- Data Package Supported Initiation of Ongoing pheNIX Clinical Trial forAdults with PKU -

BEDFORD, Mass., March 16, 2020 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the peer-reviewed publication of preclinical data that supports Homologys HMI-102 investigational gene therapy program for the treatment of adults with phenylketonuria (PKU). HMI-102 is currently being evaluated in the pheNIX Phase 1/2 clinical trial, and the Company plans to provide an update on the trial when selecting the dose for the expansion part, which is currently anticipated in mid-2020.

The published data shows that a single administration of HMI-102 (AAVHSC15-PAH) produced a sustained reduction in phenylalanine (Phe), the key biomarker in the diagnosis and management of PKU, for the lifespan of the established murine model for PKU. The data also demonstrated a concomitant increase in tyrosine (Tyr), a metabolite of Phe and precursor to neurotransmitters, indicating enzymatic activity. Additionally, brain levels of Phe, 5-HIAA (downstream serotonin metabolite) and coat color were normalized, further indicating restoration of the Phe metabolic pathway.

We developed a robust preclinical data package for our investigational HMI-102 gene therapy, which supported the initiation of our ongoing Phase 1/2 pheNIX clinical trial for adults with PKU, stated Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. These published data demonstrated that a single dose of HMI-102 was able to restore the normal biochemical pathway in the established PKU model on normal protein diet. Initial data from the pheNIX trial suggests that the increased PAH enzymatic activity after administration of HMI-102 seen in the preclinical model was also observed in the clinical study.

Key data in the publication include:

The publication, Sustained Correction of a Murine Model of Phenylketonuria Following a Single Intravenous Administration of AAVHSC15-PAH, was peer-reviewed and published in the journal Molecular Therapy: Methods & Clinical Development. For more information, please visit http://www.homologymedicines.com/publications.

About the Phase 1/2 pheNIX Clinical Trial in Phenylketonuria (PKU)The pheNIX trial is the first gene therapy clinical trial ever conducted for people with PKU. pheNIX is designed to evaluate the safety and efficacy of a single intravenous administration of HMI-102 in adult patients with PKU aged 18-55. The study design allows for expansion of the number of patients in any dose cohort pending review by the Data Monitoring Committee and the Homology Internal Data Review Team. A decision to expand would trigger the addition of the randomized, concurrently controlled Part B of the trial, which has the potential to be converted to a registrational trial. The primary efficacy endpoint of the expansion part is incidence of sustained plasma Phe concentration 360 mol/L as demonstrated by two measurements 360 mol/L between 16 and 24 weeks.

About Homology Medicines, Inc. Homology Medicines, Inc. is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homologys proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicinesin vivoeither through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visitwww.homologymedicines.com.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; plans and timing for the release of clinical data from the Phase 1/2 pheNIX trial, including the Part B expansion; plans and timing for the release of clinical data; our beliefs regarding our manufacturing capabilities; advancing our novel platform and pipeline; our goal of delivering potential cures to patients; beliefs about preclinical data; our position as a leader in the development of genetic medicines; the sufficiency of our cash, cash equivalents and short-term investments; and our participation in upcoming presentations and conferences. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the capabilities and potential expansion of our manufacturing facility; risks relating to the regulatory approval process; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs as a result of operating as a public company. These and other important factors discussed under the caption Risk Factors in our Annual Report on Form 10-K for the year ended December 31, 2019and our other filings with theSECcould cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Company Contacts:Theresa McNeelyChief Communications Officer and Patient Advocatetmcneely@homologymedicines.com781-301-7277

Media Contact:Cara MayfieldSenior Director, Patient Advocacy and Corporate Communicationscmayfield@homologymedicines.com781-691-3510

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Homology Medicines Announces Peer-Reviewed Publication of HMI-102 Investigational Gene Therapy Demonstrating Restoration of Normal Metabolic Pathway...

He swipes once. Twice. Three times.

The lidocaine goes in, to freeze the skin. Then the needle.

Slowly, precisely, Rasquinha removes spinal fluid through the lumbar puncture, commonly known as a spinal tap. He then gives him the injection that Snow and his wife, Kelsie, believe is saving his life.

