Category Archives: Genetic Therapy

Xconomy Texas

San Antonio Most diabetes treatments work by giving the body the insulin it needs to break down sugar. But that approach deals with the symptoms of diabetes. In recent years, scientists and companies have taken aim at the root cause of the condition by attempting to stimulate or replace the cells in the pancreas responsible for producing insulin in the first place. One of them is a San Antonio researcher hoping to use gene therapya potentially one-time, long lasting treatmentto do the trick.

When cells in the pancreas, known as beta cells, either get destroyed by the immune system or stop producing enough insulin, the result is type 1 or type 2 diabetes. Companies large and small-from European diabetes drug giant Novo Nordisk to privately held startups ViaCyte, of San Diego, and Semma Therapeutics, of Cambridge, MAwant to engineer stem cells that develop into pancreatic beta cells to help a patient produce insulin.

Other researchers, such as Bruno Doiron, a scientist and assistant professor at the University of Texas Health Science Center at San Antonio, have different ideas. Doiron has developed an injectible treatment consisting of three molecules glucokinase, a second that targets a protein known as PTP1B, and a third that targets a protein called Pdx-1, a so-called transcription factor that regulates genesthat, when infused into the body, are meant to help stimulate the formation of new beta cells. Doiron has tried the method on mice, and based on some encouraging early results, intends to move the work forward through a startup company.

You have to prove you can translate that to a large animal model, he says.

The San Antonio company, Syner-III, got its name because of the synergistic use of three molecules to generate the beta cells, he says. Those molecules are administered via a gene therapy procedure: theyre stuffed into a modified virus and injected directly into the pancreas in a one-time treatment, where they are meant to stimulate beta cell production. The work was published in the peer-reviewed journal Current Pharmaceutical Biotechnology in 2016.

Doiron hopes to raise as much as $10 million to complete preclinical testing.

Others, including Novartis, are considering different ways of boosting beta cell production. Researchers from the Swiss company published findings in Nature Communications that showed a group of compounds called aminopyrazines could be packed into a pill and similarly lead to more beta cells, and more insulin, in mice. Such attempts are fraught with failure, however. In an article on its own website, Novartis notes that researchers have succeeded in producing beta cells in mice many times, but havent been able to reproduce those results in humans.

The potential payoff, however, is huge. Some 29.1 million Americans have diabetes, and 1.25 million of them have type 1 diabetes, according to the American Diabetes Association. Doiron believes the therapy may be able to help both types. While stem cell research has had its share of failures and competition continues to increase in insulin therapysuch as pumps that automatically deliver the treatmentDoiron says a gene therapy, if successful, could result in a longer-lasting, more effective treatment.

When I use your own body to produce medicine, that drastically changes the field, he says.

David Holley is Xconomy's national correspondent based in Austin, TX. You can reach him at dholley@xconomy.com

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With Gene Therapy for Diabetes, San Antonio Researcher Eyes Funding - Xconomy

After deals and acquisitions with Spark Therapeutics and Bamboo, Pfizer is once again looking to bolster its rare and gene therapy pipeline as it outlines a new drug pact with Sangamo.

The collaborationlicense agreement focuses on the development and eventual sale of the biotechs gene therapy programs for hemophilia A, including SB-525, one of Sangamos four lead product candidates.

This early candidate is slated to enter the clinic this quarter, centering on testing safety as well as blood levels of Factor VIII protein, and other efficacy endpoints.

Sangamo gets $70 million upfront from the Big Pharma, and could gain $475 million in biobucks and sales royalties on any medications from the collaborationthat gain approval.

Under the deal, Sangamo will take the lead on the SB-525 phase 1/2 test as well as unspecified manufacturing activities.

Pfizer, meanwhile, will be operationally and financially responsible for subsequent research, development, manufacturing and commercialization activities for the therapy, as well as any additional products, if any.

Sangamo will also work with Pfizer on manufacturing and technical ops using viral delivery vectors.

