Ascentage Pharma Group International · HKEX:6855
Ascentage Pharma Group International — Ascentage Pharma Group — J.P. Morgan Healthcare Conference 2022
42 slides from Ascentage Pharma Group International's conference presentation, Jan 10, 2022
Slide 1: Ascentage Pharma Group: Advancing Therapies That Restore Apoptosis
Ascentage Pharma Group Advancing Therapies That Restore Apoptosis Dajun Yang, MD, PhD Chairman & CEO January 10, 2022
Slide 2: Disclaimer
Disclaimer PROPRIETARY AND CONFIDENTIAL 2
Slide 3: Innovative and Proprietary Platform Delivering Potentially First and/or Best-in-Class Drugs
Innovative and Proprietary Platform Delivering Potentially First and/or Best-in-Class Drugs Breakthrough Strong Dedicated Global science pipeline team development novel vision: building 12 a global Integrated organization in 145 issued patents compounds 1 biopharmaceutical China, 1 NDA Approval comp
Slide 4: Major Achievements in 2021
Major Achievements in 2021 NDA approval of Olverembatinib Registrational pivotal (HQP1351) for treatment of patients study of APG-2575 for with resistant CML-CP and CML-AP treatment of patients with with T315I in China CLL/SLL initiated in China 18 global studies 14 ODDs by 6 clinical and of APG-257
Slide 5: Rich Pipeline With Significant Global Opportunities
Rich Pipeline With Significant Global Opportunities Rights Product Target Indications Preclinical Ph I Ph II NDA NDA Approval Trials Regions Regions Resistant CML Resistant CML, Ph+ALL HQP1351 BCR-ABL/KIT GIST Ph+ ALL CLL/SLL WM AML MDS APG-2575 Bcl-2 Selective MM T-PLL MCL ER+/HER2- BC, solid tumor
Slide 6: Commercialization Update
Commercialization Update Maximize Commercial Value of Olverembatinib ● Increased salesforce to further explore the market value of ● Joint commercial development ● Strategic collaboration with Olverembatinib, reach higher peak with Innovent on Olverembatinib experienced partners to build up the sale
Slide 7: Multiple Ongoing Strategic Alliances
Multiple Ongoing Strategic Alliances BCL-xL MDM2-p53 BCR-ABL & BCL-2 BCL-2 BCL-2 IAP 8
Slide 8: Our Experienced Executives Team
Our Experienced Executives Team Yifan Zhai, M.D., Ph.D. Gang Zhu. Yiqing Chen CHIEF FINANCIAL OFFICER CHIEF MEDICAL OFFICER CHIEF COMMERCIAL OFFICER Dajun Yang, M.D., Ph.D. CO-FOUNDER CHAIRMAN & CHIEF EXECUTIVE OFFICER Shaomeng Wang Ph.D. Jeff Kmetz Thomas Knapp CO-FOUNDER & CSA CHIEF BUSINESS OFFIC
Slide 9: Key Financial Highlights
Key Financial Highlights Total Assets (RMB mm) • Completion of the Global headquarter 2408.2 1731 and R&D center, and the increased 1229.4 1205.1 capabilities and total assets will help to 581.7 accelerate clinical developments and Dec-17 Dec-18 Dec-19 Dec-20 Jun-21 commercialization. Revenue¹ (RMB
Slide 10: HQP1351 Olverembatinib Overview
HQP1351 Olverembatinib Overview 3rd Gen BCR-ABL/KIT Multi-kinase Inhibitor 11
Slide 11: Development Milestone: From IND Clearance to NDA Approval in 4 Years
Development Milestone: From IND Clearance to NDA Approval in 4 Years • In March, received “ Breakthrough • In Feb. NMPA issued a • In Jan, awarded “National Major Innovative Drug Project” Therapy “one-time umbrella • In Jul, entered Phase Ib clinical study for TKI rCML in US Designation “ approval”
Slide 12: Phase I Study Summary: Efficacy
Phase I Study Summary: Efficacy Highly Efficacious in TKI Resistant CML Patients 100% 100% 100% 100% 100% 90% 89% CP 84% 80% 78% 64% 64% 67% 64% 60% 55% 55% 58% 40% 20% 9% 0% CHR MCyR CCyR MMR N 13 25 9 7 22 38 11 9 22 38 11 9 22 40 12 11 No mutation T315Imutation T315i+other mutations other mutatio
Slide 13: Phase I Study Summary: Efficacy (Cont.)
