Solid Biosciences Stock Crashes Over Safety Concerns About Its Gene Therapy – Barron’s

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Solid Biosciences showed signs Tuesday morning of facing serious setbacks for its Duchenne muscular dystrophy gene therapy, sending the biotechs shares down about 70% in early trading.

Solid (ticker: SLDB) said the Food and Drug Administration had put its Phase I/II study of its experimental gene therapy treatment for Duchenne muscular dystrophy on clinical hold after one of the six patients dosed with the treatment suffered acute kidney injury, among other serious side effects.

This is the second clinical hold placed on this study. In March 2018, the FDA held the study after a patient in the low-dose cohort was hospitalized.

We are encouraged that this patient is recovering, Solid Biosciences CEO Ilan Ganot said in a statement. We remain committed to bringing meaningful new therapies to the Duchenne community and continue to believe in the differentiated construct of SGT-001 and the potential benefits it may offer to patients.

Solid is one of a number of companies seeking to be the first to bring to market a gene therapy to cure Duchenne muscular dystrophy, a genetic disorder that produces muscle weakness and dramatically shortens the life expectancy of people who suffer from it. Wall Street has increasingly seen Sarepta Therapeutics (SRPT) as having the leading Duchenne muscular dystrophy gene therapy candidate, after Solid released disappointing data earlier this year.

Pfizer (PFE) is also developing a competing gene therapy.

Ganot founded the company after his son was diagnosed with the disease. Safety concerns have long dogged Solid. In January of 2018, gene therapy pioneer James Wilson resigned from the companys scientific advisory board, according to a company filing, over emerging concerns about the possible risks of high systemic dosing of AAV, the viral vector used to deliver the gene therapy.

In its Tuesday morning statement, Solid said three patients given a lower dose of the experimental gene therapy continue to do well, as do two of the three patients given a higher dose. But one of the patients who received the higher dose fell ill.

The third patient...dosed in late October, experienced a serious adverse event (SAE) deemed related to the study drug that was characterized by complement activation, thrombocytopenia [low blood platelet count], a decrease in red blood cell count, acute kidney injury, and cardio-pulmonary insufficiency, the company said.

In a note out Tuesday morning, SVB Leerink analyst Joseph P. Schwartz noted that the new adverse event resembles the one from March 2018.

The safety profile of SGT-001 will most likely be under increased scrutiny, Schwartz wrote.

Solid Biosciences stock was recently trading 68.6% lower at $3.45.

Write to Josh Nathan-Kazis at josh.nathan-kazis@barrons.com

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Solid Biosciences Stock Crashes Over Safety Concerns About Its Gene Therapy - Barron's

Solid’s Duchenne gene therapy trial halted after patient suffers toxicity – STAT

The Food and Drug Administration has halted a clinical trial involving a Duchenne muscular dystrophy gene therapy from Solid Biosciences (SLDB) after a patient suffered serious kidney and blood-related injuries, the company said Tuesday.

This is the third time that the Cambridge, Mass.-based Solid has run into a serious safety problem with its gene therapy, called SGT-001. The FDA placed similar clinical holds on the same clinical trial after each prior incident, but later allowed the company to proceed with patient dosing.

SGT-001 uses an inactivated virus to deliver a miniaturized but functional version of the dystrophin gene to muscle cells. The gene therapy is designed to be a one-time and potentially curative treatment for all Duchenne patients, regardless of the mutation that causes their disease.


Sarepta Therapeutics (SRPT) and Pfizer (PFE) are also developing their own gene therapies targeted at Duchenne.

Six patients have been dosed with SGT-001, starting with three at a lower dose; interim results in those patients were previously reported and found to be disappointing. Three more patients were then treated at a higher dose of SGT-001.

The sixth patient became ill soon after being treated in October, experiencing an over-activation of the immune system, an acute kidney injury, reductions in platelets and red blood cells, and cardio-pulmonary insufficiency, Solid said.

All of the toxicities were deemed related to SGT-001 by the patients treating doctor. The patient is being treated and is recovering, Solid said.

Solid reported the patients status to the FDA, which then placed the clinical trial on hold. In a statement, the company said it will work with the FDA in an effort to resolve the hold and determine next steps for the clinical trial.

Pfizers Duchenne gene therapy has also been tied to similar immune system over-activation and related kidney toxicity, although its clinical trial remains active.

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Solid's Duchenne gene therapy trial halted after patient suffers toxicity - STAT

Gene Therapy in Neurology: 2019 Overview & Forecast Report – Yahoo Finance

Dublin, Nov. 12, 2019 (GLOBE NEWSWIRE) -- The "Gene Therapy in Neurology" report has been added to ResearchAndMarkets.com's offering.

Gene therapy is an evolving area in healthcare that promises to revolutionize the treatment landscapes across various therapy areas.

In this report, the focus will be on neurology indications. The report provides an analysis of the overall gene therapy pipeline that is being developed for various neurology indications with an emphasis on late-stage pipeline products. In addition to pipeline analysis, the report also focuses on trends observed in clinical trials in this area, unmet needs and challenges, as well as partnership strategies adopted by pharmaceutical companies to keep up with developments in the field of gene therapies.

Recently approved gene therapies for spinal muscular atrophy have reinvigorated the potential of such therapies to transform patient care. While various methodologies can be adopted in order to deliver therapeutic benefits of gene therapy including gene augmentation, gene suppression, and gene editing, an important component of gene therapy is whether to use viral or non-viral vectors in order to deliver such therapies to the point of care.

Ongoing collaborations between different industry players and a buildup of real-world evidence establishing safety and efficacy are expected to drive the growth of gene therapies for neurology indications. Of the 38 pipeline products that are currently in development, 45% are adeno-associated virus (AAV) based delivery platforms. Other types include Lentiviral, which accounts for 13%.

A majority of the current pipeline products are in Phase II development and the most common neurology indications - for which gene therapies are currently being evaluated - include Parkinson's disease, pain and amyotrophic lateral sclerosis. The dominance of viral vectors is expected to continue as such platforms account for the bulk of these pipeline products, with adeno-associated virus being the most common among the viral vectors.

