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FORM
CURRENT REPORT
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| Item 7.01. | Regulation FD Disclosure. |
On September 13, 2022, Akero Therapeutics, Inc. (the “Company”) issued a press release titled “In Akero Therapeutics’ Phase 2b HARMONY Study, Both the 50mg and 28mg EFX Doses Achieved Statistical Significance on Primary and Secondary Histology Endpoints after 24 Weeks.” A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information under this Item 7.01, including Exhibit 99.1 hereto, is being furnished herewith and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall such information be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 8.01. | Other Events. |
The Company from time to time presents and/or distributes to the investment community slide presentations to provide updates and summaries of its business. A copy of its HARMONY Study slide presentation is being filed herewith as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.
On September 13, 2022, the Company released topline data from HARMONY, a 24-week Phase 2b study evaluating the efficacy and safety of its lead product candidate efruxifermin (“EFX”) in patients with pre-cirrhotic nonalcoholic steatohepatitis (“NASH”), fibrosis stage 2 or 3 (“F2-F3”). The study met its primary endpoint for both the 50mg and 28mg efruxifermin (“EFX”) dose groups, with 41% and 39% of EFX-treated patients, respectively, experiencing at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24, compared with 20% for the placebo arm. The study also met a key secondary endpoint with 76% and 47% of patients treated with 50mg and 28mg, respectively, achieving NASH resolution without worsening of fibrosis, compared with 15% for placebo. In addition, 41% and 29% of patients treated with 50mg and 28mg, respectively, achieved both endpoints (NASH resolution and fibrosis improvement ≥1 stage), compared with 5% for placebo.
Patients in the HARMONY study exhibited characteristics of patients at high risk of disease progression. The mean body weight across dose groups was approximately 105 kilograms. Roughly 70% of patients across dose groups had Type 2 diabetes as well as NASH. Approximately twice as many patients in the HARMONY study had fibrosis stage 3 (66%) as fibrosis stage 2 (34%). Despite these indicators of more advanced disease, the study also demonstrated statistically significant effects in multiple secondary endpoints in both dose groups, including improvements in liver fat, liver enzymes, non-invasive fibrosis markers, HbA1c, lipoproteins, and body weight. Treatment with EFX was generally well-tolerated, with a tolerability profile comparable to that observed in the Company’s Phase 2a BALANCED study.
EFX was reported to be generally well tolerated. Across both dose groups, the most frequent adverse events (“AEs”) were grade 1 or 2 gastrointestinal events (diarrhea, nausea, increased appetite, and frequent bowel movements), which were transient in nature. A total of five patients treated with EFX were discontinued due to AEs (two in the 28mg group and three in the 50mg group, one of which was reported to be unrelated to study drug), compared with none for placebo. A single drug-related serious adverse event (“SAE”) of esophagitis was experienced by a patient in the 50mg group who had a history of gastroesophageal reflux disease. Three other SAEs were reported as unrelated to study drug.
In July of 2021, the Company initiated the SYMMETRY study, a Phase 2b trial in biopsy-confirmed NASH patients with compensated cirrhosis, Child-Pugh class A. Based on enrollment to date, Akero expects to report results from the ongoing Phase 2b SYMMETRY study in the second half of 2023. Results from a 12-week expansion cohort of the SYMMETRY study, evaluating treatment of EFX on top of GLP-1 therapy in patients with F1-F3 fibrosis, are expected in the first half of 2023.
Forward-Looking Statements
This Current Report on Form 8-K and certain materials furnished or filed herewith contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding: the Company’s business plans and objectives, including future plans or expectations for efruxifermin (EFX), the therapeutic effects and clinical benefits of EFX, as well as the dosing, safety and tolerability of EFX; and upcoming milestones, including the results, and expected timing to report such results of the Company’s Phase 2b SYMMETRY study; and the Company’s preparations for commercialization of EFX, if approved.
Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: risks related to the impact of public health epidemics affecting countries or regions in which we have operations or do business, such as COVID-19, which has been labelled a pandemic by the World Health Organization, including potential negative impacts on the Company’s employees, manufacturers, supply chain and production as well as on global economies and financial markets; the company’s ability to execute on its strategy; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in the United States; and risks related to the competitive landscape. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in the Company’s annual report on Form 10-K filed, with the United States Securities and Exchange Commission (SEC) and quarterly reports on Form 10-Q filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s other filings with the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Press Release issued by Akero Therapeutics, Inc. on September 13, 2022 | |
| 99.2 | Slide presentation of Akero Therapeutics, Inc. | |
| 104 | Cover Page Interactive Data File (embedded within Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: September 13, 2022 | AKERO THERAPEUTICS, INC. | |||||
| By: | /s/ Andrew Cheng | |||||
| Andrew Cheng, M.D., Ph.D. President and Chief Executive Officer | ||||||
Exhibit 99.1
In Akero Therapeutics’ Phase 2b HARMONY Study, Both the 50mg and 28mg EFX Doses Achieved Statistical Significance on Primary and Secondary Histology Endpoints after 24 Weeks
50mg (41%) and 28mg (39%) groups demonstrated ≥1 stage improvement in fibrosis without worsening of NASH, double the placebo rate (20%)
50mg (76%) and 28mg (47%) groups demonstrated NASH resolution without worsening of fibrosis, three to five times the placebo rate (15%)
50mg (41%) and 28mg (29%) groups demonstrated fibrosis improvement AND resolution of NASH, six to eight times the placebo rate (5%)
EFX-treated patients also experienced statistically significant improvements in liver fat, liver enzymes, noninvasive fibrosis markers, glycemic control, lipoproteins, and body weight
Investor webcast at 8:00 am ET today to further discuss data
SOUTH SAN FRANCISCO, Calif., Sept 13, 2022 — Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company developing transformational treatments for patients with serious metabolic disease marked by high unmet medical need, today released topline data from HARMONY, a 24-week Phase 2b study evaluating the efficacy and safety of its lead product candidate efruxifermin (EFX) in patients with pre-cirrhotic nonalcoholic steatohepatitis (NASH), fibrosis stage 2 or 3 (F2-F3). The study met its primary endpoint for both the 50mg and 28mg EFX dose groups, with 41% and 39% of EFX-treated patients, respectively, experiencing at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24, compared with 20% for the placebo arm.
The study also met a key secondary endpoint with 76% and 47% of patients treated with 50mg and 28mg, respectively, achieving NASH resolution without worsening of fibrosis, compared with 15% for placebo. In addition, 41% and 29% of patients treated with 50mg and 28mg, respectively, achieved both endpoints (NASH resolution and fibrosis improvement ≥1 stage), compared with 5% for placebo.
“The statistically significant histological improvements observed in the HARMONY study are among the strongest efficacy results reported in NASH to date and, together with strong results in secondary endpoints, show that EFX has the potential to treat the core facets of NASH,” said Stephen Harrison, M.D., medical director of Pinnacle Clinical Research and the HARMONY study’s principal investigator. “I believe the magnitude and general consistency of results observed across the Phase 2a BALANCED and Phase 2b HARMONY studies increase the probability of success in Phase 3 and position EFX to potentially be a foundational monotherapy for patients with NASH.”
Patients in the HARMONY study exhibited characteristics of patients at high risk of disease progression. The mean body weight across dose groups was approximately 105 kilograms. Roughly 70% of patients across dose groups had Type 2 diabetes as well as NASH. Approximately twice as many patients in the HARMONY study had fibrosis stage 3 (66%) as fibrosis stage 2 (34%). Despite these indicators of more advanced disease, the study also demonstrated statistically significant effects in multiple secondary endpoints in both dose groups, including improvements in liver fat, liver enzymes, non-invasive fibrosis markers, HbA1c, lipoproteins, and body weight. Treatment with EFX was generally well-tolerated, with a tolerability profile comparable to that observed in Akero’s Phase 2a BALANCED study.
“We believe today’s results from the HARMONY study are an important milestone not only for Akero but for the entire NASH community,” said Andrew Cheng, M.D., Ph.D., president and chief executive officer of Akero. “As the fastest growing cause of liver transplantation and liver cancer in the US and Europe,
NASH represents a substantial and growing health burden. We believe the data are very compelling and show EFX’s potential to meet the critical, global unmet need for patients by intervening across stages of disease progression, potentially addressing both early-stage metabolic drivers and later-stage inflammation and fibrosis.”
