Chimerix has two core assets that are exploited in our Discovery efforts:
There is significant unmet medical need for potent and specific antivirals that can be used orally in prevention and/or treatment of viral diseases with global impact. A common barrier to finding effective therapies is the lack of molecules that can be given orally because of poor absorption in the gut or poor tissue penetration. Chimerix has a proprietary lipid technology that can be used to enhance absorption in the gut and significantly enhance tissue penetration. This technology involves attaching lipid side-chains to antivirals, such as nucleotides, that are limited by poor gut absorption. These lipid-antiviral conjugates are thought to mimic a phospholipid in the cell membrane and thus use the natural uptake pathways in the small intestine to achieve oral bioavailability and efficient tissue penetration. It is thought that the lipid side chain facilitates efficient uptake into the target cells as evidenced by much higher concentrations in the cell. Once in the cell, the lipid is cleaved in the cytoplasmic compartment of the target cell and released as an active antiviral.
Two Chimerix lipid-nucleotide conjugates are currently in clinical development:
The antiviral drugs tenofovir and cidofovir are used for preventing and/or treating a number of human viral infections including HIV, HBV and CMV; however, these antivirals are poorly absorbed when given orally and have been associated with kidney toxicity
BCV is administered orally, circulates as BCV, and is converted to the active antiviral cidofovir diphosphate within cells as shown below. BCV shares the broad-spectrum in vitro antiviral activity of cidofovir against all five families of double stranded DNA viruses which cause disease in humans. Because of the lipid conjugate, BCV is approximately 400-fold more active against cytomegalovirus in vitro than the parent nucleotide cidofovir. Similarly, compared to cidofovir, brincidofovir is 800-fold more active against BK virus in vitro, 250-fold more potent against variola major in vitro, and 65-fold more active against adenovirus in vitro.
Because these particular lipid conjugates are not recognized by the transport mechanisms that can cause excessive accumulation of acyclic nucleoside phosphonates such as cidofovir and tenofovir in kidney cells, they have the potential for an improved safety profile and have not been associated with kidney toxicity to date.
The Chimerix Chemical Library contains a diverse array of heterocyclic ring system molecules including over 3000 structurally diverse nucleoside derivatives. Nucleoside analogs are ideally suited as potential antivirals for both DNA and RNA viruses that rely on viral encoded polymerases for their replication and are widely used in antiviral therapy. We are currently screening the library against a broad spectrum of DNA and RNA viruses.
Our Discovery strategy is to screen our collection of molecules from the Chimerix Chemical Library against selected viral targets and utilize the Chimerix Lipid Conjugate Technology to build potent antivirals that are orally absorbed and have favorable tissue penetration.
Our current focus is on novel nucleosides with activity against: