Sana Biotechnology, Inc 8-K, filed Oct 10, 2023
Sana Biotechnology, Inc. (SANA)
About this 8-K
Sana Biotechnology, Inc filed this 8-K on October 10, 2023.
Items reported
- Item 2.05: Exit or restructuring costs
- Item 7.01: Regulation FD disclosure
- Item 9.01: Financial statements and exhibits
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
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| Item 2.05 | Costs Associated with Exit or Disposal Activities |
On October 10, 2023, Sana Biotechnology, Inc. (“Sana”) announced a portfolio update to increase its focus on its ex vivo cell therapy product candidates. As part of the portfolio update, Sana plans to reduce its near-term investment in its fusogen platform for in vivo gene delivery, including by delaying the investigational new drug (IND) filing for its SG299 program, and reduce its workforce by approximately 29%. Sana anticipates that the portfolio update and associated reduction in force will be substantially complete by the fourth quarter of 2023, which is expected to result in 2024 operating cash burn of less than $200.0 million.
In connection with the portfolio update, Sana anticipates it will incur approximately $5.1 million and $1.7 million of cash-based expenses related to employee severance, benefits and related costs in the fourth quarter of 2023 and the first quarter of 2024, respectively. Sana will file an amended Current Report on Form 8-K if amounts differ materially from these estimates.
| Item 7.01 | Regulation FD Disclosure. |
On October 10, 2023, Sana issued a press release announcing its portfolio update, a copy of which is furnished as Exhibit 99.1 to this Current Report on Form 8-K (this “Current Report”) and is incorporated by reference herein.
On October 10, 2023, Sana released an updated corporate presentation (the “Corporate Presentation”), a copy of which is furnished as Exhibit 99.2 to this Current Report and is incorporated by reference herein.
The information furnished under Item 7.01 of this Current Report, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (“Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any other filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Cautionary Note Regarding Forward-Looking Statements
This Current Report contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding (i) Sana’s expected 2024 operating cash burn, including expectations regarding the effect of the portfolio update thereon; (ii) the scope and the timing of the portfolio update; and (iii) the scope and timing of expected cash-based expenses and charges for employee severance and benefits and other costs related to the portfolio update, which are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. For a discussion of these risks and uncertainties, and other important factors, any of which could cause Sana’s actual results to differ from those contained in the forward-looking statements, see the discussions of potential risks, uncertainties and other important factors in Sana’s Annual Report on Form 10-K for the year ended December 31, 2022, and in subsequent filings with the SEC. Forward-looking statements in this Current Report are made as of the date of this Current Report and Sana undertakes no duty to update any such statements unless required by law.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
See the Exhibit Index below, which is incorporated by reference herein.
EXHIBIT INDEX
| Exhibit Number |
Description | |
| 99.1 | Press Release of Sana Biotechnology, Inc. dated October 10, 2023 | |
| 99.2 | Corporate Presentation of Sana Biotechnology, Inc. dated October 10, 2023 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| Sana Biotechnology, Inc. | ||||||
| Date: October 10, 2023 | By: | /s/ Bernard Cassidy | ||||
| Bernard Cassidy | ||||||
| Executive Vice President and General Counsel | ||||||
Exhibit 99.1
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
Increasing focus on ex vivo cell therapy platform based on extensive preclinical and early translational clinical data suggesting ability of hypoimmune (HIP)-modified cells to evade immune detection
Human proof of concept data in multiple clinical settings – including oncology, autoimmune diseases, and type 1 diabetes – expected in 2023 and 2024
IND submitted to investigate SC291 in multiple B-cell-mediated autoimmune diseases with initial proof of concept data expected in 2024
Enrollment continues in SC291 Phase 1 ARDENT trial in patients with refractory B-cell malignancies with data expected in 2023 and 2024
CTA submitted for investigator sponsored trial exploring HIP-modified primary islet cells in patients with type 1 diabetes; on track for initial HIP proof of concept data in 2023 and 2024
IND submission for SC262 in patients with B-cell malignancies who have failed a CD19 therapy on track for this quarter with initial proof of concept data expected in 2024
Reducing near-term investment on fusogen in vivo delivery platform clinical and preclinical programs, including delaying SG299 IND (in vivo CD19 CAR T)
2024 operating cash burn expected below $200 million following approximately 29% headcount reduction and decreased expenses related to the fusogen platform
SEATTLE, October 10, 2023 — Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on changing the possible for patients through engineered cells, today announced a portfolio update, including both increased focus on its ex vivo cell therapy product candidates and an IND submission for SC291 in autoimmune diseases. Sana is positioned to generate clinical proof of concept from multiple programs in 2023 and 2024, with a goal of better understanding its allogeneic HIP CAR T programs in blood cancers, allogeneic HIP CAR T program in autoimmune diseases, and HIP pancreatic islet cells in type 1 diabetes. The company will reduce near-term spend on its fusogen platform for in vivo gene delivery, which postpones the planned SG299 IND and decreases its expected forward operating burn.
