UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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| Item 2.02 | Results of Operations and Financial Condition |
On August 12, 2021, Synlogic, Inc. (the “Company”) announced its financial results for the quarter ended June 30, 2021. The full text of the press release and subsequent presentations issued in connection with the announcement is furnished as Exhibit 99.1, 99.2 and 99.3, respectively, to this Current Report on Form 8-K.
The information in this Current Report on Form 8-K (including Exhibit 99.1 and 99.2) 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 in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
The following exhibit relating to Item 2.02 shall be deemed to be furnished, and not filed:
| Exhibit No. |
Description | |
| 99.1 | Press Release dated August 12, 2021 | |
| 99.2 | Presentation dated August 12, 2021 | |
| 99.3 | Presentation dated August 12, 2021 | |
| 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 hereunto duly authorized.
| SYNLOGIC, INC. | ||||||
| Date: August 12, 2021 | By: | /s/ Gregg Beloff | ||||
| Name: | Gregg Beloff | |||||
| Title: | Interim Chief Financial Officer | |||||
Exhibit 99.1
Synlogic Reports Second Quarter Financial Results and Provides Business Update
- Proof of concept studies for co-lead metabolic programs SYNB1618 in PKU and
SYNB8802 in Enteric Hyperoxaluria on track for 2H 2021 readouts –
- Immunomodulation portfolio expanded via strategic research collaboration in IBD -
- Synlogic ends 2Q 2021 with $115.5 million in cash, cash equivalents and investments
supporting projected runway into 2H 2023 -
- Management to host conference call and webcast at 8:30 a.m. ET today -
Cambridge, Mass. (PR Newswire) August 12, 2021 – Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company bringing the transformative potential of synthetic biology to medicine, today reported financial results for the second quarter ended June 30, 2021, and provided an update on its clinical and preclinical programs.
“We are executing across our co-lead metabolic programs and advancing towards proof of concept readouts of our Synthetic Biotic™ medicines for the treatment of Phenylketonuria and Enteric Hyperoxaluria,” said Aoife Brennan, M.B. Ch.B., Synlogic’s President and Chief Executive Officer. “With a next-generation strain in a Phase 1 study for the treatment of Phenylketonuria, a strategic collaboration in place to expand our IBD pipeline and an advancing pre-clinical pipeline of metabolic disease programs, we have a robust set of potential therapies that could provide meaningful benefit to patients. We look forward to communicating results and next steps over the coming months.”
Quarter Highlights
The Metabolic Portfolio:
Proof of concept data of SYNB1618 for the treatment of Phenylketonuria (PKU) anticipated in second half of 2021, Phase 1 study of SYNB1934 initiated.
| • | The SynPheny-1 Phase 2 trial of SYNB1618 continues to progress. |
| • | SynPheny-1 is designed to evaluate plasma phenylalanine (Phe) lowering of a solid oral formulation of SYNB1618 in adult PKU patients who do not benefit from, or do not tolerate, existing therapies. |
Page 1 of 7
| • | In July, the Company initiated a Phase 1 study of SYNB1934, a next-generation strain designed for the treatment of PKU, to evaluate safety, tolerability and head-to-head comparison of Phe-consumption biomarkers between SYNB1934 and SYNB1618. |
| • | SYNB1934, an evolved strain of SYNB1618 in the PKU portfolio, has the potential to provide increased benefit to patients living with PKU. |
| • | Preclinical in vivo and in vitro studies demonstrated a greater than 2-fold improvement in the ability of SYNB1934 to consume and break down Phe compared to SYNB1618. |
| • | Papers published in the journals Nature Metabolism and Communications Biology detail findings from a first-in-human study of SYNB1618 and the development of a mechanistic model to predict the function of Synthetic Biotic medicines in healthy volunteers and PKU patients. |
| • | Data from the first-in-human study of SYNB1618 showed dose-responsive, non-saturated increases in gastrointestinal consumption of Phe by SYNB1618. |
| • | These data add to the growing body of scientific research demonstrating the therapeutic potential of Synthetic Biotic medicines for the treatment of PKU. |
SYNB1618 and SYNB1934 are orally administered Synthetic Biotic medicines being developed as potential treatments for PKU. They are intended to address the needs of patients of all age groups through the consumption of Phe in the gastrointestinal (GI) tract, which has the potential to lower blood Phe levels and enable the consumption of more natural protein in the diet.
Proof of concept data of SYNB8802 for the treatment of Enteric Hyperoxaluria anticipated in second half of 2021.
| • | SYNB8802 demonstrated proof of mechanism in Part A of an ongoing Phase 1 trial, with evidence of urinary oxalate lowering in a Dietary Hyperoxaluria model in healthy volunteers given a high oxalate diet. |
| • | Urinary oxalate lowering by SYNB8802 was robust and dose-dependent. |
| • | The 3e11 dose is undergoing evaluation in Part B of the study in patients with Enteric Hyperoxaluria. |
| • | This dose was well-tolerated and resulted in a 28.6% (90% CI: -42.4 to -11.6) reduction in urinary oxalate as measured by a change from baseline compared to placebo. |
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| • | Part B of the study is continuing with the evaluation of SYNB8802 in patients with Enteric Hyperoxaluria secondary to Roux-en-Y gastric bypass surgery. |
| • | Data on the development of SYNB8802 was presented at the Synthetic Biology: Engineering, Evolution & Design (SEED) conference in June 2021. |
SYNB8802 is an orally administered Synthetic Biotic medicine being developed as a potential treatment for Enteric Hyperoxaluria. SYNB8802 is designed to consume oxalate in the GI tract to prevent the increased absorption of oxalate in Enteric Hyperoxaluria patients.
