Epstein-Barr virus associated gastric carcinoma

- Confirmed objective response rate (ORR) of 40% in PD-L1 positive (TPS ≥1%)patients with no prior checkpoint inhibitor therapy (CPI) - Median progression-free survival (PFS) of 6.3 months in PD-L1 positive patients at time of data cut off - Confirmed ORR of 50% in patients with PD-L1 high expression (TPS ≥50%) and 38% in patients with PD-L1 low expression (TPS 1-49%) - RAPT to host webcast conference call today at 10:00 am PT SOUTH SAN FRANCISCO, Calif., Nov. 03, 2023 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, today announced safety and efficacy data from its Phase 2 trial of FLX475 (tivumecirnon) in patients with advanced non-small cell lung cancer (NSCLC) who had no prior checkpoint inhibitor therapy. The trial evaluated FLX475, an oral small molecule CCR4 antagonist designed to block the migration of regulatory T cells, in combination with the checkpoint inhibitor pembrolizumab. In this cohort of NSCLC patients, 36 patients were evaluable for efficacy, of which 20 were PD-L1 positive. In these PD-L1 positive patients, the combination of FLX475 and pembrolizumab showed a 40% (8/20) confirmed ORR and a median PFS of 6.3 months as of the data cut off date, with seven patients continuing on study. For comparison, historical pembrolizumab monotherapy activity in checkpoint inhibitor-naïve and previously-treated NSCLC patients showed a confirmed ORR of 18% and a median PFS of 4.0 months. The confirmed ORR for the combination of FLX475 and pembrolizumab in PD-L1 low and high subsets were 38% (6/16) and 50% (2/4), respectively. For comparison, the ORR for pembrolizumab monotherapy in the PD-L1 low and high subsets has been previously reported as 10% and 30%, respectively. The data were presented today in a poster at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting being held in San Diego. The presenting author was Julie Brahmer, M.D., Co-director of the Upper Aerodigestive Department and Professor of Oncology, Johns Hopkins University. “We are excited by the response rates and PFS data for FLX475 in combination with a checkpoint inhibitor in this cohort of NSCLC patients. The data from this cohort, which will continue to mature and potentially improve, met our criteria to advance development of FLX475,” said Brian Wong, M.D., Ph.D., President and Chief Executive Officer of RAPT. “We are particularly intrigued to see differentiating efficacy in patients with cool (PD-L1 low) tumors, which are typically poorly responsive to checkpoint inhibitors and checkpoint inhibitor combinations, such as those with anti-TIGIT antibodies. Along with RPT193, we now have two internally discovered compounds that have demonstrated clinical proof of concept in large, commercially attractive indications.” Phase 2 Data Summary in CPI-naïve NSCLC Patients (n=20) PD-L1 Status Confirmed Responses (n) Confirmed ORR Positive (TPS ≥1%) 8/20 40% Low (TPS 1-49%) 6/16 38% High (TPS ≥50%) 2/4 50% At the time of data cut off, there was one additional response among the PD-L1 low patients awaiting confirmation. The combination of FLX475 and pembrolizumab was well tolerated in this Phase 2 NSCLC cohort. The most common treatment-emergent adverse event deemed related to study treatment was QT prolongation that was asymptomatic and reversible. FLX475 has now been dosed in more than 300 patients with various advanced cancers and has been generally well tolerated, and the combination with pembrolizumab has not increased immune-related toxicity beyond that expected with pembrolizumab alone. In previous disclosures, FLX475 showed durable objective responses as monotherapy in an EBV+ lymphoma, as well as in combination with pembrolizumab in EBV+ gastric cancer. Webcast Conference Call Information RAPT will host a webcast conference call today, November 3, 2023 at 10:00 a.m. PT. To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. The live webcast and audio archive of the presentation may be accessed on the RAPT Therapeutics website at . About FLX475 FLX475 (tivumecirnon) is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg) specifically into tumors, but not healthy tissues. Treg represent a dominant pathway for downregulating the immune response, generally correlate with poor clinical outcomes, and may limit the effectiveness of currently available therapies such as checkpoint inhibitors. FLX475 may restore naturally occurring antitumor immunity alone and may synergize with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators, cancer vaccines, and adoptive T cell therapy. About RAPT Therapeutics, Inc. RAPT Therapeutics is a clinical stage immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology. Utilizing its proprietary discovery and development engine, the company is developing highly selective small molecules designed to modulate the critical immune drivers underlying these diseases. RAPT has discovered and advanced two unique drug candidates, RPT193 (zelnecirnon) and FLX475 (tivumecirnon), each targeting C-C motif chemokine receptor 4 (CCR4), for the treatment of inflammation and cancer, respectively. The company is also pursuing a range of targets that are in the discovery stage of development. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipate,” “could,” “expect,” “look forward,” “plan,” “target,” “will” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements relate to future events and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future performances or achievements expressed or implied by the forward-looking statements. Each of these statements is based only on current information, assumptions and expectations that are inherently subject to change and involve a number of risks and uncertainties. Forward-looking statements include, but are not limited to, statements about the therapeutic potential of FLX475, plans to advance clinical development of FLX475 and RPT193, plans to seek a partner to accelerate development of FLX475 and other statements that are not historical fact. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during clinical studies, preliminary data and trends may not be predictive of future data or results, may not demonstrate safety or efficacy or lead to regulatory approval by the FDA or other regulatory agencies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, the uncertainties and timing of the regulatory approval process, the timing and results of unexpected litigation or other disputes, and the sufficiency of RAPT’s cash resources. Detailed information regarding risk factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in RAPT’s Form 10-Q for the quarter ended June 30, 2023 and subsequent filings made by RAPT with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof. RAPT disclaims any obligation to update these forward-looking statements. Investor Contact: Sylvia Wheeler swheeler@wheelhouselsa.com Media Contact: Aljanae Reynolds areynolds@wheelhouselsa.com

Preliminary clinical data from patients with relapsed/refractory EBV+ peripheral T-cell lymphoma in the pivotal NAVAL-1 trial demonstrated overall and complete response rates of 40%; follow-up from the Phase 1b/2 study demonstrated median duration of response extended to 17.3 months Additional response and durability data in patients with relapsed/refractory EBV+ diffuse large B-cell lymphoma in the Phase 1b/2 study demonstrated sustained overall response rate of 67%; median duration of response not yet reached, with several patients continuing on study treatment in ongoing response out to 42 months Partial responses observed in recurrent/metastatic EBV+ nasopharyngeal carcinoma in Phase 1b dose escalation study suggestive of dose response without any dose-limiting toxicities observed Discussion to feature Key Opinion Leaders Pierluigi Porcu, M.D. and Robert A. Baiocchi, M.D., Ph.D. today at 8:00 a.m. EDT SAN DIEGO, Oct. 04, 2023 (GLOBE NEWSWIRE) -- 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, today announced that it plans to highlight new preliminary clinical and preclinical data from studies of nanatinostat and valganciclovir (Nana-val), its all-oral investigational therapy targeting Epstein-Barr virus (EBV)-associated cancers, during an R&D Day today, Wednesday, October 4, 2023, at 8:00 a.m. EDT. “We are pleased by the growing clinical data that we believe underscores the therapeutic potential of Nana-val’s innovative ‘Kick and Kill’ approach to target EBV-positive cancer cells and address the adverse survival outcomes seen with most EBV-associated cancers,” said Mark Rothera, President and Chief Executive Officer of Viracta. “The clinical responses and favorable safety profile observed in multiple relapsed or refractory EBV-positive lymphoma patient populations continue to be encouraging. New Stage 1 clinical data from patients in the PTCL cohort of the NAVAL-1 trial demonstrated preliminary overall and complete response rates of 40%, which are consistent with our previous Phase 1b/2 study data. Importantly, the combination of response rates and duration of response observed to date in these studies exceeds the current standard of care in this relapsed/refractory patient population. We are on track to complete Stage 2 of the PTCL cohort, targeting to engage with FDA in 2024 on additional requirements for a potential accelerated approval. In addition, we are excited about the emerging signal of dose response in patients with recurrent or metastatic EBV-positive nasopharyngeal carcinoma, now with responses observed at the higher dose levels without dose-limiting toxicities. We look forward to the evaluation of our novel split daily 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 its highest priority EBV+ lymphoma indications in the pivotal NAVAL-1 trial, namely, peripheral T-cell lymphoma (PTCL) and diffuse large B-cell lymphoma (DLBCL), as well as its advanced EBV+ solid tumor program in patients with recurrent or metastatic (R/M) EBV+ nasopharyngeal carcinoma (NPC). In addition, the R&D Day will feature presentations by expert key opinion leaders who will discuss the high unmet medical needs of EBV-associated lymphomas. External speakers will include: Pierluigi Porcu, M.D., Professor of Medical Oncology, Director of the Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Department of Medical Oncology at Thomas Jefferson UniversityRobert A. Baiocchi, M.D., Ph.D., Professor of Internal Medicine, Associate Director for Translational and Clinical Science in the Division of Hematology at The Ohio State University Key R&D Day Topics and Highlights Initial preliminary data from the pivotal NAVAL-1 clinical trial of Nana-val in patients with relapsed or refractory (R/R) EBV+ lymphoma As of the data cutoff date of June 30, 2023, initial results from the first five patients with R/R EBV+ PTCL treated with Nana-val showed an overall response rate (ORR) and complete response rate (CRR) of 40%.The EBV+ PTCL cohort met the efficacy threshold for expansion into Stage 2 of the study, which was based upon having achieved two objective responses within the first five of 10 patients to be enrolled in Stage 1 of the study.Median duration of response (DoR) has not yet been reached.Anticipated 2024 milestones: Completion of enrollment into Stage 2 of the R/R EBV+ PTCL cohort,Engagement with FDA on additional requirements for accelerated approval,Presentation of Stage 2 data. Additional response and durability assessments from the Phase 1b/2 trial (Study 201) of Nana-val in patients with R/R EBV+ lymphoma as of the May 4, 2023 data cutoff date Median DoR for patients with