StemCell Therapy

Nov. 16, 2020 12:30 UTC

- Highly innovative genome editing technology platform accelerates and broadens ElevateBios cell and gene therapy enabling technologies

- LifeEDIT Therapeutics to develop its own pipeline of potentially life-transforming therapeutics

- LifeEDIT Therapeutics to leverage its novel gene editing platform with strategic partners including ElevateBio portfolio companies

CAMBRIDGE, Mass. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- ElevateBio, a Cambridge-based cell and gene therapy holding company, and AgBiome, a leader in developing innovative products from the Earth's microbial communities, today announced that LifeEDIT Therapeutics has joined ElevateBios growing portfolio of therapeutic, technology and manufacturing companies. LifeEDIT Therapeutics combines a highly innovative genome editing platform, derived from AgBiomes massive proprietary microbial library, with ElevateBios proven expertise in the discovery and development of new cell and gene therapies. LifeEDIT will continue to develop internal cell and gene therapies while further strengthening its platform of diverse genome-editing enzymes and provide gene editing expertise to strategic partners including ElevateBio portfolio companies. AgBiome retains rights for gene editing in agriculture, animal health, and diagnostics.

Genome editing technologies have revolutionized the way we develop cell and gene therapies and regenerative medicines, said Mitchell Finer, Ph.D., President, ElevateBio BaseCamp, and newly appointed Chief Executive Officer, LifeEDIT Therapeutics. However, in order to realize the promise of, and democratize, these highly innovative therapeutic approaches, the field needs to access novel RNA-guided nucleases and base editors that offer greater specificity and broader genome coverage, which LifeEDIT can provide. LifeEDITs genome editing platform is one of the most versatile in the field and was the natural fit as we continue to build a world leading cell and gene therapy offering.

Members of ElevateBio will join the newly formed LifeEDIT Therapeutics management team, which will continue to benefit from its existing visionary scientific leadership and research team. The combined executive team will include:

Over the last 18 months we have built a truly unique platform of numerous RNA-guided nucleases with diverse PAM requirements, for which weve been able to show functional activity, said Tedd Elich, Ph.D., Chief Scientific Officer, LifeEDIT Therapeutics. The wide range of gene editing enzymes across our platform increases our ability to target any genomic sequence of interest and will allow us to tackle some of the most challenging diseases, bringing desperately needed, potentially curative, therapies to patients in need.

"AgBiome's GENESISTM platform is built on our microbial collection, their complete genome sequences, and our industry-best data science platform to identify new useful functions, said Eric Ward Co-Chief Executive Officer, AgBiome. This unique resource formed the basis for the many genome editing technologies that are now part of LifeEDIT Therapeutics. We look forward to continuing to collaborate with the LifeEDIT team as they build a world-class pipeline of clinical candidates and bring a broad array of genome editing technologies to innovators across the biotechnology industry."

About Genome Editing and LifeEDIT Therapeutics Platform

Genome editing technologies have revolutionized the way cell and gene therapies and regenerative medicines are discovered and developed by allowing genetic material to be removed, added, or altered at specific locations in the genome. While these technologies are in widespread use experimentally, enzymes that offer broader coverage and greater specificity are needed for creating novel cell and gene therapies.

To meet the need for better genome editing approaches, LifeEDIT Therapeutics has built one of the worlds largest and most diverse arrays of novel RNA-guided nucleases (RGNs) and base editors that are active in mammalian cells. These RGNs were developed using AgBiomes proprietary collection of more than 90,000 microbes and their complete genomes. LifeEDIT Therapeutics is investigating these proprietary RGNs, which are sourced exclusively from non-pathogenic organisms, to develop new gene editing tools with higher fidelity, novel functionality, reduced immune response risk, and easier delivery. LifeEDIT Therapeutics nuclease collection also has a broad range of Protospacer Adjacent Motifs (PAMs) short sequences that must follow the targeted DNA sequence in order for the enzyme to make cuts that offer unprecedented access to genomic loci of interest. The LifeEDIT Therapeutics RGNs offer flexible editing options which encompass knock-out and knock-in capabilities, transcriptional regulation, and base editing when coupled with its proprietary deaminases.

LifeEDIT Therapeutics next generation editing systems will propel the development of novel human therapeutics by enabling ex vivo engineering for cell therapies and regenerative medicines and in vivo delivery of gene therapies. In addition to developing its own pipeline of cell and gene therapies, LifeEDIT Therapeutics will continue to build its platform of novel nucleases, provide gene editing expertise to strategic partners and ElevateBios portfolio companies, and form other third-party partnerships to discover and develop new therapies.

About ElevateBio

ElevateBio, LLC, is a Cambridge-based creator and operator of a portfolio of innovative cell and gene therapy companies. It begins with an environment where scientific inventors can transform their visions for cell and gene therapies into reality for patients with devastating and life-threatening diseases. Working with leading academic researchers, medical centers, and corporate partners, ElevateBios team of scientists, drug developers, and company builders are creating a portfolio of therapeutics companies that are changing the face of cell and gene therapy and regenerative medicine. Core to ElevateBios vision is BaseCamp, a centralized state-of-the-art innovation and manufacturing center, providing fully integrated capabilities, including basic and translational research, process development, clinical development, cGMP manufacturing, and regulatory affairs across multiple cell and gene therapy and regenerative medicine technology platforms. ElevateBio portfolio companies, as well as select strategic partners, are supported by ElevateBio BaseCamp in the advancement of novel cell and gene therapies.

ElevateBios investors include F2 Ventures, MPM Capital, EcoR1 Capital, Redmile Group, Samsara BioCapital, The Invus Group, Emerson Collective, Surveyor Capital (A Citadel company), EDBI, and Vertex Ventures.

ElevateBio is headquartered in Cambridge, Mass, with ElevateBio BaseCamp located in Waltham, Mass. For more information, please visit http://www.elevate.bio.

About AgBiome

AgBiome partners with the microbial world to improve our planet. AgBiome discovers and develops innovative biological and trait products for crop protection. The proprietary GENESIS discovery platform efficiently captures diverse, unique microbes for agriculturally relevant applications, and screens them with industry-best assays for insect, disease, and nematode control. Through its commercial subsidiary, AgBiome develops and sells proprietary crop protection solutions. The first of these, Howler, is a revolutionary fungicide for disease control in a broad variety of crops. AgBiome and Genective recently formed a strategic partnership to establish a new leader in insect traits, a market with over $5 billion in annual opportunities. AgBiome has a global R&D collaboration with Elanco Animal Health Incorporated (NYSE: ELAN), to develop nutritional health products for swine. AgBiomes investors include Polaris Partners, ARCH Venture Partners, Fidelity Investments Inc., UTIMCO, Pontifax AgTech, Innotech Advisors, Syngenta Ventures, Leaps by Bayer, and Novozymes. For more information, visit http://agbiome.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201116005105/en/

Excerpt from:
ElevateBio and AgBiome Announce LifeEDIT Will Join ElevateBio's Portfolio of Innovative Cell and Gene Therapy Companies - BioSpace

Maryland, US headquartered company, Orgenesis, is championing a model that aims to bring down those costs it works with partner hospitals throughout the commercialization process.

The companys CGT platform, consisting of a pipeline of licensed cell and gene therapies, scientific expertise, customised processing systems, and an ecosystem of healthcare providers and research institutes, is designed to provide a pathway for groundbreaking autologous therapies to become commercially available on an industrial scale and at prices accessible to large populations.

Orgenesis business model is one focused on decentralization, enabling precision medicines to be prepared on-site at hospitals. In this way, we can really expedite cell and gene therapy development, said Orgenesis CEO, Vered Caplan.

With operations in the US, Europe, Israel and South Korea, Orgenesis has now created an international network of point of care (POCare) centers to serve patients directly in the hospital setting.

Beyond the US, we have POCare centers in many countries in Europe such as Greece, the Netherlands, Belgium, Slovenia, Italy and Spain; we also have centers in Israel, in Korea and in India and we will be starting up soon in Dubai,said the CEO.

The goal is to make gene and cell therapies feasible for large numbers of patients, said Caplan. We used to work as a contract development and manufacturing organization (CDMO) but we sold that business to Catalent at the beginning of the year.

The centralized processing and supply chain model only served to create a frustrating working environment, with plenty of constraints, said the Orgenesis lead.

We realized very quickly that we couldnt really ramp up to large scale relying on that kind of centralized model, particularly for autologous products, which represent most of the market today. It takes six months to train someone to work in a high-grade cleanroom there is a lot of work and expense involved in that and there is a limited number of patients that can be treated in such cleanrooms the utilization rate is very low - it [centralized processing and supply] is a very inefficient and costly way to supply and to develop medicine there is so much manual work involved, she told BioPharma-Reporter.

The company had been working for a number of years, investing a huge amount of effort in developing a range of automation solutions to supplant those manual processes, as well as building its mobile CGT processing labs and units (OMPULs), she said.

We had been fielding so many requests from hospitals that wanted to collaborate with us, asking us to make or scale up their CAR-T and other therapies. We realized that in order to get this done, we needed to take a decentralized approach and that we needed to provide a solution, not only for one hospital, but for every hospital that wanted these type of therapies; and we saw that such a model brings down the price of the therapy tremendously.

A hospital gives Orgenesis a license to work on the therapy, on the processing; production of the final product is automated and supplied via an on-site point-of-care processing unit. Orgenesis then sets about democratizing the treatment,making it available to any hospital in its POCare network.

The company says the final customized, automated processing system it has developed, with the integrated specific therapy, solves a variety of processing and cost hurdles. It results in a lower required grade of cleanroom, it simplifies facility management requirements, it enables multi-batch processing per cleanroom, which means reduced technical staffing. Moreover, the localized processing eliminates the many logistical difficulties associated with traditional, centralized manufacturing and transport.

Overall, it is said to provide faster turnaround, increased safety, and improved quality control management on-site.

Hospitals really want to supply CGTs, while patients are reading about such treatments and making inquiries of healthcare providers, she added.

Ours is really a combined licensing and service model.

We are like Uber. If you have a car, you want to make some extra revenue, you call up Uber and it gives you the network, the technology and all the operating procedures to be a taxi driver. That is very much what we do in terms of hospitals we give them the ability to be biotech companies, because this is not the standard thing they do, they dont want to take responsibility for cell and gene therapy it is too much for them. They want to treat patients, but they want to have that local supply, so we give them the technology and the capabilities to do that. We give them regulatory support for clinical trials, we give them CRO support, we give them a network - so they can function and do what they need to do, which is to undertake research and treat patients.

