Ascentage Pharma Group International · HKEX:6855
Ascentage Pharma Group International — Ascentage Pharma Group — Non-Deal Roadshow (October 2021)
49 slides from Ascentage Pharma Group International's roadshow presentation, October 2021
Slide 1: Ascentage Pharma Group: Advancing Therapies That Restore Apoptosis
Ascentage Pharma Group Advancing Therapies That Restore Apoptosis October 2021 1
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 vision: building Integrated organization in 144 12 1 novel a global issued patents compounds biopharmaceutic als company China, pending 3
Slide 4: Global Leader In Developing Therapeutics That Inhibit Protein-Protein Interactions to Restore Apoptosis
Global Leader In Developing Therapeutics That Inhibit Protein-Protein interactions to Restore Apoptosis Protein-protein Focused on Interactions Apoptosis Protein-protein interactions (PPIs) Apoptosis plays a crucial role in play a crucial role in cellular developing and maintaining the processes, an
Slide 5: Major Achievements Over Last 12 Months
Major Achievements Over Last 12 Months 1 NDA with “Priority Review” Clinical Proof of Concept and “Breakthrough Therapy” (POC) of APG-2575 established for HQP1351 (Olverembatinib) in China in r/r CLL 17 global studies 12 ODDs 3 clinical and of APG-2575 in CLL, AML, and 2 FTDs commercial MM, etc.; en
Slide 6: 12 Month Clinical Milestones
12 Month Clinical Milestones Conditional approval and launch of HQP1351 in China; NDA package submission for full approval; completion of bridging Ph Ib and initiation of discussion with FDA on pivotal study in the US CDE approval on the Phase II pivotal study design of APG-2575 as a single agent fo
Slide 7: Rich Pipeline With Significant Opportunities
Rich Pipeline With Significant Opportunities Product Target Indications Preclinical Ph I Ph II NDA Trial Regions Rights regions Resistant CML HQP1351 BCR-ABL/KIT GIST Ph+ ALL CLL/SLL WM AML MM APG-2575 Bcl-2 Selective T-PLL Solid tumors ER+/HER2- Breast Cancer MDS Solid tumors(IO combo) APG-115 MDM2
Slide 8: 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 40 APG-115, APG-1252, Zanubrutinib, JS001 YS-ON-001 Orphan Drug APG-2575, HQP1351 Tislelizumab 4 ODDs 3 ODDs 3 ODDs 12 ODDs 15 HQP1351, APG-115 Fast Track 2 FTDs Abexinos
Slide 9: Commercialization update
Commercialization update Joint Commercial team of Ascentage & Innovent will accelerate the launch of Olverembatinib ● Leveraging Innovent strong commercial team, Olverembatinib will quickly penetrate 80% of potential market before NRDL, reach higher peak sales and maximize the life cycle value. ● Sh
Slide 10: Landmark Strategic Collaboration With Innovent
Landmark Strategic Collaboration With Innovent Two promising combination therapies Landmark multi-part deal in China of up to of APG-2575/HALPRYZA (CD-20) and USD 245m between two leading Chinese APG-2575/letaplimab (CD-47) with biopharma companies synergy in various oncology indications Strategic e
Slide 11: Multiple Ongoing Strategic Alliances
Multiple Ongoing Strategic Alliances BCL-xL BCL-2 MDM2-p53 BCR-ABL & BCL-2 • UNITY Biotechnology • Entered a global clinical collaboration with • Entered a global clinical collaboration with • Ascentage agreed to grant to Innovent the ("UNITY",NASDAQ:UBX), has dosed the Acerta Pharma, the hematology
Slide 12: Key Financial Highlights
