Amgen, Inc. (NASDAQ:AMGN) ATS and the Approval of IMDELLTRA Conference Call May 20, 2024 4:00 PM ET

Company Participants

Justin Claeys - Vice President of Investor Relations
Murdo Gordon - Executive Vice President, Global Commercial Operations
James Bradner - Executive Vice President, Research and Development
Jean-Charles Soria - Senior Vice President, Global Development Oncology
Susan Sweeney - Senior Vice President, Global Marketing, Access Capabilities
Primal Kaur - Vice President, Global Development, Inflammation

Conference Call Participants

Mohit Bansal - Wells Fargo
Matt Phipps - William Blair
Carter Gould - Barclays
Michael Yee - Jefferies
Matthew Dellatorre - Goldman Sachs
Evan Seigerman - BMO Capital Markets
Geoff Meacham - Bank of America
James Shin - Deutsche Bank
Kripa Devarakonda - Truist Securities
Gary Nachman - Raymond James

Operator

My name is Julianne and I'll be your conference facilitator today for Amgen's Conference Call Following The American Thoracic Society 2024 International Conference and the Approval of IMDELLTRA. All lines have been placed on mute to prevent any background noise. There will be a question-and-answer session at the conclusion of the last speakers' prepared remarks. [Operator Instructions]

I would now like to introduce Justin Claeys, Vice President of Investor Relations. Mr. Claeys, you may now begin.

Justin Claeys

Thank you, Julianne. 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 four 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 we'll make these available immediately after the call on the Investor Relations section of our website.

Let me now turn the call over to Murdo.

Murdo Gordon

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 four 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.

Turning to inflammation, Amgen has a two decade long history of serving patients with autoimmune diseases with broad coverage across the main areas of inflammatory conditions, including respiratory, dermatology, gastroenterology and rheumatology.

Today, we will share encouraging data for TEZSPIRE that reflect 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.

TEZSPIRE's 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 and inhaled TSLP inhibitor. And we'll conclude today with rocatinlimab, our potentially first and best-in-class OX40 inhibitor that's being studied in a broad Phase 3 program, including atopic dermatitis.

And with that, I'll invite Jay to walk us through the IMDELLTRA update.

James Bradner

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, a 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.

A 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, two-thirds 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 unacceptably poor prognosis with a five-year survival of only 7% for invasive disease. And indeed, more than three-quarters 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 five to seven months or four to five months in the second-line and third-line settings respectively, effectively unaffected by any differences in patient characteristics such as smoking history or local standards of care, such as the use of IO therapy in the frontline.

And these analyses performed by C4 with an 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 into IMDELLTRA. As I shared IMDELLTRA functions by bringing activated T-Cells to the site of tumor growth. Effectively, this protein therapeutic has two arms, one that binds to and activates the T-Cell via the CD3 protein on the T-Cell surface and another that binds a protein on the small-cell lung cancer surface, the DLL3 protein.

Unlike most tumor targeted therapies, there is 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.

Jean-Charles Soria

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-PDL1 therapy and around 22% of them had 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 and 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 six months or more and 40% were still responding at one-tier. This is quite remarkable taking into account the fact that these were mostly second and third-line small-cell lung cancer pre-treated 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 the 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 treatments.

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 two 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. Doses interruptions of IMDELLTRA due to adverse reaction occur in 27% of patients with adverse reactions that require dose interruptions in 2% of more patients, including fatigue, TRS and respiratory tract infection.

If we move to the next slide, you will be able to see the temporal evolution of the side effect. What is pretty remarkable is that the majority of CRS events were Grade 1 and occurred following the first two 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 occur 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 US, note that you cannot add all the third-line patients with the second-line patients because you can't be treated in both settings. The second-line and later patients have a very clear poor prognosis with an overall survival in the second-line ranging in the six to nine 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 three Phase 3 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 chemoradiotherapy. The rationale for studying IMDELLTRA into earlier lines is related to the concept of low tumor burning that has been highlighted with in situ in acute lymphoblastic leukemia.

