Light Chain Bioscience doses first patients with solid cancers

The brand Light Chain Bioscience (LCB) brings to life the research and development of novel multi-specific antibodies that rely on their light chain for their function. A distinctive feature of these multispecific antibodies is their native human structure, making them well tolerated and easy to develop.

The company's second candidate NI-1801 is a human IgG1 bispecific antibody targeting MSLN and CD47. 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 tumour-specific antigen, in this case, MSLN, to selectively block CD47 on MSLN-expressing malignant cells.

NI-1801 induces antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cell-mediated cytotoxicity of various 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 favourable pharmacokinetics in multiple non-human primate studies. h MSLN-expressing triple-negative breast, non-squamous non-small cell lung or ovarian cancer.

The ongoing LCB-1801-001 Phase 1 clinical trial is a multi-center, open-label, dose escalation and expansion, first-in-human clinical trial that is expected to enrol 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, intending to establish 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. Other objectives include evaluation of preliminary efficacy, pharmacokinetics (PK), pharmacodynamics and potential predictive biomarkers.

“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.

(Press release / RAN)