On September 1, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company developing allogeneic CAR T and in vivo gene correction therapies with its ARCUS genome editing platform, and Tiziana Life Sciences plc (Nasdaq: TLSA / LSE: TILS), a clinical stage biotechnology company focused on innovative therapeutics for oncology, inflammation, and infectious diseases, reported an exclusive license agreement to explore Tiziana’s foralumab, a fully human anti-CD3 monoclonal antibody (mAb), as an agent to induce tolerance of allogeneic CAR T cells to potentially improve the clinical outcome of CAR T cell therapy (Press release, Precision Biologics, SEP 1, 2021, View Source [SID1234587124]).
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The Cluster of Differentiation (CD) 3 is a receptor on effector T cells and an anti-CD3 antibody, such as foralumab, has the potential to eliminate or tolerize patient effector T cells. Precision’s manufacturing process, which uses ARCUS to knock out the TRAC gene and implements a CD3-depletion step, produces allogeneic CAR T candidates that are >99.9% CD3-negative. Thus, an anti-CD3 antibody, such as foralumab, might be used to enable the CAR T cells to expand, proliferate, and persist to maximize long term clinical benefits.
Under the terms of the agreement, Precision gains an exclusive license to use foralumab as a lymphodepletion agent in conjunction with its allogeneic CAR T therapeutics for the treatment of cancers. Precision will be responsible for the development, commercialization, and costs for use of foralumab, and Tiziana will receive upfront payment, certain milestone payments, and royalties for foralumab.
"We are building out an allogeneic CAR T platform with editing strategies and novel conditioning regimens, such as a lymphodepleting agent like foralumab, for a broad range of hematologic malignancies and solid tumors," said Alan List, M.D., Chief Medical Officer at Precision BioSciences. "By combining Precision’s know-how in constructing novel CAR T products with novel conditioning regimens, we will explore this approach to potentially improve durability of clinical responses to our therapeutic platform."
"We’re pleased to offer Precision the exclusive opportunity to explore foralumab, our fully human anti-CD3 monoclonal antibody, for use as a potential lymphodepletion strategy with their allogeneic CAR T programs," said Kunwar Shailubhai, Chief Executive Officer and Chief Scientific Officer of Tiziana Life Sciences. "While CAR T therapies have been clinically successful, relapse rates remain high, which continues to limit broad utility. We are impressed with Precision’s novel approaches to CAR T development, offering the potential for a meaningful off-the-shelf solution. Further, given Precision’s approach to manufacturing that produces CAR T cells virtually CD3-negative, we believe use of foralumab as a lymphodepletion or tolerizing agent has the potential, either alone or in combination with other co-stimulatory molecules, to improve the long-term success of CAR T in cancer treatment."
About Precision’s Allogeneic CAR T Platform
Precision is advancing a pipeline of cell-phenotype optimized allogeneic CAR T therapies, leveraging fully scaled, proprietary manufacturing processes. The Company’s allogeneic CAR T platform is designed to maximize the number of patients who can potentially benefit from CAR T therapy. Precision carefully selects high-quality T cells derived from healthy donors as starting material, then uses its ARCUS genome editing technology to modify the cells via a single-step engineering process. By inserting the CAR gene at the T cell receptor (TCR) locus, this process knocks in the CAR while knocking out the TCR, which is designed to create a consistent product that can be reliably and rapidly manufactured and is designed to prevent graft-versus-host disease. Precision optimizes its CAR T therapy candidates for immune cell expansion in the body by maintaining a high proportion of naïve and central memory CAR T cells throughout the manufacturing process and in the final product.
About Foralumab
Foralumab (TZLS-401, formerly NI-0401), the only entirely human anti-CD3 mAb, shows reduced release of cytokines as compared to other anti-CD3 mAbs after IV administration in patients with Crohn’s disease with decreases in the classic side effects of cytokine release syndrome and improves the overall safety profile of Foralumab. In a humanized mouse model (NOD/SCID IL2γc-/-), it was shown that while targeting the T cell receptor, orally administered Foralumab modulates immune responses of the T cells, enhances regulatory T-cells (Tregs) and thus provides therapeutic benefit in treating inflammatory and autoimmune diseases without the occurrence of potential adverse events usually associated with parenteral mAb therapy (Ogura M. et al., 2017 Clin Immunol 183, 240-246). Based on animal studies, the nasal and oral administration of Foralumab offers the potential for the immunotherapy of autoimmune and inflammatory diseases in a safe manner by the induction of Tregs.