News Article | April 10, 2017
MADISON, Wis., April 10, 2017 (GLOBE NEWSWIRE) -- Cellectar Biosciences, Inc. (Nasdaq:CLRB), an oncology-focused clinical stage biotechnology company, today announces it has appointed Douglas J. Swirsky and Frederick W. Driscoll to its board of directors. “Both Fred and Doug bring extensive operational and industry experience that should prove invaluable to Cellectar as we enter this next phase of the company’s development,” said Jim Caruso, president and CEO of Cellectar Biosciences. “We look forward to working with both and benefitting from their contributions.” Douglas J. Swirsky has served as president and chief executive officer of GenVec, Inc. since 2013, and also serves as a member of GenVec's board of directors. Mr. Swirsky also currently serves as chairman of the board of Fibrocell Science, Inc. From 2006 through 2014, he served as senior vice president, chief financial officer, treasurer and corporate secretary of GenVec. Prior to joining GenVec in September 2006, Mr. Swirsky worked at Stifel Nicolaus where he served as a managing director and the head of Life Sciences Investment Banking. Previously, Mr. Swirsky held investment banking positions at UBS, PaineWebber, Morgan Stanley, and Legg Mason. His experience also includes positions in public accounting and consulting. He received his undergraduate degree in business administration from Boston University and his M.B.A. from the Kellogg School of Management at Northwestern University. Mr. Swirsky is a certified public accountant and a CFA® charterholder. Frederick W. Driscoll served as chief financial officer at Flexion Therapeutics (Flexion) from 2013 to 2017, spearheading a successful IPO in 2014. Prior to joining Flexion, he was chief financial officer at Novavax, Inc., a publicly traded biopharmaceutical company, from 2009 to 2013. Previously, Mr. Driscoll also served as chief financial officer from 2007 to 2008, and subsequently chief executive officer from 2008 to 2009, at Genelabs Technologies, Inc., a publicly traded biopharmaceutical and diagnostics company that was acquired by GlaxoSmithKline; and chief executive officer at OXiGENE, Inc., a biopharmaceutical company, from 2000 to 2006. He has also served as chairman of the board and audit committee chair at OXiGENE and as a member of the audit committee for Cynapsus, which was sold to Sunovion Pharmaceuticals in 2016. Mr. Driscoll earned a bachelor’s degree in accounting and finance from Bentley University. About Cellectar Biosciences, Inc. Cellectar Biosciences is developing phospholipid drug conjugates (PDCs) designed to provide cancer-targeted delivery of diverse oncologic payloads to a broad range of cancers and cancer stem cells. Cellectar's PDC platform is based on the company's proprietary phospholipid ether analogs. These novel small-molecules have demonstrated highly selective uptake and retention in a broad range of cancers. Cellectar's PDC pipeline includes product candidates for cancer therapy and cancer diagnostic imaging. The company's lead therapeutic PDC, CLR 131, utilizes iodine-131, a cytotoxic radioisotope, as its payload. CLR 131 is currently being evaluated under an orphan drug designated Phase I clinical study in patients with relapsed or refractory multiple myeloma, as well as a Phase II clinical study to assess efficacy in a range of B-cell malignancies. The company is also developing PDCs for targeted delivery of chemotherapeutics such as paclitaxel (CLR 1603-PTX), a preclinical-stage product candidate, and plans to expand its PDC chemotherapeutic pipeline through both in-house and collaborative R&D efforts. For more information please visit www.cellectar.com. This news release contains forward-looking statements. You can identify these statements by our use of words such as "may," "expect," "believe," "anticipate," "intend," "could," "estimate," "continue," "plans," or their negatives or cognates. These statements are only estimates and predictions and are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk. Factors that might cause such a material difference include, among others, uncertainties related to the ability to raise additional capital, uncertainties related to the ability to attract and retain partners for our technologies, the identification of lead compounds, the successful preclinical development thereof, the completion of clinical trials, the FDA review process and other government regulation, our pharmaceutical collaborators' ability to successfully develop and commercialize drug candidates, competition from other pharmaceutical companies, product pricing and third-party reimbursement. A complete description of risks and uncertainties related to our business is contained in our periodic reports filed with the Securities and Exchange Commission including our Form 10-K for the year ended December 31, 2016. These forward-looking statements are made only as of the date hereof, and we disclaim any obligation to update any such forward-looking statements.
Patterson D.M.,Mount Vernon Hospital |
Zweifel M.,Mount Vernon Hospital |
Middleton M.R.,Oxford Radcliffe Hospitals |
Folkes L.K.,Gray Institute for Radiation Oncology and Biology |
And 8 more authors.
