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]

Core Insights - Akero Therapeutics presented promising results from the Phase 2b SYMMETRY trial for efruxifermin (EFX), indicating its potential to improve fibrosis in compensated cirrhosis caused by metabolic dysfunction-associated steatohepatitis (MASH) [1][2] Company Overview - Akero Therapeutics is a clinical-stage company focused on developing treatments for serious metabolic diseases with high unmet medical needs, particularly MASH [12] - Efruxifermin (EFX) is Akero's lead product candidate, currently undergoing evaluation in three ongoing Phase 3 studies [11][12] Clinical Trial Results - The SYMMETRY trial involved 182 patients with biopsy-confirmed compensated cirrhosis (F4) due to MASH, with 181 patients receiving EFX or placebo for 96 weeks [10] - At Week 96, 39% of patients treated with EFX 50mg showed fibrosis improvement compared to 15% in the placebo group (p=0.009) [2][3] - In the intent-to-treat (ITT) analysis, 29% of patients in the EFX 50mg group experienced fibrosis improvement versus 11% for placebo (p=0.031) [2][3] Efficacy and Safety - EFX demonstrated a significant increase in treatment effect over time, with a placebo-adjusted treatment effect doubling from 10% at Week 36 to 24% at Week 96 [5] - Non-invasive measures of liver fibrosis and injury, such as ELF test scores and liver stiffness by Fibroscan, showed continued improvement for the EFX 50mg group over 96 weeks [6] - The safety profile of EFX was consistent with previous trials, with mild to moderate gastrointestinal adverse events being the most common [8] Future Directions - Akero plans to continue evaluating EFX across all stages of MASH in the Phase 3 SYNCHRONY program [2] - The company aims to address the complex, multi-system disease state of MASH, including improvements in cardiovascular risk factors linked to the condition [11]

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] Upcoming Events - Management will present at the BofA Securities 2025 Health Care Conference on May 13, 2025, at 1:40 p.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] Clinical Development - Akero's 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 with MASH [3] - The Phase 3 SYNCHRONY program builds on results from two Phase 2b clinical trials: the HARMONY study and the SYMMETRY study [3]

Core Insights - Akero Therapeutics, Inc. is set to present significant findings related to its lead product candidate, efruxifermin (EFX), at the EASL Congress 2025, highlighting advancements in treating metabolic diseases with high unmet medical needs [1][3]. Presentation Details - The first oral presentation will focus on the results of a 96-week, randomized, double-blind, placebo-controlled Phase 2b trial (SYMMETRY) demonstrating that efruxifermin improves fibrosis in participants with compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH) [2]. - The second oral presentation will discuss the alignment of non-invasive fibrosis biomarkers and AI-based histology assessments in MASH clinical trials, providing a new roadmap for drug efficacy evaluation as demonstrated in the HARMONY trial [2]. - A poster presentation will showcase how qFibrosis enables earlier detection of fibrosis response in efruxifermin-treated patients with F2-F3 MASH in the 96-week HARMONY study [3]. Company Overview - Akero Therapeutics is a clinical-stage company focused on developing treatments for serious metabolic diseases, particularly MASH, with efruxifermin being evaluated in three ongoing Phase 3 clinical studies [3]. - The Phase 3 SYNCHRONY program builds on the results from two Phase 2b trials, the HARMONY study and the SYMMETRY study, indicating a robust pipeline for addressing metabolic diseases [3].

