BOSTON Thomas Feldborg and Daria Rokina set off nearly every afternoon to explore this city. They leave from theirhotel in theCharlestown neighborhood, pushing theirbaby carriage, some days heading deep into downtown, others choosing a path along the Charles River.

Every few minutes, Rokina stopsto peek inside and check on 16-month-old Alissa. Shegently rubs Alissa'scheek and coos a few soothing words, makingsure the little girl is warm enough in her yellow snowsuit and adjusting hersparkly unicorn earmuffs.

Alissa restsbetter in the outside air. Thedaily walksallowthecoupleto relieve some of the stress of notknowing whether their daughter will survive and if so,in what condition.

Feldborg, 50, has three older sons, and Rokina, 43, has one. Alissa, their first child together,was born Dec. 2, 2019, in Copenhagen, Denmark,where the family lives.For her first four months of life, Alissaseemed perfectly normal. She learned to roll and sit up. She babbledand grabbedfor toys.

Then her progress began to stall. By six months when Alissa wasn't trying to crawl, Rokina took her to the pediatrician. Children advance at their own pace, the doctorassured her. Nothing was wrong.

At eight months, the trouble became impossible to ignore. Alissa was hospitalized, dehydrated and unable to eat. A neurological exam turned up cherry red spots atthe back of her eyes, a devastating observation in a baby, because it indicates one of a few genetic disorders, most terrible and deadly before age5.

New hope for 16-month-old battling rare, fatal genetic disorder with gene therapy

Alissa Feldborg is 16 months old and is undergoing gene therapy for Sandhoff disease, a very rare, fatal genetic disorder.

Robert Deutsch, USA TODAY

Feldborg immediatelystarted Googling.Before Alissa received the diagnosis of Sandhoff disease, an extremely rarecondition, he already had stumbled across the idea of gene therapy. If they could just repair the faulty gene Alissa inherited from him and Rokina, she might have a shot at life.

That internet research led the couple to the University of Massachusetts, where in late January, Alissa, then nearly 14months old,became the first child in the world to receive a full dose of a new gene therapy. If it worked, it would trigger the cells in her brain to start making theenzyme they had been missing,clearing out cellular debris, so they can function normally.

CHOOSING HOPE

The first in an occasional series exploring how scientific advancesare transforming care for rare diseases.

Gene therapy like Alissa's a scientific vision for decadesis finally becoming a more common reality in the United States.

Dozens of disorders are now being treated, though most still only in clinical trials, like Alissa's. Within the next few years, experts say, gene therapies could soon be available for conditions never effectively treatable before,such as sickle cell disease, Huntington's, ALS, Parkinson's, some formsof heart disease and a host of very rare diseases.

"The exponential growth phase" of gene therapy has arrived, saidDr. Cynthia Tifft,director of the Pediatric Undiagnosed Diseases Program atthe National Institutes of Health.

"Finally, after literally decades of hearing it was just around the corner, we are witnessing some real successes," said Dr.Isaac Kohane,chair of the Department of Biomedical Informatics atHarvard Medical School and head of the federally funded Coordinating Center for the Undiagnosed Diseases Network.

At their best, gene therapies offer the possibility of a cure,truly reversing the root cause of a disease.

But as simple as the idea seems just fixing a DNA typo it is incredibly difficult to turn into an actual therapy. Scientists so far have spent decades on each step in the process.

And with such a new procedure, aimed athaving lifelong benefits, it's too early to know whether these approaches will change a child's trajectory, allow an adult to live without fear and pain,or prevent a disease from evercoming back.

"People are underestimating what it's going to take to make (gene therapy) work in the short term,"Kohane said,"and under-appreciating how transformative it will be in the long term."

On her first birthday, Dec. 2, 2020, Alissa received a colorful book and toy. She grabbed for both, excited to reach them.

But by the end of themonth, she could no longer make that simple movement. She could barely hold up her head and slipped into silence.Seizures accelerated the regression.

"She went more into herself … she was not very present anymore,"Feldborg said.

He and Rokina felt totally alone deciding whether to pursue the treatmentfor Alissa. Two other babies had similar procedures with a lower gene therapy dose, but medical privacy laws prevented the couple from speaking with their parents.

There was no doubtwhat would happen if they did nothing.

Parents of 16-month-old Alissa Rokina Feldborg, Daria Rokina and Thomas Feldborg on April 13, 2021 in Arlington, Mass.Robert Deutsch, USA TODAY

For babies with Alissa'sdisorder and a "cousin" condition called Tay-Sachs disease, "their quality of life is essentially vegetative," Tifft said. Feeding tubes and other supportive care can keep them alive for a while.But they all die by the time they should be entering kindergarten.

So, as Feldborg said, the pairdecided to "lethope conquer the fears." It was simply too awful to watch her decline without trying anything when they were among the first families in history who could try something.

But even as he and Rokina packed and boarded a plane for the U.S. in early January, theywere tormented by the idea that the therapy might onlykeep Alissa alive longer in the same miserable state.

"Instead of having this cruel, short life of two, three, maybe four years, maybe she will just have a cruel, long life," Feldborg said,while walking through a park on a brisk, early spring afternoon. "That's what we were fearing."

On Jan. 26, after weeks of testing to make sure she was still a good candidate and prepare her for the procedure, Alissa was wheeled into an operating room atUMass Memorial Medical Center in nearby Worcester for brain surgery.

Researchers felt that the best way to unclog her brain cells was to inject the gene therapy directly into her thalamus, two oval structuresdeep inside the brain that actas sort of a highway junction, connecting paths from many parts of the brain. Doctors used an image-guided robotic arm to ensure it got to the right spot.

