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Gustavo Aguirre and William Beltran, veterinary ophthalmologists and vision scientists at the University of Pennsylvania School of Veterinary Medicine, have studied a wide range of different retinal blinding disorders. But the one caused by mutations in the NPHP5 gene, leading to a form of Leber congenital amaurosis (LCA), is one of the most severe.

Children with this disorder are not visual, says Aguirre. They have a wandering, searching look on their faces and are usually diagnosed at a young age.

A nearly identical disease naturally occurs in dogs. In a new paper in the journal Molecular Therapy, Aguirre, Beltran, and colleagues at Penn and other institutions have demonstrated that a canine gene therapy can restore both normal structure and function to the retinas cone photoreceptor cells, which, in LCA patients, otherwise fail to develop normally. Delivering a normal copy of either the canine or human version of the NPHP5 gene restored vision in treated dogs.

Whats amazing is that you can take this disease in which cone cells have incompletely formed, and the therapy restores their functionthey had no function whatsoever beforeand recover their structure, says Aguirre.

That plasticity is incredible and gives us a lot of hope, Beltran says.

LCA includes a wide range of inherited vision disorders characterized by blindness that strike in early childhood. The form of LCA associated with NPHP5 mutations is rare, affecting about 5,000 people worldwide. Known as a ciliopathy, it affects the cilia of cells of the retina. The cilia cells are antennalike structures on photoreceptor cells that translate the energy from light into visual signals.

In the NPHP5 disease, rod photoreceptor cellsthose responsible for vision in low lightdegenerate and progressively die early in the disease. Yet the cone photoreceptors, which enable color vision and, in the central retina, the perception of fine detail, while abnormal structurally, survive, albeit without function.

Aguirre and Beltran, together with colleagues and coauthors on the current work, Artur Cideciyan and Samuel Jacobson in Penns Perelman School of Medicine, have found success with gene therapy approaches to treating a variety of inherited vision disorders. Often, they have aimed to treat early in the course of a retinal disease, before photoreceptor cells have died or entirely degenerated. But the fact that cone cells persisted in this form of LCA led the researchers to consider whether a therapy that targeted cones could not just stop but reverse the course of the disease.

Testing this approach, the team delivered retinal injections of adeno-associated viral vectors, a platform for ferrying the normal version of the NPHP5 gene, into one eye of each of nine five-week-old dogs with the vision disorder. Known as gene augmentation therapy, the injection is used to supply a healthy gene in disorders where the causative mutation leads to a defective or absent protein.

To determine the effectiveness of the treatment, the researchers used a technique called electroretinography, which measures the electrical response of photoreceptor cells to a light stimulus, as well as optical coherence tomography, which allows for the noninvasive imaging of fine cross sections of the retina. Both means of evaluating the experimental therapy rendered encouraging results. In the dogs treated eyes, the outer segment of the cones regrew.

In addition, when the treated dogs were about six months old, their vision was tested using an obstacle-avoidance course. When their treated eye was blindfolded, they had difficulty at navigating; however, when that eye was uncovered, their ability to avoid obstacles was notably improved.

Whats so appealing and so exciting here is that were not just stopping a disease process, were actually reverting a photoreceptor cell that is abnormal to become normal and function, says Beltran. This disease in dogs very closely parallels the disease in humans, in quite specific terms, so theres a lot of support for the thought that a similar treatment approach could also help children.

Ongoing studies suggest that the treatment may be effective even when delivered at later stages of disease. With further support, the researchers hope to move the research along the path to a clinical trial in people.

Gustavo D. Aguirre is professor of medical genetics and ophthalmology in the Department of Clinical Sciences and Advanced Medicine at the University of Pennsylvania School of Veterinary Medicine.

William Beltran is professor of ophthalmology in the Department of Clinical Sciences and Advanced Medicine and director of the Division of Experimental Retinal Therapies at Penns School of Veterinary Medicine.

Artur V. Cideciyan is a research professor of ophthalmology at the Scheie Eye Institute in the University of Pennsylvania's Perelman School of Medicine.

Samuel G. Jacobson is a professor of ophthalmology at the Scheie Eye Institute in Penns Perelman School of Medicine.

In addition to Aguirre, Beltran, Cideciyan, and Jacobson, coauthors on the study were Penn Vets Valrie L. Dufour, Ana Ripolles-Garca, Raghavi Sudharsan, Roman Nikonov, and Simone Iwabe; Penn Medicines Malgorzata Swider; and the University of Floridas Sanford L. Boye and William W. Hauswirth.

The study was supported in part by the National Eye Institute (grants EY006855, EY017549, and EY001583) with additional support from the Foundation Fighting Blindness, the Van Sloun Fund for Canine Genetic Research, Hope for Vision, the Research to Prevent Blindness Foundation, and the Sanford and Susan Greenberg End Blindness Outstanding Achievement Prize.

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Turning back the clock on a severe vision disorder | Penn Today - Penn Today

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Independent of cholesterol, gene variants raise risk of heart disease, diabetes, high blood pressure

A new study from Washington University School of Medicine in St. Louis has identified a gene called SVEP1 that makes a protein that influences the risk of coronary artery disease independent of cholesterol. SVEP1 induces proliferation of vascular smooth muscle cells in the development of atherosclerosis. Shown is a stained section of atherosclerotic plaque from a mouse aorta, the largest artery in the body. Vascular smooth muscle cells are red; proliferating cells are cyan; nuclei of any cell are blue.

