Ingenium Therapeutics announced today that the U.S. Food and Drug Administration (FDA) has provided positive feedback allowing the company to initiate a Phase 2 clinical trial of its natural killer (NK) cell therapy, Gengleucel, without conducting a preceding Phase 1 study in the United States. This regulatory milestone follows a Pre-Investigational New Drug (Pre-IND) meeting and represents a significant advancement in the development pathway for patients with measurable residual disease-positive (MRD+) acute myeloid leukemia (AML).
The South Korea-based biotechnology company has already conducted extensive clinical research in its home country, enrolling more than 140 AML patients across multiple investigator-initiated trials. This includes a Phase 2 randomized clinical trial with long-term overall survival follow-up data. The robust safety and efficacy profile demonstrated in these studies provided the foundation for the FDA's decision to allow direct entry into Phase 2 testing in the U.S.
"We are thrilled with the FDA's guidance, which reflects the rigor of our clinical research and the significant therapeutic potential of Gengleucel, especially in targeting minimal residual disease," said Kevin Koh, CEO of Ingenium Therapeutics. "Launching our U.S. Phase 2 trial at premier cancer centers marks a major milestone in our mission to deliver novel immunotherapies to AML patients with MRD."
Novel Approach to Treating Residual Disease in AML
The planned multicenter study will be conducted at leading cancer centers across the United States, including a world-renowned institution in Texas. What distinguishes this trial is its focus on MRD negativity as the primary endpoint—a first for NK cell therapies in AML. This approach targets the elimination of residual leukemic cells that remain after conventional treatment, which are often responsible for disease relapse.
AML is an aggressive blood cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with normal blood cell production. Despite achieving complete remission with standard therapies, many patients harbor residual disease at the molecular level, leading to high relapse rates and poor long-term outcomes.
Gengleucel aims to address this critical unmet need by eradicating minimal residual disease and potentially reducing the risk of relapse. The therapy has already received Orphan Drug Designation from the FDA for AML treatment, highlighting its potential significance in the treatment landscape.
Mechanism of Action and Manufacturing
Gengleucel represents a non-engineered, allogeneic NK cell therapy composed of memory NK cells with enhanced activating receptor expression. These cells demonstrate increased secretion of IFN-gamma, granzyme, and perforin—key components that drive potent anti-cancer activity and sustained persistence in the body.
Previous clinical trials have shown favorable safety, tolerability, and efficacy profiles in high-risk AML and myelodysplastic syndrome (MDS) populations. Unlike many cellular therapies that require genetic engineering, Gengleucel's approach leverages the natural cancer-fighting properties of NK cells, potentially offering manufacturing advantages and reduced complexity.
To ensure reliable clinical operations and product supply for the upcoming U.S. trial, Ingenium is currently transferring its manufacturing technology to a Texas-based manufacturing facility. This strategic move will support the trial's planned initiation in early 2026.
Clinical Trial Design and Significance
The Phase 2 trial will evaluate Gengleucel's ability to achieve MRD negativity and its impact on reducing relapse and mortality in AML patients. By focusing on MRD as an endpoint, the study addresses a clinically meaningful outcome that correlates strongly with long-term survival.
Dr. Koh emphasized that this approach could potentially accelerate the development timeline for Gengleucel, bringing this innovative therapy to patients more quickly than the traditional phased approach would allow. The FDA's decision to permit direct Phase 2 entry reflects confidence in the existing data package and recognition of the urgent need for new therapeutic options in AML.
The trial represents a significant step forward in the field of NK cell therapies for hematologic malignancies. If successful, Gengleucel could establish a new paradigm for treating residual disease in AML and potentially extend to other blood cancers where MRD remains a challenge.
Broader Implications for Cell Therapy Development
Ingenium's progress with Gengleucel highlights the evolving regulatory landscape for cell therapies with substantial existing clinical data. The ability to bypass Phase 1 studies in the U.S. based on robust foreign data could set a precedent for other developers with similar programs.
As the company prepares for this pivotal trial, Ingenium continues to advance its broader pipeline, which includes novel in vivo 5th generation CAR-NK therapies for solid tumors. The company's approach leverages deep clinical expertise, a cutting-edge cell therapy platform, and global partnerships to develop transformative immunotherapies.
With the planned U.S. trial, Gengleucel moves one step closer to potentially providing a new treatment option for AML patients with measurable residual disease, addressing a critical gap in the current therapeutic landscape.
