2% volume growth. New patient starts for Otesla grew 6% in the fourth quarter driven by strong execution and increased investment. Competitor free drug programs had a reduced impact in the quarter. Otesla is uniquely positioned to grow in 2024 and beyond given its indication for all severities of psoriasis combined with an established clinical profile, broad payer coverage, a lack of testing required for initiation and convenient oral administration. Embrel sales decreased 8% year over year for the fourth quarter driven by a 4% impact from unfavorable changes to estimated sales deductions and lower net selling price. U.S. volume grew 1% in the fourth quarter supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward we expect net selling price to continue to decline year over year driven by higher rebates to maintain broad first line payer coverage and changes in patient mix. TESPAIR continues a strong launch trajectory with $177 million in sales in the fourth quarter and $567 million for the full year. Sales increased 10% sequentially driven by volume growth. Our successful launch of a self-administered, pre-filled, single-use pen allowed us to expand coverage with major pharmacy benefit managers to over 80% contributing to higher new patient growth as the year progressed. Moving forward we expect this expanded coverage will allow TESPAIR to help even more patients with severe uncontrolled asthma. Sales of Tabneos were $44 million in the quarter and $134 million for the full year. In the fourth quarter we saw 17% quarter over quarter volume growth in the U.S. Approximately 2,700 patients have now been treated with Tabneos by over 1,700 health care professionals. Looking forward we will continue to leverage our expertise in nephrology and inflammation to bring Tabneos to even more patients with Anka-associated vasculitis. Sales for our biosimilars portfolio grew 10% year over year for the fourth quarter and 5% for the full year, driven by 27% and 29% volume growth. This volume growth was partially offset by net selling price decline. Over time we expect long-term growth in our biosimilars business to be driven by the addition of new molecules and additional launches. Overall, our execution is strong across the business underscored by our foundational commitment to serve patients. The four pillars of our portfolio position us well to serve many more patients around the world who can benefit from our innovative therapies. And with that I'll turn it over to Vikram who will cover our rare disease portfolio.
spk01: Thanks Murdo. I am glad to share an update on our rare disease business now that we are four 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 reflect sales from October 6th onwards and total $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% -over-year sales growth. Throughout the remainder of my remarks, I will reference full quarter product sales. Tepeza, an IGF-1R monoclonal antibody for patients with thyroid eye disease, generated $467 million of sales during the entire fourth quarter, representing 3% -over-quarter growth. This is the third quarter in a row of -over-quarter growth for Tepeza with the growth largely driven by the U.S. We saw a number of positive leading indicators, including a record number of unique Tepeza 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 Tepeza, 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 Tepeza in the U.S., while also recognizing there is some time lag between our execution efforts and the realization of increased patient numbers. International expansion also remains a meaningful long-term growth opportunity for Tepeza. Tepeza is approved in Brazil, and we are progressing towards approval in additional countries. Our expansion into both Japan and Europe is a high priority, with regulatory review underway in Japan and filings in the EU throughout the year. Pistexa, a pegulated uricase enzyme for patients with chronic refractory gout, delivered a record $280 million in sales for the entire fourth quarter, representing 30% -over-year growth, driven by continued strong commercial execution. Sales are now annualizing at a billion-dollar run rate. Performance was driven by execution across all phases of the patient journey, in man generation, stakeholder engagement, and adherence to treatment. Ablisna, an -CD-19 monoclonal antibody, which is now the fastest-growing biologic in NMOSD, delivered a record $70 million in sales for the entire fourth quarter, representing 68% -over-year growth. International expansion is also underway, with Ablisna now launched in multiple -U.S. markets. Our remaining ultra-rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra-rare medicines Revicti, Prusyspi, and Atemune. Looking ahead at 2024 by leveraging Amgen's world-class biologic capabilities, decades of experience in inflammation, and extensive global presence, we are ready to reach more than ever before. I will now turn it over to Jay.