Enteric Hyperoxaluria results in dangerously high urinary oxalate levels causing progressive kidney damage, kidney stone formation, and nephrocalcinosis. Enteric Hyperoxaluria has no approved treatment options. Approximately 100,000 patients in the US suffer from chronic and recurrent kidney stones as a result of severe Enteric Hyperoxaluria.
The Immunomodulation Portfolio:
Progression of SYNB1891 in combination arm dosing with PD-L1 checkpoint inhibitor in Phase 1 study in patients with advanced solid tumors or lymphoma.
| • | SYNB1891 is currently being evaluated in a Phase 1 study that has two parts: Part A is a monotherapy arm that has enrolled six dose cohorts to date. Part B is a combination arm with SYNB1891 and the PD-L1 checkpoint inhibitor atezolizumab that has enrolled two dose cohorts to date. |
| • | The study is ongoing. Mature combination therapy data is expected by the end of the year. |
SYNB1891 is an investigational drug for the intra-tumoral treatment of solid tumors and lymphoma, composed of an engineered Synthetic Biotic strain of E. coli Nissle that produces cyclic di-AMP (CDA), a stimulator of the STING (STimulator of INterferon Genes) pathway.
Advancement of preclinical programs in Inflammatory Bowel Disease.
| • | In June, Synlogic and Roche entered into a research collaboration agreement for the discovery of a novel Synthetic Biotic medicine for the treatment of inflammatory bowel disease (IBD). Under the terms of the agreement, Synlogic and Roche will collaborate to develop a Synthetic Biotic medicine addressing an undisclosed novel target in IBD. |
| • | Data on novel Synthetic Biotic approaches for the treatment of IBD was presented at Digestive Disease Week (DDW) in May 2021. |
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Corporate Update:
Synlogic strengthens Balance Sheet and advances synthetic biology capabilities.
| • | In April, Synlogic completed an underwritten public offering of 11.5 million shares, resulting in net proceeds to Synlogic of approximately $32.6 million. |
| • | Synlogic and Ginkgo Bioworks continue to advance their long-term strategic platform collaboration that provides expanded synthetic biology capabilities to Synlogic with multiple undisclosed metabolic programs now in preclinical stages of development. Additional information on these programs will be provided over the course of the year. |
Second Quarter 2021 Financial Results
As of June 30, 2021, Synlogic had cash, cash equivalents, and short-term investments of $115.5 million.
For the three months ended June 30, 2021, Synlogic reported a consolidated net loss of $14.5 million, or $0.28 per share, compared to a consolidated net loss of $15.5 million, or $0.44 per share, for the corresponding period in 2020.
Research and development expenses were $10.7 million for the three months ended June 30, 2021 compared to $12.9 million for the corresponding period in 2020.
General and administrative expenses for the three months ended June 30, 2021 were $4.1 million compared to $3.5 million for the corresponding period in 2020.
Revenue was $0.2 million for the three months ended June 30, 2021, compared to $0.4 million for the corresponding period in 2020. Revenue for the three months ended June 30, 2021 was due to the collaboration with Roche, for the discovery of a novel Synthetic Biotic medicine for treatment of inflammatory bowel disease (IBD). Under the terms of the agreement, Synlogic and Roche will collaborate to develop a Synthetic Biotic medicine addressing an undisclosed novel target in IBD. Revenue for the three months ended June 30, 2020 was due to the prior collaboration with AbbVie to develop Synthetic Biotic medicines for the treatment of inflammatory bowel disease, which was terminated in May 2020.
Financial Outlook
Based upon its current operating plan and balance sheet as of June 30, 2021 Synlogic expects to have sufficient cash to be able to fund the base operating plan into the second half of 2023.
Conference Call & Webcast Information
Synlogic will host a conference call and live webcast at 8:30 a.m. ET today, Thursday, August 12, 2021. To access the live webcast, please visit the “Event Calendar” page within the Investors and Media section of the Synlogic website. Investors may listen to the call by dialing +1 (844) 815-2882 from locations in the United States or +1 (213) 660-0926 from outside the United States. The conference ID number is 7586239. A replay will be available for 30 days on the Investors and Media section of the Synlogic website.
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About Synlogic
Synlogic™ is bringing the transformative potential of synthetic biology to medicine. With a premiere synthetic biology platform that leverages a reproducible, modular approach to microbial engineering, Synlogic designs Synthetic Biotic medicines that target validated underlying biology to treat disease in new ways. Synlogic’s proprietary pipeline includes Synthetic Biotics for the treatment of metabolic disorders including Phenylketonuria (PKU) and Enteric Hyperoxaluria. The company is also building a portfolio of partner-able assets in immunology and oncology. More information about Synlogic’s programs and pipeline can be found at https://www.synlogictx.com.
Forward-Looking Statements
This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, clinical development plans, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Synlogic may identify forward-looking statements. Examples of forward-looking statements, include, but are not limited to, statements regarding the potential of Synlogic’s platform to develop therapeutics to address a wide range of diseases including: cancer, inborn errors of metabolism, metabolic diseases, and inflammatory and immune disorders; our expectations about sufficiency of our existing cash balance; the future clinical development of Synthetic Biotic medicines; the approach Synlogic is taking to discover and develop novel therapeutics using synthetic biology; and the expected timing of Synlogic’s clinical trials and availability of clinical trial data. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including: the uncertainties inherent in the clinical and preclinical development process; the ability of Synlogic to protect its intellectual property rights; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading “Risk Factors” in Synlogic’s filings with the SEC. The forward-looking statements contained in this press release reflect Synlogic’s current views with respect to future events. Synlogic anticipates that subsequent events and developments will cause its views to change. However, while Synlogic may elect to update these forward-looking statements in the future, Synlogic specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Synlogic’s view as of any date subsequent to the date hereof.
