Category Archives: Gene Medicine

Mila Makovec loved the great outdoors. Born in November 2010, she grew up on the outskirts of Boulder, Colorado and was skiing by the age of two. Before her third birthday Mila would go on long hikes, preferring to make her own way rather than be carried in a baby backpack. Shortly after her third birthday Mila started rock-climbing. This is not just a mom boasting about her child, says her mother, Julia Vitarello. She was really outgoing and advanced. But then, she adds, I started noticing things.

Before she turned four, Mila had started walking with an inturned foot. At the doctors surgery there was little alarm. Mila was diagnosed with tibial torsion an inward twisting of the shin bones that is relatively common among toddlers. But, for Julia, the diagnosis didnt add up. Over the coming months Mila became clumsier and clumsier. She would stumble and fall; her speech, previously eloquent and exuberant, became slow and staccato. In 2015, by the time Mila was five, doctors started using the word delay suggesting that she had been born with something that was hindering her development. That didnt make sense, says Julia. Mila was advanced.

The hunt for a diagnosis was arduous, encompassing more than 100 visits to doctors and therapists. Many doctors who assessed Mila commented on how developmentally advanced she was, despite her ever-growing list of symptoms. Then came the suggestion that maybe, just maybe, she had something incredibly rare. Julia started carrying around a piece of paper to note down any symptoms of a potential neurological condition. First it was stepping on toys and breaking them. All the toys in our house were broken. I would ask her, Mila, whats that in the corner? and she would say, Oh, its a butterfly. The next day I would ask again and she would look away like she didnt know. Suspecting that Mila might have a vision problem, Julia took her to an ophthalmologist and an optometrist, both of whom said she seemed fine. They also told me to chill out, Julia says.

One day in December 2016 Julia decided she needed some air. She went for a run, got bitten by two dogs and barely flinched. I didnt even realise Id been crying the whole time for Mila. Perceiving that she could no longer cope, she packed up a duffel bag, put Mila in the car and drove her to the Emergency Room. I heard the word seizure. I heard the word blind. She couldnt even stand, Julia says. Mila spent a week in hospital and received a myriad of tests. I saw her decline so quickly. Everything changed that week. Mila was diagnosed with Batten disease, an incredibly rare genetic disorder that gets progressively worse and is always fatal. I felt enormous relief, says Julia. And I also felt very guilty. Id been told I was crazy for three years, but there it was, in her genetic code.

Children with Batten disease have a problem with their lysosomes, enzyme-filled bags within cells that clear waste molecules. With defective lysosomes, this waste builds up and kills cells, causing brain damage and, by adolescence, death. Symptoms normally appear between the ages of five and ten years. Children suffer from vision problems and seizures. Their behaviour changes, they become clumsy, their spine starts to curve. The disease is fatal and there is no treatment or cure.

Milas doctors in Colorado sequenced the protein-coding part of her genome and found an error in one copy of a gene called CLN7, which codes for a protein that it is thought help molecules move across the membrane of the lysosome bags. To have Batten disease, both copies of CLN7 one from the mother and one from the father need to have mutated. Milas doctors could only find a defective gene from Milas father. To find the other mutation, Milas whole genome would need sequencing. At the time few labs in the world let alone just in the United States could do this, and even then it was prohibitively expensive and time-consuming. Mila was already six years old and her condition was worsening by the day.

But something else was at stake. Azlan, Milas younger brother, could also have been carrying the same fatal mutations. If he did, then he would soon start to show the same symptoms. I would look at my son, who was totally normal, just like Mila was, and the pain drove me to try and figure out what the mutation was, Julia says. Without knowing what both mutations were, there was no point checking out her son. To answer that question and confirm Milas diagnosis someone, somewhere, would need to find both mutations.

Faced with such challenges, many parents look to the frontiers of medicine. Julia founded a charity in her daughters name, Milas Miracle Foundation, and set herself a fundraising target of $4 million to put towards scientific research and treatment. Her end-goal was gene therapy. Gains made in this field are slow and expensive, but the need for breakthroughs is acute. Every year 7.9 million children are born worldwide with a serious birth defect of genetic, or partially genetic, origin. Thats six per cent of all births. An estimated 3.3 million of those children will die before they reach their fifth birthday. Treatments for such diseases are scarce, and cures are almost non-existent. To raise money for research, Julia realised she needed to improve awareness of Batten disease and other similar fatal genetic diseases. I learned that my tool was telling Milas story, she says. So I started telling it to everyone. I let the press into my house, I went on the news. I hated it I was so sad. But it was the only thing I could do.

In January 2017 Julia got a phone call from a doctor named Timothy Yu, a neurologist and neurogeneticist at Boston Childrens Hospital, whose work just happened to involve sequencing the genomes of people with autism. He had read about Mila on Facebook and wondered if he could help. Yu has run a lab at Boston Childrens Hospital since 2000 and has been carrying out whole-genome sequencing since 2010. We were one of the first to apply it to human disease, says Yu. Not only did he think he could help Mila and her family, but the work also aligned perfectly with his academic interests. This gave Yu both the will and, critically, the means to track down the missing mutation. My lab has been figuring out how to use high-throughput sequencing to diagnose disease and discover new causes of disease for a long time, he says. We know that there are a lot of cases out there of genetic conditions that go undiagnosed because traditional clinical testing doesnt cut it.

Yus task was to find a fragment of a needle hidden in the haystack of Milas genetic code. The doctors in Colorado had found the mutation from Milas father, meaning that Yu and his team could focus their efforts on finding the one inherited from Julia. At first we struck out, he recalls. All the standard ways of looking at the human genome sequence gave us nothing. After two days of failure, Yu and his team took a different approach: they started painstakingly combing through the raw genetic data by hand.

The human genome is three billion base pairs long. To analyse it manually, Yu and his team split it up into chunks that are about 100 letters long and started looking for the one tiny anomaly that would confirm Milas diagnosis. After days of searching, Yus team found something. A section within the CLN7 gene inherited from Milas mother didnt match up properly with the sequence of a normal CLN7 gene. Later analysis would reveal that a 2,000-letter stretch of DNA had jumped and landed there, breaking the gene. This extra chunk of DNA caused an error in Milas cells, disrupting their ability to make protein. This, in turn, had broken her bodys ability to clear out waste molecules. When he called Julia to deliver the news, Yu also had another crucial piece of information to share: while Mila had inherited the mutations from both her mother and father, Azlan had inherited neither. That was an enormous, enormous relief, says Julia. But also a huge reminder that Mila was going to die.

Yus initial promise to Julia was to find the mutation, and nothing more. But her jumping gene was unusual. It had essentially landed on a part of the gene between the important parts that encode the instructions for making the crucial cell-cleaning protein. Milas mutation was, it turned out, merely changing the way the instructions were assembled. Most mutations destroy the instructions. In Milas case, they were disrupted but still intact.

Just as the stars had aligned to connect Mila with Yu, so they aligned again when Yu and his team started to research possible treatments. In December 2016 only weeks before Yu first spoke to Julia the Food and Drug Administration (FDA), the US federal agency responsible for drug regulation, had approved a drug called spinraza. The drug is used to treat spinal muscular atrophy, a rare neuromuscular disorder that causes muscle weakness and is a leading genetic cause of death in infants, many of whom die before the age of two. The defect that spinraza targets is the assembly of a critical gene called SMN2. Spinraza reassembles this gene by removing the defect. This type of drug is called an antisense oligonucleotide (ASO) and it works by binding to defective RNA, hiding it and tricking cells into producing a normal protein. Yu had an idea: could he create a similar kind of genetic plaster to cover Milas fatal defect?

People were talking about it being curative, says Yu. I went into neurology because there is a huge unmet need. But, in reality, there are very few curative therapies in neurology. Spinraza changed that. When we looked at what spinraza did for those kids and we looked at the mutation that we found in our patient, it was the same story. Why couldnt we pull the same trick? It was a huge undertaking, made all the more challenging by the fact that Yu and his colleagues had never made a drug before. Were an academic lab. Im a clinician, Im not a drug developer. But when I looked at the basic science I couldnt see a reason why this wouldnt work.

