Adlai Nortye Group Ltd. · NASDAQ:ANL
Adlai Nortye — Investor Presentation (May 2024)
31 slides from Adlai Nortye's investor presentation, May 24, 2024
Slide 1: Corporate Presentation May 2024
0 May 2024 Corporate Presentation NASDAQ: ANL
Slide 2: Disclaimer
1 Disclaimer This presentation is provided solely for informational purposes and has been prepared to assist interested parties in making their own evaluation with respect to a potential private placement of the securities (the “Private Placement”) of Adlai Nortye Ltd. (the “Company”). No representa
Slide 3: Who We Are
(Adlai Nortye Who We Are
Slide 4: Our Mission is to Transform Deadly Cancer into a Chronic and Eventually Curable Disease
3 Our Mission is to Transform Deadly Cancer into a Chronic and Eventually Curable Disease Synergistic Asset Portfolio Global Footprint World Class Management Strong External Collaboration Phase 3 recurrent/metastatic HNSCC after anti-PD-1/PD-L1 therapy: Potentially first-to-market Most advanced drug
Slide 5: Seasoned Management Team of Industry Veterans
4 Yang (Carsten) Lu, EMBA CEO & Chairman Seasoned Management Team of Industry Veterans Lars E. Birgerson, M.D./Ph.D. President, CMO & U.S. CEO Kaiyang (Tom) Tang, M.D., MBA SVP & Global Head of Clinical Operations Wei (Vicky) Zhang, M.Sc. Chief Financial Officer Zhiyong Yu, Ph.D. VP of Operations Na
Slide 6: Global Pipeline with First-to-Market Drug Candidates
5 Product MOA Indication Discovery IND Enabling Phase 1a Phase 1b Phase 2 Phase 3 Upcoming Milestone Partner Licensor Licensee AN2025 (buparlisib) pan-PI3K HNSCC 2/3L (+paclitaxel) OS expected in Q4’24 or Q1’25 PIK3CA mutant solid tumors 2/3L (+Tecentriq®+AN0025) Clinical update in Q2’24 AN0025 (pal
Slide 7: AN2025: Market, Clinical and Regulatory Updates
6 AN2025: Market, Clinical and Regulatory Updates
Slide 8: AN2025: A Pan-PI3K Inhibitor of Tumorigenesis and Promoter of Tumor Immunosurveillance
7 PI3Kα and PI3Kβ in Tumorigenesis • Regulates functions such as cell growth, proliferation, cell migration, and angiogenesis • Widely implicated in cancer • Promotes survival, proliferation, and migration of tumor cells Mechanism of Action AKT mTORC1 AN2025 pan-PI3K inhibitor PTEN PI3K PIP3 PIP2 Gr
Slide 9: AN2025: Market Opportunity in r/m HNSCC
8 Keytruda® +/- chemo prevails in 1L HNSCC since 2019(2), no clinically approved therapies currently available for r/m HNSCC after anti-PD-1/PD-L1 therapy About 85% patients experience disease progression after immunotherapy Preferred regimens for recurrent or metastatic head and neck cancers First-
Slide 10: Completed BERIL-1 Phase 2 Study for r/m HNSCC with Compelling Data
9 PFS: AN2025 + Paclitaxel vs. Paclitaxel 0 20 40 60 80 100 0 2 4 6 8 10 12 14 16 18 20 22 Progression-free survival (%) Time (months) 4.6 vs 3.5 mo (HR=0.65, p=0.011) Overall Response Rate (“ORR”) 39.2% 13.9% p<0.001 AN2025+ Paclitaxel Paclitaxel Major Inclusion： • Platinum-pretreated r/m HNSCC • E
Slide 11: Top Key AEs in the Study
