SUZHOU,China,Nov. 11,2024 -- Alphamab Oncology (stock code: 9966.HK) announced that the results of the first-in-human clinical study of JSKN033,a high-concentration subcutaneous co-formulation consisting of anti-HER2 bispecific antibody-drug conjugate (ADC) and PD-L1 immune checkpoint inhibitor,were presented for the first time as a poster in the Late-Breaking Abstract (LBA) session at the 39th Annual Meeting of the Society for Immunotherapy of Cancer in 2024 (SITC 2024).

The SITC Annual Meeting is one of the leading international conferences focusing on cancer immunotherapy,dedicated to exploring and analyzing the latest technology and research findings in cancer immunotherapy to advance scientific progress and improve patient prognosis. The 39th SITC Annual Meeting was held in Houston,USA,from November 6-10,2024.

Title: JSKN033,an innovative subcutaneous-injected fixed-dose combination (FDC) of biparatopic anti-HER2 antibody drug conjugate (ADC) and PD-L1 inhibitor in advanced solid tumor

Abstract Number: 1496

Presentation Type: Poster Presentation

Poster Presentation Day: Saturday,9 November 2024

Previous clinical studies have shown that combining ADC with immunotherapy (IO) can enhance treatment efficacy and substantially prolong overall survival. However,this combination approach often leads to prolonged infusion and hospitalization durations,along with increased adverse events,which can significantly impact drug exposure and patient medication compliance.

JSKN033 is the global first high-concentration subcutaneous co-formulation consisting of ADC and PD-L1 immune checkpoint inhibitor in first-in-humanclinical trials. Developed on top of the superior solubility and stability of the world's first subcutaneously injectable PD-L1 inhibitor Envaforlimab,JSKN033 combines immunotherapy (KN035) and ADC (JSKN003),makes ADC subcutaneous injectable and leads to improved safety and convenience. This innovative approach is anticipated to offer a safe,effective and more compliant treatment option for patients. In March 2024,the first patient has been successfully dosed in Australia in the phase I/II clinical study of JSKN033 (study number: JSKN033-101),and we are currently actively making the progress in this clinical study.

METHODS

JSKN033-101 (NCT06226766) is an open-label,multicenter,first-in-human Phase Ⅰ/Ⅱ clinical study designed to evaluate the safety,tolerability,and preliminary anti-cancer efficacy of JSKN033 in patients with advanced HER2-expressing solid tumor (IHC ≥ 1+) or HER2-mutant non-Small Cell Lung Cancer (NSCLC).

RESULTS

As of October 14,2024,11 patients were enrolled in the dose escalation phase and had received JSKN033 monotherapy across five dose levels (QW),among which 1 patient at the dose of 1.1mg/kg,1 patient at the dose of 2.3mg/kg,3 patients at the dose of 4.5mg/kg,3 patients at the dose of 5.6mg/kg,and 3 patients at the dose of 6.7mg/kg.

Safety: The most common Treatment-Related Adverse Events (TRAEs) were injection site reactions,all of which were grade 1 and usually resolved within 2 weeks without any treatment or with antihistamines. No dose-limited toxicity (DLT) was observed.

Efficacy: Among the ten efficacy evaluable patients,three patients showed partial response (PR),while five patients demonstrated stable disease (SD),resulting in an 80% disease control rate (DCR).

JSKN033 exhibited anti-tumor activity from the 4.5 mg/kg dose level.

All three PR patients achieved PR at their first post-baseline scans:

Two patients treated at JSKN033 5.6 mg/kg dose level: one had HR-positive/HER2-negative breast cancer (BC) with ≥four lines of prior therapy,and the other had HER2-mutated NSCLC that had progressed after IO,chemotherapy,and HER2-TKI treatment.

One patient with triple-negative BC (TNBC) who had previously received Nab-Paclitaxel and radiotherapy was treated at JSKN033 6.7 mg/kg dose level.

Seven patients were still on treatment to the data cut-off date.

CONCLUSIONS

JSKN033 presented a favorable safety profile and encouraging anti-cancer activity in heavily treated patients. These data further demonstrated the potential of IO and ADC combination and support continued exploration of JSKN033.

About JSKN033

JSKN033 is the global first high-concentration subcutaneous co-formulation consisting of ADC (JSKN003) and immune checkpoint inhibitor (Envafolimab),which is independently developed by the Company. JSKN003 is a an anti-HER2 bispecific ADC,comprising of three components: a bispecific antibody targeting two non-overlapping epitopes of HER2 extracellular domains,a cleavable linker,and a topoisomerase I inhibitor. Envafolimab is a Fc fusion protein consisting of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment,which has been approved by Chinese authorities as the global-first subcutaneous injection PD-(L)1 inhibitor in November 2021. By combining immunotherapy and ADC,JSKN033 is anticipated to significantly enhance efficacy. Leveraging the superior solubility and stability of Envafolimab,this formulation makes ADC subcutaneous injectable and leads to improved safety and convenience. The phase I/II clinical study of JSKN033 for the treatment of HER2-expression advanced or metastatic solid tumors is currently being conducted in Australia.

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.