Seres Therapeutics(MCRB) - 2022 Q4 - Annual Report

PART I Business Seres Therapeutics is a clinical-stage microbiome therapeutics company focused on developing biological drugs, with a primary focus on commercializing SER-109 for recurrent C. difficile infection Overview and Strategy The company's core strategy centers on advancing SER-109 for recurrent C. difficile infection towards commercialization, expanding its 'Infection Protection' pipeline, and leveraging its proprietary microbiome therapeutics platform - The company's highest priority is preparing for the potential commercialization of SER-109 for recurrent CDI. The FDA accepted its Biologics License Application (BLA) for Priority Review with a PDUFA target action date of April 26, 2023[24] - Seres is advancing its 'Infection Protection' approach, with SER-155 in a Phase 1b study for patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce infections and GvHD. Initial data from the first cohort is expected in May 2023[25] - Key strategic goals include supporting the SER-109 BLA and preparing for commercialization with Nestlé, maximizing the 'Infection Protection' opportunity, continuing research in Ulcerative Colitis (UC), leveraging its reverse translational platform, and developing commercial-scale manufacturing capabilities[31][35] Our Microbiome Therapeutics Platform The company employs a reverse translational microbiome therapeutics platform, integrating clinical data, a proprietary strain library, advanced bioinformatics, and in-house cGMP manufacturing for novel drug development - The platform uses a 'reverse translational' approach, starting with human clinical data to identify microbiome biomarkers and host signatures associated with disease states, which then informs preclinical drug design[34][35] - A proprietary strain library containing novel and functionally characterized bacterial species is used to design defined consortia of bacteria with specific therapeutic properties[38] - The company has established in-house cGMP manufacturing capabilities optimized for anaerobic fermentation and formulation of both spores and live bacteria, which it believes is a key competitive advantage[40] Product Pipeline Seres' pipeline is anchored by SER-109 for recurrent C. difficile infection, with SER-155 in development for infection protection, and ongoing research in Ulcerative Colitis - The lead product candidate, SER-109, is designed to reduce the recurrence of C. difficile infection (CDI) and is positioned to be a first-in-field oral microbiome drug if approved[43] - SER-155 is being developed to reduce infections and GvHD in patients receiving allo-HSCT, representing the company's 'Infection Protection' strategy[43] - Research activities in Ulcerative Colitis (UC) are ongoing to evaluate the potential for biomarker-based patient selection for future studies, following mixed results from SER-287 and SER-301 trials[44] Manufacturing Seres has established distinct manufacturing processes for donor-derived SER-109, utilizing in-house and CMO facilities, and scalable cGMP processes for cultivated products, supported by a 10,000 sq. ft. in-house facility - SER-109 is a donor-derived product manufactured from human stool obtained from highly screened donors. The process includes steps to inactivate and clear potential pathogens beyond screening alone[82][84] - To ensure sufficient commercial supply for SER-109, Seres utilizes its in-house Cambridge facility, CMO partner GenIbet, and has a long-term manufacturing agreement with Bacthera AG to build a dedicated production suite in Switzerland[85] - For cultivated product candidates, the company has developed scalable cGMP processes for fermentation, purification, and formulation, with a focus on oral delivery. These are supported by a 10,000 sq. ft. cGMP facility in-house[86][87][88] Material Agreements Key strategic agreements include a co-commercialization deal with Nestlé for SER-109, manufacturing partnerships with Bacthera and GenIbet, and a debt financing agreement with Hercules Capital for up to $100.0 million - A 2021 License Agreement with Nestlé grants co-exclusive rights to develop and commercialize SER-109 in the U.S. and Canada. The deal included a $175 million upfront payment and up to $350 million in potential regulatory and sales milestones[91][69] - A long-term manufacturing agreement was signed with Bacthera in November 2021 to construct a dedicated production suite in Switzerland to ensure future commercial supply of SER-109[92] - The company has a loan and security agreement with Hercules Capital, amended in February 2022, providing access to up to $100.0 million in term loans, contingent on certain milestones including the FDA approval of SER-109[96] Intellectual Property Seres Therapeutics protects its proprietary technology through a strategy encompassing patents, regulatory exclusivity, and trade secrets, actively filing applications globally and relying on confidentiality agreements - The company's success depends on obtaining and maintaining patent protection for its technology and products, as well as preserving trade secrets[99][100] - The patent positions of biopharmaceutical companies are generally uncertain and involve complex legal and scientific questions. The company cannot predict whether its pending applications will issue as patents or if issued patents will provide sufficient protection[101] - In addition to patents, the company relies on trade secrets and know-how, which are protected through confidentiality and invention assignment agreements with employees, consultants, and collaborators[107] Competition The company faces significant