Gene editing, including CRISPR/Cas, TALENs, Zinc Finger Nucleases and other approaches, represents the ability to treat and potentially cure genetic disorders and other forms of disease by inserting, replacing or removing DNA using “molecular scissors,” or artificially engineered gene constructs. This interview will explore the current state of the science and both near-term and longer-term clinical and research applications.
Blythe Thomson, M.D., Senior Director, Medical Affairs, Hematology and Oncology, Medpace
Alexandra Glucksmann, Ph.D., Chief Operating Officer, Editas Medicine
Sandy Macrae, Ph.D., President and CEO, Sangamo BioSciences
Prashant Mali, Ph.D., Assistant Professor, Department of Bioengineering, UC San Diego
European Society of Gene and Cell Therapy, Florence, Italy, October 18-21, 2016 On Friday, October 21, 2016, Michael Holmes, Ph.D., Sangamo's vice president of research, is an invited speaker and will present an overview of the Company's therapeutic zinc finger nuclease (ZFN)-mediated in vivo genome editing programs for Mucopolysaccharidosis Type I (MPS I, Hurler syndrome) and Mucopolysaccharidosis Type II (MPS II, Hunter syndrome).
The National Hemophilia Foundation's 13TH Workshop on Novel Technologies and Gene Transfer for Hemophilia, Washington, D.C., October 21-22, 2016 Brigit Riley, Ph.D., Sangamo's director of discovery and translational research, has been invited to present an overview of data from the Company's ZFN-mediated in vivo genome editing approach for the treatment of monogenic disease, as well as its adeno-associated virus (AAV) cDNA based gene therapy approach for the treatment of hemophilia A. Dr. Riley's presentations will take place during the Gene Editing and Cell Therapy session on Friday, October 21ST
Oct 26, 2016
5:00 PM ET Sangamo 3rd Quarter 2016 Teleconference Call
The most important catalyst upcoming in the next few weeks is the announcement of data from Cohort3 for SB-728. Phase II data announcement in Feb:
Sangamo BioSciences Presents Phase 2 Immunological Data from SB-728-T ZFP Therapeutic® HIV Program at CROI 2016 Subjects from SB-728-1101 Cohort 3* Remain Off Antiretroviral Therapy for Over a Year Immunologic and Reservoir Analyses Suggest Mechanism for Viral Load Control RICHMOND, Calif., Feb. 24, 2016 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO), the leader in therapeutic genome editing, announced the presentation of immunological data from the Company's clinical trials of SB-728-T, a ZFP Therapeutic® designed to provide functional control of HIV. Analysis of data from Sangamo's most recent SB-728-1101 study suggests key, potentially interrelated mechanisms for viral load (VL) control in treated subjects during a treatment interruption (TI) from their antiretroviral therapy (ART). The analysis was presented by Sangamo's collaborator, Rafick-Pierre Sékaly, Ph.D., Richard Fasenmeyer Chair in Immunopathogenesis, Case Western Reserve University, at the 2016 Annual Conference on Retroviral and Opportunistic Infections (CROI 2016). The meeting is being held in Boston from February 22-26, 2016.
Sangamo BioSciences, Inc. (PRNewsFoto/Sangamo BioSciences, Inc.) (PRNewsFoto/) "A significant number of subjects treated with SB-728-T have experienced a striking control of their viral load for a sustained period in the absence of ART," stated Dr. Sékaly. "This is particularly notable in cohorts treated with optimal doses of Cytoxan® in the SB-728-1101 study. Immunological and HIV reservoir analyses suggest that the best predictors for post-treatment viral control are higher levels of SB-728-T engraftment, specifically long-lived memory T-cells, evidence of polyfunctional antiviral CD8 responses during TI and lower HIV reservoir levels prior to TI. This may provide a model mechanism of action for SB-728-T and help identify HIV-infected individuals who will benefit most from this novel immune-based therapy."
"The evidence of sustained viral load control in subjects enrolled in the 1101 study is very encouraging," said Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "Four of nine subjects treated at Cytoxan doses of 1.0 and 1.5 g/m2 remain on extended TI, including two of three treated subjects in Cohort 3* who were included in this analysis and have viral loads under 1,000. The data suggest that by mimicking the characteristics of the 'elite controller' HIV subpopulation it may be possible to develop a functional cure for HIV/AIDS. Based on our extensive clinical studies, we believe that we have identified both an SB-728-T manufacturing method and patient characteristics that will aid us and a future partner in the development of this therapeutic through pivotal studies."
