Hanmi Pharmaceutical Co., Ltd. · KRX:128940
Hanmi Pharmaceutical — European Association for the Study of Diabetes (EASD) 54th Annual Meeting 2018
14 slides from Hanmi Pharmaceutical's conference presentation, October 2018
Slide 1: Neuroprotective effects of HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist
Neuroprotective effects of HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist in the neurodegenerative disease models Jeong A Kim, Sang Don Lee, Sang-Hyun Lee, Sung Min Bae, In Young Choi, and Young Hoon Kim Hanmi Pharm. Co., Ltd., Seoul, Republic of Korea
Slide 2: Presenter Disclosure
Presenter Disclosure Employee of Hanmi Pharm. Co., Ltd. European Association for the Study of Diabetes (EASD) 54th Annual Meeting, Berlin, German; 01-05 Oct., 2018
Slide 3: HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist
HM15211, a novel long-acting GLP-1/GIP/Glucagon triple agonist Hanmi’s GLP-1/GIP/GCG triple agonist is conjugated with a GLP-1/GIP/GCG triple agonist human IgG Fc fragment via flexible linker Flexible PEG Linker [General profile] • Extended half-life (t1/2 = 42.7 ~ 55 hrs in mice; 82.8 ~ 85.7 hrs in
Slide 4: Incretin hormones in central nervous system
Incretin hormones in central nervous system • Obesity is one of the risk factors for neurological disorders Parkinson’s disease Alzheimer’s disease Multiple sclerosis Insulin resistance, T2DM ↑ PD ↑ BMI, T2DM ↑ AD risk Obesity ↑ MS risk ↑ Insulin levels ↑ α-synuclein aggregation Leptin/insulin resis
Slide 5: Objective
Objective Evaluation of neuroprotective potential of HM15211… • To assess the efficacy and related mode of actions a. in Parkinson’s disease mice model b. of Alzheimer’s disease in diabetic mice model European Association for the Study of Diabetes (EASD) 54th Annual Meeting, Berlin, German; 01-05 Oc
Slide 6: Efficacy and related MoAs in Parkinson's disease mice model
Efficacy and related MoAs in Parkinson’s disease mice model European Association for the Study of Diabetes (EASD) 54th Annual Meeting, Berlin, German; 01-05 Oct., 2018
Slide 7: Parkinson's disease mouse model
Parkinson’s disease mouse model • MPTP is a specific neurotoxin affecting the nigrostriatal system. BBB Dopamine Glial cell transporter MPP+ Complex I Reactive oxygen inhibition species ATP decrease Oxidative stress Inflammation Cell death Blood • Experimental scheme Subchronic PD model Chronic PD m
Slide 8: Dopaminergic neuroprotection by HM15211
Dopaminergic neuroprotection by HM15211 Subchronic PD model + HM15211 + HM15211 Vehicle MPTP 2.5 nmol/kg 5.03 nmol/kg 150 150 TH+ area in substantia nigra *** Striatum *** TH+ area in striatum ** (% vs. vehicle) *** 100 100 *** 40x 100x * 50 50 Substantia nigra 0 0 100x Vehicle MPTP 30 mg/kg, QD + H
Slide 9: Motor function restoring by HM15211
Motor function restoring by HM15211 Subchronic PD model Rotarod (falling latency, s) 3 40 120 200 *** *** Traction test (score) Pole test (T-total, s) Pole test (T-turn, s) *** 30 90 150 2 Vehicle ** MPTP 30 mg/kg, QD 20 60 100 *** *** MPTP 30 mg/kg, QD + HM15211 2.5 nmol/kg, QW *** 1 *** *** MPTP 3
Slide 10: Anti-inflammatory effect of HM15211
Anti-inflammatory effect of HM15211 Subchronic PD model Vehicle MPTP + HM15211 + HM15211 200 200 800 2.5 nmol/kg 5.03 nmol/kg Iba1+ area in striatum *** *** *** 150 600 (% vs. vehicle) 150 Striatum IL-10 (pg/ml) IFNγ (pg/ml) ** *** *** *** *** *** 100 100 400 200x 50 50 200 0 0 0 200x_Cropped Vehicl
Slide 11: Efficacy and related MoAs of Alzheimer's disease in diabetic mice model
Efficacy and related MoAs of Alzheimer’s disease in diabetic mice model European Association for the Study of Diabetes (EASD) 54th Annual Meeting, Berlin, German; 01-05 Oct., 2018
Slide 12: Alzheimer's disease in diabetic mouse model
Alzheimer’ disease in diabetic mouse model • Experimental scheme Diabetes / Obesity D0 12w Increased insulin resistance Accumulation of AGE : Vasculature db/db ♂ 6 wks old HM15211 (Q2D for 12 weeks) AGE : Advanced Glycated Endproduct Sacrifice • Inhibition of Aβ1-42 and AGE accumulation by HM15211 I
Slide 13: Reduction of inflammation and oxidative stress by HM15211
Reduction of inflammation and oxidative stress by HM15211 120 70 db/db_HM15211 db/db _D0 (6w) db/m_vehicle db/db_Vehicle 1.08 nmol/kg 60 - 1 β ( p (pg/ml) N - γ ( p(pg/ml) 90 50 ** g /m l) g /m l) * Cortex *** 40 60 ILIL-1β I FIFN-γ ** 30 400x 20 30 10 Hippo_CA1 0 0 400x 15 a d d u c t ( (μg/ml) u g
Slide 14: Summary & Conclusion
Summary & Conclusion • In MPTP/Probenecid induced chronic Parkinson’s disease model, HM15211 inhibited the increase of alpha synuclein, which is the most prominent pathological biomarker of Parkinson’s disease. • In aged db/db mice, pathological characters of Alzheimer’s disease such as Aβ1-42 and A