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Congratulations on the approval of IND! The clinical trial of project WGI-0301 (AKT-1 antisense nucleic acid LNP for the treatment of liver cancer) by Haichang Biotech has been officially approved by the US FDA
On December 30, 2021, the IND application for project WGI-0301, a category 1.1 innovative nucleic acid drug independently developed by Zhejiang Haichang Biotech Co., Ltd., was approved by the US FDA (IND:145841), and the project officially entered the clinical trial stage.
WGI-0301 is a new-generation antisense AKT-1 inhibitor encapsulated using QTsomeTM nucleic acid delivery technology. The target of AKT-1 acts on PI3K/AKT/mTOR signaling pathway, playing a key role in cancer cell proliferation, survival, angiogenesis, metastasis and development of drug resistance, and it is overexpressed in various cancers, including hepatic cancer, renal cancer, breast cancer, colorectal cancer, gastric cancer and pancreatic cancer.
With highly selected specificity and the absence of susceptibility to drug resistance, WGI-0301 effectively addressed the key challenges such as low efficiency in the intracellular uptake of nucleic acid and underachieved targeting ability by using the QTsomeTM nucleic acid delivery technology under global-wise intellectual property protection, and thus satisfactorily meets the needs in the treatment of hepatic cancer.
Dr. Zhao Xiaobin, president of Haichang Biotech:
We were so delighted to see the IND for WGI-0301 was finally approved by the US FDA after our strenuous input in its R&D over the past four years, and it represents a major milestone in the R&D front of innovative nucleic acid drugs of Haichang Biotech. The research team of Haichang will continue to pursue its original intentions by stepping up its efforts and investment in the field of innovative nucleic acid drugs, pushing forward with the clinical studies on relevant pharmaceutical products in an optimized manner and consistently transform more technical reserve into high-quality products that can meet the clinical needs, so as to benefit more patients and making its share of contribution to the health of the human kind.
The clinical enrollment for WGI-0301 project was initiated at locations including the MD Anderson Cancer Center in America in the first quarter of 2022, with a view to investigating and exploring the safety and tolerability of WGI-0301 as a monotherapy in patients with solid tumors and obtaining the preliminary pharmacokinetics (PK) and pharmacodynamics (PD) data. The Phase II clinical trial is planned to be conducted concurrently in both China and America, enrolling patients with hepatic cancer as its main subject population, with a view to exploring the safety, tolerability and efficacy when it is used in combination with standard-of-care (SOC) therapies such as PD-1 and Sorafenib.
About AKT-1
AKT inhibitors have been an extensively pursued target under development in recent years. Quite a number of drug varieties worldwide have been developed using this as a target, but are mainly small-molecule chemotherapeutics. Capivasertib (AZD5363) developed by AstraZeneca for the treatment of breast cancer and Ipatasertib developed by Roche for the treatment of prostate cancer are currently under Phase III clinical trial, already showing significant efficacy and huge market potential. AKT-1 is one of the three members of the serine/threonine protein kinase family. The AKT family has three members, i.e., AKT1/PKBα, AKT2/PKBβ, and AKT3/PKBγ. And these proteins can all be phosphorylated by phosphoinositide 3- kinase (PI3K).
AKT/PI3K functions as a key component to various signaling pathways involving the binding of membrane-bound ligands, such as receptor tyrosine kinase, G protein-coupled receptor, and integrin-linked kinase. Thus, these AKT proteins regulate a variety of cellular functions, including cell proliferation, survival, metabolism, and angiogenesis, in both normal and malignant cells. Following the phosphorylation of phosphatidylinositol-4,5- bisphosphate (PIP2) by PI3K, AKT protein is recruited onto the cell membrane by phosphatidylinositol-3,4,5- triphosphate (PIP3). Phosphorylation of threonine residue 308 and serine residue 473 is then fully activated and phosphorylation of other residues also occurs.
PI3K/AKT signaling pathway is crucially vital for the survival of tumor cells. Survival factor can inhibit apoptosis in a transcription-independent manner by activating AKT-1, which phosphorylates AKT-1 to inactivate the components necessary for the mechanism of apoptosis. The AKT protein is also involved in mammalian mTOR signaling pathways that control the assembly of eukaryotic translation initiation factor 4F(eIF4E) complexes; in addition to responding to extracellular signals from growth factors and cytokines by this pathway, in many cancers, mutation in this gene is associated with a variety of cancers and tissue overgrowth, including Proteus syndrome and Cowden syndrome, as well as breast cancer, colorectal cancer, and ovarian cancer.
