|By PR Newswire||
|October 28, 2013 07:00 AM EDT||
RICHMOND, Calif., Oct. 28, 2013 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of new data demonstrating sustained control of HIV viral load (VL) at or below the limit of detection for 14 weeks (at last measurement) in an SB-728-T- treated HIV-infected subject who was not on antiretroviral therapy (ART). The CCR5 delta-32 heterozygote subject is enrolled in Sangamo's clinical trial (SB-728-902 Cohort 5) and, as part of the clinical trial protocol, is undergoing an ART treatment interruption (TI), which is ongoing.
Data were presented at the Annual Meeting of the European Society of Gene and Cell Therapy (ESGCT and SETGyC Collaborative Congress) which is being held in Madrid from October 25-28, 2013.
"These data demonstrate that sustained functional control of HIV in the absence of ART is possible with a single SB-728-T treatment," stated Geoff Nichol, M.B., Ch.B., Sangamo's executive vice president of research and development. "Our aim is to provide a population of immune memory cells that are protected from HIV infection and are capable of generating an effective immune response against the virus throughout the body. These data represent a further step toward demonstrating the efficacy and durability of this therapeutic approach."
Dr. Nichol added, "We continue to follow these Cohort 5 subjects and look forward to presenting a complete data set from this study, and a second ongoing trial (SB-728-1101), designed to maximize the engraftment of SB-728-T in subjects who are not CCR5 delta-32 heterozygotes, later this year."
Data from Sangamo's Phase 1 and 2 studies demonstrate that VL became undetectable during a TI from ART in three of seven evaluable CCR5 delta-32 heterozygote HIV-infected subjects, including two of six subjects that had completed TI in the ongoing SB-728-902 Cohort 5 study and an additional CCR5 delta-32 heterozygote subject from an earlier Phase 1 clinical trial of SB-728-T. In one SB-728-902 Cohort 5 subject, VL has remained undetectable (at or below the limits of quantification of the current ultra-sensitive assays for HIV) for 14 weeks (to last measurement taken) and the TI is ongoing. Reduction in VL from peak during TI showed a statistically significant correlation (p=0.015) with estimated numbers of engrafted ZFN modified cells (SB-728-T) in which both copies of the CCR5 gene had been disrupted (biallelic modification), in line with previously presented data from this program.
Collectively, data from these studies demonstrate that in all trial subjects, SB-728-T treatment results in a durable increase in total CD4 T-cells. In addition, seven of nine subjects enrolled in Sangamo's Phase 1 study (SB-728-902 Cohorts1-3) experienced a longer term reduction in the viral reservoir as measured by HIV DNA in peripheral blood mononuclear cells, a source of chronic HIV infection not addressed by current ART.
Sangamo scientists and collaborators also presented data from preclinical and research programs in hemophilia and lysosomal storage disorders, hemoglobinopathies, cancer, cystic fibrosis, immunodeficiencies and the application of ZFN-mediated CCR5 modification in stem cells for HIV.
"The presentations at the ESGCT meeting demonstrate the diversity and breadth of potential therapeutic applications of Sangamo's ZFP technology," said Edward Lanphier, Sangamo's president and CEO. "We look forward to continuing to update on our progress in the coming months at a translational medicine meeting organized by The Lancet entitled, 'What Will it Take to Achieve an AIDS-free World?' in San Francisco, from November 3-5, as well as at the Sixth International Workshop on HIV Persistence, Reservoirs & Eradication Strategies in Miami in early December. In addition, we will present data from Sangamo's preclinical programs at the Annual Meetings of the Society for Neuroscience in November and the American Society of Hematology (ASH) in early December."
