UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): May 13, 2021
Akero Therapeutics, Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 001-38944 | 81-5266573 | ||
|
(State or other jurisdiction of incorporation) |
(Commission File Number) |
(I.R.S. Employer Identification No.) |
|
601 Gateway Boulevard, Suite 350 South San Francisco, CA |
94080 | |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code (650) 487-6488
Not Applicable
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading symbol(s) | Name of each exchange on which registered |
| Common Stock, par value $0.0001 per share | AKRO | The Nasdaq Global Select Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
| Item 2.02 | Results of Operations and Financial Condition |
On May 13, 2021, Akero Therapeutics, Inc. announced its financial results for the quarter ended March 31, 2020. A copy of the press release is being furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Current Report on Form 8-K and Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 7.01 | Regulation FD Disclosure |
The Company from time to time presents and/or distributes to the investment community at various industry and other conferences slide presentations to provide updates and summaries of its business. A copy of its current corporate slide presentation is being furnished herewith as Exhibit 99.2 to this Current Report on Form 8-K. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.
The information under this Item 7.01, including Exhibit 99.2 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
| (d) | Exhibits |
| Exhibit No. |
Description | |
| 99.1 | Press release issued by Akero Therapeutics, Inc. on May 13, 2021, furnished herewith. | |
| 99.2 | Corporate slide presentation of Akero Therapeutics, Inc., furnished herewith | |
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: May 13, 2021 | AKERO THERAPEUTICS, INC. | |
| By: | /s/ Andrew Cheng | |
| Name: | Andrew Cheng, M.D., Ph.D. | |
| Title: | President and Chief Executive Officer | |
Exhibit 99.1
Akero Therapeutics Reports First Quarter 2021 Financial Results and Provides Business Update
SOUTH SAN FRANCISCO, May 13, 2021 /GLOBE NEWSWIRE/ -- Akero Therapeutics, Inc. (Nasdaq: AKRO), a cardio-metabolic biotechnology company developing transformational treatments for non-alcoholic steatohepatitis (NASH), today reported first quarter financial results for the period ending March 31, 2021.
"We continued to build on the strong foundation provided by last year’s reports from the Phase 2a BALANCED main study, with new data showing signs of reversing fibrosis in biopsy-confirmed F4 NASH patients with compensated cirrhosis after only 16 weeks of treatment,” said Andrew Cheng, M.D., Ph.D., president and chief executive officer of Akero. "Our histology results, as well as non-invasive markers of fibrosis, indicate that efruxifermin (EFX) acts both directly and indirectly to rapidly reverse fibrosis. Consistent data across three placebo-controlled clinical trials increase our confidence that EFX will be efficacious as a treatment for all stages of NASH. This confidence is reflected in our initiation of two parallel, separate Phase 2b clinical trials in F2-F3 and F4 NASH this year, for which we expect to begin reporting data in the third quarter of 2022."
First Quarter Business Highlights & Company Updates
| · | During the first quarter, Akero reported positive, topline, preliminary results for its 16-week evaluation of EFX in the treatment of adult NASH patients with compensated cirrhosis (F4), Child-Pugh Class A (BALANCED study, Cohort C). |
| o | Among 12 EFX-treated patients who volunteered to have end-of-treatment biopsies, 7 of 12 (58%) achieved either a one-stage improvement in fibrosis without worsening of NASH or NASH resolution, compared with 0 of 5 (0%) for the placebo group. |
| o | 4 of 12 (33%) EFX-treated patients achieved a one-stage improvement of fibrosis without worsening of NASH, compared to 0% for placebo, indicating rapid reversal of fibrosis among cirrhotic NASH patients after only 16 weeks of treatment. |
| o | 3 of 12 (25%) EFX-treated patients achieved NASH resolution compared to 0% for placebo. |
| o | Improvements in histology were supported by improvements in noninvasive serum-based and imaging markers of fibrosis. |
| o | EFX-treated patients also experienced improvements in ALT, serum lipids and glycemic control, with a trend toward weight loss, consistent with the results previously observed for patients with F1-F3 fibrosis. |
| · | During the first quarter, Akero initiated its HARMONY study, a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, clinical trial in biopsy-confirmed NASH patients with fibrosis stage 2 or 3, with the first patient randomized in March. |
Multiple Milestones Anticipated for 2021 and 2022
| · | Akero plans to report additional data from the BALANCED main study at the upcoming meeting of the European Association for the Study of the Liver (EASL) on June 23-26, 2021. |
| o | EASL Abstract No. 1314: “The role of reduction in liver fat content (MRI-PDFF) and ALT in predicting treatment response in NASH: A secondary analysis of the randomized, controlled BALANCED trial,” presented by Rohit Loomba, M.D. |
| o | EASL Abstract No. 1762: “Correlation between changes in liver fat content and improvements in serum markers of liver injury, fibrosis, metabolism, and in histologic parameters following treatment with efruxifermin,” presented by Stephen Harrison, M.D. |
| · | Akero plans to present new data at the upcoming meeting of the American Diabetes Association on June 25-29, 2021, for which two abstracts have been accepted for presentation. |
| · | Akero expects to initiate its planned SYMMETRY study, a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, clinical trial in biopsy-confirmed NASH patients with compensated cirrhosis (F4), Child-Pugh Class A, in the second half of 2021. |
