Ascentage Pharma Group International · HKEX:6855
Ascentage Pharma Group International — J.P. Morgan Healthcare Conference 2024
39 slides from Ascentage Pharma Group International's conference presentation, Jan 10, 2024
Slide 1: J.P. Morgan Healthcare Conference 2024
(Ticker: 6855.HK) J.P. Morgan Healthcare Conference 2024 Patient-Centric Innovation | Global Breakthrough Therapies Dr. Dajun Yang, Chairman & CEO January 10, 2024
Slide 2: Disclaimer
Disclaimer Ascentage Pharma 2
Slide 3: Ascentage Pharma
Ascentage Pharma Patient-Centric Innovation | Global Breakthrough Therapies VISION To become a global leading integrated biopharmaceutical company MISSION To address global unmet medical needs VALUE Patients first; Science-based; Data-driven Ascentage Pharma 3
Slide 4: Blood cancer market at a glance
Blood cancer market at a glance 1.24 million US$90bn Global blood cancer Global hematological annual incidence malignancy treatment market (2028E) 6% 30% of all cancer cases of total cancer therapy market Well-positioned to capture the US$10bn+ global blood cancer market opportunities CML ALL CLL AM
Slide 5: Ascentage Pharma pipeline summary
Ascentage Pharma pipeline summary Compounds Target Indications Preclinical Phase I Phase II Registration Trial NDA Approval Trial Region Rights Region Resistant CML Olverembatinib TN Ph+ ALL BCR-ABL/KIT (HQP1351) GIST Resistant CML，Ph+ ALL BTKi treated CLL/SLL (Global-FDA) r/r CLL/SLL (China) TN CLL
Slide 6: 2023 achievements
2023 achievements 3 REGISTRATIONAL OLVEREMBATINIB CLINICAL PROGRESS TRIALS CLEARED FULL APPROVAL ✓ Lisaftoclax (APG-2575) cleared for ✓ Approved for CML-CP adult patients ✓ Lisaftoclax to submit NDA in China in Phase 3 registrational trial for BTKi who are resistant and/or intolerant to 2024 previou
Slide 7: Best-in-class product portfolio: targeting US$10bn+ global markets
Best-in-class product portfolio: targeting US$10bn+ global markets Olverembatinib Lisaftoclax Global best-in-class 3rd gen BCR-ABL TKI 2nd Bcl-2 inhibitor globally Commercialized China launch in 2025 • Effective in 1G/2G/3G TKI (including ponatinib and • Best-in-class potential with better safety pr
Slide 8: 3 global registrational studies ongoing targeting Ph+ ALL and CLL/SLL
3 global registrational studies ongoing targeting Ph+ ALL and CLL/SLL Olverembatinib Lisaftoclax To become the 1st 3rd gen TKI for first Potentially the 2nd approved Bcl-2 inhibitor globally line treatment of Ph+ ALL in China FDA CDE CDE Global Phase III Registrational Trial for Global Phase III Reg
Slide 9: Olverembatinib received full approval for CML in China
Olverembatinib Olverembatinib received full approval for CML in China … The first and only marketed 3G BCR-ABL inhibitor Global best-in-class: to capture significant market in China shares Approved for CML-CP adult patients who are resistant and/or intolerant to 1G and 2G TKIs Expanding market poten
Slide 10: Next steps: Execute Phase 3 trial for Ph+ ALL and obtain FDA clearance
Olverembatinib Next steps: Execute Phase 3 trial for Ph+ ALL and obtain FDA clearance to commence registrational trial for CML Phase 1 and 2 Registrational Approved For patients with TKI-resistant CML-CP or CML-AP harboring T315I mutation Approved in China CML For adult patients with CML-CP resistan
Slide 11: Registrational phase 2 study: Efficacy versus Best Available Treatment