Presentations at the ESGCT Meeting
Saturday, October 26
- "TCR gene editing for the treatment of hematological malignancies." Chiara Bonini, San Raffaele Telethon Institute for Gene Therapy, Milan
- "Efficient site-specific integration and in situ gene correction of human long-term repopulating hematopoietic stem cells by zinc finger nucleases." Pietro Genovese, San Raffaele Telethon Institute for Gene Therapy, Milan
- "Allele-preferred targeted correction of CFTR gene in Cystic Fibrosis induced pluripotent stem cells." Brian Davis, University of Texas
Sunday, October 27
- "Gene therapy for sickle cell disease." Donald Kohn, University of California, Los Angeles
- "Genome editing with zinc finger nucleases." Michael Holmes, Sangamo BioSciences, Inc.
- "Targeted transgene integration in human hematopoietic stem cells and induced pluripotent stem cells from normal donors and SCID-X1 patients." Angelo Lombardo, San Raffaele Telethon Institute for Gene Therapy, Milan
- "Zinc finger nucleases targeting the beta-globin locus drive efficient correction of the sickle mutation in CD34+ cells." Megan Hoban, University of California, Los Angeles
- "Rescue of T-cell deficiency in Prkdc mice by transplantation of gene-edited hematopoietic cells." Rafael Yanez, Royal Holloway, University of London
- "ZFN mediated targeting of albumin: a platform for expression of multiple therapeutic genes in vivo." Xavier Anguela, The Children's Hospital of Philadelphia
- "Development of ZFN-based preclinical in vitro cell model in human embryonic stem cells for Wiskott-Aldrich syndrome." Pilar Munoz-Fernandez, GENYO, Pfizer-University of Granada.
Monday, October 28
- "Infusion of ZFN CCR5-modified CD4 T-cells (SB-728-T) led to long term reconstitution of CD4 T-cells and reduction of HIV-DNA levels in HIV-infected subjects on ART." Dale Ando, Sangamo BioSciences, Inc.
Summary of Clinical Trial Design
About SB-728-902 Cohort 5
Ten HIV-infected subjects heterozygous for the CCR5 delta-32 mutation (i.e. with one CCR5 gene that is naturally modified) who are currently on ART have been enrolled and have received a single intravenous infusion of SB-728-T (5 to 30 billion modified cells). Two months after SB-728-T treatment, subjects undergo a 16 week TI during which time their ART is discontinued. ART is reinstituted in subjects whose CD4 T-cell counts drop to <350 cells/ mm3 and/or whose HIV-RNA increases to >100,000 /mL for three consecutive weekly measurements. At the end of the TI, subjects with a sustained detectable HIV viral load are reinstituted on ART. Subjects with an undetectable viral load can remain off ART until HIV RNA levels are detectable or their CD4 T-cell count drops below 350 cell/mm3 for three consecutive weekly measurements.
A total of ten subjects have been treated in this cohort.
Of the six evaluable subjects, we observed two subjects in which their VL became undetectable during TI from ART:
- In one subject, VL suppression at, or below, the limit of quantification (LOQ) of virus was sustained from week 11 – 25 of TI and the TI is ongoing.
- In the second subject there was a transient suppression of VL at or below LOQ.
- A third subject completed the TI with 1-log decrease in VL from peak.
In three subjects, there was no reduction in VL during the TI, one completed the TI and in two the TI was terminated early due to their viral loads exceeding the upper limit allowed in the protocol. A seventh subject has not completed TI and is still being evaluated.
About SB-728-902 Cohorts 1-3
The study is an open-label Phase 1 clinical trial to evaluate the safety and tolerability of single infusions of an escalating dose of an autologous (a patient's own) CD4+ T-cell product genetically modified at the CCR5 gene by CCR5-specific ZFNs (SB-728-T). The trial enrolled nine HIV-infected subjects (three cohorts of three subjects each) who have sub-optimal T-cell levels and no detectable viral load on long-term ART. Subjects remained on their existing antiviral therapy while receiving treatment with SB-728-T.
Sangamo's drug, SB-728-T, is generated by ZFN-mediated modification of the gene encoding the CCR5 receptor in a patient's own T-cells. ZFN modification disrupts the expression of this key co-receptor for HIV entry and renders cells resistant to HIV infection. The approach is based on the observation that a naturally occurring mutation in the CCR5 gene, CCR5 delta-32, provides protection from HIV infection. Individuals in whom both copies of the CCR5 gene carry the delta-32 mutation are generally not susceptible to the most common strain of HIV.
Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 and Phase1/2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS. As part of its acquisition of Ceregene Inc., Sangamo acquired a fully-enrolled and funded, double-blind, placebo-controlled Phase 2 trial to evaluate NGF-AAV (CERE-110) in Alzheimer's disease. Sangamo's other therapeutic programs are focused on monogenic diseases, including hemophilia, Huntington's disease and hemoglobinopathies such as beta-thalassemia and sickle cell anemia. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). Engineering of ZFPs that recognize a specific DNA sequence enables the creation of sequence-specific ZFP Nucleases (ZFNs) for gene modification and ZFP transcription factors (ZFP TFs) that can control gene expression and, consequently, cell function. Sangamo has entered into a strategic collaboration with Shire AG to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases and has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the company's website at www.sangamo.com.
ZFP Therapeutic® is a registered trademark of Sangamo BioSciences, Inc.
This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references relating to research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform for the treatment of HIV/AIDS, including a potential functional cure for HIV/AIDS, the ability of a ZFP Therapeutic to control HIV infection, projected timing of release of SB-728-T clinical data, the expansion of clinical studies for HIV-infected individuals and the initiation of additional preclinical studies of ZFN-gene modification. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo's public filings with the Securities and Exchange Commission, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.
SOURCE Sangamo BioSciences, Inc.
More and more brands have jumped on the IoT bandwagon. We have an excess of wearables – activity trackers, smartwatches, smart glasses and sneakers, and more that track seemingly endless datapoints. However, most consumers have no idea what “IoT” means. Creating more wearables that track data shouldn't be the aim of brands; delivering meaningful, tangible relevance to their users should be. We're in a period in which the IoT pendulum is still swinging. Initially, it swung toward "smart for smar...
Dec. 7, 2016 07:30 AM EST Reads: 814
With major technology companies and startups seriously embracing IoT strategies, now is the perfect time to attend @ThingsExpo 2016 in New York. Learn what is going on, contribute to the discussions, and ensure that your enterprise is as "IoT-Ready" as it can be! Internet of @ThingsExpo, taking place June 6-8, 2017, at the Javits Center in New York City, New York, is co-located with 20th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry p...
Dec. 7, 2016 06:45 AM EST Reads: 1,992
@DevOpsSummit at Cloud taking place June 6-8, 2017, at Javits Center, New York City, is co-located with the 20th International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait for long developm...
Dec. 7, 2016 06:30 AM EST Reads: 1,801
Kubernetes is a new and revolutionary open-sourced system for managing containers across multiple hosts in a cluster. Ansible is a simple IT automation tool for just about any requirement for reproducible environments. In his session at @DevOpsSummit at 18th Cloud Expo, Patrick Galbraith, a principal engineer at HPE, discussed how to build a fully functional Kubernetes cluster on a number of virtual machines or bare-metal hosts. Also included will be a brief demonstration of running a Galera MyS...
Dec. 7, 2016 06:15 AM EST Reads: 5,325
"We build IoT infrastructure products - when you have to integrate different devices, different systems and cloud you have to build an application to do that but we eliminate the need to build an application. Our products can integrate any device, any system, any cloud regardless of protocol," explained Peter Jung, Chief Product Officer at Pulzze Systems, in this SYS-CON.tv interview at @ThingsExpo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Dec. 7, 2016 05:15 AM EST Reads: 1,054
"We are an all-flash array storage provider but our focus has been on VM-aware storage specifically for virtualized applications," stated Dhiraj Sehgal of Tintri in this SYS-CON.tv interview at 19th Cloud Expo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Dec. 7, 2016 04:00 AM EST Reads: 866
Internet of @ThingsExpo has announced today that Chris Matthieu has been named tech chair of Internet of @ThingsExpo 2017 New York The 7th Internet of @ThingsExpo will take place on June 6-8, 2017, at the Javits Center in New York City, New York. Chris Matthieu is the co-founder and CTO of Octoblu, a revolutionary real-time IoT platform recently acquired by Citrix. Octoblu connects things, systems, people and clouds to a global mesh network allowing users to automate and control design flo...
