GenFleet and Innovent Starts First-in-human Phase I/II Trial of KRAS G12C Inhibitor

GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, and Innovent Biologics (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, today announced that the first patient with KRAS G12C mutation has been dosed in the first-in-human trial of GFH925 (ClinicalTrials.gov, NCT05005234).

Led by Professor Yilong Wu of Guangdong Provincial People's Hospital, it is an open label, multicenter study treating advanced solid tumors patients with KRAS G12C mutation.

Designed to enroll over 100 patients with late stage NSCLC and gastrointestinal cancer, the study will evaluate the safety/tolerability/efficacy and characterize the pharmacokinetics profile of GFH925 administered orally to patients with KRAS G12C mutation. Moreover, this study will explore the potential mechanisms of primary and acquired resistance to KRAS inhibitors. Based on emerging data of GFH925 and other KRAS inhibitors including biomarkers, investigators will look to further optimize the precision treatment plans and the potential for combination therapies.

"KRAS mutation is widespread among patients of non-small cell lung cancer, pancreatic cancer, colorectal cancer, etc. Preclinical data has shown that GFH925 is differentiated from other KRAS G12C inhibiting products, and we look forward to positive results of GFH925's safety/tolerability and efficacy to benefit patients with KRAS G12C gene mutation." said Professor Yilong Wu, Director of Guangdong Lung Cancer Institute.

"Current data demonstrates the higher response to selective KRAS G12C inhibitors in population of lung cancer patients with KRAS G12C mutation. The first patient with KRAS G12C mutation administrated after precision screening is a key milestone in the clinical development of GFH925. Thanks to our joint efforts with investigators from our sites, we have completed program initiation and began patient screening in a very short amount of time. We are also confident that our collaboration with Innovent, with its successful track records of developing and commercializing novel therapies, will speed up the study process in order to bring this life-saving treatment to patients across the globe." said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet Therapeutics.

"KRAS G12C is one of the most frequently mutated oncogenes in human cancer cells and RAS used to be an undruggable target over decades. So far there have been few treatments for patients with this mutation and we can see huge unmet medical needs. We are pleased to achieve the dosing of the first patient and it's an important milestone in the development ofIBI351 (GenFleet R&D code: GFH925). Based on preclinical data, we believe that the clinical research of IBI351 in China will benefit more patients with KRAS G12C mutant lung cancer and other solid tumors and deliver more effective therapies for doctors in the world." said Hui Zhou, Senior Vice President of Clinical Development of Innovent.

About GFH925

Being developed by GenFleet Therapeutics, GFH925 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.

GenFleet Therapeutics and Innovent Biologics entered into an exclusive license agreement in early September for the development and commercialization of GenFleet's lead KRAS G12C candidate, GFH925 in China, including the Chinese mainland, Hong Kong, S.A.R., China, Macau, S.A.R., China and Taiwan, China with additional option-in rights for global development and commercialization.

About Innovent Biologics

Inspired by the spirit of "Start with Integrity, Succeed through Action,"Innocent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 25 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) and Pemazyre® (pemigatinib oral inhibitor) – officially approved for marketing, 1 asset's NDA under NMPA review, sintilimab's Biologics License Application (BLA) acceptance in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 14 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives.

About GenFleet Therapeutics

Dedicated to serving significant unmet medical needs, GenFleet Therapeutics established its proprietary R&D platform based on the deep understanding of disease biology, translational medicine, as well as the research into latest biological mechanism of cancer pathways, tumor microenvironment and human immunoregulation. GenFleet's rich and diversified pipeline 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 in development, many of which have entered clinical stages. GenFleet is expected to progress additional programs into clinics, as well as to transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.

Source: GenFleet Therapeutics