Financial Data and Key Metrics Changes - Research and development expenses increased to $13.4 million for Q3 2021 from $10.5 million in Q3 2020, primarily due to clinical study activities related to SYNB1618 and SYNB8802 [46] - General and administrative expenses rose to $3.6 million in Q3 2021 compared to $3 million in Q3 2020 [47] - The company reported a consolidated net loss of $16 million or $0.29 per share for Q3 2021, compared to a net loss of $13.2 million or $0.36 per share for the same period in 2020 [47] - Revenue for Q3 2021 was $0.9 million, attributed to a collaboration with Roche, compared to no revenue in Q3 2020 [47] - Cash and cash equivalents at the end of Q3 2021 were $150.1 million, up from $100.4 million at the end of 2020, expected to fund operations into 2024 [48] Business Line Data and Key Metrics Changes - The lead asset SYNB1618 demonstrated a statistically significant reduction in plasma Phe levels in the Phase 3 SynPheny study, marking a significant milestone in PKU drug development [5][6] - SYNB8802 showed robust consumption of oxalates in the GI tract, indicating potential as a therapy for Enteric hyperoxaluria [7][42] - SYNB1353, a new oral metabolic program for homocystinuria, was unveiled, expanding the company's metabolic portfolio [9] Market Data and Key Metrics Changes - The PKU market is characterized by a significant unmet need, with many diagnosed patients not receiving treatment due to limitations of existing therapies [16][67] - Enteric hyperoxaluria affects approximately 75,000 to 90,000 patients in the U.S., with no current treatment options available [41] - The market for homocystinuria is dynamic, with a substantial population in need of effective therapies [56] Company Strategy and Development Direction - The company is focused on rare and niche metabolic diseases, leveraging its Synthetic Biotic platform to develop targeted therapies [10] - Plans to advance SYNB1934 into a pivotal Phase 3 study based on encouraging data from the SynPheny study [24][39] - The collaboration with Roche aims to develop a Synthetic Biotic medicine for inflammatory bowel disease, with positive initial milestones achieved [61] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical potential of the Synthetic Biotic platform, particularly in addressing unmet needs in PKU and other metabolic diseases [5][10] - The company is committed to advancing its clinical programs and expects to provide meaningful updates in the coming quarters [48][50] Other Important Information - The company has made significant progress in its metabolic portfolio, with ongoing studies and collaborations enhancing its development capabilities [10][39] - The management team emphasized the importance of patient feedback in shaping the development of new therapies [21] Q&A Session Summary Question: Can you comment on the new compound SYNB1353 for HCU and its market opportunity? - Management highlighted the potential of SYNB1353 to address elevated homocysteine levels and noted a substantial unmet need in the market [52][56] Question: What are the next steps after achieving the first milestone in the Roche collaboration? - The collaboration is in the discovery phase, with further milestones and negotiations expected as the program progresses [60][61] Question: What are the key drivers for adoption in the under-penetrated PKU market? - Management indicated that the low treatment rate is due to the limited efficacy of existing therapies, emphasizing the need for a viable treatment option [64][67] Question: How does SYNB1353 differ from other programs in the clinic? - The program leverages existing knowledge from the PKU platform, utilizing similar molecular components while focusing on different biological targets [70][72] Question: Will there be pediatric trials for SYNB1618? - Management confirmed plans to pursue pediatric development once regulatory alignment is achieved [81] Question: What are the next steps for SYNB8802 if proof of concept is demonstrated? - The company plans to expand into other underlying etiologies and will consider the best path forward based on data from the proof of concept study [83] Question: Does SYNB1934 fall under the Gingko collaboration? - Management clarified that SYNB1934 was developed prior to the Gingko collaboration and does not involve milestone or royalty obligations to Gingko [85]

| --- | --- | --- | --- | --- | --- | |-----------------------------------------|-------|-------|-------|-------|-------| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Bringing the Transformative | | | | | | | Power of Synthetic Biology to Medicine | | | | | | | Corporate Presentation | | | | | | | November 2021 | | | | | | © 2021 SYNLOGIC. CORPORATE PRESENTATION. ALL RIGHTS RESERVED. © 2021 SYNLOGIC. ALL RIGHTS RESERVED. | 1 Forward Looking Statements This presentati ...

