Slides
Page 1
Uppsala IST Type 1 Diabetes Data Conference Call January 7, 2025
Page 2
2 © 2020-2025 Sana Biotechnology.All rights reserved. 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 regarding the Company’s strategy, expectations, cash runway and future financial condition, future operations, and prospects, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward- looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results to vary materially, including, among others, the risks inherent in drug development such as those associated with the initiation, cost, timing, progress and results of the Company’s current and future research and development programs, preclinical studies, and clinical trials. For a detailed discussion of the risk factors that could affect the Company’s actual results, please refer to the risk factors identified in the Company’s SEC reports, including its Quarterly Report on Form 10-Q dated November 8, 2024. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason. Cautionary Note Regarding Forward-Looking Statements
Page 3
Introduction Steve Harr, MD
Page 4
4 © 2020-2025 Sana Biotechnology.All rights reserved. Sana’s goal is to scale access to engineered cell therapies with curative intent • The impact of ex vivo engineered cell therapy has been limited by the challenges of immune rejection of allogeneic cells • Autologous cell therapy is limited in both scale and types of cells • Immunosuppression with allogeneic cells/organs has significant safety and tolerability challenges • Our hypoimmune platform (HIP) is designed to overcome rejection of allogeneic cells. It also appears to overcome immune recognition in a number of autoimmune disorders • Preclinical data, including in NHP, have provided direct evidence that HIP-edited cells overcome allogeneic immune rejection. Early clinical data with allogeneic CAR T cells have been supportive • We and our partners at Uppsala designed the current investigator-sponsored trial to study whether HIP-edited primary islet cells can evade immune detection, survive, and function in a patient with type 1 diabetes • The study achieved its goal, making us optimistic that a one-time treatment in a patient with type 1 diabetes with HIP- modified, stem-cell derived islets has the potential to lead to normal blood glucose without insulin or immunosuppression • We believe the immune evasion observed in the study is generalizable across many cell types as we continue work across our portfolio
Page 5
5 © 2020-2025 Sana Biotechnology.All rights reserved. 1. Diabetes Control and Complications Trial Research Group et. Al. N Engl J Med 1993; 329:977-986 Type 1 diabetes (T1D) introduction • T1D is caused by autoimmune destruction of insulin-producing beta cells in the pancreas and results in hyperglycemia, requiring lifelong insulin therapy • 8.4M people worldwide have T1D. Incidence is increasing annually, and the prevalence is expected to double over the next 15 years • 80% of individuals with T1D are from high-income countries • Insulin therapy was discovered ~100 years ago, and it has been transformative for patients. However, it is not curative, and patients and their families must be constantly vigilant for both hyperglycemia and hypoglycemia • T1D leads to more than a decade shorter life expectancy despite significant advances such as continuous glucose monitoring, insulin pumps, and novel forms of insulin • Complications directly related to hyperglycemia include microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (coronary artery disease, heart attacks, stroke, poor wound healing, and amputations) issues • At the other extreme, severe hypoglycemia can be rapidly fatal Improvement in glycemic control reduces microvascular complications but increases the risk of hypoglycemia1
Page 6
6 © 2020-2025 Sana Biotechnology.All rights reserved. Advancing Toward A T1D Cure For Broad T1D Population Primary islet transplants provide long-term glucose control, but supply is an issue, and patients require immunosuppression 1. The Goal: A single treatment with long-term normal blood glucose without immunosuppression or insulin therapy Stem-cell derived islets provide a scalable supply, but require still immunosuppression 2. Eliminate the need for immunosuppression 3.
Page 7
7© 2020-2025 Sana Biotechnology.All rights reserved. Allogeneic cell rejection ~75 years of transplants – immune rejection remains the largest problem Lifelong immunosuppression is current standard Genome modification efforts to date have generally been incomplete Autologous therapies have limited scalability and are only available for a small number of cell types Overcoming allogeneic immune rejection has been key limitation in transplant and cellular medicine Sana’s hypoimmune approach + CD47 - MHC I - MHC II Healthy donor cells Hypoimmune cells Disruption of MHC Class I & II expression Overexpression of CD47 1 2 3 Blocks adaptive immune system Blocks innate immune system Current clinical platform with multiple ongoing approaches in research phase.