Of the nine subjects pre-conditioned with Cytoxan doses of 1.0 and 1.5 g/m2 (Cohorts 3, 3* and 5) six subjects demonstrated durable control of viremia (VL < 10,000) during an extended TI (14-26 months duration), with two subjects showing consistent ongoing VL measurements less than 1,000 (17 and 20 months at the time of analysis). Using a univariate linear regression model, the analysis demonstrated that greater levels of engrafted CCR5-modified cells before TI (p=0.03) and higher frequencies of long-lived CD4 memory T-cells (TSCM) during TI (p=0.01) correlated with lower VLs. The data suggest that an HIV resistant, long-lived CD4 TSCM compartment is likely to be critical in establishing VL control possibly by restoring immune homeostasis and providing help to HIV-specific CD8 T-cells. Multivariate analyses were used to determine parameters that further predict VL control during TI. Results indicate that higher CD4 TSCM levels, as well as a more robust polyfunctional anti-HIV gag CD8 response during TI (p=0.04) were associated with reduced VL. Furthermore, the analysis demonstrated that HIV reservoir size prior to TI showed a significant interaction with CD8 response in this model (p=0.03). These data suggest that a smaller HIV reservoir at the beginning of the TI coupled with a strong CD8 response resulted in better VL control.
In late 2015, Sangamo enrolled five additional subjects in Cohort 3* and expects to present that data at the end of 2016. Pending the data readout for SB-728-1101 Cohort 3*, the Company intends to partner the HIV program for pivotal studies and commercialization.
About SB-728-T Sangamo's therapeutic candidate, SB-728-T, is generated by zinc finger nuclease (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.
About SB-728-1101 Cohorts 1-5 and Cohort 3* SB-728-1101 is an open-label, dose escalation, multi-center study designed primarily to evaluate the safety and tolerability of escalating doses of cyclophosphamide (Cytoxan®) administered prior to SB-728-T infusion. By protocol, HIV-infected subjects on ART were enrolled into five dose-escalating cohorts (three subjects/cohort), and received intravenous Cytoxan (200 mg, 500 mg/m2, 1.0g/m2, 1.5g/m2 and 2.0g/m2). One to three days after receiving Cytoxan, subjects were infused with SB-728-T (8.2 to 36.2 billion cells). Six weeks after SB-728-T infusion, subjects with CD4 cell counts ≥500 cells/mm3 underwent a 16 week TI during which time their anti-retroviral therapy was discontinued. At the end of the TI, subjects with a sustained detectable viral load or reduced CD4 T-cell count were reinstituted on ART. In addition to safety, the study is designed to evaluate the effect of escalating doses of Cytoxan on SB-728-T engraftment, the effect of SB-728-T treatment on viral load following ART interruption, the change in CD4+ T-cell counts in peripheral blood and the long-term persistence of SB-728-T. SB-728-1101 was expanded in 2015 to include an additional cohort, Cohort 3*. Subjects in this cohort of the study are treated with an SB-728-T preparation of up to 40 billion ZFN-modified CD4 and CD8 T-cells. Up to eight subjects will be treated, all of whom have been accrued.
Cytoxan is a drug that is used to transiently reduce the numbers of T-cells in the body, which then rapidly repopulate once the drug is discontinued, and it is into this "growth" environment that SB-728-T is infused. Such lymphodepletive treatment has been used to enhance engraftment of adoptively transferred T-cells in the treatment of cancer, and as therapy for numerous autoimmune diseases. The drug has been previously used in HIV-infected individuals and studies demonstrate that while the drug was transiently lymphodepleting, it did not significantly reduce total CD4 T-cell counts over the long term and was adequately tolerated.
