Company
Portfolio Data
Back to Company SearchVASCULAR VISION PHARMACEUTICAL CO
Address
5 FOX GLOVE CTWYNANTSKILL, NY, 12198-7801
USA
UEI: CZQSE8JMCEN1
Number of Employees: 3
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
SBIR/STTR Involvement
Year of first award: 2005
7
Phase I Awards
1
Phase II Awards
14.29%
Conversion Rate
$1,091,659
Phase I Dollars
$2,027,049
Phase II Dollars
$3,118,708
Total Awarded
Awards
Sulfated Non-Anticoagulant Heparin Nanoparticle (VVP728) for Sickle Cell Disease Management
Amount: $2,027,049 Topic: NHLBI
Summary: Sickle cell disease (SCD) primarily afflicts African-Americans in the US, exacerbating an existing health disparity. Approximately 1 in 13 African-American babies is born with the sickle cell trait and ~100,000 individuals live with SCD. Along with a range of adverse physiological effects resulting in painful vaso-occlusive crises (VOC), patients suffer from poorer quality of life and a significantly decreased life expectancy (only 54 years). A handful of drugs are currently FDA approved; however, despite their benefits, there are drawbacks. Hydroxyurea is effective for two genotypes accounting for only 60% of SCD patients and the frequency of painful episodes is reduced by only 50%. Newer drugs (L-glutamine, crizanlizumab, voxelotor) lack improvement in hemoglobin levels or lack reduction in number of VOCs. Alternative treatments, such as chronic blood transfusion therapy or hematopoietic stem cell transplantation, can provide benefit but can also lead to serious complications or impose roadblocks including cost and finding matching donors. There is a significant unmet need for potent, novel multi-modal SCD therapeutics that achieve optimal efficacy, safety, and quality of life. To meet this need, Vascular Vision proposes a sulfated oxidized non-anticoagulant low molecular weight heparin (S-NACH) to provide an extensive range of bioactivities without causing bleeding, a common dose limiting effect associated with the clinical use of low molecular weight heparins. Proof-of-concept in vitro and in vivo preclinical studies have established efficacy through multiple modes including anti-adhesion, anti-inflammation, anti-sickling, vascular antithrombotic, and endothelial relaxation. Our subcutaneous nanoformulation (VVP728) demonstrated improved SCD pharmacodynamics. This SBIR Phase II proposes IND-enabling studies to determine tolerability of nanoformulated S-NACH (VVP728) in support of first in human trials (FIH) through the following Specific Aims: Aim 1. Scale up manufacturing to establish PK/PD and support IND-enabling studies. To support preclinical PK/PD and GLP toxicology testing, we will scale up the manufacturing of research grade drug substance (DS: S-NACH) and drug product (DP: VVP728). Milestones: (1) Develop analytical and bioanalytical methods, (2) Deliver research grade DS (2 kg) and DP (1.5 kg) under GLP, and (3) Determine PK and vascular antithrombotic activity in rats and PD in Townes SCD mouse model for DS vs DP. Aim 2: Determine GLP safety profile of S-NACH. We will conduct dose range finding studies (7 days) and GLP repeated dose studies (28 days) in rodent (rat) and non-rodent (dog) as well as in vitro assessments of protein binding, transporter and CYP inhibition, effect on hERG current in transfected HEK-293 cells, and genotoxicity. In vivo central nervous system (CNS: rats), respiratory (dogs), and cardiovascular (dogs) assessments will be completed. Milestones: (1) Establish protein binding and potential for inhibition of transporters and CYPs by S-NACH, (2) Identify target organs of toxicity to inform selection of dose in FIH study, and (3) Establish genotoxic potential of S-NACH in Bacterial-Reverse Mutation and In Vitro Micronucleus Assays.