Between April and October 2017, Yu and his team created a scientific proof of principle a new drug, targeted at one tiny mutation in one patient. If it worked, it would become the first single-patient drug ever created. But they faced one additional, potentially insurmountable hurdle: the FDA. We werent looking to commercialise a drug, says Yu. We werent looking to do what a pharma company would do. What we wanted to do was apply for permission to treat our patient under emergency access. This regulatory route allows doctors caring for individual patients to, for example, apply to use a drug that has been approved for use on another disease or a drug that is still in development and has not yet gone through clinical trials. If the need is dire and the application is successful then the treatment can be used. So we decided to choose that path, says Yu. Except that path had never been undertaken for a drug that hadnt undergone some professional development before.

Yu found himself at the frontier of not just medical science, but also regulation. The drug that he and his team had conceived had been developed in an academic lab, not by a pharmaceutical company. Not sure where to start, Yu naively called up an FDA hotline. Theres a 1800 number you can call. So I called them up and told them what I wanted to do. The FDA agreed to set up a conference call, which Yu ended up taking while on holiday. Sitting on the patio of a house that he and his family had rented for the weekend, Yu addressed the 15-member FDA panel. It was after this conference call that I realised, Oh gosh, I think it might be good to get some additional advisers on our side.

All the while Milas condition was worsening. One day in the summer of 2017, around six months after the diagnosis, Julia was lying in bed with her daughter. It was dark and Mila, as had become common, was struggling to get her words out. Her sentences were getting shorter and shorter. She was saying, Mommy, Mommy and she just kept getting stuck on Mommy. She could never get the rest of the sentence out. She was driving me nuts, Julia says. But then I realised I might never hear her say Mommy again. And that happened. I took a video that night in the dark. And I heard her say Mommy and it was just horrible. It was really horrible. By the autumn of 2017 Mila could no longer speak. All her food had to be blended to the consistency of mashed potato, and even then she choked all the time. She had also been fitted with a gastrostomy tube, in preparation for the day when she would no longer be able to eat or drink.

Back in Boston, Yu and his team were grappling with two challenges: how could they prove their drug was safe to use, and how could they manufacture it quickly enough? To tackle the first challenge, Yus laboratory tested the drug they had developed on skin and blood samples they had taken from Mila. This process, Yu recalls, was simple enough. But the logistical challenges proved more complex. The drug Yu had created, like spinraza, is known as an antisense oligonucleotide. For a laboratory-grade version of this drug, Yu would expect to pay as little as $10 for a small sample. For a higher quantity, maybe $300. But clinical-grade manufacturing is more costly and complex. Yu started calling around and was told that it would take six to nine months and cost hundreds of thousands of dollars to manufacture a clinical-grade version of his drug. The laboratory-grade version could be turned around in a week. The manufacturers he contacted were also only really geared up to produce huge quantities, perhaps as much as half a kilo. Yu only needed 2030 grams. Eventually they found a company willing to manufacture the drug in the right quantity and for the right price. The negotiations with the FDA were complex, but, remarkably, Yu continued to make good progress. But time was slipping away and so, in October 2017, manufacturing of the drug began, without FDA approval.

By this point Mila was having up to 30 seizures a day. She was smashing her legs and arms against tables. She was bruised. She was going down very quickly, says Julia. Milas disease, as is typical for Batten, was manifesting as a series of plateaus and cliffs for weeks Milas condition would stabilise, then she would rapidly deteriorate, before stabilising again. Each fall took another chunk of Mila with it. In January 2018, days after Julia and Mila had arrived in Boston hoping that FDA approval was imminent, the good news arrived. I was so overwhelmed, Julia says. Yu assembled his team and asked Julia and Mila to come into Boston Childrens Hospital. They were taken to an unremarkable back room, in which sat a refrigerator packed with vials of the new drug. The drug the first of its kind ever developed for just one patient now had a name: milasen. Before she received the first dose, Milas doctors anaesthetised her and carried out one final MRI scan of her brain and spine. Once the scans were done, she was wheeled into the room next door to receive her first dose of milasen, administered via a lumbar puncture.

For Julia and Yu it was the first moment of pause for almost a year. They sat in the MRI waiting room, leaning forward, their elbows on their knees, and they paused. Id been working day and night for the previous year it was probably one of the most intense professional periods that Id encountered, says Yu. In the weeks before, people had come up to me saying I was going to lose my licence for this. This is a very risky thing to do. But there was no other help coming. It was very, very clear that if we didnt do anything, she would have no quality of life and she would die within a few short years. I really came to peace with it, professionally and ethically and clinically. So we definitely did pause and take a deep breath and reflect on where we were.

The day after was blissfully boring. Mila had no adverse reaction to the drug. The first few doses also went without a snag and, over the next six months, Milas condition started not just to stabilise, but to improve. The number of seizures she had went down drastically and also became less severe. Where before they had been long and violent, now they were short and calm. Mila also began to hold up her own body again and started eating. She even started walking. With her mother standing behind her, their arms interlocked, Mila was able to take a few, stumbling steps. It was a pretty big deal, Julia says.

As the days turned to months, and the months to years, Milas disease started progressing again though more slowly than it had before. We know its not all a fairy-tale story, says Yu. We believe this drug is definitely helping, but there are areas in which this disease has progressed that are meaningful and impactful and sad. But I think it has provided her with an improved quality of life.

Julia agrees. Mila has always been a kid who loves imagery and storytelling and songs and has reacted well to nature. I try my best to engage her mind and body. Most days, a girl the same age as Mila comes round to read her stories. If she touches Milas hands, she feels a childs hands, Julia says. When Milas brother Azlan runs around the house and screams and shouts, Mila hears a childs voice. I believe, as her mother, that shes absolutely listening and paying attention.

Milas story is about so much more than simply one patient. Its extremely important to me that all the blood, sweat and tears that we put into milasen is not just for Mila, says Julia. Its opened the eyes of everyone. Its shown whats possible. The story of Mila represents the most profound realisation of personalised medicine yet. Her legacy, it is hoped, will be to make the path to treatment easier and less expensive for the next patient in desperate need. We can imagine a situation where the tools for drug development are good enough, and accessible enough, that a scientist can apply them to a single patient, says Yu. In this respect, Milas story is a story from the future. The pharmaceutical industry has already progressed from developing drugs to treat diabetes and heart disease illnesses that affect millions of people to develop treatments like spinraza, which target diseases found in only a few thousand patients. Milasen has shown that scientists have the tools at their disposal to develop treatments that can be applied to only one patient with a specific, targetable genetic mutation.

Theres a lot more work to do to be able to prove that the work we did with milasen, as a proof of principle, can be scaled, Yu says. Now, with an example of how it can work, he believes that healthcare is on the brink of a major change. Antisense oligonucleotides the genetic plasters behind the success of milasen and spinraza will likely be the first wave of this change. These are incredibly easy to make. You make them out of a machine thats about the size of a large, soft-serve ice-cream machine, says Yu. You type in the sequence, add in the ingredients and the drug is synthesised and comes out twenty-four hours later. This, says Yu, is a field that can become cheaper and more efficient in a relatively short space of time.

But, as he found while developing milasen, two major hurdles stand in the way: a scientific hurdle and a logistical one. Im a scientist, right? And weve still only done an N of one, Yu says, using the scientific term for a clinical trial with just one patient. If a graduate student comes up to me and shows me an experiment with an N of one, I tell them to go back and do it at least three more times. So conceptually, thats what we need to do. On the logistical side, Yu realises there are more complex challenges to overcome. In order to scale, this process has to be made simpler and less expensive, he says. More than 70 people were involved in the development of milasen. The cost of the development has never been disclosed, but spinraza, the treatment for spinal muscular atrophy that inspired Yu to develop milasen, costs $750,000 in its first year and $375,000 annually thereafter, placing it among the most expensive drugs in the world.

To be available to the hundreds of thousands of children born with fatal neurodegenerative diseases that can be targeted by antisense oligonucleotides, the price of treatment needs to come down, right down and fast. For that to happen, drug manufacturers will need to develop processes and business models that enable them to make lots of drugs in very small batches with quick turnaround times. Think going from spending nine months developing one drug to spending one month developing nine drugs. Regulators will also need to introduce new pathways for targeted, small-scale treatments. This will be a huge challenge for an industry that is used to regulating, manufacturing and monetising treatments that can be taken by hundreds of thousands or millions of patients, rather than simply a handful. Or one. Milasen shows that it can be done once, and so Julia and Yu are now focusing their efforts on showing it can be done time and time again.

