Enanta Pharmaceuticals, Inc. · NASDAQ:ENTA

Enanta Pharmaceuticals — Technical Presentation (2018)

14 slides from Enanta Pharmaceuticals's technical presentation, 2018

  1. Slide 1: EDP-305, a highly selective and potent FXR agonist, reduces liver steatosis in NASH models

    EDP-305, a highly selective and potent FXR agonist, reduces liver steatosis, ballooning, and non-alcoholic fatty liver disease activity score(NAS) in two murine models of NASH Li-Juan Jiang, Ph. D. Enanta Pharmaceuticals, Inc. Watertown, MA 1

  2. Slide 2: FXR has emerged as an attractive target for the treatment of NASH & PBC

    FXR has emerged as an attractive target for the treatment of NASH & PBC • Clinical validation has been achieved in NASH and PBC with the FXR agonist obeticholic acid (OCA) • FXR is a nuclear receptor and main regulator of bile acid levels in the liver and small intestine Bile Acid • FXR responds to

  3. Slide 3: EDP-305 is a potent and selective FXR agonist

    EDP-305 is a potent and selective FXR agonist EDP-305 is >16-fold more potent than OCA and its major metabolites 240 Compound FXR (HEK) TGR5 (CHO) CHO Cells CDCA 200 EC50 nM (% efficacy)* OCA 160 Efficacy (%) EDP-305 Obeticholic Acid (OCA) 130 (150) 380 ( 72) 120 Glyco-OCA 360 (155) 720 (157) 80 Tau

  4. Slide 4: EDP-305 regulates key gene expression

    EDP-305 regulates key gene expression In vitro • Bile acid metabolism Up regulation - SHP; FGF19; OST-; BSEP; CYP7A1 Down regulation • Lipid metabolism - LDLR; PCSK9;SREBP-1C; SCD1; CD36; DGAT2; APOB; APOC3; HL; SRB1 • Inflammation - NF-B; TLR2; TLR9; TNF; IL8; IL1; IL1; IL1R1; CCL2; CCR1; CCR4

  5. Slide 5: EDP-305 exhibits its efficacy in eight different animal models

    EDP-305 exhibits its efficacy in eight (8) different animal models • Mouse model - FXR mechanism of action: SHP, CYP7A1 and FGF15 (Enanta Pharmaceuticals, Inc.) • Liver fibrosis/cirrhosis model - Thioacetamide-induced rat liver fibrosis/cirrhosis model (Icahn School of Medicine at Mt. Sinai) • Bilia

  6. Slide 6: STAM NASH Mouse Model

    STAMTM NASH Mouse Model © 2018 Enanta Pharmaceuticals, Inc. |66

  7. Slide 7: STAM mouse model

    STAMTM mouse model 0w 4w 6w 7w 10w l l l l l 1st hit Continuous 2nd hit (low dose STZ injection) (High Fat Diet, HFD) STZ: streptozotocin HFD + Vehicle 4 weeks STAM mouse model 0w Low dose STZ injection HFD + EDP-305 3 mg/kg/day 4 weeks 4 – 10 w High fat diet 5w Fatty liver evident 7w NASH evident H

  8. Slide 8: EDP-305 vs OCA in STAM mouse model

    EDP-305 vs OCA in STAMTM mouse model Non-alcoholic fatty liver disease activity score (NAS) Drug mg/kg/d n Hepatocyte NAS Ballooning Score Control -- 7 1.9 5.3 OCA 10 7 1.1 4.3 EDP-305 3 7 1.1 3.7* EDP-305 10 7 0.7* 3.4** * p<0.05; ** p<0.01 Ballooning NAS Control OCA EDP-305 EDP-305 Control OCA EDP

  9. Slide 9: Diet-induced NASH (DIN) Mouse Model

    Diet-induced NASH (DIN) Mouse Model © 2018 Enanta Pharmaceuticals, Inc. |99

  10. Slide 10: EDP-305 decreases liver steatosis, ballooning, & NAS in a DIN murine model

    EDP-305 decreases liver steatosis, ballooning, & NAS in a diet-induced NASH (DIN) murine model Steatohepatitis Steatohepatitis incipient ballooning advanced ballooning Week 0 Week 6 Week 16 C57BI/6 mice (DIN) Treatment with EDP-305 or OCA HF/HC/10% fructose EDP-305 10, 30 mg/kg/day x 10 weeks OCA 30

  11. Slide 11: EDP-305 reduces plasma and liver lipid contents

    EDP-305 reduces plasma and liver lipid contents © 2018 Enanta Pharmaceuticals, Inc. | 11 11

  12. Slide 12: EDP-305 decreases liver steatosis, ballooning and NAS (wk16)

    EDP-305 decreases liver steatosis, ballooning and NAS (wk16) © 2018 Enanta Pharmaceuticals, Inc. | 12 12

  13. Slide 13: Conclusions & EDP-305 development

    Conclusions & EDP-305 development • EDP-305 is a potent FXR agonist with no/minimal activity against other nuclear receptors and TGR5 • Treatment with EDP-305 had a significant therapeutic effect on NASH progression in preclinical animal models • EDP-305 significantly decreased liver steatosis, hepa

  14. Slide 14: Acknowledgement

    Acknowledgement Enanta Stelic, Japan Yat Sun Or Taishi Hashiguchi Yang Li Yuichiro Shibazaki Mary Chau Manuel Roqueta-Rivera Kelsey Garlick Jianyu Shang Physiogenex, France Guoqiang Wang François Briand Ruichao Shen Thierry Sulpice Yong He Jiang Long Bin Wang Jun Ma Brett Granger © 2018 Enanta Pharm

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