A Phase II, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) With Pembrolizumab (KEYTRUDA®) for Recurrent Glioblastoma or Gliosarcoma (CAPTIVE/KEYNOTE-192)

Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase II study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified oncolytic adenovirus, when delivered directly into the tumor followed by the administration of intravenous pembrolizumab (an immune checkpoint inhibitor) given every 3 weeks for up to 2 years or until disease progression.
Funding Source-FDA OOPD

Start Date06 Oct 2016

Sponsor / Collaborator

DNAtrix, Inc.

[+1]

100 Clinical Results associated with Tasadenoturev

100 Translational Medicine associated with Tasadenoturev

100 Patents (Medical) associated with Tasadenoturev

Literatures (Medical) associated with Tasadenoturev

05 Aug 2024·Neuro-Oncology

The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models

Article

Author: Gonzalez-Huarriz, Marisol ; Alonso, Marta M ; Hernaez, Mikel ; Ochoa, Maria C ; Hervás-Corpión, Irati ; van der Lugt, Jasper ; Venneti, Sriram ; Dhandapani, Laasya ; Koschmann, Carl ; Phoenix, Timothy N ; Allen, Joshua E ; Tallon-Cobos, Antonio Carlos ; Dun, Matthew D ; Fueyo, Juan ; Hernandez-Osuna, Reyes ; Gomez-Manzano, Candelaria ; Becher, Oren J ; Nazarian, Javad ; Patiño-García, Ana ; Gallego Perez-Larraya, Jaime ; Marrodan, Lucía ; Lacalle, Andrea ; Laspidea, Virginia ; García-Moure, Marc ; Mueller, Sabine ; Guruceaga, Elizabeth ; Zalacain, Marta ; Marco-Sanz, Javier ; Casares, Noelia ; Labiano, Sara ; Ausejo-Mauleon, Iker ; de la Nava, Daniel

AbstractBackgroundPediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated.MethodsThe production of functional viruses was assessed by immunoblotting and replication assays. The antitumor effect was evaluated in a panel of human and murine pHGG and DMG cell lines. RNAseq, the seahorse stress test, mitochondrial DNA content, and γH2A.X immunofluorescence were used to perform mechanistic studies. Mouse models of both diseases were used to assess the efficacy of the combination in vivo. The tumor immune microenvironment was evaluated using flow cytometry, RNAseq, and multiplexed immunofluorescence staining.ResultsThe Delta-24-RGD/ONC201 combination did not affect the virus replication capability in human pHGG and DMG models in vitro. Cytotoxicity analysis showed that the combination treatment was either synergistic or additive. Mechanistically, the combination treatment increased nuclear DNA damage and maintained the metabolic perturbation and mitochondrial damage caused by each agent alone. Delta-24-RGD/ONC201 cotreatment extended the overall survival of mice implanted with human and murine pHGG and DMG cells, independent of H3 mutation status and location. Finally, combination treatment in murine DMG models revealed a reshaping of the tumor microenvironment to a proinflammatory phenotype.ConclusionsThe Delta-24-RGD/ONC201 combination improved the efficacy compared to each agent alone in in vitro and in vivo models by potentiating nuclear DNA damage and in turn improving the antitumor (immune) response to each agent alone.

01 Jun 2024·Journal of NeuroVirology

A viral attack on brain tumors: the potential of oncolytic virus therapy

Review

Author: Mokhtarpour, Kasra ; Rezaei, Nima ; Akbarzadehmoallemkolaei, Milad

Managing malignant brain tumors remains a significant therapeutic hurdle that necessitates further research to comprehend their treatment potential fully. Oncolytic viruses (OVs) offer many opportunities for predicting and combating tumors through several mechanisms, with both preclinical and clinical studies demonstrating potential. OV therapy has emerged as a potent and effective method with a dual mechanism. Developing innovative and effective strategies for virus transduction, coupled with immune checkpoint inhibitors or chemotherapy drugs, strengthens this new technique. Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors.

