Amgen Inc. (AMGN) Earnings Call Transcript & Summary

My name is Julienne, and I will be your conference facilitator today for Amgen's conference call following the American Thoracic Society 2024 International Conference and the approval of IMDELLTRA. [Operator Instructions] I would now like to introduce Justin Claeys, Vice President of Investor Relations. Mr. Claeys, you may now begin.

Thank you, Julienne. Good afternoon, and let me welcome everyone to the call. We have met with a number of investors over the past several weeks and have been reinforcing the breadth and depth of opportunities across the 4 pillars of our business and are glad to discuss several of those in more detail with you today. We will begin with prepared remarks from Murdo Gordon, Jay Bradner, Jean-Charles Soria, Susan Sweeney and Primal Kaur, and we'll then open it up for Q&A. Through the course of our discussion, we'll be making some forward-looking statements, which are qualified by our safe harbor statement, and please note that actual results can vary materially. Please also note that we will be presenting slides to accompany the discussion on the webcast and will make these available immediately after the call on the Investor Relations section of our website. Let me now turn the call over to Murdo.

Thanks, Justin. It's an exciting time here at Amgen. We're reaching many more patients around the world with our existing medicines, and we're advancing a broad range of potential first-in-class medicines in our mid- and late-stage pipeline. We have great confidence that we're on a path to deliver attractive long-term growth through the end of the decade and beyond not just with our obesity portfolio but also from the breadth and depth of opportunities across our 4 therapeutic area pillars: general medicine, oncology, inflammation and rare disease, each of which have strong momentum and plenty of room to go. Today, we're pleased to review several of these opportunities with you. So let me start with IMDELLTRA, which is a transformative innovation for patients with small cell lung cancer. We're excited about this approval and are rapidly advancing IMDELLTRA into earlier treatment lines. This also provides further validation of our industry-leading BiTE platform as IMDELLTRA is the first T cell engaging therapy to demonstrate significant clinical activity against a common and aggressive solid tumor. This builds upon the success of BLINCYTO, which was our first approved BiTE for the treatment of acute lymphoblastic leukemia. BLINCYTO is now annualizing at over $1 billion of sales and has a PDUFA date next month for approval in the frontline setting. Let me also remind you of our next BiTE program in development, xaluritamig, which is rapidly advancing for the treatment of prostate cancer. [ Starting with ] inflammation, Amgen has a 2-decade long history of serving patients with autoimmune diseases, we have broad coverage across the main areas of inflammatory conditions, including respiratory, dermatology, gastroenterology and rheumatology. Today, we will share encouraging data for TEZSPIRE that reflects the attractive potential of this medicine in chronic obstructive pulmonary disease, the world's third leading cause of death and where new treatments are very much needed. As far as strong momentum in the market with first quarter sales for the treatment of severe asthma up 80% year-over-year, and COPD represents an important possible addition. We'll also discuss AMG 104, an inhaled TSLP inhibitor. And we'll conclude today with rocatinlimab, our potentially first and best-in-class OX40 inhibitor that is being studied in a broad Phase III program, including atopic dermatitis. And with that, I'll invite Jay to walk us through the IMDELLTRA update.

