Akero Therapeutics (AKRO) FY 2025 Conference June 10, 2025 02:40 PM ET Speaker0 Thanks everyone for joining us. I'm Andrew Newkirk, one of the biotech analysts here at Goldman Sachs. I'm really pleased to be joined by Andrew Chang, President and CEO of Akerro. Thanks so much, Andrew. Speaker1 Thanks for having me. Speaker0 Maybe at a high level, let's start with where the NASH field is now. We've obviously seen a lot of development both on the clinical development side with the commercially approved drug la ...

Summary of Akero Therapeutics (AKRO) 2025 Conference Call Company Overview - **Company**: Akero Therapeutics (AKRO) - **Industry**: Biotechnology, specifically focused on liver diseases such as NASH (Non-Alcoholic Steatohepatitis) and cirrhosis Key Points and Arguments Phase III Program Updates - Akero is currently executing multiple Phase III programs, including: - **Synchrony Real World Study**: Non-invasive study completed enrollment, results expected in the first half of 2026 [4] - **Synchrony Histology Study**: F2F3 study, results expected in the first half of 2027 [4] - **Synchrony Outcomes Study**: F4 study, first patient enrolled in September 2024, no guidance on results yet [5] Positive Phase II F4 Cirrhosis Data - Akero reported statistically significant improvement in fibrosis for cirrhotic patients, a first in the industry [7] - The effect size increased from 20% to 52% in pre-cirrhotic patients, indicating strong efficacy [8] - The company has not yet received FDA feedback on the Phase II data [10] FDA Interactions and Breakthrough Designation - Akero has breakthrough therapy designation for both pre-cirrhotic and cirrhotic patients [16] - The likelihood of filing for accelerated approval based on the recent data is considered low, but the company intends to share the data with the FDA [18] Competitive Landscape - Akero faces competition from Madrigal Pharmaceuticals, which has already received approval for its drug in the F2F3 space [57] - Other companies, including those developing FGF21 compounds, are also in the pipeline, indicating a competitive market [76] Study Design and Endpoints - The primary endpoint for the F2F3 study is a combination of fibrosis improvement and NASH resolution, which is different from other companies that may only focus on one [70] - The company is considering interim analyses based on strong data from the ongoing studies [25] Enrollment and Market Position - Enrollment for the F2F3 studies is tracking well, with expectations to complete enrollment by the first half of 2026 for a readout in the first half of 2027 [59][60] - Akero's strong F4 data has helped distinguish it from competitors, making enrollment easier [58] Pharma Interest in NASH - Recent acquisitions, such as GSK's purchase of Boston Therapeutics, indicate growing interest from large pharmaceutical companies in the NASH space [80] - Novo Nordisk is also entering the market, which could increase disease awareness and excitement in the field [82] Other Important Insights - Akero is actively engaging with large pharma companies for potential collaborations and investments [85] - The company is focused on ensuring patient safety and monitoring bone mineral density in ongoing studies [51][46] This summary encapsulates the key discussions and insights from the Akero Therapeutics conference call, highlighting the company's progress, competitive landscape, and future outlook in the biotechnology sector focused on liver diseases.

Company Overview - Akero Therapeutics, Inc. is a clinical-stage company focused on developing transformational treatments for serious metabolic diseases with high unmet medical needs, including metabolic dysfunction-associated steatohepatitis (MASH) [3] Clinical Development - The lead product candidate, efruxifermin (EFX), is currently being evaluated in three ongoing Phase 3 clinical studies: SYNCHRONY Histology, SYNCHRONY Outcomes, and SYNCHRONY Real-World, targeting different patient populations affected by MASH [3] - The Phase 3 SYNCHRONY program builds on the results of two Phase 2b clinical trials: the HARMONY study for pre-cirrhotic MASH and the SYMMETRY study for compensated cirrhosis due to MASH [3] Upcoming Events - Management will present at the Jefferies Global Healthcare Conference on June 4, 2025, at 8:45 a.m. P.T. [1] - A live webcast of the presentation will be available on the company's investor relations website, with an archived replay to follow [2]

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Akero Therapeutics (AKRO) 2025 Conference May 13, 2025 04:40 PM ET Speaker0 And I'm very pleased to have joined me in our first slot of the afternoon session, Andrew Chang, CEO of Vaccaro. Thank you so much for joining us. Speaker1 Thank you for having us, Jason. Well, perfect. Speaker0 Maybe just to start broadly to provide a little context for those newer to the story, Can you describe the role of FGF21 in the pathogenesis of liver fibrosis? Kind of acknowledging that it is somewhat early, but what are so ...