“We have increased confidence in the potential of our HIP platform, and near-term, we are increasing focus on three therapeutic areas that utilize this platform and have the potential to address large unmet needs with curative intent – allogeneic CAR T cells in oncology, allogeneic CAR T cells in autoimmune diseases, and pancreatic islet cell transplantation in type 1 diabetes. We plan to present clinical data in these areas at various times across 2023 and 2024,” said Steve Harr, President and CEO of Sana. “The SC291 IND submission for the treatment of
autoimmune diseases positions us to move into the rapidly emerging opportunity of utilizing CAR T cells in these large and underserved populations, leveraging the investments we have made to date in the HIP platform, T cell therapeutics, and scaled manufacturing that can produce hundreds of patient doses per run. We need to ensure that we have a financeable cost structure with these emerging opportunities factored in, and this strategic re-positioning enables us to deliver significant clinical data across multiple drug candidates with the current balance sheet. These changes unfortunately mean that many talented and valued colleagues will depart the company, and we thank them for their contributions and commitment to our mission.”
Select Program Review
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.
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.
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.
HIP-modified primary islet cells for the treatment of type 1 diabetes: A CTA has been submitted for an investigator sponsored trial exploring the potential of HIP modifications to allogeneic primary islet cells to enable immune evasion and overcome transplant rejection in type 1 diabetes; proof of concept data expected in 2023 and 2024.
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.
2024 Operating Burn Guidance
Sana expects 2024 operating cash burn to be below $200 million, allowing the current cash position to extend further into 2025. The strategic re-positioning will reduce headcount by approximately 29% while allowing the company to invest in clinical capabilities across multiple indications in oncology, autoimmune diseases, type 1 diabetes, and central nervous system disorders. Sana will leverage its existing allogeneic manufacturing expertise and continue development of its GMP manufacturing facility in Bothell, Washington.
About Sana Biotechnology
Sana Biotechnology, Inc. is focused on creating and delivering engineered cells as medicines for patients. We share a vision of controlling genes, replacing missing or damaged cells, and making our therapies broadly available to patients. We are a passionate group of people working together to create an enduring company that changes how the world treats disease. Sana has operations in Seattle, Cambridge, South San Francisco, and Rochester. For more information about Sana Biotechnology, please visit https://sana.com/.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements about Sana Biotechnology, Inc. (the “Company,” “we,” “us,” or “our”) within the meaning of the federal securities laws, including those related to the Company’s vision, progress, and business plans; expectations for its development programs, product candidates and technology platforms, including its pre-clinical, clinical and regulatory development plans and timing expectations, including with respect to the expected timing of IND submissions for the Company’s product candidates; the Company’s expectations regarding the timing, substance, and impact of the data from its clinical trials as well as the investigator sponsored trial exploring HIP-modified primarily islet cells in patients with type 1 diabetes; the potential ability of HIP-modified cells to evade immune detection and overcome allogeneic rejection; the Company’s expected 2024 operating cash burn; the potential impact of the Company’s reduction in its near-term spend on the fusogen program, including on the timing of an IND submission for the SG299 program and the Company’s forward operating burn; the Company’s expectations with respect to the potential therapeutic benefits and impact of its development programs and platforms, including in various indications; the potential of SC291 to treat autoimmune diseases; the potential impact of the portfolio update on the Company’s clinical and manufacturing capabilities; and the Company’s future plans with respect to its SG299 program. All statements other than statements of historical facts contained in this press release, 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 and clinical trials, as well as economic, market and social disruptions. 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 but not limited to its Quarterly Report on Form 10-Q dated August 3, 2023. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason.