Thank you, Murdo, and good afternoon, everybody. On behalf of Amgen R&D, it's my pleasure to share the exciting news and some of the pivotal data associated with IMDELLTRA. Next slide, please. We're proud here to introduce IMDELLTRA. This is the first only bispecific T cell engager therapy for extensive-stage small cell lung cancer. This has also been the first chemotherapy-free targeted immunotherapy medicine for this disease. And we regard IMDELLTRA as a major advance, if not a historic milestone in cancer treatment. For patients who are battling extensive-stage small cell lung cancer, the FDA's approval of IMDELLTRA is a truly pivotal moment. Compared to non-small cell lung cancer, which remains a challenging illness, small cell lung cancer has received comparatively less attention and even less innovation. As I'll share in a moment, a DLL3 targeting therapy, IMDELLTRA is highly active and has demonstrated durable responses in heavily pre-treated patients. In studies to date, we've seen clinically meaningful, if not unprecedented, efficacy in advanced extensive-stage small cell lung cancer with a 40% overall response rate, 9.7-month median duration of response and 14.3-month median overall survival. I'll have a chance in a moment to share just how different that is from the natural history of this horrible disease. This work further demonstrates our commitment to addressing aggressive cancers using our platform capability in Bispecific T cell Engagers or BiTE that bridge cancer cells and T cells. And as Murdo shared, we first pioneered the concept of BiTE with BLINCYTO, the CD19-CD3 Bispecific T cell Engager in acute lymphoblastic leukemia. We look forward to sharing more data on the heels of a PDUFA date for frontline therapy as maintenance this June. As we bring IMDELLTRA to extensive-stage small cell lung cancer patients after platinum-based chemotherapy today, we've already initiated studies in frontline therapy for both extensive-stage and limited-stage small cell lung cancer. We are, it's fair to say, very well prepared for the launch. Our field team is charged, ready. The trucks are gassed up, and we're armed with a strategic rollout plan designed to maximize the impact and access to IMDELLTRA, also bringing sustained growth as an Amgen medicine. Next slide, please. Small cell lung cancer is a truly devastating disease. And patients with this disease are at risk for quite rapid disease progression. As shown on this slide, 2/3 of patients are diagnosed already with extensive-stage disease, which is disease beyond the size of one radiation port. Small cell lung cancer is associated with a perilously unacceptable poor prognosis with a 5-year survival of only 7% for invasive disease. And indeed, more than 3/4 of patients with small cell lung cancer will experience disease progression. Regrettably, many patients will not survive to receive second-line or third-line therapy, underscoring the need to understand activity in frontline as we are now studying. Next slide. The poor prognosis associated with small cell lung cancer is a truly global health crisis. Shown here are real-world data from our center for outcomes research. The median overall survival across regions is approximately 5 to 7 months or 4 to 5 months in the second-line and third-line studies, respectively. [ Effectively unaffected ] in differences in patient characteristics such as smoking history or local standard of care such as the use of IO therapy in the frontline. These analyses performed by [ C4 ] with Amgen are conducted using contemporary fit-for-purpose real-world data but also a common protocol framework that defines the disease outcomes, lines of therapy and patient characteristics in a quite consistent manner. This is robust evidence and really puts into context what a 14.3 median survival can mean after platinum therapy. Next slide, please. So enter IMDELLTRA. As I shared, IMDELLTRA functions by bringing activated T cells to the site of tumor growth. Effectively, this protein therapeutic has 2 arms, one that binds to and activates the T cell via the CD3 protein on the T cell surface and another that binds the protein on the small cell lung cancer surface, the DLL3 protein. Unlike most tumor-targeted therapies, there's no requirement for a biomarker because approximately 85% to 96% of patients with small cell will express DLL3, and this expression is consistent across all stages of the disease. I now invite Dr. Jean-Charles Soria to discuss the details of the pivotal trial.

