SYNB-8802

Phenylketonuria (PKU) program on track for Phase 3 trial initiation in first half of 2023 Rare Pediatric Disease Designation granted for SYNB1934 for PKU and SYNB1353 for homocystinuria (HCU) Platform presentation and two poster presentations at SIMD Annual Meeting $77.6 million in cash, cash equivalents and marketable securities support projected runway into second half of 2024 CAMBRIDGE, Mass., March 29, 2023 (GLOBE NEWSWIRE) -- Synlogic, Inc. (Nasdaq: SYBX), the leading company advancing therapeutics based on synthetic biology, today reported financial results for the fourth quarter and full year ending December 31, 2022 and provided a business update. “Last year was a tremendous year for Synlogic and our Synthetic Biotic platform given our three positive clinical readouts in three different diseases in the fourth quarter alone,” said Aoife Brennan, M.B. Ch.B., Synlogic President and Chief Executive Officer. “We are on track to initiate Synpheny-3, the pivotal Phase 3 study for SYNB1934 in PKU, our lead program, and we were thrilled to present three data presentations – including Phase 2 PKU data as a platform presentation – at the SIMD Annual Meeting.” Fourth Quarter 2022 and Recent Highlights Received positive opinion on orphan designation from the European Medicines Agency (EMA) for SYNB1934 for PKU Presentation of data from both the Phase 2 Synpheny-1 study in PKU and the Phase 1 study with SYNB1353 for HCU at the Society for Inherited Metabolic Disorders (SIMD) 44th Annual Meeting Received Rare Pediatric Disease Designation (RPDD) from the U.S. Food and Drug Administration (FDA) for both: SYNB1934 for PKU SYNB1353 for HCU Announced positive top-line Phase 2 data for PKU; advancing SYNB1934 to Phase 3 Demonstrated proof of mechanism for SYNB1353 for HCU, based on a top-line data from a Phase 1 study using a methionine meal challenge in healthy volunteers Proof of concept achieved with Phase 1b top-line data for SYNB8802 for enteric hyperoxaluria Anticipated Upcoming Milestones Initiation of Phase 3 clinical trial of SYNB1934 for PKU in the first half of 2023 Advancing SYNB1353 to Phase 2 study in patients with HCU Presentation of data from Phase 1b studies of SYNB8802, in development for enteric hyperoxaluria Progression of preclinical pipeline programs, including partnerships Corporate Updates In January 2023, the company announced the appointment of Dr. Dave Hava as Head of Research and Development. Through the integration of the company’s research and development teams, Dr. Hava oversees the advancement of clinical stage programs in addition to progressing our collaboration with Roche and select preclinical programs. Dr. Hava joined Synlogic in 2020, as Chief Scientific Officer, and continues to assume this position within the company. Fourth Quarter 2022 Financial Results As of December 31, 2022, Synlogic had cash, cash equivalents, and short-term marketable securities of $77.6 million. Revenue was $0.1 million for the three months ended December 31, 2022, compared to $0.6 million for the corresponding period in 2021. Revenue in both periods was associated with the ongoing research collaboration with Roche for the discovery of a novel Synthetic Biotic medicine for the treatment of IBD. Research and development expenses were $13.6 million for the three months ended December 31, 2022, compared to $11.9 million for the corresponding period in 2021. General and administrative expenses for the three months ended December 31, 2022 were $3.8 million compared to $3.9 million for the corresponding period in 2021. For the three months ended December 31, 2022, Synlogic reported a consolidated net loss of $16.7 million, or $0.24 per share, compared to a consolidated net loss of $15.1 million, or $0.21 per share, for the corresponding period in 2021. Full Year 2022 Financial Results Revenues were $1.2 million for the year ended December 31, 2022, compared to $1.8 million for the same period in 2021. Revenue in both periods was associated with the ongoing research collaboration with Roche for the discovery of a novel Synthetic Biotic medicine for the treatment of IBD. Operating expenses were $68.6 million for the year ended December 31, 2022, compared to $62.5 million for the same period in 2021. For the year ended December 31, 2022, consolidated net loss was $66.1 million, or $0.92 per share, compared to a consolidated net loss of $60.6 million, or $1.09 per share, for the year ended December 31, 2021. Financial Outlook Based upon its current operating plan and balance sheet as of December 31, 2022, Synlogic expects to have sufficient cash to be able to fund operations into the second half of 2024. About Synlogic Synlogic is the leading company advancing therapeutics based on synthetic biology. Synlogic’s pipeline