Adlai Nortye Group Ltd 6-K, filed May 24, 2024
Adlai Nortye Group Ltd. (ANL)
About this 6-K
Adlai Nortye Group Ltd filed this 6-K on May 24, 2024.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
Report of Foreign Private Issuer
Pursuant to Rule 13a-16 or 15d-16
under the Securities Exchange Act of 1934
For the month of May 2024
Commission File Number: 001-41773
Adlai Nortye Ltd.
c/o PO Box 309, Ugland House
Grand Cayman, KY1-1104
Cayman Islands
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:
x Form 20-F ¨ Form 40-F
EXHIBIT INDEX
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| Adlai Nortye Ltd. | |||
| By | : | /s/ Yang Lu | |
| Name | : | Yang Lu | |
| Title | : | Chief Executive Officer and Chairman of Board of Directors | |
Date: May 23, 2024
Exhibit 99.1
Adlai Nortye Ltd. to Present Encouraging Data of the Combination of AN0025 and Definitive Chemoradiotherapy (dCRT) at ASCO 2024
SINGAPORE and NORTH BRUNSWICK, N.J. and HANGZHOU, China, May 23, 2024 -- Adlai Nortye Ltd. (NASDAQ: ANL) (the “Company” or “Adlai Nortye”), a clinical-stage biotechnology company focused on the development of innovative cancer therapies, today announced that it will present preliminary data of AN0025 in combination with definitive chemoradiotherapy (dCRT) in unresectable locally advanced or locally recurrent esophageal cancer (EC) at the upcoming American Society of Cancer Oncology (ASCO) Annual Meeting to be held in Chicago from May 31 to June 4, 2024.
AN0025 is a selective EP4 inhibitor that demonstrates antitumor activity by modulating the accumulation and function of macrophages and immunosuppressive myeloid cells in tumor microenvironment. The combination of AN0025 with CRT as neoadjuvant therapy has shown synergistic antitumor efficacy in locally advanced rectal cancer in a prior clinical trial (NCT03152370). The AN0025S0104 study is a single-arm, open-label, multicenter, Phase Ib study comprising a dose escalation phase followed by an expansion phase, aimed at evaluating the safety, tolerability, and feasibility of AN0025 plus dCRT for unresectable locally advanced or locally recurrent EC or esophagogastric junction cancer.
“Our participation in this clinical study underscores our unwavering dedication to pioneering novel cancer therapies with global reach,” said Lars Birgerson, President and Chief Medical Officer of Adlai Nortye Ltd. “As we advance oncology research, our commitment remains steadfast in addressing unmet patient needs through innovative drug discovery and strategic partnerships. We look forward to joining the oncology community in Chicago and sharing updates on our cutting-edge pipeline of programs.”
Details regarding the Adlai Nortye abstract at ASCO 2024 are as follows:
Abstract title: AN0025 in combination with definitive chemoradiotherapy (dCRT) in unresectable locally advanced or locally recurrent esophageal cancer (EC): a single-arm, open-label, multicenter, Phase Ib study (AN0025S0104)
Presenting Author: Nan Bi, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Abstract Number: e16076
Link Abstract on ASCO site: https://meetings.asco.org/abstracts-presentations/235715
About Adlai Nortye
Adlai Nortye (NASDAQ: ANL) is a global clinical-stage biotechnology company focused on the discovery and development of innovative cancer therapies for patients across the spectrum of tumor types, with global R&D centers established in New Jersey, US, and Hangzhou, China. With a strategic emphasis on oncology, the company has identified and developed a robust pipeline of six drug candidates.
Adlai Nortye has assembled a global management team and a scientific advisory board with industry leaders and influential scientists to provide important strategic guidance to its R&D, business development, and operational organizations. In addition to building its own R&D capabilities, the Company continues to seek and secure partnerships with leading multi-national pharmaceutical companies such as Eisai and Novartis, to fully realize the potential of its pipeline programs. The Company strives to become a global leader in the next wave of oncology therapies employing a combination therapy strategy. Its ultimate goal is to transform deadly cancer into a chronic and eventually curable disease.
Forward-Looking and Cautionary Statements
This announcement contains forward-looking statements. These statements are made under the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by terminology such as “will,” “expects,” “anticipates,” “future,” “intends,” “plans,” “believes,” “estimates,” “potential,” “continue,” “ongoing,” “targets” and similar statements. Among other things, statements that are not historical facts, including statements about the Company’s beliefs and expectations, the business outlook and quotations from management in this announcement, as well as the Company’s strategic and operational plans, are or contain forward-looking statements.
