Allogeneic CD22 CAR Cleared for First-in-Human Trial in B-Cell Malignancies

The FDA has cleared Sana Biotechnology’s investigational new drug (IND) clearance to initiate a trial for its CD22-targeted chimeric antigen receptor (CAR) T-cell therapy SC262 in patients with relapsed or refractory B-cell malignancies.¹

“Patients who have failed a CD19-directed CAR T therapy represent a significant unmet need, and this population is growing as more patients receive these therapies,” Doug Williams, PhD, President of Research and Development, Sana, said in a statement.¹ “SC262 represents an important potential option for these patients and is the next step in building Sana’s hypoimmune CAR T therapy platform. Over the past 12 months, Sana has received 3 IND regulatory clearances, as well as supported the authorization of an investigator-sponsored CTA, to begin new studies utilizing our hypoimmune platform in 7 different indications in oncology, B-cell mediated autoimmune diseases, and type 1 diabetes. We look forward to presenting data from all of these studies this year, including initial proof of concept data for SC262 later this year.”

SC262 is developed using Sana’s hypoimmune (HIP) platform, which is designed to overcome immunologic complications with allogeneic cells and may yield longer persistence and durability. The company stated that its allogeneic therapy uses the same CAR and CD22 binder that has been assessed and shown durable complete responses after CD19-targeted CAR T-cell therapy in multiple academic clinical trials.

Last month, Sana published data in Blood on the first patient with chronic lymphocytic leukemia treated in the phase 1 ARDENT trial (NCT05878184) of its CD19-targeted allogeneic CAR T-cell therapy, SC291.² The patient, who had had 3 prior lines of therapy, received a lymphodepletion regimen of cyclophosphamide 500 mg/m 2 and fludarabine 24 mg/m 2 daily for 3 days followed by a starting dose of 60 million CAR+ SC291 cells.

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SC291 was well tolerated with no observed cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. The patient did develop non-neutropenic fever after lymphodepletion prior to SC291 infusion. The patient had a partial response 28 days after infusion, significant (99%) B-cell reduction, and improvements in platelet levels. Investigators are continuing to analyze cellular kinetics.

“These are the first clinical data demonstrating that our HIP technology can engineer allogeneic cells to evade adaptive and innate immune detection and rejection in the context of an intact immune system, overcoming the key challenge in unlocking the potential of allogeneic cells,” Gary Meininger, MD, Chief Medical Officer, Sana, said in a statement at that time.³ “These data suggest the potential of SC291 to persist and attack cancer cells in a manner consistent with autologous cells, which combined with scaled manufacturing, encourage us about both the opportunity for SC291 and our other HIP-modified cells to provide clinical benefit for patients. The data were published as part of an abstract submitted over the summer, and we look forward to sharing more data from this ongoing clinical trial that we expect will more clearly outline SC291’s profile.”

REFERENCES

1. Sana Biotechnology Announces FDA Clearance of Investigational New Drug Application for SC262, a Hypoimmune-modified, CD22-directed Allogeneic CAR T Therapy, for Patients with Relapsed or Refractory B-cell Malignancies. News release. Sana Biotechnology. January 5, 2024. https://ir.sana.com/news-releases/news-release-details/sana-biotechnology-announces-fda-clearance-investigational-new-1
2. Neelapu SS, Budde E, McGuirk JP, et al. Phase 1 Study of SC291, a Hypoimmune, Allogeneic CD19-Directed CAR T Cell Therapy for Relapsed/Refractory B-Cell Malignancies (ARDENT) - Initial Clinical Data. Blood (2023) 142 (Supplement 1): 6852. doi: 10.1182/blood-2023-179441
3. Sana Biotechnology Publishes Early Clinical Data Showing that SC291, a CD19-directed Allogeneic CAR T Therapy, Evades Immune Detection in Presence of Intact Immune System. News release. Sana Biotechnology. December 1, 2023. https://ir.sana.com/news-releases/news-release-details/sana-biotechnology-publishes-early-clinical-data-showing-sc291