The next day, the same gene therapy was infused into the fluid aroundher spinal cord so it could penetratethe nerves there.

If it worked as planned, the added geneswould instruct cells throughout her nervous system and brain to start producing the missing enzyme.

"You don't actually need a lot of enzyme activity in order for the neurons to function better," said Dr. Pavan Cheruvu, CEO of Sio Gene Therapies, the New York-based biotech company running the trial and paying the full cost of Alissa's treatment and her parents' stay in the U.S.

One previous child had received the thalamic surgery, butthere wasn't enough of the therapy available to give hera full dose. So far, her condition has been stable at a time when most kids with the condition decline, said Dr. Terence Flotte, dean of theUMass Medical School, who is leading Alissa's trial. Another child got the spinal injection but not the thalamic one.

Alissa was the first to get a full dose in both places.Later patients in the trial will get an even higher dose. Feldborg and Rokina hopeAlissa got enough to make a profound and positive difference in the course of her life.

But for now, all they can do is wait. And walk.

Thomas Feldborg and wife Daria Rokina carry their daughter Alissa Rokina Feldborg, 16 months old, home from a therapy session on April 13, 2021 in Arlington, Mass.Robert Deutsch, USA TODAY

About 45 minutes west of Boston, a herd of Jacobsheep live in a series of pens overlooking rolling hills.

Guarded by a llama and an electric fence, both to keep coyotes away, several sheep pause to stare at strangers at the Cummings School of Veterinary Medicine at Tufts University where they live. Then they boltoff.

These 110 sheep are the descendants of a pairthat once lived on a Texas farm. In 1999, twolambs began stumbling and tripping. They developed seizures, lost sight and had trouble swallowing before dying young.OwnersFred and Joan Horak wanted to understand why.

It took a decade for a researcher from New York University Medical Center, nowNYU Langone Health,to figureout the sheep carried the same genetic mutation that causes Tay-Sachs disease. Researchers later learned cats also can inherit a similar genetic mutation.

Finding an animal model in which adisease naturally occurs is extremely helpful for developing treatments, said Douglas Martin, a professor at theAuburn University College of Veterinary Medicine in Alabamawho studies these conditions in house cats.

In animals, researcherstested and refined the virusthat eventually deliveredAlissa's gene therapy.

Stephanie Bertrand, assistant farm manager at Cummings School Farm at Cummings School of Veterinary Medicine at Tufts University, provides care for the Jacob sheep that are integral to the research being led by University of Massachusetts Medical School. Photo credit: Matthew Healey for Tufts University.Matthew Healey, Matthew Healey for Tufts University

Gene therapies are often transportedinto cells by viruses similar to howpathogens are usedto deliver the COVID-19 vaccines madeby Johnson & Johnson and AstraZeneca-Oxford University. It's taken decades to find the appropriateviruses and engineer them to safely deliver genes or editing tools.

In Alissa's trial, a virus carries DNA instructions for making the missing enzyme. Designed by Miguel Sena-Esteves, aUMass Medical School researcher who has been working on the project for more than a decade, the therapy delivers two genes, even though Alissa is only missing one. Animal studies showed that adding both the gene that causes Tay-Sachs plus a nearbyone that causes Sandhoff provides the best results for children with both conditions.

Alissa'sown DNA isn't changed in this approach, though other gene therapies rely on gene editing to altercells'DNA code.

Her immune system is kept tamped down with medication so that, if needed, she can be dosed again with the virus-carrying gene therapy, Flotte said.

Lena Labdi, a research assistant at the University of Massachusetts Medical School in Worcester, examining slides in the Sena-Esteves lab on April 13, 2021.Robert Deutsch, USA TODAY

Researchers have tried beforeto treat both conditions by providing the missing enzyme instead of adding genes, but it is too big to cross from the bloodstream into the brain.

By 2012, Sena-Esteves had shown that the virus and gene therapy worked in mice;Martin, at Auburn, provedthe samein cats, anda third colleague, HeatherGray-Edwards, now of UMass Medical School,used it to rescueJacob sheep.

Just before trying the approach in children, the team decided to test it in monkeys. The Food and Drug Administration probably wouldn't have required it after their success in other animals, but they wanted to be extra cautious.

The results were devastating. The monkeys became apathetic and lostdexterity, Edwards said. They clearly weren't helped.

It took years of research to figure out thatthe animalshad gotten too much of a good thing: The extra enzymes that helped cleanup the brain cells of other mammals was overwhelming and killing the monkey's cells.

Sena-Esteves said the day helearnedthe resultswas perhaps the worst of his professional life. Butit was far better to learn the lesson on monkeys.

The therapy given to childreniscarefully calibratedin hopes of achievinga Goldilocks balance: not too little, but not too much.

Lena Labdi, a research assistant at the University of Massachusetts Medical School, working in the Sena-Esteves lab on April 13, 2021, in Worcester, Mass.Robert Deutsch, USA TODAY

Last year, Feldborg and Rokina, both now on paid leave from their sales and logistics jobs, befriended the other two Danish families whosebabies had beendiagnosed with Sandhoff.

One child was two months older than Alissa, the other eight months older. Neither got gene therapy. Bothdied earlier this year.

Doctors selected Alissa for the trial hoping she was still young enough andher losses recent enoughthat the damage to her brain might be reversible.

"We think that there are many cells that are simply under duress" due to the toxic build-up of fats, said Dr. Florian Eichler, a pediatric neurologist at Massachusetts General Hospitalwho treatsAlissa. "If we can appropriately return a healthy copy of the gene and the enzyme, that cell can recover."