In the future, the mutations that cause rare, often-fatal diseases could be targeted with precision medicines just like milasen. As whole-genome sequencing costs come down, such checks will become more routine giving physicians access to all the data they need to make an early and accurate diagnosis. Yu sees a future where parents of children with potentially fatal genetic mutations are immediately connected to experts who can explore the feasibility of making a drug and start the process in days, not months.

Parents could even be screened before they try for a child, to find out if they have mutations that could cause a fatal or life-limiting disease. They can know that they have a one-in-four chance of having a child with this disease, says Yu. The parents would then receive counselling to help them make the best decision. A foetus with an incurable, fatal genetic mutation could be aborted. Or, if in utero procedures could correct the genetic fault, treatment could be carried out at the earliest opportunity to give the child the best chance of a long, healthy life. The potential to eradicate some fatal genetic diseases before they even exist is one of the great promises of precision medicine. The diagnostic portion is ready to implement right now, says Yu. We just need the political will and the money to do it.

Julia compares the situation she faced when Mila was diagnosed with Batten to being handed an empty toolbox. Now, that box contains one truly remarkable tool. If and its a big if another child has Batten caused by the exact same genetic mutation as Mila, then there is a fridge in Boston that contains a lifetimes worth of treatment. And if that child is diagnosed sooner than Mila, then theres a chance they could press Pause on the disease and slow its progress earlier perhaps before that child even displays any symptoms. As a clinician and as a human, I think about that all the time, says Yu. What if we could have gotten to Mila sooner? What if wed been able to make this diagnosis in Mila at age four? We only met her at age six. Batten is a disease that gains momentum cells in the brain start dying, symptoms compile and accelerate. Coupling this kind of approach with earlier diagnosis is just so critical, says Yu.

No one wants to hear the story of a dying child, says Julia. But when its told in the light of hope, people want to listen.

Mila Makovec passed away on February 11, 2021.

James Temperton is WIRED's digital editor. He tweets from @jtemperton

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A dying child, a mother's love and the drug that changed medicine - Wired.co.uk

DUBLIN--(BUSINESS WIRE)--The "Global Cell and Gene Therapy Drug Delivery Devices Market: Focus on Product Type, Commercialized Drug Delivery Devices, Country Data (16 Countries), and Competitive Landscape - Analysis and Forecast, 2020-2030" report has been added to ResearchAndMarkets.com's offering.

The global cell and gene therapy drug delivery devices market was valued at $55.75 thousand in 2019, and is expected to reach $375.13 thousand by 2030, registering a CAGR of 16.61% during the forecast.

Cell and gene therapy drug delivery industry is a transformative industry whose full potential is only just beginning to emerge. Cell and gene therapy involves the extraction of cells, protein, or genetic material (DNA) from the donor, and altering them to provide highly personalized therapy. Cell and gene therapies may offer longer-lasting effects than traditional medicines.

One of the significant drugs of the cell and gene therapy industry is CAR-T cell-based medicines, which include both cell therapy and gene therapy. Various market players are actively investing in the research and development of the cell and gene therapy industry. The players are offering improved and new products, which meet the critical needs of patients.

The growth is attributed to major drivers in this market such as the increasing prevalence of cancer and chronic diseases, increased funding in the cell and gene therapy market, rising need to develop novel treatment options for rare diseases, and rising biopharmaceutical R&D expenditure, and rising number of the FDA approvals of cell and gene therapies & clinical trials. The market is expected to grow at a significant growth rate due to various potential opportunities of growth that lie within its domain, which include drug approvals and strong pipeline of cell and gene therapies.

Various new cell and gene-based therapy approaches use biological engineering to improve the immune system's capacity to fight disease while sparing healthy tissues in the body. For instance, there are antibody-based therapies that can make T-cells more effective by increasing their interactions with cancer cells. Other modifications, such as adding complexity to the CAR-T and cancer cell interaction, which can further sharpen T-cells' cancer-targeting ability by reducing damage to normal cells.

The increase in the geriatric population and an increasing number of cancer cases, and genetic disorders across the globe are expected to translate into significantly higher demand for cell and gene therapy drug delivery devices market.

Furthermore, the companies are investing huge amount in research and development of cell and gene therapies and associated drug delivery devices products. The clinical trial landscape of various genetic and chronic diseases has been on the rise in the recent years, this will fuel the cell and gene therapy drug delivery devices market in future.

Within the research report, the market is segmented based on product type, commercialized drugs, and region. Each of these segments covers the snapshot of the market over the projected years, the inclination of the market revenue, underlying patterns, and trends by using analytics on the primary and secondary data obtained.

Competitive Landscape

The exponential rise in the application of precision medicine on a global level has created a buzz among companies to invest in the development of novel cell and gene therapy drug delivery devices.

Due to the diverse product portfolio and intense market penetration, Novartis AG, Kite Pharma Inc., and Dendreon Pharmaceuticals LLC. have been the pioneers in this field and been the major competitors in this market.

The other major contributors of the market include companies such as Vericel Corporation, Amgen Inc., Bausch & Lomb Incorporated, Spark Therapeutics, Inc., and Becton, Dickinson and Company.

Based on region, North America holds the largest share of cell and gene therapy drug delivery devices market due to substantial investments made by biotechnology and pharmaceutical companies, improved healthcare infrastructure, rise in per capita income, early availability of approved therapies, and availability of state-of-the-art research laboratories and institutions in the region. Apart from this, Asia-Pacific region is anticipated to grow at the fastest CAGR during the forecast period.

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/110jum

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Global Cell and Gene Therapy Drug Delivery Devices Market 2020-2030: Focus on Product Type, Commercialized Drug Delivery Devices, and Competitive...

- Initial data from Cohort 1 of the PEARL-1 study shows safety and tolerability of repeat KB301 injections

- Dr. Bhushan Hardas M.D., MBA appointed President, Jeune, Inc.

PITTSBURGH, March 24, 2021 (GLOBE NEWSWIRE) -- Krystal Biotech Inc., (Krystal) (NASDAQ: KRYS), the leader in redosable gene therapies for rare diseases, today announced the launch of Jeune, Inc., a wholly owned subsidiary of Krystal Biotech, and initial safety data from the ongoing Phase 1 trial of Jeunes lead product candidate, KB301 for treatment of aesthetic skin conditions.

Jeune was formed to advance innovative aesthetic medicines and has an exclusive license to a portfolio of candidates derived from Krystals proprietary technology platform. Jeunes products are designed to directly address biological changes in the skin associated with intrinsic and extrinsic aging. The lead product candidate, KB301, delivers the human COL3A1 gene to increase production of normal type III collagen at the site of administration.

My initial clinical experience with KB301 injections has been highly encouraging, said Dr. Mark Nestor, director of the Center for Clinical and Cosmetic Research and the Center for Cosmetic Enhancement. Not only were the injections well-tolerated, but we see clear signs of new collagen generation which underscores the potential of this treatment to directly address the declining levels of collagen that lead to wrinkles and other skin changes.

Initial data from Cohort 1 in the PEARL-1 studyThe Phase 1, open-label, dose-ranging study is being conducted in adult subjects aged 18-75 (NCT04540900). The primary outcome measure in this first-in-human study was to assess the safety profile of KB301. Secondary outcome measures include COL3A1 transgene expression. In Cohort 1, three different dose levels of KB301 were evaluated in seven (7) healthy subjects who received two intradermal injections into healthy buttock tissue spaced 30 days apart (day 0, day 30). KB301 injected areas were compared to uninjected or saline injected control tissue within the same subject. Treatment and control sites were biopsied at day 2 or day 32. Initial results are as follows:

More detailed data from Cohort 1 will be presented as an e-Poster talk at the Society for Investigative Dermatology (SID) Annual Meeting, held virtually May 3-8.

The presentation will be available on-demand for those registered for the SID conference from May 3, 2021 May 31, 2021. The poster will also be available on the companys website at http://www.jeuneinc.com

The company plans to begin enrollment in the efficacy cohorts of the Phase 1 study in the second half of 2021.

Jeune, Inc. LeadershipJeune has assembled a veteran team of leaders and advisors, comprised of pharmaceutical and biotechnology executives who together have decades of experience developing products in the aesthetic medicine space. Dr. Bhushan Hardas M.D., MBA will join the company on March 29th, 2021 as President of Jeune. Before joining Jeune, Dr. Hardas served as Chief Scientific Officer, Executive Vice President, Global Head of Licensing at Almirall and previously served as Chief Medical Officer of Allergan's Dermatology and Medical Aesthetics business.