[FORM 10-Q Filing Information](index=1&type=section&id=FORM%2010-Q) This section provides Synlogic, Inc.'s identification, contact, and SEC filing status for its Q3 2021 Form 10-Q [Registrant Information](index=1&type=section&id=Registrant%20Information) This section details Synlogic, Inc.'s identification, contact information, stock trading symbol, and SEC filing status for its Q3 2021 Form 10-Q - Synlogic, Inc. filed its Quarterly Report on Form 10-Q for the period ended September 30, 2021[2](index=2&type=chunk) Registrant Details | Detail | Value | | :--- | :--- | | Registrant Name | SYNLOGIC, INC. | | State of Incorporation | Delaware | | Commission File Number | 001-37566 | | Trading Symbol | SYBX | | Exchange | The Nasdaq Capital Market | | Filer Status | Non-accelerated filer, Smaller reporting company | | Common Stock Outstanding (as of Nov 3, 2021) | 69,709,236 shares | [Forward-Looking Statements](index=2&type=section&id=FORWARD-LOOKING%20STATEMENTS) This section clarifies that the report contains forward-looking statements, which are subject to risks and uncertainties that could cause actual results to differ materially from projections [Nature of Forward-Looking Statements](index=2&type=section&id=Nature%20of%20Forward-Looking%20Statements) This section defines forward-looking statements, outlines inherent risks, and disclaims any obligation to update them - The report contains forward-looking statements, identifiable by terms such as 'may,' 'will,' 'expects,' 'intends,' 'plans,' 'anticipates,' 'believes,' 'estimates,' 'predicts,' 'potential,' 'continue' or the negative of these terms[7](index=7&type=chunk) - Actual results may differ materially from current expectations due to known and unknown risks, uncertainties, and other factors, including those listed under Part II, Item 1A. 'Risk Factors'[8](index=8&type=chunk) - The company assumes **no obligation to update or revise** these forward-looking statements for any reason, even if new information becomes available in the future, except as required by law[8](index=8&type=chunk) [Key Areas of Forward-Looking Statements](index=2&type=section&id=Key%20Areas%20of%20Forward-Looking%20Statements) Forward-looking statements in the report cover various aspects of the company's operations, including R&D success, clinical trial progress, regulatory approvals, and the impact of public health concerns - Success of research and development efforts - Initiation, progress, timing, costs, and results of clinical trials for product candidates - Time and costs involved in obtaining regulatory approvals for product candidates - Success of collaborations with third parties - Progress, timing, and costs involved in developing manufacturing processes and agreements with third-party manufacturers - Rate of progress and cost of commercialization activities - Expenses incurred in marketing and selling product candidates - Revenue generated by sales of product candidates - Emergence of competing or complementary technological developments - Terms and timing of any additional collaborative, licensing, or other arrangements - Acquisition of businesses, products, and technologies - Need to implement additional infrastructure and internal systems - Need to add personnel and financial and management information systems - Development of major public health concerns, including the novel coronavirus outbreak or other pandemics, and their impact on clinical trials, business operations, and funding requirements - Other risks and uncertainties, including those listed under Part II, Item 1A. 'Risk Factors' [PART I - FINANCIAL INFORMATION](index=4&type=section&id=PART%20I%20-%20FINANCIAL%20INFORMATION) This section presents Synlogic's unaudited consolidated financial statements and management's financial analysis [Item 1. Financial Statements](index=4&type=section&id=Item%201.%20Financial%20Statements) This section provides unaudited consolidated financial statements and related notes [Unaudited Consolidated Balance Sheets](index=4&type=section&id=Unaudited%20Consolidated%20Balance%20Sheets) Total assets increased to **$190.5 million** from **$143.8 million**, primarily due to higher cash and marketable securities Consolidated Balance Sheets (in thousands) | (In thousands) | September 30, 2021 | December 31, 2020 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $62,925 | $32,507 | | Short-term marketable securities | $87,129 | $67,937 | | Total current assets | $156,602 | $106,846 | | Total assets | $190,536 | $143,840 | | **Liabilities** | | | | Total current liabilities | $10,591 | $8,301 | | Total long-term liabilities | $18,363 | $20,404 | | **Stockholders' Equity** | | | | Total stockholders' equity | $161,582 | $115,135 | | Total liabilities and stockholders' equity | $190,536 | $143,840 | [Unaudited Consolidated Statements of Operations and Comprehensive Loss](index=5&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Revenue increased from Roche collaboration, but net loss widened to **$16.0 million** (3M) and **$45.5 million** (9M) due to higher operating expenses Consolidated Statements of Operations and Comprehensive Loss (in thousands, except per share) | (In thousands, except per share) | Three Months Ended Sep 30, 2021 | Three Months Ended Sep 30, 2020 | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | | :--- | :--- | :--- | :--- | :--- | | Revenue | $916 | $— | $1,162 | $545 | | Research and development | $13,355 | $10,481 | $35,254 | $36,067 | | General and administrative | $3,616 | $2,956 | $11,528 | $10,250 | | Total operating expenses | $16,971 | $13,437 | $46,782 | $46,317 | | Loss from operations | $(16,055) | $(13,437) | $(45,620) | $(45,772) | | Net