ASGCT17 American Society of Gene & Cell Therapy conference May 10-13 Pocket guide attached Booth 814 right front corner per map Patron: Commercialization Worksop Cocktail Reception
May 10 Oral Abstract Session 112 Genome Editing: Transcriptional Regulation and Specificity 11:45 23: New Zinc Finger Nuclease Architectures for Highly Efficient Genome Engineering in Primary Cells at Large Scale with No Detectable Off-Target Effects Edward Rebar, Sangamo Therapeutics, Richmond, CA
12:00 PM 24: Sustained Tau Reduction via Zinc Finger Protein Transcription Factors as a Potential Next-Generation Therapy for Alzheimer’s Disease and Other Tauopathies Bryan Zeitler, Sangamo Therapeutics, Inc., Richmond, CA
Oral Abstract Session 113 Genome Editing and Integration Analysis in Metabolic and Endocrine Disorders 11:30 AM 30: ZFN-Mediated In Vivo Genome Editing Results in Phenotypic Correction in MPS I and MPS II Mouse Models Russell DeKelver, Sangamo Therapeutics, Richmond, CA
Friday, MAY 12 Oral Abstract Session 341 In Vivo Gene Editing 3:45 PM 509: In Vivo Genome Editing via Non-Viral Delivery of Zinc Finger Nucleases Results in Supraphysiological Levels of Therapeutic Proteins in Adult Mice Anthony Conway, Sangamo Therapeutics, Richmond, CA
4:00 PM 510: Non-Viral Delivery of Zinc Finger Nucleases Enable Greater Than 90% Protein Knockdown of Multiple Therapeutic Gene Targets In Vivo Anthony Conway, Sangamo Therapeutics, Richmond, CA
SATURDAY, MAY 13 Oral Abstract Session 412 Ex Vivo Gene Editing 11:30 AM 750: Ex Vivo Protein Replacement Using Homology Driven Genome Editing in Human B Cells by Combining Zinc Finger Nuclease mRNA and AAV6 Donor Delivery Brigit Riley, Sangamo Therapeutics, Inc., Richmond, CA
Post by Gene Editing on Apr 29, 2017 11:27:14 GMT -6
Tmunity HIV ? another hint to SGMO Expanding Indications and Varieties of Engineered T Cells - CAR-T Cell Approaches as part of an HIV Cure Strategy Expanding Indications and Varieties of Engineered T Cells - CAR-T Cell Approaches as part of an HIV Cure Strategy
Authors James L. Riley, PhD. The University of Pennsylvania, Philadelphia, PA Disclosures J.L. Riley: 1; Commercial Interest i.e. Company X; Tmunity Therapeutics. 1; What was received? i.e. Honorarium; equity ownership, Sponsored Research. 1; For what role? i.e. Speaker; Scientific Founder. 2; Commercial Interest i.e. Company X; Pfizer. 2; What was received? i.e. Honorarium; salary. 2; For what role? i.e. Speaker; Spouse Employment. 3; Commercial Interest i.e. Company X; Merck. 3; What was received? i.e. Honorarium; sponsored research. 3; For what role? i.e. Speaker; Contracted research. 4; Commercial Interest i.e. Company X; BMS. 4; What was received? i.e. Honorarium; consulting fee. 4; For what role? i.e. Speaker; consultant. 5; Commercial Interest i.e. Company X; Cellectis. 5; What was received? i.e. Honorarium; consulting fee. 5; For what role? i.e. Speaker; consultant. Abstract Redirecting T cells to B cell tumors via the infusion of CD19-specific chimeric antigen receptor (CAR) T cells has resulted in durable complete responses in many individuals who have failed state of the art therapy. In contemplating treating HIV infected individuals with T cells expressing a HIV-specific CAR several unique issues arise. For one, given HIV’s ability to escape antibody responses what is the best way to redirect T cells to HIV? Additionally, HIV-specific CD4 T cells will likely help provide durable control of HIV replication but how does one protect these T cells from infection. Lastly, in the absence of a sterilizing cure of HIV, HIV-specific CARs may have to monitor and patrol the HIV for local outbursts of the reservoir for decades. How can HIV specific CARs be engineered to persist for decades in the absence of significant quantities of HIV antigen? These topics will be addressed in the educational lecture.
Engineering Synthetic Immunity and Permanent HIV Resistance Add to Itinerary May 11, 2017, 8:00 - 8:35 AM Virginia ABC
Authors Bruce L. Levine, PhD. University of Pennsylvania, Philadelphia, PA Disclosures B.L. Levine: 1; Commercial Interest i.e. Company X; Novartis. 1; What was received? i.e. Honorarium; Licensing Agreement Distribution. 1; For what role? i.e. Speaker; Financial interest due to intellectual property and patents in the field of cell and gene therapy and specifically to CART19 technology. 2; Commercial Interest i.e. Company X; GE Heathcare. 2; What was received? i.e. Honorarium; Consulting Fee. 2; For what role? i.e. Speaker; Consultant. 3; Commercial Interest i.e. Company X; Tmunity Therapeutics. 3; What was received? i.e. Honorarium; Equity. 3; For what role? i.e. Speaker; Co-Founder. Abstract Advances in HIV drug therapy have drastically decreased mortality, morbidity and quality of life for HIV infected patients since the early days of the epidemic. However, HIV drug-resistance, drug toxicities, therapy adherence, and the need for life-long treatment remain major challenges. Recent advances in cancer immunotherapy have proven the potency of cellular gene therapies. The first chimeric antigen receptor trials in humans were however in HIV in the late 1990's. New generation approaches are now in clinic for HIV infection. A second approach to gene modified cell therapy in HIV is to genetically edit T cells to become resistant to HIV infection. These approaches are complementary and offer promise as an alternative to life long anti-retroviral therapy
Multiple interested parties were involved in this process. Puts Sangamo in a very different light. They were in the drivers seat with numerous interested parties in effect bidding for inclusion. - "Several suitors and decision was difficult" - Important to Sangamo that they retain initial manufacturing before eventually handing off per agreement - 50/50 steering committees going forward - Deal structure is NOT an opt-in agreement. Full partnership including future phases and commercialization
Just as importantly, Pfizer takes over all research and dev upon commercialization and is responsible for all costs of commercializing. If this product is successful, the financial impact will be substantial and long lasting.
