8 December 2022, Shanghai – Abbisko Therapeutics Co., Ltd. (“Abbisko Therapeutics” hereafter) announced today the preliminary Phase II efficacy and safety results of its investigational pan-FGFR inhibitor Fexagratinib (ABSK091) in patients with urothelial carcinoma harboring FGFR2 or FGFR3 alterations  in  China's mainland.

About Phase Ib/II trial of Fexagratinib (ASBK091) (NCT05086666)

NCT05086666 is an open-label Phase Ib/II clinical study. In the Phase Ib study, the safety, tolerability and PK of Fexagratinib (ASBK091) in Chinese patients with advanced solid tumors was evaluated and recommended Phase II dose (“RP2D”) was determined. In the Phase II study, the primary endpoint is to evaluate the objective response rate (“ORR”) (based on RECIST 1.1) of Fexagratinib (ABSK091) on treating patients diagnosed with locally advanced or metastatic urothelial carcinoma (“mUC”) harboring FGFR2 or FGFR3 genetic alterations. Preliminary efficacy and safety data has been analyzed for the first 13 response-evaluable patients as of October 2022. It is expected that a total of approximately 88 patients will be enrolled for the Phase II clinical trial.

Results

1) Conclusion

The preliminary efficacy results showed an ORR confirmed by Independent Review Committee (“IRC”) of 30.7% (4/13) in mUC patients with FGFR3 alteration (including mutations and/or fusions) and an IRC confirmed ORR of 44% (4/9) in patients with FGFR3 mutations, which is consistent with results from the prior BISCAY trial of Fexagratinib (ABSK091) in similar patient groups outside of China. The preliminary safety results showed that 80mg BID of Fexagratinib (ABSK091) was well-tolerated in Chinese patients, and no drug related grade 4 or above adverse effects were reported. These results support further development of Fexagratinib (ABSK091) in the ongoing Phase II trial.

2) Efficacy

·  Most of the mUC patients with FGFR3 alterations had tumor shrinkage and approximately 30.7% (4/13) of the patients achieved partial response confirmed by IRC per RECIST 1.1.

· Better efficacy was observed in mUC Patients with FGFR3 mutations with an IRC confirmed ORR of 44% (4/9) per RECIST 1.1.

3) Safety

· 80mg BID of Fexagratinib (ABSK091) was well-tolerated in Chinese patients with solid tumors, with no DLT events reported, and was determined as RP2D.

·  No drug related grade 4 or above adverse effects were reported in mUC patients.

· FGFR-specific adverse effects, such as retinal disorder, nail disorder, dry mouth, hyperphosphatemia etc., were mild to moderate, reversible and manageable.

About Fexagratinib (ABSK091)

Fexagratinib (ABSK091) is a highly potent and selective inhibitor of FGFR1-3. Results from multiple prior clinical trials outside of China have demonstrated preliminary efficacy of Fexagratinib (ABSK091) in treating urothelial carcinoma and other types of solid tumors. In November 2021, Abbisko Therapeutics initiated a Phase II trial Fexagratinib (ABSK091) in patients with urothelial carcinoma harboring FGFR2 or FGFR3 alterations in China's mainland. In February 2022, the Company also entered into partnership with BeiGene, Ltd. (“BeiGene”) on the combination therapy of Fexagratinib (ABSK091) and Tislelizumab, an anti-PD-1 antibody developed by BeiGene, for the treatment of urothelial carcinoma with FGFR2/3 genetic alterations.

In addition to urothelial carcinoma, the Company also plans to conduct clinical trials for Fexagratinib (ABSK091) in other solid tumors. In March 2022, the Company received Orphan Drug Designation granted by the U.S. Food and Drug Administration to Fexagratinib (ABSK091) in gastric cancer.

In November 2022, ABSK091 was given the generic name “Fexagratinib” by World Health Organization under the International Nonproprietary Name (“INN”) system.

About urothelial carcinoma

According to research reports, there are about 80,000 new urothelial carcinoma patients in China every year. The FGFR aberration rate in urothelial carcinoma is approximately 30%. Surgery or radical cystectomy are the recommended first-line treatment for non-muscle invasive or early-stage urothelial carcinoma. For advanced or metastatic urothelial carcinoma, systemic therapies including but not limited to gemcitabine combined with cisplatin / carboplatin, gemcitabine combined with cisplatin / carboplatin and paclitaxel, and immune checkpoint inhibitors are recommended as first-line treatment options. So far there is no FGFR inhibitor approved in China for urothelial carcinoma.

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