They believe because they want to, because they have to, and because -- against every single odd, against every single thing you've ever heard regarding amyotrophic lateral sclerosis, or ALS -- it just might be working.

Snow, a 38-year-old assistant general manager for the Calgary Flames, was diagnosed with ALS on June 17. It was not a surprise. His family has been ravaged by the familial form of the disease, with his father, two uncles and a cousin having died from ALS caused by the SOD1 genetic mutation.

ALS affects motor neurons, the cells that control muscle movement. As ALS progresses, the motor neurons die, the muscles become weaker, and eventually movement slows or becomes impossible.

It's what Snow saw happen in his right hand, how he began to suspect that the disease had come for him too. But almost immediately after his diagnosis, which usually carries a life expectancy of between six and 18 months, Snow enrolled in a phase 3 clinical trial at Sunnybrook Health Sciences Centre in Toronto for those with the SOD1 mutation, which affects 2 percent of ALS patients.

In this, he was lucky, both that it was available and that he qualified.

He has made the trip to Toronto with Kelsie every four weeks since then, though initially there was a two-in-three chance that every trip brought him an injection of tofersen, a drug that doctors and researchers hoped could slow the progression of the disease.

For the first six months of the trial, two-thirds of the study participants are given the actual drug. One-third are given a placebo.

He does not know for sure whether he was in the group given the medication or the placebo. The Snows believe he was one of the lucky ones, one of those given tofersen. They believe because they, remarkably, have not seen a progression of the disease since he entered the trial. He still does not have use of his right hand. He has use of everything else, all the things they feared might slip away from him in the weeks and months after they confirmed the diagnosis.

The injection takes two minutes, two minutes of silent meditation for Snow. He thinks about his mom, Linda, who committed suicide in 2012. "Because," as he says, "she'd be really happy and really sad if she were here. One of the things I got from her was a real joy for life. She always was happy that I was that way. So, I think about her and how I get to move on because of this." He thinks about his dad, Bob, who died of ALS in 2018, and his uncles and his cousin.

He wishes they had had the opportunity for these two minutes. For that two-in-three chance.

"I move through those thoughts fairly quickly," he says. "I usually say a prayer or two. For them. Probably in part for myself."

****

The Snows have already been at Sunnybrook for hours at this point, Feb. 20 marking their 11th visit to this hospital, his 10th lumbar puncture. At 9:15 a.m., the driver picks them up at their hotel for the 20-minute ride. When they walk in the doors at the hospital, a massive campus that looks like a small airport, Snow is on edge.

They find their way down to Room UG21, where Snow will undergo a battery of tests, all of them designed to determine whether the progress of the disease has slowed, whether it has stopped, whether it has -- God forbid -- picked up again.

They start with a detailed neurological assessment.

"Have you experienced any changes to your health since you were last here?"

"No."

"Have you noticed any difference in your speech?"

"No."

They test knowledge next, the year, the season, the province, the city. A series of words that never changes from visit to visit: apple, penny, table. He counts backward from 100 by seven.

These are the hardest weeks, when the anxiety sweeps up and the visit looms closer and the fear that "no change" might have turned into "some change" pierces the bubble they have formed around themselves.

"My bad hand, I don't have any expectations for it being better," Snow says. "It's more the opposite, that I'm always kind of concerned about and testing the good parts. The other hand, in particular. Living without one hand is not difficult. Living without two hands is difficult.

"It's testing my good hand, and then I overtire it. And then I convince myself something is wrong."

This is when Kelsie can sense his perpetual optimism faltering.

"None of the physical aspects of any of that, the lidocaine, the needle itself, I couldn't care less about those things," Snow says. "It's just the emotional anguish that you can put yourself through, with wondering, am I a little bit different? And if I'm a little bit different, what does that mean?

"Because that's totally unknown. But then you worry, that could be a slippery slope."

He does a breathing test, to determine lung capacity, and one to test muscle strength. That is the one that gives him the most anxiety, because they are testing his hand and his strength, and that is where the disease started to eat at him.

"This is our 10th time doing most of these tests," Snow says.