| · | Akero expects to report topline, preliminary results for the HARMONY study in the third quarter of 2022, based on the primary histology endpoint after 24 weeks of treatment. |
| · | Akero expects to complete manufacturing of its planned Phase 3 combination drug/device product in 2022, with release for clinical trials in the first half of 2023. |
First Quarter 2021 Financial Results
| · | Akero's cash, cash equivalents and short-term marketable securities for the period ended March 31, 2021 were $250.0 million. |
| · | Akero believes that its cash, cash equivalents and marketable securities will be sufficient to fund its current operating plan into the third quarter of 2023. |
| · | Research and development expenses for the three-month period ended March 31, 2021 were $10.6 million, compared to $8.8 million for the comparable period in 2020. These increases are attributable to higher costs related to Akero's EFX program, including third-party contract manufacturing, contract research organization costs associated with the BALANCED and HARMONY studies and internal personnel costs. |
| · | General and administrative expenses for the three-month period ended March 31, 2021 were $4.5 million, compared to $3.6 million for the comparable period in 2020. These increases are attributable to higher expenses for personnel, including non-cash stock-based compensation, and professional services and other costs associated with operating as a public company. |
| · | Total operating expenses were $15.1 million for the three-month period ended March 31, 2021, compared to $12.4 million for the comparable period in 2020. |
About NASH
Non-alcoholic steatohepatitis (NASH) is a serious, life-threatening disease that has rapidly emerged as a leading cause of liver failure in the world and is the leading indication for liver transplant among women. An estimated 17.3 million Americans had NASH in 2016, a number that is expected to increase to 27.0 million by 2030. NASH is a severe form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatocyte injury, liver inflammation, and fibrosis that can progress to scarring (cirrhosis), liver failure, cancer and death. There are currently no approved therapies for the disease.
About Cohort C
Cohort C was an expansion cohort of the Phase 2a BALANCED study, which evaluated EFX in patients with NASH who have compensated cirrhosis (F4), Child-Pugh Class A. Thirty cirrhotic NASH subjects with a biopsy-confirmed fibrosis score of F4 were randomized 2:1 to receive either 50mg of EFX or placebo for 16 weeks. The primary objective of the expansion cohort was to assess safety and tolerability of EFX in NASH patients at the greatest risk of progressing to end-stage liver disease, including liver failure and liver cancer. The trial design included various non-invasive measures of liver health, including markers of liver fibrosis such as Enhanced Liver Fibrosis (ELF) score and Pro-C3, as well as liver ultrasound imaging. The trial design also permitted patients to volunteer for end-of-treatment biopsies.
About the HARMONY Study
The Phase 2b HARMONY study is a multicenter, randomized, double-blind, placebo-controlled, clinical trial in biopsy-confirmed NASH patients with fibrosis stage 2 or 3. Patients are being randomized to receive once-weekly subcutaneous dosing of 28 or 50mg EFX or placebo. The primary endpoint for the trial is regression of fibrosis at 24 weeks. Patients will continue to receive EFX or placebo during long-term follow-up to provide additional safety data.
About Efruxifermin
Efruxifermin (EFX) is an 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. Previous clinical trials show that EFX has the potential to reverse fibrosis, resolve NASH, reduce liver fat, improve glycemic control, improve lipoprotein profile, and reduce body weight. EFX is designed to offer convenient once-weekly subcutaneous dosing.
About Akero Therapeutics
Akero Therapeutics is a clinical-stage cardio-metabolic company developing transformational treatments for non-alcoholic steatohepatitis (NASH), a disease without any approved therapies. Akero's lead product candidate, EFX, an engineered Fc-FGF21 fusion protein, is currently being evaluated in Phase 2 clinical trials as a potential treatment for NASH. Akero is headquartered in South San Francisco. Visit us at www.akerotx.com 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 EFX, upcoming milestones, and therapeutic effects of EFX, as well as the dosing, safety and tolerability of EFX; Akero’s Phase 2b HARMONY study and Phase 2b SYMMETRY study including expected timing to complete enrollment and report preliminary results; the availability of a new combination drug product-device to support Phase 3 clinical trials; expectations regarding Akero’s use of capital, expenses and other future financial results; and the potential impact of COVID-19 on strategy, future operations, enrollment and clinical trials. 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, 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.
Akero Therapeutics, Inc.
Condensed Consolidated Balance Sheets
(Unaudited)
(In thousands)
| March 31, 2021 | December 31, 2020 | |||||||
| Assets | ||||||||
| Cash, cash equivalents and short-term marketable securities | $ | 249,984 | $ | 268,387 | ||||
| Other current assets | 5,792 | 2,958 | ||||||
| Non-current assets | 1,847 | 1,994 | ||||||
| Total assets | $ | 257,623 | $ | 273,339 | ||||
| Liabilities and Stockholders’ Equity | ||||||||
| Current liabilities | $ | 10,136 | $ | 13,111 | ||||
| Non-current liabilities | 1,467 | 1,516 | ||||||
| Stockholders’ equity | 246,020 | 258,712 | ||||||
| Total liabilities and stockholders’ equity | $ | 257,623 | $ | 273,339 | ||||
Akero Therapeutics, Inc.
