This live broadcast will be available on Youtube at 11:00 AM Central time tomorrow 7/21/15.
https://www.youtube.com/watch?v=3iXvueqc_8c&list=PL_Emxk89MDn0E9yLNIwmNSjMwm6nGNc5B&index=4
Monday, July 20, 2015
Sunday, July 19, 2015
James Riley, UPENN presentation at IAS 2015
As an invited speaker James Riley, Ph.D. of the University of Pennsylvania gave the following presentation:
Engineering T Cells to Functionally Cure HIV-1 Infection.
Abstract:
Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1-resistant cells, redirecting HIV-1-specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1-specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy-mediated functional cure.
Engineering T Cells to Functionally Cure HIV-1 Infection.
Abstract:
Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1-resistant cells, redirecting HIV-1-specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1-specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy-mediated functional cure.
Saturday, July 18, 2015
Comprehensive Report on the HIV Pipeline
This 100 page comprehensive report details the state of HIV research in 2015.
Here is the mention of Sangamo's work:
A development in gene therapy that made the news earlier this year was the approval by the FDA of a clinical trial involving genetic modification of stem cells. The project involves collaboration between researchers from City of Hope Medical Center in Los Angeles, the Keck School of Medicine at the University of Southern California, and Sangamo BioSciences, with support from the California Institute for Regenerative Medicine (CIRM). Stem cells will be extracted from individuals, treated with Sangamo’s zinc finger nuclease technology to disrupt the CCR5 gene, and then reinfused with the aim of generating CCR5-negative immune cells resistant to HIV. According to a press release from CIRM, the initial study population will be HIV-positive individuals responding poorly to ART.88 Although some of the headlines described the approach as a “functional cure”89 or “potential cure,”90 this is in fact only an exploratory study, and it is wildly premature to suggest that it could be curative; previous trials involving genetic modification of stem cells have generated only low levels of gene-modified CD4+ T cells.91
Research continues into the use of the Sangamo BioSciences technology to genetically modify CD4+ T cells ex vivo. The CD4+ T cells are extracted from HIV-positive individuals, exposed to the zinc finger nuclease to disrupt the CCR5 gene, then expanded and reinfused. In studies published and presented to date,94,95 an adenovirus vector was used to deliver the zinc finger nuclease into the CD4+ T cells during the process. The company is now testing a different and potentially more efficient approach in which messenger RNA encoding the zinc finger nuclease is used instead of an adenovirus vector. Over the past year, two clinical trials have opened that will deliver CD4+ T cells modified with this method; both are using transient administration of cyclophosphamide prior to the infusion to enhance the engraftment of the altered cells.
Report:
http://www.pipelinereport.org/2015/cure-and-immune-based-and-gene-therapies
PDF:
http://www.pipelinereport.org/sites/g/files/g575521/f/201507/2015%20Pipeline%20Report%20Full.pdf
Here is the mention of Sangamo's work:
A development in gene therapy that made the news earlier this year was the approval by the FDA of a clinical trial involving genetic modification of stem cells. The project involves collaboration between researchers from City of Hope Medical Center in Los Angeles, the Keck School of Medicine at the University of Southern California, and Sangamo BioSciences, with support from the California Institute for Regenerative Medicine (CIRM). Stem cells will be extracted from individuals, treated with Sangamo’s zinc finger nuclease technology to disrupt the CCR5 gene, and then reinfused with the aim of generating CCR5-negative immune cells resistant to HIV. According to a press release from CIRM, the initial study population will be HIV-positive individuals responding poorly to ART.88 Although some of the headlines described the approach as a “functional cure”89 or “potential cure,”90 this is in fact only an exploratory study, and it is wildly premature to suggest that it could be curative; previous trials involving genetic modification of stem cells have generated only low levels of gene-modified CD4+ T cells.91
Research continues into the use of the Sangamo BioSciences technology to genetically modify CD4+ T cells ex vivo. The CD4+ T cells are extracted from HIV-positive individuals, exposed to the zinc finger nuclease to disrupt the CCR5 gene, then expanded and reinfused. In studies published and presented to date,94,95 an adenovirus vector was used to deliver the zinc finger nuclease into the CD4+ T cells during the process. The company is now testing a different and potentially more efficient approach in which messenger RNA encoding the zinc finger nuclease is used instead of an adenovirus vector. Over the past year, two clinical trials have opened that will deliver CD4+ T cells modified with this method; both are using transient administration of cyclophosphamide prior to the infusion to enhance the engraftment of the altered cells.
Report:
http://www.pipelinereport.org/2015/cure-and-immune-based-and-gene-therapies
PDF:
http://www.pipelinereport.org/sites/g/files/g575521/f/201507/2015%20Pipeline%20Report%20Full.pdf
Friday, July 17, 2015
Looks Like Sangamo Will Receive some Press for IAS 2015
In a pre-conference article the website thebodypro.com gives mention to the Sangamo related abstract,""Zinc finger nuclease gene editing for functional cure in a nonhuman primate model of HIV/AIDS " .
http://www.thebodypro.com/content/76146/research-preview-for-ias-2015-part-2-new-antiretro.html
Lets stay tuned.
http://www.thebodypro.com/content/76146/research-preview-for-ias-2015-part-2-new-antiretro.html
Lets stay tuned.
