SC291 / Sana Biotech - LARVOL DELTA

Phase 1 Study of SC291, a Hypoimmune, Allogeneic CD19-Directed CAR T Cell Therapy for Relapsed/Refractory B-Cell Malignancies (ARDENT) - Initial Clinical Data (ASH 2023) - "The initial patient, a 74-year-old male with CLL (unmutated IGHV, del(11q), BTK C481S mutation) and 3 prior lines of therapy (FCR, ibrutinib, venetoclax + rituximab), received a LD 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 (of which approximately 80% are fully HIP engineered cells). Immune assays demonstrated that the CD19 HIP CAR T cell subpopulation effectively evades the host adaptive and innate immune responses and could overcome the allogeneic barrier in humans. Additional data from the ARDENT study will be presented at the time of the conference."

CAR T-Cell Therapy • Clinical data • P1 data • Chronic Lymphocytic Leukemia • Febrile Neutropenia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD47 • CD8 • IFNG • IGH • NCAM1

Study Evaluating SC291 in Subjects With Severe r/r B-cell Mediated Autoimmune Diseases (GLEAM) (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: Sana Biotechnology | N=36 ➔ 7 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • ANCA Vasculitis • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Vasculitis

Identification of Healthy Donor Phenotypic and Functional Signatures That Predict Allogeneic, Hypoimmune CD19-Directed CAR T Cell Potency (ASH 2023) - "In vivo efficacy was evaluated using a systemic NALM-6 challenge in immune-deficient NSG mice at HIP CD19 CAR T cell doses of 5e5 and 5e6 cells per animal...Outperforming donors also showed reduced expression of MHC class II of alpha and beta heterodimers (HLA-DQA1 and HLA-DQB1). The information collected across phenotypic and functional comparisons will be compared with clinical performance."

CAR T-Cell Therapy • Clinical • B2M • CD19 • CD47 • CD8 • HLA-DQA1 • HLA-DQB1 • IFNG • IL17A • IL22 • IL5 • TRB

Hypoimmune CD19 CAR T cells evade allorejection in patients with cancer and autoimmune disease. (PubMed, Cell Stem Cell) - P1 | "The primary T cell product SC291 was engineered with a CD19 CAR, T cell receptor alpha constant (TRAC) knockout, and the hypoimmune (HIP) edits of HLA depletion and CD47 overexpression...The lack of antibodies against the HLA-replete CAR T cells was identified as a marker for deep tissue CD19 cell depletion, and all patients without such antibodies for 60 days showed concomitant B cell depletion in peripheral blood. The immune data presented support the reliability of the HIP concept to evade allorejection."

IO biomarker • Journal • Immunology • Oncology • CD47

Advancing our pipeline across multiple indications and modalities (Yahoo Finance) - "Expect to file IND for SG299 in a B-cell related disease as early as 2026; Enrolling patients in the GLEAM trial for SC291 in B-cell mediated autoimmune diseases and VIVID trial for SC262 in relapsed/refractory B-cell malignancies; expect to report clinical data from both studies in 2025."

IND • P1 data • Immunology • Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Systemic Lupus Erythematosus

Sana Biotechnology Reports Fourth Quarter and Full Year 2024 Financial Results and Business Updates (GlobeNewswire) - "Type 1 Diabetes – Sana continues the clinical development of gene-modified primary islet cells (UP421) and the pre-clinical development of SC451...Sana expects to share additional data in 2025 and file an IND as early as 2026....Enrolling patients in the GLEAM trial for SC291 in B-cell mediated autoimmune diseases and VIVID trial for SC262 in relapsed/refractory B-cell malignancies; expect to report clinical data from both studies in 2025....in vivo CAR T cells: Sana expects to file an IND for SG299 as early as 2026, and we look forward to developing it in a range of B-cell cancers and B-cell mediated autoimmune diseases."

Clinical data • IND • P1 data • ANCA Vasculitis • Immunology • Oncology • Systemic Lupus Erythematosus • Type 1 Diabetes Mellitus

Sana Biotechnology Announces Fast Track Designation for SC291 in Relapsed/Refractory Systemic Lupus Erythematosus (GlobeNewswire) - "Sana Biotechnology, Inc...announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for SC291 in relapsed/refractory systemic lupus erythematosus (SLE), which includes extrarenal lupus and lupus nephritis. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need....Sana is enrolling patients in this study and expects to share initial data in 2025."