"And there has not been any changes," research coordinator Jahan Mookshah says.

"Those are our favorite words," Kelsie says.

Kelsie bends down and ties her husband's shoes. The testing is over, for the moment.

****

There is no blood test for ALS. It's only diagnosed by process of elimination, a factor that often can be problematic, as the disease progresses while the patient is still waiting for answers. Snow was told June 10 by an EMG technician in Calgary that it was likely ALS, a diagnosis that was confirmed a week later by Dr. Michael Benatar at the University of Miami.

It was the last answer they wanted in the world. It was a death sentence.

They crumbled, seeing an unknown present, a future robbed.

"I don't know how we did it," Snow said. "We did our days, and then we cried."

Back in Calgary, fellow assistant general manager Craig Conroy got the news on the phone from Snow, while looking at Snow's kids, Cohen and Willa, now 8 and 5, who were staying at his house while their parents were in Miami. As Conroy said, "That just breaks your heart."

But there was some good news.

Snow had the best-case scenario: a family history and a mutation of the SOD1 gene. He had pressed the issue with doctors, over and over again, after starting to feel the weakness in his right hand while lifting weights during the Stanley Cup Playoffs in April, even as he wanted to believe it was a pinched ulnar nerve, desperate for any answer but this. For Snow, that meant it was only a matter of months between the onset of symptoms and the diagnosis, as opposed to 1 1/2 to 2 years, which is the average.

Which was why when the Snows talked to Benatar on June 17, it was like being flattened and lifted up in the same moment. They confirmed Snow had ALS. They also learned there was a trial, with openings for those with a fast-progressing form of the disease, like him. There was something they could do. There was a place they could go. There was a medicine he could take, produced by Biogen, a company whose corporate headquarters are on Binney Street in Cambridge, Massachusetts, the exact street where Snow lived when he moved there to work at The Boston Globe, another career and another lifetime ago.

There was -- maybe, possibly -- hope. An impossibility in this world.

"It's just like someone believably telling you you're going to die, then telling you you might not die," Kelsie said. "You can't describe that in a more dramatic way than that. You feel like you got your life back. You've got a chance. Just a chance, right?"

Most of the time ALS is sporadic -- that is, not inherited. But in 5 to 10 percent of cases, there is a familial link, an altered gene that has folded. When Kelsie researched trials in the immediate aftermath of the diagnosis, she realized that the studies that were furthest along happened to be for SOD1, Snow's mutation, the second-leading cause of familial ALS.

They would head to Toronto every month, their kids left with a rotating selection of friends, off to get the injection that might -- or might not -- include the liquid hope that his future rested on.

They had six months in which he could have been receiving either the drug or the placebo, until last month, when they were finally assured he would be getting the medication from this point on.

They told their kids that they would have to have a summer to last a lifetime.

"Because we felt like it was maybe going to have to," Kelsie said.

They jammed in everything, all the bike rides and ice cream and pictures, the trip to Merrymeeting Lake in New Hampshire, Snow's family cabin. They jammed happiness in every moment, the tears reserved for private times, for when they couldn't hold it in any longer, wiped away when the kids approached. She wondered if he would make it to February and, if he did, whether he would want to hang around once he got there. She told him to just stay the way he was. They put one foot in front of the other and, still, they don't know exactly how.

By October, they had started to feel differently. Hopeful.

Snow got back on the ice, courtesy of a Flames equipment manager, who sewed his glove into a fist, enabling him to grip a hockey stick. He shot a puck. It rang off the crossbar. Kelsie took a video. It was evident to her that the disease had not progressed, not robbed him of any more strength.

That moment, that month, changed them.

"I felt like that was probably the first moment where I could really breathe," she said.

They went public on Dec. 18, and it ricocheted around the hockey community. Kelsie wrote a letter detailing their diagnosis and their hope, something she has continued to chronicle on her blog, kelsiesnowwrites.com, and recently, in a story that ran in Sports Illustrated.

It has become a piece of her every day, every thought, something that still fells her at a moment's notice. When she is asked if there's been a day that she hasn't thought about ALS since the diagnosis, tears start to flow down her face.