High cholesterol is the most commonly understood cause of atherosclerosis, a hardening of the arteries that raises the risk of heart attack and stroke. But now, scientists at Washington University School of Medicine in St. Louis have identified a gene that likely plays a causal role in coronary artery disease independent of cholesterol levels. The gene also likely has roles in related cardiovascular diseases, including high blood pressure and diabetes.

The study appears March 24 in the journal Science Translational Medicine.

Studying mice and genetic data from people, the researchers found that the gene called SVEP1 makes a protein that drives the development of plaque in the arteries. In mice, animals missing one copy of SVEP1 had less plaque in the arteries than mice with both copies. The researchers also selectively reduced the protein in the arterial walls of mice, and this further reduced the risk of atherosclerosis.

Evaluating human genetic data, the researchers found that genetic variation influencing the levels of this protein in the body correlated with the risk of developing plaque in the arteries. Genetically determined high levels of the protein meant higher risk of plaque development and vice versa. Similarly, they found higher levels of the protein correlated with higher risk of diabetes and higher blood pressure readings.

Cardiovascular disease remains the most common cause of death worldwide, said cardiologist Nathan O. Stitziel, MD, PhD, an associate professor of medicine and of genetics. A major goal of treatment for cardiovascular disease has appropriately been focused on lowering cholesterol levels. But there must be causes of cardiovascular disease that are not related to cholesterol or lipids in the blood. We can decrease cholesterol to very low levels, and some people still harbor residual risk of future coronary artery disease events. Were trying to understand what else is going on, so we can improve that as well.

This is not the first nonlipid gene identified that has been implicated in cardiovascular disease. But the exciting aspect of this discovery is that it lends itself better to developing future therapies, according to the investigators.

The researchers including co-first authors In-Hyuk Jung, PhD, a staff scientist, and Jared S. Elenbaas, a doctoral student in Stitziels lab further showed that this protein is a complex structural molecule and is manufactured by vascular smooth muscle cells, which are cells in the walls of blood vessels that contract and relax the vasculature. The protein was shown to drive inflammation in the plaques in the artery walls and to make the plaques less stable. Unstable plaque is particularly dangerous because it can break loose, leading to the formation of a blood clot, which can cause heart attack or stroke.

In animal models, we found that the protein induced atherosclerosis and promoted unstable plaque, Jung said. We also saw that it increased the number of inflammatory immune cells in the plaque and decreased collagen, which serves a stabilizing function in plaques.

According to Stitziel, other genes previously identified as raising the risk of cardiovascular disease independent of cholesterol appear to have widespread roles in the body and are therefore more likely to have far-reaching undesirable side effects if blocked in an effort to prevent cardiovascular disease. Although SVEP1 is required for early development of the embryo, eliminating the protein in adult mice did not appear to be detrimental, according to the researchers.

The human genetic data showed a naturally occurring wide range of this protein in the general population, suggesting that we might be able to alter its levels in a safe way and potentially decrease coronary artery disease, Elenbaas said.

Ongoing work in Stitziels group is focused on seeking ways to block the protein or reduce its levels in an effort to identify new compounds or possible treatments for coronary artery disease and, perhaps, high blood pressure and diabetes. The researchers have worked with Washington Universitys Office of Technology Management (OTM) to file a patent for therapies that target the SVEP1 protein.

This work was supported in part by grants from the National Institutes of Health (NIH), grant numbers T32GM007200, T32HL134635, T32HL007081, R01HL53325, R01HL131961, UM1HG008853 and UL1TR002345; a career award from the National Lipid Association; and by The Foundation for Barnes-Jewish Hospital.

Jung I, Elenbaas JS, et al. SVEP1 is a human coronary artery disease locus that promotes atherosclerosis. Science Translational Medicine. March 24, 2021.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Scientists find genetic link to clogged arteries Washington University School of Medicine in St. Louis - Washington University School of Medicine in...

DUBLIN--(BUSINESS WIRE)--The "Gene Therapy Market - Growth, Trends, COVID-19 Impact, and Forecasts (2021 - 2026)" report has been added to ResearchAndMarkets.com's offering.

The Gene Therapy Market was estimated to be USD 6,659.93 million in 2020 and is poised to grow at a CAGR of 28.32% by 2026 to reach USD 11,739.75 million.

The COVID-19 pandemic is expected to have a positive effect on the gene therapy market. Gene and cell therapy technology is expected to be used extensively in the development of vaccines used to treat COVID-19. For example, in January 2021, vaccine candidates developed by Mass General Brigham and made by utilizing gene-therapy technology elicited strong immune responses in animal models for the treatment of COVID-19.

The vaccine candidate was named AAVCOVID and the researchers received a USD 2.1 million grant to further develop the technology from the Bill & Melinda Gates Foundation. The vaccine which is being developed is likely to be far more convenient than the ones being sold in the market currently, as it has single-dose and can be stored at room temperature.

Different approaches are being used by other researchers, like those from the University of Pennsylvania. In collaboration with Regeneron, the researchers are using adeno-associated viral vectors to transport lab-made antibodies into the body. These developments are expected to affect market growth in a positive manner.

The factors that drive market growth include technological advancements, rising investments in R&D, and the growing prevalence of target diseases.

Gene therapies are developed for the treatment of diseases by modifying genetic information, which includes inactivating genes that function improperly or replacing a gene, which causes disease with a healthy copy of the gene. Gene therapy is being used to treat several diseases and has shown promising results.

