VESPER-3 was designed to test whether patients could transition from weekly titration to monthly maintenance dosing without losing efficacy. From a clinical standpoint, how meaningful is the ability to preserve — and even extend — weight loss after reducing injection frequency four-fold?

The study reported up to 12.3% placebo-adjusted weight loss at Week 28 in the medium monthly dose arm. How should clinicians contextualize this level of weight reduction relative to other GLP-1 receptor agonists at a similar stage of development?

Investigators noted no plateau in weight loss by Week 28 after the switch to monthly dosing. What does this suggest about the pharmacologic durability of PF-08653944, and how cautious should we be when extrapolating this trend out to Week 64?

VESPER-3 tested multiple titration pathways before monthly dosing. How important is flexibility in titration design when trying to balance efficacy with gastrointestinal tolerability in obesity trials?

Despite extended exposure and higher monthly doses, gastrointestinal adverse events were mostly mild to moderate, with very few severe events. Does this safety profile alleviate concerns specific to ultra-long-acting GLP-1 receptor agonists?

Monthly injectable dosing is relatively uncommon in obesity treatment today. In your view, could reduced dosing frequency meaningfully improve adherence and long-term persistence compared with weekly regimens?

Pfizer has indicated that the low and medium monthly doses from VESPER-3 will be included in Phase 3, alongside a planned higher 9.6 mg monthly dose. What factors do regulators and clinicians typically look for when justifying escalation to higher maintenance doses?

With multiple Phase 3 studies planned across weekly and monthly regimens, how might PF-08653944 ultimately differentiate itself within the increasingly competitive GLP-1 obesity landscape — particularly if monthly dosing proves viable?