GenFleet Announces First Patient Dosed in Phase Ib/II Trial of TGF-β R1 Inhibitor in Combination with PD-1 Inhibitor in Global Multi-center Research

PERTH,Australia and TAIPEI and SHANGHAI,Oct. 21,2021 -- GenFleet Therapeutics,a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology,today announced the first patient with metastatic sigmoid adenocarcinoma has been dosed in Perth,Australia in a phase Ib/II trial of GFH018 in combination with toripalimab (anti-PD-1 monoclonal antibody) as part of global multi-center clinical research. GenFleet also received IND approval from the food and drug administrative authorities in China's Taiwan to proceed with phase Ib/II trial of GFH018 in combination with toripalimab in patients with multiple solid tumors.

Potential indications for molecules targeting TGF-β pathway span across multiple solid tumors,and no drugs have been approved for this pathway thus far. There are broad indications for GFH018 in treating solid tumors with lower response rates to PD-1 inhibitors.

The primary objective of this combination study is to evaluate the safety/tolerability of GFH018 with toripalimab. It will also characterize the pharmacokinetics of GFH018 and the efficacy of the combination therapy. GFH018 demonstrated excellent safety profile in phase I trial. Preclinical data also suggested antitumor effects of low-dose GFH018 in combination with PD-1 inhibitors.

"TGF-β signaling pathway has been validated in recent years as crucial to regulating immune-microenvironment in cancer therapeutics. Drug candidates targeting this pathway offers a critical solution for patients resistant to previous immunotherapies with poor prognosis. Compared to antibodies targeting the TGF-β pathway,GFH018 as a small molecule inhibitor specifically targets TGF-β R1 (receptor type 1). And based on preliminary data in phase I trial,we can see that GFH018 has the potential to inhibit the growth of fibroblasts,regulate tumor microenvironments,and improve the response rate to PD-1 inhibitors in combination therapies," said Yu Wang,M.D./Ph.D.,Chief Medical Officer of GenFleet.

"This multi-center trial the first POC (proof of concept) study designed by GenFleet and it's also the company's third program involving global research sites. The development of GFH018 progresses smoothly and is one of the leading drug candidates targeting TGF-β pathway and will hopefully offer a differentiated alternative to therapies in combination with immune checkpoint inhibitors. In continuous exploration of novel targets,we look forward to benefiting global patients with more innovative therapies in future," said Jiong Lan,Ph.D.,Chief Executive Officer of GenFleet.

About toripalimab

Toripalimab is an anti-PD-1 monoclonal antibody developed by Junshi Biosciences ( SH: 688180；HK: 1877). More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally,including in China and the United States. Ongoing or completed pivotal clinical trials are evaluating the safety and efficacy of toripalimab for a broad range of tumor types including cancers of the lung,nasopharynx,esophagus,stomach,bladder,breast,liver,kidney and skin.

In China,toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (TUOYI®). On December 17,2018,toripalimab was granted a conditional approval by the National Medical Products Administration (NMPA) for the second-line treatment of unresectable or metastatic melanoma. In December 2020,toripalimab was successfully included in the updated National Reimbursement Drug List. In February 2021,the NMPA granted a conditional approval to toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy. In April 2021,NMPA granted a conditional approval to toripalimab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

In the United States,the first toripalimab BLA has been submitted to the FDA for the treatment of recurrent or metastatic NPC. The FDA has granted 2 Breakthrough Therapy designations,1 fast Track designation and 3 orphan drug designations for toripalimab in the treatment of NPC,mucosal melanoma and soft tissue sarcoma.

About GFH018 and TGF-β R1

Developed by GenFleet Therapeutics,GFH018 is an orally administered TGF-β R1 inhibitor and entered into phase I clinical trial in 2019. Preclinical data showed evidence of GFH018's good anti-tumor properties against cancer cells in vivo and in vitro. Besides,translational and mechanistic studies confirmed it effectively acts on TGF-β signaling pathway and synergizes with checkpoint inhibitors.

As a multifunctional cytokine,transforming growth factor-β (TGF-β) is secreted into tumor microenvironment or peripheral circulation mainly by regulatory T cells,fibroblasts and endothelial cells. TGF-β binds to type 2 receptor (TGF-β R2) on cell membrane,and then recruits and phosphorylates type 1 receptor (TGF-β R1). The receptor dimer activates downstream SMAD-dependent & SMAD-independent signaling pathways to perform various biological functions.

In the microenvironment of advanced solid tumors,TGF-β signaling pathway can promote epithelial mesenchymal transition (EMT) & metastasis,induce the formation of cancer stem cells and their functional maintenance,inhibit anti-tumor immunity,enhance vasculature and fibrosis,and ultimately result in tumor progression. Among patients of hepatocellular carcinoma,glioma,colorectal cancer,lung cancer,pancreatic cancer,urothelial cancer and other solid tumors,high expression of genes related to TGF-β signaling pathway is frequently discovered in their blood and tumor tissues. The expression level is positively correlated to the malignancy & poor differentiation of tumor and unfavorable prognosis in patients.

About GenFleet Therapeutics

Dedicated to serving significant unmet medical needs,GenFleet Therapeutics constructs its R&D platform on the basis of disease biology and translational medicine,and researches 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 intellectual property rights.

Through years of endeavor,GenFleet has set up industry-leading capabilities and expertise in developing novel drugs - both small molecules and biologics. Its cutting-edge pipeline includes over 10 products,many of which have progressed into clinical stages. As more projects move into late-stage clinical trials,GenFleet is expected to unravel its blueprint of commercialization during the next 3-5 years.

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