Enrollment status • Fast track • P3 data • Immunology • Lupus • Lupus Nephritis • Systemic Lupus Erythematosus

Study Evaluating SC291 in Subjects With r/r B-cell Malignancies (ARDENT) (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Sana Biotechnology | Recruiting ➔ Active, not recruiting | N=57 ➔ 16 | Trial completion date: Dec 2027 ➔ Nov 2038 | Trial primary completion date: Dec 2026 ➔ Nov 2025

CAR T-Cell Therapy • Enrollment change • Enrollment closed • IO biomarker • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

Sana Biotechnology Announces Increased Focus on...B-cell Mediated Autoimmune Diseases with the Potential to Deliver Clinical Proof of Concept Data Across Multiple Studies in 2024 and 2025 (GlobeNewswire) - "SC291 (HIP-modified CD19-directed allogeneic CAR T) in autoimmune diseases: Sana continues enrollment in the Phase 1 GLEAM trial for SC291 for the treatment of B-cell mediated autoimmune diseases and expects to share clinical data in 2024 and/or 2025....SG299 (in vivo CAR T with CD8-targeted fusogen delivery of a CD19-directed CAR): Sana is continuing its preclinical development of this program, with potential in both B-cell mediated autoimmune diseases and oncology."

P1 data • Preclinical • Immunology • Lupus • Systemic Lupus Erythematosus

Phase 1 clinical trial of AAV cell therapy SC291 starts enrollment (ANCA Vasculitis News) - "A Phase 1 clinical trial evaluating the safety and preliminary efficacy of Sana Biotechnology’s candidate CAR T-cell therapy SC291 in adults with ANCA-associated vasculitis (AAV) and other autoimmune diseases has started enrollment. The study, GLEAM (NCT06294236), is recruiting up to 36 patients ranging in age from 18 to 75 at the University of Colorado in Aurora, Colorado, and the Swedish Medical Center in Seattle, Washington....Patients with certain forms of lupus, another autoimmune disease, will also take part in the study. Preliminary data are expected this year...we remain on track to share initial data from each of these studies in 2024,'...The study is expected to end in 2028."

Enrollment status • P1 data • Trial completion date • Immunology • Lupus • Vasculitis

RESULTS FROM ARDENT, A PHASE 1 STUDY OF SC291, A HYPOIMMUNE, ALLOGENEIC CD19-DIRECTED CAR T CELL THERAPY FOR RELAPSED AND REFRACTORY B-CELL MALIGNANCIES (EHA 2024) - "This abstract is embargoed until Friday, June 14, 2024 (09:00 CEST). Presentation during EHA2024: All (e)Poster presentations will be made available as of Friday, June 14, 2024 (09:00 CEST) and will be accessible for on-demand viewing until Thursday, August 15, 2024 on the Congress platform."

CAR T-Cell Therapy • P1 data • Hematological Malignancies • Oncology

Study Evaluating SC291 in Subjects With Severe r/r B-cell Mediated Autoimmune Diseases (GLEAM) (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Sana Biotechnology | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • ANCA Vasculitis • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Vasculitis

Study Evaluating SC291 in Subjects With Severe r/r B-cell Mediated Autoimmune Diseases (GLEAM) (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Sana Biotechnology

CAR T-Cell Therapy • New P1 trial • ANCA Vasculitis • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Vasculitis

Sana Biotechnology Reports Fourth Quarter and Full Year 2023 Financial Results and Business Updates (GlobeNewswire) - "Recent Corporate Highlights:...The ARDENT trial evaluates SC291 in patients with B-cell malignancies....Enrollment in this dose escalation study continues, and Sana expects to share more data in 2024."

Enrollment status • P1 data • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma

Sana Biotechnology Reports Fourth Quarter and Full Year 2023 Financial Results and Business Updates (GlobeNewswire) - "Recent Corporate Highlights:...The GLEAM trial evaluates SC291 in patients with B-cell mediated autoimmune diseases including lupus nephritis, extrarenal lupus, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The Investigational New Drug Application (IND) cleared in 4Q 2023, and Sana expects to share initial data in 2024."

IND • New P1 trial • Lupus • Lupus Nephritis • Vasculitis

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 (GlobeNewswire) - P1 | N=54 | ARDENT (NCT05878184) | Sponsor: Sana Biotechnology | "Sana Biotechnology, Inc...today announced the publication in Blood of an abstract providing initial clinical data from the first patient treated at the lowest dose in the ongoing ARDENT Phase 1 clinical trial with SC291...SC291 appeared safe and well tolerated, evaded immune detection, and induced a partial response in a patient with chronic lymphocytic leukemia (CLL)....Treatment in this dose escalation study is ongoing, and the company expects to present more data from this study at a later date in an appropriate venue."

P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology

Sana Biotechnology Announces Increased Focus on Hypoimmune-Related Pipeline with the Potential to Deliver Clinical Proof of Concept Data from Four Programs in 2023 and 2024 with a 2024 Operating Burn under $200M (GlobeNewswire) - "SC291 Autoimmune (HIP-modified CD19-directed allogeneic CAR T): Sana submitted an IND for the treatment of multiple autoimmune diseases, with preliminary clinical data expected across multiple indications in 2024."

