Category Archives: Genetic Therapy

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.

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

For Dr Jogin Desai, CEO and co-founder of Eyestem, a leading Indian cell therapy company, a meeting in 2015 with ophthalmologist Dr Rajani Battu for a medical appointment changed everything. Following the appointment, she introduced him to patients diagnosed with degenerative diseases of the eye and the terrible suffering they have to endure.

It was an eye-opener for Desai, a native of Ahmedabad and an expert in the field of drug development. Desai, at the time, was CEO of Cenduit, an industry leader in the IRT (interactive response technology) market and the eClinical field.

From school students who cannot see their blackboards to families with children suffering from blindness because of genetic disorders and senior citizens who have lost all agency due to their inability to read, the conversation opened my eyes to a world that I didnt know existed. In the same week, I met Prof S. Ramaswamy at Instem (Institute for Stem Cell and Regenerative Medicine), again for something completely unrelated, and we discussed the possibilities of how the next two-three decades will evolve with the maturation of cell and gene therapy products worldwide, recalls Desai, in a conversation with The Better India.

Following the meeting, it dawned on Desai at the time that the world is on the cusp of a fundamental change in the healthcare landscape that will evolve over the next few decades.

Today, Dr Rajani Battu is the chief medical officer at Eyestem.

Diseases that were previously incurable will start becoming curable. As I dove deeper, I understood that most of these therapies developed in the West will cost upwards of $450,000 (about Rs 3.5 Crore) per injection. This, I believe, presented a once-in-a-lifetime opportunity for a platform that can help disrupt this paradigm and create an incredible impact on the lives of patients. I made the decision to establish Eyestem within two days of these meetings in late 2015, adds Desai.

Eyestems vision is to create a scalable cell therapy platform to treat incurable diseases and democratise access to these newer technologies.

Incorporated in late 2015, Eyestem started operations in early 2017.

As cell and gene therapies become available across the world, they will only be available to the top 0.01 % of the worlds population. Our purpose is simple: We aim to democratise access by creating a therapy that is available to a large part of the bottom 99.99% of the population in the world. To our knowledge, we are the only company in the world with such a mission. While it is hard to predict the price of the therapy at this stage we anticipate the therapy to cost 80-90% cheaper than such comparable therapies in the West. The only purpose to start Eyestem has been ensuring that the therapy reaches the people that need it the most, claims Desai.

Through its flagship product Eyecyte-RPE, the company replaces lost retinal pigment epithelium cells. It is designed to restore sight for patients in the early stages of Age-Related Macular Degeneration (AMD) and arrest losses for those in the later stages.

There is no cure for Dry Age-Related Macular Degeneration in the world. It is the largest cause of blindness for people over 50. It is estimated that over 170 million people (40 million of which are in India) suffer from this disease. Eyestem is looking to take Eyecyte-RPE for Dry AMD through clinical trials and is one of six companies worldwide pursuing this treatment, he says.

Underpinning this type of treatment are Induced-Pluripotent Stem Cell (iPSC)-based products. An iPSC is a cell that can be developed into any cell of the body. At present, there are no iPSC-based products approved anywhere in the world.

Over the next ten years, Desai explains that several such products will start becoming available in the market and diseases such as inherited blindness/pulmonary fibrosis/diabetes which were hitherto considered incurable will start becoming curable.

Subsequently, an explosion in iPSC based therapeutics combined with gene engineering will be the next wave of pharma innovation. A lot of diseases occur when the cells of our body die early or are malfunctioning. At its most basic detail, one can create tissue of any kind (be it brain, heart, lung, eye, liver, kidney) through iPSC and replace the lost/damaged cells of the body. For example, in Dry AMD, the RPE layer degenerates and our treatment would be to inject that layer (from a healthy donor) back into the body part to treat the disease, he explains.

Curing Incurable Blindness and Other Diseases

So, how does Eyestems flagship product, Eyecte-RPE, work as a mode of treatment?