The Company may also make written or oral forward-looking statements in its periodic reports to the U.S. Securities and Exchange Commission (the “SEC”), in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Forward-looking statements involve inherent risks and uncertainties. Factors that could cause the Company's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the initiation, timing, progress and results of the Company's preclinical studies, clinical trials and other therapeutic candidate development efforts; the Company's ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; whether the clinical trial results will be predictive of real-world results; the Company's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of the Company's therapeutic candidates; the Company's ability to establish, manage, and maintain corporate collaborations, as well as the ability of its collaborators to execute on their development and commercialization plans; the implementation of the Company‘s business model and strategic plans for its business and therapeutic candidates; the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of the Company's expenses, future revenues, capital requirements and its needs for and ability to access sufficient additional financing; risks related to changes in healthcare laws, rules and regulations in the PRC and United States or elsewhere. Further information regarding these and other risks is included in the Company’s filings with the SEC. All information provided in this press release and in the attachments is as of the date of this press release, and the Company does not undertake any obligation to update any forward-looking statement, except as required under applicable law.
Contacts:
Investor Relations:
Charles Zhou
Amanda Kong
Adlai Nortye Ltd.
ir@adlainortye.com
| 0 May 2024 Corporate Presentation NASDAQ: ANL |
| 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 representations or warranties, express or implied, are given in, or with respect to, this presentation. The information in this presentation does not contain or purport to contain all of the information that may be relevant to an investor’s decision to participate in the Private Placement. It is the sole responsibility of each investor to make its own evaluation of the Company and the Private Placement and to ask such additional questions and obtain such additional information as such investor deems necessary. The securities to be issued in the Private Placement will not be registered under the Securities Act of 1933, as amended (the “Securities Act”), or the securities laws of any other jurisdiction. The Company intends to offer such securities in reliance on exemptions from the registration requirements of the Securities Act and other applicable laws. Any offer or sale of such securities will only be made to persons that are institutional “accredited investors” within the meaning of Rule 501(a) under the Securities Act or “qualified institutional buyers” within the meaning of Rule 144A under the Securities Act. These securities will not be approved or recommended by any federal, state or foreign securities authorities, nor will any of these authorities pass upon the merits of the Private Placement. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. This presentation and the information contained herein (the “Confidential Information”) constitutes confidential information. By receiving the Confidential Information, you agree to maintain the confidentiality of the Confidential Information and that such Confidential Information is subject to any confidentiality obligations you or your affiliates have with respect to the Company, its business, or the Private Placement. Any reproduction or distribution of the Confidential Information without the prior written consent of the Company is prohibited. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including statements relating to the Company’s financial position and results of operations; the Company’s product pipeline, including the timing, conduct and results of preclinical studies and clinical trials, market opportunities and upcoming milestones. