StemCell Therapy

Across 2019, Vertex has struck deals intended to yield a new generation of breakthrough medicines.

In June, Vertex agreed to pay $245m (220m) upfront to acquire Exonics Therapeutics for its gene editing technology and pipeline of programs targeting diseases including Duchenne muscular dystrophy (DMD). Months later, Vertex put up another $950m to buy Semma Therapeutics and its cell therapy treatment for type I diabetes.

The acquisitions moved Vertex, which started out in small molecules, into new areas, and building out capabilities in those areas will cost money.

In recent years, Vertex has grown its annual operating expenses by 10% to 14%. Talking on a recent quarterly results conference call, Vertex CFO Charles Wagner warned investors to expect costs to rise faster in 2020.

Wagner said, Our current expectation is that the rate of growth will be somewhat higher in 2020 as we invest in research and preclinical manufacturing for selling genetic therapies in support of our programs in type I diabetes, DMD and other diseases.

The move into type I diabetes also takes Vertex into territory that, to some observers, looks different than the areas the company has targeted historically.

Asked by an analyst about the shift in focus, Vertex CEO Jeff Leiden downplayed the differences, noting that type I diabetes is treated in the US in a relatively small number ofcenters that can be targeted by a speciality sales force.

Researchers have achieved positive, long-term outcomes by transplanting cadaveric islets into patients but two barriers have stopped companies from industrialising that approach.

Firstly, there are too few cadaveric islets to treat all type I diabetics. Secondly, immunosuppression is needed to stop patients from rejecting the transplanted cells.

Semma is trying to tackle the problems by differentiating stem cells and using a device to protect them from the immune system. Vertex thinks these technologies are the breakthroughs the field needs to industrialize the concept.

Leiden said, We were watching companies who are addressing those two problems for the last two, three years. And over the last six to eight months, we were convinced that Semma has actually solved both of those problems.

Vertex reached that conclusion on the strength of preclinical data. Now, Vertex is set to invest to find out whether the idea works in the clinic.

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Vertex invests in gene therapy manufacturing - BioPharma-Reporter.com

As people age, they tend to develop diseases such as heart failure, kidney failure, diabetes, and obesity, and the presence of any one disease increases the risk of developing others. Traditional drug treatments, however, each target one condition. That means patients often have to take multiple medications, increasing both the risk of negative side effects and the likelihood of forgetting one.

New research from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) suggests that it may be possible someday to tend to multiple ailments with one treatment.

In the Wyss study, a single administration of an adeno-associated virus (AAV)-based gene therapy, which delivered combinations of three longevity-associated genes to mice, dramatically improved or completely reversed multiple age-related diseases, suggesting that a systems-level approach to treating such diseases could improve overall health and lifespan. The research is reported in PNAS.

The results we saw were stunning and suggest that holistically addressing aging via gene therapy could be more effective than the piecemeal approach that currently exists, said first author Noah Davidsohn, a former research scientist at the Wyss Institute and HMS who is now chief technology officer of Rejuvenate Bio. Everyone wants to stay as healthy as possible for as long as possible, and this study is a first step toward reducing the suffering caused by debilitating diseases.

The study was conducted in the lab of Wyss core faculty member George Church as part of Davidsohns postdoctoral research into the genetics of aging. Davidsohn, Church, and their co-authors homed in on three genes that had been shown to confer increased health and lifespan benefits in mice that were genetically engineered to overexpress them: FGF21, sTGFR2, and Klotho. They hypothesized that providing extra copies of those genes to nonengineered mice via gene therapy would similarly combat age-related diseases and bring health benefits.

The team created separate gene therapy constructs for each gene using the AAV8 serotype as a delivery vehicle, and injected them into mouse models of obesity, Type 2 diabetes, heart failure, and renal failure both individually and in combination with the other genes to see whether there was a positive synergistic effect.

FGF21 caused complete reversal of weight gain and Type 2 diabetes in obese, diabetic mice following a single gene therapy administration, and its combination with sTGFR2 reduced kidney atrophy by 75 percent in mice with renal fibrosis. Heart function in mice with heart failure improved by 58 percent when they were given sTGFR2 alone or in combination with either of the other two genes, showing that a combined therapeutic treatment of FGF21 and sTGFR2 could successfully treat all four age-related conditions, therefore improving health and survival. Administering all three genes together resulted in slightly worse outcomes, likely from an adverse interaction between FGF21 and Klotho, which remains to be studied.

Importantly, the injected genes remained separate from the animals native genomes, did not modify their DNA, and could not be passed to future generations or between living animals.

Achieving these results in nontransgenic mice is a major step toward being able to develop this treatment into a therapy, and co-administering multiple disease-addressing genes could help alleviate the immune issues that could arise from the alternative of delivering multiple, separate gene therapies for each disease, said Church, who is also a professor of genetics at HMS and professor of health sciences and technology at Harvard and MIT. This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself.

Church, Davidsohn, and co-author Daniel Oliver are co-founders of Rejuvenate Bio, a biotechnology company that is pursuing gene-therapy treatments for dogs. Each holds equity in Rejuvenate Bio.

The finding that targeting one or two key genes has therapeutic effects in multiple diseases makes enormous sense from the perspective of pathophysiology, but this is not how drugs are normally developed. This ability to tackle several age-related diseases at once using gene therapy offers a potential path to make aging a more manageable and less debilitating process, said Wyss Founding Director Donald Ingber, who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Childrens Hospital, as well as professor of bioengineering at Harvards John A. Paulson School of Engineering and Applied Sciences.

Reference: Davidsohn et al. 2019.A single combination gene therapy treats multiple age-related diseases. PNAS.https://doi.org/10.1073/pnas.1910073116.

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.

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Combination Gene Therapy Could Treat Multiple Age-related Diseases - Technology Networks

Harvard synthetic biology pioneer George Church generated some buzz last year when he co-founded Rejuvenate Bio with the goal of reversing aging with gene therapy. Now, he and his co-founders say they have compelling early evidence in mice that they can use the technology to reverse multiple age-related diseases at once.

The researchers gave the mice three genes associated with longevity, either alone or in various combinations. The genes were FGF21, sTGF2betaR and alpha-Klotho. In previous experiments, they had shown that mice genetically engineered to overexpress the genes experienced benefits in both their health and life spans.

This time, they used mice that were not genetically engineered but rather models of obesity, Type 2 diabetes, heart failure and kidney failure. They wanted to prove their hypothesis that giving the mice extra copies of the genes might confer similar health benefits. They found that some combinations did improve or reverse symptoms, they reported in the journal Proceedings of the National Academy of Sciences.

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The Harvard team discovered that a combination of FGF21 and sTGF2betaRcould treat all four diseases. FGF21 administered on its own reversed weight gain and Type 2 diabetes, and, when it was combined with sTGF2betaR in mouse models of kidney failure, it lowered kidney atrophy by 75%.

Administering all three genes together turned out to be an unsuccessful strategy, however. Mice that received that combination had worse outcomes than the other animals did, the team reported. The researchers believe there may have been an adverse reaction between FGF21 and alpha-Klotho, but they said further experiments would need to be designed to confirm that.

RELATED: George Church founds cryptocurrency-fueled genomics firm

Rejuvenate Bio was launched from Churchs lab at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering in 2017 but is still largely in stealth mode. It generated some attention last year, after it started reaching out to dog owners with the opportunity to enroll their pets in a trial of a gene therapy to treat mitral valve disease. The heart condition affects some breeds in outsized numbers, including Cavalier King Charles spaniels.

The potential benefits of the three genes Churchs team investigated for the newly published study are well known. FGF21, for one, has been shown to play a beneficial role in insulin resistance and fat metabolism. And last year, researchers partially funded by diabetes drug maker Novo Nordisk discovered that a variant in the gene is present in some people with naturally low levels of body fat.

Last year, Yale researchers discovered that beta-Klotho promotes weight loss, glucose metabolism and insulin sensitivity by binding to FGF21. And a separate team led by New York University published their discovery that alpha-Klotho facilitates FGF23 signaling, which in turn modulates the aging process.

Rejuvenate Bios Church said in a statement that a one-time gene therapy to address multiple age-related diseases could offer several benefits for patients and that the mouse trial was a major step toward the companys efforts to develop gene therapies for human use.

"This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself," Church said.

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Gene therapy to fend off aging? Buzzy Harvard startup Rejuvenate Bio says it works in mice - FierceBiotech

Ger Brophy, PhDExecutive Vice PresidentBiopharma ProductionAvantor

Genuine progress is being made in the long-standing battle to effectively treat and control disease. The National Cancer Institute projects that nearly five million more U.S. citizens are expected to survive cancer in 2026 than in 20161. Therapeutic tools like next-generation sequencing and advances in immunotherapy are just two ways that fundamental scientific breakthroughs and innovative thinking are moving the potential for cancer treatment forward.

One of the most revolutionary advances in this new era is cell and gene therapy. At its most basic definition, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patients cells as a drug to treat disease. According to The Journal of Gene Medicine, just over 2,700 gene therapy clinical trials have been undertaken in 38 countries around the world as of 20182.

These clinical trials demonstrate that the recent attention being paid to gene and cell therapy is not just hype. Although initial approvals have been for relatively small patient groups, the significant pipeline of gene therapy studies for diseases such as hemophilia and various forms of blindness will significantly expand the impact of these treatments. Its exciting to see the number of trials grow, especially when one considers this technologys ability to impact patients lives.

Its true that the number of patients receiving treatment is relatively small compared to other therapeutic regimens, but thats to be expected. Many of the biopharmaceutical researchers and manufacturers started with smaller, defined patient populations as, for example, those with relapsed pediatric refractory acute lymphoblastic leukemia. In part, these early efforts were directed at this type of cancer because the researchers wanted to deal with small populations that they understood well and, in many cases, had few or no other options for treatments.

