Category Archives: Genetic medicine

CAMBRIDGE, Mass., Oct. 27, 2021 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, will report third quarter 2021 financial results after the Nasdaq Global Market closes on Wednesday, November 3, 2021. Subsequently, at 4:30 p.m. E.T., the Company will host a conference call to discuss its third quarter 2021 financial results and to provide a corporate update.

The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 7131019. Please specify to the operator that you would like to join the "Sarepta Third Quarter 2021 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

About Sarepta TherapeuticsSarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visitwww.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of InformationWe routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Investor Contact: Ian Estepan, 617-274-4052iestepan@sarepta.com

Media Contact: Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

Excerpt from:
Sarepta Therapeutics to Announce Third Quarter 2021 Financial Results and Recent Corporate Developments on November 3, 2021 - GlobeNewswire

GlaxoSmithKlines shingles vaccine Shingrix delivered a stellar quarter, but thanks in part to thedelta variant, it doesnt look like the shot will recover to last years levels.

Shingrix sales soared 41% at constant exchange rates to 502 million in the third quarter, which came 22% ahead of industry watchers expectations. It was an unusual performance given U.S. scripts remain way below last years levels.

To hear GSKs pharma chief Luke Miels tell it, the growth didnt come from people actually getting the vaccine from retail pharmacies. Instead, the showing was fueled by wholesale inventory buildingand a large proportion of injections came from doctors offices.

For the entire year, GSK expects Shingrix sales to follow a similar pattern as it had in the first nine months combined, which was a decline of around 11%, as many people prioritized their COVID-19 vaccinations.

RELATED:GlaxoSmithKline's 'much-needed' Shingrix rebound has yet to materialize, analysts say

Shingrixs drop indemand clearly correlated with a surge in the delta variant as people didnt want to go to retail pharmacies, Miels said during a conference call Wednesday. But the trend is pointing to recovery. In GSKs market research, among people who were fully vaccinated for COVID-19, a shingles vaccine was listed as the second shot they most wanted to get, behind a flu vaccine, Miels said.

When retail pharmacies started prioritizing COVID vaccinations, GSK made what then seemed like a risky move but is now paying off, Miels explained: It assigned themarketing team forrespiratory disease inhalation Trelegy to target doctors and promote the shingles vaccine. There may be some under-reporting of scripts at doctors offices, he noted.

Considering those factors and launches outside the U.S.,GSK is confident in Shingrixs recovery, Miels said. For 2022, GSK sees a record year for Shingrix with double-digit sales growth, he said. For the longer term, the company believes Shingrix could double its revenue in five years from 2020.

RELATED:GlaxoSmithKline to leave landmark global HQ after split-up as consumer health business plots 120M new home

Elsewhere in GSKs portfolio, Trelegy chalked up an impressive 77% sales increase in the third quarter to 326 million. The drug still holds 90% share in the three-in-one inhaler market in the U.S. despite the introduction of AstraZenecas rival Breztri a year ago.

The companys novel two-drug HIV regimen Dovato chipped in 110 million during the three months,more than doubling its sales from last year. Despite the pandemic suppressing overall drug switching, Dovato has gained share. Dovato holds 15.3% share of the switch market in the U.S. and 27.8% share in Europe, Deborah Waterhouse, CEO of ViiV Healthcare, told investors during the call.

ViiV is also on track for a major expansion. Cabotegravir, a component used in the companys long-acting HIV treatment Cabenuva, earned an FDA priority review last month as a PrEP option to prevent HIV. The once-monthly injection topped Gilead Sciences Truvada in two separate studies, threatening to disrupt the Big Biotechs billion-dollar monopoly.

RELATED:Spinoff or $54B sale? GlaxoSmithKline's consumer health outfit draws buyout interest: report

The drug portfolio aside, a lot of investor attention atGSK these days focuses on a planned demerger of the consumer health business. Media reports emerged a few days ago that suggested several private equity firms have circled the business for a potential buyout.

We are very committed to the demerger of at least 80% of our holding in consumer,GSK CEO Emma Walmsley said. Were absolutely on the runway for that. Weve had a tremendous amount of positive feedback from investors who are interested in owning this business.

GSK has been under pressure from activist investor Elliott Management to seek another path to separate the consumer health business. The fund has also questioned Walmsleys position at the pharma- and vaccines- focused GSKfor her lack of scientific background.

To increase the scientific expertise for GSKs board, the company on Wednesday said that Hal Dietz, M.D., a professor of genetic medicine at The Johns Hopkins University School of Medicine, will join the board starting first thing next year.

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GlaxoSmithKline: Don't count on a Shingrix rebound this year, but 2022 will bring 'record sales' - FiercePharma

Coagulation disorders refer to conditions that affect how the body controls blood clotting. If a persons blood does not clot, or coagulate, normally, they may experience complications from bleeding too much after injury or surgery or having blockages that prevent blood flow.