Phase I Study Summary: Efficacy (Cont.) Cumulative Incidence of Achieving Responses Progression-free Survival & Overall Survival ( ≥30mg ) (≥ 30mg) CP AP CML Response Criteria: Complete Hematological Response (CHR), Bone Marrow; Major Cytogenic Response (MCyR*) Complete Cytogenic Response (CCyR), Ma
Slide 14: Phase I Study Summary: Safety Profile
Phase I Study Summary： Safety Profile Prevalence of Treatment-related Adverse Events over Time ( ≥30mg ) Well-Tolerated With Minimal Dose Interruptions Source: Qian Jiang et al.(2021), Updated Safety and Efficacy Results of Phase 1 Study of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL
Slide 15: Responses by Compound Mutation
Responses by Compound Mutation Source: Qian Jiang et al.(2021), Updated Safety and Efficacy Results of Phase 1 Study of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI- Resistant Chronic Myeloid Leukemia (CML) , 2021 ASH Annual Meeting
Slide 16: Pivotal Phase 2 Study Summary
Pivotal Phase 2 Study Summary Highly Efficacious in T315I-Mutated CML Patients Treatment-related Hematologic Adverse Events CP 100% CP 71% 69% G1-2 G3-4 T315I+n = 41 81% 32% 49% 68% 49% 39% 56% 15% 22% 37% 34% 22% 17% CHR MCyR CCyR MMR Thrombocytopenia Anemia Leukopenia Neutropenia SAE: 7% SAE: 2% A
Slide 17: Olverembatinib: T315I and Beyond
Olverembatinib: T315I and Beyond First and the only 3rd generation BCR-ABL TKI Received NDA Approval in November 2021； being developed in China; granted with “Priority review” and “Breakthrough Second receiving NDA approval globally Therapy Designation” Efficacious in the TKI resistant CML patients
Slide 18: APG-2575 Overview
APG-2575 Overview Novel, orally administered Bcl-2 selective inhibitor, follow to Venclexta® 19
Slide 19: Phase I Study in the US: Safety Profile
Phase I Study in the US：Safety Profile Treatment-related adverse events (TRAEs) with APG-2575 (N = 36) Any grade AE (≥ 10%) No. (%) ≥ Grade 3 AE (≥ 5%) No. (%) Any APG-2575-related AEa: 27 (75.0) Any ≥ grade 3 APG-2575-related AE: 9 (25.0) Fatigue 10 (27.8) Neutropenia 5 (13.9) Neutropenia 8 (22.2)
Slide 20: 80% PR in Evaluable R/R CLL/SLL Patients
80% PR in Evaluable R/R CLL/SLL Patients CLL/SLL Swimmer Plot Source: Sikander Ailawadhi, et al.(2021), First-in-human study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)., 2021 ASCO Annual M
Slide 21: 100% ORR in Evaluable R/R CLL/SLL Patients at Dose ≥ 200 mg in China Phase I Study
100% ORR in Evaluable R/R CLL/SLL Patients at Dose ≥ 200 mg in China Phase I Study Swimmer’s plot: efficacy of lisaftoclax in 25 pts 0 2 4 6 8 10 12 14 16 • With a median treatment of 4 cycles, 9/25 evaluable pts achieved at least a PR • The highest response rates were seen in pts with CLL (66.7%).