The success of these initial cell therapy efforts has led to broader programs targeting larger populationsstarting with leukemia and now lymphomas. Ultimately, the most challenging opportunity, and the one with the greatest potential for beneficial outcomes, is multiple myeloma. If these patients begin to see benefits from cell and gene therapies, it will justify the incremental approach the industry has been taking.

The genuine, almost unprecedented potential for cell and gene therapy cannot be understated. For the first time, people are talking about curing these ruthless, relentless diseases. In a way never before possible, were taking control of and harnessing the patients own immune system to fight these cancers. At the recent Alliance for Regenerative Medicine Cell and Gene Therapy on the Mesa meeting, the significant response and survival rates from patients with Diffuse Large B-Cell lymphoma, Acute Lymphoblastic Leukemia, Non-Hodgkins Lymphoma, and Spinal Muscular Atrophy were noted and discussed.

The game changer here is that cell and gene therapy use the bodys own systems, either the cellular immune system or the ability to repair and replace defective or missing genes. CAR-T cell therapy is arguably among the most personalized medicines one can consider. The patients own T cells are extracted, modified, activated, expanded, purified and returned to the patient.

The promise of personalized medicine has been held out for a long time, and now were actually beginning to see real, tangible effects from decades of research into the genetics of the human genome and cancer, giving us an understanding of how the disease develops and how patients respond.

Significant growth is underway in the size and sophistication of companies and organizations entering the cell and gene therapy markets. Many of the early movers in cell and gene therapy were small biotech startups. In some cases, their treatments were supported by major hospital centers.

Now, weve seen a significant interest from the major biopharma industry. Novartis, in particular, has been active and led the way in securing approval for Kymriah. Novartiss focus in this area continued with the acquisition of AveXis and securing the approval of Zolgensma to treat spinal muscular atrophy (SMA). Since last year, weve also seen several important acquisitions by Gilead snatching Kite Pharma, Roche adding Spark Therapeutics, Bristol-Myers Squibb acquiring Celgene, and other companies in China driving large strategic partnerships with major biopharma companies. As companies of this size get involved, the hope is that they will leverage their increased breadth and depth to develop new labels, new trials and find ways to manufacture these therapies at scale.

Scalability and manufacturability are the two, closely-related challenges the industry faces, especially if cell and gene therapies are to fulfill their clinical potential. At first, the questions to be answered appear quite daunting: Can we manufacture cell and gene therapies at scale? If we can manufacture these treatments at scale, then can we do so safely? Can we do so at a reasonable cost so the populations that are affected by these diseases can access treatments?

And the problems presented are new. With autologous cell therapy, one must think about drug product in a different way. There is no inventory; the patient is waiting, and the risk/reward balance is different.

One issue is process standardization. With cell therapy, the single biggest point of variability is the patients own cells. And by its very nature, this is specific to the patient and specific to the health of the patient at the time of leukapheresis.

Variables and failure modes must be taken out of the manufacturing process. And innovations in process technology can make a real difference. We can standardize and close production systems so theyre less exposed to failure modes. Processes can be miniaturized to drive cost efficiencies and, perhaps, better clinical outcomes. We can employ better workflow technologies, such as single-use sterile-fluid transfer. Fill/finish requirements will surely be different for cell and viral products and improved excipient technologies will play a large part in better patient experience and response. Different analytical standards will apply, particularly in relation to adventitious agents during cell expansion.

In particular, the numbers around virus production for gene therapy and ex-vivo cell therapy just dont add up. Adherent process and packaging systems are inefficient. Given the high viral titer numbers indicated in recent approvals, it will be difficult to scale these manufacturing operations. Either something must change, or massive manufacturing future capacity will need to be built. In the meantime, there will be significant reliance on CMOs for capacity.

Across the board, improvements in raw material inputs and innovations in manufacturing technology are now required if we are to see the deployment of these therapies economically and at scale.

To address these challenges, cell and gene therapy producers and the supply companies that support them need to develop stronger partnerships. In areas such as cell culture components, production chemicals, single-use technologies, sterile fluid transfer, excipients, and the technology surrounding those process components, there is value to improving collaboration and trying new solutions to address the issues of manufacturability and scale.

We need to better analyze and understand the variability that comes from the research data, even at the early stages of these trials, and use it to correlate with clinical and process outcomes. Taking out manual steps as early as possible is important, as well as creating closed systems using sterile fluid transfer technologies.

One of the most significant challenges is finding solutions around side effects. As we understand how to provide a more efficacious dose, perhaps using less cells, some of the side effects of these drug therapies may improve. Furthermore, we must find scalable ways to address costs which are far too high. Ultimately, these drugs must be developed in a more cost-effective manner. Thats an area where technology providers and suppliers can play a significant role, by closing and automating systems and by understanding the contribution of labor and overhead and possible economies of scale from reducing processes.

There have been encouraging improvements in the way various global regulatory groups have supported gene and cell therapy. To a certain degree, there was a perception of an arms race between different regional bodiesthe U.S., Europe and the UK, China, and Japan and in different ways within different specialties.

More recently, it appears that regulatory bodies have been open and collaborative in acknowledging that cell and gene therapy is different from more mature biopharma cancer treatments. They are willing to put the appropriate regulatory system into place to enable these drugs to get to market and to monitor them going forward.

The U.S. FDAs support on CAR-T technologies is a good example. Regulators are allowing flexibility in the normal hierarchy of how clinical trials are performed, particularly in phase II and III trials, but the companies must still address the FDAs post-marketing comments and safety issues.

Undoubtedly, cell and gene therapies will have a significant role to play in disease treatment, given the personalized and precise nature of the treatments. But this will be against the backdrop of many existing and emerging therapy paradigms.

Both large molecules and small molecules will continue to provide trusted, effective solutions with each type of drug product finding its niche. For example, we have seen recent encouraging news in the area of monoclonal drugs for neurodegenerative diseases. And emerging fields such as nucleic acid based drugs are showing strong potential thanks to improvements in formulation and delivery.

Its worth remembering that monoclonal-based therapies and biopharmaceuticals have really only started to make a significant impact in the last 15 to 20 years. Cell and gene therapies are just emerging and have yet to make a significant market impact. With that consideration, whos to say whats next? Expanded programs in basic research to develop, understand and characterize drug targets; an exciting program of clinical development and improvements in process technologies should ensure this will be a constantly evolving landscape. And there will be many patient treatment options going forward.

All these developments are exciting and offer a great deal of hope. Gene and cell therapies work and save lives, and the challenge now is to scale the opportunity they offer to their full potential. Its clear that cell and gene therapy can succeed as one more healing tool. As with other treatments that moved from theoretical possibility to real results, we see the issues that need to be addressed more clearly, and were ready to get the next stage of development in motion.

References1.Cancer Statistics, National Cancer Institute: http://www.cancer.gov/about-cancer/understanding/statistics, 2018.2.Ginn S et al, Gene therapy clinical trials worldwide to 2017: An update, Journal of Gene Medicine: doi.org/10.1002/jgm.3015, 2018.

*(Article has been revised and updated)

Ger Brophy, PhD, is Executive Vice President, biopharma production at Avantor

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Opportunities and Challenges in Cell and Gene Therapy Development - Genetic Engineering & Biotechnology News

If you hit enough specific diseases, youre getting at the core aging components that are common to all of them, Church, a Wyss core faculty member, said in an interview Monday. Gene therapy gives you a testable therapy at scale in mice. And we can move from mice to dogs and then to humans. Were focusing on the reversal of age-related diseases so well be more healthy and youthful later in life.

The research is part of a broader emerging field, sometimes called geroscience. Its advocates believe that the best way to treat a variety of illnesses from cancers and heart disease to Alzheimers and macular degeneration is to attack the aging process itself.

Were taking a holistic approach, said Noah Davidsohn, a former research scientist in Churchs lab who is first author of the study. Rather than attack specific diseases, were trying to make patients generally healthier and, in the process, getting rid of as many age-related diseases as possible. Nobody wants to be old and in a wheelchair and not doing anything.

Bostons biomedical hub has become a hotbed of geroscience research.

Last winter, 16 of the worlds top longevity scientists, including Harvard scientist David Sinclair, professor of genetics and director of the Paul F. Glenn Center for the Biology of Aging, formed a Boston-based academy that will seek to spotlight medical research on extending human life and developing drugs to slow the aging process. The nonprofit Academy for Health and Lifespan Research will share research and lobby governments in the United States, Europe, and elsewhere to increase funding and create new paths to approve age-slowing therapies.

Previous studies in the field have also sought to slow aging and extend healthy life spans through small molecules that increase blood flow and endurance, or weed out zombie cells that send out toxins causing age-related maladies. But the Wyss Institute is the first to use therapy that combines genes to boost protein levels that diminish with aging. The genes were selected from a database developed over the past decade at Churchs lab.

We looked at the ones that had the biggest impact individually and then wanted to see if they would work more effectively in pairs and triples, Church said. Such an approach, he said, had the greatest potential to target multiple diseases through a one-and-done injection into the blood or muscle, a simple procedure akin to getting an influenza vaccine shot.

When deployed against obesity, type II diabetes, heart failure, and renal failure, a single formulation ... was able to treat all four diseases, according to the study published in PNAS. These results emphasize the promise of gene therapy for treating diverse age-related ailments, and demonstrate a new approach of combination gene therapy that may improve healthspan and longevity by addressing multiple diseases at once.

San Diego-based biotech startup Rejuvenate Bio, founded by Church and a pair of coauthors of the PNAS study, Davidsohn and Daniel Oliver, is pursuing a gene therapy to fight age-related diseases. The company has already begun working with the Cummings School of Veterinary Medicine at Tufts University in North Grafton to test the gene therapy combination in dogs.

Davidsohn, chief technology officer at Rejuvenate, said the company is focused for now on developing and marketing a treatment that can extend the health span of dogs, which can suffer from a range of age-related illnesses including heart and kidney problems, obesity, dementia, and hearing and vision loss similar to those afflicting humans.