Key Financial Highlights Revenue¹ R&D Expense Total Assets (RMB mm) (RMB mm) (RMB mm) 564.6 463.9 2408.2 14.5 12.5 13.0 317.5 1731 249.6 1229.4 1205.1 6.3 6.8 118.8 581.7 2017 2018 2019 2020 2021H1 2017 2018 2019 2020 2021H1 Dec-17 Dec-18 Dec-19 Dec-20 Jun-21 EBIT² OPEX Cash & Equivalents³ (RMB mm)
Slide 13: HQP1351 Olverembatinib Overview
1st Gen BCR-ABL Inhibition wt OR HQP-1351 HQP1351 RESISTANCE Olverembatinib Overview BCR-ABL T3151 P HQP-1351 CRKL Targeting T3151 mutation CBL 3rd Gen BCR-ABL/KIT CRK RAS- Multi-kinase Inhibitor GTP PI3K Promoting cell proliferation and Cell death survival (cancer) 14
Slide 14: Huge Unmet Medical Needs in CML
Huge Unmet Medical Needs in CML CML Patient Numbers Though TKIs have revolutionized management of CML, many patients develop resistance or intolerance to available TKIs 51,000+ 1st gen TKI 2nd gen TKIs The only 3rd gen TKI CML patients in US Imatinib Dasatinib and Nilotinib Ponatinib 75,000+ Fails i
Slide 15: China CML TKI-Resistance Patient Pool
China CML TKI-Resistance Patient Pool CML patients treated with TKI TKI resistance & T315I mut share Line of Therapy Non Resistant TKI Resistant T315I mutation • In a Chinese review analysis, 52.7%, 21.8%, 25.5% Imatinib cases among TKI resistant CML patients 1st line 12% Resistant experienced resis
Slide 16: Large Potential Market for 3rd Gen BCR-ABL Inhibitors
Large Potential Market for 3rd Gen BCR-ABL Inhibitors Worldwide Sales (US$M) Worldwide Sales (US$M) Sprycel (BMY) Dasatinib (SINOBP) Tasigna Iclusig (Takeda) Iclusig (Otsuka) Iclusig (INCY) Other 4,023 4,066 3,963 641 3,862 3,899 3,880 616 585 573 3,563 548 151 3,252 3,309 508 143 104 135 3,022 1,88
Slide 17: 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 March, received • In Sep, finished enrollment of 2 pivotal Phase II trials in China “ Breakthrough • Results of Ph I
Slide 18: Phase I Study Summary
Phase I Study Summary Highly Efficacious in TKI Resistant CML Patients Well-Tolerated With Minimal Dose Interruptions Total n=87 T315I+ n=52 T315I- n=35 CP Long Duration of Treatments Minimal Discontinuation 95% 97% 91% 82% 78% • Longest duration of treatment: • Among 101 patients enrolled, 69% 61%
Slide 19: Pivotal Phase 2 Study Summary
Pivotal Phase 2 Study Summary Highly Efficacious in T315I-Mutated CML Patients Treatment-related Hematologic Adverse Events G1-2 G3-4 CP 96.8% CP 61% T315I+n = 41 75.6% 65.9% 47% 46% 12% 37% 48.8% 49% 24% 12% 34% 23% 25% 12% CHR MCyR CCyR MMR Thrombocytopenia Anemia Leukopenia Neutropenia SAE: 5% SA
Slide 20: HQP1351 Development Plan
HQP1351 Development Plan Product Target Region Indications Study Phase I Phase Ib Phase II Pivotal NDA Approval SJ-0002 CC201 TKI resistant CML-CP China CC202 TKI resistant CML-AP Conditional Approval in 2021 CML HQP1351 BCR-ABL /KIT CC203 TKI resistant CML-CP Enrollment completed Full Approval anti
Slide 21: HQP1351: T315I and Beyond
HQP1351: T315I and Beyond First 3rd generation of BCR-ABL Ph II pivotal studies in patients with TKI being developed in China TKI resistant BP-CML, Ph+ ALL NDA was submitted to CDE as Efficacious in the patients who failed/ planned on June 15 in China, intolerant to ponatinib. Also active in the gra
Slide 22: APG-2575 Overview
APG-2575 Overview Novel, orally administered Bcl-2 selective inhibitor, follow to Venclexta® 23
Slide 23: BCL-2 is a Validated Target
BCL-2 is a Validated Target BCL-2 inhibitor Bcl-2 Selective Inhibitors Compound APG-2575 Venetoclax (ABT-199) MOA Orally available and Bcl-2 selective Orally available and Bcl-2 selective inhibitor inhibitor Clinical stage Ph Ib/II Marketed (CLL, AML) • Tumor cells may become dependent on Bcl-2 for