spk15: 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 this leadership team. The creativity of our discovery research, expert expedited clinical development, the most authoritative bio-manufacturing 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 toward the impact of our medicines and our business, and the shared conviction in this remarkable portfolio of potential -in-class and -in-class medicines. In 2023, we executed with speed across our clinical pipeline, achieving excellent enrollment and key programs, and setting up 2024 as a 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 three studies for Tarlatumab and small cell lung cancer, Lumicras and non-small cell lung cancer, and colorectal cancer, along with Dezodolibab and Sjogren's syndrome. In general medicine, as previously disclosed, top-line 52-week data from the 592-patient Maritide Phase 2 study is expected by late 2024. Leveraging the durability of weight loss observed in Phase 1 and rapid enrollment enjoyed in Phase 2, we recently added a Part 2 to this study, which explores durable weight loss beyond 52 weeks. Our planning for a comprehensive Phase 3 program across multiple indications remains on track. Lastly, you may have seen that yesterday Nature Metabolism published a manuscript from Amgen R&D that provides the integration of Maritide preclinical and Phase 1 data. Beyond Maritide, our obesity strategy encompasses several assets with AMG 786 in Phase 1 and additional preclinical assets advancing. Our approach is tailored to meet the dynamic needs of obesity treatment, demonstrating a longitudinal commitment to innovation and patient care in this field. The Phase 3 outcome study of olpaseran, our potentially -in-class Lp-a targeting small interfering RNA molecule in atherosclerotic cardiovascular disease, has enrolled more than 7,000 patients globally. This rapid enrollment, accomplished in just one year across 34 countries and over 700 sites, underscores the medical community's strong interest in and the potential impact of olpaseran. We've deliberately expanded our initial enrollment target from 6,000 to over 7,000 patients to ensure comprehensive demographic representation and to satisfy regional regulatory requirements. We are on track to complete enrollment in the first half of 2024. In oncology, we're focused on approaching high conviction targets with differentiated therapies for large effect size. We're pleased to announce that the FDA granted priority review for blincyto, an early-stage DB19-positive BALL with a PDUFA date of June 21, 2024. The ongoing Phase 3 Golden Gate study is enrolling patients to evaluate the effectiveness of alternating blincyto with low-intensity chemotherapy, here in older adults diagnosed with Philadelphia chromosome-negative BALL. We're also planning to amend this study to evaluate subcutaneous administration of blinotuma MEB with initiation anticipated in the second half of 2024, potentially allowing us to serve more patients and treating physicians. Lastly, we're pleased to announce that just today, the American Journal of Hematology published a manuscript highlighting data from the dose expansion phase of our ongoing Phase 1B study of subcutaneous blinotuma MEB as a single agent in adult patients with heavily pretreated relapsed refractory B-cell ALL. Of 27 invaluable patients treated, we observed an 85% complete response rate, of which 75% were MRD-negative. Subcutaneous blinotuma MEB was well tolerated with no observed Grade 4 cytokine release syndrome. Turning to Tartlatam MEB, a -in-class DLL3 targeting BITE molecule, the FDA granted priority review following promising results from the Phase 2 Delphi 301 clinical trial and a PDUFA date of June 12, 2024. We are rapidly advancing Tartlatam MEB into earlier lines of treatment, where we have initiated two Phase 3 studies and plan to initiate a third in the first half of 2024. Zeleridime, a -in-class STEEP1 bispecific molecule being studied in metastatic castrate-resistant prostate cancer, continues to progress following the presentation of encouraging Phase 1 data last fall. We are ahead of schedule with the monotherapy dose expansion and expect a complete enrollment in the coming weeks. We have opened a reduced monitoring cohort and are making significant progress in dose range finding studies in combination with novel hormonal therapy combinations. For AMG193, an oral MTA cooperative PRMT5 inhibitor, we are encouraged by nine responses we have seen across seven mTap null-solid tumors. AMG193 is a terrific example of a medicine targeting a genetically defined synthetically sality and a first clinical translation of our induced proximity platform. We are now swiftly moving forward with dose expansion studies and plan to enter master protocols in thoracic and gastrointestinal malignancies, exploring combinations with standard of care in the first half of 2024. In our inflammation portfolio, we continue to explore TESPYR