UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
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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 August 10, 2021, Sigilon Therapeutics, Inc. (the “Company”) issued a press release announcing the Company’s financial results for the quarter ended June 30, 2021. 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 August 10, 2021 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
Exhibit | ||
No. | Description | |
99.1 | Press Release Issued by Sigilon Therapeutics, Inc. on August 10, 2021 | |
99.2 | ||
104 | Cover Page Interactive Data File (formatted as Inline XBRL and included in Exhibit 101) |
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 hereunto duly authorized.
SIGILON THERAPEUTICS, INC. | ||
By: | /s/ Rogerio Vivaldi Coelho, M.D. | |
Rogerio Vivaldi Coelho, M.D. | ||
President and Chief Executive Officer | ||
Date: August 10, 2021
Exhibit 99.1
Sigilon Therapeutics Reports Second Quarter 2021 Financial Results and Business Highlights
Cambridge, MA—August 10, 2021—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 second quarter ended June 30, 2021 as well as certain other business highlights.
“While we remain focused on patient safety and resolving the clinical hold on our Phase 1/2 trial in hemophilia A, we are also taking important steps to advance our broad pipeline of product candidates,” said Rogerio Vivaldi, M.D., M.B.A., Chief Executive Officer of Sigilon. “Last month, we had the opportunity to present preclinical data on our candidate, SIG-005, for MPS-1 – a rare genetic disorder – and are encouraged by these results. With our CTA recently filed in the UK and Brazil and an additional filing in the U.S. anticipated, we look forward to starting our clinical journey in lysosomal diseases. If these filings are approved, we plan to initiate our second trial before year-end. In addition, we are working to streamline the manufacturing process of SIG-005 by incorporating cryopreservation of the cell component, potentially reducing the manufacturing lead times by approximately 80 percent. We remain committed to realizing the promise of our platform technology and advancing our current pipeline of product candidates, which includes programs in diabetes and immune-mediated disease. We are also continuing to look for additional opportunities, including strategic partnerships, to grow our existing portfolio.”
Recent Program Highlights
| ● | Three of our scientific abstracts were selected for presentation—including an oral presentation on mucopolysaccharidosis type I (MPS-1)—at the 16th International Symposium on MPS and Related Diseases (MPS 2021), which took place July 23 – 25, 2021. The Company also presented initial results from preclinical studies of expanded pipeline programs in immune-mediated and metabolic disorders at the American Society of Gene and Cell Therapy (ASGCT) 24th Annual Meeting in May. |
| ● | In June 2021, the Company filed a Clinical Trial Application (CTA) in the UK for SIG-005 for the treatment of MPS-1. In addition, the Company filed a CTA in Brazil for SIG-005 in July 2021. |
| ● | The Company plans to cryopreserve the cell component for the manufacture of SIG-005 in the Phase 1/2 clinical trial of MPS-1, allowing these cells to be produced in advance of the manufacture of drug product. This planned manufacturing change is expected to reduce the manufacturing lead times for patient doses of SIG-005 by approximately 80 percent. |
Corporate Updates
| ● | Deya Corzo, M.D., is stepping down as Chief Medical Officer. The Company entered into an agreement with Dr. Corzo providing for transition services until her separation on August 13, 2021. As Sigilon initiates a search for a CMO, the Board of Directors and management will work closely together on key clinical priorities. |
| ● | Philip Ashton-Rickardt, Ph.D., joined Sigilon as Chief Scientific Officer. Dr. Ashton-Rickardt is a highly regarded scientific leader in the field of immunology with a successful track record of developing cell therapies and platform technologies. |
| ● | Ajay Rai, M.B.A., joined the Company as Senior Vice President, Head of Business Development. Mr. Rai brings over two decades of business development, finance and partnering experience in the life sciences to Sigilon. |