Tagged as:
SBIR
Phase II
2022
HHS
NIH
Multi-Modal Mechanisms of Novel Sulfated Non Anticoagulant Heparin inSickle Cell Disease Management
Amount: $215,058 Topic: NHLBI
AbstractThe pathogenesis of Sickle cell diseaseSCDcomprises a complex interplay of factors associated with vascular endothelial activationintense inflammationand increased sickle cell adhesionMicrovascular occlusion in SCD is initiated by adhesion of sickle red blood cellsRBCsto the endotheliumleading to acute painful vasoocclusive crisisVOCand the clinical morbidity in SCDTreatment strategies include the use of chronic blood transfusionhydroxyureaand bone marrow transplantation but these treatments are not without significant side effectsBecause of the inherent complexity of this diseaseit is unlikely that a single therapeutic strategy will be beneficialIn this Phase I Application we propose to study a sulfated oxidized non anticoagulant low molecular weight heparinLMWHreferred to as S NACHwith an extensive range of bioactivities that constitute a multi modal approach to management of SCDOf significant importance to the development of this agent is the fact that S NACH exerts these activities without causing hemostaticbleedingside effects that are associated with the clinical use of LMWHsAdditionallyS NACH has been optimized to directly interact with hemoglobin to exert desirable therapeutic benefitsLMWHs have been tested for clinical management of VOC in SCDand we have previously shown that LMWH tinzaparin significantly shortened both duration of VOC crisis and hospitalization byand resulted in significant and more rapid reduction of painHoweverdespite the demonstrated potential benefits of LMWHs for SCDsafety concerns associated with the narrow therapeutic indexbleeding risksare a major barrier to dose escalation optimization of treatmentsConsequentlyfurther studies are clearly warrantedOur novel multi modal compound S NACH provides the opportunity to pursue studies that will conclusively establish safety and efficacyIn this proposalwe will perform proof of concept in vitro and in vivo pre clinical studieswhich would expand on our rich body of pilot data and establish efficacy in a mouse model of SCDand lay critical foundation for the potential advancement of this agent to clinical applicationsUpon successful completionwe willin Phase II studiesrigorously explore various formulations of S NACHincluding oral nanoformulationsgeared towards feasible administration in acute and chronic situationsconduct GLP scale upconduct x ray crystallography studies to ascertain the detailed nature of interactions of S NACH with Hband utilize gained knowledge to further optimize design and synthesis for efficacy and specificityconduct safety and efficacy studies in preclinical models for the advancement for acute and chronic disease management in SCD patients NARRATIVE The pathogenesis of Sickle cell diseaseSCDis a complex interplay of multiple factors associated with vascular endothelial activationintense inflammationand increased sickle cell adhesion driven by the sickling of red blood cells in SCDTreatment with low molecular weight heparinLMWHhas shown clinical efficacy in decreasing the length of hospitalization and pain scoresbut bleeding side effects limit the use of these LMWHsIn this proposalwe will test a novel Oxidized sulfated oxidized non anticoagulant LMWH called S NACHwhich is devoid of systemic anticoagulation activities but possess potent anti sicklingantiselectinanti inflammatoryand antithrombotic activities without affecting hemostasis
Tagged as:
STTR
Phase I
2019
HHS
NIH
Topic 374: Topical Delivery of Nanoformulated Bioactive Chemopreventive Agent in Skin Cancer
Amount: $288,945 Topic: NCI
We plan to evaluate the chemopreventive management of solar ultraviolet (UV) mediated DNA damage by two different Nanoformulation of epigallicatechin-3-gallate (EGCG). The formulations to be assessed under this study include: a) chitosan based formulation of EGCG (nano-EGCG), and b) EGCG containing chitosan based solid lipid nanoparticles (E-Ch-SLNPs). EGCG is well-tested and popular polyphenol in skin cancer management however its efficacy has not translated to the clinic due to i) limitations of route of administration, ii) need of long-term dosing, iii) instability, and iv) inadequate bioavailability. The following Specific Aims are proposed: Aim 1: To determine if EGCG nanoformulated exhibits enhanced stability and improved release kinetics as compared to the native agent, and investigate its topical delivery capability. We will conduct ex vivo studies to study the shelf life of both nano-EGCG and further investigate its transdermal delivery. Aim 2: To determine the ex vivo and in vivo efficacy of our EGCG nanoformulations against UV mediated damages in 3D reconstituted human skin equivalent and SKH-1 hairless mouse and analyze the presence of EGCG in the mouse skin layers and blood. We will determine the comparative efficacy of nano-EGCG, ChSLNPs and EGCG under ex vivo and in vivo situations.