The platform is being used for the other 3 trials but not this one. The platform potential is far greater than any one project should the ZFN gene editing process deliver the results in these 3 trials that are hoped for. Appears that the MPS I & II programs will quickly surpass the enrollment of SB-Fix so those are the ones expected to deliver data soonest.
"In coming years, as we continue to invest and perfect our genome editing technology, we will apply the knowledge gained into our other technology platforms"
"Likewise, our expertise in gene regulation using Zinc Finger Protein Transcription Factor Technology will continue to expand. As you know we already have a partnership with this for Shire for Huntington's using this approach. " Context: Macrae called this technology the coolest he had seen since joining Sangamo.
Macrae: "Zinc Fingers continues to outpace the Genome Editing field"
Q on Gene Editing Platform vs CRISPR: Levels of on target modifications and specificity that you can't see with other approaches. See how ZFP interacts with DNA to monitor and modify With most targets (60%) the platform allows within 10 days.
Q Lots of interest in Tau programs Delivery? we can achieve greater than 90% down-regulation by direct injection into the hippocampus. And then we showed some of our earlier-stage work that we can actually access a wider area of the CNS using the AAV that we've engineered, where we can achieve somewhere between 30% and 70% down-regulation of tau in different areas of the brain.
this is another program where we've had a lot of interest since the presentation at the Alzheimer's Conference and lots of people are coming to look and help us think about this
Q on Fabry this is an approach that's very similar to the Factor VIII approach as far as using AAV6 and using a gene therapy approach for Fabry. So, in a sense, the preclinical development plan would proceed the same way that we had proceeded with the hemophilia A program.
And therefore, in terms of the plan for moving forward with IND naming studies, we would expect to do some additional studies in some of the Fabry disease models that are in mice and other preclinical animal models as well as perform some of the IND-enabling safety studies very similar to what we did with hemophilia A
Under: Been on the sidelines for a bit holding (building) cash. Now that "BIGLEY" has rolled out the tax plan its time to jump in.
Dec 21, 2017 19:06:02 GMT -6
martyc: Looks like you are buying Msft again!
Dec 15, 2017 11:23:29 GMT -6
martyc: The news that Trump called Rupert to congratulate him sure seems to indicate that this is heading to approval
Dec 15, 2017 11:22:23 GMT -6
Under: DIS finally getting some traction.?
Dec 14, 2017 17:08:45 GMT -6
martyc: I took an entry level position in DIS. Will add eventually to overweight when it becomes clearer that the deal will go thru. Can't believe how well positioned they will be. 60% Hulu. 20% of content watched on NFLX they can pull. More in thread
Dec 14, 2017 11:05:16 GMT -6
Under: Great posts on $DIS
Dec 13, 2017 17:50:49 GMT -6
Under: $ROKU Citron on a war path.
Nov 28, 2017 15:11:20 GMT -6
Under: $HAS takeover bid for $MAT?
Nov 10, 2017 16:16:07 GMT -6
martyc: Not looking like the market will provide any discounted opp for SGMO. Call was just too professional and all signs indicate they are on a great path for commercialization. Happy with core but wish I had some trading shs
Nov 10, 2017 9:04:05 GMT -6
martyc: For anyone looking to find an entry point into SGMO, I'm almost hoping is sells off in next few days so I can add more. They are really clicking but the fact they haven't signed new deals might cause some to exit. Watching as I have room for trading shs
Nov 9, 2017 18:28:09 GMT -6
martyc: Been an interesting ride so far. I figured the Bears would be about this good but hoped the O wouldn't look so lame. Another building yr but still possible to get to 8-8 IMO
Nov 9, 2017 18:26:08 GMT -6
Under: whats up with your Bears this year Marty?
Nov 9, 2017 17:35:25 GMT -6
martyc: Hope you were long ROKU. I wanted to see Q first so missed out
Nov 9, 2017 7:08:53 GMT -6