and indications beyond severe asthma, including separate Phase 3 studies in chronic rhinosinusitis with nasal polyps, where top line data are expected in the second half of 2024, as well as in isthenophilic esophagitis. We also remain on track to present Phase 2 COPD data in the first half of 2024. Our ROCKET Phase 3 program for rocatinolamab, a first in class anti-Ox40 monoclonal antibody, has successfully enrolled over 2,400 patients with moderate to severe atopic dermatitis. We're introducing an eighth study to the ROCKET program to explore an autoinjector, and we are planning to initiate both a Phase 3 study in prurigo nodularis and a Phase 2 study in asthma this year, as we seek to broadly explore the potential of rocatinolamab. Lastly, we are encouraged by the advancements of our rare disease pipeline with several mid to late stage opportunities. In December, TPEZA received orphan drug designation in Japan, where we've also recently submitted a new drug application for TPEZA in thyroid eye disease. To serve additional patients in Japan, we have a Phase 3 study underway in the setting of chronic disease with a low clinical activity score. Beyond Japan, we are progressing TPEZA's subcutaneous administration to drive increased adoption and improved patient experience, and plan to initiate a Phase 3 study in thyroid eye disease this year. With the PLSNA, we anticipate important Phase 3 data readouts this year in myasthenia gravis and IgG4-related disease, both diseases with significant unmet need and where we have the potential to make a real difference for patients. Pesodolibep, an innovative CD40 ligand inhibitor fusion protein, has entered Phase 3 for Sjogren syndrome. This follows encouraging Phase 2 data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. Pesodolibep is the first therapy to demonstrate efficacy in this latter patient population. Closing out our rare disease efforts, we're excited about FitPax Alparand, an L-PAR1 antagonist being studied in idiopathic pulmonary fibrosis, on track for a Phase 2 proof of concept data readout in the second half of 2024. In closing, I'm delighted to report on the important progress we make advancing our innovative pipeline and I'm looking forward to sharing more pipeline milestones through 2024. I'll now turn it over to you, Peter.
spk10: 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% -over-year and non-GAAP EPS of $4.71 grew 15% -over-year. For the full year, we delivered total revenue of $28.2 billion, 7% growth -over-year and non-GAAP EPS of $18.65, 5% growth -over-year. As a reminder, both Q4 and the full year results include Horizon's results beginning October 6th. When the acquisition closes, our financial results will exclude approximately one 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 increase 20% -over-year driven by volume growth of 23%, offset by net selling price decline to 3%. Excluding the impact of Horizon, product sales increased 5% -over-year driven by volume growth of 9%. Full year total revenues of $28.2 billion grew 7% -over-year. Product sales increased 9% -over-year driven by 15% volume growth. Other revenues decreased 16% -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% -over-year, while full year non-GAAP operating expenses increased 9%. Excluding the impact of Horizon, Q4 non-GAAP operating expenses increased 3% and full year non-GAAP operating expenses increased 5%. On a non-GAAP basis, Q4 cost of sales as a percentage of product sales was flat on a -over-year basis at 16.3%. For the full year, cost of sales as a percentage of product sales increased by 1.1 percentage points to 17.0%. The full year increase was primarily driven by higher profit share and changes in our product mix, partially offset by the replacement of the Puerto Rico excise tax with an income tax beginning in 2023. Non-GAAP R&D spend in the fourth quarter increased 16% -over-year and 8% -over-year for the full year primarily due to higher spend on later stage clinical programs and marketed product support, including spend on programs acquired from the Horizon acquisition and continuing investment in our pipeline, including Maritime. Q4 non-GAAP SG&A expenses increased 20% -over-year, primarily driven by commercial and G&A expenses related to the Horizon acquisition. Full year non-GAAP SG&A expenses increased 5% -over-year, primarily driven by commercial and G&A expenses related to the Horizon acquisition, partially offset by a decline in other marketed product spend. Non-GAAP OY&E were about $635 million and expense in the fourth quarter, $168 million increase -over-year, primarily driven by increased interest expense related to the debt issued for the Horizon acquisition. Full year non-GAAP OY&E was favorable $279 million -over-year, primarily driven by change in accounting for the Beijing investment to the fair value -to-market method and by gains related to early debt retirement, partially offset by higher net