Coagulation disorders cause the body to form too many or too few blood clots. They are usually due to a genetic mutation and are often treatable with medications. Coagulation disorders can cause excessive bleeding if the body is unable to form blood clots properly. In other cases, they may cause the body to produce blood clots too readily and increase the risk of blocked blood vessels.

This article will discuss the different types, causes, and treatments of coagulation disorders.

Coagulation disorders are when the body has issues controlling blood clots. Coagulation refers to the process of forming blood clots our bodies rely on this vital process to help prevent excessive bleeding from an injured blood vessel.

Platelets are cell fragments present in the blood that help with the blood-clotting process by gathering at the site of an injury. They combine with proteins in blood plasma to form a blood clot and prevent leakage from the injury. This makes coagulation an important natural defense against injury. However, some people experience coagulation disorders that can result in too much or too little clotting.

Bleeding disorders are where the body is unable to form blood clots properly. These conditions are typically due to issues with blood clotting factors, which are proteins that help blood clots form. This can result in excessive bleeding from not forming enough clots or blockages from producing too much.

Examples of bleeding disorders where the body does not form enough blood clots include hemophilia and von Willebrands disease. Hypercoagulability describes excessive blood clotting, which can disrupt blood flow and increase the risk of problems that include deep vein thrombosis or pulmonary embolism.

People can either inherit or acquire coagulation disorders. This means individuals can get the condition from their parents or develop one during their lifetime, often from another condition or a medicine affecting blood clotting factors.

There are many types of coagulation disorders, including the below.

In rare cases, some people lack other clotting factors that may cause excessive bleeding, such as factors I, II, or V. Some individuals may also experience platelet disorders, which are rare conditions where the body produces too many, too few, or dysfunctional platelets.

People in hypercoagulable states are at risk of venous thromboembolism. This disorder causes blood clots to form in a deep vein that can break away and enter the lungs. In rare cases, individuals in hypercoagulable states could experience a blood clot that causes a heart attack or stroke.

People with bleeding disorders can experience symptoms that include:

Some causes can also lead to additional symptoms. For example, liver disease can cause tiredness, weakness, and a loss of appetite.

Additionally, people in hypercoagulable states could experience symptoms depending on the presence and location of a blood clot. For example, a blood clot near the heart or lungs could cause chest pain, shortness of breath, or discomfort around the upper body. These symptoms could indicate a heart attack or pulmonary embolism.

Symptoms of deep vein thrombosis typically include pain, swelling, and skin discoloring around the area of the blood clot, such as in the legs.

Genetics can cause many types of coagulation disorders. People inherit these genetic changes from their biological parents, or they acquire them after birth. Genes provide instructions for how the body makes blood clots some genetic mutations cause the body to make errors when forming blood clots, which can lead to a disorder.

For example, hemophilia is a condition that people usually inherit from a parent. It is due to a mutation on the X chromosome that affects clotting factors VIII or IX. Males typically possess one X chromosome and one Y chromosome, while females often have two X chromosomes. Due to only having one copy of an X chromosome, males are more likely to develop hemophilia.

Most people with von Willebrands disease inherit a genetic mutation that affects the production of von Willebrand factor. In rare cases, the mutation can occur spontaneously or due to another medical problem without a family history of the condition.

The cause of coagulation disorder is not always clear. For example, vitamin K deficiency bleeding could be due to babies who do not receive a vitamin K shot at birth, have liver or digestive diseases, or have a biological parent who uses certain medications, such as isoniazid.

Some risk factors for coagulation disorders can include:

Doctors will ask about symptoms and check a persons medical history to diagnose coagulation disorders. They will also ask about family members with any coagulation disorders, which could suggest inheritance of the same condition. A physical examination will also help identify visible symptoms, such as bruising and swelling.

If the doctor suspects a coagulation disorder, they will order additional tests to confirm the diagnosis. These could include:

The best treatment approach will depend on the type of coagulation disorder, its severity, and the persons overall health. Treatments typically aim to manage symptoms and reduce the risk of complications. Doctors might recommend one or more medications, including:

Doctors may also recommend other treatments, such as factor replacement therapy. This involves replacing missing clotting factors using blood donations or replacements from a laboratory.

People who experience a blood clot may need emergency care. A catheter-assisted thrombus removal involves a doctor using a flexible tube to break up blood clots they might insert vena cava filters into deep veins to catch blood clots before they travel to the lungs or heart.

It is essential to consult with a doctor about a coagulation disorder. The consequences of forming too few or too many blood clots can become life threatening without treatment.

Some coagulation disorders are present at birth, and a doctor might identify the problem right away. However, healthcare professionals will only screen for a coagulation disorder if there are certain risk factors, such as a biological parent with hemophilia.

It is vital to look out for symptoms and consult with a doctor immediately if there are signs of a coagulation disorder. For example, excessive bleeding, swelling, and easy bruising are all signs of a bleeding disorder.