Page 8
8© 2020-2025 Sana Biotechnology.All rights reserved. Preclinical study showed HIP-modified allogeneic islet cells can control glucose in an NHP model Type 1 diabetes is a disease of missing pancreatic beta cells Abbreviations: NHP, non-human primate; STZ, Streptozotocin Hu et al., 2024, Cell Stem Cell 31, 334–340 Study Design (N=1) NHP treated with STZ Glucose stabilized with exogenous insulin Allogeneic NHP primary islet cells isolated and HIP-modified Cells injected intramuscularly without immunosuppression STZ injection eliminates insulin production Transplant HIP- modified NHP islets Stabilize animal on exogenous insulin Insulin independence Key goals of study Demonstrate survival and function of HIP- modified allogeneic islet cells in diabetic NHP without immunosuppression Demonstrate long-term glucose normalization in diabetic NHP without exogenous insulin or immunosuppression Demonstrate the principle of graft ablation/safety switch with anti-CD47 antibody
Page 9
9© 2020-2025 Sana Biotechnology.All rights reserved. Study Design (N=1) • NHP primary islet cells isolated and HIP-modified • Cells injected intramuscularly into a diabetic, allogeneic NHP without immunosuppression Fasting glucose Preclinical study: survival & function of allogeneic hypoimmune pancreatic islet cells in diabetic NHP 6 months without immunosuppression STZ administration Cell transplantation Normal Hypoglycemia Impaired glucose tolerance Hyperglycemia anti-CD47 antibody administration Insulin DependentInsulin IndependentInsulin Dependent AM PM Serum C-peptide pre STZ post STZ* D0 D7 D14 D28 D42 M3 M5 M6 D7 D14 D28 D38 0 1 2 3 4 ng/ml After anti-CD47 antibody After islet cell transplantation Diabetic NHP Normal * Hu et al., 2024, Cell Stem Cell 31, 334–340
Page 10
UP421 – World’s first HIP-edited primary islet transplantation Interim Analysis 4 weeks after transplantation Sonja Schrepfer, MD, PhD on behalf of the Sana Team and the Uppsala/Oslo Team Note: Some data are verbally reported values and could slightly differ from CRF (which will show final documented values). The Leona M. and Harry B. Helmsley Charitable Trust generously provided support for the clinical trial.
Page 11
11© 2020-2025 Sana Biotechnology.All rights reserved. ▪ Study: Single arm, open label, Ph1 IST, 1 patient ▪ Product: ATMP (UP421) with allogeneic, HIP islet cells ▪ Primary endpoint: Safety (number of treatment-related adverse events, CTCAE grade ≥3) ▪ Secondary endpoints: Immune evasion and cell survival (stable C-peptide and signal in MRI) ▪ Dose: 25-80M. To focus on safety, trial dose will be between 2% and 7% of islet cells needed for insulin independence in intraportal location1,2 ▪ Location: intramuscular (IM; forearm muscle) ▪ Sponsor: Uppsala University Hospital (PI: Dr. Per-Ola Carlsson) Clinical study design First-in-human safety study of allogeneic HIP pancreatic islet transplantation in adult patient with type 1 diabetes (no immunosuppression) Study details Interim analysis 1 2 3 UP421 i.m. transplantation without immunosuppression 1. Shapiro A.M. James et al. N Engl J Med 2000.343:4; 230-238. 2. Pisania A et al. Laboratory Investigation 2010;90:1661–1675. ClinicalTrials.gov Identifier: NCT06239636
Page 12
12© 2020-2025 Sana Biotechnology.All rights reserved. Key Details Parameter Donor Information Blood type O+ Ischemia time 5 hours 11 mins Gender male Age 61 Islet Purity 86% HbA1c 42mmol/l (6%) Parameter Recipient Information T1D diagnosis 1987 Blood type O+ Gender male Age 42 HbA1c 96mmol/l (10.9%) Procedure performed at Uppsala University Hospital took 90 mins Transplantation on December 2nd, 2024
Page 13
13© 2020-2025 Sana Biotechnology.All rights reserved. All interim primary and secondary endpoints were met Endpoints D7 D14 D21 D28 Safety (no AE/SAE related to drug) Cell survival/function (C-peptide) Graft visibility (MRI) Not performed (as per protocol) Adaptive immune evasion Innate immune evasion Primary and Secondary Endpoints - Data Summary
Page 14
14© 2020-2025 Sana Biotechnology.All rights reserved. Basal C-peptide in peripheral blood Summary: No detectable C-peptide before transplantation; present and stable C-peptide observed after transplantation. Baseline: Below limit of detection (LOD).Sensitivity: 0.48 pmol/L. Dots represent technical triplicates. C-peptide analyzed in serum. Stable C-peptide after HIP islet cell transplantation demonstrates survival and function of cells
Page 15
15© 2020-2025 Sana Biotechnology.All rights reserved. Baseline: Below limit of detection (LOD).Sensitivity: 0.48 pmol/L. Standard deviation represent technical triplicates. C-peptide analyzed in plasma samples. Increased C-Peptide Levels with a Mixed Meal Tolerance Test (MMTT) after transplantation Summary: Pre-transplantation, C-peptide is below detection limit during MMTT. 28 days after UP421 transplantation, C-peptide is present and stimulated by MMTT.
