Sana Biotechnology Announced Hypoimmune Car T Cells Evade Both Innate And Adaptive Immune Systems In Murine Models, Even In Animals With Pre-existing Immunity to Car T Cells at ASH 2021

Benzinga · 12/12/2021 14:55
Sana Biotechnology, Inc. (NASDAQ:SANA), a company focused on creating and delivering engineered cells as medicines, presented data at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place from Saturday, December 11 to Tuesday, December 14, 2021, which highlighted further progress with key technologies supporting Sana's in vivo and ex vivo CAR T cell programs. "The data presented at ASH showcase the progress we are making with Sana's CAR T cell programs," said Terry Fry, M.D., Sana's Head of T Cell Therapeutics. "The hypoimmune and fusogen technologies are designed to address significant challenges that lead to sub-optimal patient outcomes and prevent widespread utilization of cell and gene therapies, including cell persistence and cell-specific delivery. We continue to move these potential therapies toward clinical trials in patients, with a goal of filing two INDs as early as next year." On Saturday, December 11, Sonja Schrepfer, M.D., Ph.D., Sana's Head of Hypoimmune Platform, presented a poster (Abstract 1690) titled "Engineered hypoimmune allogeneic CAR T cells exhibit innate and adaptive immune evasion even after sensitization in humanized mice and retain potent anti-tumor activity." Data demonstrated continued progress with Sana's hypoimmune allogeneic CAR T cell platform, showing in murine models that these gene-modified CAR T cells targeting CD19 can evade both the innate and adaptive immune systems without any evidence of a change in their ability to eliminate leukemia. This immune evasion was present in naïve subjects as well as in sensitized subjects that had previously rejected non-hypoimmune CAR T cells. In the study, the hypoimmune allogeneic CD19 CAR T cells did not induce activation of the adaptive immune system, T cells or B cells, in the treated subjects (p<0.0001 when compared to non-modified CD19 CAR T cells), and also evaded the subjects' innate immune responses. These findings are an important step toward the possibility of "off-the-shelf" allogeneic CD19 CAR T cells that persist without immunosuppression, including in patients that have previously been treated with a CAR T therapy. On Sunday, December 12, Terry Fry, M.D., presented a poster (Abstract 2769) titled "In vivo delivery of a CD20 CAR using a CD8-targeted fusosome in Southern pig-tail macaques (M. nemestrina) results in B cell depletion." The presentation outlined the potential to deliver a CAR gene to make CAR T cells in vivo. B cell depletion in these healthy non-human primates is used as a surrogate marker for an anti-tumor effect against B cell malignancies such as leukemia and lymphoma. Following the infusion of the CD8a-targeted fusosome carrying the gene for an anti-CD20 CAR into macaques, B cells were meaningfully reduced in 4 of 6 animals after 7 to 10 days. Scientists found the anti-CD20 CAR transcripts via measurements of mRNA expression in spleen cells isolated from treated animals; conversely, no expression was detected in tissues from control animals. Subjects in this study received no lymphodepleting chemotherapy. Additionally, the fusosome treatment was well-tolerated in all animals with no evidence of adverse effects. These findings suggest that the fusosome technology represents a novel therapeutic opportunity to treat patients with B cell malignancies, with the potential for in vivo delivery of the CAR gene to CD8 T cells. On Sunday, December 12, Sana Scientist Christie Ciarlo, Ph.D., presented a poster (Abstract 2942) titled "CD4-targeted fusosomes are capable of transducing resting T helper cells to generate highly potent CAR T cells." The presentation highlighted the ability of select fusosomes to effectively target the correct cells and to deliver an integrating CAR payload that can develop CAR T cells in vivo. CD4-targeted CD19 CAR fusosomes efficiently transduced activated T cells (34% ± 1.5% CD4+CAR+; 0.54 ± 0.18 c/dg) and resting T cells (20% ± 0.5% CD4+CAR+; 0.28 ± 0.14 c/dg). The data showed that these fusosomes were specific to certain T cells based on their functionality and also that they could deliver their payloads to helper T cells without activation, opening up new potential pathways for in vivo cell therapies. Investigators concluded that targeting the CD4 co-receptor through in vivo delivery of a genetic payload can produce potent and functional CAR T cells, with the potential to target certain cancers.