Last fall, watching their daughter slip further away, Feldborg and Rokina worried that Alissawould be disqualified from the trial because shehad already lost too much function, or that thetreatment would come too late to make a difference.

Alissa Feldborg receives treatment from Feldenkrais practitioner Matthew Wilkinson while dad Thomas and mom Daria watch on April 13, 2021 in Arlington, Mass.Robert Deutsch, USA TODAY

Doctors warned them not to expect much. No one knewifthe therapy would help or how long it might take to start seeing changes.

But just a weekafter the surgeries, Alissa's sparkling blueeyes, which had been rolling randomly and constantly, seemed to stabilize andfocus. With eyes in constant motion, she couldn't have been ableto see much.

Now that they're more focused, it's also easier to feel like there's someone present behind them.

In February, Alissa started to move her hands with some intentionandbegan eating more. Swallowing was the one skill she hadn't lost, but perhaps because of the steroids that are part of her careshebecame hungry again, accepting spoonfulsof soft food. Recently, shelearned how to suck downa bottle for the first time.

"If this development will continue, we are just so very happy," Rokina said."It'sso nice."

There also was a wonderful surprise. About two weeks after her surgeries, Alissa started smiling again. Not in response to the outside world, but to some internal moment of pleasure or humor.

A few days after that, she laughed a deep, guttural belly laugh. Feldborg said he can count on one hand the number of timesshe had laughed like that before the procedure. But for the last few weeks, she has enjoyed a private laugh nearly every day.

The sound of those belly laughshas been a gift, a balm.

The first time it happened, while giving hera bath,Feldborg said,"Wewere so happy, we just kissed each other like we had become world champions in our favorite sports."

To compensate for her lack of sight and hearing, Rokina and Feldborg tryto offerAlissa some connection to the worldthrough touch.

Rokina,a native of Russia, grew up with the tradition of giving babies massages. Before Alissa's gene therapy, months of massages and movement therapy had done little except perhapsallowher to keep swallowing.

After the surgeries, Feldborg and Rokinarenewed the practice, drivingAlissa once a week to baby massage sessions in a far-flung Boston suburb, andtwo or three mornings a week to the closer-in town of Arlington, where Matty Wilkinson triesto reconnect the little girl's brain to the body she can do so little with.

Wilkinson, who has a master's degree in child development as well as training inthe Feldenkrais Methodand the Anat Baniel Method for Children, uses small movements aimed atteaching Alissa'sbrain to once again sense her neck, arms, legs, pelvis and spine.

Feldenkrais practitioner Matthew Wilkinson provides treatment to 16-month-old Alissa while dad Thomas Feldborg and mom Daria Rokina watch on April 13, 2021 in Arlington, Mass.Robert Deutsch, USA TODAY

"She's having to rebuild a map of herself, how she can interact with her environment," he said after a recent session. "I'm trying to make the information clearer and more distinct, so she can perceive those feelings … so she can gain more choice."

Laying Alissa on her side, Wilkinson pulls gently on her left arm while touching the back of the same shoulder. She occasionally moves her mouth in a sucking motion, but otherwise lies still.

One of the first truly successful gene therapies, for a condition called spinal muscular atrophy,showed that the treatment, while immensely effective, wasn't enough on its own. Just as newborns learn to control their limbs by moving them, so children whose brains have lost the ability todirect movement ornever developed it in the first place need practice for the proper wiring to form.

"We say with the nervous system, you have to use it or you lose it," Eichler said. "There has to be continued stimulation, activity, and so all of those things Alissa's parents do so well with her are vital."

People tell Feldborg how "brave" he and his wife are for trying gene therapywith Alissa. He's not sure how to respond.

"There's a fine line between bravery and stupidity," he said. "Are we so stupid in our hope? Is it a fool's mission we're on?"

This past week,three months after her surgery, doctors began a battery of tests on Alissa to see if they can detect objective signs ofprogress. They're hoping to see evidence on herMRI scan that her brain is repairing itself.

The trial would be deemed successful if it achieved any of three possible outcomes, said the NIH's Tifft: It could slow Alissa's decline, keep her from slipping any furtheror actually help her gain skills.

"None of these children ever improve on their own. They just don't," Tifft said."In a disease that only progresses downhill, even preserving function is a win."

"Then the question is, for how long," she added.

No matter what happens, the trial represents "a huge milestone" in the treatment of Sandhoff and related diseases,Eichler said.

Tay-Sachs wasidentified more than a century ago.The chemistry of whatitand Sandhoff do to the brain has been understood for at least half that time. Now,the gene deficit itself can finallybeaddressed, Eichler said.

Still, a lotto be learnedabout the best timing for the therapy, what cells need to be targeted andwhat meaningful change looks like.

"That is the nature of progress. If we knew what works, we wouldn't need to conduct trials," Eichler said."I feel for the parents."

For their part, Feldborg and Rokina say they hope the trial will help others, but are realistic about what might be achievable for themselves. They know Alissa will never be like other children. They just want a daughter they can communicate with in some way.

"She can be in a wheelchair or whatever," Feldborgsaid, "but if we don't get a thinking person out of this,that's where I think we may have been more stupid than brave."

Contact Karen Weintraub at kweintraub@usatoday.com.

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.

Excerpt from:
An experimental gene therapy was little Alissa's only hope. Now, instead of certain death, she faces an uncertain future. - USA TODAY

Dive Brief:

BioMarin, a California biotech that built its business around drugs for rare diseases, is a leading gene therapy developer. The Food and Drug Administration reviewed the company's treatment for hemophilia A last year and,while the agency unexpectedly rejectedits application, many expect the regulator to eventually approve the therapy once BioMarin has more follow-up data in hand.

