Spark Therapeutics Trial Terminated

As reported on the Investor Village site, the Spark trial, NCT01620801 has a terminated status.

After (Updated 2016_12_18)
1	<clinical_study> <study_id> <org_full_name> Spark Therapeutics </org_full_name> <org_study_id> AAV8-hFIX19-101 </org_study_id> <nct_id> NCT01620801 </nct_id> </study_id> <is_fda_regulated> Yes </is_fda_regulated> <is_section_801> Yes </is_section_801> <delayed_posting> No </delayed_posting> <brief_title> <textblock> Hemophilia B Gene Therapy - Spark </textblock> </brief_title> <official_title> <textblock> A Phase 1 Safety Study in Subjects With Severe Hemophilia B (Factor IX Deficiency) Using a Single-Stranded, Adeno-Associated Pseudotype 8 Viral Vector to Deliver the Gene for Human Factor IX </textblock> </official_title> <study_sponsor> <lead_sponsor> <agency> Spark Therapeutics </agency> </lead_sponsor> <sponsor> <agency> Children&apos;s Hospital of Philadelphia </agency> </sponsor> <sponsor> <agency> University of Pittsburgh </agency> </sponsor> <sponsor> <agency> Royal Prince Alfred Hospital, Sydney, Australia </agency> </sponsor> <sponsor> <agency> St. James&apos;s Hospital, Ireland </agency> </sponsor> </study_sponsor> <resp_party> <resp_party_type> Sponsor </resp_party_type> </resp_party> <oversight_info> <regulatory_authority> United States: Food and Drug Administration </regulatory_authority> <regulatory_authority> United States: NIH Office of Biotechnology Activities </regulatory_authority> <regulatory_authority> Australia: Therapeutic Goods Administration </regulatory_authority> <has_dmc> Yes </has_dmc> </oversight_info> <brief_summary> <textblock> Hemophilia B is a bleeding disease in males due to very low levels of coagulation factor IX (FIX) in the blood. The current treatment is intravenous injection of FIX clotting factor concentrates, in response to bleeding. This study will focus on the severe, most common type of hemophilia B. This study plans to use a virus called adeno-associated virus (AAV), which in nature causes no disease, and can be engineered to deliver the human FIX gene (AAV8-hFIX19 vector) to liver cells, where FIX is normally made. This study will use the AAV8-hFIX19 vector. </textblock> </brief_summary> <detailed_descr> <textblock> Hemophilia B is a bleeding disease in males due to very low levels of coagulation factor IX (FIX) in the blood. The major effect on health is joint disease caused by repeated bleeds into joints like the knee, hip, ankles and elbows. Rarely, the disease causes death due to bleeding into the brain or other important organs. The current treatment is intravenous injection of FIX clotting factor concentrates, in response to bleeding. This study will focus on the severe, most common type of hemophilia B. This study plans to use a virus called adeno-associated virus (AAV), which in nature causes no disease, and can be engineered to deliver the human FIX gene (AAV8-hFIX19 vector) to liver cells, where FIX is normally made. Medical researchers in the United States and England have recently used an AAV vector similar to the one planned for this study, and found that after a single intravenous injection of the vector, blood levels of FIX reached levels greater than 1%, high enough to change the course of disease from severe to moderate. This means that the need to take FIX clotting factor concentrates has decreased, or even stopped. While these are important results, it needs to be noted that two of the six subjects who received the vector at higher doses developed inflammation of the liver. These subjects were treated with a steroid medication called Prednisolone, which is commonly used for serious types of inflammation. Prednisolone seemed to decrease the liver inflammation, as measured by a decrease in blood levels of elevated liver enzymes, and stability of FIX levels at greater than 1% of normal. This study will use the AAV8-hFIX19 vector. The vector will be injected once into a peripheral vein of each subject, while the subject is in the hospital. If everything is fine, the subject will be discharged from the hospital the next day. Three doses of vector (low, middle, and high) will be tested in up to 15 different subjects, depending on safety outcome (as determined by blood and urine tests) and results of FIX levels. If some subjects develop liver inflammation, a short, tapering course of corticosteroids will