Condensed Consolidated Statements of Operations and Comprehensive Loss
(Unaudited)
(In thousands, except share and per share amounts)
| Three Months Ended March 31, | ||||||||
| 2021 | 2020 | |||||||
| Operating expenses: | ||||||||
| Research and development | $ | 10,602 | $ | 8,791 | ||||
| General and administrative | 4,526 | $ | 3,588 | |||||
| Total operating expenses | 15,128 | 12,379 | ||||||
| Loss from operations | (15,128 | ) | (12,379 | ) | ||||
| Other income | 38 | 493 | ||||||
| Net loss | $ | (15,090 | ) | $ | (11,886 | ) | ||
| Comprehensive loss | $ | (15,089 | ) | $ | (11,835 | ) | ||
| Net loss per common share, basic and diluted | $ | (0.43 | ) | $ | (0.42 | ) | ||
| Weighted-average number of shares used in computing net loss per common share, basic and diluted | 34,744,275 | 28,499,475 | ||||||
Investor Contact:
Christina Tartaglia
212.362.1200
IR@akerotx.com
Media Contact:
650.487.6488
media@akerotx.com
Exhibit 99.2
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A Global Disease, A Pioneering Treatment Corporate Presentation May 2021 |
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CORPORATE HIGHLIGHTS - CONFIDENTIAL - |
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EXTENSIVE DEVELOPMENT AND COMMERCIALIZATION EXPERIENCE INVOLVED IN 20+ MEDICINE APPROVALS Andrew Cheng, MD, PhD | President & CEO 19 years at Gilead Chief Medical Officer & HIV Division Head Major role in 11 NDA/MAA approvals Jonathan Young, PhD, JD | Founder, EVP & COO Over 15 years in biotechnology product development, law and regulatory policy General Counsel and VP Policy, Braeburn Partner and General Counsel, FoxKiser Over 30 years at Pfizer & Glaxo CSO of Pfizer’s cardiovascular and metabolic disease unit Head of Groton & UK Discovery Research, Pfizer Major role in discovery and early clinical evaluation of two medicines: Selzentry (HIV) and Steglatro (Diabetes) Kitty Yale | EVP & Chief Development Officer Over 25 years at Gilead, Roche, Pfizer VP, Gilead Worldwide Clinical Operations Major role in 8 global approvals NDA, MAA, JNDA and CFDA 18 years in life sciences investment banking at Goldman Sachs, Citigroup and Deutsche Bank Most recently, Head of US Life Sciences Investment Banking at Deutsche Bank Advised on more than $70bn in M&A and $25bn in - CONFIDENTIAL - 3 |
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NASH: A SERIOUS AND DEBILITATING MULTI-SYSTEM DISEASE NASH epidemic fueled by rise in obesity and diabetes No treatments currently available An estimated 17 million Americans have NASH, with expectation that population will grow >50% by 2030 The number of NASH patients with advanced-stage fibrosis and cirrhosis is predicted to grow to 8 million in the US by 2030, an increase of approximately 140% from 2015 NASH is a leading cause of liver transplantation in the US and Europe The leading cause of death for NASH patients is cardiovascular disease - CONFIDENTIAL - |
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CIRRHOTIC NASH PATIENTS HAVE POOR PROGNOSIS Liver-related mortality rate increases substantially from F3 to F4 fibrosis ~60% 5-year mortality for F4 NASH patients absent transplant Fibrosis Stage Survival Free of Liver Transplantation 0 0 Cumulative Survival (%) Rate (per 1,000 PYF) 15 10 5 0 F0F1F2F3F4 Fibrosis Stage Dulai, PS et al. (2017) Hepatology 65:1557-65 Follow-up (years) - CONFIDENTIAL - 5 |
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EFX ENGINEERING POTENTIALLY OPTIMAL FOR NASH EFFICACY, WITH CONVENIENT ONCE-WEEKLY DOSING Key attributes Akero proprietary Fc-FGF21, Point mutations Increases half-life from < 2 hours to 3-4 days High affinity for β-Klotho Better translation to human pharmacology Balanced potency at FGFR1c, 2c, 3c Inactive at FGFR4 Stanislaus, S et al. (2017) Endocrinology 158(5): 1314-27; Lee, S et al. (2018) Nature 553: 501-505; Kharitonenkov, A et al. (2007) - CONFIDENTIAL - 6 |
