Ascentage Pharma Group International · HKEX:6855
Ascentage Pharma Group International — J.P. Morgan Healthcare Conference 2021
47 slides from Ascentage Pharma Group International's conference presentation, Jan 13, 2021
Slide 1: Ascentage Pharma Group: Advancing Therapies That Restore Apoptosis
Ascentage Pharma Group Advancing Therapies That Restore Apoptosis 1
Slide 2: Disclaimer
Disclaimer DISCLAIMER FOR INVESTOR MATERIALS By attending the meeting where this presentation is made, or by reading the presentation materials, you agree to be bound by the following limitations: The information in this presentation has been prepared by representatives of Ascentage Pharma Group Int
Slide 3: Ascentage: Innovative Science
Ascentage: Innovative Science Proprietary PPI Platform Delivering Potentially First and/or Best-in-class Drugs BREAKTHROUGH SCIENCE STRONG PIPELINE 90+ ISSUED PATENTS 12 NOVEL COMPOUNDS 400+ PENDING 33 INDS APPLICATIONS 40+ CLINICAL TRIALS 100+ PUBLICATIONS 10+ INDICATIONS DEDICATED TEAM GLOBAL DEVE
Slide 4: Global Leader Developing Therapeutics That Inhibit Protein-protein Interactions to Restore Apoptosis
Global Leader Developing Therapeutics That Inhibit Protein-protein Interactions to Restore Apoptosis Protein-protein Interactions Focused on Apoptosis Protein-protein interactions (PPIs) play Apoptosis plays a crucial role in a crucial role in cellular processes, and developing and maintaining the h
Slide 5: 2020 Key Achievements
2020 Key Achievements 1 NDA with “Priority Review” for HQP1351 (Olverembatinib) Clinical Proof of Concept (POC) of APG-2575 established in r/r CLL 9 global studies of APG-2575 in CLL，AML，MM etc.; entered Europe for the first time 9 ODD and 1 FTD (HQP1351 in TKI resistant CML) 2 global clinical colla
Slide 6: Rich Pipeline With Significant Opportunities
Rich Pipeline With Significant Opportunities Product Target Indications Phase I Phase II Pivotal NDA Regions CDE-NDA submission mid-2020 CML HQP1351 BCR-ABL /KIT Ph+ ALL CLL WM MM APG-2575 Bcl-2 T-PLL AML Solid Tumors Solid Tumor + IO APG-115 MDM2-p53 AML, MDS Solid Tumor + IO APG-1387 IAP/XIAP PDAC
Slide 7: More ODDs Than Any Other Chinese Biotech Companies
More ODDs Than Any Other Chinese Biotech Companies 4 Zanubrutinib JS001 Sugemalimab RC48-ADC Breakthrough 1 BTD 1 BTD 1 BTD 1 BTD 36 APG 115, APG 1252, Zanubrutinib, Tislelizumab JS001 YS-ON-001 Orphan Drug APG 2575, HQP1351 4 ODDs 3 ODDs 3 ODDs 9 ODDs 15 Abexinostat Fruquintinib HTD1801 Fast Track
Slide 8: Key Financial Highlights
Key Financial Highlights Revenue(1) R&D Expense Total Assets (RMB mm) (RMB mm) (RMB mm) 463.9 1,229 1,205 1,106 249.6 251.5 582 199.0 6.8 14.5 118.8 6.3 2.3 2.6 2017 2018 2019 1H19 1H20 2017 2018 2019 1H19 1H20 Dec-17 Dec-18 Dec-19 Jun-20 EBIT(2) Other OPEX Cash & Equivalents(3) (RMB mm) (RMB mm) (R
Slide 9: HQP1351 Olverembatinib Overview
HQP1351 Olverembatinib Overview 3rd Gen BCR-ABL/KIT Multi-kinase Inhibitor
Slide 10: Huge Unmet Medical Needs in CML