Diseases such as Cystic Fibrosis, Cancer, Heart diseases, Diabetes, AIDS, Hemophilia can be cured by this method of treatment. Gene therapy is usually used to correct the defective gene to cure a specific disease or helps the body better fight against the diseases. There has been an increasing prevalence of many target diseases, such as cancer, rheumatoid arthritis, diabetes, Parkinson's disease, Alzheimer's disease, etc. that have been cured by several gene therapies present already in the market.

There has also been an increase in several genetic and numerous life-threatening disorders, especially heart diseases, AIDS, cystic fibrosis, and age-related disorders. Although gene therapy was initially targeted for inherited diseases, it is now used in the treatment of a variety of acquired problems including cancer and HIV. Initially delivered through viruses, now there are safer direct or biochemical vectors, while in the future nano-particles might deliver the drug of choice directly to the nucleus of affected cells.

For instance, according to the World Health Organization, an estimated 17.9 million people die due to cardiovascular diseases worldwide, each year. This represents 35% of global deaths. As gene therapy provides a complete cure to patients affected with genetic and other life-threatening disorders, rather than ease symptoms that happen with other treatments, it is becoming more popular.

Investment in research and development activities is also expected to have a significant effect on the market. Companies such as Pfizer Inc., are aiming to build a gene therapy platform with a strategy focused on establishing a transformational portfolio through in-house capabilities and enhancing those capabilities through strategic collaborations, expansion of R&D activities, as well as potential licensing and M&A activities.

Competitive Landscape

The global Gene Therapy market is highly competitive and consists of a few major players. Companies like Amgen Inc., Bluebird Bio, Gilead Sciences, Inc., Novartis AG, Orchard Therapeutics, Sibiono GeneTech Co. Ltd., Spark Therapeutics (Roche AG), and UniQure N.V., among others, hold the substantial market share in the Gene Therapy market.

Key Topics Covered:

1 INTRODUCTION

1.1 Study Assumptions and Market Definition

1.2 Scope of the Study

2 RESEARCH METHODOLOGY

3 EXECUTIVE SUMMARY

4 MARKET DYNAMICS

4.1 Market Overview

4.2 Market Drivers

4.2.1 Rising Investments in the R&D

4.2.2 Technological Advancements

4.2.3 Growing Prevalence of Target Diseases like Cancer

4.3 Market Restraints

4.3.1 Lack of Standard Regulations

4.3.2 High Price of Products

4.4 Porter's Five Force Analysis

5 MARKET SEGMENTATION

5.1 By Indication

5.1.1 Cancer

5.1.2 Metabolic Disorders

5.1.3 Eye Disorders

5.1.4 Spinal Muscular Atrophy

5.1.5 Other Indications

5.2 By Technology

5.2.1 Adeno Virus Vector

5.2.2 Adeno-associated Virus Vector

5.2.3 Lentiviral Vector

5.2.4 Retroviral Vector

5.2.5 Herpes Virus Vector

5.2.6 Others

5.3 Geography

6 COMPETITIVE LANDSCAPE

6.1 Company Profiles

6.1.1 Amgen Inc.

6.1.2 Biogen Inc.

6.1.3 Bluebird Bio Inc.

6.1.4 Gilead Sciences, Inc. (Kite Pharma)

6.1.5 Novartis AG

6.1.6 Orchard Therapeutics

6.1.7 Sibiono GeneTech Co. Ltd.

6.1.8 Spark Therapeutics (Roche)

6.1.9 UniQure N.V.

6.1.10 Abeona Therapeutics

6.1.11 Generation Bio

6.1.12 Poseida Therapeutics

6.1.13 Astellas Pharma

6.1.14 Voyager Therapeutics

6.1.15 Elevate Bio

6.1.16 Editas Medicine

7 MARKET OPPORTUNITIES AND FUTURE TRENDS

For more information about this report visit https://www.researchandmarkets.com/r/j0vxpt

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$11.73 Billion Gene Therapy Markets - Global Growth, Trends, COVID-19 Impact, and Forecasts 2021-2026 - ResearchAndMarkets.com - Business Wire

uniQure announced findings from a comprehensive investigation into a case of hepatocellular carcinoma (HCC) diagnosed in one patient in the HOPE-B pivotal trial of etranacogene dezaparvovecthe conclusion was it was highly unlikely the HCC was caused by the gene therapy.

Etranacogene dezaparvovec is being evaluated for hemophilia B. The therapy consists of an AAV5 viral vector carrying a gene cassette with the Padua variant of Factor IX.

An investigation was conducted by an independent laboratory and reviewed by leading external experts in the field. These data showed the AAV vector that had integrated into the patients tissue samples was extremely rare, making up only 0.027% of the cells in the sample. They were evenly distributed apparently randomly across the patients genome, with no evidence of clonal expansion or any dominant integration event.

Whole genome sequencing of the tumor also confirmed that the patient had several genetic mutations often associated with HCC and are not linked with the integration of the gene therapy vector. Also, an analysis of the tumor gene expression as well as adjacent tissue indicated a precancerous state in the liver that is consistent with risk factors that predispose the patient to HCC.

This investigation has employed several complementary genomic approaches to evaluate the involvement of the AAV vector in the development of the liver cell cancer in this patient, said David Lillicrap, professor of the Department of Pathology and Molecular Medicine, Queens University, Kingston, Canada. The investigations that have been performed have shown no evidence to suggest that the AAV vector delivered in the HOPE-B study has played a pathogenic role in the hepatocellular cancer that has now been diagnosed in the patient.