Tagged as:
SBIR
Phase I
2018
HHS
NIH
Enabling high dose regional chemotherapy while minimizing systemic toxicity
Amount: $159,306 Topic: NCI
DESCRIPTION (provided by applicant): Enabling high dose regional chemotherapy with minimal systemic toxicity Abstract: The primary objective of this proposed study is to develop a filtration system that maximizes the removal (gt90%) of chemotherapeutic agents, such as doxorubicin, from blood while minimizing adverse effects of filtration on blood chemistry and hematological parameters. Vascular Vision Pharmaceuticals Co. (VVP) and Delcath Systems are at the forefront of cancer treatment. Delcath's proprietary technology for localized drug delivery, Percutaneous Hepatic Perfusion (PHP ), allows the delivery of significantly higher doses of anti-cancer drug directly to the cancer site as compared to systemic delivery without exposure of the entire body to potent levels of drug. Initial results from clinical studies in liver cancer patients have confirmed that delivery of higher levels of anti-cancer drug directly to the tumor site with minimal exposure of other regions of the body enhances tumor shrinkage and improves quality of life as compared to systemic cancer therapies. PHPTM is currently under testing in Phase II clinical trials for a variety of cancers of the liver. The proposed research program relates to the application of PHPTM to localized cancer therapy and targeted drug delivery. Current Delcath filters consist of activated carbon coated with polymethacrylate to insulate the blood from direct contact with the filter material. These filters exhibit low first-pass extraction capability, resulting in suboptimal removal of chemotherapeutic agent, and shedding of carbon debris, resulting in activation of the clotting cascade and damage to the blood. Thus, there is an urgent need for filters with better efficiency and biocompatibility. The specific aims of this Phase I STTR proposal are as follows: Specific Aim 1: Determine the type of filter material required for the efficient removal of doxorubicin from blood. This will be accomplished by a) preparing carbon beads with three different coatings (cellulose with heparin, PMMA and PMMA with heparin) to enhance the biocompatibility of the carbon filters during blood perfusion, and then b) testing the efficiency and capacity of coated carbon in a batch mode filter to remove doxorubicin from bovine blood. Specific Aim 2: Determine the blood biocompatibility of the different coated filters by a) measuring changes in blood coagulation parameters and b) measuring changes in platelet activation state. Specific Aim 3: Carry out a perfusion study using optimized filters. This will be accomplished as follows: a) prepare large-scale optimized coated carbon filters based on the results of Aims 1 and 2; and b) test the efficiency of the optimized filter to remove doxorubicin from bovine blood. PUBLIC HEALTH RELEVANCE: The primary objective of this proposed study is to develop a novel Polymethyl methacrylate coated activated carbon filter with different compositions including cellulose and heparin for the maximum removal chemotherapy such as doxorubicin and others from blood while minimizing filter impact on blood chemistry. Initial clinical results from studies treating hepatic cancer patients confirm that delivering more chemotherapy drug to the tumor site, and less to the other regions of the body, enhances tumor shrinkage with improved quality of life over systemic cancer therapies.
Tagged as:
STTR
Phase I
2010
HHS
NIH
Nanoparticle targeting of cathepsin-L inhibitor and doxorubicin in breast cancer
Amount: $128,350
DESCRIPTION (provided by applicant): The development of resistance to chemotherapy represents an adaptive biological response by tumor cells that leads to treatment failure and patient relapse. There is an urgent need to overcome this problem if treatments are to be successful in eradicating tumors. Tumor cell irreversible growth arrest (senescence) is an early cellular response to the stress of exposure to chemotherapeutic agents. Those cells that are able to bypass senescence ultimately exhibit resistance to chemotherapy. Recent reports provide a persuasive rationale for studying the role of cathepsin L in the process of chemotherapeutic drug resistance. We showed that specific targeting of cathepsin L using chemical inhibitors or siRNA to this molecule forced cancer cells into a state of irreversible growth arrest and suppressed development of resistance to drugs. We also demonstrated the ability of cathepsin L inhibitor to reverse drug resistance in vivo utilizing nude mice bearing xenografts of doxorubicin resistant neuroblastoma cell line SKN-SH/R drug resistant tumors. Because many chemotherapeutic agents