Huge Unmet Medical Needs in CML Though TKIs have revolutionized management of CML, many patients develop resistance or intolerance to available TKIs; • 1st gen TKI Imatinib: Fails in up to 40% of patients due to BCR-ABL1 resistant mutations, intolerance, and/or suboptimal adherence to therapy sche
Slide 11: Large Potential Market for 3rd Gen BCR-ABL Inhibitors
Large Potential Market for 3rd Gen BCR-ABL Inhibitors Global sales of dasatinib and nilotinib Global sales of ponatinib forecasted at peaked at $4,066M in 2020 $641M in 2025 700 Iclusig (Takeda) Iclusig (Otsuka) Iclusig (INCY) Other 4200 Sprycel (BMY) Dasatinib (SINOBP) Tasigna 4000 3800 3600 600 34
Slide 12: Development Milestone: From IND Approval to NDA in 4 Years
Development Milestone: From IND Approval to NDA in 4 Years • In Jan, awarded “National Major Innovative Drug Project” • In Jul, entered Phase Ib clinical study for TKI rCML in US • In Sep, finished enrollment of 2 pivotal Phase II trials in China • In Apr, submitted an • Results of Ph I trial of HQP
Slide 13: Phase I Study: Highly Efficacious in TKI Resistant CML Patients
Phase I Study: Highly Efficacious in TKI Resistant CML Patients CP AP Total n=87 T315I+ n=52 T315I- n=35 Total n=14 T315I+ n=11 T315I- n=3 95% 97% 100% 91% 82% 78% 85% 80% 69% 61% 50% 52% 55% 46% 46% 43% 37% 36% 36% 34% 15% 0% 0% 0% CHR MCyR CCyR MMR CHR MCyR CCyR MMR CML Response Criteria: Complete
Slide 14: Well-Tolerated With Minimal Dose Interruptions
Well-Tolerated With Minimal Dose Interruptions Long Duration of Treatments Minimal Discontinuation Low Cardiovascular AE Rare Liver Toxicity • Longest duration of treatment is • Among 101 patients • Much lower cardiovascular The liver toxicity was 50 months enrolled, 82 patients events reported; no
Slide 15: Pivotal Ph II Study: Highly Efficacious in T315I-Mutated CML Patients
Pivotal Ph II Study: Highly Efficacious in T315I-Mutated CML Patients CML-CP CML-AP T315I+n=41 T315I+n=23 100.00% 96.80% 100.00% 90.00% 90.00% 80.00% 75.60% 80.00% 70.00% 65.90% 70.00% 60.00% 60.90% 60.00% 48.80% 52.20% 50.00% 50.00% 40.00% 39.10% 40.00% 30.00% 30.00% 26.10% 20.00% 20.00% 10.00% 10.
Slide 16: Cumulative Incidence of Responses
Cumulative Incidence of Responses CML-CP CML-AP Response Rate % (95% CI) at 6 mo Response Rate % (95% CI) at 6 mo 100 100 MCyR 68(54-82) MCyR 52(33-74) CCyR 62(47-76) CCyR 33(17-57) 80 MMR 59(42-77) 80 MMR 29(14-54) Probability (%) Probability (%) 60 60 40 40 20 20 0 0 0 2 4 6 8 10 0 2 4 6 8 Months
Slide 17: Treatment-related Hematologic Adverse Events
Treatment-related Hematologic Adverse Events SAE: 5% SAE: 2% SAE: 17% SAE: 13% Source: Company data 18
Slide 18: HQP1351: T315I and Beyond
HQP1351: T315I and Beyond First 3rd generation of BCR-ABL TKI Ph II pivotal studies in patients with TKI being developed in China resistant BP-CML, Ph+ ALL Efficacious on the patients who NDA was submitted to CDE as failed/intolerant to ponatinib. Also active in planned on June 15 in China, grant 1s
Slide 19: APG-2575 Overview
APG-2575 Overview Novel, orally administered Bcl-2 selective inhibitor, follow to Venclexta®
Slide 20: BCL-2 is a Validated Target