"These three letters are a part of my life forever," Kelsie says. "I sure wish they weren't. But I know that a lot of good things will come to us as a result of this. And I've seen a lot of good in a lot of people because of this.

"There's so much beauty in grief, and there's so much beauty in sadness and tragedy. Because you get to see the best in people. And that's not a small thing. But I wish I didn't have a byline in Sports Illustrated. I don't want a byline in Sports Illustrated. I don't want to be telling this story. But if this is what I'm here for, then I'm OK with that. It's not small. I know that. I know that being there for somebody you love is significant. It's enough for me."

She swipes at the tears, running her fingers underneath her eyes. She sniffles.

"This is because I know you, too," Kelsie says, starting to laugh amidst the tears. "That's the problem."

****

It has been 15 years since I met Kelsie and Chris, back when she was still Kelsie Smith and he was still a baseball writer. The summer of 2005 was one of those summers that's only possible when you are young and there is no responsibility, no ties, no worry. When a White Russian just before the bar closes seems like a good idea, and a shut-off car in a parking lot is the right place to bare a soul, for a friend to reveal she just might be falling in love.

As Kelsie texted me recently, "Honestly, best summer of my life."

They were too young, realistically, for it to work. She was 21. He was 23. They met in a bar, the White Horse Tavern, down the street from the apartment that Snow would buy in Allston, Massachusetts, and that I would later buy from him and live in for the next decade.

He was the Boston Red Sox beat writer at the Globe, she was an intern in the Globe's sports department out of the University of Kansas, and I would be hired into the sports staff that summer as a general assignment reporter.

They got engaged the next summer, and married in December 2007, on a frigid, 9-degree day in St. Paul, Minnesota, where they moved after he was hired as the director of hockey operations for the Minnesota Wild, an unorthodox move that would launch him on a career in hockey and give me a chance to succeed him on the Red Sox beat at the Globe.

She covered the Minnesota Twins for the St. Paul Pioneer Press. We spent spring trainings together in Fort Myers, Florida.

It's hard to think about that day in 2007, so many years ago now, when they promised a lifetime to each other. Because, as Kelsie said, "That I have extra months is not lost on me. I know that I've been already given a gift. It's just that I want what we all thought we were getting when we got married. That we are going to grow old together."

Kelsie has always trusted in Snow, something she has never been shy about expressing. She's always believed he would do what he said, that he would succeed despite all the odds: That he would make the unheard-of jump from baseball reporter to NHL front office member; that he would figure it out after the Wild let him go; that they could find their way on one income (first hers, then his) in a new city, in a new country with a new baby.

And he did. They did.

"It was always like, Chris will figure this out," she said. "And that's probably an unfair amount of pressure that I put on him, but I just believed in him. I've always believed in him that much."

She still does, even in a battle that, up to this point, has been unwinnable.

****

At 1 p.m., after a pizza lunch, it's time to head back to UG21 for the lumbar puncture. Snow laughs about the diet he has been instructed to stick to -- high protein, high fat, high carb -- because losing weight is a marker of the disease. It's one thing he doesn't mind.

This session, too, starts with some tests. Of reflexes. Hands. Ankles. Feet. Jaw.

"This might hurt," Rasquinha says. "Sorry."

Rasquinha flips his hands over, examines them, tells Snow to relax. This is not Snow's forte.

Snow acknowledges yet again that he cannot do anything with his right hand. That went in June, and the atrophy has set in up to his elbow. Kelsie -- or, if he's at work with the Flames, one of his colleagues -- makes sure to cut his food for him, if needed; they tie his skates and his shoes. "Tight, but not too tight," as she puts it.

Testing done, it's time for the lumbar puncture. Snow is now on the open-label extension of the trial. After this visit, he is assured that the fluid sent into his spine will be tofersen. This is a comfort, even as they believe he has been receiving the medication all along.

"All right," Snow says, "let's rock and roll."

The risks are read out, the warnings given, as they always are. The Snows know this nearly by heart. Rasquinha snaps on sterile green gloves and a baby blue face mask. The lidocaine goes in. "Mosquito bite," Rasquinha calls it. "A little burn. Sorry."

