Category Archives: Genetic Therapy

The treatment which took place at UConns John Dempsey Hospital used gene therapy, a technique in which the patients genetic data is altered to fix an issue inside the genes in their cells. This treatment is the first for glycogen storage disease type Ia, and if effective could largely provide relief for patients. by Photo by Brao on Unsplash.

On Tuesday, Jan. 18, a clinical trial participant at the University of Connecticuts John Dempsey Hospital became the first person in the world to receive a Phase 3 gene therapy infusion for glycogen storage disease type Ia (GSD-Ia).

GSD-Ia is a disease in which glycogen cannot be properly stored in organs such as the liver, according to Dr. Juan Salazar, the chair of Connecticut Childrens Department of Pediatrics.

Under normal metabolism, glycogen is a source of sugar, Salazar said. We all have enzymes, specifically glucose 6-phosphatase, which helps to break up the glycogen into its smaller parts, so that we can use them for all the energy requirements that we normally have. In this disorder called glycogen storage disease, glycogen cannot be broken down.

In individuals with GSD-Ia, the glucose 6-phosphatase enzyme has a defect, which requires a constant source of sugar, according to Salazar.

In the 1970s, a mixture of cornstarch and water was discovered to work as a temporary treatment for GSD-Ia if taken in certain amounts every few hours.

Cornstarch is a source of sugar that is released in small amounts, and it gets metabolized very quickly If you take too much sugar its bad, and if you dont take enough sugar you can die from it. What the cornstarch does is it meets you halfway in the middle where you have a source that slowly releases a nutrient that is a sugar, that does not lead to accumulation of glycogen.

After 20 years of research led by Dr. David Weinstein, former director of the Glycogen Storage Disease Program at UConn Health and Connecticut Childrens, Weinstein and his team initiated trials for the gene therapy with the goal of treating GSD-affected individuals to the point that they would no longer need to take cornstarch every few hours.

In 2018, UConn Health was also the first in the world to administer the GSD-Ia gene therapy as part of the trials Phase 1/2, according to a UConn Today article.

The reason we were first overall back in 2018 was because of Dr. David Weinstein, said Julie Vigil, the administrative director of UConn Healths Department of Pediatrics. It was his lab who really created this gene therapy and had partnered with Ultragenyx [the pharmaceutical company sponsoring the gene therapy] as far as developing the whole gene therapy protocol.

The gene therapy for GSD-Ia is an adenoviral vector study targeted to the liver, according to Dr. Rebecca Riba-Wolman, the current director of the Glycogen Storage Disease Program at Connecticut Childrens and UConn Health and principal investigator for the trials.

Effectively, theyre using an empty virus to provide the liver with a correct gene for glucose 6-phosphatase, Riba-Wolman said of the gene therapy. We dont truly know the broad efficacy, but we know that we saw an average of 70% decrease [in cornstarch needs]. We know that this therapy wont affect every cell in the liver, and we know GSD affects other parts of the body as well.

The trials first phase consisted of testing and safety regulations.

Anything that youre going to put into a human requires a long process, Salazar said of Phase 1. You cant just inject people with something youve never injected. In this case, you would treat a cell, and once you treat the cell and find positive results, you go to a small animal, which is usually a mouse. From the mouse model, you move on to a larger animalin this case Maltese dogs, which have the same genetic defect.

In Phase 1/2, trial subjects received the investigational product and participated in a fasting challenge to see how long they could go without needing cornstarch.

The participants who received the product were able to last at least 15 hours without cornstarch, according to Vigil.

The subjects are able to go 15 hours without cornstarch, and thats as long as the protocol will allow, so we dont know if they can go over 15,

Phase 3 of the trial, which UConn Health and Connecticut Childrens are currently working on, is double blinded, meaning some participants will get the gene therapy infusion and others will get a placebo instead. The purpose of Phase 3 is to prove the effects of the enzyme product and eliminate any source of bias, according to Salazar.

The subject who received the Phase 3 infusion at UConn Health whose identity must be kept anonymous to preserve the integrity of the trial was chosen after having met several eligibility requirements, including a liver screening process and antibody test.