Summary of Week 24 Biopsy Endpoints
| Measure (Mean) |
Placebo (N=41) |
28mg (N=38) |
50mg (N=34) |
|||||||||
| Improvement in at least one stage of fibrosis without worsening NASH (%) |
20 | 39 | * | 41 | * | |||||||
| Resolution of NASH without worsening of fibrosis (%) |
15 | 47 | ** | 76 | *** | |||||||
| NASH resolution AND improvement in at least one stage of fibrosis (%) |
5 | 29 | ** | 41 | *** | |||||||
| * | p<0.05, ** p<0.01, *** p<0.001, versus placebo (Cochran-Mantel-Haenszel test) |
Biopsy scored independently by two pathologists; third available to adjudicate was not needed
Summary of Week 24 Changes in Liver Fat and Key Markers of Fibrosis and Liver Injury
| Measure (LS Mean Change From Baseline to Week 24) |
Placebo (N=40-42) |
28mg (N=35-38) |
50mg (N=34-36) |
|||||||||
| Hepatic Fat Fraction (MRI-PDFF) (%) |
-6 | -52 | *** | -64 | *** | |||||||
| ALT (%) |
-4 | -38 | *** | -47 | *** | |||||||
| AST (%) |
-2 | -39 | *** | -49 | *** | |||||||
| Pro-C3 (µg/L) |
+0.1 | -5.1 | *** | -5.2 | *** | |||||||
| ELF Score |
+0.1 | -0.6 | *** | -0.7 | *** | |||||||
| Liver Stiffness (kPa) (FibroScan) |
-0.7 | -2.6 | † | -4.3 | ** | |||||||
| ** | p<0.01, *** p<0.001, versus placebo (ANCOVA [Fat Fraction, Liver Stiffness]; MMRM [other endpoints]) |
| † | p<0.05, versus baseline (MMRM) |
Summary of Key Cardio-Metabolic Biomarkers
| Measure (LS Mean Change From Baseline) |
Placebo (N=42) |
28mg (N=35-37) |
50mg (N=35-36) |
|||||||||
| HbA1c (%, absolute) |
-0.0 | -0.3 | † | -0.4 | * | |||||||
| Triglycerides (%) |
+9 | -25 | *** | -29 | *** | |||||||
| HDL Cholesterol (%) |
-2 | +24 | *** | +30 | *** | |||||||
| Non-HDL Cholesterol (%) |
+8 | -13 | *** | -13 | *** | |||||||
| LDL Cholesterol (%) |
+9 | -8 | ** | -8 | ** | |||||||
| Body Weight (kg) |
-0.6 | -0.2 | -2.9 | †† | ||||||||
| * | p<0.05, ** p<0.01, *** p<0.001, versus placebo (MMRM) |
| † | p<0.05, †† p<0.01, versus baseline (MMRM) |
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EFX was reported to be generally well tolerated. Across both dose groups, the most frequent adverse events (AEs) were grade 1 or 2 gastrointestinal events (diarrhea, nausea, increased appetite, and frequent bowel movements), which were transient in nature. A total of five patients treated with EFX were discontinued due to AEs (two in the 28mg group and three in the 50mg group, one of which was reported to be unrelated to study drug), compared with none for placebo. A single drug-related serious adverse event (SAE) of esophagitis was experienced by a patient in the 50mg group who had a history of gastroesophageal reflux disease. Three other SAEs were reported as unrelated to study drug.
In July of 2021, Akero initiated the SYMMETRY study, a Phase 2b trial in biopsy-confirmed NASH patients with compensated cirrhosis (F4), Child-Pugh class A. Based on enrollment to date, Akero expects to report results from the ongoing Phase 2b SYMMETRY study in the second half of 2023. Results from a 12-week expansion cohort of the SYMMETRY study, evaluating treatment of EFX on top of GLP-1 therapy in patients with F1-F3 fibrosis, are expected in the first half of 2023.
Conference Call / Webcast Details
Akero will host a conference call and webcast with slide presentation at 8:00 a.m. ET today. The live webcast will be available on the Events & Presentations page of the Akero website, with the recording and presentation available immediately following the event.
About NASH
NASH (non-alcoholic steatohepatitis) is a serious form of NAFLD (non-alcoholic fatty liver disease) that is estimated to affect 17 million Americans. NASH is characterized by an excessive accumulation of fat in the liver that causes stress and injury to liver cells, leading to inflammation and fibrosis, which can progress to cirrhosis, liver failure, cancer and eventually death. There are no approved treatments for the condition and NASH is the fastest growing cause of liver transplants and liver cancer in the US and Europe.
About the HARMONY Study
The Phase 2b HARMONY study is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial in biopsy-confirmed adult NASH patients with fibrosis stage 2 or 3. The study enrolled a total of 128 patients, randomized to receive once-weekly subcutaneous dosing of 28mg or 50mg EFX, or placebo for 24-weeks. The primary efficacy endpoint for the study is the proportion of subjects who achieve at least a one-stage improvement in fibrosis without worsening of NASH at week 24. Secondary measures include NASH resolution, change from baseline in liver fat, liver enzymes, noninvasive markers of liver fibrosis, glycemic control, lipoproteins, and body weight at 24 weeks as well as safety and tolerability measures.