BCL-2 is a Validated Target Bcl-2 Selective Inhibitors BCL-2 inhibitor Compound APG-2575 Venetoclax (ABT-199) MOA Orally available and Bcl-2 selective inhibitor Orally available and Bcl-2 selective inhibitor Clinical stage Ph Ib/II Marketed (CLL, AML) CLL, AML, MM, MCL, MDS, NHL, ALL, Indication CLL
Slide 21: Clinical POC Established
Clinical POC Established More than 100 subjects have been enrolled into 4 Orphan Drug Designations (ODD): CLL,WM, the APG-2575 studies, including R/R CLL , FL , MM,AML MCL, DLBCL, WM, MM, AML and HCL patients, dosed ranging from 20mg to 1200mg Plan to submit the protocol for treatment of patients wi
Slide 22: APG-2575-CN-001 Ph I Interim Data: Activity
APG-2575-CN-001 Ph I Interim data I Activity Ibrutinib Resistant High Risk Patient; Rapid and Deep Response Patient 1S008: PR parameters Patient 1S008: -78.6% Nodal Response 2.5 ALC( 10^9/l) 1000 01S008 SPD PR in r/r CLL (IgVH mutation, no TP53) 2 800 1.5 600 Before APG-2575 After APG-2575 1 61.9% 7
Slide 23: Del17p CLL Patient at High Risk of TLS: Rapid & Deep Response
Del17p CLL Patient at High Risk of TLS: Rapid & Deep Response Patient 008: PR parameters Patient 008: -90% Nodal Response Durable PR in a patient with r/r CLL Before APG-2575 After APG-2575 - 89% - 90% Subject 008 (400 mg) 10 9 8 7 6 5 4 3 2 1 0 Nodal Response: C3D1-89% | C5D1-90% Cycles Potassium (
Slide 24: ALC Response Kinetics in R/R CLL Patients
ALC Response Kinetics in R/R CLL Patients 017 ALC 007 ALC 008 ALC 140 60 40 120 50 35 30 100 40 25 80 30 20 60 15 20 40 10 10 20 5 0 0 0 Source: Company data 26
Slide 25: 70% PR in Evaluable R/R CLL/SLL Patients
70% PR in Evaluable R/R CLL/SLL Patients 0.00% 003 007 008 011 017 021 026 01S008 02S003 0 2 4 6 8 10 12 14 16 01-002 50mg * -20.00% 01-003 100mg * 1S008 200mg 2S003 200mg 01-006 01-007 400mg 400mg -40.00% PR 01-008 400mg 01-011 600mg -60.00% 01-017 800mg 01-021 800mg 01-025 1000mg -80.00% 01-026 10
Slide 26: Synergistic Effects of APG-2575 in Combination with Ibrutinib
Synergistic Effects of APG-2575 in Combination with Ibrutinib V e h ic le c o n tr o l, p . o . , q d x 6 d ; n = 5 A P G - 2 5 7 5 1 0 0 m g /k g , p .o . , s ta r te d a t d 8 , q d x 6 d ; n = 5 V e h ic le R e la tiv e p -B T K p r o te in le v e l 40 3600 Ib r u tin ib 1 5 m g /k g , i.v ., s t
Slide 27: Efficacious In BTK Resistant WM PDX Model In Which Venetoclax Shows NO Activity
Efficacious In BTK Resistant WM PDX Model In Which Venetoclax Shows NO Activity 250 Tumor volume 200 150 100 50 0 kg kg kg l e ic g/ g/ g/ h m m m ve 0 0 25 10 10 ib 5 9 tin 57 19 ru -2 T- PG Ib B A A Source: Company data 29
Slide 28: APG-2575 and Venetoclax
APG-2575 and Venetoclax Differences Compared to Venetoclax: Conclusion: Efficacious in BTK resistant WM PDX model in which Venetoclax shows no effect Daily Ramp-up verse weekly ramp up No Clinical TLS, Lab TLS Short T1/2 & AUC--potentially lower risk of TLS with better tolerance profile Preliminary
Slide 29: APG-115 Overview
Milestones& Developments • Granted ODD for the treatment of AML, gastric cancer and soft tissue sarcoma • Completed Two Phase I trials (U.S. & China) in advanced solid tumors or APG-115 Overview lymphoma MDM2-p53 Inhibitor • U.S.: Completed enrollment of the Ph Ib clinical trial in combination with