Venous thromboembolism can also quickly become life threatening. Therefore, it is important for people to contact a doctor immediately if they notice warning signs, such as swelling, pain, and tenderness in the legs.

Coagulation disorders affect the bodys ability to form blood clots they either cause too few or too many blood clots, both of which can have severe consequences. Some coagulation disorders are genetic and can pass down through families. However, people can also acquire them during their lifetime from certain medications or conditions.

Anyone showing signs of a coagulation disorder should contact a doctor right away. Treatments will typically include one or more medications to manage the condition, while some people may need additional treatments, such as factor replacement.

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Coagulation disorders: Causes, symptoms, and treatments - Medical News Today

In genetic medicines, delivery is key. You want to make sure that the medicine reaches its destination in the body and doesnt cause any problems along the way. But before that, you want to ensure that the chosen delivery vehicle has enough room to carry everything it needs for the trip. ReCode Therapeutics is developing technology intended to improve on the capacity and the targeting of genetic medicines, and its first stops are the lungs.

ReCode has two programs on track toward clinical testing and the biotech has raised $80 million to advance those programs and others. Pfizer Ventures and EcoR1 co-led the Series B round of funding announced Thursday.

Many of the genetic medicines that are available as well as some still in development use engineered viruses for delivery. These viruses are very good at getting into a cell, but the body sees them as foreign, so the immune system creates antibodies against them. That means viral delivery can only be used once in a patient. Viruses can also spark dangerous side effects.

ReCode avoids the limitations of viruses by using lipid nanoparticles (LNPs). These particles are made from cholesterol and lipids, a type of fat, so the body is familiar with them, CEO David Lockhart said. That familiarity reduces the risk of an immune response. Furthermore, because LNPs dont cause the immune system to produce antibodies, they can be redosed if needed. Just as important, these particles can be designed to go to specific tissues in the body.

Weve only scratched the surface, Lockhart said. We can do even more with targeted delivery to more cell types, tissue types, beyond the liver, lung, and spleen.

LNPs have a preference for going to the liver. Thats great for genetic medicines for liver diseases, and companies such as Alnylam Pharmaceuticals have used that preference and optimized it for therapies that reach liver cells. Genetic medicines employ three or four lipids in their LNPs. ReCode adds a fifth one. The companys delivery technology comes from the lab of University of Texas Southwestern Medical Center Professor Daniel Siegwart, a co-founder of the company. Lockhart said that adding a fifth lipid changes how the LNP binds to proteins in the blood in way that removes the liver as a target, and enables delivery to other targets in the body. The technology is called Selective Organ Targeting, or SORT. In addition to the ability to target, Lockhart said that ReCodes LNPs offer greater capacity than viruses as well as the ability to carry mixed payloads of genetic cargo.

ReCode has two lead programs that are preclinical. One is for primary ciliary dyskinesia (PCD), a disease that causes dysfunction in cilia, organelles that extend from cells. The other is for cystic fibrosis (CF), a disease that leads to fluid buildup in the lungs. Both have defined genetic causes, but PCD has no treatments and while Vertex Pharmaceuticals has developed drugs that address various genetic mutations, Lockhart noted that about 10% to 13% of CF patients dont respond to those therapies.

ReCode aims to treat PCD and CF by delivering RNA and gene correction therapies. The first therapies that the company is developing are inhaled medicines for delivery to the epithelial cells that line the lung. These therapies wont need to be targeted as inhalation gets the medicine where it needs to go. But Lockhart noted that for some lung disorders, delivery to the endothelial cells that line blood vessels is needed. Those drugs, such as a gene correction CF therapy ReCode is developing, will employ SORT.

The new financing will be used to move both the PCD and CF programs closer to the clinic. Lockhart said that the preclinical research that supports an investigational new drug application (IND) will begin in the first half of next year, followed by an IND filing in the second half. Some of the capital will be used to develop additional programs that are also for respiratory disorders with defined genetic causes.

There are other companies trying to take LNPs beyond the liver. The technology of Georgia Tech spinout Guide Therapeutics screens for LNPs that can be used to deliver RNA to cells throughout the body. Beam Therapeutics saw enough promise in the approach to commit $120 million to acquire the startup earlier this year.

Though the delivery capability of ReCodes technology has applications beyond the lung, the company has no plans to pursue all of them. Lockhart said ReCode will keep respiratory disorders as a focus while exploring partnerships with other companies interested in applying the technology to diseases affecting other parts of the body. In the nearer term, ReCode will be building its own manufacturing capabilities to support its clinical trials.

ReCode raised $80 million in Series A funding last year. The latest financing added new investors Sanofi Ventures, funds managed by Tekla Capital Management, Superstring Capital, and NS Investment. Earlier investors participating in the new round include OrbiMed, Vida Ventures, MPM Capital, Colt Ventures, Hunt Technology Ventures, and Osage University Partners. Though Pfizers venture arm did co-lead the financing, Lockhart said that the pharma giant only gets a board seat and has no inside track to SORT.