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by law, we assume no obligation to update these forward looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward looking statements, even if new information becomes available in the future. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward looking statements, see the section entitled “Risk Factors” in our most recent annual report on Form 20-F filed with the Securities and Exchange Commission (the “SEC”), as well as discussions of potential risks, uncertainties, and other important factors in our other filings with the SEC. Recipients are cautioned not to place undue reliance on these forward looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. This presentation includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties as well as our own estimates of potential market opportunities. All of the market data used in this presentation involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data. Industry publications and third party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. Our estimates of the potential market opportunities for our product candidates include several key assumptions based on our industry knowledge, industry publications, third party research and other surveys, which may be based on a small sample size and may fail to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, and management is responsible for the accuracy of such assumptions and data, no independent source has verified such assumptions. |
| 2 Who We Are |
| 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 candidate by at least THREE years Fast Track Designation from FDA Countries for Trials Led by World-Renowned Principal Investigators (“PI”) Patents and Patent Applications Drug Candidates Clinical Assets Including One Phase 3 asset with First-to-Market Potential R&D Centers in U.S. & China Dedicated R&D Scientists 6 3 AN2025 2 ～90 15+ 250+ 100+ Years Cumulative Industry Experience MNCs and Big Pharma We are a Global Biotechnology Company Focused on Developing Innovative Cancer Therapies Source: Company information. Abbreviations: MNC = multinational companies. Financial Position Cash, cash equivalents and marketable securities $112mm as of Mar 31st, 2024 Runway into 2H 2025 Strong Proof of Concept (“PoC”) Data Laying Concrete Foundation for Potential Registration |
| 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 Nanhai He, Ph.D. VP of Drug Discovery Shifeng Liu, Ph.D. Head of CMC, Preclinical Research Alex Ye, Ph.D. VP of Global BD Archie Tse, Ph.D. Head of Research & Development Victoria Demby, Ph.D. SVP & Global Head of Regulatory Affairs Denotes management with extensive global commercialization and regulatory communication experience |
| 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 (palupiprant) EP4 TNBC, NSCLC, UC, CC and MSS CRC 2/3L (+Keytruda®) Clinical update in Q2’24 LA EC (+CRT) Clinical update at ASCO 2024 Neoadj RC (+CRT) Clinical update in 2025 Stage 3 NSCLC (+CRT) FPI in Q2’24 AN4005 Small molecule PD-L1 Advanced tumors Clinical update in Q2’24 AN8025 Multi-functional T cell/APC modulator Advanced tumors IND expected in H1’25 AN9025 pan-KRAS Advanced tumors PCC expected in Q2’24 AN1025 β-catenin degrader Advanced tumors PCC determination Clinical Stage Preclinical Stage Global Pipeline with First-to-Market Drug Candidates (1) Abbreviations: MOA = mechanism of action; OS = overall survival; TNBC = Triple Negative Breast Cancer; NSCLC = Non-Small Cell Lung Cancer; MSS CRC = Microsatellite Stable Colorectal Cancer; UC = Urothelial Cancer, CC = Cervical Cancer; RP2D = Recommended Phase 2 Dose; RC = rectal cancer; LA = locally advanced; EC = esophageal cancer; FPI = first patient in; IND = Investigational New Drug; PCC = Pre-Clinical Candidate. (1) In April 2023, Adlai Nortye entered into an option agreement to grant Nippon Kayaku an exclusive option to enter into a license agreement to further develop and commercialize products containing AN2025 in all therapeutic, prophylactic and/or diagnostic uses in humans in Japan, pending certain conditions being met. |
| 6 AN2025: Market, Clinical and Regulatory Updates |
