Phase Ib/II Clinical Trial Data Reported at 2019 Annual Meeting of
Nanatinostat is a Class 1 histone deacetylase (HDAC) inhibitor currently in phase Ib/II clinical trials (NCT03397706). In preclinical studies, nanatinostat has been shown to reactivate silenced transgenes in tumor cells thereby turning them into preferential targets for NK cell killing, while also serving to broadly stimulate a patient’s immune system, offering the potential for improved clinical responses in cancer patients.
The activity of HDAC inhibitors are believed to be based on the upregulation of natural killer group 2D (NKG2D) ligand expression on cancer cells, which serve as “eat-me” signals for NK cells and can drive NK proliferation, activation and cancer cell killing.
Interim results presented at the 2019 annual
EBV-associated cancers are known to be an extremely difficult cancer to treat. Early clinical data with the combination of nanatinostat and anti-viral therapy in EBV-associated lymphoma from the phase Ib/II study has provided encouraging efficacy signals. Currently, there are no approved treatments for EBV-associated lymphomas that specifically target the virus.
The combination therapy produced an objective response rate (ORR) of 58%, a complete response rate (CR) of 33% and a disease stabilization rate (DSR) of 75%. Based on these encouraging results, Viracta anticipates advancement of the clinical trial to the phase II stage that will evaluate intermittent dosing of nanatinostat (4 days on and 3 days off) in combination with daily valganciclovir.
Nanatinostat (VRx-3996) is a histone deacetylase (HDAC) inhibitor that
is being investigated in a range of clinical indications. Nanatinostat
is selective for Class 1 HDACs, including isoforms targeted in Viracta's
“Kick & Kill” therapeutic approach. Viracta is investigating
nanatinostat in a phase Ib/II clinical study [NCT03397706] in
combination with an antiviral valganciclovir for the treatment of
EBV-associated cancers. Both drugs are taken orally and can be given on
an out-patient basis. Recently, the nanatinostat plus valganciclovir
combination therapy received Orphan Drug Designation (ODD) from the
About EBV-Associated Cancers
Approximately 95% of the world's adult population is infected with Epstein-Barr Virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patients' life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV lymphomas. In addition, EBV is also associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.
With the capacity to grow active killer cells as a cancer therapy, our NK cells have been designed to induce cell death against cancers and virally infected cells by several mechanisms, including: (i) innate killing, whereby all of our NK platforms recognize the stress proteins typically found on cancer cells, which, upon binding, release toxic granules to immediately kill their targets; (ii) antibody-mediated killing with our haNK® platform, which are NK cells engineered to express antibody receptors that can bind to therapeutic antibody products, thereby enhancing the cancer cell killing effect of that antibody; and (iii) Chimeric Antigen Receptor directed killing using the taNK® platform, which includes NK cells engineered to incorporate chimeric antigen receptors (CARs) to target tumor-specific antigens found on the surface of cancer cells. All three modes of killing (innate, antibody-mediated, and CAR directed killing) are employed by our t-haNK™ platform, which is an innovative combination of our aNK, haNK® and taNK® platforms in a single product.
Our haNK®, and t-haNK™ platforms have been designed to address certain limitations of CAR T-cell therapy including the capability to infuse cell therapy in an outpatient setting which allows for potential reduction of risk for serious cytokine storms and protracted serious adverse events. In phase I and II clinical trials in patients with late stage cancer, our NK cells have been administered as an investigational outpatient infusion safely with greater than 500 infusions to date at a dose of 2 billion cells per infusion.
By leveraging an integrated and extensive genomics and transcriptomics
discovery and development engine, together with a pipeline of multiple,
clinical-stage, immuno-oncology programs, we believe
NK-92, aNK, haNK, taNK, and t-haNK are trademarks of
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995.
Forward-looking statements include statements concerning or implying
Forward-looking statements are based on management's current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements.
These and other risks regarding NantKwest’s business are described in
detail in its
Viracta is a clinical-stage drug development company focused on
advancing novel epigenetic therapeutics derived from its proprietary
“Kick & Kill” therapeutic approach to benefit patients with
viral-associated cancers and other serious diseases. Viracta has entered
into partnerships with