Theyre very excited about the technology, he said. They basically want to have a front row seat. We were very clear that there was no coupling of rights, no guarantees of access to the technology.

Photo by ReCode Therapeutics

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ReCode Therapeutics gets $80M to deliver on new RNA therapies for the lungs - MedCity News

CAMBRIDGE, Mass., Oct. 27, 2021 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (SRPT, Financial), the leader in precision genetic medicine for rare diseases, will report third quarter 2021 financial results after the Nasdaq Global Market closes on Wednesday, November 3, 2021. Subsequently, at 4:30 p.m. E.T., the Company will host a conference call to discuss its third quarter 2021 financial results and to provide a corporate update.

The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 7131019. Please specify to the operator that you would like to join the "Sarepta Third Quarter 2021 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

About Sarepta TherapeuticsSarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit http://www.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of InformationWe routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Investor Contact: Ian Estepan, 617-274-4052[emailprotected]

Media Contact: Tracy Sorrentino, 617-301-8566[emailprotected]

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Sarepta Therapeutics to Announ - GuruFocus.com

Sub-retinal delivery of closed-ended DNA (ceDNA) using a retina-specific cell-targeted LNP (ctLNP) demonstrated broad photoreceptor distribution, durable expression and tolerability in rodents; potential to address inherited retinal diseases with full gene replacement

Uniform retinal transduction and tolerability also demonstrated for ctLNP delivery of mRNA following sub-retinal injection in non-human primates; potential best-in-class non-viral delivery of mRNA for gene editing in the retina

CAMBRIDGE, Mass., Oct. 22, 2021 (GLOBE NEWSWIRE) -- Generation Bio Co. (Nasdaq: GBIO), a biotechnology company innovating genetic medicines for people living with rare and prevalent diseases, today presented new preclinical data demonstrating widespread delivery of multiple nucleic acid cargos to photoreceptors using the companys cell-targeted lipid nanoparticle (ctLNP). The findings were shared in an oral presentation at the European Society of Gene and Cell Therapy (ESGCT) 2021 Annual Virtual Congress.

Were excited to extend the benefits of our highly specific, cell-targeted LNP to the retina, where non-viral delivery of nucleic acids has long been held back by poor tolerability and low expression. Our ability to selectively deliver multiple nucleic acid cargos to the retina using ctLNP may allow us to address a variety of inherited retinal diseases using full gene replacement or gene editing, said Matthew Stanton, Ph.D., chief scientific officer of Generation Bio.

Sub-retinal delivery of Generation Bios proprietary closed-ended DNA (ceDNA) using ctLNP demonstrated broad photoreceptor distribution and durable expression in rodents. Expression was comparable to AAV5 delivery, and ctLNP-ceDNA was well-tolerated without evidence of photoreceptor degeneration, supporting the potential for full gene replacement to address inherited retinal diseases.

Data were also presented for sub-retinal delivery of mRNA using ctLNP, representing the first-ever demonstration of species translation from rodents to non-human primates with tolerability and uniform photoreceptor expression. Distribution with ctLNP was broader and more uniform than that achieved with AAV5 in mice, and total expression was comparable to AAV5. These findings suggest ctLNP as a best-in-class non-viral delivery system for mRNA, potentially enabling gene editing in the retina.

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Diseases such as Stargardt cannot be addressed with traditional viral-based genetic therapies due to the limited cargo capacity of the viral vector. We believe these data using our non-viral genetic medicine platform provide a promising path to treat this challenging disease and others like it, and may expand our platforms potential to enable multiple therapeutic modalities, including full gene replacement and gene editing, said Tracy Zimmermann, Ph.D., chief development officer of Generation Bio. "We are excited for the potential for our non-viral delivery technology to expand therapeutic opportunities in the retina as well as to target other tissue types for the treatment of a broad range of diseases.

To view the digital presentation, please visit Generation Bios website.

About Generation BioGeneration Bio is innovating genetic medicines to provide durable, redosable treatments for people living with rare and prevalent diseases. The companys non-viral genetic medicine platform incorporates a novel DNA construct called closed-ended DNA, or ceDNA; a unique cell-targeted lipid nanoparticle delivery system, or ctLNP; and a highly scalable capsid-free manufacturing process that uses proprietary cell-free rapid enzymatic synthesis, or RES, to produce ceDNA. The platform is designed to enable multi-year durability from a single dose, to deliver large genetic payloads, including multiple genes, to specific tissues, and to allow titration and redosing to adjust or extend expression levels in each patient. RES has the potential to expand Generation Bios manufacturing scale to hundreds of millions of doses to support its mission to extend the reach of genetic medicine to more people, living with more diseases, around the world.

For more information, please visit http://www.generationbio.com.