Slide 24: Clinical POC Established With Best-in-Class Safety Potential
Clinical POC Established With Best-in-Class Safety Potential More than 150 subjects have been enrolled Potential Best-in-Class IND clearance for ER+ breast cancer and into the APG-2575 studies, including R/R CLL , Safety Profile: Less TLS, no other solid tumors FL , MCL, DLBCL, WM, MM, AML and HCL D
Slide 25: Safety/tolerability profile
Safety/tolerability 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) Nausea 2 (5
Slide 26: 80% PR in Evaluable R/R CLL/SLL Patients
80% PR in Evaluable R/R CLL/SLL Patients CLL/SLL Swimmer Plot Source: Company data 28
Slide 27: APG-2575-CN-001 Phase I Interim Data I Efficacy
APG-2575-CN-001 Phase I Interim Data I Efficacy Ibrutinib Resistant High Risk Patient; Rapid and Deep Response Patient 1S008: -78.6% Nodal Response ALC (x10^9/I) 2.5 5 PR 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 C1D15 C2D15 C3D15 C4D15 C
Slide 28: Strong Pre-clinical Data in BTK Combo and BTK Resistant Pts
Strong Pre-clinical Data in BTK Combo and BTK Resistant Pts Synergistic Effects of APG-2575 in Efficacious In BTK Resistant WM PDX Model Combination with Ibrutinib In Which Venetoclax Shows No Activity Vehicle control, p.o., qd x 6d; n=5 PG-2575 100mg/kg ,p.o., started at d8, qd x 6d; n=5 250 Ibruti
Slide 29: Strong Differentiation From Venetoclax
Strong Differentiation From Venetoclax APG-2575 Compared to Venetoclax Conclusion When Selectively Targeting BCL-2 Efficacious in BTK resistant WM PDX model in which Venetoclax shows no effect Dose Escalation Daily ramp-up verse weekly ramp up (Daily Ramp) Low lab and clinical TLS PK Properties (T1/
Slide 30: APG-115 Overview
Milestones & Clinical Developments China: the first MDM2-p53 A Phase Ib/II study in Granted ODD for the inhibitor entering clinical combination with treatment of AML, gastric stage in China, with pembrolizumab for cancer ,soft tissue U.S: enrolling three clinical multiple ongoing clinical treatment
Slide 31: Initial Signs of Efficacy in IO combo
Initial Signs of Efficacy in IO combo Phase Ib Study in IO resistant/relapsed patients in combination with Keytruda® Overview & Safety Overview & Treatment Duration Treatment Related AEs (at least Grade 3) by Preferred Term 501-009 501-010 50 mg 100 mg 150 mg 200 mg Overall 501-023 (n=3) (n=3) (n=6)
Slide 32: Efficacy in IO Combo
Efficacy in IO Combo Phase II Study in multiple cohorts in combination with Keytruda® Efficacy in all Cohorts Efficacy in Patients with IO Resistant Melanoma Response Melanoma NSCL STK-11 ATM Liposarco UC MPNST Response Uveal Mucosal Cutaneous Unknown Total (n = 32) C (n = 5) (n = ma (n = 12) (n = 6
Slide 33: Efficacy in Patients with IO Resistant Cutaneous Melanoma Treated with APG-115 Plus Pembrolizumab
Efficacy in Patients with IO Resistant Cutaneous Melanoma Treated with APG-115 Plus Pembrolizumab CR, target lesion (lymph node) within normal range
Slide 34: 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
Slide 35: Safety: Treatment Emergent AEs (TEAEs)
Safety: Treatment Emergent AEs (TEAEs)
Slide 36: Combining APG-115 and APG-2575 to Achieve Synthetic Lethality
Combining APG-115 and APG-2575 to Achieve Synthetic Lethality • “Synthetic lethality” describes a strategy where Class A Class B Class A Class B Complete Response in Animal blocking two mutations result in cell death, but the Tumor Models cancerous cells only has one mutation. By artificially Viable