There we saw a dramatic improvement in overall survival and minimal residual disease-negative patients. These in situ data provide evidence that directing the T-Cells in this manner is an effective means of finding and eliminating residual cancer cells, which are primarily the drivers of recurrent 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, with 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.

Murdo Gordon

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 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 healthcare 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 in integrating this innovative technology into their practice. In addition to our existing patient support services like co-pay assistance, therapy locator, benefit verification, we're introducing a new program specifically for IMDELLTRA patients and healthcare providers.

So our Amgen Patient 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 healthcare provider education to instill trust in IMDELLTRA 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 3 data readout expected later this year.

James Bradner

Well, thank you, Murdo and Jean-Charles. I'm still hopeful for this medicine and thankful for the many patients and clinicians who've collaborated in bringing IMDELLTRA through clinical investigation. And as Murdo shared, it's an exciting time across all four pillars of the Amgen R&D portfolio. It's 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 immunosuppressors.

But we leverage a variety of mechanisms. This allows the clinician to tailor medical management to the underlying disease pathophysiology, which is increasingly understood at atomic resolution. Our four mechanistic 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. Here, 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 is 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 organize these activities in inflammation across our four broad disease areas, respiratory diseases, dermatology, gastroenterology and rheumatology. And we have 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 three 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.

Susan Sweeney

Thank you, Jay. TEZSPIRE has established itself firmly in major markets as a 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 it's 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's 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 bioeligible 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.

Primal Kaur

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 advanced that 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 core study experiment. It's a Phase 2A 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 two or more documented COPD exacerbations in 12 months prior to enrollment.

No patients were excluded based on blood eosinophilic 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 core study indicate the potential of efficacy for tezepelumab in a broader group of patients as compared to other products that have been studied till 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, tez's data shows the potential in a patient population with blood eosinophil count of 150 and above.

This account for about 65% of the bioeligible 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 core study also showed that tezepelumab led to 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.

These graph depicts the incidence of on treatment adverse events and serious adverse events and these were generally similar between the two 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 showed that TEZSPIRE numerically reduced the analyzed 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 eagerly advancing to the Phase 3 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 1 that evaluated the efficacy and safety of this inhaled product, which was administered once daily. It was studied in two parts. Part A evaluated 96 healthy patients -- healthy subject for about 14 days. And Part B evaluated 77 subjects with moderate to severe asthma who had elevated fractioned 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 milligrams 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 2B pathway study around the same time point. AMG 104 was safe and well-tolerated and we anticipate the initiation of Phase 2 trial in 2024.

With this, I hand it back to Dr. Jay Bradner.

James 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 three people worldwide with AD will endure 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.

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 diseased T-Cells. These are the cells that are pro-inflammatory and contribute to immune imbalance.

And so their removal will rebalance the immune system across a large spectrum of inflammatory diseases, here atopic dermatitis. Now 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 2B study of rocatinlimab in moderate-to-severe AD. We've reported a progressive sustained efficacy. This study recruited patients with moderate-to-severe disease who were 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 experienced 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, in Phase 2, 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 3 development program, an extensive robust program that includes eight studies that seek to support regulatory submissions of which three 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 3 program in atopic dermatitis to-date and over 3,000 patients have been enrolled to the ROCKET program. All studies are inpatients with moderate-to-severe atopic dermatitis who've had inadequate response, a contraindication or intolerance to topical medicines.

Amgen is investing in specific adolescent trials for rocatinlimab because 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 in the various programs of this ROCKET suite of studies are expected to begin later this year with a HORIZON study that extends through 2026 to fully investigate both the initiation and maintenance uses of rocatinlimab.

Notably, for extended dosing and maintenance, the ROCKET ASCEND study will seek to understand extended dosing Q4, Q8 at optimal efficacy, which may be able to be achieved with rocatinlimab and we'll round out our understanding of both induction and maintenance therapy with rocatinlimab.