I am thrilled to be joining Jeune at such an exciting time. With the ability to deliver genes directly to skin cells, this platform has tremendous potential to address underlying biological changes in aging or photo-damaged skin, noted Dr. Hardas. We are starting with KB301 and type III collagen which I look forward to advancing through the clinic, and the team is already working on pipeline programs that will address additional proteins of interest.

Prior to joining Allergan, Dr. Hardas served as Senior Vice President, Global Head of Dermatology and Aesthetics R&D and Chief Scientific Officer of the North American Business at Merz Pharmaceuticals. Dr. Hardas received advanced training in clinical immunology and molecular biology at King's College at the University of London, in London, England. He also completed a research fellowship in the Department of Dermatology at the University of Michigan, and received his Master of Business Administration degree in healthcare management from the University of California - Irvine.

We are thrilled to welcome Bhushan to Jeune, said Krish S. Krishnan, chairman and chief executive officer of Krystal Biotech. His expertise and development experience in aesthetics is an important asset presently and will help guide next steps for both the pipeline and Jeune overall.

Jeune, Inc. Board Krish Krishnan, Chairman and CEO at Krystal Biotech will serve as the Chairman of the Jeune Board. Joining Mr. Krishnan on the Board are Marc Forth, President and CEO of Aeon BioPharma and Suma Krishnan, Founder and COO of Krystal Biotech.

AboutJeune Inc. Jeune Inc., a subsidiary of Krystal Biotech, is a biotechnology company leveraging a clinically validated gene-delivery platform to fundamentally address and reverse the biology of aging and/or damaged skin. For more information, please visithttp://www.jeuneinc.com

AboutKrystal BiotechKrystal Biotech, Inc.(NASDAQ:KRYS) is a pivotal-stage gene therapy company leveraging its novel, redosable gene therapy platform and in-house manufacturing capabilities to develop therapies to treat serious rare diseases. For more information, please visit http://www.krystalbio.com.

Forward-Looking StatementsAny statements in this press release about future expectations, plans and prospects for Krystal Biotech, Inc., or its subsidiary Jeune, Inc., including but not limited to statements about the development of Krystals and Jeunes product candidates, such as plans for the design, conduct and timelines of ongoing clinical trials of KB301 the clinical utility of KB301, the ability of these candidates to fundamentally address and potentially reverse the biology of aging or damaged skin, plans to pursue research and development of other product candidates; and other statements containing the words anticipate, believe, estimate, expect, intend, may, plan, predict, project, target, potential, likely, will, would, could, should, continue, 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: the uncertainties inherent in the initiation and conduct of clinical trials, availability and timing of data from clinical trials, whether results of early clinical trials or trials will be indicative of the results of ongoing or future trials, uncertainties associated with regulatory review of clinical trials and applications for marketing approvals, the availability or commercial potential of product candidates including KB301 and such other important factors as are set forth under the caption Risk Factors in Krystals annual and quarterly reports on file with the U.S. Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Krystals views as of the date of this release. Krystal anticipates that subsequent events and developments will cause its views to change. However, while Krystal may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Krystals views as of any date subsequent to the date of this release.

CONTACTS:

Investors:Whitney Ijemwijem@krystalbio.com

Media:Mary CoyleTellMed Strategiesmary.coyle@tmstrat.com

Source: Krystal Biotech, Inc.; Jeune, Inc.

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Krystal Biotech Announces Launch of Jeune, a Gene-Based Aesthetics Company, and Initial Phase 1 Safety Data for KB301 in Aesthetic Indications -...

This was the first genome-wide association study of skin pigmentation in African Americans, according to the study authors.

Researchers in a City of Hope-led data study conducted a genome-wide association study using the data of 1076 African Americans to analyze the genetics of skin pigmentation in this group to test whether the identified genetic variants are linked to vitamin D deficiency in African Americans.

"We should not shy from this new study looking at the genetics of skin color and its effects on vitamin D deficiency because being 'colorblind' is what has led to the widespread health disparities that we as a society are now trying to address," said Rick Kittles, PhD, director of the Division of Health Equities at Beckman Research Institute of City of Hope, in a press release. "Skin color has strong social and biological significancesocial because of race and racism and biological because over 70% of African Americans are vitamin D deficient, resulting in increased risk for cancer and cardiovascular disease.

This was the first genome-wide association study of skin pigmentation in African Americans, according to the study authors. Study participants self-identified as African American, and blood samples for DNA analysis and vitamin D levels were collected at recruitment. Scientists then measured the sun-protected area of the skin in the inner upper arms of participants using a digital reflectometer.

Various factors, such as aging, outdoor activities, and consistent UV exposure over the years, may influence skin pigmentation and the association between skin pigmentation and vitamin D levels, according to the study. The researchers found that skin pigmentation gene variants, rather than skin pigmentation, measured using a reflectometer were associated with serum vitamin D levels.

Further, the scientists found 3 regions (SLC24A5, SLC45A2 and OCA2) in the genes of African Americans with strong links to skin color and severe vitamin D deficiency. The genetic variant rs2675345, which is near a region in the gene called SLC24A5, showed the strongest association with skin pigmentation and vitamin D deficiency.

Previous studies have shown that individuals with darker skin pigmentation require longer or more intense ultraviolet radiation exposure to synthesize sufficient levels of vitamin D. The current studys authors said they hope the findings lead into future investigations that examine the newly identified risk score in physicians offices, potentially creating a precision medicine tool.

"This study is an example of the interplay of race and skin color on health and how if we ignore things such as the color of a person's skin, we may be ignoring potential medical issues, thus contributing to health care disparities," Kittles said in a press release. "Our study provides new knowledge about an easily modifiable factor such as vitamin D supplementation and inherited genetic factors affecting vitamin D deficiency in African Americans. With more research, in the future physicians could offer patients of color with an inexpensive way to reduce their risk of vitamin deficiency, which ultimately could help protect against certain cancers."

REFERENCE

Genetic variants for skin color in African Americans linked to vitamin D deficiency. ScienceDaily. Published February 18, 2021. Accessed March 19, 2021. https://www.sciencedaily.com/releases/2021/02/210218142820.htm

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Study: Genetic Variants in Skin Pigmentation Linked to Vitamin D Deficiency - Pharmacy Times

Dose effects: The brains of mice producing only 35 percent of the typical levels of CHD8 protein (right) grow larger in several cortical areas, compared with those producing 50 percent (left).

Mutations that strongly curb the expression of CHD8, a top autism-linked gene, block the proliferation of developing neurons and stymie brain growth in mice, two new studies show. By contrast, mutations that only mildly dampen the genes expression increase proliferation and lead to brain overgrowth, according to one of the studies.

The new work suggests that CHD8 wields its effects on brain size by controlling the proliferation of intermediate progenitor cells, says Albert Basson, professor of developmental neurobiology at Kings College London in the United Kingdom, who led one of the studies. These cells give rise to neurons in the cortex.

People with a missing or mutated copy of CHD8 often have autism, intellectual disability and an atypically large head. But the reason for this third trait has been unclear. Mice and people with one functional copy of the gene both have about half the typical amount of CHD8 protein, but the mice generally show a smaller increase in brain size than people do.

The new studies hint at how both overgrowth and undergrowth can result from mutations in CHD8, depending on how much protein is present and which brain cells are affected.

These two results are basically telling the same thing: CHD8 is a strong promoter of brain growth, says Eunjoon Kim, director of the Center for Synaptic Brain Dysfunctions at the Korea Advanced Institute of Science and Technology in Daejeon, South Korea, who co-led one of the new studies.

In one study, Basson and his team created two new mouse models: one that produces about 35 percent of the usual amount of CHD8 protein, and another that produces about 10 percent of the typical quantity.

The former have unusually large brains, similar to whats seen in people with CHD8 mutations. The latter, on the other hand, have smaller-than-average brains.

This difference arises because CHD8 controls the expression of thousands of other genes some of which have different sensitivities to CHD8s loss, Basson says. In particular, CHD8 suppresses genes controlled by p53, a tumor-suppressing protein that helps keep cell division in check.