[The subject] just impressed me with how brave she is, Salazar said. [The infusion] may help her, it may not. She could be getting the placebo, but shes okay with that. She listens to a higher cause, which is really remarkable.

UConn Health expects to administer infusions to five or six additional subjects for Phase 3 of the trial. More information about the GSD-Ia trial and its progress can be found on Ultragenyxs website.

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UConn Health trial subject first in world to receive gene therapy infusion - UConn Daily Campus

New York, Jan. 26, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Cell & Gene Therapy Market - Global Outlook & Forecast 2022-2027" - https://www.reportlinker.com/p05827567/?utm_source=GNW 92 billion by 2027, growing at a CAGR of 39.62 % during the forecast period

The following factors are likely to contribute to the growth of the cell and gene therapy market

Merger & Acquisition Expansion of Manufacturing Plants & Technological Advancement Expanding Application for Cell & Gene Therapies Growing Demand for CAR T- Cell Therapies New Products Approvals & Increasing Pipeline Products

In the cell and gene therapy field, gene therapy gathered the pace last from 2 decades because of the discovery of several genes responsible for mutation in various diseases. The advancement in the cell & gene therapy field and innovative technologies give the new era for biological therapeutics. Also, PRIME Designation and marketing authorization for products provide a new opportunity for the manufacturers financing and revenue generation.

KEY HIGHLIGHTS

As per the American Society of Cell + Gene Therapy report in 2021, increasing the number of cellular and gene therapy products, application rate and products in clinical trials drive the market growth. As per the Dive Biopharma report 2021, biotech companies who actively engaged in regenerative medicines and therapies reported USD 14 billion funding only in six months of 2021 which was reported to be USD 19.9 billion for the overall year.

CELL AND GENE THERAPY MARKET SEGMENTS

Cell and gene therapy market is segmented on the basis of-

Therapy type Application End-users Geography

CELL AND GENE THERAPY MARKET SEGMENTATION Increasing application of gene therapies in diseases diagnosis and rapidly growing new drugs applications will give new market space in upcoming years. In 2020, around USD 2.3 billion funding was reported only from private companies for gene therapies. By 2025, the FDA is expected to approve 10?20 products each year, driving the global cell and gene therapy manufacturing market. In 2020, Medicine in Development Report 2020, around 176 products were reported in cancer therapies in development procedures.

Market segmentation by Therapy Type

Gene Therapy Cell Therapy

Market segmentation by Application

Oncology Genetic Disorders Dermatology Disorders Musculoskeletal Disorders Others

Market segmentation by End-Users

Hospitals Cancer Care Centers Wound Care Centers Others

GEOGRAPHICAL OUTLOOK

North America: High economic status and high expenditure on healthcare services drive the cell and gene therapy market in North America. National Health Institutes, industries, academic institutes, and hospitals are the significant contributors of sponsorship and financial funding for cell and gene therapy products. Europe: The increasing funding for cell and gene therapy drives the cell and gene therapy market growth consistently in Europe. Around USD 2.6 billion financings were reported in Europe for CGTs in 2020, which increased by 103% compared to previous years. In the cell therapy segment, USD 1.8 billion and in gene therapy, USD 2.3 billion funding accounted in 2020, which increased by 196% and 111% growth respectively

Market segmentation by Geography

North Americao USo Canada Europeo Germanyo Franceo UKo Spaino Italy APACo Japano Chinao South Koreao Australiao India Latin Americao Brazilo Mexico Middle East & Africao Turkeyo Saudi Arabiao UAEo South Africao Israel

VENDOR LANDSCAPE

The key players in the cell and gene therapy market are Gilead Sciences, Novartis, Smith Nephew, Amgen, Organogenesis, Roche (Spark Therapeutics), Dendreon, Vericel, and Bristol-Myers Squibb Company. An increasing number of mergers and acquisitions gives new potential to market growth. Gilead Sciences acquired Kite Pharma in 2020. Also, Novartis acquired Avexis in 2018, and Smith & Nephew acquired Osiris Therapeutics.