Thank you, Dr. Bradner. IMDELLTRA was studied in a heavily predicted population of patients with poor prognosis, as already highlighted by Dr. Bradner. Around 74% of patients included in the study received prior anti-PD-L1 therapy, and around 22% of them have brain metastases at baseline. If we move to the next slide. IMDELLTRA showed indisputable and durable efficacy in patients with extensive-stage small cell lung cancer. Among 99 patients, we saw an objective response rate that was robust at 40% with complete responses at 2% and partial responses at 38%. Those responses were rapid with a median time to objective response of 1.4 months. And interestingly, we saw a disease control rate of 70%, meaning that on top of the 40% of patients responding, an additional 30% of the patients had stable disease with a median follow-up of 10.6 months. If we can go to the next slide. Among those patients who responded to IMDELLTRA, 68% responded for 6 months or more, and 40% were still responding at 1 year. This is quite remarkable, taking into account the fact that these were mostly second and third-line small cell cancer pretreated patients. The median duration of response was 9.7 months, ranging from 2.7 months to 20.7 months and beyond. If we move to the next slide. We saw a median overall survival of 14.3 months with IMDELLTRA. The median follow-up reporting this median overall survival was 10.6 months, meaning that the maturity is yet not fully acquired. And as you see, there are quite a few censoring points. So this median overall survival might still move up probably to higher numbers. Of course, please take into account the fact that the treatment effects for this study that are based on timely related endpoints such as PFS and OS should not be interpreted in the absence of a comparator arm, but directionally, they remain very impressive when contrasted to what has been reported with the real-world data or with the published second-line treatment. If we move to the next slide. The safety and tolerability of IMDELLTRA, which was evaluated in 187 patients with extensive-stage small cell lung cancer, appear as manageable with most side effects happening at the first 2 doses. The most common adverse reactions that occur in more than 20% of patients were CRS, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia and nausea. Of note, permanent discontinuation of IMDELLTRA due to adverse reaction was low with 7% of the patients experienced such discontinuation. Dosage interruptions of IMDELLTRA due to adverse reaction occurred in 27% of patients with adverse reactions that required dose interruptions in 2% of more patients, including fatigue, CRS and respiratory tract infection. If we move to the next slide. You will be able to see the temporary evolution of the side effects. What is pretty remarkable is that the majority of CRS events were grade 1 and occurred following the first 2 doses. Of the 55% of patients who experienced CRS, 34%, 19%, 1.1% and 0.5% of patients experienced grade 1, 2, 3 and 4 CRS. Recurring CRS occurred in 23% of patients treated with IMDELLTRA. Next slide. IMDELLTRA is indicated for the treatment of other patients with extensive-stage small cell lung cancer with disease progression on or after platinum-based chemotherapy, and that encompasses second-line and later-stage patients. This overall equates to 8,000 to 10,000 patients in the U.S. Note that you cannot add all the third-line patients with the second-line patients because you can be treated in both settings. The second line and later patients have a very clear poor prognosis with an overall survival in second line ranging in the 6 to 9 months and very limited treatment options. We are rapidly advancing IMDELLTRA into earlier lines of therapies with a broad and parallel clinical plan, bringing this therapy into 3 Phase III trials. We have an ongoing second-line trial. We have a first-line trial in maintenance in combination with PD-L1. And we have an early-stage trial post chemo radiotherapy. The rationale for studying IMDELLTRA into earlier lines is related to the concept of low tumor burden that has been highlighted with BLINCYTO in acute lymphoblastic leukemia. There, we saw a dramatic improvement in overall survival in minimal residual disease negative patients. These BLINCYTO data provide evidence that directing the T cells in this manner is an effective means of finding and eliminating residual cancer cells, which are primary drivers of recurring disease. We are hopeful we can build on this insight with tarlatamab, where comparable activity in early-stage small cell lung cancer patients would be very meaningfully improving outcomes for patients facing the challenge of this aggressive cancer. In sum, we regard IMDELLTRA as a major advance as the first specific T cell engager to demonstrate efficacy in a common solid tumor, further establishing the broad potential of our Bispecific T cell Engager platform. And with that, I would like to turn it to Murdo Gordon to review our launch plans.