Orgenesis intends to leverage its network of regional partners to advance the development and commercialization of its therapeutic pipeline. Towards this end, it said its partners have committed to funding the clinical programs. In turn, the company typically grants its partners geographic rights in exchange for future royalties, and a partnership with Orgenesis to support the supply of the targeted therapies. Through this model, Orgenesis has already signed contracts, which it expect to generate over US$40M in revenue over the next three years, if fully realized.

On the therapeutic front, Orgenesis is focused on several key verticals, including immuno-oncology, anti-viral, and metabolic/auto-immune diseases.

It recently acquired Koligo Therapeutics, with the aim of leveraging Koligos 3D-V bioprinting technology across its POCare Platform. That technology, which utilizes 3D bioprinting and vascularization with autologous cells to create biodegradable and shelf-stable three-dimensional cell and tissue implants, is being developed for diabetes and pancreatitis, with longer term applications for neural, liver, and other cell/tissue transplants.

In February this year, Orgenesis announced that it has entered into a collaboration agreement with the John Hopkins University to utilize the POCare platform to develop and supply a variety of CGTs including cell-based immunotherapy technologies.

And the University of California, Davis (UC Davis) joined its POCare network in January. The collaboration will involve the scale up and integration of UC Davis lentiviral vector process.

Today we are very much in validation mode. Most of the therapies in this space, and the ones we have licensed from the hospitals I think we have about 25 today are all at different stages of clinical development. Some have been used to treat patients but that has all been done under hospital exception.

When we adopt a therapy into the network, we run it through the entire R&D, formal clinical and regulatory processes as [our goal] is a harmonized process, to have the same standard [in our closed systems] at our [POCare] centers, whether that is in Germany or Korea, said the CEO.

Excerpt from:
Orgenesis CEO talks disruption: 'We are the Uber of the cell and gene therapy space' - BioPharma-Reporter.com

UCB has struck a deal to buy gene therapy startup Handl Therapeutics. The takeover, which was disclosed alongside a separate gene therapy collaboration, positions UCB to accelerate its push into genetic medicines.

In recent years, UCB has quietly built out its genetic medicine capabilities, buying Element Genomics for a small sum in 2018 while hiring gene therapy specialists and creating plans to refurbish an ex-Eli Lilly R&D site to support its aspirations in the area. Those efforts have been overshadowed by the big-ticket gene therapy deals struck by UCBs peers but point to its interest in the space.

UCB stepped up its gene therapy expansion on Thursday with two deals. UCB has bought Handl for an undisclosed sum to gain control of technology platforms designed to facilitate the development of AAV gene therapy treatments for complex neurodegenerative diseases.

Start using real-world data to advance your clinical research

Much has been written about the promise of real-world data (RWD) in life sciences, but how does it work in practice? We address this question in a new whitepaper that demonstrates the potential benefits of new RWD technologies with a proof of concept study to show how RWD can be incorporated into clinical research.

Handl was founded by Florent Gros, a Novartis veteran, and Michael Linden, an AAV expert who set up the Pfizer Genetic Medicine Institute in London. Working out of Leuven, Belgium, Handl has used the expertise and connections of Gros, its CEO, and Linden, its CSO, to identify and license technologies from Spain, Chile, the U.K. and Belgium.

The Chilean and Spanish academic centers that struck licensing deals with Handl put out statements about their work, disclosing an interest in treating diseases including Alzheimers, amyotrophic lateral sclerosis and Parkinsons. Handl entered into a manufacturing contract with Novasep earlier this month, securing support as it wraps up ongoing IND-enabling studies and moves into the clinic.

As part of UCB, the Handl team will continue to work on that program and other projects from its base in Leuven. UCBs international research teams will collaborate with the Handl group.

UCB disclosed the Handl takeover alongside details of a collaboration with Lacerta Therapeutics, a Florida-based AAV gene therapy startup. The deal gives UCB access to Lacertas pipeline of CNS gene therapies. Lacerta will handle research, preclinical and early process development, leaving UCB to focus on IND-enabling studies and subsequent manufacturing work and clinical development.

Follow this link:
UCB inks Handl buyout to boost nascent gene therapy unit - FierceBiotech

Penn Medicine researchers have developed a new targeted approach to prevent a toxicity seen in the sensory neurons of dorsal root ganglia after gene therapy to treat neurological disorders. It's an important hurdle to clear, as the field works toward more safe and effective gene therapies for patients with disorders like spinal muscular atrophy.

"We believe that this new approach could improve safety in gene therapy universally," said first author Juliette Hordeaux, DVM, PhD, senior director of Translational Research in Penn's Gene Therapy Program.

The findings were reported online this week in theScience Translational Medicine.

The toxicity has not been reported in humans, but studies in nonhuman primates using adeno-associated viral (AAV) vectors to deliver corrected genes via the spinal cord fluid and intravenously have revealed problems of axonal degeneration in some tracts of the spinal cord and peripheral nerves. The cause was traced back to the dorsal root ganglion, or DRG, a cluster of neural cells on the outside of the spinal cord responsible for transmission of sensory messages.

This toxicity stems from the overexpression of an introduced gene, known as a transgene, in cells in the DRG, researchers from Penn's Gene Therapy Program found in the study. To correct that, they modified a transgene with a microRNA target designed to reduce the level of the transgene expression in the DRG. That alteration eliminated more than 80 percent of the transgene expression and reduced the toxicity in primates, the researchers report.

"We believe it is a safe, straightforward way to ameliorate the safety of AAV therapy for the central nervous system," said first author Juliette Hordeaux, DVM, PhD, senior director of Translational Research in Penn's Gene Therapy Program. "This approach could be used to design other gene therapy vectors to repress transgene expression in the cell types that are affected by the toxicity and not others, which is critical, because you need the expression everywhere else to effectively treat the disorder."

Gene transfer expert James M. Wilson, MD, PhD, director of the Gene Therapy Program, and professor of Medicine and Pediatrics in Penn's Perelman School of Medicine, served as the senior author of the paper.

After Penn researchers documented DRG toxicity in nonhuman primates, they began devising a way to overcome it. Though its asymptomatic in primates, the damage became clear under close study of histopathology in the CNS. Damage to the DRG in humans, researchers know, can lead to the breakdown of axons responsible for delivering impulses from nerves to the brain. Numbness and weakness in limbs, among other side effects, follow suit.

The observed toxicity in past animal studies was enough for the U.S. Food and Drug Administration to recently place a partial hold on human trials administering a gene therapy vector into the spinal cord to treat spinal muscular atrophy, the genetic disease that severely weakens muscles and causes problems with movement. In the new study, the researchers injected vectors with and without an microRNA target, first in mice and then primates. microRNA regulates gene expression and makes for an ideal target in the cells. microRNA-183 was chosen specifically because it is largely restricted to the neurons in the DRG.

Administering unmodified AAV vectors resulted in robust delivery of the new gene into target tissue and toxicity in DRG neurons. Vectors with the miRNA target, on the other hand, reduced transgene expression significantly, as well as the toxicity of DRG neurons, without affecting transduction elsewhere in the primate's brain, histological analyses of the specimens up to 90 days later showed. An immune response was first believed to be causing the toxicity; however, the researchers debunked that hypothesis through experiments that showed how immunosuppressants and steroids were unsuccessful at alleviating the toxicity.

According to the authors, toxicity of DRGs is likely to occur in any gene therapy that relies on high doses of a vector or direct delivery of a vector into the spinal cord fluid. This latest study paves a path forward to prevent that damage.

"We were concerned about the DRG pathology that was observed in most of our NHP studies," Wilson said. "This modified vector shows great promise to reduce DRG toxicity and should facilitate the development of safer AAV-based gene therapies for many CNS diseases."

Reference: Hordeaux J, Buza EL, Jeffrey B, et al. MicroRNA-mediated inhibition of transgene expression reduces dorsal root ganglion toxicity by AAV vectors in primates. Science Translational Medicine. 2020;12(569). doi:10.1126/scitranslmed.aba9188

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Read more from the original source:
New Approach Reduces the Toxicity of Brain-Targeted Gene Therapy - Technology Networks

First look at preclinical data in frontotemporal dementia with progranulin mutations (GRN-FTD) and new amyotrophic lateral sclerosis (ALS) program

NOD2 mutation revealed as Crohns disease (CD) genetic target, associated with 7-10% of all CD cases in the U.S. and Europe

Deep dive on transduction enhancers and stable cell line technology innovations that support manufacturing for larger indications

BOSTON and LONDON, Nov. 12, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today previewed details on its investigational hematopoietic stem cell (HSC) gene therapy research programs in GRN-FTD and NOD2-CD in advance of an upcoming virtual R&D investor event. The company also disclosed a new research program in ALS. A live webcast of the presentation will be available in the Investors & Media section of the companys website at http://www.orchard-tx.com starting Friday, November 13, 2020 at 9:00 a.m. ET.

We are excited to draw back the curtain at tomorrows event on our work in larger indications that form an important part of Orchards evolution as a company, including a new program in ALS, in addition to our work in genetic subsets of FTD and Crohns disease, said Bobby Gaspar, M.D., Ph.D., chief executive officer, Orchard Therapeutics. These research programs have been established using a scientific approach that has resulted in more than 160 patients being treated across multiple rare diseases and a recent positive CHMP opinion in the EU for Libmeldy. We believe that HSC gene therapy has the power to transform lives, and we are excited about the possibilities for Orchard and patients with its expanded application.

OTL-204 for GRN-FTD and new ALS research program

The GRN-FTD and ALS programs are based on the same HSC gene therapy approach that has been clinically validated with Libmeldy (OTL-200), Orchards program for metachromatic leukodystrophy, and is under clinical evaluation in the OTL-203 and OTL-201 programs for mucopolysaccharidosis type I and mucopolysaccharidosis type IIIA, respectively. Development work in GRN-FTD and ALS will be undertaken as part of a collaboration with Boston Childrens Hospital (BCH), the University of Padua (UNIPD) and Prof. Alessandra Biffi, chair of the Pediatric Hematology, Oncology and Stem Cell Transplant Division at UNIPD and co-director of the Gene Therapy Program at BCH.

Prof. Biffi commented, The ability of HSC gene therapy to restore healthy microglia function supports the use of this technology for the development of treatments for a variety of diseases with central nervous system involvement. In GRN-FTD, initial in vitro data shows progranulin expression and secretion in culture and uptake indicative of cross-correction. My previous work at BCH researching ALS supports the novel approach of treating this severe neurodegenerative condition by targeting the NOX2 pathway.

OTL-104 for NOD2-CD

Orchards preclinical program in CD targets mutations in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene, which plays a role in immune cell response to bacterial peptides in the gastrointestinal (GI) tract. The companys proposed approach leverages this link, using gene modified HSC-derived cells (monocytes) to replace GI resident macrophages, thus potentially correcting the inflammation and colitis associated with NOD2-CD.

