StemCell Therapy

Decibel Therapeutics Receives FDA Clearance of IND Application for DB-OTO, a Gene Therapy Product Candidate Designed to Provide Hearing to Individuals with Otoferlin-Related Hearing Loss  GlobeNewswire

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Decibel Therapeutics Receives FDA Clearance of IND Application for DB-OTO, a Gene Therapy Product Candidate Designed to Provide Hearing to Individuals...

News Release

Thursday, September 8, 2022

Gene augmentation rescues cilia defects in light-sensing cells derived from patients with blinding disease.

Researchers from the National Eye Institute (NEI) have developed a gene therapy that rescues cilia defects in retinal cells affected by a type of Leber congenital amaurosis (LCA), a disease that causes blindness in early childhood. Using patient-derived retina organoids (also known as retinas-in-a-dish), the researchers discovered that a type of LCA caused by mutations in the NPHP5 (also called IQCB1) gene leads to severe defects in the primary cilium, a structure found in nearly all cells of the body. The findings not only shed light on the function of NPHP5 protein in the primary cilium, but also led to a potential treatment for this blinding condition. NEI is part of the National Institutes of Health.

Its so sad to see little kids going blind from early onset LCA. NPHP5 deficiency causes early blindness in its milder form, and in more severe forms, many patients also exhibit kidney disease along with retinal degeneration, said the studys lead investigator, Anand Swaroop, Ph.D., senior investigator at the NEI Neurobiology Neurodegeneration and Repair Laboratory. Weve designed a gene therapy approach that could help prevent blindness in children with this disease and one that, with additional research, could perhaps even help treat other effects of the disease.

LCA is a rare genetic disease that leads to degeneration of the light-sensing retina at the back of the eye. Defects in at least 25 different genes can cause LCA. While there is an available gene therapy treatment for one form of LCA, all other forms of the disease have no treatment. The type of LCA caused by mutations in NPHP5 is relatively rare. It causes blindness in all cases, and in many cases it can also lead to failure of the kidneys, a condition called Senior-Lken Syndrome.

Three post-doctoral fellows, Kamil Kruczek, Ph.D., Zepeng Qu, Ph.D., and Emily Welby, Ph.D., together with other members in the research team collected stem cell samples from two patients with NPHP5 deficiency at the NIH Clinical Center. These stem cell samples were used to generate retinal organoids, cultured tissue clusters that possess many of the structural and functional features of actual, native retina. Patient-derived retinal organoids are particularly valuable because they closely mimic the genotype and retinal disease presentation in actual patients and provide a human-like tissue environment for testing therapeutic interventions, including gene therapies. As in the patients, these retinal organoids showed defects in the photoreceptors, including loss of the portion of the photoreceptor called outer segments.

In a healthy retina, photoreceptor outer segments contain light-sensing molecules called opsins. When the outer segment is exposed to light, the photoreceptor initiates a nerve signal that travels to the brain and mediates vision. The photoreceptor outer segment is a special type of primary cilium, an ancient structure found in nearly all animal cells.

In a healthy eye, NPHP5 protein is believed to sit at a gate-like structure at the base of the primary cilium that helps filter proteins that enter the cilium. Previous studies in mice have shown that NPHP5 is involved in the cilium, but researchers dont yet know the exact role of NPHP5 in the photoreceptor cilium, nor is it clear exactly how mutations affect the proteins function.

In the present study, researchers found reduced levels of NPHP5 protein within the patient-derived retinal organoid cells, as well as reduced levels of another protein called CEP-290, which interacts with NPHP5 and forms the primary cilium gate. (Mutations in CEP-290 constitute the most common cause of LCA.) In addition, photoreceptor outer segments in the retinal organoids were completely missing and the opsin protein that should have been localized to the outer segments was instead found elsewhere in the photoreceptor cell body.

When the researchers introduced an adeno-associated viral (AAV) vector containing a functional version of NPHP5 as a gene therapy vehicle, the retinal organoids showed a significant restoration of opsin protein concentrated in the proper location in outer segments. The findings also suggest that functional NPHP5 may have stabilized the primary cilium gate.

The study was funded by the NEI Intramural program. Patient samples were collected at the NIH Clinical Center.

NEI leads the federal governments efforts to eliminate vision loss and improve quality of life through vision researchdriving innovation, fostering collaboration, expanding the vision workforce, and educating the public and key stakeholders. NEI supports basic and clinical science programs to develop sight-saving treatments and to broaden opportunities for people with vision impairment. For more information, visit https://www.nei.nih.gov.

About the NIH Clinical Center:The NIH Clinical Center is the worlds largest hospital entirely devoted to clinical research. It is a national resource that makes it possible to rapidly translate scientific observations and laboratory discoveries into new approaches for diagnosing, treating, and preventing disease. Over 1,600 clinical research studies are conducted at the NIH Clinical Center, including those focused on cancer, infectious diseases, blood disorders, heart disease, lung disease, alcoholism and drug abuse. For more information about the Clinical Center, visit:https://www.cc.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Kruczek K, Qu Z, Welby E, et al. In vitro modeling and rescue of ciliopathy associated with IQCB1/NPHP5 mutations using patient-derived cells. Stem Cell Reports. Sept 8, 2022.

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NIH researchers develop gene therapy for rare ciliopathy - National Institutes of Health (.gov)

Repeated muscle injections with Engensis (VM202), Helixmiths investigational non-viral gene therapy, were generally safe and well-tolerated in people with amyotrophic lateral sclerosis (ALS), according to top-line data from a Phase 2a clinical trial.

While the sample size was too small to determine the therapys efficacy, muscle biopsies were collected and will be examined to further evaluate the underlying mechanisms of Engensis.

These data suggest that high dose, repeated treatments of Engensis, were safe and well tolerated, providing a great deal of flexibility in designing dosing schemes for future clinical studies, Helixmith stated in a company press release.

Trial analysis will continue once the full dataset is available, and the company plans to present such findings at a future conference. The next steps for Engensis development will be determined at that time.

Engensis is a non-viral gene therapy that uses Helixmiths proprietary small circular DNA molecule to deliver the hepatocyte growth factor (HGF) gene to cells in the muscle environment.

HGF provides instructions to produce a protein of the same name that helps the body form new blood vessels, prevents muscle loss, and promotes the growth and survival of nerve cells. The therapyis delivered via intramuscular (into-the-muscle) injections.

Helixsmith believes that by increasing HGF production, Engensis has the potential to promote nerve cell and muscle regeneration, thereby countering the progressive loss of motor control that characterizes ALS.

The therapy has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration, both of which are intended to speed its clinical development and regulatory review.

A previous open-label Phase 1/2 trial (NCT02039401) found that four once-weekly intramuscular injections of Engensis (to a total dose of 64 mg) were safe and well-tolerated among 18 ALS patients. Signs that the therapy could slow disease progression were also observed.

These promising findings prompted the launch of a placebo-controlled Phase 2a trial, called REViVALS-1A (NCT04632225), which began patient enrollment last year. A total of 18 ALS patients experiencing motor symptoms in their limbs for four years or less were recruited at four sites in the U.S. and one in Korea.

Participants were randomized in a 2:1 ratio to receive three cycles of either Engensis or a placebo: at studys start, at two months, and at four months. Each cycle consisted of two days of injections to upper and lower limb target muscles, spaced two weeks apart (64 mg total of Engensis or a placebo).

This meant that Engensis-treated patients received a total of 192 mg of medication over the four-month period. All participants were monitored for six months from the studys start.

The trials main goal was to assess the safety and tolerability of Engensis, while efficacy measures were included as exploratory outcomes. These included changes in disability, muscle and lung function, survival, ALS-specific health-related quality of life, and the levels of muscle shrinkage biomarkers.

Top-line data showed that the investigational treatment was generally safe and well-tolerated, with no difference in the frequency of adverse events observed between the Engensis and placebo groups (83% for each).

One case of bronchitis a condition characterized by inflammation in the main airways of the lungs due to infection was observed in the Engensis group but was determined unrelated to treatment.

Injection site reactions were reported by 50% of Engensis-treated patients and 66.7% of those in the placebo group. Most of these reactions were mild or moderate in severity and temporary; no participant discontinued treatment due to the number of injections.

According to Helixmith, efficacy was unable to be evaluated due to the fact that four participants dropped out early from the small study.

Still, muscle tissue biopsies were obtained from injection sites to undergo analyses of muscle atrophy (shrinkage) biomarkers and others.

Since data on Engensis underlying mechanisms have been largely based on animal models, these results are expected to provide valuable information on the understanding of the mechanisms of actions of Engensis, and its effects on the [activity] of human genes, which will greatly help in the development of innovative medicines, the company stated in the release.

Helixmith greatly appreciates the generous and eager participation of the ALS patients, the company added.

Engensis is also being investigated across a range of conditions associated with deficits in circulation, and nerve and/or muscle damage, such as diabetic neuropathy, coronary artery disease, and Charcot-Marie-Tooth disease.

More than 500 patients have been treated with Engensis to date across 10 clinical trials and six different diseases, according to Helixmith. Data from these studies have also supported the therapys favorable safety profile and its ability to increase HGF production.

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Engensis Gene Therapy for ALS Found Safe in Small Phase 2a Trial |... - ALS News Today

DUBLIN--(BUSINESS WIRE)--The "Cancer Gene Therapy Market By Therapy, By End User: Global Opportunity Analysis and Industry Forecast, 2020-2030" report has been added to ResearchAndMarkets.com's offering.

Cancer Gene Therapy Market was valued at $1,389.42 million in 2020 and is estimated to reach $11,359.35 million by 2030, registering a CAGR of 23.3% from 2021 to 2030.

Cancer gene therapy is a technique used for the treatment of cancer where therapeutic DNA is being introduced into the gene of the patient with cancer. Owing to the high success rate during the preclinical and clinical trials, cancer gene therapy has gained popularity.

Many techniques are used for cancer gene therapy, for example, a procedure where the mutated gene is being replaced with a healthy gene or inactivation of the gene whose function is abnormal. Recently, a new technique has been developed, where new genes are introduced into the body to help fight against cancer cells.

The rise in the prevalence of cancer, the benefits of cancer gene therapy over conventional cancer therapies, and the advancement in this field are the major factors that drive the market growth.

In addition, the surge in government support, ethical acceptance of gene therapy for cancer treatment, and rise in biotechnological funding encouraging the R&D activities for cancer gene therapy and thus fuel the growth of the cancer gene therapy market.

In addition rise in awareness regarding cancer gene therapy is a major factor that drives the global cancer gene therapy market growth.

In addition, an increase in government support for research in gene therapy, ethical acceptance of gene therapy for cancer treatment, and a rise in the prevalence of cancer boost the growth of the cancer gene therapy market. However, the high cost associated with the treatment and unwanted immune responses is expected to restrain the market growth.

Key Benefits For Stakeholders

Key Market Segments

By Therapy

By End User

By Region

Key Market Players

Key findings of the Study

Key Topics Covered:

CHAPTER 1: INTRODUCTION

CHAPTER 2: EXECUTIVE SUMMARY

CHAPTER 3: MARKET OVERVIEW

CHAPTER 4: CANCER GENE THERAPY MARKET, BY THERAPY

CHAPTER 5: CANCER GENE THERAPY MARKET, BY END USER

CHAPTER 6: CANCER GENE THERAPY MARKET, BY REGION

CHAPTER 7: COMPANY LANDSCAPE

CHAPTER 8: COMPANY PROFILES

For more information about this report visit https://www.researchandmarkets.com/r/ipoqor

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Global Cancer Gene Therapy Market Report 2022: Benefits of Gene Therapy Over Conventional Therapies Driving Adoption - ResearchAndMarkets.com -...

Hopes run high in Philadelphia that the region the scientific home of two of the first cell and gene therapies approved by the FDA will remain a major player as the cutting-edge treatments assume a bigger role in medicine.