competition from major pharmaceutical and biotechnology firms with greater resources, with commercial success dependent on product efficacy, safety, convenience, price, and reimbursement - The company competes with major pharmaceutical and biotechnology companies, some of which have greater financial resources and expertise in development, manufacturing, and marketing[109][110] - Competition exists for recruiting qualified personnel, establishing clinical trial sites, and patient enrollment[111] - Commercial success will depend on factors like efficacy, safety, convenience, price, and reimbursement compared to competitors' products, which may reach the market sooner[112][113] Government Regulation The company's products are subject to extensive and complex government regulations, including rigorous FDA requirements for testing, manufacturing, and marketing approval, as well as ongoing post-approval oversight and healthcare laws - Product candidates are regulated as biologics by the FDA, requiring submission of a Biologics License Application (BLA) for marketing approval in the U.S., a process that involves extensive preclinical and clinical trials[117] - The FDA offers expedited development programs such as Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval for drugs addressing serious conditions, which can speed up the development and review process but do not change the standards for approval[131] - Marketing products outside the U.S., particularly in the EU, requires compliance with varying international regulations, including obtaining a Marketing Authorization (MA) through centralized, decentralized, or mutual recognition procedures[145][155] - The business is subject to other healthcare laws, including the federal Anti-Kickback Statute, the False Claims Act, and pricing and reimbursement regulations, which are complex and can carry significant penalties for non-compliance[175][176][182] Human Capital As of December 31, 2022, Seres Therapeutics had 431 full-time employees, primarily in R&D, with significant expansion in 2022 to support pipeline and pre-commercialization efforts, emphasizing diversity and talent retention Employee Headcount as of Dec 31, 2022 | Category | Number of Employees | | :--- | :--- | | Total Full-Time | 431 | | Research and Development | 367 | | Administration, Operations, Commercial | 64 | - The company significantly expanded its employee base in 2022 to support research, clinical development, medical affairs, manufacturing, and commercialization capabilities[194] - Seres emphasizes diversity, equity, and inclusion initiatives, supports employee growth through training and mentoring, and conducts annual employee engagement surveys[196] Risk Factors The company faces significant risks including substantial losses, a going concern warning, high development risks for unproven microbiome therapeutics, heavy reliance on third-party collaborations, and challenges in market acceptance, competition, and intellectual property protection - The company has incurred significant losses since inception and has identified conditions that raise substantial doubt about its ability to continue as a going concern, contingent on receiving future milestone payments and its ability to raise additional capital[204][208] - The company's product candidates are based on microbiome therapeutics, an unproven approach, and clinical development is a risky, lengthy, and expensive process with an uncertain outcome[219][221] - Heavy reliance on collaboration and license agreements with Nestlé for the development and commercialization of key product candidates, including SER-109, poses a significant risk if either party fails to perform or terminates the agreements[260] - Even if approved, product candidates may fail to achieve market acceptance, and the company faces substantial competition from larger, better-resourced companies and alternative treatments like Fecal Microbiota Transplantation (FMT)[281][286] Unresolved Staff Comments The company reports no unresolved staff comments from the Securities and Exchange Commission - None[413] Properties The company's corporate headquarters in Cambridge, MA, encompasses 83,396 sq. ft. of leased office, lab, and pilot manufacturing space, with plans for strategic investments to support commercial supply - Corporate headquarters are located in Cambridge, MA, where the company leases approximately 83,396 sq. ft. of office, lab, and pilot manufacturing space. A significant portion of this lease was extended to January 2030[415] - The company conducts some manufacturing in its Cambridge facilities and plans strategic investments for commercial supply, which may include collaborations or building new facilities[417][418] Legal Proceedings A European Patent Office opposition proceeding against a University of Tokyo patent was terminated on December 19, 2022, resulting in the patent's full revocation - Seres filed a notice of opposition in 2017 against a European patent granted to The University of Tokyo. On December 19, 2022, the appeal proceeding was terminated and the patent was revoked in its entirety[419] Mine Safety Disclosures This item is not applicable to the company - Not applicable[420] PART II Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities The company's common stock trades on Nasdaq under 'MCRB', has approximately nine record holders, and has not paid cash dividends, with no unregistered securities sold or equity repurchased in Q4 2022 - Common stock trades on the Nasdaq Global Select Market under the symbol 'MCRB'[424] - The company has not paid cash dividends and does not plan to in the foreseeable future, with current