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EFX ACTS ON TWO MAJOR SOURCES OF LIVER FAT WITH POTENTIAL FOR OPTIMAL REDUCTION Sources of Fat Flowing into and Through Liver for NASH Patients Acting on both hepatic and peripheral sources of liver fat is key to optimizing liver fat reduction Dietary Fat (10-20%) Liver: De Novo Lipogenesis (30-40%) FGFR2c, 3c Adipose Tissue: Lipolysis (40-50%) FGFR1c Source of Liver Fat FGF Receptor EFX Activity Lipolysis FGFR1c ✓ De Novo Lipogenesis FGFR2c FGFR3c ✓ Lambert, JE et al. (2014) Gastroenterology 146(3): 726-35 - CONFIDENTIAL - |
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EFX DIRECT AND INDIRECT ANTI-FIBROTIC EFFECTS Kupffer Cell Activation Hepatocyte Stress & Death Direct EffectIndirect Effect Fibrosis - CONFIDENTIAL - *Cited literature available on company website 8 |
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PHASE 2A TRIAL (BALANCED) DESIGN (F1-F3 NASH) 28mg EFX (n=20) Placebo (n=20) Screening Biopsy-Confirmed NASH Randomization Safety Follow-Up Responder Paired Biopsies Primary Endpoint Absolute Liver Fat 70mg EFX (n=20) 50mg EFX (n=20) Key Secondary Endpoints Relative Liver Fat Response Rate ALT Key Exploratory Efficacy Endpoints 2-Point NAS Improvement Fibrosis Improvement NASH Resolution Serum Pro-C3 Screening Week 6Week 12 Post-Treatment Liver Biopsy MRI-PDFF Subjects achieving ≥30% relative reduction of hepatic fat at week 12 eligible for post-treatment biopsy; biopsy scoring based on NASH CRN - CONFIDENTIAL - |
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PHASE 2A EXPANSION COHORT C TRIAL DESIGN (F4 NASH) Screening Randomization Primary Endpoint Safety & tolerability 16 Weeks Placebo (n=10) EFX 50 mg (n=20) Liver Biopsy FibroScan Fibrosis Biomarkers (ELF, Pro-C3) * * Protocol amended to include voluntary end-of-treatment biopsies - CONFIDENTIAL - |
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BASELINE DEMOGRAPHICS: MAIN STUDY & COHORT C a Full Analysis Set, F1-F3 (all subjects randomized into the BALANCED main study); b Full Analysis Set, F4 (all subjects randomized into BALANCED Cohort C [except where - CONFIDENTIAL - 11 |
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HIGH RATES OF FIBROSIS IMPROVEMENT AFTER 16 WEEKS ACROSS ALL DOSE GROUPS (F1-F3 NASH) 48% 0% 19 Biopsy Reading biopsies were centrally read by a single NASH-CRN pathologist Baseline biopsies were not re-read with end-of-treatment biopsies All biopsies were read blinded to both treatment assignment and patient Fibrosis Improvement ≥1 Stage and No Worsening of NASH1,2 62% 60% 50%46% 40% 36% 30% 20% 6 8 5 10% 0% Placebo N=2 All EFX N=40 28mg N=13 50mg N=13 70mg N=14 - CONFIDENTIAL - Source Data: Liver Biopsy Evaluable Analysis Set, F1-F3 (all BALANCED main study responders who had baseline and end-of-treatment liver biopsy results)12 |
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FIBROSIS IMPROVEMENT IN F2-F3 PATIENTS: HALF OF PATIENTS IMPROVED 2 STAGES All EFX Patients (n=40) Baseline F2-F3 EFX Patients (n=22) 68% 23% 9% Change in liver fibrosis Improved No Change 68% 2-Stage Improvement (n=11, 50%) 1-Stage Improvement (n=4, 18%) 35% Worsened 23% 10%9% - CONFIDENTIAL - |
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HIGH RATE OF FIBROSIS IMPROVEMENT AFTER ONLY 16 WEEKS AMONG CIRRHOTIC PATIENTS (F4 NASH) 33% 0% 4 Biopsy Reading All baseline and end-of-treatment biopsies were read by a single NASH-CRN pathologist All biopsies were read blinded to both treatment assignment and patient Baseline biopsies were read independently of end-of-treatment biopsies, in random fashion and not paired Baseline Biopsy Timing Mean time from historical biopsy to patient screening = 6 months Fibrosis Improvement ≥1 Stage Without Worsening of NASH1,2 40% 30% 20% 10% 0% Placebo n=5 EFX 50mg n=12 - CONFIDENTIAL - Source Data: Liver Biopsy Analysis Set, F4; Topline preliminary data14 |