The Retinal Pigment Epithelium (RPE) is one of ten layers of the retina and acts as a foundation on which the rest of the retina sits. In Dry AMD, the RPE layer disintegrates and the retinal layers disintegrate just as a building collapses when the foundation collapses.

We have grown the RPE layer in our lab and this is Eyecyte-RPE, our flagship product. This product has been injected into special models of blind rats. We have proven that the rats where our product is injected can retain their sight while the ones that are controlled rats go blind. This animal experiment has been done at Oregon Health and Science University which is a global centre of excellence for macular degeneration research. The DCGI (Drugs Controller General of India) has approved manufacturing only for clinical trials and we have not yet applied for commercial manufacturing, he explains.

In addition to this, Eyestem is also among one of five companies globally advancing the treatment of Retinitis Pigmentosa (RP) to the market called Eyecyte-PRP. Eyecyte-PRP replaces the photoreceptor cells that are lost as a consequence of this disease. RP is a group of rare, genetic disorders that involve loss of the light-sensing photoreceptor cells in the retina. It affects children and causes total blindness by the time they reach their 20s and 30s. It is estimated to affect 4 million children worldwide, of which 1.5 million are in India. Human trials for Eyecyte-PRP to treat retinitis pigmentosa is expected to begin in the second half of FY 2023.

Similarly, Eyestem is also looking to treat Idiopathic Pulmonary Fibrosis (IPF), a serious chronic disease that affects the tissue surrounding the alveoli (tiny air sacs in your lungs), with a pluripotent stem cell-based approach.

Our first human trials for our Aircyte-AEC treatment to treat idiopathic pulmonary fibrosis will begin in the second half of FY2024. Aircyte-AEC is a suspension of lung alveolar epithelial cells that are lost due to this disease. It is worth noting that pulmonary fibrosis occurs as an end-stage event in several other diseases like COVID-19, Tuberculosis and Chronic Obstructive Pulmonary Disease, notes Desai.

Meanwhile, for the sake of clarification, we asked Desai whether cell therapy necessarily means stem cell therapy? Yes, it means the same from a laymans perspective. The only difference is that there are clinics that advertise stem cell therapy for patients in India as well as the US. It is important to remember that none of these stem cell therapy products are approved by the DCGI in India or the FDA in the United States, he notes.

State of Cell Therapy in India, Funding and Moving Ahead

There are only a handful of companies in India that are pursuing cell therapy. According to Desai, the developed world, especially countries like Israel, Japan and the United States, are at least two decades ahead of India in that regard.

As more incurable diseases become curable (think diabetes or cancer) it is absolutely imperative for India to develop a base of such product development research or else we will find ourselves in a situation similar to the HIV epidemic (and cell therapy is not easy to reverse engineer unlike HIV medicines). Our patients will be at the mercy of predatory pricing of global pharma unless globally innovative products are manufactured and made available locally. Our nine-member team at Eyestem, a majority of whom are cell biology scientists specializing in this field, is looking to significantly address this issue in advance, says Desai.

Meanwhile, Desai claims that his venture has been very selective in raising funds so far since its purpose is not to raise rounds of money with higher valuations but to benefit end patients. They are laser-focused on creating affordable cell therapy and hence have set themselves a benchmark of not spending more than $4 million from idea to first in human trials. Most pharmaceutical companies, he claims, spend 10 times this amount to reach this stage.

Any drug development venture needs smart money. We were fortunate to have interest from a group of investors who have multi-decade experience in global drug development. Two institutional investors (Endiya Partners and Kotak Private Equity) joined in a subsequent pre-series A round. We are currently raising our series A and we are halfway there. About 30% has been committed by current shareholders and we have a soft commitment from a global venture fund for the other 20%. We anticipate closing this round in the next 8-12 weeks. Investors invest in ventures like ours due to the promise of immense market potential for these therapies. As soon as one obtains human data, startups like ourselves reach an inflexion point and become extremely valuable, claims Desai.