Lorne Zinman enters the room. He is part of the reason for their hope, a man who oozes sunshine as he talks, despite having devoted his life to a disease that to this point has claimed every one of its victims.

"This is exciting," says Zinman, the director of the ALS/Neuromuscular Clinic at Sunnybrook and an associate professor of neurology at the University of Toronto. "This is gene therapy for ALS. I've been talking about this for, like, two decades. The fact that it's a reality and we could be helping people like Chris, it's just the happiest thing. I always say -- apology to my children -- the happiest day of my life will be when we finally have something for this disease, because I've seen too many people go through it."

It is easy for Zinman to be joyful these days. He, like all those who work with ALS, has spent years and years in the darkness, and he somehow just might see a little light emerging, a speck that grows bigger with every day that Snow, and potentially others, are stable.

"It's been decades and decades of, really, failure after failure in ALS," Zinman said. "When I give lectures, I put up a slide and I call it the graveyard of failed trials. And it's just failure after failure. The big turning point came when we found the first gene for ALS in the early '90s."

Researchers put the gene into mice, and the mice started to show signs of disease. They thought a cure would come soon after. They were wrong.

Things started to turn when advances in gene therapy led the focus to shift. They knew SOD1 made a protein, and that the protein misfolded, leading to the killing of motor neurons that led to ALS. That became their target.

On Feb. 3, Kelsie posted a video to Twitter showing Snow lifting his right hand at his wrist. It was something he hadn't been able to do since the disease took hold. They don't know what it means, and they try not to read too much into it, but the idea of stability, let alone improvement, sometimes seems like a dream they do not want to end.

And that is what makes Zinman so excited.

"We don't usually see that in ALS trials," he said. "The objective is to slow things down, not to make things improved. It's really exciting when you hear something like that, where I'm actually able to do something that I couldn't do before. You always have to take it with a grain of salt it's just really exciting when you hear something like that."

He envisions a day when a patient like Snow or one of his family members could find out he has the SOD1 mutation, that they could start him on the drugs in the pre-symptomatic phase, as a preventative, similar to the way that doctors have been able to use PrEP to keep HIV from taking hold, or the way that doctors use vaccines to prevent diseases.

"We're diagnosing ALS about five to six times a week, and three to four of our patients die every week," Zinman said. "I've been doing this for 15 years now. I see the faces of these patients, not just them, their family members and what they went through, so to be able to offer someone something like this -- research is hope."

When Zinman and I exited the room, I later learned, Snow grew emotional. He cried. It was joy and relief and release. He had finished another session at Sunnybrook. There had been no change. He soon would be assured of getting more of the medicine that has given him more, where before, he expected there would be less and less.

Because these two minutes, every four weeks, might just be saving him.

"The first few times he was dosed I had full-on panic attacks," Kelsie said. "It was all about the fact that I didn't know what [he was getting]. They'd come in and they'd put this little Ziploc baggie on the desk in there and it had this syringe in it. I remember noticing right away that it was 15 milliliters of this clear fluid. And that was every ounce of hope I had in my life."

****

The appointment over for the month, Snow walks down the corridor, a drab, shabby, beige hallway. It is hardly inspiring, with its fluorescent lights and well-trod flooring. But Snow is nearly bouncing. This is the best he feels all month, his hopes confirmed, the medication, he assumes, flowing through his body.

"Every time I walk this hallway, it's a good feeling," he says. "Because you picture yourself being wheeled."

But he can walk. He can breathe. He can do his job, almost the same way he always has, with a few simple modifications. He wears a suit without a tie these days, because he cannot tie one and, really, who needs it? He has not yet transitioned to slip-on shoes, perhaps out of stubbornness.

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Gene therapy giving Flames executive Snow hope in ALS fight - NHL.com

Barth syndromeis a rare metabolic disease caused by mutation of a gene calledtafazzinorTAZ. It can cause life-threatening heart failure and also weakens the skeletal muscles, undercuts the immune response, and impairs overall growth. Because Barth syndrome is X-linked, it almost always occurs in boys. There is no cure or specific treatment.