includes its lead program in phenylketonuria (PKU), which has demonstrated proof of concept with plans to start a pivotal, Phase 3 study in the first half of 2023, and additional novel drug candidates designed to treat homocystinuria (HCU), enteric hyperoxaluria and gout. The rapid advancement of these potential biotherapeutics, called Synthetic Biotics, has been enabled by Synlogic’s reproducible, target-specific drug design. Synlogic uses programmable, precision genetic engineering of well-characterized probiotics to exert localized activity for therapeutic benefit, with a focus on metabolic and immunological diseases. In addition to its clinical programs, Synlogic has a research collaboration with Roche on the discovery of a novel Synthetic Biotic for the treatment of inflammatory bowel disease or IBD. Synlogic has also developed two drug candidates through a research collaboration with Ginkgo Bioworks: SYNB1353, designed to consume methionine for the potential treatment of HCU, and SYNB2081, designed to lower uric acid for the potential treatment of gout. For additional information visit . 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," “look forward,” "estimate," "expect," "intend," on track,” "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 approach to Synthetic Biotics to develop therapeutics to address a wide range of diseases including: inborn errors of metabolism and inflammatory and immune disorders; our expectations about sufficiency of our existing cash balance; the future clinical development of Synthetic Biotics; the approach Synlogic is taking to discover and develop novel therapeutics using synthetic biology; and the expected timing of Synlogic's clinical trials of SYNB1934, SYNB1353, SYNB8802 and SYNB2081 and availability of clinical trial data. Actual results could differ materially from those contained in any forward-looking statements 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 U.S. Securities and Exchange Commission. 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. Media Contact: media@synlogictx.com Investor Relations:investor@synlogictx.com Synlogic, Inc. Condensed Consolidated Statements of Operations (unaudited) (in thousands,except share and per share data) For the three months ended For the years ended December 31 December 31 2022 2021 2022 2021 Revenue $ 106 $ 592 $ 1,180 $ 1,754 Operating expenses Research and development 13,639 11,873 52,044 47,127 General and administrative 3,770 3,864 16,555 15,392 Total operating expenses 17,409 15,737 68,599 62,519 Loss from operations (17,303 ) (15,145 ) (67,419 ) (60,765 ) Other income, net 607 56 1,272 204 Net loss $ (16,696 ) $ (15,089 ) $ (66,147 ) $ (60,561 ) Net loss per share - basic and diluted $ (0.24 ) $ (0.21 ) $ (0.92 ) $ (1.09 ) Weighted-average common shares used in computing net loss per share - basic and diluted 70,742,634 71,945,538 71,725,479 55,329,711 Synlogic, Inc. Condensed Consolidated Balance Sheets (in thousands, except share data) December 31, December 31, 2022 2021 Assets Cash, cash equivalents, & marketable securities $ 77,629 $ 136,629 Property and equipment, net 7,323 9,088 Other assets 25,913 29,019 Total assets $ 110,865 $ 174,736 Liabilities and stockholders' equity Current liabilities $ 12,122 $ 10,080 Long-term liabilities 16,133 17,390 Total liabilities 28,255 27,470 Total stockholders' equity $ 82,610 $ 147,266 Total liabilities and stockholders' equity $ 110,865 $ 174,736 Common stock and common stock equivalents Common stock 66,736,251 69,698,844 Common stock warrants (pre-funded) 2,548,117 2,548,117 Total common stock 69,284,368 72,246,961

Top-line Phase 1 data in healthy volunteers show that SYNB1353 reduces plasma methionine by consuming methionine in the GI tract SYNB1353 has been granted Orphan Drug Designation (ODD) from the FDA for the treatment of homocystinuria (HCU) Company confirms expectations for proof-of-concept data for SYNB8802 in enteric hyperoxaluria before year-end and Phase 3 initiation of SYNB1934 for PKU in H1 2023 Organization streamlined to best support strategic priorities CAMBRIDGE, Mass., Nov. 30, 2022 (GLOBE NEWSWIRE) -- Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company developing medicines for metabolic and immunological diseases through its proprietary approach to synthetic biology, today announced that SYNB1353 has achieved proof of mechanism and positive results in a Phase 1 study in healthy volunteers treated with multiple ascending doses of SYNB1353. SYNB1353 is an orally administered, non-systemically absorbed drug candidate designed to consume methionine in the GI tract for the potential treatment of homocystinuria (HCU). The Company also shared that the FDA has granted Orphan Drug Designation (ODD) to SYNB1353 for the treatment of HCU. ODD