SB-525 works as a AAV vector carrying a Factor VIII gene construct driven by a synthetic, liver-specific promoter. The FDA has already cleared the start of human trials for SB-525, and given it an orphan drug tag.

The deal has proved powerful for Sangamo, with its shares jumping 44% after hours on the news last night.

This marks another step into the new world of gene therapies for Pfizer, coming less than a year after its $700 million buy of Bamboo Therapeutics, adding advanced recombinant adeno-associated virus (rAAV)-based gene therapies to its pipeline.

It also has a long-standing deal with Spark Therapeutics, in hemophilia, penned in 2014. Back in January, Pfizer in fact paid a $15 million milestone bonus to Spark for hitting its marks in the ongoing hemophilia B phase 1/2 trial FDA breakthrough-tagged SPK-9001.

Pfizer also has a series of preclinical gene therapies, including a neuromuscular candidate for Duchenne muscular dystrophy (DMD), as well as preclinical candidates to treat Friedreichs ataxia and Canavan disease, and a phase I candidate for giant axonal neuropathy.

Pfizer also gained an operating gene therapy manufacturing facility that Bamboo bought from the University of North Carolina last year.

The pharma also has several academic research agreements, including one with Kings College London to develop a series of rAAV gene therapy vectors and another with the University of Iowa Research Foundation to develop a potential gene therapy for cystic fibrosis.

And its partnered with Emeryville, CA-based Molecular Therapeutics (4DMT) to discover and develop targeted next-generation rAAV vectors for cardiac disease; it made an investment in the company a few years back.

Once seen as the next big thing in research, gene therapies have however come under pressure in recent months about just how viable they are on the market. After struggling for years to make a commercial success out of Glybera, the worlds first approved gene therapy, uniQure recently called it quits on the treatment.

The drugmaker said it wouldnt bother asking European authorities to renew the $1-million-plus gene therapys marketing authorization when it expires in October, and comes after it abandoned plans to gain an approval in the U.S. Reports from MIT Technology Review suggest only one patient ever used the med.

GlaxoSmithKline has also been struggling in Europe with its bubble boy syndrome gene therapy Strimvelis. Mindful of Glyberas cost, GSK put its price tag at half that of Glybera, at $665,000, and also offered a money-back guarantee.

Its been approved in Europe for nearly a year, but it only treated its first patient this month, according to Business Insider.

Treatment is tough as the drug is not so much manufactured as it is created for each individual patient, with a site in Italy currently the only approved site in the world for this type of manufacture, and thus the only place where patients can be treated. Only around 15 patients in Europe are believed to have the condition.

Other biotechs are however working on the manufacturing side in order to try and make these therapies more available for patients, and thus open up their viability.

There are already a number of medications on the market for hemophilia, such as from Biogen spin-off Bioverativ and Sobi, with gene therapy predicted by some also working in the space, including uniQure and BioMarin, to be the next class for treating the blood disorder.

But speaking to FierceBiotech at the start of the year, Bioverativs new chief and former Biogen exec John Cox told me that while they are to working on gene therapy approaches to hemophilia, there are reasons to be cautious: There are of course question marks over gene therapy: The obvious one is safety, because of the history here, and this is a risk-averse population, for good reason, and the other question is naturally over efficacy, and how long does it last, as well as manufacturing, scale and so on.

Were all hoping for a cure, and of course were doing work on gene therapy now, but I dont think people are looking at these now as a permanent cure; the questions are over durability, rather than cure.

He said that investors and even doctors talk a lot about gene therapy in the hemophilia space, but that if you talk to hemophilia A patients about what they really want, being able to dose, once a week [which is the target with its candidate, or even just less frequently, is what they want.

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Pfizer doubles down on gene therapy pipeline with $70M Sangamo buy-in - FierceBiotech

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Abeona Therapeutics Inc. (NASDAQ: ABEO), a leading clinical-stage biopharmaceutical company focused on developing novel gene therapies for life-threatening rare diseases, announced updated data from the ongoing gene therapy clinical trial for Sanfilippo syndrome Type A (MPS IIIA) at the American Society Gene and Cell Therapy (ASGCT) 20th Annual Meeting. The ongoing Phase 1/2 trial for ABO-102 (AAV-SGSH) is a first-in-man clinical trial utilizing a single intravenous injection of AAV gene therapy for subjects with Sanfilippo syndrome (MPS IIIA), a rare autosomal-recessive lysosomal storage disease.

