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Shen M.,University of Kentucky | Eyras E.,University Pompeu Fabra | Eyras E.,Catalan Institution for Research and Advanced Studies | Wu J.,Cold Spring Harbor Laboratory | And 6 more authors.
Nucleic Acids Research | Year: 2011

We describe a new method that allows cloning of double-stranded RNAs (dsRNAs) that are generated in RNase protection experiments. We demonstrate that the mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs. Surprisingly, the majority of cloned RNAs from RNase protection experiments were derived from endogenous cellular RNA, indicating widespread antisense expression. The cloned dsRNAs could be mapped to genome areas that show RNA expression on both DNA strands and partially overlapped with experimentally determined argonaute-binding sites. The data suggest a conserved processing pattern for some C/D box snoRNAs and abundant expression of longer, non-coding RNAs in the cell that can potentially form dsRNAs. © The Author(s) 2011. Published by Oxford University Press.


BERKELEY HEIGHTS, N.J., Feb. 21, 2017 (GLOBE NEWSWIRE) -- Edge Therapeutics, Inc. (Nasdaq:EDGE), a clinical-stage biotechnology company developing novel hospital-based therapies in the management of acute, life-threatening conditions, today announced the appointment of Alyssa Wyant as Senior Vice President, Regulatory Affairs. Ms. Wyant will oversee all facets of Edge's regulatory activities, providing oversight for all U.S. and international regulatory matters, including filings and interactions with regulatory authorities. Ms. Wyant will report to Edge’s President and Chief Executive Officer, Brian Leuthner, and become part of Edge’s executive team. "We are pleased to have Alyssa join the Edge team. She has extensive regulatory experience and an outstanding track record, having supported the advancement of multiple orphan products through the regulatory approval process, including direct interaction with the U.S. Food and Drug Administration (FDA) and international regulatory agencies for both regulatory approvals and post-approval activities,” said Mr. Leuthner. “Alyssa's experience will be invaluable to Edge as we continue to advance the clinical development of EG-1962 through our Phase 3 NEWTON 2 study for aneurysmal subarachnoid hemorrhage (aSAH), and focus on driving forward pipeline products from our Precisa Platform™ in the years ahead." Ms. Wyant has nearly 20 years of global regulatory experience with a focus on the development, registration and successful launches of innovative, biologic and small molecule orphan disease products. Most recently, Ms. Wyant served as Vice President, Global Regulatory Affairs at PTC Therapeutics. While at PTC, she was responsible for the strategic planning and execution of global regulatory activities for Translarna™ (ataluren) across five orphan disease indications, acting as regulatory agency liaison for approval filings in Duchenne muscular dystrophy (DMD) and cystic fibrosis with the European Medicines Agency (EMA), FDA and Health Canada, and for maintenance of conditional approval for DMD with the EMA. As Senior Director, International Regulatory Affairs at NPS Pharmaceuticals, Ms. Wyant created and implemented global strategies for the registration and post-approval activities for orphan disease products in Europe, North America and Latin America, supporting FDA approval for Natpara® for hypoparathyroidism and the U.S. and EU launches for Gattex® / Revestive® for short bowel syndrome. Earlier in her career, she held multiple leadership positions in global regulatory affairs at Shire Human Genetic Therapies in the U.S. and Switzerland, where she was a key contributor in obtaining, maintaining, and extending registration of the enzyme replacement therapy products Elaprase®, VPRIV® and Replagal®. She also held regulatory affairs positions at Vertex Pharmaceuticals and Genetics Institute / Wyeth-Ayerst Pharmaceuticals. Ms. Wyant has a B.S. in cell and molecular biology from the University of Washington. In connection with Ms. Wyant’s new employment, the Compensation Committee of Edge’s Board of Directors has approved the grant to Ms. Wyant of non-qualified stock options to purchase 80,000 shares of Edge’s common stock. The effective date of the grant is March 1, 2017 and the exercise price for such stock options will be equal to the closing price of Edge’s common stock on such date, as reported by NASDAQ. The grant was made as an inducement material to Ms. Wyant’s acceptance of employment with Edge, in accordance with NASDAQ Listing Rule 5635(c)(4). The options have a 10-year term and vest over a period of four years, with 25 percent vesting on February 21, 2018, which is one year following Ms. Wyant’s date of hire, and the remaining 75 percent vesting in approximately equal monthly increments over the succeeding thirty-six months, subject to Ms. Wyant’s continuous employment through each applicable vesting date. In addition, the options are subject to acceleration or forfeiture upon the occurrence of certain events as set forth in Ms. Wyant’s stock option and / or employment agreements. Edge Therapeutics, Inc. is a clinical-stage biotechnology company that discovers, develops and seeks to commercialize novel, hospital-based therapies capable of transforming treatment paradigms for the management of acute, life-threatening neurological and other conditions. EG-1962, Edge’s lead product candidate, has the potential to fundamentally improve patient outcomes and transform the management of aSAH, which is bleeding around the brain due to a ruptured brain aneurysm. Edge is evaluating EG-1962 in two clinical studies: the pivotal Phase 3 NEWTON 2 study of EG-1962 delivered via external ventricular drain, and a study of direct intracisternal administration of EG-1962. For additional information about Edge, please visit www.edgetherapeutics.com. This press release and any statements of representatives of Edge Therapeutics, Inc. related thereto that are not historical in nature contain, or may contain, among other things, certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements may include, without limitation, statements with respect to Edge’s plans, objectives, projections, expectations and intentions and other statements identified by words such as "projects," "may," "will," "could," "would," "should," "believes," "expects," "anticipates," "estimates," “seeks,” "intends," "plans," "potential" or similar expressions, including statements with respect to Edge’s future clinical and regulatory plans, Edge’s ability to advance its portfolio of therapies towards commercialization and the potential effects of its products. These statements are based upon the current beliefs and expectations of Edge’s management and are subject to significant risks and uncertainties. Actual results may differ significantly from those set forth in the forward-looking statements. These forward-looking statements involve certain risks and uncertainties that are subject to change based on various risk factors (many of which are beyond Edge's control) as described under the heading "Risk Factors" in Edge’s filings with the United States Securities and Exchange Commission.