In December 2020, the U.S. Food and Drug Administration (FDA) placed a clinical hold on the companys program after the patient was diagnosed with HCC during a routine one-year follow-up. It was confirmed by surgical resection and biopsy with additional analysis to decide if the drug had integrated into the tumor and if the integration caused the cancer. The patient was at high risk for liver cancer with a long history of hepatitis C, hepatitis B, non-alcoholic fatty liver disease and advanced age. Chronic infections with hepatitis B and C are associated with about 80% of HCC cases.

The external lab analyzed more than 220,000 cells from the tissue sample and identified 60 cells with random integration events that have no known association with the development of HCC, said Ricardo Dolmetsch, president of research and development at uniQure. Moreover, whole genome sequencing of the tumor showed that this patient had large abnormalities on chromosomes 1 and 8 that are commonly associated with HCC, as well as mutation of TP53 and several other potentially oncogenic genes.

He went on to say, Taken together, the findings from this investigation strongly suggest that etranacogene dezaparvovec did not contribute to this case of HCC. We have now shared these data with the FDA and are prepared to have further communications regarding the status of the clinical hold in the second quarter of 2021. We also expect to submit the data for presentation at an upcoming industry conference yet to be determined.

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uniQure Investigation Clears Hemophilia B Gene Therapy of Causing Liver Cancer - BioSpace

DUBLIN, March 30, 2021 /PRNewswire/ -- The "Pharmaceutical Contract Development and Manufacturing Market (Pharmaceutical, Biologics, Active Pharma ingredients, tablet, Parenteral, Oral Liquid, Semi-Solids), End User (Big Pharma, Small Pharma, Generic Pharma, CRO) - Global Forecast to 2025" report has been added to ResearchAndMarkets.com's offering.

The global pharmaceutical contract development and manufacturing market are projected to reach USD 146.1 billion by 2025 from USD 100.7 billion in 2020, at a CAGR of 7.7% during the forecast period.

Market growth is driven mainly by factors such as rising demand for generics, increasing investments in pharmaceutical R&D, and investments in advanced manufacturing technologies by CDMOs. The increasing demand for biological therapies, growing focus on specialty medicines, growth in the nuclear medicines sector, and advancements in cell and gene therapies are also expected to offer market growth opportunities in the coming years.

The small and medium-sized pharmaceutical companies segment accounted for the highest growth rate in the pharmaceutical contract development and manufacturing market, by end user, during the forecast period

The pharmaceutical contract development and manufacturing market is segmented into big pharmaceutical companies, small & medium-sized pharmaceutical companies, generic pharmaceutical companies, and other end users. The small and medium-sized pharmaceutical companies segment accounted for the highest growth rate in the pharmaceutical contract development and manufacturing market in 2020. This segment's high growth can be attributed to the increasing number of emerging pharmaceutical companies that lack the in-house capabilities to manufacture and develop complex formulations and drug products.

Biologics manufacturing services segment accounted for the highest CAGR

Based on service, the pharmaceutical contract development and manufacturing market is segmented into pharmaceutical manufacturing, biologics manufacturing, and drug development services. In 2020, the biologics manufacturing services segment accounted for the highest growth rate. The major factor driving the growth of this segment is the growing demand for vaccines and biosimilars.

Asia Pacific: The fastest-growing country in the pharmaceutical contract development and manufacturing market

The pharmaceutical contract development and manufacturing market is segmented into North America, Europe, Asia Pacific, Latin America, and the Middle East & Africa. Asia Pacific is projected to register the highest CAGR during the forecast period. This growth can be attributed to factors such as growth in the manufacturing sector, favorable government regulations, growing strategic expansions from leading companies, increasing emphasis on off-patent drugs, and the presence of a highly skilled workforce.

Market Dynamics

Drivers

Opportunities

Challenges

Trends

Value Chain Analysis

Ecosystem Market Map

Supply Chain

Impact of the COVID-19 Pandemic on the Growth of the Pharmaceutical Contract Development and Manufacturing Market

Regulatory Assessment

Lists of Companies Profiled in the Report:

For more information about this report visit https://www.researchandmarkets.com/r/4e33lg

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

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Pharmaceutical Contract Development and Manufacturing Markets, 2025: Increasing Demand for Biological Therapies / Growth in the Nuclear Medicine...

BEDFORD, Mass.--(BUSINESS WIRE)--Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to addressing the underlying cause of severe diseases by up-regulating protein expression with RNA-based medicines, today announced the authorization of its Clinical Trial Application (CTA) by the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a Phase 1/2a study (ADMIRAL) of STK-001 for the treatment of Dravet syndrome.

STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome, a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures that usually begin within the first year of life. Dravet syndrome is classified as a developmental and epileptic encephalopathy resulting in developmental delay and cognitive impairment, in addition to seizure activity, that arise from the genetic mutation that causes the disease.

We are making excellent progress with our ongoing studies of STK-001 in the U.S. The high level of interest from the Dravet community underscores the urgent need for new treatment options that go beyond seizure control, said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. The ADMIRAL study complements our U.S.-based MONARCH study, enabling the evaluation of higher dose levels of STK-001 and representing an initial step in the expansion of our global clinical development efforts. Together, we anticipate that these studies will generate a comprehensive set of data that will inform our future development plans. We look forward to working with the U.K. Dravet community patients, families and healthcare providers to add to our understanding of the potential for STK-001 to be the first disease-modifying therapy for Dravet syndrome.