Monday, July 13, 2015
Sangamo Short Interest (SGMO)
DATE SHORT INTEREST
6/30/15 9,387,951
6/15/15 9,393,825
5/29/15 8,938,987
5/15/15 8,668,559
4/30/15 8,198,983
4/15/15 8,050,307
3/31/15 8,285,803
3/13/15 8,441,291
2/27/15 8,939,000
2/13/15 9,268,065
1/30/15 9,082,814
1/15/15 9,387,913
Days to cover as of 6/30/15 is 10.73
6/30/15 9,387,951
6/15/15 9,393,825
5/29/15 8,938,987
5/15/15 8,668,559
4/30/15 8,198,983
4/15/15 8,050,307
3/31/15 8,285,803
3/13/15 8,441,291
2/27/15 8,939,000
2/13/15 9,268,065
1/30/15 9,082,814
1/15/15 9,387,913
Days to cover as of 6/30/15 is 10.73
Friday, July 10, 2015
Interesting New Data on Viral Reservoir
A recent study from Australia has shown that it takes from 5 to 7 days for HIV to activate from latency following a treatment interruption. They also estimate that viral replication begins on average every six days or so, approximately 24 times more slowly than previously thought. The data also suggests that a single cell becomes actively infected around once a week when an individual is on HAART. Prior studies predicted this occurred several times a day. According to the authors calculations reducing the reservoir by 50 to 70 fold instead of SEVERAL THOUSAND FOLD, might be enough to allow for prolonged treatment interruption.
Now for the Sangamo data:
From Sangamo ICAAC Press Release dated September 8th, 2014
" A median 0.9 log decrease in the size of the HIV reservoir at 36 months was observed in nine of nine subjects treated, as demonstrated by measurement of HIV total DNA in PBMCs." "The data demonstrate that SB-728-T treatment is associated with reduction in both the VL and the levels of the reservoir."
Looks like they are on the right track.
The Australian Study:
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005000
Now for the Sangamo data:
From Sangamo ICAAC Press Release dated September 8th, 2014
" A median 0.9 log decrease in the size of the HIV reservoir at 36 months was observed in nine of nine subjects treated, as demonstrated by measurement of HIV total DNA in PBMCs." "The data demonstrate that SB-728-T treatment is associated with reduction in both the VL and the levels of the reservoir."
Looks like they are on the right track.
The Australian Study:
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005000
Thursday, July 2, 2015
Biogen and AGTC Enter into Collaboration to develop Gene Therapy
The lead development programs in the collaboration include a clinical candidate for X-linked Retinoschisis (XLRS) and a pre-clinical candidate for the treatment of X-Linked Retinitis Pigmentosa (XLRP). XLRS, a disease affecting young males beginning during the teenage years, can lead to serious complications such as vitreous hemorrhage or retinal detachment during adulthood. XLRP usually causes night blindness by the age of ten and progresses to legal blindness by an individual’s early forties. Both conditions represent significant unmet needs that may be addressed by replacing the single, faulty gene causing each disease.
Biogen will make an upfront payment in the amount of $124 million to AGTC, which includes a $30 million equity investment in AGTC at a price equal to $20.63 per share and certain prepaid research and development expenditures. Biogen will be granted a license to the XLRS and XLRP programs and the option to license discovery programs for three additional indications at the time of clinical candidate selection.
Under the collaboration, AGTC is eligible to receive upfront and milestone payments exceeding $1 billion. This includes up to $472.5 million collectively for the two lead programs, which also will carry royalties in the high single digit to mid-teen percentages of annual net sales. In addition, Biogen will make payments up to $592.5 million across the discovery programs, along with royalties in the mid single digits to low teen percentages of annual net sales. Biogen obtains worldwide commercialization rights for the XLRS and XLRP programs. AGTC has an option to share development costs and profits after the initial clinical trial data are available, and an option to co-promote the second of these products to be approved in the United States. AGTC will lead the clinical development programs of XLRS through product approval and of XLRP through the completion of first-in-human trials. Biogen will support the clinical development costs, subject to certain conditions, following the first-in-human study for XLRS and IND-enabling studies for XLRP. Under the manufacturing license, Biogen will receive an exclusive license to use AGTC’s proprietary technology platform to make AAV vectors for up to six genes, three of which are in AGTC’s discretion, in exchange for payment of milestones and royalties
Biogen will make an upfront payment in the amount of $124 million to AGTC, which includes a $30 million equity investment in AGTC at a price equal to $20.63 per share and certain prepaid research and development expenditures. Biogen will be granted a license to the XLRS and XLRP programs and the option to license discovery programs for three additional indications at the time of clinical candidate selection.
Under the collaboration, AGTC is eligible to receive upfront and milestone payments exceeding $1 billion. This includes up to $472.5 million collectively for the two lead programs, which also will carry royalties in the high single digit to mid-teen percentages of annual net sales. In addition, Biogen will make payments up to $592.5 million across the discovery programs, along with royalties in the mid single digits to low teen percentages of annual net sales. Biogen obtains worldwide commercialization rights for the XLRS and XLRP programs. AGTC has an option to share development costs and profits after the initial clinical trial data are available, and an option to co-promote the second of these products to be approved in the United States. AGTC will lead the clinical development programs of XLRS through product approval and of XLRP through the completion of first-in-human trials. Biogen will support the clinical development costs, subject to certain conditions, following the first-in-human study for XLRS and IND-enabling studies for XLRP. Under the manufacturing license, Biogen will receive an exclusive license to use AGTC’s proprietary technology platform to make AAV vectors for up to six genes, three of which are in AGTC’s discretion, in exchange for payment of milestones and royalties
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