Sana Biotechnology, Inc. · NASDAQ:SANA
Sana Biotechnology — Investor Presentation (September 2023)
47 slides from Sana Biotechnology's investor presentation, Sep 13, 2023
Slide 1: Corporate Presentation September 2023
Corporate Presentation September 2023 Exhibit 99.1
Slide 2: Cautionary Note Regarding Forward-Looking Statements
This presentation contains forward-looking statements about Sana Biotechnology, Inc. (the “Company,” “we,” “us,” or “our”) within the meaning of the federal securities laws. All statements other than statements of historical facts contained in this presentation, including, among others, statements r
Slide 3: Engineered Cells as Medicines
Sana’s ambition is to repair or replace any cell in the body. Technologies address fundamental barriers: Hypoimmune (HIP) technology: Overcoming immune rejection of allogeneic cells Fusogen technology: In vivo delivery of genomic modification reagents in a cell-specific manner Overcoming immune reje
Slide 4: Pipeline poised to deliver multiple clinical data readouts over next several years
Pipeline poised to deliver multiple clinical data readouts over next several years Sana’s platforms, technology, and programs 1IST, investigator sponsored trial. Abbreviations: ALL, acute lymphoblastic leukemia; CLL, chronic lymphocytic leukemia; HD, Huntington’s disease; IND, investigational new dr
Slide 5: Immune rejection remains the largest problem in transplant and cellular medicine
~75 years of organ and bone marrow transplants – immune rejection remains the largest problem Cell-based medicines face similar immune rejection challenges Significant immunosuppression is current standard Genome modification efforts to date have generally been incomplete Autologous therapies have l
Slide 6: Sana's hypoimmune solution: Leverage insights from nature
Sana’s hypoimmune solution: Leverage insights from nature Abbreviations: MHC, major histocompatibility complex. Current clinical platform with multiple ongoing approaches in research phase. Leverage insights from nature to create hypoimmune cells Sana’s hypoimmune approach + CD47 - MHC I - MHC II He
Slide 7: Sana's HIP modifications offer superior protection from innate cell killing
+ CD47KI + PD-L1KI + HLA-EKI + HLA-GKI + HLA-CKI HLA-I/II KO in all cells below – + PVRKo Sana’s HIP modifications offer superior protection from innate cell killing Allogeneic human iPSC without HLA (triggering innate immune response through “missing self”) Abbreviations: HLA, human leukocyte antig
Slide 8: Strategies to overcome the missing self innate immune response
No additive effect with multiple molecules Strategies to overcome the “missing self” innate immune response HLA-I/II KO + CD47KI + HLA-CKI + PVRKO + HLA-EKI + PD-L1KI + PVRKO + HLA-EKI + PVRKO + HLA-GKI +PD-L1KI + PVRKO + HLA-GKI + PVRKO + HLA-EKI + PD-L1KI + PD-L1KI + PVRKO + HLA-GKI + PD-L1KI Allo
Slide 9: Hypoimmune cells evade rejection by adaptive and innate immune system in mice
Hypoimmune cells evade rejection by the adaptive and innate immune system in mice Deuse et al. Nature Biotechnology. 2019 T cell activation (ELISPOT) No systemic T cell activation with HIP cell transplantation IgM Binding (FACS) No binding of donor-specific antibodies against HIP cells NK cell killi
Slide 10: Hypoimmune cells survive in vivo in NHP while unmodified iPSCs get rejected
Hypoimmune cells survive in vivo when transplanted in NHP while unmodified iPSCs get rejected CO, cross over; Txp, transplant Hu et al. Nature Biotechnology. 2023 A Photos/s (*106) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 105 106 107 108 Weeks Hypoimmune iPSCs D0 (day of txp) 2 wks (after txp) 5 wks (afte
Slide 11: HIP islet cells transplanted into NHPs (10 months)
HIP islet cells transplanted into NHPs (10 months) D0 12 wks 28 wks 40 wks WT results (no survival after 1 wk) D0 1 wk n=1 HIP primary islet cells; n=1 WT primary islet cells. Survival of allogeneic hypoimmune pancreatic islet cells for 10+ months without immunosuppression Study design: NHP primary
Slide 12: Survival and immune evasion after transplant for different cell types in NHP studies