Forward-Looking StatementsAny statements in this press release about future expectations, plans and prospects for the company, including statements about our strategic plans or objectives, our technology platform, our research and clinical development plans, the expected timing of the submission of IND applications and preclinical data, our manufacturing plans, our expectations regarding our new facility and other statements containing the words believes, anticipates, plans, expects, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities, the initiation and completion of preclinical studies and clinical trials and clinical development of the companys product candidates; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; uncertainties regarding the timing and ability to complete the build-out of the companys manufacturing facility and regarding the new manufacturing process; expectations regarding the timing of submission of IND applications; expectations for regulatory approvals to conduct trials or to market products; challenges in the manufacture of genetic medicine products; whether the companys cash resources are sufficient to fund the companys operating expenses and capital expenditure requirements for the period anticipated; the impact of the COVID-19 pandemic on the companys business and operations; as well as the other risks and uncertainties set forth in the Risk Factors section of our most recent annual report on Form 10-K and quarterly report on Form 10-Q, which are on file with the Securities and Exchange Commission, and in subsequent filings the company may make with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the companys views as of the date hereof. The company anticipates that subsequent events and developments will cause the companys views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the companys views as of any date subsequent to the date on which they were made.

Contacts:

InvestorsMaren KillackeyGeneration Bio541-646-2420mkillackey@generationbio.com

MediaAlicia WebbGeneration Bio847-254-4275awebb@generationbio.com

Lisa RaffenspergerTen Bridge Communications617-903-8783lisa@tenbridgecommunications.com

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Generation Bio Presents Data Demonstrating First Lipid Nanoparticle to Achieve Uniform Retinal Transduction and Tolerability via Sub-Retinal Delivery...

image:Dr. Ulrich G. Steidl view more

Credit: Albert Einstein College of Medicine

October 27, 2021(BRONX, NY)Ulrich G. Steidl, M.D., Ph.D., co-director of the Blood Cancer Institute and associate director of basic science at the Albert Einstein Cancer Center (AECC), has received a prestigious Outstanding Investigator Award from the National Cancer Institute (NCI). This award is accompanied by a seven-year, $7 million grant to study the molecular and cellular mechanisms that lead to two related blood diseases, myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Dr. Steidl is one of only 17 recipients of this award in 2021, which is given to accomplished leaders in cancer research who provide significant contributions in their field. The ultimate goal of this research is to develop new treatments and cures for these usually fatal disorders.

Clinical outcomes in MDS and AML have not significantly improved over the past half-century, and cure rates remain below 15% for most patients, said Dr. Steidl, who is also professor of cell biology and of medicine and the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein. There is an urgent need to improve our understanding of how these diseases develop and to devise more effective therapies.

MDS and AML Explained

MDS occurs when blood-forming (hematopoietic) stem cells in the bone marrow acquire genetic and non-genetic irregularities, leading to the production of abnormal, dysfunctional blood cells, which out-compete healthy cells. Common symptoms include anemia, infections, and bleeding.

The incidence of MDS in the United States is unclear, with estimates ranging from 10,000 to 40,000 new cases annually; about one-third of MDS patients will go on to develop AML. Treatment for MDS is generally limited to preventing or reducing complications, particularly severe anemia. The only cure is a bone-marrow transplanta therapy not easily tolerated and therefore often reserved for the youngest, most resilient patients. However, most people diagnosed with MDS are elderly.

AML, like MDS, begins with abnormal bone marrow stem cells. But in AML, those cells, after becoming cancerous, proliferate rapidly and quickly spread to the blood and other hematopoietic organs, such as the bone marrow and spleen, and sometimes to other tissues, causing many of the same symptoms seen in MDS, plus others. AML is often fatal within just a few months and afflicts about 21,000 Americans each year. It is usually treated with chemotherapy. Bone-marrow transplantation can cure AML in some patients.

From Stem Cells to Cancer

Recent studies led by Dr. Steidl and his research team have shown that both MDS and AML arise from pre-leukemic stems cells (pre-LSCs), a subpopulation of blood-forming stem cells that have genetic and non-genetic aberrations. Certain varieties (clones) of these pre-LSCs go on to develop into leukemic stem cells (LSCs)cancer cells that are capable of self-renewal. These LSCs lead to sustained leukemia growth and are particularly resistant to drugs. We now know that the considerable diversity of pre-LSC clones affects the development, progression, and treatment resistance of both MDS and AML, said Dr. Steidl, one of the nations leading authorities on both diseases.

What causes some pre-LSCs but not others to become leukemic is not clear, but transcription factors are thought to play a key role. Transcription factors are proteins that turn specific genes on or off, determining a cells function by regulating the activity of genes. In the case of stem cells, transcription factors guide their differentiation into mature cells. Our recent work has shown that the actions of key transcription factors are dysregulated in pre-LSCs and LSCs, meaning that the transcription factors and the molecular programs they govern behave abnormally, he added.

