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In an office in Bagsværd near Copenhagen, young biotechnologist Lotte Bjerre Knudsen has been made project manager for a promising, but uncertain project of converting the hormone GLP-1 into a drug that can prove effective in combating the rapidly growing wave of diseases such as type 2 diabetes in the 1990s. If she fails, the project will fold. Follow Episode 2 "If you don't fix this" of this advent calender from the Novo Nordisk Foundation "The Story of GLP-1". 00:00:00 - Introduction: Lotter Knudson's project on GLP-1 00:00:03 - The aim of converting GLP-1 into a drug 00:00:21 - The high stakes of the project 00:00:46 - Initial failed experiments with native GLP-1 00:01:14 - Innovative ideas for stabilizing GLP-1 00:01:50 - Use of fatty acids and albumin for protection 00:02:06 - Issues with purifying fatty acid-bound GLP-1 00:02:22 - A small crisis meeting and the biology-chemistry interplay 00:02:37 - Breakthroughs in understanding GLP-1’s biology 00:03:07 - The built-in safety switch of GLP-1 00:03:31 - Discoveries in Copenhagen on insulin and glucagon secretion 00:04:00 - Challenges in treating people with GLP-1 00:04:08 - Discovery of DPP-4 enzyme’s role 00:04:17 - Development of DPP-4 enzyme inhibitors 00:05:01 - Historical analogies with ACE inhibitors 00:05:47 - Development of DP4 inhibitors 00:06:18 - Long-acting GLP-1 analogs and their limitations 00:06:48 - Chemistry innovations to stabilize GLP-1 00:07:02 - John Eng’s discovery of Exendin-4 from Gila monster venom 00:08:02 - Challenges faced in patenting and developing Exendin-4 00:08:42 - Collaboration with Amylin Pharmaceuticals 00:09:53 - Management challenges and a deadline to fix the GLP-1 project 00:10:06 - Revisiting the initial solutions with new resources 00:10:48 - Issues in clinical trials and correct dosing 00:11:22 - Market competition and the first GLP-1 drug approval 00:12:00 - Investor skepticism and motivation to succeed

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