Investor Relations & Media:
Nicole Keith
investor.relations@sana.com
media@sana.com
Exhibit 99.2 Corporate Presentation October 2023
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 August 3, 2023. 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
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 rejection of allogeneic cells has potential to change cell therapy: Allogeneic CAR T cells that perform clinically like autologous CAR T cells can transform treatment of hematological malignancies Key to unlocking the potential of stem cell-derived therapies such as pancreatic islet cells for the treatment of type 1 diabetes Two opportunities in 2023 for clear clinical proof of concept: SC291: Cell persistence and clinical efficacy HIP primary islets in patients with type 1 diabetes Results will provide insights in CAR T cell and stem cell-based platforms – ability to overcome allogeneic and autoimmune cell rejection Pipeline poised to deliver multiple clinical data readouts over next several years: Hypoimmune allogeneic CAR T cells: SC291 (CD19 oncology), SC291 (CD19 autoimmune), SC262 (CD22), SC255 (BCMA), and beyond Regenerative medicine: SC451 (type 1 diabetes) and SC379 (CNS disorders) Balance sheet allows potential for multiple data readouts Engineered Cells as Medicines Sana Biotechnology
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 drug; NHL, non-Hodgkin’s lymphoma; PMD, Pelizaeus-Merzbacher Disease; SPMS, Secondary Progressive Multiple Sclerosis. Product Candidates Mechanism Potential Indications Potential Clinical Milestones 2024 2023 2024 SC291 (HIP) CD19-targeted allo CAR T NHL/ALL/CLL HIP primary islet cells1 Type 1 Diabetes SC291 (HIP) CD19-targeted allo CAR T Autoimmune SC262 (HIP) CD22-targeted allo CAR T NHL/ALL/CLL SC451 (HIP) Stem-cell derived pancreatic islet cells Type 1 Diabetes SC379 Glial progenitor cells PMD, HD, SPMS SC255 (HIP) BCMA-targeted allo CAR T Multiple Myeloma IND filing Clinical data
~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 limited scalability and are only available for a small number of cell types Sana’s hypoimmune platform is designed to overcome immune rejection of foreign cells, which has the potential to unlock the field of cellular medicine Overcoming allogeneic immune rejection has been key limitation in transplant and cellular medicine Drachenberg et al. Am. J. Transplant. 2008 Biopsy of acute rejection of a pancreas transplant
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 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
Sana’s team has pioneered hypoimmune technology
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 cancers continue to have a high unmet need 1Avezbakiyev et al. Blood. 2022 2Durie et al. The Oncologist. 2020 3Clarivate DRG NHL and MM Market Forecast Nov 2022; internal analysis of secondary EPI data. 4Scivida 2022 NHL Factbook Abbreviations: EU5, France, Germany, Italy, Spain, UK High mortality in lymphoma and myeloma in the US and EU5 ~250,000 annual incidence1,2 Over 100,000 deaths annually1,2 ~11,500 patients treated with CAR T in 20223 Estimated ~30 to 40% of patients treated with CAR T will experience durable complete responses4
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 protein 12b; GPRC5D, G protein–coupled receptor, class C, group 5, member D; PBMC, peripheral blood mononuclear cell. PBMCs from healthy donor 1 2 Select T cells T cell selection Expand and grow high-quality allogeneic CAR T cells at scale 5 Modify into HIP T cells 3 Genes disrupted with Cas12b nuclease Insert CAR 4 CD22 CD19 BCMA GPRC5D Produces ~450-950 doses per run1 + CD47 MHC I MHC II TCRα MHC I MHC II TCRα + CAR + CD47
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 efficacy in humanized mice model D0: Nalm6 D15 D27 Unmodified CD19 CAR T Cells Unmodified T Cells HIP CD19 CAR T Cells tumor cell re-injection Hu et al. Nature Communications. 2023
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 Non-HIP cells eliminated by patient immune system Triple knockout+ CAR expression CAR expression; incomplete knockout MHCI-or+ TCR- CAR+ CD47+++ MHCII-or+ MHCI-or+ TCR- MHCII-or+ Knockout No CAR expression Triple knockout+ CAR expression MHC I MHC II TCRα + CAR + CD47 1 month + 2-4 weeks Day 0 CAR expression; incomplete knockout MHCI-or+ TCR- CAR+ CD47+++ MHCII-or+ MHCI-or+ TCR- MHCII-or+ Knockout No CAR expression Triple Knockout and CAR expression: With success, ~100% of surviving cells fully modified
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
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 existing Allo CAR T 2 to 3 months Best-in-class Allo CAR T 3 to 6 months Comparable to Auto CAR T ≥ 6 months Better than Auto CAR T Allogeneic HIP CAR T cell MHC I MHC II TCRα + CD19 CAR + CD47 1Porter et al. Science Translational Medicine. 2015