About Efruxifermin
Efruxifermin (EFX), formerly known as AKR-001, is Akero’s lead product candidate for NASH, currently being evaluated in the ongoing Phase 2b HARMONY study. EFX is designed to reduce liver fat and inflammation, reverse fibrosis, increase insulin sensitivity and improve lipoproteins. This holistic approach offers the potential to address the complex, multi-system disease state of NASH, including improvements in lipoprotein risk factors linked to cardiovascular disease – the leading cause of death in NASH patients. Engineered to mimic the biological activity profile of native FGF21, EFX is designed to offer convenient once-weekly dosing and has been generally well-tolerated in clinical trials to date.
About Akero Therapeutics
Akero Therapeutics is a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, including non-alcoholic steatohepatitis (NASH), a disease without any approved therapies. Akero’s lead product candidate, efruxifermin (EFX), is
3
a differentiated Fc-FGF21 fusion protein that has been engineered to mimic the balanced biological activity profile of native FGF21, an endogenous hormone that alleviates cellular stress and regulates metabolism throughout the body. EFX is designed to offer convenient once-weekly subcutaneous dosing. The consistency and magnitude of observed effects position EFX to be a potentially best-in-class medicine, if approved, for treatment of NASH. EFX is currently being evaluated in two Phase 2b clinical trials: the HARMONY study in patients with pre-cirrhotic NASH (F2-F3 fibrosis), and the SYMMETRY study in patients with cirrhotic NASH (F4 fibrosis, compensated). EFX is also being evaluated in an expansion cohort of the SYMMETRY study, comparing the safety and tolerability of EFX to placebo when added to an existing GLP-1 receptor agonist in patients with pre-cirrhotic NASH (F1-F3 fibrosis) and Type 2 diabetes. Akero is headquartered in South San Francisco. Visit us at akerotx.com and follow us on LinkedIn and Twitter for more information.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, statements regarding Akero’s business plans and objectives, including future plans or expectations for efruxifermin (EFX), the therapeutic effects of EFX, as well as the dosing, safety and tolerability of EFX; and upcoming milestones, including the results, and expected timing to report such results of Akero’s Phase 2b SYMMETRY study; and Akero’s preparations for commercialization of EFX, if approved. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: risks related to the impact of COVID-19 on Akero’s ongoing and future operations, including potential negative impacts on Akero’s employees, third-parties, manufacturers, supply chain and production as well as on global economies and financial markets; the success, cost, and timing of Akero’s product candidate development activities and planned clinical trials; Akero’s ability to execute on its strategy; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; regulatory developments in the United States and foreign countries; Akero’s ability to fund operations; as well as those risks and uncertainties set forth more fully under the caption “Risk Factors” in Akero’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as filed with the Securities and Exchange Commission (SEC) as well as discussions of potential risks, uncertainties and other important factors in Akero’s other filings and reports with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Akero undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Investor Contact:
Christina Tartaglia
212.362.1200
IR@akerotx.com
Media Contact:
Sarah O’Connell
732.456.0092
soconnell@vergescientific.com
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Phase 2b HARMONY Study Results Restoring Balance. Renewing Life. September 13, 2022 Exhibit 99.2
Safe Harbor ©2022 AKERO THERAPEUTICS. This presentation and the accompanying oral commentary may contain “forward-looking statements” of Akero Therapeutics, Inc. (“we,” “us,” “our,” “Akero” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and financial conditions, including but not limited to current beliefs, expectations and assumptions regarding: the future of our business; future plans and strategies, including our expectations around the therapeutic potential and clinical benefits of Efruxifermin (“EFX”), as well as the dosing, safety and tolerability of EFX; our development plans for EFX, including our belief in the potential of EFX as a foundational NASH therapy; our preclinical and clinical results, including our safety/tolerability, laboratory measures and biopsy data from our Phase 2b HARMONY study; the Phase 2b SYMMETRY study, including its expansion into Cohort D, expected timing to complete enrollment, report preliminary results, and other related milestones; the possibility that positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; risks related to the competitive landscape; expectations regarding the Company’s use of capital, expenses and other future financial results; and the potential impact of COVID-19 on strategy, our employees, supply chain, future operations and clinical trials. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “would,” “should” and “could,” and similar expressions or words, identify forward-looking statements. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our most recent annual report on Form 10-K and quarterly report on Form 10-Q, as filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in our other subsequent filings with the Securities and Exchange Commission. All information in this presentation is as of the date hereof, and we undertake no duty to update this information unless required by law. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.