To make that happen, Philadelphias life sciences industry will need not just scientists, management, and money, but also skilled workers to help laboratories run smoothly at an ever-growing number of biotech companies in the region and eventually to manufacture cures and treatments for rare diseases and elusive types of cancer.

To help build that skilled workforce, the Wistar Institute, the University City Districts West Philadelphia Skills Initiative, and partners have launched a new biomedical technician training program.

It will enroll 18 students in a 12-week paid training program at Wistar, potentially followed by an additional 10 weeks of hands-on work at Iovance Biotherapeutics Inc. in the Navy Yard and then a $23-an-hour manufacturing job. Iovance, which now employs 150 people in Philadelphia, is developing cancer treatments using cell therapy.

Iovance did not say how many of the trainees it would hire. Iovance officials will interview them after they complete the Wistar part of the training.

We expect to have a number of opportunities to which program participants can apply, Tracy Winton, Iovances senior vice president for human resources, said in a statement.

Cell and gene therapies are still in the early stages of development, but Philadelphia scientists have long played a central part. Luxturna, a gene therapy cure for a rare form of congenital blindness, and Kymriah, a cell therapy treatment for some forms of leukemia, are based on the work of Philadelphia scientists. Both received FDA approval in 2017.

Cell therapy uses modified cells to carry treatment into the body. Gene therapy involves the replacement of defective genes that cause what are typically rare diseases.

The new training effort, scheduled to start Sept. 22, builds on one started in 2000 at Wistar, a nonprofit biomedical research institute in University City, in partnership with Community College of Philadelphia. The original Wistar program, which provided general preparation for work in biotech and until this year was spread over two summers for each cohort, has graduated 196 students.

Recruitment for the new program, which Wistar designed to specifically prepare individuals for jobs at Iovance, started Aug. 23 and runs through Friday. As of last Friday morning, 263 people had applied, according to the West Philadelphia Skills Initiative (WPSI), which for a decade has been training Philadelphians for specific jobs at individual employers, such as Childrens Hospital of Philadelphia and SEPTA.

WPSI is handling recruitment selection for the Iovance training. The selection process for the 18 open spots includes an assessment of mathematical ability and an interview, said Cait Garozzo, managing director of WPSI.

Some folks, obviously, are very desperate for a job, any job, and were not trying to connect people that just want any job to this opportunity. Were trying to connect people that want a career in this industry to this opportunity, Garozzo said.

This is the first time WPSI and Wistar have worked together. Other supporters are the Chamber of Commerce of Philadelphia and the Philadelphia Industrial Development Corp.

If this is successful, we really think this could be a game changer for this region, said Kristy Shuda McGuire, dean for biomedical studies at Wistar. We think this is something we could repeat. We could have more cohorts each year if there are single employers who are interested in this and have a lab-based position and would be interested in taking a whole cohort.

The total budget for the training program was not disclosed.

Wistars original training program which expanded this year to include Montgomery County Community College and will be open to students at Bucks County Community College and Camden County College next year typically sends graduates into biotech jobs or on to further education, McGuire said.

Among the graduates of the Wistar program that have gone on to build careers in life sciences is Lois Tovinsky, 36, who completed the program in 2013 and is now laboratory operations manager for Chimeron Bio, a biotech start-up in the Curtis Building that is working on RNA therapeutics against cancer.

Tovinsky graduated from college with a degree in political science in 2008, when the economy collapsed and jobs were hard to find. She heard about the Wistar program in a science class at Community College of Philadelphia and saw it as a chance to fulfill her interest in science and leap from her job as a dog walker into a science career.

I came to the program with no practical skills in the lab, and my knowledge of science was really just the few courses I had taken and my own interest and enthusiasm that I had for it, said Tovinsky, who now mentors students in the Wistar program.

Tylier Driscoll, 21, a biology major at Community College of Philadelphia, was one of 15 students in the Wistar training cohort that finished early last month.

I definitely wanted to do something over the summer that wasnt working at Aldi, Driscoll said. Before this, I hadnt had any lab experience and I really wanted to get a feel for what it was like to work in a lab. I was working at a supermarket at the time. This is the perfect opportunity for me to get into my field.

As part of his training, he spent five weeks working at BioAnalysis LLC, a contract research organization in Kensington that performs quality analysis on the viruses used in gene therapy.

Now, Driscoll has a part-time job at BioAnalysis that he starts Tuesday, the same day he goes back to CCP for the fall semester. He plans to finish his associate degree in the spring and then attend either Drexel University or Temple University for his bachelors degree.

Lake Paul, the president and founder of BioAnalysis, which he called a minority-owned biotech, said the Wistar program is an awesome opportunity and one that reminds him of his own experience. Paul said he grew up in the hood in Miami and wouldnt have obtained his doctorate at Purdue University without the Upward Bound programs that helped him pursue education.

It is a wonderful, exciting, and unique opportunity for these students, both underrepresented folks and regular folks. And to give them actual training like this is unparalleled, said Paul.

The Philadelphia Inquirer is one of more than 20 news organizations producing Broke in Philly, a collaborative reporting project on solutions to poverty and the citys push toward economic justice. See all of our reporting at brokeinphilly.org.

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As Philly becomes a hub for life sciences, a new program will train workers for jobs in the field - The Philadelphia Inquirer

ALDERLEY PARK, England--(BUSINESS WIRE)--Charles River Laboratories International, Inc. (NYSE: CRL) and Cure AP-4, a non-profit foundation dedicated to raising funds and awareness about Adapter-Protein 4 Hereditary Spastic Paraplegia (AP-4 HSP), today announced a manufacturing collaboration. Charles River, a contract research and development manufacturing organization (CRO/CDMO), will provide High Quality (HQ) plasmid DNA for Cure AP-4s Phase I/II gene therapy trials against AP-4 HSP.

Founded in 2016 by the families of two newly diagnosed AP-4 HSP (SPG47) patients, Molly Duffy and Robbie Edwards, Cure AP-4s gene therapy treatment will look to address the root cause of AP-4 HSP, a rare neurodegenerative disorder, and is intended as a one-time, curative treatment for the patient.

What is AP-4 HSP? AP-4 HSP, also known as AP-4 Deficiency Syndrome, includes four sub-types of HSP: SPG47, SPG50, SPG51 and SPG52. Each of these HSP sub-types is associated with a defective autosomal recessive gene which causes a failure in the AP-4 Adaptor Complex. The phenotype and prognosis for each sub-type is extremely similar. Patients afflicted with any of the AP-4 HSP genetic disorders generally present with symptoms including global developmental delay, microcephaly, seizures, brain malformation, and hypotonia (low-muscle tone). The few patients who learn to walk independently tend to lose that ability a few months or few years later as they develop hypertonia (high-muscle tone) and muscle spasticity. Of the 249 currently confirmed global AP-4 HSP cases, most patients experience mobility in some or all extremities as the disorder progresses and are severely intellectually challenged.

Plasmid DNA Manufacturing ServicesThe collaboration will leverage Charles Rivers market leading expertise in plasmid DNA production, specifically HQ plasmid, which combines key features of GMP manufacture with rapid turnaround times to accelerate the timeline to clinic. DNA plasmids are a critical starting material for many cell and gene therapy therapeutics and demand continues to outstrip supply. In response to this, Charles River recently announced the opening of a state-of-the-art HQ plasmid manufacturing center of excellence to address these supply shortages and support the growing needs of the cell and gene therapy field.

Charles River, with the acquisitions of Cognate BioServices, Cobra Biologics, and Vigene Biosciences in 2021, has extended its comprehensive cell and gene therapy portfolio to include CDMO capabilities spanning viral vector, plasmid DNA and cellular therapy production for clinical through to commercial supply.

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About Cure AP-4Cure AP-4, originally known as Cure SPG47, was founded in 2016 by the families of two newly diagnosed SPG47 patients, Molly Duffy and Robbie Edwards. At the time there were only nine other documented cases worldwide, and due to the extreme rarity of the disorder there are no known treatments or cures.

About Charles RiverCharles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them. To learn more about our unique portfolio and breadth of services, visit http://www.criver.com.

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Charles River and Cure AP-4 Announce Gene Therapy Manufacturing Collaboration - Business Wire

WAKEFIELD, Mass.--(BUSINESS WIRE)--Myrtelle Inc., (Myrtelle or the Company), a clinical stage gene therapy company focused on developing transformative treatments for neurodegenerative diseases, today announced that the European Medicines Agency (EMA) has classified the Company's lead gene therapy product candidate, rAAV-Olig001-ASPA for the treatment of Canavan disease, as an Advanced Therapy Medicinal Product (ATMP), specifically a Gene Therapy Medicinal Product (GTMP). ATMP classification, which is determined by the Committee for Advanced Therapies (CAT), was established to regulate cell and gene therapy and tissue engineered medicinal products, support development of these products, and provide a benchmark for the level of quality compliance for pharmaceutical practices. As a designated GTMP product, rAAV-Olig001-ASPA will follow the Centralized Procedure through the EMA and benefit from a single evaluation and authorization process. Additional benefits established through the ATMP regulation include pathways for Scientific Advice and significant fee reductions for such advice.

rAAV-Olig001 is a novel vector from a class of recombinant AAVs (rAAVs) that selectively target oligodendrocytes the cells in the brain responsible for producing myelin, the insulating material that enables proper function of neurons and makes up the brains white matter. The Companys lead program is in Phase 1/2 clinical development for Canavan disease (CD) a fatal childhood genetic disorder characterized by the degeneration of the white matter in the brain. The production of myelin is affected in CD due to a mutation in the Aspartoacylase gene (ASPA) leading to deficiency in Aspartoacylase enzyme (ASPA). The oligodendrocyte-targeted gene therapy using the rAAV-Olig001 vector is intended to restore ASPA function, thus enabling metabolism of N-Acetylaspartic Acid (NAA), a neurochemical abundant in the brain, and supporting myelination. Myrtelle entered into an exclusive worldwide licensing agreement with Pfizer Inc. in 2021 to develop and commercialize this novel gene therapy for the treatment of CD.

In addition to ATMP classification, rAAV-Olig001-ASPA has been granted US Orphan Drug, Rare Pediatric Disease, and Fast Track designations by the FDA which support the Companys mission to provide treatments for patients with CD. "The designation by the EMA of rAAV-Olig001-ASPA as a Gene Therapy Medicinal Product as a potential treatment for patients with Canavan disease provides important benefits in the development of this innovative therapy. The ATMP classification will facilitate discussions with the EMA as part of our strategy to seek product registration in the EU," said Nancy Barone Kribbs, PhD, Senior Vice President of Global Regulatory Affairs at Myrtelle.

ABOUT MYRTELLE

Myrtelle Inc. is a gene therapy company focused on developing transformative treatments for neurodegenerative diseases. The company has a proprietary platform, intellectual property, and portfolio of programs and technologies supporting innovative gene therapy approaches for neurodegenerative diseases. Myrtelle has an exclusive worldwide licensing agreement with Pfizer for its lead program in Canavan disease. For more information, please visit the Companys website at: http://www.myrtellegtx.com.

ABOUT CANAVAN DISEASE

Canavan disease (CD) is a fatal childhood genetic brain disease in which mutations in the Aspartoacylase gene (ASPA) prevent the normal expression of Aspartoacylase (ASPA), a critical enzyme produced in oligodendrocytes that breaks down the neurochemical N-Acetylaspartate (NAA). When not properly metabolized by oligodendrocytes, NAA accumulates in the brain and negatively affects bioenergetics, myelin production, and brain health. CD patients are impacted at birth but may appear normal until several months old when symptoms begin to develop. Poor head control, abnormally large head size, difficulty in eye tracking, excessive irritability, severely diminished muscle tone, and delays in reaching motor milestones, such as rolling, sitting, and walking, are the typical initial manifestations of CD. As the disease progresses, seizures, spasticity, difficulties in swallowing, and overall muscle deterioration emerge with most affected children developing life-threatening complications by approximately 10 years of age. Currently, there are no cures for CD and only palliative treatments are available. More information on Myrtelles clinical study in Canavan disease can be found on https://clinicaltrials.gov/ under the identifier NCT04833907 or by emailing PatientAdvocacy@MyrtelleGTX.com.

