Hanmi Pharmaceutical Co., Ltd. · KRX:128940
Hanmi Pharmaceutical — Technical Presentation (2022)
16 slides from Hanmi Pharmaceutical's technical presentation, 2022
Slide 1: Pharmacological benefits of multifaceted mode of action for HM15912 and efpeglenatide combination
Pharmacological benefits of multifaceted mode of action for a novel combination of long-acting GLP-2 analog (HM15912) and GLP-1RA (efpeglenatide) in animal model of inflammatory bowel disease Jaehyuk Choi, Jin Bong Lee, Eun Jin Park, Jung Kuk Kim, Sungmin Bae, Daejin Kim, Sang Hyun Lee, In Young Cho
Slide 2: Disclosure for Jaehyuk Choi
Disclosure for *Jaehyuk Choi* In compliance with COI policy, ESPEN requires the following disclosures to the session audience: Shareholder No relevant conflicts of interest to declare. Grant / Research Support No relevant conflicts of interest to declare. Consultant No relevant conflicts of interest
Slide 3: What GLP-2 and GLP-1 are?
What GLP-2 and GLP-1 are? Proglucagon 30 amino acids 33 amino acids Glicentin GLP‐1 IP2 GLP‐2 GRPP OXM Neuroprotec on ↑ Appe te ↓ Appetite ↓ Bone forma on ↑ Bone resorp on ↓ & resorp on ↓ Intestinal Insulin secre on ↑ L cell Gastric motility & Gastric motility & emptying ↓ secre on ↓ Intes nal growt
Slide 4: What GLP-2 and GLP-1 are?
What GLP-2 and GLP-1 are? Proglucagon 30 amino acids 33 amino acids Glicentin GLP‐1 IP2 GLP‐2 GRPP OXM Neuroprotec on ↑ Appe te ↓ Appetite Bone ↓ on ↑ forma Bone resorp on ↓ & resorp on ↓ Insulin secre on ↑ Gastric motility & Gastric motility & emptying ↓ secre on ↓ Intestinal L cell + Intes nal gro
Slide 5: What a long-acting GLP-2 analog is?
What a long-acting GLP-2 analog is? Hanmi’s GLP‐2 analog (HM15912) is conjugated with a human IgG Modified GLP‐2 Fc fragment via flexible linker analog Flexible PEG Linker [General profile] • Rationally designed GLP-2 analog to have a more potent intestinotrophic action vs human GLP-2 • Extended hal
Slide 6: What a long-acting GLP-1 receptor agonist is?
What a long-acting GLP-1 receptor agonist is? Hanmi’s GLP‐1RA (efpeglenatide) is conjugated with a human IgG Modified exndin‐4 Fc fragment via flexible linker analog Flexible PEG Linker [General profile] • Rationally designed exendin-4 analog for less desensitization of GLP-1 receptor • Extended hal
Slide 7: Hypothesis & study methods
Hypothesis & study methods HM15912 and efpeglenatide may have a COMBO potential for inflammatory bowel disease (IBD) by distinct or somewhat overlapped intestinotrophic and anti-inflammatory mode of actions Purpose Species / Strain Induction method Note Human monocyte Migration by CCL-2 1. In vitro
Slide 8: Mechanism of HM15912/efpeglenatide COMBO
Mechanism of HM15912/efpeglenatide COMBO (1) Inhibition of monocyte migration (THP-1, CCL-2 50 ng/mL) Intestinal villi Monocyte migration (%vs. Con+CCL-2 ) Anti-inflammation “Tissue injury” Small intestine □ Control ■ Control + CCL-2 ■ Efpeglenatide 0.1 μM ■ HM15912 10 μM ■ COMBO 0.1+10 μM Monocyte
Slide 9: Mechanism of HM15912/efpeglenatide COMBO
Mechanism of HM15912/efpeglenatide COMBO (1) Inhibition of monocyte migration (2) Inhibition of monocyte to MØ differentiation (THP-1, CCL-2 50 ng/mL) (THP-1, PMA 150nM) PMA 150 nM PMA + Efpe 0.1 μM Intestinal villi Monocyte migration (%vs. Con+CCL-2 ) Anti-inflammation PMA + HM5912 10 μM PMA + Comb
Slide 10: Mechanism of HM15912/efpeglenatide COMBO
Mechanism of HM15912/efpeglenatide COMBO (1) Inhibition of monocyte migration (2) Inhibition of monocyte to MØ differentiation (THP-1, CCL-2 50 ng/mL) (THP-1, PMA 150nM) PMA 150 nM PMA + Efpe 0.1 μM Intestinal villi Monocyte migration (%vs. Con+CCL-2 ) Anti-inflammation PMA + HM5912 10 μM PMA + Comb
Slide 11: Mechanism of HM15912/efpeglenatide COMBO
Mechanism of HM15912/efpeglenatide COMBO Intestinotrophic (1) Inhibition of monocyte migration (2) Inhibition of monocyte to MØ differentiation (Crypt proliferation and fission) (THP-1, CCL-2 50 ng/mL) (THP-1, PMA 150nM) Intestinotrophic PMA 150 nM PMA + Efpe 0.1 μM HM15912 (Proliferation + Fission)
Slide 12: Intestinal growth & anti-inflammatory effect in indomethacin-induced IBD rat
Intestinal growth & anti-inflammatory effect in indomethacin- induced IBD rat Experimental design Small intestine histology Indomethacin, 8 mg/kg/day, SC - Small intestine length D0 D1 D3 - Ulcer area (Evans blue) SBS rat Necropsy - Inflammation score (H&E) (n=5/group, male) Drug treatment *, Signif
Slide 13: Intestinal growth & anti-inflammatory effect in indomethacin-induced IBD rat
Intestinal growth & anti-inflammatory effect in indomethacin- induced IBD rat Experimental design Small intestine histology Indomethacin, 8 mg/kg/day, SC - Small intestine length D0 D1 D3 - Ulcer area (Evans blue) SBS rat Necropsy - Inflammation score (H&E) (n=5/group, male) Drug treatment *, Signif
Slide 14: Survival rate in indomethacin-induced IBD rat
Survival rate in indomethacin-induced IBD rat Experimental design Indomethacin 7.5 mg/kg, SC D-2 D0 D14 SBS rat Drug treatment, Q2D, SC Necropsy (n=10/group, male) Survival rate Small Intestine Length 100 Vehicle: 100% 150 Considering the result at recovery phase, 90 10% is meaningful improvement 80
Slide 15: Executive summary
Contact information: jaehyuk.choi@hanmi.co.kr Executive summary • Accumulating evidence implicates GLP-2 to have, beyond intestinal growth, a beneficial role in anti- inflammation, and GLP-1 to have, beyond glucose homeostasis, a beneficial role in the gastrointestinal tract such as intestinal growt
Slide 16: Thank you
EUROPEAN SOCIETY FOR CUNICAL NUTRITION AND METABOLISM Thank you