News Article | February 16, 2017
Site: globenewswire.com

AUSTIN, Texas, Feb. 16, 2017 (GLOBE NEWSWIRE) -- Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a biotechnology company committed to developing enzyme-based therapeutics in the field of amino acid metabolism to treat rare genetic diseases and cancer, today announced the appointment of Suzanne L. Bruhn, Ph.D. to its Board of Directors. Dr. Bruhn previously served as chief executive officer, president and director at Promedior, Inc., a clinical-stage biotechnology company, from 2012 to 2015. “Suzanne’s depth of experience in the early-stage biotechnology space and expertise in orphan diseases will be a valuable addition to our Board,” said David G. Lowe, Ph.D., co-founder, president and chief executive officer of Aeglea. “Her insights and guidance will be a tremendous asset as we further our clinical programs in order to pursue our mission of developing treatments for patients with rare genetic diseases and cancer.” During her time at Promedior, Dr. Bruhn focused the company’s strategy on clinical development for orphan diseases and negotiated the grant of an exclusive option to acquire Promedior to Bristol-Myers Squibb Company in 2015. Prior to Promedior, Dr. Bruhn held a number of roles in strategic and portfolio planning, program management and regulatory affairs at Shire Human Genetic Therapies, formerly known as Transkaryotic Therapies, between 1998 and 2012. She also served on the board of directors of Raptor Pharmaceuticals Corp., a biotechnology company focused on treating rare metabolic disorders, from 2011 until it was sold to Horizon Pharma plc in October 2016. Dr. Bruhn earned her bachelor’s degree in chemistry from Iowa State University of Science and Technology and her Ph.D. from Massachusetts Institute of Technology. About Aeglea BioTherapeutics Aeglea is a biotechnology company committed to developing enzyme-based therapeutics in the field of amino acid metabolism to treat rare genetic diseases and cancer. The company’s engineered human enzymes are designed to modulate the extremes of amino acid metabolism in the blood to reduce toxic levels of amino acids in inborn errors of metabolism or target tumor metabolism for cancer treatment. AEB1102, Aeglea’s lead product candidate, is currently being studied in two ongoing Phase 1 clinical trials in patients with advanced solid tumors and acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Additionally, Aeglea is recruiting patients into its ongoing Phase 1/2 trial of AEB1102 for the treatment of patients with Arginase I deficiency. The company is building a pipeline of additional product candidates targeting key amino acids, including AEB4104, which degrades homocystine, a target for an inborn error of metabolism, as well as two potential treatments for cancer, AEB3103, which degrades cysteine/cystine, and AEB2109, which degrades methionine. For more information, please visit http://aegleabio.com. Safe Harbor / Forward Looking Statements This press release contains “forward-looking” statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: “anticipate,” “intend,” “plan,” “goal,” “seek,” “believe,” “project,” “estimate,” “expect,” “strategy,” “future,” “likely,” “may,” “should,” “will” and similar references to future periods. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, the potential therapeutic benefits and economic value of our product candidates. Further information on potential risk factors that could affect our business and its financial results are detailed in our most recent Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, filed with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.


