Leucid Bio’s NKG2D-directed CAR-T LEU011 Cleared for Solid Tumor Clinical Trial in the UK


In September 2023, LEU011 was granted an Innovation Passport for the treatment of solid tumors expressing NKG2D ligands.

Leucid Bio has received clinical trial authorization (CTA) from the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) to evaluate LEU011, an investigational chimeric antigen receptor T-cell (CAR-T) therapy, for the treatment of patients with solid tumors in the phase 1/2 AERIAL clinical trial (NCT identifier pending).1

LEU011, which is based on Leucid Bio’s lateral CAR platform, incorporates an NKG2D receptor that allows for targeting of 1 or more of 8 human NKG2D ligands that research has indicated are found on greater than 80% of tumors in humans. LEU011’s NKG2D receptor is intended to trigger the death of cells on which NKG2D ligands are recognized.2 Participants in the open-label AERIAL study, which is going to recruit patients with relapsed/refractory solid tumors, will be treated with the CAR-T after undergoing preconditioning chemotherapy.1 The trial will begin with a dose-escalation portion; later, patients with solid tumors that with 1 or more NKG2D ligands will be enrolled in a dose-expansion portion.

“The design of the AERIAL trial, which was inspired by our exciting preclinical data for LEU011, is aimed at assessing the broad potential of the innovative cell therapy across several solid tumors expressing NKG2D ligands,” John Maher, FRCPath, MSc, the chief scientific officer of Leucid Bio, said in a statement.1 “We look forward to initiating the AERIAL study over the next few months and providing preliminary first-in-human data for LEU011 in 2024.”

In September 2023, LEU011 was granted an Innovation Passport for the treatment of solid tumors expressing NKG2D ligands. The Innovation Passport is a designation from the MHRA’s Innovative Licensing and Access Pathway (ILAP).

“The MHRA’s authorization and the ILAP designation for LEU011 highlight the strong potential of our proprietary lateral CAR-T candidate LEU011 for the treatment of solid tumors,” Filippo Petti, MS, MBA, the chief executive officer of Leucid Bio, added to the statement.1 “The development of LEU011 demonstrates our commitment to pushing the boundaries in cell therapy research and underpins our dedicated focus on pursuing novel, durable therapies for cancer patients with limited treatment options.”

In preclinical research, LEU011 showed potential for a therapeutic effect in models of colorectal, pancreatic, ovarian, and breast cancer as well as mesothelioma with a prolonged disease-free survival compared to some other CAR-T treatments, some of which are currently being evaluated in clinical trials.2 In several models, rejection of secondary tumor rechallenge indicated functional persistence of LEU011. Notably, across 12 in vivo models of 6 tumor types, LEU011 has demonstrated a 95% overall response rate.

The lateral CAR platform used in LEU011 is intended to improve tumor targeting, selectivity, and engagement by placing complementary signaling domains across the cell membrane in a way that mimics the positioning of such domains in natural immune cells. This stands in contrast to typical CAR-T products that utilize a linear placement of costimulatory domains.

“Leucid Bio is in an exciting phase of expansion as we progress to first in human proof-of-concept for our novel Lateral CAR Platform in multiple programs,” Ian Miscampbell, the interim executive chairman at Leucid Bio, said in a February 2023 statement.3 “John Maher was the first to engineer and develop CD28-based second generation CAR technology in human T-cells 20 years ago, and has continued to innovate in the field as 1 of its acknowledged experts ever since. Our proprietary platform has been built around his groundbreaking research.”

1. Leucid Bio granted MHRA clinical trial authorisation for lateral NKG2D CAR T-cell therapy LEU011. News release. Leucid Bio. September 21, 2023. Accessed October 6, 2023. https://www.prnewswire.com/news-releases/leucid-bio-granted-mhra-clinical-trial-authorisation-for-lateral-nkg2d-car-t-cell-therapy-leu011-301933863.html
2. Our Science. Leucid Bio. Website. Accessed October 6, 2023. https://www.leucid.com/cloud-solutions
3. Leucid Bio provides business update and outlook for 2023. News release. Leucid Bio. February 16, 2023. Accessed October 6, 2023. https://www.prnewswire.com/news-releases/leucid-bio-provides-business-update-and-outlook-for-2023-301748526.html
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