Thank you. Thank you, Jean-Charles. Extremely exciting. And of course, both Jay and Jean-Charles have very clearly and elegantly described the severity and aggressive nature of small cell lung cancer. And so we are working around the clock to ensure that, that last mile of us getting product to patients now is running extremely quickly and extremely effectively. So last Friday and through the weekend, our manufacturing teams were labeling inventory. All customer-facing activity commenced. We're receiving orders from key customer accounts, and we will have product in channel this week, and patients are being scheduled for treatment. So it really is an exciting time. And as we roll out IMDELLTRA, we expect the initial utilization to be in health care facilities with a track record of handling cutting-edge therapies like those found in academic centers and larger hospitals. But our goal is to make IMDELLTRA accessible where patients are receiving care. And since about 70% of small cell lung cancer patients are treated in community settings, our priority is building confidence and experience among community clinics and oncologists. So this means patients then can receive treatment closer to home and with the same level of safety and monitoring. We also recognize that many doctors treating solid tumors may be new to BiTE therapies like IMDELLTRA, and that's why we're committed to providing education resources to support them and integrating this innovative technology into their practice. In addition to our existing patient support services like co-pay systems, Therapy Locator, benefit verification, we're introducing a new program specifically for IMDELLTRA patients and health care providers. Our Amgen Navigators program will serve as a central point of contact to help navigate the complexities of transitioning between inpatient and outpatient care, answering questions about access and reimbursement, and of course, treatment logistics. Overall, we believe our strategy of cultivating widespread clinical confidence, bolstering health care provider education to instill trust in IMDELLTRA's safety profile and offering robust operational support will lead to broad adoption across academic and community centers alike. So in summary, we have an exciting opportunity here to help many patients who have had the unfortunate diagnosis and subsequent progression on or after chemotherapy -- platinum-based chemotherapy now have new hope with IMDELLTRA. I'm so very thankful for the patients who volunteered and enrolled in our clinical trials, our investigators who are conducting our clinical trial program and conducted our first approval trial and the many dedicated scientists and colleagues here at Amgen who made IMDELLTRA a reality. And with that, I will now transition back to Jay to walk through our overall inflammation strategy, including TEZSPIRE, COPD and AMG 104 data, which were presented at ATS in San Diego over the last several days and an overview of rocatinlimab in preparation for our first Phase III data readout expected later this year.

Well, thank you, Murdo and Jean-Charles. So hopeful for this medicine and thankful for the many patients and clinicians who've collaborated on bringing IMDELLTRA through clinical investigation. And as Murdo shared, it's an exciting time across all 4 pillars of the Amgen R&D portfolio. Now our pleasure to share updates on the inflammation strategy amidst the ongoing American Thoracic Society Medical Meeting in San Diego. As shown here, we're approaching serious inflammatory and autoimmune diseases in a mechanism-based manner, leveraging insights into disease biology, and where available, human genetics. Historically, the traditional approach to inflammatory disorders has been to suppress the immune system. And today, we still focus a bit on blocking cell signaling, such as blocking cytokines or cytokine pathways, as we'll have a chance to discuss. This can be much more precise than general immunosuppresses. We've leveraged a variety of mechanisms. This allows the clinician to tailor medical management to the underlying disease pathophysiology, which is increasingly understood at the time of resolution. Our 4 mechanic strategies are organized around blocking, as just shared, but also tissue repair. Barrier function is often lost in inflammatory disorders, such as the gut, the inflammatory bowel disease or the airway in asthma. We're pursuing selective cellular depletion strategies to remove pathologic cells and disease tissues. Think of CD19-positive B cell depletion with UPLIZNA or perhaps even BLINCYTO. The ultimate goal is to pursue immune tolerization, as we know that in almost all autoimmune diseases, there's a dysregulation of T regulatory cells, allowing unchecked inflammation to occur, and restoring that regulatory balance is a focus for many of our programs. We organized these activities and inflammation across 4 broad disease areas: respiratory diseases, dermatology, gastroenterology and rheumatology. And we have a specific discrete interest in each of these domains. Today, we'll share insights in respiratory disease, speaking about our work in chronic obstructive pulmonary disease, which remains the third leading cause of death globally, as well as in atopic dermatitis in dermatology. Next slide, please. So we'll focus on 3 programs in the innovative pipeline: TEZSPIRE, AMG 104 and rocatinlimab; TEZSPIRE and AMG 104, also known as AZD8630, are being developed in collaboration with our partners at AstraZeneca; rocatinlimab, formerly AMG 451, is being developed in collaboration with Kyowa Kirin. I'll now turn to Susan Sweeney and Dr. Primal Kaur to discuss TEZSPIRE.