Thanks to his new NCI grant, Dr. Steidl hopes to:

To accomplish these goals, Dr. Steidls research team will employ novel tools for analyzing stem cell clones in patients, as well as newly developed mouse models of pre-LSC progression to MDS and AML.

Developing New Cancer Therapies

The knowledge we gain from this research should enable us to develop drugs that target pre-LSCs and their aberrant transcription factors, said Dr. Steidl. Such an approach holds the promise of achieving lasting remissions and, ultimately, even cures. Hopefully, our understanding of the early events in the progression of MDS and AML may even allow us in the future to prevent these diseases by interrupting the transformation of pre-LSCs to LSCs before overt leukemia can occur.

The grant (R35CA253127) is titled Molecular and Cellular Regulation of Pre-Leukemic Stem Cells and their Therapeutic Targeting.

***

About Albert Einstein College of Medicine

Albert Einstein College of Medicine is one of the nations premier centers for research, medical education and clinical investigation. During the 2020-21 academic year, Einstein is home to 721 M.D. students, 178 Ph.D. students, 109 students in the combined M.D./Ph.D. program, and 265 postdoctoral research fellows. The College of Medicine has more than 1,900 full-time faculty members located on the main campus and at its clinical affiliates. In 2020, Einstein received more than $197 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States through Montefiore and an affiliation network involving hospitals and medical centers in the Bronx, Brooklyn and on Long Island. For more information, please visit einsteinmed.org, read our blog, followus on Twitter, like us on Facebook, and view us on YouTube.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Albert Einstein Cancer Center researcher receives NCI Outstanding Investigator Award to study two deadly blood diseases - EurekAlert

NEW YORK Delic Labs has entered into a comarketing partnership with GT Research to provide detailed genomic analyses related to commercially interesting traits found in cannabis and psychedelic mushrooms to Canadian producers, its parent company Delic said on Tuesday.

Services provided under the agreement include sample preparation, DNA extraction, whole-genome sequencing, and computational analyses.

Delic Labs, a subsidiary of Delic, focuses on identifying scalable legal psychedelic medicine opportunities. As one of Canada's few licensed psilocybin labs, it applies chemical analytics, metabolomic identification, and process optimization to the psychedelics industry.

GTR performs gene profiling and trait optimization services related to the production of cannabis and psychedelics.

"As the cannabis and psychedelic sectors grow, interest in genomic analysis of the underlying organisms is increasing. GTR is excited to offer its cutting-edge suite of capabilities in partnership with Delic, a pioneer in this space," Sam Proctor, cofounder and CEO of GTR, said in a statement.

"Delic is committed to researching and identifying the safest, highest quality psychedelic compounds for commercial use," said Matt Stang, cofounder and CEO of Delic.

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Delic Partners With GT Research for Genetic Analysis of Cannabis, Psychedelic Mushrooms - GenomeWeb

- Data from mouse models in hereditary tyrosinemia type 1 and Wilson disease showed in vivo edited hepatocytes expanded and substantially repopulated diseased livers, correlating with improvements in disease burden

Published: Oct. 21, 2021 at 7:00 AM CDT

LEXINGTON, Mass., Oct. 21, 2021 /PRNewswire/ --LogicBio Therapeutics, Inc.(Nasdaq:LOGC), a clinical-stage genetic medicine company, today is slated to present new preclinical data on its GeneRide platform at the European Society of Gene and Cell Therapy (ESGCT) Virtual Congress 2021, taking place October 19-22, 2021. The newly presented preclinical data further validate previous research in methylmalonic acidemia (MMA) and highlight selective advantage, a key feature of the GeneRide technology, in two additional indications characterized by intrinsic liver damage, hereditary tyrosinemia type 1 (HT1) and Wilson disease. Selective advantage enables edited hepatocytes carrying the corrective gene to survive and reproduce better than the endogenous mutated hepatocytes and to ultimately repopulate a part or whole of the diseased liver.

The data presented at ESGCT highlighted mouse models of the three liver indications treated with GeneRide vectors to deliver corrective genes. In all these models, expansion of the corrected healthy hepatocytes correlated with improved diseased markers.

In the HT1 models with acute liver damage, the data showed that GeneRide-corrected hepatocytes repopulated the entire liver within four weeks post-administration, replacing the diseased hepatocytes with corrected hepatocytes. HT1 mice are deficient in the gene encoding fumarylacetoacetate hydrolase (FAH), which is required to metabolize the amino acid tyrosine, resulting in the accumulation of toxic metabolites. HT1 mice that received the GeneRide-FAH vector were no longer reliant on the current standard of care for the disease, and demonstrated restored normal body growth, liver function, and undetectable succinyl acetone levels, one of the toxic metabolites that accumulates in patients with HT1. Compared to the current standard of care, treatment with the GeneRide vector resulted in superior succinyl acetone reduction and lower alfa-fetoprotein levels, a clinically validated biomarker for hepatocellular carcinoma and another risk factor for untreated HT1 patients.