An analysis of gene expression levels revealed that CHD8 protein can still perform some of its critical functions in mice that produce 35 percent of the typical levels including, Basson notes, repressing p53 target genes. However, many autism-associated and neurodevelopmental genes are downregulated in these mice.

Also in these mice, the intermediate progenitor cells proliferated more than usual, and more than other cell types did. Multiple genes associated with neural progenitor cell proliferation were upregulated in the cells, researchers found.

In the mice producing 10 percent of typical protein levels, genes regulated by p53 were dominant, driving neural progenitors to mature prematurely or die, resulting in a smaller-than-usual brain.

Deleting CHD8 in just the neural progenitor cells upregulated p53 target genes, resulting in more cell death and an even smaller brain size.

Given the importance of these progenitors in expansion of the human cortex, we suggest that [missing one copy of] CHD8 might have more pronounced effects on fetal brain development in humans, compared [with] mice, Basson says. The work appeared in February in Molecular Autism.

Other researchers should bear in mind the divergent effects of CHD8 loss, Basson says. It could help to explain why different sets of CHD8 mice have sometimes yielded conflicting results.

This uneven trajectory of CHD8 function always required some explanation, and it seems that p53 may be part of that explanation, says Konstantinos Zarbalis, associate professor of pathology and laboratory medicine at the University of California, Davis, who was not involved in the work.

Although researchers showed that CHD8 suppresses p53 function in mice more than a decade ago, this paper elegantly provided support for this, he says.

In the other study, Kims team created mice that lack both copies of CHD8 only in their excitatory neurons. These mice almost completely failed to grow cortical brain structures, according to findings published in February in Cell Reports.

The reason, as in Bassons study, may be cell death, accelerated in the absence of CHD8.

The mice in Kims lab did not show autism-like behaviors once they reached adulthood in fact, they showed increased social behavior.

We were intrigued because cortical areas are known to critically regulate social interaction, Kim says. It almost seems that the loss of cortical areas induces this increase.

Social difficulties associated with CHD8 loss may be rooted in cell types beyond the ones he and his team studied, he says.

The reduced brain size in the mice is also at odds with findings in people with CHD8 mutations. The brain enlargement in people may result from changes in cells other than excitatory neurons, Kim says, or be an indirect consequence of the genes loss something the brain does to compensate for the absence of CHD8.

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Top autism-linked gene has divergent effects on brain growth in mice - Spectrum

INDIANAPOLIS, March 26,2021 /PRNewswire/ --Sexton Biotechnologies, in partnership with Hitech Health and Med Institute, is working towards continued innovations in flexible automation. As cell and gene therapy manufacturers move to close and automate processes, the challenge of integrating existing systems is a pain point for the industry. Flexible automation of traditionally manual process offers a new solution with lower capital expenditures and greater potential for downstream success.

Sexton Biotechnologies is dedicated to providing tools that enhance flexibility and reduce the risk that comes with manual processes. The launch of Sexton's Signata CT-5 provides the first truly flexible fluid management system, capable of integrating multiple processes using the same system. To demonstrate the varied potential of the system, Sexton has engaged Hitech Health and Med Institute to show how it easily connects with other tools used in the manufacturing workflow.

"We're excited to work with these partners to demonstrate how manufacturers can easily integrate separate unit operations in a closed manner using flexible automation systems," said Sean Werner, President of Sexton. "From initial transfer into the manufacturing system through final packaging, the use of these systems provides developers improved control while supporting development iteration.The flexibility allows a user to choose the systems that work best for them, whether it's a platform like CellSeal, the first vial designed specifically for cryopreserved cellular products to be used in an approved commercial cell therapy, or traditional soft-sided bags."

Steve Charlebois, Vice President of Engineering, Regenerative Medicine at Med Institute further points to the importance of the early-stage decision making and its effects on final product.

"We are committed to keeping up with the pace of cell and gene therapy development, to make these lifesaving therapies available to patients," said Steve. "Decisions made early in the development process are critical. Through these strategic partnerships and collaborations, we are able to direct our know-how and experience to address technology bottlenecks that stand in the way of aggressive development and manufacturing timelines. Tackling challenges at each step of development, from ancillary material selection, bioreactor testing, media development, while preserving the principles of closed, flexible, and automated processes, translates to cost-effective, scalable solutions for cell and gene therapies."

Hitech Health is focused on product development, manufacture, launch, and supply of cell and gene therapies. Aoife Duffy, Cell and Gene Therapy Operations Manager, leads a team that has successfully developed multiple cell and gene therapy products.

"We think it is important to collaborate with other companies so that we can add to our expertise in operational activities," said Aoife. "Cell and gene therapy products are expensive to develop and manufacture. Working with Sexton and the Med institute to bring the new fluid management system to the market will help with making processing more efficient. Hitech Health is bringing our extensive operational and GMP Manufacturing expertise to this collaboration. We are expanding our capabilities to cell and gene therapy process development and manufacturing. Additional expertise we bring to the collaboration includes quality, QP approval, and management of supply chain. In the end, we believe that this collaboration will lead to time and cost savings, along with greater downstream success in the manufacture of cell therapy products."

The collaboration between the companies will result in detailed workflows demonstrating capabilities with bioreactors, packaging, formulation, and additional equipment. These efforts are currently underway with publication of workflows expected to begin in early 2021.

ABOUT SEXTON BIOTECHNOLOGIESSexton Biotechnologies is a revenue stage, biotechnology company focused on the development and sales of bioproduction tools for cell and gene therapy founded in 2019 as a spin out of Cook Regentec, a life science incubator/accelerator located in Indianapolis, IN. Sexton develops purpose-built CGT tools and media to enable flexible automation and scaling of cell manufacturing processes to increase the probability of positive clinical outcomes and reduce time-to-market, failure points, and labor costs. Sexton's portfolio includes the fluid handling system, Signata CT-5, CellSeal platform of cryo-storage tools and fill/finish systems, and human platelet lysate growth supplements. More information at http://www.sextonbiotechnologies.com.

For media contactsDusty Howe[emailprotected]

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Sexton Biotechnologies, Hitech Health, And Med Institute Announce Collaboration To Demonstate The Benefits Of Flexible Automation - PRNewswire

DUBLIN, March 25, 2021 /PRNewswire/ -- The "Artificial Intelligence In Genomics Market by Offering (Software, Services),Technology (Machine Learning, Computer Vision), Functionality (Genome Sequencing, Gene Editing), Application (Diagnostics), End User (Pharma, Research)-Global Forecasts to 2025" report has been added to ResearchAndMarkets.com's offering.

The global AI in genomics market is projected to reach USD 1,671 million by 2025 from USD 202 million in 2020, at a CAGR of 52.7% between 2020 and 2025.

The need to control drug development and discovery costs and time, increasing public and private investments in AI in genomics, and the adoption of AI solutions in precision medicine are driving the growth of this market. However, the lack of a skilled AI workforce and ambiguous regulatory guidelines for medical software are expected to restrain the market growth during the forecast period.

Machine learning segment is expected to grow at the highest rate during the forecast period

Based on technology, the AI in genomics market is segmented into machine learning and other technologies. The machine learning segment is projected to register a higher CAGR during the forecast period. The high growth rate of this segment is mainly as pharmaceutical companies, CROs, and biotechnology companies have widely adopted machine learning for drug genomics applications. This is because machine learning can extract insights from data sets, accelerating genomic research.

Diagnostics segment is estimated to account for the largest share of the AI in genomics market in 2019

Based on application, the AI in genomics market is segmented into diagnostics, drug discovery &development, precision medicine, agriculture & animal research, and other applications. Diagnostics was the largest application segment in the AI in genomics market in 2019. The large share of this segment can be attributed to the increasing research on diseases and the decreasing cost of sequencing.

North America is expected to dominate the AI in genomics market in 2020

In 2019, North America accounted for the largest share of the AI in genomics market, followed by Europe. The large share of North America can be attributed to the increasing research funding and government initiatives for promoting precision medicine in the US. The market in the Asia Pacific region, on the other hand, is projected to register the highest CAGR during the forecast period. Emerging countries in the APAC, such as India and China, offer lucrative growth opportunities for market players, primarily due to the increasing public and private funding, improving healthcare infrastructure, and rapid economic growth.