01 Mar 2024·Molecular Therapy

Chimeric oncolytic adenovirus evades neutralizing antibodies from human patients and exhibits enhanced anti-glioma efficacy in immunized mice

Article

Author: Fueyo, Juan ; Fan, Xuejun ; Kim, Debora ; Ene, Chibawanye I ; Lang, Frederick F ; Lopez-Rivas, Andres R ; Singh, Sanjay K ; Gumin, Joy ; Sohoni, Sagar S ; Nguyen, Teresa T ; Gomez-Manzano, Candelaria ; Jiang, Hong ; Alonso, Marta M ; Shin, Dong Ho ; Parthasarathy, Akhila ; Gillard, Andrew G

Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent virus neutralization and maximize oncolysis. Thus, we generated a chimeric virus, Delta-24-RGD-H43m, by replacing the capsid protein HVRs from the serotype 5-based Delta-24-RGD with those from the rare serotype 43. Delta-24-RGD-H43m evaded neutralizing anti-Ad5 antibodies and conferred a higher rate of long-term survival than Delta-24-RGD in glioma-bearing mice. Importantly, Delta-24-RGD-H43m activity was significantly more resistant to neutralizing antibodies present in sera of glioma patients treated with Delta-24-RGD during a phase 1 clinical trial. These findings provide a framework for a novel treatment of glioma patients that have developed immunity against Delta-24-RGD.

News (Medical) associated with Tasadenoturev

01 May 2023

·www.prnewswire.com

Significant Positive Shift in the Glioma Market with 13% CAGR During the Study Period (2019-2032) Expected by Analysts at DelveInsight

