Washington, D.C. 20549



Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): March 14, 2023


(Exact name of registrant as specified in its charter)




(State or other jurisdiction


(IRS Employer

of incorporation)

File Number)

Identification No.)

100 Binney Street, Suite 600, Cambridge, MA


(Address of principal executive offices)

(Zip Code)

(Registrant’s telephone number, including area code): (617) 336-7540

Not Applicable

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:


Name of each exchange

Title of each class




on which registered

Common Stock, $0.001 par value per share


The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

Item 2.02 Results of Operations and Financial Condition.

On March 14, 2023, Sigilon Therapeutics, Inc. (the “Company”) issued a press release announcing the Company’s financial results for the quarter and fiscal year ended December 31, 2022. A copy of this press release is furnished as Exhibit 99.1 and is incorporated herein by reference.

The information in this Form 8-K (including Exhibit 99.1 attached hereto) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any filing by the Company, under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filling.

Item 7.01 Regulation FD Disclosure.


On March 14, 2023, the Company updated its corporate presentation, attached as Exhibit 99.2 to this Current Report on Form 8-K. The corporate presentation will also be available in the investor relations section of the Company’s website at https://ir.sigilon.com/news-and-events/events-and-presentations. Representatives of the Company will use the presentation in various meetings with investors, analysts and other parties from time to time. The Company plans to use its website to disseminate future updates to the presentation and may not necessarily file or furnish a Current Report on Form 8-K alerting investors if the presentation is updated.

The information in this Form 8-K (including Exhibit 99.2 attached hereto) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any filing by the Company, under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filling.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits





Press Release Issued by Sigilon Therapeutics, Inc. on March 14, 2023


Sigilon Therapeutics, Inc. Corporate Presentation


Cover Page Interactive Data File (embedded within the Inline XBRL document)


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 hereunto duly authorized.



/s/ Rogerio Vivaldi Coelho, M.D.

Rogerio Vivaldi Coelho, M.D.

President and Chief Executive Officer 

Date: March 14, 2023

Exhibit 99.1



Advancing IND-enabling activities for lead program in diabetes, SIG-002, with plans to conduct non-human primate studies in second half of 2023

SIG-002 demonstrated efficacy and durability in in vivo mouse models for up to 17 weeks

Extended anticipated cash runway into 2025

Cambridge, MA—March 14, 2023—Sigilon Therapeutics, Inc. (NASDAQ: SGTX), a biotechnology company that seeks to develop functional cures for chronic diseases through its Shielded Living Therapeutics™ platform, today reported financial results for the fourth quarter and year ended December 31, 2022 as well as certain other business highlights.

“Reflecting on 2022, we made many important strategic decisions that will help shape the future of our Company, including conducting research that informed the optimization of our SLTx platform, as well as refocusing our pipeline to prioritize our diabetes candidate, SIG-002, in a fiscally disciplined manner,” said Rogerio Vivaldi, M.D., President and CEO of Sigilon. “I am pleased to say that our team has made great progress in advancing our diabetes program, namely developing a differentiation protocol for producing functional human islets from induced pluripotent stem cells (iPSC). In combination with improvements to our encapsulation platform, this groundbreaking work has laid an important foundation for the transition of this program into the IND-enabling stage. We look forward to the initiation of what we believe will be an innovative non-human primate study with the goal of further de-risking our approach. Having lived with diabetes for most of my life as well as being a treating physician, I am truly excited about the direction of our program, including our early preclinical efficacy and durability data – which we believe is unparalleled in comparison to the published data for other programs. We believe our focused development strategy will help conserve resources and extend our cash runway into 2025, enabling us to successfully perform the activities needed to advance SIG-002 into the clinic, with an expected IND submission in 2024, and build upon the early successes of this program.”

Recent Program Highlights and Anticipated Milestones

Sigilon has prioritized its product candidates based on their potential to provide meaningful clinical benefits to patients, rapid time to proof of concept, clear regulatory path, and validated biology and clinical endpoints. Based on these criteria, the Company is focusing its efforts on its product candidate for type 1 diabetes, SIG-002, which is

being developed in collaboration with Eli Lilly and Company. Sigilon expects to initiate Investigational New Drug (IND)-enabling activities for SIG-002 in 2023.

