Genomeweb review of CAR T-cell Therapies: Sangamo Mention

The
Genomeweb website has an excellent review of the CAR-T landscape. It also delves into the benefits of various gene editing techniques. The article can be found here:
https://www.genomeweb.com/gene-silencinggene-editing/gene-editing-drives-development-cancer-t-cell-therapies
Here are some relevant quotes:
With numerous receptors to target, CAR T cells could be engineered every which way to target many kinds of cancer — there's even evidence they could be used to treat solid tumors. But so far they only work as an autologous treatment, where the T cells are isolated from the patient, engineered ad hoc, grown to great numbers, and reintroduced to that same patient. Otherwise, if the T cells came directly from another patient, they would likely turn against the body, inducing graft versus host disease (GVHD).
"From an operational standpoint, it's almost a nightmare," Friesen said of autologous CAR T cell treatment. "It's very difficult and commercially that's not a very viable proposition."

Both Janssen and Cellectis, a Paris-based firm that recently opened a CAR T-cell research center in New York, are pursuing development of an off-the-shelf, or allogeneic, CAR T-cell product that would not cause GHVD. To do this, they'll need to engineer cells so that they don't attack the cells in the body and vice versa, and to make it happen they've both made bold decisions on genome-editing technologies.  Janssen recently partnered with Transposagen to use CRISPR/Cas9, while Cellectis is going a different route with transcription activator-like effector nucleases (TALENs).

Other companies that have announced CAR T cell projects include Kite, Bluebird, and Sangamo Biosciences. Sangamo is trying to engineer T cells to eliminate HIV, using its exclusive zinc finger nuclease gene-editing technology.

But Janssen — and anybody else who is using CRISPR to engineer T cells — may run into problems, André Choulika, CEO of Cellectis, told GenomeWeb.
"It's a new technology for underfunded academic labs, but it's not a technology for industrial therapeutic labs," he said. "The technology is not ready yet."
Cellectis plans to use TALENs in its CAR T cell development, a technology for which it has acquired an exclusive license from the University of Minnesota. Dan Voyntas, a professor there and inventor of TALENs, is the head of Cellectis' plant sciences division.
But Choulika said the company has done its due diligence and prefers TALENs for a variety of reasons. "We've tried them all — Meganucleases, ZFNs, CRISPR. We benchmarked them, comparing all the different technologies," he said, adding that TALENs come out on top in a number of important metrics for engineering CAR T cells.
Choulika said Cellectis can routinely get TCR alpha knockout efficiency of 80 to 95 percent with TALENs. Cellectis measured CRISPR/Cas9 knockout efficiency at around 25 percent, thus any cost savings would be partially lost due to lower effectiveness.
Another problem at this stage in CRISPR/Cas9 technology development is the off-target effects. "You can get your knockouts, but the T cell will lose one thing, which is t-cell expansion. Most of the cells won't be able to amplify," Choulika said.

Sangamo gets mention in International Business Times Article

The relevant section:
If the idea that a virus can improve health still seems a bit far-fetched, know that viruses aren’t the only solution, though the alternatives have yet to make it through clinical trials and some are experiencing setbacks. Scientists may also use tools such as zinc-finger nucleases or Crispr. Both methods can cut a strand of DNA in two, remove a problematic base pair, and insert a new section, but neither of these methods has passed clinical trials. Sangamo BioSciences in Richmond, California, is currently testing zinc-finger nucleases as a way to interrupt a protein that HIV relies on to attack immune cells.


http://www.ibtimes.com/how-live-longer-scientists-are-pushing-make-120-new-70-1900609

PJ Analyst Schimmer " even modest penatration of sickle cell market will be worth over $1 Billion"

To flesh out the report that JBWIN posted on InvestorVillage this morning, I want to add a comment found on the analystratings.com website. This Website contains a quote from PJ analyst Joshua Schimmer that reiterates even a minor penetration of the sickle cell market is worth $1 Billion dollars. http://www.analystratings.com/2015/04/30/biogen-or-bluebird-which-will-lead-in-scd/402054/

"Schimmer also analyzes the pipeline drug developed in partnership between Biogen and Sangamo BioSciences (NASDAQ: SGMO), though he focuses his analysis on Biogen. The two companies are working on a ZFN approach to target BCL11a, meaning the use of artificial enzymes to target a specific protein. Schimmer notes that this approach offers “a viable alternative” to LentiGlobin. If the product is successful, Schimmer believes that “even modest penetration” in the market will deliver over $1 billion. "


I also wanted to reemphasize the point that the PJ analysts made yesterday, that Sangamo has a very good chance of its therapy succeeding.


