About This Program

This program aims to develop c-MET x CTLA-4 therapeutic bispecific antibody for non-small-cell lung cancer immunotherapy.

Rationale for our program:

• Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide, and the development of clinically effective therapies has had limited success. It highlights the urgent need to advance the development of novel therapies.
• Bispecific antibody (BsAb) is a novel antibody that mediates specific killing by targeting two different antigens and selectively redirecting effector cells to target cells. This enhanced synergistic anti-tumor effect highlights a promising approach to immunotherapy.
• The mesenchymal-epithelial transition factor (c-MET) affects cancer cell morphogenesis, angiogenesis and in vitro cell protection, and is highly expressed in a variety of solid tumors including NSCLC.
• Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an important negative regulator of T cell responses leading to T cell failure. Blocking CTLA-4 may, therefore, provide promising immunotherapy for anti-tumor T cell immunity.

c-MET x CTLA-4

c-MET is a high-affinity receptor that binds to hepatocyte growth factor (HGF). Up-regulation of c-MET expression contributes to the promotion of tumor progression, invasion, metastasis and angiogenesis in different types of solid tumors, including NSCLC. In addition, studies have shown that activation of the HGF/c-MET pathway in solid tumors can stimulate lymphangiogenesis, leading to lymph node metastasis. Currently, c-MET inhibitors have entered Phase II clinical trials for the treatment of patients with hepatocellular carcinoma. However, these c-MET inhibitors are closely related to potential side effects. Therefore, it is necessary to develop new types of therapies.

CTLA-4 is a negative regulator of important T cell responses leading to T cell failure. T cell dysfunction occurs in many types of cancer, so blocking CTLA-4 may provide promising therapies for anti-tumor T cell immunity. Currently, there is no mAb blocking CTLA-4 in NSCLC.

Published Data

The following data support the rationale for the development of c-MET x CTLA-4 BiAbs with an improved therapeutic index for the treatment of NSCLC.

• BsAb-5 (anti- c-MET x CTLA-4) contributes to the anti-tumor effect in human NSCLC xenograft mouse model.

(Li, 2019)

NSCLC

• The global NSCLC drug market is expected to post a CAGR of more than 13% during the period 2019-2023.

• The global NSCLC drug market is expected to increase by more than $25 billion between 2018 and 2026.

• The global non-small cell lung cancer therapeutics market share, by therapy.

Clinical efforts of target therapy to date have failed to demonstrate widespread efficacy and are associated with severe toxicity. Therefore, immunotherapy will represent the next generation NSCLC treatment.

Ongoing Clinical Trials

• Currently, only One anti-c-MET x CTLA-4 BiAb (namedJNJ-61186372) is being investigated in phase I against NSCLC.

NCT ID	Status	Conditions	Lead Sponsor	Phase	Update Time
NCT04077463	Recruiting	Carcinoma, Non-Small-Cell Lung	Janssen Pharmaceutical K.K.	Phase 1	September 17, 2019

We believe that this dual targeting strategy will provide insights into the tumor immunotherapy, especially in the treatment of NSCLC. In an effort to optimally leverage C-MET x CTLA-4-mediated immune response, our next-IO™ C-MET x CTLA-4 targeted antibody program attempts to explore the optimal combination strategy by involving other immunomodulatory agents.

Program Plan

Creative Biolabs has 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 c-MET x CTLA-4 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.

Reference

• Li, J.; et al. A novel bispecific c-MET/CTLA-4 antibody targetting lung cancer stem cell-like cells with therapeutic potential in human non-small-cell lung cancer. Bioscience reports. 2019, 39(5).

For Research Use Only | Not For Clinical Use