The dynamics of the glioma market are anticipated to change in the coming years owing to the positive outcomes of the emerging pipeline candidates during the developmental stage by key players, such as Bayer, VBL Therapeutics, Candel Therapeutics, AstraZeneca, DNAtrix, DelMar Pharmaceuticals, Chimerix, KaryoPharma, VBI Vaccines, Kazia Therapeutics, and others LAS VEGAS, May 1, 2023 /PRNewswire/ -- DelveInsight's Glioma Market Insights report includes a comprehensive understanding of current treatment practices, glioma emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan]. Key Takeaways from the Glioma Market Report As per DelveInsight analysis, the glioma market size in the 7MM was approximately USD 1 billion in 2022. According to the assessment done by DelveInsight, the estimated total incident glioma cases in the 7MM were approximately 47K in 2022. Leading glioma companies such as Bayer, Chimerix, Aivita Biomedical, Denovo Biopharma, Northwest Therapeutics, VBL Therapeutics, Laminar Pharmaceuticals, MedImmune, DNAtrix, Immunomic Therapeutics, Imvax, MimiVax, CNS Pharmaceuticals, Epitopoietic Research Corporation (ERC), Istari Oncology, SonALAsense, Kintara Therapeutics, Bristol Myers Squibb, Medicenna Therapeutics, BioMimetix, Eisai and Merck Sharp & Dohme, Kazia Therapeutics, Oblato, Genenta Science, Enterome, Inovio Pharmaceuticals, Karyopharm Therapeutics, VBI Vaccines, TME Pharma, Day One Biopharmaceuticals, Servier, Orbus Therapeutics, TVAX Biomedical, AnHeart Therapeutics, Beigene, SpringWorks Therapeutics, Forma Therapeutics, Hoffmann-La Roche, Incyte Corporation, Eli Lilly, and others are developing novel glioma drugs that can be available in the glioma market in the coming years. The promising glioma therapies in the pipeline include Regorafenib, ONC201, AV-GBM-1, Enzastaurin (DB-102), DCVax-L, Ofranergene Obadenovec (VB-111), LAM561 (2-OHOA), MEDI4736 (durvalumab), Tasadenoturev (DNX-2401), ITI-1000 (pp65 DC Vaccine), IGV-001, SurVaxM, Berubicin, GLIOVAC (Sitoiganap), Lerapolturev + Pembrolizumab, SONALA-001 + Exablate 2.0 Device, VAL-083 (dianhydrogalactitol), Pomalidomide, MDNA55, BMX-001, Lenvatinib ± Pembrolizumab, Paxalisib (GDC-0084), OKN-007, Temferon, EO2401, INO-5401+ INO-9012+ LIBTAYO (cemiplimab), Selinexor (KPT-330), Olutasidenib (FT-2102), VBI-1901, NOX-A12 (Olaptesed Pegol), Tovorafenib (DAY101), Vorasidenib (AG-881), Eflornithine, TVI-Brain-1, AB-218, BGB-290, Mirdametinib, FT-2102 (Olutasidenib), Vinblastine + Bevacizumab, Cobimetinib, PEMAZYRE (Pemigatinib), VERZENIO (abemaciclib) , and others. In December 2022, Chimerix announced the successful launch of the ONC201 Phase III ACTION study in patients with H3 K27M-mutant glioma. In June 2022, Day One Biopharmaceuticals announced positive initial data from its pivotal Phase II (FIREFLY-1) study with tovorafenib (DAY101) in relapsed pediatric low-grade glioma (pLGG). Discover which therapies are expected to grab the major glioma market share @ Glioma Market Report Glioma Overview Glioma is the most common kind of glial cell tumor in the central nervous system (CNS). Gliomas are infiltrative tumors that affect the brain tissue surrounding them. Glioblastoma is the most hazardous type of brain tumor, whereas pilocytic astrocytomas are the least dangerous. Previously, diffuse gliomas were classified into subgroups and grades depending on histopathologies, such as diffuse astrocytomas, oligodendrogliomas, or mixed gliomas/oligoastrocytomas. The specific etiology of glioma, like other primary brain tumors, remains unknown. However, certain variables may increase the risk of getting a brain tumor. Glioma symptoms vary depending on tumor type, size, location, and growth rate. Some common glioma symptoms include headache, nausea or vomiting, memory loss, urine incontinence, speech problems, and others. A medical history and a physical examination are used for glioma diagnosis. Glioma Epidemiology Segmentation DelveInsight estimates that there were approximately 47K incident cases of glioma in the 7MM in 2022. As per our analysis, the United States contributed to the largest incident population of glioma, acquiring ~40% of the 7MM in 2022. The glioma market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Total glioma incident cases Glioma grade-specific cases Glioma age-specific cases Glioma type-specific cases Download the report to understand which factors are driving glioma epidemiology trends @ Glioma Epidemiological Insights Glioma Treatment Market Glioma treatment is based on the type of glioma, its size and location, and the patient's unique characteristics. Chemotherapy and radiation therapy will be administered after surgery, particularly in individuals when the tumor cannot be removed entirely because it has invaded critical parts of the brain or is inaccessible. The typical glioma treatment protocol comprises surgery, chemotherapy, and radiation. Chemotherapy may include carmustine (BCNU), lomustine (CCNU), or gleostine (generic), cisplatin, carboplatin, etoposide, and irinotecan in case of low-grade glioma whereas temozolomide (TEMODAR) is the standard chemotherapy used in case of high-grade glioma majorly, Gliadel wafer implants (biodegradable discs injected with BCNU) are usually given as adjunctive treatment after surgery, although usage of Gliadel wafers remains a point of controversy due to its questionable survival benefits. Avastin (Genentech) and Temodar/Temodal (Merck), among others, are approved medications for HGG. However, due to patent expiration, the generic version of Temodar and biosimilars of Avastin are available on the glioma market. As generics and biosimilars are more cost-effective for patients than new medicines, intense competition exists among them. Furthermore, due to a lack of knowledge concerning bevacizumab's overall survival benefit, it is not recommended in unselected patients with newly diagnosed GBM. Currently, only one medication for LGG is approved, Tafinlar (dabrafenib) plus Mekinist (trametinib). Moreover, the current therapeutic market lacks