Evaluating efruxifermin (EFX), An Fc-FGF21 Fusion Protein ©2022 AKERO THERAPEUTICS. Statistically Significant Effects after 24 Weeks Fibrosis Improvement NASH Resolution Fibrosis Improvement AND NASH Resolution
HARMONY Trial Design: Pre-Cirrhotic (F2-F3) NASH ©2022 AKERO THERAPEUTICS. MRI-PDFF Liver Biopsy Screening Randomization EFX 28mg Placebo 24 Weeks EFX 50mg Placebo EFX Continuation Dose TBD Long-Term Safety Follow-Up Phase 2b Key Inclusion Criteria F2-F3 NASH NAS ≥4 Liver Fat (MRI-PDFF) ≥8% Phase 2b Primary Endpoint ≥ 1-stage fibrosis improvement without worsening of NASH Key Secondary Efficacy Endpoints NASH Resolution & No Worsening of Fibrosis Fibrosis Markers Lipoproteins Glycemic Control Weight Change MRI-PDFF Liver Injury Markers Regulatory Requirements for Phase 3 Trials FDA accepts one of two endpoints for Phase 3 registrational trials: (1) Fibrosis improvement ≥1 stage & no worsening of NASH or (2) NASH resolution and no worsening of fibrosis1 EMA requires both endpoints to be met for marketing approval2 1 FDA Draft Guidance, Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment (2018) 2 EMA, Draft Reflection paper on regulatory requirements for the development of medicinal products for chronic non-infectious liver diseases (PBC, PSC, NASH) (2018)
Week 24 Patient Disposition & Analysis Sets ©2022 AKERO THERAPEUTICS. Randomized (N=128) Completed Week 24 (N=115) Biopsies Collected (N=113) Randomized Not Dosed EFX (N=2) Discontinued Prior to Week 24 (N=11) Dosed (N=126) Due to AEs EFX (N=5) Administrative EFX (N=5) Placebo (N=1) Biopsies Not Collected EFX (N=1); Placebo (N=1) Full Analysis Set – All subjects who were randomized Key Analysis Sets Safety Set – All subjects who received at least one dose of study drug Liver Biopsy Analysis Set – All subjects who have Baseline and Week 24 liver biopsy results Primary Endpoint Biomarker Analysis Set – All subjects who have baseline and on-study biomarker measurement at given timepoint 28mg (N=38) 50mg (N=34) Placebo (N=41)
Baseline Demographics ©2022 AKERO THERAPEUTICS. Parameter (Mean) Placebo (N=43) EFX 28mg (N=42) EFX 50mg (N=43) Age (Years) 55 57 52 Sex (% Female) 63 69 53 Weight (kg) 108 104 103 Type 2 Diabetes (%) 65 76 70 Fibrosis Stage (% F3)1 70 64 63 Enhanced Liver Fibrosis (ELF) Score 9.8 9.7 9.8 Pro-C32 (μg/L) 16.5 15.3 18.4 Liver Stiffness by VCTE3 (FibroScan) (kPa) 15 14 16 Hepatic Fat Fraction by MRI-PDFF4 (%) 17.1 18.5 17.5 NAFLD Activity Score (NAS) 5.4 5.1 5.6 Alanine Aminotransferase (ALT) (U/L) 62 50 63 Aspartate Aminotransferase (AST) (U/L) 57 42 52 HbA1c (%) 6.8 6.8 6.7 Triglycerides (mg/dL) 170 158 154 LDL-Cholesterol (mg/dL) 94 96 111 1 All patients either fibrosis stage 2 (F2) or stage 3 (F3); 2 Procollagen 3 N-Terminal Propeptide; 3 Vibration-controlled transient elastography; 4 Magnetic Resonance Imaging Proton Density Fat Fraction
Consensus Reading of Biopsies: Rigorous Approach to Histopathology Based on FDA Input to Minimize Variability ©2022 AKERO THERAPEUTICS. Different Scores Slides Prepared From Tissue Samples Score 1 Score 2 Same Score Consensus Score Adjudicated Score No Consensus Consensus Meeting Final Score QC’d and Reported to Study Portal Key Features of EFX Biopsy Analysis Plan Biopsies independently scored by two pathologists, with a third pathologist available to adjudicate in absence of consensus Pathologists underwent protocol-specific training to align on NASH-CRN scoring interpretation Pathologists blinded to subject, treatment, and sequence No paired biopsy reads (i.e., pre- and on-treatment biopsies not read side-by-side) Consensus Biopsy Analysis Flow Chart