| ● | Sigilon has initiated a search for a full-time Chief Financial Officer and, in the meantime, has engaged Michael Wyzga, M.B.A., former Chief Financial Officer of Genzyme, to provide finance-related services on an interim basis. |
| ● | Brooke Story, M.B.A., was appointed to the Company’s Board of Directors. Ms. Story has more than 20 years of extensive commercial and operating experience in the healthcare industry. |
Anticipated Milestones
| ● | Sigilon expects to initiate a Phase 1/2 trial of SIG-005 in patients with MPS-1 in the second half of 2021. |
| ● | The Company expects to disclose up to 9 months of follow-up data for three patients from the Phase 1/2 safety and dose-ranging study of SIG-001 in severe to moderate-severe hemophilia in the third quarter of 2021. |
Financial Results
| ● | Cash Position: Cash was $162.4 million as of June 30, 2021 compared to $202.2 million as of December 31, 2020. |
| ● | R&D Expenses: Research and development expenses were $17.8 million for the second quarter of 2021 compared to $12.5 million for the second quarter of 2020. The increase in research and development expenses was primarily related to ongoing platform, pipeline, and development activities related to Sigilon’s SIG-005 and SIG-007 programs, which received orphan drug designation in December 2020 and March 2021, respectively. Personnel expenses increased primarily as a result of the increase in headcount in Sigilon’s research and development function and increases in stock-based compensation. Stock-based compensation expense increased to $0.9 million from $0.3 million for the three months ended June 30, 2021 and 2020, respectively. |
| These increases were partially offset by a reduction of $0.5 million and $0.6 million associated with Sigilon’s SIG-001 and SIG-002 programs, respectively. The decrease in SIG-001-related expenses was due to the timing of manufacturing activities in the second quarter of 2020 and the decrease in SIG-002-related expenses was due to changes in the timeline for preclinical activities. |
| ● | G&A Expenses: General and administrative expenses were $5.0 million for the second quarter of 2021 compared to $2.8 million for the second quarter of 2020. The increase in general and administrative expenses was primarily driven by a $0.8 million in increased costs from operating as a public company in the second quarter of 2021. In addition, personnel expenses increased by $1.0 million primarily as a result of the increase in headcount in Sigilon’s general and administrative function and increases in stock-based compensation. Stock-based compensation expense increased to $1.1 million from $0.4 million for the three months ended June 30, 2021 and 2020, respectively. |
| ● | Net Loss: Net loss was $20.4 million for the second quarter ended June 30, 2021 compared to $13.5 million for the same period of 2020. |
About Sigilon Therapeutics
Sigilon Therapeutics seeks to develop functional cures for chronic diseases 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 factors needed by patients living with chronic diseases such as hemophilia, lysosomal diseases and diabetes. The engineered cells are protected by Sigilon’s Afibromer™ biomaterials matrix, which shields them from immune rejection and fibrosis. 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 modularity of our pipeline programs and the potential benefits of our platform, the timing for the initiation of our Phase 1/2 clinical trial of SIG-005 in MPS-1 as well as the filings related thereto, our ability to cryopreserve cell components of SIG-005 and other product candidates and the associated impact on manufacturing lead times, the timing for the submission of regulatory filings for MPS-1 and other product candidates, and the timing and scope of disclosure of initial data relating to our Phase 1/2 clinical study of SIG-001 in Hemophilia A. 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 favorable preclinical results are not predictive of clinical trial results, our ability to resolve the clinical hold on SIG-001, the FDA or other regulators may request additional preclinical studies or clinical trials beyond those that we currently anticipate, manufacturing changes may not have the desired effect, and the risks identified under the heading “Risk Factors” in our Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2021, 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. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.
Sigilon Therapeutics, Inc.