Olverembatinib Registrational phase 2 study: Efficacy versus Best Available Treatment (BAT)¹ in TKI-resistant CML-CP patients Olverembatinib significantly improved event-free survival (EFS) at 21.22 months, compared with BAT arm EFS at 2.86 months Olverembatinib reduced the event risk 65%, compared
Slide 12: Phase 1 5-year data on R/R CML: Durable efficacy and differentiated safety profile
Olverembatinib Phase 1 5-year data on R/R CML: Durable efficacy and differentiated safety profile ✓ 80% and 71% of CML-CP patients achieved MCyR and CCyR, respectively ✓ Therapy responses increased over time and correlated with favorable long-term outcomes ✓ 80% of patients remain on therapy for mor
Slide 13: Global phase 2 study: Favorable clinical benefit in heavily pretreated patients
Olverembatinib Global phase 2 study: Favorable clinical benefit and tolerability in heavily pretreated, particularly ponatinib- or asciminib-failed patients Olverembatinib monotherapy in heavily pre-treated CML-CP patients (N=44) (N=49) (N=15) (N=16) (N=7) (N=8) 60.0% 56.8% 53.3% 50.0% 42.9% 42.9% 4
Slide 14: Olverembatinib + venetoclax and reduced-intensity chemotherapy for newly diagnosed Ph+ ALL
Olverembatinib Olverembatinib + venetoclax and reduced-intensity chemotherapy for patients with newly diagnosed Ph+ ALL High rates of CMR Survival Outcome Response n/N (%） Median follow-up time: 8 months (range, 3-14) in the absence of intensive CR/CRi 45/45 (100) chemotherapy or immunotherapy No re
Slide 15: Olverembatinib + chemo for 1L Ph+ ALL
Olverembatinib Olverembatinib + chemo for 1L Ph+ ALL Combination of olverembatinib and VP regimen as Frontline combination of olverembatinib and pdt-all- first-line therapy for adult Ph+ ALL patients 2016 pediatric inspired protocol in Ph+ ALL patients ◼ 100% overall response, including 96% CR and 4
Slide 16: Olverembatinib + blinatumomab for Ph+/Ph-like ALL patients
Olverembatinib Olverembatinib + blinatumomab for Ph+/Ph-like ALL patients ◼ All patients achieved CR after one cycle of ◼ 100% 6-month OS rate and 87.5% 6-month EFS rate treatment and CMR within 3 months of treatment Fewer cardiovascular adverse events that required discontinuation of treatment comp
Slide 17: MVHO therapy in pediatric patients with R/R AML
Olverembatinib MVHO (liposome mitoxantrone, venetoclax, homo-harringtonine and olverembatinib) therapy in pediatric patients with R/R AML MVHO therapy was effective and reasonably well tolerated in pediatric patients with R/R AML, suggesting that it may comprise a suitable first-line treatment optio
Slide 18: Olverembatinib: global best-in-class 3rd generation BCR-ABL TKI
Olverembatinib Olverembatinib: global best-in-class 3rd generation BCR-ABL TKI ¹ Effective in other 3G TKI failed patients Efficacy Safety Safety ◼ Effective in CML patients who are ◼ Effective and durable anti-leukemic effects in CML and Ph+ ALL patients ◼ 80% of patients continue treatment after r
Slide 19: Lisaftoclax to launch in China in 2025
Lisaftoclax Lisaftoclax to launch in China in 2025 FDA clearance for phase 3 registrational trial Globally the 2nd Bcl-2 selective inhibitor entering global registrational clinical trial China launch in 2025 for r/r CLL To submit NDA in 2024 and to be approved in 2025 Global registrational Ph3 for C
Slide 20: Unique and differentiated clinical design
Lisaftoclax Unique and differentiated clinical design Daily Dose Ramp-up: More convenient to HCPs & patients, lower TLS risks and faster to achieve therapeutic dose Lisaftoclax and BTKi combination therapy can begin quickly (Cycle 1 Day 8) Daily Ramp-up 20 50 100 200 400 X target dose Lisaftoclax