The drugmaker also has gene therapies in earlier stages of testing for a metabolic condition known in shorthand as PKU and a rare disease called hereditary angioedema.

But BioMarin has also been exploring gene therapy for diseases of the central nervous system, although it hasn't publicly commented on its work in the space until Wednesday's announcement of the deal with the Allen Institute.

While targeting CNS diseases presents its own challenges, particularly around delivery of treatment, many gene therapy developers are nonetheless working on would-be therapies. According to a count by Cowen, an investment bank, a third of all disclosed preclinical or clinical gene therapy programs as of January 2021 were in neurology, which encompasses more prevalent diseases like Parkinson's as well as rarer conditions like ALS and Huntington's.

For BioMarin, the Allen Institute could provide a better tool to target some of these diseases. Adeno-associated viruses are a common delivery tool for gene therapy, but the technology is decades old and has limitations. Several biotech startups, as well as academic laboratories and groups like the Allen Institute, have been researching how to improve the usefulness of AAVs.

Under Wednesday's deal, scientists from BioMarin and the Allen Institute will work together to evaluate the nonprofit's modified AAVsfor potential use in building more precise CNS-targeted therapies.

"Combining the Allen Institute's leadership in large-scale genomic science in the central nervous system with BioMarin's proven experience in developing transformational therapies for rare genetic diseases, lays the foundation to potentially deliver multiple investigational gene therapies to the clinic," said Lon Cardon, BioMarin's chief scientific strategy officer, in a statement.

The research behind the Allen Institute's work on modified AAVs was published last month in the journals Neuron and Cell Reports.

Originally posted here:
BioMarin partners with Allen Institute to develop gene therapies for the brain - BioPharma Dive

By the end of this year, Amryts Filsuvez could become the first approved treatment for the rare skin disorder epidermolysis bullosa. Despite mixed pivotal data, regulators in the US and Europe might be swayed by the lack of available treatments.

More durable options could come with gene therapies, and phase 3 studies of these will start to report later this year. However, gene therapyprocedures can be complex, and Amryt will hope that the convenience ofFilsuvez, a topical gel that can be applied at home, could make it the first-line treatment of choice.

First mover advantage

Epidermolysis bulllosa (EB) is a group of inherited skin disorders that cause fragile, blistering skin. Current treatments aim to help alleviate symptoms, including bandaging and bathing open wounds and trying to manage patients pain.

Late last month, Amryt completed the US rolling submission for Filsuvez for junctional and dystrophic forms of EB, and the EMA began its reviewof the project.

The pivotal Ease study was not an emphatic victory, however.The trial met the primary endpoint, the complete closure of the target wound within 45 days, but several secondary measures were missed. These included90-day target wound closure, and the pain endpoint.

Driving the primary treatment effect was a group of patients with the recessive form of dystrophic EB. This was the main patient group in the study, which also recruited junctional and dominant dystrophic EB patients.

Lack of available treatment options means that regulators might look favourably on Filsuvez, but restricting its use torecessive dystrophic patients cannot be ruled out.

According to Stifel analysts the recessive form makes up 15% of patients; they reckon that even if Filsuvez only gets the nod in this population it could still bring in$342m in 2027. This rises to $421m that year with a broader label.

Gene therapy race

As EB is an inherited condition, gene therapy could be the way forward in treating the underlying cause. Amryts own topical gene therapy, AP103, is due to start clinical studies next year, but others are much further ahead, with Krystal, Abeona and Castle Creek all in phase 3.

By the fourth quarter, pivotal data should be available with Krystal Biotechsberemagene geperpavec(B-Vec), atopically applied gene therapy designed to induce local collagen production.

If the project can show strong signs of durability it could differentiate itself from Filsuvez. There are some questions about B-Vec's longevity, however, as in itsphase 1/2 studysome lesions that had closed later reopened (Gene therapys duration is less than Krystal clear, October 29, 2019).

The primary endpoint of the upcoming pivotal Gem-3 trial is complete wound healing at weeks 22 and 24, or weeks 24and 26; only wounds that are completely healed for at least two weeks count as a positive response.

Approximately 30 adult and paediatric patients are being enrolled with recessive or dominant dystrophic EB.Subjects will act as their own controls, receiving either B-Vec or placebo once weekly on different wounds.

B-Vec does not represent a "once-and-done" gene therapy; due to the rapid turnover of skin cells, it still requires frequent applications.

In Gem-3, the project was administered in the clinic butKrystal is hopeful that, if approved,B-Vec could be given at home. If clinic visits are required, thiscould prove problematic as travel can be hard for EB patientsdue to their extremely fragile skin.

Complicated procedures

Further behind are Abeona and Castle CreeksEB-101 and D-Fi respectively. Both offer a personalised treatment approach that is a far cry from the ease of topical application.

With both therapies, biopsiesare taken and skin cells are corrected by gene transfer. Abeonas treatment involves surgically transplanting sheets of cells onto patients wounds while Castle Creeks uses intradermal injections.

Top-line data from Abeonas open-label phase 3 Viital study, inlarge chronic wounds, are due in mid-2022. The trial will enrol 10-15 recessive dystrophic EB patients with wound sites that are larger than 20cm2, which have been present for more than six months.

The primary endpoint is the proportion of wound sites with 50% or greaterhealing from baseline at 24 weeks. This differs from the complete wound closure measure for competitors' treatments, presumably due to the large size of the wounds being treated.

In an earlier study run by Stanford University, wound healing of 50% or greater was present in 95% of wounds treated with EB-101 versus 0% of untreated control wounds at 24 weeks. At two years, 71% of treated wounds had 50% or greater healing compared with 17% of control wounds.

