Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on treating and preventing virus-related cancers affecting patients worldwide, today announced plans to highlight new data from studies Preliminary clinical and preclinical data for naatinostat and valganciclovir (Nana-val), its all-oral investigational therapy for Epstein-Barr virus (EBV)-related cancers, today (Wednesday, October 4, 2023) in the United States Taking place during the R&D Day at 8:00 AM Eastern Time.
“We are pleased with the growing clinical data, which we believe underscore the innovative therapeutic potential of Nana-val “Kick to kill” “We are developing approaches that target EBV-positive cancer cells and address the poor survival outcomes in most EBV-related cancers,” said Mark Rothera, President and CEO of Viracta. “Across multiple patient populations with relapsed or refractory EBV-positive lymphoma The observed clinical response and favorable safety profile continue to be encouraging. New Phase 1 clinical data from the PTCL cohort of patients in the NAVAL-1 trial showed preliminary overall and complete response rates of 40%, which is consistent with data from our previous Phase 1b/2 study. Importantly, the combination of response rates and duration of response observed in these studies to date exceeds the current standard of care in this relapsed/refractory patient population. We are on track to complete Phase 2 of the PTCL cohort with the goal of engaging with the FDA in 2024 regarding additional requirements that may expedite approval. Additionally, we are excited about the emerging dose-response signal in patients with recurrent or metastatic EBV-positive NPC, with responses now being observed at higher dose levels without dose-limiting toxicities. “We look forward to evaluating our novel daily divided dosing regimen in patients with advanced EBV-positive solid tumors based on compelling preclinical data.”
The R&D Day will feature presentations by members of Viracta’s senior management team, focusing on the top priority EBV+ lymphoma indications from the pivotal NAVAL-1 trial, namely peripheral T-cell lymphoma (PTCL) and diffuse large B-cell lymphoma (DLBCL), and An advanced EBV+ solid tumor program for patients with recurrent or metastatic (R/M) EBV+ nasopharyngeal carcinoma (NPC). In addition, the R&D Day will feature presentations from expert key opinion leaders who will discuss the high unmet medical need in Epstein-Barr virus-associated lymphoma.
External speakers will include:
- Pierluigi Porcu, MD, Professor of Medical Oncology and Chief of the Section of Hematological Malignancies and Hematopoietic Stem Cell Transplantation at Thomas Jefferson University
- Robert A. Baiocchi, MD, PhD, Professor of Internal Medicine and Associate Chief of Translational and Clinical Sciences, Division of Hematology, The Ohio State University
Main themes and highlights of the R&D Day
Preliminary preliminary data from Nana-val’s pivotal NAVAL-1 clinical trial in patients with relapsed or refractory (R/R) EBV+ Lymphoma
- Preliminary results from the first five R/R EBV+ PTCL patients treated with Nana-val as of the data cutoff date of June 30, 2023, show an overall response rate (ORR) and complete response rate (CRR) of 40%.
- The EBV+ PTCL cohort met the efficacy threshold for expansion into Phase 2 of the study, based on achieving two objective responses in the first 5 of 10 patients enrolled in the Phase 1 study.
- The median duration of response (DoR) has not been reached.
- Expected 2024 Milestones:
- Complete the second phase of registration for the R/R EBV+ PTCL queue,
- Engage with FDA regarding additional requirements for accelerated approval,
- Presentation of Phase II data.
Additional response and durability evaluation from the Phase 1b/2 trial of Nana-val in patients with R/R EBV (Study 201)+ Lymphoma as of data cutoff May 4, 2023
- The median DoR in patients with R/R EBV+ PTCL was 17.3 months, and the ORR/CRR was 50%/38% (n=8).
- In patients with R/R EBV+ DLBCL, additional response assessment in the formulation pharmacokinetics bridging substudy included two additional responders, one complete response (CR) and one partial response (PR), resulting in an ORR/CRR of 67%/33% (n=9).
- The median DoR in the R/R EBV+ DLBCL cohort has not been reached, with three patients remaining in response and continuing study treatment, with DoRs of 11.1 months (CR), 36.8 months (PR), and 41.9 months (CR), respectively. .
- Additional follow-up further demonstrated that Nana-val was generally well tolerated and toxicities were manageable, if not reversible; the most common treatment-emergent adverse events were hematological or gastrointestinal adverse events and low-grade creatinine elevations .
New Interim Clinical Data from Phase 1b/2 Study of Nana-val in Advanced EBV+ Solid Tumors (Study 301) highlights opportunities for further dose escalation through innovative dosing regimens supported by new preclinical data, potentially driving additional responses in this patient population
- Enrollment was completed through the fifth dose level of the dose-escalation portion of the Phase 1b trial, and no dose-limiting toxicities were reported.
