Indapta Therapeutics Shares Data on NK Cell Therapy at Immunotherapy Meeting

15 November 2024
Indapta Therapeutics, Inc., a biotechnology firm still in the clinical stage, has recently presented significant findings at the Society for Immunotherapy of Cancer meeting in Houston, Texas. The company, based in Houston and Seattle, focuses on developing advanced cell therapies to treat cancer and autoimmune diseases. The data presented included both clinical and preclinical results that highlight the potential of their proprietary g-NK cell therapies.

One of the clinical presentations, titled "Activity of IDP-023 Allogeneic g-NK Cells Without Antibody Targeting in First-in-Human Phase 1/2 Study in Patients with Advanced Multiple Myeloma or Non-Hodgkin Lymphoma" (Abstract #1483), provided insights from the safety run-in of a Phase 1 clinical trial. In this study, patients were administered one to three doses of IDP-023, with or without interleukin-2 (IL-2). The treatment was generally well-tolerated, with no dose-limiting toxicities observed. The most common side effects were cytopenias related to the conditioning chemotherapy. Objective responses were noted in five out of nine patients treated. Specifically, among the five patients treated with IDP-023 and IL-2, four exhibited an objective response, which included one very good partial response, two partial responses, and one minimal response. Additionally, in eight patients with relapsed/refractory myeloma, the average maximum decrease in serum M-protein or light chain was 73%, with three patients experiencing a reduction of 84% or greater.

Dr. Robert Sikorski, the Chief Medical Officer of Indapta, expressed optimism about the clinical activity observed, even at the lowest cell dose and without a targeting antibody. He emphasized that future studies will involve multiple myeloma patients receiving IDP-023 alongside a CD38-targeting monoclonal antibody and non-Hodgkin’s lymphoma patients receiving IDP-023 with a CD20-targeting monoclonal antibody. Preclinical models have shown that the inclusion of a targeting monoclonal antibody significantly enhances efficacy.

In another presentation (Abstract #365), titled "Artificial Intelligence-Based Dynamic Single-Cell Imaging Reveals Enhanced Migration and Immune Synapse Formation by IDP-023, an Allogeneic g-NK Cell Product," researchers showcased that the enhanced antibody-dependent cellular cytotoxicity (ADCC) of g-NK cells is partly due to faster cell migration and a higher frequency of synapse formation with target cells compared to conventional NK cells. This increased migration is associated with higher expression of CD2 (LFA-2), a protein involved in leukocyte adhesion, suggesting it plays a role in the elevated migration and cytotoxic functions of IDP-023.

Further findings were presented in Abstract #1285, titled "IDP-023 has superior single agent and antibody-dependent cytotoxicity against solid tumor cell lines compared to conventional NK cells," where g-NK cells showed potent activity against HER2 and EGFR positive cell lines, both with and without tumor-targeting antibodies. Analysis of public datasets of patients treated with trastuzumab, a monoclonal antibody for HER2-positive cancers, revealed that patients with higher levels of naturally occurring g-NK cells had better pathological complete response rates and improved distant disease-free survival.

Stefanie Mandl-Cashman, Chief Scientific Officer of Indapta Therapeutics, highlighted the differentiated mechanism of g-NK cells and their potential efficacy in solid tumors. She also pointed out that clinical outcomes in patients treated with trastuzumab underscore the strong antibody-dependent cellular toxicity of g-NK cells.

Indapta's proprietary cell therapy platform utilizes a unique subset of naturally occurring NK cells called "g minus" NK cells or "g-NK" cells, which arise from epigenetic changes due to cytomegalovirus (CMV) exposure. The process to generate IDP-023 involves expanding g-NK cells from healthy donors, ensuring low variability between donors. IDP-023 showcases several differentiated mechanisms for targeting and killing cells without genetic engineering, including robust ADCC, targeting HLA-E expressing cells via the NKG2C receptor, and inherent anti-viral properties. Preclinical studies have demonstrated that IDP-023, especially when combined with cancer-targeting monoclonal antibodies, exhibits potent and durable antitumor activity superior to conventional NK cells.

Indapta Therapeutics remains committed to developing and commercializing its diverse pipeline of cell therapies to address unmet medical needs in patients with blood and solid-tumor cancers and autoimmune diseases. The company’s unique g-NK cell platform aims to deliver highly effective, accessible, and scalable cell therapies.

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