Industry Overview - The bear market caused by the Federal Reserve's monetary tightening ended in 2023, but the biotech sector continues to lag behind the broader market, with the SDPR S&P Biotech ETF trading at levels similar to 2017 [1] - Despite the skepticism surrounding biotech stocks post-COVID-19 pandemic, there are signs of potential recovery in 2025, driven by companies making progress on new drugs and innovative therapies [2] Company Highlights Vertex Pharmaceuticals - Vertex Pharmaceuticals has been a leader in developing cystic fibrosis treatments, including Kalydeco and Trikafta, and has recently gained FDA approval for Journavx, a novel non-opioid pain medication [6][7] - Despite a recent 15% stock decline and an earnings miss, Vertex is still rated as a Moderate Buy with an average price target of $515, indicating potential upside [8] Regeneron Pharmaceuticals - Regeneron Pharmaceuticals, known for its blockbuster drug Eyelea, reported over $14 billion in sales last year and has expanded its portfolio with drugs like Dupixent and Kevzara [9][10] - Although Regeneron's stock has dropped over 45% in the past year, analysts maintain a consensus Moderate Buy rating with an average price target of $892, suggesting significant upside potential [12] Akero Therapeutics - Akero Therapeutics focuses on liver disease treatments, particularly efruxifermin for metabolic dysfunction-associated steatohepatitis (MASH), currently in Phase 3 trials [13][14] - The stock saw a significant increase in January following positive Phase 2 trial results, and analysts unanimously rate it as a Buy, with a consensus price target of $76, indicating over 90% upside potential [14]

PART I. FINANCIAL INFORMATION [Condensed Consolidated Financial Statements](index=7&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements) The company reported a net loss of $70.7 million for Q1 2025, with total assets increasing to $1.16 billion, primarily driven by a follow-on offering [Nature of the Business and Liquidity](index=11&type=section&id=1.%20Nature%20of%20the%20business%20and%20basis%20of%20presentation) Akero is a clinical-stage company developing EFX for MASH, with $1.128 billion in cash sufficient for 12 months of operations - The company's lead product candidate is efruxifermin (EFX), an analog of FGF21, for the treatment of MASH, with a global Phase 3 program called SYNCHRONY ongoing[34](index=34&type=chunk) - The company has incurred recurring losses, with a net loss of **$70.7 million** for the three months ended March 31, 2025, and an accumulated deficit of **$896.9 million** as of that date[38](index=38&type=chunk)[161](index=161&type=chunk) - As of March 31, 2025, the company had **$1.128 billion** in cash, cash equivalents, and marketable securities, expected to fund operations for at least 12 months from the report's issuance date[40](index=40&type=chunk) [Loan Payable and Warrant Liability](index=19&type=section&id=6.%20Loan%20Payable%20and%20Warrant%20Liability) The company has a $150 million loan with Hercules Capital, with $35 million drawn and compliance with covenants as of March 31, 2025 - The company has a term loan agreement with Hercules for up to **$150 million**, with **$35 million** drawn across Tranche I and II commitments as of the report date[79](index=79&type=chunk)[80](index=80&type=chunk) - The loan bears a variable interest rate and requires interest-only payments until January 1, 2026, followed by principal and interest payments until the maturity date of March 1, 2027[81](index=81&type=chunk) Loan Payable Details (as of March 31, 2025) | (In thousands) | Amount | | :--- | :--- | | Total principal outstanding | $35,000 | | Unamortized discount and issuance costs | ($1,573) | | **Loan Payable (Net)** | **$35,475** | | Loan Payable - current | $6,664 | | Loan Payable - noncurrent | $28,811 | [Stockholder's Equity](index=21&type=section&id=7.%20Stockholder's%20equity%20(deficit)) The company raised $378.4 million net in Q1 2025 through a follow-on offering, significantly increasing stockholder's equity - In March 2024, a follow-on public offering of 12,650,000 shares of common stock generated net proceeds of **$344.8 million**[99](index=99&type=chunk) - In January 2025, the company sold 6,427,170 shares of common stock and 1,958,247 pre-funded warrants in a public offering, receiving net proceeds of **$378.4 million**[102](index=102&type=chunk) - In January 2025, the company sold 380,488 shares of common stock under its ATM agreement, generating gross proceeds of **$10.6 million**[101](index=101&type=chunk) [Commitments and Contingencies](index=29&type=section&id=12.