What is hepatitis C?

Hepatitis C (HCV) is a blood borne viral infection of the liver that causes both acute and chronic infections. The HCV virus has six different variants (genotypes), which differ among each other by 30-35% of their gene sequences. Infection with HCV genotypes 1-3 is most common worldwide, with regional prevalence variations, while genotypes 4-6 have important prevalence in global subregions.

Globally, chronic HCV infections are a major cause of serious liver damage, including fibrosis (scarring), cirrhosis, liver failure, and liver cancer. The majority of the millions of chronic HCV patients have yet to be diagnosed.

According to the World Health Organization (WHO), over 71 million people worldwide suffer from chronic hepatitis C – including 2.4 million in the U.S. In fact, new HCV infections tripled in the U.S. from 2011 to 2017. Despite efforts by the WHO and others to eradicate HCV, recent analyses indicate that the disease will continue to be a considerable global burden beyond 2050 [1]. Public health programs to identify HCV infected patients are intensifying in the U.S. and worldwide. These efforts will add to the pool of identified patients needing treatment for many years to come.

[1]Razavi H, Sanchez Y, Pangerl A, Cornberg M. Global timing of hepatitis C virus elimination: estimating the year countries will achieve the World Health Organization elimination targets. J Hepatol 2019;70 e748.


A shorter HCV treatment regimen with high rates of sustained efficacy.

While existing therapies have demonstrated that HCV is curable for large segments of infected patients, there remains a substantial need for improved therapeutics. This is particularly true for patients with cirrhosis, HIV co-infection and patients with other liver diseases for whom protease inhibitor-based regimens may pose increased risk of severe adverse events as well as potential drug interaction issues with other medicines.

In 2018, the FDA initiated a warning about the potential for severe toxicities with HCV treatment regimens that include protease inhibitors. It caused current therapies, particularly regimens that include protease inhibitors, to require pre-treatment baseline assessments of the stage of underlying liver damage. These assessments helped identify patients who may be at risk for severe treatment-related toxicities due to underlying cirrhosis.

Once treatment ensues, prescribers must closely monitor and assess patients for signs and symptoms of worsening liver function. This necessity for extensive pre- and on-treatment assessments has the potential to be a substantial burden for each patient, prescriber and payor.

For HCV therapies to be suitable for simple prescribing worldwide, the therapy must be pan-genotypic, meaning active against all six HCV genotypes. We believe that a safe, pan-genotypic and highly effective nucleotide-based combination therapy with a potent HCV NS5A inhibitor (but no protease inhibitor) would constitute a significant therapeutic advance. The majority of patients, including those with compensated cirrhosis, would receive the therapy for 8 weeks or less, while in some populations, treatment duration may be a short as 6 weeks.

Such an ideal therapy would have equally high cure rates in patients with or without cirrhosis. In patients with decompensated cirrhosis, a highly compromised population with limited survival expectations, this regimen would also eliminate the need for adjunctive ribavirin treatment. Ribavirin is a toxic drug with many side effects, given with currently approved HCV therapies in patients with cirrhosis.

A doctor writing a prescription.

~399,000 people die from chronic HCV infections each year, primarily as a result of cirrhosis-related liver failure and liver cancer (hepatocellular carcinoma).


AT-787: Best-in-class profile potential for treating HCV.

Our proprietary pan-genotypic product candidate, AT-787, was created to address the efficacy challenges of existing HCV therapies. This direct-acting antiviral is a single fixed-dose tablet that combines AT-527, a purine nucleotide prodrug NS5B polymerase inhibitor, and AT-777, a novel NS5A inhibitor that has potent pan-genotypic activity against HCV replication in vitro.

Targeting an underserved market.

AT-787 is a pan-genotypic fixed-dose drug combination, specifically developed to offer a short duration protease-sparing regimen for HCV-infected patients with or without cirrhosis. In patients with decompensated cirrhosis, a life-threatening stage of liver disease, AT-787 offers the potential to treat patients without the co-administration of ribavirin.

Protease-sparing regimens (such as Harvoni® or Epclusa®) are the only treatments approved for HCV-infected patients with decompensated cirrhosis. However, treatment with these therapies extends for a minimum of 12 weeks and requires adjunctive use of ribavirin to boost curative effectiveness. Ribavirin is carcinogenic in animal studies and has significant side effects including anemia, gastrointestinal, and nervous system side effects, making its use problematic in patients with cirrhosis, who are already quite ill with cirrhosis-associated low blood counts, gastrointestinal symptoms, and frequent nervous system complaints.

Our highly differentiated NS5B inhibitor: AT-527.

The unique chemical structure of AT-527 results in improved pharmacologic and antiviral properties in comparison with sofosbuvir – an NS5B inhibitor currently approved and marketed as a component of several commercialized HCV combination products (Harvoni™, Epclusa™, and Vosevi™).

In a Phase 1b/2a clinical trial, AT-527 was administered as a single agent for 7 days was well-tolerated and demonstrated potent pan-genotypic efficacy in HCV-infected patients with or without cirrhosis. Viral kinetic modeling from clinical data suggests that AT-527 clears infected patient hepatocytes three times faster than sofosbuvir. This clinical data was consistent with laboratory studies in which AT-527 was found to be ten times more potent than sofosbuvir.

An effective combination.

A subsequent Phase 2 clinical trial evaluated the efficacy, safety and tolerability of AT-527 administered in combination with daclatasvir, the only stand-alone commercially approved NS5A inhibitor, for durations of 8 to 12 weeks. Interim results demonstrated that this combination was well-tolerated, with high rates of sustained virologic response (SVR).

The available clinical data support further evaluation of AT-787 for HCV treatment durations of 8 weeks or less, enabled by rapid viral clearance to very low or non-detectable levels in the first 2 weeks of treatment.

In 2020, we anticipate initiating further clinical development of AT-787.

A pile of blank, white pills, representative of oral treatment.