be used. </textblock> </detailed_descr> <status_block> <status>	<clinical_study> <study_id> <org_full_name> Spark Therapeutics </org_full_name> <org_study_id> AAV8-hFIX19-101 </org_study_id> <nct_id> NCT01620801 </nct_id> </study_id> <is_fda_regulated> Yes </is_fda_regulated> <is_section_801> Yes </is_section_801> <delayed_posting> No </delayed_posting> <brief_title> <textblock> Hemophilia B Gene Therapy - Spark </textblock> </brief_title> <official_title> <textblock> A Phase 1 Safety Study in Subjects With Severe Hemophilia B (Factor IX Deficiency) Using a Single-Stranded, Adeno-Associated Pseudotype 8 Viral Vector to Deliver the Gene for Human Factor IX </textblock> </official_title> <study_sponsor> <lead_sponsor> <agency> Spark Therapeutics </agency> </lead_sponsor> <sponsor> <agency> Children&apos;s Hospital of Philadelphia </agency> </sponsor> <sponsor> <agency> University of Pittsburgh </agency> </sponsor> <sponsor> <agency> Royal Prince Alfred Hospital, Sydney, Australia </agency> </sponsor> <sponsor> <agency> St. James&apos;s Hospital, Ireland </agency> </sponsor> </study_sponsor> <resp_party> <resp_party_type> Sponsor </resp_party_type> </resp_party> <oversight_info> <regulatory_authority> United States: Food and Drug Administration </regulatory_authority> <regulatory_authority> United States: NIH Office of Biotechnology Activities </regulatory_authority> <regulatory_authority> Australia: Therapeutic Goods Administration </regulatory_authority> <has_dmc> Yes </has_dmc> </oversight_info> <brief_summary> <textblock> Hemophilia B is a bleeding disease in males due to very low levels of coagulation factor IX (FIX) in the blood. The current treatment is intravenous injection of FIX clotting factor concentrates, in response to bleeding. This study will focus on the severe, most common type of hemophilia B. This study plans to use a virus called adeno-associated virus (AAV), which in nature causes no disease, and can be engineered to deliver the human FIX gene (AAV8-hFIX19 vector) to liver cells, where FIX is normally made. This study will use the AAV8-hFIX19 vector. </textblock> </brief_summary> <detailed_descr> <textblock> Hemophilia B is a bleeding disease in males due to very low levels of coagulation factor IX (FIX) in the blood. The major effect on health is joint disease caused by repeated bleeds into joints like the knee, hip, ankles and elbows. Rarely, the disease causes death due to bleeding into the brain or other important organs. The current treatment is intravenous injection of FIX clotting factor concentrates, in response to bleeding. This study will focus on the severe, most common type of hemophilia B. This study plans to use a virus called adeno-associated virus (AAV), which in nature causes no disease, and can be engineered to deliver the human FIX gene (AAV8-hFIX19 vector) to liver cells, where FIX is normally made. Medical researchers in the United States and England have recently used an AAV vector similar to the one planned for this study, and found that after a single intravenous injection of the vector, blood levels of FIX reached levels greater than 1%, high enough to change the course of disease from severe to moderate. This means that the need to take FIX clotting factor concentrates has decreased, or even stopped. While these are important results, it needs to be noted that two of the six subjects who received the vector at higher doses developed inflammation of the liver. These subjects were treated with a steroid medication called Prednisolone, which is commonly used for serious types of inflammation. Prednisolone seemed to decrease the liver inflammation, as measured by a decrease in blood levels of elevated liver enzymes, and stability of FIX levels at greater than 1% of normal. This study will use the AAV8-hFIX19 vector. The vector will be injected once into a peripheral vein of each subject, while the subject is in the hospital. If everything is fine, the subject will be discharged from the hospital the next day. Three doses of vector (low, middle, and high) will be tested in up to 15 different subjects, depending on safety outcome (as determined by blood and urine tests) and results of FIX levels. If some subjects develop liver inflammation, a short, tapering course of corticosteroids will be used. </textblock> </detailed_descr> <status_block> <status>
2	Active, not recruiting	Terminated