Forward-Looking Statements

This press release contains forward-looking statements. Words such as may, believe, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements are based upon current estimates and assumptions and include statements regarding rAAV-Olig001-ASPA as a potential treatment for patients with Canavan disease. While Myrtelle believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based in information available to us on the date of this release. These forward-looking statements are subject to various risks and uncertainties, many of which are difficult to predict, that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, Myrtelles program demonstrating safety and efficacy, as well as results that are consistent with prior results, the ability to generate the data needed for further development of this novel gene therapy in the patients with CD, and the ability to continue its trials and to complete them on time and achieve the desired results. All forward-looking statements are based on Myrtelles expectations and assumptions as of the date of this press release. Actual results may differ materially from these forward-looking statements. Except as required by law, Myrtelle expressly disclaims any responsibility to update any forward-looking statement contained herein, whether as a result of new information, future events or otherwise.

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Myrtelle's rAAV-Olig001-ASPA Gene Therapy Candidate for Canavan Disease Receives Advanced Therapy Medicinal Product Classification from the European...

Tegan Taylor: There are a few things in life that are just inevitable; death, taxes, the genes you're born with. At least, that has been the case for pretty much every generation up until now. Gene therapies have the potential to change the trajectory of disease, and I've been talking to two people on the frontline of that shift.

Until about three years ago, Robert Lamberth had a disease that was incurable. I mean, it was literally in his genes.

Robert Lamberth: Not as a newborn, but yes, very, very young when I had my first bleed. Three, I think it might have been for me, back in the early '80s it was, a long time ago now.

Tegan Taylor: When he was born, he inherited a certain recessive gene that stopped his body from producing one of the essential factors you need for your blood to clot.

Robert Lamberth: Bleeding internally into my major weight-bearing joints, so ankles and knees. And as I got older, I'd have more odd bleeding into muscles in my legs and parts of my stomach and those sorts of things, so it was a little bit more serious when you have large muscle bleeds. The pressure of the bleeding can affect your organs, so that's quite serious.

Tegan Taylor: Managing haemophilia A is miles easier than it was a couple of decades ago. When he was little, Robert needed intravenous injections of his missing clotting factor, given in a hospital. When he got older, he didn't need to go to hospital anymore. Regular injections of the clotting factor were a feature of his life all the way through into his 30s. But not anymore.

John Rasko: We dream of cures in gene therapy but hesitate to use the word

Tegan Taylor: For decades, John Rasko has been chasing ways to change people's fates.

John Rasko: For the last 20-plus years we've been doing clinical trials using viral vectors to transfer a gene into humans for a therapeutic purpose.

Tegan Taylor: Professor Rasko is a haematologist and pathologist who spent much of his career studying genes, stem cells and basically how to hack processes inside the human body. And he is one of many scientists around the world trying to figure out ways of swapping out disease-causing genes in a way that, in time, could be used for pretty much any genetic disease.

John Rasko: When we reflect on rare diseases, it's often worth remarking and reminding ourselves that rare diseases of course by definition are rare, usually less than one in 5,000 or 10,000 people, but collectively rare diseases are very common when you add them all up because there are many thousands of them, lead to a burden of disease such as the commonality of diabetes or even some forms of cancer. So the problem is that of all the rare diseases, which some people say are more than 4,000 affecting humans, 80% of those rare diseases have a genetic basis. And of those diseases, only 5% have a specific therapy. So this is an incredible unmet need in human health.

Tegan Taylor: And the solution he and his colleagues have come up with might sound a bit familiar. It works in a similar way to the Covid vaccine made by AstraZeneca. It uses a harmless virus to take a genetic message into the body.

John Rasko: And that vector system is used to then ferry that genetic payload intravenously to the liver where it takes up residence, and hopefully after a single injection, corrects that person's genetic abnormality for the rest of their life. It's unimaginable, but a single injection can alter the course of a genetic disease that would otherwise affect a person from birth to death.

Tegan Taylor: Robert was part of the clinical trial Professor Rasko was involved in, testing the gene therapy.

Robert Lamberth: It would be three years ago now in May 2019 when I had that one single dose of the good stuff, and then that clearly worked its magic and now I'm growing my own factor VIII. I've had one breakthrough bleed.

Gene therapy for me, Tegan, has been quite revolutionary, so from a position of having 0.5% of clotting factor in my blood, I'm now growing my own factor VIII in my liver and I'm at about 15% clotting factor, which is an extraordinary growth.

Tegan Taylor: In August, Europe granted conditional approval for a haemophilia A therapy like the one Robert received. It hasn't been approved in Australia yet, although we do use gene therapy for other conditions, like spinal muscular atrophy, and genetic causes of blindness.

John Rasko: We are only at the very start of this genetic revolution. There are thousands of genetic diseases that affect humans, and we've only just started scratching the surface of where we can go with these gene-based therapeutics.

Tegan Taylor: Because Robert got the gene therapy as an adult, he's still living with the damage haemophilia A had already done to his body, but that doesn't mean it hasn't been transformative.

Robert Lamberth: I can just do so much more. I can be out there doing everything that I love at work and at play and going to the gym, without fear of having a micro-bleed the next day and being cross and crotchety and painful and grumpy at work, and then it turning into a more major bleed and then having to go and seek therapy, which means even more down-time. The sooner that we could roll out some gene therapy for younger people would be great.

Tegan Taylor: Robert Lamberth, who received gene therapy for haemophilia A, finishing us off there. And we also heard from Professor John Rasko from Royal Prince Alfred Hospital and the Centenary Institute at the University of Sydney.

Norman Swan: It's interesting how things have advanced there, Tegan. A few years ago, not so long ago, gene therapy could have been quite toxic because of the virus that they were using to carry the gene in, and you've got to hit the target, it can't be wasteful, and sometimes the virus did harm in its own right. So it's taken a long time to get that right, but the potential, as John Rasko says, is huge and it goes from cancer through to these inborn errors that you get such as haemophilia A.

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The gene therapy that could transform the lives of millions - ABC News

IRVINE, Calif. & BASEL, Switzerland--(BUSINESS WIRE)--Urovant Sciences, a wholly owned subsidiary of Sumitovant Biopharma Ltd., receives coveted Best in Category award for an interim 12-week analysis from the ongoing Phase 2a trial of an investigational novel gene therapy product, URO-902 (plasmid human cDNA encoding maxi-K channel). The award-winning abstract was presented at the 2022 International Continence Society annual meeting on September 8, 2022. The 2022 ICS Annual meeting is being held September 7-10, 2022, in a hybrid format with both online and in person participation (Vienna, Austria).

According to ICS, this honor is awarded to the highest-scoring abstract in each category. Scores are awarded by the ICS scientific committee members, external reviewers, and scientific session chairs. Abstracts are judged based on criteria of scientific merit, originality/topicality, and clinical relevance. Review the full 2022 Abstract Awards List here.

The podium presentation at ICS 2022 took place on Thursday, September 8, at 10:20 Central European Time (CET). Presentation #6 in Scientific Podium Session S1, Best Urology, was titled, Efficacy and Safety of a Novel Gene Therapy (URO-902; PVAX/HSLO) in Female Patients with Overactive Bladder Syndrome and Urge Urinary Incontinence: Results from a Phase 2A Trial. The presentation described a prespecified, 12-week interim analysis of a 48-week multicenter, randomized, double-blind, placebo-controlled, dose-escalation study (NCT04211831). URO-902 was administered using direct intradetrusor injections via cystoscopy under local anesthesia. The presenting author was Kenneth Peters, M.D., Principal Investigator, and Chief of the Department of Urology at Beaumont Hospital, Royal Oak; Medical Director of the Beaumont Womens Urology and Pelvic Health Center; and Professor and Chair of Urology of the Oakland University William Beaumont School of Medicine in Rochester, Mich.

We are delighted that this presentation has received the Best in Category Prize: Overactive Bladder, reflecting the high-quality scientific research involved, said Dr. Peters. The promising interim safety and efficacy findings from this prespecified analysis indicate that URO-902 has potential as a therapeutic option for overactive bladder patients who have failed oral pharmacologic therapy.

At week 12, both URO-902 24 mg and 48 mg were associated with clinically relevant improvement in mean daily micturition (urination), urgency episodes, UUI episodes, OAB questionnaire symptom bother score, and proportion of patient global impression of change responders. Treatment-emergent adverse events occurred in 45.5% of patients receiving URO-902 24 mg, 46.2% receiving 48 mg, and 50.0% receiving placebo. The most commonly occurring adverse event was urinary tract infection (0% in individuals receiving the 24 mg dose of URO-902; 15.4% in those receiving the 48 mg dose; and 3.8% in those receiving placebo). One patient in the 48 mg arm of the study had asymptomatic elevated post-void residual urine volume at week 2; this resolved spontaneously and did not require catheterization.

URO-902 is a unique potential treatment for OAB. It brings together the accessibility of the anatomy of the condition with a new innovative approach to therapy, said Sef Kurstjens, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Urovant Sciences. Later this year, Urovant anticipates 48-week data from the Phase 2a trial, at that point, well have a greater sense of the durability of the therapy and our proposed next steps.

The data were first presented earlier this year at the 2022 annual meeting of the American Urological Association (AUA2022) in New Orleans, La., from May 13-16, 2022.

About Overactive Bladder

Overactive bladder (OAB) is a clinical condition that occurs when the bladder muscle contracts involuntarily. Symptoms may include urinary urgency (the sudden urge to urinate that is difficult to control), urgency incontinence (unintentional loss of urine immediately after an urgent need to urinate), frequent urination (usually eight or more times in 24 hours), and nocturia (waking up more than two times in the night to urinate).1

While 33 million US adults experience the bothersome symptoms of OAB, approximately 546 million people 20 years are affected by OAB worldwide. 1,2

About the Phase 2a Study of URO-902

The 48-week multicenter study was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single physician administered dose of URO-902, a novel gene therapy being developed for patients with OAB who have not been adequately managed with oral or transdermal pharmacologic therapy. URO-902 is administered via direct intradetrusor injections into the bladder wall under local anesthesia in patients who are experiencing OAB symptoms and urge urinary incontinence (UUI).

The Phase 2a trial enrolled 80 female patients in two cohorts: the first cohort received either a single administration of 24 mg of URO-902 or matching placebo, and the second cohort received 48 mg of URO-902 or matching placebo into the bladder wall. Multiple outcome measures were explored, including the effect on the number of micturitions, urgency episodes, and quality-of-life indicators compared to placebo, 12 weeks post-administration, as well as an assessment of the safety and tolerability of this potential new therapy. Patients were followed for up to 48 weeks after initial administration.

About URO-902

URO-902 (plasmid human cDNA encoding maxi-K channel) has the potential to be the first gene therapy for patients with OAB. If approved, this innovative treatment has the potential to address an unmet need for patients who have failed oral pharmacologic therapies.

References: 1. Irwin DE, Kopp ZS, Agatep B, Milsom I, Abrams P. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int. 2011;108(7):1132-1138. doi:10.1111/j.1464-410X.2010.09993.x

2. Leron E, Weintraub AY, Mastrolia SA, Schwarzman P. Overactive bladder syndrome: evaluation and management. Curr Urol. 2017;11:117-125. doi:10.1159/000447205

About Urovant Sciences

Urovant Sciences is a biopharmaceutical company focused on developing and commercializing innovative therapies for areas of unmet need, with a dedicated focus in Urology. The Companys second product candidate, URO-902, is a novel gene therapy being developed for patients with OAB who have failed oral pharmacologic therapy. Urovant Sciences, a wholly-owned subsidiary of Sumitovant Biopharma Ltd., intends to bring innovation to patients in need in urology and other areas of unmet need.