Slide 21: Updated data from 14-month follow-up in R/R CLL patients
Lisaftoclax Updated data from 14-month follow-up in R/R CLL patients Favorable tolerability and efficacy in R/R CLL patients, including heavily pretreated and BTKi-treated patients No significant new or unmanageable safety findings were observed Best overall responses mPFS was 18.53 months mOS not r
Slide 22: Global phase 2 study: Lisaftoclax efficacy on CLL
Lisaftoclax Global phase 2 study: Lisaftoclax efficacy on CLL ORR Lisaftoclax + Acalabrutinib (N=74) %ΔSPD lymph node Monotherapy 67% (n=43) Lisaftoclax + Rituximab 79% (n=34) Lisaftoclax + Acalabrutinib (TN) 100% (n=16) Lisaftoclax + Acalabrutinib (R/R) 98% (n=57) Lisaftoclax + Acalabrutinib (R/R)
Slide 23: Global phase 2 study: Lisaftoclax safety profile in CLL patients
Lisaftoclax Global phase 2 study: Lisaftoclax safety profile in CLL patients Lisaftoclax + acalabrutinib Reported Treatment Emergent AEs in ≥ 10% of pts (n = 79) Neutropenia 9 23 ◼ No DLTs observed Diarrhea 28.2 1.3 ◼ MTD has not been reached Covid-19 infection 17 11.5 Anemia 13 10 ◼ No DDI in combi
Slide 24: Preliminary anti-tumor activity and safety in R/R MM or AL amyloidosis
Lisaftoclax Demonstrated preliminary anti-tumor activity and favorable safety profile in R/R MM or AL amyloidosis patients 30 patients (with a median of 4 lines of prior therapy) Favorable safety profile; grade 3 or 4 AEs were minimal were enrolled in this multi-center trial and tolerated Best ◼ A t
Slide 25: Encouraging clinical efficacy and tolerability in AML and MDS patients
Lisaftoclax Encouraging clinical efficacy and tolerability in AML and MDS patients Lisaftoclax + azacitidine (AZA) resulted in 75% and 71% ORR Favorable tolerability as monotherapy and when combined in R/R AML and TN older/unfit AML patients, respectively with AZA or HHT As of July 19, 2023, 115 pts
Slide 26: Lisaftoclax: potential best-in-class Bcl-2 inhibitor globally
Lisaftoclax Lisaftoclax: potential best-in-class Bcl-2 inhibitor globally Improved benefit-risk and superior overall convenience Clinical validation Efficacy Safety Unique clinical profile • 800+ subjects enrolled • Clinical benefit shown in • Lower incidence of • Highly convenient to patients into
Slide 27: First-in-class pipeline: multiple shots-on-goal in untapped markets
First-in-class pipeline: multiple shots-on-goal in untapped markets • APG-115 Conducting clinical studies in melanoma, MPNST, AML, CMML, MDS, liposarcoma and pediatric neuroblastoma and solid tumors ¹ MDM2-P53 inhibitor • Potential synergies with APG-2575 to achieve “synthetic lethality” • APG-1252
Slide 28: Alrizomadlin (APG-115)
Alrizomadlin Product highlights (APG-115) ◼ Orally bioavailable, highly selective, small molecule inhibitor targeting MDM2-p53. Designed to restore the activation of p53 tumor suppressor activity by blocking the MDM2-p53 interaction PPI (protein-protein interaction) MDM2-p53 inhibitor ◼ 6 orphan dru
Slide 29: Alrizomadlin in combination with lisaftoclax in pediatric tumors
Alrizomadlin (APG-115) in combination with lisaftoclax has promising potential in the treatment of pediatric tumors Targeting the MDM2-P53 and BCL-2 apoptosis pathways simultaneously can achieve "synthetic lethality" Clinical Needs Mechanism Progress Update ◼ Pediatric tumors are the leading cause ◼
Slide 30: APG-2449: Potentially the 1st ALK/FAK/ROS1 triple inhibitor globally