%20Commitments%20and%20contingencies) The company has $34.2 million in purchase commitments and an operating lease, with a stockholder lawsuit dismissed - As of March 31, 2025, the company had non-cancelable purchase and other commitments with contract research and manufacturing organizations totaling **$34.2 million**[144](index=144&type=chunk) - A stockholder lawsuit filed on April 26, 2024, alleging misstatements regarding the Phase 2b SYMMETRY study, was dismissed without prejudice on May 5, 2025, and the company intends to vigorously defend against the lawsuit if an amended complaint is filed[148](index=148&type=chunk)[211](index=211&type=chunk) Condensed Consolidated Balance Sheets (Unaudited) | (In thousands) | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $185,922 | $340,238 | | Marketable securities (Short & Long-term) | $942,374 | $457,591 | | Total current assets | $713,151 | $770,380 | | **Total assets** | **$1,155,843** | **$825,886** | | **Liabilities and Stockholders' Equity** | | | | Total current liabilities | $42,439 | $39,754 | | Loan payable, noncurrent | $28,811 | $35,297 | | **Total liabilities** | **$71,997** | **$75,774** | | **Total stockholders' equity** | **$1,083,846** | **$750,112** | | **Total liabilities and stockholders' equity** | **$1,155,843** | **$825,886** | Condensed Consolidated Statements of Operations and Comprehensive Loss (Unaudited) | (In thousands, except per share amounts) | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $69,567 | $50,650 | | General and administrative | $11,315 | $9,304 | | **Total operating expenses** | **$80,882** | **$59,954** | | Loss from operations | ($80,882) | ($59,954) | | Interest and other income, net | $11,311 | $7,601 | | **Net loss** | **($70,725)** | **($53,344)** | | Net loss per common share, basic and diluted | ($0.90) | ($0.90) | Condensed Consolidated Statements of Cash Flows (Unaudited) | (In thousands) | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | ($67,664) | ($35,140) | | Net (cash used in) provided by investing activities | ($482,183) | $57,849 | | Net cash provided by financing activities | $395,531 | $366,938 | | **Net (decrease) increase in cash and cash equivalents** | **($154,316)** | **$389,647** | | Cash and cash equivalents at end of period | $185,922 | $623,854 | [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=32&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses a $70.7 million net loss for Q1 2025, driven by increased R&D, with $1.128 billion in cash expected to fund operations into 2028 - The company is a clinical-stage company focused on its lead product candidate, efruxifermin (EFX), for the treatment of MASH, with its ongoing global Phase 3 program, SYNCHRONY, designed to support marketing approval applications[155](index=155&type=chunk) - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities of **$1.128 billion**, which is believed to be sufficient to fund the current operating plan into 2028[165](index=165&type=chunk) - The company has incurred significant operating losses since inception, with a net loss of **$70.7 million** for the three months ended March 31, 2025, and an accumulated deficit of **$896.9 million**[161](index=161&type=chunk) [Results of Operations](index=37&type=section&id=Results%20of%20operations) The company's net loss increased to $70.7 million for Q1 2025, driven by a 37% rise in R&D and 22% rise in G&A expenses Comparison of Results of Operations (Q1 2025 vs Q1 2024) | (in thousands) | Q1 2025 | Q1 2024 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Research and development | $69,567 | $50,650 | $18,917 | 37% | | General and administrative | $11,315 | $9,304 | $2,011 | 22% | | **Total operating expenses** | **$80,882** | **$59,954** | **$20,928** | **35%** | | **Net loss** | **($70,725)** | **($53,344)** | **($17,381)** | **33%** | - R&D expenses increased by **$18.9 million (37%)** YoY, primarily due to a **$10.9 million** increase in CRO expenses for ongoing clinical trials and a **$6.6 million** increase in third-party contract manufacturing expenses for EFX[178](index=178&type=chunk) - G&A expenses increased by **$2.0 million (22%)** YoY, mainly due to a **$1.0 million** increase in legal and professional services and a **$0.6 million** increase in stock-based compensation[179](index=179&type=chunk) [Liquidity and Capital Resources](index=38&type=section&id=Liquidity%20and%20capital%20resources) The company financed operations through equity offerings, providing $395.5 million in Q1 2025, holding $1.128 billion in