| 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 Growth factor receptor Protein synthesis Tumor growth, progression, resistance to therapy PI3Kδ and PI3Kγ in Immunity • Other isoforms of Class I PI3Ks, i.e., PI3Kδ and PI3Kγ, play important roles in immune systems • PI3Kδ is well established to control the function and integrity of regulation T cells • PI3Kγ and PI3Kδ help recruit suppressive myeloid cells into tumor microenvironments and strengthen their inhibitory effects on anti-tumor T cell immune responses Mechanism of Action AN2025: A Pan-PI3K Inhibitor of Tumorigenesis and Promoter of Tumor Immunosurveillance CD8 Th1 Th2 Treg MDSC DC TAM (M1) TAM (M2) PI3Kδ inhibitors IFN λ IL4 IL12 PI3K inhibitors λ Source: Okkenhaug et al., 2016. |
| 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-line: • Pembrolizumab/platin (cisplatin or carboplatin)/5-FU (category 1) • Pembrolizumab (for tumors that express PD-L1 with CPS>=1) (category 1) (NCCN Guidelines Version 2.2024) AN2025: Market Opportunity in r/m HNSCC r/m HNSCC in 2028 1 therapy 32,000 U.S. Incidence(1) 89,000 7MM Incidence(1) NSCLC after PD-L1 therapy r/m HNSCC after anti-PD-1 / PD-L1 therapy 15,000+ U.S. Incidence(1) 50,000+ 7MM Incidence(1) Fast track designation from FDA based on positive data from a randomized Phase 2 BERIL-1 study Market Opportunities – r/m HNSCC after anti-PD-1 / PD-L1 therapy Current Treatment Paradigm Abbreviation: r/m = refractory and metastatic. (1) Pharma Intelligence Disease Analysis of HNSCC by Informa, 2022. 7MM stands for seven major markets (the U.S., the U.K., Germany, France, Italy, Spain, and Japan). (2) FDA approval on June 10, 2019. |
| 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 • ECOG 0/1 Primary Endpoint： • PFS Secondary Endpoints： • OS ORR, DoR • TTR, DCR, HRQoL Randomized AN2025 100mg/day + Paclitaxel 80mg/m2/week in a 28-day treatment cycle Placebo + Paclitaxel 80mg/m2/week in a 28-day treatment cycle N=79 N=79 A Randomized, Double-blind, Placebo-Controlled Phase 2 Trial (BERIL-1) Completed BERIL-1 Phase 2 Study for r/m HNSCC with Compelling Data 0 20 40 60 80 100 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Progression-free survival (%) Time (months) OS: AN2025 + Paclitaxel vs. Paclitaxel 10.4 vs 6.5 mo (HR=0.72, p=0.041) AN2025+Paclitaxel Placebo+Paclitaxel AN2025+Paclitaxel Placebo+Paclitaxel Source: Soulières et al., 2017. Abbreviations: TCR: Time-to-Response; DCR: Disease Control Rate. |
| 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% 0 0 19% 0 0 Stomatitis 22% 9% 0 12% 1% 0 Decreased appetite 24% 7% 0 14% 5% 0 Asthenia 20% 8% 0 18% 4% 0 Nausea 24% 3% 0 17% 0 0 Vomiting 22% 4% 0 14% 0 0 Decreased bodyweight 25% 0 0 9% 3% 0 Cough 21% 0 0 23% 0 0 Constipation 18% 0 0 10% 0 0 Headache 17% 1% 0 8% 0 0 Key Take-Away Messages Similar tolerance of AN2025 plus paclitaxel compared to paclitaxel Similar discontinuation rate of AN2025 plus paclitaxel compared to paclitaxel The frequency of hyperglycemia was higher with AN2025 plus paclitaxel versus paclitaxel, suggesting effective PI3K pharmacodynamics inhibition Known adverse events (“AEs”) associated with AN2025 are manageable 1 3 2 4 BERIL-1 Phase 2 Study in r/m HNSCC: Safety Profile Summary Source: Soulières et al., 2017. Note: For the complete list of AEs observed in the study, please refer to Appendix. |
| 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 Globally Renowned Principal Investigators (“PIs”) Study Design: AN2025 BURAN Phase 3 Trial in r/m HNSCC After Anti-PD-1/PD-L1 Treatment: Addressing Unmet Medical Need The BURAN study is a randomized, open-label Phase 3 study assessing the treatment effect of once-daily AN2025 in combination with weekly paclitaxel compared to weekly paclitaxel alone in patients with r/m HNSCC that have progressed after: 1. Prior anti-PD-L1 monotherapy; 2. Prior anti-PD-L1 therapy in combination with platinum-based therapy; or after 3. Sequential treatment of anti-PD-L1 therapy, either prior to or post platinum-based therapy Prof. Denis Soulières Prof. Lisa Licitra Prof. Barbara Burtness Lead PI of BERIL-1 for AN2025 and KEYNOTE-048 for Pembrolizumab Lead PI of BERIL-1 for AN2025 and KEYNOTE-048 for Pembrolizumab Lead PI of KEYNOTE-048 for Pembrolizumab Abbreviations: ECOG: Eastern Cooperative Oncology Group Performance Status Scale; OS: Overall Survival; PFS: Progression-Free Survivor; DoR: Duration of Response; HRQoL: Health-Related Quality of Life. |