Slide 37: APG-1387
Immuno-Oncology Development • Only SMAC mimetic to inhibit both IAP1/2 and XIAP in the clinic • Completed 3 Oncology Phase-1 dose escalation trials; known MTD and RP2D; AEs were mild to moderate, manageable and reversible • Preliminary efficacy signal seen in combination with pembrolizumab, no addit
Slide 38: Initial Signs of Efficacy in IO Combo
Initial Signs of Efficacy in IO Combo Phase Ib IO resistant/relapsed patients| combination with pembrolizumab A potential host immune modulator Anti-tumor Activity 6 IL-12 Change from baseline All tumor Breast NSCLC Colorectal HNSCC Ovarian Pancreatic 4 Response types cancer Others (n=4) (n=16) canc
Slide 39: APG-1252 Pelcitoclax
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 Pelcitoclax Ø A Phase Ib/II study of APG-1252 plus Ruxolitinib in patients with myelofibrosis in the United
Slide 40: APG-1252 Phase I Safety Data: Well-Managed Platelet Toxicity
APG-1252 Phase I Safety Data: Well-Managed Platelet Toxicity APG-1252 Solves Platelet Toxicity by Design; 240mg QW RP2D APG-1252 240mg dose cohort 10-160mg dose cohorts (N=13) 10mg-BIW 240mg-QW 20mg-BIW 240mg-BIW 600 40mg-BIW 500 80mg-BIW 160mg-BIW Platelet counts (x10^9/L) Platelet counts (x10^9/L)
Slide 41: APG-2449
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 ALK/FAK/ROS1 combination with other agents in pr
Slide 42: Pre-Clinical Assets
Focused on validated targets with clear biomarker, clinical indications and fast regulatory approval High unmet medical needs Pre-Clinical Assets First-in-class or EED Selective/MDM2-p53 Degrader best-in-class potential Transformative new technology 44
Slide 43: 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) Pfeiffer 0.14 0.7 In vivo activity (KARPAS-422 xenograft) APG-5918 Vehicle
Slide 44: 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 PROTACs MDM2 protein degrader • Removal of a disease-causing protein by degradation • The molecule is well-tolerated in mice, rats and d
Slide 45: PROTAC MDM2 Degrader
PROTAC MDM2 Degrader >100-fold improved cell growth Potent and complete degradation of Dramatic survival benefit in inhibition activity by the molecule MDM2 protein in acute leukemia cells disseminated leukemia mouse model over MDM2 inhibitor MI-63 RS4;11 (t = 2 h) 100 RS4;11 (4 day) 90 MI-63 APG-26
Slide 46: Our Experienced Executives Team
Our Experienced Executives Team Dajun Yang, M.D., Ming Guo, Ph.D. Yifan Zhai, M.D., Gang Zhu CO-FOUNDER CHIEF COMMERCIAL OFFICER Ph.D. EX-PRESIDENT & Ph.D. CO - F O U N D E R CHIEF OPERATING OFFICER CHIEF MEDICAL OFFICER CH A IR M A N & CH IE F E X E C U T IV E O F F IC E R Jeff Kmetz Thomas Knapp J
Slide 47: 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 • Professor in Medicine, University • CEO of ASCO from 2006-2016 • Chief of the Immuno-Oncology Service, of Michigan • Dean of the University of Michigan The Lloyd J. Old Chair
Slide 48: IP Portfolio for Key Clinical Assets
IP Portfolio for Key Clinical Assets Year Patent Core Compound Patent Type Expires HQP1351 Product (Core compound structure); Process; Combination; Use; Formulation 2031-2039/40* APG-2575 Product (Core compound structure); Combination; Process; Use 2037-2039/40* APG-115 Product (Core compound struct
Slide 49: Ascentage Pharma Group
Ascentage Pharma Group Advancing Therapies That Restore Apoptosis
Ascentage Pharma Group — Non-Deal Roadshow (October 2021) on 6ix