Slide 1: Novel combination of GLP-1/GIP/Glucagon triple agonist (HM15211) and once-weekly basal insulin
Novel combination of GLP-1/GIP/Glucagon triple agonist (HM15211) and once-weekly basal insulin offers improved glucose lowering and weight loss in a diabetic animal model Jung Kuk Kim, Jong Suk Lee, Jaehyuk Choi, Sang Hyun Lee, In Young Choi, and Sun Jin Kim Hanmi Pharm. Co., Ltd., Seoul, Republic o
Slide 2: Presenter Disclosure
Presenter Disclosure Employee of Hanmi Pharm. Co., Ltd. • This presentation only includes content to scientific data and research results • All treatment options in the therapeutic area will be addressed in this presentation American Diabetes Association’s (ADA) 78th Scientific Sessions, Orlando FL,
Slide 3: Photography Prohibited
PHOTOGRAPHY PROHIBITED PLEASE DO NOT take photos of this presentation European Association for the Study of Diabetes (EASD) 53rd Annual Meeting, Lisbon, Portugal; 11-15 Sep., 2017
Slide 4: Efficacy and safety profiles of intensified insulin therapy
Efficacy and safety profiles of intensified insulin therapy Basal Insulin mono • The most potent therapeutics Pros. • Individualized dosing by titration • Little effect on PPGcontrol • With increasing dose higher risk for - Weight gain - Hypoglycemia Cons. American Diabetes Association’s (ADA) 78th
Slide 5: Efficacy and safety profiles of intensified insulin therapy
Efficacy and safety profiles of intensified insulin therapy 1. Basal/Bolus insulin Basal Insulin mono • The most potent therapeutics Pros. • Individualized dosing by titration • Little effect on PPGcontrol • With increasing dose higher risk for - Weight gain - Hypoglycemia Cons. 2. Basal insulin/GLP
Slide 6: Efficacy and safety profiles of intensified insulin therapy
Efficacy and safety profiles of intensified insulin therapy 1. Basal/Bolus insulin DUAL VII (Novo nordisk) Basal Insulin mono • The most potent therapeutics Pros. IGlar + IAsp + metformin • Individualized dosing by titration T2DM patient w/ HbA1c: 7.0 ~ 10.0% IGlar: 20 ~ 50U + metformin 26 weeks • L
Slide 7: Efficacy and safety profiles of intensified insulin therapy
Efficacy and safety profiles of intensified insulin therapy 1. Basal/Bolus insulin Basal Insulin mono -1.46 % 84.1 U 1.66 episodes/PYE* 2.64 kg • The most potent therapeutics Pros. • Individualized dosing by titration Glycemic control Total INS Weight control Hypo. Risk • Little effect on PPGcontrol
Slide 8: Efficacy and safety profiles of intensified insulin therapy
Efficacy and safety profiles of intensified insulin therapy 1. Basal/Bolus insulin Basal Insulin mono -1.46 % 84.1 U 1.66 episodes/PYE* 2.64 kg • The most potent therapeutics Pros. • Individualized dosing by titration Glycemic control Total INS Weight control Hypo. Risk • Little effect on PPGcontrol
Slide 9: HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist
HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist GLP-1/GIP/GCG Hanmi’s GLP-1/GIP/GCG triple agonist is conjugated triple agonist with a human IgG Fc fragment via flexible linker Flexible PEG Linker [General profiles] • Extended half-life (t1/2 = 42.7 ~ 55 hrs in mice; 82.8 ~ 85.7 hrs i
Slide 10: Enhanced energy expenditure by HM15211 via browning of WAT
Enhanced energy expenditure by HM15211 via browning of WAT HM15211 enhances energy expenditure by beige adipocyte induction Vehicle Liraglutide HM15211 1)Browning 2) Energy expenditure (Mitochondria biogenesis) (Thermogenesis) H&E 100μm H PGC-1α White adipocyte Beige adipocyte H + + Heat ↑ Energy
Slide 11: Hypothesis
Hypothesis Basal Insulin Blood glucose lowering Body weight gain Long-acting basal Insulin HM12460A [Ph1, US] • LAPSInsulin • Human insulin conjugated to human IgG Fc fragment • Targeting once-weekly basal insulin • Under efficacy evaluation in diabetic patients (P1b) American Diabetes Association’s
Slide 12: Hypothesis
Hypothesis Basal Insulin Triple agonist • Potential for enhanced Blood glucose lowering glycemic control Body weight gain • Efficient weight loss, not weight gain neutralization Long-acting basal Insulin Long-acting triple agonist HM12460A [Ph1, US] HM15211 [Ph1, US] • LAPSInsulin • IgG Fc fragment
Slide 13: Objective & study strategies
Objective & study strategies Combination of HM15211 with long-acting basal insulin might provide benefits in 1) glycemic control and 2) body weight management in… Genetic diabetic model Acquired diabetic model db/db mice DIO/STZ rats : Obesity and T2DM phenotype by leptin receptor deficient : Ob
Slide 14: Glycemic control by HM15211/HM12460A COMBO in db/db mice
Glycemic control by HM15211/HM12460A COMBO in db/db mice Non-fasting blood glucose profile HbA1c after 2 weeks treatment (db/db mice, n=7) (db/db mice, n=7) 600 8 B lo o d G lu c o s e ( m g /d L ) 500 † 7 7.1 H b A 1 c (% ) 400 ** 6.6 * 300 6 ** *** *** 6.0 200 5.7 *** 5 *** 100 0 4 0 2 4 6 8 10 12
Slide 15: Body weight control by HM15211/HM12460A COMBO in db/db mice
Body weight control by HM15211/HM12460A COMBO in db/db mice Body weight profile Body weight change after 2 weeks treatment (db/db mice, n=7) (db/db mice, n=7) 45 20 ††† *** B W C (% v s . D 0 ) B o d y w e ig h t ( g ) 10 40 0 35 -1 0 30 -2 0 *** 25 0 2 4 6 8 10 12 14 -3 0 ††† T im e (D a y s ) Vehi
Slide 16: Blood glucose lowering by HM15211/HM12460A COMBO in DIO/STZ rats
Blood glucose lowering by HM15211/HM12460A COMBO in DIO/STZ rats Study Design Drug treatment for 8 weeks Vehicle Liraglutide 15 nmol/kg, BID (1.8 mg in human) -4 -2 0 8 Time (weeks) HM12460A 16.2 nmol/kg, Q3D (6 nmol/kg in human) STZ STZ HM12460A 16.2 nmol/kg, Q3D + HM15211 5.9 nmol/kg, Q3D 30 mg/kg
Slide 17: Glycemic and body weight control by HM15211/HM12460A COMBO in DIO/STZ rats
Glycemic and body weight control by HM15211/HM12460A COMBO in DIO/STZ rats HbA1c after 8 weeks treatment Body weight change after 8 weeks treatment (DIO/STZ rats, n=6) (DIO/STZ rats, n=6) ††† 7 60 ** 6.8 40 p=0.0761 B W C (% v s . D 0 ) 6 by unpaired t-test 6.1 H b A 1 c (% ) 20 *** 5 0 5.4 -2 0 4 *
Slide 18: Summary & Conclusion
Summary & Conclusion • Despite improved glycemic control efficacy, current insulin COMBO therapies (basal/bolus INS and INS/GLP-1RA combination) had relatively marginal effect on weight control • HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist, could provide efficient weight loss via