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, 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 the breadth of Amgen's commitment of pioneering treatments for critical unmet needs across the spectrum of diseases and have a chance today to share innovations in two of these four pillars.

The approval of IMDELLTRA is a real milestone in the treatment of small-cell lung cancer and it well dedicates our dedication to 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 for uncontrolled 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 to the business at the end of this decade and through the end of this decade and beyond and look forward to sharing more updates on the other pillars in the fullness of time.

I'll turn it back over to you Murdo for some Q&A.

Murdo Gordon

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

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] Our first question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Mohit Bansal

Great. Thank you very much for taking my question and congrats on the progress. I have one question regarding lung function in asthma trial. What do you think is meaningful? Is it like 100 [Technical Difficulty] better or is there a threshold that it could start to become more meaningful improvement. And then the second part is, I mean, the market will have a lot of options. I mean, GP is there, obviously, the buyer has a benefit there given that it works among the lower [Technical Difficulty] in the presence of IL-33 as well, how do you think market will shape up in coming years? Thanks again.

Murdo Gordon

So Mohit, if I heard your question correctly, 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 it, also I'm assuming in COPD.

Mohit Bansal

Exactly. Thank you.

Murdo Gordon

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

Primal Kaur

Yes. The FEV1, which is a measure 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.

Murdo Gordon

Thank you, Primal. Susan?

Susan Sweeney

And then as we noted, the COPD market has significant unmet medical need and there is room for therapies 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 two at the time. However, in course, we recruited a broad population of COPD patients, including patients with both high and low eosinophils 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 2 to move into a study in Phase 3 to better define TEZSPIRE in this population and meet the needs that are in the market.

Murdo Gordon

Thanks, Susan. Thanks, Mohit, for the question. Julianne, and our next question, please.

Operator

Thank you, Mohit. Our next question comes from Gregory Renza from RBC Capital Markets. Please go ahead. Your line is open.

Unidentified Analyst

Hi. Thank you so much for taking our questions. This is [indiscernible] 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 occurred around BEC greater than 150 cells per microliter? Is that 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 150,000 microliter? Thank you.

Murdo Gordon

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

Primal Kaur

Yeah. 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.

Murdo Gordon

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

Operator

Thank you. Our next question comes from Matt Phipps from William Blair. Please go ahead. Your line is open.

Matt Phipps

Hi. Thanks for taking my question. 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 of Phase 2? Do you think you need another dose level in the Phase 3?

Murdo Gordon

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

Primal Kaur

Sure. Thank you, Murdo. Matt, this is a proof-of-concept Phase 2A 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 improvements 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 3. Thank you.

Murdo Gordon

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

Operator

Thank you, Matt. Our next question comes from Carter Gould from Barclays. Please go ahead, your line is open.

Carter Gould

Hi, good afternoon. Thanks for taking the question and 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, but 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.

Murdo Gordon

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

Primal Kaur

Thank you. In the Phase 2 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 are thinking. We are looking at all other parameters and evaluating the details of datasets to have a definite answer on that one.

James Bradner

Thanks again. 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 I think a great example of that. At this more case report or case series level, 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 leading inflammatory group that depleting the whole of the CD19 B-cell compartment, it could be very different, it could be much more efficacious than say just the 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 B-cell depletion using the therapeutics in our portfolio.

Murdo Gordon

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

Operator

Thank you, Carter. Our next question comes from Michael Yee from Jefferies. Please go ahead. Your line is open.

Michael Yee

Hey, guys, thanks for the updates on all of these. Two-part question. One on tezepelumab, can you just maybe comment about whether you see any broader implications or benefits beyond just the 150 and above? Obviously, your primary competitor Dupi is 300 and above and I appreciate it's a larger market, but in some cases, some docs say they don't necessarily rely so much on a eosinophil baseline counter, it's moving around. So it's a little complicated just by thinking about the eosinophil count. And then on OX40, you brought that into the conversation, which was great. There's a lot of controversy around whether your mechanism would have more infection risk. Can you comment about how you feel about that with the ongoing study and whether we just need more longer-term data in some of your other follow-ons? Thank you.