New Name : Sangamo Therapeutics - New Website

www.sangamo.com

Change in IR Dept:

McDavid Stilwell

Vice President, Corporate Communications and Investor Relations

Spark Therapeutics Announces $15 Million Milestone Payment from Pfizer for Progress in Hemophilia B Gene Therapy Program

Second milestone achieved under 2014 global license agreement with Pfizer

PHILADELPHIA, Jan. 04, 2017 (GLOBE NEWSWIRE) -- Spark Therapeutics (NASDAQ:ONCE), a fully integrated gene therapy company dedicated to challenging the inevitability of genetic disease, today announced that it has earned a $15 million payment from Pfizer Inc. (NYSE:PFE) for achieving a pre-specified safety and efficacy profile development milestone in the ongoing hemophilia B Phase 1/2 trial of investigational SPK-9001. SPK-9001 has received breakthrough therapy and orphan product designations from the U.S. Food and Drug Administration.

"We continue to make strong, tangible progress with our hemophilia pipeline, and achievement of this second milestone marks further advancement in the development of our investigational gene therapy for hemophilia B," said Jeffrey D. Marrazzo, chief executive officer of Spark Therapeutics. "We look forward to reporting additional data as we continue to document the clinical experience with SPK-9001."
Under the terms of the license agreement with Pfizer, Spark Therapeutics received a $20 million upfront payment upon entering into the agreement in 2014, and a $15 million milestone payment in December 2015 for progress with the development program. The company is eligible to receive up to an additional $230 million in aggregate for achieving future development and commercial milestones, as well as royalties calculated as a low-teen percentage of net sales on any potential SPK-FIX products. Spark Therapeutics maintains responsibility for the clinical development of SPK-FIX product candidates through the completion of Phase 1/2 trials. Thereafter, Pfizer has responsibility for further clinical development, achieving regulatory approvals and potential global commercialization.
The SPK-FIX program leverages a more than two-decade long history of hemophilia gene therapy research and clinical development conducted by Spark Therapeutics and its founding scientific team. SPK-9001 is a novel bio-engineered adeno-associated virus (AAV) capsid expressing a codon-optimized, high-activity human factor IX variant enabling endogenous production of factor IX.

Sangamo Files for CT Order 12/8/16

SECURITIES AND EXCHANGE COMMISSION
8 December 2016
ORDER GRANTING CONFIDENTIAL TREATMENT
UNDER THE SECURITIES EXCHANGE ACT OF 1934
Sangamo BioSciences, Inc.
File No. 0-30171 -- CF# 34340
_____________________
Sangamo BioSciences, Inc. submitted an application under Rule 24b-2 requesting
confidential treatment for information it excluded from the Exhibits to a Form 10-Q filed
on October 27, 2016.
Based on representations by Sangamo BioSciences, Inc. that this information
qualifies as confidential commercial or financial information under the Freedom of
Information Act, 5 U.S.C. 552(b)(4), the Division of Corporation Finance has determined
not to publicly disclose it. Accordingly, excluded information from the following
exhibit(s) will not be released to the public for the time period(s) specified:
Exhibit 10.1 through January 8, 2019
Exhibit 10.2 through July 10, 2022
Exhibit 10.3 through September 20, 2026
For the Commission, by the Division of Corporation Finance, pursuant to
delegated authority:
Brent J. Fields
Secretary

2012 Dow Agro Inks Reseach License with Agriculture Victoria, 2016 Commercial License

From 2012:

Aug 31, 2012

NEW YORK (GenomeWeb News) – Dow AgroSciences has struck a collaboration with Australia's Victoria Department of Primary Industries (DPI)to develop new genetics technologies to boost crop performance, the Dow Chemical subsidiary said this week.
Under the agreement, the partners plan to develop elite crop varieties with improved productivity and product quality traits.
The collaboration expands an earlier research and development program, launched in 2009, between DPI and Dow AgroSciences, a subsidiary of Dow Chemical.

Today:

Dec. 7, 2016

Source: Dow AgroSciences news release

New and innovative forage products are on the horizon driven by continued collaboration between Dow AgroSciences, a wholly owned subsidiary of The Dow Chemical Company (NYSE: DOW), and Agriculture Victoria, Australia.

