On August 2, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that the FDA has authorized Sorrento’s IND application for the Phase 1 clinical testing of its allogeneic anti-CD38 Dimeric Antigen Receptor (DAR) – T Cell therapy for relapsed or refractory multiple myeloma (Press release, Sorrento Therapeutics, AUG 2, 2021, View Source [SID1234585537]). The proprietary CD38 DAR-T cell therapy candidate demonstrated strong cytotoxic activity in preclinical studies. DAR-T product candidates are produced using Sorrento’s proprietary, non-viral knockout-knockin (KOKI) technology, which potentially allows for improved specificity, stability and potency, and enables an off-the-shelf treatment approach, thereby eliminating the need for patients to undergo leukapheresis and undesirable treatment delays to perform cell harvesting, manufacturing and release prior to treatment for each individual cancer patient.

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Sorrento’s KOKI-enabled DAR-T platform uses DAR-modified T cells from a normal healthy donor which are engineered to be specific to the cell surface marker of interest, in this case CD38, a clinically validated antigen in myeloma, to target tumor cells. The combination of KOKI and DAR-T technologies offers potential advantages over conventional CAR-T therapies, including removing the ability for DAR-expressing T cells to illicit undesired immune reaction to the cancer patient, thereby reducing or eliminating the possibility of graft versus host disease (GvHD) following treatment. Additionally, once DAR-T cells are manufactured, they can be stored at the clinic site, allowing patients to be screened and treated within days. This is compared to existing approved CAR-T therapies, which typically require 6-8 weeks of screening, cell production and qualification before a patient can receive treatment. Because of this timeframe, it is not unusual for cancer patients to no longer be eligible for CAR-T treatment due to disease progression. Also, autologous CAR-T cells pose several manufacturing challenges, including issues that relate to quality control and single-lot-release, and often do not meet the release criteria following the manufacturing process. DAR-T technology is designed to potentially provide a significant advancement to the timeliness and potency of treatments for patient populations who have already undergone multiple rounds of chemotherapy and are suffering from persistent disease.

DAR-T technology is readily adaptable to dozens of cancer targets and Sorrento has developed a preclinical product pipeline with specific fully human antibodies discovered from Sorrento’s G-MAB library. Sorrento expects to file additional IND applications now that the first DAR-T Phase 1 trial has been cleared to proceed by the FDA.

"This FDA clearance of our first allogeneic DAR-T cell therapy is a seminal event for our cutting-edge KOKI and DAR-T technologies," said Henry Ji, Ph.D., Chairman and CEO of Sorrento. "We foresee the first "Off-the-Shelf" DAR-T trial will open the door to numerous other DAR-T cell therapies for other indications to follow."

About the DAR-T Platform

Sorrento’s DAR-T technology is a proprietary, next-generation cell therapy platform that offers potential advantages over conventional Chimeric Antigen Receptor (CAR) T cell therapy:

The proprietary DAR construct utilizes a natural antibody Fab (antigen-binding fragment) structure instead of an artificial scFv (single-chain variable fragment) sequence.
Preclinical in vitro and in vivo studies have demonstrated that DAR-T cells provide better target specificity and functionality, due to higher inherent stability of the Fab and stronger affinity of DAR vs. CAR receptors on the T cell surface.
DAR-T cells may reduce potential undesirable side effects, such as CAR-T induced cytokine release syndrome (CRS) and graft-versus-host disease (GvHD).
About KOKI Technology

Sorrento’s proprietary, non-viral knockout-knockin (KOKI) technology provides DAR-T cells with several potential benefits over virus-based transduction currently used for CAR-T therapies:

"Off-the-Shelf": DAR-T cells are cryo-preserved engineered T cells designed to be delivered to patients on-demand without delays in treatment due to the lengthy and individualized manufacturing process for CAR-T.
"Allogeneic": DAR-T cells are produced from pre-screened healthy volunteers; while autologous CAR-T cells are patient-specific and made from and for individual cancer patients.
"Mass Production": DAR-T cell manufacturing is scalable (potentially hundreds to thousands of doses per manufacturing run) and can meet high demand while autologous CAR-T cell therapy requires a single-lot-release process that can only be performed one patient at a time.