Abeona continues to advance gene therapy for MPS IIIA patients and we are excited about the positive dose response in the CNS seen in Cohort 2. The observation of a dose response supports our clinical approach, and we are encouraged to observe further reductions in central nervous system (CNS) heparan sulfate, reduction in liver volume, and preliminary evidence of slowed neurocognitive decline, are very encouraging. We look forward to accelerating enrollment with the recently initiated global sites (Spain and Australia) and reporting additional clinical data in the ABO-102 global MPS IIIA trial later this year, stated Timothy J. Miller, Ph.D., President and CEO of Abeona Therapeutics.

Per the design of the clinical trial, subjects received a single, intravenous injection of ABO-102 to deliver the AAV viral vector systematically throughout the body to introduce a corrective copy of the gene that underlies the cause of the MPS IIIA disease. Subjects are evaluated at multiple time points post-injection for safety assessments and initial signals of biopotency and clinical activity, which suggest that ABO-102 successfully reached target tissues throughout the body, including the central nervous system. Highlights reported data on five (n=3 Cohort 1, n=2 Cohort 2) out of the six patients treated to date in the gene therapy trial included:

Biopotency: positive dose response observed in Cohort 2.--At 30 days post-injection, two patients in the Cohort 2 demonstrated 60.7%(+/- 8.8%) reduction in cerebral spinal fluid (CSF) heparan sulfate (HS).

Hepatosplenomegaly: consistent reduction in liver volume observed.--At 30 days post-injection, Cohort 2 subjects demonstrated reductions in liver volumes of 14.81% (+/- 1.2%).--The natural history study in 25 subjects with MPS III (Truxal et. al., 2016, Mol. Genet. Metab.) demonstrated that subjects had increased liver volumes averaging 116% at baseline that did not change over a year of follow-up.

Cognitive Assessments: evidence of cognitive stabilization at six months in Cohort 1. --Cognitive assessments, taken at baseline, at the six-month timepoint for the Cohort 1 (n=3), subjects showed evidence of stabilization or improvement in the Leiter-R non-verbal IQ and Vineland (adaptive behavior) scales.--Cognitive assessments are taken at six-month and twelve-month follow-up visits.--Leiter Nonverbal IQ assessments in Cohort 1 subjects demonstrated stabilized or improved scores at six-months post-injection. Notably, one subject improved +10 (+/-6) points, while age-matched controls in the Natural History study would have predicted a decrease of -11.1 (+/-2.7) points over 6 months.--Vineland assessments in Cohort 1 at six months post-injection suggest stabilization in adaptive behavior scores.

Safety: well-tolerated in all subjects through 1100 days cumulative post-injection.--No serious adverse events (SAEs) reported in subjects in either cohort receiving ABO-102 (Cohort 1: 5E12 vg/kg and Cohort 2: 1E13 vg/kg).

We remain encouraged by signs of tolerability and biological effects that we have observed in Cohort 1 and in the initial two subjects of Cohort 2, stated Kevin M. Flanigan, M.D., principal investigator, Director of the Center for Gene Therapy at Nationwide Childrens Hospital and Professor of Pediatrics and Neurology at The Ohio State University College of Medicine. We are pleased to see decreases in CSF HS compared to the Cohort 1 at 30 days post-injection, and we look forward to enrolling additional high-dose patients.

The ongoing Phase 1/2 clinical trial, which has received FastTrack designation, Orphan Product Designation, and Rare Pediatric Disease designation by the FDA, is designed to evaluate safety and efficacy of ABO-102 in patients with MPS IIIA. The global clinical study is supported by a 25-subject MPS III Natural History Study, which included potential efficacy assessments consisting of neurocognitive evaluations, biochemical assays and MRI data generated over one year of follow-up assessments.

