```markdown [Executive Summary & Corporate Updates](index=1&type=section&id=Executive%20Summary%20%26%20Corporate%20Updates) [Second Quarter 2025 Highlights](index=1&type=section&id=Second%20Quarter%202025%20Highlights) 89bio reported its Q2 2025 financial results and provided updates on its **Phase 3** clinical trials for pegozafermin in MASH and SHTG, reiterating key data timelines and a strong cash position - ENLIGHTEN-Fibrosis and ENLIGHTEN-Cirrhosis **Phase 3** topline histology data expected in **1H 2027** and **2028**, respectively, designed to support accelerated approval for MASH[1](index=1&type=chunk) - ENTRUST **Phase 3** topline data in severe hypertriglyceridemia (SHTG) expected in **1Q 2026**[1](index=1&type=chunk) Cash, Cash Equivalents, and Marketable Securities | Metric | Amount (as of June 30, 2025) | | :----- | :--------------------------- | | Cash, cash equivalents, and marketable securities | $561.2 million | [Clinical Development & Milestones](index=1&type=section&id=Recent%20Highlights%20and%20Anticipated%20Milestones) The company provided detailed updates on the progress and anticipated timelines for its **Phase 3** ENLIGHTEN trials for MASH (**F2-F3** and **F4**) and the ENTRUST trial for SHTG, outlining regulatory strategies for accelerated approval [Metabolic Dysfunction-Associated Steatohepatitis (MASH) Program](index=1&type=section&id=Metabolic%20Dysfunction-Associated%20Steatohepatitis%20(MASH)) The **Phase 3** ENLIGHTEN-Fibrosis (**F2-F3** MASH) and ENLIGHTEN-Cirrhosis (**F4** MASH) trials are actively enrolling patients, with topline histology data expected in **1H 2027** and **2028**, respectively, aiming for accelerated approval based on FDA and EMA alignment - **Phase 3** ENLIGHTEN-Fibrosis (non-cirrhotic **F2-F3** MASH) and ENLIGHTEN-Cirrhosis (compensated cirrhotic **F4** MASH) trials continue to enroll patients[5](index=5&type=chunk) - Topline histology data from ENLIGHTEN-Fibrosis expected in **1H 2027**, and ENLIGHTEN-Cirrhosis in **2028**, supporting accelerated approval filings[3](index=3&type=chunk)[5](index=5&type=chunk) - Both trials will continue for outcomes to potentially support full approval, with pegozafermin aiming for best-in-class relative risk ratio on histology endpoints, favorable safety, and convenient dosing[3](index=3&type=chunk)[5](index=5&type=chunk) [Severe Hypertriglyceridemia (SHTG) Program](index=1&type=section&id=Severe%20Hypertriglyceridemia%20(SHTG)) The **Phase 3** ENTRUST trial for SHTG is evaluating pegozafermin's efficacy, safety, and tolerability, with topline data anticipated in **Q1 2026**, focusing on the percent change from baseline in fasting triglycerides at **Week 26** - ENTRUST is a randomized, double-blind, placebo-controlled global study evaluating pegozafermin (**30 mg**, **20 mg**) or placebo once weekly for **52 weeks** in SHTG patients[5](index=5&type=chunk) - Primary endpoint is the percent change from baseline in fasting triglycerides at **Week 26** compared to placebo[5](index=5&type=chunk) - Topline data from the **Phase 3** ENTRUST trial in SHTG are expected in the **first quarter of 2026**[5](index=5&type=chunk) [Financial Results](index=2&type=section&id=Financial%20Results) [Second Quarter 2025 Financial Overview](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Results) 89bio reported a significant increase in R&D and G&A expenses for Q2 2025 compared to Q2 2024, primarily due to advancing **Phase 3** MASH trials, a non-recurring payment for a commercial-scale production facility, and higher personnel costs, leading to an increased net loss Key Financial Metrics | Metric | Q2 2025 (in millions) | Q2 2024 (in millions) | Change (YoY) | | :----------------------- | :-------------------- | :-------------------- | :----------- | | Cash, cash equivalents, and marketable securities (as of June 30) | $561.2 | N/A | N/A | | R&D Expenses | $103.9 | $44.9 | +131.4% | | G&A Expenses | $11.9 | $8.6 | +38.4% | | Net Loss | $(111.5) | $(48.0) | +132.3% | - Increase in R&D expenses driven by **Phase 3** ENLIGHTEN trials in MASH and a non-recurring **$42.4 million** payment for commercial-scale pegozafermin production facility construction, with a remaining **$13.5 million** obligation in **2026**[7](index=7&type=chunk) - Increase in G&A expenses primarily due to higher personnel-related expenses, including stock-based compensation, driven by increased headcount[8](index=8&type=chunk) - Increased net loss primarily driven by higher R&D expenses (contract manufacturing, MASH programs) and personnel-related expenses[9](index=9&type=chunk) [Condensed Consolidated Statement of Operations and Comprehensive Loss](index=4&type=section&id=Condensed%20Consolidated%20Statement%20of%20Operations%20and%20Comprehensive%20Loss) The condensed consolidated statement of operations shows a significant increase in operating expenses and net loss for both the three and six months ended June 30, 2025, compared to the prior year, primarily due to increased R&D and G&A activities Condensed Consolidated Statement of Operations and Comprehensive Loss | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $103,902 | $44,865 | $168,296 | $92,293 | | General and administrative | $11,922 | $8,571 | $23,437 | $18,420 | | Total operating expenses | $115,824 | $53,436 | $191,733 | $110,713 | | Loss from operations | $(115,824) | $(53,436) | $(191,733) | $(110,713) | | Net loss | $(111,504) | $(47,971) | $(182,779) | $(99,652) | | Net loss per share, basic and diluted | $(0.71) | $(0.48) | $(1.20) | $(1.02) | | Weighted-average shares used to compute net loss per share, basic and diluted | 157,880,203 | 99,831,111 | 152,154,469 | 97,838,926 | [Condensed Consolidated Balance Sheet Data](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheet%20Data) As of June 30, 2025, 89bio's cash, cash equivalents, and marketable securities significantly increased to **$561.2 million** from **$439.9 million** at December 31, 2024, contributing to a rise in total assets and stockholders' equity Condensed Consolidated Balance Sheet Data | Metric (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Cash, cash equivalents and marketable securities | $561,164 | $439,955 | | Total assets | $603,485 | $478,685 | | Total current liabilities | $39,611 | $36,129 | | Non current liabilities | $42,141 | $41,767 | | Total stockholders' equity | $521,733 | $400,789 | | Total liabilities and stockholders' equity | $603,485 | $478,685 | [Company Information](index=2&type=section&id=Company%20Information) [About 89bio](index=2&type=section&id=About%2089bio) 89bio is a clinical-stage biopharmaceutical company focused on developing therapies for liver and cardiometabolic diseases, with its lead candidate pegozafermin in **Phase 3** trials for MASH and SHTG, utilizing a unique glycoPEGylated FGF21 analog technology - 89bio is a clinical-stage biopharmaceutical company developing therapies for liver and cardiometabolic diseases[10](index=10&type=chunk) - Lead candidate, pegozafermin, is in **Phase 3** trials for MASH with advanced fibrosis (including compensated cirrhosis) and SHTG[10](index=10&type=chunk) - Pegozafermin is an engineered fibroblast growth factor 21 (FGF21) analog with glycoPEGylated technology for optimized biological activity and extended half-life[10](index=10&type=chunk) [Forward-looking Statements](index=2&type=section&id=Forward-looking%20Statements) This section contains cautionary statements regarding future expectations, including therapeutic potential, trial outcomes, regulatory approvals, and financial resources, emphasizing that actual results may differ due to various risks and uncertainties outlined in SEC filings - Statements regarding therapeutic potential, efficacy, clinical benefits, trial designs, development plans, and timing for pegozafermin, including topline data and accelerated/conditional approval possibilities, are forward-looking[11](index=11&type=chunk) - Undue reliance should not be placed on these statements, which are subject to various risks and uncertainties, including trial outcomes, competition, economic conditions, regulatory changes, and capital sufficiency[12](index=12&type=chunk) - 89bio disclaims any obligation to update or alter these statements, except as required by law, and claims protection under the Safe Harbor of the Private Securities Litigation Reform Act of 1995[12](index=12&type=chunk) [Investor and Media Contacts](index=3&type=section&id=Investor%20Contacts) Contact information for investor relations and media inquiries is provided for 89bio, Inc - Investor contacts: Annie Chang (investors@89bio.com), Eva Bilange (eva.bilange@89bio.com)[13](index=13&type=chunk) - Media contact: Sheryl Seapy, Real Chemistry (sseapy@realchemistry.com)[13](index=13&type=chunk) ```

Financial Data and Key Metrics Changes - The company is experiencing significant excitement in the NASH space, particularly with the approval of Resdiffera, which has validated the potential for effective treatments in this large market [3][4] - The company anticipates that the market for NASH will expand significantly due to increased awareness and screening, particularly as new mechanisms come into play [5][6] Business Line Data and Key Metrics Changes - The company is focused on both pre-cirrhotic and cirrhotic patient populations, with ongoing studies that are expected to yield significant data in the coming years [8][33] - Pegazifirman is positioned to differentiate itself from competitors based on efficacy, safety, tolerability, and dosing convenience [10][12] Market Data and Key Metrics Changes - The FGF21 class is expected to dominate the advanced fibrosis market, with the company projecting to capture over 50% of this market due to its better safety and tolerability profile [68][71] - The company believes that there is a large market opportunity in advanced fibrosis patients, which includes millions of patients who are at risk of progressing to cirrhosis [69][70] Company Strategy and Development Direction - The company is developing pegazifirman with a focus on advanced fibrosis patients, aiming to prevent progression to cirrhosis while also considering the potential for combination therapies with GLP-1s [67][71] - The company is exploring co-formulation opportunities with GLP-1s, which could enhance its market position and provide additional benefits to patients [72] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of pegazifirman to deliver significant benefits in the treatment of cirrhosis and advanced fibrosis, citing strong data from ongoing studies [36][64] - The company is optimistic about the regulatory environment, having received positive feedback from the FDA regarding its study designs and endpoints [63][66] Other Important Information - The company is actively managing enrollment in its clinical trials, with no significant impact from the approval of ResDiffera reported to date [41][42] - Management highlighted the importance of patient tolerability in clinical trials, as it directly affects patient compliance and study outcomes [39][40] Q&A Session Summary Question: How does pegazifirman differentiate from others in the FGF21 class? - The company highlighted differences in efficacy, safety, tolerability, and dosing convenience as key differentiators for pegazifirman compared to other FGF21 drugs [10][12] Question: What gives the company confidence regarding bone mineral density loss? - Management stated that data through week 48 showed no clinically meaningful changes in bone mineral density or biomarkers, providing confidence in the drug's safety profile [24][25] Question: How has enrollment been impacted by the availability of ResDiffera? - Management reported no significant impact on enrollment due to ResDiffera, with many patients still opting to participate in clinical studies [41][42] Question: What is the company's strategy for the phase three program? - The company is focused on powering its studies based on historical placebo responses and aims for a robust design to ensure statistically significant outcomes [48][50] Question: How does the company view the commercial opportunity for pegazifirman? - Management believes pegazifirman will have a dominant position in the advanced fibrosis market, particularly among compensated cirrhotic patients [67][68]

Company Overview - 89bio, Inc. is a clinical-stage biopharmaceutical company focused on developing innovative therapies for liver and cardiometabolic diseases [3] - The company is headquartered in San Francisco and aims to provide best-in-class treatment options for patients lacking optimal therapies [3] Key Developments - The company will participate in a fireside chat at the Goldman Sachs 46th Annual Global Healthcare Conference on June 11, 2025, at 11:20 AM EDT [1] - Management will also engage in one-on-one investor meetings during the conference [1] Product Focus - 89bio is advancing its lead candidate, pegozafermin, through Phase 3 clinical development for metabolic dysfunction-associated steatohepatitis (MASH) and severe hypertriglyceridemia (SHTG) [3] - Pegozafermin is a fibroblast growth factor 21 (FGF21) analog utilizing glycoPEGylated technology to enhance biological activity and extend half-life [3]

Market Performance - The NASDAQ Biotechnology Index increased by 1.55%, closing at 4,177.9 points [1][2] - Notable gainers included Akero Therapeutics, which rose by 22.71%, and Sana Biotechnology, which increased by 22.02% [1][2] - Other significant performers were 89bio with a 20.97% rise, CureVac NV ADR up by 10.47%, and Moderna gaining 6.31% [1][2] Decliners - Anavex Life Sciences experienced a decline of 9.95%, while Prime Medicine fell by 15.01% [1][2] - Alumis saw a significant drop of 16.89% [1][2] Trading Volume - Akero Therapeutics had a trading volume of 6.77 million shares, while Sana Biotechnology traded 10.2 million shares [2] - 89bio recorded a trading volume of 7.16 million shares [2]

Summary of 89Bio (ETNB) Conference Call Company Overview - **Company**: 89Bio - **Focus**: Development of FGF21 analogs for treating NASH (Non-Alcoholic Steatohepatitis) and related liver disorders Key Industry Insights - **NASH as a Metabolic Disorder**: NASH is primarily a metabolic dysregulation affecting the liver, leading to inflammation, fibrosis, and potentially cirrhosis [6][12] - **FGF21 Mechanism**: FGF21 is an endogenous metabolic hormone that regulates energy and lipid metabolism, with direct effects on the liver, distinguishing it from other treatments like GLP-1 [7][8] Clinical Development Highlights - **Pivotal Study Results**: The phase 2b study of pegosafirmin (FGF21 analog) involved 220 patients, showing significant improvements in liver histology markers, including fibrosis reduction and NASH resolution [8][9] - **Comparison with Competitors**: Recent data from competitors like efruxifirman supports the potential of FGF21 in severe patient populations (F4) with high unmet needs [10][12] - **Cirrhosis Reversal**: Over 45% of patients in a small dataset showed cirrhosis reversal without worsening NASH, indicating the potential of FGF21 analogs [12][13] Regulatory Pathway - **Accelerated Approval Potential**: 89Bio has received written confirmation from the FDA that demonstrating fibrosis reversal could lead to accelerated approval in the US and conditional approval in Europe [15][16] - **Study Design**: The ongoing phase 3 study will include a repeat biopsy after 24 months to assess liver healing, crucial for patients with dense fibrotic matrices [14][15] Study Enrollment and Design - **F4 Study Enrollment**: The F4 study aims to enroll approximately 750 compensated cirrhotic patients, with a focus on histology and outcomes [20][21] - **Outcome Measures**: The study will track decompensation events, mortality, and liver transplant rates, with a modified definition of decompensation to allow for earlier event detection [21][22] Manufacturing and Supply Chain - **Manufacturing Locations**: Currently, clinical products are manufactured in Europe, with commercial scaling in China. The company is exploring options to mitigate tariff impacts by transforming the API in Europe [33][35][36] Conclusion - **Market Need**: The FGF21 analogs represent a promising therapeutic avenue for patients with NASH and cirrhosis, with ongoing studies expected to provide critical data for regulatory approval and market entry [19][22]