Condensed Consolidated Balance Sheets
(in thousands, except share and per share amounts)
(Unaudited)
| | June 30, | | December 31, | ||
|
| 2021 |
| 2020 | ||
Assets |
| |
|
| |
|
Current assets: |
| |
|
| |
|
Cash | | $ | 162,406 | | $ | 202,229 |
Accounts receivable (inclusive of $63 and $63 from a related party at June 30, 2021 and December 31, 2020, respectively) | |
| 178 | |
| 177 |
Prepaid expenses and other current assets | |
| 3,611 | |
| 1,729 |
Restricted cash—current | |
| 75 | |
| 75 |
Total current assets | |
| 166,270 | |
| 204,210 |
Property and equipment, net | |
| 3,630 | |
| 2,991 |
Right-of-use assets | |
| 14,928 | |
| 16,731 |
Restricted cash | |
| 1,293 | |
| 1,118 |
Total assets | | $ | 186,121 | | $ | 225,050 |
Liabilities, convertible preferred stock and stockholders’ equity (deficit) | |
| | |
|
|
Current liabilities: | |
| | |
|
|
Accounts payable | | $ | 4,661 | | $ | 1,988 |
Accrued expenses and other current liabilities | |
| 8,693 | |
| 7,892 |
Lease liabilities, current portion | |
| 5,075 | |
| 5,361 |
Deferred revenue from related party, current portion | |
| 25,957 | |
| 31,777 |
Total current liabilities | |
| 44,386 | |
| 47,018 |
Deferred revenue from related party, net of current portion | |
| 272 | |
| — |
Lease liability, net of current portion | |
| 10,279 | |
| 11,893 |
Long-term debt, net of discount | |
| 19,941 | |
| 19,807 |
Other liabilities | |
| 176 | |
| 176 |
Total liabilities | | $ | 75,054 | | $ | 78,894 |
Stockholders’ equity | |
|
| |
|
|
Common stock, par value $0.001 per share; 175,000,000 shares authorized at June 30, 2021 and December 31, 2020; 31,864,020 and 31,464,989 shares issued and outstanding at June 30, 2021 and December 31, 2020, respectively | |
| 32 | |
| 31 |
Preferred stock, par value $0.001 per share; 25,000,000 shares authorized at June 30, 2021 and December 31, 2020; no shares issued and outstanding at June 30, 2021 and December 31, 2020 | |
| — | |
| — |
Additional paid-in capital | |
| 286,373 | |
| 282,053 |
Accumulated deficit | |
| (175,338) | |
| (135,928) |
Total stockholders’ equity | |
| 111,067 | |
| 146,156 |
Total liabilities, convertible preferred stock and stockholders’ equity | | $ | 186,121 | | $ | 225,050 |
Sigilon Therapeutics, Inc.
Condensed Consolidated Statements of Operations and Comprehensive Loss
(in thousands, except per share data)
(Unaudited)
| | Three Months Ended June 30, | | Six Months Ended June 30, | ||||||||
|
| 2021 |
| 2020 |
| 2021 |
| 2020 | ||||
Revenue |
| |
|
| |
|
| |
|
| |
|
Collaboration revenue (inclusive of $2,662, $5,606, $1,951 and $5,417 from a related party for the three and six months ended June 30, 2021 and 2020, respectively) | | $ | 2,704 | | $ | 1,951 | | $ | 5,662 | | $ | 5,417 |
Operating expenses: | |
| | |
| | |
| | |
| |
Research and development | |
| 17,751 | |
| 12,452 | |
| 33,736 | | | 25,726 |
General and administrative | | | 4,992 | | | 2,818 | | | 10,532 | | | 5,689 |
Total operating expenses | |
| 22,743 | |
| 15,270 | |
| 44,268 | |
| 31,415 |
Loss from operations | |
| (20,039) | |
| (13,319) | |
| (38,606) | |
| (25,998) |
Other income (expense), net: | |
|
| |
|
| |
|
| |
|
|
Interest income | |
| 71 | | | 35 | |
| 157 | | | 238 |
Interest expense | |
| (494) | | | (196) | |
| (982) | | | (404) |
Other expense | |
| 25 | | | (11) | |
| 21 | | | (27) |
Change in fair value of preferred stock warrant liability | |
| — | | | 1 | |
| — | | | (34) |
Total other expense, net | |
| (398) | |
| (171) | |
| (804) | |
| (227) |
Net loss and comprehensive loss | | $ | (20,437) | | $ | (13,490) | | $ | (39,410) | | $ | (26,225) |
Net loss per share attributable to common stockholders—basic and diluted | | $ | (0.65) | | $ | (2.54) | | $ | (1.25) | | $ | (5.09) |
Weighted average common stock outstanding—basic and diluted | |
| 31,571,704 | |
| 5,320,427 | |
| 31,529,939 | |
| 5,152,477 |
SOURCE: Sigilon Therapeutics, Inc.