About Sumitovant Biopharma

Sumitovant is a technology-driven biopharmaceutical company accelerating development of new potential therapies for patients with high unmet medical need. Through our subsidiary portfolio and use of embedded computational technology platforms to generate business and scientific insights, Sumitovant has supported development of FDA-approved products and advanced a promising pipeline of early-through late-stage investigational assets for other serious conditions. Sumitovants subsidiary portfolio includes wholly-owned Enzyvant, Urovant, Spirovant, and Altavant, and one majority-owned subsidiary that is publicly listed: Myovant (NYSE: MYOV). Sumitomo Pharma is Sumitovants parent company. For more information, please visit http://www.sumitovant.com.

UROVANT, UROVANT SCIENCES, the UROVANT SCIENCES logo are trademarks of Urovant Sciences GmbH, registered in the U.S. and in other countries. All other trademarks are the property of their respective owners. 2022 Urovant Sciences. All rights reserved.

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Urovant Sciences Receives Best in Category Award for Abstract Highlighting Investigational Novel Gene Therapy, URO-902, Presented at 2022...

GRENOBLE, France--(BUSINESS WIRE)--Carroucell, the microcarrier supplier for cell culture in bioreactor, announced today that it has raised a total of 1.5 million. The funding includes the closing of a Series A financing, led by the Novalis Biotech Acceleration fund and with participation of Crdit Agricole des Savoie (CADS), as well as support from Bpifrance. The funding will be used to accelerate corporate growth through industrialization of the companys platform technology and ramping up of mass production processes to GMP standards.

Carroucell has developed a disruptive technological platform that offers unique flat shape microcarriers with a glass xenofree composition for cell culture in bioreactors. Unlike existing technologies, the combination of these novel microcarriers combined with the flexibility of the production process enables a faster, more optimized scale-up of the clinical phases. This more cost-effective process could provide customers with a more accelerated time and pathway to market.

For the first time, microcarrier customization and a more customer-oriented service are available for the development of the new applications into the cell culture and bioproduction market. There are many challenges with biomanufacturing performance. We believe our unique microcarrier technology and ability to address customer specific needs will overcome most challenges and stimulate a revolution in the sector moving forward, said Tarek Fathallah, Founder and President of Carroucell.

Carroucell is creating a new standard in biomanufacturing, which could help to facilitate patient access to many more innovations in cell and gene therapy in the future, said Jan Van den Berghe, co-founder and managing director of Novalis Biotech, who has also been appointed to the board of directors. When customers adopt Carroucell's technology platform, they are able to optimize the yield and the quality of the cell culture, solving the low-performance problem in bioproduction we see today.

The complex environment of cell culture in bioreactors and the increasing number of new applications requires an innovative approach to guarantee the balance of the system. Carroucells microcarrier plays the role of regulator of this system by ensuring its optimization, said Takis Breyiannis, CEO of Carroucell.

About Novalis BiotechNovalis Biotech (Ghent, Belgium) is an early-stage venture capital investor in technologies that revolutionize healthcare. The companys core competence lies in digitalization in the life sciences with a focus on bioinformatics, genomics and diagnostics. Novalis strongly believes in applying innovative enabling technology to advance the prevention, diagnosis, or treatment of a disease. For more information, please visit http://www.noval.is.

About CarroucellCarroucell is disrupting the biomanufacturing sector with its patented, innovative microcarrier and flexible process solution for customers. The microcarriers are based on a major innovation in the field of sol-gel process, which allows the production of bioactive microstructures not achievable by existing technologies. In the bioreactor, cells can cling and multiply in "3D" and allows cultivation of a large quantity of cells in a restricted volume. Carroucell has a partnership with Etablissement Franais du Sang (EFS), which enabled the validation of its microcarriers and facilitated first commercial orders. Carroucell was founded in 2016 by Tarek Fathallah. For more information, visit http://www.carroucell.com.

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Carroucell Raises 1.5 Million to Introduce Breakthrough Microcarriers and Customizable Processes to Cell and Gene Therapy Market - Business Wire

At 44, Janet Waterhouse should have been the picture of health; a former Division I soccer player, she taught yoga, enjoyed running, and didnt drink alcohol. Despite her healthy and active lifestyle, over a span of decades she experienced a number of unexplained symptoms.

Her symptoms continued to worsen into her 20s when she began to sporadically lose function of her hands and experience severe bouts of vertigo. Most doctors attributed her symptoms to stress and anxiety. During this time, Waterhouse was seeing a pain management specialist, who was concerned enough about her worsening symptoms to run a blood test, where he found irregularly shaped blood cells, called acanthocytes.

A series of serendipitous referrals led Waterhouse to Ali Hamedani, an assistant professor of neurology and ophthalmology in the Perelman School of Medicine. Based on her symptoms and exam, he suspected a genetic condition called chronic progressive external ophthalmoplegia (CPEO) and referred her to Laynie Dratch, a certified genetic counselor in the Penn Neurogenetics Therapy Center, for genetic testing.

In May of 2022, Dratch gave Waterhouse what she had been chasing for decades: a diagnosis. When the genetic counselor told me they found the genetic mutation they were looking for, I cried for a solid five minutes out of relief, Waterhouse says.

Waterhouses case of CPEO was found to be caused by a variation on her RRM2B gene, which affects the mitochondria in her cells. While the condition is very rare and can sometimes take years to locate and diagnose, Hamedanis hunch about the gene mutation led them right to it.

Because little is known about CPEO, treatment options are limited. Most people would be discouraged by the uncertainty, she says, but it thrills me to get to be the blueprint. I get to show people how to live with this.

Launched in March 2020, the Penn Neurogenetics Therapy Center has a team of clinicians, nurses, genetic counselors, and clinical research staff who are devoted to the care of patients with inherited neurological disorders and to participating in clinical trials of novel gene and molecular therapies.

The programs mission is twofold: first, they utilize the expertise of clinicians and researchers throughout the department of Neurology and across Penn Medicine to achieve a genetic diagnosis for as many patients like Waterhouse as possible, creating a database of eligible patients for new treatments and clinical trials. Second, they work to establish clinical trials using novel gene and molecular therapies for patients with genetically-based neurological disorders.

Our genetics counselors are some of the best in the country, and are incredibly effective at diagnosing patients and matching them with effective treatments and clinical trials, says Steven Scherer, a professor of neurology and director of the Neurogenetics Therapy Center. Now we can utilize this expertise to design tomorrows therapies.

Read more at Penn Medicine News.

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Solving medical mysteries with genetics: The Penn Neurogenetics Therapy Center | Penn Today - Penn Today

BEIJING, Sept. 08, 2022 (GLOBE NEWSWIRE) -- George Clinical, a global clinical research organization with an extensive presence throughout the Asia-Pacific region, continues to expand the organizations team in China with the addition of Helen Xu as Project Director and Cell Gene Therapy Head. She will be based in Beijing and joins a rapidly growing team responsible for expanding clinical research activity in China with biopharmaceutical, medical device and diagnostic sponsors.

Dr. Xu obtained her MD in clinical medicine from Peking University Health Center. She is a licensed physician specialized in central nervous system (CNS) and has worked in the hospital setting for four years. Dr. Xu entered the pharmaceutical industry in 2007 starting as a clinical research associate (CRA) and has since accumulated 15 years of valuable clinical research experience in China.

I am sure Helen will make an incredibly valuable contribution to the growth and development of clinical research operations and cell gene therapy studies across China, said Zhenfei Yin, country head and regional head project operations, China.

Before joining George Clinical, Dr. Xu had served GSK, BI, Wuxiapp, a Chinese clinical research organization, CASI, and Carsgen, a CAR-T biotech firm. Her clinical trial experience covers the whole development lifecycle starting from phase I through PMS, the majority of the trial experiences being with pivotal trials. Therapeutic areas of expertise include cell therapy, immunotherapies, blood tumors (MM, AML, thalassemia), solid tumors (lymphoma, gastric and pancreatic cancer, prostate cancer, lung cancer), respiratory disease (IPF, asthma), SSc-ILD, CNS (stroke, schizophrenia, GAD), HCV, cirrhosis, psoriasis, and in vitro diagnostics (IVDs) devices. Her responsibilities spanned the full duration of studies from bid defense, strategic planning, feasibility, and start-up to project close-out. The majority of these pivotal global trials experienced global audits and authority inspections from entities such as FDA, EMA, and NMPA.

Additional new team members will be joining the organization to support the team in China with medical expertise

With a growing presence across the country, it is an honor to be part of global CRO able to bring further clinical research to China that can positively impact cancer care around the world, Xu said.

About George Clinical

George Clinical is a leading global clinical research organization founded in Asia-Pacific driven by scientific expertise and operational excellence. With over 20 years of experience and more than 400 people managing 39 geographical locations throughout the Asia-Pacific region, USA, and Europe, George Clinical provides the full range of clinical trial services to biopharmaceutical, medical device, and diagnostic customers, for all trial phases, registration and post-marketing trials.

LinkedIn: https://www.linkedin.com/company/george-clinical-pty-ltd

Twitter: https://twitter.com/george_clinical

Facebook: https://www.facebook.com/georgeclinical

Wechat: https://mp.weixin.qq.com/.

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George Clinical Expands China Team with New Project Director and Cell Gene Therapy Head Helen Xu - AsiaOne

Mumbai: Nearly 14 months after the clinical trials of the indigenously developed CAR-T technology for blood cancer treatment was kicked off at the Tata Memorial Centre (TMC), researchers have concluded the first phase of trials and called the results encouraging.

This is the first time that gene therapy indigenously developed by researchers at the Indian Institute of Technology (IIT), Bombay, was tested on patients in India.

Phase I clinical trial data demonstrates that Indias first indigenously developed novel CAR-T Cell therapy is safe and shows promising early sign of efficacy in treating Lymphoma, a type of blood cancer, said a statement released by IIT B, late on Sunday evening.

In June 2020, the central governments National Biopharma Mission (NBM) -Biotechnology Industry Research Assistance Council (BIRAC) had approved 18.96 crore to the team for conducting a first-in-human phase-I/II clinical trial of the CAR-T cells. The drug has the potential to benefit cancer patients, who currently are forced to opt for only palliative care.

While existing treatments work towards increasing the life of patients by a few years or months, CAR-T technology holds the promise of curing certain types of cancers. Unlike chemotherapy, this drug is administered only once to a patient.

Dr Gaurav Narula, principal investigator of the paediatric-Acute Lymphocytic Leukemia (ALL), TMC and Dr Hasmukh Jain, principal investigator of the adult B-cell lymphoma study, started recruiting patients in early 2021. So far, six patients in pediatric-ALL and 10 patients in adult lymphoma studies were treated with indigenous HCAR19.

The trials were conducted at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), the research and development wing of TMC.

The participants received autologous HCAR19 therapy. None of the participants had immune effector cell-associated neurotoxicity syndrome. Three out of ten participants had a complete response post CAR-T cell therapy and none of the participants required ICU admission. There was no CAR-T treatment related death. Overall, the novel humanized HCAR19 tested in Phase I clinical trials for adult lymphoma was found to be safe and has shown promising early signs of activity, said Dr Hasmukh Jain, who presented the data in the Annual Symposium of Cell and Gene Therapy, CMC Vellore.

Chimeric Antigen Receptor T (CAR-T) cells are genetically engineered to produce an artificial T-cell receptor, which is widely used in developed nations for immunotherapy during treatment for cancer. As part of gene therapy, these cells are used with an intent to cure certain types of blood cancers. However, the technology is still unavailable in India.

IIT Bombay and Tata Memorial Hospital (TMH) started their R&D collaboration in 2015 to develop the novel CAR-T cell therapy platform for cancers and immune-disorders. Dr Rahul Purwar, Associate Professor, IIT Bombay (on-lien) and currently appointed as CEO of ImmunoACT, designed and developed the indigenous CAR-T platform and patented anti-CD19 CAR-T product (HCAR19). In early 2021, HCAR19 product entered into two Phase 1 clinical trials at TMH, Mumbai.