cash - In January 2025, the company raised gross proceeds of **$402.5 million** from a follow-on public offering and **$10.6 million** from its ATM offering[182](index=182&type=chunk) - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities totaling **$1.128 billion**[183](index=183&type=chunk) Summary of Cash Flows (Three Months Ended March 31) | (in thousands) | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | ($67,664) | ($35,140) | | Net (cash used in) provided by investing activities | ($482,183) | $57,849 | | Net cash provided by financing activities | $395,531 | $366,938 | [Quantitative and Qualitative Disclosures About Market Risk](index=41&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is exposed to interest rate, foreign currency, and inflation risks, with no material impact expected from a 10% rate change - **Interest Rate Risk:** The company's investments in marketable securities and its variable interest rate term loan are subject to interest rate risk, though a hypothetical **10%** change in rates is not expected to have a material impact[201](index=201&type=chunk)[203](index=203&type=chunk) - **Foreign Currency Risk:** The company has some transactions in foreign currencies (primarily Euro and British Pound) and is subject to foreign exchange risk, though the impact of a **10%** change is not considered material[204](index=204&type=chunk) - **Inflation Risk:** Rising inflation could increase the costs of clinical trials, manufacturing, and labor, potentially affecting the company's operations and product development[205](index=205&type=chunk) [Controls and Procedures](index=41&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls were effective as of March 31, 2025, with no material changes to internal control - The CEO and CFO concluded that as of March 31, 2025, the company's disclosure controls and procedures were effective at the reasonable assurance level[207](index=207&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that materially affected, or are reasonably likely to materially affect, the company's internal control over financial reporting[208](index=208&type=chunk) PART II. OTHER INFORMATION [Legal Proceedings](index=43&type=section&id=Item%201.%20Legal%20Proceedings) A stockholder lawsuit alleging misstatements was dismissed without prejudice on May 5, 2025 - A class-action lawsuit, Klobus v. Akero Therapeutics, Inc., was filed on April 26, 2024, alleging misstatements regarding the Phase 2b SYMMETRY study for stock purchased between September 13, 2022, and October 9, 2023[211](index=211&type=chunk) - On May 5, 2025, the court dismissed the lawsuit without prejudice, and the company intends to vigorously defend against the suit if an amended complaint is filed[211](index=211&type=chunk) [Risk Factors](index=43&type=section&id=Item%201A.%20Risk%20Factors) The company faces numerous risks related to EFX development, manufacturing, regulatory approval, financial condition, and intellectual property [Risks Related to Clinical Development and Manufacturing](index=43&type=section&id=Risks%20Related%20to%20the%20Clinical%20Development%20and%20Manufacturing%20of%20our%20Product%20Candidate) The company faces clinical development and manufacturing risks, including patient enrollment, competition, and reliance on third parties - Patient enrollment for MASH clinical trials is challenging due to difficulties in diagnosis and significant competition for recruiting patients, which could cause delays[213](index=213&type=chunk)[214](index=214&type=chunk) - The company faces intense competition from numerous large pharmaceutical and biotechnology companies (e.g., Eli Lilly, Novo Nordisk, Madrigal) that have greater financial and technical resources[217](index=217&type=chunk) - The company relies on third-party manufacturers (Boehringer Ingelheim for API, Vetter for drug product) and CROs, exposing it to risks of production difficulties, supply delays, and failure to meet regulatory standards like cGMP and GCP[226](index=226&type=chunk)[232](index=232&type=chunk)[235](index=235&type=chunk) [Risks Related to Business, Industry and Intellectual Property](index=50&type=section&id=Risks%20Related%20to%20Our%20Business,%20Industry%20and%20Intellectual%20Property) The company's business is heavily dependent on EFX success, relies on an Amgen license, and faces significant IP challenges - The company is heavily dependent on the success of EFX, its only product candidate, and failure to gain regulatory approval or successfully commercialize EFX would severely impact the business[246](index=246&type=chunk) - The