Survival and immune evasion after transplant for different cell types in multiple NHP studies Abbreviations: RPE, retinal pigment epithelium. HIP primary islets HIP iPSC-derived RPE HIP iPSC-derived cardiomyocytes HIP iPSC
Slide 13: Sana's team has pioneered hypoimmune technology
Sana’s team has pioneered hypoimmune technology
Slide 14: Hematologic cancers continue to have a high unmet need
Challenges Autologous CAR T cell scalability Many patients fail CAR T treatment Allogeneic CAR T cells immune rejection limits persistence and efficacy Opportunity Known targets Known efficacy and safety bar Sana’s HIP CAR T platform can address challenges and exploit opportunities Hematologic cance
Slide 15: HIP CD19 CAR T cells demonstrate persistence and efficacy in humanized mice
D55 D87 D75 D83 SC291 tumor control comparable at early timepoints to standard CD19 CAR T cells SC291 tumor control superior at later timepoints to standard CD19 CAR T cells SC291 controls tumors when animals are rechallenged with tumor HIP CD19 CAR T cells demonstrate persistence and continued effi
Slide 16: ARDENT trial will provide rapid insight into hypoimmune immune evasion
ARDENT trial will provide rapid insight into hypoimmune immune evasion SC291 is a mixture of HIP and non-HIP CAR T cells HIP CAR T cells survive after immune recovery T cells and NK cells recover Triple Knockout and CAR expression: 40-50% are fully modified cells 80-85% have all three gene knockouts
Slide 17: CAR T cells remain detectable in majority of patients in ZUMA-1
Locke et al. Lancet Oncology. 2019 CAR T cells remain detectable in the majority of patients with ongoing response treated in ZUMA-1 trial Patients with CAR gene-marked cells (%) Month n=37 n=37 n=33 n=34 n=34 n=33 n=31 n=32
Slide 18: SC291: Sana's CD19 HIP allogeneic CAR T
SC291: Sana’s CD19 HIP allogeneic CAR T First clinical data in 2023 Data show CAR T cell persistence correlates with long term complete response (CRs) rates1 Improved persistence can lead to best-in-class allogeneic CAR T platform CAR T Persistence Potential Efficacy Outcome ≤ 1 month Comparable to
Slide 19: CAR T cells have potential to transform autoimmune disorders
CAR T cells have the potential to transform autoimmune disorders like they have in blood cancers Depth of B-cell depletion correlates with clinical benefit CD19 CAR T cell therapy results in deep B-cell depletion Potential to deliver durable long-term remissions SC291 has the scale and potential pro
Slide 20: Autologous CD19 CAR T results in drug-free remission in refractory SLE
Autologous CD19 CAR T therapy results in drug-free remission in refractory SLE patients Abbreviations: SLE, systemic lupus erythematosus; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome. Mackensen et al. Nature Medicine. 2022 Improvement in signs and sym
Slide 21: SC291 offers potential to address unmet need in autoimmune disorders
SC291 product candidate offers potential to address large unmet need in various autoimmune disorders SC291: CD19 HIP allogeneic CAR T for treatment of autoimmune disorders Allogeneic HIP CAR T cell MHC I MHC II TCRα + CD19 CAR + CD47 >75 different types of autoimmune disorders with high unmet need a
Slide 22: SC262: Targeting patients with inadequate response to CD19 therapy
SC262: Targeting growing population of patients with inadequate response to CD19 therapy 1US, EU5, and Japan. 2Clarivate DRG NHL Market Forecast Nov 2021; 2027 Forecast is 2L+ LBCL patients; internal analysis of secondary EPI data. 3Di Blasi et al. Blood.2022; DESCAR-T registry. ~65% ~35% 100% ~12K
Slide 23: SC262: Licensed CD22 CAR produced strong clinical data in CD19 failures
2023 DAVA Frank/Stanford SC262 Goals: File IND this year; clinical data in 2024 N=38 SC262: Licensed CD22 CAR produced strong clinical data in CD19 failures when part of autologous CAR T N=16 N=21 >50% 6-month CR rate in CD19 CAR failure DLBCL patients High rate of CRs in CD19 failure ALL patients ~
Slide 24: SC255: Licensed BCMA CAR produced strong clinical data in myeloma
