I-Mab Announces Multiple Presentations at the 2022 American Association for Cancer Research (AACR) Annual Meeting

I-Mab (the “Company”) (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, today announced that two poster presentations featuring translational research data of enoblituzumab (also known as TJ271) and preclinical data of TJ-C64B will be presented at the American Association for Cancer Research (AACR) 2022 Annual Meeting, to be held April 8-13, 2022.

“We continue to make significant progress in advancing our innovative pipeline to generate the next wave of novel cancer therapeutics for patients around the world,” said Dr. Andrew Zhu, President of I-Mab. “The translational research data of enoblituzumab provide compelling rationale to further investigate combination therapy for increased clinical efficacy against multiple cancer types. In addition, the preclinical data of TJ-C64B provide the underlying mechanism of action for further clinical development of this novel bispecific antibody.”

Enoblituzumab is a highly differentiated humanized monoclonal antibody directed against the immune regulator B7-H3, which has been associated with poor prognosis and is widely expressed in multiple cancers. Enoblituzumab mediates the antibody-dependent killing of cancer cells and has demonstrated strong anti-tumor activity in preclinical studies. Currently, I-Mab is conducting a phase 2 trial in China for enoblituzumab in combination with pembrolizumab (Keytruda®) in patients with solid tumors, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and other selected cancers.

TJ-C64B is the third bispecific antibody with a conditional T cell engager based on 4-1BB-activation platform. It binds simultaneously to Claudin 6 (CLDN6)-expressing cancer cells and the costimulatory molecule 4-1BB. CLDN6 is a tight junction transmembrane protein hardly detected in adult normal tissues, but aberrantly expressed in a variety of tumors, including ovarian cancer, testicular cancer, hepatocellular and lung adenocarcinoma. TJ-C64B is designed to conditionally activate T cells through 4-1BB stimulation upon CLDN6 engagement, positioning it as a potential novel immunotherapy for ovarian cancer and other CLDN6 positive tumors.

Details for the 2022 AACR presentations are as follows:

Summary:

• The function of B7-H3 and enoblituzumab in regulating immune response was investigated in human PBMCs using the Nanostring nCounter platform for gene expression and CyTOF mass cytometry for immunophenotyping.
• Data confirmed the immunosuppressive function of B7-H3 and demonstrated the immunoregulatory function of enoblituzumab as evidenced by the activation of cytolytic T cell and NK cells, reinvigoration of exhausted cells, and suppression of M2-like myeloid cells.
• Enoblituzumab exhibited tumor killing activity against ES-2, a B7-H3-expressing ovarian cancer cell line in vitro. Consistent with the enoblituzumab-associated increased 4-1BB expression in T and NK cells, activation of 4-1BB by urelumab, a 4-1BB agonist, further enhanced enoblituzumab-mediated tumor killing activity.
• These findings provide rationale for combination therapy with blockade of B7-H3 by enoblituzumab with other immunotherapies to achieve increased clinical efficacy against multiple cancer types.

Summary:

• Data have confirmed the novel CLDN6-targeted 4-1BB bispecific antibody TJ-C64B to induce potent 4-1BB stimulation and anti-tumor activity in a CLDN6-dependent manner while minimizing the risk of liver toxicity.
• In humanized 4-1BB syngeneic mouse model, TJ-C64B exhibited significant tumor growth inhibition, associated with elevation in tumor infiltrating CD45 and CD8 cells as well as CD8/Treg ratio.
• From the safety perspective, there were no significant changes in liver enzymes following repeated TJ-C64B administration, suggesting a minimal risk for liver toxicity commonly induced by other 4-1BB agonist antibodies.
• Taken together, these data support further development of TJ-C64B towards clinical development subsequently.

Source: I-Mab