His own 5-year-old dog, Bear, whom Davidsohn adopted while working in the Wyss Institute lab, was an inspiration and now holds the honorary title of chief inspiration officer at Rejuvenate. The company was launched in stealth mode about a year ago and now has eight employees.

While dogs will be an important market in their own right for the combination gene therapy, Davidsohn said, We would be happy if this ended up in humans.

Church said testing the experimental therapy in dogs is likely to take about two years. Then, if regulators approve it, clinical trials could begin in humans. But even if all goes well, he said, the gene therapy probably wont be available as a marketed product for more than a decade.

By then, he said, the cost of a gene therapy which now can top $1 million per patient for rare diseases could drop to thousands of dollars per patient in what would be a much larger market to treat multiple age-related diseases.

Some supporters of age-slowing research, such as Jay Olshansky, public health professor at the University of Illinois at Chicago, have cautioned against expectations that scientists can radically lengthen life spans. Instead, they believe, the goal should be, as Olshansky puts it, pushing out the red zone, the time of frailty and disability at the end of life.

Church, however, has a more ambitious vision.

The important thing is getting good at age reversal, he said. If age reversal truly works, there is no upper limit on how long healthy lives can be extended.

Robert Weisman can be reached at robert.weisman @globe.com. Follow him on Twitter @GlobeRobW.

Correction: An earlier version of this story incorrectly characterized the status of the collaboration between Rejuvenate Bio and George Churchs Wyss Institute Lab.

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Harvard study advances gene therapy in fighting age-related diseases - The Boston Globe

A new protein that can enhance the accuracy of CRISPR gene therapy was recently developed by researchers from City University of Hong Kong (CityU) and Karolinska Institutet. This work, published in the Proceedings of the National Academy of Sciences, could potentially have a strong impact on how gene therapies are administered in the future.

CRISPR-Cas9, often referred to as just CRISPR, is a powerful gene-editing technology that has the potential to treat a myriad of genetic diseases such as beta-thalassemia and sickle cell anemia. As opposed to traditional gene therapies, which involve the introduction of healthy copies of a gene to a patient, CRISPR repairs the genetic mutation underlying a disease to restore function.

CRISPR-Cas9 was discovered in the bacterial immune system, where it is used to defend against and deactivate invading viral DNA. Cas9 is an endonuclease, or an enzyme that can selectively cut DNA. The Cas9 enzyme is complexed with a guide RNA molecule to form what is known as CRISPR-Cas9. Cas9 is often referred to as the molecular scissors, being that they cut and remove defective portions of DNA. Being that it is not perfectly precise, the enzyme will sometimes make unintended cuts in the DNA that can cause serious consequences. For this reason, enhancing the precision of the CRISPR-Cas9 system is of paramount importance.

Two versions of Cas9 are currently being used in CRISPR therapies: SpCas9 (derived from the bacteriaStreptococcus pyogenes) and SaCas9 (derived fromStaphylococcus aureus). Researchers have engineered variants of the SpCas9 enzyme to improve its precision, but these variants are too large to fit into the adeno-associated viral (AAV) vector that is often used to administer CRISPR to living organisms. SaCas9, however, is a much smaller protein that can easily fit into AAV vectors to deliver gene therapy in vivo. Being that no SaCas9 variants with enhanced precision are currently available, these CityU researchers aimed to identify a viable variant.

This recent research led to the successful engineering of SaCas9-HF, a Cas9 variant with high accuracy in genome-wide targeting in human cells and preserved efficiency. This work was led by Dr. Zheng Zongli, Assistant Professor of Department of Biomedical Sciences at CityU and the Ming Wai Lau Centre for Reparative Medicine of Karolinska Institutet in Hong Kong, and Dr. Shi Jiahai, Assistant Professor of Department of Biomedical Sciences at CityU.

Their work was based on a rigorous evaluation of 24 targeted human genetic locations which compared the wild-type SaCas9 to the SaCas9-HF. The new Cas9 variant was found to reduce the off-target activity by about 90% for targets with very similar sequences that are prone to errors by the wild-type enzyme. For targets that pose less of a challenge to the wild-type enzyme, SaCas9-HF made almost no detectable errors.

Our development of this new SaCas9 provides an alternative to the wild-type Cas9 toolbox, where highly precise genome editing is needed, explained Zheng. It will be particularly useful for future gene therapy using AAV vectors to deliver genome editing drug in vivo and would be compatible with the latest prime editing CRISPR platform, which can search-and-replace the targeted genes.

Dr. Shi and Dr. Zheng are the corresponding authors of this publication. The first authors are PhD student Tan Yuanyan from CityUs Department of Biomedical Sciences and Senior Research Assistant Dr. Athena H. Y. Chu from Ming Wai Lau Centre for Reparative Medicine (MWLC) at Karolinska Institutet in Hong Kong. Other members of the research team were CityUs Dr. Xiong Wenjun, Assistant Professor of Department of Biomedical Sciences, research assistant Bao Siyu (now at MWLC), PhD students Hoang Anh Duc and Firaol Tamiru Kebede, and Professor Ji Mingfang from the Zhongshan Peoples Hospital.

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Modified Protein Enhances the Accuracy of CRISPR Gene Therapy - DocWire News

The larger contract manufacturing and development organization (CDMO) have developed an appetite for acquiring capabilities in the cell and gene therapy space.

For instance, Lonza filled a strategic gap in its own portfolio through the acquisition of PharmaCell providing it with a base in the Netherlands with cell and gene manufacturing capabilities.

Rival CDMOs have followed suit, with large sums changing hands in the deals that saw Thermo Fisher takeover gene therapy specialist Brammer Bio and Catalent acquire Paragon.

With increased competition in the space, some have raised concerns about the numbers of talent needed to serve this space and the challenges of keeping them once hired.

BioPharma-Reporter (BPR) spoke to Marc Funk (MF), CEO of Lonza, to gain a leadership perspective about the challenges of recruiting in the space and more broadly about the challenges facing cell and gene therapy manufacture.

BPR: Cell and gene therapy space is developing quickly how are you ensuring that talent are brought in and retained?

MF: We need to be aware of staff retention, but it's not necessarily specific to the cell and gene therapy space. The focus is training the right talent, bringing them on board, and helping the industry cope with the unmet need in cell and gene therapy. In this regard, we are not different to anybody else, but what we can say is that we do not have talent erosion people that come to our sites are happy to stay.

BPR: What are the main challenges in cell and gene therapy?

MF:The major challenge is how to make sure that the industry brings robust, scalable, industrialized manufacturing processes, as fast as possible. That's the main problem.

We are addressing this by capitalizing on our knowledge in mammalian technology, bringing in more innovation: for example, automation for autologous manufacturing and moving from 2D stacks to 3D bioreactors for allogeneic and viral vector manufacturing.

BPR: How important is automation for cell and gene therapy manufacture?

MF: For cell and gene therapies, this is an essential move that has to be accelerated. There are certain processes today that are manual but have no reason to be. That's one of the critical barriers to making the manufacturing of these medicines more robust.

BPR: Are you looking at hiring to bring in experts to improve automations? For instance, experts in AI or machine learning?

MF: We are currently doing that consciously and with high expectations that this will bring better solutions.

BPR: In particular, how do you work to entice talent to work at the Visp site?

MF: The first thing is to have a great project one that young talent can identify with. Within Lonza, that means attracting people who wish to help deliver better medicines in this world.

The second thing is to make sure that we build the right infrastructure here, in partnership with the local communities. We work closely with the authorities and schools in Valais (the Swiss canton where Visp is located) to offer apprenticeships and develop local talent. For employees coming from outside the local area, were working to make sure that the right infrastructure is in place in the region around the site, such as childcare and support for people coming to Switzerland for the first time. All of this is starting to take shape today.

BPR: How is Lonza preparing for the future?

MF: I think that the move we have made to develop the biopark here in Visp redesigning our plant and our business model is already a lesson in how we want to be set up for the future. Although we acknowledge that how we manufacture biologics will change, even within the next two to three years.

The way we are designing the plant today is set up to respond to the changes coming, with space for expansion and the flexibility that changing technology requires. But there are some things we need to do even better now, for example, improving downstream processes. That's an area that we, and the industry in general, is looking at to make sure that we have much better productivity. In addition, the industry needs to be able to bring molecules in clinical development through at a much faster pace than today.

Marc Funk has been CEO at Lonza since March 2019 and a member of the executive committee since April 2012. Prior to his time at Lonza, Funk held leadership roles at Merck Serono and Geneprot.

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Automating cell and gene therapy manufacture 'has to be accelerated', says Lonza CEO - BioPharma-Reporter.com

BRISBANE, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, today announced that hemophilia A gene therapy clinical data and hemoglobinopathies ex vivo gene-edited cell therapy data will be featured in poster presentations at the 61st Annual Meeting of the American Society of Hematology (ASH). The ASH abstracts, which were submitted on August 3, 2019, were released online this morning. The conference will take place in Orlando, FL, from December 7-10, 2019.

Gene Therapy

The SB-525 poster will show updated Alta study data including durability of Factor VIII (FVIII) levels, bleeding rate, factor usage, and safety, for all five patients in the high dose cohort of 3e13 vg/kg, with approximately 4 months to 11 months of follow-up after treatment with SB-525.

As of the abstract submission date, four patients in the 3e13 vg/kg cohort achieved FVIII levels within the normal range with no bleeding events reported up to 24 weeks post-administration. These patients did not require FVIII replacement therapy following the initial prophylactic period of up to approximately 3 weeks post-SB-525 administration. The fifth patient in the 3e13 vg/kg cohort had only recently undergone treatment with SB-525 at the time of the abstract submission. As previously reported, one patient had treatment-related serious adverse events (SAEs) of hypotension and fever, which occurred approximately 6 hours after completion of the vector infusion and resolved with treatment within 24 hours, with no loss of FVIII expression. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.

