Management Changes at uniQure

Sep 22, 2016

uniQure Announces Management and Board Changes

Lexington, MA and Amsterdam, the Netherlands, September 22, 2016 — uniQure N.V. (NASDAQ: QURE), a leader in human gene therapy, today announced that its Board of Directors has accepted the resignation of Daniel Soland as chief executive officer (CEO) and an executive member of the Board, effective immediately.  The Board is pleased to announce that Matthew Kapusta, the Company’s chief financial officer (CFO) since January 2015 who also serves as an executive member of the Board, has been appointed interim CEO.  In addition, Philip Astley-Sparke, a member of the Board of Directors and former President of uniQure’s US operations, has been elected unanimously by the Board to serve as its Chairman.

“My decision to resign as Chief Executive Officer is due solely to personal family reasons,” stated Mr. Soland, “I regret the abrupt nature of this decision but believe that it is in the best interests of uniQure, its employees and shareholders to ensure that the business has the fully committed leadership it requires. I have continued confidence in the Company’s gene therapy platform, its research and clinical development programs and its leadership in manufacturing.  I wish everyone associated with the Company tremendous success.”

“We thank Dan for his service to uniQure and wish him well,” stated Philip Astley-Sparke, chairman of the board of uniQure.  “We are fortunate to be able to rely on the continued leadership of Matt Kapusta as interim CEO.  Since joining the Company nearly two years ago, Matt has been instrumental in completing our landmark collaboration with Bristol-Myers Squib, recapitalizing the Company and, more recently, guiding an ongoing, comprehensive strategic planning process.  The Board looks forward to working closely with Matt and the leadership team.”

“This is an exciting and important time for the Company as we advance our hemophilia B program into a potential pivotal trial and more clearly define our focus through the completion of our strategic planning process,” stated Mr. Kapusta.  “I am personally energized and fully committed to driving success at uniQure and ensuring the execution of our key objectives.”

Mr. Kapusta will continue to serve as CFO and rely on the support of the company’s Global Controller, Christian Klemt, to advance the daily responsibilities of the finance team.

“At this time, the Board has elected not to initiate a search process for a permanent CEO while the Company focuses on implementing the corporate strategy being finalized with Matt and the leadership team,” stated Mr. Astley-Sparke.

Following Mr. Soland’s resignation, the Company’s Board of Directors currently consists of seven members, of whom four are independent within the meaning of the applicable Nasdaq rules.  As a consequence, the Company is in compliance with Nasdaq Listing Rule 5605, which requires that at least a majority of the Board consist of independent directors.

About uniQure
uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. We are leveraging our modular and validated technology platform to rapidly advance a pipeline of proprietary and partnered gene therapies to treat patients with liver/metabolic, central nervous system and cardiovascular diseases. www.uniQure.com

Nature Mag - Gene therapy: A new chapter - Sangamo Mention

http://www.nature.com/nature/journal/v537/n7621_supp/full/537S158a.html
Lots of competition !
Great review of LSD programs, here is the Sangamo mention:

The AAVs' payload can be combined with nuclease enzymes for gene editing. This enables the gene to be spliced into the cell's DNA at a predetermined location, reducing the risk of an off-target insertion. Researchers at Sangamo BioSciences in Richmond, California, use AAVs to deliver zinc-finger nucleases and IDUA to liver cells in the patient's body.
“We only have to edit a small number of liver cells, predicted to be less than 1%,” says Michael Holmes, Sangamo's vice-president of research. “That will give a sufficient amount of enzyme to be therapeutic.” As the liver grows, it replicates the edit, generating enzymes throughout the person's life. Sangamo is planning a phase I/II trial involving up to 12 adults with Hurler syndrome this year, and hopes to begin a trial for Hunter syndrome (MPS II) next year.

