复旦大学：《药物化学》授课资料_Introduction to Protein Engineering（诺和诺德，Jesper Lau）

翅工 ntroduction to Pharmaceutical Protein and Peptide Engineering Jesper Lau, PhD Vice President Protein Engineerin Novo Nordisk A/s Peptide synthesis pilot plai Bagsvaerd, Denmark A

Introduction to Pharmaceutical Protein and Peptide Engineering Jesper Lau, PhD Vice President Protein Engineering Novo Nordisk A/S Peptide synthesis pilot plant Bagsvaerd, Denmark

Presentation outline Novo nordisk Why engineer peptides(and proteins Type 2 diabetes The discovery of the first once daily gLp-1 Further engineering of long acting GLP-1 PLEASE INTERRUPT AND ASK!

• Novo Nordisk • Why engineer peptides (and proteins) • Type 2 diabetes • The discovery of the first once daily GLP-1 • Further engineering of long acting GLP-1 Presentation Outline 2 PLEASE INTERRUPT AND ASK!

PRODUCTS MARKETED IN AFFUIATES EN 75 Novo nordisk 180 COUNTRIE at a glance R&D CEntres IN CHINA. DENMARK Novo Nordisk is a global INDIA AND US healthcare company with more than 90 years of innovation and leadership in diabetes care. MEMPLOYS APPROXIMATELY DKK 42,000 PEOPLER This heritage has given us IN TOTAL REVENUE experience and capabilities that also enable us to help people defeat other serious chronic STRATEGIC conditions: haemophilia growth PRODUCTION SITES disorders and obesity. IN BRAZIL CHINA DENMARK 200,000 FRANCE AND US novonordisk fonden SHAREHOLDERS DISORDERS noVO LF OF THE 24, 400,000 WORLD'S INSULIN PEOPLE USE OUR PRODUCTS

Novo Nordisk at a glance Novo Nordisk is a global healthcare company with more than 90 years of innovation and leadership in diabetes care. This heritage has given us experience and capabilities that also enable us to help people defeat other serious chronic conditions: haemophilia, growth disorders and obesity. Novo Nordisk - Corporate Presentation 3 3 Novo Nordisk - Corporate Presentatio n PRODUCTS MARKETED IN 180 COUNTRIES STRATEGIC PRODUCTION SITES IN BRAZIL, CHINA, DENMARK, FRANCE AND US SUPPLIER OF MORE THAN HALF OF THE WORLD’S INSULIN 24,400,000 PEOPLE USE OUR PRODUCTS AFFILIATES IN COUNTRIES R&D CENTRES IN CHINA, DENMARK, INDIA AND US DKK 111.8 BILLION IN TOTAL REVENUE 200,000 SHAREHOLDERS 75 EMPLOYS APPROXIMATELY 42,000 PEOPLE DIABETES OBESITY GROWTH DISORDERS HAEMOPHILIA

NOVO NORDISK MARKETS ITS PRODUCTS IN Our global DOENEMAREK 77 AFFILTATES 180 COUNTRIES presence WORLDWIDE REGIONAL HEADQUARTERS IC, EUROPE, US AND IO 5 STRATEGIC PRODUCTION SITES BRAZIL, CHINA, DENMARK, FRANCE, US 6 R&D CENTRES CHINA, DENMARK INDIA AND US

Our global presence Novo Nordisk - Corporate Presentation 4 REGIONAL 5HEADQUARTERS CHINA, PACIFIC, EUROPE, US AND IO R&D 6CENTRES CHINA, DENMARK, INDIA AND US STRATEGIC PRODUCTION SITES 5BRAZIL, CHINA, DENMARK, FRANCE, US 77AFFILIATES NOVO NORDISK MARKETS ITS PRODUCTS IN COUNTRIES 180 WORLDWIDE DENMARK GLOBAL HEADQUARTERS

Based on net turnover Novo nordisk is the 15th largest pharmaceutical company in the world Source: Novo Nordisk internal benchmark report based on individual annual reports published by each pharmaceutical compar changing Reported net turnover figures are converted in

Based on net turnover Novo Nordisk is the 15th largest pharmaceutical company in the world 0 50 100 150 200 250 300 350 400 450 (Billion DKK) Source: Novo Nordisk internal benchmark report based on individual annual reports published by each pharmaceutical company. Reported net turnover figures are converted into DKK

e Modern insulins Nov。 Rapid DIABETES Product CARE Glucagon-like peptide-1 Victor portfolio ● Human insulins Insulatard Actrapid represent s ot a produsts are a Diabetes devices HexPen ovoPen*s NovoPen eCHoer InnoLet available in all markets. some lifferent product brand nan nde e Oral antidiabetic agents some markets. Please contact relevant local Novo Nordisk affiliates for further informati OBESITY Saxenda' HAEMOPHILIA [=〔 HUMAN GROWTH HORMONE Norditropin

