Indapta Therapeutics is a clinical-stage biotechnology company focused on developing new treatments for cancer. The company’s work centers on a specialized type of immunotherapy that uses certain immune cells to combat diseases. This approach aims to leverage the body’s natural defenses to fight various forms of cancer.
The G-NK Cell Platform
Natural Killer (NK) cells are a type of white blood cell that plays a significant role in the body’s innate immune system. These cells constantly patrol the bloodstream and tissues, identifying and destroying unhealthy cells, such as those infected with viruses or cancerous cells, without needing prior exposure to specific threats. NK cells are known for their rapid response, acting as a first line of defense and releasing signaling proteins called cytokines to coordinate other immune responses.
Indapta Therapeutics has developed a technology centered on a naturally occurring subset of NK cells known as G-NK cells. These cells are distinct from conventional NK cells due to specific epigenetic changes, often linked to prior exposure to cytomegalovirus (CMV), which result in them being deficient in the FceR1γ protein. This characteristic contributes to their enhanced capabilities.
G-NK cells exhibit several advantages, including increased secretion of immune-activating proteins, higher levels of cell-killing enzymes, and a more favorable metabolic profile that supports their persistence in the body. They also demonstrate superior antibody-dependent cell-mediated cytotoxicity (ADCC). Indapta’s platform utilizes an “allogeneic” or “off-the-shelf” approach, meaning these G-NK cells are sourced from healthy donors rather than being engineered from each individual patient. This allows for large-scale manufacturing and broad accessibility, providing a cryopreserved product with reduced variability for immediate use in patients.
Mechanism of Action
The effectiveness of Indapta’s G-NK cells in combating cancer primarily stems from antibody-dependent cell-mediated cytotoxicity (ADCC). This mechanism involves the targeting and destruction of cancer cells that have been marked by therapeutic antibodies. Initially, specific therapeutic antibodies, designed to recognize unique markers on cancer cells, bind to these malignant cells.
Once these antibodies attach, they act like a “flare,” signaling the presence of a cancerous cell to the immune system. Indapta’s G-NK cells recognize these marked cells through a specific receptor on their surface, called FcγRIIIA, which binds to the tail end of the therapeutic antibodies. This binding activates the G-NK cell’s destructive capabilities.
Upon activation, the G-NK cell releases specialized cytotoxic granules directly at the marked cancer cell. These granules contain proteins, such as perforin and granzymes, that puncture the cancer cell’s membrane and induce programmed cell death, eliminating the threat. This targeted approach allows G-NK cells to efficiently destroy cancer cells that have been identified by therapeutic antibodies, making them a component in combination therapies.
Targeted Diseases and Clinical Development
Indapta Therapeutics is focusing its G-NK cell therapy, IDP-023, on treating specific blood cancers, including multiple myeloma and B-cell lymphomas, such as non-Hodgkin’s lymphoma. The company has advanced IDP-023 into Phase 1 clinical trials to evaluate its potential.
The primary objectives of this initial trial phase are to assess the safety of IDP-023, determine the optimal dosage, and look for early indicators of its effectiveness in patients. Patients in the trial initially receive IDP-023 either alone or in combination with interleukin-2 (IL-2), a protein that helps stimulate immune cell growth. Subsequent cohorts of patients are planned to receive IDP-023 alongside established monoclonal antibodies like rituximab for non-Hodgkin’s lymphoma and daratumumab or Sarclisa for multiple myeloma, to explore potential synergistic effects.
Preliminary findings from the safety run-in portion of the Phase 1 trial have been positive, showing that IDP-023 was well-tolerated, with no dose-limiting toxicities observed. The most common side effects reported were reductions in blood cell counts, associated with the conditioning chemotherapy patients receive. In patients with relapsed or refractory multiple myeloma, early data indicated a mean maximum reduction of 73% in serum M-protein or light chain levels, with some patients achieving reductions of 84% or greater, even when IDP-023 was administered as a monotherapy at the lowest dose without a targeting antibody.
The U.S. Food and Drug Administration (FDA) granted IDP-023 Fast Track designation for both non-Hodgkin’s lymphoma and multiple myeloma in February 2024, to expedite its development and review. Indapta has also collaborated with Sanofi to investigate the combined efficacy and safety of IDP-023 with Sanofi’s monoclonal antibody, Sarclisa, in multiple myeloma patients. Furthermore, Indapta secured $22.5 million in funding in December 2024 to accelerate the clinical development of IDP-023, including its exploration for autoimmune diseases like multiple sclerosis.