Piper hosted a call on sickle cell. The focus was largely on what is likely to be technically required for a gene therapy approach to work. Regarding SGMO, the analysis seems to indicate that knock-out of Bcl11a is likely to succeed, with the ever-present caveats of impact of off-target DNA breaks as well as off-target effects of the desired genome modification. The above mentioned erythroid-specific-enhancer knockout for Bcl11a we think typifies the sophistication of Sangamo’s approach to gene therapy. In any case, the Piper analysts estimate that roughly 10-30% bone marrow chimerism could rescue sickle cell, and our discussions with SGMO suggest that level of rescue should be within reach.

ViroMed in Phase III Gene Therapy for DN

This should look familiar to long term investors in Sangamo BioSciences (SGMO) although SGMO did not get past phase II in Diabetic Neuropathy.

VM202-DPN is an innovative new biopharmaceutical that can induce the regeneration of damaged microvasculature and nerve cells
□ Differs from currently used pain killers by providing fundamental treatment for the disease

ViroMed Co., Ltd. (KOSDAQ: 084990:KS) today announced that VM202-DPN, the company's proprietary DNA medicine for the treatment of diabetic peripheral neuropathy (DPN), has received approval from the US FDA for a Phase III clinical trial.
VM202-DPN is an innovative new drug that induces regeneration of damaged microvasculature and nerve cells. When VM202-DPN is injected, a protein called Hepatocyte Growth Factor (HGF) is produced around the injection sites, which induces the formation of new blood vessels and regeneration of nerve cells. The HGF protein produced can treat the extreme pain experienced by diabetic peripheral neuropathy patients. This pain relieving effect has been confirmed through phase I and II clinical study conducted in both the US and Korea.
ViroMed submitted phase III IND based on these results and received approval from US FDA without any additional modification. This indicates that the US FDA, once again, confirms the superb safety and efficacy profile of VM202-DPN. VM202-DPN phase III will be a double-blind study targeting diabetic peripheral neuropathy patients distributed between placebo and VM202-DPN treated groups. The total number of patients will be 477 and the efficacy evaluation will be based on comparison with the placebo group.
Mr. Yong Soo Kim (CEO) commented “If VM202-DPN phase III is successfully completed, it will be the first Korean biopharmaceutical to challenge entry into global market. Currently, we are considering partnership with a global pharmaceutical company to enter the global market.”. 

Sangamo BioSciences Dominates at ASGCT 2015

The American Society for Gene and Cell Therapy has released abstracts for ASGCT 2015.
Sangamo BioSciences (SGMO) has over 20 oral and poster presentations of their ZFN technology by the company or their collaborators.
The abstracts can be viewed here: http://www.abstracts2view.com/asgct/
JBWIN on the Investor Village Message Board has posted the abstracts to save you the search time. The IV board can be viewed here: http://www.investorvillage.com/smbd.asp?mb=1933
Start with message 72663.

Dow Agro Deal to Bolster Sangamo's Bottom Line

Sangamo Biosciences (SGMO) receives license fees and royalties from Dow Agro for licensing Sangamo's technology. Dow has named the product Exazct Precision Technology.
Dow AgroSciences LLC, a wholly owned subsidiary of The Dow Chemical Company (NYSE: DOW), Arcadia Biosciences, Inc. and Bioceres, S.A. announced today an agreement to develop and commercialize innovative traits in soybeans. The collaboration leverages Dow AgroSciences’ technology, regulatory expertise, and commercial seed capabilities with a leading soybean abiotic stress platform and unique grower relationships in South America represented by Verdeca LLC, a joint venture between Arcadia and Bioceres.
Under the collaboration, the companies will develop new soybean traits using Dow AgroSciences’ EXZACT™ Precision Technology platform to generate soybean trait stacks. These stacks will combine Verdeca’s agronomic performance and product quality traits with Dow AgroSciences’ herbicide-tolerant and insect-resistant traits. The EXZACT Precision Technology platform will facilitate the development of multiple trait stacks with greater degrees of precision and speed-to-market. This collaboration is expected to result in products that provide soybean growers around the world with unique and powerful options to achieve greater yields and improved on-farm economics. Dow AgroSciences has developed the EXZACT Precision Technology platform under an exclusive license and collaboration agreement in plants with Sangamo BioSciences, Inc

Phil Gregory Speaking at MIT Synthetic Biology Workshop Today

Philip D. Gregory, D. Phil. , Chief Scientific Officer  and Senior  Vice President, Research of Sangamo BioSciences (SGMO) is presenting at mSBW2.0. This is the International Workshop on Mamilian Synthetic Biology 2.0  Recognizing the fast emergence and potential significance of this field, the aim of this workshop series is to bring practitioners of mammalian synthetic biology together with experts from other relevant fields. The general goals of the workshop are to nucleate the nascent mammalian synthetic biology community, reach out to experts from other fields that can benefit from and contribute to this field, and define the important challenges and future directions. The workshop provides a forum for exposition of the latest developments in the field and discussions of how experts from other fields can benefit from and contribute to mammalian synthetic biology.

Agenda

 

Saturday April 25, 2015
8:00	Registration
8:15	Welcome and Introduction
	Ron Weiss, MIT
8:30	Keynote Speaker
	Professor Elaine Fuchs, The Rockefeller University: "Skin Stem Cells and Their Cancers"
9:30 – 10:30	Session 1 - Foundational Technologies
	George Church, Harvard University: "Engineering mammalian genetic systems, neuro-systems and ecosystems"
	Remus Wong, Stanford University: RNA Regulation of Expression
10:30 – 10:45	Break
10:45 – 12:15	Session 2 - Directing Cell Phenotype
	Charles Gersbach, Duke University: "Epigenome Engineering to Control Cell Phenotype"
	Wendell Lim, UCSF: "Redesigning the T Cell"
	Wilson Wong, Boston University: "Robust and scalable biocomputers in mammalian cells" (short talk)
	Michael Todhunter, UCSF: "Rapid Synthesis of 3D Tissues by Chemically Programmed Assembly" (short talk)
12:15 – 1:30	Lunch
1:30 – 3:00	Session 3 - Design and Optimization of Genetic Circuits
	Michael Elowitz, Caltech: "Design principles for signaling and memory circuits"
	Leonidas Bleris, University of Texas, Dallas: "Custom architectures for control in mammalian cells"
	Silvana Konermann, MIT: "An engineered CRISPR/Cas9 complex for genome-scale transcriptional activation" (short talk)
	Tasuku Kitada, MIT: "RNA ­encoded circuits with small molecular based regulation for 'smart vaccination'" (short talk)
3:00 – 3:15	Break
3:15 – 4:45	Session 4 - Functions of Multicellular Systems
	Ed Boyden, MIT: "Tools for Mapping and Controlling Complex Biological Systems"
	Geraldine Hamilton, Emulate: "Organs-on-Chips: A unique window into human biology and disease"
	Jonathan Brunger, Duke University: "Targeted genome engineering of iPSCs to produce auto-regulated inflammation resistance for regenerative medicine" (short talk)
	Daniel Woodsworth, Genome Sciences Centre: "A lymphocyte based cell-to-cell therapeutic delivery system" (short talk)
4:45 – 5:00	Break
5:00 – 6:00	Session 5 - Gene Regulation and Epigenetic Control
	Karmella Haynes, Arizona State University: "Regulating human cancer epigenomes with synthetic chromatin"
	Kobi Benenson, ETH: "Biological Computing Meets Synthetic Biology"
6:00 -  8:00	Poster Session and Reception
Sunday, April 26, 2015
8:00 – 8:30	Breakfast
8:30-9:30	Closing Plenary
	Professor David Baltimore, California Institute of Technology: "Engineering the Immune System"
9:30-10:30	Session 1 - Circuits and Pathways
	Joshua Leonard, Northwestern University: "Engineering Cell-based Devices that Interface Robustly with Host Physiology"
	Timothy Lu, MIT: "Massively Parallel Combinatorial Genetics"
10:30-10:45	Break
10:45-12:00	Session 2: Industry Research
	Sean Stevens, Synthetic Genomics, Inc.: "Synthetic Biology and Cell Engineering for Biomedical Use"
	Jon Chesnut, Thermo Fisher Scientific: "Democratizing cell engineering: New tools for simplifying and shortening the genome editing workflow"
	Jose-Carlos Gutierrez-Ramos, Pfizer BioTherapeutics
	Philip Gregory, Sangamo Biosciences: "Therapeutic Genome Editing - An Industry Perspective"
	Emily Leproust, Twist Biosciences
12:00-1:00	Lunch
1:00-2:30	Session 3 - Towards cell-based therapies
	Michel Sadelain, Memorial Sloan Kettering Cancer Center: "CAR therapy and the promise of T cell engineering"
	Yvonne Chen, University of California: "Engineering Smarter and Stronger T Cells for Cancer Therapy"
2:30-2:45	Closing Remarks
	Ron Weiss, MIT
2:45	Adjourn