Potentially the 1st ALK/FAK/ROS1 triple inhibitor globally APG-2449 ◼ Innovative drug aiming at high FAK-expressing tumors and ALK/ROS1 fusion mutant NSCLC ◼ Through (1) effective ALK/ROS1 inhibitor and (2) FAK inhibitor in combination with ALK/FAK/ROS1 chemotherapy or targeted therapies, effectivel
Slide 31: Novel FAK/ALK inhibitor APG-2449 could overcome ALK resistance in NSCLC
Novel FAK/ALK inhibitor APG-2449 could overcome ALK resistance in NSCLC Efficacy Best tumor response (%) in patients with 2nd Best tumor response (%) in patients with TKI-naïve pFAK fold change from baseline in PBMCs Best tumor response vs. pFAK expression at the gen TKI resistant ALK+ NSCLC ALK/ROS
Slide 32: Pelcitoclax (APG-1252)
Product highlights ◼ Restore apoptosis through dual inhibition of the Bcl-2 and Bcl-xL proteins ◼ Novel combination in solid tumors and hematologic malignancies Pelcitoclax ◼ ODD received from FDA for the treatment of SCLC (APG-1252) ◼ A total of 205 patients have been treated with pelcitoclax as mo
Slide 33: Pelcitoclax plus osimertinib in EGFR-mutant NSCLC patients
Pelcitoclax plus osimertinib is well tolerated, and preliminary efficacy observed in EGFR-mutant NSCLC patients Pelcitoclax plus osimertinib may improve clinical outcomes of patients with NSCLC harboring TP53- and EGFR- positive mutations Best tumor 1G TKI 3G TKI TKI-naïve response resistant n=7 res
Slide 34: APG-1387
Chronic HBV infection ◼ Completed phase I study of monotherapy in treatment-naïve CHB patients APG-1387 ◼ Conducting phase II clinical trial of APG-1387 combined with entecavir in CHB patients, compared to entecavir monotherapy An Antagonist of IAP/XIAP (SMAC Mimetic) Dimmer Solid tumors ◼ Complete
Slide 35: APG-5918
China's first EED inhibitor to enter clinical trials ◼ APG-5918 binds to the H3K27me3-interacting EED domain, resulting in a conformational change in the EED H3K27me3 binding pocket, and prevents EED APG-5918 from interacting with histone methyltransferase EZH2 ◼ APG-5918 has potent in vitro and in
Slide 36: Key catalysts in 2024
Key catalysts in 2024 Olverembatinib FDA clearance for registrational trial • Olverembatinib to obtain FDA clearance for phase 3 registrational trial for CML Lisaftoclax NDA • Lisaftoclax to file NDA for R/R CLL/SLL in China Execution of global registrational trials • Lisaftoclax – adds-on clinical
Slide 37: Addressing clinical needs through innovative therapeutics: Substantial global opportunities
Addressing clinical needs through innovative therapeutics: Substantial global opportunities Global sales China sales Leading international Twin product engines biopharma with multiple driving sales blockbuster products Olverembatinib full Executing global approved and NRDL registrational trials Lisa
Slide 38: Patient-Centric Innovation | Global Breakthrough Therapies
Patient-Centric Innovation | Global Breakthrough Therapies Products strategically target the US$10bn+ global blood cancer market • Products cover all major hematological malignancies, with each product entering billion+ USD market Focus on global BIC and FIC products with unique and valuable advanta
Slide 39: Patient-Centric Innovation; Global Breakthrough Therapies
Patient-Centric Innovation; Global Breakthrough Therapies CML Olverembatinib MM ALL Lisaftoclax Major Bcl-2 Selective Inhibitor Hematology Malignancy +Anemia MDS CLL AML Alrizomadlin MDM2-p53 Inhibitor Contact us: 68 Xinqing Road, Suzhou 700 King Farm Blvd., Suite 510 Suite 30.03, Level 30, ir@ascen
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