Welcome!

News Feed Item

First-In-Man Study Of Genome Editing Using Sangamo's ZFN Technology Published In New England Journal Of Medicine

Treatment with Sangamo's ZFN- Modified T-cells (SB-728-T) Provides Functional Control of HIV without Antiretroviral Drugs

RICHMOND, Calif., March 5, 2014 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the publication in the New England Journal of Medicine of the first clinical study of its proprietary zinc finger nuclease (ZFN)-based genome editing technology in humans. Data from the study, carried out in HIV-positive subjects, demonstrate that the T-cell genome can be safely engineered to mimic a naturally occurring mutation that provides resistance to HIV infection. ZFN-modified T-cells are well tolerated when reinfused and treatment is associated with decreased viral loads (VLs) in several subjects who were taken off their antiretroviral therapy (ART) including one whose viral load became undetectable. The study demonstrates the feasibility of this novel genome editing approach to achieve functional control of HIV.

Sangamo BioSciences, Inc.

Additional data on the ongoing SB-728-T ongoing clinical trials in HIV will be presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2014), which is taking place in Boston, March 3-6, 2014.

"We have used Sangamo's ZFN technology to safely genetically engineer an HIV-infected individual's own T-cells and to make those cells resistant to infection by the virus," said Carl June, M.D., Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania, and a senior author of the paper.  "This study demonstrates that ZFN-modified cells can be safely administered back to the individual; are able to persist and circulate throughout the body to key reservoirs of HIV infection; and show preferential survival over unmodified cells when antiviral drugs are withdrawn, potentially keeping the virus under control without the use of drugs. Our experience reinforces our belief that an immunological approach is a promising approach to enable functional control of HIV infection and eliminate the need for lifelong ART."

Summary of Study Results
In the study, T-cells from HIV subjects were isolated and edited with ZFNs to make them resistant to the virus by knocking out the CCR5 gene which encodes a coreceptor required for HIV infection.  After modification, the cells (SB-728-T) were returned to the subject, in a so-called "autologous infusion," and subjects were monitored for safety and a variety of immunological parameters.  The modified cells readily engrafted and were able to traffic throughout the body to key sites of HIV persistence such as the gut-associated lymphoid tissue. The data demonstrate that the modified cells persist and moreover appear to have a selective advantage, showing a preferential survival compared to unmodified cells when exposed to HIV during a planned interruption of ART. SB-728-T treatment was associated with an increase in the levels of total circulating CD4 T-cells and was well tolerated.

One of six subjects undergoing a treatment interruption experienced the longest delay in rebound of viral load when ART was withdrawn and achieved a decrease in VL to undetectable levels during the 12-week period. This subject was later found to carry a natural mutation of CCR5, CCR5 delta-32, in one of the two CCR5 genes (making the individual a CCR5 delta-32 heterozygote).  Thus, following exposure to the ZFNs targeting CCR5, at baseline this subject to had a greater percentage of T-cells that were modified at both sites (biallelic modification) and were fully resistant to HIV infection. Preliminary analyses suggest that the levels of circulating cells with biallelic modification of CCR5 may correlate with control of viral load.  Sangamo has ongoing clinical studies in CCR5 delta-32 heterozygotes (SB-728-902, Cohort 5) and in subjects undergoing Cytoxan pre-conditioning (SB-728-1101) to further study this relationship.

"The publication of this study in the New England Journal of Medicine represents a milestone in the development of ZFN-mediated genome editing as a new therapeutic approach," stated Edward Lanphier, Sangamo's president and chief executive officer. "Our ZFN technology functions at the DNA level, enabling us to make precise and persistent changes to the properties of cells that result in therapeutic benefit. Our goal is to use this powerful technology to engineer genetic cures for diseases that have thus far been treated as chronic conditions, including HIV and a wide range of monogenic diseases. The study represents an important first step in our development of this novel immunological therapy for HIV.  However, we now have clinical data from additional trials that confirm and extend the data presented in this early clinical trial.  We look forward to providing an update on our ongoing clinical trials at CROI and to providing guidance as to the future direction of this program."

Study Design
The study was an open-label, Phase 1 study of a single dose of approximately 10 billion ZFN-modified autologous T-cells in 12 HIV-infected subjects whose virus was well controlled by antiretroviral medications. Subjects were divided into two cohorts of six subjects each. Subjects in Cohort 1 were identified as immune responders who had demonstrated adequate recovery of CD4 T-cells after ART (>450 cells /mm3).Subjects in Cohort 2 were identified as individuals who had demonstrated inadequate recovery of CD4 T-cells after ART (200-500 cells /mm3), so-called immunologic non-responders.  Four weeks after SB-728-T treatment, Cohort 1 subjects underwent an interruption from ART of up to 12 weeks.  Cohort 2 remained on their ART throughout the study. The primary objective of the study was to assess safety and tolerability of administration of a single dose of SB-728-T.  Secondary outcomes included measures of immune reconstitution and HIV resistance. The study was carried out at the Hospital of the University of Pennsylvania and the Jacobi Medical Center, Albert Einstein College of Medicine and was supported in part by an NIAID Program Project Grant.

N.Eng. J. Med. 2014: 370:897-906 "Gene Editing of CCR5 in Autologous CD4 T-cells of Persons Infected with HIV." In addition to scientists and clinicians Perelman School of Medicine at the University of Pennsylvania, coauthors included researchers from the Albert Einstein School of Medicine and Sangamo BioSciences. Dr. June reports no financial disclosures related to Sangamo BioSciences.