The rapid kinetics of Factor VIII expression, durability of response, and the relatively low intra-cohort variability in the context of a complete cessation of bleeding events and elimination of exogenous Factor VIII usage continues to suggest SB-525 is a differentiated hemophilia A gene therapy, said Bettina Cockroft, M.D., M.B.A., Chief Medical Officer of Sangamo, commenting on the published abstract. We are pleased with the progress of the program toward a registrational Phase 3 study led by Pfizer, who announced it has enrolled its first patient in the 6-month Phase 3 lead-in study. We have recently completed the manufacturing technology transfer to Pfizer and initiated the transfer of the IND.

Ex Vivo Gene-Edited Cell Therapy

The ST-400 beta thalassemia poster will show preliminary results from the first three patients enrolled in the Phase 1/2 THALES study. In this study, hematopoietic stem progenitor cells (HSPCs) are apheresed from the patient, edited to knock out the erythroid specific enhancer of the BCL11A gene, and cryopreserved prior to infusion back into the patient following myeloablative conditioning with busulfan. The first three patients all have severe beta thalassemia genotypes: 0/0, homozygous for the severe + IVS-I-5 (G>C) mutation, and 0/+ genotype including the severe IVS-II-654 (C>T) mutation, respectively.

As of the abstract submission date, Patient 1 and Patient 2 had experienced prompt hematopoietic reconstitution. Patient 1 had increasing fetal hemoglobin (HbF) fraction that contributed to a stable total hemoglobin. After being free from packed red blood cell (PRBC) transfusions for 6 weeks, the patient subsequently required intermittent transfusions. Patient 2 had rising HbF levels observed through 90 days post-infusion. For both patients, as of the most recent follow-up reported in the abstract, on-target insertions and deletions (indels) were present in circulating white blood cells. Patient 3 had just completed ST-400 manufacturing at the time of abstract submission. As previously disclosed, Patient 1 experienced an SAE of hypersensitivity during ST-400 infusion considered by the investigator to be related to the product cryoprotectant, DSMO, and which resolved by the end of the infusion. No other SAEs related to ST-400 have been reported and all other AEs have been consistent with myeloablation. No clonal hematopoiesis has been observed. Longer follow-up will be required to assess the clinical significance of these early results. ST-400 is being developed as part of a global collaboration between Sangamo and Sanofi, along with support through a grant from the California Institute for Regenerative Medicine (CIRM).

The first three patients enrolled in the THALES study all have severe beta thalassemia genotypes that result in almost no endogenous beta globin production. The increases in fetal hemoglobin and presence of on-target indels in circulating blood cells suggests successful editing using zinc finger nucleases. The results are preliminary and will require additional patients and longer-term follow-up to assess their clinical significance, said Adrian Woolfson, BM., B.Ch., Ph.D., Head of Research and Development. It is important to note that myeloablative hematopoietic stem cell transplantation reboots the hematopoietic system, and that sufficient time is required for the stem cells to fully repopulate the marrow and for new blood cells to form. In other myeloablative conditioning studies in a similar patient population, full manifestation of the effects of gene modification in the red blood cell compartment has taken as long as 12 months or more to become evident.

Sanofis in vitro sickle cell disease poster details a similar approach to ST-400, using mobilized HSPCs from normal donors and SCD patients and utilizing the same zinc finger nuclease for gene editing, delivered as transient non-viral RNA, and designed to disrupt the erythroid specific enhancer of the BCL11A gene, which represses the expression of the gamma globin genes, thereby switching off HbF synthesis. Results from ex vivo studies demonstrated enriched biallelic editing, increased HbF, and reduced sickling in erythroid cells derived from non-treated sickle cell disease patients. Sanofi has initiated a Phase 1/2 trial evaluating BIVV003, an ex vivo gene-edited cell therapy using ZFN gene editing technology to modify autologous hematopoietic stem cells using fetal hemoglobin to produce functional red blood cells with higher BhF content that are resistant to sickling in patients with severe sickle cell disease. Recruitment is ongoing.

About the Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 gene therapy in patients with severe hemophilia A. SB-525 was administered to 11 patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11 vg/kg, 2e12 vg/kg, 1e13vg/kg and 3e13vg/kg) with expansion of the highest dose cohort by 3 additional patients. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency.

About the THALES study

The Phase 1/2 THALES study is a single-arm, multi-site study to assess the safety, tolerability, and efficacy of ST-400 autologous hematopoietic stem cell transplant in 6 patients with transfusion-dependent beta thalassemia (TDT). ST-400 is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology. The THALES study inclusion criteria include all patients with TDT (0/0 or non- 0/0) who have received at least 8 packed red blood cell transfusions per year for the two years before enrollment in the study. The FDA has granted Orphan Drug status to ST-400.

About Sangamo Therapeutics

Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic medicines with the potential to transform patients' lives using gene therapy, ex vivo gene-edited cell therapy, in vivo genome editing, and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Forward-Looking Statements

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements regarding the Company's ability to develop and commercialize product candidates to address genetic diseases with the Company's proprietary technologies, as well as the timing of commencement of clinical programs and the anticipated benefits therefrom. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the outcomes of clinical trials, the uncertain regulatory approval process, uncertainties related to the execution of clinical trials, Sangamo's reliance on partners and other third-parties to meet their clinical and manufacturing obligations, and the ability to maintain strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that Sangamo and its partners will be able to develop commercially viable product candidates. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission and Sangamo's most recent Quarterly Report on Form 10-Q. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

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Sangamo Announces Gene Therapy and Ex Vivo Gene-Edited Cell Therapy Data Presentations at the American Society of Hematology Annual Meeting - Business...

GERMANTOWN, Md., Nov. 7, 2019 /PRNewswire/ -- Triple-Gene LLC, a clinical stage cardiovascular gene therapy company and majority owned subsidiary of Intrexon Corporation (NASDAQ: XON), today announced the completion of enrollment and dosing in its Phase 1 trial of INXN-4001, a multigenic investigational therapeutic candidate under evaluation for the treatment of heart failure, the leading cause of death worldwide. The Phase 1 open label study is designed to investigate the safety of INXN-4001 delivered via Retrograde Coronary Sinus Infusion (RCSI) in patients with an implanted Left Ventricular Assist Device (LVAD) for mechanical support of end-stage heart failure, either as a bridge to transplant or destination therapy (clinical trial identifier: NCT03409627).

"We are excited to have reached this important milestone in the clinical evaluation of INXN-4001 for treatment of end-stage heart failure," stated Amit Patel, MD, MS, Co-Founder and Medical Director of TripleGene. "Heart failure rarely results from a single genetic defect, and while single gene therapy approaches have been studied, these treatments may not fully address the causes of the disease. Our unique multigenic approach is designed to stimulate biological activity targeting multiple points in the disease progression pathway."

Triple-Gene's investigational therapy uses non-viral delivery of a constitutively expressed multigenic plasmid designed to express human S100A1, SDF-1, and VEGF165 gene products, which affect progenitor cell recruitment, angiogenesis, and calcium handling, respectively, and target the underlying molecular mechanisms of pathological myocardial remodeling. The plasmid therapy is delivered via RCSI which allows for cardiac-specific delivery to the ventricle.

"Heart failure is the leading cause of death worldwide and represents a significant and growing global health problem. Aside from heart transplant and LVAD, current treatment options for those patients with end-stage disease are limited," commented Timothy Henry, MD, FACC, MSCAI, Medical Director of the Carl and Edyth Lindner Center for Research and Education at The Christ Hospital and a member of the Triple-Gene Medical Advisory Board. "The INXN4001 investigational therapy represents a biologically-based method focused on repairing the multiple malfunctions of cardiomyocytes, and I look forward to seeing the results of this initial safety study and further exploring the promise of this innovative treatment approach."

Triple-Gene will present preliminary data from the Phase 1 study at the American Heart Association Scientific Sessionsat the Pennsylvania Convention Center in Philadelphia. A poster titled "Safety of First in Human Triple-Gene Therapy Candidate for Heart Failure Patients" will be presented on Sunday, November 17th from 3:00 pm - 3:30 pm ETin Zone 4 of the Science and Technology Hall.

About the Phase 1 Trial of INXN-4001INXN-4001 is being evaluated in a Phase I open label study in adult patients with implanted Left Ventricular Assist Device (LVAD). The study is designed to investigate the safety and feasibility of supplemental cardiac expression of S100A1, SDF-1 and VEGF-165 from a single, multigenic plasmid delivered via Retrograde Coronary Sinus Infusion (RCSI) in stable patients implanted with a LVAD for mechanical support of end-stage heart failure. Twelve stable patients with an implanted LVAD were allocated into 2 cohorts (6 subjects each) to evaluate the safety and feasibility of infusing 80mg of INXN4001 in either a 40mL (Cohort 1) or 80mL (Cohort 2) volume. The primary endpoint of safety and feasibility is assessed at the 6-month endpoint. Daily activity data are also collected throughout the study using a wearable biosensor. Dosing on both Cohorts 1 and 2 has been completed, and patients continue follow-up per protocol.

About Triple-GeneTriple-Gene LLC is a clinical stage gene therapy company focused on advancing targeted, controllable, and multigenic gene therapies for the treatment of complex cardiovascular diseases. The Company's lead product is a non-viral investigational gene therapy candidate that drives expression of three candidate effector genes involved in heart failure. Triple-Gene is a majority owned subsidiary of Intrexon Corporation(NASDAQ: XON) co-founded by Amit Patel, MD, MS, and Thomas D. Reed, PhD, Founder and Chief Science Officer of Intrexon. Learn more about Triple-Gene at http://www.3GTx.com.