Clinical Cancer Research | Year: 2012
Purpose: Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents. Experimental Design: Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors. Results: Doses were escalated in single-patient cohorts from 0.06 to 1.92 mg/m 2, then expanded cohorts to 15.4 mg/m 2 in 43 patients. Common adverse drug reactions were hypertension, tumor pain, anemia, lymphopenia, and easily controllable nausea/vomiting and fatigue. Five patients experienced different drugrelated dose-limiting toxicities, atrial fibrillation, increased troponin, blurred vision, diplopia, and tumor lysis. Prophylactic amlodipine failed to prevent adverse events. Pharmacokinetics showed dose-dependent linear increases in peak plasma concentrations and area under the curve value of OXi4503. One partial response was seen in a heavily pretreated patient with ovarian cancer. Dynamic contrast-enhanced MRI confirmed a dose effect and showed significant antivascular effects in 10 of 13 patients treated at doses of 11 mg/m 2 or higher. Conclusions: The maximum tolerated dose was 8.5 mg/m 2 but escalation to 14 mg/m 2 was possible with only temporary reversible cerebrovascular toxicity by excluding hypertensive patients. As a tumor response was seen at 14 mg/m 2 and maximum tumor perfusion reductions were seen at doses of 11 mg/m 2 or higher, the recommended phase II dose is from 11 to 14 mg/m 2. ©2012 AACR.
Workman P.,Cancer Research UK Research Institute |
Aboagye E.O.,Imperial College London |
Balkwill F.,Center for Cancer and Inflammation |
Balmain A.,University of California at San Francisco |
And 16 more authors.
British Journal of Cancer | Year: 2010
Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice. © 2010 Cancer Research UK All rights reserved.
Nathan P.,Mount Vernon Cancer Center |
Zweifel M.,Mount Vernon Cancer Center |
Padhani A.R.,Paul Strickland Scanner Center |
Koh D.-M.,Royal Marsden Hospital |
And 12 more authors.
Clinical Cancer Research | Year: 2012
Purpose: The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity. Experimental Design: Patients with advanced solid malignancies received CA4P at 45, 54, or 63 mg/m2 on day 1, day 8, and then every 14 days. Bevacizumab 10 mg/kg was given on day 8 and at subsequent cycles four hours after CA4P. Functional imaging with dynamic contrast enhanced-MRI (DCE-MRI) was conducted at baseline, after CA4P alone, and after cycle 1 CA4P + bevacizumab. Results: A total of 63 mg/m2 CA4P + 10 mg/kg bevacizumab q14 is the recommended phase II dose. A total of 15 patients were enrolled. Dose-limiting toxicities were grade III asymptomatic atrial fibrillation and grade IV liver hemorrhage in a patient with a history of hemorrhage. Most common toxicities were hypertension, headache, lymphopenia, pruritus, and pyrexia. Asymptomatic electrocardiographic changes were seen in five patients. Nine of 14 patients experienced disease stabilization. A patient with ovarian cancer had a CA125 response lasting for more than a year. DCE-MRI showed statistically significant reductions in tumor perfusion/vascular permeability, which reversed after CA4P alone but which were sustained following bevacizumab. Circulating CD34+ and CD133+ bone marrow progenitors increased following CA4P as did VEGF and granulocyte colony-stimulating factor levels. Conclusions: CA4P in combination with bevacizumab appears safe and well tolerated in this dosing schedule. CA4P induced profound vascular changes, which were maintained by the presence of bevacizumab. ©2012 AACR.
Zweifel M.,Mount Vernon Cancer Center |
Jayson G.C.,University of Manchester |
Reed N.S.,Beatson Oncology Center |
Osborne R.,Poole Hospital NHS Foundation Trust |
And 8 more authors.
Annals of Oncology | Year: 2011
Background: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer. Patients and methods: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m 2 minimum 18 h before paclitaxel 175 mg/m 2 and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks. Results: Five of the first 18 patients' disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%. Conclusions: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
MacDonough M.T.,Baylor University |
Strecker T.E.,Baylor University |
Hamel E.,U.S. National Institutes of Health |
Hall J.J.,Baylor University |
And 3 more authors.
Bioorganic and Medicinal Chemistry | Year: 2013
The discovery of a 2-aryl-3-aroyl indole-based small-molecule inhibitor of tubulin assembly (referred to as OXi8006) inspired the design, synthesis, and biological evaluation of a series of diversely functionalized analogues. In the majority of examples, the pendant 2-aryl ring contained a 3-hydroxy-4-methoxy substitution pattern, and the fused aryl ring featured a 6-methoxy group. Most of the variability was in the 3-aroyl moiety, which was modified to incorporate methoxy (33-36), nitro (25-27), halogen (28-29), trifluoromethyl (30), or trifluoromethoxy (31-32) functionalities. In two analogues (34 and 36), the methoxy substitution pattern in the fused aryl ring varied, while in another derivative (35) the phenolic moiety was translocated from the pendant 2-aryl ring to position-7 of the fused aryl ring. Each of the compounds were evaluated for their cytotoxicity (in vitro) against the SK-OV-3 (ovarian), NCI-H460 (lung), and DU-145 (prostate) human cancer cell lines and for their ability to inhibit tubulin assembly. Four of the compounds (30, 31, 35, 36) proved to be potent inhibitors of tubulin assembly (IC50 <5 μM), and three of these compounds (31, 35, 36) were strongly cytotoxic against the three cancer cell lines. The most active compound (36) in this series, which incorporated a methoxy group at position-7, was comparable in terms of inhibition of tubulin assembly and cytotoxicity to the lead compound OXi8006. © 2013 Elsevier Ltd. All rights reserved.