Investor Contacts
Rob Windsor
Sigilon Therapeutics, Head of Investor Relations
robert.windsor@sigilon.com
617-586-3837
Media Contact
Amy Bonanno
Solebury Trout
abonanno@soleburytrout.com
914-450-0349
##
Exhibit 99.2
| Advancing Potential Functional Cures for Patients With Chronic Diseases ©2021 Sigilon Therapeutics, Inc. August 2021 0 |
| Disclaimer This presentation has been prepared by Sigilon Therapeutics, Inc. (“we,” “us,” “our,” “Sigilon” or the “Company”) and is made for informational purposes only and not for any other purpose. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and Sigilon makes no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources. While the Company believes its internal research is reliable, such research has not been verified by any independent source. This presentation 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,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” 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; the initiation, timing, progress and results of our research and development programs, preclinical studies and clinical trials, including the timing of our clinical trials for SIG-001 and SIG-005 and the submission of INDs or CTAs for our other product candidates; 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 SLTx platform; 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. The Company’s business is subject to substantial risks and uncertainties. Applicable risks and uncertainties include, among others, that we have incurred significant losses since inception and our need for additional funding; the SLTx 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 and any favorable preclinical results are not predictive of results that may be observed in clinical trials; we may be unable to obtain and maintain patent protection and other intellectual property rights for SIG-001, SIG-005 or any other product candidates and for our SLTx platform, or the scope of the patent and other intellectual property protection obtained may not be sufficiently broad; that we may be unable to resolve the clinical hold on SIG-001; the FDA or other regulators may request additional preclinical studies or clinical trials beyond those that we currently anticipate for SIG-001, SIG-005 or other product candidates, that manufacturing changes may not have the desired effect; and other risks and uncertainties identified under the heading “Risk Factors” and in our Annual Report on Form 10- K for the year ended December 31, 2020, our Quarterly Report on Form 10-Q for the period ended June 30, 2021 and in any subsequent filings with the Securities and Exchange Commission. 1 Non-confidential |
| SHIELDED LIVING THERAPEUTICS PLATFORM Sigilon Therapeutics Designed to Develop Functional Cures • Non-viral engineered cell-based therapy • No interference with patient’s DNA • Redosable and retrievable • No immunosuppression required • Scalable and flexible manufacturing 2 2 |
| 2020 Our Company History 2018 – 2019 2016 - 2017 1980 - 2015 Sigilon created by Flagship Pioneering Foundational partnership Developed our modular platform Hemophilia A Orphan Drug Designation (FDA) Key publications in peer-reviewed journal, Nature Seminal work by Drs. Robert (Bob) Langer and Daniel Anderson at MIT led to discovery of AfibromerTM Evidence of fibrosis No fibrosis observed Series A $26M Lilly Deal $75M + With AfibromerTM Without AfibromerTM Expanded our pipeline 3 IPO $145M Secured Series B financing of $105M Completed one- year NHP study of empty spheres Received 3 Orphan Drug Designations Dosed first patients in Phase 1/2 study of SIG- 001 for Hem A |