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RAPID IMPROVEMENTS IN FIBROSIS BIOMARKERS CONSISTENT WITH HISTOLOGICAL IMPROVEMENTS (F1-F3 NASH) Pro-C3, LS Mean Change from Baseline Pro-C3, LS Mean (ug/L) 10% 0% -10% BLW1W4W8W12 -20% -30% -40% -50% Dose Group Baseline Δ Week 12 Placebo 16.1 -1.5 28mg 19.2 -6.1*** 50mg 16.2 -5.9*** 70mg 17.2 -6.7*** *** *** *** *** *** *** *** *** Enhanced Liver Fibrosis (ELF) Score, LS Mean Dose Group Baseline Δ Week 12 Placebo 9.4 0.0 28mg 9.5 -0.7*** 50mg 9.5 -0.8*** 70mg 9.6 -0.4* *** p<0.001, versus placebo (MMRM) * p<0.05, *** p<0.001 versus placebo (ANCOVA) - CONFIDENTIAL - |
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IMPROVEMENTS IN FIBROSIS BIOMARKERS IN CIRRHOTIC NASH PATIENTS SUPPORT HISTOLOGY RESULTS (F4 NASH) LS Mean Change From Baseline to Week 16 Liver Stiffness1 (kPa) 0 -1 -1.9 -2 -3 -4 -5 -5.7†† -6 PlaceboEFX 50mg n=10n=20 Pro-C3 (µg/L) 0 -2 -3.4 -4 -6 -8 -9.0* -10 PlaceboEFX 50mg n=10n=20 ELF Score 0.3 0.2 +0.3 0.1 0.0 -0.1 -0.2 -0.3 -0.4** -0.4 PlaceboEFX 50mg n=10n=20 1 Measured by FibroScan †† p<0.01, versus baseline (ANCOVA) p<0.05, versus placebo (ANCOVA) ** p<0.01, versus placebo (ANCOVA) - CONFIDENTIAL - Liver Stiffness Analysis Set, F4 (all Cohort C subjects with baseline and interpretable on-study measure of Liver Stiffness); Topline preliminary data16 |
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INTERPRETING THE RAPID REVERSAL OF FIBROSIS OBSERVED IN NASH PATIENTS TREATED WITH EFX ↓ Inflammation↓ Liver fat ↓ Collagen Synthesis ↓ Hepatocyte Stress Directly anti-fibrotic Indirectly anti-fibrotic EFX Fibrosis reversal in cirrhotic patients (F4), two-stage improvement of fibrosis in F2/F3 patients, and corroborating non-invasive markers of fibrosis improvement likely reflects direct anti-fibrotic activity Fibrosis reversal is especially advantageous for cirrhotic patients who face high risk of mortality and severe morbidity Addressing underlying NASH disease drivers may indirectly contribute to fibrosis reversal for F1-F3 patients with adequate time for the liver to regenerate Redress of the underlying NASH disease drivers is necessary to sustain fibrosis reversal in F1-F4 Supports broader metabolic improvements - CONFIDENTIAL - |
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SUBSTANTIAL REDUCTIONS IN LIVER FAT AT WEEK 12 ACROSS ALL DOSE GROUPS (F1-F3 NASH) MRI-PDFF Images for Patient Treated with 50mg EFX Baseline 22.2% Liver Fat Week 12 2.0% Liver Fat (↓90%) Proton Density Fat Fraction (PDFF) Analyzed with LiverMultiScan LS Mean Reduction in Liver Fat Placebo 28mg 50mg 70mg 0 -3 -0% -6 -9 -63% -12 -71% -12.3*** -72% -15 -13.4*** -14.1*** Absolute Reduction (%) - CONFIDENTIAL - |
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SUBSTANTIAL REDUCTIONS IN MARKERS OF LIVER INJURY AFTER 16 WEEKS OF TREATMENT (F1-F3 NASH) ALT, LS Mean Change from Baseline AST, LS Mean Change from Baseline 40% BL W1W4W8W12W16W20 40% BL W1W4W8W12W16W20 20% 20% 0%0% -20% -40% -60% *** *** *** *** *** *** *** *** *** ** ** *** -20% -40% -60% *** *** *** *** *** *** *** *** *** *** *** *** Placebo28mg50mg70mg ** p<0.01, *** p<0.001, versus placebo (MMRM) Placebo28 mg50 mg70 mg *** p<0.001, versus placebo (MMRM) Similar dose-related improvements observed for GGT & ALP - CONFIDENTIAL - |
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HIGH RESPONSE RATES ON NASH RESOLUTION AFTER 16 WEEKS ACROSS ALL DOSE GROUPS (F1-F3 NASH) NASH Resolution1,2 and No Worsening of Fibrosis 70% 60% 54% 50%46%43% 40% 30% 676 10% 0% Placebo N=2 All EFX N=40 28mg N=13 50mg N=13 70mg N=14 2 Secondary and exploratory histological endpoints were not powered for statistical significance - CONFIDENTIAL - Source Data: Liver Biopsy Evaluable Analysis Set, F1-F320 |
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NASH RESOLUTION ALSO OBSERVED IN CIRRHOTIC PATIENTS (F4 NASH) NASH Resolution1,2 30% 20% 10% 0% Placebo n=5 EFX 50mg n=12 25% 0% ≥2 Point NAS Reduction 1 NAS score of 0 or 1 for lobular inflammation and a score of 0 for ballooning 2 Study not powered to assess statistical significance of histological endpoints - CONFIDENTIAL - |