Dow AgroSciences works on a variety of projects with Agriculture Victoria through its commercial arm, Agriculture Victoria Services Pty Ltd. (AVS), and today announces that AVS is taking a commercial license to the EXZACT™ Precision Technology Platform to continue the development and commercialization of new forage grass varieties to benefit farmers in Australia and around the world.

The commercial license agreement focuses on the development of forage grass varieties and associated fungal endophytes developed using precision genome editing technologies. It builds on the major Research License Agreement AVS has with Dow AgroSciences to conduct research using the company's proprietary EXZACT™ Technology.

The announcement of a milestone commercial license between Dow AgroSciences and AVS recognizes the advances Agriculture Victoria has made researching and developing innovative forage products using this gene editing platform that Dow AgroSciences has developed under an exclusive license and collaboration agreement in plants with Sangamo BioSciences, Inc.

"Our focus is on the farmer, and this commercial license validates the broad application of the EXZACT™ technology that can translate into new products for farmers around the world, and also illustrates the power of collaboration to advance technology," said Daniel R. Kittle, Ph.D., vice president, Research and Development, Dow AgroSciences.

"Our most productive collaboration with Dow AgroSciences has enabled the development of a suite of innovations for crop improvement. It has also provided us with access to the EXZACT™ technology for its application in forage grasses with global reach, to deliver benefits on-farm to dairy, beef and sheep industries," said Professor German Spangenberg, Agriculture Victoria's Executive Director Biosciences Research. 