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-more-
Synlogic, Inc.
Condensed Consolidated Statements of Operations
(unaudited)
| (in thousands,except share and per share data) | For the three months ended | For the six months ended | ||||||||||||||
| June 30, 2021 | June 30, 2020 | June 30, 2021 | June 30, 2020 | |||||||||||||
| Revenue |
$ | 246 | $ | 445 | $ | 246 | $ | 545 | ||||||||
| Operating expenses |
||||||||||||||||
| Research and development |
10,719 | 12,909 | 21,899 | 25,586 | ||||||||||||
| General and administrative |
4,061 | 3,473 | 7,912 | 7,294 | ||||||||||||
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| Total operating expenses |
14,780 | 16,382 | 29,811 | 32,880 | ||||||||||||
|
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|
|
|
|||||||||
| Loss from operations |
(14,534 | ) | (15,937 | ) | (29,565 | ) | (32,335 | ) | ||||||||
| Other income, net |
49 | 402 | 109 | 972 | ||||||||||||
|
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|||||||||
| Net loss |
$ | (14,485 | ) | $ | (15,535 | ) | $ | (29,456 | ) | $ | (31,363 | ) | ||||
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| Net loss per share - basic and diluted |
$ | (0.28 | ) | $ | (0.44 | ) | $ | (0.63 | ) | $ | (0.91 | ) | ||||
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| Weighted-average common shares used in computing net loss per share - basic and diluted |
52,049,424 | 34,967,761 | 46,876,216 | 34,604,738 | ||||||||||||
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Synlogic, Inc.
Condensed Consolidated Balance Sheets
(unaudited)
| (in thousands, except share data) | ||||||||
| June 30, 2021 | December 31, 2020 | |||||||
| Assets |
||||||||
| Cash, cash equivalents, and short-term investments |
$ | 115,462 | $ | 100,444 | ||||
| Fixed assets |
$ | 9,928 | 10,776 | |||||
| Other assets |
$ | 31,494 | 32,620 | |||||
|
|
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|
|
|||||
| Total assets |
$ | 156,884 | $ | 143,840 | ||||
|
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|||||
| Liabilities and stockholders’ equity |
||||||||
| Current liabilities |
$ | 9,633 | $ | 8,301 | ||||
| Long-term liabilities |
$ | 19,173 | 20,404 | |||||
|
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|||||
| Total liabilities |
28,806 | 28,705 | ||||||
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|||||
| Total stockholders’ equity |
$ | 128,078 | 115,135 | |||||
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|||||
| Total liabilities and stockholders’ equity |
||||||||
| $ | 156,884 | $ | 143,840 | |||||
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|||||
| Common stock and common stock equivalents |
||||||||
| Common stock |
52,375,344 | 38,183,273 | ||||||
| Common stock warrants (pre-funded) |
2,548,117 | 2,548,117 | ||||||
|
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|
|||||
| Total common stock |
54,923,461 | 40,731,390 | ||||||
Page 6 of 7
| MEDIA CONTACT: | INVESTOR CONTACT: | |
| Christen Baglaneas |
Daniel Rosan | |
| Synlogic, Inc. |
Synlogic, Inc. | |
|
Phone: 617-401-9152 |
Phone: 617-401-9152 | |
| Email: christen.baglaneas@synlogictx.com |
Email: dan.rosan@synlogictx.com | |
###
Page 7 of 7
Bringing the Transformative Power of Synthetic Biology to Medicine Q2 Financial Results & Business Update 12 August 2021 Exhibit 99.2
Forward Looking Statements This presentation contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this presentation regarding strategy, future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this presentation, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants may identify forward-looking statements. Examples of forward-looking statements include, but are not limited to, the approach we are taking to discover and develop novel therapeutics using synthetic biology; statements regarding the potential of our platform to develop therapeutics to address a wide range of diseases, including: metabolic diseases, inflammatory and immune disorders, and cancer; the future clinical development of Synthetic Biotic medicines; the potential of our technology to treat phenylketonuria and cancer; the expected timing of our anticipated clinical trial initiations and availability of clinical data; the benefit of orphan drug and fast track status; the adequacy of our capital to support our future operations and our ability to successfully initiate and complete clinical trials; the results of our collaborations; and the difficulty in predicting the time and cost of development of our product candidates. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the uncertainties inherent in the preclinical development process; our ability to protect our intellectual property rights; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading “Risk Factors” in our filings with the SEC. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in our quarterly report on Form 10-Q filed with the SEC on August 12, 2020, and in any subsequent filings we make with the SEC. The forward-looking statements contained in this presentation reflect our current views with respect to future events. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our view as of any date subsequent to the date hereof.