Company Conference Call Details: Abeona will host a live conference call briefing today at 10:00am EDT. Analysts and investors can participate in the conference call by dialing 877-269-7756 for domestic callers and 201-689-7817 for international callers.

Sanfilippo syndromes (or mucopolysaccharidosis (MPS) type III): a group of four inherited genetic diseases each caused by a single gene defect, described as type A, B, C or D, which cause enzyme deficiencies that result in the abnormal accumulation of glycosaminoglycans (GAGs, or sugars) in body tissues. MPS III is a lysosomal storage disease, a group of rare inborn errors of metabolism resulting from deficiency in normal lysosomal function. The incidence of MPS III (all four types combined) is estimated to be 1 in 70,000 births. Mucopolysaccharides are long chains of sugar molecule used in the building of connective tissues in the body. There is a continuous process in the body of replacing used materials and breaking them down for disposal. Children with MPS III are missing an enzyme which is essential in breaking down the used mucopolysaccharides called heparan sulfate. The partially broken down mucopolysaccharides remain stored in cells in the body causing progressive damage. In MPS III, the predominant symptoms occur due to accumulation within the central nervous system (CNS), including the brain and spinal cord, resulting in cognitive decline, motor dysfunction, and eventual death. Importantly, there is no cure for MPS III and treatments are largely supportive care.

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Abeona Therapeutics (ABEO) Announces Updated Data from Gene ... - StreetInsider.com

A child in Europe has become the second individual ever to receive a commercial gene therapy, according to GlaxoSmithKline.

The treatment, called Strimvelis, can provide an outright cure for a rare inherited immune deficiency by revising a patients genetic makeup (see Gene Therapys First Out-and-Out Cure Is Here).

Gene therapy has been widely explored in experimental medical studies, but its commercial potential is largely untested

GlaxoSmithKline spokesperson Anna Padula said the company treated its first patient in March, nearly a year after Strimvelis was approved for sale in Europe in May 2016.

Gene therapies are more complex than ordinary pills, and the diseases they treat affect few people. But sky-high prices have raised questions about whether patients can access them. Strimvelis, used to treat an ultra-rare immune deficiency, has a list price of 594,000 euros, or $648,000, making it one of the most expensive drugs available (see Gene-Therapy Cure Has Money-Back Guarantee).

Strimvelis treats a rare disease called severe combined immunodeficiency due to adenosine deaminase deficiency, or ADA-SCID, which leaves babies without a fully functioning immune system and vulnerable to infections.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:A Year After Approval, Gene-Therapy Cure Gets Its First Customer

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Bubble boy hope: Strimvelis gene therapy revises genetic make-up, offers rare immune deficiency cure - Genetic Literacy Project

Rarefied Cures

This March, child with severe combined immune deficiency (SCID) became the second commercial gene therapy patient ever. The patientstarted receiving a drug called Strimvelis from GlaxoSmithKline a drug that appears to be able to cure the rare,inherited immune disorder SCID. The drug was approved for use in commercial gene therapy in May of 2016, but delays beset the process. Most of the delays according to MIT Technology Reviews report of comments from the Strimvelis project leader were the result ofdifficulties traversing national borders and arranging for reimbursement.

Gene therapies, which revise the genetic makeup of patients in an attempt to cure them, are far more complex and costly than traditional treatments. This is in part because they target rare diseases which, by nature, affect few people. Strimvelis, for example, has a list price of 594,000 euros($648,000) and very few people have SCID the disease it treats. Somewhere between40 to 100 are diagnosed with SCID each year in the U.S., and 15 in the EU. That being said, untreated children with the disease rarely live past the age of two.

The first gene therapy patient received the therapy called Glybera, which was subsequentlypulled from the market after that single treatment for lack of demand and impracticality of commercialization. Panned as the worlds most expensive medicine, Glybera cost $1 million. For this reason, many have been watching to see how Strimvelis fares commercially at market, hoping for more success than Glybera enjoyed. Theyre also waiting to see signs of failurewhich might be portents for other therapies.