Cell & Gene Meeting on the Mesa Oct 5-7 Sandy Macrae - Panelist

About the Event The Cell & Gene Meeting on the Mesa is a three-day conference bringing together senior executives and top decision-makers in the industry with the scientific community to advance cutting-edge research into cures. The meeting features a nationally recognized Scientific Symposium, attended by leading researchers and clinical experts from around the globe, in conjunction with the industry's premier annual Partnering Forum, the first event of its kind dedicated solely to facilitating connections in this sector. Combined, these meetings attract over 800 attendees, fostering key partnerships through more than 700 one-on-one meetings while highlighting the significant clinical and commercial progress in the field. Oct 5 GENE EDITING INTERVIEW {Ballroom 1}

10:30am – 11:15am

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.

Chair:

Blythe Thomson, M.D., Senior Director, Medical Affairs, Hematology and Oncology, Medpace

Speakers:

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 OCT 6 COMPANY PRESENTATIONS {Ballroom 1} 1:00pm – 1:15pm Sangamo BioSciences 1:15pm – 1:30pm bluebird bio 1:30pm – 1:45pm Editas Medicine 1:45pm – 2:00pm Intellia Therapeutics 2:00pm – 2:15pm Dimension Therapeutics 2:15pm – 2:30pm Voyager Therapeutics 2:30pm – 2:45pm Adverum Biotechnologies

Prospective Grant of Exclusive Patent License: The Development of an Anti-CD19 Chimeric Antigen Receptor (CAR) for the Treatment of Human Cancers

A Notice by the National Institutes of Health on 09/07/2016

AGENCY:

National Institutes of Health, HHS.

ACTION:

Notice.

SUMMARY:

This notice, in accordance with 35 U.S.C. 209 and 37 CFR part 404, that the National Institutes of Health, Department of Health and Human Services, is contemplating the grant of an exclusive patent license to practice the inventions embodied in the following Patents and Patent Applications and all continuing U.S. and foreign patents/patent applications to Sangamo BioSciences, Inc. located in Richmond, California, USA:

Intellectual Property

U.S. Provisional Patent Application 62/006,313, filed 2 June 2014 and entitled “Chimeric Antigen Receptors Targeting CD-19” [HHS Ref. E-042-2014/0-US-01]; and PCT Patent Application PCT/US2015/033473, filed 1 June 2015 and entitled “Chimeric Antigen Receptors Targeting CD-19” [HHS Ref. E-042-2014/0-PCT-02].

The patent rights in these inventions have been assigned and/or exclusively licensed to the Government of the United States of America.

The prospective exclusive license territory may be worldwide and the field of use may be limited to the use of Licensed Patent Rights for the following: “The integration of a monospecific anti-CD19 chimeric antigen receptor (CAR) into genome-edited, allogeneic T cells (where the donor and recipient are different), where the monospecific CAR has at least: (a) The complementary determining region (CDR) sequences of the anti-CD19 47G4 antibody; and (b) a T cell signaling domain, for the prophylaxis and treatment of CD19-positive malignancies.”

DATES:

Only written comments and/or applications for a license which are received by the NIH Office of Technology Transfer on or before September 22, 2016 will be considered.

ADDRESSES:

Requests for copies of the patent application, inquiries, comments, and other materials relating to the contemplated exclusive license should be directed to: David A. Lambertson, Ph.D., Senior Licensing and Patenting Manager, National Cancer Institute, 9609 Medical Center Drive, Rm. 1-E530 MSC9702, Rockville, MD 20850-9702, Email: david.lambertson@nih.gov.