UPENN-SANGAMO Genetically engineered T cells render HIV's harpoon powerless

PHILADELPHIA-- When HIV attacks a T cell, it attaches itself to the cell's surface and launches a "harpoon" to create an opening to enter and infect the cells. To stop the invasion, researchers from the Penn Center for AIDS Research at the University of Pennsylvania and scientists from Sangamo BioSciences, Inc. have developed genetically engineered T cells armed with a so-called "fusion inhibitor" to disrupt this critical step and prevent a wide range of HIV viruses from entering and infecting the T cells. The findings were reported today online in a preclinical study in PLOS Pathogens.
HIV medicine experienced a breakthrough in the early 2000s with a unique class of drugs known as "fusion inhibitors." Unlike most drugs that block virus replication inside of T cells, these drugs prevent HIV from entering cells in the first place. The drug, enfuvirtide, modeled after a peptide from the viral envelope and used today in combination with other antiretroviral therapies, has been shown to keep the virus at bay. However, patients need to inject enfuvirtide daily under their skin, limiting its utility and acceptability to patients, especially when compared to many other orally available drugs. HIV can also become resistant to enfuvirtide.
Building on this approach with a powerful genetic technique, researchers developed a novel way to deliver the fusion inhibitor peptide precisely to the spot on the cell surface where the virus attaches and launches its envelope, like a harpoon. The team genetically altered T cells by introducing a so-called C34 peptide, modeled after enfuvirtide, directly onto receptors, CXCR4 and CCR5, which are crucial for HIV entry. By using these molecules to deliver the C34 peptide to the site where the virus enters, these investigators showed that HIV was potently inhibited and that this inhibition extended to genetically diverse HIVs, including those that were resistant to the drug, enfuvirtide.
The most impressive results were seen when the C34 peptide was attached to CXCR4, where the Penn investigators showed that T cells expressing this molecule were protected in a mouse model of HIV infection.
"We believe that our approach to precisely target an inhibitory drug to the site of viral entry creates a new way to engineer human T cells to become resistant to HIV infection," said senior author James Hoxie, MD, a professor of Medicine in the division of Hematology/Oncology in the Perelman School of Medicine at the University of Pennsylvania. "It's potent and very broad. Every strain of HIV we tried was sensitive to it, regardless of whether the virus used CCR5 or CXCR4, which is a big advantage, since HIV typically uses CCR5 to establish infection, but can over time, evolve to use a CXCR4 instead. With this approach, it doesn't matter where the virus came from or what cellular molecule it needs to infect cells."
The findings set the stage for an upcoming phase I clinical trial in HIV-positive patients to determine the safety and appropriate dosage of a patient's own T cells engineered to express the C34-CXCR4 molecule, as well as to demonstrate their ability to resist infection when antiretroviral therapy is interrupted.
The research team also includes James L Riley, PhD, an associate professor of Microbiology, Pablo Tebas, MD, a professor of Medicine and director of the AIDS Clinical Trials Unit at the Penn CFAR, along with co-first authors, George Leslie, PhD, a senior research investigator in Hoxie's lab, Jianbin Wang, PhD and Michael C. Holmes, PhD, of Sangamo Biosciences, Inc. and Max W. Richardson, PhD, a senior research investigator in Riley's Lab.
Peptides derived from the HIV-envelope protein inhibit HIV entry by interfering with the formation of what is termed the 6-helix bundle during fusion of the viral and cellular membranes that occurs during viral entry. This is how enfuvirtide works, although when injected as a drug, enfuvirtide is distributed throughout the entire body. In the work described by the Penn and Sangamo researchers, performed in the laboratory and in a humanized mouse model, the C34 peptide attached to the CXCR4 molecule delivered the peptide to where fusion was actually occurring.
In the lab, the researchers found that T cells expressing either C34-CCR5 or C34-CXCR4 were enriched in the presence of HIV infection, going from 25 percent of the T cell population to greater than 60 percent after 7-10 days of additional culture. This enrichment was observed against a wide array of HIV strains, suggesting that this approach will be highly effective in a vast majority of individuals. Similar data was obtained using a humanized mouse model of HIV infection. In the experiments, only CD4 T cells expressing C34-CXCR4 were able to resist HIV infection and survive within the mouse. For this reason, C34-CXCR4 was chosen to be used in a phase I clinical trial.
This work builds off past experimental, genetic HIV techniques. In 2014, Penn researchers successfully genetically engineered the immune cells of HIV positive patients to resist infection, and decreased the viral loads of some patients taken off therapy entirely. The group used the zinc finger nuclease (ZFN) technology developed by Sangamo BioSciences to modify the T cells in the patients--a "molecular scissors," of sorts, to eliminate the CCR5 surface proteins. Without it, the virus couldn't enter. However, there are some limitations with this approach: it only addresses viruses that use CCR5 and both CCR5 alleles need to be knocked out for the T cells to be protected from infection.
The clinical trial investigating the work with C34 is slated to start in December 2016. The researchers will infuse C34-CXCR4 expressing T cells into well-controlled HIV infected individuals. It will be a dose-escalation study in which 1, 3, or 10 billion engineered T cells will be infused. After infusion, an "analytical treatment interruption" will occur for about 16 weeks and time to viral rebound and enrichment for the C34-CXCR4 expressing cells will be monitored. At present, patients infected with HIV must continue to take anti-HIV drugs to prevent the virus from replicating and causing disease. Efforts are underway at Penn and throughout the world to develop strategies that will enable drug therapy for HIV to be discontinued safely.
"This may provide a successful novel strategy to supplement anti-viral immune responses that complement approaches to target or control HIV reservoirs in patients infected with the virus," the authors said.

###

Co-authors on the study include Beth Haggarty, Kevin L. Hua, Jennifer Duong, Anthony J. Secreto, Andrea P.O. Jordon, Josephine Romano, Kritika Kumar, Joshua J. DeClercq, Philip D. Gregory, Carl H. June, and Michael J. Root.
The study was supported with grants from the National Institutes of Health (U19 AI117950, U19 AI082628, and P30 AI045008) and the Penn Center for AIDS Research

UniQure to cut up to 25% of Staff

http://www.uniqure.com/investors-newsroom/press-releases.php

uniQure expects to realize €5 to €6 million of annualized cost savings

 in personnel and other related operating expenses as a 

result of the elimination

 of approximately 50 to 60 positions, or 20% to 25% of global headcount,

 by the end of 2017. Additionally, the Company expects to

 further reduce planned 

operating expenses by €11 to €15 million over the next two years through

 the focusing of its pipeline. Based on its strong cash position

 and the above actions,

 uniQure believes its existing cash resources will be

 sufficient to fund operations into 2019