According to GlaxoSmithKlines comments to MIT Technology Review, one of the reasons the delay was so significant in this first case had to do with the complexity of the treatment. Strimvelis is an ex vivo gene therapy, meaning that the bone marrow cells of the patient are repaired outside their bodies and then replaced. This complex process demands a specialized environment;the therapy is only available in Milanat present.Each country of the EU is responsible for making up for the costs of accessing the treatment under the EUs provisions for cross-border healthcare.

Moving forward, the real question is whether the next patients will be able to move faster; in other words, how much of the delay was due to instituting the process and how much was inevitable? The company is also working on being able to freeze patients cells, which would rendertravel unnecessary. Until then, if the delays remain as significant, the company may not be able to profit.

Gene therapyis here to stay, slow start or not. Last week Vivet Therapeutics, a gene therapy startup, was funded by Novartis, Roche, and others. It will soon begin its pursuit of gene therapy treatment of rare diseases. Likewise,Spark Therapeutics is on track to release its gene therapy treatment for blindness later this year. The goal for most biotech companies working in gene therapy has always been to move from rare diseases to more common ones, and as each step forward is taken, the industry gets a little closer to that goal. While more progress and speed with Strimvelis treatments will help gene therapy progress as a whole, failure for this treatment wont stop the rest of the industry.

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A New Gene Therapy Cure Just Treated Its First-Ever Patient - Futurism

Newly born European biotech Vivet Therapeutics has started life with 37.5 million ($41 million) and an executive team made up of Novartis, Sanofi and Gensight veterans, as the company looks to get to work on its gene therapies for a host of rare diseases.

Novartis Venture Fund and Columbus Venture Partners led the round, with Roche Venture Fund, HealthCap, Kurma Partners and Ysios Capital also taking part.

The cash boost will go toward early work on a group of rare and inherited metabolic diseases, including Wilson disease, progressive familial intrahepatic cholestasis types 2 and 3, and citrullinemia type I.

Vivet's lead gene therapy program, VTX801, is first targeting Wilson disease, a rare genetic disorder caused by a defective gene in liver cells encoding the ATP7B protein, which can lead to organ damage, neurologic symptoms and potentially death. Around 10,000 patients in the U.S. and 15,000 patients in the EU are estimated to have the disease.

The biotechs therapy uses a modified AAV vector to move a truncated functional version of the ATP7B gene into the liver cells carrying the defective gene, which should treat the underlying cause of the disease.

This is designed to restore copper metabolism, reduce liver damage and improve liver function, reversing the problems inherent in Wilsons. Human trials for the med in this setting are slated to start next year.

Vivets pipeline comes out of tech developed through its partnerships with, and exclusive licenses from, the Fundacin para la Investigacin Mdica Aplicada, a not-for-profit foundation at the Centro de Investigacin Medica Aplicada; the University of Navarra based in Pamplona, Spain; and Massachusetts Eye and Ear Infirmary in Boston.

Vivet Therapeutics was born last year in Paris, with a wholly owned subsidiary in Spain, and founded by Jens Kurth (formerly of Anokion and Novartis) as well as Jean Philippe Combal (who has served stints at Gensight Biologics and Sanofi).

Combal, its co-founder and CEO, said: Vivet is delighted to have attracted such a substantial investment from these high-profile life sciences investors. This fundraising reflects our shared excitement about the potential of our lead candidate VTX801 and our technology for generating further novel gene therapies targeting rare inherited metabolic diseases. Early results from preclinical studies with VTX801 are very promising, and we are now well funded to advance this candidate into the clinic, while developing our portfolio and technologies.

Florent Gros, MD at Novartis Venture Fund, said of its investment: We have searched extensively for next generation AAV technologies and clinical applications. We are very excited by Vivet Therapeutics clinical and commercial prospects; the company has outstanding management, assets and capabilities.

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Swiss majors Roche and Novartis back gene therapy upstart - FierceBiotech