In terms of completed, ongoing and planned clinical trials, academic institutes account for 21% of these trials, despite industry sponsors being most dominant. A deeper analysis of these clinical trials also suggest that across most indications, the average trial duration for a viral based product is longer compared to a non-viral based product such as oligonucleotides or plasmid DNA.

There are also challenges associated with the development of gene therapies, most prominent being their high price points. Key opinion leaders (KOLs) interviewed highlighted the need to create sustainable funding solutions so that such therapies become accessible to patients everywhere irrespective of where patients are located. In terms of unmet needs, KOLs highlighted the need for a favorable route of administration that is both sustainable in terms of usage of healthcare resources and favorable from a patient perspective.

While development of gene therapies are expected to pick up pace, the next wave of such therapies are expected to be ones that target diseases that are more frequent. While monogenic rare diseases are the obvious first-to-go choice for which gene therapies can be developed, targeting more frequent diseases will need a holistic approach in order to address a wider mechanism of action. If gene therapies for frequent diseases do become available, then that will result in a more pronounced effect on healthcare not only in terms of providing better treatment options for patients but also test the ability of healthcare organizations to adapt with high price points of these therapies.


Reasons to Buy

Key Topics Covered

1 Preface

2 Executive Summary2.1 Key Findings2.2 KOL Insights on Competitive Landscape for Gene Therapy for Neurology Indications

3 Overview - Gene Therapy in Neurology3.1 Objectives of Gene Therapy 3.2 Gene Therapy Versus Conventional Therapies3.3 Optimization of Gene Expression3.4 Gene Transfer Methods and Vectors Used for Gene Therapy3.5 Classifications of Gene Therapy3.6 Sources

4 Gene Therapy in the 8MM4.1 Global Regulatory Agencies' Definitions of Gene Therapy4.2 Gene Therapy in the US 4.3 Gene Therapy in the EU4.4 Gene Therapy in Japan4.5 Gene Therapy in China4.6 Currently Marketed Gene Therapies in Neurology4.7 Sources

5 Pipeline Assessment in the 8MM 5.1 Pipeline Overview 5.2 Pipeline Products - Phase III5.3 Pipeline Products - Phase II5.4 Orchard Therapeutics' OTL-200 5.5 Biogen's Tofersen Sodium5.6 Roche's RG-5.7 Sylentis' Tivanisiran5.8 ViroMed's Donaperminogene Seltoplasmid5.9 Sources

6 Clinical Trials Mapping and Design6.1 Clinical Trial Mapping for all Pipeline Products by Phase, by Sponsor, and by Location6.2 Clinical Trial Mapping for all Pipeline Products by Status and by Indication6.3 Clinical Trial Mapping by Phase and Indication for Phase III Therapies6.4 Clinical Trial Mapping by Phase for Phase II Therapies6.5 Clinical Trial Duration by Indication for Phase III Therapies (By Types of Molecules)6.6 Clinical Trial Duration by Indication for Phase II Therapies (By Types of Molecules)6.7 Ongoing Clinical Development of Phase III Gene Therapies

7 Unmet Needs, Barriers, and Key Company Strategies 7.1 Unmet Needs Within Gene Therapy for CNS Indications7.2 Challenges and Other Factors to Consider During Different Stages of Product Development7.3 Key Company Strategies: Acquisitions7.4 Key Company Strategies: Strategic Partnerships7.5 Sources

8 Payer Perspective on Gene Therapies in Neurology8.1 Current Neurology Space8.2 Challenges Associated with Reimbursement of Novel Gene Therapies8.3 Cost of Gene Therapies8.4 Strategies to Tackle the Cost of Gene Therapies8.5 Innovative Reimbursement Models and Clinical Comparators

9 Market Outlook9.1 Phase III Gene Therapy Pipeline for Neurology9.2 Key Launch Dates for Phase III Gene Therapy Pipeline Products

Companies Mentioned

Story continues

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Gene Therapy in Neurology: 2019 Overview & Forecast Report - Yahoo Finance

How Gene Therapy Is Evolving to Tackle Complex… – Labiotech.eu

Gene therapy has traditionally been applied to well-understood diseases where a single genetic mutation was to blame. A new generation of technology is expanding the potential of gene therapy to treat conditions that were previously unreachable.

Since the first gene therapy clinical trials in the 1990s, the technology has made its way into the market for conditions ranging from blindness to cancer.

Gene therapy has the potential to fix any genetic mutation causing disease by inserting a new copy of the faulty gene. However, its reach has historically been limited.

Weve been constrained with the things we can do with gene therapy, said Dmitry Kuzmin, Managing Partner at 4BIO Capital, a London-based VC that specifically invests in advanced therapies. If you look across the successes in gene therapy in the last five years, most of these were in diseases that are pretty straightforward from the engineering perspective.

Technical limitations have meant that gene therapy has been restricted to rare diseases caused by a single genetic mutation, as well as to certain areas of the body, such as the eye and the liver.

According to Kuzmin, there have been so far three generations of gene therapy technology. Generation one would be classic single-gene replacement, such as Luxturna, a gene therapy to fix a specific genetic mutation causing blindness. Generation two would consist of using gene therapy to introduce new functions. An example is Kymriah, where immune cells are equipped with a molecule that helps them hunt down cancer cells.

The third generation is the one that could hold the key to unlocking the full potential of gene therapy. It englobes several technologies that can be used to introduce a new drug target into the patient, making it possible to turn the therapy on and off as well as to tune its intensity.

As the first two generations get optimized and the third generation enters the clinic, we are now expanding our reach into areas that have been previously rather inaccessible, Kuzmin told me. One of them is the brain.

Treating the brain has long been a huge challenge for medicine. Take epilepsy, for example.

Epilepsy affects 1% of the whole population and about 30% of people with seizures of epilepsy continue to have seizures despite medication, said Dimitry Kullmann, Professor at University College London. Theres a paradox. We have a good understanding of the mechanisms behind epilepsy, but were unable to suppress seizures in a significant proportion of people with epilepsy.

The reason is that the molecules that we use for drugs dont target the epileptic zone of the brain; they bathe the entire body with medication, Kullmann told me. These drugs dont differentiate between neurons and synapses that derive the seizures, and those parts of the brain that are responsible for memory, sensory functions, motor functions and balance.