Key Topics Covered:

1 Introduction

2 Research Methodology

3 Executive Summary

4 Premium Insights4.1 AI in Genomics: Market Overview4.2 AI in Genomics Market, by End-user4.3 North America: AI in Genomics Market, by Technology & Country (2019)4.4 Geographical Snapshot of the AI in Genomics Market

5 Market Overview5.1 Introduction5.2 Market Dynamics5.2.1 Drivers5.2.1.1 Need to Control the Time and Costs of Drug Development and Discovery5.2.1.2 Increasing Investments in AI in Genomics5.2.1.3 Rising Adoption of AI in Precision Medicine5.2.1.4 Growing Genomic Datasets5.2.2 Restraints5.2.2.1 Lack of Skilled AI Workforce and Ambiguous Regulatory Guidelines for Medical Software5.2.3 Opportunities5.2.3.1 Focus on Developing Human-Aware AI Systems5.2.4 Challenges5.2.4.1 Lack of Curated Genomic Data5.2.4.2 Data Privacy Concerns5.3 Impact of COVID-19 on the AI in Genomics Market5.4 Ecosystem

6 Artificial Intelligence in Genomics Market, by Offering6.1 Introduction6.2 Software6.2.1 Benefits Offered by Software & Strong Demand Among End-users Are Driving Market Growth6.3 Services6.3.1 Services Segment to Witness the Highest Growth During the Forecast Period

7 Artificial Intelligence in Genomics Market, by Technology7.1 Introduction7.2 Machine Learning7.2.1 Deep Learning7.2.1.1 Deep Learning is the Fastest-Growing and Largest Subsegment of Machine Learning7.2.2 Supervised Learning7.2.2.1 Supervised Learning Can Help Create Predictive Models7.2.3 Reinforcement Learning7.2.3.1 APAC to Show the Highest Growth in the Reinforcement Learning Market7.2.4 Unsupervised Learning7.2.4.1 Unsupervised Learning Algorithms Allow for Complex Processing Tasks, Exceeding the Capabilities of Supervised Systems7.2.5 Other Machine Learning Technologies7.3 Other Technologies

8 Artificial Intelligence in Genomics Market, by Functionality8.1 Introduction8.2 Genome Sequencing8.2.1 Genome Sequencing Holds the Largest Share of the Market, by Functionality8.3 Gene Editing8.3.1 Growing Implementation of Machine Learning in Gene Editing May Help Reduce Time and Costs8.4 Clinical Workflows8.4.1 Machine Learning Can Help Increase the Efficiency of the Clinical Workflow8.5 Predictive Genetic Testing & Preventive Medicine8.5.1 AI in Genomics Can Predict Outcomes and the Risks Associated in Curing Genetic Diseases, Based on the Available Data

9 Artificial Intelligence in Genomics Market, by Application9.1 Introduction9.2 Diagnostics9.2.1 Diagnostics Forms the Largest and Fastest-Growing Application Segment of the AI in Genomics Market9.3 Drug Discovery & Development9.3.1 Growing Application of AI in Genomics in Drug Discovery & Development to Propel Market Growth9.4 Precision Medicine9.4.1 Precision Medicine Focuses on Identifying the Most Effective Medical Treatments for Patients9.5 Agriculture & Animal Research9.5.1 AI in Genomics Helps in Improving the Productivity of Crops and Livestock9.6 Other Applications

10 Artificial Intelligence in Genomics Market, by End-user10.1 Introduction10.2 Pharmaceutical & Biotechnology Companies10.2.1 Rising Demand for Solutions to Cut Time and Costs of Drug Development Have Drawn End-User Attention to AI in Genomics10.3 Research Centers, Academic Institutes, & Government Organizations10.3.1 Rising Research Activity to Drive the Usage of AI in Genomics Systems Among Academic & Government Institutes10.4 Healthcare Providers10.4.1 Increasing Demand for Pharmacogenomics to Drive the Acceptance of Ngs in Hospitals10.5 Other End-users

11 Artificial Intelligence in Genomics Market, by Region11.1 Introduction11.2 North America11.2.1 US11.2.1.1 The US Dominates the North American AI in Genomics Market11.2.2 Canada11.2.2.1 Increasing Research in Genomics to Drive Market Growth11.3 Europe11.3.1 UK11.3.1.1 UK to Register the Highest CAGR in the European Market During the Forecast Period11.3.2 Germany11.3.2.1 Availability of Funding for AI Initiatives to Boost the Market Growth in Germany11.3.3 France11.3.3.1 Increasing Government Investments in Genomics to Boost the Growth of the French Market11.3.4 RoE11.4 Asia-Pacific11.4.1 Efforts to Develop It Infrastructure Will Drive the Market for AI in the APAC11.5 RoW

12 Competitive Landscape12.1 Overview12.2 AI in Genomics Market: Ranking Analysis (2019)12.3 Competitive Scenario (2018-2020)12.3.1 Key Agreements, Contracts, and Partnerships (2018-2020)12.3.2 Key Product Launches (2018-2020)12.3.3 Key Expansions (2018-2020)12.3.4 Key Acquisitions (2018-2020)12.4 Competitive Leadership Mapping12.5 Vendor Inclusion Criteria12.5.1 Stars12.5.2 Emerging Leaders12.5.3 Pervasive Players12.5.4 Emerging Companies

13 Company Profiles13.1 IBM13.2 Nvidia13.3 Microsoft Corporation13.4 Deep Genomics13.5 BenevolentAI13.6 Fabric Genomics13.7 Verge Genomics13.8 Freenome Holdings13.9 Molecularmatch13.10 Cambridge Cancer Genomics13.11 Sophia Genetics13.12 Data4Cure13.13 Precisionlife13.14 Genoox13.15 Lifebit13.16 Diploid13.17 Fdna13.18 DNAnexus13.19 Empiric Logic13.20 Engine Biosciences

14 Appendix14.1 Discussion Guide14.2 Available Customizations14.3 Related Reports14.4 Author Details

For more information about this report visit https://www.researchandmarkets.com/r/cz1n76

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

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The Worldwide Artificial Intelligence in Genomics Industry is Expected to Reach $1.6 Billion by 2025 - PRNewswire

Over the past several years, the oncology community has witnessed a significant improvement in identifying genetic mutations associated with increased risk of breast malignancies.1 As the understanding of genetic risk factors in breast cancer continues to grow, professional organizations have sought to provide specific recommendations for genetic testing that would prevent overtesting yet still diagnose as many mutations as possible in patients.

In general, the gold standard [for guidelines] is clinical utility, said Susan M. Domchek, MD, the Basser Professor in Oncology at Penn Medicine in Philadelphia, executive director of the Basser Center for BRCA, and director of MacDonald Womens Cancer Risk Evaluation Center. Were all looking at the same data, and it just comes down to perspective for how you interpret those data.

Currently, controversy surrounds guideline recommendations for eligibility in genetic testing. The US Preventive Services Task Force and the National Comprehensive Cancer Network (NCCN) guidelines recommend genetic testing for patients with breast cancer and a family history associated with germline BRCA1/2 mutations or who have a personal history with an increased risk of BRCA1/2 mutations.1,2 Utilizing testing criteria recommended by the NCCN may not identify a small number of individuals who have no family history but carry pathogenic variants of high-risk breast cancer genes.

The guidelines from the NCCN focus on the likelihood of finding genes where we have specific information [on] how to use that and how helpful it is to patients, for instance, [with] BRCA and other [high-penetrance] gene mutations, said Domchek.

Conversely, the American Society of Breast Surgeons (ASBrS) recommends genetic testing for all patients with breast cancer.3 However, the paradigm shift from genetic testing in individuals with a family history to the testing of all patients with breast cancer, as recommended by ASBrS, may lead to unnecessary testing and the potential for harm.4 The optimal model for genetic testing in patients with breast cancer has not yet been identified, though some strategies have been proposed.

According to results of a recently published single-center, prospective study, population-based genetic testing in patients with breast cancer younger than 65 years may optimize the identification of germline pathogenic variants.5 The sensitivity and specificity of NCCN and ASBrS criteria for germline pathogenic variants were assessed. The primary analysis evaluated 9 established, actionable breast cancer predisposition genes (ATM, BRCA1/2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). In the entire population evaluated (N=3907), 6.2% had germline pathogenic variants, with CHEK2, BRCA2, BRCA1, and ATM occurring at the highest frequency.

CHEK2 and ATM are challenging because theyre strongly modified by family historyso we view it as a risk factor, Domchek said.