Product portfolio This product portfolio overview represents Novo Nordisk’s global portfolio. Not all products are available in all markets. Some products may be available under different product brand names in some markets. Please contact relevant local Novo Nordisk affiliates for further information. DIABETES CARE FlexTouch® FlexPen® NovoPen® 5 NovoPen® 4 NovoPen Echo® InnoLet® NovoNorm® PrandiMet® Victoza® Insulatard® Actrapid® Mixtard® 30 Levemir® NovoRapid® NovoMix® 30 NovoMix® 50 NovoMix® 70 New generation insulins Modern insulins Glucagon-like peptide - 1 Human insulins Diabetes devices & accessories OBESITY Tresiba® Ryzodeg® Xultophy® Saxenda® Oral antidiabetic agents Norditropin® Norditropin FlexPro® Norditropin NordiFlex® NordiPen PenMate® SimpleXx® NordiLet® HAEMOPHILIA HUMAN GROWTH HORMONE Novo Seven® Novo Eight® Novo Thirteen®

Novo Nordisk's vision and strategy STRATEGIC PRIORITIES CORE CAPABILITIES Engineering Efficient Planning and Expand leadership in DIABETES production of nd d proteins position in protein-based new products Driving change to defeat diabetes Establish presence in and other serious OBESITY chronic conditions Pursue leadership in HAEMOPHILIA Expand leadership in GIROWTH DISORDERS Novo Nordisk Way

Novo Nordisk’s vision and strategy Expand leadership in DIABETES Establish presence in OBESITY Expand leadership in GROWTH DISORDERS Pursue leadership in HAEMOPHILIA Engineering, formulating, developing and delivering protein-based treatments Deep disease understanding Efficient large-scale production of proteins Planning and executing global launches of new products Building and maintaining a leading position in emerging markets STRATEGIC PRIORITIES CORE CAPABILITIES Driving change to defeat diabetes and other serious chronic conditions Novo Nordisk Way

Presentation outline Novo nordisk Why engineer peptides (and proteins) Type 2 diabetes The discovery of the first once daily gLp-1 Further engineering of long acting GLP-1 PLEASE INTERRUPT AND ASK!

• Novo Nordisk • Why engineer peptides (and proteins) • Type 2 diabetes • The discovery of the first once daily GLP-1 • Further engineering of long acting GLP-1 Presentation Outline 8 PLEASE INTERRUPT AND ASK!

More Biologics are becoming Block Buster 's he100 Hing drugs in 2015 Indication/drug type 2015 sales(sm) Autoimmune(various) 14012 Best selling drugs Gilead 13864 7327 2003:0 biologics in top 20 2009:7 biologics in top 20 2015: 7 biologics in top 10 Januvia/Janumet Merck & Co Revlimid (various op 100 biggest selling Astrazeneca pharmaceutical products Neulasta Glivec generated combined sales of Spiriva Boehringer Ingelheim CO $265 billion in 2015 Tecfidera Multiple 13638 Atripla ) Nordisk

More Biologics are becoming Block Buster´ s 9 Best selling drugs: 2003: 0 biologics in top 20 2009: 7 biologics in top 20 2015: 7 biologics in top 10 Top 100 biggest selling pharmaceutical products generated combined sales of $265 billion in 2015

Trends in clinical development Number of Therapeutic Peptides in Clinical Study has nearly doubled since the 1990 Status of 3 34 therapeutic peptides 149 terminated peptides entering clinical trials 18 131 in development 16 o41 at phase 1 B14 12 ●72 in phase2 o16 in phase 3 8 54 approved by at least 2 one agency 0.2 3 40s 50's 60s 70s 80s 90s 00-08 Source: Tufts Center for the study of Drug Development 2010 http://www.peptidetherapeuticsorg/ptf_reporT_sUmmaRy_2010.pdf

Slide no 10 Trends in clinical development Status of 334 therapeutic peptides: 149 terminated: 131 in development: •41 at phase 1 •72 in phase 2 •16 in phase 3 54 approved by at least one agency Source: Tufts Center for the study of Drug Development 2010: http://www.peptidetherapeutics.org/PTF_report_summary_2010.pdf Number of Therapeutic Peptides in Clinical Study has nearly doubled since the 1990 peptides entering clinical trials