Plasmablastic Lymphoma

First orphan drug designation for Nana-val granted in EBV+ solid tumors Seventh orphan drug designation for Nana-val globally; fifth granted by the FDA SAN DIEGO, Dec. 12, 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 the U.S. Food and Drug Administration (FDA) has granted an orphan drug designation (ODD) to Nana-val (nanatinostat in combination with valganciclovir), the company's all-oral investigational therapy targeting Epstein-Barr virus (EBV)-associated cancers, for the treatment of nasopharyngeal carcinoma (NPC). This represents the first ODD granted for Nana-val in Epstein-Barr virus-positive (EBV+) solid tumors and outside of EBV-associated lymphomas. The FDA previously granted Nana-val ODD for the treatment of T-cell lymphoma, post-transplant lymphoproliferative disorder, plasmablastic lymphoma, and EBV+ diffuse large B-cell lymphoma, not otherwise specified. "This orphan drug designation highlights the urgent need for new targeted treatment options for patients with rare diseases such as nasopharyngeal carcinoma, which is highly associated with EBV," said Mark Rothera, President and Chief Executive Officer of Viracta. "We are encouraged by the interim data from the Phase 1b/2 study of Nana-val in patients with recurrent or metastatic EBV-positive nasopharyngeal carcinoma, supporting the continued advancement of the study with a new split daily dosing regimen at higher doses. With sites open and enrolling the sixth dose cohort of the study, we are on track to expand into the Phase 2 portion in 2024. The growing clinical data in both the lymphoma and solid tumor settings, further validates the therapeutic potential of Nana-val to treat EBV-positive cancers, an underserved area of high unmet medical need.” The FDA’s Office of Orphan Products Development grants orphan status to drugs and biologics being developed to treat, diagnose, or prevent a rare disease or condition affecting fewer than 200,000 people in the U.S. ODD is designed to provide drug developers with various benefits to support the development of novel drugs, including the potential for seven years of market exclusivity upon FDA approval for the disease or condition for which the drug has ODD, eligibility for tax credits toward qualified clinical trial costs, exemptions from certain FDA application fees, reduced annual product user fees, clinical trial protocol design and drug development assistance, and potential qualification for expedited drug development programs. 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 select 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). Along with the U.S. Food and Drug Administration’s Project Optimus initiative, at the start of Phase 2, up to 40 patients with R/M EBV+ NPC will be randomized to receive either the RP2D or a dose level below the RP2D in a dose-optimization cohort. Once the RP2D has been confirmed, 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. 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 Forward-Looking Statements This 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 or will file, with the SEC from time to time and available at 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 Barreto Head of Investor Relations & Corporate Communications Viracta Therapeutics, Inc. abarreto@viracta.com SOURCE Viracta Therapeutics, Inc.

Data shared today on PK/PD and safety from additional KT-333 and KT-413 patient dose escalation cohorts show target knockdown at or near levels associated with clinical efficacy in preclinical tumor models No dose limiting toxicities observed in either program KT-333 data will be presented in a poster session at the International Conference on Malignant Lymphoma (ICML) on June 16 WATERTOWN, MA, USA I June 14, 2023 I Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation (TPD) to deliver novel small molecule protein degrader medicines, today shared new data demonstrating that its oncology programs KT-333 and KT-413 continue to demonstrate robust dose-dependent target knockdown in ongoing Phase 1a dose escalation clinical trials, with no dose limiting toxicities (DLTs) observed. The KT-333 clinical data will be presented in a poster at the International Conference on Malignant Lymphoma (ICML) on June 16, 2023, in Lugano, Switzerland. “Our focus this year for our ongoing KT-333 and KT-413 clinical trials will be to analyze the degradation profiles and safety of these first-in-class mechanisms and evaluate their biological and clinical impact in the appropriate patient populations. We continue to see encouraging data from the trials’ dose escalation phases as they show fidelity of PK/PD translation from preclinical models to patients, demonstrating target degradation without any dose limiting toxicities observed, and approaching levels we believe are needed to achieve antitumor activity,” said Nello Mainolfi, Founder, President and CEO, Kymera Therapeutics. “We are proud and excited to be the first company to have shown clinical translation of our degraders’ profiles across three programs and across multiple diseases and indications. We look forward to sharing additional data evaluating antitumor activity in the target patient populations for these programs later this year.” KT-333 STAT3 Program KT-333 is designed as a potent degrader of STAT3, a transcriptional regulator that has been linked to numerous cancers as well as to inflammatory and autoimmune diseases. KT-333 is being developed for the treatment of STAT3-dependent hematological malignancies and solid tumors. The Phase 1 clinical trial of KT-333 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-333 dosed weekly on 28-day cycles in adult patients with relapsed and/or refractory lymphomas, leukemias and solid tumors. As of the data cut-off