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XL184 is being evaluated in a Phase III study in patients with advanced medullary thyroid cancer and in Phase II studies in patients with glioblastomamultiforme and non-small-cell lung cancer that has progressed after previous benefit with erlotinib

Peripheral effects Via the AMY2 and AMY3 receptors Cagrilintide acts peripherally: Slowing of gastric emptying , stronger than with GLP-1 Suppression of postprandial glucagon , helps control postprandial glycemic spikes Modulation of bone remodeling (via AMY3), a neutral effect, but clinically monitored Synergy with GLP-1 (the mechanistic basis of CagriSema) The main innovation is the complementarity with the GLP-1 pathway : GLP-1 suppresses appetite via the arcuate nucleus of the hypothalamus (POMC neurons, AgRP/NPY inhibition) Amylin suppresses appetite via the area postrema (CGRP-like neurons) Two independent centers, two independent mechanisms

Artificial Intelligence may allow for more accurate personalisation of therapy to predict the optimum cocktail of mono agonist therapies based on the genetics and metabolomics of an individual and may quicken the process of drug development [70, 71]

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