Kostenko V.,University of Calgary | Lyczak J.,Shire Human Genetic Therapies | Turner K.,Attogen, Inc | Martinuzzi R.J.,University of Calgary
Antimicrobial Agents and Chemotherapy | Year: 2010

The long-term antimicrobial efficacy of silver dressings against bacterial biofilms was investigated in a 7-day treatment in vitro model where the protein-rich medium was refreshed daily in order to mimic the conditions found in a wound bed. The use of plate-to-plate transfer assays demonstrated measurable differences in the effectivenesses of several silver dressings on the viability of biofilm bacteria and their susceptibility to antibiotics. Whereas after the first day of treatment, all dressings used resulted in a significant reduction in the number of viable cells in the biofilms and disruption of the biofilm colonies, during prolonged treatment, the efficacy of dressings with hydrophilic base materials diminished with daily transfers, and bacterial populations recovered. For dressings with hydrophobic base materials, the level of efficacy correlated with the silver species loaded. Biofilm bacteria, which survived the initial silver treatment, were susceptible to tobramycin, ciprofloxacin, and trimethoprim-sulfamethoxazole, in contrast to untreated biofilms, which were highly tolerant to the same antibiotics. This acquired susceptibility was unaffected by the longevity of pretreatment with the silver dressings but depended on the dressing used. The antimicrobial efficacy of the dressings correlated with the type of the dressing base material and silver species loaded. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Maurer M.,Charité - Medical University of Berlin | Aberer W.,Medical University of Graz | Bouillet L.,Grenoble University Hospital Center | Caballero T.,Hospital La Paz Health Research Institute IdiPaz | And 5 more authors.
PLoS ONE | Year: 2013

Background: Attacks of hereditary angioedema (HAE) are unpredictable and, if affecting the upper airway, can be lethal. Icatibant is used for physician- or patient self-administered symptomatic treatment of HAE attacks in adults. Its mode of action includes disruption of the bradykinin pathway via blockade of the bradykinin B2 receptor. Early treatment is believed to shorten attack duration and prevent severe outcomes; however, evidence to support these benefits is lacking. Objective: To examine the impact of timing of icatibant administration on the duration and resolution of HAE type I and II attacks. Methods: The Icatibant Outcome Survey is an international, prospective, observational study for patients treated with icatibant. Data on timings and outcomes of icatibant treatment for HAE attacks were collected between July 2009-February 2012. A mixed-model of repeated measures was performed for 426 attacks in 136 HAE type I and II patients. Results: Attack duration was significantly shorter in patients treated <1 hour of attack onset compared with those treated ≥1 hour (6.1 hours versus 16.8 hours [p<0.001]). Similar significant effects were observed for <2 hours versus ≥2 hours (7.2 hours versus 20.2 hours [p<0.001]) and <5 hours versus ≥5 hours (8.0 hours versus 23.5 hours [p<0.001]). Treatment within 1 hour of attack onset also significantly reduced time to attack resolution (5.8 hours versus 8.8 hours [p<0.05]). Self-administrators were more likely to treat early and experience shorter attacks than those treated by a healthcare professional. Conclusion: Early blockade of the bradykinin B2 receptor with icatibant, particularly within the first hour of attack onset, significantly reduced attack duration and time to attack resolution. © 2013 Maurer et al.


Elstein D.,Shaare Zedek Medical Center | Cohn G.M.,Shire Human Genetic Therapies | Wang N.,Shire Human Genetic Therapies | Djordjevic M.,Mother and Child Health Care Institute | And 2 more authors.
Blood Cells, Molecules, and Diseases | Year: 2011

Introduction: Therapeutic goals have been described to monitor achievement, maintenance and continuity of therapeutic response in patients with type 1 Gaucher disease receiving enzyme replacement therapy. Aim: To benchmark the impact of velaglucerase alfa treatment against therapeutic goals for 5 key clinical parameters of type 1 Gaucher disease (anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology). Methods: In an open-label Phase I/II study, twelve adults with symptomatic type 1 Gaucher disease and intact spleens received velaglucerase alfa for 9. months (60. U/kg infusion every other week [EOW]). Eleven patients completed the study and 10 enrolled in a long-term extension. After 1. year, patients who achieved ≥ 2 hematological or organ goals began step-wise dose reduction from 60 to 45 then 30. U/kg EOW. Data for anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology at baseline and 4. years are available for 8 patients (3 male, 5 female). The proportion of patients at goal for anemia, thrombocytopenia, hepatomegaly and splenomegaly at baseline was compared with the proportion achieving each goal at 4. years. The proportion achieving the skeletal pathology goal was determined on the basis of Z-score improvement from baseline to 4. years. The proportion of patients who achieved all 5 goals at 4. years was compared with the proportion at goal for all 5 parameters at baseline. Results: At baseline, no patient was at goal for all clinical parameters. After 1. year of treatment, all patients maintained goals present at baseline, and all achieved ≥ 2 goals. All 8 patients began step-wise dose reduction from 60 to 30. U/kg EOW between 15 and 18. months. By year 4 of treatment, all patients met goals for all 5 clinical parameters; therefore 100% achievement was seen for each of the 5 long-term, therapeutic goals. Discussion: In this velaglucerase alfa Phase I/II and extension study, clinically meaningful achievement of each long-term, therapeutic goal was observed for each patient, despite dose reduction after 1. year. This is the first report of a cohort where all patients receiving ERT for type 1 Gaucher disease achieved all 5 of these long-term, therapeutic goals within 4. years of starting treatment and after ≥ 2. years dose reduction. © 2010 Elsevier Inc.