At the Cell and Gene Therapy Meeting on the Mesa in October 2022, the Company presented encouraging data showing its proprietary iPS cell differentiation protocol for SIG-002. The Company’s protocol has generated stem cell-derived human islets that are similar to human cadaveric islets with a high percentage of beta cells, high levels of insulin content and glucose-regulated insulin secretion. In addition, the Company has demonstrated that SIG-002 is efficacious in an STZ-induced diabetes mouse model for up to 17 weeks.

The Company has incorporated several changes into its SLTx platform intended to avoid immune responses to its product candidates, including changes to the cross-linking chemistry designed to strengthen the integrity and stability of the spheres. The Company’s current programs, including SIG-002, have incorporated a number of these platform optimizations. Furthermore, Sigilon continues to utilize its innovative predictive preclinical models of pericapsular fibrotic overgrowth, including in vitro macrophage attachment assays and in vivo humanized mouse models, to support the continued development of its current and future product candidates.

In the first quarter of 2023, Sigilon decreased its external spend relating to the mucopolysaccharidosis type 1 (MPS-1) program to preserve capital. For MPS-1 and other lysosomal disorders, Sigilon is continuing to advance engineering techniques and other cell line strategies designed to minimize or otherwise avoid a patient’s immune response to the Company’s product candidates, as well as optimize blood-brain-barrier penetration and product half-life.

Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $69.6 million as of December 31, 2022 compared to $123.4 million as of December 31, 2021. The decrease was primarily driven by $51.5 million used in operating activities and $1.7 million of debt principal repayments. The Company expects that its cash, cash equivalents and marketable securities as of December 31, 2022 will be sufficient to support its currently anticipated operating expenses and capital expenditure requirements into 2025.

R&D Expenses: Research and development expenses were $5.9 million for the fourth quarter of 2022 compared to $14.7 million for the fourth quarter of 2021. The decrease in research and development expenses was primarily related to decreased activity in ongoing platform and other early-stage program development, personnel expenses, facility-related expenses, which were offset by increased expenses related to the Company’s diabetes program. The decrease in platform and other early-stage program activity and personnel expenses was primarily due to the Company’s reprioritization of the development of the MPS-1 program, diabetes program and platform optimization

following the Company’s restructuring activities in December 2021. The decrease in facility-related expenses was primarily due to the sublease of a portion of the Company’s facility.

G&A Expenses: General and administrative expenses were $4.5 million for the fourth quarter of 2022 compared to $4.6 million for the fourth quarter of 2021.

Net Loss: Net loss was $6.7 million for the fourth quarter of 2022 compared to $17.7 million for the fourth quarter of 2021, primarily due to the decrease in R&D expenses discussed above.

About Sigilon Therapeutics

Sigilon Therapeutics seeks to develop functional cures for patients with a broad range of chronic diseases by harnessing the power of the human cell through its Shielded Living Therapeutics™ platform. Sigilon’s product candidates are non-viral engineered cell-based therapies designed to produce the crucial proteins, enzymes or other therapeutic molecules needed by patients living with chronic diseases, such as diabetes and lysosomal diseases. The engineered cells are encapsulated by Sigilon’s Afibromer™ biomaterials matrix, which is designed to shield them from immune rejection. Sigilon was founded by Flagship Pioneering in conjunction with Daniel Anderson, Ph.D., and Robert Langer, Sc.D., of the Massachusetts Institute of Technology.