Approximately 48% of patients met NCCN guidelines criteria for genetic testing, whereas 52% of patients did not. Individuals who met NCCN criteria were more likely to have a pathogenic variant in 1 of the 9 genes, 9.0% versus 3.5%, compared with individuals who did not meet NCCN criteria (P<.001). The primary analysis revealed a sensitivity of 70.1% and a specificity of 53%. When the investigators modified the NCCN criteria to include patients who were 65 years old at the time of receiving a diagnosis and family history, the sensitivity increased to over 90% for pathogenic variants in 9 predisposition genes.5 Currently, the clinical utility in genetic testing in women over 65 years is unknown because the probability of detecting a germline pathogenic variant decreases with age.4

To improve upon a previous study by Yadav et al, Desai et al proposed to test individuals with breast cancer under 60 years.4 The sensitivity for detecting pathogenic variants decreased slightly when testing patients under 60 years compared with patients who were 65 years or younger, 98.1% versus 95.3% for BRCA1/2, respectively. The sensitivity for detection of pathogenic variants in 6 high-risk genes also decreased with age 60 years and under compared to 65 years and under, 94.8% versus 91%, respectively. For patients who received a breast cancer diagnosis who were over 60 years, the investigators concluded that using the NCCN family-based criteria would be appropriate. However, the investigators noted there might be an increased detection of variance of unknown significance (VUS) with this approach.

In addition to the controversy of patient selection for genetic testing, a lack of consensus exists regarding the number of genes that the testing panel should include. The introduction of next-generation sequencing has allowed genetic testing to become more accessible with a lower financial burden.6 There are over 170 breast cancer susceptibility variants identified based on the largest genome-wide association study.7

Costs are coming down, but when people at low risk get genetic testing, were more likely to find things [such as] VUS, which are changes in the genetic code that we dont understand, than we are to find something important. The risk-benefit ratio changes depending on [what] the risk is to begin with, said Domchek.

A study using Surveillance, Epidemiology, and End Results (SEER) data evaluated 187,535 patients with breast cancer.8 However, only 25.2% of those patients had genetic testing analysis. This genetic testing demonstrated a prevalence of BRCA1/2 pathogenic variants in 5.2% of individuals, whereas other genetic variants (APC, CDH1, MLH1, MSH2, MSH6, NF1, PMS2, PTEN, RET, and TP53) were associated with an increased risk of breast cancer in 4.9% of individuals.

We dont do a great job of testing individuals who currently meet testing criteria, and we have a real problem with disparity. We want to make sure that people at the highest risk are being tested. Thats a clear priority, stated Domchek.

Another study that evaluated the prevalence of germline pathogenic variants used a US-based consortium, Cancer Risk Estimates Related to Susceptibility Genes (CARRIERS).9 The analysis included 12 studies that were part of the population-based CARRIERS analysis with 32,247 case patients and 32,544 controls. There were 12 established breast cancer predisposition genes assessed (ATM, BARD1, BRCA1/2, CDH2, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53). The prevalence of germline pathogenic variants in the population-based analysis was 5.03% (95% CI, 4.79%-5.27%) in case patients and 1.33% (95% CI, 1.50%-1.78%) in controls (FIGURE).9 The highest rates of prevalence of pathogenic variants were seen with BRCA2, CHEK2, and BRCA1 genes.

Regarding the study, Domchek said, If you look at 12 genes that are putatively associated with breast cancer, 5% of patients have mutations in those genes, but several of those [genes] are not clearly associated with risk.

Results also determined pathogenic variants in BRCA1 (odds ratio [OR], 7.62; 95% CI,5.33-11.27) and BRCA2 (OR, 5.23; 95% CI, 4.09-6.77) were associated with high breast cancer risk. Moderate breast cancer risk was observed in pathogenic variants in PALB2 and CHEK2 (OR, 3.83; 95% CI, 2.68-5.63; and OR, 2.47; 95% CI, 2.02-3.05), respectively.

Furthermore, different pathogenic variants were associated with specific breast cancer subtypes. Pathogenic variants in BARD1, RAD51C, and RAD51D placed the individual at moderate risk for estrogen receptor (ER) negative breast cancer and triple-negative breast cancer (TNBC). Conversely, pathogenic variants in ATM, CDH1, and CHEK2 were associated with ER-positive breast cancer. Additionally, there was a higher prevalence of pathogenic variants in BRCA1/2 and PALB2 observed with TNBC compared with ER-positive breast cancer, 8.13% versus 1.84%, respectively.

Another large study analyzed data from 44 studies in the Breast Cancer Association Consortium with 60,466 patients and 53,461 controls.10 For the purpose of population-based analysis, 48,826 patients and 50,703 controls were included from the total number of individuals in the study. Results showed pathogenic variants in 5 genes were associated with an increased risk of breast cancer (P <.0001). Additional pathogenic variants associated with high-risk breast cancer were found in BARD1, RAD51C, RAD51D, and TP53 (P <.05). There were also associations with pathogenic variants and different subtypes of breast cancer. As in the CARRIERS study, CHEK2 was associated with ER-positive compared with ER-negative breast cancer (OR, 2.67; 95% CI, 2.30-3.11; vs OR, 1.64; 95% CI, 1.25-2.16). Pathogenic variants in ATM were more frequently found in ER-positive than in ER-negative breast cancer (OR, 2.33; 95% CI, 1.87-2.91; vs OR, 1.01; 95% CI, 0.64-1.59). Additionally, there were more pathogenic variants (BARD1, BRCA1/2, PALB2, RAD51C, and RAD51D) associated with ER-negative compared with ER-positive breast cancer (P <.05).

The appropriate identification of patients and important pathogenic variants in genetic testing may lead to optimization of care in the age of precision medicine. The results from genetic testing may have implications for patients ranging from surgical, radiation, and targeted therapeutic intervention, as well as prevention strategies for patient family members.6 Patients with BRCA1/2 mutations with metastatic breast cancer may benefit from targeted therapy with PARP inhibitors.6,11

In the early-stage [breast cancer] setting, were testing BRCA1/2 to talk about removal of the ovaries and the consideration for removal of the [contralateral] breast. The clearly actionable [genes] are BRCA1/2 and PALB2, said Domchek.

A population-based cohort study evaluated pathogenic variants and clinical treatment pathways in patients with breast cancer using SEER registries in 20,568 individuals.11 Patients were nonexclusively stratified into 3 separate treatment subgroups including surgery, radiation, and chemotherapy. The results demonstrated an increased prevalence of bilateral mastectomy (n=15,126) and chemotherapy treatment (n= 8509) for individuals with pathogenic variants in BRCA1/2 or other genes (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53). Individuals with BRCA1/2 and other genetic pathogenic variants were more likely to undergo bilateral mastectomy compared with those with VUS (OR, 5.52; 95% CI, 4.73-6.44; and OR, 2.41; 95% CI, 1.92-3.03; vs OR, 0.99; 95% CI, 0.89-1.1, respectively). Additionally, individuals with BRCA1/2 and other genetic pathogenic variants were more likely to receive chemotherapy treatment compared with those with VUS (OR, 1.76; 95% CI, 1.31-2.34; and OR, 1.27; 95% CI, 0.87-1.86; vs OR, 0.95; 95% CI, 0.81-1.11, respectively). There is currently no consensus on patient selection or gene selection.

Our goal is to make sure that every candidate who is a good candidate for genetic testing gets tested regardless of their race, ethnicity, or socioeconomic status. Family history should be taken, and [patients] should know about the availability of testing and be counseled on their level of risk, said Domchek. This is the intersection among regulations, insurance coverage, and prior probability. I do think that genetic testing is only going to become more widespread, and our job is to make sure that patients understand what tests are being sent and the potential implications of the results.