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DRUG-RELATED TREATMENT-EMERGENT ADVERSE EVENTS (TEAE) (F1-F3 NASH) *Across EFX dose groups a Muscular Weakness & Myalgia; b Nausea, Vomiting & Dysgeusia; Panic Attack and Anxiety-Linked Tremor; c Dysphagia (Not Drug Related); Acute Pancreatitis (also an SAE); Vomiting; Fatigue & Nausea; d Related to pre-dosing liver biopsy - CONFIDENTIAL - |
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TOLERABILITY OVERVIEW (F4 NASH) Most Frequent (>15%) Drug-Related AEs Placebo (N=10) EFX 50mg (N=17) Diarrhea 1 (10%) 7 (41%) Nausea 1 (10%) 5 (29%) Injection site reaction 0 5 (29%) Injection site erythema 0 4 (24%) Headache 0 3 (18%) TEAE/SAE Disposition Placebo EFX 50mg Study Discontinuations 1a 1b Serious Adverse Events (SAE) 1c 0 Deaths 0 0 Key Observations Encouraging tolerability given population with more advanced disease All injection site AEs Grade 1 No reports of tremor a Withdrawal of consent b abdominal distension, constipation, diarrhea, pruritus c pulmonary embolism - CONFIDENTIAL - at baseline who received at least one dose of study drug); Topline preliminary data23 |
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WEIGHT LOSS OBSERVED FOR ALL DOSE GROUPS (F1-F3 NASH) Mean Change in Body Weight (kg) BL W1 W4 W8 W12 W16 0 -1 -2 -3 -4 Placebo 28mg 50mg 70mg Mean Change in Body Weight at Week 16 (kg) +0.1 0 -1 -0.3 -2 -2.3 -3 -3.7 -4 Placebo28mg 50mg 70mg - CONFIDENTIAL - |
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IMPROVED LIPOPROTEIN PROFILE (F1-F3 NASH) LS Mean Change From Baseline to Week 16 (%) Triglycerides 10% 0% -10% +6% -20% -30% -40% -39% *** -48% -46% -50% *** Placebo 28mg50mg *** 70mg HDL Cholesterol 50% 40% *** *** +39% +41% 30% *** +34% 20% 10% +4% 0% Placebo 28mg50mg70mg Non-HDL Cholesterol 0% -5% -1% -10% -15% -15% * -20% -22% *** -17% ** -25% Placebo 28mg50mg70mg LDL Cholesterol 0% 0% -5% -2% -6% -10% -15% -16% * -20% Placebo 28mg50mg70mg *** p<0.001, versus placebo (ANCOVA) *** p<0.001, versus placebo (ANCOVA) * p<0.05, ** p<0.01, *** p<0.001, versus placebo (ANCOVA) * p<0.05, versus placebo (ANCOVA) - CONFIDENTIAL - |
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CLINICALLY MEANINGFUL IMPROVEMENTS IN GLYCEMIC CONTROL AFTER 16 WEEKS (F1-F3 NASH) LS Mean Change From Baseline to Week 16 (%) Type 2 DM Patients (N=41) 0.1 0.0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 +0.0 +0.1 -0.6 Placebo 28mg50mg -0.9 ** 70mg HbA1c1 Type 2 DM Patients (N=41) 20% 10% 0% -10% -5% -20% -27% -30% Placebo 28mg -28% * 50mg -33% * 70mg C-Peptide2 All Patients (N=80) 0.1 0.0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 +0.1 -0.1 -0.4 -0.5 * ** Placebo 28mg 50mg70mg All Patients (N=80) 20% +21% 10% 0% -10% -20% -24% -22% -29% * * -30% * Placebo 28mg50mg70mg * p<0.05, ** p<0.01, versus placebo (ANCOVA) 2 Relative percent change from baseline * p<0.05, versus placebo (ANCOVA) - CONFIDENTIAL - |
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NASH DEVELOPMENT LANDSCAPE: FIBROSIS IMPROVEMENT (F1-F3) Proportion of Subjects with ≥1 Stage Improvement in Fibrosis and No Worsening of NAS1 Efruxifermin 16 Wks (Ph2a) Weekly Injection Lanifibranor 24 Wks (Ph2b) Daily Oral Aldafermin 24 Wks (Ph2a) Daily Injection Resmetirom 36 Wks (Ph2a) Daily Oral Seladelpar 52 Wks (Ph2a) Daily Oral Semaglutide 72 Wks (Ph2b) Daily Injection Ocaliva 78 Wks (Ph3) Daily Oral 24 Wks Increasing dosing duration 78 Wks 48% 34% 36% 62% 48% 0% 24% 18% 32% 20% 24% 12% 23% PboAll EFX 50mg Pbo0.8g1.2g Pbo1mg PboAll Pbo20mg50mg Pbo0.2mg 0.4mg Pbo10mg25mg (N=2) (N=40) (N=13) (N=62) (N=63) (N=69) (N=22) (N=50) (N=34) (N=79) (N=25) (N=42) (N=46) (N=80) (N=78) (N=82) (N=311)(N=312)(N=308) Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. No head-to-head clinical trials have been conducted. Inventiva (2020) June 16 Corporate Presentation; NGM Bio (2020) June 3 Corporate Presentation; Harrison, S et al. (2019) Lancet 394(10213):2012-24; CymaBay (2020) March 12 Press Release; Novo Nordisk (2020) June 19 R&D Investor Presentation; Younossi Z et al. (2019) Lancet 394(10215):2184-96. All trademarks are the property of their respective owners. - CONFIDENTIAL - |