Slide 30: APG-115: a Novel, Potent MDM2-P53 Inhibitor
APG-115：a Novel, Potent MDM2-P53 Inhibitor Most potent MDM2 inhibitor in clinical development. Best-in-class potential Blocks MDM2-P53 PPI & Effectively induces apoptosis activates the tumor with the best-in-class potential suppressor P53 Synergy with PD-1 blockade in both TP53WT and TP53MUT Directl
Slide 31: APG-115 US-002
APG-115 US-002 Ph Ib | Overview and Treatment Ph Ib IO resistant/relapsed patients| combination with pembrolizumab Overview & Tolerance Overview & Treatment Duration • MTD not reached, No DLT observed • RP2D is determined as 150mg QOD • No new tolerance finding when combined with pembrolizumab • PK:
Slide 32: APG-115: Promising Activity
APG-115: Promising Activity Ph Ib | Combined with pembrolizumab APG-115 and pembrolizumab achieves a CR in heavily pre-treated, ATM-mutated Ovarian Cancer CA125 Fall as a Function of Time on Treatment Baseline: 3.23.18 C9D1 C23D1: 2.27.20 450 400 CA125 350 300 250 200 150 100 50 Right Paratracheal L
Slide 33: Synthetic Lethality: Combination of APG-115 + APG-2575
Synthetic Lethality Combination of APG-115 + APG-2575 • “Synthetic lethality” describes a strategy where Complete Response in Animal Tumor Models blocking two mutations result in cell death, but the cancerous cells only has one mutation. By artificially 3000 V e h ic le c o n t r o l; n = 5 R it u x
Slide 34: APG-1387
Immuno-Oncology Development • The only IAP-targeting drug to enter clinical trials in China and completed the Ph I monotherapy clinical trials in solid tumors in US and China APG-1387 • A Phase Ib clinical trial in combination with Keytruda in solid tumors ongoing An Antagonist of IAP/XIAP • In 2020
Slide 35: APG-1387 Clinical Development
APG-1387 Clinical Development Ph Ib | Immune Modulation and Activity Ph Ib IO resistant/relapsed patients| combination with pembrolizumab A potential host immune modulator Anti-tumor Activity Plasma was collected from patients pre- & post- APG-1387 treatment at 4 & 24 hours on Day 1 & Day 15 • Human
Slide 36: APG-1252 pelcitoclax
Clinical Development APG-1252 • Two Phase I dose-escalation trials in patients with advanced cancers in the United States and Australia ongoing pelcitoclax • A Phase I dose-escalation/expansion trial as a monotherapy in patients with SCLC in China ongoing BCL-2/BCL-xL Inhibitor • 65 Patients are inv
Slide 37: APG-1252 Phase I Tolerance Data: Well-managed Platelet Toxicity
APG-1252 Phase I Tolerance Data: Well-managed Platelet Toxicity APG-1252 Solves Platelet Toxicity by Design; 240mg QW RP2D APG-1252 10mg-BIW 10-160mg dose cohorts 20mg-BIW 40mg-BIW 80mg-BIW 160mg-BIW 240mg-QW 240mg-BIW Source : American Society of Clinical Oncology (ASCO), Virtual Scientific Program
Slide 38: APG-1252 Phase I Interim Activity Data
APG-1252 Phase I Interim activity Data Single agent activity in advances solid tumors (n=42) SCLC, 002-001 Durable PR in a patient with SCLC Prostate Cancer, 001-016, Ovarian Cancer, 002-030, Pancreatic Cancer, 001- Before APG-1252 After APG-1252 001 Gastric Cancer, 001-003 Partial Response Atypical