R/R EBV+ PTCL was 17.3 months with an ORR/CRR of 50%/38% (n=8).In patients with R/R EBV+ DLBCL, additional response assessments from a 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).Median DoR in the R/R EBV+ DLBCL cohort has not yet been reached, with three patients remaining in response and on continued study treatment with DoRs of 11.1 months (CR), 36.8 months (PR), and 41.9 months (CR).Additional follow-up further demonstrated that Nana-val was generally well tolerated with manageable, if not reversible, low-grade toxicities; the most commonly observed treatment-emergent adverse events were hematologic or gastrointestinal in nature as well as low-grade creatinine elevations. New interim clinical data in Phase 1b/2 study of Nana-val in advanced EBV+ solid tumors (Study 301) highlight the opportunity to dose escalate further with an innovative dosing regimen supported by new preclinical data to potentially drive additional responses in this patient population Enrollment completed through the fifth dose level of the Phase 1b dose escalation portion of the trial without any dose-limiting toxicities reported.Best responses to date included two PRs (one ongoing for more than seven months) at the higher dose levels plus five stable diseases in 17 patients with R/M EBV+ NPC.In a preclinical murine EBV+ gastric cancer xenograft model, split daily Nana-val dosing had superior anti-tumor activity than intermittent (four days on/three days off) once-daily dosing, which supports the evaluation of this split daily dosing (SDD) regimen in patients with advanced EBV+ solid tumors.Anticipated 2024 milestones: Up to three additional dose levels are planned with Nana-val on an SDD schedule to select a recommended Phase 2 dose,Initiation of the clinical trial’s randomized Phase 2 expansion cohort designed to evaluate Nana-val at the recommended Phase 2 Dose (RP2D) with or without pembrolizumab in patients with R/M EBV+ NPC,Initiation of the clinical 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. R&D Day Webcast InformationA live video webcast of the presentation will be available here and on the Investors section of the Viracta website under "Events and Webcasts". A replay of the presentation will be available approximately one hour after the presentation and will be archived and available for at least 30 days following the event at the same location. 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. This trial employs a Simon two-stage design where, in Stage 1, participants are enrolled into one of three prioritized 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 TumorsThis 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 CancersApproximately 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. About Viracta Therapeutics, Inc.Viracta is a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide. Viracta’s lead product candidate is an all-oral combination therapy of its proprietary investigational drug, nanatinostat, and the antiviral agent valganciclovir (collectively referred to 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 multiple subtypes of relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma (NAVAL-1), as well as a multinational, open-label Phase 1b/2 clinical trial for the treatment of patients with recurrent or metastatic (R/M) EBV+ nasopharyngeal carcinoma (NPC) and other advanced EBV+ solid tumors. Viracta is also pursuing the application of its “Kick and Kill” approach in other virus-related cancers. For additional information, please visit www.viracta.com. Forward-Looking StatementsThis communication contains "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding: the details, timeline and expected progress for Viracta's ongoing and anticipated clinical trials and updates regarding the same, the Company’s expectations of the significance and implications of the preliminary interim data from its clinical trials and preclinical studies disclosed herein, the Company’s expectations related to the FDA submission process and timelines and expectations regarding our target patient populations. Risks and uncertainties related to Viracta that may cause actual results to differ materially from those expressed or implied in any forward-looking statement include, but are not limited to: Viracta's ability to successfully enroll patients in and complete its ongoing and planned clinical trials; Viracta's plans to develop and commercialize its product candidates, including all oral combinations of nanatinostat and valganciclovir; the timing of initiation of Viracta's planned clinical trials; the timing of the availability of data from Viracta's clinical trials; previous preclinical and clinical results may not be predictive of future clinical results; the timing of any planned investigational new drug application or new drug application; Viracta's plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits, and market acceptance of Viracta's product candidates and Viracta's ability to manufacture or supply nanatinostat, valganciclovir, and pembrolizumab for clinical testing. If any of these risks materialize or underlying assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included under the caption "Risk Factors" and elsewhere in Viracta's reports and other documents that Viracta has filed, or will file, with the SEC from time to time and available at www.sec.gov. The forward-looking statements included in this communication are made only as of the date hereof. Viracta assumes no obligation and does not intend to update these forward-looking statements, except as required by law or applicable regulation. Investor Relations Contact:Ashleigh BarretoHead of Investor Relations & Corporate CommunicationsViracta Therapeutics, Inc.abarreto@viracta.com SOURCE Viracta Therapeutics, Inc.