company's rights to EFX are based on a license agreement with Amgen, and a breach of this agreement could lead to the loss of development and commercialization rights[261](index=261&type=chunk)[262](index=262&type=chunk) - The company's success depends on its ability to obtain and maintain intellectual property protection, with risks that patents may not issue, may be invalidated, or may not provide sufficient protection against competitors[278](index=278&type=chunk)[279](index=279&type=chunk) [Risks Related to Government Regulation](index=64&type=section&id=Risks%20Related%20to%20Government%20Regulation) The company faces significant regulatory risks, including lengthy FDA approval, post-market scrutiny, healthcare reforms, and compliance with various laws - The regulatory approval process is lengthy, time-consuming, and unpredictable, and the company has limited experience conducting late-stage clinical trials and has never obtained approval for a product[319](index=319&type=chunk)[320](index=320&type=chunk) - Even if approved, products remain subject to extensive regulatory scrutiny, including potential labeling changes, post-marketing studies, or withdrawal from the market if new safety issues arise[336](index=336&type=chunk) - Healthcare reform, such as the Inflation Reduction Act (IRA), could impact drug pricing through government negotiations and rebates, potentially affecting the ability to profitably sell products if approved[346](index=346&type=chunk)[352](index=352&type=chunk) [Risks Related to Financial Condition and Need for Capital](index=79&type=section&id=Risks%20Related%20to%20Our%20Financial%20Condition%20and%20Need%20for%20Additional%20Capital) The company has a history of significant losses, requires substantial additional capital, and its debt agreement contains restrictive covenants - The company has a history of significant losses, reporting a net loss of **$70.7 million** for Q1 2025 and an accumulated deficit of **$896.9 million** as of March 31, 2025[389](index=389&type=chunk) - The company will require substantial additional capital to complete the development and commercialization of EFX, and future funding may not be available on acceptable terms, or at all[395](index=395&type=chunk) - The term loan with Hercules subjects the company to restrictive covenants and requires repayment in an event of default, which could adversely affect the business[400](index=400&type=chunk)[403](index=403&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=95&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) During the three months ended March 31, 2025, the company did not issue or sell any unregistered securities that had not been previously disclosed - No unregistered sales of equity securities occurred during the quarter ended March 31, 2025[467](index=467&type=chunk) [Defaults Upon Senior Securities](index=95&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reported no defaults upon senior securities - None[468](index=468&type=chunk) [Mine Safety Disclosures](index=95&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[469](index=469&type=chunk) [Other Information](index=95&type=section&id=Item%205.%20Other%20Information) The company disclosed an officer adopted a Rule 10b5-1 trading plan on January 6, 2025, for 20,000 securities Rule 10b5-1 Trading Plan Adoption | Name and Title | Date Adopted | Duration | Aggregate Securities to be Sold | | :--- | :--- | :--- | :--- | | Patrick Lamy, Senior Vice President Commercial Strategy | January 6, 2025 | 365 days | 20,000 | [Exhibits](index=96&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Form 10-Q, including corporate governance documents and CEO/CFO certifications - The report includes certifications from the CEO and CFO pursuant to Sarbanes-Oxley Act Sections 302 and 906[473](index=473&type=chunk) - The exhibit list includes corporate governance documents such as the Fourth Amended and Restated Certificate of Incorporation and Amended and Restated Bylaws[473](index=473&type=chunk)