In 2014, to get a better understanding of the disease,William Pu, MD, and colleagues at Boston Childrens Hospital collaborated with the Wyss Institute to create a beatingheart on a chip model of Barth syndrome. The model used heart-muscle cells with theTAZmutation, derived from patients own skin cells.It showedthatTAZis truly at the heart of cardiac dysfunction: the heart muscle cells did not assemble normally, mitochondria inside the cells were disorganized, and heart tissue contracted weakly. Adding a healthyTAZgene normalized these features, suggesting that gene replacement therapy could be a viable treatment.

But to fully capture Barth syndrome and its whole-body effects, Pu and colleagues needed an animal model. The animal model was a hurdle in the field for a long time, says Pu, director of Basic and Translational Cardiovascular Research at Boston Childrens and a member of the Harvard Stem Cell Institute. Efforts to make a mouse model using traditional methods had been unsuccessful.

As described in the journalCirculation Research, most mice with the whole-bodyTAZdeletion died before birth, apparently because of skeletal muscle weakness. But some survived, and these mice developed progressive cardiomyopathy, in which the heart muscle enlarges and loses pumping capacity. Their hearts also showed scarring, and, similar to human patients with dilatedcardiomyopathy, the hearts left ventricle was dilated and thin-walled.

Mice lackingTAZjust in their cardiac tissue, which all survived to birth, showed the same features. Electron microscopy showed heart muscle tissue to be poorly organized, as were the mitochondria within the cells.

Pu, Wang, and colleagues then used gene therapy to replaceTAZ, injecting an engineered virus under the skin (in newborn mice) or intravenously (in older mice). Treated mice with whole-bodyTAZdeletions were able to survive to adulthood.TAZgene therapy also prevented cardiac dysfunction and scarring when given to newborn mice, and reversed established cardiac dysfunction in older mice whether the mice had whole-body or heart-onlyTAZdeletions.

Thats where the challenge will lie in translating the results to humans. Simply scaling up the dose of gene therapy wont work: In large animals like us, large doses risk a dangerous inflammatory immune response. Giving multiple doses of gene therapy wont work either.

The problem is that neutralizing antibodies to the virus develop after the first dose, says Pu. Getting enough of the muscle cells corrected in humans may be a challenge.

Another challenge is maintaining populations of gene-corrected cells. While levels of the correctedTAZgene remained fairly stable in the hearts of the treated mice, they gradually declined in skeletal muscles.

The biggest takeaway was that the gene therapy was highly effective, says Pu. We have some things to think about to maximize the percentage of muscle cell transduction, and to make sure the gene therapy is durable, particularly in skeletal muscle."

Reference: Wang et al. (2020).AAV Gene Therapy Prevents and Reverses Heart Failure in A Murine Knockout Model of Barth Syndrome.Circulation Research.https://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.119.315956.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Link:

Gene Therapy Reverses Heart Failure in Mouse Model - Technology Networks

Alia (2nd from left) and her father (left) with Dr Arif Khan (3rd from left), paediatric ophthalmologist and ocular geneticist at Cleveland Clinic Abu Dhabi, and other hospital doctors at a press conference in Abu Dhabi. Alia and her sister, Hessa, were the first to receive gene therapy in the UAE. Picture by Samihah Zaman, Image Credit:

Abu Dhabi: Two Emirati sisters from Abu Dhabi have become the first to receive gene therapy in the UAE, it was announced in the capital today.

The therapy was conducted with the aim of saving the vision of Alia, 13, and Hessa, 11, who suffered from retinal damage due to a defective gene.

The vision-saving surgery was performed at Cleveland Clinic Abu Dhabi in January (2020), and doctors said at a press conference that they are hopeful it will slowly improve the vision of both patients.

"The prospect of slowly losing one's vision from an untreatable condition is traumatic for both children and their parents. This genetic therapy means we can now replace the faulty gene in the eye, saving and even improving the vision of an individual who would otherwise have eventual irreversible blindness," said Dr Arif Khan, paediatric ophthalmologist and ocular geneticist at the hospital.

