SUZHOU,China,Sept. 16,2024 --Alphamab Oncology (stock code: 9966.HK) announced that the latest clinical data from two studies on anti-HER2 bispecific antibody-drug conjugate (ADC) JSKN003 were presented at the 2024 European Society for Medical Oncology Congress (ESMO Congress 2024) from September 13 to 17,2024,in Barcelona,Spain. Both were pooled analysis of two phase I clinical studies of JSKN003 conducted in Australia and China on platinum-resistant ovarian cancer and advanced HER2-positive (IHC 3+) solid tumors.

Title: JSKN003,a HER2-targeting antibody-drug conjugate,in patients with platinum-resistant ovarian cancer: A pooled analysis of two studies

Presentation Number: 759P

Onsite Poster display date: Saturday,14 September 2024

Speaker: Qunxian Rao,Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Ovarian cancer is one of the three major malignant tumors of the female reproductive system. It is often diagnosed at an advanced stage,with a high recurrence rate,posing a serious threat to women's health.The standard treatment regimens recommended by authoritative guidelines both domestically and internationally include surgery combined with platinum-based chemotherapy and targeted therapy maintenance. However,about 70% of ovarian cancer cases recur after treatment and progress to platinum-resistant,with approximately 20% of patients exhibiting primary platinum resistance. The 2024 NCCN guideline recommend non-platinum cytotoxic drugs and targeted monotherapy as the preferred treatment option for patients with platinum-resistant ovarian cancer.Previous studies have shown that the objective response rate of platinum-resistant ovarian cancer treated with non-platinum chemotherapy alone is only 4% to 13%,highlighting an urgent need for new treatment options.

METHODS

JSKN003-101 (NCT05494918) is a phase I dose-escalation and dose-expansion study in Australian patients with advanced/metastatic solid tumors. JSKN003-102 (NCT05744427) is a phase I (dose escalation and dose expansion) and phase II (cohort expansion) study in Chinese patients with advanced solid tumors. A pooled analysis of the two studies evaluated the safety and efficacy of JSKN003 in patients with platinum-resistant ovarian cancer (PROC).

RESULTS

As of July 15,50 patients with PROC had received JSKN003 across five dose levels,among which 2 patients at the dose of 4.2mg/kg,2 patients at the dose of 5.2mg/kg,44 patients at the dose of 6.3mg/kg,1 patient at the dose of 7.3mg/kg,and 1 patient at the dose of 8.4mg/kg. Among the enrolled 50 patients based on the central laboratory testing,there were 17 patients with HER2 expression (IHC 1+,2+ and 3+) (only 2 patients with HER2 IHC 3+),17 patients with IHC 0,and 16 patients had no HER2 results because they had not been tested by July 15. 28 patients (56.0%) had at least three prior lines of systemic treatment,37 patients (74.0%) had received bevacizumab treatment,and 28 patients (56.0%) had received PARP inhibitor treatment.

The median duration of treatment was 12.4 weeks (range: 0.7 - 51.0 weeks),with 32 patients (64.0%) remained on treatment to the data cut-off date.

Safety: Among all the enrolled 50 patients,3 patients experienced interstitial lung disease (ILD)/pneumonitis. 5 patients (10.0%) experienced grade 3 treatment-related adverse events (TRAEs),with the most common being diarrhea (2.0%) and anemia (2.0%). No TRAEs led to death.

Efficacy:Among the 44 efficacy evaluable patients who had at least one post-baseline tumor assessment,the objective response rate (ORR) was 56.8% (95% CI: 41.0,71.7),with 39 patients (88.6%) showing tumor shrinkage. The ORR in patients with centrally confirmed HER2 IHC 0 and HER2 expression (IHC 1+,2+ and 3+) was 52.9% (95% CI: 27.8,77.0) and 68.8% (95% CI: 41.3,89.0),respectively. For 33 patients who received prior bevacizumab treatment the ORR was 54.5% (95% CI: 36.4,71.9),for 26 patients who received prior PARP inhibitor treatment the ORR was 46.2% (95% CI: 26.6,66.6).

CONCLUSIONS

JSKN003 exhibited a favorable tolerability and safety profile,with lower occurrence of gastrointestinal toxicity and hemotoxicity. JSKN003 demonstrated promising efficacy in heavily pretreated patients with PROC,irrespective of HER2 expression. These data support further clinical exploration of JSKN003 in this population.

Title: Evaluation of the safety and efficacy of JSKN003 in patients with advanced HER2-positive (IHC 3+) solid tumors (excluding breast cancer)

Presentation Number: 675P

Onsite Poster display date: Saturday,14 September 2024

Speaker: Lin Shen,Beijing Cancer Hospital

METHODS

Results of the pooled analysis of patients enrolled in JSKN003-101 (NCT05494918) conducted in Australia and JSKN003-102 (NCT05744427) conducted in China with histologically documented HER2-positive (IHC 3+) solid tumors,were presented at the ESMO Congress 2024. Patients who have failed prior standard therapy,were enrolled and received JSKN003 monotherapy to evaluate safety and efficacy of JSKN003.

RESULTS

As of July 15,29 patients (9 colorectal cancer,6 gastric cancer,4 biliary tract carcinoma,3 esophageal carcinoma,2 ovarian cancer,1 head and neck cancer and 4 others) were enrolled and received JSKN003 monotherapy intravenously (Q3W). 12 patients (41.4%) had at least three prior lines of systemic treatment,14 patients (48.3%) had received anti-HER2 treatment and 7 patients (24.1%) had received anti-HER2 ADC treatment.

The median duration of treatment was 23.6 weeks (range: 4.7~52.0 weeks),and 14 patients remained on treatment to the data cut-off date.

Efficacy: Among the 28 efficacy evaluable patients,the ORR and disease control rate (DCR) were 75.0% and 89.3%,respectively. For 7 patients who received prior anti-HER2 ADC,the ORR was 71.4%. The ORR of gastric cancer and colorectal cancer were 83.3% (5/6) and 66.7% (6/9) respectively.

Safety: Among all the enrolled 29 patients,6 patients (20.7%) experienced grade 3 or higher TRAEs,including neutrophil count decreased (6.9%),vomiting (3.4%),fatigue (3.4%),white blood cell decreased (3.4%) and appetite decreased (3.4%). No TRAEs led to death.

CONCLUSIONS

JSKN003 exhibited a favorable tolerability and safety profile,with a lower incidence of hematological toxicity. Encouraging antitumor activity was observed in heavily pretreated patients with advanced HER2-positive solid tumors. Promising ORR was observed in patients with high HER2 expressing gastrointestinal tumors,which supports further clinical evaluation of JSKN003 in this field.

Electronic version of the posters is available on the Company's website at www.alphamabonc.com.

About JSKN003

JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (bis-ADC),which is developed inhouse with Alphamab's proprietary Glycan-specific conjugation platform. Compared with its ADC counterparts,JSKN003 demonstrated better serum stability and stronger bystander effect,which effectively expands the therapeutic window. Multiple clinical studies of JSKN003 are currently being conducted in Australia and China,and we are also actively making the progress in its pivotal clinical trial in advanced HER2 low-expression breast cancer in China.

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,single domain antibody,and multi-functional 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 new drug candidates are in early clinical stage.

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.