Ascletis Pharma, Inc. · HKEX:1672
Ascletis Pharma — European Congress on Obesity (ECO) 2025
17 slides from Ascletis Pharma's conference presentation, May 14, 2025
Slide 1: ASC47, An Adipose-Targeted, Muscle-Preserving Weight Loss Drug Candidate For Obesity
ON OBESITY oe 11-14 MAY, 2025 | MALAGA, SPAIN ASC47, An Adipose-Targeted, Muscle-Preserving Weight Loss Drug Candidate For Obesity, Demonstrated Significant Weight Loss And Preserved Muscle In DIO Mice Jinzi Jason Wu Chengfei Wu Ascletis Pharma (China) Co., Limited, Hong Kong (~) BRL let
Slide 2: Disclosure
Disclosure EASO Dr. Jinzi Jason Wu is an employee of Ascletis Pharma (China) Co., Limited, Hong Kong Cy Ril 2 ‘ww ascletis
Slide 3: Overview of ASC47
Overview of ASC47 ASC47 is a thyroid hormone receptor B (THR§) selective small molecule agonist. * ASC47 was designed with unique and differentiated properties to enable targeted delivery to adipose tissue. « ASC47 is a muscle-preserving weight loss drug candidate to treat obesity. * ASC47 demonstra
Slide 4: ASC47 is 133-fold more potent than resmetirom in vitro
ASC47 is133-fold more potent than resmetirom in vitro Binding activity of ASC47 to THRB by TR-FRET -e Resmetirom 1007) = Asca7 80 THR selectivity of ASC47 over THRa 10 Compound ID EC,,a(yM) EC,,B (uM) 8B selectivity 20 Resmetirom 2.867 0.133 21.54 oj a ASC47 0.0369 0.001 36.90 Saaaaeda Activity g 20
Slide 5: Study Design: ASC47 tissue distribution in DIO mice
Study Design: ASC47 tissue distribution in DIO mice 5-week-old C57BL/6J Treatment: mice were fed with 60% @ Pde Rone a ASC47, 15/45 mg/kg, SQ, Q2W Tissue collection In vivo study period (HFD-maintenance) J Termination Homogenize ASC47 were dosed on Day1, Day15 and Day29 as indicated (orange arrow) J
Slide 6: ASC47 is an adipose-targeted THRB small molecule agonist
ASC47 is an adipose-targeted THRB small molecule agonist Inguinal WAT Epididymal WAT Liver 1108 15000 3000 § 5 s Hy 7.5%105 Hy tno00 : 2000 ©&IDIO, ASC47(15 mg/kg), Q2W, SQ a a 8 DIO, ASC47(45 mg/kg), Q2W, SQ 5 10° 52 8 on 5000 1000 G 2.5105 3 8 QD QD < < < 0 Data were presented as truncated 0 0 vio
Slide 7: Study Design: Weight change of ASC47 vs Sema in DIO mice
Study Design: Weight change of ASC47 vs Sema in DIO mice 5-week-old C57BL/6J Treatment: mice were fed with 60% Semaglutide(30nmol/kg=0.12mg/kg), SQ, QD HFD for 16 weeks ASC47, SQ,Q2W Semaglutide were dosed every day as indicated (blue arrow) TNT L A TET The bth dhe ttt | termination Assay/Histology
Slide 8: ASC47 Q2W produced similar weight loss to Sema QD
ASC47 Q2W produced similar weight loss to Sema QD 2K — 20 2K = OK 2 sh] Ef) xs 10.7% 10.4% £0 32 S 2 ge 10 £3 5S 3 8 5 g 07 >$ £4 id 2@> 105 3 23 o 307 T T T y T T 2 ® -204 12.7% 7 14 21 28 35 42 a 8 Days S 130 ; ; 22.3% 24.2% > Non-obese mice, Vehicle, Q2W, SQ mm Non-obese mice, Vehicle, Q2W, SQ >