Slide 22: APG-2575-CN-001 Phase I Interim Data: Efficacy
APG-2575-CN-001 Phase I Interim Data I Efficacy Ibrutinib Resistant High Risk Patient; Rapid and Deep Response Patient 01S008: Complete Response ALC (x10^9/I) 2.5 5 CR in r/r CLL (IGVH mutation, No TP53) 2.0 4 K 1.5 3 Ca Before APG-2575 After APG-2575 1.0 2 0.5 1 P 0.0 0 C2D1 C2D15 C3D1 C3D15 C4D1 C
Slide 23: Clinical POC Established With Best-in-Class Safety Potential
Clinical POC Established With Best-in-Class Safety Potential More than 200+ subjects enrolled into the Potential Best-in-Class with IND clearance for ER+ Initiated registrational pivotal APG-2575 studies, including r/r CLL, FL, MCL, well tolerated safety profile, breast cancer and Phase II study for
Slide 24: Strong Differentiation From Venetoclax
Strong Differentiation From Venetoclax APG-2575 Compared to Venetoclax Product, Patient, Provider Attributes Efficacious in BTK resistant WM PDX model in When Selectively Targeting BCL-2 which Venetoclax shows no effect Daily ramp-up verse weekly ramp up Dose Escalation (Daily Ramp) Extremely low la
Slide 25: APG-115 Milestones & Clinical Developments
Milestones & Clinical Developments APG-115 • Granted ODD for the treatment of AML, gastric cancer, soft tissue sarcoma, retinoblastoma, melanoma • FDA granted Fast Track Designation for the treatment of unresectable, metastatic MDM2-p53 Inhibitor melanoma, relapsed/refractory to prior immuno-oncolog
Slide 26: APG-115 Delivers Anti-tumor Activity by Multiple MOAs
APG-115 Delivers Anti-tumor Activity by Multiple MOAs Tumor Cells Tumor Apoptosis microenvironment Activates WT p53-dependent Activates innate immunity by intrinsic apoptosis. reprograming macrophages M2 to M1 to suppress tumorigenesis (Fang et al. 2019). T-Cell Mediated Anti-tumor Immunity Syntheti
Slide 27: APG-115 is a host immunomodulator
APG-115 is a host immunomodulator ▪ STAT5 activation is important for CD8⁺ T-cell survival APG- 115 and function. ▪ MDM2 competes with c-Cbl and prevents c-Cbl- mediated STAT5 degradation. ▪ APG-115 synergizes with IO and enhances T-cell mediated antitumor immunity. Zhou J et al. Nat Immunol 2021;22
Slide 28: Efficacy in all Cohorts
Efficacy in all Cohorts Response Melanoma NSCLC STK-11 ATM Liposarcoma UC MPNST (n = 5) (n = 11) (n = 17) (n = 12) (n = 6) (n = 32) (n = 19) ORR 24.1% 6.7% 0 0 6.2% 12.5% 16.7% (CR + PR) (7/29) (1/15) (1/16) (1/8) (1/6) DCR 55.2% 46.7% 25% 44.4% 81.2% 12.5% 66.7% (CR + PR + (16/29) (7/15) (1/4) (4/9
Slide 29: Efficacy in Patients with IO Resistant Melanoma
Efficacy in Patients with IO Resistant Melanoma Response Uveal Mucosal Cutaneous Unknown Total (n = 8) (n = 5) (n = 16) primary (N = 32) (n = 3) ORR 14.3% 40% 26.7% 0 24.1% (CR + PR) (1/7) (2/5) (4/15) (7/29*) DCR 71.4% 40% 46.7% 100% 55.2% (CR+ PR+ SD) (5/7) (2/5) (7/15) (2/2) (16/29) Best overall
Slide 30: Efficacy in Patients with IO Resistant Uveal Melanoma Treated with APG-115 Plus Pembrolizumab
Efficacy in Patients with IO Resistant Uveal Melanoma Treated with APG-115 Plus Pembrolizumab CR, target lesion (lymph node) within normal range Anthony Tolcher, MD, FRCPC 32
Slide 31: Efficacy in Patients with IO Resistant Uveal Melanoma Treated with APG-115 Plus Pembrolizumab
Efficacy in Patients with IO Resistant Uveal Melanoma Treated with APG-115 Plus Pembrolizumab Anthony Tolcher, MD, FRCPC 33