Murdo Gordon

Thanks, Michael. I'll ask Primal to answer the first part of your question on tezepelumab and then Jay will handle OX40.

Primal Kaur

Yeah. Thank you, Murdo. In terms of the enrollment of the patients, I think baseline blood eosinophil count was one of the criteria. As we plan to include these patients in clinical trials, we also look at whether they fit the gold criteria and what is their lung capacity and the lung function. So all of those elements are very good indicators for physicians to understand which patients would be the right patients for, for example, tezepelumab or others.

James Bradner

Yeah. Thank you, Michael, for the question about rocatinlimab and I'll avoid making any overt contrast or comparisons to our peer company's medicines. But this capacity of targeting OX40 to really just take-out more pathologic tissue resident T-Cells versus the naive T-Cell, but remember what I said that this has a chance to really open up the therapeutic index, but by removing the pathologic cell, have a meaningful and actually quite durable potential impact on atopic dermatitis. And now with that, we have to be very careful when depleting any T-Cells that were quite organized and making the measurements necessary to assure clinicians of safety. And the safety data from the more than 400 subjects exposed to at least one-dose of rocatinlimab are quite supportive of a favorable safety profile. And this includes the results from the Phase 2b study that I shared a moment ago that was more than 250 patients. And thus far, no relevant complications including the development of autoimmune diseases or malignancies of above the rate as expected in the two arms. The most common effects, as you know, are fevers, less so chills is usually a first-dose effect and the first or second day of dosing and the vast majority are resolved within 24 hours. And so the safety profile of rocatinlimab is ultimately to be confirmed with the completion of the ROCKET program. And given the scope, more than 3,000 patients in that program will have a strong understanding of just how safe this medicine is, but thanks for your question.

Murdo Gordon

Thank you, Jay. Thank you, Primal. Thanks for the questions, Michael. Julianne, next caller, please.

Operator

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

Matthew Dellatorre

Hey, thanks. This is Matt on for Salveen. So I know discussions with the FDA are ongoing, but could you share anything further on how you're thinking about the Phase 3 design and strategy? I mean, given the data, it seems clear you would include all patients with BEC greater than 150, but could you even pursue a broader label with no BEC restrictions given the favorable impact on severe exacerbations as well as overall positive effect based on other characteristics? And then what's a good estimate for a Phase 3 start date? Thank you.

James Bradner

Thanks for your question. At this time, we're not intending to share the design principles of the Phase 3 study. But all of these discussions are progressing very well with our partner and we'll have a chance to guide on the opening of the study in the near-term. Thank you, Matt.

Murdo Gordon

Thanks, Jay. Julianne?

Operator

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

Evan Seigerman

Hey, guys, thank you so much for taking my question and congrats on the data. Looking at the response of patients with the FeNO above 25 PBB, so really strong favoring of the teze treatment. Do you think that could factor into any further trial design? Is this subpopulation worth further exploration? Thank you.

Murdo Gordon

Thanks, Evan. I'll ask Primal to comment on that, please.

Primal Kaur

Well, thank you for the question. We are putting all of these parameters on the table while we are evaluating for the final population for Phase 3.

Murdo Gordon

Thanks, Primal. Julianne, next caller, please .

Operator

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

Geoff Meacham

Hey, guys. Thanks for taking the questions. There have been a lot on TEZSPIRE, so I wanted to ask on the IMDELLTRA approval. So I know DLL3 is mostly small-cell and neuroendocrine, but what do you guys think about a broader basket study and what would that show with respect to breadth of expression? And then as you move into earlier lines of therapies, I appreciate the unmet medical need, but what would you say would be the benchmark and what would success look like with respect to things like duration of therapy perhaps? Thank you very much.