References:

1. NCCN. Clinical Practice Guidelines in Oncology. Genetic/familial highrisk assessment: breast, ovarian, and pancreatic, version 2.2021. Accessed February 8, 2021. https://bit.ly/3uc4qqY

2. BRCA-related cancer: risk assessment, genetic counseling, and genetic testing. US Preventive Services Task Force. August 20, 2019. Accessed February 8, 2020. https://bit.ly/37o7EOo

3. Manahan ER, Kuerer HM, Sebastian M, et al. Consensus guidelines on genetic testing for hereditary breast cancer from the American Society of Breast Surgeons. Ann Surg Oncol. 2019;26(10):3025-3031. doi:10.1245/ s10434-019-07549-8

4. Desai NV, Yadav S, Batalini F, Couch FJ, Tung NM. Germline genetic testing in breast cancer: rationale for the testing of all women diagnosed by the age of 60 years and for risk-based testing of those older than 60 years. Cancer. Published online November 4, 2020. doi:10.1002/cncr.33305

5. Yadav S, Hu C, Hart SN, et al. Evaluation of germline genetic testing criteria in a hospital-based series of women with breast cancer. J Clin Oncol. 2020;38(13):1409-1418. doi:10.1200/JCO.19.02190

6. Angeli D, Salvi S, Tedaldi G. Genetic predisposition to breast and ovarian cancers: how many and which genes to test? Int J Mol Sci. 2020;21(3):1128. doi:10.3390/ijms21031128

7. Zhang H, Ahearn TU, Lecarpentier J, et al. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nat Genet. 2020;52(6):572-581. doi:10.1038/ s41588-020-0609-2

8. Kurian AW, Morrow M, Katz S. Trends in genetic testing and results for women diagnosed with breast cancer or ovarian cancer, 2013-2017. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-12, 2020; virtual. Abstract PD10-01.

9. Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. N Engl J Med. 2021;384(5):440- 451. doi:10.1056/NEJMoa2005936

10. Breast Cancer Association Consortium, Dorling L, Carvalho S, et al. Breast cancer risk genes - association analysis in more than 113,000 women. N Engl J Med. 2021;384(5):428-439. doi:10.1056/NEJMoa1913948

11. Kurian AW, Ward KC, Abrahamse P, et al. Association of germline genetic testing results with locoregional and systemic therapy in patients with breast cancer. JAMA Oncol. 2020;6(4):e196400. doi:10.1001/jamaoncol.2019.6400

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Next-Generation Sequencing Informs Genetic Testing in Breast Cancer - Targeted Oncology

-- Application website is now open for the 2021 Scholarship Program --

-- The Company will award up to 15 academic scholarships to individuals diagnosed with Duchenne muscular dystrophy --

CAMBRIDGE, Mass., March 23, 2021 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that the website for Route 79, The Duchenne Scholarship Program, is officially open and accepting applications. Academic scholarships of up to $5,000 will be awarded to up to 15 individuals chosen by an independent committee of Duchenne community members based on an applicants community involvement, personal essay, and recommendation letter. The Route 79 program is designed to help students with Duchenne pursue their post-secondary educational goals.

We are thrilled to be launching Route 79, The Duchenne Scholarship Program, for the fourth year. Over the course of the program, weve had the privilege of granting over 50 scholarships to students with Duchenne, as they work to achieve their unique and varied educational goals. Each year brings new applicants, along with impressive examples of resilience, ambition, and commitment to learning. It is our great pleasure to offer this scholarship to support these students in their pursuit of higher education. We look forward receiving and evaluating applications for the next group of Route 79 scholars for the 2021-2022 school year, said Diane Berry, Sareptas Senior Vice President of Global Health Policy, Government and Patient Affairs.

The underlying cause of Duchenne is a mutation or error in the gene coding for dystrophin. Dystrophin is an essential protein that plays a pivotal role in muscle structure, function and preservation. The numerical significance of the scholarships name, Route 79, ties to the 79 exons of the dystrophin gene.

To apply for a scholarship through the Route 79 program, applicants must be accepted to or enrolled in an accredited college or university or a trade, technical or vocational school located in the United States and be diagnosed with Duchenne muscular dystrophy. College seniors or college graduates accepted to or enrolled in graduate school are also eligible to apply. Previous recipients of Route 79 scholarships are eligible to apply for the 2021 Scholarship Program and prior recognition in the Program will have no bearing on 2021 applications. No consideration will be given to whether an applicant was previously, is currently, or expects to be in the future, undergoing treatment with a Sarepta product or investigational therapy.

Applications will be accepted until May 11, 2021 at 11:59 p.m. PDT. Recipients will be notified prior to August and awards will be distributed in time for fall 2021 enrollment. Students may learn more about the program and how to apply by clicking here.

AboutSarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive and competitive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis Type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy 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.

Sarepta Therapeutics, Inc.

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

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

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Sarepta Therapeutics Announces Fourth Year of Route 79, The Duchenne Scholarship Program - GlobeNewswire

THURSDAY, March 25, 2021 (HealthDay News) -- Women with advanced ovarian cancer often face grim statistics, with less than half surviving for five years after their diagnosis. However, a new study suggests that so-called "maintenance therapy" with a targeted cancer drug may add years to some patients' lives.

In findings described by some experts as "remarkable," the study showed that women with advanced ovarian cancer linked to the BRCA gene were much more likely to be alive with no signs of their cancer coming back in five years if they receive Lynparza (olaparib), a targeted cancer therapy known as a PARP inhibitor.

This class of drugs blocks an enzyme called PARP that cancer cells need to repair damage to their genetic material, and blocking it causes cancer cells to die. There are two other PARP inhibitors approved to treat ovarian cancer, Zejula (niraparib) and Rubraca (rucaparib).

PARP inhibitors are particularly effective against cancers linked to BRCA genes. Often thought of as the breast cancer genes, BRCA1 and BRCA2 are responsible for roughly 25% of ovarian cancer cases.

The new study provides five-year follow-up data from a clinical trial of women with BRCA-positive advanced ovarian cancer who received Lynparza for two years after their initial treatment ended.

Happily, the survival benefits lasted five years out regardless of how aggressive the cancers were, said study author Dr. William Bradley, a gynecologic oncologist at Froedtert Health and Medical College of Wisconsin in Milwaukee.

It's still too early to use the word cure, but that may be where this is headed, he added. "Maintenance therapy with Lynparza really should be considered standard of care for BRCA-positive advanced ovarian cancer," Bradley said.

The study included 391 women with a BRCA mutation and advanced ovarian cancer who completed chemotherapy; 260 received Lynparza and 131 received a placebo. When compared with women on the placebo pill, more than twice as many women on Lynparza were still alive with no progression of their cancer five years after the study began. The trial was funded by Lynparza maker AstraZeneca.

"This is really good news," Bradley said. "Women enjoyed the benefit for the next three years when off therapy."

Calling the new results "quite remarkable," Dr. Konstantin Zakashansky, director of gynecologic oncology at Mount Sinai West in New York City, said that the new findings may well be akin to a cure for these women.

"Even after five years, there is quite a significant benefit," said Zakashansky, who wasn't part of the study. "We have never seen anything like this before with ovarian cancer."

PARP inhibitors do have their share of side effects, including risk for blood abnormalities that can leave women more prone to infection or fatigue, but the follow-up data showed that these do not get worse with time, researchers said. "The safety signal did not progress or become ominous," Bradley said.

These women will now be followed indefinitely, he added.

The new findings suggest that maintenance therapy with Lynparza has a lasting impact for women with BRCA-positive advanced ovarian cancer, and time will answer all remaining questions, said Dr. Deborah Armstrong, a professor of oncology at Johns Hopkins Kimmel Cancer Center in Baltimore. She was not involved in the new study.

"Is it possible that two years of therapy with this drug is nipping cancer cells in the bud or are they just quieted down and will come back later?" Armstrong asked.

Another point is that the new drug may be cost-prohibitive for some women, she said. "It is extremely expensive, costing $10,000 to $12,000 a month, and even people with really good insurance have high copays."

The findings were presented at the Society of Gynecologic Oncology's virtual annual meeting, held March 19-25. Findings presented at medical meetings are considered preliminary until published in a peer-reviewed journal.

More information

The National Ovarian Cancer Coalition offers more on ovarian cancer treatment options.

SOURCES: William Bradley, MD, gynecologic oncologist, Froedtert Health and Medical College of Wisconsin, Milwaukee; Deborah K. Armstrong, MD, professor, oncology, professor, gynecology and obstetrics, Johns Hopkins Kimmel Cancer Center, Baltimore; Konstantin Zakashansky, MD, director, gynecologic oncology, Mount Sinai West, and associate professor, obstetrics and gynecology, Icahn School of Medicine, Mount Sinai, New York City; Society of Gynecologic Oncology, virtual annual meeting; March 19-25, 2021

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Drug Boosts Survival for Women With Advanced Ovarian Cancer - HealthDay News