10 Top 15 Key AEs in the Study Key AEs AN2025 + Paclitaxel N=76 Placebo + Paclitaxel N=78 Grade 1-2 Grade 3 Grade 4 Grade 1-2 Grade 3 Grade 4 Hyperglycemia 41% 22% 0 32% 3% 0 Anaemia 22% 18% 0 31% 12% 0 Fatigue 33% 8% 0 12% 10% 0 Diarrhea 37% 1% 0 15% 1% 0 Neutropenia 16% 16% 1% 6% 4% 1% Alopecia 32
Slide 12: AN2025 BURAN Phase 3 Trial Study Design
11 Major Inclusion： • PD-L1-pretreated r/m HNSCC • ECOG 0/1 Primary Endpoint： • OS Secondary Endpoints： • PFS, ORR • DoR, HRQoL Randomized AN2025 100mg/day + Paclitaxel 80mg/m2/week in a 21-day treatment cycle Paclitaxel 80mg/m2/week in a 21-day treatment cycle N=322 N=161 Clinical Trials Led by Glo
Slide 13: Competitive Landscape of Treatment Paradigm in r/m HNSCC after PD-(L)1 therapy
12 Competitive Landscape of Treatment Paradigm in r/m HNSCC after PD-(L)1 therapy AN2025 is the most advanced drug candidate in a Phase 3 trial of r/m HNSCC after PD-1/PD-L1 therapy, an unmet medical need with a sizable market Phase 2 (n = 4) Phase 3 (n =3) Marketed (n = 0) Phase 1/2 (n = 8) Buparli
Slide 14: HNSCC Global Phase 3 First-to-Market: AN2025 Key Highlights
13 Clinical Phase Host Indication # of Patients Trial Status Phase 2 (NCT01852292) r/m HNSCC (after platinum-based chemotherapy) 158 Completed Phase 3 (NCT04338399) r/m HNSCC (after anti-PD-1/PD-L1 treatment) 487 Active, not recruiting HNSCC Global Phase 3 FIRST-TO-MARKET AN2025 – Key Highlights • F
Slide 15: Our Pipeline: Earlier Stage Clinical Assets
14 Earlier Stage Clinical Assets Our Pipeline:
Slide 16: AN0025: Potentially Synergistic Effects in Combination with Checkpoint Inhibitors
15 AN0025: Potentially Synergistic Effects in Combination with Checkpoint Inhibitors Cancer cell EP4 Monocytes Monocytes PGE2 DC EP4 EP4 CD8+ Effector T cell MDSC M2MΦ AN0025 AN0025 AN0025 Mechanism of Action 2-Way ANOVA *:p<0.05 **:p<0.01 ***:p<0.001 ****:p<0.0001 0 500 1,000 1,500 2,000 10 20 30 4
Slide 17: AN0025 + Chemoradiotherapy in Locally Advanced Esophageal Cancer
16 AN0025 + Chemoradiotherapy (CRT) in Locally Advanced (LA) Esophageal Cancer (EC) AN0025: A Potential Enhancer of Radiotherapy An open-label Phase 1b trial: Main inclusion criteria: • Locally advanced/locally recurrent EC • Clinical Stage 2 to 4a (8th AJCC), or Stage 4b • Unresectable, no prior ra
Slide 18: AN0025: Multi-Indication Potential to Address Massive Unmet Need
17 AN0025: Multi-Indication Potential to Address Massive Unmet Need Patient Number Age Gender Dose level T N M Clinical stage 01-003 62 M 250mg qd T4b N3 M0 IVA 01-004 52 M 250mg qd T4b N1 M0 IVA 01-007 64 M 250mg qd T2 N1 M0 II 01-008 61 M 250mg qd T3 N1 M0 III 01-009 58 M 250mg qd T3 N1 M0 III 01-
Slide 19: AN0025 + Chemoradiotherapy in Locally Advanced Esophageal Cancer (Cont'd)
18 AN0025 + Chemoradiotherapy in Locally Advanced Esophageal Cancer AN0025: Multi-Indication Potential to Address Massive Unmet Need (Cont’d) Encouraging Preliminary Efficacy • Overall DCR = 92% (11/12) • 15-month PFS rate = 73% (8/11(1)) • Patients having target lesions at baseline (N=8): ORR = 87.