interest expense. Our non-GAAP tax rate increased 2.5 percentage points -over-year to .9% in the fourth quarter and 2.7 percentage points -over-year to .5% for the full year, primarily due to the 2022 Puerto Rico tax law change mentioned previously. The company generated $7.4 billion of free cash flow in 2023, compared with $8.8 billion in 2022. The decrease is driven by a rough the Horizon transaction and integration costs, higher repatriation tax payments, and higher capital expenditures. We expect to continue to generate strong cash flows with the addition of Horizon and are on track with our deleveraging plans to return to our efficient capital structure by the end of 2025. In summary, we continue to execute on our multiple capital allocation priorities. First, we continue to prioritize investments in both internal and external innovation. Our increased spending and non-GAAP R&D of 8% in 2023 over 2022, coupled with the acquisition of Horizon Therapeutics, continues to broaden and strengthen our balanced portfolio across therapeutic areas. With our strong late-stage innovative pipeline moving forward through development, we expect our non-GAAP R&D to continue to increase in 2024. Second, we continue investing in our business for long-term growth, including our -the-art manufacturing facilities in Ohio and North Carolina. Amgen, Ohio, our new advanced assembly and final product packaging plant, has just received licensure from the FDA for commercial production in January, roughly two years after we broke ground. And our innovative drug substance plan under construction in North Carolina is expected to be operational by 2026. In addition, we've positioned the organization to accelerate investments in innovation, including leveraging the power of generative artificial intelligence. And third, we return capital to shareholders through growing dividends, including $2.13 per share in the quarter. This represented a 10% increase over that pay in each of 2022's four quarters. Turning to the outlook for the business for 2024. First, because this is the first full year incorporating the impact of Horizon, we're providing some additional granularity in our guidance, which we don't expect to repeat to the same extent in the future. For 2024, we're expecting revenue of $32.4 billion to $33.8 billion and non-GAAP earnings per share of $18.90 to $20.30. As we continue to integrate Horizon, we expect the acquisition to be accretive to non-GAAP in 2024. And we're on track to meet the synergies target previously communicated of at least $500 million in pre-tax costs by year three after closing or in 2026. Our revenue range reflects our strong growth outlook driven by numerous opportunities across our four therapeutic area pillars. We will record a full year of legacy Horizon product sales, and we expect continued volume-driven growth in our priority products, Repatha, Tespyre, Avenity, Otezla, Perle, and Blin-Sito. Consistent with industry trends in our recent history, we expect -single-digit price declines for our portfolio in 2024. As a reminder, as you model the first quarter of 2024 and consistent with our historical trends, we expect first quarter product sales to be the lowest quarter as a percentage of the full year due to benefit plan changes, insurance re-verifications, and increased co-pay charges. So, we expect the first quarter of 2024 total revenue to grow roughly 20% -over-year. For the full year, we expect other revenue to be in the range of approximately $1.3 to $1.4 billion. And we continue to efficiently run the business through a disciplined approach to managing operating expenses. In 2024, we're making incremental R&D investments to support our promising late-stage pipeline, including our rapidly advancing oncology programs as discussed following ESMO in October and other programs, including Maritime. Furthermore, the addition of Horizon has an impact on the 2024 operating margin given the timing of when synergies are realized. As a result, we project the full year non-GAAP operating margin as a percentage of product sales to be roughly 48%. Note that we expect non-GAAP operating margin growth to accelerate in each of the quarters following the first quarter. There are primarily three reasons for this. First, typical lower product sales in Q1, as I mentioned above, than in each of the following quarters. Second, increased spend on our commercial brands will continue, building on the investments we made in the second half of 2023, including Repatha, O'Tesla, and our phone portfolio of Entity and Prolia. And third, Q1 2024 reflects the addition of Horizon, for which we are just at the beginning stages of realizing synergies given the acquisition close date of October 6. So we expect non-GAAP operating margin to be roughly 43% in the first quarter. I would reiterate that we expect operating margin growth to accelerate in each of the quarters following the first quarter. We project non-GAAP