Akero Therapeutics Stock

Akero Therapeutics, Inc. operates as a clinical-stage company.

The company is dedicated to developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, including non-alcoholic steatohepatitis, or NASH, a disease without any approved therapies.

The company’s lead product candidate, efruxifermin, or EFX, is an analog of fibroblast growth factor 21, or FGF21, which is an endogenously expressed hormone that protects against cellular stress and regulates metabolism of lipids, carbohydrates and proteins throughout the body.

The company reported Week 24 results of the Phase 2b HARMONY study in patients with pre-cirrhotic NASH (F2-F3) fibrosis in September 2022. Both the 50mg and 28mg EFX dose groups achieved statistical significance on primary and secondary histology endpoints after 24 weeks. The company also observed 41% and 29% response rates for the 50mg and 28mg dose groups, respectively, on a combined endpoint of at least a one-stage improvement in fibrosis and NASH resolution, which were approximately six to eight times the 5% placebo rate.

EFX is being evaluated in two Phase 2b clinical trials in patients with biopsy-confirmed NASH: a long-term follow-up period for the HARMONY study in patients with pre-cirrhotic NASH (F2-F3 fibrosis), for which the company reported results after 24 weeks of treatment, and the SYMMETRY study in patients with cirrhotic NASH (F4 fibrosis, compensated). The SYMMETRY study includes an expansion cohort, known as Cohort D, evaluating the safety and tolerability of EFX compared to placebo when added to an existing GLP-1 receptor agonist in patients with pre-cirrhotic NASH (F1-F3 fibrosis) and Type 2 diabetes. The company expects to report the results of Cohort D in the second quarter of 2023 and the results of the SYMMETRY study in the fourth quarter of 2023.

In June 2018, the company acquired exclusive global development and commercialization rights to EFX from Amgen Inc., or Amgen, which leveraged its deep protein engineering expertise to design and develop EFX. As of March 6, 2023, the company’s patent portfolio relating to EFX and other peptides included 169 issued patents and 15 pending patents worldwide, with expected patent exclusivity up to 2034 in the United States, including potential patent term extension. Since EFX is a biologic, marketing approval would also provide twelve years of market exclusivity from the approval date of a Biologics License Application, or BLA, in the United States.

The company’s pipeline is anchored by EFX, a potential best-in-class FGF21 analog for the treatment of NASH, if approved. The company has one EFX program focused on patients with pre-cirrhotic NASH (F2-F3), which is supported by the HARMONY study, an ongoing Phase 2b clinical trial. The company has a second EFX program focused on patients with cirrhotic NASH (F4, compensated), which is supported by the SYMMETRY study, an ongoing Phase 2b clinical trial. These two programs align with the U.S Food and Drug Administration (FDA) guidance published in 2018 and 2019, which recommends different regulatory approval pathways for patients with pre-cirrhotic and cirrhotic NASH. NASH is diagnosed through liver biopsy and its severity is measured using scoring systems that assess the extent and severity of steatosis, lobular inflammation, hepatocellular ballooning and fibrosis. Some patients may be diagnosed with NASH after presenting with symptoms, such as general fatigue and nondescript abdominal discomfort.

The company has two active EFX programs supported by two ongoing, parallel Phase 2b clinical trials: the HARMONY study in pre-cirrhotic patients with F2-F3 fibrosis and the SYMMETRY study in patients with cirrhosis due to NASH (F4, compensated). Each of the company’s two Phase 2b clinical trials is precedented by Phase 2a data in patients with biopsy-confirmed NASH.

The company’s lead program focuses on development of EFX for the treatment of pre-cirrhotic NASH (F2-F3 fibrosis). The ongoing Phase 2b HARMONY study in patients with F2-F3 fibrosis is precedented by data from the previously completed Phase 2a BALANCED study in patients with F1-F3 fibrosis. The company’s belief in EFX’s potential to be an effective treatment for patients with cirrhosis due to NASH is based on the combined results of the BALANCED and HARMONY studies in patients with pre-cirrhotic NASH, as well as the results of an expansion cohort of the BALANCED study evaluating patients with cirrhosis due to NASH.

In June 2018, the company entered into an exclusive license agreement with Amgen Inc., or Amgen, pursuant to which it has been granted an exclusive, royalty-bearing license to certain intellectual property rights owned or controlled by Amgen, to commercially develop, manufacture, use, distribute and sell therapeutic products, or Products. In particular, the company has been granted licenses under patents filed in both the United States and foreign jurisdictions that are owned or controlled by Amgen, including an exclusive license under certain patents claiming polypeptides consisted of an FGF21 portion with certain point mutations, a linker, and an Fc domain. The company’s exclusively licensed patents include, but are not limited to, the composition of EFX and methods of using the same. In connection with the license, Amgen also licensed and transferred to the company certain know-how related to the manufacture of EFX, as well as certain quantities of EFX drug substance manufactured to Good Manufacturing Practices, or GMP, for clinical use, master cell bank, not-for-human use EFX drug product suitable for nonclinical studies and critical reagents.