Dr Gaurav Narula will present the results of Phase I trial of paediatric B-ALL in the Asia Pacific Blood and Marrow Transplantation (APBMT) 2022 meeting soon. The clinical trials will now enter Phase-II, post approvals from the Central Drug Standard Control Organisation (CDSCO) and is expected to be available for commercial clinical usage in 2024.

Points for graphic:

IIT Bombay and Tata Memorial Hospital (TMH) started their R&D collaboration in 2015 to develop the novel CAR-T cell therapy platform for cancers and immune-disorders

This is the first time that gene therapy indigenously developed by researchers at the Indian Institute of Technology (IIT), Bombay, was tested on patients in India

CAR-T cells are genetically engineered to produce an artificial T-cell receptor, which is widely used in developed nations for immunotherapy during treatment for cancer

While existing treatments work towards increasing the life of patients by a few years or months, CAR-T technology holds the promise of curing certain types of cancers. Unlike chemotherapy, this drug is administered only once to a patient.

Shreya Bhandary is a Special Correspondent covering higher education for Hindustan Times, Mumbai. Her work revolves around finding loopholes in the current education system and highlighting the good and the bad in higher education institutes in and around Mumbai....view detail

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IIT-B-Tata hosp cancer therapy trials show promising results - Hindustan Times

This renewed international congress brings together around 800 experts in the field of Myology and neuromuscular diseases from all over the world (35 countries). More than 70 international speakers will take the floor during 18 plenary and parallel sessions and more than 400 scientific posters will be discussed during these four days.

Among these, 60 researchers and clinicians from the Institute of Myology, Centre of expertise on muscle and its diseases, will be there to highlight their work and last scientific results in the field of neuromuscular diseases. From fundamental research to therapeutic advances no less than 59 communications (6 oral presentations & 53 posters) will be presented by our neuromuscular scientific experts.

This congress is also the opportunity for Institute of Myology to present its complete environment and activities. From its Center of Research in Myology, its unique Neuromuscular Investigation Center (including 4 labs of excellence) and its clinical activities with two clinical trial platforms I-Motion - for neuromuscular patients and a dedicated clinical hospital unit, to its ambition to create a future Foundation of Myology, the Institute of Myology is the first Center of this kind for Muscle in its pathologies in France.

>> Tuesday, September 13th Motor neuron diseases (13 PM Parallel 1)

4.30 PM - Piera Smeriglio: The role of DNA epigenetics in modulating Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a motor neuron disorder caused by mutation in the SMN1 gene. In human, the presence of the SMN2 paralog can partially compensate for the SMN1 loss and the copy number of SMN2 inversely correlates to disease severity. We uncovered that DNA epigenetic regulation is altered in human and mouse SMA models, leading to abnormal profile of methylation and hydroxymethylation on the SMN2 gene and genome-wide. These defects promote the aberrant expression of SMN2 and of genes acting on the inflammatory response pathways, suggesting a direct epigenetics role in SMA pathogenesis.

5.20 PM - Giorgia Querin: Spinal cord MRI for early detection of presymptomatic pathology in C9orf72-mutation carriers: a longitudinal neuroimaging study

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) share genetic susceptibility and a large portion of familial cases are due to C9orf72 gene mutations. Brain and spinal cord (SC) imaging studies in asymptomatic C9orf72 carriers have demonstrated white (WM) and grey matter (GM) degeneration up to 20 years before the expected symptom onset.

Objective of this study is to longitudinally analyze cervical spinal degeneration in asymptomatic carriers of the C9Orf72 mutation using different multimodal MRI sequences with the aim of tracking longitudinal degeneration at the spinal level and of identifying possible prognostic factors of disease evolution.

>> Tuesday, September 13th Development, regeneration & ageing - part 3 (13 PM Parallel 2)

5.00 PM - Alfredo Lopez Kolkovsky: Preliminary results of a multiparametric quantitative NMR ageing study at rest and during exercise in the lower leg in healthy subjects between 20 and 65 years of age

The progressive decline in muscle strength and performance during ageing negatively affects the quality of life in elderly subjects and increases the risk of falls, disability and frailty. The age-related loss of muscle mass, strength and quality is a complex multifactorial process whose mechanisms are incompletely understood.

Nuclear magnetic resonance (NMR) allows evaluating anatomical, structural and physiological aspects of muscle tissue non-invasively in vivo. Functional NMR also enables, for instance, to image during an exercise paradigm the tissue blood flow (BF) or energy metabolism using P MR spectroscopy (MRS).

We designed a protocol where multiple quantitative and complementary measures were performed at rest and during a plantar flexion exercise in 26 subjects. Age-related changes were observed for muscle water T1 relaxation times and muscle fat fraction as well as cellular membrane turnover and mitochondrial stress biomarkers. This study demonstrates the interest of a multiparametric NMR approach in aging studies.

5.45 PM - Massire Traore: Therapeutic approach based on GDF5 to counteract age-related muscle wasting

Sarcopenia is a disease defined as progressive age-related loss of muscle strength, function and mass, which results in increased mortality. Several mechanisms have been proposed to explain the onset and progression of sarcopenia, however, some pathophysiological aspects are still not very well understood and no cure has been established to date.

Our previous work demonstrated that GDF5 (Growth Differentiation Factor 5) overexpression in old mouse prevented muscle mass decline, although a deeper report on the mechanisms and consequences of GDF5 implement on aged muscle was missing. Here, we demonstrate that GDF5 overexpression in muscle during aging induces muscle mass gain and improves neuromuscular connectivity and endplate morphology. In addition, we present the characterization of the cellular and molecular effects of GDF5 in muscle during aging and show its rejuvenating signature. Based on this proof of concept, we defined a cutting-edge therapeutic approach describing how the treatment with the recombinant GDF5 protein is able to counteract the age-related skeletal muscle wasting in mice and might have a strong curative potential on humans.

>> Wednesday, September 14th Myotonic syndromes (14 AM Parallel 1)

10.30 AM - Denis Furling: Decoy gene therapy for Myotonic Dystrophy

Myotonic Dystrophy type 1 (DM1), one of the most common neuromuscular disorders in adults, is characterized by progressive muscle weakness and wasting, myotonia, cardiac defects, endocrine troubles and cognitive impairments. This autosomal dominant disease is caused by an expanded tract of CTG repeats within the 3 non-coding region of the DMPK gene. Expression of mutant transcripts containing expanded CUG repeats (CUGexp) leads to a toxic RNA gain-of-function mechanism affecting functions of specific RNA binding proteins (RBPs) and consequently, RNA metabolism. To date, there is no cure for DM1 but several therapeutic strategies including small molecule and antisense oligonucleotide approaches are under development.

Here we assessed a gene therapy approach for DM1 using a modified RBP with a high affinity for CUGexp that aims at acting as a decoy and displaces sequestered endogenous MBNL proteins from

RNA foci to reverse RNA toxicity. For this purpose, we engineered a truncated MBNL1 protein that keeps its zing finger domains required for the binding to CUGexp but lacks the C-terminal domain involved in splicing activity and homodimerization. Our decoy has a reduced splicing activity but can still compete with MBNL1 for CUGexp-binding. Effect of this decoy was next assessed in both human DM1 muscle cells and HSA-LR mouse model. We showed that the binding of the decoy to CUGexp in DM1 muscle cells allows the release of sequestered endogenous MBNL1 from nuclear foci, restores MBNL1 activity and corrects the transcriptomic signature of DM1. In vivo, local or systemic delivery of the decoy into skeletal muscles of DM1 mice using AAV9 vectors leads to long-lasting correction, up to one year, of both splicing defects and myotonia, hallmarks of DM1. This proof-of-concept study (Arandel et al., Nature Biomedical Engineering, 2022) supports the development of decoy-RBPs with high binding affinities for CUGexp as a therapeutic strategy for DM1.

11.45 AM - Mona Bensalah: Muscle fibrosis: a vicious circle between human fibroadipogenic progenitors and muscle fibers

Fibrosis is described in many organs as an excessive accumulation of extracellular matrix (ECM) proteins that replace tissue and alter its function. In skeletal muscle, fibrosis is a pathological feature common to many dystrophies including Oculopharyngeal Muscular Dystrophy (OPMD), a late-onset disorder, where only a small group of muscles are primarily affected and characterized by an exacerbated fibrosis, fiber atrophy and inflammation. While the cellular and molecular mechanisms regulating muscle fibrosis has been extensively studied in mouse, our understanding of the exact nature and role of mesenchymal cells involved in fibrosisis limited in human and theirimplication in dystrophic muscle progression remains to be clarified.

We investigated the role and nature of nonmyogenic cells (fibro/adipogenic progenitors, FAPs) from human fibrotic muscles of healthy individuals and OPMD patients, and compared them to nonmyogenic cells from human nonfibrotic muscle. Our data underline the key role of FAPs and their cross-talk with muscle cells through a paracrine signaling pathway in fibrosis of human skeletal muscle, and identify endothelin as a new druggable target to counteract fibrosis.

Beside these six oral presentations, no less than 53 posters will be presented by researchers from the Institute of Myology during break sessions in Rhodes exhibition hall:

The Institute of Myology, a unique centre of expertise on muscle

The Institute of Myology was created in 1996 by AFM-Telethon to diagnose and treat patients, and to study diseased muscle, in partnership with five public bodies (the AP-HP, the CEA, Inserm, Sorbonne Universit and the CNRS). This centre of expertise is globally unique and promotes the existence and recognition of the field of myology by bringing together, in a single location, fundamental and applied research, clinical research, physiological assessment, care and teaching. Eight centres, bringing together 250 doctors and researchers, are dedicated to the muscle in all its states, from the national reference centre for the diagnosis, management and monitoring of neuromuscular diseases, to the research centre, a clinical research platform with innovative investigational and measurement tools, and a centre for training and dissemination of knowledge in the field of myology. The Institute is patient-centred and brings together diagnosis, clinical care, assessment and research.

http://www.institut-myologie.org/en

Press contact:

Stphanie Bardon presse@afm-telethon.fr Tel.: +33 (0)1 69 47 29 01

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7th International Congress of Myology Nice - EurekAlert

August 8, 2022

Delivering the protein EPS8 via gene therapy rescues malfunctioning inner ear hair cells that transduce sound

LA JOLLAScientists from the Salk Institute and the University of Sheffield co-led a study that shows promise for the development of gene therapies to repair hearing loss. In developed countries, roughly 80 percent of deafness cases that occur before a child learns to speak are due to genetic factors. One of these genetic components leads to the absence of the protein EPS8, which coincides with improper development of sensory hair cells in the inner ear. These cells normally have long hair-like structures, called stereocilia, that transduce sound into electrical signals that can be perceived by the brain. In the absence of EPS8, the stereocilia are too short to function, leading to deafness.

The teams findings, published in Molecular Therapy Methods & Clinical Development online on July 31, 2022, show that delivery of normal EPS8 can rescue stereocilia elongation and the function of auditory hair cells in the ears of mice affected by the loss of EPS8.

Our discovery shows that hair cell function can be restored in certain cells, says co-senior author Uri Manor, assistant research professor and director of the Waitt Advanced Biophotonics Core at Salk. I was born with severe to profound hearing loss and feel it would be a wonderful gift to be able to provide people with the option to have hearing.

The cochlea, a spiral tube structure in the inner ear, enables us to hear and distinguish different sound frequencies. Low-frequency regions of the cochlea have longer stereocilia while high-frequency regions have shorter stereocilia. When sound travels through the ear, fluid in the cochlea vibrates, causing the hair cell stereocilia to vibrate. These hair cells send signals to neurons, which pass on information about the sounds to the brain.

Manor previously discovered that the EPS8 protein is essential for normal hearing function because it regulates the length of hair cell stereocilia. Without EPS8, the hairs are very short. Concurrently, co-senior author Walter Marcotti, professor at the University of Sheffield, discovered that in the absence of EPS8 the hair cells also do not develop properly.

