Intellia bags option on autoimmune CAR-T prospect, handing Kyverna rights to use CRISPR tech to create off-the-shelf cell therapy 

Intellia Therapeutics has found a new CAR-T use for its CRISPR/Cas9 platform: autoimmune diseases. By teaming up with Kyverna Therapeutics, Intellia has secured an option on an allogeneic anti-CD19 CAR-T based on a construct from the lab that discovered Yescarta.

The deal gives Kyverna, which broke cover in 2020 with investments from Vida Ventures and Gilead Sciences, the chance to use Intellia’s CRISPR/Cas9-based platform for the development of allogeneic cell therapy candidate KYV-201. Kyverna disclosed the licensing of the construct used in KYV-201—plus its autologous sibling—from the laboratory of James Kochenderfer, M.D., at the National Cancer Institute on Monday.

Partnering with Intellia will allow Kyverna to develop the licensed construct in a CRISPR/Cas9-engineered allogeneic CD19 CAR-T for B-cell mediated autoimmune diseases. While originally developed in oncology, Kyverna sees the construct as a way to translate the B-cell depletion and powerful efficacy CAR-Ts have achieved in animal models of autoimmune diseases into humans.

The construct uses a fully human anti-CD19 CAR with costimulatory domains engineered to minimize cytokine release. Kochenderfer’s lab generated early clinical data suggesting the features resulted in a better tolerability profile. In a phase 1 cancer trial, Kochenderfer and his colleagues saw lower rates of severe neurologic toxicity than when they tested the Yescarta construct. By delivering that tolerability in an off-the-shelf cell therapy, Kyverna aims to position KYV-201 for outpatient use.

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Intellia’s platform is critical to the off-the-shelf plan. In return for rights to its platform, Intellia has gained an equity stake in Kyverna and secured a chance to profit from the success of KYV-201. Intellia is eligible to receive milestones and royalties and can choose to lead commercialization of the cell therapy in the U.S. in return for an opt-in fee and a commitment to pay half the development costs. For now, Kyverna is in full control and will lead and fund preclinical and clinical development of KYV-201.

The deal comes around six months after Intellia teamed up with Blackstone Life Sciences and Cellex Cell Professionals to form AvenCell, a startup that is using its CRISPR/Cas9 genome editing technology to create off-the-shelf CAR-T treatments for hematological malignancies and solid tumors. The two deals are underpinned by similar thinking.

“Today’s announcement is another example of our strategy to fully leverage the power of our genome editing technology to address diseases that are inadequately treated with existing medicines. While our core focus remains on advancing therapies within our own research and clinical pipeline, we recognize that our proprietary technology can have additional impact when we strategically partner with others who possess complementary capabilities,” Intellia CEO John Leonard, M.D., said in a statement.