Pre-Conference Day

This workshop addresses the field’s most pressing challenge: determining optimal receptor targeting strategies. The session will explore the complex receptor system (amylin I, II, III, and calcitonin receptors), examining the debate between amylin selective versus dual amylin-calcitonin receptor agonist (DACRA) approaches. Participants will analyze preclinical data from rats suggesting amylin III importance versus emerging human data showing different profiles, discuss the lack of translatable antibodies to RAMPs limiting receptor distribution mapping, and evaluate signaling bias (beta-arrestin vs G-protein pathways) and its impact on efficacy and tolerability. 

What attendees will gain:

Attendees will leave with a framework for evaluating receptor selectivity strategies, understanding the trade-offs between precision targeting and broad receptor coverage, and insights into how receptor profiles may predict clinical outcomes.

Key questions to be addressed:

• Which amylin receptor subtype (I, II, or III) is most critical for weight loss efficacy in humans, and how does this differ from rodent models?
• Should next-generation therapeutics target amylin receptors selectively or employ a DACRA approach, and what are the mechanistic rationales for each strategy?
• How does signaling bias (beta-arrestin vs G-protein recruitment) influence tolerability, efficacy, and quality of weight loss?
• What tools and methodologies are needed to definitively map receptor distribution in human brain and peripheral tissues?
• How can we overcome the species translation challenge when rodent receptor profiles don’t match human profiles?

This workshop tackles the fundamental question of where amylin therapeutics fit in the treatment landscape relative to GLP-1s. Participants will examine clinical readouts comparing amylin analogs to incretins, analyzing whether improved tolerability profiles allow higher dosing and greater efficacy. The session will explore the relationship between half-life and both efficacy and tolerability, discussing whether longer-acting molecules provide smoother pharmacokinetics with reduced GI side effects. Critical focus will be placed on patient populations: Do non-responders to GLP-1s respond better to amylins? Can amylins serve as maintenance therapy post-GLP-1 weight loss? The workshop will integrate preclinical biology with clinical data to understand how molecular design translates to patient outcomes.

What attendees will gain:

Attendees will develop strategies for positioning amylin therapeutics in clinical development, understanding patient segmentation opportunities, and designing molecules that optimize the efficacy-tolerability balance.

Key questions to be addressed:

• Do patients who don’t respond to or can’t tolerate GLP-1s respond better to amylin based therapeutics?
• How does half-life influence the efficacy-tolerability trade-off, and what is the optimal pharmacokinetic profile?
• Can amylins deliver better quality weight loss (lean mass preservation, reduced weight rebound) compared to GLP-1s?
• What is the ideal patient segmentation strategy for amylin therapeutics (first-line, second-line, maintenance, specific populations)?
• How do we link in vitro receptor pharmacology and in vivo preclinical data to predict clinical tolerability and efficacy?