Kernal Bio awarded up to $48M to develop blood cancer treatments
US agency aiming to advance cheaper, more efficient CAR T-cell therapies
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.”
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