Next-IO™ Anti-FGL2 Monoclonal Antibody Program

About This Program

This program is to develop therapeutic monoclonal antibody against the novel target – FGL2 (Fibrinogen-like Protein 2). The highlight feature of this program is that the potential therapeutic target, FGL2, was identified as a CNS tumor suppressor.

Fibrinogen-like Protein 2 (FGL2)

FGL2, a member of the fibrinogen superfamily, can be expressed either as a membrane-associated protein with coagulation activity, or in a secreted form with unique immune suppressive functions. It is identified not only as a disease marker, but also the therapeutic target. Previous studies have shown that FGL2 promotes tumorigenesis and metastasis in mice models, and can function as an immune suppressive modulator in CNS tumor-glioblastoma multiform (GMB).

Here are highlight features of FGL2.

• FGL2 is highly expressed in primary glioblastoma cells and associated with poor prognosis in glioma patients;
• FGL2 knockout in-tumor cells completely impairs GBM progression in immune competent mice models;
• FGL2 promotes CNS tumor progression by suppressing CD103⁺ dendritic cell differentiation;
• Low level of FGL2 expression with concurrent high granulocyte-macrophage colony-stimulating factor (GM-CSF) expression are associated with longer survival rate.

All of these points provide a rationale for therapeutic inhibition role of FGL2 in CNS tumors. Using this relation, our program is to develop a therapeutic antibody that inhibits FGL2, thereby inhibiting tumor progression in CNS.

Published Data

• FGL2 mediates immunosuppression in tumor microenvironment.

• FGL2 knockout in tumor cells inhibits tumor progression.

Fig.2 FGL2 knockout in tumor cells inhibits tumor progression.¹

• Low expression level of FGL2 and high expression level of GM-CSF are associated with better survival rate in GBM patients.

Fig.3 The expression level of FGL2 and GM-CSF in GBM patients.¹

• Anti-FGL2 antibody induces changes on immunosuppression phenotype, and promotes survival in tumor-bearing mice.

Glioblastoma Multiform (GBM)

GBM is one of the most deadly cancers because of its aggressive growth in cancer cells, poor immunogenicity and invasion of surrounding tissues. It is formed by the most malignant gliomas among other astrocytic tumors, and according to WHO, it is graded as IV. 70% - 80% . This means that most patients with GBM only survive about 3-6 months, while only 10% of the patients can survive more than 1 year.

• The survival rate of GBM patients is severe.

Previous studies have shown that FGL2 knockout in tumor cells can induce active adaptive immune responses, which result in tumor suppression in various brain tumor model systems - GL261, DBT, and LLC. (see published data)

Clinical Trials under Progress

• There are currently no clinical trials investigating the FGL2 target for the treatment of GBM. Only 3 studies have been selected, while their focus are on chronic hepatitis C infection, and liver transplantation. Our program will be a pioneer in this field.

• As a novel target, FGL2 will be a shining star and propose certain marketing prospect in the future. The therapeutic anti-FGL2 discovery will focus on monoclonal anti-FGL2 antibody to block the GBM tumor progression function.

Program Plan

We have extensive experience in performing comprehensive program development and problem-solving. We are committed to reporting progress periodically to our partners and delivering the final complete program to our partners within about 1.5 year. The exact timetable will be determined case by case. Here is only a very simple draft timeline for quick browsing.

Fig.4 The timeline of Next-IO™ programs.

Collaboration

Creative Biolabs is looking for potential partners to gain collaboration opportunities to develop anti-FGL2 antibody program. We offer global strategies and trusted partnerships with partners all over the world. Guided by our advanced business strategies, we are dedicated to making drug discovery and development programs the most effective through a collection of efforts. Our rich experience and streamlined management enable us to successfully develop the therapeutic candidate in immuno-oncology field. With our skills and expertise, We believe our Next-IOTM programs can advance your research/project.

If you are interested in our programs (not limited to GBM and FGL2, but also other indications and targets you are interested), please feel free to contact us for more details.

References

• Yan, Jun.; et al. "FGL2 promotes tumor progression in the CNS by suppressing CD103+ dendritic cell differentiation." Nature communications. (2019) 10,1 448.