a viable method for curing glioblastoma; therefore, the survival rate of people diagnosed with glioma remains poor. Glioma is incurable, and treatment choices are limited. Furthermore, the tumor has a high recurrence rate and a poor patient prognosis. In addition, there is currently no approved therapy for the unmethylated MGMT patient pool. To know more about glioma treatment guidelines, visit @ Glioma Management Glioma Therapies and Key Companies Regorafenib: Bayer ONC201: Chimerix AV-GBM-1: Aivita Biomedical Enzastaurin (DB-102): Denovo Biopharma DCVax-L: Northwest Therapeutics Ofranergene Obadenovec (VB-111): VBL Therapeutics LAM561 (2-OHOA): Laminar Pharmaceuticals MEDI4736 (durvalumab): MedImmune Tasadenoturev (DNX-2401): DNAtrix ITI-1000 (pp65 DC Vaccine): Immunomic Therapeutics IGV-001: Imvax SurVaxM: MimiVax Berubicin: CNS Pharmaceuticals GLIOVAC (Sitoiganap): Epitopoietic Research Corporation (ERC) Lerapolturev + Pembrolizumab: Istari Oncology SONALA-001 + Exablate 2.0 Device: SonALAsense VAL-083 (dianhydrogalactitol): Kintara Therapeutics Pomalidomide: Bristol Myers Squibb MDNA55: Medicenna Therapeutics BMX-001: BioMimetix Lenvatinib ± Pembrolizumab: Eisai and Merck Sharp & Dohme Paxalisib (GDC-0084): Kazia Therapeutics OKN-007: Oblato Temferon: Genenta Science EO2401: Enterome INO-5401+ INO-9012+ LIBTAYO (cemiplimab): Inovio Pharmaceuticals Selinexor (KPT-330): Karyopharm Therapeutics VBI-1901: VBI Vaccines NOX-A12 (Olaptesed Pegol): TME Pharma Tovorafenib (DAY101): Day One Biopharmaceuticals Vorasidenib (AG-881): Servier Eflornithine: Orbus Therapeutics TVI-Brain-1: TVAX Biomedical AB-218: AnHeart Therapeutics BGB-290: Beigene Mirdametinib: SpringWorks Therapeutics FT-2102 (Olutasidenib): Forma Therapeutics Vinblastine + Bevacizumab: Hoffmann-La Roche Cobimetinib: Hoffmann-La Roche PEMAZYRE (Pemigatinib): Incyte Corporation VERZENIO (abemaciclib): Eli Lilly Learn more about the FDA-approved drugs for glioma @ Drugs for Glioma Treatment Glioma Market Dynamics Glioma market growth can be ascribed to various factors, including an aging population, evolving research, better diagnostic tests, developing surgical procedures, improved radiotherapy techniques, and novel systemic medicines. Commercially, there is a greater emphasis on high-grade glioma than low-grade glioma because patients with low-grade glioma often live longer than those with high-grade glioma. As a result, just a few therapies are in late-stage studies, while the majority are in early-stage trials. In the case of GBM, on the other hand, the pipeline is robust, with numerous potential therapies in late and mid-stage research that have yet to be marketed. The pipeline includes drugs with varied modes of action and administration routes. It is interesting to note that the emerging market of glioma includes budding gene therapy, i.e., ofranergene obadenovec (VB-111) by VBL Therapeutics, followed by four vaccine/immunotherapy candidates such as VBI-1901, AV-GBM-1 and ITI-1000 (pp65 DC Vaccine), tasadenoturev (DNX-2401) by VBI Vaccines, Aivita Biomedical, Immunomic Therapeutics, and DNAtrix, respectively, and these therapies are going to alter the glioma market dynamics in the upcoming years. The current glioma market has been categorized based on the dominant treatment pattern across the 7MM, which shows slight variances in the overall prescription pattern. The forecast model considers surgery, chemotherapy/radiation therapy, bevacizumab + radiotherapy/chemotherapy, and OPTUNE with temozolomide. The anticipated launch of new therapies and improved integration of early patient screening, medication in secondary care and other clinical settings, research on optimum implementation methods, and increased awareness may eventually facilitate the development of successful treatment alternatives. However, there are a few challenges to the timely identification and treatment of these patients, such as a lack of a reliable biomarker that can aid in diagnosis and patient classification and identifying recurrence and signaling medication response. Furthermore, the failure rate of high-phased drug trials is significant, making it impossible to predict trial success, exacerbating the need for medicines that could assist ease the patient segment with this severe kind of cancer. Scope of the Glioma Market Report Therapeutic Assessment: Glioma current marketed and emerging therapies Glioma Market Dynamics: Conjoint Analysis of Emerging Glioma Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's Views, Analyst's Views, Glioma Market Access and Reimbursement Discover more about glioma drugs in development @ Glioma Clinical Trials Table to Contents Related Reports Glioma Epidemiology Forecast Glioma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted glioma epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Glioma Pipeline Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key glioma companies, including PTC Therapeutics, Ono Pharmaceuticals, Philogen, SpringWorks Therapeutics, Xennials Therapeutics, AnHeart Therapeutics, Istari Oncology, among others. High-Grade Glioma Pipeline High-Grade Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key high-grade glioma companies, including PTC Therapeutics, Aadi, Lee's Pharmaceutical, among others. Malignant Glioma Pipeline Malignant Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key malignant glioma companies, including Bexion Pharmaceuticals, Inc., Lee's Pharmaceutical Limited, Merck & Co, Oblato, Inc., OncoSynergy, Inc, among others. Recurrent Malignant Glioma Pipeline Recurrent Malignant Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key recurrent malignant glioma companies, including Bexion Pharmaceuticals, Inc., Merck, Oblato, OncoSynergy, Inc, among others. Glioblastoma Pipeline Glioblastoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key glioblastoma companies, including AstraZeneca, BioNTech, Merck, Pfizer, Roche, among others. 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It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

