Next-IO™ Anti-SSTR2 × CD3 Therapeutic Bispecific Antibody Program

About This Program

This program aims to develop anti-SSTR2 × CD3 therapeutic Bispecific Antibody for immuno-oncology.

Rationale when developing the program:

• The somatostatin receptor (SSTR) is a transmembrane protein from the GPCR family. It is highly expressed in neuroendocrine tumors (NETs) and small cell lung cancer (SCLC).
• Treatment options for NETs include the use of somatostatin analogs and radionuclides; however, these therapies are not effective because of the short half-life, modest efficacy and toxicity.
• Treatments for SSTR2, such as monoclonal antibodies, ADCs, have shown potential antineoplastic activity.
• Emerging clinical data reveals that T cell engagers biotherapeutics can direct T cells to specific tumor cells, resulting in increased potency and tumor selectivity.

Given the above, we propose a novel combination - SSTR2 / CD3 therapeutic BiTE, which we believe will provide insights into next-generation.

Somatostatin receptor Type II (SSTR2)

SSTR2 belongs to the superfamily of G protein-coupled receptors (GPCRs), has seven transmembrane-spanning domains. Somatostatin receptors pose multiple functions in human health tissues, and they are also expressed in a variety of tumor types, including breast cancer, prostate cancer, pancreatic cancer, neuroendocrine cancer, and breast cancer. We focus on SSTR2 for the reason it is the most distinctive member of the SSTR family with the following features:

• SSTR2 has either direct and indirect effects on cell cycle, angiogenesis, apoptosis.
• SSTR2 inhibits calcium influx by downregulating adenylate cyclase signaling. It acts primarily using downstream mitogen-activated protein kinases (MAPK) and protein kinase B (AKT).

SSTR2 is an inhibitory receptor on cell growth, but it can also serve as an important promoting signal for tumor growth in an environment outside of its norm.

Fig.1 SSTR signaling pathway.

SSTR2 × CD3 in Cancer Studies

Here are some published data about SSTR2 × CD3 working as a potential target for cancer immunotherapy.

• SSTR2 BiTE(XmAb 18087) displays strong anti-tumor activity in lung cancer mice model.

(From Xenco Laboratories)

Ongoing Clinical Trials

• According to the report, only one anti-SSTR2 × CD3 therapeutic Bispecific Antibody (called XmAb 18087) is being evaluated in a clinical study. Multiple preclinical data are emerging, demonstrating the potential of SSTR2-based immunotherapy.
• With the support of sufficient evidence, we believe SSTR2 × CD3 Bispecific Antibody is a compelling combination for cancer immunotherapy. In an effort to optimally leverage SSTR2-mediated immune response, our next-generation SSTR2 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. 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 anti-SSTR2 × CD3 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 advance their programs with more chance to succeed. Look forward to cooperating with you in the near future.

References

• Palamiuc L., et al. SSTR2 brings new flavors to PI3K signaling: A role for glutamate in prostate cancer[J]. The Journal of Experimental Medicine, 2017: jem.20172050.
• Leconet W., et al. Anti-SSTR2/CD3 Bispecific Antibody Delivery and Antitumor Activity Using a Polymeric Depot Formulation[J]. Large Molecule Therapeutics, 2018 10.1158/1535-7.
• Friedrich M., et al. Regression of Human Prostate Cancer Xenografts in Mice by AMG 212/BAY2010112, a Novel SSTR2/CD3-Bispecific Bispecific Antibody Antibody Cross-Reactive with Non-Human Primate Antigens[J]. Molecular Cancer Therapeutics, 2012, 11(12): 2664-2673.
• Hernandez-Hoyos G., et al. MOR209/ES414, A Novel Bispecific Antibody Targeting SSTR2 For The Treatment of Metastatic Castration-Resistant Prostate Cancer[J]. Molecular Cancer Therapeutics, 2016: 1535-7163.MCT-15-0242.

For Research Use Only | Not For Clinical Use