James Bradner

Jeff, thanks so much for the question. It is true that DLL3 can be a cell surface marker in malignancies beyond just small-cell lung cancer. And not as characteristic or uniform in its expression and not as homogeneously expressed, but neuroendocrine tumors beyond the lung do feature DLL3 positivity. There are some challenges to studying these tumors and that they're heterogeneous arising in the pancreas or genitourinary system or elsewhere in the GI tract and a basket type study would be a smart way to go about that and gaining experience with this medicine is a priority. But we do not as yet have announced a registration path to thinking about IMDELLTRA use beyond small-cell lung cancer, but know that the community with its availability will be interested for us together to build that experience. As you asked about the earlier lines of therapy, here I would just have to hazard a guess. And -- so if you permit this as being a bit exploratory, our experience developing BiTE technologies for acute lymphoblastic leukemia taught us a couple of things that we can't say are generalizable insights, but they are influencing the way that we're studying IMDELLTRA in frontline therapy for small-cell. We've learned that the BiTE therapies with ALL, BLINCYTO namely, work better after tumors developed in or near the minimal residual disease state. Second, we've learned that you want to go in with a strong dose coming right out of the gates. And third, that dose can need to be optimized. It's not a case of maximum tolerated dosing. And we're bringing all of those learnings into the frontline development of IMDELLTRA. You must know that small-cell lung cancer clinically is a bit of an ironic disease to treat because it responds very well to chemotherapy upfront, but then patients invariably progress. And so for a medicine like IMDELLTRA, we will give this medicine after upfront chemotherapy in a more maintenance approach in order to treat with a lower disease burden. What could this translate into, you asked. My hope is that it would translate into a greater durability of that upfront chemo response, which is just not durable enough potentially and we will seek to measure improvements in progression-free and overall survival. So I wouldn't hazard a guess at this point, but these studies are well designed to explore this.

Murdo Gordon

Thank you, Jay. Thanks, Geoff, for the question. Julianne, next caller with next question please.

Operator

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

James Shin

Hi. Thank you for the question. For teze, can you share the baseline number of mod-severe exacerbation? It looks like based on the baseline characteristics, teze Phase 2A had slightly higher baseline exacerbation than Dupi's BOREAS in noticed populations.

James Bradner

Yeah, thanks for the question, but I'll take this one. It's Jay here. It's really hard with cross-trial comparisons. I think it's especially hard in these baseline demographics of these studies. I did review the notice presentation. And I would say that these were largely on par. They quoted an average of 2.1% to 2.2% with a trailing one year. We observed in our studies to date 60% of patients with more than 2% and 40% more than 3%, maybe we skew even a little more with exacerbations. But I think this is all within the overlapping and wiggle room of baseline characteristics. I think it's one word to highlight any difference is whereas we've shared, very taken with this finding of the blood eosinophil count of greater than 150 and that commands further attention.

Murdo Gordon

Thanks, Jay. Thanks, James. Julianne, next question please.

Operator

Thank you, James. Our next question comes from Kripa Devarakonda from Truist Securities. Please go ahead. Your line is open.

Kripa Devarakonda

Hey, guys, thank you so much for taking my question and congrats on approval of IMDELLTRA. That's where I have a question. I was wondering if you can talk about CRS with IMDELLTRA and how that was managed on the trial and what level of experienced solid tumor doctors have to deal with CRS, particularly since you talk about 70% being treated in community. Number one, can you talk about what kind of additional educational efforts you might need for them? And also a little bit more about your commercial strategy given 70% are in community? Thank you.

Murdo Gordon

Thank you, Kripa, for the question. I think it would be best to perhaps have Jean-Charles start from the clinician's point-of-view on how we anticipate our community and academia-based physicians? And then I'll comment at the end on how we're handling the commercial rollout? Jean-Charles?

Jean-Charles Soria

Yes. Thank you, Murdo. Thank you for the question. And we do have CRS with IMDELLTRA. Nevertheless, the prevalence of the CRS, the magnitude of the CRS and the dynamics of the CRS are very different and much milder if you compare with something like BLINCYTO. That being said, as for any innovation once you bring in to the community, there is a learning moment. Community doctors have to get to know, how to handle the toxicity of innovative immune checkpoint blockers and they have managed to do so. So we believe we will be able to accompany them in getting to learn this CRS. The key message is that these events happen at first and second dose and once you have managed through that, the frequency of event is very rare and the severity is mostly just great one. This is as much as which I would like to say, Murdo.