Key Vendors

Gilead sciences Novartis Smith Nephew (Osiris Therapeutic) Amgen Organogenesis Roche (Spark Therapeutics) Dendreon Vericel Bristol-Myers Squibb

Other Prominent Vendors

Abeona Therapeutics APAC Biotech Pvt Ltd Alnylam Allovir Tego Sciences Avita Medical Anterogen AnGes Inc. BioSolution Co. Ltd. Cheisi Farmaceutici CollPlant CO.DON Corestem Bluebird Bio Inc Biosolution Stempeutics Research GC Cell Sanofi Gensight biologics Human Stem Cells Institute JW CreaGene Co. Ltd JCR Pharmaceuticals Japan Tissue Engineering (J-TEC) Kolon TissueGene Medipost MolMed Nuvasive Inc. Nipro Corporation Orchard Therapeutics Orthocell Pfizer Pharmicell Sibiono Genetech Shanghai Sunway Biotech RMS Regenerative Medical System Takeda Pharmaceuticals Company Terumo

Upcoming Vendors

Biomarin Pharmaceutical Bellicum Pharmaceutical Castle Creek Biosciences Inc Libella Gene Therapeutics CARsgen Therapeutics Hrain Biotechnology Co. Ltd Helixmith Krystal Biotech Inc. JW Therapeutic Poseida Therapeutics

KEY QUESTIONS ANSWERED:

1. How big is the global cell & gene therapy market?2. What are the latest trends in the cell & gene therapy market?3. Who are the key players in the cell & gene therapy market?4. Which region has the highest share in the cell & gene therapy market?5. Who are the end-users of the cell & gene therapy market?Read the full report: https://www.reportlinker.com/p05827567/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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The cell and gene therapy market size was valued at USD - GlobeNewswire

A Phase 2 trial can begin investigations on MCO-010 gene therapy as treatment for patients with Stargardt disease. The multi-characteristic opsin ambient-light activatable optogenetic monotherapy may restore vision in patients with this rare macular degeneration.

The developer of MCO-010, Nanoscope Therapeutics Inc, announced that it received investigational new drug (IND) clearance from the US Food and Drug Administration (FDA).

The trial is expected to start in H1-2022. MCO-010 is designated as an orphan drug by the FDA for Stargardt disease and retinitis pigmentosa (RP).

The clincal-stage biotechnology company is currently conducting a Phase 2b multicenter, randomized, sham-controlled, double-masked study of MCO-010 for patients with retinitis pigmentosa.

Retinitis pigmentosa is a group of rare, genetic disorders associated with difficulty seeing at night and the inability to see peripherally due to the breakdown and loss of cells in the retina.

Stargardt is an inherited rare disease that affects children and adults. As a result of this retinal disease, photoreceptors in the eye degenerate. MCO-010 gene therapy makes them photosensitive by reprogramming the healthy retinal cells.

MCO-010 is a single intravitreal injection administered in a medical office setting. Proprietary AAV2 vectors deliver the MCO genes to the cells where they express polychromatic opsins and enable vision.

Patients with Stargardt and retinitis pigmentosa can utilize this therapy regardless of underlying gene mutations.

"Presently allexisting trialsattemptto slow down the progressionof vision loss in patients with Stargardt disease, Optogenetic approach is to restore vision. Thiscan bea groundbreaking attempt to evaluate optogenetic gene therapyto improve vision inStargardt patients. I'm excited by the potential MCO-010 has to restore vision for many patients with sight loss caused by outer retinal dystrophies including dry age-related macular degeneration," David Boyer, MD, Retina-Vitreous Associates Medical Group, adjunct clinical professor of ophthalmology, Keck School of Medicine, University of Southern California said in a statement.

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FDA Clears MCO-010 Gene Therapy as IND for Stargardt Macular Degeneration - MD Magazine

24-Jan-2022

Vaisala shares its successful case study of the Lonza Houston cell and gene therapy facility

Swiss drug manufacturer Lonza Ltd. is a leading global supplier of contract manufacturing services to pharmaceutical and biotechnology industries. Lonza combines technological innovation with world-class manufacturing and process excellence to provide services in pharma, biotech, nutrition and specialty ingredients.