ADMIRAL is an open-label, multi-center, Phase 1/2a study designed to assess the safety and tolerability of multiple doses of up to 70mg of STK-001, as well as to characterize human pharmacokinetics. Secondary endpoints include change in seizure frequency and quality of life measures. The study is expected to enroll approximately 22 children and adolescents with Dravet syndrome across multiple clinical sites in the United Kingdom. Patient enrollment and dosing are expected to start in the second half of 2021.

Current treatments for Dravet syndrome help us manage seizures, but some of the most devastating effects of the disease such as developmental and intellectual disabilities are not addressed by current therapies, said Professor Helen Cross, Honorary Consultant in Paediatric Neurology at Great Ormond Street Hospital for Children NHS Foundation Trust. There is great hope that a new approach, such as STK-001, that targets the root cause of the disease, may address the seizures as well as the myriad of devastating comorbidities that have impacts on patients and their families. Im pleased to be helping lead the effort to bridge the treatment gap by conducting the first study of STK-001 in the U.K. as the lead investigator for the ADMIRAL study.

MONARCH Phase 1/2a Clinical Trial is Ongoing in the United States

Enrollment of children and adolescents in the first two single ascending dose (SAD) cohorts (10mg and 20mg) is complete and enrollment and dosing in the third (30mg) SAD cohort is underway. Dosing above 30mg in this study remains on partial clinical hold with the U.S. Food and Drug Administration (FDA). Preliminary safety and pharmacokinetic data from the SAD portion of the MONARCH study are expected in the second half of 2021.

In addition, enrollment and dosing in the multiple ascending dose (MAD) portion of the MONARCH study is underway at the 20mg dose level. Patients who participated in the MONARCH study are eligible to continue treatment in SWALLOWTAIL, an open label extension (OLE) study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001. Enrollment and dosing in SWALLOWTAIL are underway.

About STK-001

STK-001 is an investigational new medicine for the treatment of Dravet syndrome and is being evaluated in a Phase 1/2a clinical trial. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to up-regulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-001. STK-001 has been granted orphan drug designation by the FDA as a potential new treatment for Dravet syndrome.

About the Phase 1/2a MONARCH Clinical Study (United States)

The MONARCH study is a Phase 1/2a open-label study of children and adolescents ages 2 to 18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study are to assess the safety and tolerability of STK-001, as well as to characterize human pharmacokinetics. A secondary objective is to assess the effect as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency over a 12-week treatment period. Stoke also intends to measure non-seizure aspects of the disease, such as quality of life, as secondary endpoints. Enrollment and dosing are ongoing in MONARCH and Stoke plans to enroll approximately 48 patients in the study across 20 sites in the United States.

Additional information about the MONARCH study can be found at https://www.monarchstudy.com/.

Patients who participated in the MONARCH study are eligible to continue treatment in SWALLOWTAIL, an open label extension (OLE) study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001. Enrollment and dosing in SWALLOWTAIL are underway.

About the Phase 1/2a ADMIRAL Study (United Kingdom)

The ADMIRAL study is a Phase 1/2a open-label study of children and adolescents ages 2 to <18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study are to assess the safety and tolerability of multiple doses of STK-001, as well as to characterize human pharmacokinetics. A secondary objective is to assess the effect of multiple doses of STK-001 as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency over a 24-week treatment period. Stoke also intends to measure non-seizure aspects of the disease, such as overall clinical status and quality of life, as secondary endpoints. Stoke plans to enroll approximately 22 patients in the study across multiple sites in the United Kingdom.

About Dravet Syndrome

Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often include severe intellectual disabilities, severe developmental disabilities, motor impairment, speech impairment, autism, behavioral difficulties and sleep abnormalities. The disease is classified as a developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Approximately 85% of those diagnosed with Dravet syndrome have a mutation of the SCN1A gene. Dravet syndrome affects approximately 35,000 people in the United States, Canada, Japan, Germany, France and the United Kingdom, and it is not concentrated in a particular geographic area or ethnic group.

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to addressing the underlying cause of severe diseases by up-regulating protein expression with RNA-based medicines. Using the companys proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach Stoke is developing antisense oligonucleotides (ASOs) to selectively restore protein levels. The companys first compound, STK-001 is in clinical testing for the treatment of Dravet syndrome, a severe and progressive genetic epilepsy. Dravet syndrome is one of many diseases caused by a haploinsufficiency, in which a loss of ~50% of normal protein levels leads to disease. The company is pursuing treatment for a second haploinsufficient disease, autosomal dominant optic atrophy (ADOA), the most common inherited optic nerve disorder. Stokes initial focus is haploinsufficiencies and diseases of the central nervous system and the eye, although proof of concept has been demonstrated in other organs, tissues, and systems, supporting the companys belief in the broad potential for its proprietary approach. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow the company on Twitter at @StokeTx.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: enrollment in the ADMIRAL study and the studys ability to support our clinical development plans; our expectation about timing and execution of anticipated milestones; our ability to use ADMIRAL or MONARCH study data to advance the development of STK-001; the ability of STK-001 to treat the underlying causes of Dravet syndrome and the expected benefits thereof; and the ability of TANGO to design medicines to increase protein production and the expected benefits thereof. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize STK-001, any potential clinical candidate for OPA1 and future product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities and activities in international jurisdictions; the risk that regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; failure to protect and enforce our intellectual property and other proprietary rights; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; failure to comply with legal and regulatory requirements in the United States and abroad; and the other risks and uncertainties that are described in the Risk Factors section of our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this press release. We do not undertake any obligation to publicly update any forward-looking statements.

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Stoke Therapeutics Announces MHRA Authorization to Initiate Phase 1/2a Clinical Trial of STK-001 for Dravet Syndrome in the United Kingdom - Business...