Please Note: The Better India does not verify for the future efficacy of any therapy or medical treatment mentioned in the article. Kindly consult your doctor for an informed medical opinion.

(Edited by Vinayak Hegde)

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Doctor Innovates Cell Therapy in India; Seeks to Make Vision Restoration 80% Cheaper - The Better India

There are new cancer concerns swirling around a gene therapy approach designed to preventthe sickling of blood cells (above).

By Jocelyn KaiserFeb. 16, 2021 , 6:15 PM

A company has stopped its clinical studies of a promising gene therapy for the blood disorder sickle cell disease after two people who participated developed leukemia-like cancer. Bluebird bio is now investigating whether a virus it uses to deliver a therapeutic gene caused the cancers, reviving old concerns about the risks of this approach.

Its also possible the cancers stemmed from chemotherapy the patients received to prepare their bodies for the genes delivery. This is really a sad development whatever the cause, says Donald Kohn of the University of California, Los Angeles, who has led gene therapy trials for sickle cell and other diseases.

In the bluebird bio trials, scientists remove a patients blood stem cells and treat them in a dish with a modified virus related to HIV. It carries DNA encoding the oxygen-carrying protein hemoglobin and is intended to compensate for the patients defective gene for this molecule. After this step, called ex vivo because a patients cells are treated outside the body, doctors infuse the cells back into the person. Fourteen people who have received the latest version of the bluebird bio therapy are now virtually free of the pain crises their sickled red blood cells once caused.

But today came thenewsthat a patient treated 5 years ago in one of the studies has developed acute myeloid leukemia (AML). Another has myelodysplastic syndrome (MDS), which can develop into AML. A previous patient in the same studydeveloped MDS in 2018, but tests showedit had likely resulted from the DNA-damaging chemotherapy that wipes out a patients blood cells to make room for treated blood cells.

Still, the gene therapy could play a more direct role. In past small clinical trials, several boys with an inherited immune disorder who received similar ex vivo gene therapy developed leukemia. In those cases, a mouse virus ferrying a curative gene into cells landed its genetic cargo in a location that turned on a cancer gene. Researchers then switched to a potentially safer delivery system, a lentivirus that also inserts the genes it carries into the hosts DNA but in sites less likely to trigger a cancer gene. A 2019 report that a monkey treated with a lentiviral gene therapy had developed a leukemia-like condition suggested, however, that thecancer risk had not been eliminated.

Bluebird biotold investors todaythat although its scientists have found the virus inserted DNA into the chromosomes of the leukemia cells of the treated sickle cell patient with AML, they dont yet know its location. Theyll look to see whether the viral DNA landed near a known cancer-promoting gene, perhaps driving its activity. The company says these tests should take a matter of weeks.

Meanwhile, bluebird bio has also halted sales in Europe of an approved treatment that uses the same vector to treat the blood disorder beta-thalassemia. The companys stock price plunged 38% today.

Another sickle cell disease clinical trial that uses the CRISPR gene-editing tool to turn on a fetal form of hemoglobinreported promising results last year. That treatment doesnt rely on a virus to deliver CRISPR; instead, it uses a zap of electricity to get CRISPR editing molecules into cells in a dish. However, CRISPR itself can make off-target effects and rearrange chromosomes, and whether that can trigger cancer may not be known for several years.

The bluebird bio news comes on the heels of a December 2020 report thata patient in a gene therapy trial for hemophilia had developed a liver tumor. The company, uniQure, planned to explore the possible role of its vector, an adeno-associated virus (AAV). Even though AAVs are supposed to be safer than lentiviruses for gene therapy because they are not designed to insert their cargo into a cells genome, animal studies have found they sometimes can.

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Gene therapy trials for sickle cell disease halted after two patients develop cancer - Science Magazine

Novartis and the Bill and Melinda Gates Foundation are joining forces to discover and develop a gene therapy to cure sickle cell disease with a one-step, one-time treatment that is affordable and simple enough to treat patients anywhere in the world, especially in sub-Saharan Africa where resources may be scarce but disease prevalence is high.