Both EFX Doses Achieved Statistical Significance on Primary Endpoint (Fibrosis Improvement) ©2022 AKERO THERAPEUTICS. Source Data: Liver Biopsy Analysis Set *39%* Fibrosis Improvement ≥1 Stage & No Worsening of NASH1 at Week 24 1 Improvement in liver fibrosis greater than or equal to one stage and no worsening of NASH (defined as no increase in NAS for ballooning, inflammation, or steatosis) 39% 20% * p<0.05, versus placebo (Cochran–Mantel–Haenszel test [CMH]) EFX 28mg N=38 EFX 50mg N=34 Placebo N=41 *41%* 41%
*** Obeticholic Acid Phase 3 (F2-F3) 54% F3 72 Wks / ITT3 Consensus Readers Placebo 10% 14% 22% (N=311) (N=308) (N=312) 10mg 25mg 12% 4% Akero Efruxifermin Phase 2b (F2-F3) 66% F3 24 Wks / Completers1 Consensus Readers (N=41) (N=34) (N=38) 41% 39% 2% 28mg 50mg Placebo * * 20%† 21% EFX Fibrosis Improvement in Context: Pre-Cirrhotic NASH (≥1 Stage Improvement in Fibrosis and No Worsening of NASH) Placebo Novo Nordisk Semaglutide Phase 2b (F2-F3) 69% F3 72 Wks / ITT3 Consensus Readers (N=58) (N=56) (N=59) 33% 32% 43% 0.2mg 0.4mg 10% Madrigal Resmetirom Phase 2 (F1-F3) 20% F3 36 Wks / Completers4 Single Reader (N=34) (N=73) % % All Placebo 5% Inventiva Lanifibranor Phase 2b (F1-F3) % F3 Not Reported 24 Wks / Completers2 Single Reader (N=62) (N=69) (N=63) 32% % 29% 0.8g 1.2g Placebo * 17% 3% Madrigal Pegozafermin Phase 1b/2a (F2-F3) 65% F3 20 Wks / Completers5 Single Reader No Placebo Arm (N=19) 27mg 26% Effect Size Unknown By Reported Effect Size (Treatment Minus Placebo) ©2022 AKERO THERAPEUTICS. HARMONY Placebo Rate 1 Baseline and Week 24 biopsies available; 2 End-of-study biopsy available with no major protocol deviations; 3 Missing biopsies were imputed as non-responders; 4 Completed 36 weeks of treatment and had end-of-study biopsy; 5 End-of-study biopsy available. Lanifibranor - Francque et al. (2021) New Engl J Med 385, 1547–1558; Obeticholic acid - Intercept (2022) July 7 Press Release; Semaglutide - Newsome et al. (2020) New Engl J Med 384, 1113–1124; Resmetirom - Harrison, S et al. (2019) Lancet 394(10213):2012-24; Pegozafermin - 89Bio (2022) August 1 Corporate Presentation. All trademarks are the property of their respective owners. Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. * p<0.05, *** p<0.001, versus placebo † 39.47 - 19.51 = 19.96
Both EFX Doses Achieved Statistical Significance on Key Secondary Endpoint (NASH Resolution) ©2022 AKERO THERAPEUTICS. Source Data: Liver Biopsy Analysis Set 1 NAS score of 0 or 1 for lobular inflammation and a score of 0 for ballooning NASH Resolution1 & No Worsening of Fibrosis at Week 24 EFX 28mg N=38 EFX 50mg N=34 Placebo N=41 15% ** p<0.01, *** p<0.001, versus placebo (CMH) **47%** 47% ***76%*** 76%
Novo Nordisk Semaglutide Phase 2b (F2-F3) 69% F3 72 Wks / ITT2 Consensus Readers EFX NASH Resolution in Context: Pre-Cirrhotic NASH (NASH Resolution and No Worsening of Fibrosis) ©2022 AKERO THERAPEUTICS. 32% (N=19) 27mg * p<0.05, ** p<0.01, *** p<0.001, versus placebo Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. 