cost of sales to be in the range of 17 to 18% as a percentage of product sales for the 2024 year. Taking into account the full year of Horizon related expenses, we expect non-GAAP R&D expenses in 2024 to increase approximately 20% year over year, with investments also increasing to advance key pipeline assets including AMG 193, Maritide, Rocatin-LaMab, and Tarlatamab. We see significant potential in our innovative pipeline, and it is important that we strategically invest now to fully unlock the opportunities ahead to create long-term value for patient, staff, and shareholders. And for non-GAAP SG&A spend, we expect 2024 full year amounts as a percentage of product sales to be between 21 and 22%. We anticipate non-GAAP OINE to be in the range of $2.6 to $2.7 billion. As mentioned on our Q3-23 call, the 24 guidance includes the interest expense related to the $28 billion of debt rates for the Horizon acquisition. We expect a non-GAAP tax rate of 16 to 17%. Our guidance is primarily being driven by two factors. The first is the jurisdictional mix of income, including the full year benefits associated with the Horizon transaction, and the legal entity rationalization undertaken in the fourth quarter of 2023, in part to integrate the Horizon entities into our existing U.S. headquartered legal entity structure. The second is the benefits from a planned payment to the IRS as an advanced deposit, as we've done in the past to stop the accrual of interest on uncertain tax positions. There is no change in our belief in the merits of our legal arguments with the IRS as we prepare for trial. Given the interest rate environment, although the deposit negatively affects our cash flow in 2024, if any of the deposit is returned to us upon the resolution of our litigation, those funds would accrue interest income. Therefore, the rate arbitrage makes this payment a prudent use of our capital. Once again, out of an abundance of clarity, this represents no change in our belief in the merits of the tax court case. The guidance also includes the impact of the adoption of the OECD 15% minimum tax by certain jurisdictions. Based on our individual footprint, we don't anticipate any significant effects of the new rules in 2024, but we're closely watching the global tax landscape for future impacts as the framework continues to be considered by additional jurisdictions and new rules take effect. We expect governments around the world, including the United States, to continue to look for more sources of tax revenue from large multinational corporations that could result in higher taxes in the coming years. Similar to 2023, we expect share repurchases not to exceed $500 million. In 2024, we expect that we will continue to increase our dividend. We expect capital expenditures of approximately $1.1 billion in 2024, consistent with our capital allocation priority to invest in our
spk21: business,
spk10: including the Ohio and North Carolina facilities I mentioned ahead and into the rare disease pillar. In summary, we delivered another strong year of financial results in 2023. Our confidence in the long-term growth of Amgen is strong and we believe that our new rare disease pillar, one of our four pillars, will be an important, additive source of growth for the company. This concludes the financial update. My thanks to my approximately ,000-plus colleagues at Amgen around the world for their commitment to our mission of serving patients and their tireless efforts in 2023. I'll turn it back to Bob for Q&A.
spk04: Okay, thank you. Let's open the line and we'll take questions from our callers. And Julianne, why don't you remind them of the procedures so we can get through these questions here efficiently for everyone.
spk20: Thank you. If you would like to ask a question, please press star followed by 1 on your telephone keypad. If for any reason you would like to remove that question, please press star followed by 1. Again, to ask a question, press star 1. Our first question comes from Michael Yee from Jefferies. Please go ahead. The line is open.
spk06: 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 I 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 level about the profile versus competitors. Thank you so much.
spk15: Yes, thanks a lot, Michael. We really appreciate the consideration the Phase I 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, seven cohorts, multiple ascending dose, three cohorts, three monthly doses, patients with obesity being migrating 30. And we were quite pleased with the outcome. Looking at the 420-milligram dose as an example, which was the highest dose study, .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, lipids, blood pressure, and A1C. And I would just caution that this is a Phase I trial, that 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, you know, all are directionally favorable. And so we have, we take no concern whatsoever from those measurements on this study.