- Best responses to date include 2 PRs (1 lasting >7 months) at higher dose levels in 17 patients with R/M EBV+ NPC, and 5 stable disease.
- In a preclinical mouse EBV+ gastric cancer xenograft model, divided daily administration of Nana-val had superior antitumor activity than intermittent (four days on/three days off) once-daily administration, supporting the This divided-daily-dose (SDD) treatment regimen was evaluated in patients with advanced EBV+ solid tumors.
- Expected 2024 Milestones:
- Nana-val plans up to three additional dose levels in the SDD schedule to select the recommended Phase 2 dose,
- Initiating a randomized phase 2 expansion cohort of a clinical trial designed to evaluate Nana-val at the recommended phase 2 dose (RP2D) with or without pembrolizumab in patients with R/M EBV+ NPC,
- An exploratory Phase 1b expansion cohort of this clinical trial was initiated to evaluate the Nana-val of RP2D in patients with other advanced EBV+ solid tumors, including gastric cancer, leiomyosarcoma, and lymphoepithelioma.
R&D Day webcast informationA live video webcast of the presentation will be available here and “Events and webcasts“. A replay of the presentation will be available approximately one hour after the presentation and will be archived and available at the same location for at least 30 days after the event.
About NAVAL-1NAVAL-1 (NCT05011058) is a global, multicenter clinical trial of Nana-val in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma. The trial uses a Simon two-stage design, with participants enrolled in one of three priority indication cohorts based on EBV+ lymphoma subtype in the first stage. If lymphoma subtypes (n=10) in Phase 1 reach prespecified antitumor activity thresholds, additional patients will be enrolled in Phase 2, for a total of 21 patients. Following discussions with regulatory agencies, EBV+ lymphoma subtypes that have shown promising anti-tumor activity in Phase 2 may be further expanded to support registration.
About the Phase 1b/2 Study of Nana-val in R/M EBV+ NPC and other Epstein-Barr viruses+ solid tumorsThe Phase 1b/2 trial (NCT05166577) is an open-label, multinational clinical trial evaluating Nana-val alone and in combination with pembrolizumab. The dose-escalation portion of Phase 1b is designed to evaluate safety and determine the recommended Phase 2 dose (RP2D) of Nana-val in patients with recurrent or metastatic (R/M) Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinoma (NPC). )). In Phase 2, up to 60 patients with R/M EBV+ NPC will be randomized to receive Nana-val with or without pembrolizumab at RP2D to further evaluate anti-tumor activity, safety and tolerability, drug kinetics and potential pharmacodynamic biomarkers. Additionally, patients with other advanced EBV+ solid tumors will be enrolled in the Phase 1b dose expansion cohort to receive Nana-val with RP2D.
About Nana-val (Nanatinostat and Valganciclovir)Nanatinostat is an oral histone deacetylase (HDAC) inhibitor developed by Viracta. Nanatinostat is selective for specific subtypes of class I HDACs, which are critical for the induction of epigenetically silenced viral genes in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being studied in combination with the antiviral drug valganciclovir as an all-oral combination therapy, Nana-val, to treat various subtypes of EBV-related malignancies. Ongoing trials include a pivotal, global, multicenter, open-label phase 2 basket trial in multiple subtypes of relapsed or refractory (R/R) EBV+ lymphoma (NAVAL-1), and a multinational 1b in patients /Phase 2 Clinical Trial: Recurrent or Metastatic (R/M) EBV+ NPC and other EBV+ solid tumors.
About EBV-related cancersApproximately 90% of the world’s adult population is infected with EBV. Infection is usually asymptomatic or associated with mononucleosis. After infection, the virus remains latent in a small subset of cells throughout the patient’s life. Cells containing latent viruses are increasingly susceptible to malignant transformation. Immunocompromised patients are at increased risk of developing EBV-positive (EBV+) lymphoma. EBV is estimated to be responsible for approximately 2% of the global cancer burden, including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.
About Viracta Therapeutics, Inc.Viracta is a clinical-stage precision oncology company focused on the treatment and prevention of virus-related cancers affecting patients worldwide. Viracta’s lead product candidate is an all-oral combination therapy of its proprietary investigational drug natininostat and the antiviral drug valganciclovir (collectively known as Nana-val). Nana-val is currently being evaluated in multiple ongoing clinical trials, including a pivotal, global, multicenter, open-label Phase 2 basket trial for the treatment of relapsed or refractory (R/R) Epstein-Barr virus-positive multiple subtype (EBV+) lymphoma (NAVAL-1), and a study for the treatment of recurrent or metastatic (R/M) EBV+ nasopharyngeal carcinoma (NPC) and other advanced EBV+ solid tumors Multinational open-label Phase 1b/2 clinical trial in patients. Viracta is also looking to apply its “Kick and Kill” approach to other virus-related cancers.
For more information, please visit www.viracta.com.