Thank you, Jay. TEZSPIRE has established itself firmly in major markets as the top choice for patients with severe uncontrolled asthma. With that momentum, the brand is preparing for an expansion into new indications: chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis and COPD. With our partners at AZ, TEZSPIRE is reaching patients across the globe with approvals now in 51 countries. As we look to expand into COPD, COPD is an area with high unmet medical need and is the world's third leading cause of death. Prevalence varies between countries with 14 million patients in the United States diagnosed with COPD. The patient burden is severe, limiting activities and oftentimes has long delays to diagnosis. With the current standards of care focused on steroids and bronchodilators, there are no approved biologic options. Of these patients, we estimate that the bio-eligible patients would be between 1.1 million and 1.5 million patients. Now let me hand it over to Primal to talk more about the data.

Thank you, Susan. Next slide, please. This slide sets the stage for the experiment that we ran in COPD called COURSE. This explains that there are many triggers in uncontrolled severe asthma, such as viruses, allergens, pollutants, smoke and bacteria. And we know now with the biology advance, these are similar in COPD as well. When these triggers interact with the epithelium of the airway, as shown in the picture, there is increased expression of TSLP in COPD as well as in asthma. And this is the basis of our testing for TSLP inhibition in COPD. Our current success and future planning for TEZSPIRE will continue to focus on how to block TSLP, and TSLP blockage can regulate multiple downstream pathways on COPD similar to what it does in asthma. And with this, next slide, please. We set up the COURSE study experiment. It's a Phase IIa multicenter, randomized, double-blind, placebo-controlled, 52-week study. This trial was designed to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe COPD who were receiving triple inhaled maintenance therapy and having had 2 or more documented COPD exacerbations in 12 months prior to enrollment. No patients were excluded based on blood eosinophil counts, chronic bronchitis or emphysema during the enrollment of this trial. The primary endpoint of this trial was annualized rate of moderate to severe COPD exacerbation over the course of 52 weeks. Key secondary endpoints also focused on severe COPD exacerbation, pre-bronchodilator FEV1 and key quality life measures such as SGRQ. Next slide, please. This chart shows the baseline demographics and characteristics. And generally, these were balanced between the treatment groups. As we mentioned, this includes a broad range of baseline blood eosinophil counts and irrespective of emphysema, chronic bronchitis or smoking status of the patients enrolled in the trial. Next slide, please. This proof-of-concept study showed that in patients with blood eosinophil count 150 cells per microliter or above, tezepelumab led to nominally significant reduction of about 37% in the rate of moderate or severe exacerbation as compared with placebo. As we scan through this plot, the subgroup analysis also showed consistent reductions across the group of patients with blood eosinophil counts equal and above 150 cells per microliter. Next slide. Overall, these data from the COURSE study indicate the potential of efficacy for tezepelumab in a broader group of patients as compared to other products that have been studied to date. Current biologics being studied in COPD are limited to high eosinophil count in the COPD population, around 300 cells per microliter or above, which accounts to about 30% of the market. And as mentioned, teze's data shows the potential in a population with blood eosinophil count of 150 and above. This accounts for about 65% of the bio-eligible patients in COPD who have an eosinophil count of 150 or above. In addition to these nominal significant reductions at this baseline of 150, the COURSE study also showed that tezepelumab led to a numerical reduction of about 46% in the rate of moderate and severe exacerbation with patients who had eosinophil count 300 and above. Next slide, please. This graph depicts the incidence of on-treatment adverse events and serious adverse events. And these were generally similar between the 2 treatment groups in the COURSE study. And in general, these safety findings are very consistent with what has been previously reported for tezepelumab. Next slide, please. So in summary, the COURSE study shows that TEZSPIRE numerically reduced the annualized rate of moderate to severe COPD exacerbation in these patients enrolled in the trial who had moderate to very severe COPD with exacerbations. The magnitude of this effect increased with increasing the baseline blood eosinophil counts, including the nominally significant reductions of AERs of 37% in patients with blood eosinophil count of 150. This trend was also observed in pre-bronchodilator FEV1 and SGRQ total score. At this point, we are easily advancing to the Phase III clinical program evaluating tezepelumab in patients with COPD. And we are discussing the trial designs with regulatory authorities. Next slide, please. I also want to briefly mention about AMG 104. AMG 104 is a fragment antibody against TSLP, an inhaled version of TSLP that's being developed as a treatment for patients of uncontrolled asthma. If successful, this would expand the potential of TSLP franchise to the patients who do not have access to systemic biologics. Next slide, please. AMG 104 has been studied in a Phase I that evaluated the efficacy and safety of this inhaled product, which was administered once daily. It was studied in 2 parts. Part A evaluated 96 healthy patients -- healthy subjects for about 14 days. And Part B evaluated 77 subjects with moderate to severe asthma, who had elevated fraction exhaled nitric oxide equal and above 30 parts per billion. Next slide, please. With this study, the AMG 104 data demonstrated about 23% reduction of FeNO in patients who had moderate to severe asthma with an increased elevated baseline FeNO. At the highest dose of 8 milligram studied in this trial, 23% showed reduction at day 14, and it was maintained at day 28. And these are very comparable to about 25% reduction that was seen in TEZSPIRE's Phase IIb PATHWAY study around the same time point. AMG 104 was safe and well tolerated, and we anticipate the initiation of Phase II trial in 2024. With this, I hand it back to Dr. Jay Bradner.