Gene therapy could provide a solution for this problem. Kullmanns group has been researching this approach for years and is now getting ready to start the first clinical trial in humans within a year.

A gene therapy can be directly injected in the area of the brain causing seizures. Furthermore, using DNA sequences called promoters, it is possible to restrict the effect of gene therapy to specific neurons within that area. In the case of epilepsy, gene therapy can be used to decrease the activity of only excitatory neurons, which cause epileptic seizures when they are overactive.

Another approach that Kullmans group is testing is chemogenetics. The idea here is to use gene therapy to put a specific receptor into the neurons, explained Kullmann. This receptor is designed to respond to a drug that, when given to the patient, decreases the activity of the neuron to suppress seizures.

The advantage is that you can switch on and off the therapeutic effect on demand by just giving, or not giving the drug, Kullmann said. This approach can thus make gene therapy more precise, being able to tune it to the specific needs of each patient. In addition, it reduces the big challenge of getting the dose right in a one-off treatment.

Ultimately, this technology could allow scientists to target a wide range of conditions that come under the umbrella of epilepsy, rather than just a specific form of the condition caused by a genetic mutation.

The approach could be extended to other conditions involving the brain, such as Parkinsons, ALS and pain. However, this kind of research is still at an early stage and it will take a while until its potential is proven in humans.

Blindness has been a major target of gene therapy because of the fact that the eye is an ideal target for this technology. The activity of the immune system is suppressed in the eye, minimizing the chances of rejection. In addition, unlike other cells in the body, those involved in vision are not renewed over time, being able to retain the injected DNA for years.

However, there are hundreds of genetic mutations that can cause blindness. With the classical gene therapy approach, a different therapy would have to be developed from scratch for each mutation. While some companies are doing just this for the most common mutations causing blindness, many other less frequent mutations are being left behind.

Others are turning to new generations of gene therapy technology. We figured out that it would be very, very difficult to use the classical gene therapy approach in each individual mutation, said Bernard Gilly, CEO of GenSight, a Parisian biotech developing gene therapies for blindness.

While the companys leading programs follow this classical approach, the company has also started clinical trials using a technology called optogenetics. Following a similar principle to gene therapy, optogenetics consists of introducing a protein that reacts to light into a cell.

GenSight is using optogenetics to develop a single therapy for the treatment of retinitis pigmentosa. This genetic condition can be caused by mutations in any of over 200 genes and results in progressive vision loss in children due to the degeneration of photoreceptor cells that perceive light and send signals to the brain.

With optogenetics, it would be possible to transfer the lost photoreceptor function to the cells in the retina that are responsible for relaying visual information to the brain. Using specialized goggles, the images captured by a camera are transformed into light patterns that stimulate these cells in the precise way needed for the brain to form images.

The company is currently testing this approach in clinical trials. We believe that this approach will allow us to restore vision in those patients who became blind because of retinitis pigmentosa, Gilly told me.

Optogenetics would not work a miracle, but it might be able to give people back the ability to navigate an unknown environment with a certain level of autonomy. Recognizing faces is a more challenging goal; although reading is not yet on the horizon, according to Gilly.

Still, the potential of optogenetics to address multiple genetic mutations with a single treatment might be revolutionary. As long as the neurons responsible for sending light signals to the brain are intact, this approach could be extended to other forms of blindness. In addition, conditions affecting the brain such as epilepsy, Parkinsons or ALS could be treated with this approach by introducing an implant to shine light on the target neurons.

However, approaches applying optogenetics to the brain are still further down the line. While optogenetics technology has been around for over 20 years, its application in humans is still very limited and in the early stages of research.

Chemogenetics and optogenetics are just two out of a wave of new technologies addressing the historical limitations of gene therapy. Other approaches are in development, such as using thermogenetics, which consists of introducing proteins that are activated by the heat created by infrared light.

With a growing range of tools available, it is becoming easier than ever for scientists to develop gene therapies that can address the specific challenges of different conditions affecting areas of the body. Traditionally, locations such as the heart, the lungs or the pancreas have been particularly difficult to target with gene therapy. That might soon stop being the case.

As we go forward, were interested in taking gene therapy out of this little box and trying to use all the knowledge we have to benefit patients in larger indications, said Kuzmin.

As gene therapy expands into more mainstream conditions, it could take precision medicine to a whole new level and help address the big variability that is often seen across patients with the same diagnosis.

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How Gene Therapy Is Evolving to Tackle Complex... - Labiotech.eu

Gene Therapy Payment Models Could Be One Focus For ‘Cures II’ – Pink Sheet

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Lonza taps Cryoport to bolster cell and gene therapy delivery – BioPharma Dive

Dive Brief:

Lonza is betting big on the future of gene and cell therapy and trying to offer customers an end-to-end solution to meet the complex challenges that come with the field.

Every stage of cell therapy, from patient apheresis through transport, genetic engineering and reinfusion comes with critical requirements for temperature control, speed and chain of identity.

Cryoport operates in more than 100 countries and supports more than 413 clinical trials. Notably, the company also supports three approved therapies: Gilead's Yescarta(axicabtagene ciloleucel), Novartis' Kymriah(tisagenlecleucel) and Bluebird bio's Zynteglo.

Demand for specialized manufacturing and distribution services is growing as researchers figure out new ways to manipulate cells so they can fight cancer and other diseases, Cryoport CEO Jerrell Shelton said in the statement.Cryoport's temperature-controlled supply chain systems fit well with Lonza's manufacturing services, he added.

For Lonza, cell and gene therapies are a new focus, part of a broader turn to the pharmaceutical side of the contract manufacturer's business.

In April 2018, the Swiss CDMO opened the doors to a 300,000 square-foot plant in Texas dedicated to producing the complex treatments.

CEO Marc Funk told BioPharma Dive in an interview earlier this year that Lonza has now worked with over 45 customers seeking supply of viral vectors, which are used to deliver gene therapies.

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Lonza taps Cryoport to bolster cell and gene therapy delivery - BioPharma Dive

Pfizer’s ‘brainstorming’ payment deals as gene therapies advance, exec tells Bloomberg – FiercePharma

Gene therapies offer a "world of wonders" for patients, but with some 10,000 of the pricey therapies in development, pharma companies and payers need to get outcomes-based payments nailed down, a top Pfizer exec told Bloomberg.