Slide 9: To treat obesity: Two major mechanisms of action (MOA)
ASC47 to treat obesity: Two major mechanisms of action (MOA) m@ Induce satiety and decrease caloric intake m@ Preserve muscle and reduce fat Cy Sil 9 ‘ww ascletis
Slide 10: ASC47 induced satiety and decreased caloric intake in DIO mice
ASC47 induced satiety and decreased caloric intake in DIO mice = 2 £ EK = = 600 = £ $s 2 2 2 400 5 10 8s = Be 3 5 =~ 200 o Ss ire 3 ot E t) 7 14 21 28 35 42 8 0 Days <q —> DIO, Vehicle, Q2W, SQ Data were presented as Mean + @™ DIO, Vehicle, Q2W, SQ -e DIO, ASC47(45 mg/kg), Q2W, SQ SEM, t-test was ap
Slide 11: ASC47 preserved muscle while semaglutide reduced muscle
ASC47 preserved muscle while semaglutide reduced muscle ns S 2 = 10 wR Td af 5 = RK es se 10 6.37% 5.79% £9 4. ag 3.86% o2 Be 5 gz 5 Ss SH ag oa 0 £ 8 -10 of oe? & Ses gf 5 oa = -20 2 = 10: r T T T T T 1 Ea = 0 7 #14 21 28 35 42 3 5 agl : : Days —* Non-obese mice, Vehicle, Q2W, SQ mm Non-obese mice,
Slide 12: Adipose-targeted ASC47 reduced significantly more fat than semaglutide
Adipose-targeted ASC47 reduced significantly more fat than semaglutide | > o 48.8% 5% Fat mass change (%) vs baseline DayO -39.6% -37.8% & o Total fat mass change (%) on Day42 vs baseline DayO r T T T T T 1 0 7 #14 21 28 #35 42 Days 63.5% 100 T T T T mm Non-obese mice, Vehicle, Q2W, SQ -* Non-obese
Slide 13: Adipose-targeted ASC47 reduced adipose cell size
Adipose-targeted ASC47 reduced adipose cell size Semaglutide 30nmol/kg Non-obese DIO rf 7 MA X a ASC47 15 mg/kg mWAT-Average fat area/um 13 ° @m Non-obese mice, Vehicle, Q2W, SQ @m DIO, Vehicle, Q2W, SQ @ DIO, Semaglutide(30 nmol/kg), QD, SQ m™m DIO, ASC47(15 mg/kg), Q2W, SQ mm DIO, ASC47(45 mg/kg),
Slide 14: ASC47 reduced blood glucose and insulin resistance
ASC47 reduced blood glucose and insulin resistance AK PTL FAKE CK e 80 3 3 60 32” z 5 < s¢2 s 40 me 5 2 £ 20 3 J uw i) Data were presented as Mean + SEM, One way ANOVA followed by Tukey test by Prism GraphPad; N=10. **** p<0.0001 mm Non-obese mice, Vehicle, Q2W, SQ mm DIO, Vehicle, Q2W, SQ |= DIO, S
Slide 15: ASC47 reduced more blood lipids than semaglutide
ASC47 reduced more blood lipids than semaglutide RAK ARK ok RK —1 1 RK ek KK KK 8 — J 20 J eK =~ a6 715: oR 3 v7 3 € € E4 E10 a 9 3 a G2 Sos ° e S mm Non-obese mice, Vehicle, Q2W, SQ Data were presented as Mean + , SEM, One way ANOVA followed by mm DIO, Vehicle, A2W, SQ Tukey test by Prism GraphPad;
Slide 16: Summary
ASC47 Summary « ASC47 is an adipose-targeted, ultra-long-acting and THRB selective small molecule agonist. « ASC47 demonstrates similar weight loss to semaglutide but preserves muscle in DIO mice. * ASC47 is safe and well tolerated in Phase Ib study with healthy subjects and participants with obesit
Slide 17: Thanks
Thanks Innovative cures liberate life to the fullest
Ascletis Pharma — European Congress on Obesity (ECO) 2025 on 6ix