SC255: Licensed BCMA CAR produced strong clinical data in myeloma when part of autologous CAR T 4 3 ORR: 98.9% 5 ORR: 96% ORR: 75% Total N=101 SC255 Goal: File IND as early as 2024 Prior CAR T n=12 No prior CAR T n=89 1 ~82.4% patients MRD negative at 12 months ~87.3% patients in CR/sCR with median
Slide 25: HIP platform can create a regenerative pipeline for allogeneic CAR T therapies
Sana’s HIP platform can create a regenerative pipeline for allogeneic CAR T therapies 1~450 doses assumes the middle dose in the ARDENT Phase 1 study and ~950 doses assumes an autoimmune dose consistent with public data on current autoimmune dose levels. Abbreviations: Cas12b, CRISPR associated prot
Slide 26: Type 1 diabetes represents a large unmet need
Disease caused by autoimmune destruction of insulin-producing beta cells in the pancreas; results in inability to control blood glucose Type 1 diabetes is a large unmet need with 1.9M patients in the U.S. and 2.4M in Europe2 Long-term complications: end-organ damage, including heart attack, stroke,
Slide 27: SC451: allogeneic iPSC-derived hypoimmune pancreatic islet cell therapy
Sana’s solution: SC451 is an allogeneic iPSC-derived hypoimmune pancreatic islet cell therapy Hu et al. Nature Biotechnology. 2023 Differentiate iPSCs into glucose-responsive islet cells that are hypoimmune + CD47 HLA I HLA II Hypoimmune iPSC-derived islet cells Create iPSC GMP master cell bank Star
Slide 28: HIP islet cells transplanted into NHPs (10 months)
HIP islet cells transplanted into NHPs (10 months) D0 12 wks 28 wks 40 wks WT results (no survival after 1 wk) D0 1 wk n=1 HIP primary islet cells; n=1 WT primary islet cells. Survival of allogeneic hypoimmune pancreatic islet cells for 10+ months without immunosuppression Study design: NHP primary
Slide 29: Proprietary type 1 diabetes model: unmodified islet cells do not survive
D0 D3 D7 D5 D9 No glucose control Patient T cells eliminate islet cells due to autoimmunity Sana’s immunology, gene modification, & stem cell capabilities create proprietary type 1 diabetes model Abbreviations: T1DM, type 1 diabetes mellitus Hu et al. Sci Transl Med. 2023 Patient with T1DM PBMCs Aut
Slide 30: HIP islet cells from T1DM patient evade autoimmune killing and control glucose
D7 D0 D23 D29 D13 HIP iPSC-derived pancreatic islet cells from patient with T1DM evade autoimmune killing and control glucose Abbreviations: BLI, bioluminescence imaging Hu et al. Sci Transl Med. 2023. BLI: Islet Survival C-peptide Glucose Control
Slide 31: HIP-modified allogeneic islet cells normalize glucose in diabetic NHP
HIP-modified allogeneic islet cells lead to normal blood glucose with no insulin and no immunosuppression in diabetic NHP Normal Hypoglycemia Impaired fasting glucose Hyperglycemia D78 Cell transplantation D85-D89 Reduce exogenous insulin D0 STZ D3 Start exogenous insulin Study Design (N=1) NHP prim
Slide 32: Investigator sponsored trial of primary human HIP islet cells in type 1 diabetes
Investigator sponsored trial Primary human HIP islet cells transplantation in type 1 diabetes patients Goal: Cell survival with no immunosuppression Goal: Data in 2023 Insight for SC451 Path to potential clinical validation of hypoimmune islet cells in T1DM patients in 2023 Cell survival & immune ev
Slide 33: Goal is to build a best-in-class portfolio across cancers and autoimmune diseases
Goal is to build a best-in-class portfolio to treat patients with a range of cancers, autoimmune diseases, and beyond 1Avezbakiyev et al. Blood. 2022 2Durie et al. The Oncologist. 2020 Unlocking the potential of our hypoimmune platform across multiple patient populations Value Time CD19 CD22 BCMA Au
Slide 34: Fusosome technology: cell-specific in vivo delivery platform
Fusosome technology: Development of cell-specific in vivo delivery platform Source: CDC website 3 2 1 Sana approach: Leverage insights from nature to deliver various payloads to specific cells F G Fusosome
Slide 35: Fusogen technology may eliminate conditioning chemotherapy and ex vivo manufacturing