The three-year collaboration, announced Wednesday, has initial funding of $7.28 million.

Current gene therapy approaches being developed for sickle cell disease are complex, enormously expensive, and bespoke, crafting treatments for individual patients one at a time. The collaboration aims to instead create an off-the-shelf treatment that bypasses many of the steps of current approaches, in which cells are removed and processed outside the body before being returned to patients.

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Sickle cells cause is understood. The people it affects are known. But its cure has been elusive, Jay Bradner, president of the Novartis Institutes for BioMedical Research, told STAT.

We understand perfectly the disease pathway and the patient, but we dont know what it would take to have a single-administration, in vivo gene therapy for sickle cell disease that you could deploy in a low-resource setting with the requisite safety and data to support its use, he said. Im a hematologist and can assure you that in my experience in the clinic, it was extremely frustrating to understand a disease so perfectly but have so little to offer.

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Sickle cell disease is a life-threatening inherited blood disorder that affects millions around the world, with about 80% of affected people in sub-Saharan Africa and more than 100,000 in the U.S. The mutation that causes the disease emerged in Africa, where it protects against malaria. While most patients with sickle cell share African ancestry, those with ancestry from South America, Central America, and India, as well as Italy and Turkey, can also have the hereditary disease.

The genetic mutation does its damage by changing the structure of hemoglobin, hampering the ability of red blood cells to carry oxygen and damaging blood vessels when the misshapen cells get stuck and block blood flow. Patients frequently suffer painful crises that can be fatal if not promptly treated with fluids, medication, and oxygen. Longer term, organs starved of oxygen eventually give out. In the U.S., that pain and suffering is amplified when systemic and individual instances of racism deny Black people the care they need.

Delivering gene therapy for other diseases has been costly and difficult even in the best financed, most sophisticated medical settings. Challenges include removing patients cells so they can be altered in a lab, manufacturing the new cells in high volume, reinfusing them, and managing sometimes severe responses to the corrected cells. Patients also are given chemotherapy to clear space in their bone marrow for the new cells.

Ideally, many of those steps could be skipped if there were an off-the-shelf gene therapy. That means, among other challenges, inventing a way to eliminate the step where each patients cells are manipulated outside the body and given back the in vivo part of the plan to correct the genetic mutation.

Thats not the only obstacle. For a sickle cell therapy to be successful, Bradner said, it must be delivered only to its targets, which are blood stem cells. The genetic material carrying corrected DNA must be safely transferred so it does not become randomly inserted into the genome and create the risk of cancer, a possibility that halted a Bluebird Bio clinical trial on Tuesday. The payload itself mustnt cause such problems as the cytokine storm of immune overreaction. And the intended response has to be both durable and corrective.

In a way, the gene delivery is the easy part because we know that expressing a normal hemoglobin, correcting the mutated hemoglobin, or reengineering the switches that once turned off normal fetal hemoglobin to turn it back on, all can work, Bradner said. The payload is less a concern to me than the safe, specific, and durable delivery of that payload.

For each of these four challenges delivery, gene transfer, tolerability, durability there could be a bespoke technical solution, Bradner said. The goal is to create an ensemble form of gene therapy.

Novartis has an existing sickle-cell project using CRISPR with the genome-editing company Intellia, now in early human trials, whose lessons may inform this new project. CRISPR may not be the method used; all choices are still on the table, Bradner said.

Vertex Pharmaceuticals has seen encouraging early signs with its candidate therapy developed with CRISPR Therapeutics. Other companies, including Beam Therapeutics, have also embarked on gene therapy development.

The Novartis-Gates collaboration is different in its ambition to create a cure that does not rely on an expensive, complicated framework. Novartis has worked with the Gates Foundation on making malaria treatment accessible in Africa. And in October 2019, the Gates Foundation and the National Institutes of Health said together they would invest at least $200 million over the next four years to develop gene-based cures for sickle cell disease and HIV that would be affordable and available in the resource-poor countries hit hardest by the two diseases, particularly in Africa.