Efruxifermin (EFX) Efficacy and Safety - Efruxifermin (EFX) demonstrated unprecedented fibrosis improvement after 96 weeks of treatment, with a 39% improvement in completer analysis versus 15% for placebo[10]. - The Phase 2b SYMMETRY study reported the first-ever statistically significant reversal of cirrhosis, with 29% of patients showing improvement compared to 12% for placebo[10]. - 50mg EFX treatment resulted in a 50% improvement in fibrosis with no worsening of MASH at Week 96, compared to 12% in the placebo group[57]. - 70% of patients receiving EFX 28mg and 50mg achieved MASH resolution at Week 96, significantly higher than the 13% in the placebo group[68]. - EFX 50mg achieved a 75% response rate for ≥1 stage fibrosis improvement at Week 96, significantly higher than the placebo[121]. - EFX 50mg demonstrated a 23% improvement in fibrosis at Week 96 compared to 2% in the placebo group, with statistical significance (p<0.01)[130]. - 68% of patients with F3 fibrosis at baseline showed ≥2 stage improvement in fibrosis with EFX 50mg, while only 14% in the placebo group achieved this[137]. - EFX 50mg resulted in a 60% rate of ≥1 stage fibrosis improvement and MASH resolution at Week 96, significantly higher than the 9% in the placebo group (p<0.01)[152]. - EFX 50mg treatment group achieved a significant liver fat reduction of 65% compared to a 9% reduction in the placebo group at Week 12, p<0.001[186]. - 90% of patients in the EFX 50mg group achieved a ≥50% relative reduction in liver fat, compared to 10% in the placebo group, p<0.001[192]. - The EFX 50mg group showed a reduction in liver stiffness by 2.7 kPa, while the placebo group showed no significant change[196]. - EFX 50mg treatment resulted in a decrease in ALT levels from a baseline of 35 U/L to a reduction of 5.3 U/L, while the placebo group showed an increase[200]. Clinical Trials and Study Design - The Phase 3 SYNCHRONY program is actively enrolling patients, with a total of approximately 3,500 participants across three studies focusing on different fibrosis stages[24]. - The SYNCHRONY program includes a comprehensive evaluation of safety, tolerability, and efficacy, with primary endpoints focused on fibrosis improvement and MASH resolution[24]. - The company plans to report results for the primary endpoints of the SYNCHRONY studies in the first half of 2026 and 2027[25]. - The Phase 3 studies are expected to provide critical data on the long-term clinical outcomes and safety of EFX in a broad patient population[24]. - The total treatment duration for the Phase 3 SYNCHRONY trial is approximately 260 weeks, with a randomization of 1:1 for EFX 50mg and placebo[96]. - The study included a total of 1150 patients, with a focus on compensated cirrhosis due to MASH[96]. Safety and Adverse Events - Treatment-emergent adverse events (TEAEs) leading to discontinuation were 3% in placebo, 11% in EFX 28mg, and 18% in EFX 50mg[71]. - The most frequent drug-related treatment-emergent adverse events (TEAEs) included diarrhea (40% for EFX 28mg and 37% for EFX 50mg)[158]. - No deaths were reported in any treatment group, with serious adverse events occurring in 9% of placebo, 10% of EFX 28mg, and 16% of EFX 50mg groups[158]. - 33% of patients in the EFX 50mg group experienced nausea as a treatment-emergent adverse event, compared to 10% in the placebo group[183]. - 5% of patients in the EFX 50mg group discontinued treatment due to drug-related adverse events[183]. Demographics and Baseline Characteristics - As of December 31, 2024, the company has approximately $800 million in cash, sufficient to fund the Phase 3 SYNCHRONY studies through their primary endpoints into the second half of 2027[36]. - The baseline demographics showed that 82% of patients had type 2 diabetes, with an average age of 61 years across the study population[49]. - The baseline demographics indicated that 70% of the placebo group had fibrosis stage F3, while the EFX 50mg group had 63%[110]. - The baseline hepatic fat fraction was 11% in the EFX 50mg group compared to 15% in the placebo group[179]. - 76% of patients in the EFX 50mg group were on Metformin, compared to 70% in the placebo group[181].

Core Viewpoint - Mid-cap stocks, while less prominent than large caps, exhibit significant volatility that can create substantial investment opportunities for those willing to take on risk [1][10]. Group 1: H&E Equipment Services - H&E Equipment Services Inc. (NASDAQ: HEES) has experienced a remarkable 120% increase since mid-January, largely due to acquisition rumors from Herc Holdings Inc. (NYSE: HRI) at a price of $104.89 per share [2][3]. - The stock closed at $98, approximately 7% below the rumored buyout price, presenting a potential low-risk arbitrage opportunity for traders [3]. - Analysts forecast a 12-month price target of $71.33, indicating a downside of 25.69%, with a high forecast of $92.00 and a low of $60.00 [2]. Group 2: Oklo - Oklo Inc. (NYSE: OKLO) has seen a pullback of over 30% after a significant rally, driven by initial optimism regarding its potential for cheap and clean nuclear power [4][5]. - The stock's forecast indicates a 12-month price target of $44.50, representing a 37.66% upside, with a high of $58.00 and a low of $31.00 [4]. - The recent decline may serve as a necessary reset, with expectations for a more measured recovery rather than the previous extreme volatility [6]. Group 3: Akero Therapeutics - Akero Therapeutics Inc. (NASDAQ: AKRO) has maintained a 140% gain since mid-January, supported by strong Phase 2b trial results for its MASH drug, targeting a lucrative market [7][8]. - The stock has a 12-month price forecast of $75.86, suggesting a 58.86% upside, with a high forecast of $109.00 and a low of $38.00 [7]. - Institutional support is evident, with Bank of America upgrading the stock to a Buy and setting a new price target of $63, indicating over 20% upside from its recent closing price of $52 [9].