What's more, Pfizer biopharma president Angela HwangtoldBloomberg's Cynthia Koons, gene therapies present some unique scientific and manufacturing challenges.

Gene therapies currently target monogenic diseases, or diseases that are characterized by a single genetic mutation, Hwang said. There are about 3,000 such disorders, and they're all considered rare diseases. Pfizer itself has three gene therapies in development for hemophilia A, hemophilia B and Duchenne muscular dystrophy.

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Overall, there are 10,000 gene therapy programs in development,Hwang said. If 10% of them end up working,you start to see that potentially gene therapy can become a mainstaytherapyin how we manage diseases," she said in the Bloomberg interview.

That necessitates the key question about payment.Currently, payment systems are centered on paying for individual drug doses. Hwang said the industry needs to get outcomes-based payments worked out, adding that the process could become easier as science advances and data collection improves.

RELATED:Pfizer amps up gene therapy manufacturing with another North Carolina facility

Looking ahead, new gene therapy launches will necessarily drive us to come up with different solutions other than the ones we have today, Hwang said in the interview, referencingsubscription-based payments as one option.Her company is already brainstorming with payers, she added.

There are just two launched U.S. gene therapiesNovartis'Zolgensmaand Spark Therapeutics' Luxturna. Roche is in the process of acquiring Spark, but the buyout has been held up by antitrust regulators.

With already approved gene therapies, the market is adapting. Novartis has offered to allow payers to fund its spinal muscular atrophy gene therapyZolgensmawhich costs $2.125 millionover a period of five years. Thedrugmakerhas also proposed pay-for-performance deals.

Bluebird bio recently won European approval for itsbeta-thalassaemiagene therapyZyntegloand is allowing payers to pay for the drug over several yearsas long asthe med continues to workfor patients.

For its part, Pfizer is buildinga gene therapy manufacturing plant in North Carolina to manufacture clinical trial supplies and potential commercial products following approvals.

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Pfizer's 'brainstorming' payment deals as gene therapies advance, exec tells Bloomberg - FiercePharma

Why This Startup Sent Wine to Space; Dog Gene Therapy ‘Treat’ment – Cheddar

On this episode of Cheddar Innovates: Gene therapy is being tested in dogs that may be able to treat ailments in humans in the future; A new study finds that invasive grass could be causing more frequent wildfires in California; A startup sends French wine to the International Space Station for an aging experiment; A full-body CGI of late actor James Dean is set to star in an upcoming film.

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Why This Startup Sent Wine to Space; Dog Gene Therapy 'Treat'ment - Cheddar

Next generation cell and gene therapies: fine tuning the promise – Business Weekly

On 19 November, the UK BioBeat19 summit goes to Stevenage to discuss the potential of cell and gene therapy and how to accelerate these transformational medicines.

Victoria Higgins of GSK and Miranda Weston-Smith from BioBeat spoke to two panellists who gave a sneak peek of their remarks and agree wholeheartedly that the discovery side and clinical side work best when they are teamed up.

Sophie Papa, an oncologist at Guys Cancer at Guys and St Thomas NHS Trust, and Aisha Hasan, a clinical development lead at GSK, both recognise the big challenge ahead for cell therapy researchers: to dial up efficacy and dial down toxicity.

Cell and gene therapies, with their remarkable potential to transform medicine, have seen some important but hard-won milestones: it took 20 years of combined academic and industry research to deliver the first gene therapy approval in 2016 and today there are two CAR-Ts approved for haematological malignancies.

Whilst CAR-Ts recognise proteins expressed on the tumour cell surface, making them ideal for targeting blood cancers, more complicated but with greater potential to address solid tumours are the gene modified TCR-T technologies.

These harness the power of T cells to specifically target and destroy tumours even on the inside of cells. TCR-Ts come with an additional level of complexity, but potentially open the door to a range of untreatable cancer types.

Looking at the TCR opportunity is where Sophie Papa sees the inherent trade-off between risk and benefit as an academic clinician whos now evaluating modified T-cell based therapies in clinical trials.

Sophie urges her peers to take courage. It is important to be brave and tolerant of certain toxicities. Academic clinicians and drug researchers need to work closely together to engage the regulators in early discussion, so that we can move cell therapies earlier in treatment schedules as soon as feasible.

Timing is critical to enable patients to be treated when they are physically fit so they can better tolerate these complex and potentially toxic treatments.

From her perspective, this is not an either/or, but an area where discussion and open dialogue will allow us to make the most of the opportunity. By allowing clinical academics to play a lead role in developing guidelines to manage patient safety, we can address legitimate concerns but not let them stand in the way of clinical development, she says.

Aisha brings the perspective of drug discovery and development and starts by asking what is in the realm of the possible from a design perspective.

She says: A superior T-cell therapy will require engineering approaches that enhance efficacy on one-end while also incorporating switches to minimise toxicity.

For example, in a counter-intuitive way, a T-cell with high-killing capacity actually can create dangerous levels of inflammation in the body, due to the rapid death of cancer cells. But the beauty of drug design opens up options:By building a switch within the engineered T-cells, researchers can inactivate the T-cells and prevent harm to the patient, says Aisha.

But this creative problem solving requires open dialogue between clinicians and pharma. Aisha says: The more we talk about clinical need and toxicity benchmarks, the more sophisticated we can be when developing the next generation of enhanced engineered cell therapies.

Theres no doubt that the challenges of delivering cell and gene therapy span the full spectrum of issues related to medicine development. However, the potential for both curative therapy and commercial opportunity is tremendous.

The scientific, clinical, technical, regulatory and commercial challenges are all surmountable when everyone in the ecosystem work together towards a shared goal, united by an unwavering focus on the patient.

Sophie and Aisha are speaking about the translational journey from science to bedside at the BioBeat19 summit.

The BioBeat19 summit on Accelerating cell and gene therapy, 1-6pm, Tuesday 19 November, GSK Stevenage. Guarantee your place by registering at http://www.biobeat19.org

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Next generation cell and gene therapies: fine tuning the promise - Business Weekly

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

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

Scientists are using gene therapy to treat a heart disease in dogs. Could humans be next? – 10News

Scientists are working to eliminate a type of heart disease in dogs using gene therapy.

