On August 14, 2023 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported a business update and provided financial results for the second quarter of 2023 (Press release, Viracta Therapeutics, AUG 14, 2023, View Source [SID1234634381]).

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"In the second quarter of 2023, we achieved key milestones in the pivotal NAVAL-1 study of Nana-val by enabling the advancement of this global clinical trial into Stage 2 and establishing EBV-positive PTCL as Nana-val’s leading indication. This milestone was based on a strong signal of efficacy with a favorable safety profile, consistent with our promising Phase 1b/2 clinical trial data," said Mark Rothera, President and Chief Executive Officer of Viracta. "Given the high unmet medical need in patients with EBV-positive PTCL and our positioning of Nana-val as a potential important treatment option for these patients, our goal is to move forward rapidly towards registration in the U.S. We intend to complete Stage 2 enrollment and meet with the U.S. Food and Drug Administration in 2024 to discuss additional requirements for regulatory approval."

Darrel P. Cohen, M.D., Ph.D., Chief Medical Officer of Viracta commented, "We are thrilled to have our Phase 1b/2 study results published in a high-quality peer-reviewed journal, such as Blood Advances, which underscores the potential of Nana-val to treat patients with EBV-positive lymphoma and elevates the importance of the NAVAL-1 trial. Following the advancement of the PTCL cohort and to optimize our resources behind this trial, we have strategically prioritized key subtypes of EBV-positive lymphoma where we can address high unmet medical needs, increase the probability of success, and focus on the largest EBV-positive lymphoma patient populations."

Clinical Trial Updates and Anticipated Milestones

Pivotal NAVAL-1 study of Nana-val in patients with relapsed or refractory (R/R) EBV+ lymphoma

The EBV+ peripheral T-cell lymphoma (PTCL) cohort of the pivotal NAVAL-1 clinical trial met the efficacy threshold for expansion into Stage 2 of the study, which was based upon a pre-specified minimum number of objective responses achieved; initial data are consistent with results from the Phase 1b/2 study and establish EBV+ PTCL as Nana-val’s leading indication.
Strategically prioritized three lymphoma subtypes: (1) EBV+ PTCL, a T-cell lymphoma with high unmet medical need; (2) EBV+ diffuse large B-cell lymphoma (DLBCL), an aggressive and distinct B-cell lymphoma subtype characterized by adverse clinical outcomes, and (3) EBV+ PTLD, a potentially fatal complication after transplantation, which is highly associated with EBV.
Prioritization also enables the allocation of resources to those indications with the greatest probability of success and market opportunity in key geographies.
Enrollment into HIV-lymphoma and Hodgkin lymphoma cohorts will be discontinued.
Patients with extranodal NK/T-cell lymphoma (ENKTL) and other ultra-rare subtypes of EBV+ lymphoma will continue to be enrolled.
Completion of enrollment into Stage 2 of the R/R EBV+ PTCL cohort and engagement with FDA on additional requirements for regulatory approval is anticipated in 2024.
Phase 1b/2 clinical trial of Nana-val in patients with R/R EBV+ lymphoma

In August 2023, Viracta announced the publication in Blood Advances featuring results from an open-label, multicenter, Phase 1b/2 study of Nana-val in patients with R/R EBV+ lymphoma titled, "Targeted therapy with nanatinostat and valganciclovir in recurrent Epstein-Barr virus-positive lymphoid malignancies: a Phase 1b/2 study."
The publication included a more recent data cut reflecting multiple patients with an ongoing durable response exceeding 30 months across multiple EBV+ lymphoma subtypes, including EBV+ PTCL and EBV+ DLBCL, and two patients with an ongoing response of approximately 36 months.
Nana-val was generally well tolerated with reversible low-grade toxicities. The most commonly observed treatment emergent adverse events were reversible cytopenias, low-grade creatinine elevations, and gastrointestinal symptoms.
Phase 1b/2 study of Nana-val in patients with recurrent or metastatic (R/M) EBV+ nasopharyngeal carcinoma (NPC) and other advanced EBV+ solid tumors

Enrollment completed through the fifth dose level of the Phase 1b dose escalation portion of the trial without any dose-limiting toxicities reported.
The Company remains on track to report complete Phase 1b dose escalation data and select a Recommended Phase 2 Dose (RP2D) of Nana-val in the second half of 2023.
Initiation of the trial’s randomized Phase 2 expansion cohort designed to evaluate Nana-val at the RP2D with or without pembrolizumab in patients with R/M EBV+ NPC is expected in the second half of 2023.
Initiation of the trial’s exploratory Phase 1b expansion cohort designed to evaluate Nana-val at the RP2D in patients with other advanced EBV+ solid tumors, including gastric carcinoma, leiomyosarcoma, and lymphoepithelioma, is expected in the second half of 2023.
Business Updates

