SAN FRANCISCO & BASEL, Switzerland—Indapta Therapeutics, Inc., a biotechnology company focused on developing and commercializing a proprietary, first-in-class, off-the-shelf, non-engineered, allogeneic G-NK (FcRγ-deficient Natural Killer) cell therapy to treat multiple cancers, has announced a strategic partnership with Lonza Group AG.
“We believe our first-in-class, off-the-shelf, allogeneic G-NK cell therapy will drive the next critical phase in the evolution of cancer therapies following CAR T-cell therapies,” said Guy DiPierro, founder and chief executive officer of Indapta Therapeutics. “Current autologous CAR T-cell therapies have proven efficacy in various hematologic cancers but have been beset with serious clinical and manufacturing challenges. By providing an off-the-shelf solution with our G-NK cell therapy, we can eliminate the need for a patient-specific therapy. Additionally, because our investigational cell therapies are not engineered, they are likely to be more effective, less costly and have a simpler regulatory pathway.”
Indapta Therapeutics’ proprietary G-NK cells are a specific and potent subset of NK cells which have undergone an epigenetic change after coming into contact with cytomegalovirus (CMV)-infected cells. As a result, they lack the FcεRIγ signaling adapter and instead use a different adapter protein, which predisposes them to a far more activated state of antibody-dependent cell-mediated cytotoxicity in the presence of a monoclonal antibody. When the monoclonal antibody binds to the tumor target and to the Fc receptor on G-NK cells, it initiates the release of dramatically more immune-stimulating cytokines and cell-killing enzymes than conventional NK cells, causing the direct killing of tumor cells and driving tumor cell death.
G-NK cells have been demonstrated to be safe; in vivo studies have demonstrated that they do not cause graft-vs-host disease or cytokine release syndrome, which can occur with CAR-T cell therapies. Preclinical research conducted under NIH grants by scientists at the University of California, San Francisco has demonstrated the safety and efficacy of G-NK cells administered in combination with a therapeutic monoclonal antibody. When administered in combination with a monoclonal antibody, G-NK cells have been shown to be highly persistent (lasting four to nine months), to have the ability to preferentially bind to a therapeutic monoclonal antibody in the presence of a tumor cell, and to demonstrate superior ADCC function compared with conventional NK cells.
Clinical models of multiple myeloma and lymphoma demonstrated improved survival, a statistically significant decrease in tumor growth, and a statistically significant increase in the activity of the monoclonal antibody without causing graft-vs-host disease. Under a second Indapta NIH grant, researchers at Stanford University will be conducting in vivo studies in additional tumor models.
“Lonza, with its demonstrated expertise in cell therapy manufacturing, is the ideal strategic partner to help us advance our clinical program and scale the production of our G-NK cell therapy. We are currently completing Investigational New Drug-enabling studies and plan to submit an IND application in late 2020 and initiate a first-in-human Phase 1/2 study in early 2021,” noted Ronald Martell, co-founder and executive chairman of Indapta Therapeutics.
Under the terms of the agreement, Lonza will manufacture Indapta’s off-the-shelf, allogeneic G-NK cell therapy under current good manufacturing practices (cGMP) for use in clinical studies. The process development and manufacturing will take place in Lonza’s state-of-the-art cell and gene therapy manufacturing facility in Houston, Tx.
“Indapta’s world-class team of NK cell scientists and clinicians and cell therapy experts has created an innovative off-the-shelf immuno-oncology therapy based on a subset of cancer-killing NK cells that could make a truly meaningful impact in the treatment of hematologic malignancies and solid tumors,” stated Scott Waldman, chief strategy officer at Lonza.
Indapta’s off-the-shelf G-NK cell therapy is differentiated from an autologous therapy in that it isn’t necessary to collect cells from individual patients and produce a unique therapy for every patient. It is derived from cells from healthy volunteers, which are highly functional and persistent. Indapta’s process for producing G-NK cell therapy for use as an immunotherapy involves taking blood from CMV-seropositive donors, identifying and sorting G-NK cells from these samples, and expanding G-NKs cells using the company’s proprietary, patented expansion method, which preferentially expands and activates GNK cells. Indapta has also developed a proprietary method for freezing and storing the G-NK cells in a GMP master cell bank for use as off-the-shelf allogeneic outpatient immunotherapy in cancer patients.
Developing off-the-shelf G-NK cells may sidestep some of the clinical and financial challenges presented by other, more customized and engineered immuno-oncology approaches, which involve time-consuming and costly manufacturing processes and often can only be delivered in specialized centers. The manufacturing COGS for Indapta’s program will be relatively inexpensive, compared to CAR-T or engineered NK cell therapies. And the regulatory approval process for Indapta’s program may be more straightforward than that for autologous CAR-T cell therapy or engineered NK cells, because it doesn’t involve complicated cell engineering.
Alberto Santagostino, senior vice president, head of Cell & Gene Technologies at Lonza, added that “With our long-standing experience in cell therapy manufacturing, we are committed to providing Indapta with the expertise, resources and services it needs for cGMP manufacturing to advance its promising program into the clinic and beyond.”