Only centre in region with procedure

Cleveland Clinic Abu Dhabi is only one of 10 centres worldwide, and the only one in the region, that is qualified to offer this procedure - the first gene therapy that was approved by the Food and Drug Administration in the United States, doctors said. But its availability opens the doors for more gene therapies to be offered to treat conditions as varied as diabetes and spinal muscular atrophy, they added.

Weve travelled abroad multiple times to find some treatment for our daughters, and this procedure has been a godsend. It has only been a month since the therapy however, and we are hoping for much more improvement to their vision over time, Fatima, the girls mother, told Gulf News.

The procedure

Alia and Hessa were born with RPE65-related retinal dystrophy, a genetic dystrophy in which the RPE65 protein is lacking because a child inherits two copies of the defective RPE65 from both parents. It is a recessive disease and therefore rare, and known to affect one in 200,000 people worldwide. But the condition is also more common in the region because of the limited genetic pool and cultural preferences for consanguineous marriages.

Patients with the condition face gradual damage to their retinas, the photosensitive layer at the back of the eye, and could eventually end up with irreversible blindness.

The gene therapy to treat the condition uses a vector - a bioengineered non-pathogenic virus to deliver normal copies of the RPE65 gene to the eye.

The procedure takes only about an hour, but it is very delicate. The retina can be considered an offshoot of the brain because its cells are very thin, like brain tissue. We use advanced microscopes to create openings in the white of the eye, then use a specialized canula to reach under the retina and inject the vector into the specific area, which can be as small as one-tenth of a millimeter, explained Dr Emad Abboud, chief of the department of the posterior segment at the hospitals Eye Institute.

Post-surgical recovery takes only about a week, but outcomes take a while to become obvious.

As Dr Khan explained, the main benefits for patients receiving the therapy is an improvement of vision in low-light conditions, and an improvement of the visual field.

Vision is a complex sense, involving photosensitivity, visual field, visual acuity, colour sensitivity, motion sensitivity, and the ability to navigate. But [at the least], this therapy prevents the progressive deterioration of the retina, he explained.

What the family said

My handwriting has definitely gotten better, Alia told Gulf News when asked about how the therapy has helped.

I cant tell what else will get better but I already feel that this has been life-changing, she added.

According to Fatima, she noticed her daughters had visual impairment when they were as young as two months old.

The doctor pointed out to me that they were not focusing or making eye contact. So we were aware of the condition. It definitely made life very challenging, especially as their development was delayed, the mother explained.

Alia and Hessa both crawled and walked late, and have needed assistance getting around. While they kept pace with their peers at school, it took Hercualean efforts from both girls, their parents, shadow teachers and at-home tutors, and required the use of Braille and visual aid resources.

Fatima and her husband, Mubarak, kept looking for treatments for both girls, travelling to Germany, India and Spain.

In 2016, we visited the Cleveland Clinic Abu Dhabi, and it was then that we heard of this revolutionary treatment. It was still not approved by the FDA, but we kept dreaming, she said.

It has been a month since the surgery and the doctors said they are more photosensitive now and that this is a good sign. Of course, as a mother, I would love for them to eventually have complete vision, Fatima added.

What is the therapy?

The UAE Ministry of Health and Prevention (MoHAP) approved the gene therapy for RPE65-related retinal dystrophy, Luxturna, in June 2019.

In a statement released at the time, the MoHAP said its registration of Luxturna was only the third global registration of the drug at the health authority level, and was aimed at paving the way for future gene-based therapies for complex conditions.

The United States Food and Drug Administration only approved Luxturna, developed by gene therapy developer, Spark Therapeutics, and the Childrens Hospital of Philadelphia, in late 2017.

The gene therapy to treat the condition uses a vector - a bioengineered non-pathogenic virus to deliver normal copies of the RPE65 gene to the eye with the defective gene.

While the Cleveland Clinic Abu Dhabi did not provide the cost of treatment, international media reports put it at $425,000 (Dh1.56 million) per eye.

Benefits of gene therapy

Dr Khan said at the press conference that us familiar with a few more families with the RPE65-related retinal disorder.