For this study, Manor and Marcotti joined forces to see if adding EPS8 to stereocilia hair cells could restore their function to ultimately improve hearing in mice. Using a virus to help deliver the protein to hair cells, the team introduced EPS8 into the inner ears of deaf mice who lacked EPS8. They then used detailed imaging to characterize and measure the hair cell stereocilia.

The team found that EPS8 increased the length of the stereocilia and restored hair cell function in low-frequency cells. They also found that after a certain age, the cells seemed to lose their ability to be rescued by this gene therapy.

EPS8 is a protein with many different functions, and we still have a lot more to uncover about it, says Manor. I am committed to continuing to study hearing loss and am optimistic that our work can help lead to gene therapies that restore hearing.

Future research will include looking at how well EPS8 gene therapy might work to restore hearing during different developmental stages, and whether it might be possible to lengthen the therapeutic window of opportunity.

Other authors on the study are Colbie Chinowsky, Tsung-Chang Sung and Yelena Dayn of Salk; Jing-Yi Jeng, Adam Carlton, Federico Ceriani and Stuart Johnson of the University of Sheffield; Richard Goodyear and Guy Richardson of the University of Sussex; and Steve Brown and Michael Bowl of the MRC Harwell Institute.

The research was supported by the Biotechnology and Biological Sciences Research Council (BB/S006257/1, BB/T016337/1), Waitt Foundation, Grohne Foundation, National Institutes of Health (CA014195, R21DC018237), National Science Foundation (NeuroNex Award 2014862), Chan-Zuckerberg Initiative (Imaging Scientist Award) and Dudley and Geoffrey Cox Charitable Trust.

DOI: 10.1016/j.omtm.2022.07.012

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Discovery advances the potential of gene therapy to restore hearing loss - Salk Institute

Published: Published Date - 09:21 PM, Wed - 10 August 22

Hyderabad: This concept may seem quite fictional and even futuristic. However, this is what geneticists worldwide through gene therapy are pursuing, while trying to find cure for a wide range of diseases that challenge modern medicine including cancers, heart diseases, diabetes, haemophilia, AIDS, genetic disorders, among others.

Gene therapy involves altering the genes inside the cells of the human body, in order to treat or prevent the disease progression. Essentially, geneticists worldwide are exploring ways to utilise gene therapy to alter genetic composition of cells that are responsible for causing diseases and in the process find a long term cure for diseases. The potential to unlock the cure for a wide range of diseases has become a major driving force for researchers and pharma giants worldwide to focus their energies and resources on gene therapy.

So what exactly is gene and gene therapy?

The Gene Therapy Advisory and Evaluation Committee (GTAEC), which monitors clinical trials across India on gene therapies, defines Gene is the most basic and functional unit of heredity and inheritance and consists of a specific sequence of nucleotides in DNA or RNA located on chromosomes that encodes for specific proteins. The human genome comprises more than 20,000 genes. Gene therapy refers to the process of introduction, removal or change in content of an individuals genetic material with the goal of treating the disease and a possibility of achieving long term cure.

The genetic material that has to be introduced to the diseased cell is done through a vector, whch is usually a virus. Viruses are the preferred vectors or vehicles as they are adaptable and efficient in delivering genetic material, the GTAEC, said.

While worldwide major pharmaceutical companies are developing gene therapies for treatment of single gene defects like haemophilia and muscular dystrophy, the Department of Biotechnology (DBT), Government of India, Tata Memorial Hospital, Mumbai and IIT-Mumbai have collaborated to start clinical trials of gene therapy on cancer in India.

Gene therapy in cancer:

In the last few years, CAR- (Chimeric Antigen Receptor) T therapy, a form of gene therapy has emerged as a breakthrough treatment for cancer, especially for leukemia, lymphoma (cancer of the lymphatic system) and multiple myeloma or the cancer of the plasma cells.

The CAR-T cells are genetically engineered in a laboratory and they bind with the cancer cells and kill them. The therapy is available in a few cancer research centres (on clinical trials basis) in US and cost of treatment ranges anywhere from Rs 3 crore to Rs. 4 crore.

To reduce treatment costs, promote and support development CAR-T cell technology against cancers, for the first time in India, Biotechnology Industry Research Assistance Council (BIRAC), established by DBT, Tata Memorial Hospital and IIT Bombay, have launched clincal trials of CAR-T gene therapy to treat cancers. The CAR-T cells were designed and manufactured at Bioscience and Bioengineering (BSBE) department of IIT Bombay. The gene therapy study on cancers is in early phase clinical trials at Tata Memorial in Mumbai.

Regulation of gene therapy:

Realising the potential of gene therapies in treating complex diseases, the GOI is providing financial and even technical guidance to researchers through ICMR, DBT and DST. To ensure gene therapies are introduced in India and clinical trials for gene therapies are performed in an ethical, scientific and safe manner, the ICMR has also framed National Guidelines for Gene Therapy Product Development and Clinical Trials document.

Original post:
Health and Tech: The promise of gene therapy to cure cancers - Telangana Today

DUBLIN--(BUSINESS WIRE)--The "Global Gene Therapy Market by Vectors (Non-viral(Oligonucleotides), Viral(Retroviral, Adeno-associated)), Indication (Cancer, Neurological, Hepatological Diseases, Duchenne Muscular Dystrophy), Delivery Method (In Vivo, Ex Vivo), and Region - Forecast to 2027" report has been added to ResearchAndMarkets.com's offering.

The global gene therapy market is valued at an estimated USD 7.3 billion in 2022 and is projected to reach USD 17.2 billion by 2027, at a CAGR of 18.6% during the forecast period. Factors such as rising cases of neurological diseases and cancer, growing gene therapy product approvals, and increasing investment in gene therapy related research and development drive the market growth. However, factors like high cost of gene therapy is restraining the growth of this market.

The cancer segment accounted for the highest growth rate in the gene therapy market, by indication, during the forecast period

In 2021, cancer segment accounted for the highest growth rate. Growing disease burden of cancer across the globe coupled with rising demand for gene therapies to treat cancer will augment the segmental growth of cancer over the forecast period.

Asia-Pacific: The fastest-growing region in the gene therapy market

The Asia-Pacific market is estimated to record the highest CAGR during the forecast period. The high growth rate of this market can be attributed to the improving healthcare expenditure in emerging economies, increasing product launches, and increasing incidence of cancer and neurological diseases.

Research Coverage

This report provides a detailed picture of the global gene therapy market. It aims at estimating the size and future growth potential of the market across different segments such as vectors, indication, delivery method, and region. The report also includes an in-depth competitive analysis of the key market players along with their company profiles recent developments and key market strategies.

List of Companies Profiled in the Report

Premium Insights

Market Dynamics

Drivers

Opportunities

Challenges

Key Topics Covered:

1 Introduction

2 Research Methodology

3 Executive Summary

4 Premium Insights

5 Market Overview

6 Gene Therapy Market, by Vector

7 Gene Therapy Market, by Indication

8 Gene Therapy Market, by Delivery Method

9 Gene Therapy Market, by Region

10 Competitive Landscape

11 Company Profiles

For more information about this report visit https://www.researchandmarkets.com/r/vhssny

See the article here:
Global Gene Therapy Market 2022-2027: High Incidence of Cancer & Other Targeted Diseases to Drive Growth - ResearchAndMarkets.com - Business Wire

DUBLIN, Aug. 8, 2022 /PRNewswire/ --The "Gene Therapy Market by Type of Therapy, Type of Gene Delivery Method Used, Type of Vector Used, Target Therapeutic Areas, Route of Administration, and Key Geographical Regions: Industry Trends and Global Forecasts, 2022-2035" report has been added to ResearchAndMarkets.com's offering.

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Gene Therapy Market (5th Edition) report features an extensive study of the current market landscape and the likely future potential associated with the gene therapy market, primarily focusing on gene augmentation-based therapies, oncolytic viral therapies, immunotherapies and gene editing therapies.

One of the key objectives of the report was to estimate the existing market size and the future opportunity associated with gene therapies, over the next decade. Based on multiple parameters, such as target patient population, likely adoption rates and expected pricing, we have provided informed estimates on the evolution of the market for the period 2022-2035.

Over the last two decades, there have been several breakthroughs related to the development of gene therapies. In 2020, LibmeldyT, an ex vivo gene therapy received approval for the treatment of metachromatic leukodystrophy. To provide more context, the treatment regimen of such therapies, encompassing gene replacement and gene-editing modalities, is aimed at correction of the mutated gene in patients using molecular carriers (viral and non-viral vectors).

Further, post the onset of the COVID-19 pandemic, there has been a steady increase in the investigational new drug (IND) applications filed for cell and gene therapies. In fact, in 2021, more than 200 gene therapies were being evaluated in phase II and III studies. Moreover, in 2022, six gene therapies are expected to receive the USFDA market approval. Promising results from ongoing clinical research initiatives have encouraged government and private firms to make investments to support therapy product development initiatives in this domain.

Story continues

In 2021 alone, gene therapy developers raised around USD 9.5 billion in capital investments. Taking into consideration the continuous progress in this domain, gene therapies are anticipated to be used for the treatment of 1.1 million patients suffering from a myriad of disease indications, by 2035.

Presently, more than 250 companies are engaged in the development of various early and late-stage gene therapies, worldwide. In recent years, there has been a significant increase in the integration of novel technologies, such as gene modification, gene-editing, genome sequencing and manipulation technologies (molecular switches), in conjugation with gene delivery methods.

For instance, the CRISPR-Cas9 based gene-editing ool is one of the remarkable technological advancements, which enables the precise alteration of the transgene. It is worth mentioning that the new generation delivery platforms, including nanoparticles and hybrid vector systems, have been demonstrated to be capable of enabling effective and safe delivery of gene based therapeutics.

Further, a variety of consolidation efforts are currently ongoing in this industry. Such initiatives are primarily focused on expanding and strengthening the existing development efforts; this can be validated from the fact that 56% of the total acquisitions reported in the domain were focused on drug class consolidation.

Driven by the collective and consistent efforts of developers and the growing demand for a single dose of effective therapeutic, the gene therapy market is anticipated to witness significant growth in the foreseen future.

Key Questions Answered

Who are the key industry players engaged in the development of gene therapies?

How many gene therapy candidates are present in the current development pipeline? Which key disease indications are targeted by such products?

Which types of vectors are most commonly used for effective delivery of gene therapies?

What are the key regulatory requirements for gene therapy approval, across various geographies?

Which commercialization strategies are most commonly adopted by gene therapy developers, across different stages of development?

What are the different pricing models and reimbursement strategies currently being adopted for gene therapies?

What are the various technology platforms that are either available in the market or are being designed for the development of gene therapies?

Who are the key CMOs/CDMOs engaged in supplying viral/plasmid vectors for gene therapy development?

What are the key value drivers of the merger and acquisition activity in the gene therapy industry?

Who are the key stakeholders that have actively made investments in the gene therapy domain?

Which are the most active trial sites (in terms of number of clinical studies being conducted) in this domain?

How is the current and future market opportunity likely to be distributed across key market segments?

