AMG 133 (Obesity Drug Development)
Q: Can you discuss the recent Phase I data for AMG 133 and its competitive profile?
A: We are pleased with the Phase I results of AMG 133, where the highest dose of 420 mg led to 14.5% weight loss by day 85, with effects durable up to day 150 and mild gastrointestinal side effects. The Phase II study is exploring 11 dosing cohorts to find the optimal dose and schedule, including less frequent dosing than monthly. We believe the data supports our ongoing efforts to develop this therapy to benefit patients with obesity.

AMG 133 Phase III Plans
Q: What informs your next indications for AMG 133 and timing of the Phase III program?
A: Obesity is a major public health crisis, and we plan to develop AMG 133 in all indications where its dual mechanism can improve public health. We are actively planning an expansive Phase III program, expecting to move multiple indications forward in parallel as soon as we have the requisite data.

AMG 133 Dosing and Patient Experience
Q: Can you provide insight into AMG 133 dosing and its clinical profile compared to competitors?
A: The doses we are using are well within scope for a modern biotherapeutic, and we have the capabilities to deliver this medicine at any required dose and schedule. Our antibody inhibits the GIP receptor, a choice supported by strong genetic insights showing reduced BMI with GIP inhibition. We anticipate a positive and simple patient experience, drawing from our experience with other biologics.

TEPEZZA Growth Strategy
Q: What are your priorities for TEPEZZA to continue growing the patient base?
A: We are seeing growth with a record number of unique TEPEZZA patients and increased patient starts. We have expanded payer coverage to over 50% of U.S. covered lives. With low penetration among the approximately 100,000 eligible patients in the U.S., we are focusing on continued execution to drive uptake. We are also excited about the international opportunity and investments in innovation for thyroid eye disease patients.

TEZSPIRE in COPD Differentiation
Q: How will you differentiate TEZSPIRE in COPD given competitive data from Dupixent?
A: Our Phase II COPD study includes 337 patients with moderate to severe COPD who continue to have exacerbations despite triple therapy, reflecting the unmet need. TEZSPIRE targets TSLP upstream, potentially impacting disease biology more effectively and treating a broader patient population. We believe we can help patients refractory to existing therapies.

UPLIZNA Expansion Opportunities
Q: Where do you see UPLIZNA fitting into the MG treatment paradigm and expansion opportunities?
A: UPLIZNA is growing nicely in neuromyelitis optica spectrum disorder (NMOSD), becoming the fastest-growing biologic in that indication. CD19 is a valuable target, and we see opportunities to expand into additional autoimmune diseases by targeting all B cells except plasma cells.

Xaluritamig Positioning in Prostate Cancer
Q: What are your data disclosure plans for Xaluritamig, and how is it positioned against competitors?
A: Xaluritamig is a STEAP1 CD3 bispecific being studied in advanced castrate-resistant prostate cancer. Our priorities include establishing reduced monitoring and exploring combinations with novel agents. We plan to present the regulatory path in due course and are encouraged by the clinically meaningful response rates in patients with advanced disease.

GIP Antagonism vs. Agonism Debate
Q: Do you have any response to competitors favoring GIP agonism over antagonism?
A: The argument for GIP receptor antagonism comes from robust scientific data, including genetic studies showing reduced BMI with GIP inhibition. We feel confident in our approach and the potential benefits of AMG 133.

Subcutaneous TEPEZZA Delivery
Q: Can you provide details on the technology for subcutaneous TEPEZZA delivery?
A: We are moving forward with developing a subcutaneous formulation of TEPEZZA but are not commenting on the specific technology provider at this time.

Daxtilimab Development in Lupus
Q: What is your level of confidence in daxtilimab for lupus, and when will we see data?
A: It's early days for daxtilimab, but we have strong preclinical support and believe in its potential based on the underlying biology. The target helps control central signaling in autoimmune diseases, and we are focused on generating clinical data.

AMG 786 Progress
Q: What's driving the delay in AMG 786 progress, and when should we expect data?
A: AMG 786 is an oral medicine being developed for obesity, and the study is progressing well. We expect to have the Phase I readout in the first half of 2024.

AMG 133 Impact on Blood Pressure and Lipids
Q: Do you expect AMG 133 to impact blood pressure and lipids similar to tirzepatide?
A: It's too early to draw conclusions, but we are making these measurements and will have data at the end of Phase II. We are focused on understanding the full clinical profile of AMG 133.

AMG 133 Discontinuations and Liver Enzyme Elevations
Q: Can you comment on discontinuations at high doses and liver enzyme elevations in AMG 133 trials?
A: Four out of eight patients at the 420 mg dose declined further participation mainly for logistical reasons, with adverse events comparable to other patients. Regarding liver enzyme elevations, it's too early to provide patient-level insights.

AMG 133 Lipid Effects
Q: Is it too early to attribute triglyceride changes to GIP antagonism in AMG 133?
A: Yes, it's too early to attribute lipid changes to antagonism versus agonism. Lipids are variable and indirect biomarkers; we are making measurements in Phase II.

TEZSPIRE Commercial Strategy
Q: How are you planning to commercialize TEZSPIRE effectively in the COPD market?
A: With our unique and differentiated mechanism, we aim to treat a broader patient population, including those refractory to current therapies. We have strong commercial capabilities with our partner AstraZeneca and are well-positioned to bring TEZSPIRE to market.