CAMBRIDGE, Mass., March 30, 2021 /PRNewswire/ --Omega Therapeutics, Inc. ("Omega"), a development-stage biotechnology company leveraging its proprietary epigenomic programming platform to biologically engineer a new class of programmable epigenetic medicines, today announced the closing of an upsized Series C financing of $126 million. Joining Flagship Pioneering, Omega's institutional founder and principal backer, are leading life science investors including Invus, Fidelity Management & Research Company, funds and accounts managed by BlackRock, Cowen, Point72, Logos Capital, Mirae Asset Capital and other undisclosed new and returning institutional investors. With this financing, Omega has raised over $210 million since its founding in 2017.

Proceeds from the financing will be used to support the advancement of Omega's lead epigenomic controller candidate, OTX-2002, and to advance the next wave of novel pipeline therapeutics that it expects to be generated by the company's proprietary Omega Epigenomic ProgrammingTM platform, with an initial focus in oncology, regenerative medicine, inflammation, autoimmune, metabolic and rare genetic diseases. The proceeds will also be used to continue developing the Omega Epigenomic Programming platform and build a manufacturing footprint.

"We are grateful to our new and existing investors for the commitment to our bold vision of creating the industry's first fully programmable epigenetic medicines," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "This financing enables us to advance OTX-2002 through the required IND-enabling studies with the goal of filing an IND and entering the clinic thereafter. It also allows us to continue unlocking the potential of our Omega Epigenomic Programming platform where we expect to be unveiling several additional drug candidates addressing a wide range of high unmet need diseases during 2021."

"Omega is at a pivotal stage of its development, as it prepares to debut several new pipeline assets and advance each toward clinical trials. We look forward to partnering with our new and existing investors to build out a robust pipeline, bring exciting new medicines to patients in need, and significantly grow value for all of our stakeholders," commented Roger Sawhney, Chief Financial Officer of Omega Therapeutics.

"In a short three years since its founding, Omega has made significant progress by leveraging its deep expertise of nature's universal operating system for gene control to power its Omega Epigenomic Programming platform," said Noubar Afeyan, Ph.D., Co-founder and Chairman of the Board for Omega Therapeutics and Chief Executive Officer of Flagship Pioneering. "We welcome this exceptional group of new investors as Omega continues to pioneer and works to establish a new class of transformative programmable medicines."

In January 2021, Omega unveiled OTX-2002, its first epigenomic controller development candidate and the industry's first programmable epigenetic medicine. OTX-2002 is engineered to specifically control c-myc (MYC) oncogene expression. In preclinical models of hepatocellular carcinoma (HCC), OTX-2002 potently downregulated MYC expression, a result that has historically eluded many prior attempts and therapeutic approaches. The Company is currently advancing OTX-2002 into Investigational New Drug (IND)-enabling studies. Omega plans to nominate additional development candidates in 2021, with an initial focus on regenerative medicine, inflammatory diseases, acute respiratory distress syndrome (ARDS) associated with COVID-19, alopecia, neutrophilic dermatoses, non-small cell lung cancer (NSCLC) and an additional oncogene target.

About Omega Epigenomic Programming Platform and Omega Epigenomic Controllers

Omega Therapeutics leverages its pioneering Epigenomic Programming platform to identify novel targets, develop first-in-class programmable epigenetic medicines, and enable rational drug development and manufacturing. Omega examines Insulated Genomic Domains (IGDs), the three-dimensional architecture of the human genome and its accompanying regulators, and has identified and classified thousands of genomic "zip codes" across the ~15,000 IGDs as new drug targets. Omega's new class of medicine, called Omega Epigenomic Controllers, modulate IGDs using therapeutics that can be programmed to precisely up or down regulate single or multi-gene expression with controlled durability. These epigenomic controllers intervene at the pre-transcriptional level and they function without altering the native human genetic code or nucleic acid sequences. Using a rational and robust target identification and validation process, enhanced by a strong computational and data driven foundation, Omega is able to efficiently design and optimize potential epigenomic controllers from its platform. This entirely new and breakthrough approach allows the Company's product candidates to also drug previously 'undruggable' targets across a broad range of diseases.

About Omega Therapeutics

Omega Therapeutics is a privately held, development-stage biotechnology company leveraging its proprietary epigenomic programming platform to biologically engineer a new class of programmable epigenetic medicines, known as Omega Epigenomic Controllers. Using these epigenomic controllers, Omega is seeking to transform the practice of human medicine through highly selective and direct control of the human genome to treat and cure disease.Omega's breakthrough science has enabled it to safely and precisely tune genomic expression of single, multiple, and historically 'undruggable' gene targets, to desired therapeutic levels with high specificity and durability of effect. Omega Therapeutics was founded by Flagship Pioneering in 2017 and currently has eight programs in various stages of preclinical development. The Company is strategically pursuing specific disease targets that have not been successfully addressed through conventional modalities, including certain oncology indications, liver disease, serious inflammatory conditions, and acute respiratory distress syndrome (ARDS) among others. Omega's mission is to deliver the transformative therapies of tomorrow.

For more information, visit omegatherapeutics.com, or follow us on Twitterand LinkedIn.

Investor contact:Joseph RayneArgot Partners212.600.1902joseph@argotpartners.com

Media contact:David RosenArgot Partners212.600.1902david.rosen@argotpartners.com

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Antitrust regulators are seeking to block the $7 billion deal by gene-sequencing supplier Illumina to acquire Grailthe company at the forefront of efforts to screen for many kinds of cancer with a blood test. The Federal Trade Commission filed an administrative action Tuesday afternoon to stop the merger, which it alleges would stifle innovation and raise prices for such multi-cancer early detection tests.