Lonzas 300,000-square-foot plant located outside Houston, Texas is the worlds largest cell and gene therapy manufacturing plant. The plant produces therapies that can alleviate underlying causes of genetic diseases and improve patient outcomes for acquired diseases. With production costs a major hurdle in getting new therapies to market, a state-of-the-art facility is required to ensure cost-efficient manufacturing and high quality products. Lonzas Texas facility houses cutting-edge technologies and in-house expertise to support their extensive offering, which includes tailored processes and analytical development, cost- effective manufacturing, and cGMP-compliant operations.

We have been using theVaisala viewLinc Monitoring Systemfor about nine years, says David Teer, Senior Engineering Manager for Viral-based Therapeutics at Lonza Houston. We used the system in a limited capacity at our previous facility. At that time, we were learning about viewLincs capabilities. As our operations have grown weve come to use the system in more applications.

Building GMP environments can be costly and complex. Our facility also has a building automation and control system. The system is dependable, but we are very concerned with monitoring, says Teer.

After many years of successfully using Vaisalas wired DL-series data loggers for monitoring, Lonza Houston integrated some of Vaisalas wireless VaiNet data loggers. We were interested in the signal strength of the wireless data loggers, says Teer. Generally speaking, signal interference is a concern with wireless technology. But, we saw that the VaiNet wireless devices could communicate through buildings with significant infrastructure obstacles including concrete and steel.

Along with that, the ability to have so many measurement points sending data to the software with a single CAT6 Ethernet cable was a real benefit. We were used to running hard-wired twisted pair cables to ensure coverage. That involved a lot of labor and expense. Worse, if a cable was ever cut, you could never get that data back. The Vaisala data loggers have onboard memory that ensures the data is recorded at the point of measurement. Thats huge for us.

The Lonza Houston facility includes research and development laboratories, manufacturing and warehouse areas, as well as cleanrooms. In 2012, Lonza Houston installed their first cleanroom monitoring cabinet from Vaisala, the CAB100.

The cleanroom cabinets are a convenient solution, says Teer. Prior to that, we were building our own panels to monitor the cleanrooms. We would buy the pressure transmitters, the power supply, etc. and wire it all up. Now Vaisala provides cabinets that integrate all the things we need. Its a great way to reduce labor costs. We specify what we need and Vaisala builds it for us. That reduces the overall construction budget of a cleanroom. Cleanroom construction has to be efficient; often we are racing to market with a product. So the faster we can have the monitoring system set up, the better.

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Endless monitoring applications at Lonza's cell and gene therapy facility - Cleanroom Technology

WUHAN, China and SAN DIEGO, Jan. 25, 2022 /PRNewswire/ -- Neurophth Therapeutics, Inc., (hereinafter referred to as "Neurophth"), today announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) granted the orphan drug designation (ODD) for the Company's leading gene therapy drug candidate, NR082 (rAAV2-ND4), for the treatment of Leber's hereditary optic neuropathy (LHON) associated with mtND4 mutation. Please see Public Summary of the COMP opinion on EMAwebsite Union Register of medicinal products - Public Health - European Commission (europa.eu).

"The positive opinion from the COMP acknowledges the compelling IND-enabling data and clinical data of 186 subjects from three investigator-initiated trials (IITs)," said Dr. Bin Li, Founder of Neurophth. "Some of the subjects in the earlier IIT were followed for up to 75-90 months, demonstrating excellent clinical durability. Our integrated Phase 1/2/3 registrational trial is ongoing, and the data from this trial are intended to support global regulatory filings."

"This orphan drug designation is an important milestone toward addressing the unmet need of families and patients living with LHON, and it follows the ODD previously granted in 2020 by the US. Food and Drug Administration (FDA) for this same gene therapy drug candidateas a potential treatment for mtND4-LHON," said Xin Zhang, M.D., M.Sc., Chief Medical Officer and Chief Operations Officer at Neurophth. "In China, for Global - as Neurophth expands its regulatory strategy in Europe, we will continue to make meaningful changes in the lives of patients with genetic diseases around the world."