[Report Overview and Business Updates](index=1&type=section&id=Report%20Overview%20and%20Business%20Updates) [First Quarter 2025 Highlights](index=1&type=section&id=First%20Quarter%202025%20Highlights) Akero Therapeutics reported significant progress in Q1 2025, highlighted by statistically significant reversal of cirrhosis in its Phase 2b SYMMETRY study for its lead candidate, efruxifermin (EFX), accompanied by publication in the New England Journal of Medicine and a successful $402.5 million public offering boosting cash reserves to over $1.1 billion - The Phase 2b SYMMETRY study demonstrated a statistically significant reversal of compensated cirrhosis (F4) due to MASH after 96 weeks of treatment with efruxifermin (EFX)[2](index=2&type=chunk) - The SYMMETRY study results were published in the prestigious New England Journal of Medicine, underscoring the importance of the findings[2](index=2&type=chunk)[3](index=3&type=chunk) - **Successfully raised $402.5 million in gross proceeds from a follow-on public offering in January 2025**[2](index=2&type=chunk) - **As of March 31, 2025, the company held $1.128 billion in cash, cash equivalents, and marketable securities**[2](index=2&type=chunk)[3](index=3&type=chunk) [Clinical Trial Updates](index=1&type=section&id=Clinical%20Trial%20Updates) The company presented positive 96-week data from its Phase 2b SYMMETRY and HARMONY studies at the EASL Congress 2025, demonstrating EFX's potential to reverse both cirrhosis (F4) and pre-cirrhotic fibrosis (F2-F3), with the global Phase 3 SYNCHRONY program actively enrolling across three trials to further evaluate EFX's safety and efficacy [Phase 2b SYMMETRY Study (Cirrhosis - F4)](index=1&type=section&id=Phase%202b%20SYMMETRY%20Study%20(Cirrhosis%20-%20F4)) The Phase 2b SYMMETRY study showed that EFX is the only known investigational MASH drug to demonstrate a statistically significant reversal of compensated cirrhosis (F4) in a placebo-controlled trial, with 39% of patients on 50mg EFX achieving at least a one-stage improvement in fibrosis without worsening MASH at 96 weeks, a significant 24% effect size over placebo, and non-invasive measures also showing significant improvements SYMMETRY Study: Week 96 Key Biopsy Results | Metric | 50mg EFX Group | Placebo Group | p-value | | :--- | :--- | :--- | :--- | | ≥1-stage fibrosis improvement (no worsening of MASH) | 39% | 15% | 0.009 | | ≥1-stage fibrosis improvement (ITT analysis) | 29% | 12% | 0.031 | SYMMETRY Study: Week 96 Non-Invasive Measures vs. Placebo | Metric | 50mg EFX Group | Placebo Group | p-value | | :--- | :--- | :--- | :--- | | Mean reduction in ELF score | -0.53 | +0.22 | <0.001 | | Mean relative reduction in liver stiffness | -24% | -8% | <0.05 | - Newly presented analyses showed EFX's potential to reverse cirrhosis across key subgroups, including patients with cryptogenic cirrhosis and type 2 diabetes[10](index=10&type=chunk) [Phase 2b HARMONY Study (Pre-Cirrhotic - F2-F3)](index=2&type=section&id=Phase%202b%20HARMONY%20Study%20(Pre-Cirrhotic%20-%20F2-F3)) Data from the HARMONY study, presented at EASL 2025, demonstrated EFX's potential to reverse fibrosis in pre-cirrhotic MASH patients (F2-F3), with an AI-based qFibrosis® analysis showing a strong response rate in the EFX group across multiple fibrosis endpoints compared to placebo, increasing confidence in the treatment effect - **An AI-based qFibrosis® analysis showed 57% of patients on 50mg EFX were responders across three key fibrosis endpoints (qFibrosis®, FibroScan®, ELF Score), compared to only 3% in the placebo group**[10](index=10&type=chunk) - A post-hoc analysis suggested that the AI tool qFibrosis® may detect fibrosis improvement earlier than conventional histopathology[11](index=11&type=chunk) [Phase 3 SYNCHRONY Program Update](index=3&type=section&id=Phase%203%20SYNCHRONY%20Program%20Update) The ongoing global Phase 3 SYNCHRONY program consists of three trials (Real-World, Histology, Outcomes) evaluating EFX for both pre-cirrhotic and cirrhotic MASH, with enrollment for the Real-World study's double-blind portion complete and topline results expected in H1 2026, while the Histology study's 52-week results are anticipated in H1 2027 - **The program comprises three trials: SYNCHRONY Real-World (F1-F4), SYNCHRONY Histology (F2-F3), and SYNCHRONY Outcomes (F4)**[14](index=14&type=chunk) - **The SYNCHRONY Real-World study completed enrollment of its 601-patient double-blind cohort, with preliminary topline results expected in the first half of 2026**[14](index=14&type=chunk) - **The SYNCHRONY Histology study (~1,650 patients) remains on track to report 52-week results for primary histology endpoints during the first half of 2027**[14](index=14&type=chunk) [Corporate and Financial Updates](index=2&type=section&id=Corporate%20and%20Financial%20Updates) Akero significantly strengthened its financial position by raising approximately $402.5 million through a public offering in January 2025, reporting a net loss of $70.7 million for Q1 2025, with increased R&D and G&A expenses driven by the advancement of its Phase 3 program, and the current cash position expected to fund operations into 2028 [Follow-On