Next-IO™ Anti- FRα Antibody-Drug Conjugate Program

About This Program

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

The folate receptor (FR) is a recognized target to study due to its overexpression on various 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. During tumorigenesis, the cell structure changes completely, resulting in a weak interaction with endothelial cells. Because of this, FRα cannot localize on the polarized cell and will randomly distribute across the entire cell surface, allowing FRα to contact the drug conjugate in the blood circulation. This feature makes FR a good choice for developing ADCs.

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 treatment 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.

Potential treatment approaches targeting FRα. (Anthony, et al., 2016) Fig.1 Potential treatment approaches targeting FRα.3

FRα in Cancer Studies

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

Indication

FRα is overexpression in tumors such as ovarian, breast and lung cancers, low and restricted distribution in normal tissues. We intend to develop various program (not limited to one specific type), in which FRα is highly expressed.

FOLR1 gene expression data showing the levels of mRNA expression for the FOLR1 gene in various cancer cell types. (Anthony, et al., 2016) Fig.3 FOLR1 gene expression data showing the levels of mRNA expression for the FOLR1 gene in various cancer cell types.3

Ongoing Clinical Trials

Program Planning and Management

We have extensive knowledge in developing. end-to-end program. For each program, we are committed to delivering the final complete program to our clients within 1.5 years before entering the IND stage.

Project pipeline management of therapeutic monoclonal antibody. (Creative Biolabs Original)Fig.4 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 ADC 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

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