About Intrexon CorporationIntrexon Corporation (NASDAQ: XON) is Powering the Bioindustrial Revolution with Better DNAto create biologically-based products that improve the quality of life and the health of the planet through two operating units Intrexon Health and Intrexon Bioengineering. Intrexon Health is focused on addressing unmet medical needs through a diverse spectrum of therapeutic modalities, including gene and cell therapies, microbial bioproduction, and regenerative medicine. Intrexon Bioengineering seeks to address global challenges across food, agriculture, environmental, energy, and industrial fields by advancing biologically engineered solutions to improve sustainability and efficiency. Our integrated technology suite provides industrial-scale design and development of complex biological systems delivering unprecedented control, quality, function, and performance of living cells. We call our synthetic biology approach Better DNA, and we invite you to discover more at http://www.dna.comor follow us on Twitter at @Intrexon, on Facebook, and LinkedIn.

TrademarksIntrexon, Powering the Bioindustrial Revolution with Better DNA,and Better DNA are trademarks of Intrexon and/or its affiliates. Other names may be trademarks of their respective owners.

Safe Harbor Statement Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon our current expectations and projections about future events and generally relate to our plans, objectives and expectations for the development of our business. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties and actual future results may be materially different from the plans, objectives and expectations expressed in this press release.

For more information contact:

Investor Contact:

Steven Harasym

Vice President, Investor Relations

Intrexon Corporation

Tel: +1 (301) 556-9850

investors@dna.com

Corporate Contact:

Marie Rossi, PhD

Vice President, Communications

Intrexon Corporation

Tel: +1 (301) 556-9850

publicrelations@dna.com

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Triple-Gene Announces Completion of Enrollment and Dosing in Phase 1 Trial of INXN-4001, First Multigenic Investigational Therapeutic Candidate for...

European regulations might be responsible for lower numbers of advanced therapy clinical trials running in the region when compared to the US and Asia.

Europe has historically been a pioneer in advanced therapies, such as cell and gene therapy. Europe was the first region to approve a gene therapy, and it boasts the highest number of marketing authorizations of advanced therapies worldwide.

However, in the past four years, the number of clinical trials with advanced therapies has stalled in Europe, growing by just below 2%. Meanwhile, the number of trials went up in North America and Asia by 36% and 28%, respectively, in the same period.

This conclusion was drawn from the analysis of the 2,097 clinical trials of advanced therapies conducted worldwide between 2014 and the first half of 2019. The study was carried out by the Alliance for Regenerative Medicine (ARM), an international community of stakeholders in the development of new medical technologies.

Current EU regulations could be to blame. Any clinical trial that is conducted across multiple European countries requires separate review and approval in each country.

When national authorities review clinical trial authorizations independently, they may have diverging opinions that create a delay for the companies, said Annie Hubert, Senior Director of European Policy at the ARM.

The issue becomes even bigger with advanced therapies, as the requirements regarding testing donors and starting materials vary across different countries.

In particular, gene therapies are the most affected. The study found that while in North America 71% of advanced therapy trials involve any form of gene therapy or gene editing, in Europe that percentage is only 55%.

Gene therapies face an additional hurdle in Europe; they are considered genetically modified organisms and must therefore additionally comply with GMO regulation, which falls under the umbrella of environmental or agricultural legislation depending on the country.

The complexity in the GMO regulation may be the reason why we see fewer clinical trials with gene therapy in Europe compared to other regions, Hubert told me.

A company that applies for a clinical trial with a gene therapy needs to secure the review and approval by the GMO authority in that country on top of having the approval for the clinical trial for the medicinal product. There have been situations where, for the same gene therapy, the decision from different GMO authorities in Europe was different.

The study concluded that streamlining the regulatory process might make Europe more competitive in the development of advanced therapies. This can already be seen in certain European countries, such as Belgium, Denmark and Switzerland, where the amount of clinical trials is actually higher than in the US when accounting for their size.

Belgium for instance has an approval time of 15 days for phase I clinical trials. That acts as an incentive, said Hubert. In the UK and in Denmark, companies have access to a central point of contact that liaises with the GMO authorities and facilitates the review of clinical trial applications.

The European Commission has been aware of these issues for several years. Previous studies reported that the current clinical trial legislation, which dates to 2001, resulted in a decline in the overall number of clinical trials running in Europe.

The Commission has already created new regulations that seek to address some of these problems through a centralized application system where one national authority takes the lead in reviewing the application, while the others can either agree or disagree with it.

However, there have been delays in the creation of the application platform and the regulations have not yet been implemented. Hubert expects this could happen sometime in late 2020 or 2021.

I think we need to be realistic. Any significant change will probably take a number of years before we can see the number of clinical trials increasing significantly in Europe.

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EU Regulations Are Holding Back Gene and Cell Therapy Clinical... - Labiotech.eu

PTC Therapeutics announced a strategic partnership with Aldevronto ensure the production of high-quality plasmid DNA to be used with PTCs investigational gene therapies, including AGIL-AS for the treatment of Angelman syndrome (AS).

PTCs growing gene therapy pipeline for genetic disorders of the central nervous system (CNS) also includes an investigational gene therapy for AADC deficiencythats nearing submission to the U.S. Food and Drug Administration (FDA), as well as candidates for Friedreichs ataxiaand Angelman syndrome that are at earlier development stages. Other candidates for cognitive disorders and inherited retinal disorders are in preclinical research.

Our strategic collaboration with Aldevron represents our continued commitment to produce and provide the highest quality product to patients, Neil Almstead, PhD, PTCs chief technical operations officer, said in a press release.

Our gene therapy pipeline is addressing the unmet needs of multiple patient populations, and we feel an urgent need to develop safe products with the utmost speed. The development of relationships with top-tier companies like Aldevron aligns with our goal of partnering with the best collaborators as we drive meaningful improvements in the lives of patients, Almstead said.

PTCs gene therapy candidate for Angelmans syndrome is called AGIL-AS. It uses a modified virus that does not cause infection called an adeno-associated virus (AAV) to deliver a working copy of the UBE3Agene, the faulty gene in Angelman syndrome, to the brain and spinal cord of patients. The process is designed to restore production of the E6-AP protein produced by the UBE3A gene, this way improving cell function and rescuing neurological defects in Angelman syndrome.

Preclinical studieshave shown that AGIL-AS targets nerve cells in the brain, increases levels of E6-AP, and eases AS-like cognitive deficits in animal models of the disease.

AGIL-AS was granted orphan drug designationfrom the U.S. Food and Drug Administration in 2015, followed by a similar designation from theEuropean Commission in 2016.

Under the agreement, Aldevron will manufacture the plasmid DNA (circular molecules of DNA) where the functional version of UBE3A gene will be enclosed for delivery. The company ensures the materials are produced under Good Manufacturing Practice (GMP), a set of guidelines allowing products to be consistently made and controlled according to quality standards.

It is truly an honor to work with PTCs motivated team of experts. They are making enormous contributions to the future of genetic medicine, saidMichael Chambers, founder and CEO of Aldevron.

This is Aldevrons mission to serve scientists and researchers who are relentlessly pursuing cures for people who need them, he added.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.

Total Posts: 11

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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PTC, Aldevron Partner to Advance Angelman and Other Gene Therapy Candidates - Angelman Syndrome News

WATERTOWN, Mass. and RESEARCH TRIANGLE PARK, N.C., Nov. 07, 2019 (GLOBE NEWSWIRE) -- SQZ Biotechnologies (SQZ), and Asklepios BioPharmaceutical, Inc. (AskBio), announced a research collaboration to create tolerizing antigen carriers (TACs) containing AAV (adeno-associated virus) components to solve one of gene therapys biggest challenges the barrier to treatment posed by patients immune systems generating neutralizing antibodies toward therapeutic AAVs. SQZ and AskBio will combine their proprietary cell and gene therapy platform technologies to open the door to new treatment paradigms with potential impact across many genetic diseases.

Gene therapies utilizing AAV vectors can be transformative for patients with genetic diseases, but neutralizing antibodies can prevent large populations of patients from benefitting from AAV gene therapies. Patients immune systems develop neutralizing antibodies after receiving their first dose of AAV, or they can be pre-existing. This collaboration will strive to give these patients access to novel therapeutics and enable them to take multiple or repetitive doses to gain the full, durable benefit these treatments can provide. Expanding patient eligibility and allowing repeat treatment could change the future of how products are developed and significantly impact the long-term health of millions in need.

This is a tremendous opportunity to bring together the power of both cell and gene therapy for patients. AskBio has been an innovative leader in gene therapy and shares our patient-centric philosophy. By working together and leveraging the potential of both our platforms, we hope to bring more effective, more durable treatments to patients suffering from devastating rare genetic disorders, said Armon Sharei, PhD, founder and chief executive officer of SQZ Biotech.

The collaboration between SQZ and AskBio will evaluate the administration of SQZ TACs and AskBios gene therapies to potentially address AAV immunogenicity. SQZ is a pioneer in cell therapy, and the companys knowledge and expertise, as well as their advance capabilities in manufacturing, are critical to this collaborations approach to synergizing cell and gene therapies. Preclinical data from SQZ has demonstrated that SQZ TACs specifically inhibit undesired immune responses in multiple contexts, including AAV models. As a leader in the AAV field, AskBio brings expertise in AAV technology, capsid design, clinical processes and manufacturing that would allow for application of these novel methods to overcome immunogenicity. The two companies have a shared goal to increase world-wide access of transformative therapeutics.

R. Jude Samulski, PhD, chief scientific officer and co-founder of AskBio, noted, AskBio is firmly committed to improving the lives of underserved patients, such as those suffering from Pompe, Huntingtons and various neuromuscular and central nervous system diseases. Addressing AAV immunogenicity is essential to the future of gene therapy as it is one of the most significant limiting factors plaguing the gene therapy space today. SQZs pioneering approach to tolerance could offer a solution to this problem. Our collaboration with SQZ is exemplary of our goal to broadly explore potential redosing of AAV gene therapies, added Sheila Mikhail, chief executive officer and co-founder of AskBio. We are thrilled to be working with SQZ and are hopeful that this initial research collaboration utilizing two of the most promising therapeutic modalities currently available, cell and gene therapy, will ultimately provide options to improve patients immune response to gene therapy.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy platform company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process known as Pro10 and an extensive AAV capsid library. Based in Research Triangle Park, N.C., the company has generated hundreds of proprietary third-generation gene vectors, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production, chimeric vectors, and self-complementary DNA. AskBio maintains a portfolio of clinical programs across a range neurodegenerative and neuromuscular indications with a current pipeline that includes therapeutics for Pompe disease, Limb Girdle Muscular Dystrophy and congestive heart failure as well as out-license clinical indications for Hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne Muscular Dystrophy (Bamboo Therapeutics acquired by Pfizer). For more information, visit http://www.askbio.com.

