nanatinostat (VRx-3996) / Viracta Therap, Chroma Therap - LARVOL DELTA

Single-Cell Profiling of HDAC Inhibitor-Induced EBV Lytic Heterogeneity Defines Abortive and Refractory States in B Lymphoblasts. (PubMed, bioRxiv) - "We therefore characterized the impact of pan-HDAC inhibitor, panobinostat, and class I HDAC inhibitor, nanatinostat, on the growth, survival, and lytic reactivation of four EBV-positive cell lines: P3HR1-ZHT BL, Jijoye BL, IBL-1 immunoblastic lymphoma, and de novo infection derived lymphoblastoid cell lines (LCL). Single-cell RNA sequencing provided evidence of upregulated immune signaling pathways in this abortive lytic population. This study provides in depth characterization of lytic reactivation with a biologically relevant stimulus."

Heterogeneity • IO biomarker • Journal • Burkitt Lymphoma • Epstein-Barr Virus Infections • Gastric Cancer • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Infectious Disease • Lymphoma • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • TNFRSF9

A propidium iodide-based in vitro screen of the "Bug Box" against Babesia duncani reveals potent inhibitors. (PubMed, Antimicrob Agents Chemother) - "A screen of the 41-compound library Structural Genomics Consortium Bug Box was conducted, yielding five hits: trimethoprim, atovaquone, SDDC M7, diphenyleneiodonium chloride, and panobinostat. Dose-response testing of structurally related compounds revealed multiple potential leads, including nanatinostat and quisinostat, both of which were potent at the nanomolar level and showed favorable selectivity index in cytotoxicity studies. High-throughput screening using PI and 384-well plates is an advance in drug discovery for babesiosis, and HDAC inhibitors show promise as lead compounds worthy of further investigation."

Journal • Preclinical • Infectious Disease

NAVAL-1: An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas (clinicaltrials.gov) - P2 | N=102 | Terminated | Sponsor: Viracta Therapeutics, Inc. | Trial completion date: Dec 2026 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Dec 2024; Sponsor Decision

Trial completion date • Trial primary completion date • Trial termination • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

A Mass Balance Study of [14C]-Nanatinostat and Relative Bioavailability Study of Nanatinostat in Patients With Advanced Cancers (clinicaltrials.gov) - P1 | N=8 | Terminated | Sponsor: Viracta Therapeutics, Inc. | N=14 ➔ 8 | Trial completion date: Oct 2025 ➔ Jan 2025 | Recruiting ➔ Terminated; Sponsor Decision

Enrollment change • Trial completion date • Trial termination • Oncology

VT3996-301: Nanatinostat Plus Valganciclovir in Patients With Advanced EBV+ Solid Tumors, and in Combination With Pembrolizumab in EBV+ RM-NPC (clinicaltrials.gov) - P1 | N=26 | Terminated | Sponsor: Viracta Therapeutics, Inc. | Phase classification: P1/2 ➔ P1 | Trial completion date: Oct 2025 ➔ Jan 2025 | Active, not recruiting ➔ Terminated; Sponsor Decision

Phase classification • Trial completion date • Trial termination • Epstein-Barr Virus Infections • Gastric Cancer • Head and Neck Cancer • Leiomyosarcoma • Nasopharyngeal Carcinoma • Oncology • Sarcoma • Solid Tumor

NAVAL-1: An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas (clinicaltrials.gov) - P2 | N=140 | Active, not recruiting | Sponsor: Viracta Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

Viracta Therapeutics Announces Closure of NAVAL-1 Clinical Trial and Exploration of Strategic Alternatives (GlobeNewswire) - "To maximize its cash runway while the Board conducts its review of strategic alternatives, Viracta has elected to close its ongoing pivotal Phase 2 clinical trial of Nana-val in relapsed/refractory EBV+ lymphomas (the NAVAL-1 trial). The company emphasized that its decision to voluntarily close the trial is not the result of any new safety finding....Viracta is making this announcement to inform shareholders and the public that the Company is engaging in discussions for strategic alternatives with the goal of maximizing value. Potential alternatives include, but are not limited to, a merger, licensing agreement, sale or other strategic transaction. There can be no assurance that the exploration of strategic alternatives will result in any agreements or transactions, or as to the timing of any such agreements or transactions."

Commercial • Trial status • Diffuse Large B Cell Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

VT3996-301: Nanatinostat Plus Valganciclovir in Patients With Advanced EBV+ Solid Tumors, and in Combination With Pembrolizumab in EBV+ RM-NPC (clinicaltrials.gov) - P1/2 | N=26 | Active, not recruiting | Sponsor: Viracta Therapeutics, Inc. | N=130 ➔ 26

Combination therapy • Enrollment change • Metastases • Epstein-Barr Virus Infections • Gastric Cancer • Head and Neck Cancer • Leiomyosarcoma • Nasopharyngeal Carcinoma • Oncology • Sarcoma • Solid Tumor

Viracta Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "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."