of May 1, 2023, thirteen patients received a mean of five doses across the first four dose levels (DL1-4) of the trial, including patients with solid tumors as well as peripheral and cutaneous T-cell lymphoma. This includes 2 patients enrolled in DL4, which remains open to accrual. As of the cut-off date, there were no AEs reported in DL4. Data reported from the 3 completed dose levels (DL1-3) found: KT-333 Poster Presentation at ICML Title: Phase 1 Trial of KT-333, a STAT3 Degrader, in Patients with Relapsed or Refractory Lymphomas, Large Granular Lymphocytic Leukemia and Solid Tumors Presentation ID: 424 Session Time: 12:30 p.m. - 1:00 p.m. CEST, June 16, 2023 Location: Marquee Parco Ciani Presenter: Dr. Adam Olszewski, Lifespan Cancer Institute, Rhode Island Hospital KT-413 IRAKIMiD Program KT-413 is a novel heterobifunctional degrader targeting both IRAK4 and the IMiD substrates Ikaros and Aiolos. Designed to address both the IL-1R/TLR and Type 1 IFN pathways synergistically with a single molecule, KT-413 is in development for the treatment of MYD88-mutant B-cell malignancies. The Phase 1 clinical trial of KT-413 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-413 administered as an IV infusion once every 3 weeks to adult patients with relapsed and/or refractory B-cell non-Hodgkin's lymphomas. As of the data cut-off of June 1, 2023, DL1-3 have been completed and DL4 remains open to accrual. Five patients were treated across DL1-4 and received a mean of 2.2 doses. These included patients with transformed activated B-cell-like (ABC)-diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma, and plasmablastic lymphoma, all of whom were MYD88 wild-type except for one who had a MYD88 gain-of-function mutation. Data reported across the 4 DLs through the cut-off date show: Updated data with more details for both programs can be found in the Kymera corporate presentation on the Company’s website, as well as the KT-333 ICML poster presentation . About Kymera Therapeutics Kymera is a biopharmaceutical company pioneering the field of targeted protein degradation, a transformative approach to address disease targets and pathways inaccessible with conventional therapeutics. Kymera’s Pegasus platform is a powerful drug discovery engine, advancing novel small molecule programs designed to harness the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. With a focus on undrugged nodes in validated pathways, Kymera is advancing a pipeline of novel therapeutic candidates designed to address the most promising targets and provide patients with more effective treatments. Kymera’s initial programs target IRAK4, IRAKIMiD, and STAT3 within the IL-1R/TLR or JAK/STAT pathways, and the MDM2 oncoprotein, providing the opportunity to treat patients with a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors. Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” company by Fierce Biotech and has been recognized by both the Boston Globe and the Boston Business Journal as one of Boston’s top workplaces. For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn. SOURCE: Kymera Therapeutics

Data shared today on PK/PD and safety from additional KT-333 and KT-413 patient dose escalation cohorts show target knockdown at or near levels associated with clinical efficacy in preclinical tumor models No dose limiting toxicities observed in either program KT-333 data will be presented in a poster session at the International Conference on Malignant Lymphoma (ICML) on June 16 WATERTOWN, Mass., June 14, 2023 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation (TPD) to deliver novel small molecule protein degrader medicines, today shared new data demonstrating that its oncology programs KT-333 and KT-413 continue to demonstrate robust dose-dependent target knockdown in ongoing Phase 1a dose escalation clinical trials, with no dose limiting toxicities (DLTs) observed. The KT-333 clinical data will be presented in a poster at the International Conference on Malignant Lymphoma (ICML) on June 16, 2023, in Lugano, Switzerland. “Our focus this year for our ongoing KT-333 and KT-413 clinical trials will be to analyze the degradation profiles and safety of these first-in-class mechanisms and evaluate their biological and clinical impact in the appropriate patient populations. We continue to see encouraging data from the trials’ dose escalation phases as they show fidelity of PK/PD translation from preclinical models to patients, demonstrating target degradation without any dose limiting toxicities observed, and approaching levels we believe are needed to achieve antitumor activity,” said Nello Mainolfi, Founder, President and CEO, Kymera Therapeutics. “We are proud and excited to be the first company to have shown clinical translation of our degraders’ profiles across three programs and across multiple diseases and indications. We look forward to sharing additional data evaluating antitumor activity in the target patient populations for these programs later this year.” KT-333 STAT3 Program KT-333 is designed as a potent degrader of STAT3, a transcriptional regulator that has been linked to numerous cancers as well as to inflammatory and autoimmune diseases. KT-333 is being developed for the treatment of STAT3-dependent hematological malignancies and solid tumors. The Phase 1 clinical trial of KT-333 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-333 dosed weekly on 28-day cycles in adult patients with relapsed and/or refractory lymphomas, leukemias and solid tumors. As of the data cut-off of May 1, 2023, thirteen patients received a mean of five doses across the first four dose levels (DL1-4) of the trial, including patients with solid tumors as well as peripheral and cutaneous T-cell lymphoma. This includes 2 patients enrolled