Well, thank you, Primal, and congratulations to all colleagues and collaborators associated with these innovations and presentations. Truly remarkable data. We will now pivot from TSLP signaling to the OX40 pathway from airway epithelial cells to the interplay of pathologic T cells and keratinocytes. Next slide, please. Atopic dermatitis has, for sure, enjoyed meaningful progress in therapeutic development but remains an area of significant unmet medical need. The prevalence of AD is striking. 15% to 20% of children, up to 10% of adults in the United States alone. Atopic dermatitis remains a global challenge and a burdensome challenge. One in 3 people worldwide with AD will endure a moderate to severe disease. And for patients, atopic dermatitis can feel quite unpredictable, characterized by erratic flares resulting in real impact to quality of life and also mental health. The most common symptoms associated with moderate to severe atopic dermatitis are itch and pain, and over half of patients with moderate to severe disease have inadequately controlled disease with all currently available therapies, and that includes existing biologics. Next slide. We've taken the approach to target the OX40 pathway here via engagement of the OX40 receptor itself right on the surface of the pathogenic immune cell. Targeting the OX40 receptor directly provides a chance to achieve durable efficacy by directly modulating the pathologic cells that drive inflammation and those that contribute to disease severity and chronicity. The rocatinlimab antibody was designed specifically to remove activated pathologic or disease T cells. These are the cells that are pro-inflammatory and contribute to immune imbalance. And so the removal will rebalance the immune system across a large spectrum of inflammatory diseases here, atopic dermatitis. And notably, rocatinlimab does not target naive or resting T cells, those that do not express OX40, and this is very important for tolerability. Next slide. Shown here are the results of the Phase IIb study of rocatinlimab in moderate to severe AD. We've reported progressive sustained efficacy. This study recruited patients with moderate to severe disease who are inadequately controlled with topical therapy in all dosing regimens of rocatinlimab, produce greater improvement in the clinically relevant so-called EASI score as compared with placebo. All rocatinlimab cohorts showed improvements in the primary endpoint, and most cohorts showed significant improvements in secondary endpoints versus placebo by week 16. Progressive improvement in efficacy was observed after week 16 with sustained efficacy off treatment for 20 weeks. You see patients with atopic dermatitis frequently experience relapse, necessitating long-term treatment. This prolonged effect might reflect the unique mechanism of rocatinlimab, which I shared inhibits T cell activation but also expansion of inflammatory T cells. Next slide, please. Overall, Phase II rocatinlimab demonstrated a favorable safety profile. This table here highlights the most common adverse events, those that registered in more than 5% of patients in the total rocatinlimab group as observed in the double-blind period through week 18. Fever and chills were observed in less than 20% of patients and occurred primarily after the first administration of rocatinlimab and did not lead to treatment discontinuation. Next slide, please. We're quite committed to the development of rocatinlimab through the ROCKET Phase III development program, an extensive, robust program that includes 8 studies that seek to support regulatory submissions, of which 3 have closed enrollment. This program will evaluate the efficacy, safety and tolerability of rocatinlimab monotherapy and combination therapy in adult and adolescent patients. This is the largest and most comprehensive Phase III program in atopic dermatitis to date, and over 3,000 patients have been enrolled to the ROCKET program. All studies are in patients with moderate to severe atopic dermatitis who've had inadequate response of contraindication or intolerance to topical medicines. Amgen is investing in specific adolescent trials for rocatinlimab because of the growing recognition that the burden of AD in adolescence is quite high. And focusing on this patient population will lead to more appropriate therapy and hopefully better long-term control of the disease. The study readouts and the various programs of this ROCKET suite of studies are expected to begin later this year with the HORIZON study that extends through 2026 to fully investigate both the initiation and maintenance uses of rocatinlimab. Notably, for extended dosing and maintenance, ROCKET ASCEND site will seek to understand extended dosing [ Q4, Q8 ] at optimal efficacy, which may be able to be achieved with rocatinlimab and will round out our understanding of both induction and maintenance therapy with rocatinlomab. Thank you for joining us for these presentations. And we'll send it back to Murdo for some Q&A. Just to conclude, we thought today to update all on the real progress in the development of IMDELLTRA for small cell lung cancer, and in the context of this American Thoracic Society Meeting, to give a sense of the depth and breadth of Amgen's commitment to pioneering treatments for critical unmet needs across the spectrum of diseases and has had a chance today to share innovations in 2 of these 4 pillars. The approval of IMDELLTRA is a real milestone in the treatment of small cell lung cancer and well validates our dedication in medicines that truly make a difference in patients' lives and approach the root cause of disease. Additionally, this encouraging data for TEZSPIRE and COPD highlights the ongoing effort to address the needs of patients with respiratory conditions. And looking ahead, we're excited about the potential of AMG 104 from controlled asthma using an inhaled TSLP inhibitor and rocatinlimab for atopic dermatitis. We're confident that through these medicines and beyond, we're on a path to deliver long-term growth for the business at the end of this decade and -- through the end of this decade and beyond and look forward to sharing more updates in the other pillars in the fullness of time. I'll turn it back over to you, Murdo, for some Q&A.