| 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) Buparlisib+Paclitaxel Adlai Nortye Tipifarnib+Alpelisib Kura Palbociclib+Cetuximab Pfizer Tisotumab vedotin Seagen/Genmab Monalizumab +Cetuximab AstraZeneca / Innate CUE-101 Cue Biopharma Lenvatinib+Pembrolizumab Merck Sharp & Dohme Ficlatuzumab+Cetuximab LG Chem/AVEO Petosemtamab Merus NT219+Cetuximab Purple MRG003 Lepu Biopharma NBTXR3+RT+IO Nanobiotix/JNJ FPI: Mar 2023 China-only trial pts w/ HRAS or PIK3CA mut Start in Nov 2023 pts of HPV-neg Phase 3 planned in mid 2024 LPI: Nov 2023 Start in Apr 22, IIT (n=81) pts w/ CDKN2A mut, HPV-neg CyPep-1+Pembrolizumab Cytovation Magrolimab+CT/IO Gilead NCT04338399 NCT04966481 NCT06064877 NCT05751512 NCT03526835 NCT04428151 NCT04854499 FS118±Paclitaxel InvoX NCT04590963 NCT03978689 NCT03485209 NCT04997902 NCT04474470 NCT05383170 NCT04862455 NCT03440437 ISA101+Cemiplimab ISA Pharma NCT04398524 Legend – Mechanisms of Action Targeted Therapies Other Therapies PI3K inhibitor FTIs Multiple tyrosine kinase inhibitor CDK inhibitor Cancer Immunotherapy anti-NKG2A Antibody-drug conjugate IL-2/HPV-16 E7 Anti-HGF/c-MET EGFR/LGR5 BsAb STAT3 & IRS1/2 inhibitor Radio enhancer anti-CD47 Membrane destabilizer LAG-3/PD-L1 BsAb Cancer vaccine Duvelisib +Docetaxel Secura Bio NCT05057247 Sources: clinicaltrials.gov, Informa, public filings, and company presentations. Note: Faded out molecules are no longer in active clinical development. Abbreviations: CT = chemotherapy; RT = radiotherapy; pts = patients; neg = negative, FPI = first patient in; LPI = last patient in. |
| 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 • Fast track designation from FDA • Solid Phase 2 clinical PoC data • Potentially the first on-label drug globally for r/m HNSCC after anti-PD-1/PD-L1 treatment • Sizable TAM after anti-PD-1/PD-L1 therapy becoming primary treatment since approval of Keytruda® as first-line therapy for r/m HNSCC in 2019 Robust Clinical Development First Patient In Apr 2021 Planned NDA Submission Nov 2023 H1 2025 Multi-Regional Clinical Setting with patients to be enrolled in approximately 180 clinical trial sites in the U.S., Canada, UK, Spain, Italy, Germany, France, Poland, Hungary, Belgium, Russia, mainland China, Hong Kong, Taiwan, Japan, South Korea, Australia, and Argentina Key Highlights and Upcoming Catalysts CLEAR CLINICAL PATH Entered Option Agreement with Nippon Kayaku Apr 2023 • Clinical trials in Japan will be conducted by Adlai Nortye • Regulatory pathway in Japan will be managed by Nippon Kayaku (1) Enrollment completed Q4 2024 or Q1 2025 OS readout (1) In April 2023, Adlai Nortye entered into an option agreement to grant Nippon Kayaku an exclusive option to enter into a license agreement to further develop and commercialize products containing AN2025 in all therapeutic, prophylactic and/or diagnostic uses in humans in Japan, pending certain conditions being met. Please refer to the prospectus “Business — License and collaboration agreements — Option agreement with Nippon Kayaku” section for details. |
| 14 Earlier Stage Clinical Assets Our Pipeline: |
| 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 40 Tumor volume (mm³) Days post cell injection Vehicle An0025 anti-PD-1 AN0025+anti-PD-1 Vehicle AN0025,100 mpk QD Anti-PD-1,5 mpk BIW AN0025,100 mpk QD+Anti-PD-1,5 mpk BIW **** * **** AN0025 + anti-PD-1 in CT26 Model AN0025 + anti-PD1 in Advanced Solid Tumors An open-label basket Phase 1b trial: Main inclusion criteria: • Locally advanced, non-resectable or metastatic • ECOG 0/1 Primary endpoints Safety and tolerability Secondary endpoints： ORR, PFS, DoR, OS All enrolled patients will be treated with AN0025 and Keytruda until the patient experiences disease progression, unacceptable toxicity or withdraws consent, or for a maximum of 35 cycles Currently in cohort expansion stage Clinical results will be presented in Q2 2024 Progressed on anti-PD-1/PD-L1 treatment Progressed on SoC, no prior anti-PD-1/PD-L1 treatment MSS CRC NSCLC TNBC Cervical Cancer Urothelial Carcinoma |