Manufacturing Innovations to Support Work in Larger IndicationsTransduction enhancers (TEs) and stable cell line technology (SCLT)

Orchard has completed a thorough TE screening process and identified and validated several novel TE compounds, which in combination, facilitate lentiviral vector entry into HSCs and have shown a greater than 50% reduction in vector requirements. The enhancers mode of action is expected to be effective in each of Orchards HSC gene therapy programs. An evaluation of enhancer-treated HSC engraftment potential in mice is currently underway.

The company has worked extensively with SCLT, including the technology licensed from GSK for certain programs, to both develop processes to efficiently create SCLs for new vectors and scale up the production of SCLs to clinical grade. Results have delivered consistent levels of high-titer lentiviral production comparable to those seen using conventional methods. Selection of single high-titer clones for new vectors using this method has been achieved within three months. Work at Orchard is ongoing to develop upstream and downstream processes to further improve productivity and scalability.

We have a clear roadmap for Orchards future that prioritizes strategic growth and draws on the many synergies across our scientific, manufacturing and emerging commercial platforms, said Frank Thomas, president and chief operating officer. Over the next 12 months we have an array of exciting commercial, regulatory and clinical milestones that will continue to showcase the breadth and depth of our advanced HSC gene therapy portfolio.

Webcast Information

A live webcast of the presentation New Horizons in Gene Therapy will be available under Events in the Investors & Media section of the companys website at http://www.orchard-tx.com. A replay of the webcast will be archived on the Orchard website following the presentation.

About Orchards Research Collaborations

In connection with its previously disclosed collaboration with Prof. Alessandra Biffi, Orchard has signed agreements with Boston Childrens Hospital and the University of Padua to develop and exclusively license new ex vivo HSC gene therapy programs, patents and technologies for the treatment of neurodegenerative disorders. As part of the collaboration, Orchard has initiated sponsored research agreements and obtained exclusive options to license multiple new preclinical programs, including frontotemporal dementia with progranulin mutations (GRN-FTD), amyotrophic lateral sclerosis (ALS) and other rare and less rare indications.Orchard continues to support Professor Biffis labs in the development of new proprietary technology focused on enhancing the application of gene-modified HSC therapy for CNS disorders.

About Orchard

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter and LinkedIn), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as anticipates, believes, expects, plans, intends, projects, and future or similar expressions that are intended to identify forward-looking statements.Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, including with respect to its manufacturing strategy, expected future milestones, and its plans and expectations for the development of its product candidates, including the product candidates referred to in this release, and the therapeutic and commercial potential of its product candidates.These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that any one or more of Orchards product candidates, including the product candidates referred to in this release, will not be approved, successfully developed or commercialized; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials of Orchards product candidates will not be repeated or continue in ongoing or future studies or trials involving its product candidates; the risk that the market opportunity for its product candidates may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on preclinical and clinical development, its supply chain and commercial programs. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading Risk Factors in Orchards quarterly report on Form 10-Q for the quarter ended September 30, 2020, as filed with the U.S. Securities and Exchange Commission (SEC), as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaChristine HarrisonVice President, Corporate Affairs+1 202-415-0137media@orchard-tx.com

1Knopman DS, Roberts RO. J Mol Neurosci. 2011, Onyike CU, Diehl-Schmid J. Int Rev Psychiatry. 2013 and Riedl L, et al Neuropsychiatr Dis Treat. 20142 Centers for Disease Control and Prevention; European Crohns and Colitis Organisation (ECCO); Ashton, James J et al.Clin Transl Gastroenterol. 2020 Feb

See the original post here:
Orchard Therapeutics Unveils Details on New HSC Gene Therapy Research Programs as Part of R&D Investor Event Tomorrow at 9:00 a.m. ET - GlobeNewswire

Belgium-headquartered UCB has strengthened its gene therapy capabilities with a pair of deals a collaboration agreement with Lacerta Therapeutics and the acquisition of Handl Therapeutics.

Handl Therapeutics based in Leuven, Belgium specialises in adeno-associated virus (AAV) capsid technology and has a focus on developing disease modifying gene therapies to treat neurodegenerative diseases.

In addition to its own capabilities, Handl has built an international network to access expertise from a number of institutions. This includes platforms licensed from KU Leuven in Belgium, the Centre for Applied Medical Research in Spain, the University of Chile and Kings College London in the UK.

UCBs global footprint and scientific expertise in neurodegenerative diseases, coupled with our shared cultures of scientific advancement and commitment to patients, creates an exceptional environment in which we can accelerate the development of gene therapies and change patients lives, said Florent Gros, founder and chief executive officer of Handl Therapeutics.

UCB did not disclose the financial terms of the acquisition, although it did add in a statement that the Handl team will continue to be based in Handl and will work closely with UCBs international research team.

The Lacerta deal is focused on developing AAV-based therapies for patients with a central nervous system disease with a high unmet need. Like the Handl acquisition, UCB did not offer the financial details of the Lacerta research collaboration and licensing agreement.

Lacerta is set to lead research and preclinical activities as well as the early manufacturing process development, with UCB planning to lead IND-enabling studies, manufacturing and clinical development.

UCBs ambition for patients relies on our ability to innovate and deliver highly differentiated medicines, said Dhavalkumar Patel, chief scientific officer of UCB.

The acquisition of Handl Therapeutics and the new partnership with Lacerta Therapeutics offers us the potential to drive a fundamental change in how diseases are treated, by moving us from treating symptoms to disease modification and eventually towards a cure. he added.

The Handl and Lacerta deals build on UCBs previous acquisition of Element Genomics in 2018.

UCB paid $30m to access Elements platform of technologies aimed at improving the understanding of genome structure and function including CRISPR editing technologies used for genomic and epigenomic regulatory region analysis and modulation.

Go here to see the original:
UCB boosts gene therapy offering with a pair of new deals - PMLiVE

Researchers from Penn Medicine have developed a new targeted approach that modifies viral vectors and inhibits toxicities in the sensory neurons of dorsal root ganglia (DRG) that commonly occur following the use of gene therapy for neurological diseases.

This strategy will likely have several important research and clinical implications, as investigators in the field have worked tirelessly for years to develop safer and more effective gene therapies for neurological disorders. We believe that this new approach could improve safety in gene therapy universally, said lead author Juliette Hordeaux, DVM, Ph.D., senior director of Translational Research in Penns Gene Therapy Program, in a statement.

Many gene therapies use viral vectors, but these vectors can have adverse neurological effects. While these toxicities have not yet been observed in humans, nonhuman primate studies using adeno-associated viral (AAV) vectors to deliver corrected genes via the spinal cord fluid have shown issues of axonal degeneration in spinal cord and peripheral nerve tracts. In these studies, the cause of the issues led back to the DRG, comprising a cluster of neural cells found on the outside of the spinal cord that are responsible for delivering sensory messages.

In a recent paper published in Science Translational Medicine, Dr. Hordeaux and colleagues found a way of modifying these vectors so they ultimately avoid these dangerous side effects. They first found that the toxicities appear to come from overexpression of a transgene in cells in the DRG.

The researchers altered a transgene with a microRNA target that was designed to reduce transgene expression levels in the DRG. Ultimately, this modification eliminated over 80% of the transgene expression and resulted in drastic toxicity reduction in the studied primates

We believe it is a safe, straightforward way to ameliorate the safety of AAV therapy for the central nervous system, said Hordeaux about the studied modification. This approach could be used to design other gene therapy vectors to repress transgene expression in the cell types that are affected by the toxicity and not others, which is critical, because you need the expression everywhere else to effectively treat the disorder.

Senior author of the paper was gene transfer expert James M. Wilson, MD, Ph.D., professor of Medicine and Pediatrics in Penns Perelman School of Medicine. Dr. Wilson, who left Solid Biosciences two years ago. Dr. Wilson has been discussing the potential adverse neurological effects of AAV vectors for several years.

Drs. Hordeaux and Wilson injected vectors with and without a microRNA target miRNA183 in mice and primates in the new study. The administration of unaltered AAV vectors led to robust delivery of the gene into target tissue as well as toxicities in DRG neurons. These effects occurred without impacting transduction in elsewhere in the brain, according to histological analyses conducted up to 90 days later.

The authors of the study suggest the toxicity of DRGs likely occur in a gene therapy relying on high vector doses or direct vector delivery into the fluid of the spinal cord. We were concerned about the DRG pathology that was observed in most of our nonhuman primate studies, noted Wilson. This modified vector shows great promise to reduce DRG toxicity and should facilitate the development of safer AAV-based gene therapies for many central nervous system diseases.

Continue reading here:
New Targeted Approach Could Prevent Toxicities Associated with Neurological Gene Therapies - BioSpace

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a lifetime of genetic disease, today announced positive new data across its clinical programs in Gaucher disease type 1, Fabry disease and cystinosis, further reinforcing the potential of ex vivo lentiviral gene therapy for lysosomal disorders. Additionally, AVROBIO is further expanding its lysosomal disorder pipeline with a new program in Gaucher disease type 3, which joins the recently announced program in Hunter syndrome in a synergistic portfolio of six programs designed to prevent, halt or reverse genetic disease.

Were delighted to report substantial new data across our three clinical programs. Three months post-gene therapy infusion, the first Gaucher disease patients levels of the toxic metabolite plasma lyso-Gb1, as well as plasma chitotriosidase, were lower than the baseline levels when the patient was still on enzyme replacement therapy (ERT). With our Fabry disease data continuing to reflect sustained and durable results, with our first patient now out 3.5 years from dosing, we are planning our strategy to seek accelerated approvals in one or more major markets, said Geoff MacKay, president and CEO of AVROBIO. Additionally, the first patient in the investigator-sponsored trial for cystinosis, now out one year, remains off both oral and eye drop cysteamine and we are thrilled to announce that a third patient has been dosed.

As we move into the next stage of company growth, were expanding our lysosomal disorder pipeline with a new program for Gaucher disease type 3 and we plan to dose the first Hunter syndrome patient next year. We expect to be the first lentiviral gene therapy to the clinic across all six of these indications and in some cases, the first to be in the clinic with an investigational gene therapy of any type. We believe the new data weve announced today help de-risk our portfolio which leverages the same lentiviral gene therapy approach across indications, MacKay added. With strong clinical trial enrollment momentum coming out of the COVID-19-related slowdown, we anticipate dosing, enrolling or consenting five patients across our clinical trials this quarter, and dosing a total of 30 patients cumulatively across our clinical programs by the end of 2021.

