Investment in Orforglipron Manufacturing
Q: How are you balancing investment in capacity with orforglipron's probabilities?
A: We're investing fully to create new capacities - , building ahead of Phase III for orforglipron at risk due to its potential. -

Opportunity for Oral GLP-1s
Q: How do you view the opportunity for oral GLP-1s like orforglipron?
A: With over 110 million obese in the U.S. - , injectables can't reach all; orforglipron offers an oral option with competitive weight loss and no food restrictions - , appealing to patients reluctant to use injectables. -

Manufacturing Capacity Strategies
Q: Will you buy rather than build to overcome manufacturing bottlenecks?
A: We're not capital-constrained, but existing capacity isn't available - ; building new capacity takes 3-4 years, so buying doesn't solve immediate needs - ; over time capacity will increase, and new technologies like orforglipron will help. -

Impact of Novo's Acquisition of Catalent
Q: Does Novo's acquisition of Catalent impact your supply strategy?
A: We have questions about the transaction and need to learn more - ; our focus is on ensuring uninterrupted supply and holding Catalent accountable to contracts. -

Future Plans for Tirzepatide in NASH
Q: Why hasn't Lilly initiated a Phase III trial of tirzepatide in NASH?
A: We just received positive Phase II data and are determining next steps - ; nothing in the data prevents us from proceeding, but we may have better molecules like retatrutide. -

SYNERGY-NASH Trial Prospects
Q: Is there a prospect for accelerated approval from SYNERGY-NASH?
A: We're excited about the promising data from a small trial (190 participants) showing clinically meaningful improvement in fibrosis - , and we look forward to discussing next steps with the FDA. -

SURPASS-CVOT Trial Timing
Q: Does the delay in SURPASS-CVOT imply interim results, and is superiority needed?
A: We don't comment on interims; the delay is due to slower event rates, which is good for patients. - Superiority would be beneficial, but we remain focused on the trial's completion. -

GIP Agonism vs. Antagonism
Q: How do you view GIP agonism versus antagonism?
A: We're extremely confident in the benefits of GIP agonism based on extensive data - ; antagonism may have negative effects like increased free fatty acids - , while agonism may improve tolerability. -

Zepbound Payer Coverage Expansion
Q: Will most payers who cover Wegovy add Zepbound this year?
A: We have 35% commercial access early in launch - , aiming to expand to levels similar to competitors, around 50%. -

International GLP-1 Launch Expansion
Q: What are the hurdles to closing the ex-U.S. gap in your GLP-1 franchise?
A: We've launched Mounjaro in markets like Australia, Canada, Germany, and Poland - , received QuickPen approval in the U.K. - , and will continue launching as we get approvals and increase supply capacity throughout this year and into 2025. -

Lean Muscle Loss and Tirzepatide
Q: What's Lilly's take on lean muscle loss with tirzepatide vs. semaglutide?
A: Tirzepatide improves lean-to-fat mass ratio, losing more fat than lean mass - ; the ratios you mentioned seem correct, possibly due to GIP agonism benefits. -

Duration of GLP-1 Therapy Use
Q: Any updates on duration of GLP-1 use in diabetes and obesity patients?
A: It's still early, but Mounjaro shows encouraging persistency similar to other injectable incretins - ; too early to gauge for Zepbound. -

Extended Dosing and Sustainability
Q: What's your view on extended dosing like monthly administration and sustained efficacy off-therapy?
A: The data on extended dosing and sustained efficacy are underwhelming - ; weight loss is lower than needed for Phase III - ; convenience matters but isn't the most important factor for providers and patients. -

Downstream Opportunities for GLP-1 Therapies
Q: How are you sizing downstream opportunities for tirzepatide in NASH and other indications?
A: Key drivers are increased employer opt-in and access in Medicare Part D, supported by data in comorbidities like cardiovascular and NASH. -

Orforglipron Safety and DDI Profile
Q: What do you mean by orforglipron having lots to prove, and will it work with SGLT2s?
A: As we're starting Phase III, we need to confirm safety - ; we expect coadministration with SGLT2s to be possible and have it ongoing in trials. -

Tirzepatide in Sleep Apnea
Q: How much benefit is needed in sleep apnea for clinical meaningfulness?
A: There's no established threshold, but we're optimistic about tirzepatide's potential and will assess various measures to determine clinical meaningfulness. -

Purpose of Lilly Direct Platform
Q: Is Lilly Direct just to streamline access, or is there a monetization model?
A: Lilly Direct aims to streamline access for patients and serve them better - , not intended as a new retail distribution business. -

Tirzepatide Branding Outside the U.S.
Q: Why not launch Zepbound outside the U.S. but expand Mounjaro's label?
A: Branding decisions depend on regulatory, competitive, and payer dynamics - ; we're optimistic about commercialization under different brand scenarios. -