About SB-728-T
SB-728-T is an autologous CD4+ T-cell product in which the gene for CCR5, a co-receptor for HIV entry, is modified via ZFN-mediated genome editing to disrupt the CCR5 protein.  T-cells with a disrupted CCR5 protein are resistant to infection by the most common strain of HIV.

About Sangamo
Sangamo BioSciences, Inc. is focused on Engineering Genetic CuresTM for monogenic and infectious diseases by deploying its novel DNA-binding protein technology platform in therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS (SB-728-T) and NGF-AAV for Alzheimer's disease (CERE-110). Sangamo's other therapeutic programs are focused on monogenic and rare diseases.  The company has formed a strategic collaboration with Shire International GmbH to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases, and with Biogen Idec for hemoglobinopathies, such as sickle cell disease and beta-thalassemia. It has also 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 and projected timing of release of SB-728-T clinical data. 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.

Logo - http://photos.prnewswire.com/prnh/20130102/SF35903LOGO

SOURCE Sangamo BioSciences, Inc.

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
"CA has been doing a lot of things in the area of DevOps. Now we have a complete set of tool sets in order to enable customers to go all the way from planning to development to testing down to release into the operations," explained Aruna Ravichandran, Vice President of Global Marketing and Strategy at CA Technologies, in this SYS-CON.tv interview at DevOps Summit at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
High-velocity engineering teams are applying not only continuous delivery processes, but also lessons in experimentation from established leaders like Amazon, Netflix, and Facebook. These companies have made experimentation a foundation for their release processes, allowing them to try out major feature releases and redesigns within smaller groups before making them broadly available. In his session at 21st Cloud Expo, Brian Lucas, Senior Staff Engineer at Optimizely, discussed how by using ne...
Gemini is Yahoo’s native and search advertising platform. To ensure the quality of a complex distributed system that spans multiple products and components and across various desktop websites and mobile app and web experiences – both Yahoo owned and operated and third-party syndication (supply), with complex interaction with more than a billion users and numerous advertisers globally (demand) – it becomes imperative to automate a set of end-to-end tests 24x7 to detect bugs and regression. In th...
"Cloud Academy is an enterprise training platform for the cloud, specifically public clouds. We offer guided learning experiences on AWS, Azure, Google Cloud and all the surrounding methodologies and technologies that you need to know and your teams need to know in order to leverage the full benefits of the cloud," explained Alex Brower, VP of Marketing at Cloud Academy, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clar...
"ZeroStack is a startup in Silicon Valley. We're solving a very interesting problem around bringing public cloud convenience with private cloud control for enterprises and mid-size companies," explained Kamesh Pemmaraju, VP of Product Management at ZeroStack, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
In his session at 21st Cloud Expo, Carl J. Levine, Senior Technical Evangelist for NS1, will objectively discuss how DNS is used to solve Digital Transformation challenges in large SaaS applications, CDNs, AdTech platforms, and other demanding use cases. Carl J. Levine is the Senior Technical Evangelist for NS1. A veteran of the Internet Infrastructure space, he has over a decade of experience with startups, networking protocols and Internet infrastructure, combined with the unique ability to it...
"Codigm is based on the cloud and we are here to explore marketing opportunities in America. Our mission is to make an ecosystem of the SW environment that anyone can understand, learn, teach, and develop the SW on the cloud," explained Sung Tae Ryu, CEO of Codigm, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
"There's plenty of bandwidth out there but it's never in the right place. So what Cedexis does is uses data to work out the best pathways to get data from the origin to the person who wants to get it," explained Simon Jones, Evangelist and Head of Marketing at Cedexis, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
Large industrial manufacturing organizations are adopting the agile principles of cloud software companies. The industrial manufacturing development process has not scaled over time. Now that design CAD teams are geographically distributed, centralizing their work is key. With large multi-gigabyte projects, outdated tools have stifled industrial team agility, time-to-market milestones, and impacted P&L stakeholders.
Enterprises are moving to the cloud faster than most of us in security expected. CIOs are going from 0 to 100 in cloud adoption and leaving security teams in the dust. Once cloud is part of an enterprise stack, it’s unclear who has responsibility for the protection of applications, services, and data. When cloud breaches occur, whether active compromise or a publicly accessible database, the blame must fall on both service providers and users. In his session at 21st Cloud Expo, Ben Johnson, C...
"Infoblox does DNS, DHCP and IP address management for not only enterprise networks but cloud networks as well. Customers are looking for a single platform that can extend not only in their private enterprise environment but private cloud, public cloud, tracking all the IP space and everything that is going on in that environment," explained Steve Salo, Principal Systems Engineer at Infoblox, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Conventio...
Data scientists must access high-performance computing resources across a wide-area network. To achieve cloud-based HPC visualization, researchers must transfer datasets and visualization results efficiently. HPC clusters now compute GPU-accelerated visualization in the cloud cluster. To efficiently display results remotely, a high-performance, low-latency protocol transfers the display from the cluster to a remote desktop. Further, tools to easily mount remote datasets and efficiently transfer...
"Akvelon is a software development company and we also provide consultancy services to folks who are looking to scale or accelerate their engineering roadmaps," explained Jeremiah Mothersell, Marketing Manager at Akvelon, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
"MobiDev is a software development company and we do complex, custom software development for everybody from entrepreneurs to large enterprises," explained Alan Winters, U.S. Head of Business Development at MobiDev, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
"We're developing a software that is based on the cloud environment and we are providing those services to corporations and the general public," explained Seungmin Kim, CEO/CTO of SM Systems Inc., in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.