show systemic toxicities, and because cathepsin L inhibitors to be used in these studies are peptides subject to biodegradation, we will address these limitations by encapsulation of agents using PEG-PLGA nanoparticles targeted to either the sites of tumor neovascularization (1v integrin) or to MCF7 tumor cells via HER2 antibody. Female nude mice will have drug-resistant MCF7 human breast cancer cells implanted orthotopically into the fourth mammary gland. We will study two commercially available Cathepsin L inhibitors, Z-Phe-Try (t-Bu)-diazomethylketone and 1-Naphthalenesulfonyl-Ile-Trp- Aldehyde given either alone or with doxorubicin with respect to their effects on tumor cell growth and drug-resistance. Specific Aim 1: Prior to performance of nanoparticle-targeted therapy studies in nude mice, preliminary experiments to determine optimum formulations of nanoparticles will be performed in vivo in the chick chorioallantoic membrane (CAM) tumor implant model of tumor angiogenesis and growth. This model permits in vivo pre-screening for bioactivity while limiting the use of more sentient and costly murine species. Specific Aim 2: Nanoparticle formulations that show optimum anti-tumor and anti-angiogenesis activity in the CAM model will be tested in the mouse breast cancer model. In these studies, we will evaluate the effectiveness of cathepsin L inhibitors in reducing doxorubicin resistance as evidenced by improved anti-tumor activities. Comparisons will be made between non-targeted and targeted therapies with respect to anti-tumor efficacy and doxorubicin-associated toxicities. Cancer cells have the unique ability to develop resistance to chemotherapeutic drugs, and so research on ways to reverse this phenomenon would have significant value in the treatment of cancer patients. This project will use a combination of two drugs, one of which impairs the cancer cell's ability to develop drug resistance, in a mouse model of breast cancer. A novel technology, the use of nanoparticles to encapsulate the test drugs, will be tested to determine whether these nanoparticles can improve the delivery of drugs and minimize the associated toxicities.
Tagged as:
STTR
Phase I
2007
HHS
NIH
Tissue Factor/Vlla modulation in Ocular angiogenesis
Amount: $100,000
DESCRIPTION (provided by applicant): Diabetic retinopathy is the most common cause of new-onset vision loss in young people in the USA and other industrialized countries, and retinal neovascularization is the significant contributory factor to this vision loss. There is a critical need to develop new therapeutic agents and treatment modalities to prevent diabetic retinopathy. The focus of this application is on agents that modulate Tissue Factor (TF)/Vlla interaction. Although TF has been characterized best for its role in blood coagulation, recent studies have suggested a role for this molecule in physiologic processes distinct from homeostasis. Studies from the literature and our own laboratories support our focus on TF modulation as a strategy to regulate pathological angiogenesis. Overview: The studies proposed in Phase I will investigate the efficacy for prevention of ocular neovascularization of compounds which have shown significant inhibition of pro-angiogenic processes and angiogenesis in ovo. Proof of efficacy in Phase I studies will be followed in Phase II by investigation of topical formulations of these agents to study the impact of sustained release formulations on neovascularization in the murine retinopathy of prematurity (ROP) model. In the present application we will pursue strategies to evaluate the efficacy for treatment of retinal neovascularization of Tissue Factor Pathway Inhibitor (TFPI) provided in two ways: 1) directly in the form of recombinant TFPI (r-TFPI), providing an exogenous source of this molecule. 2) Administration of oxidized ultra-low molecular weight heparins (LMWH) with limited to no systemic anticoagulant effects that induce the localized release of TFPI from the endothelium, endogenous production of TFPI. Specific Aim 1. Recombinant TFPI or Oxidized ultra-LMWH (SA Mousa, U.S. Provisional Patent Application Serial No. 60/411,851) will be administered either subcutaneously or by intra-vitreal injection to mice in the ROP model to determine their effectiveness in preventing or attenuating retinal neovascularization. Eyes will be removed and quantification of retinal neovascularization performed. Specific Aim 2. Recombinant TFPI or oxidized ultra-LMWH will be administered to co-cultures of human retinal endothelial cells (EC) with Muller cells exposed to hypoxia/ischemia, and effectiveness in preventing capillary formation will be evaluated by digital image analysis of capillaries stained with EC-specific antibody to CD31-PECAM.