is granted by the FDA to drugs or biologics intended to treat a rare disease or condition, which generally affects less than 200,000 individuals in the U.S. ODD-granted therapies entitle companies to development incentives including tax credits for qualified clinical trials, user fee exemptions, and the potential for seven years of market exclusivity after approval. Following the recent successful completion of the Company’s Phase 2 study in phenylketonuria (PKU), and now with proof of mechanism achieved in the Phase 1 for HCU, the Company also shared a plan to focus on advancing its clinical stage and prioritized preclinical research programs. Top-line Findings: The goal in treating HCU is to reduce and control severely elevated levels of total homocysteine (tHcy), thereby reducing risk of acute, potentially life-threatening blood clots and chronic, multisystem complications. A diet low in methionine, a precursor to homocysteine, is standard in HCU; SYNB1353 is engineered to metabolize methionine in the GI tract to prevent its absorption and conversion into homocysteine. An objective of this Phase 1 study was to assess effects of methionine consumption by SYNB1353 in healthy volunteers, assessed primarily through a dietary model using a methionine meal challenge. This dietary model was intended to capture in healthy volunteers a transient elevation in methionine following a meal challenge, in order to demonstrate proof of mechanism of consumption of methionine by SYNB1353. Top-line findings include: Dosing of SYNB1353 resulted in a reduction in plasma methionine when measured over 24-hours as area under the curve (AUC) following a methionine meal challenge. SYNB1353 was generally well tolerated. Adverse events (AEs) were all mild to moderate, transient, and predominantly GI in nature. Frequency and severity of GI-related AEs were similar in the active and control group. “We are pleased to share this important milestone for our HCU program and our second positive data readout for the Synthetic Biotic platform in 2022,” said Aoife Brennan, M.B. Ch.B., Synlogic President and Chief Executive Officer. “HCU is an extremely challenging disease and patients need new treatment options. The difficulty of current treatments, including the low methionine diet, results in many patients remaining at risk of life-threatening consequences. We are very pleased that SYNB1353 has demonstrated promise to provide a safe, oral treatment option through its novel approach, and look forward to its continued development, including evaluation for proof of concept in HCU patients.” “With today’s favorable study results, we are also sharing news of our realigned organization, now optimized to execute against our strategic priorities and create a stronger, more agile company. We are grateful for the dedication of our departing colleagues to our mission. Their tremendous contributions have helped us pioneer Synthetic Biotics, and most of all, provided hope to many patients and families in need of new treatments.” The SYNB1353 Phase 1 Study The phase 1 study included a double-blind, dose-escalation, randomized, placebo-controlled, multiple-ascending dose (MAD) design in healthy volunteers in an inpatient setting. The objectives were to evaluate the safety and tolerability, assess clearance measured with quantitative polymerase chain reaction following dosing, and evaluate the pharmacodynamic effects on plasma methionine following a methionine loading study, providing a dietary model of HCU. Synlogic has completed dosing of 30 total subjects over four cohorts which evaluated three different dose levels (3x1011, 6x1011 and 1x1012 live cells) and two different formulations at the 1x1012 dose. In each cohort, the subjects were randomly assigned to receive either SYNB1353 or a placebo (6 active/2 placebo per cohort). A methionine loading study was performed on day -1 and day 7 after an overnight fast, followed by a 24-hour collection period for the AUC assessments. Subjects were followed in the study for at least 28 days after the last dose. At the 1x1012 dose, SYNB1353 decreased plasma methionine levels, as measured by the change in AUC from baseline, by -24.8% (95% CI -36.7,-10.6) and -26.2% (95% CI -39.0,-10.9) for the two different SYNB1353 formulations, compared to -2.1% (95% CI -15.7, 13.7) in the placebo group. There were no serious adverse events (SAEs). One subject discontinued dosing due to an adverse event (AE). AEs were mild to moderate, transient and predominantly GI in nature. Frequency and severity of GI-related AEs were similar in the SYNB1353 and placebo groups (7 of 22 SYNB1353 compared to 3 of 8 placebo subjects had at least 1 GI-related AE). All subjects completing the 28-day analysis cleared SYNB1353 in feces. Full results of the study will