Slide 32: Safety: Treatment Emergent AEs (TEAEs)
Safety: Treatment Emergent AEs (TEAEs) 34
Slide 33: Highlights of APG-115 Phase II Study
Highlights of APG-115 Phase II Study • First clinical study of MDM2 inhibitor in combination with IO globally. • APG-115 not only plays an important role in inducing apoptosis in tumor cells, but also acts as a host immune modulator, enhancing specific T cell-mediated antitumor activities through no
Slide 34: APG-1387 Milestones & Clinical Developments
Milestones & Clinical Developments Immuno-Oncology Development • Completed 3 Oncology Phase-1 dose-escalation trials; known MTD and RP2D; AEs were mild to moderate, manageable, and reversible APG-1387 An Antagonist of IAP/XIAP • Preliminary efficacy signal was seen in combination with (SMAC Mimetic)
Slide 35: APG-1252 Milestones & Clinical Developments
Milestones & Clinical Developments • Potentially the best-in-class Bcl-2/Bcl-xL inhibitor with novel combination in solid and hematological malignancies APG-1252 • Entered 2 combination trials ➢ A Phase Ib study of APG-1252 plus Osimertinib in patients BCL-2/BCL-xL Inhibitor with NSCLC in China ➢ A
Slide 36: APG-1252 Efficacy
Efficacy Best response, n (%) Dose determination 240mg (n=6) Dose determination 160mg (n=5) Expansion Arm-1 (n=20) Expansion Arm-2 (n=22) Partial response (unconfirmed) 0 (0.0) 1 (20.0) 3 (15.0) 13 (59.1) Partial response (confirmed) 0 (0.0) 0 (0.0) 1 (5.0) 8 (36.4) Stable disease 5 (83.3) 2 (40.0)
Slide 37: Highlights of APG-1252 NSCLC Study
Highlights of APG-1252 NSCLC Study • Combination treatment with APG-1252 and osimertinib at RP2D was safe and feasible. • Preliminary synergy and efficacy of both APG-1252 and osimertinib were also observed in some patients with EGFR TKI osimertinib-resistant and naïve NSCLC. • In treatment-naive an
Slide 38: APG-2449 Milestones & Clinical Developments
Milestones & Clinical Developments • APG-2449 is a next-generation novel potent kinase inhibitor with multiple targets including FAK, ALK and ROS1 proteins APG-2449 • APG-2449 demonstrated effectiveness in multi-tumor type models as monotherapy or in combination with other ALK/FAK/ROS1 agents in pre
Slide 39: Pre-Clinical Assets
Focused on validated targets with clear biomarker, clinical indications and fast regulatory approval High unmet medical needs Pre-Clinical Assets -EED Selective -APG-5918 First-in-class or -MDM2-p53 Degrader –APG-265 best-in-class potential Transformative new technology 41
Slide 40: IP Portfolio for Key Clinical Assets
IP Portfolio for Key Clinical Assets Key Clinical Assets Estimated Patent Expired Year HQP1351 2035-2041* APG-2575 2037-2041* APG-115 2035-2041* APG-1387 2033-2041* APG-1252 2034-2041* *including composition, process, formulation, combination, use, new indication etc；(issued or pending) Source: Comp
Slide 41: Investment Highlights
Investment Highlights Global leader in apoptosis targeting To discovery and development of 1 therapy with commercial stage product innovative first- and best-in-class therapies to address unmet medical needs globally. 2 Product pipeline with the first- and/or best-in-class potential 3 Strong global
Slide 42: Ascentage Pharma Group
Ascentage Pharma Group Advancing Therapies That Restore Apoptosis
Ascentage Pharma Group — J.P. Morgan Healthcare Conference 2022 on 6ix