Summary of 89Bio (ETNB) Conference Call Company Overview - **Company**: 89Bio - **Focus**: Development of picocefermin, an FGF21 analog for treating NASH (Non-Alcoholic Steatohepatitis) and severe hypertriglyceridemia (SHTG) [3][52] Key Points on FGF21 and NASH - **Mechanism of Action**: FGF21 is a unique FGF21 analog that addresses metabolic dysregulation, liver fat reduction, and fibrosis directly [3][4][6] - **Clinical Efficacy**: FGF21 shows benefits in fibrosis improvement as early as 24 weeks, compared to other drugs that may take longer [6][10] - **Market Dynamics**: Recent successful drug approvals in the NASH space have increased confidence in the market, with a shift towards more potent second-generation products [7][10] Competitive Landscape - **Recent Deals**: GSK's acquisition of Boston Pharmaceuticals' efemulsipherman for $800 million validates interest in the NASH market and the FGF21 mechanism [11][12] - **Market Potential**: The F4 cirrhotic population represents the highest unmet need and pricing power in the NASH market [13][14] Differentiating Characteristics of Pegosafirman - **Dosing and Administration**: Pegosafirman can be dosed once a week or every two weeks, with a favorable tolerability profile compared to competitors [18][21][23] - **Efficacy Data**: In phase 2 studies, pegosafirman showed a 20% placebo-adjusted delta in fibrosis improvement, with a relative risk benefit of 3.5 [18][19][20] - **Tolerability**: Lower rates of gastrointestinal adverse events compared to other FGF21 agents, which is crucial for patient compliance [21][22] Physician and Patient Perspectives - **Physician Preferences**: Key criteria include fibrosis benefit, tolerability, and the ability to address steatohepatitis [27][28][30] - **Patient Preferences**: Patients prioritize dosing convenience, adverse event profiles, and affordability [32][33] Market Strategy and Future Outlook - **Targeting Endocrinologists**: As the market evolves, endocrinologists are expected to play a significant role in treating NASH, especially with the approval of GLP-1s [34][35] - **Market Size**: The F4 space alone could exceed $5 billion, indicating significant potential for multiple successful players [38] Combination Therapies - **Potential Combinations**: The combination of FGF21 with GLP-1s could yield synergistic benefits, but safety and tolerability will be critical factors [49][50] Severe Hypertriglyceridemia (SHTG) Strategy - **Target Population**: Patients with triglycerides above 500 mg/dL, often with metabolic dysfunction, represent a significant market opportunity [52][53] - **Efficacy in SHTG**: Phase 2 studies showed a 57% to 63% reduction in triglycerides, positioning pegosafirman as a second-line therapy for refractory patients [54][55] Conclusion - **Overall Outlook**: 89Bio is well-positioned in the NASH and SHTG markets with a differentiated product profile and a strong focus on patient and physician needs, supported by promising clinical data and market validation through recent industry deals [56]

Company Overview - 89bio, Inc. is a clinical-stage biopharmaceutical company focused on developing innovative therapies for liver and cardiometabolic diseases [3] - The company is headquartered in San Francisco and is dedicated to creating best-in-class treatments for patients lacking optimal options [3] Product Development - 89bio is currently in Phase 3 trials for its lead candidate, pegozafermin, targeting metabolic dysfunction-associated steatohepatitis (MASH) with advanced fibrosis and severe hypertriglyceridemia (SHTG) [3] - Pegozafermin is a fibroblast growth factor 21 (FGF21) analog utilizing glycoPEGylated technology to enhance biological activity through an extended half-life [3] Investor Engagement - The company will participate in the BofA Securities 2025 Health Care Conference on May 14, 2025, at 1:40 PM ET [1] - Additionally, 89bio will be present at the RBC Capital Markets Global Healthcare Conference on May 20, 2025, at 9:30 AM ET [2] - Webcasts of these fireside chats will be available on the investor section of 89bio's website, with replays accessible for approximately 30 days post-conference [2]