Slide 20: AN0025: Multi-Indication Potential to Address Massive Unmet Need (Cont'd)
19 AN0025: Multi-Indication Potential to Address Massive Unmet Need (Cont’d) • No dose-limiting toxicity occurred at either dose level, and the maximum tolerated dose was not reached • As of 19 Feb 2024, most frequent TEAEs by preferred term and maximum CTCAE Grade (>=30%) AN0025 250mg QD (N=5) AN00
Slide 21: Competitive Landscape in Locally Advanced Esophageal Cancer
20 Competitive Landscape in Locally Advanced Esophageal Cancer AN0025: Multi-Indication Potential to Address Massive Unmet Need (Cont’d) Study name/NCT number Phase Sponsor Study drug Indication Sample size Regimen Treatment line Primary endpoint Start date (FPI) Anticipated completion date BGB-A317
Slide 22: Preoperative AN0025 + Chemoradiotherapy in Rectal Cancer
21 Preoperative AN0025 + Chemoradiotherapy in Rectal Cancer AN0025: A Potential Enhancer of Radiotherapy (Cont’d) An open-label Phase 1b trial: Main inclusion criteria: • Locally advanced rectal cancer, no metastatic disease • Primary resection without CRT is unlikely to achieve clear margins as def
Slide 23: Preoperative AN0025 + Chemoradiotherapy in Rectal Cancer (Cont'd)
22 Preoperative AN0025 + Chemoradiotherapy in Rectal Cancer AN0025: A Potential Enhancer of Radiotherapy (Cont’d) A Phase 2, open-label, randomized controlled trial (140 pts) Main inclusion criteria: • Biopsy-proven rectal adenocarcinoma; ECOG PS 0-1 • T3b-4a or TanyN1-2 or TanyEMVI+ or with a threa
Slide 24: AN4005: Orally Available, Small-Molecule PD-L1 Inhibitor
23 Market Opportunity AN4005: Orally Available, Small-Molecule PD-L1 Inhibitor • No small-molecule PD-L1 inhibitor approved in any jurisdiction globally • Effectively induce and stabilize PD-L1 dimer formation/dimerization • Opportunity for oral administration, improved tumor penetration, and lack o
Slide 25: Preliminary Efficacy Summary
24 Preliminary Efficacy Summary • As of March 31st, 2024, 23 patients in U.S. and China were dosed. 74% patients (17/23) had received at least two prior lines of systemic therapy. • Overall DCR was 39% (9/23 with 1 CR and 8 SD). • 43% patients (10/23) have relapsed from immunotherapy; 2 out of these
Slide 26: Preliminary Efficacy – Responder Case Review
25 Preliminary Efficacy – Responder Case Review • 50-yr, Asian, female • Diagnosed with Stage 4 colon adenocarcinoma with metastasis in peritoneum at baseline • CPS 30%, MSI-H, KRAS p.G13D mutation, BRAF mutation Demographics and Baseline Characteristics Prior Treatment • Prior surgery: Left colon e
Slide 27: Our Pre-clinical Pipeline: Preclinical Assets with Near-Term INDs
26 Preclinical Assets with Near-Term INDs Our Pre-clinical Pipeline:
Slide 28: AN8025: Multi-Functional T cell/APC modulator
27 AN8025’s Ability to Fully Induce Immune Response in Vitro AN8025: Multi-Functional T cell/APC modulator Compared to an anti-PD-L1 mAb, where almost no co-simulation signals were detected, AN8025 showed significantly stronger co-stimulation signals, which represented enhanced interactions between
Slide 29: AN9025: An Oral Small-Molecule Pan-KRAS Inhibitor
28 AN9025: An Oral Small-Molecule Pan-KRAS Inhibitor • Addresses broad range of KRAS mutations (one of the most commonly mutated proteins in cancer) in multiple tumor types • Efficiently inhibited cancer types with KRAS mutations including pancreas adenocarcinoma, lung adenocarcinoma, and colorectal
Slide 30: AN1025: An Oral Small-Molecule Degrader of Beta-Catenin
29 Mechanism of Action LRP5/6 FZD β-catenin Axin Proteosomal degradation p p x GSK3β β-catenin β-catenin Axin DVL APC p β-catenin β-catenin p WNT Intact Wnt Aberrant Wnt GSK3β β-catenin APC Transcription activation (C-myc, SOX9, CD44) TCF/LEF DVL AN1025: An Oral Small-Molecule Degrader of Beta-Caten
Slide 31: AN1025: Inhibits Wnt Signaling and Suppresses Proliferation of Wnt-altered Tumor Cells
30 AN1025: Inhibits Wnt Signaling and Suppresses Proliferation of Wnt-altered Tumor Cells in Vivo • AN1025 treatment led to the reduction of β-catenin level in tumor cells • β-catenin serves as a biomarker of sensitivity to AN1025 • AN1025 showed anti-tumor activities in colo205 xenograft mice model