Cohn G.M.,Shire Inc | Morin I.,Shire Human Genetic Therapies | Whiteman D.A.H.,Shire Inc
European Journal of Pediatrics | Year: 2013

The Hunter Outcome Survey (HOS), an international, long-term observational registry of patients with Hunter syndrome, was used to develop a simple mnemonic screening tool (HUNTER) to aid in the diagnosis of Hunter syndrome. Data regarding the prediagnosis prevalence of ten specific signs and symptoms present in individual patients enrolled in the HOS were used to develop the HUNTER mnemonic screening tool. A total score of 6 or greater using a weighting scheme in which certain manifestations were assigned a weight of 2 (facial dysmorphism, nasal obstruction or rhinorrhea, enlarged tongue, enlarged liver, enlarged spleen, joint stiffness) and others assigned a weight of 1 (hernia, hearing impairment, enlarged tonsils, airway obstruction or sleep apnea) correctly identified 95 % of patients who had no family history of Hunter syndrome or who were not diagnosed prenatally. No association between age at diagnosis and HUNTER score was found. Conclusion: The HUNTER mnemonic appears to be a useful screening tool. Further validation in the clinical setting will be necessary to confirm its utility. © 2013 The Author(s).


News Article | November 22, 2016
Site: www.prnewswire.com

BOSTON, Nov. 22, 2016 /PRNewswire/ -- Leading life science real estate developer BioMed Realty today announced that Shire Human Genetic Therapies, Inc., a subsidiary of Shire, Plc, will become the next anchor tenant of its iconic 500 Kendall Street building in the heart of Kendall Square....


Stock T.C.,Pfizer | Bloom B.J.,Shire Human Genetic Therapies | Wei N.,Arthritis Treatment Center | Ishaq S.,Northshore Rheumatology | And 4 more authors.
Journal of Rheumatology | Year: 2012

Objective. To evaluate efficacy and safety of CE-224,535, a selective P2X7 receptor antagonist, versus placebo, in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX). Methods. In our phase IIA study (ClinicalTrials.gov no. NCT00628095; A6341009), patients aged ≥ 18 years with active RA were randomized to receive either CE-224,535 (500 mg bid) or placebo for 12 weeks; all patients continued a stable background dose of ≥ 7.5 mg MTX. Results. The American College of Rheumatology 20% (ACR20) response rate (primary efficacy endpoint) was not significantly different from placebo for CE-224,535 (34.0% vs 36.2%; p = 0.591) at Week 12, or at any timepoint over the 12-week treatment period. There was no significant difference at Week 12 for the ACR20 response rate following subgroup analyses by age, sex, baseline disease activity, baseline duration of disease, geographic region, or concomitant use of steroids. ACR50/ACR70 response rates and change from baseline in Disease Activity Score 28-joint C-reactive protein (DAS28-3-CRP) and Health Assessment Questionnaire-Disability Index for CE-224,535 were not significant at Week 12 versus placebo. Treatment-emergent adverse events (AE) were reported by 62.3% (CE-224,535) and 55.3% (placebo) of patients; the most common AE were nausea (11.3%, CE-224,535; 4.3%, placebo) and diarrhea (7.5%, CE-224,535; 4.3%, placebo). The proportion of patients discontinuing due to an AE was 9.4% (CE-224,535) and 6.4% (placebo); no deaths were reported. Serious AE occurred in 3.8% (CE-224,535) and 2.1% (placebo) of patients; none was considered treatment-related. Conclusion. CE-224,535 was not efficacious, compared with placebo, for the treatment of RA in patients with an inadequate response to MTX. CE-224,535 demonstrated an acceptable safety and tolerability profile. The Journal of Rheumatology Copyright © 2012. All rights reserved.


The present invention provides, among other things, effective treatment for Sanfilippo Syndrome Type A (MPS IIIA) based on intrathecal delivery of recombinant heparin N-Sulfatase (HNS) enzyme. In some embodiments, the present invention includes methods of treating Sanfilippo Syndrome Type A (MPS IIIA) Syndrome by intrathecal administration of a recombinant HNS enzyme at a therapeutically effective dose and an administration interval for a period sufficient to decrease glycosaminoglycan (GAG) heparan sulfate level in the cerebrospinal fluid (CSF) and/or urine relative to a control.

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