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 whose antiviral activity is strictly dependent on the sequence-independent activity of phosphorothioate oligonucleotides as biocompatible polymers that interact with exposed hydrophobic surfaces in proteins. This exposed hydrophobic feature is rare in mammals but is common in the life cycles of many different infectious agents. The high affinity “annealing” of NAPs along these hydrophobic surfaces is not sensitive to the development of drug resistance (like small molecules and siRNA) and efficiently blocks structural reorganizations essential for viral replication.

Unlike all other classes of oligonucleotide-based medicines like antisense oligonucleotides, synthetic interfering RNA (siRNA), or micro RNA (miRNA), 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 with a nucleotide sequence that retains antiviral activity but which eliminates immunoreactivity or off-target effects common with other oligonucleotide-based drugs. Additionally, naturally occurring nucleotide modifications identifying themselves as “host” molecules do not interfere with the activity of NAPs. With all of these optimizations in place, the current lead NAP candidate, REP 2139, has shown a remarkable safety and tolerability in pre-clinical and clinical studies unmatched by any other drug in its class.

Our Focus

As REP 2139 targets both hepatitis B (HBV) and hepatitis delta (HDV), 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 four 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 the 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:
    • HBsAg and HBeAg seroconversion.
    • Clearance of HBV and HDV from the blood.
    • Early inhibition of HBV viral replication and HBsAg reduction in the liver.
  • 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 90% of patients that are maintained after therapy is removed, consistent with the inactivation/clearance of cccDNA in the liver observed in pre-clinical studies.

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.