Next-IO™ Anti-YTHDF1 Therapeutic Monoclonal Antibody Program

About This Program

This program aims to develop anti-YTHDF1 therapeutic monoclonal antibody for colorectal cancer immunotherapy.

Rationale for our program:

• Colorectal cancer (CRC) is one of the most common malignancies in humans and ranks second in cancer mortality. The 5-year relative survival rate of patients was only 64.9%.
• Cancer stem cells (CSC) are thought to be closely related to the occurrence and development of tumors. Recently, a large number of studies have shown that CSCs play an important role in CRC. Therefore, targeting genes that regulate stem cells in CRC may be a potential therapeutic approach to CRC.
• YTH N6-methyladenosine (m6A) RNA binding protein 1 (YTHDF1) is a core factor regulating RNA methylation modification. It has been reported that YTHDF1 is significantly associated with CRC proliferation and chemosensitivity in CRC.

Given the above, YTHDF1 is a potential candidate for the treatment of CRC.

YTHDF1

YTHDF1 is a member of the YTH domain family, which includes YTHDF1, 2 and 3, and YTHDC1 and 2. In the cytosol, YTHDF1 acts as a "reader" of the m6A modified mRNA in concert with the initiation factor to facilitate translation initiation. Multiple research has shown:

• RNA m6A modification regulates the anti-tumor immune response via YTHDF1.
• The specific deletion of YTHDF1 in classical dendritic cells (DC) triggers the ability of CD8⁺ T cell immune responses and inhibits tumor growth.
• In YTHDF1-deficient mice, the administration of PD-L1 antibody showed an enhanced anti-tumor effect, resulting in complete tumor regression.

Fig.1 The role of m6A RNA methylation in cancer. (Sun, 2019)

Supporting Data

• YTHDF1 mRNA is expressed at a higher level in CRC tissue (T) than in adjacent normal tissue (N).



• The YTHDF1 inhibitor GB1107 inhibits the growth and metastasis of lung adenocarcinoma in vivo.

(Bai, 2019)

These data support the rationale for the development of the first-in-class human anti-YTHDF1 with an improved therapeutic index for the treatment of CRC.

Colorectal Cancer

• CRC is one of the most common malignancies in humans. It is estimated that nearly 881,000 new deaths occurred in 2018, ranking second in cancer mortality.
• The global CRC drug market size estimate for 2018 is $994 million, and the compound annual growth rate is expected to be close to 3% between 2019 and 2023.
• The global immunotherapy market size for CRC in 2018 is estimated at 5 billion.

Ongoing Clinical Trials

• Currently, NO anti- YTHDF1 therapeutic monoclonal antibodies have been evaluated in clinical trials.
• We believe that this novel targeting strategy will provide insights into the tumor immunotherapy, especially in the treatment of NSCLC cancer. In an effort to optimally leverage YTHDF1-mediated immune response, our next-IO™ YTHDF1 targeted antibody program attempts to explore the optimal combination therapy trials by involving other immunomodulatory agents, particularly immune checkpoints.

Program Plan

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

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop YTHDF1 therapeutic monoclonal antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and achieve a meaningful partnership together. For any partners interested 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 further their programs with more chances to succeed. Look forward to cooperating with you in the near future.

References

• Sun, T.; et al. The role of m6A RNA methylation in cancer. Biomedicine & Pharmacotherapy. 2019, 112: 108613.
• Bai Y.; et al. YTHDF1 regulates tumorigenicity and cancer stem cell-like activity in human colorectal carcinoma. Frontiers in oncology. 2019, 9: 332.

For Research Use Only | Not For Clinical Use