Lastly to Castle Creeks D-Fi, which was previously known asFCX-007 andoriginated at Fibrocell. Aphase 1/2 trial found that after a single dose, 63% of treated woundshad completely closed at 12 weeks, versus none in the untreated cohort.

The phase 3 trial, DeFI-RDEB, is enrolling patients with recessive dystrophic EB, and wounds will be treated for two or more sessions. The primary endpoint is complete wound closure of the first wound pair at week 24, and the study has a primary completion date of April next year.

Here is the original post:
Epidermolysis bullosa gene therapies wait in the wings - Vantage

LEXINGTON, Mass. and AMSTERDAM, The Netherlands, April 28, 2021 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that five data presentations, of which two are oral presentations, will be delivered at the American Society of Gene and Cell Therapy (ASGCT) Virtual 2021 Annual Meeting being held May 11-14.

"Our presentations at ASGCT showcase our gene therapy expertise in hemophilia and Huntingtons disease, as well as advantages of the AAV5 vector in dosing through pre-existing neutralizing antibodies, stated Ricardo Dolmetsch, Ph.D.president of research and development at uniQure. In addition, we look forward to presenting preclinical data demonstrating the potential of the miQURE technology used in our CNS product candidates to be effective in liver-based diseases as well.

Specific details on uniQures presentations at ASGCT include:

About uniQure uniQure is delivering on the promise of gene therapy single treatments with potentially curative results. We are leveraging our modular and validated technology platform to rapidly advance a pipeline of proprietary gene therapies to treat patients with hemophilia B, Huntington's disease, Fabry disease, spinocerebellar ataxia Type 3 and other diseases.www.uniQure.com

uniQure Contacts:

See the original post here:
uniQure Announces Presentations at Upcoming American Society of Gene and Cell Therapy (ASGCT) Annual Meeting - GlobeNewswire

The US Food and Drug Administration (FDA) has removed a clinical hold on Dutch biotech uniQures haemophilia B gene therapy, following concerns over a case of cancer in a patient in a pivotal trial.

In December 2020, the FDA placed a hold on uniQures haemophilia B clinical programme following the diagnosis of hepatocellular carcinoma (HCC) a type of liver cancer in a patient in the HOPE-B trial evaluating AMT-061 (etranacogene dezaparvovec).

In a statement, uniQure said that the patient diagnosed with HCC had multiple risk factors associated with this type of cancer. This included a 25-year history of hepatitis C (HCV) as well as a history of hepatitis B (HBV). Chronic infections with both HCV and HBV are associated with around 80% of HCC cases.

Multiple analyses, following a surgical resection of both the patients tumour and adjacent liver tissue, showed that AAV vector integration in the tissue sample was extremely rare, accounting for 0.027% of the cells in the sample.

The integration events that were present were randomly distributed, the company added, with no signs of clonal expansion or any dominant integration event.

Whole genome sequencing of the tumour also confirmed that it had genetic mutations characteristic of HCC, independent of vector integration.

UniQure noted that a gene expression analysis of the tumour and adjacent tissue suggested a precancerous state in the liver that could have predisposed the patient to developing HCC.

Patient safety is our top priority, and we are grateful to our advisors and the FDA for their help in resolving this clinical hold, said Ricardo Dolmetsch, president of research and development at uniQure.

Our comprehensive investigation showed that AMT-061 is very unlikely to have contributed to the HCC in our patient. We look forward to announcing top-line 52-week data from the HOPE-B pivotal trial later this quarter, he added.

UniQure added that all patients in its haemophilia clinical programme have abdominal ultrasounds performed one year after dosing, with patients continuing to receive this test every six months.

AMT-061 has been granted breakthrough therapy designation by the FDA and a priority medicine (PRIME) designation by the European Medicines Agency (EMA).

Read the original post:
FDA removes clinical hold on uniQure's haemophilia gene therapy - PMLiVE

When Bluebird Bio secured European approval for its gene therapy to treat beta thalassemia in 2019, the biotech entered pricing negotiations confident that a shared risk plan could convince governments to pay $1.8 million per patient for the one-time, potentially curative treatment.

But two years later, Bluebird is pulling its gene therapy, called Zynteglo, from Germany after government officials would not budge from an offer to pay less than half of the companys list price. The stalemate is a significant setback for Bluebirds business ambitions in Europe, but it also raises broader questions about whether Europe can ever become a viable commercial market for other expensive gene therapies.

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Bluebird talks in Germany may be bad omen for gene therapy in Europe - STAT

Bayer's cell and gene therapy ambitions have quickly taken flightas the German conglomerate locks up new partners and pumps cash into promising up-and-comers. Now, the company is looking to beef up its cell offerings at the Berkeley campus where it has separately blueprinted a $1.2 billion, 30-year expansion.

Bayer has drawn up plans for a $200 million cell therapy plantin Berkeley, where a separatecell culture facility and cell and gene therapy labs are due to come online later this year, Bioprocess International reports.

Called the Cell Therapy Launch Facility, the new plant is the latest in a series of cell and gene therapy movesby Bayer, as the company rapidly carves out a foothold inthe bustling field. In the past few monthsalone,it bought out adeno-associated virus (AAV)specialist Asklepios BioPharmaceutical, launched a cell and gene therapy platform and plugged millions of investment dollarsintogene therapy players Metagenomi and Senti Biosciences.

As for the latestfacility, the 98,000-square-foot plantand first production moduleshould be ready to goby mid-2023, a Bayer spokesperson told the news outlet.

To start, the factory will turn out clinical materials for Bayer's cell therapy pipeline, though both the launch facility and the cell culture plant, dubbed theCell Culture Technology Center (CCTC), will eventually chip in on "global commercial launches of multiple products," the spokesperson said.

