On June 4, 2019 NantKwest Inc. (Nasdaq:NK) reported that its strategic partner Viracta Therapeutics presented updated clinical data on its HDAC inhibitor, nanatinostat (VRx-3996) at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, IL, from May 31st – June 4th, 2019 (Press release, NantKwest, JUN 4, 2019, View Source [SID1234536879]).
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In April 2017, NantKwest announced that it was the lead investor in Viracta’s Series B financing round. Concurrent with the financing, NantKwest secured an exclusive license with commercialization rights to nanatinostat for use in combination with natural killer (NK) cell therapies, including NantKwest’s NK cell platforms.
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.
NantKwest is preparing to initiate clinical trials that include nanatinostat in combination with its haNK and t-haNK cell therapy platforms, which we believe will work synergistically to enhance the efficacy of the company’s NK cell therapies and further distinguish us in the market.
Interim results presented at the 2019 annual ASCO (Free ASCO Whitepaper) meeting from the phase Ib portion of the ongoing phase Ib/II clinical trial of nanatinostat was in combination with the antiviral valganciclovir for the treatment of relapsed/refractory Epstein Barr Virus (EBV)-associated lymphomas. Three doses of the combination were evaluated with responses seen at all dose levels. Both drugs are taken orally and can be administered in an out-patient setting.
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.
Patrick Soon-Shiong, M.D., Chairman and CEO of NantKwest commented, "EBV-associated lymphomas represent a heterogenous group of cancers that are often aggressive and poorly responsive to available therapy. In this phase Ib stage, we are pleased to see encouraging objective responses including a 33% complete response rate in relapsed/resistant EBV positive cancer patients. We look forward to our continued partnership with Viracta to transition to phase II clinical trials, while also moving nanatinostat forward in combination with NantKwest’s haNK and t-haNK cell therapies."
Ivor Royston, M.D., Viracta’s CEO added, "Our ASCO (Free ASCO Whitepaper) presentation and clinical trial update highlights the potential of our proprietary ‘Kick & Kill’ therapeutic approach to treat a wide range of EBV positive cancer patients, with responses seen across all doses in both T cell and B cell lymphomas in our ongoing phase Ib/II study. "This data enable us to move forward with the phase II portion of our study with a well-tolerated dose combination of nanatinostat with valganciclovir, which we expect to initiate in the third quarter of 2019."
About Nanatinostat
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 U.S. Food & Drug Administration (FDA) for three sub-types of EBV-associated cancers: post-transplant lymphoproliferative disorder (PTLD), plasmablastic lymphoma, and angioimmunoblastic T cell lymphoma.
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.