Positive clinical data out as far as 3.5 years across a broad lysosomal disorder gene therapy pipeline

New clinical updates announced today include:

At three months post-gene therapy, no unexpected safety events or trends have been identified in the trial, with no serious adverse events related to AVR-RD-02 reported in the first patient dosed as of the safety data cut-off date, Nov. 3, 2020.

The company reported durable and sustained response in enzyme activity, substrate levels and VCN across patients in both the Phase 1 and Phase 2 trials as of the data cut-off date, indicating successful engraftment of genetically modified cells and endogenous production of the functional enzyme needed to break down toxic substrate and metabolites in patients. Updated biomarker data on kidney function show generally stable estimated glomerular filtration rate (eGFR) in both Phase 1 and Phase 2 patients. Historically, people living with Fabry disease experience a progressive, faster-than-normal rate of decline in kidney function, as measured by eGFR, whether or not they are on ERT, the current standard of care. AVROBIO believes the stability in eGFR for patients in its clinical trials to be clinically significant and relevant.

No unexpected safety events or trends have been identified in the trials as of the safety data cut-off date, Oct. 8, 2020. The eight serious adverse events reported in the two Fabry disease trials have been consistent with the conditioning regimen, stem cell mobilization, underlying disease or pre-existing conditions. Pre-existing low anti-AGA antibody titers have been detected in four patients in the Fabry Phase 1 trial and a transient low titer was observed but not detectable in subsequent measures in one patient in the Fabry Phase 2 trial.

No unexpected safety events or trends have been identified in the trial, with no serious adverse events reported as of the Nov. 2, 2020, safety data cut-off date.

Pioneering approach to personalized conditioning to leverage advantages of busulfan

The company also shared new data on the safety and tolerability profile of precision conditioning with busulfan prior to gene therapy administration. AVROBIO is pioneering a new approach called targeted concentration intervention (TCI) that enables precise dosing designed to optimize engraftment durability and head-to-toe reach of ex vivo lentiviral gene therapies. TCI aims to maximize the likelihood of engraftment while minimizing the risk of out-of-range side effects by targeting busulfan exposure to an area under the curve of 90 mg x hr/L over four days, called Bu90-TCI.

In AVROBIOs clinical trials to date, data suggest that side effects from its single-agent, single-cycle approach to Bu90-TCI conditioning may be predictable, manageable and transient. The side effects have tended to be mild to moderate in nature and typically presented one week after dosing and peak over three to four days before quickly subsiding. Unlike other conditioning agents, Bu90-TCI is lymphocyte sparing, meaning that important components of the adaptive immune system, B and T cells, are expected to be minimally affected.

Strategic pipeline expansion into relentlessly progressive lysosomal disorders

AVROBIO announced the addition of Gaucher disease type 3 to its pipeline, following the recent addition of Hunter syndrome, which is planned to enter the clinic next year. Together with the existing program in Pompe disease, these make up AVROBIOs second wave of clinical programs focused on life-threatening lysosomal disorders, with the goals of preventing the central nervous system and systemic deterioration that make lysosomal disorders so devastating, normalizing lifespan and lifting the burden of chronic treatment with ERT. New preclinical data suggest that AVROBIOs proprietary tagging technology, part of its industry-leading plato gene therapy platform toolbox, further enhances the potential of its investigational gene therapies in these disorders.

We believe that all six of our pipeline programs share tremendous synergies in clinical development, manufacturing, regulatory processes and commercialization. This second wave of programs will evaluate our promising investigational therapies in diseases with high unmet medical need for patients and families, said Chris Mason, M.D., Ph.D., chief scientific officer at AVROBIO. We believe the opportunity we have to potentially prevent patients, especially children, from developing the disabilities that would otherwise result from their inherited genetic code to perhaps give them the possibility of a full and healthy life is humbling. That is our purpose; it drives all of us at AVROBIO every day.

Preclinical updates include:

End-to-end plato platform ready to enable global commercialization

AVROBIO also presented data on its industry-leading plato platform highlighting advances in chemistry, manufacturing and controls (CMC) to prepare for planned upcoming trials and potential global commercialization.

The optimized processes embedded in plato are designed to enable robust product characterization and efficient production of potent, consistent drug product on two continents, with a third site slated to become operational in Europe in 2021. New advances include:

R&D Day webcast information

A live webcast of Virtual R&D Day and accompanying slides will be available under Events and Presentations in the Investors section of the companys website at http://www.avrobio.com. An archived webcast recording of the event will be available on the website for approximately 30 days.

About AVROBIO

Our vision is to bring personalized gene therapy to the world. We aim to prevent, halt or reverse disease throughout the body with a single dose of gene therapy designed to drive durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our ex vivo lentiviral gene therapy pipeline includes clinical programs in Fabry disease, Gaucher disease type 1 and cystinosis, as well as preclinical programs in Hunter syndrome, Gaucher disease type 3 and Pompe disease. AVROBIO is powered by its industry leading plato gene therapy platform, our foundation designed to deliver gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

Forward-Looking Statement

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will, and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates, results of preclinical studies, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, and the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, including the use of a personalized and ultra-precision busulfan conditioning regimen. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

1 Collaborator-sponsored Phase 1/2 clinical trial of AVR-RD-04 is funded in part by grants to UCSD from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH).

Here is the original post:
AVROBIO Announces New Positive Clinical Data and Preclinical Data, as Well as Expanded Leading Lysosomal Disorder Gene Therapy Pipeline - Business...

People with blood cancers and rare genetic diseases in NSW may benefit from a $50 million funding boost for innovative cell and gene therapies.

Treasurer Dominic Perrottet said the funding allocated in Tuesday's budget would provide better access to cutting-edge and lifesaving treatments, including CAR T-cell therapy.

"This funding offers real hope to the families of children suffering from rare and often fatal diseases by opening the door to new, innovative therapies," Mr Perrottet said.

"This is an exciting time in medicine. There is a wave of cell and gene therapies now available for rare, previously untreatable, often fatal conditions."

Health Minister Brad Hazzard said NSW had played a leading role in global research in the development of novel cell and gene therapies to treat rare, fatal conditions.

"This investment will help ensure NSW children with these rare and life-threatening conditions are given every chance possible at a longer, happier and healthier life."

The funding will give more access to CAR T-cell therapy which modifies a person's own immune cells to attack cancer, offering hope for remission and long-term survival for children and young adults with acute lymphoblastic leukaemia and adults with diffuse large B-cell lymphoma.

It will also provide potentially sight-saving gene therapy for children with the genetic blinding eye disease, retinitis pigmentosa.

Also available would be monoclonal antibody therapy for neuroblastoma, which vastly improves the outcomes for children with that type of cancer.

The funding would also provide gene-based therapies for spinal muscular atrophy, a fatal condition with few treatment options until recently.

Excerpt from:
NSW boost for new cell and gene therapies - Yahoo News Australia

PHILADELPHIA, Nov. 11, 2020 (GLOBE NEWSWIRE) -- Passage Bio Inc. (Nasdaq: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system (CNS) disorders, today commends the newly published research of the University of Pennsylvanias (Penn) Gene Therapy Program (GTP) regarding a novel targeted approach to prevent a selective neurotoxicity seen in the sensory neurons of dorsal root ganglia (DRG) after gene therapy treatment. As previously published, this DRG toxicity has been observed after both systemic and central nervous system (CNS) delivery of gene therapy and across a variety of vectors in pre-clinical models, but clinical manifestations have not been observed.1

As part of its unique collaboration agreement with Penn, Passage Bio has certain rights to this novel DRG technology for the indications the company progresses with Penn.

Although our safety studies for our programs have not shown any clinical manifestations of DRG toxicity, we are excited about the promising approach developed by Penns GTP, said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. As part of our mission to develop transformative therapies for patients, we remain committed to advancing the field of gene therapy. If in the future this new approach shows clinical benefit for patients, we will be in a strong position to incorporate it into our programs. Our relationship with Penns GTP is an important distinguishing characteristic of Passage Bio. Through our collaboration, we have ready access to world-class expertise and groundbreaking research that we can rapidly apply, if appropriate, to our therapeutic programs.

GTPs research on preventing DRG toxicity published online this week in Science Translational Medicine. According to the researchers, DRG toxicity is the result of over expression of an introduced gene, known as a transgene, in cells in the DRG, a cluster of neural cells on the outside of the spinal cord responsible for transmission of sensory messages. To correct this over expression, the GTP research team modified a transgene with a microRNA target designed to reduce the level of the transgene expression in DRG neurons as well as toxicity in DRG neurons, without affecting transduction elsewhere in the brain. That alteration eliminated more than 80 percent of the transgene expression in DRG neurons and reduced the related DRG toxicity in preclinical studies with primates.

James M. Wilson, M.D., Ph.D., director of Penns GTP and a chief scientific advisor at Passage Bio, served as a senior author of the published manuscript. Juliette Hordeaux, DVM, Ph.D., senior director of Translational Research in Penns GTP is first author. They reported that their microRNA target approach may be a straightforward way to potentially make AAV therapy for the central nervous system more safe.

As previously reported, results from preclinical toxicology studies for Passage Bios lead therapeutic programs, PBGM01 (GM1 gangliosidosis), PBKR03 (Krabbe disease), PBFT02 (FTD-GRN), were consistent with this overall AAV platform observation, and showed no clinical manifestations in detailed neurological examinations or daily observations. To proactively determine whether there is appearance of clinical signs of DRG toxicity in our clinical programs, Passage Bio will implement monitoring of patients, consisting of both nerve-conduction studies and neurological exams focused on sensory and peripheral nerve functions.

Passage Bio is advancing six programs, which include the lead programs for GM1 gangliosidosis (GM1), Krabbe disease, and frontotemporal dementia (FTD), as well as three additional programs for amyotrophic lateral sclerosis (ALS), metachromatic leukodystrophy (MLD) and Charcot-Marie-Tooth disease Type 2a (CMT2a). The company anticipates that the initial three clinical candidates will be in clinical trials in 2021. Through its collaboration agreement with Penn, Passage Bio has the option to license a total of 17 programs focused on rare, monogenic disorders of the CNS.

About Passage Bio

At Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming gene therapies for patients with rare, monogenic CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvanias Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. This provides our team with unparalleled access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies into clinical testing. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies. More information is available at http://www.passagebio.com.