Thank you, Jay, Susan, Primal and Jean-Charles. Exciting new developments here. We'll open it up, Julienne, to see if we have our first question.

[Operator Instructions] Our first question comes from Mohit Bansal from Wells Fargo.

Congrats on the progress. I have one question regarding lung function and asthma trial. What do you think is meaningful? Is it like [ 100 ml is ] better? Or is there a [ threshold when it ] starts to become more meaningful improvement? And then the second part is, I mean, the market will have a lot of options. I mean dupi is there. Obviously, TEZSPIRE has a benefit there given that it was [indiscernible] in the presence of IL-33 as well, how do you think market will shape up in coming years?

So Mohit, if I heard your question correctly, the first part was about lung function in COPD with TEZSPIRE. And then the second one was market options and how that market might evolve as we enter into also, I'm assuming, COPD.

Exactly.

Okay. So the first part, perhaps, Primal, you could handle. And then we'll ask Susan to comment on the commercial question.

Yes. The FEV1, which is a matter of lung function, is actually evaluated in the COURSE trial. And the data actually shows that the lung function improves and at the continuum of the baseline eosinophil count. At the count 150 and above, there is significant improvement, and it actually gets jumped to a higher rate of about 146 mL improvement of FEV1 when the count of eosinophil goes higher than 300 and above. So we did see improvement in the lung functions along with improvement in exacerbations.

Thank you, Primal. Susan?

And then as we noted, the COPD market has significant unmet medical need, and there is room for therapy that can help patients. With regards to comparisons with TEZSPIRE and DUPIXENT, as there's no head-to-head studies conducted, we can't make a comparison between the 2 at the time. However, in COURSE, we recruited a broad population of COPD patients, including patients with both high and low eosinophil irrespective of the inflammatory driver, and patients were stratified by region and number of prior exacerbations. The BOREAS study limited recruitment to patients with the baseline of BEC greater than 300, which represents about 20% to 40% of the overall COPD population. So overall, we think that we're in a good position with the work coming out of the Phase II to move into a study in Phase III to better define TEZSPIRE in this population and meet the needs that are in the market.