Forward-Looking Statements

This press release includes forward-looking statements. These forward-looking statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “may,” “will,” “believe,” “estimate,” “forecast,” “goal,” “project,” and other words of similar meaning. These forward-looking statements address various matters, including the initiation and timing of IND-enabling activities and non-human primate studies for SIG-002, our ability to complete process development and scale up activities for SIG-002 and advance our diabetes program into the clinic, and our expected cash runway. Each forward-looking statement contained in this press release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others, that if negative results of preclinical or clinical studies of any of our product candidates could adversely affect our business and may require us to discontinue or delay development of other product candidates, which are all based on the same SLTx platform; the SLTx platform consists of novel technologies that are not yet clinically validated for human therapeutic use and the approaches we are taking to discover and develop novel therapeutics are unproven; we may not be successful in our efforts to identify and develop product candidates; if clinical trials of our current and future product candidates fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities or do not otherwise produce positive results, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of such product candidates; if we are unable to obtain and maintain patent and other intellectual property protection our product candidates, our SLTx platform may be adversely affected, and the risks identified under the heading “Risk Factors” in our Quarterly Report on Form 10-Q for

the quarter ended September 30, 2022, and filed with the Securities and Exchange Commission (the “SEC”), as well as the other information we file with the SEC. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at www.sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this document, and we undertake no obligation to update or revise any of these statements, except as required by law.


Consolidated Balance Sheets

(in thousands, except share and per share amounts)


December 31, 

December 31, 










Current assets:





Cash and cash equivalents





Marketable securities



Accounts receivable





Unbilled accounts receivable


Prepaid expenses and other current assets





Restricted cash—current





Total current assets





Property and equipment, net





Right-of-use assets





Restricted cash





Total assets





Liabilities and stockholders’ equity (deficit)





Current liabilities:





Accounts payable





Accrued expenses and other current liabilities





Lease liabilities, current portion





Current portion of long-term debt





Deferred revenue from related party, current portion





Total current liabilities





Deferred revenue from related party, net of current portion




Lease liability, net of current portion





Long-term debt, net of discount and current portion





Other liabilities




Total liabilities



Stockholders’ equity





Common stock, par value $0.001 per share; 175,000,000 shares authorized at December 31, 2022 and December 31, 2021; 32,466,737 and 32,359,895 shares issued and outstanding at December 31, 2022 and December 31, 2021, respectively





Preferred stock, par value $0.001 per share; 25,000,000 shares authorized at December 31, 2022 and December 31, 2021; no shares issued and outstanding at December 31, 2022 and December 31, 2021



Additional paid-in capital





Accumulated other comprehensive loss



Accumulated deficit





Total stockholders’ equity





Total liabilities and stockholders’ equity






Consolidated Statements of Operations and Comprehensive Loss

(In thousands, except per share data)


Three Months Ended

December 31, 

Year Ended

December 31, 















Collaboration revenue









Operating expenses:




Research and development








General and administrative






Total operating expenses








Loss from operations








Other income (expense), net:







Interest income





Interest expense





Other income, net





Total other expense, net








Net loss attributable to ordinary shareholders









Net loss per share attributable to common stockholders—basic and diluted









Weighted average common stock outstanding—basic and diluted





SOURCE: Sigilon Therapeutics, Inc.

Investor Contact
Robert Windsor, Jr., J.D.

VP, Head of Investor Relations

Sigilon Therapeutics

Media Contacts
Amy Bonanno
Solebury Strategic Communications


Exhibit 99.2


©2023 Sigilon Therapeutics, Inc. March 2023 Leading the Next Frontier of Allogeneic Cell Therapy


Forward-looking statements This presentation has been prepared by Sigilon Therapeutics, Inc. (“we,” “us,” “our,” “Sigilon” or the “Company”) and contains forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “anticipate,” “could,” “intend,” “potential” or “aim” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning: our current cash runway; our ability to advance any product candidates that we may develop and successfully complete any clinical studies, including the manufacture of any such product candidates; our ability to leverage our initial programs to develop additional product candidates using our platform technologies; our belief that, at commercial scale, the cost of goods for some of our programs will be significantly lower than existing cell or gene therapies; and our ability to successfully scale our manufacturing capabilities. Any forward-looking statements represent the Company’s views only as of today and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements, except as required by law. The Company’s business is subject to substantial risks and uncertainties that could cause these statements to be inaccurate. Applicable risks and uncertainties include, among others, that we have incurred significant losses since inception and our need for additional funding; failure in clinical development of our diabetes and other preclinical programs could adversely effect our business and may require us to discontinue or delay development of other product candidates; there may be undesirable side effects related to our product candidates or clinical studies, or limited efficacy of product candidates arising from our platform; the platform consists of novel technologies that are not yet clinically validated for human therapeutic use; that we do not have any results from the testing of any of our product candidates in clinical trials other than SIG-001 and any favorable preclinical results are not predictive of results that may be observed in clinical trials; the FDA or other regulators may request additional preclinical studies or clinical trials beyond those that we currently anticipate for our product candidates; and other risks and uncertainties identified under the heading “Risk Factors” and in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2022 and in any subsequent filings with the Securities and Exchange Commission. Investors, potential investors, and others should give careful consideration to these risks and uncertainties. Non-Confidential 2