loss | $(16,016) | $(13,222) | $(45,472) | $(44,585) | | Net loss per share - basic and diluted | $(0.29) | $(0.36) | $(0.91) | $(1.27) | | Comprehensive loss | $(16,018) | $(13,357) | $(45,477) | $(44,616) | [Unaudited Consolidated Statements of Stockholders' Equity](index=6&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Stockholders%27%20Equity) Stockholders' equity significantly increased from **$115.1 million** to **$161.6 million**, primarily driven by proceeds from common stock issuances Consolidated Statements of Stockholders' Equity (in thousands, except share amounts) | (In thousands, except share amounts) | Balance at Dec 31, 2020 | Balance at Sep 30, 2021 | | :--- | :--- | :--- | | Common stock, $0.001 par value (shares) | 38,183,273 | 69,707,541 | | Common stock, $0.001 par value (amount) | $38 | $70 | | Additional paid-in capital | $345,394 | $437,286 | | Accumulated deficit | $(230,311) | $(275,783) | | Total stockholders' equity | $115,135 | $161,582 | - Proceeds from issuance of common stock (underwritten public offerings), net of issuance costs: **$81,019 thousand** for the nine months ended September 30, 2021[20](index=20&type=chunk) - Proceeds from issuance of common stock (ATM offering), net of issuance costs: **$8,050 thousand** for the nine months ended September 30, 2021[20](index=20&type=chunk) [Unaudited Consolidated Statements of Cash Flows](index=7&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased to **$39.1 million**, while net cash provided by financing activities significantly increased to **$89.5 million**, leading to a net increase in cash of **$30.4 million** Consolidated Statements of Cash Flows (in thousands) | (In thousands) | Nine Months Ended Sep 30, 2021 | Nine Months Ended Sep 30, 2020 | | :--- | :--- | :--- | | Net cash used in operating activities | $(39,138) | $(29,665) | | Net cash (used in) provided by investing activities | $(19,946) | $25,373 | | Net cash provided by financing activities | $89,502 | $4,923 | | Net increase in cash, cash equivalents and restricted cash | $30,418 | $631 | | Cash, cash equivalents and restricted cash at end of period | $64,022 | $27,912 | - Financing activities for 9M 2021 included **$81.2 million** from common stock offerings and **$8.0 million** from ATM offerings[23](index=23&type=chunk) - Investing activities for 9M 2021 included **$98.0 million** in purchases of marketable securities, offset by **$77.3 million** from maturities and **$1.3 million** from redemptions[23](index=23&type=chunk) [Notes to Unaud

Synlogic, Inc. (NASDAQ:SYBX) Q2 2021 Earnings Conference Call August 12, 2021 8:30 AM ET Company Participants Daniel Rosan - SVP and IR Aoife Brennan - President and CEO David Hava - Chief Scientific Officer Conference Call Participants Unidentified Analyst - H.C. Wainwright & Co. Unidentified Analyst - SVB Leerink Mark Breidenbach - Oppenheimer & Co. Ted Tenthoff - Piper Jaffray & Co. Keay Nakae - Chardan Unidentified Analyst - BTIG Operator Good morning and welcome to Synlogic’s Second Quarter 2021 Confer ...

[PART I - FINANCIAL INFORMATION](index=3&type=section&id=PART%20I%20-%20FINANCIAL%20INFORMATION) [Item 1. Financial Statements](index=4&type=section&id=Item%201.%20Financial%20Statements) This section presents Synlogic, Inc.'s unaudited consolidated financial statements for the quarter ended June 30, 2021, including balance sheets, statements of operations and comprehensive loss, stockholders' equity, and cash flows, along with detailed notes explaining accounting policies, financial instruments, equity, and collaboration agreements [Unaudited Consolidated Balance Sheets](index=4&type=section&id=Unaudited%20Consolidated%20Balance%20Sheets) This section provides a snapshot of Synlogic's financial position, detailing assets, liabilities, and equity as of June 30, 2021, and December 31, 2020 Consolidated Balance Sheet Highlights (in thousands) | Metric | June 30, 2021 | December 31, 2020 | Change | | :-------------------- | :------------ | :---------------- | :----- | | Total Assets | $156,884 | $143,840 | +$13,044 | | Total Liabilities | $28,806 | $28,705 | +$101 | | Total Stockholders' Equity | $128,078 | $115,135 | +$12,943 | [Unaudited Consolidated Statements of Operations and Comprehensive Loss](index=5&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) This section presents Synlogic's financial performance, including revenue, expenses, and net loss for the three and six months ended June 30, 2021 and 2020 Consolidated Statements of Operations and Comprehensive Loss (in thousands, except per share) | Metric | 3 Months Ended June 30, 2021 | 3 Months Ended June 30, 2020 | Change (YoY) | 6 Months Ended June 30, 2021 | 6 Months Ended June 30, 2020 | Change (YoY) | | :------------------------------------ | :--------------------------- | :--------------------------- | :----------- | :--------------------------- | :--------------------------- | :----------- | | Revenue | $246 | $445 | $(199) | $246 | $545 | $(299) | | Research and development | $10,719 | $12,909 | $(2,190) | $21,899 | $25,586 | $(3,687) | | General and administrative | $4,061 | $3,473 | $588 | $7,912 | $7,294 | $618 | | Total operating expenses | $14,780 | $16,382 | $(1,602) | $29,811 | $32,880 | $(3,069) | | Loss from operations | $(14,534) | $(15,937) | $1,403 | $(29,565) | $(32,335) | $2,770 | | Net loss | $(14,485) | $(15,535) | $1,050 | $(29,456) | $(31,363) | $1,907 | | Net loss per share - basic and diluted | $(0.28) | $(0.44) | $0.16 | $(0.63) | $(0.91) | $0.28 | [Unaudited Consolidated Statements of Stockholders' Equity](index=6&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Stockholders'%20Equity) This section details changes