| 2021 Highlights •$372 million in funding to date •Completed IPO in December 2020 with $144.9 million in gross proceeds (priced at $18) •Current cash runway into Q4 2022 (~$162 million at the end of Q2 21) •Phase 1/2 study of SIG-001 (Hem A) on clinical hold due to SAE; investigation of potential contributing factors ongoing •Filed CTA for SIG-005 in MPS-1 (UK & Brazil) in June & July 21 with US IND filing to follow •Pipeline with +3 CTA/IND filings expected by YE 22 STRONG FINANCIAL POSITION EXTENSIVE PIPELINE Inner Compartment: • genetically modified human cells that express BDD-hFVIII; hIDUA; hGLA … • modified alginate designed to optimize cell function Outer Layer: • modified alginate chemically linked to small molecule to minimize PFO (Afibromer) 4 |
| ++ 1. Cells Selection criteria based on: Safety Durability Scalability Ability to switch transgene allows for plug‐n‐play 3 pillars of our modular platform technology Modular SLTx Product Platform From Cell Function to Potential Functional Cure 2. Sphere 3. Manufacturing Process Dual layer sphere optimized to: Prevent immune response Enhance cell longevity and productivity No significant changes required from product to product Standardized processes: Cell expansion Biomaterial manufacturing Proprietary methods for encapsulation Scalable and flexible Strategic manufacturing development will potentially reduce COGS Modular platform allows for production of novel SLTx product candidates with the potential to treat broad range of chronic diseases 4. Placement 5 Afibromer Matrix Administration via IP port |
| PROGRAM CELL PRODUCT DISCOVERY LEAD OPTIMIZATION IND ENABLING PHASE 1/2 PHASE 3 Rare Blood Disorders SIG-001 – Hemophilia A BDD-FVIII SIG-009 – FVII Deficiency FVII SIG-003 – Hemophilia B Padua-FIX Lysosomal Diseases SIG-005 – MPS-1 Human IDUA SIG-007 – Fabry Human GLA SIG-018 – MPS-2 Human IDS SIG-020 – MPS-6 Human ARSB Endocrine & Other Chronic Diseases SIG-002 – Type 1 Diabetes Insulin & others SIG-XXX – IMD Interleukins Addressing a Broad Range of Chronic Diseases Platform could be foundation for multiple products to enable treatment of vast array of disorders that require chronic protein administration 6 Note: IDUA = alpha‐L‐iduronidase; GLA= alpha‐galactosidase A ; IDS= iduronate sulfatase; ARSB= Arylsulfatase b |
| Broad and Deep IP Portfolio* *As of 30 June 2021; expiry assumes 20 year term for issued patents, additional term for patent term extensions may be available in some countries 30 Patent Families • 9 families licensed from MIT • Expiry between 2032 and 2038 • 21 families owned by Sigilon • Expiry between 2037 and 2042 • 16 issued U.S. patents • 25 issued ex-U.S. patents • >120 pending applications 6 Trademark Families • 6 U.S. & 73 ex-U.S. registrations • 10 ex-U.S. pending applications Patent Strategy: Protect SLTxTM platform and pipeline Engineered Cells: Novel expression constructs Monoclonal cell lines Sphere Components: Configuration Outer layer matrix Inner compartment matrix Manufacturing: Afibromer Small Molecule Modified Alginates Encapsulation 7 |
