SUZHOU,China,Dec. 13,2024 -- Alphamab Oncology (stock code: 9966.HK) announced that the latest clinical data from a phase II clinical study on PD-L1/CTLA-4 bispecific antibody KN046 in combination with axitinibas first-line treatment for advanced non-small cell lung cancer (NSCLC) were presented at the European Society for Medical Oncology Immuno-Oncology Congress 2024 (ESMO IO Congress 2024).

ESMO Immuno-Oncology (IO) Congress is a global immunotherapy conference organized by the European Society For Medical Oncology (ESMO),one of the most influential societies in Europe. The ESMO IO Congress 2024 was held in Geneva,Switzerland,from December 11th to 13th,focusing on the latest cutting-edge achievements in immunotherapy to further promote the development of clinical oncology.

Title: The efficacy and safety of KN046 combined with Axitinib for previously untreated and checkpoint inhibitor treated advanced non-small cell lung cancer: a single-arm,open-label,multicenter phase II clinical trial

Presentation Type: Poster Presentation

Presentation Number: 133P

Lecture Time: Thursday,12 December 2024

Speaker: Li Zhang,Sun Yat-Sen University Cancer Center

KN046 is a bispecific antibody that targets both PD-L1 and CTLA-4 immune checkpoints,which can more effectively activate T cells and enhance antitumor effects. Axitinib is a new generation of tyrosine kinase inhibitors that can inhibit tyrosine kinase receptors,including the vascular endothelial growth factor receptor (VEGFR),thereby inhibiting angiogenesis,tumor growth,and progression. KN046-209 is a multi-center,open-label phase II clinical study to evaluate the efficacy,safety and tolerability of KN046 in combination with axitinib in the treatment of advanced NSCLC patients. Preliminary data of this study have been reported at ESMO Congress 2023 for the first time (2023 ESMO 1449P),demonstrating superior tolerability,safety and efficacy signals of KN046 in combination with axitinib as first-line treatment for advanced NSCLC. Results from Cohort A (previously untreated and PD-L1 TPS≥1%) and cohort B (progressed on CPIs) were reported at this ESMO IO Congress.

METHODS

Stage IIIB-IV NSCLC patients without driver mutations,were enrolled in KN046-209(NCT05420220),and received KN046 (5mg/kg,IV,Q3W) and axitinib (5mg or 3mg,PO,BID). The primary endpoint is the objective response rate (ORR),the secondary endpoints include safety,disease control rate (DCR),duration of response (DoR),progression-free survival (PFS) and overall survival (OS).

RESULTS

As of September 1,2024,53 and 32 patients were treated in Cohort A and B,the median follow-up time was 14.6 months and 11.2 months,respectively. 95.3% patients had ECOG PS=1,85.9% patients had stage IV disease,and 49.4% patients had squamous disease. By central lab testing,67.1% and 24.7% patients had PD-L1 TPS≥1% and≥50%,respectively.

In Cohort A,the ORR in PD-L1 TPS≥1% (N=44) and≥50% (N=15) patients were 56.8% (95%

CI 41.0,71.7) and 73.3% (95% CI 44.9,92.2); confirmed ORR were 54.5% (95% CI 38.8,

69.6) and 66.7% (95% CI 38.4,88.2). The DCR were 90.9% (95% CI 78.3,97.5) and 93.3% (95% CI 68.1,99.8). The mDoR were 13.2 months (95% CI 6.6,NE) and NE (95% CI 4.1,NE). The mPFS were 8.3 months (95% CI 6.8,13.9) and 12.4 months (95% CI 4.9,NE). The mOS was not reached yet.

In Cohort B (N=32),the ORR and confirmed ORR were both 9.4% (95% CI 2.0,25.0) and the DCR was 81.3% (95% CI 63.6,92.8). The mDoR was 7.4 months (95% CI NE,NE). The mPFS was 5.6 months (95% CI 2.8,7.0). The mOS was 11.9 months (95% CI 9.9,NE).

58.8% patients had grade≥3 treatment-related adverse events (TRAEs). The most common grade ≥3 TRAEs were ALT increased,AST increased and hypertension (10.6%),PPE and diarrhoea (7.1%). Further exploration study with 3mg Axitinib combo reduced to large extend G3 AE without compromise the efficacy.

CONCLUSIONS

KN046-Axitinib combination showed encouraging efficacy and tolerability in advanced NSCLC patients. Further validation in a large-scale trial is warranted.3mg Axitinib combo demonstrated comparable response rate with 5mg cohort but much better safety. PD-L1 high expression was found to be correlated to higher response and longer duration.

About KN046

KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Alphamab. Its innovative designs include: a novel mechanism - CTLA-4 fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression,and Treg (suppress tumor immunity) clearing function.

Multiple clinical trials of KN046 at different stages covering different types of tumors including non-small cell lung cancer (NSCLC) have been conducted in China,the United States and Australia. The results of these clinical trials have shown advantages in survival for patients.

About Alphamab Oncology

Alphamab Oncology is a leading biopharmaceutical company committed to the development,manufacturing,and commercialization of cutting-edge biotherapeutics for the treatment of cancer. On December 12,2019,the company was successfully listed on the Main Board of the Hong Kong Stock Exchange,trading under the stock code 9966.

Our integrated platform seamlessly combines research,development,and manufacturing capabilities for biologics. We take pride in our extensive intellectual property portfolio,which encompasses protein/antibody engineering,antibody screening,and multi-module/multi-functional antibody modification.

Distinguished by a globally competitive pipeline,Alphamab Oncology specializes in antibody-drug conjugation (ADC),single domain antibody,and bispecific antibodies. Notably,Envafolimab,the world's first subcutaneously injectable PD-L1 inhibitor,was approved by Chinese authorities in 2021,making a significant breakthrough in the convenience and accessibility of cancer treatment. Three assets are currently undergoing Phase III or pivotal clinical trials,and several other bispecific ADC new drug candidates are in early clinical stage. Multiple strategic collaborations based on innovative products or technology platforms have been established with partners such as CSPC,Arrivent,and Glenmark.

Our overarching mission is to make cancer manageable and curable by addressing unmet clinical needs in oncology. Alphamab Oncology is dedicated to the development of safe,effective and affordable drugs,leveraging a global competitive edge.