in Synlogic's stockholders' equity, including additional paid-in capital and accumulated deficit, for the periods presented Stockholders' Equity Highlights (in thousands) | Metric | June 30, 2021 | June 30, 2020 | | :-------------------- | :------------ | :------------ | | Total Stockholders' Equity | $128,078 | $131,672 | | Additional paid-in capital (6 months) | $387,782 | $333,925 | | Accumulated deficit (6 months) | $(259,767) | $(202,501) | - Proceeds from issuance of common stock, net of issuance costs, for the six months ended June 30, 2021, included **$32,575 thousand** from a public offering and **$8,050 thousand** from an at-the-market (ATM) offering[20](index=20&type=chunk) - Equity-based compensation expense for the six months ended June 30, 2021, was **$1,753 thousand**[20](index=20&type=chunk) [Unaudited Consolidated Statements of Cash Flows](index=7&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Cash%20Flows) This section outlines Synlogic's cash inflows and outflows from operating, investing, and financing activities for the six months ended June 30, 2021 and 2020 Consolidated Statements of Cash Flows Highlights (in thousands) | Cash Flow Activity | 6 Months Ended June 30, 2021 | 6 Months Ended June 30, 2020 | Change | | :-------------------------------- | :--------------------------- | :--------------------------- | :----- | | Net cash used in operating activities | $(25,321) | $(21,467) | $(3,854) | | Net cash (used in) provided by investing activities | $(18,591) | $22,915 | $(41,506) | | Net cash provided by financing activities | $40,649 | $3,718 | $36,931 | | Net (decrease) increase in cash, cash equivalents and restricted cash | $(3,263) | $5,166 | $(8,429) | [Notes to Unaudited Consolidated Financial Statements](index=8&type=section&id=Notes%20to%20Unaudited%20Consolidated%20Financial%20Statements) This section provides detailed explanations of Synlogic's accounting policies, financial instruments, equity, and collaboration agreements - Synlogic, Inc. is a clinical-stage biopharmaceutical company focused on the drug discovery and development of **Synthetic Biotic™ medicines**, leveraging a proprietary platform to develop beneficial microbes for therapeutic functions[24](index=24&type=chunk)[85](index=85&type=chunk) - As of June 30, 2021, the Company had approximately **$115.5 million** in cash, cash equivalents, and short-term marketable securities, and an accumulated deficit of approximately **$259.8 million**. Management believes it has sufficient cash to fund operations for **at least twelve months**[26](index=26&type=chunk)[134](index=134&type=chunk)[145](index=145&type=chunk) Fair Value Measurements at June 30, 2021 (in thousands) | Description | Fair Value | Level 1 | Level 2 | Level 3 | | :------------------------------------ | :--------- | :------ | :------ | :------ | | Money market funds | $29,243 | $29,243 | $— | $— | | Commercial paper | $67,959 | $— | $67,959 | $— | | Corporate debt securities | $9,481 | $— | $9,481 | $— | | U.S. government agency securities and treasuries | $8,778 | $8,778 | $— | $— | | Total | $115,461 | $38,021 | $77,440 | $— | - During the six months ended June 30, 2021, the Company sold **2,447,211 shares** of common stock through an at-the-market (ATM) offering program, generating net proceeds of approximately **$8.1 million**[44](index=44&type=chunk) - Total equity-based compensation expense was approximately **$1.8 million** for the six months ended June 30, 2021, compared to **$2.2 million** for the corresponding period in 2020[55](index=55&type=chunk)[56](index=56&type=chunk) - In June 2021, Synlogic entered into a Pilot Collaboration and Option Agreement with Roche for the research and pre-clinical development of a Synthetic Biotic medicine for inflammatory bowel disease (IBD). Roche paid an upfront nonrefundable technology access fee of **$1.0 million** (received in July 2021) and the Company is eligible for up to **$5.0 million** in milestone payments[57](index=57&type=chunk)[58](index=58&type=chunk)[59](index=59&type=chunk)[103](index=103&type=chunk)[104](index=104&type=chunk) - The collaboration with AbbVie for IBD treatment was terminated in May 2020, with Synlogic regaining all rights to IBD Synthetic Biotic medicines. No revenue was recognized from the AbbVie collaboration for the three months ended June 30, 2021, compared to **$0.4 million** in the prior year period[71](index=71&type=chunk)[73](index=73&type=chunk)[112](index=112&type=chunk) - The Company made a **$30.0 million** prepayment to Ginkgo Bioworks, Inc. for foundry services over an initial five-year term. As of June 30, 2021, remaining prepaid research and development costs related to this transaction were **$4.5 million** (current) and **$7.5 million** (non-current)[70](index=70&type=chunk)[82](index=82&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=17&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section reviews Synlogic's business, pipeline progress, and financial performance for the three and six months ended June 30, 2021, addressing liquidity, funding, and COVID-19 impacts - Synlogic is a clinical-stage biopharmaceutical company focused on developing **Synthetic Biotic™ medicines** for **metabolic disorders** (**Phenylketonuria (PKU)** and **Enteric Hyperoxaluria**) and building a portfolio in **immunology and oncology**[85](index=85&type=chunk) - **SYNB1618** for **PKU**: Initiated a **Phase 2 clinical trial** (SynPheny-1 Study) in **Q3 2020** to evaluate safety, tolerability, and potential to lower blood Phe levels in adult PKU patients[94](index=94&type=chunk) - **SYNB8802** for **Enteric Hyperoxaluria**: Initiated a **Phase 1 clinical trial** in **Q4 2020**. Part A results (**March 2021**) demonstrated proof of mechanism and dose-responsive reductions in urinary oxalate in healthy volunteers, leading to advancement to Part B in patients[97](index=97&type=chunk)[98](index=98&type=chunk) - **SYNB1891** for **Oncology**: Initiated a **Phase 1 clinical trial** in **January 2020** for advanced solid tumors and lymphoma. Interim data (**December 2020**) showed target engagement and STING activation. The combination arm with atezolizumab was initiated in **December 2020**[100](index=100&type=chunk) Key Financial Performance (Three Months Ended June 30, in thousands) | Metric | 2021 | 2020 | Change | | :-------------------- | :--- | :--- | :----- | | Revenue | $246 | $445 | $(199) | | R&D Expense | $10,719 | $12,909 | $(2,190) | | G&A Expense | $4,061 | $3,473 | $588 | | Net Loss | $(14,485) | $(15,535) | $1,050 | Key Financial Performance (Six Months Ended June 30, in thousands) | Metric | 2021 | 2020 | Change | | :-------------------- | :--- | :--- | :----- | | Revenue | $246 | $545 | $(299) | | R&D Expense | $21,899 | $25,586 | $(3,687) | | G&A Expense | $7,912 | $7,294 | $618 | | Net Loss | $(29,456) | $(31,363) | $1,907 | - As of June 30, 2021, the Company had approximately **$115.5 million** in cash, cash equivalents, and short-term marketable securities. Net cash provided by financing activities for the six months ended June 30, 2021, totaled **$40.6 million**, primarily from common stock issuances[134](index=134&type=chunk)[137](index=137&type=chunk)[142](index=142&type=chunk) - The Company expects to incur **substantial net losses** for the foreseeable future and will require **additional funding** to complete product development and potential commercialization[144](index=144&type=chunk)[145](index=145&type=chunk) - The COVID-19 pandemic may **significantly disrupt clinical trial activities**, **patient enrollment**, and **regulatory reviews**, potentially **impacting business operations and funding requirements**[110](index=110&type=chunk)[203](index=203&type=chunk)[204](index=204&type=chunk)[205](index=205&type=chunk)[207](index=207&type=chunk) [Item 3. Quantitative and Qualitative Disclosures about Market Risk](index=28&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) As a smaller reporting company, Synlogic is not required to provide quantitative and qualitative disclosures about market risk - Synlogic, Inc. is a **smaller reporting company** and is therefore **not required** to provide quantitative and qualitative disclosures about market risk[153](index=153&type=chunk) [Item 4. Controls and Procedures](index=28&type=section&id=Item%204.%20Controls%20and%20Procedures) Management evaluated the effectiveness of the company's disclosure controls and procedures as of June 30, 2021, concluding they were effective. No material changes in internal controls over financial reporting were identified during the quarter - The principal executive officer and principal financial officer concluded that the company's disclosure controls and procedures were **effective** as of June 30, 2021[156](index=156&type=chunk) - **No changes** in internal controls over financial reporting were identified during the fiscal quarter ended June 30, 2021, that **materially affected**, or are reasonably likely to materially affect, the company's internal controls[157](index=157&type=chunk) [PART II - OTHER INFORMATION](index=26&type=section&id=PART%20II%20-%20OTHER%20INFORMATION) [Item 1. Legal Proceedings](index=29&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings - Synlogic, Inc. is **not currently a party** to any **material legal proceedings**[159](index=159&type=chunk) [Item 1A. Risk Factors](index=29&type=section&id=Item%201A.%20Risk%20Factors) This section outlines significant risks to Synlogic's financial condition, product development, regulatory approvals, intellectual property, and commercialization, including external factors - Synlogic is a clinical-stage biopharmaceutical company with a history of **significant operating losses** (accumulated deficit of approximately **$259.8 million** as of June 30, 2021) and expects to **continue incurring losses**, with **no guarantee of achieving profitability**[108](index=108&type=chunk)[166](index=166&type=chunk) - The company will require **substantial additional funding** for research and development, clinical trials, regulatory approvals, manufacturing, and marketing, which may **not be available on acceptable terms**, potentially leading to **delays or termination of programs**[168](index=168&type=chunk)[170](index=170&type=chunk) - Clinical trials are **costly, time-consuming, and inherently risky**, with potential for **delays** due to patient enrollment difficulties, adverse events, or regulatory holds, and **no guarantee of demonstrating safety and efficacy** to regulatory authorities' satisfaction[178](index=178&type=chunk)[180](index=180&type=chunk) - The company's synthetic biology approach for novel therapeutics is **unproven**, and product candidates may cause **undesirable side effects**, leading to **clinical trial interruptions**, **restrictive labeling**, or **significant negative consequences** post-marketing approval[182](index=182&type=chunk)[187](index=187&type=chunk)[188](index=188&type=chunk) - Even if regulatory approval is obtained, the company will remain subject to **ongoing regulatory requirements** (manufacturing, labeling, safety reporting), and **non-compliance** could result in **penalties, withdrawal of approval, or market restrictions**[211](index=211&type=chunk)[214](index=214&type=chunk)[215](index=215&type=chunk) - The company relies on a combination of **patents, trade