Slide 39: Pre-Clinical Asset
Focused on validated targets with clear biomarker, clinical indications and fast regulatory approval High unmet medical needs Pre-Clinical Asset EED Selective/KRAS/MDM2-p53 Degrader First-in-class or best-in- /Allosteric BCR-ABL class potential Transformative new technology
Slide 40: APG-5918: A Best-in-Class EED Inhibitor in IND-Enabling Studies
APG-5918: A Best-in-Class EED Inhibitor in IND-Enabling Studies Items APG-5918 MAK683 (Novartis) Binding affinity to EED protein (IC50 (nM)) 1.2 34 ± 18 (EED226) Karpas422 1.94±0.6 3.3 Cell Growth Inhibition Assay (IC50, nM) 0.14 Pfeiffer 0.7 In vivo activity (KARPAS-422 xenograft) Vehicle control;
Slide 41: KRAS G12C Program
KRAS G12C Program ●Ascentage Pharma has developed multiple classes 1200 V e h ic le c o n tro l; n = 5 T u m o r v o lu m e (M e a n ± S E M ; m m ) 3 of highly potent KRAS G12C mutant specific A S 1 1 0 9 , 3 0 m g /k g , Q D × 1 5 D ; n = 5 inhibitors; 1000 A S 1 1 0 9 , 1 0 0 m g /k g , Q D × 1 5
Slide 42: PROTACs: A Transformative New Therapeutic Strategy by Inducing Protein Degradation
PROTACs: A Transformative New Therapeutic Strategy by Inducing Protein Degradation PROTACs (proteolysis-targeting chimeras) PROTAC: A transformative new technology: Removal of a disease-causing protein by degradation instead of inhibition of the activity of a protein; Achieving extremely high p
Slide 43: Strategic Alliances
Strategic Alliances BCL-xL BCL2 MDM2-p53 • UNITY Biotechnology ("UNITY",NASDAQ:UBX), • Entered a global clinical collaboration with Acerta • Entered a global clinical collaboration with has dosed the first patient in a Phase I clinical study Pharma, the hematology research and MSD; of drug candidate
Slide 44: Our Experienced Executives Team
Our Experienced Executives Team Yifan Zhai, M.D., Ph.D. Gang Zhu. Dajun Yang, M.D., Ph.D. Ming Guo, Ph.D. CO-FOUNDER CO-FOUNDER CHAIRMAN & CHIEF MEDICAL OFFICER CHIEF COMMERCIAL OFFICER PRESIDENT & CHIEF EXECUTIVE OFFICER CHIEF OPERATING OFFICER Thomas Knapp Jeff Kmetz Su Zhang James (Jim) Tripp SVP
Slide 45: Renowned & Globally Recognized Advisors
Renowned & Globally Recognized Advisors Shaomeng Wang Ph.D. Allen S. Lichter Jedd D. Wolchock M.D., FASCO M.D., PhD, FASCO • Chief of the Immuno-Oncology • Professor in Medicine, Service, The Lloyd J. Old Chair in University of Michigan • CEO of ASCO from 2006-2016 Clinical Investigation at Memorial
Slide 46: IP Portfolio for Major Clinical Compounds
IP Portfolio for Major Clinical Compounds Core Compound Patent Type Year Patent Expires APG-1252 Product (Core compound structure)Process; Formulation; Combination; Use 2034-2039/40* APG-2575 Product (Core compound structure); Combination; Process; Use 2037-2039/40* APG-115 Product (Core compound st
Slide 47: Ascentage Pharma Group
Ascentage Pharma Group Advancing Therapies That Restore Apoptosis
Ascentage Pharma Group International — J.P. Morgan Healthcare Conference 2021 on 6ix