M I S S I O N : We aim to deliver functional cures to patients by harnessing the power of the human cell Non-Confidential 3


Strong Foundation to Support Sustained Growth Company Background Our Potential Attributes 1 No chronic immune suppression 2 Sense and respond to disease 3 Retrievable and redosable 4 Safe & Durable Scalable to tackle high cell counts 5 Non-Confidential o Seminal work at MIT by Langer & Anderson with the discovery of Afibromer™ o Sigilon created by Flagship Pioneering (2016) o Ongoing Lilly partnership for T1D w/ $75M upfront + up to $415M milestones (2018) o NASDAQ: SGTX; IPO $145M (Dec 2020) o Clinical experience (FIH in Hem A in 2020) o Broad intellectual property (patent expiry ranging from 2032-2043) o Cash runway anticipated into 2025 4


Industry leaders with a proven track record of creating value Rogerio Vivaldi, MD, MBA President, Chief Executive Officer Olivia Kelly, PhD SVP, Head of Diabetes Research Matthew Kowalsky, JD Chief of Staff; Chief Legal & Administrative Officer Rogerio Vivaldi, MD, MBA Sigilon Therapeutics Robert Ruffolo, Jr., PhD Former Head of R&D, Wyeth Pharmaceuticals Eric Shaff, MBA Seres Therapeutics Stephen Oesterle MD Former CTO, Medtronic PLC Kavita Patel MD The Brookings Institution Board of Directors: Josias Pontes, MBA SVP, Chief Financial Officer Philip Ashton-Rickardt, PhD Chief Scientific Officer Sarah Yuan, PhD Chief Technical Operations Officer John Cox Former CEO, Bioverativ Robert Windsor Jr, JD VP, Investor Relations Bernd Kullmann, MBA SVP, Head of Operations & Project Management Doug Cole, MD Chairman, Managing Partner Flagship Pioneering Non-Confidential 5


40+ year journey in search of sustainable cell therapies Lim et al. Science Vol 210 p908 1980 Fibrosis Immediate Immune Response 6 Lim et al. Science Vol 210 p908 1980 Main Challenges ➢ Immune rejection ➢ Poor Engraftment ➢ Prohibitive Cost Non-Confidential 6


Optimized Product 7 Key Learnings Guide Our Approach KEY REQUIREMENTS No chronic immunosuppression Exposure control Safe Scalable, with acceptable costs Appropriate indications Non-Confidential


Allowing for the exploration of a broad range of indications, including acute and chronic, rare and prevalent disease Multiple Cell Lines Existing Technologies & Capabilities Right Indication Platform Strategy Vision to become cell therapy powerhouse, leveraging encapsulation platform and manufacturing capabilities across multiple cell types to deliver groundbreaking and durable therapeutics 8 Epithelial cells iPSC cells (undisclosed) Process & Analytical Dev/MFG/Quality/Clinical Dev Cell encapsulation Proprietary Immunity/Efficacy Characterization Proprietary Cell Differentiation iPSC islet derived cells Product Optimization Tox/PK-PD Characterization Non-Confidential


Novel approach to de-risk programs Immunogenicity is one of the critical barriers to allogeneic cell therapy Therapeutic concept Powerful, Precision Proprietary Cell Differentiation Proprietary models to predict and prevent immunogenicity 9 61% % of Beta cells In-vitro MA Assay PFO & Clumps In-vivo huBLT Red dots=macrophages SIG-002 SIG-002 SIG-005 SIG-005 No PFO* No macrophages *PFO=Pericapsular fibrotic overgrowth Non-Confidential