spk04: Okay.
spk20: Thank you, Michael. Let's go
spk04: to the next question.
spk20: Thank you, Michael. Our next question comes from Salvin Richter from Goldman Sachs. Please go ahead. Your line is open.
spk17: 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.
spk15: 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, dose in different ways. We've recently added a Part II 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 and tolerated and efficacious dose to carry into Phase III clinical investigation.
spk03: Yeah. 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 dose 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, Julian. We'll go to the next question.
spk20: Thank you, Salvin. Our next question comes from Jay Olsen from Oppenheimer. Please go ahead. Your line is open.
spk08: Oh, hey. Thank you so much for taking the question and congrats on the progress. Another question on 133. Talk about whether or not the data that we see later this year will include patients from Part II of the study. And do you think it's possible that 133 could be dosed once every two or three months? And also if you could just comment on the rollover rate of patients from Part I to Part II. Thank you.
spk04: Jay, could you catch all that, some of what Jay asked was broken up there at the beginning? The third
spk15: part was a little bit broken up of your question. I heard a better explanation of Part II frequency of dosing and then I did not hear your third part. I think it was five months later. Oh, if you
spk08: just comment on the rate of patients rolling over from Part I to Part II. Thanks.
spk15: Okay. Yeah. Thank you for the question, Jay. Let me give a little bit of context on this Part II study that I think will help answer them. In Part II, the intent is to really look at durable weight loss beyond 52 weeks. And so by durable weight loss, patients eligible for Part II, which begins at the end of 52 weeks, will be responding to this medicine. And then they'll be re-randomized to four cohorts that'll 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 II will be established as the Phase II study continues to progress this year.
spk14: Thank you, Julianne. On the next question.
spk20: Thank you, Jay. Our next question comes from Chris Schott from JPMorgan. Please go ahead. Your line is open.
spk23: Great. Thanks very much. Just maybe to pivot over to Pesce 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.
spk04: Sure, Chris. Just maybe we'll take it in a couple parts, but Vikram, share your thoughts first.
spk01: Yes. Thank you for the question. I think if you focus a little bit on what are the underlying factors that are driving Tepesa growth, we saw a record number of unique Tepesa 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 update across the full spectrum of TED patients. 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 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've said before, it can take up to 90 days once a patient is identified for therapy for that patient to actually get on therapy. We're pretty happy with all of our leading indicators and the execution that we have seen coming out of last year.
spk04: Chris, the only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunities 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 TEPESA will play in that. All right, next question, Julianne.
spk20: Thank you, Chris. Our next question comes from Evan Seigerman from BMO Capital Markets. Please go ahead. Your line is open.
spk13: Hi, guys. Thank you so much for taking my question. I wanted to touch on TESSPIRE specifically and COPD. How are you planning to differentiate given the pretty competitive data we saw from DUPIX, 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 -to-apples comparison?
spk15: Yeah, then thanks for the question. Myrtle, why don't I start and then you add on? So, it's a great and timely question. The Phase II COPD study of TESSPIRE, 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 just by being on triple therapy, and so reflective of the current unmet need and inadequacy of therapy for patients with COPD. This is a slightly broader population than DUPIX that we're studying here. We're totally on track for the readout. We quite like the mechanism here. You must know that T-SLIP works as a signaling factor upstream, and by blocking it with our unique biotherapeutic, we block T-SLIP, IL-25, IL-33 signaling. T-SLIP hits so many cell types, modulating this airway type II response. By hitting T-SLIP upstream, we think we can really have an impact on the disease biology. We see T-SLIP elevated in the serum of patients, in bronchial mucosa, and bronchial levage 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 DUPIX, we have a chance to really figure out who the responder is. Murta?
spk03: I think you've covered all the bases. I would just add this, Evan, that with the unique and differentiated mechanism, as Jade 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 TESPIRE. 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 three. Great. All right. Thank you, Julia. Next question.