Phase 3Phase 2VaccineImmunotherapy

04 Mar 2021

·www.biospace.com

DNAtrix Announces First Patient Dosed in Clinical Study of DNX-2440, an OX40 Ligand Expressing Immunotherapy, in Colorectal Cancer and Other Cancers with Liver Metastasis

HOUSTON, March 4, 2021 /PRNewswire/ --DNAtrix, Inc. a biotech company advancing virus-driven immunotherapies for cancer, today announced the treatment of the first patient in a Phase 1 dose-escalation and dose-expansion study of DNX-2440, an OX40 ligand encoding oncolytic adenovirus, in patients with resectable liver metastasis. Expression of OX40 ligand on the surface of tumor cells is expected to enhance anti-tumor immune responses by providing costimulatory signals to T cells within the tumor microenvironment. "We are excited to clinically explore the potential of one of our immunotherapy drug candidates, which is based on our proprietary adenovirus platform technology, in additional cancer indications," said Jeffrey Knapp, chief executive officer of DNAtrix. "Our preclinical work with DNX-2440 has demonstrated that infection of human tumor cell lines with this agent leads to viral replication, high level expression of OX40 ligand on tumor cells and effective tumor cell killing. Mouse tumor models showed specific anti-tumor immune memory, abscopal effect, and improved survival. This two-part clinical study is designed to directly demonstrate the activity of DNX-2440 and potential as therapy for colorectal cancer, as well as data with other tumor types where liver metastases occur." The Phase 1 clinical trial of DNX-2440 will be conducted in 24-30 patients with resectable multifocal (≥ 2 lesions) liver metastasis, who are scheduled to have liver resection with curative-intent. Patients will receive two sequential (2 weeks apart) intra-tumoral injections of DNX-2440 into a liver metastasis prior to surgery for liver resection to evaluate safety and biological endpoints. The first part of the Phase 1 study is a dose-escalation phase evaluating three different dose levels of DNX-2440 in 12-18 patients with liver metastasis from tumors of various origins. Following the completion of dose-escalation, the selected dose will be further evaluated in an expansion phase where DNX-2440 will be administered using the same schedule to 12 patients with colorectal cancer liver metastasis. The primary endpoint of the study is to establish safety and identify a maximum tolerated dose. Secondary endpoints include evaluating tumor cell killing of injected and uninjected tumors, determining viral replication in the injected tumor and measuring local and systemic anti-tumor immune responses. Daniel A. Anaya, M.D., FACS, head of the Hepatobiliary Group and chief of the Division of GI Surgery in the Department of Gastrointestinal Oncology at the Moffitt Cancer Center, and principal investigator of the study, added, "DNX-2440 is an innovative therapy that has shown promising preclinical results, including durable tumor responses. As a leading cancer center, we are committed to providing cutting-edge treatment approaches in our fight against cancer and are pleased to launch this collaborative clinical study." About DNX-2440 DNX-2440 is an oncolytic adenovirus expressing the immune modulator OX40 ligand, a powerful costimulatory molecule known to enhance T cell responses directed to tumors. DNX-2440 is in Phase 1 clinical testing following the demonstration of anti-cancer activity in preclinical studies, including tumor reductions, immune memory, and abscopal effect. About DNAtrix DNAtrix is a privately held biotech company developing virus-driven immunotherapies to treat cancer. Its proprietary adenovirus platform is based on an engineered version of the common cold virus that is designed to selectively infect and kill cancer cells while leaving healthy cells unharmed. The company's lead product candidate is DNX-2401, which will enter into a global pivotal Phase 3 clinical study for patients with recurrent glioblastoma. DNX-2401 is also being evaluated in a Phase 1 study for diffuse intrinsic pontine glioma, for which it has received FDA Fast Track and Rare Pediatric Disease designations. A second product candidate, DNX-2440, is in Phase 1 clinical testing in patients with colorectal and other cancers with liver metastasis. The company's investors include Morningside Ventures and Mercury Fund. For more information, please visit the company website at . Investor and Media Contacts: Sylvia Wheeler Wheelhouse Life Science Advisors swheeler@wheelhouselsa.com Alexandra Santos Wheelhouse Life Science Advisors asantos@wheelhouselsa.com