Penn Financial Disclosure

Dr. Wilson is a Penn faculty member and also a scientific collaborator, consultant and co-founder of Passage Bio. As such, he holds an equity stake in the Company, receives sponsored research funding from Passage Bio, and as an inventor of certain Penn intellectual property that is licensed to Passage Bio, he may receive additional financial benefits under the license in the future. The University of Pennsylvania also holds equity and licensing interests in Passage Bio.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including our planned IND submissions, initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators and partners ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; and the ability of our lead product candidates to treat the underlying causes of their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with theSecurities and Exchange Commission(SEC), and other reports as filed with theSEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Investors:Sarah McCabe and Zofia MitaStern Investor Relations, Inc.212-362-1200sarah.mccabe@sternir.comZofia.mita@sternir.com

Media:Gwen FisherPassage Bio215-407-1548gfisher@passagebio.com

1 Juliette Hordeaux, Elizabeth L. Buza, et al. Adeno-Associated Virus-Induced Dorsal Root Ganglion Pathology, Human Gene Therapy, published online June 25, 2020.

The rest is here:
Passage Bio Highlights University of Pennsylvania's Gene Therapy Program's Newly Published Research to Prevent Toxicity Associated with Gene Therapy -...

DetailsCategory: DNA RNA and CellsPublished on Monday, 09 November 2020 18:03Hits: 291

NEW YORK, NY, USA I November 09, 2020 I Axovant Gene Therapies Ltd. (NASDAQ: AXGT), a clinical-stage company developing innovative gene therapies, today announced that the U.S. Food and Drug Administration (FDA) has lifted its clinical hold and cleared the Investigational New Drug (IND) Application to initiate a registrational study of AXO-AAV-GM2 gene therapy to treat patients with Tay-Sachs disease and Sandhoff disease. AXO-AAV-GM2 is the first investigational gene therapy to achieve IND clearance for Tay-Sachs and Sandhoff diseases. The Company received a letter from the FDA indicating that it has satisfactorily addressed all issues related to the clinical hold.

The IND clearance of AXO-AAV-GM2, the first potentially curative treatment for Tay-Sachs and Sandhoff diseases to enter the clinic, marks a seminal moment for the entire GM2 gangliosidosis community. Along with AXO-AAV-GM1 for GM1 gangliosidosis, todays announcement represents the second IND clearance for Axovants gene therapy pipeline in the last 12 months, said Gavin Corcoran, M.D., Chief R&D Officer of Axovant. AXO-AAV-GM1 and AXO-AAV-GM2 are the first gene therapies to enter active clinical development in their indications. Each program captures the essence of our mission to liberate patients from debilitating neurological diseases by rapidly advancing these gene therapy programs into clinical development. We look forward to working with our study investigators, academic partners, the patient community, and families to begin enrollment in the study promptly.

Sue Kahn, Executive Director of the National Tay-Sachs & Allied Diseases Association (NTSAD), added, This is a big step toward a potential therapy for the GM2 community. It has been a long journey since NTSAD started supporting this promising gene therapy research in 2006. We are thrilled that it is now entering the clinic, bringing tremendous hope to families and the entire NTSAD community.

Axovant aims to advance the program through strategic partnerships with leading research organizations. The Company recently announced a partnership with Viralgen, an AskBio subsidiary, to support AAV-based vector manufacturing of clinical trial material for the registrational study. Additionally, through an existing genetic testing collaboration with Invitae, ongoing partnership with GM2 gangliosidosis patient groups, and collaboration with leading academic researchers at the University of Massachusetts Medical School and Massachusetts General Hospital, Axovant expects to begin patient identification and site startup activities in preparation for dosing children in the planned clinical study.

AXO-AAV-GM2 is an investigational gene therapy for Tay-Sachs and Sandhoff diseases, which are rare, monogenic neurodegenerative lysosomal storage disorders caused by mutations in the genes that encode -Hexosaminidase A, HEXA and HEXB. Children affected by Tay-Sachs and Sandhoff diseases suffer from a progressively debilitating disease course and reduced life expectancy. AXO-AAV-GM2 delivers two vectors encoding the HEXA and HEXB genes directly to the central nervous system to produce a fully functional -Hexosaminidase A enzyme. In 2019, clinical evidence from two patients under an investigator-initiated study found that treatment with AXO-AAV-GM2 was generally well-tolerated and associated with improved bioactivity outcomes. In addition, the data demonstrated the attainment of normal neurodevelopmental milestones and improvement in myelination. AXO-AAV-GM2 has been granted Orphan Drug and Rare Pediatric Disease Designation by the FDA.

The study will enroll both infantile and juvenile subjects with GM2 gangliosidosis in the U.S. The two-part trial, sponsored by Axovant, will consist of (1) a dose ranging cohort evaluating the safe and efficacious dose of the gene therapy, followed by (2) an efficacy cohort, both of which form the basis of the registrational program. Terence R. Flotte, M.D., Professor of Pediatrics and Dean at the University of Massachusetts Medical School, will serve as principal investigator on the clinical trial.

About AXO-AAV-GM2

AXO-AAV-GM2 is an investigational gene therapy for GM2 gangliosidosis (also known as Tay-Sachs and Sandhoff diseases), a set of rare and fatal pediatric neurodegenerative genetic disorders caused by defects in theHEXA(leading to Tay-Sachs disease) orHEXB(leading to Sandhoff disease) genes that encode the two subunits of the -hexosaminidase A (HexA) enzyme. These genetic defects lead to progressive neurodegeneration and shortened life expectancy. AXO-AAV-GM2 aims to restore HexA function by introducing a functional copy of theHEXAandHEXBgenes via delivery of two co-administered AAVrh8 vectors.

About Axovant Gene Therapies

Axovant Gene Therapies is a clinical-stage gene therapy company focused on developing a pipeline of innovative product candidates for debilitating neurodegenerative diseases. Our current pipeline of gene therapy candidates target GM1 gangliosidosis, GM2 gangliosidosis (also known as Tay-Sachs disease and Sandhoff disease), and Parkinsons disease. Axovant is focused on accelerating product candidates into and through clinical trials with a team of experts in gene therapy development and through external partnerships with leading gene therapy organizations. For more information, visit http://www.axovant.com.

In 2018, Axovant licensed exclusive worldwide rights from the University of Massachusetts Medical School for the development and commercialization of gene therapy programs for GM1 gangliosidosis and GM2 gangliosidosis, including Tay-Sachs and Sandhoff diseases.

SOURCE: Axovant Gene Therapies

Read more here:
Axovant Gene Therapies Announces FDA Clearance of IND for AXO-AAV-GM2 Gene Therapy in Tay-Sachs and Sandhoff Diseases | DNA RNA and Cells | News...

PhoreMost Limited, the UK-based biopharmaceutical company and Oxford Biomedica plc (LSE:OXB) (Oxford Biomedica), a gene and cell therapy group, today announced that they have entered into a discovery collaboration to develop next-generation CAR-T cell therapies. Financial details of the agreement are not disclosed.

PhoreMost will deploy its in-house expertise and next-generation phenotypic screening platform, SITESEEKER, to identify therapeutic candidates for Oxford Biomedicas LentiVector gene therapy delivery system. The program will initially focus on CAR-T therapy and aims to develop next-generation cell therapies with significantly improved efficacy and durability.

Dr Chris Torrance, CEO, PhoreMost, said: This collaboration with Oxford Biomedica, a global pioneer in cell and gene therapies, is further recognition of the power of SITESEEKER, offering an exciting opportunity to discover and accelerate the development of clinical stage products. The natural complementarity between SITESEEKER and LentiVector offers great promise for this and future collaborations between the two companies.

John Dawson, CEO of Oxford Biomedica, said: We are excited to apply this next-generation technology to our LentiVector platform. The collaboration has the potential to deliver more effective CAR-T therapies, and we look forward to working closely with the PhoreMost team.

SITESEEKER exploits protein shape diversity to find functionally active peptides linked to any chosen disease setting, significantly enhancing the power of phenotypic screening and translation into therapeutic modalities. Based on proprietary protein interference, or PROTEINi, technology, SITESEEKER is able to systematically probe the entire proteome in a live cell environment to identify and exploit novel drug targets.

Oxford Biomedica is a world-leading pioneer of cell and gene therapies. Its LentiVector platform enables the successful development of breakthrough gene and cell-based medicines, and through collaborations with pharmaceutical partners, has delivered the first FDA and EMA approved CAR-T cell therapy.

View original post here:
PhoreMost and Oxford Biomedica Enter Gene Therapy Discovery Collaboration - Technology Networks

BOSTON and LONDON, Nov. 09, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that the company is scheduled to present at the Barclays Gene Editing & Gene Therapy Summit on November 16, 2020 at 11:15 AM ET.

A live webcast of the presentation will be available under "News & Events" in the Investors & Media section of the company's website at http://www.orchard-tx.com. A replay of the webcast will be archived on the Orchard website following the presentation.

About Orchard

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter and LinkedIn), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Story continues

Contacts

Investors

Renee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

Read more here:
Orchard Therapeutics to Present at Barclays Gene Editing & Gene Therapy Summit - Yahoo Finance

Final Report will add the analysis of the impact of COVID-19 on this industry.

November 2020:

The global Cell and Gene Therapy Market research report offers all the vital data in the domain. The latest report assists new bees as well as established market participants to analyze and predict the Cell and Gene Therapy market at the regional as well as global level. It covers the volume [k MT] as well as revenues [USD Million] of the global Cell and Gene Therapy market for the estimated period. Numerous key players Amgen, Biogen, BioMarin Pharmaceuticals, Bristol-Myers Squibb Company, GlaxoSmithKline, Novartis, Pfizer, Regeneron Pharmaceuticals and Sanofi, Spark Therapeutics, Agilis Biotherapeutics, Angionetics AVROBIO, Freeline Therapeutics, Horama, MeiraGTx, Myonexus Therapeutics, Nightstar Therapeutics, Kolon TissueGene, Inc., JCR Pharmaceuticals Co., Ltd., and MEDIPOST. are dominating the global Cell and Gene Therapy market. These players hold the majority of share of the global Cell and Gene Therapy market.

DownloadSamplecopy + All Related Graphs & Charts @: https://www.coherentmarketinsights.com/insight/request-sample/2475

The data presented in the global Cell and Gene Therapy market offers budding opportunities, which help users to make strategic moves and prosper their business. The report highlights the impact of numerous factors that might result in obstructing or propelling the Cell and Gene Therapy market at global as well as local level. The global Cell and Gene Therapy market research report offers the summary of key players dominating the market including several aspects such as their financial summary, business strategy, and most recent developments in these firms.