They're zoning in on a heart condition called mitral valve disease thats common in 6% of dogs.

Scientists are using Cavalier King Charles spaniels for the research.

They tend to develop it at a younger age.

Scientists at Tufts University have already tested gene therapy in mice.

A virus is injected into them to deliver DNA to cells which causes them to create a protein.

What it essentially does is stops the heart valve from getting thicker, stopping the valve from leaking.

Researchers are now moving on to testing this in dogs.

But they think the treatment could go beyond just canines.

Many of the dog diseases are naturally occurring and really great models for human disease, says Dr. Vicky Yang, a veterinary cardiologist and research assistant professor at Cummings School of Veterinary Medicine at Tufts University. And I can see this, if it becomes successful in dogs, potentially going into thinking about treatment for humans for mitral valve disease.

The biotech company behind the treatment agrees. It says it could also expand beyond heart problems.

I think a larger question, though, is if we are able to prove this thesis of treating aging, making the animal generally healthier, could also treat heart failure, what other diseases could we treat in dogs? says Daniel Oliver, the CEO of Rejuvenate Bio. And could we progress this treatment onto past dogs and other animals and possibly humans?

The gene therapy would only be used for dogs just starting to experience heart problems.

Researchers still need to make sure the gene therapy is safe for all breeds before they make it available to the public.

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Scientists are using gene therapy to treat a heart disease in dogs. Could humans be next? - 10News

Updated Alta Trial Results Support SB-525 Gene Therapy for Hemophilia A – Hemophilia News Today

Updated results from the Alta trial show that a single infusion with the highest dose of SB-525, an investigational gene therapy, yields dose-dependent and durable increases in clotting factor VIII (FVIII). The trial, in adults with severe hemophilia A , found no bleeding episodes up to 24 weeks following the infusion.

That highest dose of SB-525 31013 vector genomes, vg/kilogram, kg led patients to reach normal FVIII activity. Participants no longer needed replacement therapy following a short preventive course post-SB-525-administration.

With these promising results, Pfizer has initiated a lead-in study (NCT03587116) to support SB-525 advancement to a Phase 3 registrational clinical trial. The six-month study will evaluate the current efficacy and safety of preventive replacement therapy in the usual care setting. It is currently recruiting participants worldwide.

The Alta trials most recent findings will be shared at the upcoming 61st Annual Meeting of the American Society of Hematology (ASH), to be held Dec. 7-10 in Orlando, Fla.

Data will be featured in a poster titled Updated Follow-up of the Alta Study, a Phase 1/2, Open Label, Adaptive, Dose-Ranging Study to Assess the Safety and Tolerability of SB-525 Gene Therapy in Adult Patients with Severe Hemophilia A.

SB-525 is a gene therapy candidate to treat hemophilia A thats being developed by Sangamo Therapeutics in collaboration with Pfizer. It consists of a DNA sequence coding for the production of a working FVIII the clotting factor missing in hemophilia A. That FVIII is carried and delivered to liver cells, where clotting factors are produced, using a harmless adeno-associated viral (AAV) vector.

The goal of the therapy is for patients to regain the ability to continuously produce the coagulation factor, and reduce or eliminate the need for FVIII replacement therapy.

The therapys safety and effectiveness for the treatment of adults with severe hemophilia A are currently being evaluated in the open-label Phase 1/2 Alta trial (NCT03061201).

The study is testing a single infusion into the vein (intravenous) of one of four ascending doses of SB-525: 91011 vg/kg; 21012 vg/kg; 11013 vg/kg; and 31013 vg/kg. Two people have been dosed per group, except for the highest dose group, which was expanded to five patients.

Updated trial data now released show the results for the two patients dosed in the third group those given 11013 vg/kg and the five individuals receiving the highest dose of 31013 vg/kg.

In the third group, a single infusion of SB-525 resulted in stable and clinically relevant increases in FVIII activity.

Stronger results were seen with SB-525s highest dose. Of the five patients treated, data were available for four. For these participants, a single infusion with the highest dose of SB-525 led to normal FVIII levels with no bleeding events reported up to 24 weeks post-administration. These individuals no longer needed replacement therapy after the initial prophylactic period of up to about three weeks after SB-525 dosing.

In addition, preliminary tests from the high-dose group indicate similar activity of SB-525-derived FVIII and the clotting factor provided by Xyntha, Pfizers recombinant therapy for hemophilia A.

As to safety, one patient had treatment-related serious adverse events, namely low blood pressure and fever, occurring about six hours after infusion. These effects resolved with treatment within 24 hours, with no loss of FVIII expression.

Some patients also showed elevated blood levels of liver enzymes(ALT, alanine aminotransferase). However, these were reported to be mild and temporary increases, which were treated in a timely manner with corticosteroids.

Dosing in the fourth group is ongoing. At the upcoming meeting, Sangamo will disclose additional analyses of the trial data, including a follow-up of approximately 4 to 11 months after treatment.

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, Bettina Cockroft, MD, MBA, chief medical officer of Sangamo said in a press release.

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 [investigational new drug].

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: 121

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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Updated Alta Trial Results Support SB-525 Gene Therapy for Hemophilia A - Hemophilia News Today

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

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...

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

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.


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

Triple-Gene Announces Completion of Enrollment and Dosing in Phase 1 Trial of INXN4001, First Multigenic Investigational Therapeutic Candidate for…

"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 theAmerican 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 17thfrom 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 ofIntrexon 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 atwww.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 atwww.dna.comor follow us on Twitter at@Intrexon, onFacebook, andLinkedIn.

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.

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Triple-Gene Announces Completion of Enrollment and Dosing in Phase 1 Trial of INXN4001, First Multigenic Investigational Therapeutic Candidate for...

Five benefits of gene therapies – Echo Live

GENES are the building blocks of life but like all things, they can sometimes go wrong, resulting in a range of conditions and diseases.

Repairing or replacing these genes with good ones, however, could solve or at the very least treat the problem, and this is what the emerging science of gene therapy is all about.

It was first suggested in the early-1970s that using good DNA (genes are short sections of DNA) to replace defective DNA could treat inherited diseases, and since then scientists have been trying to work out how to do it, both for inherited conditions and many others.