| 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 radiotherapy in the esophageal region Primary endpoints • Safety and tolerability • MTD and/or RP2D Secondary endpoints： • Preliminary efficacy: ORR, DCR, PFS, DOR (RECIST 1.1), OS, PK Currently in cohort expansion phase Clinical results will be presented at ASCO 2024 AN0025 + RT in CT26 model AN0025 combined with Radiotherapy demonstrated improved anti-tumor activity and prolonged survival, compared with each compound alone, and antitumor memory T-cell response in mice AN0025 AN0025 AN0025 RT+AN0025 |
| 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 01-011 70 F 500mg qd T3 N2 M0 III 02-001(1) 56 M 500mg qd T3 N1 M0 III 02-002 61 M 500mg qd T2 N2 M0 III 02-003 60 M 500mg qd T3 N3 M0 IVA 02-004 65 M 500mg qd T3 N2 M1 IVB 03-006 64 M 500mg qd T3 N2 M0 III 03-007 69 M 500mg qd T3 N2 M0 III AN0025 + Chemoradiotherapy in Locally Advanced Esophageal Cancer Patient demographics and baseline characteristics 12 Chinese patients (11 males and 1 female, median age 62) with histologically confirmed esophageal squamous cell carcinoma (ESCC) were enrolled and received the study treatment (1) 02-001: locally recurrent esophageal cancer. Prior anti-cancer therapies include: neoadjuvant therapy (Tislelizumab, a PD-1 antibody approved in China + Nab- paclitaxel + Nedaplatin), May 20, 2021 to Jun 10, 2021; esophagectomy, Jul 12, 2021; adjuvant therapy (Sintilimab, a PD-1 antibody approved in China + Nab- paclitaxel + Nedaplatin), Sep 9, 2021 to Oct 22, 2021. |
| 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 = 87.5% (7/8, include 1 CR), DCR = 100% • Patients having non-target lesions at baseline (N=4): DCR = 75% (3/4, include 1 pCR) As of February 19, 2024 (median follow-up is 15.4 months), the tumor response and treatment duration are: Patients that only have non-measurable lesions at baseline Locally recurrent ESCC Abbreviation: DCR = disease control rate; PFS = progression-free survival; ORR = objective response rate; pCR = pathologic complete response; CR = complete response; PR = partial response; SD = stable disease; NE = not evaluable; PD = progressive disease (1) Patient 01-004 was censored because the patient underwent surgery after the treatment and was confirmed as pCR. |
| 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) AN0025 500mg QD (N=7) Total (N=12) Preferred term All grade n (%) Grade≥3 n (%) All grade n (%) Grade≥3 n (%) All grade n (%) Grade≥3 n (%) Total 5 (100.0) 5 (100.0) 7 (100.0) 5 ( 71.4) 12 (100.0) 10 ( 83.3) Anemia 5 (100.0) 0 7 (100.0) 1 ( 14.3) 12 (100.0) 1 ( 8.3) Lymphocyte count decreased 5 (100.0) 5 (100.0) 6 ( 85.7) 5 ( 71.4) 11 ( 91.7) 10 ( 83.3) White blood cell count decreased 5 (100.0) 2 ( 40.0) 6 ( 85.7) 1 ( 14.3) 11 ( 91.7) 3 ( 25.0) Weight decreased 3 ( 60.0) 1 ( 20.0) 6 ( 85.7) 0 9 ( 75.0) 1 ( 8.3) Hypoalbuminaemia 4 ( 80.0) 0 4 ( 57.1) 0 8 ( 66.7) 0 Radiation oesophagitis 3 ( 60.0) 0 5 ( 71.4) 0 8 ( 66.7) 0 Neutrophil count decreased 5 (100.0) 2 ( 40.0) 2 ( 28.6) 1 ( 14.3) 7 ( 58.3) 3 ( 25.0) COVID-19 1 ( 20.0) 1 ( 20.0) 6 ( 85.7) 0 7 ( 58.3) 1 ( 8.3) Hypokalaemia 3 ( 60.0) 1 ( 20.0) 2 ( 28.6) 1 ( 14.3) 5 ( 41.7) 2 ( 16.7) Asthenia 1 ( 20.0) 0 3 ( 42.9) 1 ( 14.3) 4 ( 33.3) 1 ( 8.3) Vomiting 2 ( 40.0) 0 2 ( 28.6) 1 ( 14.3) 4 ( 33.3) 1 ( 8.3) Hypocalcaemia 3 ( 60.0) 0 1 ( 14.3) 0 4 ( 33.3) 0 Pyrexia 4 ( 80.0) 0 0 0 4 ( 33.3) 0 Diarrhoea 2 ( 40.0) 0 2 ( 28.6) 0 4 ( 33.3) 0 Insomnia 1 ( 20.0) 0 3 ( 42.9) 0 4 ( 33.3) 0 Platelet count decreased 2 ( 40.0) 0 2 ( 28.6) 0 4 ( 33.3) 0 Hyponatremia 1 (20.0) 0 3 (42.9) 0 4 (33.3) 0 Platelet count decreased 2 (40.0) 0 2 (28.6) 0 4 (33.3) 0 Radiation skin damage 0 0 4 (57.1) 0 4 (33.3) 0 Abbreviation: TEAEs = treatment emergent adverse events; CTCAE = common terminology criteria for adverse events. AN0025 + Chemoradiotherapy 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-A317-311 (NCT03957590) III BeiGene Tislelizumab (PD-1) Locally advanced ESCC 366 (1:1), CN only Tislelizumab + dCRT vs. placebo + dCRT (concurrent mode) 1st-line PFS 2019-6-11 2024-12-30 (fully enrolled on 