Clinical data • IND • Immunology

Sana Biotechnology Announces Increased Focus on Hypoimmune-Related Pipeline with the Potential to Deliver Clinical Proof of Concept Data from Four Programs in 2023 and 2024 with a 2024 Operating Burn under $200M (GlobeNewswire) - "Select Program Review: (i) SC291 Oncology (HIP-modified CD19-directed allogeneic CAR T): Enrollment continues in Sana’s ARDENT Phase 1 study for the treatment of B-cell lymphomas and leukemias with clinical data expected in 2023 and 2024 ;(ii) SC262 (HIP-modified CD22-directed allogeneic CAR T): Sana expects to submit an IND in 4Q 2023 for the treatment of B-cell lymphomas and leukemias in patients who have failed CD19-directed CAR T therapies, with preliminary clinical data expected in 2024; (iii) SG299 (in vivo CAR T with CD8-targeted fusogen delivery of a CD19-directed CAR): Sana will continue its focused research on this innovative platform but not submit an IND at this time as previously planned."

Enrollment status • IND • P1 data • Leukemia • Non-Hodgkin’s Lymphoma

Sana Biotechnology Highlights Preclinical Data from Hypoimmune and Fusogen Platforms at the International Society for Stem Cell Research (ISSCR) 2023 Annual Meeting (GlobeNewswire) - "Sana Biotechnology, Inc...announced preclinical data from six presentations, including two oral presentations, at the International Society for Stem Cell Research (ISSCR) 2023 Annual Meeting....In all mice treated, tumor control was initially rapidly achieved with both the unmodified CAR T cells and HIP CAR T cells. However, in mice treated with unmodified CAR T cells, tumor control did not last throughout the study or respond to rechallenge with tumor cells. In contrast, in HIP CAR T cell-treated mice, tumor control was maintained, including following a rechallenge with tumor cells over 80 days after administration of the HIP CAR T cells, demonstrating that the cells persist and remain functional over multiple months in an allogeneic immune system."

Preclinical • Oncology • Solid Tumor

Study Evaluating SC291 in Subjects With r/r B-cell Malignancies (ARDENT) (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Sana Biotechnology

CAR T-Cell Therapy • New P1 trial • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Sana Biotechnology Reports First Quarter 2023 Financial Results and Business Updates (GlobeNewswire) - "SC291 is an ex vivo hypoimmune-modified CD19-directed allogeneic CAR T cell therapy....Began enrollment in the ARDENT Phase 1 study. Granted Fast Track Designation for SC291 by the FDA for the treatment of relapsed/refractory (r/r) large B-cell lymphoma and r/r chronic lymphocytic leukemia."

Fast track designation • Trial status • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Engineered hypoimmune CAR T cells provide lasting tumor control in immunocompetent allogeneic humanized mice even with re-challenge (AACR 2023) - "By contrast, in HIP CD19 CAR T injected mice, tumor control was maintained throughout the study, including following a rechallenge at day 83 with NALM6 cells without further administration of HIP CD19 CAR T cell. Flow cytometry at endpoint from bone marrow and spleen confirmed persistence of HIP CD19 CAR T cells.These findings show that HIP CD19 CAR T cells are immune evasive in allogeneic recipients and data suggest that HIP CD19 CAR T cells are able to persist and maintain efficacy without immunosuppression."

CAR T-Cell Therapy • Preclinical • Oncology • B2M • CD19 • CD47

Sana Biotechnology Highlights Preclinical Hypoimmune Data for its Allogeneic CAR T Platform and Advancements with its In Vivo Fusogen Platform with Four Presentations at the 2023 AACR Annual Meeting (GlobeNewswire) - "Sana Biotechnology...announced data from four presentations at the 2023 American Association for Cancer Research (AACR) Annual Meeting....The poster (abstract 4091)...described preclinical data on hypoimmune (HIP)-modified allogeneic CD19 directed CAR T cells. The study results showed that HIP CD19-directed CAR T cells were functionally immune evasive in allogeneic humanized mouse models. The cells persisted and remained functional over multiple months in an allogeneic immune system, even with tumor re-challenge after 90 days."

Preclinical • Oncology

Sana Biotechnology Announces FDA Clearance of Investigational New Drug Application for SC291, a Hypoimmune-modified, CD19-targeted Allogeneic CAR T Therapy for Patients with B-Cell Malignancies (GlobeNewswire) - "Sana Biotechnology...announced the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application to initiate a first-in-human study of SC291 in patients with various B-cell malignancies....'We expect initial clinical data from the SC291 study later this year and believe insights from this study will better inform our opportunities across the broader platform, both for CAR T cells and for programs outside of cancer such as our pancreatic islet cell therapy for patients with type 1 diabetes'."

IND • New P1 trial • Diabetes • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Sana Biotechnology Reports Third Quarter 2022 Financial Results and Business Updates (GlobeNewswire) - "SC291 (HIP-modified CD19-targeted allogeneic CAR T) – We remain on track to file an IND this year. We intend to study this therapy in a range of B cell malignancies and report data beginning next year....SC276 (HIP-modified, CD22/CD19-targeted allogeneic CAR T) – We remain on track for an IND in 2023."

Clinical data • IND • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology