A nucleotide prodrug for an ultra-rare Mitochondrial DNA Depletion syndrome


Targeting the Liver Manifestations of Deoxyguanosine Kinase Deficiency

CERC-913 is a nucleotide prodrug being developed for an ultra-rare mitochondrial DNA depletion syndrome (MDS) known as Deoxyguanosine Kinase (DGUOK) deficiency.

CERC-913 incorporates ProTide prodrug chemistry to overcome the key limitations of direct substrate replacement. This approach has been successfully utilized in several approved drugs, including Sovaldi (Sofosbuvir).

ProTide nucleotides have been shown to significantly increase plasma stability and cell permeability relative to the parent compound and have also demonstrated the ability to bypass nucleoside kinases to circumvent the rate limiting step in nucleic acid synthesis.

CERC-913 has demonstrated proof-of-concept in patient-derived & animal-based disease models.

of CERC-913

  • ProTide moiety similar to approved drugs and advanced clinical candidates
  • Proof-of-concept in patient-derived & animal-based disease models
  • Metabolite ID & PK profile in dog support translational PKPD

About DGUOK Deficiency

There are currently no FDA-approved therapies to treat DGUOK Deficiency.

MDS are a group of inherited, metabolic disorders caused by single enzyme defects that hinder the ability to synthesize mitochondrial DNA (mtDNA). The resultant depletion of mtDNA compromises mitochondrial function, which can have broad clinical implications dependent on the target tissue and/or organ primarily affected, ranging from progressive muscle myopathy to liver failure. MDS are ultra-rare diseases with high infant morbidity and mortality. There are currently no FDA-approved therapies to treat MDS.

Some MDS, such as DGUOK Deficiency, are due to loss-of-function mutations in one of several mitochondrial nucleoside kinases. In this subset of MDS, the inability to produce deoxynucleoside monophosphates (e.g., dGMP), the rate-limiting step of mtDNA synthesis, causes mtDNA depletion.

Mechanism of Action

CERC-913 is a ProTide prodrug of deoxyguanosine monophosphate (dGMP) designed to act as a substrate replacement therapy. Oral administration of CERC-913 is expected to increase intracellular availability of dGMP for mitochondrial DNA (mtDNA) synthesis, particularly in the liver.