Ms. Yiyuan Chen, Head of Global Regulatory Affairs of Neurophth, commented, "We are very pleased to receive EMA's orphan drug designation, which is another good news following the recent US IND clearance of NR082 and the grant of US Orphan Drug Designation of NFS-02. This is a true reflection of the company's operational excellence. We will continue to deliver our promise to bring transformative treatments to patients around the world."

About Orphan Drug Designation

EMA orphan designation is designed to encourage the development of new treatments to treat a seriously debilitating or life-threatening condition that affects fewer than 5 in 10,000 people in the European Union (EU), and there must be sufficient non-clinical or clinical data to suggest the investigational medicine may produce clinically relevant outcomes. Medicines that meet the EMA's orphan designation criteria qualify for several incentives, including 10 years of market exclusivity, clinical protocol assistance, differentiated evaluation procedures for Health Technology Assessments in certain countries, access to a centralized marketing authorization procedure valid in all EU member states, and potentially reduced fees for regulatory activities. Applications for orphan designation are examined by the EMA's Committee for Orphan Medicinal Products (COMP), using the Committee's network of experts.

About Leber's Hereditary Optic Neuropathy (LHON)

Leber hereditary optic neuropathy (LHON) is a maternally inherited blinding bilateral optic atrophy[1] with a prevalence of around 1 in 31,000 to 1 in 54,000 particularly in young adult males[2]. There are three mitochondrial DNA point mutations account for about over 90% of all LHON cases, namely, G3460A in ND1, G11778A in ND4 and T14484C in ND6, with G11778A mutation in NADH-dehydrogenase subunit 4 (ND4) gene causing a ND4 subunit arginine to be incorrectly replaced by a histidine and reducing the activity of NADH dehydrogenase by 50-80% as being the most common mutation worldwide[1,3,4]. These mutations affect complex I subunits of the mitochondrial respiratory chain, impairing mitochondrial function and increasing the production of reactive oxygen species. The retinal ganglion cells (RGCs) appear to be selectively vulnerable to mitochondrial dysfunction resulting in apoptotic cell death, optic nerve degeneration, and the development of optic atrophy[4]. Thus, the pathophysiology of LHON is characterized by selective loss of RGCs and their axons, which leads to rapidly progressive bilateral vision loss. The visual prognosis is poor, and most patients progress to vision worse than 20/200 within the first year after disease onset[3]. There is currently no approved effective treatment for LHON and the current treatment remains limited[5].

About NR082

Investigational NR082 (rAAV2-ND4), a novel recombinant adeno-associated viral vector, serotype 2, containing a mitochondria codon-optimized NADH-dehydrogenase subunit 4 (ND4) gene under the control of the cytomegalovirus promoter and enhancer, is a novel gene therapy product that is being developed for the treatment of Leber hereditary optic neuropathy (LHON) associated with mtND4 mutations. The U.S.Food and Drug Administration (FDA) granted orphan-disease designation to NR082 in September 2020[6]. Safety and efficacy of mtND4 gene therapy have been evaluated in three investigator-initiated trials (IITs) with clinical durability up to 90 months in the first IIT. The results of these three IITs of 186 LHON patients demonstrated that an intravitreal injection of rAAV2-ND4 in subjects with LHON is well tolerated and can be effective at improving visual acuity[7,8,9].

About Neurophth

Neurophth is China's first gene therapy company for ophthalmic diseases. With subsidiaries in China (Wuhan, Shanghai, and Suzhou) and US (San Diego, California), Neurophth, a fully-integrated company, is striving to discover and develop genomic medicines for patients suffering from genetic diseases globally. Our validated AAV platform, which has been published in Nature - Scientific Reports, Ophthalmology, and EBioMedicine, has successfully delivered proof-of-concept investigator-initiated trials data of 186 subjects with investigational gene therapies in the retina. Our most advanced investigational gene therapy drug candidate, NR082 (rAAV2-ND4), in development for the treatment ofmtND4-mediated LHON, has been granted orphan drug designation (ODD) by theU.S. FDA, an integrated Phase 1/2/3 clinical trial has been initiated with the first patient dosed in June 2021 after the IND clearance by the China NMPA in March 2021, and US IND has recently been cleared by US FDA. The pipeline also includesmtND1-mediated LHON (the Company's 2nd US ODD), autosomal dominant optic atrophy, optic neuroprotection (e.g., glaucoma), vascular retinopathy (e.g., diabetic retinopathy), and five other preclinical candidates. Neurophth has scaled up in-house manufacturing capability in Suzhou facility utilizing single-use technologies to support future commercial demand. To learn more about us and our growing pipeline, visitwww.neurophth.com.