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 profile to change patient outcomes Drug product from oncology studies ready for use PoC studies across multiple diseases in near term B-cell targeting validated across multiple autoimmune diseases Adapted from Zhang et al. Frontiers in Immunology. 2023; Oh et al. Immune Network. 2023; Lee et al. Nature Reviews Drug Discovery. 2021 Field has spent 25+ years identifying Systemic lupus erythematosus (SLE) Lupus Nephritis Vasculitis (Granulomatosis with polyangiitis & Microscopic polyangiitis) Neuromyelitis optical spectrum Pemphigus Relapsing and progressive MS Rheumatoid Arthritis Sjogren syndrome NMDAR encephalitis Thrombocytopenic purpura Amyloidosis Scleroderma Autoimmune Hemolytic Anemia Chronic immune demyelinating polyradiculoneuropathy Immune-mediated necrotizing myopathy Membranous nephropathy
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 and underlying B cell pathology Lupus nephritis alone impacts ~100,000 people in the US Utilize SC291 Phase 1 supply for potential rapid path to clinic Submitted IND with clinical data in 2024
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% ~12K ~12K Potential of ~7,800 CAR T failures annually by 20272; median survival of ~5 months post-CD19 CAR T therapy failure3 Estimated ~12,000 B cell malignancy patients treated with CD19 CAR T by 20272 Estimated ~4,200 CAR T patients with durable complete responses4 Allogeneic HIP CAR T cell CD19 CAR T relapsed patients represent large and growing unmet need1 SC262 utilizes a clinically- validated CD22 CAR MHC I MHC II TCRα + CD47 + CD22 CAR
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 ~80% patients with prior CD19 therapy 2022 ASH Miklos/Stanford 2018 Nature Med Fry, et al. CR CR Expand our allo T platform to CD22 with Sana’s SC262 candidate Allogeneic HIP CAR T cell MHC I MHC II + CD47 + CD22 CAR TCRα
SC255: Licensed BCMA CAR produced strong clinical data in myeloma when part of autologous CAR T ORR: 98.9% ORR: 96% ORR: % Total N=101 sCR CR PR VGPR 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 follow-up ~1 year 2023 ASCO Nanjing IASO Expand our allo T platform to BCMA with Sana’s SC255 candidate High response rate in multiple myeloma with 95% of patients MRD negative Allogeneic HIP CAR T cell Abbreviations: CR, complete response; ORR, objective response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. MHC I MHC II TCRα + BCMA CAR + CD47
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, blindness, and kidney failure SC451 goal is euglycemia without exogenous insulin or immunosuppression Type 1 diabetes represents a large unmet need with a loss of ~15 years of life1 1Rawshani et al. Lancet. 2018 2Clarivate Type 1 Diabetes Landscape & Forecast, December 2022; internal analysis of secondary EPI data. DIGICOMPHOTO/SCIENCE PHOTO LIBRARY
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 Starting iPSC cell CD47 HLA I HLA II 1. Hypoimmune technology overcomes allogeneic rejection and autoimmunity 3. Intramuscular implantation site improves access and function 2. iPSC-derived islet cells can be scaled to treat many patients Graft site
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 islet cells isolated and HIP-engineered Cells injected intramuscularly into a healthy, allogeneic NHP without immunosuppression WT HIP Survival NHP unmodified islet cells (wt) and NHP hypoimmune islet cells (HIP) Hu et al. Nature Biotechnology. 2023
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 Autologous iPSC-derived islet cells Humanized T1DM mice Autologous iPSCs HIP autologous iPSC-derived islet cells Unmodified stem cell-derived islet cells from patient with T1DM do not survive PBMCs from patient with T1DM used to generate stem cell-derived islet cells and to humanize immune system in mice
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
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 primary islet cells isolated and HIP-modified Cells injected intramuscularly into a healthy, allogeneic NHP without immunosuppression C-peptide Fasting Glucose Normal Exogenous insulin treatment Insulin independence © 2020-2023 Sana Biotechnology. All rights reserved.
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 evasion C-peptide Glycemic control Key Measured Outcomes Overview Transplant into T1DM patient without immunosuppression HIP gene modification of islet cells Donor cadaveric islet cells 1 2 3
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 Autoimmune Unlocked by HIP validation Solid Tumors New Targets Hematologic Malignancies GPRC5D Known ü >100,000 potential cancer patients worldwide1,2 Future State Validated CAR constructs for allogeneic platform ü Validated targets ü Type 1 diabetes Solid tumors ü HIP platform understood in preclinical models Other stem cell-derived products Potential for SLE and other autoimmune disorders ü
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 Cell-specific delivery of genomic modification material Engineered cells into new therapeutic areas Ex Vivo – Hypoimmune In Vivo – Fusogen + CD47 MHC I MHC II Allogeneic HIP CAR T cell HIP islet cell Modified G protein F protein 2023 MHC I MHC II TCRα + CAR + CD47