debt agreements prohibiting such payments[430] - No unregistered securities were sold or equity repurchased during the quarter ended December 31, 2022[432][434] Management's Discussion and Analysis of Financial Condition and Results of Operations In 2022, the company reported a net loss of $250.2 million, driven by decreased collaboration revenue and increased operating expenses, with management expressing substantial doubt about its going concern ability without additional funding and SER-109 approval Results of Operations For 2022, revenue significantly decreased to $7.1 million due to a prior-year Nestlé upfront payment, while R&D and G&A expenses increased, leading to a net loss of $250.2 million Consolidated Results of Operations (2022 vs. 2021) | | Year Ended December 31, | | Change | | :--- | :--- | :--- | :--- | | | 2022 | 2021 | | | | (in thousands) | (in thousands) | (in thousands) | | Total revenue | $7,128 | $144,927 | $(137,799) | | Total operating expenses | $253,618 | $209,420 | $44,198 | | Loss from operations | $(246,490) | $(64,493) | $(181,997) | | Net loss | $(250,157) | $(65,578) | $(184,579) | - The $137.8 million decrease in revenue was primarily due to collaboration revenue recognized in 2021 upon the transfer of the SER-109 license to Nestlé under the 2021 License Agreement[498] Research and Development Expenses Breakdown (2022 vs. 2021) | | Year Ended December 31, | | Change | | :--- | :--- | :--- | :--- | | | 2022 | 2021 | | | | (in thousands) | (in thousands) | (in thousands) | | Microbiome therapeutics platform | $36,142 | $34,784 | $1,358 | | SER-109 | $48,649 | $40,510 | $8,139 | | SER-287 | $1,715 | $9,881 | $(8,166) | | Early stage programs | $6,828 | $4,953 | $1,875 | | Personnel-related | $79,586 | $51,763 | $27,823 | | Total R&D expenses | $172,920 | $141,891 | $31,029 | - The $31.0 million increase in R&D expenses was mainly due to a $27.8 million increase in personnel costs and an $8.1 million increase in SER-109 program expenses related to manufacturing scale-up and pre-commercialization activities[499] Liquidity and Capital Resources As of December 31, 2022, the company held $181.3 million in cash and investments, with net cash used in operations at $228.8 million, and management expressed substantial doubt about going concern without additional funding and SER-109 approval - As of December 31, 2022, the company had cash, cash equivalents, and investments totaling $181.3 million and an accumulated deficit of $864.5 million[509] - Management has concluded that substantial doubt exists about the Company's ability to continue as a going concern, as it will likely require additional funding in early 2024. This conclusion excludes potential milestone payments from Nestlé ($125.0 million) and Hercules ($25.0 million) contingent on SER-109 approval, as they are not considered probable under accounting standards[510][448] Summary of Cash Flows (2022 vs. 2021) | | Year Ended December 31, | | | :--- | :--- | :--- | | | 2022 | 2021 | | | (in thousands) | (in thousands) | | Cash (used in) provided by operating activities | $(228,816) | $6,688 | | Cash provided by investing activities | $82,428 | $64,088 | | Cash provided by financing activities | $129,602 | $1,178 | | Net (decrease) increase in cash | $(16,786) | $71,954 | - In 2022, the company raised $96.7 million from a registered direct offering and $4.4 million from its ATM equity program. It also drew down an additional $27.6 million from its credit facility with Hercules[542][508] Quantitative and Qualitative Disclosures about Market Risk The company's primary market risk stems from interest rate fluctuations affecting investments and variable-rate debt, though a 10% change is not expected to have a material impact due to the short-term nature of investments - The company's primary market risk is related to interest rate fluctuations affecting its investment income and debt obligations[561] - Due to the short-term nature of its investment portfolio, an immediate 10% change in market interest rates is not expected to have a material impact on its fair market value or financial results[562] - The variable interest rate on the Hercules credit facility is tied to the Prime Rate, but a 10% change is not expected to materially impact debt-related obligations[563] Financial Statements and Supplementary Data This section refers to the full consolidated financial statements and related notes, appended to the report starting on page F-1 - The full financial statements required by this item are appended to the report, with an index on page F-1[624][563] Changes in and Disagreements with Accountants on Accounting and Financial Disclosure The company reports no changes in or disagreements with its accountants on accounting and financial disclosure - None[564] Controls and Procedures Management concluded that the company's disclosure controls and internal control over financial reporting were effective as of December 31, 2022, with no material changes reported in the most recent fiscal quarter - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2022[568] - Management concluded that the company's internal control over financial reporting was effective as of December 31, 2022. This assessment was audited by PricewaterhouseCoopers LLP[571] - There were no changes in internal control over financial reporting during the most recent fiscal quarter that materially affected, or are reasonably likely to materially affect, internal controls[573] Other Information The company reports no other information for this item - None[574] Disclosure Regarding Foreign Jurisdictions that Prevent Inspections This item is not applicable