© 2020 SYNLOGIC. QU©AR2T0E1R9LYSYRNELSOUGLTICS.. AALLLL RRIIGGHHTTSS RREESSEERRVVEEDD.. || 33 Opening Remarks Dr. Aoife Brennan MB CHB President & CEO
Solid Tumors Monotherapy: target engagement, meaningful pharmaco-dynamic effects, good safety Combination with anti-PDL1: ongoing Inflammatory Bowel Disease Advancing research collaboration with Roche on novel IBD target Metabolic programs: Two PoC opportunities Immunology Clinical proof of concept data expected across multiple programs in 2021 Phenylketonuria (PKU) Proof of mechanism demonstrated in Phase 1 with healthy volunteers SYNB1618 Phase 2 SynPheny patient data expected second half of 2021 SYNB1934 Head to Head data with SYNB1618 in healthy volunteers expected second half of 2021 Enteric Hyperoxaluria Proof of mechanism demonstrated by SYNB8802 in Phase 1A with dietary hyperoxaluria induced in healthy volunteers Phase 1B patient data expected second half of 2021 Potential to demonstrate clinical benefit of the Synthetic Biotic platform in two high value indications in 2021
Phenylketonuria (PKU) SYNB1618 Immuno-Oncology SYNB1891 Inflammatory Bowel Disease Enteric Hyperoxaluria SYNB8802 SYNB1618 Undisclosed Metabolic Program #1 Undisclosed Metabolic Program #2 PoC H2 ‘21 PoC H2 ‘21 Combo study late ‘21 Robust pipelines with meaningful catalysts Metabolic pipeline Metabolite consumption in the GI tract Immunology pipeline SYNB1934 Undisclosed IBD Program #1 Exploratory Preclinical IND-Enabling Studies Phase 1 Phase 2
© 2020 SYNLOGIC. QUARTERLY RESULTS. ALL RIGHTS RESERVED. | 9 Progress in Metabolic Programs Dr. David Hava, PhD Chief Scientific Officer
Phenylketonuria (PKU) Current and emerging treatment options leave many patients behind SYNB1618 demonstrates potential to lower Phe in PKU patients SYNB1618 Phase 2 Phe-lowering trial ongoing SYNB1934 Phase 1 study initiated
ΔdapA Hippuric Acid (HA) (TCA) LAAD P araC PAL3 P fnr Trans-cinnamic acid (TCA) Phe Phenylpyruvate (PP) Phe Phenyl-lactic Acid (PLA) PheP Phenylalanine (Phe) Component Design Therapeutic strategy Metabolite consumption: Built from Synthetic Library Specifically to Consume Phe Bacterial Chassis E. coli Nissle Effector(s) SYNB1618: Wild Type PAL3 Enzyme SYNB1934: Evolved PAL3 Enzyme Degrades Phe to TCA (measurable biomarker of activity) LAAD Enzyme: Alt. Phe-consuming pathway Pump PheP: Pumps Phe into cell Switch SYNB1618: FNR & AraC promoters SYNB1934: Ptac Control gene expression Safety Features Δ dap: Auxotrophy – requires diaminopimelic acid (DAP) to grow SYNB1618 & SYNB1934 Design
SYNB1934: An evolved strain with potential for improved Phe-lowering Directed Evolution Non-Human Primates: Biomarker of Phe-Consumption
SynPheny POC Study in PKU Study powered for 20% reduction in labelled plasma Phe, providing clinically meaningful endpoint for patients without other treatment options Reduction in labelled plasma Phe after a meal challenge, not influenced by diet Reduction in fasting plasma Phe (on treatment relative to baseline, holding diet steady) Consistency in response: Responder population or consistent response across subjects Learning opportunities in SynPheny
PKU Portfolio: Data Catalysts Most compelling clinical profile will be taken forward into late phase development for PKU H2 2021 SYNB1618 SYNB1934
Enteric Hyperoxaluria (HOX) Enteric Hyperoxaluria results in significant, irreversible, and progressive kidney damage SYNB8802 proof of mechanism established: potential for best-in-class urinary oxalate lowering Proof of concept on track for 2021 data read out
The Enteric Hyperoxaluria Patient Experience Patients with underlying GI disorders faced with the burden of chronic and recurrent kidney stones High levels of pain No approved treatment options Risk of impaired kidney function Source: Patel et al, 2017; Synlogic market research “I would rather experience the pain of childbirth every year for the rest of my life than ever have one more stone.” - C., Female, 53 yrs. old, 7 stones 75,000 - 90,000 US patients with recurrent kidney stones have no available therapeutic options
Ph1 design provides POC opportunity in 2021 Dietary hyperoxaluria model is translationally relevant to patient population Phase 1A Dietary Hyperoxaluria (Healthy Volunteers) Multiple Ascending Dose High oxalate & low calcium diet run-in Induce dietary hyperoxaluria N = 45 subjects Endpoints Primary: Safety & tolerability Secondary: Microbial kinetics of strain Exploratory: (1) Plasma and urine biomarkers (2) Dose frequency assessment Phase 1B Enteric Hyperoxaluria Patients Cross-over Enteric Hyperoxaluria patients (Roux-en-Y population) Three times/day (TID) dosing N = 20 patients, baseline UOx >70 mg/day Endpoints: Primary: Change in Urinary Oxalate Secondary: (1) Microbial kinetics of strain (2) Safety and tolerability
SYNB8802 3e11 live cells dose advancing to Ph1B in patients LS mean change over Placebo, +/- 90% std error of measurement, all days; and 24hr UOx after 5 days of dosing, +/- 90% std error of measurement. 600mg daily oxalate. Change in UOx UOx Levels Clinically meaningful lowering of urinary oxalate demonstrated at a well tolerated dose Upper limit of normal
Opportunity for multiple clinically relevant outcomes in Phase1B Potential to demonstrate meaningful urinary oxalate lowering in patients with active disease Learning opportunities in Phase 1 SYNB8802 has established urinary oxalate lowering in dietary hyperoxaluria (HV) model Potential for urinary oxalate lowering in Enteric Hyperoxaluria population (Roux-en-Y) Degree of colonic activity of SYNB8802 and potential for less frequent dosing
Balance Sheet (unaudited) 30 June 2021 31 December 2020 Cash, Cash Equivalents, and Marketable Securities $115.5 M $100.4 M Statement of Operations (unaudited) 30 June 2021 30 June 2020 R&D Expenses $10.7 M $12.9 M G&A Expenses $4.1 M $3.5 M Net Loss $(14.5 M) $(15.5 M) Net loss per share – basic and diluted* $(0.28) $(0.44) Weighted Average Shares Outstanding* 52.0 M 34.9 M Three Months Ended * weighted average shares used in computing net loss per shares - basic and diluted Second Quarter, 2021 Summary Results