PART I. FINANCIAL INFORMATION [Financial Statements (Unaudited)](index=3&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) The unaudited financial statements for Q1 2025 show total assets increased to $685.0 million due to a public offering, while net loss rose to $71.3 million from increased R&D expenses [Condensed Consolidated Balance Sheets](index=3&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets increased to $685.0 million by March 31, 2025, primarily due to a rise in cash and cash equivalents, significantly boosting stockholders' equity Condensed Consolidated Balance Sheet Highlights (in thousands) | Balance Sheet Item | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $315,396 | $126,060 | | Marketable securities | $323,384 | $313,895 | | Total current assets | $682,944 | $476,450 | | **Total assets** | **$685,031** | **$478,685** | | **Liabilities & Equity** | | | | Total current liabilities | $37,884 | $36,129 | | Total liabilities | $79,573 | $77,896 | | Total stockholders' equity | $605,458 | $400,789 | | **Total liabilities and stockholders' equity** | **$685,031** | **$478,685** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=4&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Net loss for Q1 2025 increased to $71.3 million due to higher R&D expenses, though net loss per share decreased to $0.49 due to more shares outstanding Condensed Consolidated Statements of Operations Highlights (in thousands, except per share data) | P&L Item | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $64,394 | $47,428 | | General and administrative | $11,515 | $9,849 | | Total operating expenses | $75,909 | $57,277 | | Loss from operations | $(75,909) | $(57,277) | | **Net loss** | **$(71,275)** | **$(51,681)** | | **Net loss per share, basic and diluted** | **$(0.49)** | **$(0.54)** | | Weighted-average shares outstanding | 146,365,115 | 95,846,740 | [Condensed Consolidated Statements of Stockholders' Equity](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders%27%20Equity) Stockholders' equity significantly increased to $605.5 million by March 31, 2025, primarily driven by $269.9 million from a public offering, partially offset by net loss - In Q1 2025, the company issued common stock and pre-funded warrants in a public offering, raising net proceeds of **$269.9 million**[16](index=16&type=chunk) - The increase in equity was offset by a net loss of **$71.3 million** and other comprehensive loss of **$0.2 million** for the quarter[16](index=16&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operations increased to $71.7 million in Q1 2025, but a $268.9 million inflow from financing activities led to a net increase in cash to $315.4 million Cash Flow Summary (in thousands) | Cash Flow Activity | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(71,737) | $(39,720) | | Net cash used in investing activities | $(7,833) | $(79,898) | | Net cash provided by financing activities | $268,906 | $21,030 | | **Net change in cash and cash equivalents** | **$189,336** | **$(98,588)** | | **Cash and cash equivalents at end of period** | **$315,396** | **$217,573** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=7&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) The notes confirm the company's clinical-stage focus on pegozafermin, an accumulated deficit of $895.8 million, and sufficient cash of $638.8 million for at least one year, alongside key financial commitments - The company is a clinical-stage biopharmaceutical company developing pegozafermin for MASH and SHTG[21](index=21&type=chunk) - As of March 31, 2025, the company had an accumulated deficit of **$895.8 million** but believes its cash, cash equivalents, and marketable securities of **$638.8 million** are sufficient to fund operations for at least one year[23](index=23&type=chunk)[24](index=24&type=chunk) - In February 2025, the company raised net proceeds of approximately **$269.9 million** from an underwritten public offering[62](index=62&type=chunk) - The company has a term loan facility for up to **$150.0 million**, with **$35.0 million** drawn as of March 31, 2025; access to the **$30.0 million** Tranche 2 is not anticipated[56](index=56&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=20&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the advancement of pegozafermin in Phase 3 trials, a $17.0 million increase in R&D expenses, and $638.8 million in cash, which is deemed sufficient for at least one year of operations [Overview](index=20&type=section&id=Overview) The company is a clinical-stage biopharmaceutical firm developing pegozafermin, with Phase 3 trials for MASH and SHTG progressing and commercial supply preparations underway - Lead product candidate, pegozafermin, is in Phase 3 development for MASH and SHTG[76](index=76&type=chunk) - The Phase 3 ENLIGHTEN program for MASH is enrolling patients, with topline data for the F2-F3 cohort expected in **H1 2027** and the F4 cohort in **2028**[78](index=78&type=chunk)[80](index=80&type=chunk) - The Phase 3 ENTRUST trial for SHTG has completed enrollment, with topline data expected in **Q1 2026**[79](index=79&type=chunk)[81](index=81&type=chunk) - A collaboration with BiBo is in place to construct a production facility for pegozafermin's commercial supply[82](index=82&type=chunk) [Results of Operations](index=23&type=section&id=Results%20of%20Operations) Q1 2025 R&D expenses increased by $17.0 million to $64.4 million, driven by Phase 3 MASH trials, while G&A expenses also rose Change in Operating Expenses (in thousands) | Expense Category | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | **Research and development** | **$64,394** | **$47,428** | **$16,966** | | Clinical development | $33,795 | $17,924 | $15,871 | | Contract manufacturing | $19,057 | $21,351 | $(2,294) | | Personnel-related expenses | $10,673 | $7,733 | $2,940 | | **General and administrative** | **$11,515** | **$9,849** | **$1,666** | [Liquidity and Capital Resources](index=25&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2025, the company held $638.8 million in cash and equivalents, bolstered by a $269.9 million public offering, sufficient to fund operations for at least one year - The company had cash, cash equivalents, and marketable securities of **$638.8 million** as of March 31, 2025[96](index=96&type=chunk) - In February 2025, a public offering raised net proceeds of **$269.9 million**[100](index=100&type=chunk) - Existing cash is expected to fund operations for at least one year from the filing date of the 10-Q[105](index=105&type=chunk) - The company does not anticipate meeting the condition to access Tranche 2 (**$30.0 million**) of its Term Loan Facility[106](index=106&type=chunk) [Contractual Obligations and Commitments](index=30&type=section&id=Contractual%20Obligations%20and%20Commitments) The company has significant future financial commitments, including $35.0 million in outstanding debt, potential $65.0 million milestone payments to Teva, and a $13.5 million payment to BiBo for a production facility - Obligated to pay Teva up to **$65.0 million** upon achievement of specified commercial milestones for pegozafermin[118](index=118&type=chunk) - A remaining **$13.5 million** is payable to BiBo for a production facility upon achieving a certain milestone[119](index=119&type=chunk) - The outstanding principal of **$35.0 million** under the Loan Agreement matures on October 1, 2028[117](index=117&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=30&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company states that there have been no material changes in its market risk from the information provided in its Annual Report on Form 10-K for the year ended December 31, 2024 - There have been no material changes in market risk since the last Annual Report on Form 10-K[122](index=122&type=chunk) [Controls and Procedures](index=30&type=section&id=Item%204.%20Controls%20and%20Procedures) Management, including the CEO and CFO, evaluated the company's disclosure controls and procedures and concluded they were effective as of March 31, 2025 - Management concluded that disclosure controls and procedures were effective as of March 31, 2025[124](index=124&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that have materially affected, or are reasonably likely to materially affect, internal controls[125](index=125&type=chunk) PART II. OTHER INFORMATION [Legal Proceedings](index=33&type=section&id=Item%201.%20Legal%20Proceedings) The company reports that it is not currently a party to any material legal proceedings - The company is not currently a party to any material legal proceedings[128](index=128&type=chunk) [Risk Factors](index=33&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks including dependence on pegozafermin's success, clinical and regulatory uncertainties, capital needs, reliance on third-party manufacturers, competition, and intellectual property disputes [Risks Related to Business and Industry](index=34&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20Industry) Risks include the company's dependence on pegozafermin, the uncertain and costly nature of clinical trials, the need for additional capital, reliance on third-party manufacturers, and intense competition - The company is a clinical-stage biopharmaceutical company with a history of net losses and its business depends entirely on the success of pegozafermin[131](index=131&type=chunk)[136](index=136&type=chunk) - The company will require substantial additional capital to finance operations, which may not be available on acceptable terms[140](index=140&type=chunk) - Reliance on third-party manufacturers, including BiBo in China, exposes the company to supply chain, geopolitical, and regulatory risks like the proposed BIOSECURE Act[147](index=147&type=chunk)[148](index=148&type=chunk)[154](index=154&type=chunk) - The company faces substantial competition from other companies developing therapies for MASH and SHTG, some with greater resources[163](index=163&type=chunk) [Risks Related to Regulatory Approvals](index=54&type=section&id=Risks%20Related%20to%20Regulatory%20Approvals) Significant regulatory risks include the uncertainty of pegozafermin's approval, potential post-market issues, and the limitations of expedited designations, compounded by FDA disruptions and evolving requirements - Pegozafermin has not received regulatory approval, and the process is lengthy, expensive, and uncertain[189](index=189&type=chunk)[193](index=193&type=chunk) - Even if approved, pegozafermin could face post-market difficulties, including potential revocation of approval if harmful side effects are discovered[192](index=192&type=chunk) - Breakthrough Therapy and PRIME designations do not guarantee a faster review or ultimate approval[195](index=195&type=chunk)[196](index=196&type=chunk) - Disruptions at the FDA and other government agencies, including policy changes and budget constraints, could negatively affect the review of regulatory submissions[199](index=199&type=chunk) [Risks Related to Intellectual Property](index=61&type=section&id=Risks%20Related%20to%20Intellectual%20Property) Intellectual