Fusogen technology has potential to eliminate conditioning chemotherapy and ex vivo manufacturing Current ex vivo approaches have limitations Fusogen platform offers potential to overcome these limitations June et al. Annu Rev Med. 2014
Slide 36: T cell fusosome delivers CAR construct directly to T cells in vivo
T cell fusosome delivers CAR construct directly to T cells in vivo CAR activity Expression/recognition Amplification Target cell killing Target cell killing T cell amplification Specificity CD4/CD8 T cell transduction Expression Transgene integration and CAR expression Function Targeted cell killing
Slide 37: IV CD19 CAR by fusosome clears B cell tumors in humanized mice
IV administration of CD19 CAR delivered by fusosome can clear B cell tumors in humanized mice comparably to ex vivo CD19 CAR T Saline SG295 & Activated PBMC SG295 & Non-Activated PBMC CD19 CAR delivered by fusosome: in vivo CD19 CAR T: ex vivo Saline CD19 CAR T D3 D7 D15 D19 D27 D7 D10 D17 D24 D31
Slide 38: CD19 CAR delivered by fusosome, SG299
Significant improvements may lead to a better therapy: CD19 CAR delivered by fusosome, SG299 Abbreviations: TU, transduction units. Potential for: Better efficacy Greater safety Higher yields and lower cost of goods SG299 results in >50X potency improvement SG299 transduces more T cells at the same
Slide 39: Tumor control with fusosomes targeting other cell types and antigens
Tumor control achieved with fusosomes targeting other cell types and alternate tumor antigens CD4 T cell targeting fusosomes delivering CD19 CAR achieve tumor control in mice CD8 T cell targeting fusosomes delivering CD22 CAR achieve tumor control in mice Nalm6 Tumor Only Nalm6+ PMBC (Mock) CD4-CD19
Slide 40: Sana aspiration: Engineered cells as medicines
Sana aspiration: Engineered cells as medicines 1Does not incorporate hypoimmune genomic modifications Allogeneic CAR T Franchise Oncology: SC291, SC262, SC255 Autoimmune: SC291 Stem Cell-Derived Type 1 Diabetes: SC451 CNS: SC3791 In vivo CAR T: SG299 Cell-specific in vivo HSC editing: SG418 Cell-spe
Slide 41: Thank You
Thank You Sana Biotechnology www.sana.com a N a Biotechnology
Slide 42: Appendix
Appendix ee @ ee8@ e©@e@@ e©e8 OM) ee8@ °.° Ws °.° @ e@ CX 2 e@ *e e3°@ Cn ee) e @ @ e e on e : atmteenete ° ee @ @ eee eé ee @ . 0 © © e Oo: Cc 0: 2)
Slide 43: Overcoming the allogeneic immune barrier is crucial for off-the-shelf approaches
Overcoming the allogeneic immune barrier is crucial for off-the-shelf approaches Fetomaternal border proteins: MHC downregulation Indolamin-di-oxygenase (IDO) Fas-L PD-L1 HLA-E HLA-G HLA-C CD47 CCL-22 CEA TRAIL Galectin-1 CD155 Etc. MHC downregulation or KO+ Indolamin-di-oxygenase (IDO) Fas-L PD-L1
Slide 44: Only subpopulations of NK cells express receptors for HLA and PD-L1
Receptors expressed on % NK cells PD-L1 HLA-E HLA-G HLA-C PVR CD94 CD47 SIRPa DNAM-1 PD-1 ILT2 KIR2DL 33.4% 28.1% 61.8% 3.2% 38.7% Only subpopulations of NK cells express the appropriate receptors for HLA-C, HLA-E, HLA-G, PD-L1, PVR 99.9% SSC KIR2DL SSC CD94 SSC ILT2 SSC PD-1 SSC SIRPa SSC DNAM-1 De
Slide 45: Persisting CAR T cells are solely HIP phenotype
Persisting CAR T cells are solely HIP phenotype *HIP cells = HLA-I/II neg and CD47 OE; Hu et al. Nature Communications. 2023 CAR+ Cells in Spleen All Surviving CD19 CAR T cells in Spleen on D95 are HIP* CAR+ Cells in Bone Marrow All Surviving CD19 CAR T Cells in Bone Marrow on D95 are HIP* Bulk HIP
Slide 46: Humanized immune system provided proof of concept of HIP CAR T cell selection
Humanized immune system provided preclinical proof of concept of HIP-modified CAR T cell selection D55 D87 D75 D83 D0: Nalm6 D15 D27 Unmodified CD19 CAR T Cells Unmodified T Cells HIP CD19 CAR T Cells tumor cell re-injection Surviving CD19 CAR T cells in Spleen on D95 are HIP Surviving CD19 CAR T Ce
Slide 47: NK cells recover within thirty days of CD19 CAR T cell therapy
NK cells recover within thirty days of CD19 CAR T cell therapy Logue et al. Hematologica. 2021 (Data from 85 Yescarta® patients treated at Moffitt Cancer Center between 2016 and 2019) CD56 value measures NK cells
Sana Biotechnology — Investor Presentation (September 2023) on 6ix