Ascentage Pharma Group International · HKEX:6855
Ascentage Pharma Group International — Non-Deal Roadshow (2020)
46 slides from Ascentage Pharma Group International's roadshow presentation, 2020
Slide 1: Ascentage Pharma Group: Advancing Therapies That Restore Apoptosis
Ascentage Pharma Group Advancing Therapies That Restore Apoptosis 1
Slide 2: Disclaimer
Disclaimer PROPRIETARY AND CONFIDENTIAL 2
Slide 3: Ascentage: Innovative Science
Ascentage: Innovative Science Proprietary PPI Platform delivering first-and/or best-in-class potential drugs BREAKTHROUGH SCIENCE STRONG PIPELINE 80 ISSUED PATENTS 12 NOVEL COMPOUNDS 300+ PENDING 24 INDS APPLICATIONS 40+ CLINICAL TRIALS 90+ PUBLICATIONS 10+ INDICATIONS DEDICATED TEAM GLOBAL DEVELOPM
Slide 4: Global Leader Developing Protein-Protein Interactions Drugs
Global Leader Developing Protein-Protein Interactions Drugs Protein-protein interactions (PPIs) play a crucial role in cellular processes, and are implicated in many diseases, from cancer to viral infections PPI targets can’t be penetrated by large molecules, leaving small molecules the only viable
Slide 5: Focused on Apoptosis
Focused on Apoptosis Apoptosis (programmed cell death) is an essential biological process. The average adult human loses between 50 to 70 billion cells each day due to apoptosis. • Apoptosis plays a crucial role in developing and maintaining the health of the body by eliminating old and unhealthy ce
Slide 6: 2020 H1 Key Achievements
2020 H1 Key Achievements Submitted NDA for HQP1351 in patients with T315I-mutant CP- CML and AP-CML in China in June 2020 Started 4 new Phase Ib/II studies of APG-2575 both in China and U.S. APG-115, APG-1387 and APG-1252 entered into phase Ib/II studies respectively. Obtained 2 orphan drug designat
Slide 7: 12 Month Clinical Milestones
12 Month Clinical Milestones Launch of 3rd Bcr-Abl inhibitor HQP1351 in China Bcl-2 selective inhibitor APG-2575 in Ph II r/rCLL reaches POC MDM2-p53 APG-115 + Keytruda® reaches POC in targeting checkpoint resistant/relapsed NSCLC or melanoma patients IAP/XIAP Dimer APG-1387 + Keytruda® reaches Ph I
Slide 8: High Value Portfolio Opportunities
High Value Portfolio Opportunities Validated targets Novel targets Timeline 2020 2021 2022 2023 Product Target Indications IND Phase I Phase II NDA Approval Market HQP1351 BCR-ABL /KIT CML CDE-NDA submission mid-2020 Leukemia (AML) APG-2575 Bcl-2 Leukemia (CLL/SLL) Waldenström’s Solid Tumor + IO APG
Slide 9: Key Financial Highlights
Key Financial Highlights Revenue(1) R&D Expense Total Assets (RMB mm) (RMB mm) (RMB mm) 1,229 1,205 463.9 1,106 6.8 14.5 249.6 251.5 582 6.3 2.3 2.6 199.0 118.8 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 10: HQP1351 Olverembatinib Overview
HQP1351 Olverembatinib Overview 3rd Gen BCR-ABL/KIT Multi-kinase Inhibitor PROPRIETARY AND CONFIDENTIAL 11
Slide 11: BCR-ABL a Validated Target
BCR-ABL a Validated Target Global sales of ponatinib forecasted at Unmet Needs for Targeting BCR-ABL $641M • One of the most frequent BCR-ABL mutations is T315I, ranging from 5 to 25% of CML cases • Amongst multiple BCR-ABL mutations T315I is also the deadliest mutation; it is resistant to second ge
Slide 12: HQP1351 Olverembatinib Development Milestones
Development Milestones • Submitted NDA to the CDE in China in July 2020 • Fast Track Designation approved by FDA for CML in April 2020 • Orphan Drug Designation approved for CML in April 2020 HQP1351 • Ph Ib bridging trial in US enrolling patients at MD Anderson Cancer Center Olverembatinib • Result
Slide 13: Well-tolerated with minimal dose interruptions
Well-tolerated with minimal dose interruptions Ph I: HQP1351 is well-tolerated Summary of all Grade 3 | 4 AEs • 92 out of 101 patients have finished three cycles of treatment: and SAEs in overall subjects • Longest duration of treatment is 45 months AE (>10% of Patients Grade 3, 4 n(%) SAE n (%) • T
Slide 14: Responses in Total Patients
Responses in Total 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 Hematological Response(CHR), CML Re
Slide 15: CML Patient Numbers
CML Patient Numbers China’s CML patient by lines of treatment 51,000+ CML patients in US ~25% 75,000+ 2L+ CML 28% CML patients in China 1L Over 25% of patients with CML BCR-ABL-mutated CML 72% have the T315I mutation2, which has been associated with resistance to treatment and poor outcomes3 PROPRIE
Slide 16: China CML TKI-Resistance Patient Pool
China CML TKI-Resistance Patient Pool CML patients treated with TKI TKI resistance & T315I mut share may have resistance Line of Non Resistant TKI Resistant Therapy • In a Chinese review analysis, 52.7%, 21.8%, 25.5% cases experienced 1st line Imatinib 12% resistance to imatinib , nilotinib and Resi
Slide 17: APG-2575 Overview
APG-2575 Overview BCL-2 Selective Inhibitors PROPRIETARY AND CONFIDENTIAL 18
Slide 18: 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 19: Venetoclax is projected to generate ~$6 Bn WW sales in 2026
Venetoclax is projected to generate ~$6 Bn WW sales in 2026 250+ Active Trials | 89 Sponsored | 13 Potential New Indications Venetoclax ~ $6 Bn Worldwide sales Forecasted 2026 r/r MCL 2019 WW Sales + Ibrutinib Other $792 Million 3L+ MM 1L CLL t(11:14) + Gazyva + Ibrutinib 1L AML 1L AML 1L AML r/r MM
Slide 20: APG-2575 Summary of Key Results
Summary of Key Results • Ph I trial of APG-2575 in hematologic malignancies enrolling US & Australia • 21 patients enrolled up to 800mg (7 dose cohorts), all with daily dose ramp-up • CLL (n=8) completed daily dose ramp-up with no clinical TLS • 6/8 patients reached criteria for hematologic CR or PR
Slide 21: APG-2575 Clinical Development
APG-2575 Clinical Development Progress to Proof of Concept Trial 1 - U.S. & Australia Study Design of APG-2575 Ph I Trials • 21 patients with hematologic malignancies have been treated with APG-2575 up to 800mg (6 dose levels) • All 8 CLL patients completed the daily dose ramp-up without TLS. • 4 CL
Slide 22: APG-2575 and Venetoclax
APG-2575 and Venetoclax • Venetoclax was the first Oncology PPI drug approved by the FDA (AbbVie 20+ years) • Venetoclax is the third transformative therapy for lymphoma, after Rituxan and Imbruvica • >250 Venetoclax trials are being conducted, potentially expanding to >13 indications Differences Co
Slide 23: APG-1387 Overview
APG-1387 Overview An Antagonist of IAP/XIAP (SMAC Mimetic) Dimmer PROPRIETARY AND CONFIDENTIAL 24
Slide 24: APG-1387 Immuno-Oncology Development
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 • A Phase Ib clinical trial in combination with pembrolizumab (“Keytruda”) in solid tumors ongoing APG-1387 • In 2020, two Ph
Slide 25: 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 Antitumor Activity Plasma was collected from patients pre- & post- APG-1387 treatment at 4 & 24 hours on Day 1 & Day 15 • Human
Slide 26: APG-1387 A Novel Pan-IAP Antagonist
APG-1387 A Novel Pan-IAP Antagonist (SMAC Mimetic) Dimmer • Class I original innovation drugs, multiple small molecule IAPs antagonists, which can block the activity of IAPs family proteins (XIAP, cIAP-1, cIAP-2 and ML-IAP) and induce apoptosis. • Preclinical studies suggest that it may be a new way
Slide 27: APG-1387 Chronic Hepatitis B Clinical Development
APG-1387 Chronic Hepatitis B Clinical Development Study Design of APG-1387 Monotherapy in CHB • As of latest evaluable day, a total of 30 patients were involved Objective: safety, in studies. Dose Escalation Levels: Ranging from 7mg up to 30mg MTD, PK and PD Treatment Period Follow-Up Period • The M
Slide 28: APG-1252 Overview
APG-1252 Overview Bcl-2/Bcl-xL Inhibitor PROPRIETARY AND CONFIDENTIAL 29
Slide 29: APG-1252 pelcitoclax Clinical Development
Clinical Development • Two Phase I dose-escalation trials in patients with advanced cancers in the United States and Australia ongoing • A Phase I dose-escalation/expansion trial as a monotherapy in patients APG-1252 with SCLC in China ongoing pelcitoclax • 65 Patients are involved in the dose escal
Slide 30: Palcitoclax (APG-1252) Ph I Interim Efficacy Data
Palcitoclax (APG-1252) Ph I Interim Efficacy Data | n=42 Single agent activity in advances solid tumors 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 Respon