© 2020 SYNLOGIC. QU©AR2TE1R9LYSYRNELSOUGLTICS.. AALLLL RRIIGGHHTTSS RREESSEERRVVEEDD.. || 1414 Concluding Remarks Dr. Aoife Brennan MD CHB President & CEO
Synlogic is entering a data rich period in the clinic Robust portfolio with significant clinical readouts in 2021 H1 2021 H2 2021 PKU Immuno-Oncology SYNB1891 Ph1 Arm 2 combination read-out SYNB1618 Ph2 SynPheny proof of concept read-out Enteric Hyperoxaluria SYNB8802 Ph1A study in HV read-out SYNB8802 Initiate Ph1B study in patients SYNB8802 Ph1B proof of concept read-out SYNB1934 Head to Head data in HV SYNB1934
Available For Questions Dave Hava, PhD Chief Scientific Officer Daniel Rosan Head of Finance & Investor Relations Aoife Brennan, MB ChB President & CEO Antoine Awad Chief Operating Officer
Bringing the Transformative Power of Synthetic Biology to Medicine Corporate Presentation August 2021 Exhibit 99.3
Forward Looking Statements This presentation contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this presentation regarding strategy, future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this presentation, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants may identify forward-looking statements. Examples of forward-looking statements include, but are not limited to, the approach we are taking to discover and develop novel therapeutics using synthetic biology; statements regarding the potential of our platform to develop therapeutics to address a wide range of diseases, including: metabolic diseases, inflammatory and immune disorders, and cancer; the future clinical development of Synthetic Biotic medicines; the potential of our technology to treat phenylketonuria and cancer; and the expected timing of our anticipated clinical trial initiations and availability of clinical data; the benefit of orphan drug and fast track status; the adequacy of our capital to support our future operations and our ability to successfully initiate and complete clinical trials; the results of our collaborations; and the difficulty in predicting the time and cost of development of our product candidates. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the uncertainties inherent in the preclinical development process; our ability to protect our intellectual property rights; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading “Risk Factors” in our filings with the SEC. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in our annual report on Form 10-K filed with the SEC on August 12, 2021, and in any subsequent filings we make with the SEC. The forward-looking statements contained in this presentation reflect our current views with respect to future events. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our view as of any date subsequent to the date hereof.
Solid Tumors Monotherapy: target engagement, meaningful pharmaco-dynamic effects, good safety Combination with anti-PDL1: ongoing Inflammatory Bowel Disease Advancing research collaboration with Roche on novel IBD target Metabolic programs: Two PoC opportunities Immunology Clinical proof of concept data expected across multiple programs in 2021 Phenylketonuria (PKU) Proof of mechanism demonstrated in Phase 1 with healthy volunteers SYNB1618 Phase 2 SynPheny patient data expected second half of 2021 SYNB1934 Head to Head data with SYNB1618 in healthy volunteers expected second half of 2021 Enteric Hyperoxaluria Proof of mechanism demonstrated by SYNB8802 in Phase 1A with dietary hyperoxaluria induced in healthy volunteers Phase 1B patient data expected second half of 2021 Potential to demonstrate clinical benefit of the Synthetic Biotic platform in two high value indications in 2021
A new class of medicines Enabling engine of synthetic biology, manufacturing and translational capabilities Creates multiple product opportunities Robust pipeline Rare metabolic therapies that consume toxic metabolites from the GI tract Therapies that leverage the ability of bacteria to interact with the immune system Synthetic Biotic platform Targeted & controllable, patient friendly treatment Non-pathogenic bacterial chassis + Programable, engineering Toxin Promoter Inducer Effector Biomarker Biomarker
Phenylketonuria (PKU) SYNB1618 Immuno-Oncology SYNB1891 Inflammatory Bowel Disease Enteric Hyperoxaluria SYNB8802 SYNB1618 Undisclosed Metabolic Program #1 Undisclosed Metabolic Program #2 PoC H2 ‘21 PoC H2 ‘21 Combo study late ‘21 Robust pipelines with meaningful catalysts Metabolic pipeline Metabolite consumption in the GI tract Immunology pipeline SYNB1934 Undisclosed IBD Program #1 Exploratory Preclinical IND-Enabling Studies Phase 1 Phase 2
Rationale High unmet need across inherited and acquired metabolic diseases Multiple large and underserved markets Diseases with known pathophysiology Dietary intervention validates GI approach Bacteria evolved to survive in the GI tract Ability to deploy multiple enzyme pathways Drug-like approach without genetic drift or colonization Multiple programs demonstrate SYNB compounds can consume toxic metabolites in the human GI tract Validated Biology Unmet Medical Need Unique Advantages Proof of Mechanism Why metabolic disease? Why Synthetic Biotic medicine? Synthetic Biotic medicines: a novel approach to metabolic disease
Applying Synthetic Biotic medicines to PKU and Enteric Hyperoxaluria Unique Advantages Platform Proof of Mechanism Validated Biology Unmet Medical Need Phenylketonuria (PKU) Enteric Hyperoxaluria (HOX) Many patients unable to control Phe ~70% pts do not respond to BH4 oral therapy Recurrent and chronic kidney stones; Increased risk of chronic kidney disease progression No effective interventions or treatments Lower dietary Phe intake = lower plasma Phe levels = improved cognitive outcomes Lower dietary oxalate intake = lower urinary oxalate = improved kidney outcomes Modality able to consume Phe in the GI tract before it can cause damage Modality able to consume oxalate throughout GI tract, including colon SYNB1618 consumes Phe and produces the TCA biomarker in both HVs and patients SYNB8802 consumes oxalate in healthy volunteers at clinically meaningful levels