Strategy

The key components of the company’s strategy are to advance EFX through clinical development in both pre-cirrhotic (F2/F3) and cirrhotic (F4, compensated) NASH; scale its capabilities to support development and commercialization of EFX; leverage its knowledge of FGF21 biology to bring EFX to additional patients with metabolic diseases; and enhance its position as a leading metabolic disease company by developing, acquiring or in-licensing additional investigational product candidates.

Intellectual Property

As of March 6, 2023, the company had licensed from Amgen Inc. approximately 184 patents and pending patent applications worldwide, including 169 issued patents and 15 pending patent applications.

As of March 6, 2023, the company’s patent portfolio relating to EFX included twelve issued U.S. patents, one pending U.S. patent application, and issued and pending foreign counterpart patents in Europe, Asia, Canada, Australia, and Mexico. Seven issued U.S. patents include claims directed to the EFX product, the FGF21 polypeptide component of the EFX product, nucleic acids encoding the product and related polypeptides, polypeptide multimers, related compositions, and methods of using EFX to, e.g., treat diabetes, lower blood glucose in patients suffering from a metabolic disorder, improve glucose tolerance, lower body weight, or reduce triglyceride levels in patients. These issued U.S. patents are expected to expire in 2029. The pending U.S. patent application and related foreign counterparts are directed to a method of treating a patient with non-alcoholic steatohepatitis (NASH); if issued, the resulting U.S. patent is expected to expire in 2029. The company anticipates that a composition of matter patent will be eligible for patent term extension to 2034 in the U.S. The portfolio further includes five issued U.S. patents that are directed to related polypeptides and methods of use. An international patent application is pending relating to EFX formulations.

Manufacturing and Supply

The company has an agreement with Boehringer Ingelheim Biopharmaceuticals GmbH, or Boehringer Ingelheim, to manufacture DS for clinical development and plan to enter into a future agreement for commercial supply at an appropriate time. Whereas the company’s Phase 2a BALANCED study was supplied by DS acquired by Amgen, its ongoing Phase 2b HARMONY and SYMMETRY studies are being supplied by DS manufactured by Boehringer Ingelheim. Analysis of the Boehringer Ingelheim GMP DS confirmed it met the same release specification as previously used for Amgen GMP DS and was comparable to Amgen GMP DS across a number of protein characterization studies.

The company has an agreement with Vetter Pharma International GmbH, or Vetter, to manufacture EFX drug product, or DP, for clinical development and plan to enter into a future agreement for commercial supply at an appropriate time. The GMP DP being used for the company’s ongoing HARMONY and SYMMETRY studies is similar to that for the BALANCED study, which was stored as a frozen liquid until immediately before administration to trial subjects. Analysis of the Vetter GMP DP confirmed that it met the same release specification as previously used for the DP manufactured from Amgen GMP DS.

The company plans to use a newly developed lyophilized DP formulation for Phase 3 clinical trials and as the initial commercial presentation, if EFX is approved. This drug-device combination product, employing Vetter’s Lyo-Ject 3S dual-chamber syringe, was selected for convenient subcutaneous patient self-administration. Manufacturing of the product-device combination has been scaled up at Vetter and GMP lots have been released for use in Phase 3 clinical trials.

Sales and Marketing

The company expects to begin making plans for commercialization in parallel with its ongoing HARMONY and SYMMETRY studies. The company has also contracted with a third-party manufacturer, Vetter, to support clinical development and the potential commercialization of EFX with commercial-scale manufacturing. The company intends to develop the commercial infrastructure required for bringing EFX to patients in the United States, if approved, in parallel with an anticipated Phase 3 clinical trial. The company also plans to evaluate options for delivering EFX, if approved, to patients in other key markets, such as Europe, Japan and China, which may include strategic collaborations.

Research and Development

The company’s research and development expenses were $85.3 million for the year ended December 31, 2022.

Government Regulation

The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of biologics, medical devices and combinations of biologics and devices, or combination products, such as those the company is developing.

Prior to beginning the first clinical trial with a product candidate, the company must submit an investigational new drug application (IND) to the FDA.

In the United States, the company’s current and future operations are subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare and Medicaid Services (CMS), other divisions of the U.S. Department of Health and Human Services (HHS) (such as the Office of Inspector General, Office for Civil Rights and the Health Resources and Service Administration), the U.S. Department of Justice (DOJ), and individual U.S. Attorney offices within the DOJ, and state and local governments.

In addition to the foregoing, local, state and federal laws regarding such matters as safe working conditions, manufacturing practices, environmental protection, fire hazard control and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect the company’s business.

History

The company was founded in 2017. It was incorporated under the laws of the state of Delaware in 2017. The company was formerly known as Pippin Pharmaceuticals, Inc. and changed its name to Akero Therapeutics, Inc. in 2018.