FDA filing • New trial • P2 data • Diffuse Large B Cell Lymphoma • Peripheral T-cell Lymphoma

Viracta Therapeutics Announces Reprioritization of Resources to Enhance Focus on Nana-val Development Program in Patients with Relapsed or Refractory EBV-Positive Peripheral T-Cell Lymphoma (GlobeNewswire) - "Viracta Therapeutics...announced that the company has implemented a reprioritization of resources intended to enhance the company’s focus on its Nana-val development program in patients with relapsed or refractory (R/R) EBV-positive peripheral T-cell lymphoma (PTCL). To further align resources with current pipeline priorities, Viracta is announcing today that it has implemented a further reduction in force that impacts approximately 42% of the company’s employees. Viracta expects to recognize approximately $0.7 million in total expenses for severance and related benefits for employees impacted by the reduction in force."

Commercial • Peripheral T-cell Lymphoma

VT3996-301: Nanatinostat Plus Valganciclovir in Patients with Advanced EBV+ Solid Tumors, and in Combination with Pembrolizumab in EBV+ RM-NPC (clinicaltrials.gov) - P1/2 | N=130 | Active, not recruiting | Sponsor: Viracta Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Epstein-Barr Virus Infections • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Leiomyosarcoma • Nasopharyngeal Carcinoma • Oncology • Sarcoma • Solid Tumor

NAVAL-1: PHASE 2 TRIAL EVALUATING NANATINOSTAT IN COMBINATION WITH VALGANCICLOVIR IN PATIENTS WITH EPSTEIN-BARR VIRUS-POSITIVE RELAPSING/REFRACTORY LYMPHOMAS (EBV+). ONGOING TRIAL (SIE 2024) - P2 | "Nstat induces expression of the lytic BGLF4 PK, which activates the nucleoside analog ganciclovir via phosphorylation. Additional data from Stage 2 of combination therapy will be presented. Figure 1."

Clinical • Combination therapy • P2 data • Cardiovascular • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Disorders • Hematological Malignancies • Influenza • Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Septic Shock

A Global Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With EBV-Positive (EBV+) Relapsed/Refractory Peripheral T Cell Lymphomas (NAVAL-1) (SOHO 2024) - "Combination Nstat+VGCV is a promising, generally well-tolerated treatment for patients with R/R EBV+ PTCL that has much greater efficacy than Nstat alone."

Clinical • Combination therapy • P2 data • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Viracta Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Research and development expenses were approximately $6.5 million and $16.5 million for the three and six months ended June 30, 2024, respectively, compared to approximately $8.2 million and $15.8 million for the same periods in 2023. The decrease in research and development expenses for the three months ended June 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."

Commercial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

Viracta Therapeutics Announces…Updated Nana-val Clinical Development Plan (GlobeNewswire) - "Pause the EBV+ solid tumor program to focus resources on the more advanced EBV+ lymphoma program. The recommended Phase 2 dose in patients with advanced EBV+ solid tumors is expected to be determined in the second half of 2024. Report additional data from the ongoing expansion phase of the NAVAL-1 trial in second-line EBV+ PTCL patients in the fourth quarter of 2024. Report Stage 1 data from patients with R/R EBV+ diffuse large B-cell lymphoma (DLBCL) in the first half of 2025."

P2 data • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor

Viracta Therapeutics Announces Positive Data from the Phase 2 NAVAL-1 Trial, Regulatory Progress, and Updated Nana-val Clinical Development Plan (GlobeNewswire) - P2 | N=140 | NAVAL-1 (NCT05011058) | Sponsor: Viracta Therapeutics, Inc. | "Key Takeaways from the R/R EBV+ PTCL Cohort of the Phase 2 NAVAL-1 Trial...In the R/R EBV+ PTCL population: The overall response rate (ORR) was 33% and the complete response rate (CRR) was 19% in the intent-to-treat (ITT) population (n=21); the ORR was 41% and the CRR was 24% in the efficacy-evaluable (EE) population (n=17). In the second-line EBV+ PTCL subpopulation: The ORR was 60% and the CRR was 30% in the ITT population (n=10); the ORR was 67% and the CRR was 33% in the EE population (n=9). Median duration of response (DOR) has not yet been reached. Two responding patients proceeded to hematopoietic stem-cell transplant without relapse, one of whom remains in response over 16 months."

P2 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

Viracta Therapeutics Announces…Regulatory Progress, and Updated Nana-val Clinical Development Plan (GlobeNewswire) - "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. Present interim analysis outcomes from the expansion phase of the NAVAL-1 trial 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."