Dec. 7, 2016 02:00 AM EST Reads: 627
In addition to all the benefits, IoT is also bringing new kind of customer experience challenges - cars that unlock themselves, thermostats turning houses into saunas and baby video monitors broadcasting over the internet. This list can only increase because while IoT services should be intuitive and simple to use, the delivery ecosystem is a myriad of potential problems as IoT explodes complexity. So finding a performance issue is like finding the proverbial needle in the haystack.
Dec. 7, 2016 01:45 AM EST Reads: 6,163
Between 2005 and 2020, data volumes will grow by a factor of 300 – enough data to stack CDs from the earth to the moon 162 times. This has come to be known as the ‘big data’ phenomenon. Unfortunately, traditional approaches to handling, storing and analyzing data aren’t adequate at this scale: they’re too costly, slow and physically cumbersome to keep up. Fortunately, in response a new breed of technology has emerged that is cheaper, faster and more scalable. Yet, in meeting these new needs they...
Dec. 7, 2016 01:15 AM EST Reads: 1,879
Data is the fuel that drives the machine learning algorithmic engines and ultimately provides the business value. In his session at 20th Cloud Expo, Ed Featherston, director/senior enterprise architect at Collaborative Consulting, will discuss the key considerations around quality, volume, timeliness, and pedigree that must be dealt with in order to properly fuel that engine.
Dec. 7, 2016 01:00 AM EST Reads: 1,618
When it comes to cloud computing, the ability to turn massive amounts of compute cores on and off on demand sounds attractive to IT staff, who need to manage peaks and valleys in user activity. With cloud bursting, the majority of the data can stay on premises while tapping into compute from public cloud providers, reducing risk and minimizing need to move large files. In his session at 18th Cloud Expo, Scott Jeschonek, Director of Product Management at Avere Systems, discussed the IT and busin...
Dec. 7, 2016 12:45 AM EST Reads: 3,938
According to Forrester Research, every business will become either a digital predator or digital prey by 2020. To avoid demise, organizations must rapidly create new sources of value in their end-to-end customer experiences. True digital predators also must break down information and process silos and extend digital transformation initiatives to empower employees with the digital resources needed to win, serve, and retain customers.
Dec. 7, 2016 12:45 AM EST Reads: 1,244
The WebRTC Summit New York, to be held June 6-8, 2017, at the Javits Center in New York City, NY, announces that its Call for Papers is now open. Topics include all aspects of improving IT delivery by eliminating waste through automated business models leveraging cloud technologies. WebRTC Summit is co-located with 20th International Cloud Expo and @ThingsExpo. WebRTC is the future of browser-to-browser communications, and continues to make inroads into the traditional, difficult, plug-in web co...
Dec. 7, 2016 12:15 AM EST Reads: 1,377
In his general session at 19th Cloud Expo, Manish Dixit, VP of Product and Engineering at Dice, discussed how Dice leverages data insights and tools to help both tech professionals and recruiters better understand how skills relate to each other and which skills are in high demand using interactive visualizations and salary indicator tools to maximize earning potential. Manish Dixit is VP of Product and Engineering at Dice. As the leader of the Product, Engineering and Data Sciences team at D...
Dec. 7, 2016 12:15 AM EST Reads: 1,033
The Internet of Things (IoT) promises to simplify and streamline our lives by automating routine tasks that distract us from our goals. This promise is based on the ubiquitous deployment of smart, connected devices that link everything from industrial control systems to automobiles to refrigerators. Unfortunately, comparatively few of the devices currently deployed have been developed with an eye toward security, and as the DDoS attacks of late October 2016 have demonstrated, this oversight can ...
Dec. 7, 2016 12:00 AM EST Reads: 1,278