property risks include the uncertainty of patent protection, reliance on a critical license from Teva, and the potential for costly litigation to defend or enforce IP rights - Success depends on the ability to obtain and maintain intellectual property protection for products and technologies, which is highly uncertain[209](index=209&type=chunk)[213](index=213&type=chunk) - The company relies on a license from Teva for the glycoPEGylation technology essential for pegozafermin; termination of this license would materially harm the business[217](index=217&type=chunk) - The company may become involved in expensive and unsuccessful lawsuits to protect its intellectual property or defend against infringement claims from third parties[220](index=220&type=chunk)[223](index=223&type=chunk) [Risks Related to Ownership of Our Common Stock](index=67&type=section&id=Risks%20Related%20to%20Ownership%20of%20Our%20Common%20Stock) Risks to common stock ownership include significant price volatility, potential depression from substantial share sales, and dilution from future equity offerings - The price of the company's common stock may be volatile and fluctuate significantly due to clinical developments, competitor news, and market trends[225](index=225&type=chunk) - Sales of a substantial number of shares, or the perception of such sales, could depress the stock price[226](index=226&type=chunk) - Raising additional capital through equity offerings may cause significant dilution to existing stockholders[229](index=229&type=chunk) [General Risk Factors](index=69&type=section&id=General%20Risk%20Factors) General risks include substantial control by insiders, inherent limitations of internal controls, and exclusive forum provisions that may limit stockholders' judicial options - Directors, executive officers, and holders of **5%** or more of the stock have substantial control over the company[232](index=232&type=chunk) - The company's disclosure and internal controls have inherent limitations and may not prevent all errors or fraud; failure to maintain effective controls could harm investor confidence[233](index=233&type=chunk)[235](index=235&type=chunk) - The company's ability to use its net operating loss (NOL) carryforwards may be limited, and a potential tax assessment from Israeli authorities could impact NOLs and financial condition[239](index=239&type=chunk)[240](index=240&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=72&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales of equity securities during the period - None[242](index=242&type=chunk) [Other Information](index=72&type=section&id=Item%205.%20Other%20Information) The company states that none of its directors or executive officers adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement during the first quarter of 2025 - No directors or executive officers adopted or terminated a Rule 10b5-1 trading plan during the three months ended March 31, 2025[245](index=245&type=chunk) [Exhibits](index=73&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Quarterly Report on Form 10-Q, including corporate governance documents, forms of warrants, and officer certifications - The report includes a list of all exhibits filed, such as the Certificate of Incorporation, Bylaws, forms of warrants, and officer certifications required by the SEC[247](index=247&type=chunk)

[89bio First Quarter 2025 Financial Results and Corporate Updates](index=1&type=section&id=89bio%20Reports%20First%20Quarter%202025%20Financial%20Results%20and%20Corporate%20Updates) [Recent Highlights and Anticipated Milestones](index=1&type=section&id=Recent%20Highlights%20and%20Anticipated%20Milestones) 89bio advances global Phase 3 MASH trials with data expected by 2028, significantly enhancing its financial position - **Topline histology data** from ENLIGHTEN-Fibrosis expected **1H 2027**, and ENLIGHTEN-Cirrhosis in **2028**[2](index=2&type=chunk)[4](index=4&type=chunk) - The Phase 3 ENTRUST trial for SHTG is **fully enrolled**, with **topline data expected in Q1 2026**[2](index=2&type=chunk)[10](index=10&type=chunk) - Pegozafermin shows potential for **fibrosis improvement and MASH resolution**, supported by a *Hepatology* meta-analysis[3](index=3&type=chunk) - The company concluded Q1 2025 with **$638.8 million in cash and equivalents** following a **$287.5 million gross proceeds equity offering**[2](index=2&type=chunk) [Clinical Program Updates](index=1&type=section&id=Clinical%20Program%20Updates) Three global Phase 3 trials are actively enrolling, with MASH histology data expected by 2028 and SHTG data by Q1 2026 [Metabolic dysfunction-associated steatohepatitis (MASH)](index=1&type=section&id=Metabolic%20dysfunction-associated%20steatohepatitis%20(MASH)) ENLIGHTEN-Fibrosis and ENLIGHTEN-Cirrhosis trials are actively enrolling globally, with histology data expected by 2028 - The Phase 3 ENLIGHTEN-Fibrosis (F2-F3 MASH) and ENLIGHTEN-Cirrhosis (F4 MASH) trials are **actively enrolling patients globally**[3](index=3&type=chunk)[4](index=4&type=chunk) - **Topline histology data** is anticipated in **1H 2027** for ENLIGHTEN-Fibrosis and in **2028** for ENLIGHTEN-Cirrhosis[4](index=4&type=chunk) - Trials are designed with **FDA and EMA alignment** to support **accelerated approval** via histology data, while collecting outcomes for full approval[5](index=5&type=chunk) [Severe Hypertriglyceridemia (SHTG)](index=2&type=section&id=Severe%20Hypertriglyceridemia%20(SHTG)) The global Phase 3 ENTRUST trial for SHTG is fully enrolled, with topline data expected in Q1 2026 - The global Phase 3 ENTRUST trial is **fully enrolled**[2](index=2&type=chunk) - **Topline data** from the ENTRUST trial is expected in **Q1 2026**[10](index=10&type=chunk) - ENTRUST is a **52-week trial** evaluating **weekly pegozafermin doses (30 mg and 20 mg)** versus placebo[10](index=10&type=chunk) [Corporate Updates](index=2&type=section&id=Corporate%20Updates) Q1 2025 saw 89bio secure **$287.5 million** from an equity offering and implement a flexible global manufacturing strategy - A **follow-on equity offering** in Q1 2025 generated **$287.5 million in gross proceeds**[10](index=10&type=chunk) - The company holds a **$150 million credit facility** with K2 HealthVentures, with **$35 million drawn**[10](index=10&type=chunk) - A **flexible, global manufacturing strategy** is implemented with alternative suppliers to mitigate risks[3](index=3&type=chunk)[10](index=10&type=chunk) [First Quarter 2025 Financial Results](index=2&type=section&id=First%20Quarter%202025%20Financial%20Results) Q1 2025 saw 89bio report a **$71.3 million net loss** due to increased expenses, while maintaining a **$638.8 million cash position** - As of March 31, 2025, **cash, cash equivalents, and marketable securities totaled approximately $638.8 million**[6](index=6&type=chunk) Key Financial Metrics | Financial Metric | Q1 2025 (in millions) | Q1 2024 (in millions) | Change Driver | | :--- | :--- | :--- | :--- | | **R&D Expenses** | $64.4 | $47.4 | Increased clinical development for Phase 3 MASH trials and higher personnel costs | | **G&A Expenses** | $11.5 | $9.8 | Increased personnel-related expenses due to higher headcount | | **Net Loss** | $71.3 | $51.7 | Higher R&D and G&A expenses | [Financial Statements](index=5&type=section&id=Financial%20Statements) Unaudited Q1 2025 financial statements show a **$71.3 million net loss**, **$685.0 million total assets**, and **$605.5 million stockholders' equity** [Condensed Consolidated Statement of Operations and Comprehensive Loss](index=5&type=section&id=Condensed%20Consolidated%20Statement%20of%20Operations%20and%20Comprehensive%20Loss) The statement details a **net loss of $71.3 million** for Q1 2025, driven by **$75.9 million in total operating expenses** | (In thousands, except per share data) | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $64,394 | $47,428 | | General and administrative | $11,515 | $9,849 | | **Total operating expenses** | **$75,909** | **$57,277** | | Loss from operations | $(75,909) | $(57,277) | | Interest income and other, net | $6,038 | $6,556 | | **Net loss** | **$(71,275)** | **$(51,681)** | | Net loss per share, basic and diluted | $(0.49) | $(0.54) | | Weighted-average shares outstanding | 146,365,115 | 95,846,740 | [Condensed Consolidated Balance Sheet Data](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheet%20Data) The balance sheet shows **total assets of $685.0 million** as of March 31, 2025, with **cash and equivalents at $638.8 million** | (In thousands) | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash, cash equivalents and marketable securities | $638,780 | $439,955 | | **Total assets** | **$685,031** | **$478,685** | | Total current liabilities | $37,884 | $36,129 | | **Total liabilities and stockholders' equity** | **$685,031** | **$478,685** |

Core Insights - 89bio, Inc. is advancing its clinical-stage biopharmaceutical development, focusing on therapies for liver and cardiometabolic diseases, particularly targeting metabolic dysfunction-associated steatohepatitis (MASH) and severe hypertriglyceridemia (SHTG) [11] Clinical Trials - The Phase 3 ENLIGHTEN-Fibrosis and ENLIGHTEN-Cirrhosis trials are designed to support accelerated approval for treating patients with MASH, with topline data expected in 1H 2027 and 2028, respectively [1][5] - The ENTRUST trial for SHTG has been fully enrolled, with topline data anticipated in 1Q 2026 [1][5] - Pegozafermin has been recognized in a meta-analysis as one of the most effective agents for fibrosis improvement and MASH resolution, highlighting its potential in the market [2] Financial Position - As of March 31, 2025, the company reported cash, cash equivalents, and marketable securities totaling approximately $638.8 million, an increase from $439.9 million at the end of 2024 [7][15] - The company completed a follow-on equity offering in 1Q 2025, generating gross proceeds of $287.5 million [4] - A $150 million credit facility with K2 HealthVentures has been established, with $35 million drawn down [4] Expenses and Losses - Research and development expenses for Q1 2025 were $64.4 million, up from $47.4 million in Q1 2024, primarily due to increased clinical development costs [8] - General and administrative expenses rose to $11.5 million in Q1 2025 from $9.8 million in Q1 2024, driven by higher personnel-related costs [9] - The net loss for Q1 2025 was reported at $71.3 million, compared to a net loss of $51.7 million in Q1 2024, attributed to higher R&D and G&A expenses [10]