Detailed Segmentation:

By Therapy Type:Cell TherapyStem CellsT CellsDendritic CellsNK CellsTumor CellsGene TherapyGlobal Cell and Gene Therapy Market, By Indication:Cardiovascular DiseaseCancerGenetic DisorderInfectious DiseaseNeurological DisordersOthers

By Region

North America (U.S., Canada, Mexico)

Asia Pacific (India, China, Japan, South Korea, ASEAN, Rest of Asia Pacific)

Europe (Italy, Germany, France, Spain, Central & Eastern Europe, Rest of Europe)

Middle East & Africa (GCC, Turkey, Rest of the Middle East & Africa)

South America (Brazil, Argentina, Rest of South America)

The study encompasses profiles of major companies operating in the Cell and Gene Therapy Market. Key players profiled in the report includes: Amgen, Biogen, BioMarin Pharmaceuticals, Bristol-Myers Squibb Company, GlaxoSmithKline, Novartis, Pfizer, Regeneron Pharmaceuticals and Sanofi, Spark Therapeutics, Agilis Biotherapeutics, Angionetics AVROBIO, Freeline Therapeutics, Horama, MeiraGTx, Myonexus Therapeutics, Nightstar Therapeutics, Kolon TissueGene, Inc., JCR Pharmaceuticals Co., Ltd., and MEDIPOST.

Key points of the global Cell and Gene Therapy market

The oretical analysis of the global Cell and Gene Therapy market stimulators, products, and other vital facets

Recent, historical, and future trends in terms of revenue and market dynamics are reported

Pin-point analysis of the competitive market dynamics and investment structure is predicted to grow

Future market trends, latest innovations, and various business strategies are reported

Market dynamics include growth influencers, opportunities, threats, challenges, and other crucial facets

The global Cell and Gene Therapy market research report offers users with an all-inclusive package of market analysis that includes current market size, expansion rate, and value chain analysis. The global Cell and Gene Therapy market is segmented on a regional basis Europe, North America, Latin America, Asia Pacific, and Middle East & Africa as well. To offer a comprehensive view and competitive outlook of the global Cell and Gene Therapy market, our review team employs numerous methodological procedures, for instance, Porters five forces analysis.

This research report includes the analysis of various Cell and Gene Therapy market segments. The bifurcation of the global market is done based on its present and prospective inclinations. The regional bifurcation involves the present market scenario in the region along with the future projection of the global Cell and Gene Therapy market. The global market report offers an overview of expected market conditions due to changes in the technological, topographical, and economic elements.

Need a discount?

Note: *The discount is offered on the Standard Price of the report.

Ask for the discount @ https://www.coherentmarketinsights.com/insight/request-discount/2475

Questions answered in the report include

What is the expected market size by the end of the forecast period?

What are the major factors initiating the global Cell and Gene Therapy market growth?

What are the latest developments and trending market strategies that are influencing the growth of the Cell and Gene Therapy market?

What are the key outcomes of the Cell and Gene Therapy market developments?

Who are the key players in the market?

What are the opportunities and challenges faced by the key players?

Key Reasons for Purchasing Global Cell and Gene Therapy Market Report

New approaches and latest development trend that describe the structure of the market

Advanced market breakdown structure

Historical data and future market scope

In-depth market analysis based on statistics, growth stimulators, and market developments

Statistical data representation through figurative, numerical, and theoretical elaboration

Report provides insight of the business and sales activities

Why Coherent Market Insights:

Explore extensive library of market reports

Accurate and Actionable insights

Focus on Key Trends and Market Movements

Critical Consulting Project Execution

24/7 Online and Offline Support

Most-detailed market segmentation

Access research reports that are tailored specifically for you and your organization in order to explore practical growth strategies and recommendations

Promo-code: CMIFIRST1000

Buy This Complete A Business Report @:https://www.coherentmarketinsights.com/insight/buy-now/2475

NOTE:Our team is studying Covid-19 and its impact on various industry verticals and wherever required we will be considering Covid-19 footprints for a better analysis of markets and industries. Cordially get in touch for more details

Interested about who is winning the race of COVID-19 Vaccine. Coherent Market Insights (CMI)

providesCOVID-19 Vaccine Trackerfor all the latest updates about COVID-19 Vaccine.

Customization of the Report:

If you do not think that you are looking into Artificial Pancreas Device Systems report or need any clear preconditions, please contact our custom research team at([emailprotected])

Thanks for reading this article; you can also get individual chapter wise section or region wise report version like North America, Europe or Asia.

About Us:

Coherent Market Insights is a prominent market research and consulting firm offering action-ready syndicated research reports, custom market analysis, consulting services, and competitive analysis through various recommendations related to emerging market trends, technologies, and potential absolute dollar opportunity.

Contact Us:Mr. ShahCoherent Market Insights1001 4th Ave,#3200Seattle, WA 98154Tel: +1-206-701-6702Email: [emailprotected]

Link:
Increase in the Adoption of Cell and Gene Therapy to Propel the Growth of the Cell and Gene Therapy Market Between 2020-2027 - Eurowire

The global Gene Therapy market is rife with several new opportunities for market growth. This study provides a comprehensive description of the various propensities and trends that are aiding the growth of this market. The review takes a holistic approach in analyzing and decrypting the various forces of market growth. The all-inclusive review covers multiple insights on the historic trends and future projections that have shaped the current fettle of the market. It is worthwhile to note that the review is written with careful evaluation of various outliers and exceptions to market growth. In order to reconcile the exceptions, the projections made in the review leave scope for scaling and optimization.

Get Sample Copy of this Report https://www.factmr.com/connectus/sample?flag=S&rep_id=4648

The global Gene Therapy Market is projected to reach a value of US$ XX Mn/Bn by the end of the forecast period. These projections are based on evidence-based research and analysis of the various parameters of market growth.

The global Gene Therapy market consists of the following key players:

The report takes a cognitive approach to decode the business strategies of each of the leading players. Besides, the report also gauges the impact of recent market developments on the growth trajectory of the global Gene Therapy market. The insights presented in the report are written after taking due cognizance of the various trends that currently exist in the industry.

The declaration of the coronavirus disease as a global health emergency, and successively a pandemic, created formidable challenges for the vendors within the global Gene Therapy market. The COVID-19 crisis caused a global economic downturn, aggravated by industrial shutdowns and supply chain disruptions. The vendors operating in the global Gene Therapy market are expected to make relentless efforts to minimize the damage caused by the pandemic over the coming years. Companies that deployed strategies of business continuity management and damage control were able to weather the storm. Therefore, COVID-19 pandemic has been a subjective crisis for various industries and players.

The report covers the following key regions:

Based on products, the Gene Therapy market can be segmented into the following categories:

A Customization of this Report is Available upon Request https://www.factmr.com/connectus/sample?flag=RC&rep_id=4648

The report gives an objective and pragmatic outlook on key trends pertaining to:

The report answers, in detail, the following key questions pertaining to market expansion:

The Gene Therapy market makes projections for the following phases:

Why Choose Fact.MR?

Fact.MR follows a multidisciplinary approach to extract information about various industries. Our analysts perform thorough primary and secondary research to gather data associated with the market. With modern industrial and digitalization tools, we provide avant-garde business ideas to our clients. We address clients living across parts of the world with our 24/7 service availability.

Contact:

Unit No: AU-01-H Gold Tower (AU), Plot No: JLT-PH1-I3A,

Jumeirah Lakes Towers, Dubai, United Arab Emirates

MARKET ACCESS DMCC Initiative

Email: sales@factmr.com

Web: https://www.factmr.com/

Link:
Gene Therapy Market to Witness Marginal decline in Near Term amid COVID-19 Pandemic, Projects Fact.MR 2020 2026 - The Cloud Tribune

A new gene therapy may lessen traits of Angelman syndrome, but its makers may need to limit the dose.

By Giorgia Guglielmi, SpectrumNov. 5, 2020 , 9:30 AM

Originally published onSpectrum

A small clinical trial of a gene therapy for Angelman syndromea rare genetic condition related to autismis on hold after two participants temporarily lost the ability to walk. The safety issue is important to resolve, experts say, given that the therapy otherwise appears to be effective, and the trial could guide treatment strategies for similar brain conditions.

Biopharmaceutical companyUltragenyxin Novato, California, in collaboration with Florida-based biotech startupGeneTx, launched the trial in February to assess the safety of a therapy forAngelman syndrome, a neurodevelopmental condition characterized by intellectual disability, balance and motor problems, seizures, sleep problems and, in some cases, autism.

Angelman syndrome results from the mutation or absence of a gene calledUBE3A. People inherit two copies of UBE3A. Typically, only the maternal copy is active in neurons and the paternal copy is silent. But in people with Angelman syndrome, the maternal copy is mutated or missing, so their brain cells express no active UBE3A protein.

The drug developed by Ultragenyx and GeneTx, called GTX-102, is a short snippet of RNA called an antisense oligonucleotide thatactivates the paternal copy of UBE3Aand aims to restore the protein to typical levels. Three other companiesRoche, Biogen, and Ionisare pursuing similar therapies for the syndrome.

On 26 October, Ultragenyx and GeneTx reported that the clinical trial hadenrolled five individualswith Angelman syndrome, aged 5 to 15. The plan had been to administer to each participant a dose of GTX-102 once a month over four months. Researchers injected the drug directly into the nutrient-rich solution that envelops the brain and spinal cord through a site in the lower back.

The participants were to receive increasing doses, but all started with different amounts: Two began at the lowest dose, two started with the second-lowest dose, and one started at the second-highest dose. The final dose was about 10 times higher than the lowest dose.

After a single dose at the second-highest level, one participant developed leg weakness. The other four participants experienced the same adverse effect after taking the highest dose. The symptoms emerged one to four weeks after the participants last dose.

Two of the patients were not able to support themselves to walk and three were, but they were weaker, saysElizabeth Berry-Kravis, professor of child neurology at Rush University Medical Center in Chicago, Illinois, where the five children were treated.

The side effects appear to be a result of inflamed nerves where the drug was injected, perhaps due to accumulation of the drug in that area. In animal studies, the drug didnt cause similar adverse effects, says Ultragenyx chief executive officer,Emil Kakkis. We do know, though, that antisense oligonucleotides are known to have local toxic effects if given at high concentrations.

The participants all recovered after they received drugs that decrease inflammation, Berry-Kravis says. Even those who couldnt support themselves on their legs are walking around finethey actually are somewhat more coordinated now than they were before the study.

When the researchers evaluated the participants at day 128, all five showed significant improvements in some traits, including communication, sleep, and motor skills, Berry-Kravis says. Within weeks of the initial doses, parents and caregivers reported that the participants had acquired new words and gestures.

Were seeing things like using a fork independently for the first time ever, learning to swim on their own, using their augmentative communication device, being able to play an interactive game with the family, Berry-Kravis says. But, she adds, you cant go on with an adverse event.