Scientists have discovered a potential target for gastric cancers associated with Epstein-Barr Virus. Now, scientists at The Wistar Institute have discovered a potential target for gastric cancers associated with Epstein-Barr Virus; study results were published in the journal mBio. In the paper, Wistar's Tempera lab investigates the epigenetic characteristics of gastric cancer associated with the Epstein-Barr Virus: EBVaGC. In evaluating EBVaGC's epigenetics -- the series of biological signals associated with the genome that determines whether a given gene is expressed -- the Tempera lab highlights a target that could advance as a future treatment for this type of cancer. The work of Italo Tempera, Ph.D., associate professor in the Gene Expression & Regulation Program in the Ellen and Ronald Caplan Cancer Center, at The Wistar Institute, and collaborators demonstrates that an epigenetically active compound called decitabine disrupts the genome of EBVaGC by epigenetically modifying the cancer's DNA, a finding that offers the potential for a new approach to treating EBVaGC. "What we have identified is essentially a self-destruct button within this kind of cancer, and our paper shows that we figured out how to press that self-destruct button," said Tempera. "Normally, a latent virus that reactivates and starts to kill cells is a bad thing. But by switching that viral lytic process back on in these cancer cells by using epigenetic signaling, we're effectively getting the virus to kill the cancer cells that it's responsible for in the first place." The research -- supported by a research program project grant, otherwise known as a P01-series grant, from The National Institute of Health (NIH) -- includes scientists from The Wistar Institute, The Coriell Institute for Medical Research and Brigham and Women's Hospital of Harvard Medical School. In EBVaGC, the cancer cells' DNA is hypermethylated: the DNA contains a high percentage of cytosine with a 5-methyl group attached to it (relative to normal, unmethylated cytosine). As a silencer of gene expression, DNA methylation allows EBV to remain latent. This methylation pattern plays a significant role in regulating the EBV latency-lysis cycle within the cancer cells. DNA methylation, as an epigenetic factor, usually functions as a gene-silencing mechanism, particularly in certain regions of the genome; a methylated gene still exists within the genome -- methylation does not delete the genetic information -- but methylation can prevent the protein the gene encodes from being transcribed. To disrupt this epigenetic profile, the researchers turned to decitabine, a compound known for its ability to reduce DNA methylation levels (i.e., to hypomethylate the DNA). Tempera and his co-authors treated two cell lines that were derived from EBVaGC tumors with decitabine. The cell lines that received the treatment demonstrated massive reductions in DNA methylation across the genome relative to the control as assessed by a variety of epigenetic assay techniques. In observing the effects of decitabine treatment on EBVaGC, Tempera's team found a significant disruption of the cancer's epigenetic profile. The EBV genome within EBVaGC treated with decitabine resulted in widespread, mostly uniform hypomethylation of the EBVaGC epigenome (with a few regional exceptions). Tempera and his co-authors discovered that the hypomethylating effect of decitabine treatment reactivated the lytic cycle of the latent EBV in the cancer cells. Because lysis is lethal to cells, the epigenetic reactivation of lysis within gastric cancer associated with EBV offers a promising potential treatment for the specific subset of EBVaGC. "Now we know that we can use the epigenome of Epstein Barr Virus against the gastric cancer that it affects -- that's an exciting potential cancer therapy we have as a result of investigating the interplay between epigenetic patterns and disease lifecycle," explained Tempera.