Murdo Gordon

Thanks, Jean-Charles. Kripa, I would just add that we are obviously very focused on making sure that a treating physician and patient have a good experience with their first cycle of IMDELLTRA. And so the monitoring aspect 22 to 24 hours will be really, really important here. And so there will be in the beginning some centers where that's a capability that they've got up and running, ready to go, scheduling patients, moving them through. And then it will take a bit of time in some of the community centers or even regional cancer centers to come online, if you will, with their monitoring capabilities or observation capabilities. This is not unfamiliar territory to us. There were complications with how to dose BLINCYTO in the beginning and we were very clear with our prescribers on how to handle the CIV nature of BLINCYTO. And we now actually have fairly broad use of BLINCYTO in the community and in academic and regional cancer centers. So our medical teams are fully deployed. As I mentioned in my prepared remarks, we have a very capable patient-focused service that we've launched for this product to help with logistics. And we're quite optimistic that we'll be able to handle what is a far and away a very big advance in the treatment of small-cell lung cancer. And I think given the hope that this product provides, we're already seeing physicians who are familiar with this product from clinical trials and those who are aware of what it can do for extensive-stage patients who have progressed. And I think that's what's going to carry the day is providing that option, that hope to a progressing small-cell lung cancer patient. Thank you. Julianne, given that we're at the top of the hour, maybe we have time for one more.

Operator

Thank you. Our last question will come from Gary Nachman from Raymond James. Please go ahead. Your line is open.

Gary Nachman

Okay, thanks and good afternoon. So first on IMDELLTRA, when will you have data on the earlier lines, those three studies? Just talk about the timelines there. And then for TEZSPIRE and COPD, maybe you could describe how the data look by subgroup for patients greater than two or greater than three annual exacerbations. Was it very consistent across those patient populations just in terms of the magnitude of effect, if you could give us some color on that. Thanks.

Murdo Gordon

Okay. Thanks, Gary. Jay, you want to handle the first part and then Primal?

James Bradner

Yeah. No, thank you, Gary. These studies and there are three Phase 3 studies that have been activated to study IMDELLTRA in earlier lines of therapy. One is a dedicated study on all-in second-line and two are frontline studies, one that's in extensive stage disease and one is in limited stage disease. The upfront treatment is quite different, even though the outcomes of both diseases can be quite poor. We've not provided as yet guidance as to when do you expect data for those trials, but we'll keep the community posted as those studies enroll and complete enrollment and readout. Regarding TEZSPIRE, as presented at the Thoracic Society meeting, it's -- small numbers of patients in this measure that are truly distinct. But among those patients with either two or greater than three prior exacerbations, there is a trend that those greater than three derive a bit more benefit with a ratio -- it has ratio of 0.7. That does cross one. It's 0.46 to 1.07. And for two, there was no overt correlation. So I can't say with any statistical significance, but there's a trend towards a better improvement with a greater number of prior exacerbations, which we will measure in the context of the subsequent studies. Thanks, Gary.

Murdo Gordon

All right, Julianne, I think we're ready to wrap-up here.

Operator

Thank you, Gary. We have no further questions. I would like to turn the call back over to Justin Claeys for closing remarks.

Justin Claeys

Okay. Yes. Well, let me first thank everyone again for your time and joining the call today. As you heard, a lot of exciting developments here at Amgen and we're pleased to share those with you. And as always, the Investor Relations team is available to answer any follow up questions that you might have and we look forward to speaking with you. And finally, as I mentioned earlier, the materials that we reviewed today, specifically the slides will be posted onto our website. So thanks again and have a good rest of the day.

Operator

This concludes our Amgen Conference Call following the American Thoracic Society 2024 International Conference and the approval of IMDELLTRA. You may now disconnect.