Rustin G.J.,Mount Vernon Cancer Center |
Shreeves G.,Mount Vernon Cancer Center |
Nathan P.D.,Mount Vernon Cancer Center |
Gaya A.,Mount Vernon Cancer Center |
And 8 more authors.
British Journal of Cancer | Year: 2010
Background:The vascular disrupting agent combretastatin A4 phosphate (CA4P) causes major regression of animal tumours when given as combination therapy.Methods:Patients with advanced cancer refractory to standard therapy were treated with CA4P as a 10-min infusion, 20 h before carboplatin, paclitaxel, or paclitaxel, followed by carboplatin.Results:Combretastatin A4 phosphate was escalated from 36 to 54 mg m 2 with the carboplatin area under the concentration curve (AUC) 4-5, from 27 to 54 mg m 2 with paclitaxel 135-175 mg m 2, and from 54 to 72 mg m 2 with carboplatin AUC 5 and paclitaxel 175 mg m 2. Grade 3 or 4 neutropenia was seen in 17%, and thrombocytopenia only in 4% of 46 patients. Grade 1-3 hypertension (26% of patients) and grade 1-3 tumour pain (65% of patients) were the most typical non-haematological toxicities. Dose-limiting toxicity of grade 3 hypertension or grade 3 ataxia was seen in two patients at 72 mg m 2. Responses were seen in 10 of 46 (22%) patients with ovarian, oesophageal, small-cell lung cancer, and melanoma.Conclusion:The combination of CA4P with carboplatin and paclitaxel was well tolerated in the majority of patients with adequate premedication and had antitumour activity in patients who were heavily pretreated. © 2010 Cancer Research UK All rights reserved.
Tanpure R.P.,Baylor University |
Strecker T.E.,Baylor University |
Chaplin D.J.,OXiGENE Inc. |
Siim B.G.,OXiGENE Inc. |
And 2 more authors.
Journal of Natural Products | Year: 2010
Synthetic routes have been established for the preparation of regio-and stereoisomerically pure samples of the mono-β-d-glucuronic acid derivatives of combretastatin A-1, referred to as CA1G1 (5a) and CA1G2 (6a). Judicious choice of protecting groups for the catechol ring was required for the regiospecific introduction of the glucuronic acid moiety. The tosyl group proved advantageous in this regard. The two monoglucuronic acid analogues demonstrate low cytotoxicity (compared to CA1, 2) against selected human cancer cell lines, with CA1G1 being slightly more potent than CA1G2. © 2010 The American Chemical Society and American Society of Pharmacognosy.
PubMed | OXiGENE Inc.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
3550 Background: The vascular disruptive agent (VDA) CA4P induces significant tumor necrosis as a single agent. Vascular shut down is reversible and tumors can re-grow due to vascularisation of the surviving tumor rim. Pre-clinical models have demonstrated that the addition of an anti-VEGF antibody to a VDA significantly increases anti-tumor activity.Patients with advanced solid malignancies received CA4P at 45mg/m2 (cohort 1), 54mg/m63mg/mCA4P in combination with bevacizumab appears safe and well tolerated in this dosing schedule with early evidence of clinical activity. CA4P induced profound vascular changes which were maintained by the presence of bevacizumab. CA4P induced an acute rise in circulating bone marrow progenitors which may in part be mediated by GCSF and VEGF release. [Table: see text].
PubMed | Baylor University, OXiGENE Inc. and University of Texas Southwestern Medical Center
Type: Journal Article | Journal: Cancer letters | Year: 2015
This study describes the vascular disrupting ability and the mechanism of action of the indole-based tubulin-binding compound, OXi8006, and its water-soluble phosphate prodrug OXi8007. Treatment of rapidly proliferating human umbilical vein endothelial cells (HUVECs), used as a model for the tumor vasculature, with OXi8006 or OXi8007, caused potent microtubule disruption followed by extensive reorganization of the cytoskeletal network. The mechanism of action involved an increase in focal adhesion formation associated with an increase in phosphorylation of both non-muscle myosin light chain and focal adhesion kinase. These effects were dramatically diminished by an inhibitor of RhoA kinase, a downstream effector of RhoA. Cell cycle blockade at G2/M and cytotoxicity toward rapidly proliferating HUVECs were also observed. Capillary-like networks of HUVECs were disrupted by the action of both OXi8006 and OXi8007. The prodrug OXi8007 exhibited potent and rapid dose-dependent antivascular activity assessed by dynamic bioluminescence imaging (BLI) in an MDA-MB-231-luc breast cancer xenograft mouse model. By 6 hours post treatment, over 93% of the BLI signal was abolished with only a slight recovery at 24 hours. These findings were confirmed by histology. The results from this study demonstrate that OXi8007 is a potent vascular disrupting agent acting through an anti-microtubule mechanism involving RhoA.