RELATED:Bayer unveils first look at its post-Xarelto, post-Eylea lifeand it's better than expected

A second production module isalready planned for the site, which could eventually produce up to four cell therapy products at the same time, Jens Vogel, SVP and global head of biotech at Bayer, said in a recentinterview with San Francisco Business Times.

Bayer counts a number of early-stage cell and gene hopefuls among its pipeline, includinggene therapiesfor congestive heart failure, Parkinson's and Pompe disease, as well as a CAR-T cell therapy candidate forhigh mesothelin-expressing tumors.

Bayer didn't say when construction on the launch facility would begin, and the company didn't immediately respond to Fierce Pharma's request for comment. The 40,000-square-foot, $150 million technology centeris expected to be up and running in late 2021.

The launch facility is separate from Bayer's bigger expansion plans in Berkeley, the company told Bioprocess International. In July, Bayer proposed a site development plan that would addabout 1 million square feet of new work space and double its workforce in Berkeleyby some1,000 employees.

The CCTC, expected to open later this year, will "combine automation, digital capabilities and single-use bioprocessing technologies to streamline production" on Bayer's cardiology and oncology pipeline,Judy Chou, former global head of Bayer Biotech, said in a May 2019 statement.

RELATED:Bayer looks for pharma growth in 2021 as new drugs start to take shape

Bayer has been a tenant in Berkeley, where it cranks out hemophilia A treatments, since the 1970s. The site received a $100 million facelift in 2017but was also victim ofjob cuts in 2018 as the companyreorganized manufacturing of its hemophilia factor VIII replacement therapiesKogenate, Kovaltry andJivi.

Meanwhile, Bayer has taken a page out of the M&A playbook as it looks to solidify its place in the cell and genefield. In October, the company agreed to pay $2 billion upfront and potentially $2 billion more in milestones to snap upadeno-associated virus (AAV) gene therapy specialist Asklepios BioPharmaceutical.

Asklepios, also known as AskBio, boasts a pipeline ofpreclinical and clinical candidates for neuromuscular, central nervous system, cardiovascular and metabolic diseases, and came on board withgene therapy manufacturing capabilities, which the company now uses in a CDMO capacity.

On the cell therapy front, Bayer in December teamed up withAtara Biotherapeutics to work on anoff-the-shelf T-cell immunotherapy fortough-to-treat lung cancers. That same month, the company launched a cell and gene platform to assist its swelling Rolodex of partners across the product lifecycle. And amid all that, Bayer co-leda $65 million funding round forgene editing player Metagenomi and a$105 million series Bfor next-gen gene therapy startup Senti Biosciences.

A little more than a year before that, Bayer laid out$240 million to nab theremaining stake in its cell therapy joint venture, BlueRock Therapeutics.

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Bayer, intent on its cell therapy ambitions, plots $200M plant at overhauled Berkeley campus: report - FiercePharma

NEW YORK, and RESEARCH TRIANGLE PARK, N.C., April 28, 2021 (GLOBE NEWSWIRE) -- Sio Gene Therapies Inc. (NASDAQ: SIOX), a clinical-stage company focused on developing gene therapies to radically transform the lives of patients with neurodegenerative diseases, today announced four upcoming oral presentations at the 24th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), to be held virtually between May 11th to May 14th, 2021.

The AXO-AAV-GM1 presentation will include a review of patient-level data on safety and efficacy at 6 months follow up from the low-dose cohort of the Companys ongoing clinical study. Additionally, Dr. Cynthia Tifft, the lead investigator for the study, will present 6-month biomarker data from cerebrospinal fluid (CSF) in the 5 children who received intravenous AAV9 gene therapy.

Oral Presentation Details:

Presentation Title: AXO-AAV-GM1 for the Treatment of GM1 Gangliosidosis: Preliminary Results from a Phase I-II trialAbstract Number: 162Session: Clinical Trials and Advanced Preclinical Studies for Neurologic DiseasesPresenting Author: Cynthia Tifft, MD, PhD, Deputy Clinical Director, National Human Genome Research InstitutePresentation Date and Time: Thursday, May 13, 2021 6:15 PM 6:30 PM EDT

Presentation Title: AXO-Lenti-PD gene therapy for Parkinsons disease: efficacy, safety, and tolerability data from the second cohort in open-label dose evaluation study SUNRISE-PD at 6 months post administrationAbstract Number: 163Session: Clinical Trials and Advanced Preclinical Studies for Neurologic DiseasesPresenting Author: Gavin Corcoran, MD, Chief R&D Officer Presentation Date and Time: Thursday, May 13, 2021 6:30 PM 6:45 PM EDT

Presentation Title: Immune Modulation Preceding AAV9-GLB1 Gene Therapy Preserves the Possibility for Re-Dosing in Children with GM1 GangliosidosisAbstract Number: 179Session: Immunotherapy and VaccinesPresenting Author: Precilla DSouza, DNP, MSN, CRNP, National Human Genome Research InstitutePresentation Date and Time: Thursday, May 13, 2021 7:00 PM 7:15 PM EDT

Presentation Title: A GLP Safety and Biodistribution Study of AXO-Lenti-PD Manufactured via Two Processes Delivered at a Higher Volume and Flow RateAbstract Number: 256Session: Pharmacology/Toxicology Studies or Assay DevelopmentPresenting Author: Thomas Pack, PhD, Sio Gene TherapiesPresentation Date and Time: Friday, May 14, 2021 from 1:45 PM 2:00 PM EDT

About AXO-AAV-GM1

AXO-AAV-GM1 delivers a functional copy of theGLB1gene via an adeno-associated viral (AAV) vector, with the goal of restoring -galactosidase enzyme activity for the treatment of GM1 gangliosidosis. The gene therapy is delivered intravenously, which has the potential to broadly transduce the central nervous system and treat peripheral manifestations of the disease as well. Preclinical studies in murine and a naturally-occurring feline model of GM1 gangliosidosis have supported AXO-AAV-GM1s ability to improve -galactosidase enzyme activity, reduce GM1 ganglioside accumulation, improve neuromuscular function, and extend survival.