Phenylketonuria (PKU) Current and emerging treatment options leave many patients behind SYNB1618 demonstrates potential to lower Phe in PKU patients SYNB1618 Phase 2 Phe-lowering trial ongoing SYNB1934 Phase 1 study initiated
Patient need: parents expect their children to reach full potential Reality: 25% – 65% of patients still struggle to maintain blood Phe within target range Historically Prospect of severe mental disability and institutionalization. Parents wanted PKU child to avoid institutionalized care before adulthood. Early diagnosis and strict diet control enables better Phe management. Parents expect PKU child to achieve full potential. Julia, living with PKU Today
An innovative approach in area of high unmet medical need Synlogic has initiated a Ph2 Study in PKU patients (SynPheny) Our approach Oral therapy, 3 x day with meals Meaningful biomarker-driven outcomes Addition of more natural protein into the diet Lower blood Phe Increase Phe-metabolites such as TCA Convert dietary Phe to harmless metabolites (TCA) Reduce plasma Phe
Significant market opportunity, large unmet need, with potential for new products to capture share Disease Goal Patients Product Use Monotherapy Combination Prescribed with Kuvan Out of Phe Control In Phe control Lower blood Phe Addition of more natural protein/day Adults ~12,300 U.S. 65% out of Phe control Pediatrics ~5,000 U.S. 25% of out of Phe control ~70% fail to respond to Kuvan Multiple areas of unmet need continue across PKU patient types
Includes 7,500 “lost to follow up” SYNB1618 is uniquely positioned to address those needs Marketed Marketed Phase 1/2 Phase 3 Mechanism does not depend on genotype Appropriate for pediatrics and adults Benign safety profile, no systemic exposure Oral administration Phase 2 SYNB1618 Marketed Development Partial Response Infants, up to age 2 ~500 Pediatrics, up to age 12 ~2,800 Pediatrics, up to age 16 ~1,200 REMS Adults & 16+ ~13,0001 Bh4 Responsive Only
Solid oral SYNB1618 reduced Phe and elevated biomarkers in Ph1 Achieved Proof of Mechanism: SYNB1618 consumed D5 Phe in GI tract & lowered plasma D5 Phe Data are means and 90% CI D5 Phe Converted to D5 TCA Plasma D5 Phe Blunted D5 TCA Converted to D5 HA
SynPheny-1 design enables Proof of Concept 3 days Dose 1 1e11 Dose 3 1e12 Dose 4 2e12 7 days Diet run-in 6 days 2 days D5-Phe AUC Baseline Fasting Phe Dose 2 3e11 3 days D5-Phe AUC Day 14 Fasting Phe TRIAL DESIGH Plasma Phe lowering in fasted state at 1e12 live cells over 7 days Post meal D5-Phe AUC lowering at 2e12 live cells Strict dietary management to maintain constant Phe intake Understand relationship of strain specific biomarkers with plasma Phe lowering Phe lowering in patients Validation of PD models TRIAL OUTPUTS Safety & tolerability Continuously assessed throughout dosing period N = 12
SynPheny POC Study in PKU Study powered for 20% reduction in labelled plasma Phe, providing clinically meaningful endpoint for patients without other treatment options Reduction in labelled plasma Phe after a meal challenge, not influenced by diet Reduction in fasting plasma Phe (on treatment relative to baseline, holding diet steady) Consistency in response: Responder population or consistent response across subjects Learning opportunities in SynPheny
SYNB1934: An evolved strain with potential for improved Phe-lowering Directed Evolution Non-Human Primates: Biomarker of Phe-Consumption
Enteric Hyperoxaluria (HOX) Enteric Hyperoxaluria results in significant, irreversible, and progressive kidney damage SYNB8802 proof of mechanism established: potential for best-in-class urinary oxalate lowering Proof of concept on track for 2021 data read out
The Enteric Hyperoxaluria Patient Experience Patients with underlying GI disorders faced with the burden of chronic and recurrent kidney stones High levels of pain No approved treatment options Risk of impaired kidney function Source: Patel et al, 2017; Synlogic market research “I would rather experience the pain of childbirth every year for the rest of my life than ever have one more stone.” - C., Female, 53 yrs. old, 7 stones 75,000 - 90,000 US patients with recurrent kidney stones have no available therapeutic options
Hyperoxaluria: Primary vs. Enteric Number of Patients Affected Primary Hyperoxaluria Enteric Hyperoxaluria Pathology Rare genetic condition Dietary oxalate hyperabsorption Onset Pediatric Adult Trigger Genetic liver enzyme deficiency Underlying insult to bowel: including IBD, bariatric surgery, other chronic GI conditions UOx. Levels 90 – 500 mg / 24 hrs (~10x normal) 45 – 130 mg / 24 hrs (~3x normal) U.S. Patients ~5,000 – 8,000 ~200,000 – 250,000 Key Players Clinical consequences Limited ability to manage with diet | Nephrocalcinosis | Recurrent, chronic kidney stones | Impaired renal function | Systemic Oxalosis
Oral therapy An innovative approach in an area of high unmet medical need Our approach Consume Oxalate in the GI Tract Reduce Oxalate in the urine Differentiation from other approaches Ph 1B Proof of Concept in Enteric Hyperoxaluria patients (Roux-en-Y population) initiated Consumes oxalate in each GI compartment, throughout GI tract
Absorbs oxalate throughout GI tract, esp. in colon Dietary Oxalate Stomach Small intestine Colon Oxalate absorption Healthy state Disease state Healthy people absorb ~10% of dietary oxalate, mostly via stomach and small intestine Patients absorb ~20-30% of dietary oxalate, through entire GI tract including colon Pathway Absorption Oral enzyme Oxalobacter formigenes Optimal treatment SYNB8802 consumes Oxalate throughout the GI tract ?