Slide 31: Palcitoclax (APG-1252) Ph I Safety Data
Palcitoclax (APG-1252) Ph I Safety Data | 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 PROPRIETARY AND CONFIDENTIAL Source : American Society of Clinical Oncology (ASCO), V
Slide 32: MDM2-p53
MDM2-p53 Activates p53 tumor suppression via MDM2-p53 PPI PROPRIETARY AND CONFIDENTIAL 33
Slide 33: APG-115 Overview Clinical Development
Clinical Development • Completed Two Phase I trials in the U.S. and China, respectively in advanced solid tumors or lymphoma • Completed enrollment of the Ph Ib clinical trial (19 patients were treated) treated in combination with Keytruda® with 4 dose-escalation cohorts in the U.S. • A Ph II trial
Slide 34: APG-115 US-101 Single Agent Activity
APG-115 US-101 Single Agent Ph I Study Results Single Agent Activity 80mm 36 mm Baseline Cycle 2 ~55% Decrease • 39 yr old Female, with Lipomatoid Liposarcoma, lymphatic metastasis (T2N1M0） • 5 cycles of AD Chemo (Adriamycin+ Dacarbazine) • APG-115: 150mg QOD PROPRIETARY AND CONFIDENTIAL Source: Com
Slide 35: APG-115 US-002 Ph Ib Overview and Treatment
APG-115 US-002 Ph Ib | Overview and Treatment Ph Ib IO resistant/relapsed patients| Combination with Keytruda® Overview & Safety Overview & Treatment Duration • MTD not reached, No DLT observed • RP2D is determined as 150mg QOD • No new safety finding when combined with pembrolizumab • PK: AUC & Cma
Slide 36: APG-115: Promising Efficacy
APG-115: Promising Efficacy Ph Ib | Combined with Keytruda ), Virtual Scientific Program, May 29-31, 2020, Abstract Number: #351 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 LN 20mm RPLN << 10mm 0 RPLN
Slide 37: Synthetic Lethality: Combination of APG-115 + APG-2575
Synthetic Lethality Combination of APG-115 + APG-2575 • “Synthetic lethality” describes a strategy where blocking Complete Response in Animal Tumor Models two mutations result in cell death, but the cancerous cells only has one mutations. By artificially inducing a second V e h ic le c o n t r o l;
Slide 38: Pre-Clinical Asset
Pre-Clinical Asset MCL-1 inhibitor/ EED Selective/ BCR-ABL PROPRIETARY AND CONFIDENTIAL 39
Slide 39: MoA of Mcl-1 Inhibitor and EED Inhibitor
MoA of Mcl-1Inhibitor and EED Inhibitor Mcl-1 Inhibitor EED Inhibitor PROPRIETARY AND CONFIDENTIAL 40
Slide 40: MoA of BCR-ABL1 Allosteric Inhibitor
MoA of BCR-ABL1 Allosteric Inhibitor Inhibition of BCR-ABL1 kinase activity by allosteric inhibitors Active Inactive Constitutively active Inactive Autoinhibition of ABL1 kinase activity by Loss of autoinhibition due to Inhibition of BCR-ABL1 BCR-ABL1 gene kinase activity by allosteric engagement of
Slide 41: Strategic Alliances
Strategic Alliances BCL2 MDM2-p53 • Entered a global clinical collaboration with Acerta Pharma, the hematology • Entered a global clinical collaboration with MSD; research and development center of excellence of AstraZeneca; • We will sponsor an open-label, multicenter, phase Ib/II study • Ascentage
Slide 42: Our Experienced Executives Team
Our Experienced Executives Team Yifan Zhai, M.D., Ph.D. Dajun Yang, M.D., Ph.D. Ming Guo, Ph.D. CO-FOUNDER CO-FOUNDER CHAIRMAN & CHIEF MEDICAL OFFICER PRESIDENT & CHIEF EXECUTIVE OFFICER CHIEF OPERATING OFFICER Thomas Knapp Jeff Kmetz Su Zhang James (Jim) Tripp SVP, GENERAL COUNSEL CHIEF BUSINESS OF
Slide 43: 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 44: 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 APG-2575 Product (Core compound structure); Combination; Process; Use 2037 APG-115 Product (Core compound structure); Process;
Slide 45: Investment Highlights
Investment Highlights 1 2 3 4 5 6 Global leader Product pipeline with Compelling combination Strong global Experienced and Global Collaboration with in apoptosis targeting first- and best-in-class opportunities with intellectual property visionary management Leading Companies and therapy development
Slide 46: Ascentage Pharma Group
Ascentage Pharma Group Advancing Therapies That Restore Apoptosis
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