| Industry Leaders with Proven Track Record of Driving Value Rogerio Vivaldi, MD, MBA President, CEO Bernd Kullmann, MBA VP, Head of Mfg / Supply Chain Vanya Sagar, MPA Chief Human Resources Officer Olivia Kelly, PhD VP, Head of Diabetes Research Melodie Henderson, JD VP, Intellectual Property Counsel Martha Rook, PhD Chief Technical Operations Officer Matthew Kowalsky, JD Chief Legal Officer Susan Drapeau, PhD SVP, Head of Preclinical Development Josias Pontes, MBA VP, Head of Finance Elina Makino, PhD VP, Head of Rare Diseases Research Rogerio Vivaldi, MD, MBA Sigilon Therapeutics Doug Cole, MD Chairman Flagship Pioneering Robert Ruffolo, Jr., PhD Former Head of R&D, Wyeth Pharmaceuticals Eric Shaff, MBA Stephen Oesterle MD Former CTO, Medtronic PLC John Cox Repertoire Kavita Patel MD The Brookings Institution Board of Directors: Jiang Wu, PhD VP, Head of Bioanalytical & CMC Analytical Development Non-Confidential Robert Windsor Jr., JD VP, Head of Investor Relations Philip Ashton-Rickardt, PhD Chief Scientific Officer Brooke Story, MBA Seres Therapeutics BD Integrated Diagnostic Solutions Ajay Ria SVP, Head of Business Development 8 |
| Platform Preclinical Programs NHP studies in Hem A (SIG-001) and MPS-I (SIG-005) confirmed bioavailability in plasma Multiple rodent studies in Hem A, MPS-1, Fabry, FVII, & Hem B demonstrated bioavailability in plasma BIOAVAILABILITY FROM IP PLASMA Product delivery method evaluated in mice, pigs, NHP and human cadavers Hem A, MPS-1, Fabry, FVII Def & Hem B dose/response in animal models Efficacy demonstrated by substrate reduction for MPS-I and Fabry 1000+ mice studied in multiple safety & tox studies over 3 programs 125+ NHP evaluated in safety & tox studies Full biocompatibility 4-month NHP islets 12-month rat Islet in STZ mouse model 6-month in NSG mice (SIG-001, SIG-005, SIG-007) 6 & 12-month NHP (empty spheres) NONCLINICAL SAFETY DOSING, CONTROL, & REDOSING DURABILITY OF SLTX PLATFORM 9 |
| Bioavailability Demonstrated in NHP for SIG-001 and SIG-005 10 110 1 100 1 100 2 1003 1102 110 3 0 10 20 30 40 50 FVIII Expression in Plasma (%) Spheres expressing human protein administered intraperitoneally in cynomolgus monkeys Quantifiable plasma levels achieved for both programs demonstrate bioavailability Plasma IDUA Activity U/mL FVIII Expression IDUA Activity BIOAVAILABILITY |
| Efficacy Demonstrated in Lysosomal Disease Mice Across Three Programs 11 U/mg SIG‐005 MPS‐I Program Heparan Sulfate Level in Liver SIG‐007 Fabry Program GLA Activity in Liver SIG‐018 MPS‐2 Program Heparan Sulfate Level in Liver Low dose SIG-007 Med dose SIG-007 High dose SIG-007 Fabrazyme ng HS/mg total protein Equivalent substrate reduction for fresh and cryopreserved drug substance in SIG-005 spheres LMHSham 0 5 10 50 100 150 **** **** **** Equivalent substrate reduction for all three doses of SIG-020 in MPS-2 mouse model Medium and high dose SIG-007 equivalent or superior to Fabrazyme in Fabry mouse model DOSING |
| SLTx Designed to Provide Important Advantages Versus Gene Therapy 12 Recent Gene Therapy Setbacks: Declining efficacy (including loss of all expression) Unpredictable overdosing Insertional mutagenesis risk with AAV (genotoxicity risk) Insertional mutagenesis risk with alkylating agents Serious Adverse Events: blindness/deaths |
| SIG-001 for Hem A: Efficacy, Durability and Controllability Observed in Preclinical Studies * -Statistically significant reduction in bleeding time relative to HA + wt (p<0.05). Bleeding time (in sec) 0 500 1000 1500 2000 WT Mice HA Mice + Control Spheres HA Mice + SIG-001 * Efficacious Controllable Durable Rare Blood Disorders Hem A mice Hem A mice NSG mice 0 0.5 1 1.5 2 2.5 SIG‐001 Low dose SIG‐001 Mid dose SIG‐001 High dose hFVIII:C (IU/mL) Normal range 30 spheres 75 spheres 140 spheres Orphan Drug Designation 13 |