FDA event • FDA filing • New trial • P2 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma

Phase 2 trial of nanatinostat and valganciclovir in patients with EBV-positive (EBV+) relapsed/refractory lymphomas (NAVAL-1) (BSH 2024) - P1/2 | "The oral combination of nanatinostat (Nstat), a potent Class I HDACi, and valganciclovir (VGCV), a pro-drug of ganciclovir (GCV), is a novel mechanism to kill EBV+ tumour cells through inducing the expression of the lytic BGLF4 protein kinase to activate the nucleoside analogue GCV via phosphorylation, resulting in termination of DNA replication and apoptosis...Patients with T/NK-NHL (n=15) had an ORR/CR of 60%/27%; in EBV+ DLBCL, NOS (n=6), the ORR/CR was 67%/33% (both CRs were patients refractory to first-line RCHOP)...Median duration of response (DoR) has not been reached. Enrolment began in May 2021."

Clinical • P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Viracta Therapeutics Announces Positive Topline Nana-val Results from Stage 1 of the NAVAL-1 Trial in Patients with Relapsed or Refractory Epstein-Barr Virus-Positive (EBV+) Peripheral T-Cell Lymphoma (GlobeNewswire) - P2 | N=140 | NAVAL-1 [NCT05011058] | Sponsor: Viracta Therapeutics, Inc. | "Efficacy was evaluated as of the February 7, 2024 data cutoff date. In the Nana-val arm, the overall response rate (ORR) was 50% and the complete response rate (CRR) was 20% in the intent-to-treat (ITT) population (N=10); the ORR was 71% and the CRR was 29% in the efficacy-evaluable population (N=7). In the nanatinostat monotherapy arm, the ORR and CRR were 10% and 0%, respectively, in the ITT population (N=10), and the ORR was 13% in the efficacy-evaluable population (N=8)....The most common treatment-related adverse events in both treatment arms were thrombocytopenia, anemia, fatigue, decreased appetite, nausea, diarrhea, and weight loss."

P2 data • Peripheral T-cell Lymphoma

Trial in progress: A global phase 2 basket trial of nanatinostat in combination with valganciclovir in patients with EBV-positive (EBV+) relapsed/refractory lymphomas (NAVAL-1) (ICKSH 2024) - P1/2, P2 | "The all-oral combination of nanatinostat (Nstat), a potent Class-I HDACi, and valganciclovir (VGCV), a pro-drug of ganciclovir (GCV), is a novel mechanism to kill EBV+ tumor cells through inducing the ex- pression of the lytic BGLF4 protein kinase to activate the nucleoside analog GCV, resulting in termination of DNA replication and apop- tosis. Results : Enrollment began in May 2021 with more than 75 study sites worldwide. NCT No.: NCT05011058."

Clinical • Combination therapy • P2 data • Pan tumor • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Lymphoma • Oncology

Viracta Therapeutics to Present Topline Nana-val Results from Stage 1 of the NAVAL-1 Trial at the 2024 Annual Congress of The Hematology Society of Taiwan (GlobeNewswire) - "Viracta Therapeutics, Inc...today announced that topline results from Stage 1 of the NAVAL-1 trial of Nana-val (nanatinostat in combination with valganciclovir) in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) peripheral T-cell lymphoma (PTCL) will be featured in an oral presentation during the 2024 Joint Annual Congress of Taiwan Society of Blood and Marrow Transplantation and The Hematology Society of Taiwan."

P2 data • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma

A Mass Balance Study of [14C]-Nanatinostat and Relative Bioavailability Study of Nanatinostat in Patients With Advanced Cancers (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Viracta Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology

A Mass Balance Study of [14C]-Nanatinostat and Relative Bioavailability Study of Nanatinostat in Patients With Advanced Cancers (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: Viracta Therapeutics, Inc.

Metastases • New P1 trial • Oncology

Viracta Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Update (GlobeNewswire) - "Anticipated 2024 Milestones: (i) Present topline Stage 1 data from both arms of the R/R EBV+ PTCL cohort (in patients treated with nanatinostat with [n=10] or without [n=10] valganciclovir) in the second quarter of 2024; (ii) Engage with U.S. Food and Drug Administration (FDA) in mid-2024, to align on requirements for accelerated approval; (iii) Enroll patients into the post-Phase 2 expansion cohort to support potential accelerated approval; (iv) Present Stage 1 + Stage 2 data (n=21) in the R/R EBV+ PTCL cohort in patients treated with Nana-val in the third quarter of 2024; (v) Report Stage 1 data from patients with R/R EBV+ diffuse large B-cell lymphoma (DLBCL) and R/R EBV+ post-transplant lymphoproliferative disorder (PTLD) by year-end 2024."

Enrollment status • FDA event • P2 data • Diffuse Large B Cell Lymphoma • Peripheral T-cell Lymphoma

Viracta Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Update (GlobeNewswire) - "Anticipated 2024 Milestones: (i) Determine the recommended Phase 2 dose (RP2D) in the second half of 2024; (ii) Initiate a dose-optimization cohort to confirm the RP2D as part of the study’s Phase 2 expansion by year-end 2024."

Trial status • Nasopharyngeal Carcinoma