Wilson disease results from a defect in copper transport, leading to toxic accumulation of copper and damage to tissues. In a Wilson disease mouse model, GeneRide-corrected hepatocytes repopulated the liver over time, and treated mice showed improvements in liver function, hepatomegaly, and urinary copper excretion.

"We are very excited to present these preclinical data in HT1 and Wilson disease. These data demonstrated repopulation of a diseased liver using our in vivo genome editing technology, resulting in GeneRide-edited corrected hepatocytes. The results in HT1 were particularly encouraging, demonstrating complete liver repopulation after treatment. These data further validate our technology and represent an important step as we continue on our mission to deliver the hope of genetic medicine to people impacted by devastating diseases," said Mariana Nacht, Ph.D., chief scientific officer of LogicBio.

Shengwen Zhang, director, molecular and cellular pharmacology at LogicBio, will give an oral presentation highlighting GeneRide's successful delivery of corrective genes in HT1, Wilson disease and MMA. Selective advantage and expansion of corrected hepatocytes was observed in these preclinical models, demonstrated by detection of increasing levels of a tagged albumin protein, albumin-2A, a technology-related biomarker indicating site-specific gene insertion and protein expression, as well as immunohistochemistry for the corrective protein in liver sections. Results also showed increasing levels of albumin-2A correlated with increased expression of the corrective gene and improved disease burden. The company believes that these data support the development of GeneRide vectors to durably treat multiple genetic diseases with liver dysfunction.

Additional posters presented at ESGCT highlight the Company's adeno-associated virus (AAV) technology platform advancements. One poster detailed the combination of LogicBio's proprietary plasmids and optimized transfection process in suspension HEK293 cells, which resulted in a 10- to 25-fold increase in titers using an LK03 capsid in 50L bioreactors. A separate poster highlighted recent development of anion exchange (AEX)-based high-pressure liquid chromatography, allowing LogicBio to use an analytical method to measure the percentage of full capsids in any given sample of AAV-LK03.

Additional information on the meeting can be found on the ESGCT website.

The oral presentation and posters will be made available on thePresentations section of the Company website at https://investor.logicbio.com/events-and-presentations/presentations.

AboutLogicBio Therapeutics

LogicBio Therapeuticsis a clinical-stage genetic medicine company pioneering genome editing and gene delivery platforms to address rare and serious diseases from infancy through adulthood. The company's genome editing platform, GeneRide, is a new approach to precise gene insertion harnessing a cell's natural DNA repair process potentially leading to durable therapeutic protein expression levels. The company's gene delivery platform, sAAVy, is an adeno-associated virus (AAV) capsid engineering platform designed to optimize gene delivery for treatments in a broad range of indications and tissues. The company is based inLexington, MA.For more information, visitwww.logicbio.com, which does not form a part of this release.

Forward-Looking Statements

Statements in this press release regarding LogicBio's strategy, plans, prospects, expectations, beliefs, intentions and goals are forward-looking statements within the meaning of theU.S.Private Securities Litigation Reform Act of 1995, as amended, including but not limited to statements regarding validation of previous research; the potential of the GeneRide platform; and the company's belief that preclinical data supports the development of GeneRide vectors to durably treat multiple genetic diseases with liver dysfunction. The terms "believe," "validate" and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including the risk that existing preclinical data may not be predictive of the results of ongoing or later preclinical and/or clinical results; the potential direct or indirect impact of the COVID-19 pandemic on our business, operations, and the markets and communities in which we and our partners, collaborators and vendors operate; manufacturing risks; risks associated with management and key personnel changes and transitional periods; the actual funding required to develop and commercialize product candidates, including for safety, tolerability, enrollment, manufacturing or economic reasons; the timing and content of decisions made by regulatory authorities; the actual time it takes to initiate and complete preclinical and clinical studies; the competitive landscape; changes in the economic and financial conditions of LogicBio; and LogicBio's ability to obtain, maintain and enforce patent and other intellectual property protection for LB-001 and any other product candidates. Other risks and uncertainties include those identified under the heading "Risk Factors" in LogicBio's Annual Report on Form 10-K for the year endedDecember 31, 2020and other filings that LogicBio may make with theU.S. Securities and Exchange Commissionin the future. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release, and LogicBio does not undertake, and specifically disclaims, any obligation to update any forward-looking statements contained in this press release.

Investor Contacts: Laurence WattsGilmartin Group(619) 916-7620laurence@gilmartinir.com

Stephen JasperGilmartin Group(858) 525-2047stephen@gilmartinir.com

Media Contacts:Jenna UrbanBerry & Company Public RelationsW: 212-253-8881C: 203-218-9180jurban@berrypr.com

Bill BerryBerry & Company Public RelationsW: 212-253-8881C: 917-846-3862bberry@berrypr.com

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LogicBio Therapeutics Announces Successful Repopulation of Diseased Livers in Mice with Healthy Corrected Hepatocytes in Two New Indications Using...