| SIG-001 Phase 1/2 Dose Escalation Study Rare Blood Disorders • Clinical Hold Investigation: • SAE on patient 3 due to low titer inhibitor • Investigation of potential contributing factors ongoing • Additional analyses on clinical samples • Safety Review Committee monitoring • Significant Milestones: • GMP manufacturing • Logistics of fresh product • Measurable plasma FVIII activity SIG-001 spheres (omentum) Administration catheter 8mmCatheter Port 14 5mmCamera Port UK UK US |
| Lysosomal Diseases • Our modular platform can be applied across a range of lysosomal storage diseases and lead to significant improvements in speed to clinic • In preclinical studies, platform cells produce sustained high levels of biochemically active enzyme with characteristics identical to the deficient human enzyme. • Potential sustained substrate reduction • Preclinically demonstrated Enzyme transported to target tissues, even the hard-to- reach tissues • Received Orphan Drug Designation ( ) for SIG-005 (MPS-1) and SIG- 007 (Fabry) Lysosomal Diseases 15 |
| SIG-005: Phenotypic Correction in Bone After 5 Months Of Treatment in Mice With MPS-1 Reduced thickness in cortical areas Sustained reduction in GAGs Reduction in bone volume Mineral density, mgHA/cm3 Reduction in mineral density Female Male 0.8 1.0 1.2 1.4 1.6 Average area of bone, Ct.Ar p=0.089 p=0.012 ng BM652/mg total protein SIG-005 Untreated 0 2000 4000 6000 pmol 4MU/hour/mg of protein IDUA activity in liver *microCT data is from the femur bone Lysosomal Diseases 16 |
| SIG-005: Substrate Reduction in Different Tissues after 5 Months of Treatment in Mice with MPS-1 Heart Kidney Liver Lung Treated Untreated Zeiss 20x; Alcian blue; Black arrow indicates substrate (Untx: G7-1; Tx: G3-1); * Glomerulus; * Bronchiole Lysosomal Diseases 17 |
| SIG-005 Cryopreserved Drug Substance Decreases Manufacturing Lead Time by 80% SIG‐005 MPS‐I Program Heparan Sulfate Level in Liver ng HS/mg total protein Equivalent substrate reduction for fresh and cryopreserved drug substance in SIG-005 spheres SIG‐001 (Fresh DS) SIG‐005 (Cryo DS) Lysosomal Diseases Non-confidential 18 |
| SIG-005 Clinical Design and Status • Filed CTA (UK) in June 2021 and CTA (Brazil) in July 2021 • Next step expected to include IND filing in the US 19 Lysosomal Diseases * Dose escalation may occur • Phase 1/2 Safety and Dose Ranging Study • Open‐label; Sequential dose escalation • N = 9 patients • Male and female adults (age 18 and over) with attenuated MPS‐1 (Hurler‐Scheie or Scheie) on ERT • Primary endpoint: Safety • Secondary endpoints: IDUA and GAG levels: urine and blood samples • Physical function: 6‐minute walk test, lung function test; special tests to evaluate your organs (heart, liver, spleen); holter ECG, MRI of the whole body; • Exploratory endpoints: quality of life 1st Dose Level Safety review* 1st Dose Level Safety review* 1st Dose Level Safety review* Non-confidential |
| SIG-007: Reduction Lyso-gb3 Across Tissues in Mice With Fabry After 1 Month of Treatment Lysosomal Diseases Presented at the 17th Annual WORLDSymposium™ February 8th -12 th 2021, virtually. N=6/group; L:low dose; M: medium dose; H:high dose; Unt: untreated; unpaired t‐test vs untreated: ****p<0.001; ***p<0.001; **p<0.01; *p<0.05; nsp>0.05 20 |