Public Offering](index=2&type=section&id=Follow-On%20Public%20Offering) On January 30, 2025, Akero closed an underwritten public offering, raising gross proceeds of approximately $402.5 million by issuing 6.427 million common shares at $48.00 per share and 1.958 million pre-funded warrants - **Closed an underwritten public offering on January 30, 2025, raising approximately $402.5 million in gross proceeds**[5](index=5&type=chunk) [First Quarter 2025 Financial Results](index=3&type=section&id=First%20Quarter%202025%20Financial%20Results) Akero ended Q1 2025 with $1.128 billion in cash and marketable securities, believed to be sufficient to fund operations into 2028, while total operating expenses rose to $80.9 million from $60.0 million year-over-year, primarily due to increased R&D costs for the Phase 3 SYNCHRONY program - **Cash, cash equivalents, and marketable securities totaled $1,128.3 million as of March 31, 2025, providing a cash runway into 2028**[14](index=14&type=chunk) Q1 2025 vs Q1 2024 Operating Expenses (in millions) | Expense Category | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Research and development | $69.6 | $50.7 | | General and administrative | $11.3 | $9.3 | | **Total operating expenses** | **$80.9** | **$60.0** | [Financial Statements](index=6&type=section&id=Financial%20Statements) [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2025, Akero reported total assets of $1.156 billion, a significant increase from $825.9 million at year-end 2024, primarily driven by the proceeds from the public offering, with total stockholders' equity growing to $1.084 billion from $750.1 million over the same period Condensed Consolidated Balance Sheets (in thousands) | | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Total assets** | **$1,155,843** | **$825,886** | | Total liabilities | $71,997 | $75,774 | | **Total stockholders' equity** | **$1,083,846** | **$750,112** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For the three months ended March 31, 2025, Akero reported a net loss of $70.7 million, or ($0.90) per share, compared to a net loss of $53.3 million, or ($0.90) per share, for the same period in 2024, with the increased loss driven by higher R&D expenses for the Phase 3 program, which rose to $69.6 million Condensed Consolidated Statements of Operations (in thousands, except per share data) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Total operating expenses | $80,882 | $59,954 | | Loss from operations | $(80,882) | $(59,954) | | **Net loss** | **$(70,725)** | **$(53,344)** | | **Net loss per common share** | **$(0.90)** | **$(0.90)** | [Company and Product Information](index=4&type=section&id=Company%20and%20Product%20Information) [About MASH and Cirrhosis](index=4&type=section&id=About%20MASH%20and%20Cirrhosis) MASH (metabolic dysfunction-associated steatohepatitis) is a severe form of liver disease affecting an estimated 17 million Americans, characterized by liver fat accumulation, inflammation, and fibrosis, which can progress to cirrhosis, liver failure, and cancer, and is the fastest-growing reason for liver transplants in the US and Europe, with no currently approved treatments - **MASH is a serious form of MASLD estimated to affect 17 million Americans**[15](index=15&type=chunk) - **It is the fastest-growing cause of liver transplants and liver cancer in the US and Europe, and there are no approved treatments**[15](index=15&type=chunk) - **An estimated 3 million Americans are projected to have MASH cirrhosis by 2030**[16](index=16&type=chunk) [About Efruxifermin (EFX)](index=4&type=section&id=About%20Efruxifermin%20(EFX)) Efruxifermin (EFX) is Akero's lead product candidate, an engineered FGF21 analog being evaluated in three Phase 3 studies for MASH, which has shown potential in Phase 2 trials to reverse fibrosis (including compensated cirrhosis), resolve MASH, and improve cardiovascular risk factors, offering a holistic treatment approach with a convenient once-weekly dosing schedule - **EFX is engineered to mimic the biological activity of native FGF21 and is designed for convenient once-weekly dosing**[17](index=17&type=chunk) - **In multiple Phase 2 studies, EFX has been observed to reverse fibrosis, resolve MASH, reduce non-invasive markers of fibrosis, and improve insulin sensitivity and lipoprotein profile**[17](index=17&type=chunk) [About Akero Therapeutics](index=4&type=section&id=About%20Akero%20Therapeutics) Akero Therapeutics is a clinical-stage company focused on developing transformational treatments for serious metabolic diseases with high unmet medical need, with its lead product candidate, efruxifermin (EFX), currently being evaluated in a comprehensive Phase 3 program (SYNCHRONY) for the treatment of MASH - **Akero is a clinical-stage company developing treatments for serious metabolic diseases, including MASH**[18](index=18&type=chunk) - **The lead product candidate, EFX, is being evaluated in three ongoing Phase 3 clinical studies: SYNCHRONY Histology, SYNCHRONY Outcomes, and SYNCHRONY Real-World**[18](index=18&type=chunk)