The British Society for Gene and Cell Therapy (bsgct.org) says the first approved human gene therapy took place in 1990, on four-year-old Ashanti DeSilva who had ADA-SCID an inherited disease that prevents normal development of the immune system. The therapy made a huge difference, meaning the little girl no longer needed to be kept in isolation and could go to school.

When the human genome was mapped nearly 20 years ago, the notion that it could potentially unlock therapies capable of fixing genes responsible for some of the worlds most devastating diseases was an idea of the future, says gene therapy expert Professor Bobby Gaspar, speaking on behalf of Jeans for Genes Day, the annual campaign for Genetic Disorders UK (geneticdisordersuk.org).

We are at the forefront of a new era of treatment for genetic diseases using gene and cell therapies. Some of these are one-time, potentially curative investigational therapies that could provide life-changing benefits to patients and their families.

Gaspar says there are currently more than 10 cell and gene therapy products approved in the European Union, ranging from products that treat cancer to rare immune deficiencies. A number of these are approved in the UK and available on its National Health Service in specialised centres.

And with nearly 3,000 clinical gene therapy trials underway worldwide, the number of available treatments is expected to grow significantly over the next few years.

Here, Gaspar a professor of paediatrics and immunology at the UCL Great Ormond Street Institute of Child Health and chief scientific officer at Orchard Therapeutics, a gene therapy company that seeks to permanently correct rare, often-fatal diseases outlines five of the ways gene therapy can cure, stop, or slow a disease...

A variety of efforts are underway to use gene therapy to treat cancer. Some types of gene therapy aim to boost the bodys immune cells to attack cancer cells, while others are designed to attack the cancer cells directly.

One way the body protects itself from cancer is through T-cells, a main component of the immune system. But some cancers are good at avoiding these protection mechanisms, says Gaspar.

Chimeric antigen receptor, or CAR T-cell therapy, is a new form of immunotherapy that uses specially altered T-cells to more specifically target cancer cells.

Some of the patients T-cells are collected from their blood, then genetically modified to produce special CAR proteins on the surface.

When these CAR T-cells are reinfused into the patient, the new receptors help the T-cells identify and attack cancer cells specifically and kill them.

There are more than 250 genetic mutations that can lead to a type of blindness called inherited retinal diseases, or IRD. People with a defect in the RPE65 gene start losing their vision in childhood.

As the disease progresses, patients experience gradual loss of peripheral and central vision, which can eventually lead to blindness.

Gene therapy for some IRD patients became available in 2017, delivering a normal copy of the RPE65 gene directly to the retinal cells at the back of the eye using a naturally-occurring virus as a delivery vehicle.

For children with the genetic disorder spinal muscular atrophy, or SMA, a rare muscular dystrophy, motor nerve cells in the spinal cord are damaged, causing patients to lose muscle strength and the ability to walk, eat or even breathe, says Gaspar.

SMA is caused by a mutation in a gene called SMN which is critical to the function of the nerves that control muscle movement. Without this gene, those nerve cells cant properly function and eventually die, leading to debilitating and often fatal muscle weakness.

Researchers recently developed the first US-approved gene therapy to treat children less than two years of age with SMA.

The therapy is designed to target the cause of SMA by replacing the missing or nonworking gene with a new, working copy of a human SMN gene, helping motor neuron cells work properly.

Researchers believe targeted gene therapy and gene editing may have widespread application for a range of infectious diseases that arent amenable to standard clinical management, including HIV.

Although HIV isnt a hereditary disease, the virus does live and replicate in DNA, Gaspar explains.

Another early but encouraging approach uses a gene editing technology combined with a new long-acting, antiretroviral treatment to suppress HIV replication and eliminate HIV from cells and organs of infected animals.

Gene editing is an approach that precisely and efficiently modifies the DNA within a cell. In this approach, gene editing can knock out a receptor called CCR5 on immune cells used by HIV to enter and invade cells. Without CCR5, HIV may no longer invade and cause disease.

One approach being investigated for a number of rare, often-fatal diseases uses gene-modified blood stem cells with a goal of permanently correcting the underlying cause of disease.

Blood stem cells are taken from the patient, and corrected outside the body by introducing a working copy of the gene into the cells. The gene-corrected cells are then put back into the patient to potentially cure the disease.

Gene-modified blood stem cells have the capacity to self-renew and, once taken up in the bone marrow, can potentially provide a lifelong supply of corrected cells. Because of their ability to become many different types of cells in the body, this approach has the potential to provide a lasting treatment for many different severe and often life-limiting inherited disorders, many of which have no approved treatment options available, says Gaspar.

For instance, ADA-SCID, sometimes referred to as bubble baby syndrome, is a disease where babies lack almost all immune protection, leading to frequent and devastating infections. Left untreated, babies rarely live past two years of age. Standard treatment options are not always effective or can carry significant risks. In 2016, the European Medicines Agency approved Strimvelis, a blood stem cell gene therapy for the treatment of ADA-SCID. Strimvelis was the first approved ex vivo gene therapy product in Europe.

Jeans for Genes Day helped fund some of the earliest work using this type of gene therapy at Great Ormond Street Hospital in 2002, when Rhys Evans, a little boy with SCID, became one of the first children worldwide to be treated by gene therapy.

Jeans for Genes Day aims to raise money for children with life-altering genetic disorders by asking people to donate money for wearing jeans to work, school or wherever they like, on any day between September 16-20. Visit jeansforgenesday.org.

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Five benefits of gene therapies - Echo Live

Reprogramming the Human Computer: Silicon Valley Meets Cell and Gene Therapy – BioBuzz

How will Cell and Gene Therapy Usher in a New Industrial Revolution?

Cell and gene therapy companies are on the verge of transforming how we treat unmet medical needs such as cancer, rare diseases, genetic disorders and diabetes, to name only a few. By using a patients own cells and genes to fight disease, cell and gene therapy treatments deliver highly-targeted therapies and cures for unserved and underserved patients in need of solutions to a wide variety of intractable diseases.