In a roughly flat stock market Tuesday, the news sent Illumina stock (ticker: ILMN) down 6.6%, to a $368.96 close.

Grail was spun off in 2016 by Illumina to develop cancer detection tests based on Illuminas gene sequencing technology. Last year, Grail reported that its liquid biopsy blood screen could find up to 50 kinds of cancers, many of which lack any current screen. In September, Grail filed a registration for an initial public offering. But before the IPO went effective, Grail agreed to Illuminas deal to buy the 85% of Grail it doesnt own. Grail plans to launch its test under the name Galleri in the second quarter of this year.

In the FTCs announcement, the agency said that Grail was one of several competitors racing to develop cancer-screening blood tests. Like Grail, the rivals use Illuminas DNA sequencers and supplies, which the FTC said are the industrys only viable option. The agency warned that Illumina would be in a position to delay Grails rivals and raise the price of a critical input.

The value of cancer-screening tests could be enormous. The vast majority of cancers, which account for about 80 percent of cancer deaths, are only detected after patients exhibit symptoms. That is often too late to treat effectively, said the FTCs acting chairwoman Rebecca Kelly Slaughter, in the release. She called such tests a game changer for cancer patients and their loved ones.

Illumina vowed to vigorously defend the deal in administrative court and federal district court. We strongly believe that bringing the two companies together will accelerate patient access to this breakthrough, chief executive Francis deSouza told Barrons. We could save tens of thousands more lives every year than we would if the two companies were separate.

We also believe that this deal will save billions of dollars in U.S. healthcare costs, said deSouza. It is our intent to pass those savings on to patients. Illuminas resources would speed regulatory approvals for Grail and clear a path for Grails rivals to bring their tests to market, he said.

Grails tests wouldnt be the first products that Illumina has marketed in competition with customers who use its sequencers. In 2013, Illumina began offering prenatal genetic tests and, more recently, began offering sequencing-based therapy selection tests for cancer patients. In both cases, deSouza said, competitors have multiplied, sequencing costs have declined, and the market has expanded for everyone.

To allay concerns of Grails cancer-testing rivals, Illumina says that it has offered contractual guarantees of equal access and pricing on its sequencing supplies, with a commitment to drive down prices by more than 40% by 2025.

The FTC wasnt persuaded by Illuminas arguments in the investigation ahead of Tuesdays vote, in which the commissioners agreed 4-to-0 to authorize the staff to seek a temporary restraining order in the U.S. District Court for the District of Columbia. A trial is scheduled to begin in August.

The governments case wont be easy. Illumina says that its combination with Grail is whats called a vertical merger because they compete in separate industries. The government has only gone to court once in the last 40 years to challenge a vertical merger when AT&T agreed to acquire Time Warner. The government lost.

Illumina has come to dominate the market for gene sequencingthat is, reading the DNA code of living thingsby drastically reducing the technologys cost and increasing its speed, over the last decade and a half.

It is those sequencing economies that encouraged the development of genetic screens for cancer. Several companies offer liquid biopsies for already diagnosed cancer patients. They include the Foundation Medicine unit of Roche Holding (RHHBY), Guardant Health (GH), Natera (NTRA), Invitae (NVTA), and Chinas Burning Rock Biotech (BNR).

Racing Grail to perfect multi-cancer early-detection tests is Exact Sciences (EXAS). It paid $2 billion last year to acquire Thrive Earlier Detection, which reported on the first clinical trial of a multi-cancer screen in early 2020.

Write to editors@barrons.com

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The FTC Wants to Block Illumina's Deal For Cancer-Test Pioneer - Barron's

CAMBRIDGE, Mass. & MONTREAL--(BUSINESS WIRE)--Repare Therapeutics Inc. (Repare or the Company) (Nasdaq: RPTX), a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics, today announced it will host a virtual Investor Day on Thursday, April 8, 2021, from 10:30 a.m. to 12:00 p.m. Eastern Time. Repare Therapeutics executive management team will be joined by two distinguished physicians:

The event will focus on RP-6306, a potent and selective inhibitor of a novel target that is synthetic lethal with CCNE-1 amplification. The Company expects to begin a Phase 1 clinical trial in the second quarter of 2021, one quarter earlier than prior guidance.

To access the event virtual event, please dial (833) 638-9655 (U.S. and Canada) or (602) 585-9856 (international) at least 10 minutes prior to the start time and refer to conference ID 1093819. A live video webcast will be available in the Investor section of the Companys website at https://ir.reparerx.com/news-and-events/events. A webcast replay will also be available on the corporate website at the conclusion of the call.

About RP-6306

RP-6306 is the result of Repares proprietary drug discovery program for tumors with genetic alterations characterized by CCNE1 amplification, which typically do not respond well to platinum or PARP inhibitor treatment. Through Repares SNIPRx screen campaign for targets that are SL with CCNE1 amplification, the Company has identified and validated a novel SL gene that is believed to have the characteristics of a therapeutic target. Subsequently, the Company developed novel and selective inhibitors against the target that have repeatedly demonstrated compelling anti-tumor activity and announced the advancement of a clinical candidate for this potential first-in-class program. Repare anticipates initiating a Phase 1 clinical trial for RP-6306 in the second quarter of 2021. This trial is expected to enroll patients suffering from recurrent tumors characterized by CCNE1 amplification and other genomic alterations predicted to be sensitive to RP-6306. The primary objective of the trial is to establish the recommended Phase 2 dose and schedule for RP-6306 for further studies as monotherapy and to assess preliminary safety in patients. An additional trial is planned to evaluate combination with approved anticancer agents.