Going forward, the companies plan to limit the maximum dose to a range in which the drug appears to improve traits without causing leg weakness. They also intend to change how they administer the drug so it cannot accumulate at the site of injection. The drug solution will be given to the patient with their head down to allow the drug to flow toward the brain more efficiently, Kakkis says.

Before resuming the study, the companies will seek approval from the U.S. Food and Drug Administration, says Scott Stromatt, chief medical officer of GeneTx. We hope dosing will start in the next one to two months, he says. Parents are pretty excited to resume because of the positive changes theyve observed in their children.

All drugs have a side effect at some point, saysMark Zylka, professor of cell biology and physiology at the University of North Carolina at Chapel Hill, who was not involved in the study. It seems like theyre just going to need to dial in the dosage better.

Zylka is working on atherapy for Angelman syndromethat uses the gene-editing technology CRISPR to unmute the paternal copy of UBE3A. The rapid improvement observed in the trial participants is encouraging, he says. It suggests that this idea of turning on the dads copy of the gene really has the potential to help individuals with Angelman.

Others are excited about what the trial results might mean for other brain conditions. One of the biggest questions in the field is how long the therapeutic window remains open in neurodevelopmental disorders like Angelman syndrome, saysTimothy Yu, assistant professor of pediatrics at Harvard University. The preliminary findings from the Ultragenyx and GeneTx trial suggest that the therapy can work even in teenagers.

Its still early days, and we have to be careful, Yu says. But if this result continues to hold true, thats going to be really game-changing.

This article was reprinted with permission fromSpectrum,the home of autism research news and analysis.

Go here to see the original:
Gene therapy for autism-linked condition weakened legs, robbing two people of ability to walk - Science Magazine

Stand by: A new gene therapy may lessen traits of Angelman syndrome, but its makers may need to limit the dose.

Courtesy of Ultragenyx

A small clinical trial of a gene therapy for Angelman syndrome a rare genetic condition related to autism is on hold after two participants temporarily lost the ability to walk. The safety issue is important to resolve, experts say, given that the therapy otherwise appears to be effective, and the trial could guide treatment strategies for similar brain conditions.

Biopharmaceutical company Ultragenyx in Novato, California, in collaboration with Florida-based biotech startup GeneTx, launched the trial in February to assess the safety of a therapy for Angelman syndrome, a neurodevelopmental condition characterized by intellectual disability, balance and motor problems, seizures, sleep problems and, in some cases, autism.

Angelman syndrome results from the mutation or absence of a gene called UBE3A. People inherit two copies of UBE3A. Typically, only the maternal copy is active in neurons and the paternal copy is silent. But in people with Angelman syndrome, the maternal copy is mutated or missing, so their brain cells express no active UBE3A protein.

The drug developed by Ultragenyx and GeneTx, called GTX-102, is a short snippet of RNA called an antisense oligonucleotide that activates the paternal copy of UBE3A and aims to restore the protein to typical levels. Three other companies Roche, Biogen and Ionis are pursuing similar therapies for the syndrome.

On 26 October, Ultragenyx and GeneTx reported that the clinical trial had enrolled five individuals with Angelman syndrome, aged 5 to 15. The plan had been to administer to each participant a dose of GTX-102 once a month over four months. Researchers injected the drug directly into the nutrient-rich solution that envelops the brain and spinal cord through a site in the lower back.

The participants were to receive increasing doses, but all started with different amounts: Two began at the lowest dose, two started with the second-lowest dose, and one started at the second-highest dose. The final dose was about 10 times higher than the lowest dose.

After a single dose at the second-highest level, one participant developed leg weakness. The other four participants experienced the same adverse effect after taking the highest dose. The symptoms emerged one to four weeks after the participants last dose.

Two of the patients were not able to support themselves to walk and three were, but they were weaker, says Elizabeth Berry-Kravis, professor of child neurology at Rush University Medical Center in Chicago, Illinois, where the five children were treated.

The side effects appear to be a result of inflamed nerves where the drug was injected, perhaps due to accumulation of the drug in that area. In animal studies, the drug didnt cause similar adverse effects, says Ultragenyx chief executive officer, Emil Kakkis. We do know, though, that antisense oligonucleotides are known to have local toxic effects if given at high concentrations.

The participants all recovered after they received drugs that decrease inflammation, Berry-Kravis says. Even those who couldnt support themselves on their legs are walking around fine they actually are somewhat more coordinated now than they were before the study.

When the researchers evaluated the participants at day 128, all five showed significant improvements in some traits, including communication, sleep and motor skills, Berry-Kravis says. Within weeks of the initial doses, parents and caregivers reported that the participants had acquired new words and gestures.

Were seeing things like using a fork independently for the first time ever, learning to swim on their own, using their augmentative communication device, being able to play an interactive game with the family, Berry-Kravis says. But, she adds, you cant go on with an adverse event.

Going forward, the companies plan to limit the maximum dose to a range in which the drug appears to improve traits without causing leg weakness. They also intend to change how they administer the drug so it cannot accumulate at the site of injection. The drug solution will be given to the patient with their head down to allow the drug to flow toward the brain more efficiently, Kakkis says.

Before resuming the study, the companies will seek approval from the U.S. Food and Drug Administration, says Scott Stromatt, chief medical officer of GeneTx.

We hope dosing will start in the next one to two months, he says. Parents are pretty excited to resume because of the positive changes theyve observed in their children.

All drugs have a side effect at some point, says Mark Zylka, professor of cell biology and physiology at the University of North Carolina at Chapel Hill, who was not involved in the study. It seems like theyre just going to need to dial in the dosage better.

Zylka is working on a therapy for Angelman syndrome that uses the gene-editing technology CRISPR to unmute the paternal copy of UBE3A. The rapid improvement observed in the trial participants is encouraging, he says. It suggests that this idea of turning on the dads copy of the gene really has the potential to help individuals with Angelman.

Others are excited about what the trial results might mean for other brain conditions. One of the biggest questions in the field is how long the therapeutic window remains open in neurodevelopmental disorders like Angelman syndrome, says Timothy Yu, associate professor of pediatrics at Harvard University. The preliminary findings from the Ultragenyx and GeneTx trial suggest that the therapy can work even in teenagers.

Its still early days, and we have to be careful, Yu says. But if this result continues to hold true, thats going to be really game-changing.

See the article here:
Gene therapy trial for autism-linked condition is put on hold - Spectrum

Global Hemophilia Gene Therapy Market: Overview

The global hemophilia gene therapy market is predicted to increase at a stellar pace in the years to follow. The medical fraternity has shown immense resilience in dealing with bleeding disorders, backed by the research excellence of the microbiology sector. The growing incidence of diseases related to genetic dysfunctions has out the healthcare industry on its toes. Research related to genetic mutations have given an impetus to the healthcare sector. There has been a renewed interest in genetic studies amongst researchers and scientists. The commendable results achieved from next-generation genetic studies has created a myriad of opportunities for growth within healthcare. The aforementioned factors are expected to drive sales across the global hemophilia gene therapy market.

Read Report Overview - https://www.transparencymarketresearch.com/hemophilia-gene-therapy-market.html

This review on the global hemophilia gene therapy market gives a concise description of the leading factors responsible for market expansion. The review analyses the growing relevance of gene therapies to make forecasts related to market expansion. The trends and propensities exhibited by the healthcare sector have also been enunciated herein. Henceforth, the review is an evidence-based commentary on the factors that can drive market demand over the near future. The COVID-19 crisis has had adverse impacts on several markets and industries, save the healthcare sector. Therefore, the review also points to the marked increase in revenues across this market due to the pandemic.

Request Brochure of Report - https://www.transparencymarketresearch.com/sample/sample.php?flag=B&rep_id=79725

Global Hemophilia Gene Therapy Market: Competitive Dynamics

Next-generation DNA sequencing and genetic mutations have played a vital role in enhancing healthcare treatments across a range of specializations. For this reason, leading players in the hemophilia gene therapy market are upping their game with genetic research. The ability of these vendors to produce visible results in patient care shall be a sound driver of market demand. A number of companies are also assisting patients in defining their own clotting factor with the help of new aids and technologies.

Request for Analysis of COVID-19 Impact on Hemophilia Gene Therapy Market - https://www.transparencymarketresearch.com/sample/sample.php?flag=covid19&rep_id=79725

Some of the market vendors have acquired visible expertise in the use of a modified virus for treatment of blood clotting. This virus is different from the one that caused the disease, enabling it to help in encoding the clotting factor. Market players can grow at the back of these advancements and distinctions over the next decade. Some of the leading vendors operating in the global hemophilia gene therapy market are Spark Therapeutics, UniQure NV, Pfizer, Inc., Ultragenyx Pharmaceutical, and Shire PLC Sangamo Therapeutics, Inc.

Request for Custom Research - https://www.transparencymarketresearch.com/sample/sample.php?flag=CR&rep_id=79725

Global Hemophilia Gene Therapy Market: Key Trends

The presence of a seamless industry for studying and analysing diseases related to blood clotting or bleeding has given an impetus to market growth. The next decade is expected to witness a surge in demand for hemophilia treatments. The proven excellence of gene therapy in preventing excessive bleeding in ailing individuals shall also play a vital role in market growth and maturity.

Prolonged external or internal bleeding can also be a cause of several other diseases and disorders. This has also led to increased investments in treatment of diseases related to blood clots. The next decade is expected to usher an era of advancements in gene therapy, giving a thrust to growth across the global market.

Pre Book Hemophilia Gene Therapy Market Report - https://www.transparencymarketresearch.com/checkout.php?rep_id=79725&ltype=S

Global Hemophilia Gene Therapy Market: Regional Landscape

On the basis of regions, the global hemophilia gene therapy market can be segmented into North America, Asia Pacific, South America, Europe, and the Middle East and Africa. The excellence of the US and Canada in gene therapy has given a thrust to the growth of the North America hemophilia gene therapy market.

About Us

Transparency Market Research is a next-generation market intelligence provider, offering fact-based solutions to business leaders, consultants, and strategy professionals.

Our reports are single-point solutions for businesses to grow, evolve, and mature. Our real-time data collection methods along with ability to track more than one million high growth niche products are aligned with your aims. The detailed and proprietary statistical models used by our analysts offer insights for making right decision in the shortest span of time. For organizations that require specific but comprehensive information we offer customized solutions through ad hoc reports. These requests are delivered with the perfect combination of right sense of fact-oriented problem solving methodologies and leveraging existing data repositories.

TMR believes that unison of solutions for clients-specific problems with right methodology of research is the key to help enterprises reach right decision.