Financial Performance - The company reported net losses of $252.1 million, $151.8 million, and $112.0 million for the years ended December 31, 2024, 2023, and 2022, respectively, with an accumulated deficit of $826.2 million as of December 31, 2024[528]. - The net loss for the year ended December 31, 2024, was $252.1 million, compared to a net loss of $151.8 million in 2023, reflecting a 66% increase in losses[545]. - The comprehensive loss for 2024 was $251,382,000, compared to $151,526,000 in 2023, representing a 65.9% increase[610]. - The company's accumulated deficit grew to $826,156,000 in 2024, compared to $574,096,000 in 2023, an increase of 44.0%[608]. - The company has not generated any revenue since inception and does not expect to do so in the near future[533]. Capital and Funding - The company has raised capital through various means, including a $25.0 million equity investment from Pfizer, Inc. in 2022 and a $35.0 million term loan from Hercules Capital, Inc.[528]. - The company raised gross proceeds of $127.4 million in 2023 and $80.3 million in 2024 through common stock offerings, with an additional $402.5 million raised in January 2025[557]. - The company raised $344.84 million from a follow-on public offering in 2024, compared to $216.20 million in 2023[617]. - The company anticipates requiring additional funding to complete the clinical development and commercialization of EFX, pending regulatory approval[625]. - The company has outstanding borrowings of $35.0 million under a loan agreement with Hercules, with the potential to borrow an additional $30.0 million until June 15, 2025[569]. Research and Development - The Phase 3 SYNCHRONY program consists of three trials evaluating EFX for patients with compensated cirrhosis (F4) and pre-cirrhotic MASH (F2-F3), with enrollment for the trials beginning in Q4 2023[525][526]. - The company anticipates significant increases in research and development expenses as it advances EFX through later-stage clinical development[535]. - Research and development expenses rose to $247.5 million in 2024, up from $141.8 million in 2023, marking a 75% increase, primarily due to increased costs associated with the EFX program[546]. - The company expects substantial increases in research and development expenses to support ongoing clinical development activities for the EFX program[547]. - The company has entered into various agreements for research and development, with costs recorded as expenses as incurred[641]. Clinical Trials and Product Development - In the SYMMETRY Phase 2b trial, 39% of patients treated with 50mg EFX experienced reversal of cirrhosis at week 96, compared to 15% for the placebo group[522]. - In the HARMONY Phase 2b trial, response rates for ≥1 stage improvement in fibrosis at week 96 were 75% for the 50mg EFX group and 46% for the 28mg EFX group, compared to 24% for placebo[523]. - EFX has shown statistically significant fibrosis regression and MASH resolution in previous Phase 2b trials with over 300 patients treated for up to 96 weeks[619]. - The first clinical milestone payment of $7.5 million was made to Amgen in December 2023, related to the Phase 3 SYNCHRONY program[576]. - The company is focused on developing treatments for metabolic diseases, particularly metabolic dysfunction-associated steatohepatitis (MASH)[619]. Operating Expenses - For the year ended December 31, 2024, total operating expenses increased to $285.4 million from $172.9 million in 2023, representing a 65% increase[545]. - Cash used in operating activities for 2024 was $230.1 million, significantly higher than $145.4 million in 2023, indicating increased operational expenditures[560]. - General and administrative expenses increased to $37.9 million in 2024 from $31.1 million in 2023, a rise of 22% due to higher stock-based compensation and staffing costs[548]. - Stock-based compensation expense was $29.7 million for the year ended December 31, 2024, compared to $21.5 million in 2023, showing an increase in compensation costs[583]. Liquidity and Assets - As of December 31, 2024, the company had cash, cash equivalents, and marketable securities totaling $797.8 million, with an additional $402.5 million raised from a public offering in January 2025[532]. - Cash, cash equivalents, and marketable securities totaled $797.8 million as of December 31, 2024, providing a strong liquidity position for future operations[558]. - Total current assets increased to $770,380,000 as of December 31, 2024, up from $559,962,000 in 2023, representing a 37.5% increase[608]. - Cash and cash equivalents increased to $340,238,000 in 2024 from $234,207,000 in 2023, reflecting a 45.2% growth[608]. - The total fair value of short-term and long-term marketable securities was $771,683 as of December 31, 2024, up from $541,965 in 2023[667]. Stock and Equity - The weighted-average number of shares used in computing net loss per common share increased to 67,136,772 in 2024 from 52,568,159 in 2023, a rise of 27.7%[610]. - The company issued 12.65 million shares in a follow-on offering in 2024, contributing to an increase in total shares outstanding to 72.38 million[617]. - The company has reserved 577,089 options under the 2018 Stock Option and Grant Plan and 6,983,360 options under the 2019 Stock Option and Incentive Plan as of December 31, 2024[697]. - The total intrinsic value of stock options outstanding as of December 31, 2024, was $46,487,000, up from $35,133,000 at the end of 2023[710]. - Stock-based compensation classified within research and development expense for 2024 was $11,294,000, compared to $7,579,000 in 2023[717]. Debt and Liabilities - The Company has a Loan Payable under a Loan Agreement with Hercules Capital, with amendments made on June 7, 2023, and February 28, 2024[648]. - The total principal outstanding loan payable is $35,000,000, with an end of term charge of $2,048,000, leading to a total of $37,048,000 including the end of term charge[681]. - The Company reported accrued external research and development expenses of $28,925 as of December 31, 2024, compared to $10,041 in 2023[670]. - The Term Loan bears interest at a variable rate of at least 7.65% and matures on March 1, 2027[673]. - The company has a contingent liability to issue warrants for up to an additional 211,137 shares of common stock under the Loan Agreement as of December 31, 2024[681].

