- Provides preclinical proof-of-concept data on efficacy of single-agent PV-10 for treatment of neuroblastoma
- Supports use of checkpoint inhibitors with PV-10 treatment backbone to further enhance activity in patients with relapsed and refractory neuroblastoma
KNOXVILLE, TN & NEW YORK, NY, Feb. 19, 2019 (GLOBE NEWSWIRE) -- Provectus (OTCQB: PVCT) and the Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC), a group of 10 top-tier academic medical centers developing new pediatric cancer therapies, today announced that OncoTargets and Therapy (OTT) has published preclinical results from in vitro and animal tumor model studies on PV-10 for the treatment of neuroblastoma. This work was led by Dr. Aru Narendran and his team at the University of Calgary’s POETIC Preclinical and Drug Discovery Laboratory. Prior preclinical and clinical studies by other researchers have shown that intratumoral injection of PV-10 can yield immunogenic cell death in adult solid tumors and stimulate tumor-specific reactivity in circulating T cells.1-4
This article, entitled “Potent in vitro and xenograft antitumor activity of a novel agent, PV-10, against relapsed and refractory neuroblastoma,” may be accessed at https://www.dovepress.com/potent-in-vitro-and-xenograft-antitumor-activity-of-a-novel-agent-pv-1-peer-reviewed-article-OTT.
According to the POETIC authors, “Our studies provide preclinical proof-of-concept data on the efficacy of PV-10 in neuroblastoma. Mechanistically, we have found that PV-10 acts by disrupting lysosomes, inducing cell cycle changes and initiating cell death by apoptosis. We have also identified several commonly used treatments with which PV-10 shows synergistic anti-tumor activity. Furthermore, we have validated the efficacy of PV-10 in vivo, using neuroblastoma xenograft mouse experiments. Our experiments, carried out in representative cell lines and in tumor bearing mice, provide evidence for the direct cytotoxic potential of PV-10, as well as mechanisms by which this agent may induce target modulatory effects in cancer cells. We have also identified agents that can be combined to generate treatment synergy, providing the framework for the formulation of early phase clinical trials. This, in addition to the expected immunostimulatory effect of PV-10 described previously, provides support for a potential approach where a PV-10 backbone regimen can be combined with agents such as immune checkpoint inhibitors to further enhance its activity in patients with relapsed or refractory neuroblastoma.”
Among the authors’ results:
- PV-10 is cytotoxic to neuroblastoma cell lines,
- Treatment with PV-10 disrupts lysosomes,
- Treatment with PV-10 induces both apoptosis and necrosis in neuroblastoma,
- PV-10 is synergistic with different anticancer agents,
- PV-10 induces radiosensitivity in neuroblastoma cell lines, and
- PV-10 leads to tumor regression in vivo.
Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, “These preclinical neuroblastoma data, together with studies completed by the POETIC Preclinical and Drug Discovery Laboratory on other refractory pediatric solid tumors, support the rationale for a first-in-children’s cancer trial of PV-10 for the treatment of relapsed and refractory solid tumor malignancies.”
About Neuroblastoma
As noted in the OTT article, the overall survival rate for children with pediatric solid tumors is lower than that for children with hematological malignancies.5 The most common extracranial pediatric solid tumor is neuroblastoma, which is a leading cause of death in children aged 1-4 years.6
About PV-10
Provectus’ lead investigational oncology drug, PV-10, the first small molecule oncolytic immunotherapy, can induce immunogenic cell death. PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and preclinical study for pediatric cancers. The U.S. Food and Drug Administration granted orphan drug designation to PV-10 for the treatment of neuroblastoma in 2018.
About the Pediatric Oncology Experimental Therapeutics Investigators' Consortium
The Pediatric Oncology Experimental Therapeutics Investigators' Consortium (POETIC) was founded in February 2003 by Dr. Tanya Trippett at Memorial Sloan Kettering Cancer Center and Dr. Lia Gore at the University of Colorado Cancer Center. POETIC is composed of ten large academic medical centers in North America with a major emphasis on comprehensive cancer care and research that provide the collaborative and research strength needed to complete intensive phase I and II studies. Each of the institutions is uniquely suited to complete early studies in the pediatric and adolescent populations. POETIC's assets include membership in NCI-designated Comprehensive Cancer Centers, on-site NIH-funded pediatric and/or general clinical translational research centers (CTRCs/CTSAs), and active collaborations with developmental therapeutics programs for adults at a majority of its member institutions. The availability of strong basic science and translational research programs at the institutions allows focus on the development and evaluation of new therapeutic strategies for patients with cancer and related disorders. POETIC's pediatric oncology studies focus on the biologic basis for anti-cancer therapy, and in particular, attempt to explore and evaluate novel agents and/or combinations of therapies early in clinical development as well as new approaches to targeted delivery. For additional information about POETIC, please visit the Consortium's website at www.poeticphase1.org.
About Provectus
Provectus Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company leading the development of a new class of drugs based on halogenated xanthenes, which are chemical small molecules. Information about the Company’s clinical trials can be found at the NIH registry, www.clinicaltrials.gov. For additional information about Provectus, please visit the Company's website at www.provectusbio.com.
References
1. Wachter et al. Functional Imaging of Photosensitizers using Multiphoton Microscopy. Proceedings of SPIE 4620, 143, 2002.
2. Liu et al. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget 7, 37893, 2016.
3. Qin et al. Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death. Cell Death and Disease 8, e2584, 2017.
4. Liu et al. T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model. PLoS One 13, e0196033, 2018.
5. Chen et al. Pediatric solid tumor genomics and developmental pliancy. Oncogene. 2015;34(41):5207–5215.
6. Moreno et al. Accelerating drug development for neuroblastoma – new drug development strategy: an innovative therapies for children with cancer, European network for cancer research in children and adolescents and international society of paediatric oncology Europe neu. Expert Opin Drug Discov. 2017; 12(8):1–11.
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