292 million people have chronic hepatitis B. We’re developing the cure..

Science Overview

Replicor is a clinical-stage biopharmaceutical company developing NUCLEIC ACID POLYMERS (NAPs). These compounds are oligonucleotides designed as biocompatible polymers whose antiviral activity is driven by the sequence independent annealing of NAPs with exposed hydrophobic surfaces in proteins. These exposed hydrophobic surfaces are rare in mammals but are commonly found in the life cycles of many different infectious agents and the hepatitis delta virus (HDV). The high affinity annealing of NAPs along these hydrophobic surfaces is not sensitive to the development of drug resistance (like small molecules, siRNA and antisense oligonucleotides) and efficiently blocks structural reorganizations essential for viral replication.

Unlike all other classes of oligonucleotide-based medicines, NAPs do not rely on the sequence of nucleotide building blocks for their activity. As a result of this unique property, NAPs can be engineered that retain their antiviral activity, but have no immunoreactivity or off target effects common with other oligonucleotide-based drugs. Naturally occurring nucleotide modifications identifying NAPs as “host” molecules are also critical to their excellent safety and tolerability and also do not interfere with their activity. With all of these optimizations in place, the current lead NAP candidate, REP 2139, has shown a remarkable safety and tolerability profile in pre-clinical and clinical studies unmatched by any other oligonucleotide drug. For the latest published overviews of NAP technology, please see here and here .

Our Focus

In HBV infection, REP 2139’s unique and highly selective interaction with the host chaperone critical for the assembly of HBV subviral particles (see here) drives its profound effect in clearing HBsAg in both hepatitis B (HBV) and hepatitis D (HDV) infections (please see here and here). With this unique dual functionality, Replicor has focused its efforts on developing a cure for HBV and HDV with REP 2139-based combination therapies. Pre-clinical and clinical studies (including five proof of concept phase II clinical trials) have demonstrated that REP 2139-based combination therapy is well tolerated and has two unique and potent antiviral effects: 1) preventing replenishment of HBsAg into the blood and 2) efficiently blocking HDV replication at multiple steps in its lifecycle. These primary antiviral effects are accompanied by:

  • Rapid reduction of the HBsAg protein in 90% of patients, with the majority experiencing > 5 log reductions or loss of HBsAg from the blood. This is a unique and industry leading effect unmatched by any other antiviral agent currently approved or in development.
  • Accompanying potent antiviral responses including:
    • Early inhibition of HBV viral replication and HBsAg reduction in the liver.
    • HBsAg and HBeAg seroconversion.
    • Clearance of HBV and HDV from the blood.
  • Dramatic potentiation of immunotherapy when used during HBsAg reduction including:
    • Dramatic increases in anti-HBsAg antibodies
    • Strong and therapeutic transaminase flares in most patients – indirect evidence of clearance of infected cells from the liver.
    • Restoration of immunological control of HBV and HDV infection in up to 78% of patients with 39% of these patients with functional cure of HBV accompanied by inactivation / clearance of infection in the liver.

Continuing updates of mechanistic and clinical data will be presented at all major liver disease and hepatitis B and D related-conferences. Replicor’s latest clinical data can be viewed here and here.