2022-3-1) SHR-1210-III-323 (NCT04426955) III Hengrui Camrelizumab (PD-1) Locally advanced ESCC 390 (1:1), CN only Camrelizumab + dCRT vs. placebo + dCRT (concurrent mode) 1st-line PFS 2020-6-30 2023-12-1 (fully enrolled on 2021-8-2) KUNLUN (NCT04550260) III AZ Durvalumab (PD-L1) locally advanced ESCC 600 (2:1), global Durvalumab + dCRT vs. placebo + dCRT (concurrent mode) 1st-line PFS 2020-10-19 2026-11-30 KEYNOTE-975 (NCT04210115) III MSD Pembrolizumab (PD-1) Locally advanced EC 700 (1:1), global Pembrolizumab + dCRT vs. placebo + dCRT (concurrent mode) 1st-line EFS, OS 2022-2-28 2027-4-15 SKYSCRAPER-07 (NCT04543617) III Roche Atelizumab (PD-L1) +/- Tiragolumab (TIGIT) locally advanced ESCC 760 (1:1:1), global Atelizumab + Tiragolumab vs. Atelizumab vs. Placebo (consolidation mode following dCRT) 1st-line PFS, OS 2020-9-28 2027-3-31 (fully enrolled on 2023-9- 28) 1 therapy Locally advanced esophageal cancer in 2028 9,500 U.S. Incidence(1) 46,700 7MM Incidence(1) Market Opportunities – Locally Advanced Esophageal Cancer Abbreviation: ESCC = Esophageal Squamous Cell Carcinoma; dCRT = definitive chemoradiation therapy; EFS = event free survival; OS = overall survival • The concurrent administration of Immune Checkpoint Inhibitors (ICI) and dCRT can pose challenges or create bottlenecks (e.g. PACIFIC-2(2), KEYNOTE-412(3)) • AN0025 + dCRT has the potential to provide novel treatment other than ICI in LA EC (1) Data from Informa, 2023. 7MM stands for seven major markets (the U.S., the U.K., Germany, France, Italy, Spain, and Japan). (2) https://www.astrazeneca.com/media-centre/press-releases/2023/update-on-pacific-2-phase-iii-trial-for-imfinzi.html (3) The Lancet Oncology, doi: https://doi.org/10.1016/S1470-2045(24)00100-1 |
| 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 defined by MRI Primary endpoints • Safety and tolerability • MTD and/or RP2D Secondary endpoints： • pCR, CRM, pTRG, MRI-confirmed down staging in T stage, DFS, PK Long course 20% • No need for surgery • Able to avoid proctectomy 16% + • No residual tumor • Pathological cure Note: Based on 25 evaluable patients TEAE All Grade ≥Grade3 Any 19 (67.9%) 2 (7.1%) Fatigue 8 (28.6%) 1 (3.6%) Diarrhea 4 (14.3%) 1 (3.6%) Nausea 3 (10.7%) - Decreased Appetite 3 (10.7%) - Headache 3 (10.7%) - Paresthesia 3 (10.7%) - No DLTs Observed Note: Only listing TEAEs that occurred in >10% patients, N=28 Short course Encouraging Preliminary Efficacy cCR pCR • AN0025 was well tolerated in combination with CRT • Preliminary efficacy results are encouraging and support the further development of AN0025 in combination with CRT in this indication |
| 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 threatened (<1mm) or involved mesorectal fascia resection margin, or low tumors with involvement of the anal intersphincteric plane or with levator involvement Primary endpoints • Clinical Complete Response rate at 6 months post start of RT Secondary endpoints： • Acute and late toxicity, HRQoL, surgical outcomes, response assessment, organ preservation, DFS, OS LCCRT = long course chemoradiotherapy; SCRT = short course radiotherapy Neoadjuvant rectal cancer in 2028 1 therapy 19,000 U.S. Incidence(1) 50,000 7MM Incidence(1) Study Information Market Opportunities – neoadjuvant Rectal Cancer 1 therapy • FPI in May 2024 • Collaborated with Leeds University, UK Abbreviation: EMVI = Extramural vascular invasion. (1) Data from Informa, 2023. 7MM stands for seven major markets (the U.S., the U.K., Germany, France, Italy, Spain, and Japan). |
| 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 of immunogenicity Benefits Over Antibodies AN4005 as a Backbone for Our Future Oral Combination Therapies Robust Activity in Tumor Models First-in-Human, Dose Escalation study of AN4005 Main inclusion criteria: • Advanced unresectable or metastatic solid tumors, or r/r lymphomas • No standard therapy available • ECOG 0/1 Primary endpoints Safety, tolerability, MTD and/or RP2D Secondary endpoints： PK, food effect, preliminary efficacy including ORR, PFS, DoR, OS As of March 2024, 24 eligible patients were enrolled in 6 dose levels in escalation part in the US and China No DLT observed to date Preliminary clinical efficacy was also observed Clinical update will be presented in Q2 2024 50 mg BID N=2 100 mg BID N=4 200 mg QD N=3 300 mg QD N=4 600 mg QD N=6 1000 mg QD and potential further dose escalation RP2D Food effect N=6 Chinese Patients N=6 |