be presented at a future medical meeting. Organizational Changes To focus resources on advancing and optimizing the value of the Company’s clinical stage and prioritized preclinical research programs, Synlogic has implemented a structural realignment, including a reduction in the Company’s workforce by 25%, which is expected to extend its cash runway into the second half of 2024. The Company estimates that it will incur approximately $0.8 million of costs in connection with the reduction in workforce related to severance pay and other related termination benefits. The Company communicated the workforce reduction on November 30, 2022 and expects the majority of the costs associated with the reduction in force plan to be incurred during the fourth quarter ending December 31, 2022 and the first quarter ending March 31, 2023. The Company may also incur other material charges not currently contemplated due to events that may occur as a result of, or associated with, these actions. Next Steps Synlogic also confirmed the following anticipated milestones: Share proof of concept data for SYNB8802 for enteric hyperoxaluria in Q4 2022 Initiate Phase 3 pivotal study of SYNB1934 for PKU in H1 2023 About Homocystinuria (HCU) & SYNB1353 HCU is a rare metabolic disease and inborn error of metabolism characterized by extreme levels of homocysteine and caused by an inherited deficiency in an enzyme known as cystathionine beta-synthase (CBS). When CBS is absent, homocysteine builds up in the blood and urine, putting patients at risk of multisystem complications, including acute thromboembolic events, optical damage from lens dislocation, skeletal deficiencies, and neurocognitive impairments. SYNB1353 is a novel, orally administered, non-systemically absorbed drug candidate designed to lower homocysteine levels in patients with HCU by consuming methionine, a precursor to homocysteine, in the gastrointestinal tract. It is the first drug candidate developed through a research collaboration between Synlogic and Ginkgo Bioworks and the first investigational medicine developed on Ginkgo's platform to enter the clinic. The U.S. Food and Drug Administration (FDA) granted Fast Track designation and Orphan Drug Designation (ODD) to SYNB1353 for the potential treatment of HCU. Synlogic holds worldwide development and commercialization rights to SYNB1353. About Synlogic Synlogic is a clinical-stage biotechnology company developing medicines through its proprietary approach to synthetic biology. Synlogic’s pipeline includes its lead program in phenylketonuria (PKU), which has demonstrated proof of concept with plans to start a pivotal, Phase 3 study in the first half of 2023, and additional novel drug candidates designed to treat homocystinuria (HCU), enteric hyperoxaluria and gout. The rapid advancement of these potential biotherapeutics, called Synthetic Biotics, has been enabled by Synlogic’s reproducible, target-specific drug design. Synlogic uses programmable, precision genetic engineering of well-characterized probiotics to exert localized activity for therapeutic benefit, with a focus on metabolic and immunological diseases. In addition to its clinical programs, Synlogic has a research collaboration with Roche on the discovery of a novel Synthetic Biotic for the treatment of inflammatory bowel disease or IBD. Synlogic has also developed two drug candidates through a research collaboration with Ginkgo Bioworks: SYNB1353, designed to consume methionine for the potential treatment of HCU, and SYNB2081, designed to lower uric acid for the potential treatment of gout. For additional information visit . 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," “look forward,” "estimate," "expect," "intend," on track,” "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 approach to Synthetic Biotics to develop therapeutics to address a wide range of diseases including: inborn errors of metabolism and inflammatory and immune disorders; our expectations about sufficiency of our existing cash balance; the future clinical development of Synthetic Biotics; the approach Synlogic is taking to discover and develop novel therapeutics using synthetic biology; and the expected timing of Synlogic's clinical trials of SYNB1618, SYNB1934, SYNB1353, SYNB8802 and SYNB2081 and availability of clinical trial data. Actual results could differ materially from those contained in any forward-looking statements 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 U.S. Securities and Exchange Commission. 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. MEDIA CONTACT: INVESTOR CONTACT: Bill Berry Berry & Company Public Relations Phone: 212-253-8881 Email: bberry@berrypr.com Andrew Funderburk Kendall Investor Relations Phone: 617-401-9152 Email: afunderburk@kendallir.com