secret protection, and regulatory exclusivity** (e.g., BPCIA) to protect its intellectual property, but obtaining and maintaining broad, enforceable protection is **uncertain** and subject to **challenges and third-party infringement claims**[247](index=247&type=chunk)[249](index=249&type=chunk)[251](index=251&type=chunk)[258](index=258&type=chunk)[261](index=261&type=chunk) - **Reliance on third parties** for research, preclinical, clinical studies, and manufacturing introduces risks of **unsatisfactory performance, delays, or non-compliance**, which could **adversely affect product development and commercialization schedules**[275](index=275&type=chunk)[276](index=276&type=chunk)[281](index=281&type=chunk) - Commercial success depends on **developing internal sales and marketing capabilities** or **securing third-party collaborations**, and achieving **market acceptance** by physicians, patients, and payors, which is **uncertain**, especially given **substantial competition and pressure on reimbursement**[290](index=290&type=chunk)[295](index=295&type=chunk)[297](index=297&type=chunk)[300](index=300&type=chunk)[303](index=303&type=chunk) - The COVID-19 pandemic may **materially and adversely affect business operations**, including **clinical trial activities, patient enrollment, and regulatory reviews**, and could **impact the company's ability to access capital**[203](index=203&type=chunk)[204](index=204&type=chunk)[205](index=205&type=chunk)[207](index=207&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=59&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) During the six months ended June 30, 2021, employees surrendered shares to cover tax withholding obligations upon the vesting of restricted stock awards, which is not considered a share buyback program - Employees surrendered **18,187 shares** to the company during the six months ended June 30, 2021, for the payment of minimum tax liability withholding obligations upon the vesting of restricted stock. This is **not considered a share buyback program**[320](index=320&type=chunk) [Item 3. Defaults Upon Senior Securities](index=59&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reported no defaults upon senior securities during the period - There were **no defaults** upon senior securities reported by the company[321](index=321&type=chunk) [Item 4. Mine Safety Disclosures](index=59&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to Synlogic, Inc - Mine Safety Disclosures are **not applicable** to Synlogic, Inc[322](index=322&type=chunk) [Item 5. Other Information](index=59&type=section&id=Item%205.%20Other%20Information) No other information was reported under this item - **No other information** was provided under this item[323](index=323&type=chunk) [Item 6. Exhibits](index=60&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed with the Form 10-Q, including various agreements and certifications - Key exhibits filed include a **License and Services Agreement** with Azzur Cleanrooms-On-Demand, a **Pilot Collaboration and Option Agreement** with Roche, and **Certifications** of the Chief Executive Officer and Interim Chief Financial Officer[328](index=328&type=chunk) [Signatures](index=61&type=section&id=Signatures) The report is duly signed on behalf of Synlogic, Inc. by its President and Chief Executive Officer, Aoife Brennan, and Interim Chief Financial Officer, Gregg Beloff - The report was signed by **Aoife Brennan**, President and Chief Executive Officer, and **Gregg Beloff**, Interim Chief Financial Officer[332](index=332&type=chunk)

Clinical Program Updates - Synlogic expects clinical proof of concept data across multiple programs in 2021, including two opportunities in metabolic programs: Phenylketonuria (PKU) and Enteric Hyperoxaluria[8] - For Phenylketonuria (PKU), SYNB1618 Phase 2 SynPheny patient data and SYNB1934 Head to Head data with SYNB1618 in healthy volunteers are expected in the second half of 2021[9] - For Enteric Hyperoxaluria, SYNB8802 has demonstrated proof of mechanism in Phase 1A with dietary hyperoxaluria induced in healthy volunteers, and Phase 1B patient data is expected in the second half of 2021[9] - SYNB8802 at a dose of 3e11 live cells is advancing to Phase 1B in patients with Enteric Hyperoxaluria[37] - A Phase 2 SynPheny proof of concept read-out for SYNB1618 in PKU is expected in H2 2021[29, 51] - A Phase 1B proof of concept read-out for SYNB8802 in Enteric Hyperoxaluria is expected in H2 2021[29, 51] - In a Phase 1A study, SYNB8802 demonstrated a clinically meaningful lowering of urinary oxalate, with a 28.6% LS mean change over Placebo[39, 40] Financial Results - Synlogic reported cash, cash equivalents, and marketable securities of $115.5 million as of June 30, 2021, compared to $100.4 million as of December 31, 2020[45] - Research and Development (R&D) expenses for the three months ended June 30, 2021, were $10.7 million, compared to $12.9 million for the same period in 2020[46] - General and Administrative (G&A) expenses for the three months ended June 30, 2021, were $4.1 million, compared to $3.5 million for the same period in 2020[46] - Net loss for the three months ended June 30, 2021, was $14.5 million, or $0.28 per share, compared to a net loss of $15.5 million, or $0.44 per share, for the same period in 2020[46]

| --- | --- | --- | --- | --- | --- | |-----------------------------------------|-------|-------|-------|-------|-------| | | | | | | | | | | | | | | | | | | | | | | Bringing the Transformative | | | | | | | Power of Synthetic Biology to Medicine | | | | | | | Corporate Presentation | | | | | | | June 2021 | | | | | | 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 Secu ...