spk20: Thank you, Evan. Our next question comes from Umar Rafet from Evercore ISI. Please go ahead. Your line is open.
spk16: Hi, guys. Thanks for taking my question. I wanted to touch up on AMG 133 as well, two-part question. First, on the discontinuation of 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? This is a 420 done separately, which is not part of the 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.
spk15: Yes, thanks, Umar. 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 I 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 .5% after these three monthly doses. This was the group that proved actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting, largely for 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.
spk05: Dave, do you? No, I mean, we can get back to you on that. I don't know that we reported that, those data in the discontinuation rate.
spk14: All right. Julianne, let's go to the next question.
spk20: Thank you, Umar. Our next question comes from Colin Bristow from UBS. Please go ahead. Your line is open.
spk12: 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 the path of 420 milligrams takes over five minutes by infusion or three consecutive injections. So I was wondering if you could give any insight there. And then in terms of the relative affinity for GIT versus GLIT, maritide seems to have or preferentially favor GLIT 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 GLIT one versus competitive GIT GLIT? Thanks.
spk15: Yeah, 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 a biotherapeutic that's an antibody drug conjugate with a peptide antibody ratio two to one 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, you know, 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 arrive at. So no concerns there for me whatsoever. Regarding the balance of the pharmacology, you know, you do invoke a difference between our medicine and medicines developed by peer 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 GIP 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 ask 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.
spk03: And Colin, this is Murdo. I would just add that from a patient experience perspective, we've learned a lot from other biologics and, you know, 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.
spk04: Just as we go to the next question, let me observe that we're almost up to the hour that we asked you 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 per 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.
spk14: Yep. All right, Julia, next
spk04: question,
spk14: please.
spk20: Thank you, Colin. Our next question comes from Yaron Werber from TD Cowan. Please go ahead. Your line is open.
spk18: All right, great. Thanks. This is Brendan for your own 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 a blizna. Where do you kind of see a blizna 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 can do longer-term growth.
spk04: First of all, we asked 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.
spk01: Yep. Thanks for the question. A blizna 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. 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 a 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? Yeah,
spk15: no, I'm happy to. As you may know, I'm 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 a blizna 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, is it not lost on our team and we're working through indication expansion priorities presently.
spk14: All right, Julian, let's go to the next question.
spk20: Thank you. Our next question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.
spk02: Great. Thank you very much for taking my question. I have a question regarding the subcutaneous delivery of Stapaza. You do have planned to initiate a phase three study. Can you talk a little bit about which technology you are using? Is this the pre-existing halosome technology or are you using something else from this development? Thank you.
spk03: I'm sorry. I had trouble understanding the question. The question is what technology we're using for the subcutaneous injectable form of Stapaza.
spk14: Yeah, maybe I'll just jump in. Mohit, we're not commenting at this point on the provider. We just said that we're going forward with the subcube. Great. Okay, Julian, we'll go to the next question.
spk20: Thank you, Mohit. Our next question comes from Jeff Meacham from Bank of America. Please go ahead. Your line is open.
spk22: Hey, guys. Thanks for the question. Another one on 133. When you think about the phase three 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 two data in hand or is this something that you could roll out sort of at risk? Thank you.
spk15: Yeah, thanks for the question, Jeff. 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 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 two 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 two program, as you know. And obesity has a strong genetic component and we locked on to gibber inhibition based on genetic insights. So the opportunity space is quite large. You asked the question, you know, 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 three program.
spk04: And in terms of the day, if you want to add the regulatory piece.
spk05: Yeah, I think, you know, Jeff, this is a Dave Reese. I would just add that, you know, we're planning a very expansive phase three 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, you know, as you as you're aware, regulatory authorities around the world require a certain body of safety data before phase three launches. And so, of course, we will be complying with that. But our goal is to launch phase three as quickly as possible. Once we have the requisite data set in regulatory approval.
spk14: Great. I, Julianne, go to the next question,
spk20: please. Thank you, Jeff. Our next question comes from David rising or from Lee rank partners. Please go ahead. Your line is open.
