Kernal Biologics Secures Up to $48 Million from ARPA-H to Advance In Vivo CAR T-Cell Therapy for Cancer and Autoimmune Diseases
Kernal Biologics, Inc., a venture-backed TechBio innovator pioneering next-generation therapeutics that program human cells directly within the body, has announced a major milestone in its mission to revolutionize cell therapy. The company has been awarded up to $48 million in funding from the Advanced Research Projects Agency for Health (ARPA-H), a division of the U.S. Department of Health and Human Services dedicated to high-impact, transformative health research. This grant will support the clinical development of Kernal Bio’s lead in vivo CAR T-cell program, KR-402, under ARPA-H’s EMBODY (Engineered Multi-cellular Biologic On-Demand in Your body) initiative.
The EMBODY program, led by ARPA-H Program Manager Daria Fedyukina, Ph.D., is specifically designed to accelerate the engineering of immune cells directly inside the human body—bypassing the need for complex, costly, and time-consuming ex vivo manufacturing processes that currently define the CAR T-cell therapy landscape. As part of this ambitious project, Kernal Bio will collaborate with three prestigious sub-awardees: Stanford University School of Medicine, Dana-Farber Cancer Institute, and The Jackson Laboratory. Together, this consortium will work to engineer highly targeted, mRNA-encoded chimeric antigen receptors (CARs), develop novel manufacturing strategies, and establish advanced preclinical models to rigorously test the safety and efficacy of in vivo CAR T-cell therapies.
KR-402, Kernal Bio’s flagship therapeutic candidate, represents a paradigm shift in cellular immunotherapy. Unlike conventional CAR T-cell treatments—which require extracting a patient’s T cells, genetically modifying them in a laboratory over several weeks, and then reinfusing them back into the patient—KR-402 is designed to reprogram T cells directly inside the body using mRNA technology. This approach targets both hematological malignancies and autoimmune conditions, with initial indications including acute lymphoblastic leukemia (ALL), large B-cell lymphoma, chronic lymphocytic leukemia (CLL), and multiple sclerosis (MS).
“We’re honored to join the elite cohort of ARPA-H awardees,” said Dr. Yusuf Erkul, M.D., MBA, co-founder and CEO of Kernal Bio. “Current CAR-T therapies heralded a true revolution in cancer treatment. Yet, they have significant limitations—including a three-week vein-to-vein turnaround time, tumor resistance leading to relapse, and serious side effects such as cytokine release syndrome or even secondary T-cell malignancies. At Kernal Bio, we believe we have the tools to evolve the CAR-T modality toward in vivo therapies that are safer, faster, and more accessible.”
At the core of KR-402 is Kernal Bio’s proprietary mRNA 2.0 platform, which leverages a dual-layered strategy to achieve unprecedented precision in cell targeting and reprogramming. The first layer involves the design of a highly selective mRNA molecule that only translates into functional CAR proteins in specific T-cell subsets. This selectivity is achieved through deep computational analysis of thousands of multi-omics data points—including transcriptomic, epigenomic, and proteomic profiles—across diverse human cell types. By identifying unique molecular signatures present only in target T cells, Kernal Bio engineers mRNA sequences that remain silent in off-target cells, drastically reducing the risk of unintended immune activation or toxicity.
The second layer of precision comes from the delivery system: a custom-engineered lipid nanoparticle (LNP) decorated with antibodies that specifically bind to surface markers on the desired T-cell populations. This targeted LNP acts like a “homing missile,” delivering the mRNA payload exclusively to the intended immune cells within the body. Once internalized, the mRNA instructs the T cells to produce the CAR on their surface, effectively converting them into tumor- or autoantigen-targeting therapeutic agents—without ever leaving the patient’s body.
This in vivo approach offers multiple transformative advantages over traditional ex vivo CAR T-cell manufacturing. First, it eliminates the need for leukapheresis (the process of drawing and separating white blood cells), which can be logistically challenging and inaccessible to many patients, especially those in rural or underserved areas. Second, it removes the requirement for lymphodepleting chemotherapy—a toxic preconditioning regimen used before CAR T-cell infusion to make space for the engineered cells. Lymphodepletion carries significant risks, including prolonged immunosuppression, infections, and organ toxicity, and often disqualifies frail or elderly patients from receiving therapy.
“Manufacturing ex vivo CAR-T therapies is a complex and expensive process,” noted Burak Yilmaz, President of Kernal Bio. “However, with our proprietary platform, there is potential to reduce the cost of manufacturing in vivo CAR T-cell therapies by as much as 100-fold. In addition, chemotherapy drugs used for lymphodepletion prior to CAR-T therapies carry significant toxicity, making these therapies viable for just a small group of patients. We believe that with our technology—and the support of our world-class partners and ARPA-H—we can greatly transform access to this category of life-saving treatments.”
The implications of this technology extend beyond cost and accessibility. Because KR-402 uses transient mRNA rather than viral vectors for genetic modification, it avoids the risk of permanent genomic integration—a concern that has led to cases of secondary T-cell cancers in some ex vivo CAR T-cell recipients. The transient nature of mRNA also allows for better control over CAR expression duration, potentially mitigating severe side effects like cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).
Moreover, the platform’s modularity means it can be rapidly adapted to target different diseases by simply swapping the CAR sequence or adjusting the LNP targeting moiety. This flexibility positions Kernal Bio to address a broad spectrum of oncologic and autoimmune disorders with a single, scalable therapeutic engine.
The collaboration with Stanford, Dana-Farber, and The Jackson Laboratory brings together complementary expertise in immunology, oncology, neurology, and preclinical modeling. Stanford will contribute cutting-edge insights into T-cell biology and autoimmune mechanisms, particularly relevant for the multiple sclerosis indication. Dana-Farber, a global leader in hematologic malignancies, will guide clinical translation and biomarker development for B-cell cancers. The Jackson Laboratory will develop and validate sophisticated humanized mouse models to evaluate KR-402’s efficacy and safety in physiologically relevant settings.
With this ARPA-H award, Kernal Bio is poised to accelerate KR-402 toward clinical trials, potentially ushering in a new era of “off-the-shelf,” in vivo cell therapy that is not only more effective but also democratizes access for millions of patients worldwide. As the field moves beyond the limitations of ex vivo manufacturing, Kernal Bio’s vision—of programming the immune system from within—could redefine the future of precision medicine.
