Orca-T: A New Allogeneic Cell Therapy - Defining Orca-T and Potential Advantages Compared With Conventional AlloHSCT

Summary for Physicians:

Orca-T is a novel allogeneic cell therapy that aims to improve conventional allogeneic hematopoietic stem cell transplantation (alloHSCT) by leveraging an engineered approach to reduce the risk of GVHD.

Key Features of Orca-T:

• Donor T cell depletion: Orca-T involves the use of T-cell-depleted donor grafts, which helps minimize the risk of GVHD while preserving the graft-vs-leukemiaeffect.
• Engineered approach: The therapy uses a novel, proprietary method to enhance the graft’s ability to engraft and reduce immune-mediated complications. This is in contrast to conventional alloHSCT, which uses full-intensity conditioning and can involve higher GVHD risks, particularly with mismatched or haploidentical donors.

Rationale for Single-Agent Tacrolimus:

• Reduced immune suppression: The combination of Orca-T with single-agent tacrolimus, as opposed to more traditional multi-drug regimens, is designed to offer a more targeted approach to GVHD prevention while minimizing broader immunosuppression.
• Advantages: Using a single-agent regimen may help reduce the toxicities associated with broader immunosuppressive protocols, such as infections or long-term organ damage, by limiting the overall immune suppression burden. It also allows for a more controlled, less aggressive immune modulation while still preventing GVHD.

This approach with Orca-T represents a promising step forward in improving alloHSCT outcomes by balancing immune response and reducing complications typically seen with traditional transplant methods.

Nelli Bejanyan reports consulting or advisory role for CareDx, Medexus Pharmaceuticals, Orca Biosystems, AlloVir, TScan Therapeutics, and Pfizer; and research funding from CRISPR Therapeutics. Everett Meyer reports sponsored research from Orca Biosciences, Kyverna; and a scientific advisor role and equity holder for GigaMune, Indee, TRACT, Jura Biosciences.Caspian Oliai reports no relevant disclosures (investigator on the Orca T trial funded by Orca Biosciences). Arpita P. Gandhi reports roles with OncLive, MJH Life Sciences, OrcaBio (research), CareDx (Advisory Board). Amandeep Salhotra reports received funding from Rigel, Bristol Myers Squibb and Orca Biosciences; and speakers bureau for Incyte and Sanofi.