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COHORT C RESULTS IN CONTEXT: FIBROSIS IMPROVEMENT* (F4) Fc-FGF21 GAL-3 Efruxifermin 16 Wks (Ph2a) SC Injection ASK-1 Selonsertib ACC Firsocostat FXR Cilofexor Belapectin 52 Wks (Ph2b) Oral LOXL2 Simtuzumab 48 Wks Increasing dosing duration 96 Wks 13 13 14 14 15 14 13 7 8 8 5 Pbo6mg18mg (n=172)(n=351)(n=354) Pbo20mg (n=21)(n=20) Pbo30mg (n=21)(n=19) 2 Pbo2mpk8mpk (n=45)(n=46)(n=41) Pbo200mg700mg (n=75)(n=75)(n=79) 0 PboEFX 50mg (n=5) (n=12) - CONFIDENTIAL - Harrison, SH et al. (2020) J Hepatol 73(1):26-39; Loomba, R et al. (2020) Hepatol 73(2):625-43; Chalasani, N et al. (2020), Gastro 158:1334–45; Harrison, SH et al. (2018) Gastro 155:1140-53 Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. No head-to-head clinical trials have been conducted. 28 |
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NASH DEVELOPMENT LANDSCAPE: NASH RESOLUTION (F1-F3) Proportion of Subjects with Resolution of NASH and No Worsening of Fibrosis1 Efruxifermin 16 Wks (Ph2a) Weekly Injection Lanifibranor 24 Wks (Ph2b) Daily Oral Aldafermin 24 Wks (Ph2a) Daily Injection Resmetirom 36 Wks (Ph2a) Daily Oral Seladelpar 52 Wks (Ph2a) Daily Oral Semaglutide 72 Wks (Ph2b) Daily Injection 24 Wks 40% 49% 23% 50% 48% Ocaliva 78 Wks (Ph3) Daily Oral Increasing dosing duration 47% 78 Wks 24% 25% 26% 19% 23% 9% 8% 8% 11% 12% Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. No head-to-head clinical trials have been conducted. Inventiva (2020) June 16 Corporate Presentation; NGM Bio (2020) June 3 Corporate Presentation; Harrison, S et al. (2019) Lancet 394(10213):2012-24; CymaBay (2020) March 12 Press Release; Novo Nordisk (2020) June 19 R&D Investor Presentation; Younossi Z et al. (2019) Lancet 394(10215):2184-96. All trademarks are the property of their respective owners. - CONFIDENTIAL - |
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NEXT STEPS FOR EFX: PARALLEL 2B TRIALS IN F2/F3 & F4 Phase 2aPhase 2b F1-F3 F4 F2/F3 F4 - CONFIDENTIAL - |
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PHASE 2B (F2/F3) TRIAL DESIGN (HARMONY) Key Inclusion Criteria F2-3 NASH NAS ≥4 Liver fat ≥8% Phase 2b Primary Endpoint Fibrosis Improvement Key Secondary Efficacy Endpoints NASH Resolution Fibrosis Markers Lipoproteins Glycemic Control• Liver Injury Weight Change MRI-PDFF Markers EFX* EFX 28mg EFX 50mg Screening Randomization Phase 2b Long-Term Safety Follow-Up Placebo Placebo Liver Biopsy MRI-PDFF Meeting Phase 3 Initiation* - CONFIDENTIAL - |
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STRONG FINANCIAL POSITION COMPLETED UPSIZED FOLLOW-ON OFFERING July 10 , 2020 ~$106M Raised in aggregate gross proceeds ~$216M Raised in aggregate gross proceeds ~$250M Current cash, cash equivalents and marketable securities are expected to be sufficient to fund current operating plan into the third quarter of 2023 - CONFIDENTIAL - |
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CONSISTENT RECORD OF MILESTONE DELIVERY Amgen License $45M Series A June $45.5M Series B December ~$106M Upsized IPO June BALANCED Initiation July BALANCED F1-F3 MRI-PDFF Read-out March BALANCED F1-F3 Liver Biopsy Read-out June ~$216M Upsized Offering July HARMONY F2/F3 Ph2b Initiation February BALANCED F4 Liver Biopsy Read-out March SYMMETRY F4 Ph2b Initiation 2H (Expected) HARMONY F2/F3 Ph2b Read-out 3Q (Expected) 2018 2019 2020 2021 - CONFIDENTIAL - |
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Backup Slides |
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Randomized (80) Randomized Not Dosed EFX (1) Dosed (79) Week 12 MRI-PDFF (68) Non-Responders Placebo (18) MRI-PDFF Responders (50) (≥ 30% Relative Reduction) Biopsies Not Collected Due to COVID-19 EFX (8) - CONFIDENTIAL - |
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Randomized/Dosed (n=30) Confirmed F4 (n=27 ) Not Confirmed F4 by central reader (3) Discontinued (2) Withdrawn Consent Placebo (1) Due to AEs EFX(1) Did not consent to end-of-treatment biopsy (8) - CONFIDENTIAL - |