Financial Data and Key Metrics Changes - The company reported a consolidated net loss of $15 million or $0.36 per share for Q1 2021, compared to a net loss of $15.8 million or $0.46 per share for the same period in 2020, indicating a slight improvement in loss per share [57] - Research and development expenses decreased to $11.2 million in Q1 2021 from $12.7 million in Q1 2020, reflecting a reduction in spending [55] - The company ended Q1 2021 with approximately $94.4 million in cash, cash equivalents, and short-term investments, which is expected to fund operations through the second half of 2023 [60] Business Line Data and Key Metrics Changes - The metabolic disease pipeline is advancing, with SYNB1618 and SYNB8802 showing proof of mechanism in humans, with clinical trials ongoing [9][27] - SYNB1618 is currently in a Phase II study called Symphony 1, which is enrolling well and aims to demonstrate the potential to lower blood phenylalanine levels in adult PKU patients [16][33] - SYNB8802 has shown a 28.6% reduction in urinary oxalate levels in a dietary hyperoxaluria model, indicating its potential effectiveness in treating enteric hyperoxaluria [40][46] Market Data and Key Metrics Changes - The company is expanding its manufacturing footprint by over 50% to support late-stage clinical development of SYNB1618 and SYNB8802, which will enhance its capacity for fermentation and lyophilization [12][100] - The collaboration with Ginkgo Bioworks continues to be strong, with expectations that Ginkgo's IPO will not negatively impact the partnership but rather enhance resource allocation for joint projects [90][94] Company Strategy and Development Direction - The company aims to demonstrate clinical potential through its Synthetic Biotic platform, focusing on metabolic diseases and expanding its manufacturing capabilities to support clinical trials [9][12] - The strategy includes advancing both SYNB1618 and SYNB8802 towards proof of concept readouts later in 2021, with a focus on addressing unmet medical needs in PKU and enteric hyperoxaluria [25][63] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress made in 2021, highlighting the successful demonstration of proof of mechanism in both lead programs and the potential for meaningful clinical readouts later this year [25][63] - The company is committed to maintaining a strong balance sheet and capital stewardship to support ongoing and future clinical programs [24][60] Other Important Information - The company had no revenues in Q1 2021, compared to $0.1 million in Q1 2020, as previous collaborations have been terminated [58] - The company is focused on capital-efficient manufacturing processes, which will allow for necessary expansions without significant financial strain [99][102] Q&A Session Summary Question: Can you describe the Phase Ib urinary oxalate pattern in healthy volunteers? - Management indicated that the placebo group showed increasing urinary oxalate excretion until treatment day 2, after which it plateaued, while the treatment group showed a consistent difference [66][68] Question: What is the expected order of data release for SYNB1618 and SYNB8802? - Management stated that both studies are neck and neck in execution, with data expected in the second half of the year [71][73] Question: What considerations were made for dose selection in the Phase Ib study of SYNB8802? - Management expressed optimism that the healthy volunteer data would translate well to patients, with expectations to meet or exceed the 28.6% treatment difference observed [75][80] Question: How will Ginkgo Bioworks' IPO affect its relationship with Synlogic? - Management confirmed that the collaboration remains strong and that Ginkgo's success could provide additional resources for their partnership [90][94] Question: What are the CapEx requirements for the CMC expansion? - Management indicated that the expansion will be capital-efficient, with low single-digit millions expected for the investment, which is manageable within the current financial framework [96][99]

PART I - FINANCIAL INFORMATION [Financial Statements](index=4&type=section&id=Item%201.%20Financial%20Statements) Synlogic reported a net loss of $14,971 thousand for Q1 2021, an improvement from the prior year, primarily due to decreased R&D expenses and positive financing cash flow Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2021 | December 31, 2020 | | :--- | :--- | :--- | | Cash and cash equivalents | $26,704 | $32,507 | | Total current assets | $101,197 | $106,846 | | Total assets | $135,745 | $143,840 | | Total current liabilities | $6,986 | $8,301 | | Total liabilities | $26,695 | $28,705 | | Total stockholders' equity | $109,050 | $115,135 | Consolidated Statements of Operations Highlights (in thousands, except per share data) | Account | Q1 2021 | Q1 2020 | | :--- | :--- | :--- | | Revenue | $0 | $100 | | Research and development | $11,180 | $12,677 | | General and administrative | $3,851 | $3,821 | | Loss from operations | $(15,031) | $(16,398) | | Net loss | $(14,971) | $(15,828) | | Net loss per share | $(0.36) | $(0.46) | Consolidated Statements of Cash Flows Highlights (in thousands) | Activity | Q1 2021 | Q1 2020 | | :--- | :--- | :--- | | Net cash used in operating activities | $(13,976) | $(12,479) | | Net cash provided by investing activities | $154 | $5,817 | | Net cash provided by (used in) financing activities | $8,019 | $(69) | | Net decrease in cash, cash equivalents and restricted cash | $(5,803) | $(6,731) | - In April 2021, the company completed an underwritten public offering, selling **11,500,000 shares** of common stock at **$3.00 per share**, resulting in net proceeds of approximately **$32.6 million**[70](index=70&type=chunk) - During Q1 2021, the company sold **2,447,211 shares** of common stock through its at-the-market (ATM) offering program, generating net proceeds of approximately **$8.1 million**[46](index=46&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=16&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's clinical-stage Synthetic Biotic™ medicine pipeline, highlighting decreased R&D expenses and sufficient cash reserves for the next 12 months - The company's proprietary pipeline includes Synthetic Biotic medicines for Phenylketonuria (PKU) with SYNB1618, Enteric Hyperoxaluria with SYNB8802, and an immuno-oncology candidate, SYNB1891[73](index=73&type=chunk) R&D Expense Breakdown by Program (in thousands) | Program | Q1 2021 | Q1 2020 | | :--- | :--- | :--- | | SYNB1618 | $977 | $3,634 | | SYNB1891 | $762 | $372 | | SYNB8802 | $1,741 | $0 | | SYNB1934 | $90 | $0 | | Other External & Internal R&D | $7,610 | $8,671 | | **Total R&D Expense** | **$11,180** | **$12,677** | - The decrease in R&D expense was primarily due to a **$3.3 million** reduction in nonclinical development costs and a **$0.5 million** decrease in clinical costs for SYNB1618, partially offset by a **$1.8 