1 Baseline and Week 24 biopsies available; 2 Missing biopsies were imputed as non-responders; 3 End-of-study biopsy available with no major protocol deviations; 4 Completed 36 weeks of treatment and had end-of-study biopsy; 5 End-of-study biopsy available. Semaglutide - Newsome et al. (2020) New Engl J Med 384, 1113–1124; Lanifibranor - Francque et al. (2021) New Engl J Med 385, 1547–1558; Resmetirom - Harrison, S et al. (2019) Lancet 394(10213):2012-24; Obeticholic acid - Intercept (2022) July 7 Press Release; Pegozafermin - 89Bio (2022) August 1 Corporate Presentation. All trademarks are the property of their respective owners. Obeticholic Acid Phase 3 (F2-F3) 54% F3 72 Wks / ITT2 Consensus Readers Akero Efruxifermin Phase 2b (F2-F3) 66% F3 24 Wks / Completers1 Consensus Readers Madrigal Resmetirom Phase 2 (F1-F3) 20% F3 36 Wks / Completers4 Single Reader Inventiva Lanifibranor Phase 2b (F1-F3) % F3 Not Reported 24 Wks / Completers3 Single Reader Madrigal Pegozafermin Phase 1b/2a (F2-F3) 65% F3 20 Wks / Completers5 Single Reader 76% 47% 15% (N=41) (N=34) (N=38) 28mg 50mg Placebo ** *** 32% 62%† 40% 49% 23% (N=62) (N=69) (N=63) 0.8g 1.2g Placebo * ** 17% 26% 25% 15% (N=34) (N=73) All Placebo 10% 17% 36% 59% (N=58) (N=56) (N=59) 0.2mg 0.4mg Placebo *** 19% 42% 10mg 25mg Placebo 4% 6% 7% (N=311) (N=308) (N=312) EFX Effect Sizes HARMONY Placebo Rate No Placebo Arm Effect Size Unknown By Reported Effect Size (Treatment Minus Placebo) † 76.47 - 14.63 = 61.84
Both EFX Doses Achieved Statistical Significance on Composite Endpoint (Fibrosis Improvement and NASH Resolution) ©2022 AKERO THERAPEUTICS. Source Data: Liver Biopsy Analysis Set 1 Improvement in liver fibrosis greater than or equal to one stage 2 NAS score of 0 or 1 for lobular inflammation and a score of 0 for ballooning Fibrosis Improvement1 AND NASH Resolution2 at Week 24 EFX 28mg N=38 EFX 50mg N=34 Placebo N=41 5% ** p<0.01, *** p<0.001, versus placebo (CMH) **29%** 29% ***41%*** 41% Placebo (N=41) EFX 28mg (N=38) EFX 50mg (N=34) 5% 16% 15% Patients Achieving Fibrosis Improvement ≥2 Stages and No Worsening of NASH at Week 24
EFX 50mg Endpoint Placebo (N=42) EFX 28mg (N=38) EFX 50mg (N=35) Relative Reduction in Liver Fat ≥50% 2% 63% *** 77% *** Normalization of Liver Fat Content ≤5% 2% 34% *** 51% *** Magnitude of Reduction and Normalization of Liver Fat Comparable to Phase 2a BALANCED Study1 ©2022 AKERO THERAPEUTICS. Proportion of Patients Achieving Fat Reduction Thresholds at Week 24 *** p<0.001, versus placebo (CMH) -6% LS Mean Relative Percent Change From Baseline in Liver Fat at Week 24 *** -52% *** *** p<0.001, versus placebo (ANCOVA) EFX 28 mg Placebo N=38 N=42 N=35 Source Data: MRI-PDFF Analysis Set (All subjects who have Baseline and Week 24 liver fat measurements) 1 The Phase 2a BALANCED study was a 12-week randomized clinical trial in patients with F1-F3 NASH -52% *** -52% *** -64%
Rapid and Sustained Statistically Significant Improvements in Markers of Liver Injury ©2022 AKERO THERAPEUTICS. ALT, LS Mean Percent Change from Baseline AST, LS Mean Percent Change from Baseline ** p<0.01, *** p<0.001, versus placebo (MMRM1) *** p<0.001, versus placebo (MMRM1) Source Data: Full Analysis Set *** *** *** *** *** *** *** *** *** *** -47%*** -49%*** -4% -2% 1 Mixed Model Repeated Measures
