July 13, 2022 I Light Chain Bioscience – Novimmune SA (LCB), is an antibody discovery and development company located in Geneva, Switzerland. LCB announces that the first patient was dosed in the Phase 1, first-in-human trial of NI-1801 in patients with advanced, metastatic, or recurrent solid malignancies expressing mesothelin (MSLN). NI-1801 is a human IgG1 bispecific antibody based on LCB’s , targeting MSLN and CD47. “NI-1801 is the second κλ body entering clinical evaluation. This represents an important milestone in the development of LCB’s pipeline of bispecific antibodies featuring a truly native human IgG structure,” said Nicolas Fischer, Chief Executive Officer.

The surface protein CD47 is an innate immune checkpoint that allows tumor cells to escape immune surveillance, thus acting as a don’t eat me signal. LCB’s bispecific antibody approach simultaneously targets CD47 and a tumor-specific antigen, here MSLN, to selectively block CD47 on MSLN-expressing malignant cells. “As CD47 is ubiquitous, measures need to be taken to limit the immune response to tumor cells. NI-1801 represents a promising novel treatment approach for several cancers with high medical need. We are excited to further investigate this in our Phase 1 study,” said Dr. med. Anja Seckinger, Chief Medical Officer.

The LCB-1801-001 Phase 1 trial is a multi-center, open-label, dose escalation and expansion, first-in-human clinical trial that is expected to enroll approximately 40 patients with MSLN-expressing triple-negative breast, non-squamous non-small cell lung or ovarian cancer. The primary objectives of the dose escalation portion (Part A) are to assess the safety and tolerability of escalating doses of NI-1801, with the goal of establishing a maximum-tolerated dose (MTD) and non-tolerated toxic dose. The expansion part (Part B) will further evaluate the safety and efficacy of NI-1801 administered at or below the MTD in up to 20 additional patients to determine the recommended Phase 2 dose. Additional objectives include evaluation of preliminary efficacy, pharmacokinetics (PK), pharmacodynamics and potential predictive biomarkers.

NI-1801 induces antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cell-mediated cytotoxicity of a variety of MSLN-positive cancer cell lines in vitro. ADCP is negligible or unaffected by a CD47-sink effect mimicked by CD47-expressing red blood cells. NI-1801 does not induce in vitro hemagglutination or platelet aggregation.  In multiple preclinical (xenograft) models, NI-1801 inhibits tumor growth in mice. NI-1801 was well tolerated and demonstrated favorable pharmacokinetics in multiple non-human primate studies.

Additional information on the trial can be found at ClinicalTrials.gov (NCT05403554; https://clinicaltrials.gov/ct2/home ).

SOURCE: Light Chain Bioscience