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MAGNITUDE OF LIVER FAT REDUCTION (F1-F3 NASH) 1 A single placebo responder lost 25 pounds over 16 weeks (11% weight reduction) - CONFIDENTIAL - Source Data: MRI-PDFF Evaluable Analysis Set (all BALANCED main study subjects who had baseline and Week 12 MRI-PDFF37 |
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EXPANDING EFX TO CIRRHOTIC PATIENT POPULATION (F4) Developing Treatments for Cirrhotic (F4) NASH FDA draft guidance specific for F4 patients Projected ~3.5M US F4 patients in 2030 FDA: The goals of treatment for compensated NASH cirrhosis are to halt or slow progression of fibrosis, prevent clinical decompensation, reduce the need for liver transplantation, and improve survival - CONFIDENTIAL - |
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CIRRHOSIS REGRESSION IS ASSOCIATED WITH IMPROVED CLINICAL OUTCOMES Pooled treatment groups from STELLAR 4 and simtuzumab cirrhosis study Hazard Ratio: 0.16 p=0.0104 7.2 69/957 1.1 2/176 69/834 0.7 2/300 Liver-related events (%) 6 5 4 3 1 0 Hazard Ratio: 0.08 p=0.0004 8.3 No fibrosis regression Fibrosis regression NASH CRN fibrosis stageIshak fibrosis stage Cirrhosis regression observed in 16% of patients (treatment and placebo groups) over 48 weeks Sanyal A, et al. AASLD TLMdX2020. #90 Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. No head-to-head clinical trials have been conducted. - CONFIDENTIAL - |
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REDUCTIONS IN MARKERS OF LIVER INJURY (F4 NASH) LS Mean Change from Baseline to Week 16 ALT (U/L) 0 -2 -1.3 -4 -6 -8 -10.3** -10 PlaceboEFX 50mg n=10n=20 AST (U/L) 0 -2 -4.5 -4 -6 -8 -9.6††† -10 PlaceboEFX 50mg n=10n=20 ** p<0.01, versus placebo (ANCOVA) ††† p<0.001, versus baseline (ANCOVA) - CONFIDENTIAL - |
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IMPROVED LIPOPROTEIN PROFILE (F4 NASH) LS Mean Change From Baseline to Week 16 (%) LDL Cholesterol 20% 15% +16% 10% 5% 0% -5% -8% Triglycerides 10% 5% 0% -5% -10% -15% -20% -25% -30% +1% -29% ** HDL Cholesterol 35% 30% ** +33% 25% 20% 15% 10% 5% +3% Non-HDL Cholesterol 15% 10% 5% 0% -5% -10% -15% +12% -14% *** ** p<0.01, versus placebo (ANCOVA)** p<0.01, versus placebo (ANCOVA)*** p<0.001, versus placebo (ANCOVA) - CONFIDENTIAL - |
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IMPROVED GLYCEMIC CONTROL; TREND TOWARD WEIGHT LOSS (F4 NASH) LS Mean Change From Baseline to Week 16 (%) HbA1c1 0.3 0.2 +0.1 0.1 0.0 -0.1 -0.2 -0.3 -0.4 -0.4 ** -0.5 PlaceboEFX 50mg n=10n=20 Adiponectin2 100% *** +95% 75% 50% 25% +4% 0% PlaceboEFX 50mg n=10n=20 C-Peptide2 0% -5% -7% -10% -15% -20% -20% †† -25% PlaceboEFX 50mg n=10n=20 Body Weight2 1.0% 0.5% +0.9% 0.0% -0.5% -1.0% -1.5% -2.0% -2.2% -2.5% PlaceboEFX 50mg n=10n=20 1 Absolute change from baseline, % ** p<0.01, versus placebo (ANCOVA) 2 Relative percent change from baseline *** p<0.001, versus placebo (ANCOVA) 2 Relative percent change from baseline †† p<0.01, versus baseline (ANCOVA) 2 Relative percent change from baseline - CONFIDENTIAL - |
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FGF21 DEVELOPMENT LANDSCAPE Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. No head-to-head clinical trials have been conducted. NR, not reported Sanyal et al (2019) Lancet; 89Bio October 5 Corporate Presentation - CONFIDENTIAL - |
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Change from Baseline to End of Study Change from Baseline to End of Study Adiponectin 100% 80% 60% 40% 20% 0% -20% pbo2850 QW QW EFX (Akero) pbo 1020 QD QW BMS pbo 182736 QW QW Q2W 89Bio* Triglycerides 10% 0% -10% -20% -30% -40% -50% pbo2850 QW QW EFX (Akero) pbo 1020 QD QW BMS pbo 182736 QW QW Q2W 89Bio* Sanyal et al (2019) Lancet; 89Bio October 5 Corporate Presentation - CONFIDENTIAL - |
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FGF21 DEVELOPMENT LANDSCAPE: SUMMARY - CONFIDENTIAL - |
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A Global Disease, A Pioneering Treatment NASDAQ: AKRO |