Core Insights - Akero Therapeutics announced results from the 96-week Phase 2b HARMONY trial of efruxifermin (EFX) for patients with pre-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) [1][6] - The study demonstrated the antifibrotic activity of EFX, with over half of patients treated with 50mg EFX classified as responders by AI-based digital pathology and non-invasive tests, compared to fewer than 5% of placebo patients [2][3] Group 1: Study Details - The HARMONY study was a multicenter, randomized, double-blind, placebo-controlled trial involving 128 biopsy-confirmed adult MASH patients with fibrosis stage 2 or 3 [6] - Patients received either 28 mg or 50 mg EFX or placebo for 24 weeks, with the study continuing for up to 96 weeks [6] - The primary efficacy endpoint was the proportion of subjects experiencing ≥1-stage fibrosis improvement without worsening of MASH [6] Group 2: Results and Analysis - AI-based qFibrosis® analysis showed that after 24 weeks, the antifibrotic effect of EFX was greater than conventional pathology, with 18 patients identified as responders compared to 10 by conventional methods [3] - At Week 96, consistency was observed between conventional pathology and qFibrosis®, with 77% and 81% of patients classified as responders, respectively [3] Group 3: Presentations and Speakers - An oral presentation titled "Alignment of response assessed by non-invasive fibrosis biomarkers and HistoIndex AI-based qFibrosis histology in metabolic dysfunction associated steatohepatitis (MASH) clinical trials" was given by Prof. Quentin M. Anstee [4] - A poster presentation titled "qFibrosis enables earlier detection of fibrosis response in Efruxifermin-treated patients with F2-F3 MASH in 96-week HARMONY study" was presented by Dr. Jörn M. Schattenberg [5] Group 4: About EFX - Efruxifermin (EFX) is Akero's lead product candidate for MASH, currently evaluated in three ongoing Phase 3 studies [7][8] - EFX has shown potential to reverse fibrosis, resolve MASH, and improve insulin sensitivity and lipoprotein profiles, addressing the complex disease state of MASH [7]

Core Insights - The publication of the Phase 2b SYMMETRY trial results in the New England Journal of Medicine highlights the potential benefits of efruxifermin (EFX) in improving fibrosis in patients with compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH) after 96 weeks of treatment [1][3][4] Company Overview - Akero Therapeutics is a clinical-stage company focused on developing treatments for serious metabolic diseases, including MASH, with its lead product candidate being efruxifermin (EFX) [5][10] - The company is currently conducting three ongoing Phase 3 clinical studies related to EFX, building on the results of previous Phase 2b trials [5][10] Study Details - The SYMMETRY trial was a Phase 2b, multicenter, randomized, double-blind, placebo-controlled study involving 182 patients with biopsy-confirmed compensated cirrhosis (F4, Child-Pugh A) due to MASH [9] - The primary endpoint was defined as ≥1-stage fibrosis improvement without worsening of MASH at 36 weeks, with secondary outcomes assessed at 96 weeks [3][9] Efficacy Results - At 36 weeks, 19% of participants in the EFX 50mg group and 18% in the EFX 28mg group met the primary endpoint, compared to 13% for placebo [3] - At 96 weeks, 29% of participants in the EFX 50mg group and 21% in the EFX 28mg group showed fibrosis improvement without MASH worsening, compared to 11% in the placebo group [3] Safety and Tolerability - EFX was associated with improvements in noninvasive markers of liver injury and fibrosis, as well as markers of insulin sensitivity and lipid metabolism compared to placebo [4] - The safety profile of EFX was consistent with previous trials, with observed adverse events primarily being mild to moderate gastrointestinal issues [4] Disease Context - MASH is estimated to affect 17 million Americans and is characterized by excessive fat accumulation in the liver, leading to inflammation and fibrosis [6] - Approximately 20% of patients with MASH may progress to cirrhosis, which poses a higher risk of mortality [6][8]