End Preamble Start Supplemental Information

SUPPLEMENTARY INFORMATION:

This invention concerns an anti-CD19 chimeric antigen receptor (CAR) and methods of using the CAR for the treatment of CD19-expressing cancers, including B cell malignancies. With regard to the proposed license, the CAR covered by the invention will be integrated into a genome-edited allogeneic (where the donor and recipient of the T cell are different individuals) T cell, and the resulting anti-CD19 CAR-expressing genome-edited allogeneic T cell will be introduced into a cancer patient to exhibit a therapeutic effect. CD19 is a cell surface antigen that is preferentially expressed on certain types of cancer cells, particularly cancers of B cell origin such as Non-Hodgkin's Leukemia (NHL), acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). The anti-CD19 CARs of this technology contain (1) antigen recognition sequences that bind specifically to CD19 and (2) signaling domains that can activate the cytotoxic functions of a T cell. The anti-CD19 CAR can be integrated into genome-edited allogeneic T cells; from there, genome-edited allogeneic T cells expressing the anti-CD19 CAR are selected, expanded and then introduced into a patient. Once the anti-CD19 CAR-expressing genome-edited allogeneic T cells are introduced into the patient, the T cells can selectively bind to CD19-expressing cancer cells through its antigen recognition sequences, thereby activating the T cell through its signaling domains to selectively kill the cancer cells. Through this mechanism of action, the selectivity of the a CAR allows the T cells to kill cancer cells while leaving healthy, essential cells unharmed. This can result in an effective therapeutic strategy with fewer side effects due to less non-specific killing of cells.

The prospective exclusive license will be royalty bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR part 404.7. The prospective exclusive license may be granted unless within fifteen (15) days from the date of this published notice, the NIH receives written evidence and argument that establishes that the grant of the license would not be consistent with the requirements of 35 U.S.C. 209 and 37 CFR part 404.7.

Complete applications for a license in the prospective field of use that are filed in response to this notice will be treated as objections to the grant of the contemplated Exclusive Patent License Agreement. Comments and objections submitted to this notice will not be made available for public inspection and, to the extent permitted by law, will not be released under the Freedom of Information Act, 5 U.S.C. 552.

Start Signature

Dated: August 31, 2016.

Richard U. Rodriguez,

Associate Director, Technology Transfer Center, National Cancer Institute.

End Signature End Supplemental Information

[FR Doc. 2016-21366 Filed 9-6-16; 8:45 am]

BILLING CODE 4140-01-P

Additional Source of Revenue - Merck

Merck Launches New Gene Editing Technology to Engineer Virus Resistant CHO Cell Lines

PR Newswire

DARMSTADT, Germany, Sept. 8, 2016

– Enhances viral safety while maintaining cell line productivity, protein quality
DARMSTADT, Germany, Sept. 8, 2016 /PRNewswire/ — Merck, a leading science and technology company, today launched a first-of-its-kind gene editing technology to modify CHO cell lines to be resistant to minute virus of mice (MVM), a common contamination threat that remains despite the shift to chemically defined, animal component-free manufacturing processes. CHO cells are commonly used in the manufacture of biologics.
Photo – http://photos.prnewswire.com/prnh/20160906/404353
Merck’s new Centinel^™ technology targets genes which play a role in MVM susceptibility. Viral contaminations like MVM can have major consequences for biopharmaceutical manufacturers, costing hundreds of millions of dollars, according to industry reports. The greatest impact of such contamination is on patients, as access to therapies can be put in jeopardy. Centinel^™ technology provides manufacturers with an additional path for mitigating the risk of MVM contamination, while maintaining an equivalent level of protein quality and cell line productivity.
“The Centinel^™ program is just one example of how we are combining years of expertise and credibility in process development, biologics manufacturing and gene editing tools to increase safety for our customers and their patients,” said Udit Batra, member of the Merck Executive Board and CEO, Life Science. “We are also leveraging this unique combination of experience and technologies to address some of the industry’s most complex challenges and exciting applications, including cell therapy.”
Under the Centinel^™ program, Merck can modify customers’ CHO cell lines to provide viral resistance to MVM. A patent application has been submitted for the technology used in the gene editing approach to viral resistance.
The company’s BioReliance^® testing services can validate MVM resistance and demonstrate the virus is not propagated in the cell line. Alternatively, customers can purchase the zinc finger nuclease pairs to engineer cell lines directly.
Merck’s new Centinel^™ technology builds on the company’s expertise in gene editing and biomanufacturing processes, as well as its in-depth understanding of the regulatory environment. In addition to enhancing the safety of biomanufacturing, Merck is also applying this expertise and approach to develop other technologies and services, including those supporting the cell therapy industry.
All Merck news releases are distributed by email at the same time they become available on the Merck website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service. 

Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases

http://www.nature.com/mtna/journal/v5/n8/full/mtna201652a.html

Carmen F Bjurström¹, Michelle Mojadidi¹, John Phillips², Caroline Kuo³, Stephen Lai¹, Georgia R Lill¹, Aaron Cooper¹, Michael Kaufman¹, Fabrizia Urbinati¹, Xiaoyan Wang⁴, Roger P Hollis¹ and Donald B Kohn^1,3

1. ¹Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA
2. ²Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, California, USA
3. ³Department of Pediatrics, University of California, Los Angeles, Los Angeles, California, USA
4. ⁴Department of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, California, USA

Correspondence: Donald B Kohn, Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, 3163 Terasaki Life Sciences Building (TLSB) 610 Charles E. Young Drive, East, Los Angeles, California 90095–7364, USA. E-mail: dkohn@mednet.ucla.edu

Received 17 April 2016; Accepted 18 April 2016

Abstract

We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34⁺ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA) (pU6.g1) or in vitro transcribed gRNA (gR.1). Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34⁺ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34⁺ cells had the capacity to engraft in NOD-Prkdc^SCID-IL2Rγ^null mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34⁺ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs), highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs.

FierceBiotech Reports: Shire Abandons Baxalta Aquired Hemophilia Program

From the FierceBiotech website:
http://www.fiercebiotech.com/biotech/shire-cans-baxalta-hemophilia-b-gene-therapy-thinning-field-for-uniqure-spark

Shire ($SHPG) has scrapped plans to further develop BAX 335, a hemophilia B gene therapy it gained in its $32 billion takeover of Baxalta. The move will see Shire focus its attention on a preclinical gene therapy program it thinks has a better chance of success, clearing the path for uniQure ($QURE) and Spark Therapeutics ($ONCE) to beat their bigger rival to market.
Baxalta had advanced the gene therapy as far as a Phase I/II clinical trial, early data from which were released more than one year ago. Those results showed the gene therapy, which uses an AAV8 vector to deliver factor IX (FIX) Padua, elevated the FIX activity of one participant by 20% to 25% for a full year. Yet, while this represented a success for this one patient over that period of time, the overall, longer-term dataset has failed to convince Shire that BAX 335 is worth pursuing.
“The expression was good but it was a little inconsistent between different patients. And, with time for some patients, the level of expression decreased,” Philip Vickers, head of R&D at Shire, said on a conference call with investors to discuss the company’s second-quarter results.
Shire plans to use the experience gained in the clinic to shape a preclinical program. Vickers said the team has an idea of some of the technical factors that could account for the inconsistency and slide in activity over time. And, with the Phase I/II trial showing that when the AAV8 vector works, it works well, Shire thinks it has the makings of an effective asset. Baxalta, through its then parent company Baxter ($BAX), acquired the AAV8 vector in the $70 million takeover of Chatham Therapeutics.
The decision to scrap BAX 335 removes one of the more advanced riders from the congested race to bring a hemophilia B gene therapy to market. As recently as last month, Baxalta was revising the list of clinical trial sites in the Phase I/II study and BAX 335 was still penciled in to start Phase III this year. Now, Shire has pulled the plug on the trial, shortening the odds that one of the biotechs leading the pack will bring a hemophilia B gene therapy to market before their bigger rival.
UniQure and Spark have both delivered some clinical data on their gene therapies, while Dimension Therapeutics ($DMTX) and Sangamo Biosciences ($SGMO) are closing in on that point, too. Of the group, uniQure is seen by investors as having the most to gain from the scrapping of BAX 335. The share price of the Dutch biotech, which has taken repeated hits over the past year, rose 8.5% on the day Shire revealed its decision. Dimension, Sangamo and Spark all closed down.