About SQZ BiotechSQZ Biotech is a privately held, clinical-stage company creating innovative treatments by transforming cells into sophisticated therapeutics. Using its proprietary platform, SQZ has the unique ability to precision engineer virtually any cell type and deliver multiple materials, potentially resulting in powerful, multifunctional cell therapies for a range of diseases with an initial focus on cancer and autoimmune disease. The companys initial applications leverage SQZs ability to generate target-specific immune responses, both in activation for the treatment of solid tumors, and immune suppression for the treatment of immune reactions and diseases. For more information please visit http://www.sqzbiotech.com.

About SQZ TACsSQZ tolerizing antigen carriers (TACs) are being developed to induce tolerance to aberrant or unwanted immune activity. TACs are developed from red blood cells (RBCs) SQZd with target-specific antigens and piggyback on the natural process of RBC destruction in the body, also known as eryptosis. A process moderated by our liver and spleen, eryptosis causes macrophages to take up aged or senescent RBCs. When our bodies process RBCs for destruction, their components are presented in a tolerogenic manner, reminding our immune systems not to attack our own red blood cells. SQZ TACs drive targeted antigensthrough this powerful natural mechanism, specifically tolerizing the immune system, potentially stopping undesired immune responses.

AskBio Contacts: Mark Rosenbergmark@trueparallel.com919-412-7378

Roger Friedensen, APRroger@trueparallel.com919-349-3206

SQZ Contacts:Rebecca CohenSenior Manager, Corporate Relationsrebecca.cohen@sqzbiotech.com617-758-8672 ext. 728

Cait Williamson, PhDLifeSci Public Relations cait@lifescipublicrelations.com646-751-4366

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SQZ Biotech and AskBio Announce Research Collaboration to Create Immune Tolerization Products for AAV Gene Therapies - GlobeNewswire

Cell therapy CDMO Cognate Bioservices will add plasmid DNA and viral vector capabilities through the acquisition of Swedish manufacturer Cobra Biologics.

Memphis, Tennessee-based contract development and manufacturing organization (CDMO) Cognate has entered into an agreement to acquire Cobra for an undisclosed fee, led by existing Cognate investor EW Healthcare Partners.

The deal adds to Cognates presence in the regenerative medicine space by bringing on board plasmid DNA and viral vector manufacturing capacity and expertise, complementing its own autologous and allogeneic cell-based and cell-mediated gene therapy capabilities.

Image: iStock/Good_Stock

According to Cognate, the deal will create a fully integrated cell and gene therapy CDMO providing more scalable solutions to its clients.

This acquisition is central to Cognates strategy to build on its existing offerings and create an enterprise platform for life cycle management of cell and gene therapy products, accelerating the availability of new technologies to patients that need them most, said Cognate CEO J. Kelly Ganjei.

The combined Cognate-Cobra expertise, infrastructure, and geographical footprint immediately positions both businesses to better respond to current and future market needs more quickly, effectively, and comprehensively.

The transaction is subject to receipt of approval for the US authorities under the Hart-Scott-Rodino Antitrust Improvements Act of 1976.

Peter Coleman, CEO of Cobra Biologics, told Bioprocess Insider the two companies will operate as different business units and he will continue to be involved with Cobra following the acquisition.

There will be elements of integration, in particular linking the technical capabilities together, but the intention is to operate as two separate business units each with its own specialization and track record.

Cognate operates an 80,000 square-foot site in Memphis, originally built in 2017 for autologous cell therapy manufacturing but now produces various cell types for customers clinical projects. Our largest phase of clinical grade production was an autologous product for phase III clinical trials, mostly manufactured in Memphis with products shipped to more than 80 clinical sites in four countries, the company states.

Cobra brings to the table two GMP approved facilities: an advanced therapy medicinal product (ATMP) production site in northwest UK offering DNA and viral vector services, and an ATMP production site in Matfors, Sweden offering DNA and microbiota services.

Last month, Cobra inked a deal to manufacture the adeno-associated viral vector (AAV) for Nordic gene therapy company Combigenes epilepsy candidate CG01 from its facility in the UK.

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Cognate buys Cobra to boost gene therapy CDMO - Bioprocess Insider - BioProcess Insider

A team of scientists from City University of Hong Kong (CityU) and the Karolinska Institute has created a novel protein that can increase the target accuracy in genome editing. Their findings are published in the journal Proceedings of the National Academy of Sciences (PNAS).Meet CRISPRThe gene editing technology Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 looks set to revolutionize modern medicine, agriculture, and synthetic biology.The ability to edit the genome in vivo offers the potential to develop novel gene therapies for diseases that currently lack viable treatment options. Several clinical trials are underway exploring the utility of CRISPR technology in treating specific cancers, blood disorders and eye diseases.CRISPR-Cas9 as a gene editing tool is superior over other techniques due to its ease of use. In traditional gene therapy, additional copies of the "normal" gene are introduced into cells. Using CRISPR technology, this isnt necessary; CRISPR-Cas9 enters the cell and "repairs" the problematic gene by removing it or correcting it to restore normal physiological function.

There are different components to the CRISPR mechanism. Cas9 is the enzyme that flags and locates the problematic DNA throughout the genome, acting in a "hunting" fashion. However, the precision of Cas9 cannot always be established, and occasionally modifications of DNA at unintended places can occur. If CRISPR is to be utilized to repair faulty genes in patients, potential off-target genome editing could have serious adverse effects.

There are currently two versions of the Cas9 enzyme commonly adopted in CRISPR research: SpCas9 (Cas9 nuclease from the bacteria Streptococcus pyogenes) and SaCas9 (Cas9 nuclease from Staphylococcus aureus). Both of these enzymes are limited in that they possess a certain level of imprecision.

Thus, scientists have endeavored to develop variants of both enzymes, with the aim being to increase their precision and reduce off-target effects. The issue with SpCas9 is that the modified variants are often too large to "fit" in the delivery system adopted for inserting gene therapies into patients, known as adeno-associated viral (AAV) vectors.SaCas9 is advantageous over SpCas9 in that it can be easily packaged into the AAV vectors for delivering gene-editing contents in vivo. However, at present, there is no SaCas9 variant that possesses high accuracy in genome-wide editing. Until now.Now meet SaCas9-HFIn the new study published in Proceedings of the National Academy of Sciences (PNAS), a research team led by Zheng Zongli, Assistant Professor of Department of Biomedical Sciences at CityU and the Ming Wai Lau Centre for Reparative Medicine of the Karolinska Institute in Hong Kong, and Shi Jiahai, Assistant Professor of Department of Biomedical Sciences at CityU, has successfully engineered SaCas9-HF, a CRISPR Cas9 variant which has demonstrated high accuracy in genome-wide targeting in human cells without compromising on-target efficiency.In the study, the scientists conducted an extensive evaluation of 24 targeted human genetic locations comparing the original (known as wild-type) SaCas9, and the new variant, SaCas9-HF. They discovered that for targets with highly similar sequences in the genome (and therefore often disposed to off-target editing by wild-type Cas9), SaCas9-HF decreased the off-target activity by ~90%. When assessing targets that had relatively less off-targeting editing by wild-type SaCas9, the SaCas9-HF enzyme produced little to no detectable off-target effects.

"Our development of this new SaCas9 provides an alternative to the wild-type Cas9 toolbox, where highly precise genome editing is needed. It will be particularly useful for future gene therapy using AAV vectors to deliver genome editing 'drug' in vivo and would be compatible with the latest 'prime editing' CRISPR platform, which can 'search-and-replace' the targeted genes," said Dr Zheng.Reference: Tan et al. 2019. Rationally engineered Staphylococcus aureus Cas9 nucleases with high genome-wide specificity. Proceedings of the National Aacademy of Sciences (PNAS). DOI: https://doi.org/10.1073/pnas.1906843116

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A Highly Precise Cas9 Enzyme, SaCas9-HF, Is Added to the CRISPR Toolbox - Technology Networks

7-Nov-2019

Design and Build

Canadian cleanroom builder to work in the US on a new 1,600-sq-ft site of ISO Class 7

The New Jersey Innovation Institute is located in Newark, in the United States

Mecart, the Canadian cleanroom specialist, has been selected by the US-based New Jersey Innovation Institute (NJII) for a new GMP cleanroom at its Cell and Gene Therapy Development Center. The NJII is based in Newark, US.

Commenting on the project with Mecart, Dr Haro Hartounian, NJII Senior Executive Director, Biotechnology and Pharmaceutical Innovation, said: We were excited to meet with the Mecart team, travel to Quebec City to visit with their leadership, and review the project in detail with them. It has been a great experience thus far and we know that we picked the best partner for this critical project.

The project represents a new GMP cleanroom of approximately 1,600 square feet of ISO 7 space developed specifically for advanced cell and gene therapy processing and manufacturing operations.

Its an honour to work with such an innovative company that focuses on local collaboration with its technological resources, like this new cleanroom, said Patrice Genois, General Manager of Mecart and Vice President of PolR.

The NJII is an NJIT corporation that applies the intellectual and technological resources of the states science and technology university to challenges identified by industry partners.

Upon completion, the new GMP site will also serve as a training facility and a venue for collaborating with local manufacturing.

Charles Lipeles, Vice President of US Operations, commented: When NJII approached Mecart, they were clear that lead time was crucial as was a very tight specification for their state-of-the-art GMP cleanroom. They had very aggressive goals, made more challenging when dealing with an institution with government ties, but we were ready for the challenge. We are excited to work with the NJII and NJIT teams and help them exceed their goals with this new suite of cleanrooms."