AXO-AAV-GM1 has received both Orphan Drug Designation and Rare Pediatric Disease Designation from theFood and Drug Administrationand is the only gene therapy in clinical development for both Type I and Type II GM1 gangliosidosis.

In 2018, Sio licensed exclusive worldwide rights from theUniversity of Massachusetts Medical Schoolfor the development and commercialization of gene therapy programs for GM1 gangliosidosis and GM2 gangliosidosis, including Tay-Sachs and Sandhoff diseases.

About AXO-Lenti-PDAXO-Lenti-PD is an investigational gene therapy for the treatment of Parkinsons disease that is designed to deliver three genes (tyrosine hydroxylase, cyclohydrolase 1, and aromatic L-amino acid decarboxylase) via a single lentiviral vector to encode a set of critical enzymes required for dopamine synthesis, with the goal of reducing variability and restoring steady levels of dopamine in the brain. The investigational gene therapy aims to provide patient benefit for years following a single administration.Axovantexpects to dose the first patient in EXPLORE-PD, a randomized, sham controlled study in 2021.

AboutSio Gene TherapiesSio Gene Therapiescombines cutting-edge science with bold imagination to develop genetic medicines that aim to radically improve the lives of patients. Our current pipeline of clinical-stage candidates includes the first potentially curative AAV-based gene therapies for GM1 gangliosidosis and Tay-Sachs/Sandhoff diseases, which are rare and uniformly fatal pediatric conditions caused by single gene deficiencies. We are also expanding the reach of gene therapy to highly prevalent conditions such as Parkinsons disease, which affects millions of patients globally. Led by an experienced team of gene therapy development experts, and supported by collaborations with premier academic, industry and patient advocacy organizations, Sio is focused on accelerating its candidates through clinical trials to liberate patients with debilitating diseases through the transformational power of gene therapies. For more information, visitwww.siogtx.com.

Forward-Looking StatementsThis press release contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as believe, "estimate," may be and other similar expressions are intended to identify forward-looking statements. For example, all statements Sio makes regarding costs associated with its operating activities, funding requirements and/or runway to meet its upcoming clinical milestones, and timing of its upcoming clinical milestones are forward-looking. All forward-looking statements are based on estimates and assumptions by Sios management that, although Sio believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Sio expected. Such risks and uncertainties include, among others, the impact of the Covid-19 pandemic on our operations; the actual funds and/or runway required for our clinical and product development activities and anticipated upcoming milestones; actual costs related to our clinical and product development activities and our need to access additional capital resources prior to achieving any upcoming milestones; the initiation and conduct of preclinical studies and clinical trials; the availability of data from clinical trials; the development of a suspension-based manufacturing process for Axo-Lenti-PD; the scaling up of manufacturing, the expectations for regulatory submissions and approvals; the continued development of our gene therapy product candidates and platforms; Sios scientific approach and general development progress; and the availability or commercial potential of Sios product candidates. These statements are also subject to a number of material risks and uncertainties that are described in Sios most recent Quarterly Report on Form 10-Q filed with theSecurities and Exchange CommissiononFebruary 9, 2021, as updated by its subsequent filings with theSecurities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. Sio undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

Contacts:

Media

Josephine Belluardo, Ph.D. LifeSci Communications(646) 751-4361jo@lifescicomms.cominfo@siogtx.com

Investors and Analysts

Parag V. Meswani, Pharm.D.Sio Gene Therapies Inc.Chief Commercial Officer investors@siogtx.com

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Sio Gene Therapies Announces Four Upcoming Oral Presentations at the 24th Annual Meeting of the American Society of Gene and Cell Therapy -...

ARLINGTON, Va. (PRWEB) April 27, 2021

The market for selected technologies and supplies commonly used in cell and gene therapy (CGT) research, development, clinical trial, and product manufacturing exceeded $2.1 billion in 2020. This was the finding made in Cell & Gene Therapy Technologies and Supplies, a market research report by Strategic Directions International, part of Science and Medicine Group.

SDi's report breaks the market into specific categories with defined markets. The market is led by cell expansion products, driven by costly GMP-grade consumables that are necessary for the culture of cells that are destined for infusion into humans. Currently, clinical trials account for a greater portion of cell expansion revenues than approved clinical use, but this dynamic will shift as an increasing number of CGTs gain approval and enter the market.

Gene therapies can target any gene in the human genome and transfer modified genetic material to specific cells. It requires editing the cellular genetic code to change specific target cells. A viral vector like adeno-associated virus (AAV) carries genetic instructions to the cell of interest. Non-viral transport vectors can also be employed for the purpose of treating or curing disease. Typically, diseases treated with gene therapy have a single gene or protein aberration responsible for the disorder. Once in, the genetic instructions find the appropriate cells and gene addition, inhibition, correction, reprogramming, and/or cell elimination is induced. These types of gene therapies are common for immune diseases caused by protein production abnormalities, like arthritis, connective tissue disorders, and rare genetic disorders such as sickle cell.