Leading to scalable & cost-effective manufacturing Product Optimization Tox/PK-PD Characterization • Mice / NHP • PK/PD 10 0 10 20 30 40 50 60 70 80 90 100 110 120 0 200 400 600 800 SG-VIVO8018-1 E217 Blood Glucose Levels Time (days) Blood Glucose (mg/dL) GMP Manufacturing FIH Encapsulation Off the Shelf Drug Product Campaigned Production Non-Confidential


Ongoing Optimization Mitigating the risks of PFO and optimize SLTx platform + + Cells Sphere Manufacturing Placement O P T I M I Z A T I O N : ❖ iPSC derived cells are less immunogenic than epithelial cells ❖ Exploring lower cell density through higher potency expression ❖ Exploring ImmunoQuiet cells to mitigate antigen response OPTIMIZATION : ❖ Scale up drug substance manufacturing ❖ Automate and scale up drug product manufacturing ❖ Develop cryopreserved drug product OPTIMIZATION : ❖ Minimally invasive, interventional radiology guided sphere delivery with local anesthesia OPTIMIZATION : ❖ Strengthened sphere integrity and stability with the addition of dXL (ionic + covalent crosslinking = dXL) Non-Confidential 11


PFO is a Complex Immunological Process Non-Confidential 12


Non-Confidential SIG-000 (No Cells) SIG-005 SIG-002 Polystyrene Beads SIG-0SIG-0 5 SIG-0 2 Polystyrene Beads 0 50 100 150 200 500 1000 1500PFO Response at Day 35 (huBLT model) Total Weight of Clumped Spheres (mg) Clumps No Clumps PFO in Humanized BLT mouse model SIG-000: No cells SIG-005: ARPE cells SIG-002: iPSC-derived Islets Pericapsular Fibrotic Overgrowth (PFO) in vitro Macrophage Assay SIG-002 SIG-005 Macrophages shown in Red color No Macrophage Attachment Macrophage Attachment Observed • SIG-002 SC-islet containing spheres, with dXL, show no clumping or evidence of PFO similar to the empty negative control spheres. New Assays and Experiments to Assess PFO 13


PROGRAM CELL PRODUCT/TYPE DISCOVERY LEAD OPTIMIZATION IND ENABLING PHASE 1/2 SIG-002 – Type 1 Diabetes Human Insulin Lysosomal Diseases SIG-205 – CNS MPS-1 BBB-Human IDUA SIG-207 – Fabry Human GLA SIG-218 – CNS MPS-2 BBB-Human IDS SIG-220 – MPS-6 Human ARSB Liver Diseases SIG-XXX – Undisclosed ApoL-IL10 SIG-XXX – Undisclosed Human Hepatocyte E I E E E I Pipeline E 14 I iPSC derived E Epithelial Cell Cell type Constitutive Sense & Response MOA Non-Confidential


Mechanism Maintain blood glucose level by sensing and responding to glucose excursions Recapitulate pancreas function Insulin independence from exogenous insulin without immunosuppression Non-Confidential 15 Our Strategic Partner Glucose Insulin Glucagon Afibromer™ Encapsulation • $75 million up front • $415 million in milestones • Tiered single-to-low double-digit sales-based royalties Lilly’s Financial Commitment Our Diabetes Program


16 Non-Confidential Directed Differentiation of iPSC to Islets Sneddon et al 2018 Cell Stem Cell 22:810- 823 Iworima et al 2021 Stem Cells Transl. Med. 1-11 Islet Cell Therapy SIG-002: Sigilon Spheres with iPSC-Islets Functional Cure for Type 1 Diabetes Insulin Independence Without Immunosuppression


Non-Confidential Brissova et al 2005 Human Islets beta 0 20 40 60 80 100 Islet Cell Population (%) (61%) SC-islets Sigilon Human Islets (n=17) SC-Islets (n=13) 0 400 800 1200 Insulin Content nU/cell Dynamic Insulin Secretion SC-islets (n=6): 70±31 pU/cell/min average peak at high glucose Our SC-islets compare favorably to human islets in cellular composition and potency in preclinical studies 17