Construction is planned to begin later this year and will be completed in Q1 of 2020.

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NJ Innovation Institute chooses Mecart for cell and gene therapy centre - Cleanroom Technology

Registrational Trial for Wiskott-Aldrich Syndrome Met Key Primary and Secondary Endpoints at Three Years; Data from Integrated Analysis Reinforce Treatment Benefits of Gene Therapy and Durability of Effect in Additional Patients

Similar Profiles Reported Between Cryopreserved and Fresh Formulations of OTL-101, Further Supporting Upcoming Regulatory Filing and Broad Patient Availability

BOSTON and LONDON, Nov. 06, 2019 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a leading commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies, today announced the upcoming presentation of registrational data from multiple programs at the 61st American Society of Hematology (ASH) Annual Meeting in Orlando, FL.

Investigators will describe ongoing clinical progress for two lead development programs in the companys primary immune deficiencies portfolio: OTL-103, an investigational gene therapy in development for the treatment of Wiskott-Aldrich syndrome (WAS) at theSan Raffaele-Telethon Institute for Gene Therapy(SR-Tiget) inMilan, Italy; and OTL-101, an investigational gene therapy in development for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID).

In addition, investigators will deliver an oral presentation featuring updated data from the ongoing proof-of-concept study of OTL-203, an investigational gene therapy in development for the treatment of mucopolysaccharidosis type I (MPS-I) atSR-Tiget.

This growing body of positive data, from dozens of patients across multiple diseases, provides a solid foundation as we advance each program toward its next phase of development, including upcoming regulatory submissions for ADA-SCID and WAS, saidMark Rothera, president and chief executive officer ofOrchard Therapeutics. We now have two supportive data sets one from our OTL-101 program in ADA-SCID and one from our OTL-200 program in metachromatic leukodystrophy that demonstrate cryopreserved formulations are engrafting as expected, similar to the fresh formulation. This supports our strategy for making these therapies, if approved, broadly available to patients in need throughout the world.

We are extremely pleased with our continued clinical progress, including the duration of benefits seen in our WAS trial, which is the longest published follow-up of hematopoietic stem cell gene therapy durability to date using lentiviral vector transduction, said Bobby Gaspar, M.D., Ph.D., chief scientific officer of OrchardTherapeutics. The totality of these data underscores the broad applicability of our gene therapy platform approach and the opportunity we have to deliver potentially curative treatments for a variety of devastating and rare genetic disorders.

Full presentation details are below:

Poster Presentation Details

Lentiviral Hematopoietic Stem and Progenitor Cell Gene Therapy for Wiskott-Aldrich Syndrome (WAS): Up to 8 Years of Follow up in 17 Subjects Treated Since 2010Publication Number: 3346Session: 801. Gene Therapy and Transfer: Poster IIDate and time:Sunday, December 8, 6:00-8:00pm ET

This presentation includes results from an integrated analysis of 17 patients treated with OTL-103 for the treatment of WAS, including the complete data set for the eight patients from the registrational study and nine who received OTL-103 as part of an expanded access program (EAP). Participants have been followed for a median of three years.

In the eight-patient registrational trial, investigators reported that the study achieved its key primary and secondary endpoints at three years, including the elimination of severe bleeding episodes and a significant reduction in the frequency of moderate bleeding episodes. Successful engraftment was observed within three months, leading to an increase in WAS protein expression and a vector copy number that has been maintained for up to eight years. Nine months post-administration, all patients stopped receiving platelet transfusions, and no severe bleeding events were reported. A significant reduction in the rate of severe infections was also observed and all patients were able to stop immunoglobin replacement therapy (IgRT), suggesting a complete reconstitution of immune function with durability of effect of up to eight years of follow-up post-gene therapy.

Similar clinical results were seen in the integrated analysis of 17 patients and overall survival was 94% (16/17). One death occurred among the EAP cohort that was considered by the investigator to be unrelated to OTL-103.

Across the original and integrated data sets, there were no adverse events considered to be related to OTL-103, including no evidence of oncogenesis, replication competent lentivirus or abnormal clonal proliferation. Clinical benefit was also attained in patients older than five years of age, a group considered at higher risk when treated with allogeneic hematopoietic stem cell transplantation (HSCT).

Lentiviral Gene Therapy with Autologous Hematopoietic Stem and Progenitor Cells (HSPCs) for the Treatment of Severe Combined Immune Deficiency Due to Adenosine Deaminase Deficiency (ADA-SCID): Results in an Expanded CohortPublication Number: 3345Session: 801. Gene Therapy and Transfer: Poster IIDate and time: Sunday, December 8, 6:00-8:00pm ET

This presentation details the safety and efficacy of OTL-101 in 30 individuals with ADA-SCID, treated with either fresh (n=20) or cryopreserved (n=10) formulations. Patients were followed for a median of 24 months (range 12-24 months overall and 12-18 months for patients treated with the cryopreserved formulation), and results were compared with a historical cohort of 26 ADA-SCID patients treated with allogeneic hematopoietic stem cell transplantation (HSCT), including HSCT both with, and without, a matched related donor.

Results showed engraftment of genetically modified hematopoietic stem cells in 29 of 30 OTL-101 patients by six to eight months, which persisted through follow-up in both studies. Analysis of both the vector copy number in granulocytes (a measure of engraftment) and T-cell reconstitution (a relevant measure of immune recovery) showed consistent performance across the fresh and cryopreserved-treated patients.

In the OTL-101 treated patients, overall survival was 30/30 (100%) and event-free survival was 29/30 (97%). One of the 30 patients restarted treatment with enzyme replacement therapy (ERT) and subsequently withdrew from the study and received a rescue HSCT. In the historical control population, 42% of HSCT patients required re-initiation of ERT, rescue HSCT or other intervention, or died. As expected, there was no incidence of graft versus host disease in the OTL-101 group, compared with eight patients who received HSCT.

Eighteen of 20 patients (90%) in the fresh formulation study stopped immunoglobin replacement therapy (IgRT) after two years, compared to 52% of HSCT patients. Of the seven patients treated with the cryopreserved formulation with 18 months of follow-up, five had discontinued IgRT (71%), which is comparable to the 18-month data for patients treated with the fresh formulation.

Oral Presentation Details

Extensive Metabolic Correction of Hurler Disease by Hematopoietic Stem Cell-Based Gene Therapy: Preliminary Results from a Phase I/II TrialPublication Number: 607Session: 801. Gene Therapy and Transfer: Gene Therapies for Non-Malignant DisordersDate and time:Monday, December 9, 7:00am ET

Investigators will present updated analyses from the ongoing proof-of-concept trial of OTL-203 for mucopolysaccharidosis type I (MPS-I).

About ADA-SCID and OTL-101Severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID) is a rare, life-threatening, inherited disease of the immune system caused by mutations in the ADA gene resulting in a lack of, or minimal, immune system development.1-4The first symptoms of ADA-SCID typically manifest during infancy with recurrent severe bacterial, viral and fungal infections and overall failure to thrive, and without treatment the condition can be fatal within the first two years of life. The incidence of ADA-SCID is currently estimated to be one in 500,000 live births inthe United Statesand between one in 200,000 and one in 1 million inEurope.3OTL-101 is an autologous,ex vivo,hematopoietic stem cell-based gene therapy for the treatment of patients diagnosed with ADA-SCID being investigated in multiple clinical trials inthe United StatesandEurope, including a registrational trial at theUniversity of California, Los Angeles(UCLA). OTL-101 has received orphan drug designation from theU.S. Food and Drug Administration(FDA) and the European Medicines Agency (EMA) for the treatment of ADA-SCID, and Breakthrough Therapy Designation from theFDA.

About WAS and OTL-103Wiskott-Aldrich Syndrome (WAS) is a life-threatening inherited immune disorder characterized by autoimmunity and abnormal platelet function and manifests with recurrent, severe infections and severe bleeding episodes, which are the leading causes of death in this disease. Without treatment, the median survival for WAS patients is 14 years of age. Treatment with stem cell transplant carries significant risk of mortality and morbidities. OTL-103 is anex vivo,autologous, hematopoietic stem cell-based gene therapy developed for the treatment of WAS that Orchard acquired from GSK in April 2018 and has been developed at theSan Raffaele-Telethon Institute for Gene Therapy(SR-Tiget) inMilan, Italy. The global incidence of WAS is estimated to be about 100-260 births per year, with a global prevalence of 2,900-4,700 patients.

About MPS-I and OTL-203Mucopolysaccharidosis type I (MPS-I) is a rare inherited neurometabolic disease caused by a deficiency of the IDUA (alpha-L-iduronidase) lysosomal enzyme required to break down glycosaminoglycans (also known as GAGs or mucopolysaccharides). The accumulation of GAGs across multiple organ systems results in the symptoms of MPS-I including neurocognitive impairment, skeletal deformity, loss of vision and hearing, hydrocephalus, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births.5There are three subtypes of MPS-I; approximately 60 percent of MPS-I patients have the severe Hurler subtype and, when untreated, these patients rarely live past the age of 10.IdTreatment options for MPS-I include hematopoietic stem cell transplant and chronic enzyme replacement therapy, both of which have significant limitations. Though early intervention with enzyme replacement therapy has been shown to delay or prevent some clinical features of the condition, it has only limited efficacy on neurological symptoms. OTL-203 is anex vivo, autologous, hematopoietic stem cell-based gene therapy being studied for the treatment of MPS-I. Orchard was granted an exclusive worldwide license to intellectual property rights to research, develop, manufacture and commercialize the gene therapy program for the treatment of MPS-I developed by theSan Raffaele-Telethon Institute for Gene TherapyinMilan, Italy.

About Orchard Orchard Therapeuticsis a fully integrated commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies.