Strengthened the leadership team with the appointment of Darrel P. Cohen, M.D., Ph.D. as Chief Medical Officer (CMO)

In August 2023, Dr. Cohen was appointed as CMO to oversee the clinical development and regulatory advancement of Viracta’s pipeline. Dr. Cohen is a highly accomplished physician and biopharmaceutical executive with more than 25 years of oncology clinical research and drug development experience in both solid tumors and hematologic malignancies. Dr. Cohen was involved in multiple successful regulatory submissions of new targeted cancer drugs such as SUTENT (sunitinib), XALKORI (crizotinib), and IBRANCE (palbociclib) while at Pfizer Oncology.
Strengthened intellectual property estate

In July 2023, Viracta received a Notice of Allowance from the US Patent and Trademark Office on Viracta’s patent claims directed to a next-generation formulation of nanatinostat. This Notice of Allowance supports Viracta’s life-cycle management strategy, and upon issuance, the claims will expire in October 2041.
Second Quarter 2023 Financial Results

Cash position – Cash, cash equivalents, and short-term investments totaled approximately $72.9 million as of June 30, 2023, which Viracta expects will be sufficient to fund its operations into late 2024 excluding any additional borrowing under a $50.0 million credit facility, of which $25.0 million remains available, at the Company’s request and subject to the discretion of the lenders.
Research and development expenses – Research and development (R&D) expenses were approximately $8.2 million and $15.8 million for the three and six months ended June 30, 2023, respectively, compared to approximately $6.3 million and $12.4 million for the same periods in 2022. This increase in R&D expenses was primarily driven by increases in costs incurred to support the advancement and expansion of our clinical development programs, including incremental costs to support NAVAL-1, our pivotal study of Nana-val in patients with R/R EBV+ lymphoma, and the initiation of our Phase 1b/2 study of Nana-val for the treatment of patients with EBV+ solid tumors, as well as an increase in personnel-related costs.
General and administrative expenses – General and administrative (G&A) expenses were approximately $4.3 million and $8.9 million for the three and six months ended June 30, 2023, respectively, compared to $4.2 million and $8.5 million for the same periods in 2022. The increase in G&A expenses can be primarily attributed to an increase in personnel-related costs.
Net loss – Net loss was approximately $12.5 million, or $0.32 per share, (basic and diluted) for the quarter ended June 30, 2023, compared to a net loss of $10.6 million, or $0.28 per share, (basic and diluted) for the same period in 2022. Net loss was approximately $24.7 million, or $0.64 per share, (basic and diluted) for the six months ended June 30, 2023, compared to a net loss of $21.1 million, or $0.56 per share, (basic and diluted) for the same period in 2022.
About NAVAL-1
NAVAL-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. This trial employs a Simon two-stage design where, in Stage 1, participants are enrolled into one of six indication cohorts based on EBV+ lymphoma subtype. If a pre-specified antitumor activity threshold is reached within a lymphoma subtype in Stage 1 (n=10), then additional patients will be enrolled in Stage 2 for a total of 21 patients. EBV+ lymphoma subtypes demonstrating promising antitumor activity in Stage 2 may be further expanded following discussion with regulators to potentially support registration.

About the Phase 1b/2 Study of Nana-val in R/M EBV+ NPC and Other EBV+ Solid Tumors
This Phase 1b/2 trial (NCT05166577) is an open-label, multinational clinical trial evaluating Nana-val alone and in combination with pembrolizumab. The Phase 1b dose escalation part is designed to evaluate safety and to 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 at the RP2D with or without pembrolizumab to further evaluate antitumor activity, safety and tolerability, pharmacokinetics, and potential pharmacodynamic biomarkers. Additionally, patients with other advanced EBV+ solid tumors will be enrolled to receive Nana-val at the RP2D in a Phase 1b dose expansion cohort.

About Nana-val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-val, in various subtypes of EBV-associated 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) as well as a multinational Phase 1b/2 clinical trial in patients with recurrent or metastatic (R/M) EBV+ NPC and other EBV+ solid tumors.

About EBV-Associated Cancers
Approximately 90% of the world’s adult population is infected with EBV. Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV-positive (EBV+) lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.