Ph1 design provides POC opportunity in 2021 Dietary hyperoxaluria model is translationally relevant to patient population Phase 1A Dietary Hyperoxaluria (Healthy Volunteers) Multiple Ascending Dose High oxalate & low calcium diet run-in Induce dietary hyperoxaluria N = 45 subjects Endpoints Primary: Safety & tolerability Secondary: Microbial kinetics of strain Exploratory: (1) Plasma and urine biomarkers (2) Dose frequency assessment Phase 1B Enteric Hyperoxaluria Patients Cross-over Enteric Hyperoxaluria patients (Roux-en-Y population) Three times/day (TID) dosing N = 20 patients, baseline UOx >70 mg/day Endpoints: Primary: Change in Urinary Oxalate Secondary: (1) Microbial kinetics of strain (2) Safety and tolerability
High oxalate diet successfully elevated UOx levels in HV Historically Uox in HV is <40 mg/24h. Examples: Langman 2018, (27 mg), Quintero 2020, (19.8mg), Captozyme 2018 (28 mg). Mean +/- SD shown. American diet contains approx. 200-250 mg oxalate/day HV subjects were given a high oxalate, low calcium diet (HOLC) during the diet run-in and treatment phases of the study HV subjects absorb approx. 10% of dietary oxalate Urinary oxalate levels elevated to >1.5X typically observed in healthy volunteers Dietary intake carefully measured on in-patient unit, incl. weighing of meals consumed Baseline Urinary Oxalate after HOLC diet Typical observed HV UOx
Dose-responsive and reproducible Uox lowering demonstrated Efficacy Analysis (% Change from Baseline in 24h UOx over Pbo) 600mg Daily Oxalate 400mg Daily Oxalate Lower is better Lower is better LS mean change over Placebo, +/- 90% CI, all days baseline and treated
SYNB8802 3e11 live cells dose advancing to Ph1B in patients LS mean change over Placebo, +/- 90% std error of mean, all days; and 24hr UOx after 5 days of dosing, +/- 90% std error of mean. 600mg daily oxalate. Change in UOx UOx Levels Clinically meaningful lowering of urinary oxalate demonstrated at a well tolerated dose Upper limit of normal
Opportunity for multiple clinically relevant outcomes in Phase1B Potential to demonstrate meaningful urinary oxalate lowering in patients with active disease Learning opportunities in Phase 1 SYNB8802 has established urinary oxalate lowering in Dietary Hyperoxaluria (HV) model Potential for urinary oxalate lowering in Enteric Hyperoxaluria population (Roux-en-Y) Degree of colonic activity of SYNB8802 and potential for less frequent dosing
SYNB8802 Summary: 3e11 live cells moving into patients SYNB8802 was generally well tolerated in healthy volunteers. No serious or systemic adverse events. Most frequent AEs mild or moderate, transient, and GI-related Dose responsive changes in urinary oxalate levels were observed with a significant reduction in urinary oxalate relative to placebo across three dose levels Baseline urinary oxalate reduction of 28.6% compared to placebo Mean 24-hour urinary oxalate level of 40.1 mg for subjects, compared to 58.1 mg for placebo, at the end of dosing 3e11 live cells dose will advance to patient studies
Synlogic is entering a data rich period in the clinic Robust portfolio with significant clinical readouts in 2021 H1 2021 H2 2021 PKU Immuno-Oncology SYNB1891 Ph1 Arm 2 combination read-out SYNB1618 Ph2 SynPheny proof of concept read-out Enteric Hyperoxaluria SYNB8802 Ph1A study in HV read-out SYNB8802 Initiate Ph1B study in patients SYNB8802 Ph1B proof of concept read-out SYNB1934 Head to Head data in HV SYNB1934
Balance Sheet (unaudited) 30 June 2021 31 December 2020 Cash, Cash Equivalents, and Marketable Securities $115.5 M $100.4 M Statement of Operations (unaudited) 30 June 2021 30 June 2020 R&D Expenses $10.7 M $12.9 M G&A Expenses $4.1 M $3.5 M Net Loss $(14.5 M) $(15.5 M) Net loss per share – basic and diluted* $(0.28) $(0.44) Weighted Average Shares Outstanding* 52.0 M 34.9 M Three Months Ended * weighted average shares used in computing net loss per shares - basic and diluted Second Quarter, 2021 Summary Results
Collaborators Board of Directors Experienced leadership team and Board Peter Barrett, Chair Atlas Venture Mike Burgess Turnstone Biologics Michael Heffernan Collegium Patricia Hurter Lyndra Therapeutics Lisa Kelly-Croswell Boston Medical Center Health System Nick Leschly Bluebird Bio Ed Mathers NEA Richard Shea Syndax Daniel Rosan Head of Finance & Investor Relations Dave Hava, PhD Chief Scientific Officer Aoife Brennan, MB ChB President & CEO Antoine Awad Chief Operating Officer Caroline Kurtz, PhD Chief Development Officer Leadership Team
Engineering Synthetic Biotic Medicines
Toxin Promoter Inducer Effector Biomarker Biomarker Reusable parts enable rapid iteration of rationally designed prototypes Non-pathogenic bacterial chassis Programable, controllable engineering Drug-like properties Does not colonize No in vivo reproduction or risk of genetic drift Inducer-Promoter Switch Effector Design Safety Features E. coli Nissle Synthetic Biotic Medicine A new class of medicines
Synthetic Biotic Platform accelerates pathway into the clinic Validated biology Unmet medical need Unique SYBX advantages Target selection Enabling Engine Internal GMP manufacturing Modular SynBio components Translational, clinical and regulatory Deep synthetic biology expertise Resulting portfolio Metabolic pipeline: Metabolite consumption in the GI tract Immunology pipeline: Potential for partnership Synthetic Biotic Platform
