Cell No. 4 Interpretation of a cancer cell, provided by Angela Canada Hopkins, daughter of a cancer patient.

Cell No. 4 Interpretation of a cancer cell, provided by Angela Canada Hopkins, daughter of a cancer patient.

Kick & Kill Platform

Viracta’s Kick & Kill Platform is designed as a targeted approach to treat a range of viral-associated cancers and other serious diseases. Nanatinostat (aka VRx-3996; formerly known as tractinostat or CHR-3996) is Viracta’s investigational drug that is a Class I histone deacetylase (HDAC) inhibitor – a class of epigenetic-modifying drug that affects coiling of DNA around histones to change epigenetically-controlled expression patterns. In Viracta’s Kick & Kill approach, we are exploring applications of nanatinostat as the Kick to activate genes that have been epigenetically suppressed by the virus or cancer. As described below, the Kill can be provided by activating drugs to selectively and directly kill virus-harboring cells and/or activating suppressed immune response genes to enable patients’ endogenous immune system to kill diseased cells, which can be augmented by combining with a range of immunotherapy modalities.

* Valganciclovir is orally administered pro-drug form of ganciclovir (GCV)

In EBV+ cancers, genes are selectively, epigenetically suppressed, including viral genes for proteins necessary to activate antiviral pro-drugs, such as ganciclovir (Valcyte) or valacyclovir (Valtrex). Epigenetic suppression of these genes renders this drug ineffective. Induced viral-thymidine kinase and -protein kinase proteins initiate conversion of inactive ganciclovir to its active triphosphate form. The Kill is provided by this ganciclovir-triphosphate - a nucleoside analog that is incorporated into DNA chains of dividing cells - inhibiting propagation of the chain. Non-clinical human cell-based and animal model studies have shown that this DNA chain termination mechanism-of-action kills the cancer cell as it is no longer viable and dies by apoptosis. Non-dividing cells or cells that do not harbor virus are not affected. This provides a targeted therapy to selectively kill cancer cells that harbor the virus.

Viracta’s treatment approach to viral-associated malignancies utilizing the Kick & Kill platform is to administer two oral drugs for a highly targeted, non-immunosuppressive therapy that can be given on an out-patient basis. Viracta is exploring application of the nanatinostat-Kick, coupled with activated-valganciclovir-Kill to trigger targeted cancer cell killing mechanism. Resulting apoptotic cancer cell death may also release neo-antigens that patients’ immune system can recognize and fight any residual disease and help enhance innate and adaptive arms of the immune system ability to Kill disease cells.

In addition to its investigational role to serve as the Kick to enable activated-ganciclovir-Kill of EBV+ cancer cells, Viracta will also explore how nanatinostat may also serve as a Kick to enhance efficacy of immunotherapies. This may include augmenting the power of patient’s endogenous immune systems with checkpoint inhibitors and/or adding adoptive cell immunotherapies as additional means to Kill disease cells. The treatment approach holds potential to fit into a holistic treatment regimen for a range of non-viral as well as viral-associated cancers and may hold potential to address latent viral infections such as HIV/AIDS which may be evaluated in the future.

Kick & Kill Platform

Viracta’s Kick & Kill Platform is designed as a targeted approach to treat a range of viral-associated cancers and other serious diseases. Nanatinostat (aka VRx-3996; formerly known as tractinostat or CHR-3996) is Viracta’s investigational drug that is a Class I histone deacetylase (HDAC) inhibitor – a class of epigenetic-modifying drug that affects coiling of DNA around histones to change epigenetically-controlled expression patterns. In Viracta’s Kick & Kill approach, we are exploring applications of nanatinostat as the Kick to activate genes that have been epigenetically suppressed by the virus or cancer. As described below, the Kill can be provided by activating drugs to selectively and directly kill virus-harboring cells and/or activating suppressed immune response genes to enable patients’ endogenous immune system to kill diseased cells, which can be augmented by combining with a range of immunotherapy modalities.

* Valganciclovir is orally administered pro-drug form of ganciclovir (GCV)

In EBV+ cancers, genes are selectively, epigenetically suppressed, including viral genes for proteins necessary to activate antiviral pro-drugs, such as ganciclovir (Valcyte) or valacyclovir (Valtrex). Epigenetic suppression of these genes renders this drug ineffective. Induced viral-thymidine kinase and -protein kinase proteins initiate conversion of inactive ganciclovir to its active triphosphate form. The Kill is provided by this ganciclovir-triphosphate - a nucleoside analog that is incorporated into DNA chains of dividing cells - inhibiting propagation of the chain. Non-clinical human cell-based and animal model studies have shown that this DNA chain termination mechanism-of-action kills the cancer cell as it is no longer viable and dies by apoptosis. Non-dividing cells or cells that do not harbor virus are not affected. This provides a targeted therapy to selectively kill cancer cells that harbor the virus.

Viracta’s treatment approach to viral-associated malignancies utilizing the Kick & Kill platform is to administer two oral drugs for a highly targeted, non-immunosuppressive therapy that can be given on an out-patient basis. Viracta is exploring application of the nanatinostat-Kick, coupled with activated-valganciclovir-Kill to trigger targeted cancer cell killing mechanism. Resulting apoptotic cancer cell death may also release neo-antigens that patients’ immune system can recognize and fight any residual disease and help enhance innate and adaptive arms of the immune system ability to Kill disease cells.

In addition to its investigational role to serve as the Kick to enable activated-ganciclovir-Kill of EBV+ cancer cells, Viracta will also explore how nanatinostat may also serve as a Kick to enhance efficacy of immunotherapies. This may include augmenting the power of patient’s endogenous immune systems with checkpoint inhibitors and/or adding adoptive cell immunotherapies as additional means to Kill disease cells. The treatment approach holds potential to fit into a holistic treatment regimen for a range of non-viral as well as viral-associated cancers and may hold potential to address latent viral infections such as HIV/AIDS which may be evaluated in the future.