Page 16
16© 2020-2025 Sana Biotechnology.All rights reserved. Day 28 MRI showing further evidence of graft survival MR T2-STIR-weighted trans images showing signal in musculus brachioradialis after injection of UP421 The MR T2-STIR-weighted sequence is sensitive to water and fluid and is a fat suppression technique to suppress the high signal from fat. D28 MRI showing several punctual signals at the site of graft injection, no inflammation and no safety/ pathological related observations red arrows indicate the location of some examples of injected cells
Page 17
17© 2020-2025 Sana Biotechnology.All rights reserved. Immune analysis was performed using donor islet cells and patient’s immune cells CD47HLA I HLA II + CD47 HLA I HLA II CD47HLA I HLA II Donor Immune analysis using patient’s (recipient) immune cells after transplantation HIP islet cells dKO islet cells WT islet cells ▪ T cells ▪ Donor-specific antibodies ▪ Natural killer cells ▪ Whole blood *Mixed cell population in drug product allows for detailed immune analysis*
Page 18
18© 2020-2025 Sana Biotechnology.All rights reserved. WT islet cells: Patient’s T cells are activated and kill WT islet cells with peak at 7 days after transplant no killing killing D7Baseline no killing no killing no killing no killing Baseline BaselineD7 D7 Adaptive Immunity: HIP islet cells evade patient's T cell response up to 28 days after transplantation dKO islet cells: No killing of HLA deficient cells by patient’s T cells HIP islet cells: No killing of HIP islet cells by patient’s T cells D14 D14 D14 D21 D21 D21 D28D28D28 killing no killing no killing killing killing no killing no killing no killing no killing
Page 19
19© 2020-2025 Sana Biotechnology.All rights reserved. WT islet cells: Patient’s B cells produce donor-specific antibodies (switch from IgM to IgG at D14) Adaptive Immunity: No patient donor-specific antibodies against HIP islet cells up to 28 days after transplantation dKO islet cells: No binding of donor-specific antibodies to HLA deficient cells IgM IgM IgM IgG IgG IgG HIP islet cells: No binding of donor- specific antibodies to HIP islet cells
Page 20
20© 2020-2025 Sana Biotechnology.All rights reserved. no killing no killing killing D28 Baseline Baseline Baseline D28 D28 Results from D7, D14, and D21 timepoints are similar to the D28 results in each assay. WT islet cells: No killing of WT cells by patient’s NK cells dKO islet cells: Patient’s NK cells are killing HLA I/II deficient cells (due to “missing-self”) HIP islet cells: No killing of HIP islet cells by patient’s NK cells killing no killingno killing Innate Immunity: HIP islet cells evade patient's NK cell response up to 28 days after transplantation
Page 21
21© 2020-2025 Sana Biotechnology.All rights reserved. no killing no killingkilling Adaptive and innate immunity: No detectable immune response in the patient toward HIP islet cells D28 Baseline Baseline Baseline D28 D28 PBMC (containing all immune cell populations) plus serum (containing antibodies and complement) killing assay. WT islet cells: Adaptive immune killing dKO islet cells: Innate immune killing HIP islet cells: No immune response killingkilling no killing Results from D7, D14, and D21 timepoints are similar to the D28 results in each assay.
Page 22
22© 2020-2025 Sana Biotechnology.All rights reserved. HIP cells overcome patient's allogeneic and autoimmune barrier Video Donor islet cells with editing profile in column title NK cellsActual assay time = 4 hours. D7 sample. PBMC (containing all immune cell populations) plus serum (containing antibodies and complement) killing assay. Still image before movie
Page 23
23© 2020-2025 Sana Biotechnology.All rights reserved. HIP cells overcome patient's allogeneic and autoimmune barrier Video Donor islet cells with editing profile in column title NK cellsActual assay time = 4 hours. D7 sample. PBMC (containing all immune cell populations) plus serum (containing antibodies and complement) killing assay. Still image after movie
Page 24
24© 2020-2025 Sana Biotechnology.All rights reserved. Summary ▪ Transplantation of HIP primary islet cells is safe with no AE/SAE related to the drug product ▪ Stable C-peptide after transplantation and increase after Mixed Meal Tolerance Test (MMTT) demonstrate survival and function of HIP islet cells (supported by MRI) ▪ Drug product is a mixture of partially and fully gene edited islet cells: ▪ Immune responses against all partially edited islet cells ▪ HIP primary islet cells evade allogeneic and autoimmune responses in spite of rejection of partially edited islet cells This first-in-human proof-of-concept study for the HIP platform shows that transplanted fully allogeneic islet cells survive and function without any immunosuppression. My hope for the future: Off-the-shelf therapies without the need for immunosuppression for Anyone, Anytime, Anywhere". Sonja Schrepfer Dec. 2nd with UP421 © 2020-2025 Sana Biotechnology.All rights reserved.
Page 25
SC451 Program Dhaval Patel, MD, PhD
Page 26
26© 2020-2025 Sana Biotechnology.All rights reserved. Sana’s approach to treat type 1 diabetes Make hypoimmune islet cells from well- characterized PSC line 1 + CD47MHC I MHC II Manufacture at scale 2 Deliver as a one-time IM therapy without immunosuppression 3 SC451 program – HIP stem cell-derived islet cell therapy – delivered with no immunosuppression • We are taking the time to get it right the first time • We believe that this therapy can transform the life of every type 1 diabetic if we can successfully develop and build the needed scale
Page 27
27© 2020-2025 Sana Biotechnology.All rights reserved. Four major challenges to realizing the vision of SC451 1. Overcoming immune rejection without immunosuppression. • We believe this challenge has now been solved. 2. Differentiating PSCs into islet cells at a purity, potency and yield to enable clinical trial dosing. • Many groups have done this successfully and so has Sana. 3. Generating a gene-modified master cell bank (MCB) from a GMP-compliant PSC line that is genetically stable and remains so after gene editing and differentiation into islet cells. • We have done it in research. 4. Manufacturing enough product to treat the patients that need it. • We’re working on the challenges of manufacturing at scale
Page 28
© 2020-2025 Sana Biotechnology.All rights reserved. HIP-modification, differentiation and expansion of PSC-derived islet cells HLA-I HLA-II CD47 74.1-fold NK-cells 15 30 45 60 75 90 -0.5 0.0 0.5 1.0 1.5 hours normalized cell index No killing Macrophages 15 30 45 60 75 90 -0.5 0.0 0.5 1.0 1.5 hours normalized cell index No killing Expected results DTZ Stain Insulin 1 Vial of Banked Cells Yield Billions of Islet Cells
Page 29
29© 2020-2025 Sana Biotechnology.All rights reserved. PSC differentiated islet cells transplanted into muscle engraft and are vascularized H&E blood vessels (mouse CD31) blood vessels Muscle tissue blood vessels H&E D10
Page 30
30© 2020-2025 Sana Biotechnology.All rights reserved. 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 0 200 400 600 Time post-transplant (weeks) Blood Glucose (mg/dL) Diabetic ULOQ STZ iPSC-islets Diabetic (STZ) control *ULOQ: upper limit of quantification; Diabetic threshold at 250 mg/dL; data reported as mean ± S.E.M. **plasma human c-peptide after 5 hr fast (pre) and 30 min after I.P. 3 g/kg dextrose bolus (post); data is mean ± S.D. nonfasted blood glucose* glucose-stimulated human c-peptide** graft morphology performed at week 51 pre- glucose post- glucose 0 500 1000 1500 2000 human c-peptide (pM) c-peptide hCD47 c-peptide hCD47 HIP-modified PSC differentiated islet cells transplanted into muscle persist and control blood glucose in mice for >64 weeks • Maintain normoglycemia (64+ weeks) Secrete c-peptide in response to glucose • Retain strong expression of hCD47 Densely vascularized blood vessels human nuclei D458
Page 31
Clinical Context Gary Meininger, MD