Reference

SOURCE Neurophth Therapeutics, Inc.

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Neurophth Therapeutics' Treatment of Leber's Hereditary Optic Neuropathy Gene Therapy NR082 was Granted Orphan Drug Designation by EMA - PRNewswire

A team of scientists in New York has created small molecules called antisense oligonucleotides that could be used to skip over the mutated part of theCFTR gene to treatcystic fibrosis (CF) patients with a specific nonsense mutation and no available therapies.

Findings were published in the study, Exon-skipping antisense oligonucleotides for cystic fibrosis therapy, published in the journalPNAS.

CF is caused by mutations in theCFTR gene, which provides instructions for making the CFTR protein. This protein is important for regulating the movement of water and salts in and out of cells.

In recent years, a class of medications called CFTR modulators such as the triple-combo therapy Trikafta, by Vertex Pharmaceuticals has become widely available to treat CF. These medicines can increase the activity of the CFTR protein, but they only work in people with certain disease-causing mutations.

Many mutations in the CFTR gene are not responsive to drugs used to treat CF, Young Jin Kim, a doctoral student at Stony Brook University and the studys first author, said in a press release.

In particular, CFTR modulators do not work as treatments of nonsense mutations. A nonsense mutation is a change in the genetic code that results in a stop signal halfway through a gene kind of like putting a period in the middle of a sentence.

There is a significant unmet therapeutic need for patients with this type of mutation, Kim said.

A nonsense mutation called W1282X is the sixth most common CF-causing mutation. Its present in about 1.2% of patients and tends to be associated with more severe disease.

Within a cells DNA, genes are divided into sections called exons. When a gene gets read, all the exons are strung together in the messenger RNA (mRNA) sent to the cells protein-making machinery (ribosomes).

The W1282X mutation is located in exon 23 of theCFTRgene. Here, researchers tested if skipping over this exon might allow cells to produce a shorter, but still functional, version of the CFTR protein. Similar approaches have been successfully developed to treat disorders such as Duchenne muscular dystrophy.

In initial proof-of-concept experiments, the researchers illustrated that a shortened CFTR protein, made without exon 23, is biologically active. Based on measures of salt movement in and out of cells, the shortened protein was roughly half as active as the unmutated protein when treated with Trikafta.

As low as 10% of normal CFTR function would provide a significant therapeutic benefit for CF patients who have a near-complete loss of CFTR function, as is the case for the W1282X mutation, the scientists wrote, noting their findings support this overall treatment approach.

Researchers then designed antisense oligonucleotides, or ASOs, which are basically short pieces of genetic code that can modulate the genetic activity of the cell. Two ASOs that could promote skipping of exon 23 were identified

The team showed that treatment with the two ASOs, plus the two CFTR modulators present in Orkambi (ivacaftor/lumacaftor), could increase CFTR activity in cells carrying the W1282X mutation. (Orkambi is approved to treat patients with the common F508del mutationin bothCFTR gene copies.)

CFTR activity in these treated cells is likely less than 10% what it is in cells with no mutation, the scientists said. We anticipate that combining the ASO cocktail with Trikafta may further increase the CFTR activity, they wrote.

These researchers are now hoping to progress their approach toward clinical trials.

Our results thus provide an avenue for developing a therapeutic strategy based on [exon-skipping] ASO, in the era of CFTR-modulator therapy, they concluded.

Read more:
For CF Nonsense Mutations, Exon-Skipping May Be Promising Approach - Cystic Fibrosis News Today