Key Topics Covered:

1. PREFACE

2. EXECUTIVE SUMMARY

3. INTRODUCTION3.1. Context and Background3.2. Evolution of Gene Therapies3.3. Classification of Gene Therapies3.3.1. Somatic and Germline Gene Therapies3.3.2. Ex Vivo and In Vivo Gene Therapies3.4. Routes of Administration3.5. Mechanism of Action3.6. Overview of Gene Editing3.6.1. Evolution of Genome Editing3.6.2. Applications of Genome Editing3.6.3. Available Genome Editing Techniques3.7. Advantages and Disadvantages of Gene Therapies3.7.1 Ethical and Social Concerns Related to Gene Therapies3.7.2. Constraints and Challenges Related to Gene Therapies3.7.3. Therapy Development Concerns3.7.4. Manufacturing Concerns3.7.5. Commercial Viability Concerns

4. GENE DELIVERY VECTORS4.1. Chapter Overview4.2. Viral and Non-Viral Methods of Gene Transfer4.3. Viral Vectors for Genetically Modified Therapies4.4. Types of Viral Vectors4.5. Types of Non-Viral Vectors

5. REGULATORY LANDSCAPE AND REIMBURSEMENT SCENARIO5.1. Chapter Overview5.2. Regulatory Guidelines in North America5.3. Regulatory Guidelines in Europe5.4. Regulatory Guidelines in Asia-Pacific5.5. Reimbursement Scenario5.6. Commonly Offered Payment Models for Gene Therapies

6. MARKET OVERVIEW6.1. Chapter Overview6.2. Gene Therapy Market: Clinical and Commercial Pipeline6.3. Gene Therapy Market: Early-Stage Pipeline6.4. Gene Therapy Market: Special Drug Designations6.5. Analysis by Phase of Development, Therapeutic Area and Type of Therapy (Grid Representation)

7. COMPETITIVE LANDSCAPE7.1. Chapter Overview7.2. Gene Therapy Market: List of Developers7.3. Key Players: Analysis by Number of Pipeline Candidates

8. MARKETED GENE THERAPIES8.1. Chapter Overview8.2. Gendicine (Shenzhen Sibiono GeneTech)8.3. Oncorine (Shanghai Sunway Biotech)8.4. Rexin-G (Epeius Biotechnologies)8.5. Neovasculgen (Human Stem Cells Institute)8.6. Imlygic (Amgen)8.7. Strimvelis (Orchard Therapeutics)8.8. LuxturnaT (Spark Therapeutics)8.9. ZolgensmaT (Novartis)8.10. Collategene (AnGes)8.11. ZyntelgoT (bluebird bio)8.12. LibmeldyT (Orchard Therapeutics)

9. KEY COMMERCIALIZATION STRATEGIES9.1. Chapter Overview9.2. Successful Drug Launch Strategy: ROOTS Framework9.3. Successful Drug Launch Strategy: Product Differentiation9.4. Commonly Adopted Commercialization Strategies based on Phase of Development of Product9.5. List of Currently Approved Gene Therapies9.6. Key Commercialization Strategies Adopted by Gene Therapy Developers9.6.1. Strategies Adopted Before Therapy Approval9.6.1.1. Participation in Global Events9.6.1.2. Collaboration with Stakeholders and Pharmaceutical Firms9.6.1.3. Indication Expansion9.6.2. Strategies Adopted During/Post Therapy Approval9.6.2.1. Geographical Expansion9.6.2.2. Participation in Global Events9.6.2.3. Patience Assistance Programs9.6.2.4. Awareness through Product Websites9.6.2.5. Collaboration with Stakeholders and Pharmaceutical Firms9.7. Concluding Remarks

10. LATE STAGE (PHASE II/III AND ABOVE) GENE THERAPIES10.1. Chapter Overview10.2. Lumevoq (GS010): Information on Dosage, Mechanism of Action, Clinical Trials and Clinical Trial Results10.3. OTL-10310.4. PTC-AADC10.5. BMN 27010.6. rAd-IFN/Syn310.7. beti-cel10.8. eli-cel10.9. lovo-cel10.10. SRP-900110.11. EB-10110.12. ProstAtak10.13. D-Fi10.14. CG007010.15. VigilT-EWS10.16. Engensis10.17. VGX-310010.18. InvossaT (TG-C)10.19. VYJUVEKTT10.20. PF-0693992610.21. PF-0683843510.22. PF-0705548010.23. SPK-801110.24. AMT-06110.25. VB-11110.26. Generx10.27. ADXS-HPV10.28. AGTC 50110.29. LYS-SAF30210.30. NFS-0110.31. AG0302-COVID1910.32. RGX-31410.33. Hologene 5

11. EMERGING TECHNOLOGIES11.1. Chapter Overview11.2. Gene Editing Technologies11.2.1. Overview11.2.2. Applications11.3. Emerging Gene Editing Platforms11.3.1. CRISPR/Cas9 System11.3.2. TALENs11.3.3. megaTAL11.3.4. Zinc Finger Nuclease11.4. Gene Expression Regulation Technologies11.5. Technology Platforms for Developing/Delivering Gene Therapies

12. KEY THERAPEUTICS AREAS12.1. Chapter Overview12.2. Analysis by Therapeutic Area and Special Designation(s) Awarded12.3. Oncological Diseases12.4. Neurological Diseases12.5. Ophthalmic Diseases12.6. Metabolic Diseases12.7. Genetic Diseases

13. PATENT ANALYSIS13.1. Chapter Overview13.2. Gene Therapy Market: Patent Analysis13.3. Gene Editing Market: Patent Analysis13.4. Overall Intellectual Property Portfolio: Analysis by Type of Organization

14. MERGERS AND ACQUISITIONS14.1. Chapter Overview14.2. Merger and Acquisition Models14.3. Gene Therapy Market: Mergers and Acquisitions

15. FUNDING AND INVESTMENT ANALYSIS15.1. Chapter Overview15.2. Types of Funding15.3. Gene Therapy Market: Funding and Investment Analysis15.4. Concluding Remarks

16. CLINICAL TRIAL ANALYSIS16.1. Chapter Overview16.2. Scope and Methodology16.3. Gene Therapy Market: Clinical Trial Analysis16.4. Analysis by Type of Sponsor16.5. Analysis by Prominent Treatment Sites16.6. Gene Therapy Market: Analysis of Enrolled Patient Population16.7. Concluding Remarks

17. COST PRICE ANALYSIS17.1. Chapter Overview17.2. Gene Therapy Market: Factors Contributing to the Price of Gene Therapies17.3. Gene Therapy Market: Pricing Models

18. START-UP VALUATION18.1. Chapter Overview18.2. Valuation by Year of Experience

19. BIG PHARMA PLAYERS: ANALYSIS OF GENE THERAPY RELATED INITIATIVES19.1. Chapter Overview19.2. Gene Therapy Market: List of Most Prominent Big Pharmaceutical Players19.3. Benchmark Analysis of Key Parameters19.4. Benchmark Analysis of Big Pharmaceutical Players

20. DEMAND ANALYSIS20.1. Chapter Overview20.2. Methodology20.3. Global Demand for Gene Therapies, 2022-2035

21. MARKET FORECAST AND OPPORTUNITY ANALYSIS21.1. Chapter Overview21.2. Scope and Limitations21.3. Key Assumptions and Forecast Methodology21.4. Global Gene Therapy Market, 2022-203521.5. Gene Therapy Market: Value Creation Analysis21.6. Gene Therapy Market: Product-wise Sales Forecasts21.6.1. Gendicine21.6.2. Oncorine21.6.3. Rexin-G21.6.4. Neovasculgen21.6.5. Strimvelis21.6.6. Imlygic21.6.7. LuxturnaT21.6.8. ZolgensmaT21.6.9. Collategene21.6.10. LibmeldyT21.6.11. Lumevoq (GS010)21.6.12. OTL-10321.6.13. PTC-AADC21.6.14. BMN 27021.6.15. rAd-IFN/Syn321.6.16. beti-cel21.6.17. eli-cel21.6.18. lovo-cel21.6.19. SRP-900121.6.20. EB-10121.6.21. ProstAtak21.6.22. D-Fi21.6.23. CG007021.6.24. VigilT-EWS21.6.25. Engensis21.6.26. VGX-310021.6.27. InvossaT (TG-C)21.6.28. VYJUVEKTT21.6.29. PF-0693992621.6.30. PF-0683843521.6.31. PF-0705548021.6.32. SPK-801121.6.33. AMT-06121.6.34. VB-11121.6.35. Generx21.6.36. AMG00121.6.37. OAV-10121.6.38. ADXS-HPV21.6.39. AGTC 50121.6.40. LYS-SAF30221.6.41. NFS-0121.6.42. AG0302-COVID1921.6.43. RGX-31421.6.44. Hologene 5

22. VECTOR MANUFACTURING22.1. Chapter Overview22.2. Overview of Viral Vector Manufacturing22.3. Viral Vector Manufacturing Process22.4. Bioprocessing of Viral Vectors22.5. Challenges Associated with Vector Manufacturing22.6. Contract Service Providers for Viral and Plasmid Vectors

23. CASE STUDY: GENE THERAPY SUPPLY CHAIN23.1. Chapter Overview23.2. Overview of Gene Therapy Supply Chain23.3. Implementation of Supply Chain Models23.4. Logistics in Gene Therapies23.5. Regulatory Supply Chain Across the Globe23.6. Challenges Associated with Gene Therapy Supply Chain23.7. Optimizing Cell and Advanced Therapies Supply Chain Management23.8. Recent Developments and Upcoming Trends

24. CONCLUSION24.1. Chapter Overview

25. INTERVIEW TRANSCRIPTS25.1. Chapter Overview25.2. Buel Dan Rodgers (Founder and CEO, AAVogen)25.3. Sue Washer (President and CEO, AGTC)25.4. Patricia Zilliox (President and CEO, Eyevensys)25.5. Christopher Reinhard (CEO and Chairman, Gene Biotherapeutics (previously known as Cardium Therapeutics))25.6. Adam Rogers (CEO, Hemera Biosciences)25.7. Ryo Kubota (CEO, Chairman and President, Kubota Pharmaceutical Holdings (Acucela))25.8. Al Hawkins (CEO, Milo Biotechnology)25.9. Jean-Phillipe Combal (CEO, Vivet Therapeutics)25.10. Robert Jan Lamers (former CEO, Arthrogen)25.11. Tom Wilton (former CBO, LogicBio Therapeutics)25.12. Michael Tripletti (former CEO, Myonexus Therapeutics)25.13. Molly Cameron (former Corporate Communications Manager, Orchard Therapeutics)25.14. Cedric Szpirer (former Executive and Scientific Director, Delphi Genetics)25.15. Marco Schmeer (Project Manager) and Tatjana Buchholz, (former Marketing Manager, PlasmidFactory)25.16. Jeffrey Hung (CCO, Vigene Biosciences)

26. APPENDIX 1: TABULATED DATA

27. APPENDIX 2: LIST OF COMPANIES AND ORGANIZATIONS

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Cell culture and cell lines

The mouse cell lines MCA205 H-2b (MCA, methylcholanthrene derived sarcoma, provided by Dr. Guido Kromer, France) and B16F10 (B16, melanoma, kindly provided by Dr. Roger Chammas, ICESP) were maintained in a humidified incubator at 37C with 5% CO2 and cultivated in Roswell Park Memorial Institute (RPMI) medium (Thermo Fisher Scientific, Waltham, MA, USA), supplemented with 10% fetal bovine serum (Invitrogen) as well as 1X Anti-Anti (AntibioticAntimycotic -100X, Thermo Fisher Scientific). HEK293 cells were cultivated in Dulbeccos modified Eagle medium (both from Thermo Fisher Scientific), supplemented and maintained in the same conditions as above.

Here we use the MCA sarcoma cell line and employed an intratumoral (i.t) application model since it was demonstrated under these conditions the ability of Dox to unleash ICD and stimulate immune responses in vivo11. We also used the B16 cell line, as it was with this model that we revealed the cell death and immune stimulatory events of our p19Arf/IFN treatment. With regard to the treatment order, we based our approach on the work of Fridlender and collaborators (2010) that showed that association of an adenoviral vector encoding IFN with chemotherapy is more effective when gene transfer is applied first23.

The MCA-DEVD cell line was generated by transduction with a lentivirus reporter for caspase-3 activity and selection for puromycin resistance (0.5g/ml). This vector, previously described24, encodes a constitutively expressed luciferase-GFP protein separated from a polyubiquitin domain via a caspase-3 cleavage site and was generously provided by Dr. Chuan-Yuan Li (Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA).

