Next-IO™ Anti- FRα Therapeutic Monoclonal Antibody Program

About This Program

This program aims to develop anti-folate receptor alpha (FRα) therapeutic monoclonal antibody for immuno-oncology.

The folate receptor (FR) is a recognized target to study due to its overexpression on various of tumors. Folate receptor alpha (FRα) and its ligand folate are central mediators for cell growth regulation, single carbon metabolism, and DNA biosynthesis, repair and methylation. Studies have shown that FRα is highly expressed in tumor tissues and can promote tumor growth and metastasis, highlighting a clear rationale for FP-based cancer immunotherapy.

FRα

Folate receptors (FRs) are 35-40 kDa glycoproteins that have three different isotypes: FRα, FRβ, and FRγ. Alpha and beta variants are secured on the cell membrane by glycosylphosphatidylinositol (GPI) anchoring, whereas FRγ is found only in hematopoietic cells and lacks GPI components, making it relatively easy to dissolve.

The FRα subtype has the most potential to be studied in cancer treatments because:

Among all FR isoforms, FRα is the most widely expressed in a large number of epithelial-derived cancers cells, including breast, lung, kidney and ovarian cancers.
FRα is overexpressed in cancer tumors but reamains low or restricted distribution in normal tissues.
FRα is known to promote tumor progression and correlates with cancer prognosis.
FRs are flexible to use in various treatment approaches such as CAR-T, ADC, and other nanoparticals.

Fig.1 Approaches for targeting FRs as therapies for cancer and inflammatory diseases.¹

FRα in Cancer Studies

Here are some published data about FRΑ working as a potential target for cancer immunotherapy.

Fig.2 Growth curves and weight measurements of resected WHIM02 PDTX tumors of the partly-immuno-humanized mice treated with 10 mg/kg MOv18-IgG1.²

Anti- FRα antibody (MOv18-IgG1) treatment reduces tumor volume in CAL51 tumors.

Fig.3 Basal-like/TNBC is associated with upregulated FRα gene expression, (a) Relationship between FOLR1 and FOLH1 in the KCL dataset. (b) Association of FRα expression (upper quartile) with ten-year overall survival.²

FRα gene expression is unregulated in triple-negative breast cancers (TNBCs).

Fig.4 FOLR1 gene expression levels in cancer models.³

Indication

FRα is overexpressed in tumors such as ovarian, breast and lung cancers, but low and restricted distributed in normal tissues. We are intended to develop various programs (not limited to one specific type), in which FRα is highly expressed.

Clinical Trials under Progress

At present, there are two anti-FRA therapeutic monoclonal antibodies, Farletuzumab and MOv18 IgG, are being evaluated in clinical trials. An increasing number of FRA antibodies are getting confirmed on its role in immune responses and early clinical trial data shows great promise. However, the efficacy, safety, and combination strategies have not yet to be specified.
In this case, FRΑ is still a compelling target for cancer immunotherapy. Our program will be the pioneer in the field.

Program Planning and Management

Creative Biolabs has extensive knowledge in developing end-to-end therapeutic antibody programs. For each program, we are committed to delivering the final complete program to our clients within 1.5 years before entering the IND stage.

Fig.5 Project pipeline management of therapeutic monoclonal antibody.

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop anti-FRΑ therapeutic monoclonal antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and achieve a meaningful partnership. For any partners interest in our Next-IO™ programs, Creative Biolabs welcomes collaboration.

Here are two ways for your choice, and please contact us for more details.

1) Collaborate with us and co-develop the programs from the discovery phase to IND enabling. Costs will be shared.
2) Become a licensed candidate for our programs.

With our quality control protocol and knowledge of global regulatory requirements, we can help our partners advance their programs with more chance to succeed. Look forward to cooperating with you in the near future.

References

Frigerio, B.; et al. Folate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases. Journal of Experimental & Clinical Cancer Research, 2019, 38(1).
Anthony, C.; et al. Anti-Folate Receptor alpha-directed Antibody Therapies Restrict the Growth of Triple Negative Breast Cancer. Clinical cancer research, 2018, 24(20):5098-5111.
Anthony, C.; et al. Targeting folate receptor alpha for cancer treatment. Oncotarget, 2016, 7(32).

For Research Use Only | Not For Clinical Use