†-2.6† -2.6 ***-5.1*** Liver Stiffness by FibroScan (kPa) EFX 28 mg Placebo N=38 N=42 EFX 50mg N=36 -0.7 ** p<0.01, versus placebo (ANCOVA1) † p<0.01, versus baseline (ANCOVA) ELF Score EFX 28 mg Placebo N=37 N=42 EFX 50mg N=34 +0.1 *** p<0.001, versus placebo (MMRM1) -5.1 EFX 28mg Placebo N=37 N=40 Pro-C3 (µg/L) EFX 50mg N=35 +0.1 *** p<0.001, versus placebo (MMRM1) Statistically Significant Reductions in Non-Invasive Markers Reflect Histological Improvement in Fibrosis ©2022 AKERO THERAPEUTICS. LS Mean Change From Baseline to Week 24 Source Data: Biomarker Analysis Set (Pro-C3 and ELF); Full Analysis Set (Liver Stiffness) (non-missing values only, no imputation) 1 Analysis of Covariance ***-5.2*** -5.2 ***-0.6*** -0.6 ***-0.7*** -0.7 **-4.3** -4.3
Treatment-Emergent Adverse Events (TEAE) ©2022 AKERO THERAPEUTICS. TEAE Overview Placebo (N=43) EFX 28mg (N=40) EFX 50mg (N=43) TEAE Leading to Death 0 (0%) 0 (0%) 0 (0%) Drug-Related Serious Adverse Event (SAE) 0 (0%) 0 (0%) 1 (2%)a,b TEAE Leading to Discontinuation 0 (0%) 2 (5%)c 3 (7%)d Most Frequent (≥15%) Drug-Related TEAEs Placebo EFX 28mg EFX 50mg Diarrhea 6 (14%) 14 (35%) 14 (33%) Nausea 5 (12%) 10 (25%) 14 (33%) Increased Appetite 2 (5%) 7 (18%) 10 (23%) Frequent Bowel Movements 1 (2%) 8 (20%) 0 (0%) Injection Site Erythema 5 (12%) 6 (15%) 7 (16%) Injection Site Bruising 1 (2%) 6 (15%) 3 (7%) a (1) Esophagitis b There were three additional non-drug-related SAEs: (1) Edema; (2) Covid-19; (3) Pancreatitis c (1) Increased appetite & weight gain; (2) diarrhea d (1) Esophagitis & vomiting; (2) Nausea; (3) Lymphadenopathy (not drug-related) Source Data: Safety Set
+16% Placebo EFX 28mg EFX 50mg N=28 N=26 N=26 T2D Subset +9% Placebo EFX 28mg EFX 50mg N=37 N=41 N=35 All All EFX 50mg 0.0 Placebo EFX 28mg N=37 N=42 N=36 T2D Subset 0.0 Placebo EFX 28mg EFX 50mg N=28 N=27 N=27 Clinically Meaningful Improvements Observed in Glycemic Control and Insulin Sensitivity, Particularly in Patients with T2D ©2022 AKERO THERAPEUTICS. LS Mean Change From Baseline to Week 242 Source Data: Biomarker Analysis Set * p<0.05, versus placebo (MMRM); † p<0.05, versus baseline (MMRM) ** p<0.01, *** p<0.001, versus placebo (MMRM) HbA1c(%)1 C-Peptide3 1 Absolute change from baseline, %; 2 Patients remained on diabetic medications; 3 Relative percent change from baseline *-0.5%* -0.5% **-17%** -17% *-0.4* -0.4 †-0.3† -0.3 **-22%** -22% **-16%** -16% ***-23%*** -23% *-0.5%* -0.5%
HDL Cholesterol *** p<0.001, versus placebo (MMRM) -2% Placebo EFX 28mg EFX 50mg N=35 N=42 N=35 LDL Cholesterol ** p<0.01, versus placebo (MMRM) +9% Placebo EFX 28mg EFX 50mg N=35 N=42 N=35 Significant Improvements Observed in Lipoprotein Profile ©2022 AKERO THERAPEUTICS. LS Mean Change From Baseline to Week 24 (%) Source Data: Full Analysis Set, non-missing values only, no imputation Non-HDL Cholesterol *** p<0.001, versus placebo (MMRM) +9% Placebo EFX 28mg EFX 50mg Triglycerides *** p<0.001, versus placebo (MMRM) +8% Placebo EFX 28mg EFX 50mg N=35 N=42 N=35 N=35 N=42 N=35 ***-25%*** -25% ***-29%*** -29% **-8%** -8% ***-13%*** -13% ***+24%*** +24% ***+30%*** +30% **-8%** -8% ***-13%*** -13%
Weight Loss Observed for 50mg EFX Dose Group ©2022 AKERO THERAPEUTICS. Source Data: Full Analysis Set, non-missing values only, no imputation -0.2 Body Weight, LS Mean Change at Week 24 (kg) Placebo EFX 28mg EFX 50mg -0.6 N=37 N=42 N=36 -2.6%†† †† p<0.01, versus baseline (MMRM) ††-2.9†† -2.9
©2022 AKERO THERAPEUTICS. addressing all core aspects of NASH pathogenesis in a single treatment Fibrosis Improvement NASH Resolution Fibrosis Improvement AND NASH Resolution Healthy Metabolism Restoration Liver Health Improvement After 24 Weeks EFX: A Potentially Foundational NASH Therapy
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