Core Insights - Akero Therapeutics reported significant advancements in its clinical programs for Efruxifermin (EFX), particularly in the treatment of metabolic dysfunction-associated steatohepatitis (MASH) and compensated cirrhosis [2][5][13] Clinical Development - The Phase 2b SYMMETRY study demonstrated a statistically significant reversal of compensated cirrhosis (F4) in patients treated with 50mg EFX for 96 weeks, with 39% of patients showing ≥1 stage improvement in fibrosis [6][11] - The Phase 3 SYNCHRONY program is ongoing, consisting of three randomized, placebo-controlled trials aimed at evaluating the safety and efficacy of EFX in patients with MASH and compensated cirrhosis [10][13] - Preliminary results from the SYNCHRONY Real-World study, which enrolled 601 patients, are expected in the first half of 2026 [10] Financial Performance - For the year ended December 31, 2024, Akero reported cash, cash equivalents, and short- and long-term marketable securities totaling $797.8 million, with a follow-on offering raising $402.5 million in January 2025 [9][10] - Research and development expenses increased to $247.5 million for the year, up from $141.8 million in 2023, primarily due to costs associated with clinical trials [9][17] - The net loss for the year was $252.1 million, compared to a net loss of $151.8 million in 2023, reflecting increased operational expenses [17] Market Context - MASH is a serious condition affecting approximately 17 million Americans, with no approved treatments currently available, highlighting a significant unmet medical need [12][13] - The condition is the fastest-growing cause of liver transplants and liver cancer in the US and Europe, emphasizing the urgency for effective therapeutic options [12]

Akero Therapeutics, Inc. (NASDAQ:AKRO) - Grabar Law Office is investigating whether certain officers and directors of Akero breached their fiduciary duties owed to the company [1] - A securities fraud class action complaint alleges that Akero made false and misleading statements regarding the SYMMETRY study, including that approximately 20% of enrolled patients had cryptogenic cirrhosis and did not have definitive NASH at baseline [3] - The complaint also claims that the results from cryptogenic cirrhosis patients were to be excluded from the calculation of NASH resolution secondary endpoints, and that Akero introduced a confounding factor into the study's design [3] - Akero allegedly misrepresented the nature of the SYMMETRY trial and its usefulness in supporting any new drug application, impacting the likelihood of EFX becoming a commercial treatment for NASH cirrhotics [3] Crocs, Inc. (NASDAQ:CROX) - Grabar Law Office is investigating claims on behalf of shareholders of Crocs, Inc. regarding potential breaches of fiduciary duties by certain officers and directors [5] - A securities fraud class action complaint alleges that Crocs made materially false and misleading statements about the nature and sustainability of HEYDUDE's revenue growth following its acquisition [7] - The complaint indicates that the revenue growth was driven by stocking third-party wholesalers and retailers, and that destocking of excess inventory negatively impacted financial results [8] Extreme Networks, Inc. (NASDAQ:EXTR) - Grabar Law Office is investigating claims on behalf of Extreme Networks shareholders concerning potential breaches of fiduciary duties by certain officers [10] - A securities fraud class action complaint alleges that Extreme Networks made false and misleading statements regarding adverse client demand trends and the fulfillment of backlog orders [12] - The complaint states that Extreme Networks was drawing down its backlog at a faster rate than represented, leading to a misrepresentation of organic demand, revenue growth, and market share gains [12] Domino's Pizza, Inc. (NASDAQ:DPZ) - Grabar Law Office is investigating claims on behalf of Domino's shareholders regarding potential breaches of fiduciary duties by certain officers [14] - A securities fraud class action complaint alleges that Domino's made materially false and misleading statements about its business and financial prospects, particularly concerning challenges faced by its largest master franchisee [16] - The complaint suggests that Domino's was unlikely to meet its previously issued long-term guidance for annual global net store growth, leading to overstated business prospects [16]