18 Non-Confidential 0 30 60 90 120 0 200 400 600 800 SG-VIVO7966-1 Day 70 Oral Glucose Tolerance Test Time (min) Blood Glucose (mg/dL) 0 10 20 30 40 50 60 70 80 90 100 110 120 0 200 400 600 800 SG-VIVO8307-1 Blood Glucose Time (days) Blood Glucose (mg/dL) SIG-002 is efficacious and durable in immune-deficient diabetic mice


SLTx Encapsulation May Have Significant Advantages Over Hypoimmune Approaches SLTx PLATFORM – POTENTIAL ADVANTAGES • No antibody-mediated cytotoxicity • Known biology and IP landscape • Minimal gene edits to reduce risk of off-target effects • Designed to block antibody and immune cell infiltration, including pre-existing T1D autoantibody response NAKED ISLET THERAPY – CHALLENGES • Prone to antibody mediated cytotoxicity • Uncertain biology and FTO • Multi-gene edits increase risk of off-target effects • Protection from autoantibody induced islet rejection of T1D is uncertain Prevent allo-antigen induced immune response Spheres block antibody effector mechanisms Afibromer inhibits macrophage attachment Spheres prevent direct or indirect immune rejection Non-Confidential 19


Designing Product Candidates for Lysosomal Diseases to Enable Blood Brain Barrier Penetration BBB-penetrant Camelid HCAb BBB VHH Cargo Protein Half-life VHH Half-life extending Camelid HCAb VH + - 32% Technology Details Good systemic tissue penetration and functional activity towards target substrate Total Heparan sulfate reduction in systemic tissues Liver Spleen Kidney Lung Heart 0 50 100 150 200 Total Heparan sulfate reduction in systemic tissues Percent of Untreated BBB-hIDUA Untreated ✱ ✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱ Brain Heparan Sulfate Reduction BBB-hIDUA Untreated 0 50 100 Brain heparan sulfate reduction Percent of Untreated ✱✱✱✱ Liver Spleen Kidney Lung Heart 0 50 100 150 200 Total Heparan sulfate reduction in systemic tissues Percent of Untreated BBB-hIDUA Untreated ✱ ✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱ Non-Confidential 20


M ANU F A C T U R E ANY T I M E 4 W E E K S 21 Non-Confidential Full Release Differentiation Filled DS Cryopreservation WCB Thaw Staged Release DS Thaw Encapsulation Thaw Drug Substance Encapsulation Cell Expansion & Cryopreservation ~4 Weeks Up to 300mL Pooled SIG-005 Final Filled DP SIG-005 QC Release Testing Bulk Drug Product (DP) ~1 week for Manufacture & Initial Release Fully Released Drug Substance Manufacture Any Time Initiate 1 week prior to patient administration Final Filled DP M ANU F A C T U R E 1 W E E K PR I O R T O PAT I E NT AD M I NI S T R A T I O N 1 W E E K Cryopreserved drug substance (DS) expected to decrease manufacturing lead times by 80%


Stem Cell Differentiation Drug Product Cryopreservation Hospital Pharmacy Patients 22 Non-Confidential • Scale up drug substance manufacturing • Automate and scale up drug product manufacturing • Develop cryopreserved drug product Off the Shelf Drug Product On-demand Administration Campaigned Production Manufacturing strategy to enable off-the-shelf products with competitive cost of goods


23 Upcoming expected milestones 1. Initiate IND-enabling studies for Type 1 Diabetes with optimized spheres 2. In vivo PoC / PFO models (including first of its kind NHP study) 1. Completion of IND-enabling studies for Type 1 Diabetes 2. IND for Type 1 Diabetes 3. Lead optimization for 3 - 4 new targets 2023 2024 2025 1. FIH for Type 1 Diabetes 2. First Readout for Type 1 Diabetes 3. IND enabling studies for 3 - 4 new targets Non-Confidential


Thank you