What was once relegated to science fictionlike the miniaturized heroes sent into a human body in the Fantastic Voyage sci-fi movie of 1966has, to a large degree, become reality with modified cells being put into patients to act as virtual bots capable of clearing diseaseseven cancersfrom the body. New technologies are empowering science to do what would never have been thought possible years ago.

Understanding the complexities of how these novel personalized medicines actually work can be daunting and confusing for many people, especially for the patients who are in need of these new medicines and those who are non-scientific minded.

Jeff Galvin, CEO of American Gene Technologies (AGT), has helped a wide variety of audiences understand this new technology by explaining the similarities between the human cell and an organic computer. He explains that DNA is the operating system of the human cell. It contains commands for the cellular machinery called genes, which are coded in four symbols: A, G, T, and C (for the nucleotides adenine, guanine, thymine, and cytosine). The order of these nucleotides determines the instruction that a gene provides to the machine just like the order of 1s and 0s in your personal computer or cell phone determine the commands to be executed by the device. Galvin coined this human computer analogy to describe the work that his company is doing and what is actually taking place with cell and gene therapies to make new solutions for formerly unaddressable human diseases.

Galvin describes gene and cell therapy as the software revolution for the next 100 years: reprogramming DNA in cells to improve health. Scientists have long understood that viruses infect cells and hijack them with new instructions (viral DNA) to cause disease. Over the last few decades, methods have been developed to crack open viruses, scoop out their bad instructions that make cells sick, and replace them with new good instructions that improve the operation of the cell. In a way, the gene and cell therapy industry is hijacking the hijacker, says Galvin. We are taking viruses and converting them to updates to fix bugs or improve the operating system (DNA) of human cells. Just like viruses and updates on your computer work. The possibilities are endless. We can use these updates to repair a broken gene that is the root cause of a disease, insert new instructions into cells to improve their operation allowing them to do their jobs better, clear or protect the body from disease, or even change the operation of cells to make them little bots that can carry out functions that they would not normally do in your body, like clearing cancer. All of these things are within the scope of reprogramming the human computer.

American Gene Technologies (AGT), a biotech company located in Rockville, Maryland, is a company where Silicon Valley tech innovation and the human computer mindset is converging to rethink the approach to developing medicine.

AGTs CEO Jeff Galvin has shared that he and other cell and gene therapy leaders are on a mission to reprogram the human computer to save lives and improve outcomes for patients fighting infectious diseases, monogenic disorders, cancer and other devastating illnesses.

A serial tech innovator, Galvin made his mark as a Silicon Valley entrepreneur. He retired in his early 40s in 2002. His retirement was short-lived. When Galvin discovered the groundbreaking viral vector work of the National Institute of Healths (NIH) Dr. Roscoe Brady, he exited retirement to do what he always does: Vigorously pursue what he loves.

Galvin leapt out of retirementin 2007 to start AGT, and to continue developing Bradys technology.

I was very lucky to meet Roscoe Brady. When he showed me viral vectors and I realized we now had the ability to modify DNA with viruses, I immediately felt that this is the future of pharmaceuticals, stated Galvin. I could see the inherent power in this approach and how viral vectors could bring opportunities to new biotech companies to cure diseases that were formerly untreatable or incurable.

Bradys commitment to solving diseases and improving lives was also infectious. Dr. Brady was retiring, and it looked like this brilliant work was going to be shelved. explains Galvin. I saw it as too valuable and potentially world-changing to ignore. Dr. Brady agreed to stay on as a scientific advisor and I founded AGT with the mission to find the most efficient, effective, and fastest ways to bring this cutting edge technology to patients in need.

A lot of what I imagined as a computer programmer and software/IT specialist coming from the West Coast is actually coming true for this technology. This vision has fortunately attracted a lot of great scientists to our company and they are doing all of the rocket science. The concept is correct: We can use viral vectors to hijack the viruses that have been hijacking our cells for 1.5 billion years, using the inherent ability of viruses to infect cells and carry malevolent genetic code to deliver benevolent code instead,. Galvin stated.

What I am witnessing in our part of this industry is that high tech has come to drug development. The capabilities of everything we are doing is doubling every yearits like the computer revolution; every year youre getting more power while the price of the technology is going down, so youre getting exponential growth in power and value, Galvin commented.

Our approach is a major shift from old-style drug development, which relies on the random generation of thousands or tens of thousands of molecules. And then you try to screen them down via a cell model that gives you the effect youre looking for. And generally after two years and $10 million of investment, you have a few (drug programs) you can test in a mouse, and then one in 19 get into the clinic, stated Galvin.

What were doing at AGT and in the cell and gene therapy field is just different. Gene and cell therapy is about directed development. You can create highly targeted drugs that hit a specific cellular pathway and you can even narrow that down using specific promoters or chimeric envelopes so you can direct that drug to a certain cell type or even to a certain disease indicator, stated Galvin. By narrowing the drug to the particular tissue or particular disease indicator you are sparing all the healthy tissue, which is the main reason drugs drop out of clinical development, the side effects. Gene and cell therapy largely avoids this issue.

We can test some of these in cell models at the bench, then in animal models and be able to get to a go-no-go decision after $100K in investment. We might be able to characterize it so well at the bench that the clinical development becomes highly predictable. This turned out to be true with our HIV therapy, stated Galvin.

Galvin believes that AGTs cell and gene therapy platform will help contributeas part of a wider cell and gene therapy revolutionto the eradication of the $2 to $4 trillion in palliative care treatment costs replaced with one-and-done cures. Viral-vector based drug development platforms like the one AGT deploys will help find new gene and cell therapy treatments and cures for the approximately 7,000 rare diseases that impact approximately one in ten people across the globe.

The future of drug development, in my mind, is that the toolset will keep evolving like computers and software. Software developers used creativity to leverage a limited toolset to create value in the market. At AGT, were thinking about correcting DNA to improve human health and mitigate disease. Everything about technology is playing in our favor. If you were in computers a while ago and you saw mainframes turn into mini-computers and then micro computers you would have said, Eventually we will have these things in our pocket and you would have been right. The same is now true about drug development, stated Galvin, Nearly anything will be possible in the future as this technology continues to exponentially improve. In this high-tech revolution of gene and cell therapy, if you can dream it, you will eventually be able to do it!

AGT is part of an evolving, growing and groundbreaking cell and gene therapy cluster thriving in the BioHealth Capital Region.