In vivo gene therapy involves direct injection, grafting, or intravenous administration of a vector with therapeutic genetic material into the body. The process can be systemic or localized to a specific cell type or tissue of interest. Ex vivo gene therapy genetically modifies the cells of interest outside of the patients body, which is the basis of many cell therapies.

Hundreds of suppliers participate in the market for cell and gene therapies technologies and supplies. While the leading vendors are broad-based companies with offerings in all product categories, most participants provide more niche products. The top suppliers in the market in 2020 were Thermo Fisher, MilliporeSigma, Gibco (Thermo Fisher), and Cytiva (Danaher). The rapid development of the market has driven much innovation of new and existing technologies. This has created opportunities for market participants, and numerous new analytical instrumentation and supply companies have been formed to serve the CGT market.

As development and market entries of CGTs accelerate, the market for suppliers of laboratory and clinical tools within the CGT R&D and manufacturing spaces will see very rapid growth. The Cell & Gene Therapy Technologies and Supplies examines the global market for analytical technologies and products used throughout the various stages of CGT development and manufacturing, evaluating 21 technologies grouped into six categories. The goal of this report is to provide demand growth projections by technique, region, and function, while also providing comprehensive views of the competitive landscape for each technology.

The report can be found at: https://strategic-directions.com/product/2021-cell-gene-therapy-technologies-and-supplies-report/

About Strategic Directions InternationalStrategic Directions International (SDi), part of Science and Medicine Group, is the leading business intelligence firm in the highly specialized field of analytical and life science instruments. Its client list includes virtually every major analytical instrumentation company in the United States, Europe, and Japan. Founded in 1981, the Los Angeles-based company has published hundreds of market reports and provided proprietary consulting services for a multitude of clients.

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2 Billion Dollar Tools Market for Cell and Gene Therapy, Says Report - PR Web

SAN DIEGO, April 28, 2021 (GLOBE NEWSWIRE) -- Otonomy, Inc.(Nasdaq: OTIC), a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology, today announced the upcoming presentation of preclinical proof-of-concept data for OTO-825 at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting on May 13, 2021. OTO-825 is the clinical candidate targeting the gap junction beta-2 (GJB2) gene developed under the companys collaboration with Applied Genetic Technologies Corporation (Nasdaq: AGTC). Mutations in the GJB2 gene are the most common cause of congenital hearing loss and typically result in moderate to severe hearing impairment.

"We are excited to present these preclinical results for OTO-825 that build on our previous presentations demonstrating gene expression in support cells of the cochlear, which are the target cells for GJB2 gene therapy, using novel AAV vectors identified through our collaboration with AGTC, said Alan C. Foster, Ph.D., chief scientific officer of Otonomy. Based on these encouraging results that demonstrate hearing recovery and improved cochlear morphology following OTO-825 administration, the companies have initiated IND-enabling activities and look forward to providing additional details of the program in the next several months.

The oral presentation entitled AAV-mediated GJB2 gene therapy rescues hearing loss and cochlear damage in a mouse model of congenital hearing loss caused by conditional Connexin26 knockout by Mathur et al., will be presented on May 13 at 6:30 p.m. EDT.

About Otonomy

Otonomy is a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology. The company pioneered the application of drug delivery technology to the ear in order to develop products that achieve sustained drug exposure from a single local administration. This approach is covered by a broad patent estate and is being utilized to develop a pipeline of products addressing important unmet medical needs with a focus on hearing loss and tinnitus. For additional information please visit http://www.otonomy.com.

Cautionary Note Regarding Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements generally relate to future events or the future financial or operating performance of Otonomy. Forward-looking statements in this press release include, but are not limited to, statements related to plans and expectations regarding OTO-825; and statements by Otonomys chief scientific officer.

Otonomys expectations regarding these matters may not materialize, and actual results in future periods are subject to risks and uncertainties. Actual results may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to: delays and disruption resulting from theCOVID-19pandemic; Otonomys ability to obtain additional financing; the uncertainties inherent in the clinical drug development process, including, without limitation, Otonomys ability to adequately demonstrate the safety and efficacy of its product candidates and the nonclinical and clinical results for its product candidates, which may not support further development; the risks of the occurrence of any event, change or other circumstance that could impact the performance under or give rise to the termination of Otonomys collaboration, co-promotion or license agreements, including its collaboration agreement with AGTC, or that could impact Otonomys ability to repay or comply with the terms of the loan provided by Oxford Finance LLC; side effects or adverse events associated with Otonomys product candidates; competition in the biopharmaceutical industry; Otonomys dependence on third parties to conduct nonclinical studies and clinical trials, and for the manufacture of its product candidates; Otonomys ability to protect its intellectual property in the United States and throughout the world and to ensure compliance with various laws and regulations in countries in which it conducts clinical trials; expectations regarding potential therapy benefits, market size, opportunity and growth; Otonomys ability to manage operating expenses; implementation of Otonomys business model and strategic plans for its business, products and technology; general economic and market conditions;and other risks. Information regarding the foregoing and additional risks may be found in the section entitled "Risk Factors" in Otonomys Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 11, 2021, and Otonomys future reports to be filed with the SEC. The forward-looking statements in this press release are based on information available to Otonomy as of the date hereof. Otonomy disclaims any obligation to update any forward-looking statements, except as required by law.

Contacts:

Media InquiriesSpectrum ScienceChlo-Anne RamseyVice President404.865.3601cramsey@spectrumscience.com

Investor InquiriesWestwicke ICRRobert H. UhlManaging Director858.356.5932robert.uhl@westwicke.com

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Otonomy and AGTC to Present Preclinical Proof-of-Concept Results for OTO-825 Gene Therapy at ASGCT Annual Meeting - GlobeNewswire