SHANGHAI,Aug. 23,2024 -- GenFleet Therapeutics,a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology,announced China's National Medical Products Administration has approved Dupert®（fulzerasib,GFH925/IBI351）for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring KRAS G12C mutationwho have received at least one systemic therapy. Fulzerasib was the first China-developed KRAS G12C inhibitor that had its NDA submission accepted with Priority Review Designation in 2023,and the monotherapy was also granted two Breakthrough Therapy Designations (BTD) for treating advanced KRAS G12C-mutant NSCLC and colorectal cancer (CRC) patients.

The NDA approval is based on the results from a single-arm registrational study (NCT05005234) intended to evaluate the efficacy and safety of fulzerasib monotherapy in advanced NSCLC patients with KRAS G12C mutation who failed or were intolerant to the standard treatment in China. The updated data from this registration study has been published in full manuscript in the Journal of Thoracic Oncology (JTO) and selected for oral presentation at the 2024 World Conference on Lung Cancer (WCLC) .

As of the data cutoff date (Dec 13,2023),a total of 116 NSCLC subjects were enrolled and evaluable. Fulzerasib was generally well-tolerated and demonstrated encouraging antitumor activity. The confirmed objective response rate (ORR) assessed by the Independent Radiology Review Committee (IRRC) was 49.1% (95% CI: 39.7-58.6). Disease control rate (DCR) was 90.5% (95%CI: 83.7,95.2). The median duration of response (DoR) was not reached. Median progression-free survival (PFS) was 9.7 months (95%CI: 5.6-11.0),and median overall survival (OS) was not yet reached.

NSCLC comprises approximately 85% of all lung cancer diagnoses,with KRAS being the most frequently mutated driver gene in NSCLC.The rarity of co-mutations with EGFR or ALK in KRAS-mutated scenario,substantially reduces the clinical benefits of approved EGFR or ALK-targeting therapies for KRAS-mutant or driver-gene-negative NSCLC patients. They are confronted with limited later-line therapeutic options upon disease progressing through the current first-line standard of care (SOC).

"KRAS has long been considered an 'undruggable' target despite being a common oncogenic driver mutation. The advent of KRAS G12C inhibitors has opened new avenues for precision medicine in cancers harboring this mutation. We are proud to be part of the clinical research and development of Dupert®,the first KRAS G12C inhibitor approved in China. We hope that Dupert® will soon benefit more patients with advanced lung cancer harboring KRAS G12C mutations,driving the progress of precision treatment for lung cancer."Stated Professor Yi-Long Wu from Guangdong Lung Cancer Institute,Guangdong Provincial People's Hospital.

Beyond monotherapy,the combination of KRAS and EGFR inhibitors exhibits a synergistic biological mechanism and thus enables the potential of fulzerasib to serve as a first-line treatment option. In 2023,GenFleet initiated a first-line NSCLC combination study (KROCUS) of fulzerasib and cetuximab in Europe,led by world-renowned Professor Rafael Rosell. The analysis of preliminary phase II data was selected for late-breaking abstract and oral presentation at the ASCO conference in June 2024: as of Apr. 19 2024,a total of 33 subjects had at least one post-treatment tumor assessment. The ORR was 81.8% (95% CI: 64.5,93) and the DCR was 100% (95% CI: 89.4,100). The ORR was 70% among those with brain metastases (32.5% of enrolled patients).

"Initiated in 2018,the fulzerasib's development has been moving forward rapidly and yielded positive results. We are delighted at the approval of fulzerasib in China and thankful for the collaborative efforts of Innovent Biologics and the investigators. Given the high G12C prevalence among advanced NSCLC patients in western countries,GenFleet has embarked on the KROCUS study in Europe,a pioneering trial of first-line therapy integrating KRAS and EGFR inhibitors. In specific patient populations,the KROCUS study has demonstrated efficacy and safety potentially comparable or even superior to immunotherapy combined with chemotherapy,positioning the fulzerasib/cetuximab combination as a potentially novel first-line SOC for G12C-mutated NSCLC patients." stated Yu Wang,M.D.,Ph.D.,Chief Medical Officer of GenFleet.

Alongside with NSCLC treatment,the efficacy of fulzerasib monotherapy for CRC also outperformed other single-agent KRAS G12C inhibitors in terms of ORR and mPFS; the efficacy was also comparable to combinations of other G12C inhibitors with anti-EGFR antibodies. Notably,the FDA has granted approval in April this year for GenFleet's phase III study investigating fulzerasib in G12C-mutated refractory,metastatic CRC patients. Furthermore,fulzerasib holds the distinction of being the first G12C inhibitor that received a BTD for CRC treatment in China.

About Dupert® (fulzerasib,KRAS G12C Inhibitor)

RAS protein family can be divided into KRAS,HRAS and NRAS categories. KRAS mutations are detected in nearly 90% of pancreatic cancer,30-40% of colon cancer,and 15-20% lung cancer patients. The occurrence of KRAS G12C mutation subset is more frequently observed than those with ALK,ROS1,RET and NTRK 1/2/3 mutations combined.

Discovered by GenFleet Therapeutics,fulzerasib (GFH925/IBI351) is a novel,orally active,potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange,an essential step in pathway activation,by modifying the cysteine residue of KRAS G12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently,GFH925 effectively inhibits the downstream signal pathway to induce tumor cells' apoptosis and cell cycle arrest.

In September 2021,Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of GFH925 in China (including the Chinese mainland,Hong Kong,Macau and Taiwan) with additional option-in rights for global development and commercialization.

In January 2023,the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for fulzerasib for the treatment of patients with advanced NSCLC harboring KRAS G12C mutation who have received at least one systemic therapy. In May 2023,the CDE of China's NMPA granted another BTD for fulzerasib for the treatment of advanced CRC patients with KRAS G12C mutation who have received at least two systemic therapies.

In August 2024,the CDE of NMPA has approved fulzerasib for the treatment of advanced NSCLC patients harboring KRAS G12C mutation who have received at least one systemic therapy.

About GenFleet Therapeutics

GenFleet Therapeutics,a clinical-stage biotechnology company focusing on cutting-edge therapies,is dedicated to serving significant global unmet medical needs in oncology and immunology. Based on the deep understanding of disease biology and translational medicine,GenFleet's proprietary and fully integrated R&D platform highlights multiple cutting-edge products with novel mechanisms and global IP.

Since its inception in 2017,GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 10 programs,many of which have entered later-stage or pivotal clinical trials across China (including Taiwan),the United States,Europe and Australia. Dupert® (fulzerasib) is the first approved KRAS G12C inhibitor in China and the third globally; it also received NDA priority review designation and two breakthrough therapy designations in 2023. Additionally,the first-line combination therapy of fulzerasib and cetuximab has progressed into phase II study in Europe,marking the world's first treatment integrating KRAS and EGFR inhibitors for first-line non-small cell lung cancer.

With accomplished capabilities in developing RAS-pathway targeted therapies,GenFleet's also vigorously pursuing the development of other innovative therapies and novel modalities. Furthermore,it's expanding commercial collaborative network through strategic out-licensing agreements or clinical cooperations with prestigious listed companies including Innovent,Verastem,SELLAS and Merck,BeiGene. GenFleet is expected to progress additional programs into the clinic,as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.