An artificial intelligence-based technology rapidly diagnoses rare disorders in critically ill children with high accuracy, according to a report by scientists from University of Utah Health and Fabric Genomics, collaborators on a study led by Rady Childrens Hospital in San Diego. The benchmark finding, published in Genomic Medicine, foreshadows the next phase of medicine, where technology helps clinicians quickly determine the root cause of disease so they can give patients the right treatment sooner.

This study is an exciting milestone demonstrating how rapid insights from AI-powered decision support technologies have the potential to significantly improve patient care, says Mark Yandell, co-corresponding author on the paper. Yandell is a professor of human genetics and Edna Benning Presidential Endowed Chair at U of U Health, and a founding scientific advisor to Fabric Genomics.

Worldwide, about 7 million infants are born with serious genetic disorders each year. For these children, life usually begins in intensive care. A handful of NICUs in the U.S., including at U of U Health, are now searching for genetic causes of disease by reading, or sequencing, the 3 billion DNA letters that make up the human genome. While it takes hours to sequence the whole genome, it can take days or weeks of computational and manual analysis to diagnose the illness.

For some infants, that is not fast enough, Yandell says. Understanding the cause of the newborns illness is critical for effective treatment. Arriving at a diagnosis within the first 24 to 48 hours after birth gives these patients the best chance to improve their condition. Knowing that speed and accuracy are essential, Yandells group worked with Fabric to develop the new Fabric GEM algorithm, which incorporates AI to find DNA errors that lead to disease.

In this study, the scientists tested GEM by analyzing whole genomes from 179 previously diagnosed pediatric cases from Radys Childrens Hospital and five other medical centers from across the world. GEM identified the causative gene as one of its top two candidates 92% of the time. Doing so outperformed existing tools that accomplished the same task less than 60% of the time.

Dr. Yandell and the Utah team are at the forefront of applying AI research in genomics, says Martin Reese, CEO of Fabric Genomics and a co-author on the paper. Our collaboration has helped Fabric achieve an unprecedented level of accuracy, opening the door for broad use of AI-powered whole-genome sequencing in the NICU.

GEM leverages AI to learn from a vast and ever-growing body of knowledge that has become challenging to keep up with for clinicians and scientists. GEM cross-references large databases of genomic sequences from diverse populations, clinical disease information and other repositories of medical and scientific data, combining all this with the patients genome sequence and medical records. To assist with the medical record search, GEM can be coupled with a natural language processing tool, Clinithinks CLiX focus, which scans reams of doctors notes for the clinical presentations of the patients disease.

Mark Yandell, Ph.D., professor of human genetics and Edna Benning Presidential Endowed Chair at U of U Health.

Critically ill children rapidly accumulate many pages of clinical notes, Yandell says. The need for physicians to manually review and summarize note contents as part of the diagnostic process is a massive time sink. The ability of Clinithinks tool to automatically convert the contents of these notes in seconds for consumption by GEM is critical for speed and scalability.

Existing technologies mainly identify small genomic variants that include single DNA letter changes, or insertions or deletions of a small string of DNA letters. By contrast, GEM can also find structural variants as causes of disease. These changes are larger and are often more complex. Its estimated that structural variants are behind 10% to 20% of genetic diseases.

To be able to diagnose with more certainty opens a new frontier, says Luca Brunelli, a neonatologist and professor of pediatrics at U of U Health, who leads a team using GEM and other genome analysis technologies to diagnose patients in the NICU. His goal is to provide answers to families who would have had to live with uncertainty before the development of these tools. He says these advances now provide an explanation for why a child is sick, enable doctors to improve disease management, and, at times, lead to recovery.

This is a major innovation, one made possible through AI, Yandell says. GEM makes genome sequencing more cost-effective and scalable for NICU applications. It took an international team of clinicians, scientists, and software engineers to make this happen. Seeing GEM at work for such a critical application is gratifying.

Fabric and Yandells team at the Utah Center for Genetic Discovery have had their collaborative research supported by several national agencies, including the National Institutes of Health and American Heart Association, and by the Us Center for Genomic Medicine. Yandell will continue to advise the Fabric team to further optimize GEMs accuracy and interface for use in the clinic.

The research was published online on Oct. 14, 2021, as Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases.

Additional centers that participated in the study include Boston Childrens Hospital, Christian-Albrechts University of Kiel & University Hospital Schleswig-Holstein, HudsonAlpha Institute of Biotechnology, Tartu University Hospital and the Translational Genomics Research Institute (TGen).

Competing interests: Yandell has received stock options and consulting fees from Fabric Genomics, Inc. Reese is an employee of Fabric Genomics, Inc.

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AI quickly identifies genetic causes of disease in newborns | @theU - @theU