million** increase for SYNB8802 and a **$0.4 million** increase for SYNB1891[109](index=109&type=chunk) - The company believes its cash, cash equivalents, and short-term marketable securities of **$94.4 million** as of March 31, 2021, will be sufficient to meet anticipated cash requirements for at least the next 12 months[112](index=112&type=chunk)[121](index=121&type=chunk) - Revenue in Q1 2020 was **$0.1 million** from the AbbVie collaboration, which was terminated in May 2020, with no revenue recognized in Q1 2021[95](index=95&type=chunk)[108](index=108&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=25&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) As a smaller reporting company, Synlogic is exempt from providing quantitative and qualitative disclosures about market risk - As a smaller reporting company, Synlogic is exempt from providing quantitative and qualitative disclosures about market risk[128](index=128&type=chunk) [Controls and Procedures](index=25&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2021, with no material changes to internal controls over financial reporting - The company's principal executive officer and principal financial officer concluded that disclosure controls and procedures were effective as of the end of the period covered by the report[131](index=131&type=chunk) - No material changes to the company's internal controls over financial reporting were identified during the fiscal quarter ended March 31, 2021[132](index=132&type=chunk) PART II - OTHER INFORMATION [Legal Proceedings](index=26&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings - As of the filing date, the company is not involved in any material legal proceedings[133](index=133&type=chunk) [Risk Factors](index=26&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant financial, development, regulatory, intellectual property, and operational risks, including reliance on third parties and potential impacts from the COVID-19 pandemic - **Financial Risks:** The company is a clinical-stage entity with a history of losses (**$245.3 million** accumulated deficit as of March 31, 2021), expects to incur future losses, and will require substantial additional funding to continue operations[138](index=138&type=chunk)[141](index=141&type=chunk)[143](index=143&type=chunk) - **Development & Technology Risks:** The company's Synthetic Biotic™ medicine approach is novel and unproven, which may never lead to marketable products, and clinical trials are costly, time-consuming, and their outcomes are uncertain[138](index=138&type=chunk)[157](index=157&type=chunk) - **Pandemic Risk:** The COVID-19 pandemic may materially and adversely affect business and financial results, including potential interruptions to clinical trial activities, patient recruitment, and regulatory reviews[140](index=140&type=chunk)[178](index=178&type=chunk) - **Intellectual Property Risks:** The company may not be successful in obtaining or maintaining necessary patent protections for its product candidates, and could face third-party claims of intellectual property infringement[140](index=140&type=chunk)[218](index=218&type=chunk)[233](index=233&type=chunk) - **Third-Party Reliance:** The company relies on third parties to conduct aspects of product formulation, research, clinical studies, and manufacturing, and their failure to perform satisfactorily could delay development[140](index=140&type=chunk)[250](index=250&type=chunk)[251](index=251&type=chunk) - **Commercialization Risks:** The company faces substantial competition from larger, better-funded companies and must gain market acceptance from physicians, patients, and payors to be successful, with no guarantee of adequate reimbursement for its products if approved[140](index=140&type=chunk)[267](index=267&type=chunk)[275](index=275&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=56&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) Employees surrendered 15,970 shares of common stock to satisfy tax obligations related to restricted stock vesting during Q1 2021 - In Q1 2021, employees surrendered **15,970 shares** to the company to cover tax liabilities upon the vesting of restricted stock awards[295](index=295&type=chunk) [Defaults Upon Senior Securities](index=56&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reports no defaults upon senior securities - The company reports no defaults upon senior securities[296](index=296&type=chunk) [Mine Safety Disclosures](index=56&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - This item is not applicable to the company[297](index=297&type=chunk) [Other Information](index=56&type=section&id=Item%205.%20Other%20Information) The company reports no other information for this item - The company reports no other information for this item[298](index=298&type=chunk) [Exhibits](index=57&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including CEO/CFO certifications and Inline XBRL documents

Clinical Programs & Data - Synlogic expects clinical proof of concept data across multiple programs in 2021[5] - For Phenylketonuria (PKU) program SYNB1618, Phase 2 SynPheny patient data is expected in the second half of 2021[5] - For Enteric Hyperoxaluria program SYNB8802, Phase 1B patient data is expected in the second half of 2021[5] - For Solid Tumors program SYNB1891, combination with anti-PD1 and dose escalation are ongoing[6] Financial Status - As of December 31, 2020, Synlogic had $100.4 million in cash, cash equivalents, and marketable securities[79] compared to $127.1 million as of December 31, 2019[79] - R&D expenses for the year ended December 31, 2020, were $47.5 million, compared to $41.9 million for the year ended December 31, 2019[79] - Net loss for the year ended December 31, 2020, was $(59.2) million, or $(1.65) per share, compared to $(51.4) million, or $(1.70) per share for the year ended December 31, 2019[79] Technology Platform - Synlogic's Synthetic Biotic platform is designed to create therapies that consume toxic metabolites from the GI tract and interact with the immune system[9] - The company's approach to PKU involves an oral therapy (SYNB1618) to consume Phe in the GI tract and reduce plasma Phe, with a Phase 2 study (SynPheny) initiated[28, 29] - For Enteric Hyperoxaluria, Synlogic's approach (SYNB8802) involves an oral therapy to consume oxalate throughout the GI tract and reduce oxalate in the urine, with Ph 1B Proof of Concept in Enteric Hyperoxaluria patients initiated[52, 53] SYNB8802 Clinical Trial Results - In a Phase 1A study, a high oxalate, low calcium diet elevated urinary oxalate levels to >1.5X typically observed in healthy volunteers[61] - SYNB8802 demonstrated dose-responsive and reproducible UOx lowering[64] - A 28.6% baseline urinary oxalate reduction compared to placebo was observed[71] - The mean 24-hour urinary oxalate level was 40.1 mg for subjects, compared to 58.1 mg for placebo, at the end of dosing[71]