About This Program

This program aims to develop LAG-3 × PD-L1 therapeutic bispecific antibody for colorectal cancer immunotherapy.

Rationale for our program:

• Blocking of the PD-1 / L1 axis has shown durable responses and prolonged overall survival in a variety of cancer types. However, there is still a significant unmet need for relapsed patients.
• Translational studies indicate that resistance to cancer immunotherapy can be mediated through additional immune checkpoints such as lymphocyte activation gene 3 (LAG-3).
• Current therapeutic antibody treatment interventions for LAG-3 have shown great promise for cancer immunotherapy.

Here, we propose a novel combination: LAG-3 × PD-L1 therapeutic bispecific antibody, which may synergistically improved anti-tumor response by specifically activating PD-L1 expressing cells in the tumor niche where LAG-3 is simultaneously expressed.

LAG-3 × PD-L1

Binding of PD-L1 to PD-1 on activated T cells inhibits expansion and survival of CD8-positive T cells, suppresses the immune system and leads to immune evasion. Blocking PD-1 abolishes T cell inhibition, activates antigen-specific T lymphocytes and enhances cytotoxic T cell-mediated tumor cell lysis, which may result in reduced tumor growth.

LAG-3 (CD223) is a cell surface molecule expressed on activated T cells, NK cells, B cells, and plasmacytoid dendritic cells, which play an important role in the function of these lymphocyte subsets.

Recent studies have shown that:

• A mLAG-3/PD-L1 bispecific antibody inhibits growth of mouse colorectal cancer models.

Fig.1 The antitumor activity of a mLAG-3/PD-L1 bispecific antibody in vivo. (Kraman, et al., 2020)

• A PD-1/LAG-3 bispecific antibody inhibited tumor growth in a dose-dependent manner.

Fig.2 Anti-tumor effect of a PD-1/LAG-3 bispecific antibody in the humanized mouse model. (Shi, et al., 2022)

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, only one biotechnology company (F-star Biotechnology Ltd) presented preclinical data on the LAG-3 × PD-L1 BsAb they were developing at the poster meeting of the American Association for Cancer Research (AACR) Annual Meeting in April 2019. Therefore, NO bispecific anti-LAG-3 × PD-L1 antibody is undergoing clinical trial.
• We believe that this dual targeting strategy will provide insights into the tumor immunotherapy, especially in the treatment of colorectal cancer. In an effort to optimally leverage LAG-3 × PD-L1-mediated immune response, our Next-IO™ LAG-3 × PD-L1 targeted antibody program attempts to explore the optimal combination strategy - that is, how to exert the best anti-tumor outcome while synergistically produce LAG-3 × PD-L1.

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 LAG-3 × PD-L1 therapeutic bispecific 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

• Ciardiello, D.; et al. Immunotherapy of colorectal cancer: Challenges for therapeutic efficacy. Cancer treatment reviews. 2019, 76: 22-32.
• Kraman, M. et al. FS118, a bispecific antibody targeting LAG-3 and PD-L1, enhances T-cell activation resulting in potent antitumor activity. Clinical cancer research. 2020, 26(13):3333-44.
• Shi, N. et al. PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy. Frontiers in Immunology. 2022, 13.

For Research Use Only | Not For Clinical Use