Kernal gets $48M to develop easier, cheaper CAR T-cell therapies. Kernal Biologics has been awarded up to $48 million in funding to accelerate the development of KR-402, a next-generation CAR T-cell therapy for multiple sclerosis (MS) and certain blood cancers. The funds come from the Advanced Research Projects Agency for Health's (ARPA-H) EMBODY program, which aims to support the development of more affordable immune therapies where immune cells are transformed inside the body (in vivo) rather than in a lab. Kernal is developing one of these therapies. CAR-T cell therapies involve collecting a patient's immune T-cells, engineering them in a lab to boost their ability to recognize and destroy disease-causing cells, and reinfusing them back into the patient's bloodstream. While highly effective, these therapies are expensive to produce and take time to manufacture. They are also available only at specialized centers. "Manufacturing [current] CAR-T therapies is a complex and expensive process," Burak Yilmaz, president of Kernal Bio, said in a company press release. "However, with our proprietary platform, there is a potential of reducing the cost of manufacturing in vivo CAR T-cell therapies by as much as 100-fold." Current therapy also requires chemotherapy drugs, which "carry significant toxicity, making these therapies viable for just a small group of patients," Yilmaz said. "We believe that with our technology and the support of our partners and ARPA-H, we can greatly transform access to this category of therapies." Speeding treatment, lowering costs. "We're honored to join the elite cohort of ARPA-H awardees," said Yusuf Erkul, MD, cofounder and CEO of Kernal. "Current CAR-T therapies heralded a true revolution in cancer treatment. Yet, they have their limitations, including a three-week vein-to-vein turnaround time... and side effects such as cytokine release syndrome or secondary T-cell malignancies. At Kernal Bio, we believe that we have the tools to evolve the CAR-T modality towards in vivo therapies." MS is caused by the immune system mistakenly attacking healthy parts of the brain and spinal cord. B-cells, which normally produce antibodies to fight off infections, are key immune cells involved in this attack, and are also involved in certain blood cancers. By targeting and depleting harmful B-cells, KR-402 aims to both suppress the autoimmune attacks that drive MS and eliminate the malignant cells in B-cell blood cancers. The next-generation therapy uses Kernal's mRNA 2.0 platform, where a messenger RNA (mRNA) molecule containing the instructions for making a chimeric antigen receptor (CAR) that targets B-cells is delivered to patients. An mRNA molecule is one cells naturally make when reading genetic instructions that is then used as a template to make proteins. In KR-402, the mRNA molecule is inserted inside lipid nanoparticles that are highly specific to T-cells, ensuring that the therapy is selectively delivered to those cells. A second key feature in KR-402's design is that the treatment is active only inside those cells, further reducing the potential for affecting other cells. Because KR-402 works directly inside the body, it eliminates two major steps required for conventional CAR-T therapies: the collection and reinfusion of engineered T-cells, and the use of chemotherapy to deplete white blood cells before treatment to support CAR T-cell expansion and survival. The company expects this to reduce costs and improve the experience for patients. The $48 million grant will be used to create mRNA molecules for in-body CAR-T therapies, develop new manufacturing strategies for these therapies, and create preclinical models to evaluate the treatments' safety and effectiveness. Kernal said it will collaborate with researchers at the Stanford University School of Medicine, Dana-Farber Cancer Institute, and the Jackson Laboratory to conduct the studies. Michela Luciano, PhD Michela Luciano is a Science Writer at BioNews. Originally from the picturesque mountain town of L'Aquila, Italy, Michela holds a PhD in Molecular Biology from the University of Salzburg, where her research focused on the role of inflammation in acute myeloid leukemia. With a deep passion for scientific communication, Michela transitioned into her first role as Scientific Writer in 2022. Outside of work she enjoys street photogtaphy, mountain hikes, running, and spending as much time as possible outdoors. Living with MS.

Kernal Bio awarded up to $48M to develop blood cancer treatments. The Advanced Research Projects Agency for Health (ARPA-H) has awarded up to $48 million to Kernal Bio to support the development of more efficient, cheaper CAR T-cell therapies for the treatment of some types of blood cancer. ARPA-H is an independent entity within the National Institutes of Health, created in 2022 to support health research with the potential to be transformational for patients. "We're honored to join the elite cohort of ARPA-H awardees," Yusuf Erkul, MD, cofounder and CEO of Kernal, said in a company press release. Erkul noted that the advent of CAR-T therapies - the first was approved in the U.S. in 2017 to treat a type of leukemia - "heralded a true revolution in cancer treatment." T-cells are immune cells that act as the body's assassins, able to kill other cells that have become infected with a virus or turned cancerous. CAR T-cell therapy is a recent type of treatment in which T-cells are equipped with a chimeric antigen receptor or CAR, a human-made protein that acts as a molecular weapon directing the T-cells to go after a specific target - for example, a protein expressed by cancer cells. Although CAR T-cell therapies have shown great promise to treat various blood cancers, available treatments have some notable drawbacks. With most of these therapies, T-cells need to be collected from a patient and taken to a lab to equip them with a CAR before infusing the cells back into the patient - a process that's time-consuming and costly. Plus, CAR T-cell therapies can cause serious side effects like cytokine release syndrome (an inflammatory reaction) and secondary T-cell cancers. Erkul noted the treatment has its "limitations, including a three-week vein-to-vein turnaround time, tumor resistance leading to relapse, and side effects such as cytokine release syndrome or secondary T-cell malignancies." Kernal advancing its KR-402 treatment candidate for blood cancer. Kernal's experimental therapy KR-402 is designed to act as an in vivo CAR T-cell therapy. In other words, the treatment aims to engineer T-cells inside a patient's body, removing the need to collect cells and take them to a lab. The therapy works by delivering a specialized messenger RNA (mRNA), which is a template molecule produced when cells read genes to make proteins. The mRNA encodes for a CAR that targets a protein expressed by B-cells, a type of immune cells whose uncontrolled growth can cause several types of blood cancers. Among such cancers are acute lymphoblastic leukemia, large B-cell lymphoma, and chronic lymphocytic leukemia. With KR-402, the mRNA is delivered to T-cells using a lipid nanoparticle, which is essentially a bubble of fatty molecules designed to deliver molecules into cells. To avoid accidentally targeting other types of cells, the lipid nanoparticle is engineered specifically to deliver its cargo to T-cells, and the mRNA is designed to only be active in specific cells. With our proprietary platform, there is a potential of reducing the cost of manufacturing... CAR T-cell therapies [used inside the human body] by as much as 100 [times]. Prior to infusion with traditional CAR T-cell therapies, patients usually need to undergo lymphodepletion - intensive chemotherapy and/or radiation to eliminate existing immune cells and make room for the therapeutic cells. In addition to simplifying treatment and reducing costs, KR-402 aims to remove the need for lymphodepletion, which could make this type of therapy safer and more accessible. "With our proprietary platform, there is a potential of reducing the cost of manufacturing in vivo CAR T-cell therapies by as much as 100 [times]," said Burak Yilmaz, president of Kernal Bio, who noted that in vivo treatments "[offer] tremendous cost efficiencies over traditional ex vivo therapies," or those using a laboratory. "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," Yilmaz said. "We believe that with our technology and the support of our partners and ARPA-H, we can greatly transform access to this category of therapies." Marisa Wexler, MS Marisa holds a Master of Science in cellular and molecular pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. Her areas of expertise include cancer biology, immunology, and genetics, and she has worked as a science writing and communications intern for the Genetics Society of America.