Thanks, Susan. Thanks, Mohit, for the question. Julienne, our next question, please.

Our next question comes from Gregory Renza from RBC Capital Markets.

This is Supawat on for Greg. I'm just curious about the TEZSPIRE results with regard to why do you think the significant inflection on the annualized rate of COPD exacerbation or [ call it about ] BEC greater than 150 cell per microliter. Is there a particular reason why? And then I'm just curious how confident are you and your partner on potentially moving forward in a population that has BEC greater than 150 cell per microliter.

All right. Primal, do you want to take that one, please?

Yes. Thank you, Murdo. The continuum of the blood eosinophil count is showing the intensity of the inflammatory load that happens in these diseases, and it's very similar to what we've seen in asthma. The COPD data also shows similar increase in the blood eosinophil count and improvement with anti-inflammatory therapies. So I would say the fact that the 150 and below do not show the significant improvement that above 150 shows is accounted for the mechanisms of inflammatory pathways that play a role. And I think the improvement of 150 and above in many different parameters of the disease evaluation in the clinical trial provide us a lot of confidence in moving forward along with our partners in AstraZeneca.

Thank you, Primal. Julienne, next question, please.

Our next question comes from Matt Phipps from William Blair.

I guess curious if you can give us a little additional detail on why you chose the 420 mg dose level in this study. Why not study multiple doses in the Phase II? Do you think you need another dose level in the Phase III?

Primal, would you like to handle Matt's question, please?

Sure. Thank you, Murdo. Matt, this is a proof-of-concept Phase IIa study that we planned and executed along with our partners in AstraZeneca. And it's very typical for us to have a broader population and higher doses to ensure that we are seeing signals of improvement in populations within COPD. Having said that, we are evaluating with our partners and talking to regulators about the appropriate doses that would go into Phase III. Thank you.

Thanks for the question, Matt. Julienne, next question, please.

Our next question comes from Carter Gould from Barclays.

Congrats on the IMDELLTRA approval. I guess first, on the TEZSPIRE data, there did seem to be somewhat of a trend in terms of those patients with older age having a less pronounced response. Maybe you can either put my concerns there to bed or address that in any way. And Jay made an interesting comment in his opening comments around sort of selective cellular depletion, sort of teasing out a potential role for BLINCYTO there. Is there anything you want to say on that front? Or is that just more of a theoretical comment?

Thank you, Carter. Let's start then with your TEZSPIRE question with Primal, and Jay, I'll let you comment.

Happy to.

Thank you. In the Phase II COURSE data, we did see slightly better improvement in age group of 40 to 60 as compared to the older group. And this could be possible of the differences in the diseases between the age groups. These diseases can eventually lead to scarring of the tissue. So those are the possible differences we're thinking. We are looking at all other parameters and evaluating the details of data sets to have a definite answer on that one.

Thank you. And thanks also for your question. I didn't mean to be so leading. It is an exciting time to consider CD19 B cell depletion in autoimmune diseases and the remarkable activity that we've seen with UPLIZNA is, I think, a great example of that. It's more a case report or case series level that we're now seeing in the scientific and medical literature, as I'm sure you're well aware, depletion of CD19-positive B cells with complex cell therapies like CAR T cell therapies and even small series with our own blinatumomab through investigator activities. This is a company that's quite knowledgeable about the depth, durability and different pharmacologic approaches to B cell depletion via CD19. That is not lost on us also as a leading inflammatory group that completing the whole of the CD19 B cell compartment, it could be very different. It could be much more efficacious than, say, just a mature CD20-positive B cell. In the fullness of time, we'll have a chance to share more, but we're well organized around the opportunity to think about and explore CD19 cell -- B cell depletion using the therapeutics in our portfolio.

Thank you, Jay. Thanks, Primal. Julienne, next question, please.