CollaborateSmall molecular drugImmunotherapyFast Track

11 Feb 2021

·www.biospace.com

DNAtrix Announces Preclinical Data Demonstrating Anti-Tumor Activity of DNX-2401 in Models of Pediatric Tumors (AT/RT and CNS-PNET) Published in Clinical Cancer Research

HOUSTON, Feb. 11, 2021 /PRNewswire/ -- DNAtrix, a biotech company advancing virus-driven immunotherapies for cancer, today announced preclinical data evaluating the use of DNX-2401 against the pediatric brain malignancies atypical teratoid/rhabdoid tumor (AT/RT) and primitive neuroectodermal tumors (PNETs) was published in Clinical Cancer Research. The data demonstrate that the oncolytic immunotherapy, DNX-2401 (tasadenoturev; Delta-24-RGD), induces a potent anti-tumor immune response, hinders the development of disseminated disease, and leads to longer survival in these difficult-to-treat tumors. "These preclinical data for DNX-2401 show encouraging signals of anti-tumor activity against devastating CNS cancers that we had not previously studied," said Jeffrey Knapp, chief executive officer of DNAtrix. "We now have preclinical and clinical data of DNX-2401's efficacy across a range of difficult-to-treat adult and pediatric tumors, thus further establishing the activity of this potent immunotherapy. We look forward to the continued advancement of DNX-2401, as well as our pipeline of other oncolytic immunotherapies being developed for the treatment of solid tumors." The administration of DNX-2401 resulted in extended overall survival in early and advanced PNET and AT/RT mouse models, including models of disseminated disease. Importantly, DNX-2401 also generated a proinflammatory environment at tumor sites by boosting anti-tumor immune responses and inducing the secretion of damage-associated molecular patterns (DAMPs) into the extracellular medium by infected tumor cells. Marta Alonso, Ph.D., associate professor at the Clinic University of Navarra-CIMA in Pamplona, Spain, added, "AT/RTs and CNS-PNETs are aggressive pediatric brain tumors that are associated with poor survival and have few therapeutic options. Based on promising clinical data of DNX-2401 in adult glioblastoma and pediatric diffuse intrinsic pontine glioma (DIPG), we evaluated its activity in AT/RT and CNS-PNET. These preclinical data demonstrate in vivo efficacy of DNX-2401 in established models that recapitulate important features of these tumors, including models for disseminated AT/RT lesions and in immunocompetent humanized mice. These data underscore the therapeutic potential of DNX-2401 and provide a strong foundation for translation to the clinical setting for these indications." About DNX-2401 DNX-2401 is an oncolytic adenovirus engineered specifically to infect, replicate in, and directly kill cancer cells, as well as elicit a broader anti-tumor immune response. DNX-2401 is currently being evaluated as a potential treatment for highly aggressive brain tumors, including recurrent glioblastoma in adults and newly-diagnosed diffuse intrinsic pontine glioma (DIPG) in children. Clinical studies have demonstrated that DNX-2401 was well tolerated and extended survival for patients with recurrent glioblastoma. DNX-2401 has been granted Fast Track and Orphan designation by the FDA and PRIME and Orphan designation by the EMA. About DNAtrix DNAtrix is a privately held biotech company developing virus-driven immunotherapies to treat cancer. Its proprietary adenovirus platform is based on an engineered version of the common cold virus that is designed to selectively infect and kill cancer cells while leaving healthy cells unharmed. The company's lead product candidate is DNX-2401, which will enter into a global pivotal Phase 3 clinical study for patients with recurrent glioblastoma. DNX-2401 is also being evaluated in a Phase 1 study for diffuse intrinsic pontine glioma, for which it has received FDA Fast Track and Rare Pediatric Disease designations. A second product candidate, DNX-2440, is in Phase 1 clinical testing in patients with colorectal and other cancers with liver metastasis. The company's investors include Morningside Ventures and Mercury Fund. For more information, please visit the company website at . Investor and Media Contacts: Sylvia Wheeler Wheelhouse Life Science Advisors swheeler@wheelhouselsa.com Alexandra Santos Wheelhouse Life Science Advisors asantos@wheelhouselsa.com

ImmunotherapyFast Track

100 Deals associated with Tasadenoturev

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Malignant Glioma	Phase 1	US	DNAtrix, Inc.	01 Feb 2009
Glioma	Phase 1	-	Merck Sharp & Dohme Corp.	-
Brain Stem Glioma	Preclinical	ES	Clínica Universidad de Navarra	26 May 2017
Recurrent Glioblastoma	Preclinical	US	DNAtrix, Inc.	06 Oct 2016
Ovarian Cancer	Preclinical	US	University of Michigan Comprehensive Cancer Center	-
Brain Stem Glioma	Discovery	ES	DNAtrix, Inc.	26 May 2017
Diffuse Intrinsic Pontine Glioma	Discovery	ES	DNAtrix, Inc.	26 May 2017
Gliosarcoma	Discovery	US	DNAtrix, Inc.	06 Oct 2016
Gliosarcoma	Discovery	CA	DNAtrix, Inc.	06 Oct 2016
Recurrent Glioblastoma	Discovery	CA	DNAtrix, Inc.	06 Oct 2016

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02798406 (phase 1/2 trial, Pubmed \| Nat Med)	Phase 1/2	Recurrent Glioblastoma	49	DNX-2401 + Pembrolizumab	(bjlwoapaai) = fdfgnfpqej pghbmcguej (cbfiyiands, 4.2 - 20.7) View more	Positive	01 Jun 2023
EUCTR2016-001577-33-ES \| NCT03178032 (Pubmed \| Br Dent J)	Phase 1	Diffuse Intrinsic Pontine Glioma	12	DNX-2401	(uulviioxmk) = ggtbxpmipc pyzozvhbjt (gqzsegiskw )	Positive	30 Jun 2022
NCT02798406 (KEYNOTE-192 \| CAPTIVE, PRNewswire) Manual	Phase 2	Recurrent Glioblastoma	-	Tasadenoturev+Pembrolizumab	(dzcaksvkwg) = kozfpviskp adzyxlqyvs (lhcmxzflgf ) View more	Positive	20 Nov 2020
NCT02798406 (KEYNOTE-192 \| CAPTIVE, PRNewswire) Manual	Phase 2	Recurrent Glioblastoma	-	Lomustine+Temozolomide	-	Positive	20 Nov 2020
NCT02197169 (ASCO2017)	Phase 1	Recurrent Glioblastoma	27	DNX-2401	(uxnykjzvth) = The most frequent grade 3-4 AEs across treatment groups were fatigue twfxzhmyiu (xeapxyalrc ) View more	Positive	30 May 2017
NCT03178032 (Pubmed \| Breast Cancer Res Treat)	Phase 1	Brain Stem Neoplasms	12	Delta-24-RGD	xqjgrnveqv(cndvdwhrsl) = wzqfjuakdf frozrivxys (wozoujhwba )	-	19 Sep 2007

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