spk24: Yes, thanks very much. So I have another question on AMG one thirty. Please, could you add some more color on your expectations for the impacts on blood pressure and lipids in phase two, specifically, whether you anticipate to zip a tide like efficacy on those metrics. Thanks very much.
spk15: 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 one program, the medicines are 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 two towards the end of this calendar year.
spk05: And the best extrapolation that you can have is from the preclinical data that were just published. I'd urge you to take a look at that.
spk14: Okay, Julianne, go to the next question,
spk20: please. Thank you, David. Our next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead. Your line is open.
spk11: Okay, it's E.K. on for Michael. Thanks for taking our questions. A quick one on Zaloridomac. 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 emergent agents based on different mechanisms such as ADC or ART creators in prostate cancer? Thank
spk15: you. Yeah, thanks for this outstanding question, Michael. And Zaloridomac is a very interesting and exciting molecule. For those on the call, this is a steep one, CD3 bispecific. We have been studying this in advanced castrate resistant prostate cancer. We have expanded a cohort, the phase one monotherapy. We're opening to reduce monitoring as well 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 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 will 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 to other medicines. These are often apples to oranges comparisons. We have looked at that, of course, and we really like the offering of Zaloridomac. 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 radioligand therapies. 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.
spk04: Jay, in terms of the data sharing, do you want to share? In terms of data availability, as
spk05: Jay mentioned, we're nearly complete in terms of dose expansion enrollment. 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 in the next year. Okay,
spk14: Julian, we'll go to the next question, please.
spk20: Thank you, Michael. Our next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.
spk07: 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, you know, 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.
spk15: Hey Tim, this is Jay. I'd open it up to anyone else who wants to contribute to this. I don't believe that engaging in a dialogue around this adds 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, you know, a million patients studied among those who have variation 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.
spk14: Okay, Jillian, we'll go to the next question, please.
spk20: Thank you, Tim. Our next question comes from Robin Karnofkas from Truis Securities. Please go ahead. Your line is open.
spk19: Hi, good evening. Thanks so much for taking my question. This is Nicole on for Robin. So on DAX-Gilimab targeting ILT-7 for lupus, can you talk about your level of confidence in this target in light of the competitive landscape and we can see that you're doing a great job. I'm a senior term from safety analysis.
spk15: Sure. Jay
spk04: and Dave,
spk15: come in. Yeah, well, it's very early days with this medicine. There's strong preclinical support from the published literature and our own preclinical work. You know, it's nicely for patients, a very competitive landscape, but this is, you know, the earliest phases of clinical investigation. And so, you know, we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying.
spk05: Yeah, I would say, you know, 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, you know, at this point, I think, you know, it's all efforts towards generating the clinical data.
spk14: Okay, Julia, next question, please.
spk20: Thank you, Nicole. Our next question comes from James Shin from Deutsche Bank. Please go ahead. Your line is open.
spk21: Hey, 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's 420-milligram dose has a slight lipid triglyceride 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.
spk15: The short answer is it's too early to chalk it up to antagonism versus agonism. As I said before and I meant it, that these lipids are a labile and indirect biomarker of this pharmacology. This is an early-stage study that had one or three 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 two.
spk14: Great. Ben, I think we have time for one more, Julian.
spk20: Thank you, James. Our last question will come from Carter Gold from Barclays. Please go ahead. Your line is open.
spk09: Good evening. Thanks for taking the questions. Maybe just one on 786. Can you walk through exactly what's sort of driving, or maybe, let me take it to the 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.
spk15: 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 increase, and though we've not as yet disclosed its target or pathway, this study is progressing fine. The readout of the phase one is on track for the first half of 2024. We've completed initial dose escalation cohorts, and we're just collecting and analyzing data. I'm expecting the readout in the first half of this year.
spk14: Great. Julian, we're going to turn it back to Bob for some closing remarks.
spk04: 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, and 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'll look forward to talking to you at the rare disease day or at our first quarter results call. Thank you.
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