Maryland is at the epicenter of the gene and cell therapy technological explosion Its all about the resources. They are starting to hit a critical mass here, added Galvin.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

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Reprogramming the Human Computer: Silicon Valley Meets Cell and Gene Therapy - BioBuzz

FDA approves 2nd gene therapy cancer drug from Durham’s Precision Bio for clinical trial – WRAL Tech Wire

DURHAM Precision BioSciences, a genome-editing company based in Durham, has received authorization from the U.S. Food and Drug Administrationto advance its second genome-edited cancer therapy to clinical trials.

The FDA has accepted Precisions Investigational New Drug application for PBCAR20A to treat non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CCL), and small lymphocytic lymphoma (SSL).

Precisions technology is part of a new approach to fighting cancer using T cells a type of immune system cell that recognizes invading germs or cancer cells. T cells are engineered to carry a cancer bullet called a tumor-targetingchimericantigenreceptor (CAR). These engineered cells have the potential to save the lives of many patients unresponsive to traditional chemotherapy and radiation regimens.

Precision Biosciences

Autologous CAR T therapies currently on the market rely on patient-derived T cells, which are extracted and individually manufactured for each patient using that patients own cells. They require a complex and lengthy process.

Precisions allogeneic CAR T product candidates use T cells derived from qualified donors. The T cells are manufactured in large batches and are cryopreserved (safely preserved, intact, at extremely low temperatures) for shipment, storage and off-the-shelf use.

These allogeneic CAR T product candidates rely on Precisions ARCUS genome-editing platform to remove the T cell receptor to prevent graft versus host disease without the need for donor-patient matching. ARCUS editing also enables targeted insertion of the CAR gene into a single, specific location in the T cell genome for more controlled, consistent expression.

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The company said it will begin a Phase1/2a clinical trial later this year in non-Hodgkin lymphoma patients, including a subset of patients with a cancer called mantle cell lymphoma, for which Precision has received the FDAs Orphan Drug designation.

PBCAR20A is Precisions second off-the-shelf cell therapy. The company is also studying the precursor to PBCAR20A PBCAR0191 in adult patients who are not responding to other therapies. Technically, these are designated as patients with relapsed or refractory (R/R) NHL or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL).

Both of Precisions treatments use the companys ARCUS genome editing technology to produce CAR T cells derived from healthy donors, rather than relying on cancer patients own blood. The development of these allogeneic CAR Ts is designed to overcome the manufacturing limitations of traditional autologous CAR T therapies, to target a broader range of malignancies, and to increase the number of patients who can potentially benefit.

FDA clearance to begin clinical trials with our anti-CD20 off-the-shelf therapy candidate is a significant milestone for Precision, said Matt Kane, the companys CEO and co-founder. Todays announcement demonstrates our ability to advance multiple product candidates in parallel into the clinic, leveraging the unique capabilities of our ARCUS genome editing platform, CAR T development approach and highly differentiated manufacturing process developed in-house.

Precision uses ARCUS to remove T cell receptors to prevent graft versus host disease, thus avoiding the need for donor-patient matching that is required in traditional tissue donation procedures. And the ARCUS technology also provides for the targeted insertion of the CAR gene into a single, specific location in the T cell genome for controlled, consistent expression. Precisions product candidates can be made in advance, manufactured in large batches and then cryopreserved for shipment, storage and off-the-shelf use.

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PBCAR20A, if approved, will fill an important gap in current cancer treatments. In the United States, B-cell malignancies account for 85 percent of all non-Hodgkin lymphoma. And CLL and SLL represent 25 to 30 percent of leukemia cases. Precision said that, while front-line treatments benefit more than half of newly diagnosed NHL patients, at least a third of those achieve only partial remission or relapse after remission.And patients with CLL have limited success with autologous CAR T therapies. An allogeneic CAR T like PBCAR20A may overcome treatment resistance and offer the possibility of combination treatments.

It is our hope that PBCAR20A will provide a new allogeneic CAR T therapy option with the benefits of reliable, off-the-shelf access and optimized cellular activity to patients living with NHL or CLL/SLL, where a significant need for new treatment options remains, said David Thomson, Precisions chief development officer.

Precision Biosciences is a 2006 Duke University spin-out dedicated to improving life by using its ARCUS gene editing technology to treat human diseases and create healthy and sustainable food and agriculture solutions.

In 2018 the company created a new name and brand identity for its food and agriculture business,Elo Life Systems. The business is using Precisions ARCUS platform and other new technologies for applications in crop improvement, animal genetics, industrial biotechnology and sustainable agriculture.

(C) N.C. Biotech Center

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FDA approves 2nd gene therapy cancer drug from Durham's Precision Bio for clinical trial - WRAL Tech Wire

7-Year-Old Receives New FDA-Approved Retina Gene Therapy – University of Michigan Health System News

Kari Branham, M.S., a genetic counselor at Kellogg, worked with Zions family to help them understand the genetic basis for Zions condition.

SEE ALSO: Retinitis Pigmentosa in Children: 5 Facts Families Should Know

We have seen such amazing progress with these conditions over the last 15-20 years,says Branham. We used to tell patients and their families that we would have to wait and see what happens, but now we can actually do something to help.

By going through the gene therapy process, Branham says the team is hopeful that this has changed Zions prognosis.

The treatment is designed to stop or slow the death of specialized cells in the retina, called photoreceptors, that send visual information to the brain.

Patients who have Leber congenital amaurosis have night blindness, says Besirli. One of the first treatment effects after receiving Luxturna is that (patients) are telling us that they function much better in dark.

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They can play outside much longer, they can navigate around the house and dont need nightlights anymore and can participate in indoor sports. Thats been a huge change in their lives.

Seven months after treatment, Zion, now age 7, and his family are back to their normal routine in Montrose, Mich., and monitor his progress during follow-up appointments at Kellogg.

Zion says hes looking forward to playing football and, with improved vision -- playing outside at night with his brothers.

We hope that with Zion we have changed the trajectory for him to the point that in his 20s he wont have significant vision loss we see with him now, says Branham.


7-Year-Old Receives New FDA-Approved Retina Gene Therapy - University of Michigan Health System News