Construction and production of AdRGD-PG adenoviral vectors (serotype 5) containing modification with the RGD motif in the fiber as well as the p53-responsive promoter (PGTx, PG) has been described previously14. Titration of adenoviral stocks was performed using the Adeno-X Rapid Titer Kit (Clontech, Mountain View, CA, USA) and titer yields were: AdRGD-CMV-LacZ (3.6109IU/mL, infectious units/milliliter), AdRGD-PG-LUC (11011IU/mL), AdRGD-PG-eGFP (51010IU/mL), AdRGD-PG-p19 (1.31010IU/mL) and Ad-RGD-IFN (51010IU/mL). This biological titer was used to calculate multipilicity of infection (MOI).

MCA or B16 cells (1105) were plated in 6 well plates containing 1mL of RPMI media and transduced with adenovirus at the desired MOI. After an overnight transduction period (1216h), 2mL of media was added and cells kept in culture until needed. When combining adenoviral transduction with chemotherapy, Dox (doxrubicin hydrochloride, Sigma, St. Louis, MO, USA) was added immediately after the overnight transduction using the concentration indicated for each experiment. Importantly, in the Dox single treatment condition, Dox was added at the same moment as in the association group, 12 to 16h after cell plating. After 12h treatment with Dox (1mg/mL) or Nutlin-3 (10M, Sigma), expression of eGFP from AdRGD-PG-eGFP was analyzed by flow cytometry (Attune, Life Technologies). Cell viability was assessed by MTT assay where, 8h after transduction in 6 well plates, 2104 cells/well were plated in 96 well plates, treated with Dox, and analyzed after 16h of incubation. Non-transduced cells were used as viable control and protocol was carried out as described previously25. Cell cycle analysis by propidium iodide (PI) staining was carried out 72h after p19Arf/IFN and Dox single treatment, as previously described16. Analysis of caspase 3 activity in vitro was performed 16h after combined treatment using the CellEvent Caspase-3/7 Green Reagent (Thermo Fisher Scientific) by flow cytometry, following manufacturers instructions. Last, analysis of ICD markers upon p19Arf/IFN+Dox was conducted as detailed previously14. Briefly, detection of calreticulin+ and PI- cells was made 14h after combined treatment, by staining with a CRT-specific antibody (1:100, Novus, Biologicals, CO, USA) and after cells were washed with PBS, they were incubated with Alexa488-conjugated anti-rabbit secondary antibody (1:500, Thermo Fisher Scientific) followed by PI staining to exclude dead cells, immediately before flow cytometry. Accumulation of ATP in the cell supernatant was detected using the ENLITEN ATP Assay (Promega, Madison, WI, USA), as per the manufacturer's instructions. Luminescence was observed using a GloMax Plate Reader (Promega). HMGB1 in cell supernatant was detected by Western blot after conditioned medium was supplemented with protease inhibitor cocktail (Thermo Fisher Scientific). Then, 180l of the medium was concentrated (Concentrator PlusEppendorf, Hamburg, Germany) and subjected to western blotting. Unrelated, high molecular weight regions of the membrane were removed before detection was performed using anti-HMGB1 (Abcam ab79823, Cambridge, UK) and a secondary antibody conjugated with horseradish peroxidase before visualization using ECL (GE Healthcare, Chicago, IL, USA) and the ImageQuant LAS4000 imaging platform (GE Healthcare). See Supplementary Information Westerns S2 for original images from three independent assays. Additional Western blots were performed using cell lysates, high-molecular weight regions of the membranes were removed and then detection was performed using anti- PARP (Cell Signaling, Danvers, MA, USA, #9542), anti-Actin (Santa Cruz Biotechnology, Dallas, TX, USA, #47778), anti-Caspase 3 (Cell Signaling, #9662), anti-Tubulin (Millipore, Burlington, MA, USA, #05-829) and the appropriate secondary antibodies conjugated with horseradish peroxidase (anti-mouseSigma #A9044 e anti-rabbitSigma #A0545). See Supplementary Information Westerns S2 for original images from two independent assays.

The influence of two independent variables, namely, MOI of adenoviral vectors encoding p19Arf/IFN and the concentration of Dox, was investigated on MCA and B16 cells using factorial experiments in five levels (Table S1), with the percentage of hypodiploid cells as the variable response. The experiments were carried out employing central composite rotational design (CCRD) where, for each cell line, a set of twelve combinatory assays containing a central composite factorial matrix plus rotation points, central points and controls was performed (Table S2, where the assays and conditions are provided in detail). To better visualize the effects and interactions of MOI and Dox concentration on the percentage of hypodiploid cells, assessed by PI staining after 20h of treatment, the results were plotted in response surface graphs.

Importantly, the statistical significance of the independent variables and their interactions was determined by Fishers post-test for an analysis of variance (ANOVA) and Pareto chart analysis, both at a confidence level of 95% (p0.05). Moreover, five repetitions at the central point (CP) assays were used to minimize the error term of the ANOVA. Experimental designs, data regression and graphical analysis were performed using the Statistica software v.7.0 (Statsoft, Inc., Tulsa, OK, USA).

Both C57BL/6 and Nude mice were female, 7weeks old, obtained from the Centro de Bioterismo da FMUSP and kept in the animal facility in the Centro de Medicina Nuclear (CMN) in SPF conditions, with food and water ad libitum. The methods are reported in accordance with ARRIVE guidelines. The well-being of the mice was constantly monitored and all methods, including vaccination protocols, in vivo gene therapy, imaging, echocardiographic assessments, anesthesia and euthanasia were carried out in accordance with relevant guidelines and regulations of Brazil and our institution whose ethics committee (Committee for the Ethical Use of Animals, CEUA, University of So Paulo School of Medicine, FMUSP) approved this project (protocol n 165/14).

In the first step of the immunotherapy model, nave C57BL/6 mice were inoculated (s.c) in the right flank (tumor challenge site) with fresh untreated MCA (2105) or B16 (6104) cells and in the second step, vaccinated (s.c) on days+3,+9 and+15 with 3105 ex vivo treated cells applied in the left flank (vaccine site). Ex vivo treatment was carried out as follows: MCA or B16 cells were seeded in 10cm plates with 2mL of media and co-transduced with the AdRGD-PG-p19 and AdRGD-PG-IFN (MOI 500 for each) for 4h before the addition of 8mL of fresh media. Then, cells were kept in culture for 16h and in the p19Arf/IFN+Dox or Dox groups, Dox (14M) was added for 6h, until cells were harvested, washed twice with cold PBS, counted and resuspended in 100 L of cold PBS. For the DEAD cell+GFP control group, cells were transduced with the AdRGD-PG-eGFP vector (MOI 1000) and after 16h, harvested, washed twice with cold PBS, resuspended and lysed by three cycles of freezing and thawing.

MCA (2105) or B16 (5105) cells were harvested, washed twice with cold PBS, resuspended in 100 L of PBS per mouse and then inoculated subcutaneously (s.c) in the left flank of immune competent C57BL/6 or immune deficient Balb/c Nude (Foxn1n) mice. While mice were not randomized after injection of cells, but there was no specific selection of animals for each treatment group. No blinding of group allocation was performed at any phase of experimentation. No animals were excluded from the data. Approximately 8days later, palpable (60 mm3) tumors were treated three times, once every 2days, with intratumoral (i.t) injections (administered with precision Hamilton glass syringes (volume 100L) and 26G needles) of the following adenoviral vectors, AdRGD-CMV-LacZ or AdRGD-PG-LUC (4108IU, resuspended in 25 L final volume of PBS/mouse) or treated with the combination of AdRGD-PG-p19 and AdRGD-PG-IFN (2108IU, for each vector and maintaining the 25 L final volume per mouse). For the Dox single treatment model, chemotherapy was applied (i.t) once on day 12 with the following doses: 60, 20, 10 or 5mg/kg (in the final volume of 30 L of PBS/mouse). Whereas in the association model, adenoviral vectors were injected as explained above and Dox given 2days after the last viral injection (day 14), following the injection method as the Dox single treatment group. Tumor progression was measured by calipers every two days and volume calculated as described17. For the survival analysis comparing C57BL/6 and Nude mice, treated mice were euthanized by anesthesia with ketamine/xylazine followed by CO2 inhalation when tumor volume reached 1000 mm3 unless otherwise noted. See figure legends for the number of animals in each experimental group.

For the analysis of caspase 3 in vivo, MCA-DEVD tumors were treated in situ as described above and 24 and 48h after the last treatment injection, mice were submitted to bioluminescence imagining (IVIS Spectrum, Caliper Life Science) to detect the luciferase activity from the DEVD reporter. To this end, 10mg/kg luciferin (Promega) was administered by intraperitoneal (i.p) injection of each mouse and these were anesthetized with isoflurane (Cristalia, So Paulo, Brazil) using the Xenogen anesthesia system before imaging. Images were captured and only the strongest signal from each tumor was included in the analysis with Living Imaging 4.3 software (PerkinElmer, Waltham, MA, USA). Luciferase activity was obtained from the average radiance value [p/s/cm2/sr]. To calculate the fold activity overtime, average radiance values obtained for each mouse 48h post-treatment were divided by its respective value at 24h. Parental MCA tumors were used as negative control and no emission was detected (data not shown).

The systolic cardiac function was assessed by echocardiography. Exams were performed 10days after treatments with AdRGD-PG-eGFP (adenovirus control), Dox 10mg/kg, Dox 20mg/kg and p19Arf/IFN+Dox 10mg/kg. Mice were anesthetized with 1.5 to 2.5% isoflurane (in 100% oxygen ventilation). They were trichotomized and placed in supine decubitus to obtain cardiac images. Parasternal-long and short axis images were captured using VEVO 2100 ultrasound equipment (Vevo 2100 Imaging System, VisualSonics, Toronto, Canada) with a 40MHz linear-transducer. Analyses were performed off-line using VevoCQ LV Analysis software (VisualSonics). Parameters such as systolic and diastolic volumes were calculated using Simpsons modified algorithms present in the analysis software (parasternal-long axis images). Based on these volumes, stroke volume (L) and left ventricle ejection fraction (LVEF, %) were calculated. Also, linear measurements were obtained from parasternal short axis images. Left ventricle shortening fraction (LVSF, %) was calculated, using systolic and diastolic diameters. Left ventricle mass (LV mass, mg) was estimated by linear measurements. Beating rate (beats per minute, BPM) was recorded directly by an animal table-ECG system connected to the VEVO 2100 system. Echocardiographic results were interpreted considering the American Society of Echocardiography recommendations concerning the mouse model26. All parameters were shown as the mean values of three consecutive cardiac cycles. Transthoracic echocardiography image acquisition and analysis was performed by an expert investigator who was blind to the experimental groups.

Data are presented as meanSEM. Statistical differences between groups are indicated with p values, being *p<0.05, **p<0.01 and ***p<0.001. Statistical tests are indicated in each figure legend along with the number of independent experiments performed or number (n) of mice in each group. These analyses were made using the GraphPad Prism 5 (La Jolla, CA, USA) software, with the exception of the CCRD analysis (explained above).

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Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy | Scientific Reports -...

DALLAS, Aug. 09, 2022 (GLOBE NEWSWIRE) -- Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric, pivotal-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS) in both rare and large patient populations, today announced that it will report its financial results for the second quarter ended June 30, 2022, and host a corporate update conference call and webcast on Thursday, August 11, 2022, at 8:00 AM Eastern Time.

About Taysha Gene Therapies

Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to eradicate monogenic CNS disease. With a singular focus on developing curative medicines, we aim to rapidly translate our treatments from bench to bedside. We have combined our teams proven experience in gene therapy drug development and commercialization with the world-class UT Southwestern Gene Therapy Program to build an extensive, AAV gene therapy pipeline focused on both rare and large-market indications. Together, we leverage our fully integrated platforman engine for potential new cureswith a goal of dramatically improving patients lives. More information is available atwww.tayshagtx.com.

Company Contact:Kimberly Lee, D.O. Chief Corporate Affairs OfficerTaysha Gene Therapiesklee@tayshagtx.com

Media Contact:Carolyn HawleyEvoke Canalecarolyn.hawley@evokegroup.com

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Taysha Gene Therapies to Release Second Quarter 2022 Financial Results and Host Conference Call and Webcast on August 11 - GlobeNewswire