On November 13, 2024 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 financial results for the third quarter of 2024 and provided a business update (Press release, Viracta Therapeutics, NOV 13, 2024, View Source [SID1234648290]).

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"Last quarter, based on productive feedback from FDA, we announced a sharpened focus on the second-line EBV-positive PTCL subpopulation in the NAVAL-1 trial’s expansion phase, which is ongoing," said Mark Rothera, President and Chief Executive Officer of Viracta. "To optimally support both the NAVAL-1 trial as well as a randomized controlled trial that we are planning for the second half of next year and reduce cash burn, we recently announced a reprioritization of resources intended to right-size our organization and further reduce our operating expenses. With a clearly defined regulatory path forward for Nana-val, we believe this will allow us to be efficient while we work toward the possible submission of a New Drug Application in 2026 and seek to introduce the first EBV-targeted therapy for lymphoma patients, subject to obtaining requisite funding."

"We are pleased to have determined a recommended Phase 2 dose for Nana-val in patients with advanced EBV-positive solid tumors," said Darrel P. Cohen, M.D., Ph.D., Chief Medical Officer of Viracta.

"Although the EBV-positive solid tumor program has been paused, clinical development in this patient population is ready for Phase 2, with additional financing or with a partner, using nanatinostat and valganciclovir doses that were well tolerated with evidence of antitumor activity."

Clinical Trial Updates and Anticipated Milestones

Phase 1b/2 trial of Nana-val (nanatinostat in combination with valganciclovir) in patients with recurrent/metastatic (R/M) Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinoma (NPC) and other advanced EBV+ solid tumors (Study 301)

Clinical Trial Update:

In October, determined the recommended Phase 2 dose in patients with advanced EBV+ solid tumors.
Phase 2 NAVAL-1 trial of Nana-val (nanatinostat in combination with valganciclovir) in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma

Clinical Trial Updates:

In August, announced positive combined Stage 1 and Stage 2 data (n=21) in the R/R EBV+ PTCL cohort of patients treated with nanatinostat (20 mg orally once daily, 4 days/week) in combination with valganciclovir (900 mg orally once daily, 7 days/week) across the first two stages of the study.
Combined data from Stages 1 and 2 demonstrated Nana-val’s substantial antitumor activity and generally well-tolerated safety profile with a median duration of response (DOR) that has not yet been reached.
In August, announced that a productive FDA meeting was held to align on a potential regulatory path forward for Nana-val in patients with R/R EBV+ PTCL.
Based on feedback from the FDA and the particularly robust response rates observed in the second-line treatment setting, and to target its resources, Viracta will focus the primary analysis on the second-line EBV+ PTCL subpopulation in the ongoing NAVAL-1 trial’s expansion phase.
The Company plans to begin a randomized controlled trial (RCT) of Nana-val in the second-line treatment of EBV+ PTCL patients in the second half of 2025, subject to obtaining financing.
Anticipated Milestones

Viracta plans to deliver on the following milestones, subject to obtaining financing:

Meet with the FDA to finalize the proposed RCT design in the second-line treatment of patients with EBV+ PTCL in the first half of 2025.
Initiate the RCT in the second half of 2025.
Report preliminary data from the expansion phase of the NAVAL-1 trial in second-line EBV+ PTCL patients in the first half of 2025.
Report Stage 1 data from patients with R/R EBV+ diffuse large B-cell lymphoma (DLBCL) in the first half of 2025.
Present interim analysis outcomes from the NAVAL-1 trial’s expansion phase in second-line EBV+ PTCL patients in 2026.
File NDA for accelerated approval in 2026 based on interim analysis of the NAVAL-1 trial’s expansion cohort.
Business Updates

Announced on November 6th a reprioritization of resources intended to enhance focus on the Company’s lead program, reduce cash burn, and drive shareholder value:
Included a reduction in force affecting approximately 42% of the Company’s employees.
Also reduced the size of its Board of Directors from 10 to 6 seats following voluntary resignations from 4 directors.
Third Quarter 2024 Financial Results

Cash position – Cash, cash equivalents, and short-term investments totaled approximately $21.1 million as of September 30, 2024, which Viracta expects will be sufficient to fund operations late into the first quarter of 2025.
Research and development expenses – Research and development expenses were approximately $7.2 million and $23.7 million for the three and nine months ended September 30, 2024, respectively, compared to approximately $8.2 million and $24.0 million for the same periods in 2023. The decrease in research and development expenses for the three months ended September 30, 2024 compared to the same period in 2023, was driven by decreases in costs incurred to support the advancement and expansion of our clinical development programs, including incremental costs to support NAVAL-1, our Phase 2 trial of Nana-val in patients with R/R EBV+ lymphomas and personnel-related costs. The decrease in research and development expenses for the nine months ended September 30, 2024 compared to the same period in 2023, was largely due to decreases in costs incurred related to our clinical development programs and personnel-related costs, partially offset by a non-cash adjustment for insurance costs related to the February 2021 reverse merger with Sunesis Pharmaceuticals of $1.8 million.
General and administrative expenses – General and administrative expenses were approximately $3.0 million and $10.0 million for the three and nine months ended September 30, 2024, respectively, compared to $4.3 million and $13.2 million for the same periods in 2023. The decrease in general and administrative expenses was largely due to decreases in personnel-related costs, corporate liability insurance premiums and consulting and legal costs.
Net loss – Net loss was approximately $10.6 million, or $0.27 per share (basic and diluted), for the quarter ended September 30, 2024, compared to a net loss of $12.6 million, or $0.33 per share (basic and diluted), for the same period in 2023. This change was primarily the result of decreases in research and development expenses and personnel-related costs. Net loss was approximately $29.5 million, or $0.75 per share, (basic and diluted) for the nine months ended September 30, 2024, compared to a net loss of $37.3 million, or $0.97 per share, (basic and diluted) for the same period in 2023. This change was primarily the result of $5.0 million of other income received related to the monetization of a pre-commercialization, event-based milestone from Day One Biopharmaceuticals, Inc. in March 2024, and decreases in costs related to our clinical development programs and personnel-related costs, partially offset by the non-cash adjustment for insurance costs related to the February 2021 merger of $1.8 million.
About the NAVAL-1 Trial
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 three indication cohorts based on EBV+ lymphoma subtype. If two objective responses are achieved 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 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 potentially registrational, 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 advanced EBV+ solid tumors.

About Peripheral T-Cell Lymphoma
T-cell lymphomas comprise a heterogeneous group of rare and aggressive malignancies, including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). There are approximately 5,600 newly diagnosed T-cell lymphoma patients and approximately 2,600 newly diagnosed PTCL-NOS and AITL patients in the U.S. annually. Approximately 70% of these patients are either refractory to first-line therapy, or eventually experience relapse of their disease. Clinical trials are currently recommended for all lines of PTCL therapy, and most patients with R/R PTCL have poor outcomes, with median progression-free survival and median overall survival times reported to be 3.7 and 6.5 months, respectively. Approximately 40% to 65% of PTCL is associated with EBV, the incidence of EBV+ PTCL varies by geography, and reported outcomes for patients with EBV+ PTCL are inferior to those whose disease is EBV-negative. There is no approved targeted treatment specific for EBV+ PTCL, and therefore this represents a high unmet medical need.

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.