Tagged as:
SBIR
Phase I
2006
HHS
NIH
Enhancing tumor uptake of chemotherapeutics by novel heparin-derived compounds
Amount: $100,000
DESCRIPTION (provided by applicant): Many cancer patients reportedly have a hypercoagulable state with recurrent thrombosis due to the impact of cancer cells and chemotherapy or radiotherapy on the coagulation cascade. Studies have demonstrated that heparin or its derivatives, low molecular weight heparins (LMWHs), interfere with various processes involved in tumor growth and metastasis. These include fibrin formation; binding of heparin to angiogenic growth factors; modulation of tissue factor via the enhanced endothelial tissue factor pathway inhibitor (TFPI) release; and inhibition of various matrix-degrading enzymes. Clinical trials have suggested a clinically relevant effect of LMWH, as compared to standard heparin, on the survival of cancer patients with deep vein thrombosis. We hypothesize that tumor-associated thrombosis and fibrin generation provide a significant microenvironment for tumor survival and in creating a barrier to the penetration of natural killer cells and chemo- or radiotherapies resulting in chemo- resistance. In this proposal we will investigate the efficacy of TF-associated strategies in reducing tumor-associated fibrin deposition and thereby augmenting the uptake of chemotherapeutic agents into the tumor. Specifically, we will test two groups of agents: 1) a commercially available LMWH, Tinzaparin, to provide proof-of-concept and 2) two oxidized ultra-LMWHs with limited-to-no systemic anticoagulant effects but rather intravascular anticoagulant and antithrombotic effects through the release of TFPI and with limited effects on hemostasis. The studies proposed in this Phase I application will test the following: (1) whether LMWHs function by increasing uptake of chemotherapeutic agents using noninvasive PET imaging, 2) if LMWHs given in conjunction with the chemotherapeutic agent Paclitaxel would limit tumor proliferation and/or angiogenesis, and 3) if LMWHs given in conjunction with Paclitaxel work to limit the amount of fibrin production in the tumor interstitium, thereby reducing a barrier to drug uptake. Ultimately, the goal of such studies would be improved uptake of chemotherapy (non-invasive imaging) using novel heparin-derived compounds, and subsequent improved outlook in terms of tumor growth, tumor markers, and apoptosis markers. Protocols utilizing adjuvant therapy with novel heparin-derived compounds could lead to improved tumor chemotherapy uptake, efficacy, and safety.
Tagged as:
SBIR
Phase I
2006
HHS
NIH
kininiogen in Ocular angiogenesis-mediated disorders
Amount: $100,000
Retinal and choroidal angiogenesis are major causes of vision loss, and the pathogenesis of this angiogenesis process is still unclear. However, several key steps of the angiogenic cascade have been elucidated. In retinal angiogenesis, hypoxia is the initial stimulus that causes upregulation of various factors, which results in endothelial cell proliferation and migration. Although the steps of choroidal angiogenesis seem to be similar to those of retinal angiogenesis, there are some major differences between these two processes. Several anti-angiogenic approaches are being developed in animal models as well as in clinical trials to prevent ocular angiogenesis by blocking the key steps in the angiogenic cascade. Intact Kininogen (HK) is known to promote inflammation, complement activation, release bradykinin (permeability factor), and activate coagulation; more recently, it was shown to stimulate angiogenesis that might be mediated by its multiple mediators. These characteristics of HK suggest that its blockade might have significant benefits in the complex etiology of retinal and choroidal neovascularization. Studies from our laboratories have documented the antiangiogenic activity of cleaved HK (HKa) and its domain 5 (D5) to be due to their zinc-dependent binding to uPAR, which initiates signaling that interferes with the cell cycle and the proangiogenic activity exerted through the activation by intact HK. We have demonstrated that D5 or certain of its constituent peptides inhibit angiogenesis. We hypothesize that intact HK is proangiogenic and functions by liberating bradykinin among other mechansims and a monoclonal antibody (mAb C11C1) that interferes with the binding of HK to cell receptors would inhibit ocular angiogenesis. Based on our findings, we hypothesize that mAb C11C1 and D5 will inhibit angiogenesis in experimental models of retinal neovascularization. This novel strategy might alter the pathogenesis of retinal angiogenesis and provide an alternative pharmacological approach for ocular angiogenesis-mediated disorders.
Tagged as:
SBIR
Phase I
2005
HHS
NIH