Tuesday, July 28, 2015

All the BIG GUNS (or should I say Cannons) Speaking Thursday Night

Speakers Include:
Paula Cannon
John Zaia
Dale Ando

The City of West Hollywood is co-sponsoring the upcoming HIV Matters town hall event — Countdown to a Cure: California Leads the Way. The quarterly HIV Matters town hall forum is a collaborative effort between AIDS Project Los Angeles (APLA) and community partners. Each HIV Matters forum focuses on updates regarding HIV treatment, prevention, and care efforts in Los Angeles County and worldwide.
The upcoming town hall will take place on Thursday, July 30, 2015 from 5:30 p.m. to 8:30 p.m. at Plummer Park’s Fiesta Hall, located at 7377 Santa Monica Boulevard. Dinner will be served at 5:30 p.m.; an educational program will begin at 6:35 p.m. The event is free and is open to the public.
The forum will bring together members of the HIV community and leading researchers to discuss clinical trials that are now underway, and other approaches that are being investigated to cure AIDS. Speakers will include Paula Cannon, Ph.D., Associate Professor, Keck School of Medicine of USC; David Hardy, M.D., Chief Medical Officer, Calimmune; John Zaia, M.D., Chair of Virology, City of Hope, Duarte; Dale Ando, M.D., Vice President of Therapeutic Development and Chief Medical Officer, Sangamo BioSciences; and Jeff Sheehy, CIRM Board Patient Advocate Member for HIV/AIDS.
The City of West Hollywood, incorporated in 1984, has been disproportionally impacted by HIV and AIDS. It was the first city to fund services for most of the local organizations established in the mid-1980s in the early response to the AIDS crisis. Today, the City of West Hollywood continues to provide funding to support HIV and AIDS education, prevention, and medical services — as well as programs for mental health, food, housing, and community enhancement — for community members.
Since its founding in 1983, AIDS Project Los Angeles (APLA) has grown to become of the largest and most effective AIDS service organizations in the nation. Services and programs are offered to 11,000 clients each year.

Wednesday, July 22, 2015

Youtube video IAS 2015 Dr. Chris Peterson ZFN Gene Editing

Here is the presentation that Dr. Peterson of the Fred Hutchinson Cancer gave on ZFN editing of Stem Cells in Non-Human primates.

17 minutes
https://www.youtube.com/watch?v=-uJE1b75Yuw

Monday, July 20, 2015

Recap of Sangamo Related topics at IAS 2015

From I-base.info
http://i-base.info/htb/28625

In the second plenary, long-time HIV positive activist Matt Sharp, expanded on cure research from a personal perspective from early involvement in community responses in San Francisco in the 1980s through to achieving five year follow-up after having been an early participant in the first zinc finger nuclease-based gene therapy safety study: while his CD4 cells have doubled, there is little understand of the clinical implications and ageing takes him into unchartered waters as a subject for research.
Diagnosed in 1988 and recently having celebrated his 60th birthday, Matt gave a calm, steady and sober evaluation of being part of a community response that included fellow activists Martin Delaney (in whose name much of the US public cure research programme is named after) and Bob Munk, the popular long-time activist whose death in the week before the conference left many of us saddened after a long and inspiring fight against progressively debilitating HIV-related complications

The plenary talk on approaches to engineering T cells was given by James Riley from the University of Pennsylvania who stressed the potential for gene therapy to improve on CD4 responses which in the context of cure research will need to be sustained for decades if ART is to be stopped.
In addition to the history of this field from early studies in 1996 that included antisense molecules targeting integrated proviral DNA, this talked focused on the use of zinc finger nuclease (ZFN) and Sangamo compound SB-728 that modifies and reinfuses CD4 cells to carry CCR5 deletions.
A new compound C34 is building on this technology with the aim of producing a greater percentage of HIV resistant cells with the hope that this will have a greater impact on viral suppression.

Official 2015 IAS Press Conference: Towards an HIV CURE Youtube 7/21/15

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

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.

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

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.

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

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

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