About This Program

This program aims to develop anti- P-cadherin (CDH3) × CD3 bispecific DART protein for immuno-oncology.

Rationale when developing the program:

• P-cadherin is a classical cell adhesion molecule that expressed in many malignancies.
• P-cadherin is working as a tumor suppressor gene in malignant melanoma to inhibit tumor invasion and metastasis.
• However, in some tumor models like breast cancer, ovarian cancer, prostate cancer, endometrial cancer, skin cancer, stomach cancer, pancreatic cancer, and colon tumors, P-cadherin has tumor promotion effect.
• Dual-affinity re-targeting (DART) bispecific molecule specifically recognize two distinct epitopes, simultaneously, on the surface of T cells and tumor cells, which can maximize the activation of T cell immune responses.

Given the above, we propose the novel combination - CDH3 / CD3 bispecific DART protein, which we believe will provide insights to next-generation cancer treatment.

CDH3

CDH3 (P-cadherin), also known as placental cadherin, is a class of Ca²⁺-dependent membrane glycoproteins. Cadherin has a cell type-specific expression pattern, meaning it can be distinguished by its tissue distribution. For example, CDH1 / E-cadherin (epithelial cells), CDH2 / N-cadherin (neuron), CDH3 / P-cadherin (placenta) and CDH4 / R- Cadherin (retina). For this reason, the behavior of P-cadherin in the malignant environment is heavily influenced by its cellular environment.

Fig.1 P-cadherin signaling pathways in the malignant setting. (Vieira, 2015)

CDH3 × CD3 in Cancer Studies

Here are some published data about CDH3 × CD3 working as a potential target for cancer immunotherapy.

• P-cadherin / anti-CD3 bispecific DART (PF-06671008) shows great anti-tumor efficacy in colorectal tumor.

(Root, 2016)

Indication

Tumor-promoting or tumor-suppressing effects associated with P-cadherin expression based on their cell and tissue background.

Ongoing Clinical Trials

• According to the report, only one anti-CDH3 × CD3 bispecific DART protein (called PF-06671008) has shown robust preclinical anti-tumor activity. The detail is still under investigation in the clinical study. Cumulative preclinical data is emerging to explain its important role in cancer progression.
• With all the supporting data, we believe CDH3 × CD3 DART is a compelling combination to research in cancer immunotherapy. In an effort to optimally leverage CDH3-mediated immune response, our next generation of CDH3 targeting treatment attempts to explore combination therapy trials by involving other immunomodulatory agents.

Program Planning and Management

Creative Biolabs has extensive knowledge of end-to-end program development. Our Next-IO™ immunotherapeutic team already establish a novel Dual-Affinity Re-Targeting (DART) Platform. It allows us to cooperate with our partners more efficiently. For each project, we are promised to provide our client with a complete plan within 1.5 years before entering the IND phase.

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop anti-CDH3 × CD3 bispecific DART protein 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 to advance their programs with more chance to succeed. Look forward to cooperating with you in the near future.

References

• Vieira, A.F.; Paredes, J. P-cadherin and the journey to cancer metastasis. Molecular cancer. 2015, 14(1): 1-12.
• Root, A.R.; et al. Development of PF-06671008, a highly potent anti-P-cadherin/anti-CD3 bispecific DART molecule with extended half-life for the treatment of cancer. Antibodies. 2016, 5(1): 6.

For Research Use Only | Not For Clinical Use