Gene therapies might help end the threat of diseases like sickle cell, but only if we can make them far more affordable and practical for low-resource settings, Trevor Mundel, president of global health at the Gates Foundation, said in a statement about the Novartis collaboration. Its about treating the needs of people in lower-income countries as a driver of scientific and medical progress, not an afterthought.

Asked which is the harder problem to solve: one-time, in vivo gene therapy, or making it accessible around the world, David Williams, chief of hematology/oncology at Boston Childrens Hospital, said: Both are going to be difficult to solve. The first will likely occur before the therapy is practically accessible to the large number of patients suffering the disease around the world.

Williams is also working with the Gates Foundation, as well as the Koch Institute for Integrative Cancer Research at MIT, Dana-Farber Cancer Institute, and Massachusetts General Hospital, on another approach in which a single injection of a reagent changes the DNA of blood stem cells. But there are obstacles to overcome there, too, that may be solved by advances in both the technology to modify genes and the biological understanding of blood cells.

Bradner expects further funding to come to reach patients around the world, once the science progresses more.

There is no plug-and-play solution for this project in the way that mRNA vaccines were perfectly set up for SARS-CoV-2. We have no such technology to immediately redeploy here, he said. Were going to have to reimagine what it means to be a gene therapy for this project.

More:
Novartis, Gates Foundation pursue a simpler gene therapy for sickle cell - STAT

The new gene therapy target,GJB2 coding for the Connexin 26 protein, has been added to Sensorions development portfolio: with the target the third candidate to emerge from the R&D collaboration with Institut Pasteur. It represents the largest gene therapy opportunity for the French biotech to date.

The GJB2 program will focus on major new markets with an estimated patient population of 300,000 children and adults in Europe and the US alone.

Sensorion, a French clinical-stage biotech based in Montpellier, was founded in 2009 to develop novel therapies to restore, treat and prevent hearing loss disorders.

The GJB2 program draws on new research from Institut Pasteur which shows that the same genes that underly congenital deafness are also involved in severe forms of presbycusis (age-related hearing loss). These forms of presbycusis appearing to be monogenic types of hearing loss that can be potentially treated by gene therapy.

Although the types ofGJB2mutations in children and adults may differ, Sensorion says gene therapy could potentially provide a solution to both.

Mutations inGJB2are believed to alter a gap junction protein widely expressed in the inner ear, disturbing intercellular exchanges of molecules and leading to hearing loss that is severe-to-profound in a majority of cases.

Institut Pasteur research now shows three pathologies related to GJB2 mutations: congenital deafness;age-related hearing loss in adults; and progressive forms of hearing loss in children. Sensorion will prioritize the latter two forms, saying it is the first company to address these needs and offering the potential of large market opportunities.

The emergence of a new gene therapy target candidate validates our conviction that long-term solutions for restoring hereditary hearing loss will arise from an in-depth analysis of the "genetic landscape" of hearing loss," saidNawal Ouzren, CEO of Sensorion.

"It was clear that mutations in the GJB2 gene are important in severe to profound childhood hearing loss. However, the new discovery made by our collaborators at Institut Pasteur shows that alteration of this gene in adults offers new opportunities for Sensorion. It marks significant potential expansion of our pipeline and supports our goal of becoming a global leader in the field of gene therapies for hearing loss disorders.

Sensorions collaboration with Institut Pasteur initiated in 2019 has already led to gene therapy candidate programs in two other indications. Its USHER-CT gene therapy development program aims to restore inner ear function for patients suffering from Usher Syndrome Type 1 by providing a healthy copy of the USH1G gene coding for the SANS protein.

Meanwhile, the OTOF-GT gene therapy development program seeks to restore hearing in people with Otoferlin deficiency, one of the most common forms of congenital deafness.

Both of these have been proved in concept in preclinical studies.

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Sensorion and Institut Pasteur announce new gene therapy collaboration - BioPharma-Reporter.com