About Repare Therapeutics, Inc.

Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics. The Company utilizes its genome-wide, CRISPR-enabled SNIPRx platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair. The Companys pipeline includes its lead product candidate RP-3500, a potential best-in-class ATR inhibitor currently in Phase 1/2 clinical development, as well as RP-6306, a CCNE1-SL inhibitor, and a Pol inhibitor program. For more information, please visit reparerx.com.

SNIPRx is a registered trademark of Repare Therapeutics Inc.

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Repare Therapeutics to Introduce RP-6306, a Potent and Specific Inhibitor of a Novel Target, at Virtual Investor Day on April 8 - Business Wire

When Omega Therapeutics pulled back the curtains for a peek at its work last summer, it revealed a new class of medicines that regulate genes and address undruggable targets. The startup has since offered some additional details about its plans and on Tuesday it unveiled $126 million to back a lead program making progress against an elusive cancer target, potentially paving the way for more drugs that work in the same manner.

The new cash, a Series C round of funding, comes eight months after Cambridge, Massachusetts-based Omega raised $85 million.

Most drugs work by binding to a site on a target and either blocking that molecule from doing something or sparking a desired therapeutic effect. Like a light switch, theyre either off or on. Omega Therapeutics is developing medicines that it calls epigenomic controllers. These drugs are more like a programmable dimmer switch that can be set to dial the activity of a gene up or down.

We tune it up or down to the right level, not on or off, CEO Mahesh Karande said. We tune it to right biological level to resolve the condition.

An Omega drug binds to three-dimensional structures on DNA called insulated genomic domains (IGDs). The companys technology has identified about 15,000 IGDs that have been classified as drug targets. The gene-regulating drugs are fusion proteins, comprised of a targeting protein that directs the therapy to its genetic destination and an epigenomic effector that regulates the genes activity. This approach does not alter the genetic code or nucleic acid sequences. The Omega drugs are delivered via lipid nanoparticles.

Omega announced its lead epigenomic controller candidate, OTX-2002, during the J.P. Morgan Health Care Conference. The drug aims to regulate c-myc, a gene whose excessive activity has been linked to the spread of up to 50% of cancers, according to Omega.

When [myc] goes out of whack in cancer, it leads to proliferation of cancer cells and uncontrolled growth, Karande said. Those cancer cells become over dependent on myc and grow out of control.

However, the myc protein has proven to be an elusive drug target. It doesnt have binding pockets where small molecule drugs typically attach. Also, this protein is found on the inside of cells, making it unsuitable for drugging with antibodies that bind to targets on a cells surface.

Biotech companies have tried other ways to drug myc. Dicerna Pharmaceuticals of Lexington, Massachusetts, used RNA interference, an approach intended to stop a gene from producing a disease-causing protein. For a time, Dicernas myc drug was the companys lead program. That candidate was a potential treatment for a hepatocellular carcinoma, a type of liver cancer characterized by amplification of myc. In 2016, the biotech stopped work on its myc drug, saying preliminary clinical results did not meet expectations.

Myc is a tricky target, and not just because its hard to get a molecule to bind to it. Healthy cells rely on the gene, too, so completely turning it off might stop its role in cancer but could also lead to problems elsewhere, Karande said. Rather than turning myc off, Omegas approach tunes down the myc genes activity. Liver cancer is OTX-2002s disease target. Karande said that the company wanted a liver indication because lipid nanoparticles have already demonstrated that they can deliver therapies to the liver. Furthermore, the company wanted a lead indication in oncology.

In preclinical research in hepatocellular carcinoma, Omega said its drug potently downregulated myc expression. The company is advancing its drug toward clinical trials, though Karande declined to say when human testing is expected to start.

Chief Financial Officer Roger Sawhney said that the new capital will support further development of Omegas lead drug candidate. The company also plans to build a manufacturing site, giving the company both control and flexibility. Some of the funds will support development of the rest of Omegas drug pipeline, which encompasses regenerative medicine, inflammatory disorders, acute respiratory distress associated with Covid-19, alopecia, neutrophilic dermatoses, non-small cell lung cancer, and an additional undisclosed oncogene target.

What Omega will not be doing is testing OTX-2002 against multiple cancers the way many companies assess their drug candidates. The IGDs that Omegas drug targets are found everywhere in the body but Karande said that the same IGD will function differently in different tissues and cell types. That means a gene-regulating drug for lung cancer would require a different configuration than the one OTX-2002 uses for liver cancer. He added that Omegas technology enables it to engineer these configurations quickly.

Omegas latest round of funding included investment from Flagship Pioneering, the venture capital firm that founded the company and is its main financial backer. Other participants in the round included Invus, Fidelity Management & Research Company, funds and accounts managed by BlackRock, Cowen, Point72, Logos Capital, Mirae Asset Capital and other undisclosed investors.

Karande acknowledged that an IPO has crossed his mind, but he said Omega is looking at multiple ways to finance its work. Because the companys technology is a platform that could support dozens of programs in many therapeutic areas, Karande said Omega is exploring partnerships with larger companies as another way to further advance the startups research.

Image by Flickr user Ed Uthman via a Crreative Commons license

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Omega Therapeutics adds $126M to move programmable drugs closer to the clinic - MedCity News