Orchards portfolio ofex vivo, autologous, hematopoietic stem cell (HSC) based gene therapies includes Strimvelis, a gammaretroviral vector-based gene therapy and the first such treatment approved by theEuropean Medicines Agencyfor severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID). Additional programs for neurometabolic disorders, primary immune deficiencies and hemoglobinopathies are all based on lentiviral vector-based gene modification of autologous HSCs and include three advanced registrational studies for metachromatic leukodystrophy (MLD), ADA-SCID and Wiskott-Aldrich syndrome (WAS), clinical programs for X-linked chronic granulomatous disease (X-CGD), transfusion-dependent beta-thalassemia (TDT) and mucopolysaccharidosis type I (MPS-I), as well as an extensive preclinical pipeline. Strimvelis, as well as the programs in MLD, WAS and TDT were acquired by Orchard from GSK inApril 2018and originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene TherapyinMilan, Italyinitiated in 2010.

Orchard currently has offices in the UK and the U.S., including London, San Francisco and Boston.

Forward-Looking StatementsThis 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, 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, the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release, Orchards expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product candidate or candidates referred to in this release, the timing of announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates, including any cryopreserved formulations of such product candidates, and the likelihood of approval of such product candidates by the applicable regulatory authorities. 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, the risks and uncertainties include, without limitation: the risk that any one or more of Orchards product candidates, including the product candidate or candidates referred to in this release, will not be successfully developed or commercialized, the risk of cessation or delay of any of Orchards ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates, the delay of any of Orchards regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchards ability to commercialize its product candidates, if approved.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 annual report on Form 20-F for the year endedDecember 31, 2018as filed with theU.S. Securities and Exchange Commission(SEC) onMarch 22, 2019, as well as subsequent filings and reports filed with theSEC. 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.

1Orphanet. SCID due to ADA deficiency.2Whitmore KV, Gaspar HB. Front Immunol. 2016;7:314.3Kwan A, et al. JAMA. 2014;312:729-738.4Sauer AV, et al. Front Immunol. 2012;3:265. 5Beck et al. The Natural History of MPS I: Global Perspectives from the MPS I Registry. Genetics in Medicine 2014, 16(10), 759.

Contacts

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

MediaMolly CameronManager, Corporate Communications+1 978-339-3378media@orchard-tx.com

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Orchard Therapeutics to Present New Registrational Data of Investigational Gene Therapies at the 61st American Society of Hematology Annual Meeting -...

St. Jude Childrens Research Hospital and the National Institutes of Health to present updated MB-107 clinical data for the treatment of X-linked severe combined immunodeficiency

Fred Hutchinson Cancer Research Center to present overview of ongoing MB-106 Phase 1/2 clinical trial

NEW YORK, Nov. 06, 2019 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, announced today that updated Phase 1/2 clinical data for MB-107 lentiviral gene therapy for X-linked severe combined immunodeficiency (XSCID) have been selected for oral and poster presentations at the 61st American Society of Hematology (ASH) Annual Meeting. ASH will be held December 7-10, 2019, at the Orange County Convention Center in Orlando, FL.

MB-107 is currently being assessed in two Phase 1/2 clinical trials for XSCID: the first in newly diagnosed infants under the age of two at St. Jude Childrens Research Hospital, UCSF Benioff Childrens Hospital and Seattle Childrens Hospital and the second in patients over the age of two who have received prior hematopoietic stem cell transplantation at the National Institutes of Health. Positive Phase 1/2 clinical data from the trial for infants under the age of two were published in the New England Journal of Medicine in April 2019 and positive Phase 1/2 clinical data from the trial in patients over the age of two were published in Science Translational Medicine in April 2016. The U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to MB-107 for the treatment of XSCID in August 2019.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, We are extremely pleased that additional clinical data on MB-107, a lentiviral gene therapy for the treatment of XSCID, will be presented in oral and poster sessions at the 2019 ASH Annual Meeting. The curative potential of MB-107 based on previously announced compelling Phase 1/2 data is impressive, and we look forward to working with St. Jude and NIH to advance the development of this important treatment option.

Details of the MB-107 presentations are as follows.

Oral Presentation:Title: Enhanced Transduction Lentivector Gene Therapy for Treatment of Older Patients with X-Linked Severe Combined ImmunodeficiencySession: 801. Gene Therapy and Transfer: Gene Therapies for Non-Malignant DisordersAbstract Number: 608Date and Time: Monday, December 9, 2019, 7:15 a.m. ET Location: Orange County Convention Center, Valencia BC (W415BC)Presenter: Harry Malech, M.D., Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA

Poster Presentation:Title: Lentiviral Gene Therapy with Low Dose Busulfan for Infants with X-SCID Results in the Development of a Functional Normal Immune System: Interim Results of an Ongoing Phase I/II Clinical StudySession: 801. Gene Therapy and Transfer: Poster IAbstract Number: 2058Date and Time: Saturday, December 7, 2019, 5:30-7:30 p.m. ETLocation: Orange County Convention Center, Hall BPresenter: Ewelina Mamcarz, M.D., Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Childrens Research Hospital, Memphis, TN, USA

In addition, Mustangs collaborator Fred Hutchinson Cancer Research Center will present a poster about the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted CAR T for high-risk B-cell non-Hodgkin lymphomas.

Details of the MB-106 presentation are as follows.

Poster Presentation:Title: CD20 Targeted CAR-T for High-Risk B-Cell Non-Hodgkin LymphomasSession: 704. Immunotherapies: Poster IIAbstract Number: 3235 Date and Time: Sunday, December 8, 2019, 6-8 p.m. ETLocation: Orange County Convention Center, Hall BPresenter: Mazyar Shadman, M.D., M.P.H., Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Copies of the abstracts can be viewed online through the ASH website at http://www.hematology.org.

About Mustang BioMustang Bio, Inc. (Mustang) is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T and CRISPR/Cas9-enhanced CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for XSCID. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission. Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking Statements This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Company Contacts:Jaclyn Jaffe and William BegienMustang Bio, Inc.(781) 652-4500ir@mustangbio.com

Investor Relations Contact:Daniel FerryLifeSci Advisors, LLC(617) 430-7576daniel@lifesciadvisors.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 940-0135tplohoros@6degreespr.com

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Mustang Bio Announces MB-107 Lentiviral Gene Therapy and MB-106 CD20-Targeted CAR T Data Selected for Presentations at 61st American Society of...

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Cancer Genome Sequencing Market Report | What will be the Market size and the growth rate by 2025? - Health News Office

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Global Medical Casting & Splinting Market: Sales, Consumption, Demand and Forecast 2019-2023: 3M, DJO Global, BSN Medical, ssur, Zimmer Biomet,...

A New business Strategy report released by HTF MI with title Global Live Cell Imaging Consumables Market Insights, Forecast to 2025 . This Global Live Cell Imaging Consumables market report brings data for the estimated year 2019 and forecasted till 2025 in terms of both, value (US$ MN) and volume (MT). The report also consists of forecast factors, macroeconomic factors, and a market outlook of the Live Cell Imaging Consumables market. The study is conducted using top-down and bottom-up approaches and further analyzed using analytical tools such as porters five force analysis and uncover Opportunities, Challenges, restraints, and trends of the Global Live Cell Imaging Consumables market. This report also states import/export consumption, supply and demand Figures, cost, price, revenue and gross margins. Some of the Major Companies Profiled in the reports are Carl Zeiss AG (Germany), Leica Microsystems (Germany), Nikon Corporation (Japan), Molecular Devices, LCC (U.S.), PerkinElmer, Inc. (U.S.), GE Healthcare (U.K.), Becton, Dickinson and Company (U.S.), Olympus Corporation (Japan), Sigma Aldrich Corporation (U.S.) & Thermo Fisher Scientific, Inc.(U.S.) etc.

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On the Basis of Product Types of Live Cell Imaging Consumables Market: , Assay Kits, Reagents, Media & Others

The Study Explores the Key Applications/End-Users of Live Cell Imaging Consumables Market: Cell Biology, Stem Cells, Developmental Biology & Drug Discovery

Global Live Cell Imaging Consumables Competitive Analysis:The key players are extremely aiming innovation in fabrication skills to increase efficiency and shelf life. The best long-term growth opportunities for this sector can be captured by ensuring constant process improvements and economic flexibility to spend in the optimal schemes. Company profile section of players such as Carl Zeiss AG (Germany), Leica Microsystems (Germany), Nikon Corporation (Japan), Molecular Devices, LCC (U.S.), PerkinElmer, Inc. (U.S.), GE Healthcare (U.K.), Becton, Dickinson and Company (U.S.), Olympus Corporation (Japan), Sigma Aldrich Corporation (U.S.) & Thermo Fisher Scientific, Inc.(U.S.) etc. includes its basic information like legal name, website, headquarters, its market position, historical background and top 5 closest competitors by Market capitalization / revenue along with contact information.

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Most important Highlights of TOC:1 Introduction of Live Cell Imaging ConsumablesMarket1.1 Overview of the Market1.2 Scope of Report

2 Exclusive Summary

3 Research Methodology3.1 Primary Interviews3.2 Data Mining3.3 Validation3.4 List of Statistics

4 Live Cell Imaging Consumables Market Segment & Geographic Analysis4.1 By Type [2014 -2025]4.2 By Application [2014-2025]4.3 By Region [2014-2025]

5 Live Cell Imaging Consumables Market Outlook5.1 Overview5.2 Market Dynamics5.2.1 Opportunities5.2.2 Restraints5.2.3 Drivers5.3 Porters Five Force Model5.4 Value Chain Analysis

6 Live Cell Imaging Consumables Market Competitive Landscape6.1 Overview6.2 Key Development Policies6.3 Company Market Standing

Read Detailed Index of Live Cell Imaging Consumables Market report @:https://www.htfmarketreport.com/reports/1366687-global-live-cell-imaging-consumables-market-6

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Live Cell Imaging Consumables Market Evolving to a Next-Generation Strategy with New Partnerships, Technologies and Targets by 2023 key players LCC...