Synthetic Biotic Platform is enabling engine for drug development Rapid pipeline expansion possible with reusable engineering >200 humans dosed with Synthetic Biotic medicines 5 INDs opened with the U.S. FDA Supportive regulatory feedback from global agencies Safe chassis organism (>100 years of human experience) Internal process development and GMP manufacturing of live biotherapeutic Modular SynBio components enables rapid, iterative product development Translational, clinical and regulatory experience for live biotherapeutic medicine Deep synthetic biology expertise: Internal + Ginkgo Bioworks Synthetic Biotic Platform Synthetic Biotic Platform
Versatile platform enables diverse therapeutic strategies for range of diseases Pfnr Enzyme Metabolism Non-Toxic Toxic Metabolite Consumption Pfnr Production Payload Surface Display Effector Secretion Small molecule production Enzyme Pfnr Catalysis Payload Pfnr Production Processing Synthetic Biotic Platform
Toxin Promoter Inducer Effector Biomarker Biomarker Biomarker 2 P Component Library of parts Therapeutic strategy Metabolite consumption, small molecule production, effector secretion or surface display Bacterial Chassis Probiotic: Decades of human use & safety data Effector(s) Proteins for activity: Can generate biomarkers Pump Transports metabolites or proteins across cell membrane Switch Inducer-promoter pair: Controls gene expression Safety Features Auxotrophies: Prevents growth within or external to the body Reusable parts enable rapid iteration of rationally designed prototypes Effector 2
ΔdapA Hippuric Acid (HA) (TCA) LAAD P araC PAL3 P fnr Trans-cinnamic acid (TCA) Phe Phenylpyruvate (PP) Phe Phenyl-lactic Acid (PLA) PheP Phenylalanine (Phe) Component Design Therapeutic strategy Metabolite consumption: Built from Synthetic Library Specifically to Consume Phe Bacterial Chassis E. coli Nissle Effector(s) SYNB1618: Wild Type PAL3 Enzyme SYNB1934: Evolved PAL3 Enzyme Degrades Phe to TCA (measurable biomarker of activity) LAAD Enzyme: Alt. Phe-consuming pathway Pump PheP: Pumps Phe into cell Switch SYNB1618: FNR & AraC promoters SYNB1934: Ptac Control gene expression Safety Features Δ dap: Auxotrophy – requires diaminopimelic acid (DAP) to grow SYNB1618 & SYNB1934 Design
Ox/ formate Pump (OxLT) CoA+ ATP Ppi+ AMP OxdC FEC Formate Oxalate Oxalyl CoA Formyl CoA Oxalate Formate ΔthyA Component SYNB8802 Design Therapeutic strategy Metabolite consumption: Engineered to Convert Oxalate to Formate for the Treatment of Enteric Hyperoxaluria Bacterial Chassis E. coli Nissle Effector(s) OxdC and associated components: Catalyzes conversion of oxalate to formate Pump OxLT: Pumps oxalate in & formate out Switch FNR promoter: Inducer-promoter pair Safety Features Δ thyA: Controls growth SYNB8802 Design
Focus on Immuno-Oncology
Immuno-Oncology SYNB1891 potential for improved efficacy relative to other STING approaches SYNB1891 monotherapy demonstrated meaningful pharmacodynamic effects Phase 1 in combination with Tecentriq initiated: Data will be available in 2021
daC ΔthyA ΔdapA ATP + ATP Cyclic-di-AMP (STING Agonist) P fnr Component SYNB1981 Design Therapeutic strategy Small molecule production: Leveraging the ability of bacteria to interact with the immune system to turn a cold tumor hot Bacterial Chassis E. coli Nissle: Targeting to antigen presenting cells in the tumor microenvironment. Innate immune activation Effector(s) STING Agonist: Innate immune activator compounds with chassis effect Pump Not necessary Switch STING-agonist production restricted to hypoxic TME for sustained payload delivery Safety Features Dual auxotrophies inhibit bacterial proliferation outside of tumor SYNB1891 Design
Phase 1 design: multidose tolerability, IT mono and combo Arm 1: Monotherapy Cohorts Arm 2: Combination Cohorts - Atezolizumab Sentinel Patient Day 7 safety Eval Patient 2 & 3 Safety Evaluation Repeat for each cohort Arm 1 Cohort 4 Starting dose Arm 1 Cohort 3 level (1x107) Sentinel Patient Day 7 safety Eval Patient 2 & 3 Safety Evaluation Repeat for each cohort Recommended Ph2 Dose (RP2D) Enroll <20 patients at RP2D Proof of mechanism: exploratory biomarkers in advanced solid tumors or lymphomas PD response (tumor biopsy): TILs, IFN b, IFN dependent gene expression (Nanostring) Immunohistochemistry Kinetics of SYNB1891 (qPCR) Systemic PD effects (blood): Serum cytokines levels Kinetics of SYNB1891 (qPCR) Combination with PD-1 will identify Phase 2 dose, provide evidence of target engagement, safety, and support for target tumor type POM/Exploratory Biomarkers
SYNB1891 advanced into combo. therapy arm of Ph. 1 with Tecentriq SYNB1891 is safe and well-tolerated as an intratumoral injection with no dose limiting toxicities or infections to date Combination therapy data will be available in late 2021 Monotherapy dose escalation will continue in parallel to combination dose escalation of SYNB1891 with fixed dose of Atezolizumab (Tecentriq) SYNB1891 demonstrates meaningful pharmacodynamic effects including systemic cytokine responses observed in two subjects Evidence of durable stable disease was observed in two patients SYNB1891 demonstrates target engagement as assessed by upregulation of IFN-stimulated genes and T-cells