AKRO Akero Therapeutics Inc

Akero’s global Phase 3 SYNCHRONY clinical trial program consists of three ongoing global, randomized, placebo-controlled trials to support marketing applications for treatment of compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH) and pre-cirrhotic MASH.

SYNCHRONY Outcomes is a two-cohort trial recruiting patients with compensated cirrhosis (F4) due to MASH to receive weekly injections of EFX 50mg or placebo. The primary histology endpoint (Cohort 1 only) is fibrosis regression without worsening of MASH after 96 weeks of treatment based on histology. Patients will continue treatment as randomized to be evaluated for the primary outcomes endpoint measured as time to first occurrence of any of the pre-defined, adjudicated events across both Cohort 1 and 2.

SYNCHRONY Histology is enrolling patients with pre-cirrhotic MASH, fibrosis stage 2 or 3 (F2-F3) to receive weekly injections of EFX 28mg, EFX 50mg, or placebo. The primary endpoint, to support an application for accelerated approval, is the proportion of patients experiencing ≥ 1-stage fibrosis improvement AND resolution of NASH/MASH after 52 weeks of treatment. After 52 weeks, patients will continue treatment as randomized in SYNCHRONY Histology to be followed for long-term clinical outcomes.

SYNCHRONY Real-World is enrolling patients with MASH or MASLD to receive weekly injections of EFX 50mg or placebo. The primary endpoint of safety and tolerability will be assessed after 52 weeks of treatment.

In all EFX Phase 3 studies, patients are using the LyoJect 3S dual chamber syringe, a pre-filled device designed for self-administration and intended for commercial use in the event EFX is approved for marketing.

In June 2024, Akero presented analyses of data from the Phase 2b HARMONY study evaluating the efficacy and safety of EFX in patients with pre-cirrhotic MASH, fibrosis stage 2 or 3 (F2-F3), in two presentations at the European Association for the Study of the Liver (EASL) Congress 2024.

A late-breaking oral presentation featured 96-week data demonstrating that response rates for ≥1-stage improvement in fibrosis with no worsening of MASH were 75% (p<0.001) for 50 mg EFX and 46% (p=0.07) for 28 mg EFX, vs 24% for placebo.

The study also met additional histology endpoints at week 96. Notably 36% (p<0.01) and 31% (p<0.01) of patients treated with 50 mg EFX and 28 mg EFX, respectively, had a 2-stage improvement in fibrosis without worsening of MASH, more than 10-fold the placebo rate of 3%.

Among patients with more advanced F3 fibrosis at baseline, 68% and 40% of patients treated with 50mg EFX and 28mg EFX, respectively, experienced at least a one-stage improvement in fibrosis without worsening of MASH, compared with 14% for placebo.

A comparison of week 96 with week 24 results showed that treatment response among EFX-treated patients deepened and expanded with longer treatment, particularly among the 50 mg EFX group, with >80% of all EFX-treated patients with improved fibrosis at week 24 exhibiting sustained improvement through week 96.

Treatment with EFX was generally well tolerated, with no drug-induced liver injury or decompensation events, and no deaths. The most frequent adverse events were transient Grade 1 or 2 gastrointestinal events, with an overall event profile between weeks 24 and 96 that was similar to that observed during the first 24 weeks for EFX and comparable to placebo at week 96.

A poster presentation featured results from a post-hoc analysis of biomarkers associated with collagen synthesis and degradation after 24 weeks treatment with EFX in the HARMONY study. Key observations included:

A shift from deposition to degradation of fibrillar (pathological) collagen.

Beneficial changes in the extracellular matrix (ECM) with regeneration of structural collagens (basement membrane), and regression of interstitial collagens (fibrils).

Correlation of remodeling of ECM biomarkers with reductions in markers of liver injury and regression of fibrosis by histopathology.

In April 2024, Akero expanded its leadership team with the appointment of Scott Gangloff as Chief Technical Officer, bringing a track record of successful CMC (chemistry, manufacturing and control) development supporting global approvals and launch of several biologics. Scott’s extensive knowledge and experience of establishing and optimizing supply chains will support a robust manufacturing capability for EFX at launch, if approved for marketing.

The ongoing Phase 2b SYMMETRY study, evaluating the efficacy and safety of EFX in patients with compensated cirrhosis due to MASH (F4), remains on track to report week 96 results in the first quarter of 2025.

Akero’s cash, cash equivalents and short and long-term marketable securities as of June 30, 2024, were $848.3 million.

Akero believes that its current cash, cash equivalents, and short- and long-term marketable securities will be sufficient to fund its Phase 3 SYNCHRONY Histology and Real-World studies through readout of their respective primary endpoints and Akero’s current operating plan into the second half of 2027.

Research and development expenses for the three-month period ended June 30, 2024 were $55.3 million, compared to $28.0 million for the comparable period in 2023. These increases were attributable to higher expenses associated with completion of the Phase 2b HARMONY study, the ongoing SYMMETRY study, the ongoing Phase 3 SYNCHRONY Histology and SYNCHRONY Real-World studies, initiation of the Phase 3 SYNCHRONY Outcomes study, and manufacture of clinical supplies for Phase 3 and potential marketing applications, as well as higher expenses for personnel.

General and administrative expenses for the three-month period ended June 30, 2024 were $10.4 million, compared to $7.6 million for the comparable period in 2023. These increases are attributable to higher expenses for personnel, professional services and other costs associated with operating as a public company.

Total operating expenses were $65.7 million for the three-month period ended June 30, 2024, compared to $35.6 million for the comparable period in 2023.

Assets

Cash, cash equivalents and short-term marketable securities

Other current assets

Non-current assets

Total assets

Liabilities and Stockholders’ Equity

Current liabilities

Non-current liabilities

Stockholders’ equity

Total liabilities and stockholders’ equity

Operating expenses:

Research and development

General and administrative

Total operating expenses

Loss from operations

Interest expense

Interest and other income, net

Net loss

Comprehensive loss

Net loss per common share, basic and diluted

Weighted-average number of shares used in computing net loss per common share, basic and diluted