in DL4, which remains open to accrual. As of the cut-off date, there were no AEs reported in DL4. Data reported from the 3 completed dose levels (DL1-3) found: Plasma exposure increased with dose, reaching levels close to those predicted to be efficacious.KT-333 demonstrated dose-dependent STAT3 degradation with up to 88% mean maximum reduction in peripheral blood mononuclear cells (PBMCs), with evidence of STAT3 pathway inhibition and downregulation of inflammatory biomarkers in peripheral blood. Degradation profiles at DL-3 were near levels of knockdown that led to profound antitumor activity in preclinical models.No DLTs were observed in the study. KT-333 Poster Presentation at ICML Title: Phase 1 Trial of KT-333, a STAT3 Degrader, in Patients with Relapsed or Refractory Lymphomas, Large Granular Lymphocytic Leukemia and Solid TumorsPresentation ID: 424Session Time: 12:30 p.m. - 1:00 p.m. CEST, June 16, 2023 Location: Marquee Parco CianiPresenter: Dr. Adam Olszewski, Lifespan Cancer Institute, Rhode Island Hospital KT-413 IRAKIMiD Program KT-413 is a novel heterobifunctional degrader targeting both IRAK4 and the IMiD substrates Ikaros and Aiolos. Designed to address both the IL-1R/TLR and Type 1 IFN pathways synergistically with a single molecule, KT-413 is in development for the treatment of MYD88-mutant B-cell malignancies. The Phase 1 clinical trial of KT-413 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-413 administered as an IV infusion once every 3 weeks to adult patients with relapsed and/or refractory B-cell non-Hodgkin's lymphomas. As of the data cut-off of June 1, 2023, DL1-3 have been completed and DL4 remains open to accrual. Five patients were treated across DL1-4 and received a mean of 2.2 doses. These included patients with transformed activated B-cell-like (ABC)-diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma, and plasmablastic lymphoma, all of whom were MYD88 wild-type except for one who had a MYD88 gain-of-function mutation. Data reported across the 4 DLs through the cut-off date show: Plasma exposure increased with dose, reaching levels close to those predicted to be efficacious.KT-413 achieved dose-dependent degradation of up to 70% IRAK4 and 96-100% Ikaros and Aiolos in PBMC after a single dose. Degradation profiles at DL3-4 were consistent with knockdown levels associated with profound antitumor activity in preclinical models of MYD88 mutant lymphomas.No DLTs or drug-related neutropenia were observed in the study. Updated data with more details for both programs can be found in the Kymera corporate presentation on the Company’s website, as well as the KT-333 ICML poster presentation. About Kymera TherapeuticsKymera is a biopharmaceutical company pioneering the field of targeted protein degradation, a transformative approach to address disease targets and pathways inaccessible with conventional therapeutics. Kymera’s Pegasus platform is a powerful drug discovery engine, advancing novel small molecule programs designed to harness the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. With a focus on undrugged nodes in validated pathways, Kymera is advancing a pipeline of novel therapeutic candidates designed to address the most promising targets and provide patients with more effective treatments. Kymera’s initial programs target IRAK4, IRAKIMiD, and STAT3 within the IL-1R/TLR or JAK/STAT pathways, and the MDM2 oncoprotein, providing the opportunity to treat patients with a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors. Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” company by Fierce Biotech and has been recognized by both the Boston Globe and the Boston Business Journal as one of Boston’s top workplaces. For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements by Kymera Therapeutics regarding its: strategy, business plans and objectives for the IRAKIMiD and STAT3 degrader programs; plans and timelines for the preclinical and clinical development of its product candidates, including the therapeutic potential, clinical benefits and safety thereof; expectations regarding timing, success and data announcements of current ongoing preclinical and clinical trials. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of COVID-19 on countries or regions in which we have operations or do business, as well as on the timing and anticipated results of our current and future preclinical studies and clinical trials, supply chain, strategy and future operations; the delay of any current and future preclinical studies or clinical trials or the development of Kymera Therapeutics' drug candidates; the risk that the results of current preclinical studies and clinical trials may not be predictive of future results in connection with current or future preclinical and clinical trials, including those for KT-474, KT-333, KT-413 and KT-253; Kymera Therapeutics' ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of the Kymera Therapeutics' planned interactions with regulatory authorities; obtaining, maintaining and protecting its intellectual property; and Kymera Therapeutics' relationships with its existing and future collaboration partners. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 filed on May 4, 2023, as well as discussions of potential risks, uncertainties, and other important factors in Kymera Therapeutics' subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Kymera Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Kymera Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor Contact: Bruce Jacobs Chief Financial Officer investors@kymeratx.com 857-285-5300 Chris Brinzey Managing Director, Westwicke chris.brinzey@westwicke.com 339-970-2843 Media Contact: Todd Cooper Senior Vice President, Corporate Affairs media@kymeratx.com 857-285-5300