to the company - Not applicable[575] PART III Directors, Executive Officers and Corporate Governance This section details biographical information for directors and executive officers, outlines their roles and committee assignments, confirms the adoption of a Code of Business Conduct and Ethics, and incorporates further information by reference from the 2023 Proxy Statement - Provides detailed biographical information for the 10 members of the Board of Directors, including their committee assignments (Audit, Compensation, Nominating, Science & Clinical Development)[578][579][580] - Lists the 8 executive officers of the company and provides their professional biographies[592] - The company has adopted a Code of Business Conduct and Ethics, available on its website. Other required information is incorporated by reference from the 2023 Proxy Statement[601][603] Executive Compensation Information regarding executive compensation is incorporated by reference from the company's definitive Proxy Statement for its 2023 Annual Meeting of Stockholders - Information is incorporated by reference from the 2023 Proxy Statement[605] Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters Information regarding security ownership of certain beneficial owners and management is incorporated by reference from the company's 2023 Proxy Statement - Information is incorporated by reference from the 2023 Proxy Statement[606] Certain Relationships and Related Transactions and Director Independence Information concerning certain relationships, related transactions, and director independence is incorporated by reference from the company's 2023 Proxy Statement - Information is incorporated by reference from the 2023 Proxy Statement[607] Principal Accountant Fees and Services Information regarding principal accountant fees and services is incorporated by reference from the company's 2023 Proxy Statement - Information is incorporated by reference from the 2023 Proxy Statement[608] PART IV Exhibits and Financial Statement Schedules This section provides an index to the consolidated financial statements and lists all exhibits filed with the 10-K, including corporate governance documents, material contracts, and SEC certifications - Provides an index to the Consolidated Financial Statements, which begin on page F-1[610] - Lists all exhibits filed with the 10-K, including key material contracts such as the collaboration and license agreements with Nestlé and the loan and security agreement with Hercules[611][612] Form 10-K Summary The company reports no summary for this item - None[617] Financial Statements Consolidated Financial Statements For fiscal year 2022, Seres Therapeutics reported total assets of $348.8 million, total liabilities of $338.0 million, a net loss of $250.2 million, and net cash used in operations of $228.8 million, with auditors noting substantial doubt about going concern Consolidated Balance Sheet Data | | Dec 31, 2022 | Dec 31, 2021 | | :--- | :--- | :--- | | | (in thousands) | (in thousands) | | Cash, cash equivalents, and investments | $181,341 | $291,199 | | Total Assets | $348,784 | $354,859 | | Total Current Liabilities | $85,596 | $82,258 | | Total Liabilities | $338,001 | $223,352 | | Total Stockholders' Equity | $10,783 | $131,507 | Consolidated Statement of Operations Data | | 2022 | 2021 | 2020 | | :--- | :--- | :--- | :--- | | | (in thousands) | (in thousands) | (in thousands) | | Total Revenue | $7,128 | $144,927 | $33,215 | | Total Operating Expenses | $253,618 | $209,420 | $121,345 | | Loss from Operations | $(246,490) | $(64,493) | $(88,130) | | Net Loss | $(250,157) | $(65,578) | $(89,127) | | Net Loss Per Share | $(2.31) | $(0.72) | $(1.12) | Consolidated Statement of Cash Flows Data | | 2022 | 2021 | | :--- | :--- | :--- | | | (in thousands) | (in thousands) | | Net cash (used in) provided by operating activities | $(228,816) | $6,688 | | Net cash provided by investing activities | $82,428 | $64,088 | | Net cash provided by financing activities | $129,602 | $1,178 | | Net (decrease) increase in cash | $(16,786) | $71,954 | - The independent auditor's report highlights substantial doubt about the Company's ability to continue as a going concern due to recurring losses, negative cash flows, and the need to raise additional capital[631] Notes to Consolidated Financial Statements The notes provide detailed accounting policies, financial instruments, and contractual obligations, including the going concern analysis, Nestlé collaboration revenue, Hercules debt facility, lease commitments, stock-based compensation, and net operating loss carryforwards with a full valuation allowance - Note 1 reiterates that management has concluded substantial doubt exists about the Company's ability to continue as a going concern, as it will likely require additional funding in early 2024, absent the approval of SER-109 and related milestone payments[660][661] - Note 11 details the accounting for the Nestlé collaboration agreements. For the 2021 agreement, $131.3 million of the upfront payment was recognized as revenue in 2021 upon transfer of the license. The remaining portion is recognized over time as services are performed[799] - Note 8 describes the New Credit Facility with Hercules, with $50.0 million outstanding as of Dec 31, 2022. An additional $25.0 million tranche is available upon FDA approval of SER-109[746][755] - As of December 31, 2022, the company had federal and state net operating loss (NOL) carryforwards of $501.8 million and $481.9 million, respectively. A full valuation allowance has been established against deferred tax assets due to uncertainty of realization[846][848]