GenFleet Therapeutics Receives Clinical Trial Approval from China's NMPA for GFS202A, a Bispecific Antibody Targeting GDF15 and IL-6, in a Phase I Study Treating Cancer Cachexia Patients

GenFleet Therapeutics, a commercial-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced China's National Medical Products Administration has approved the clinical trial application for GFS202A in an open-label, multi-center phase I study treating cancer patients with precachexia and cachexia. Cachexia is highly prevalent in cancer, and it severely affects patients' survival rate and tolerance to cancer treatments. Extensive research conducted worldwide has identified the key roles of GDF15 and IL-6 in the progression of cachexia. To date, no therapies targeting both GDF15 and IL-6 have been approved in the world, and GFS202A is the first China-developed GDF15-targeted therapy entering clinical stage.

The trial will take place at multiple sites including the prestigious Sun Yat-sen University Cancer Center in Guangdong, China. The phase I study aims to evaluate the safety/tolerability of GFS202A among trial participants, and to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Additionally, the study will assess GFS202A's pharmacokinetic profile, and its impact on improving body weight and appetite.

According to preclinical research, GFS202A exhibits high affinity and specificity for binding to GDF15 and IL-6, thus enabling potent inhibition of their signaling pathways. Body weight, adipose tissue and muscle mass also increase dose-dependently in animal models; notably, GFS202A effectively reduces animal models' C-reactive protein level and alleviates inflammatory responses.

"We are delighted at the clinical trial approval for GFS202A developed by GenFleet. Cancer cachexia is highly prevalent in numerous tumor types and most patients rely on nutritional support or hormone therapies, thus leaving crucial unmet clinical need. In recent years, we are excited to see a variety of GDF15 antibodies entering clinical trials globally. We look forward to more novel treatments benefiting global patients and anticipate this GDF15/IL-6 bispecific antibody to demonstrate good safety and efficacy in the study," stated Professor Li Zhang, Sun Yat-sen University Cancer Center.

Cachexia is a complex disease characterized by debilitating symptoms including disrupted metabolic regulation, substantial weight loss, and progressive muscle breakdown. Cachexia occurs frequently in chronic conditions such as cancer, AIDS, heart failure, chronic obstructive pulmonary disease (COPD), and chronic nephritis. The prevalence of cachexia exceeds 50% in certain cancer types and contributes to a mortality rate of up to 30%. Overexpression of GDF15 and IL-6, commonly observed in cachexia, is relevant to significant morbidity and mortality among cancer patients.

Overseas clinical studies of GDF15 antibodies have achieved proof of concept, validating the improvement of cachexia symptoms through GDF15 inhibition. Furthermore, animal experiments and clinical reports both suggest systemic inhibition of IL-6/IL-6R improves weight loss and reduces inflammatory responses. GFS202A thereby holds the potential to enhance therapeutic efficacy through a dual-target approach, mitigating the inflammatory responses and the adverse effects from cancer treatments.

"GFS202A is the first bispecific antibody to reach the clinical stage in GenFleet's pipeline. The development of this product is firmly grounded in robust mechanistic exploration and innovative molecular design, and we have seen encouraging efficacy and tolerability of GFS202A in preclinical research. Preliminary validation has been achieved for GDF15 antibodies in overseas clinical studies; given the correlation between cachexia and inflammation, as well as the complexity of this metabolic syndrome, IL-6 is selected as another target for our bispecific antibody. We eagerly expect GFS202A to deliver superior safety and efficacy through its dual-target synergistic mechanism in the upcoming trial," stated Yu Wang, M.D., Ph.D., Chief Medical Officer of GenFleet.

About GDF15, IL-6 and GFS202A

GDF15 (Growth Differentiation Factor-15) is a member of the TGF- (Transforming Growth Factor-beta) superfamily of proteins, while the glial cell-derived neurotrophic factor receptor alpha (GFRAL) is the specific receptor for GDF-15. Numerous studies have indicated that the level of GDF-15 is significantly elevated in cancer patients. GDF-15 can activate downstream signaling pathways, thereby promoting growth, migration, and proliferation of cancer cells. Additionally, it inhibits DC (dendritic cell)-mediated T-cell stimulation and the activation and infiltration of cytotoxic T cells.

IL-6 (Interleukin-6) is a member of the glycoprotein 130 (gp130) family. IL-6 can enter the central nervous system and, through the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis, induce atrophy in peripheral tissues such as muscle. It can also act peripherally by activating the JAK/STAT and MAPK signaling pathways, inducing apoptosis in skeletal muscle cells and the breakdown of adipose tissue. Persistent high levels of IL-6 are strongly associated with shorter survival.

In preclinical research of GFS202A (a GDF15/IL-6 bispecific antibody), the body weight, adipose tissue and muscle mass increase dose-dependently in animal models; notably, GFS202A effectively reduces C-reactive protein levels and alleviates inflammatory responses. GFS202A also demonstrated favorable safety/tolerability profile in preclinical animal studies.

About GenFleet Therapeutics

With a focus on cutting-edge therapies, GenFleet Therapeutics is dedicated to serving significant unmet medical needs globally in oncology and immunology. Leveraging its deep understanding of disease biology and translational medicine, GenFleet has established a proprietary and fully integrated R&D system that yields a robust pipeline of 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 spanning small molecules and biologics. Its pipeline comprises numerous programs that have advanced to later-stage or pivotal clinical trials across China, the United States and Europe. Dupert Registered (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. Additionally, the first-line combination therapy of fulzerasib and cetuximab has progressed into phase II study in Europe, marking the world's first integration of KRAS and EGFR inhibitors for first-line non-small cell lung cancer treatment.

With proven success in developing RAS-pathway targeted therapies, GenFleet is also vigorously expanding its portfolio that includes other innovative therapies and novel modalities. Furthermore, it's strengthening its commercial collaborative network through strategic out-licensing agreements or clinical cooperations with prestigious listed companies across the world.
Media Contact
Company Name: GenFleet Therapeutics
Contact Person: Benwu Yang
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Country: China
Website: http://www.genfleet.com

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