Contact

Mr. Rohit BhiseyTransparency Market Research

State Tower,

90 State Street,

Suite 700,

Albany NY - 12207

United States

USA - Canada Toll Free: 866-552-3453

Email: sales@transparencymarketresearch.com

Website: https://www.transparencymarketresearch.com/

Originally posted here:
Hemophilia Gene Therapy Market: Growing prevalence of diseases related to blood clotting or bleeding to drive the market - BioSpace

As more and more gene therapies are approved, the elements that determine their success depend, increasingly, on the business decisions made early on.

There is nuance to every program but, (across-the-board) the cost of production is a big challenge, Mike Clayman, M.D., CEO and co-founder of Flexion, told BioSpace.

Flexions lead candidate, FX201 (humantakinogene hadenovec), is a case in point. This is an intra-articular gene therapy product for osteoarthritis (OA). It uses a helper-dependent adenovirus (HDAd) vector whose genetic construct the payload is a gene that expresses the interleukin-1 receptor antagonist (IL-1Ra) in the joint to control inflammation.

Inflammation is a known cause of pain, and chronic inflammation is believed to play a key role in the progression of OA, he explained.

FX201 is taken up rapidly by cells lining the joint, converting them into factories to make IL-1Ra. It quells the inflammation and then turns off the gene construct, Clayman said. It has the potential to provide long-term pain relief, functional improvement, and to actually delay the progression of the disease.

By injecting the product directly into the approximately 5 ml volume of the knee joint, he continued, The absolute amount of protein you need to create an effective intra-articular concentration is far less than that which would be needed to achieve systemic therapeutic levels. That translates into what we expect will be much lower doses of FX201, which would reduce manufacturing cost and give us flexibility to charge a price that would still be proportional to value delivered.

The product entered Phase I, a single ascending dose study, this year. Preclinical work suggests that once injected, there is no significant distribution outside the joint.

It is a non-integrating, non-replicating vector, Clayman said. There is preclinical evidence that it delivers meaningful improvement for at least one year, with the slowing of disease progression.

Company scientists believe a single injection FX201 has the potential to provide at least 6 to 12 months of pain relief and functional improvement in addition to possibly slowing disease progression, Clayman said. We believe this product profile, if realized, would represent a transformative new treatment for knee OA.

Currently, Flexion is actively pursuing the possibility of identifying sub-populations of OA patients who may differentially benefit, Clayman said.

The initial study is open broadly to OA patients to evaluate safety and tolerability. Once those data are analyzed, he said subsequent studies will consider and, if possible, incorporate biomarker, phenotypic or genotypic criteria to focus on a more restricted population.

There may be a marker perhaps a serum marker to identify a patient subset that may most benefit from the therapy, Clayman said. With 15 million patients in the U.S. with knee symptoms of OA, and 8 million annual injections to relieve knee pain, it behooves companies to identify a focal population that can most benefit.

But, he acknowledged, The genetics of OA are very complex. Its clearly a multigene disease with additional contributions from environmental and other external factors. Its not as though there are clearly defined genetic subtypes of the disease.

FX201 isnt the first OA product Flexion has developed. Zilretta (triamcinolone acetonide extended-release injectable suspension), an extended-release, intra-articular corticosteroid, was approved by the FDA in 2017 to relieve OA-related knee pain. In Phase III trials, it significantly reduced knee pain for 12 weeks and, for some patients, 16 weeks or more. Since approval, it has completed a Phase IIIb trial for synovitis.

Flexion also is developing FX301 (funapide, a selective sodium channel blocker, formulated in a thermosensitive gel) for acute post-operative pain.

This isnt a gene therapy, Clayman said. This is a peripheral nerve block that is expected to enter the clinic in 2021. The preclinical data so far suggest it may durably prevent post-op pain while preserving motor function.

The FDA and EMA are up-to-speed on gene therapy now. At Claymans meetings with the FDA, We had very robust scientific exchanges. I left impressed with the sophistication that was applied to the discussion. The EMA was similarly sophisticated, he said.

Coincidentally, the criteria for RMAT designation comparable to breakthrough designation for other products illustrating the points for clinical conditions, used OA as the example.

This indicates the FDA is thinking about creative approaches to complex diseases, Clayman said. If we have compelling data, we would not hesitate to pursue RMAT designation.

Flexion already has begun its health economics and outcomes research, modeling this therapeutic in terms of its ability to delay the need for knee replacement (which costs $25,000 to $50,000), and quality of life.

Whether payers will reimburse for gene therapies often depends as much on the price as on delivered value.

Our dose likely will give us manufacturing costs that will allow us to price FX201 much lower than a systemic therapy, which puts us in a better position, Clayman said. Of course, We still must generate compelling data.

Read more from the original source:
Bringing Flexion's OA Gene Therapy to Market Starts with Cost and Benefits in Mind - BioSpace

Known as the City of Brotherly Love, Philadelphia, Pennsylvania, now has a new monickerCellicon Valleyto honor the cell and gene therapies that companies such as Spark Therapeutics are bringing to it.

Science@Work

Nov. 6, 2020 , 2:00 PM

Affectionally named Cellicon Valley, Philadelphia is the birthplace of cell and gene therapy and home to more than 30 companies dedicated to cell and gene therapy research. Philadelphia-based Spark Therapeutics became the first to bring a U.S. Food and Drug Administration (FDA)-approved gene therapy to market and has been expanding its footprint in this biotech hotspot for gene and cell therapy ever since, according to Chief Scientific Officer Federico Mingozzi, Ph.D.

Headquartered in Philadelphia, Pennsylvania, Spark Therapeutics is helping the city become a premier spot for cell and gene therapy.

In 2013, Spark Therapeutics was founded as a result of the technological and scientific know-how developed at the Childrens Hospital of Philadelphia (CHOP). Now part of the Roche Group, the company is committed to further growing Philadelphia as a global hub of cell and gene therapy. With ambitious growth plans, the company remains focused on extending its scientific platform and unique competencies to evaluate and select a portfolio of gene therapies targeting diseases of the retina, hemophilia A, lysosomal storage disorders, and neurodegenerative diseases. They currently have four programs in clinical trials advancing therapies to treat hemophilia A, Pompe disease, and choroideremia.

Chief Scientific Officer Federico Mingozzi, Ph.D.

With Roches worldwide reach and resources, we are closer than weve ever been before to fulfilling our vision of living in a world where no life is limited by genetic disease, Mingozzi says. Although many gene therapy studies focus on genetic diseases, Mingozzi notes, there is an appetite to expand gene therapy to more common indications.

Despite the challenges of 2020, there has been tremendous growth at Spark. The company now employs more than 500 people and has a growing footprint in West Philadelphia. Spark has hired more than 130 employees since the start of 2020 and does not intend to slow down as the company heads into the upcoming year. Part of that expansion brought Senior Research Associate Phillip Price, Ph.D. to Spark in February. Drawn by the companys passion and commitment to treating genetic diseases, Price recalls thinking, I knew I wanted to be part of this.

At the time he was hired by Spark, Price had recently completed his doctorate in neuroscience at Emory University and was serving as a visiting researcher at the Mayo Clinic in Jacksonville, Florida. His strong conviction about the need to bring more treatments to more patients living with genetic disease, in tandem with a seamless interviewing process, propelled Price to make the leap from Florida to Pennsylvania.

Senior Research Associate Phillip Price, Ph.D.

Despite working virtually, Price says he was able to get plugged into the company quickly and find a strong relationship between the employer and the employees, who encouraged both personal and professional growth. Price mentions that the company also made significant efforts to understand and respond to the changing dynamics resulting from the pandemic, such as working remotely. He has benefitted from the strong lines of communication from Sparks leadership andits unique employee programs such as half days every other Friday, which have enabled him to step away from work and relax while learning more about Philadelphia.

Although Price experienced some hesitancy in transitioning from academia to industry, that disappeared when he found that throughout the Spark workforce people are dedicated to the learning, listening, and innovation needed to bring the best treatments to patients. Price appreciates that high level of motivation. Gene therapy is not just about therapeutic targets of the future, he notes. This is here now, and the door is open! At Spark, he finds even more excitement since being a part of Roche provides a platform to reach globally.

With experience in studying spinal muscular atrophy, an inherited disorder, Price fits right in with Sparks central nervous system (CNS) team, which has treatments in its pipeline for other genetic diseases, including Huntingtons disease and Batten disease. Already, he describes the environment as very dynamic and based on beneficial processes that help cultivate ideas. Plus, he quickly felt like part of the team, where he says, everyone has a voice.

This is the hope: Philadelphia will continue to attract and grow the community of biotechnology experts and become one of the most important hubs for gene and cell therapy in the world.

The thriving life sciences industry in Philadelphia also appealed to Price. More than 42,000 Philadelphians work in life sciences and the city is now rated the fifth largest research and development (R&D) hub in the nation, boasting $10.5 billion spent annually in R&D, according to statistics provided by Life Sciences Pennsylvania. Plus, international information firm EqualOcean reports, More than 700 life science companies have chosen to come to Philadelphia to develop their products.

In addition to CHOP, the region is home to a number of other world-class life sciences institutions, including the University of Pennsylvania Perelman School of Medicine, Temple University, and the Drexel University College of Medicine. The combination of Philadelphias academic institutions with the thriving environment it provides for biotech start-ups has resulted in an excellent system for networking and collaborating, according to Price.

Assay development scientist Stephanie Kutza at work in Sparks labs.

Mingozzi agrees. He added that Spark is one of a cluster of many active companies in gene and cell therapy that are creating a vibrant biotech center in the city. Having a hub attracts talent from other cities and retains the talent that is already here, Mingozzi says. For example, he notes that Philadelphia is a place where people come for training and then stay for work. Overall, its an incredible success story for Philadelphia, and the field of gene and cell therapy is driving this success, he says.

Still, Mingozzi sees this as just the beginning for Philadelphia. Youll see that the driver of this hub will be a couple of companies, like Spark, and that people trained in Philadelphia will start new companies here, he says. Then gene therapy will become a major contributor for the local economy.

This diverse city, however, offers much more than science. Price lives downtown, which he describes as a very lively and inspiring atmosphere. As a history buff, he enjoys exploring Philadelphia with its many important sites, including Independence Hall, the Liberty Bell and the Betsy Ross House. Thinking of the architecture, museums, and parks, Price has nothing but appreciation for the City of Brotherly Love, saying its really quite beautiful here.

Notwithstanding its beauty, even more biotech growth lies ahead in Philadelphias future. As Mingozzi sees it, This is the hope: Philadelphia will continue to attract and grow the community of biotechnology experts and become one of the most important hubs for gene and cell therapy in the world.

Spark ranks among the top employers in Science Careers 2020 Top Employer survey. Read more

See the article here:
The City of Biotech Love - Science Magazine