| SIG-018: Substrate Reduction Across Tissues in Mice With MPS-2 Mouse Tissues After 1 Week of Treatment LMHSham 0 5 10 50 100 150 **** **** **** ng HS/mg total protein as % of sham LMHSham 0 50 100 150 200 ng HS/mg total protein as % of sham ** * ** ng HS/mg total protein as % of sham LMHSham 0 50 100 150 **** ** **** HS heparan sulfate; L Low Dose; M Medium Dose; H High Dose; Each dose level, n=4; Sham, n=4; **** p<0.001; *** p<0.001; ** p<0.01; * p<0.05; n.s. p>0.05 Liver Liver Kidney Kidney Spleen Spleen Heart Heart Lung Lung Plasma Plasma Lysosomal Diseases 21 |
| SIG-020: Substrate Reduction Across Tissues in Mice With MPS-6 After 7 Days of Treatment Lysosomal Diseases 22 |
| Sigilon and Lilly Collaborating to Develop Potential Functional Cure for Type 1 Diabetes • Sigilon is responsible for execution of the program through IND • Eli Lilly, a global leader in diabetes, will develop and commercialize program worldwide if approved • Financial Terms: • $75 million initial commitment • $415 million in milestones & tiered (from single- to-low double digit) sales-based royalties Endocrine Diseases 23 |
| Diabetes Program Progresses Toward IND Blood Glucose (mg/dL) Mean ± SEM 600 500 400 300 200 100 0 Time (Days) 600 500 400 300 200 100 0 330 300 270 240 210 180 150 120 90 60 30 0 Review Article by Langer R; Molecular Frontiers Journal (2017) Rat donor islets in STZ mice (12 months) Endocrine Diseases 24 ~3,000 IEQ Encapsulated Human Islets in Diabetic Mice Our goal: Insulin independence in the absence of immunosuppression |
| Sa li ne Co n A 3T3 mIL-10 + ConA 0 2 4 6 Developing Products for Liver Diseases 25 Liver Necrosis Immune Mediated Diseases • Autoimmune hepatitis • Hepatocyte destruction by pro- inflammatory cytokines • Pathology shared with common liver diseases • IL-10 • Cytokine that resolves inflammation • IL-22 • Cytokine that regenerates the liver Saline Concanavalin A (ConA) mIL ‐ 22 spheres + ConA Proof of concept for inflammatory diseases SLTx ‐ IL ‐ 10 SLTx ‐ IL ‐ 22 Saline Concanavalin A (ConA) mIL ‐ 10 spheres + ConA Hepatocyte Necrosis Salin e Co nA 3 T3 m I L -22 + ConA 0 2 4 6 Protection from liver damage |
| Plasma Concentration CTLA ‐ 4 ‐ Ig ( g/ml) Days Post‐Implantation Developing Products for Graft Versus Host Disease Immune Mediated Diseases Loss of Body Weight Survival Sustained production of CTLA-4-Ig by SLTx Spheres No Treatment Controls Control Spheres CTLA‐4‐Ig Spheres SLTx mediated CTLA-4-Ig production ameliorates human PBMCs-driven GvHD SLTx-CTLA4-Ig • Targeting T-cell mediated GvHD • Induce sustained transplant tolerance to avoid graft rejection • Prolong graft survival 26 Non-confidential |
| Manufacturing Optimization for Off-the-Shelf Product at Scale 27 Bulk Drug Product Manufacturing Cryopreservation 28-day fresh cell culture process transitioning to cryopreserved off-the-shelf product 1 Day Manufacturing Automated Encapsulation Scale & Speed Large scale production for > 4L Drug Product /wk 3D Cell Culture Scale & Speed Large scale production for ~ 200L Drug Substance per batch Non-confidential |
| Multiple Milestones Targeted Initiating 2nd Clinical Program H2 21 •Up to 9-month follow-up Phase 1/2 data (3 patients): SIG-001/Hem A •Completion of the Clinical Hold investigation •Phase 1/2 Initiation: SIG-005/MPS-1 (pending CTA/IND approval) Potential for Three Clinical Programs 2022 •IND/CTA submission: 3rd and 4th undisclosed program •Ongoing clinical development: SIG-001/Hem A •Continue enrollment Phase1/2: SIG-005/MPS-1 (pending CTA/IND approval) 28 |
| Thank You |