| 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 10 patients showed partial response to prior immunotherapy. DCR was 50% (5/10 with 1 CR and 4 SD) • 57% Patients (13/23) who have not received prior immune checkpoint inhibitors (ICIs) due to specific indications were found not to be covered by ICI labels. DCR was 31% (4/13 with 4 SD) Dose Level Pt ID Year of birth Gender Race Primary tumor type PD-(L)1 sensitive? Prior immunotherapy? Prior immunotherapy information AN4005 treatment duration (days) BOR in this trial 300 mg qd 20021003 1973 Female Asian Colon adenocarcinoma (PD-L1 TPS 30%, MSI-H) Yes Yes BOR was PR 340 CR (cycle(1) 13) 600 mg qd 20021005 1979 Male Asian Colon adenocarcinoma (EGFR+, pMMR/MSS, PD-L1 TPS<1%) No Yes BOR was PR 229 -SD (TTF -7.6 months) 100 mg bid 10051001 1956 Male Asian Thymic cancer No Yes BOR was SD 399 -SD (TTF ~13.3 months) 200 mg qd 20031007 1956 Male Asian Lung adenocarcinoma No No NA 181 SD (TTF ~6 months) 600 mg qd 10031008 1952 Female White Uterus endometrial adenocarcinoma No Yes BOR was SD 164 SD (cycle(1) 7) 300 mg qd 20021002 1972 Female Asian Ovarian cancer No No NA 145 -SD (TTF ~4.8 months) 26% (6/23) pts dosed with AN4005 among six dose levels reached the TTF (time to failure) ≥ 4.2 months. Abbreviation: DCR = disease control rate; CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; TTF = time to failure; BOR = best of response. (1) 1 cycle = 28 days |
| 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 extended radical resection • Prior systemic therapy: 1) XELOX as adjuvant treatment from Dec 2020 to Apr 2021 followed by one dose of XELOX plus Camrelizumab (an approved PD-1 antibody in China) on 8 May 2021 2) Raltitrexed+Bevacizumab+Camrelizumab/Toripalimab (an approved PD-1 antibody in China) from Jun to Nov 2021 with BOR of PR and progressed in Aug 2022 3) Envolimab (an approved PD-L1 antibody in China) from Sep to Nov 2022 with BOR of PR and progressed in Feb 2023 AN4005 Treatment Course • Single dose at 300mg on 10 Apr 2023 • Multiple doses at 300mg QD started from 17 Apr 2023, 28 days per cycle, is still on treatment (cycle 13) SLD (mm) (peritoneum) Non-target lesion (colon) New lesions Overall response Baseline 12 NA NA NA 1st TA (C3D1) 11 Present No SD 2nd TA (C5D1) 5 Present No PR 3rd TA (C6D1) 5 Present No PR 4th TA (C8D1) 0 Present No PR 5th TA (C11D1) 0 Absent No CR Tumor Assessment 0 -8.3 -58.3 -58.3 -100 -100 -100 -80 -60 -40 -20 0 Baseline C3D1 C5D1 C6D1 C8D1 C11D1 %Change in SLD compared with that at baseline by RECIST 1.1 Abbreviations: TA = tumor assessment; SLD = sum of longest diameters of target lesions; RECIST = response evaluation criteria in solid tumors; SD = stable disease; PR = partial response; CR = complete response. |
| 26 Preclinical Assets with Near-Term INDs Our Pre-clinical Pipeline: |
| 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 T cells and APC PD-L1 Abs AN8025 AN8025 improved the quantity and quality of antigen presenting cells Currently in IND enabling stage; IND filing expected in H1 2025 AN8025’s Ability to Induce Stronger T Cell Response than PD-L1 Antibody in Vitro |
| 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 adenocarcinoma with sub-nM IC50 values • Shows deep, sustained, and durable anti-tumor efficacy in KRAS-driven xenograft mice models • Development candidate expected in Q2 2024 |
| 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-Catenin • Wnt/β-catenin pathway is one of the key tumor-promoting signaling cascades that regulate cell cycle progression, epithelial-mesenchymal transition, angiogenesis, stemness, and tumor immune microenvironment • Aberrant activation of Wnt signaling as a result of genetic mutation has been linked to different cancers. Therefore, this pathway represents a promising target for therapeutic intervention Source: McCord et al., 2017. |
| 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 models |