Over time, gene therapy could be used to treat many conditions. The eye is uniquely suited for these therapies because it is a self-contained organ. But at least five other genetic therapies are in development, some at the human trial level, he explained.

Consider gene delivery to be like providing a protein factory to the body. So for instance, some diabetic patients require regular insulin injections. If a gene could be engineered to make insulin, and it could be delivered to the patient, he wouldnt need these regular injections, Dr Khan added.

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UAE's first gene therapy improves eyesight of two Emirati sisters - Gulf News

Deals and Financings

Nanjing Legend Biotech, a subsidiary of GenScript (HK: 1548) (OTC:GNNSF), has filed for an IPO on a US exchange. In 2017, Legend surprised the world when its CAR-T therapy produced a 94% response rate in pretreated multiple myeloma patients. Six months later, Johnson & Johnson (NYSE:JNJ) partnered the treatment in a deal that paid Legend $350 million upfront, plus unspecified milestones and royalties. The CAR-T candidate, JNJ-4528, is now in Phase II trials in the US.

Harbour BioMed (HBM) raised $75 million in a Series B+ round to advance its clinical-stage compounds and portfolio of next-gen biotherapies for cancer and immunological diseases. The company builds its portfolio by in-licensings and via its proprietary Harbour Mice program. Harbour develops drugs for China and US markets, while it has entered partnerships to discover candidates for China companies Innovent (OTCPK:IVBIY) and BeiGene (NASDAQ:BGNE), along with other prominent global biopharmas. The company previously completed an $85 million Series B financing in August 2018. HBM is headquartered in Cambridge, MA, and it conducts R&D in Suzhou and Shanghai.

GenFleet Therapeutics (Shanghai) closed a $57 million Series B financing, co-led by CDH Investments and Shenzhen Capital Group. Founded in 2017, GenFleet is developing novel large and small therapeutic molecules for oncology and immunology targets. The company says its projects are potential first-in-class therapeutics with technical advantages and large markets. It will use the capital for ex-China development and clinical trials of its existing pipelines, plus expanding its immunology platform, working on new projects and building an industrial base.

Arctic Vision of Shanghai in-licensed greater China rights to Xipere, a treatment for macular edema associated with uveitis, from Clearside Bio (NASDAQ:CLSD) in a $35.5 million agreement. Founded last year, Arctic in-licenses breakthrough ophthalmology products for China. Xipere is its first deal. Arctic plans to acquire China rights to 3-5 products and then expand to a combination of global rights and internal discovery for additional drugs. Clearside, which is located in Alpharetta, Georgia, said Xipere is a proprietary suspension of the corticosteroid triamcinolone acetonide.

Exuma Biotech (formerly F1 Oncology), a Florida-Shanghai company developing CAR-T products for solid tumors, closed a $19 million Series B round. The financing included investments from MSD Partners and F1 BioVentures, plus conversion of notes held by individual investors. Exuma's Logic Gated CAR-T products become activated only when the target antigen and the tumor microenvironment are both present, reducing off-tumor side effects. The company has started clinical trials of two candidates. Exuma's Shanghai subsidiary oversees the company's development, manufacturing, and commercial units in Shanghai and Shenzhen.

OBiO Technology (Shanghai) completed a B+ Round of more than $15 million for its viral-based gene therapy CRO services and genetic drug CDMO/CMO services. Founded in 2013, OBiO collaborated with GE Healthcare (NYSE:GE) to establish the first domestic GMP viral production workshop in China and supply CRO/CDMO/CMO services for viral drugs. At the same time, OBiO is incubating gene therapy drugs for cancer therapy with three ADC candidates for oncotherapy that have proprietary IP. The B+ Round investors included GP Capital, Sinowisdom and Efung Capital.

Shanghai OPM Biosciences raised $14 million from China Life Medical Fund to support its CDMO service platform. The company offers serum-free media for cell cultures based on animal cells, as well as a full-range of cell culture development services. It customizes high-quality personalized animal cell culture media to optimize the cell culture process and reduce production costs. OPM has developed a variety of chemically defined CHO/HEK293 cell culture media and nutritional products. The company claims its media improve cell growth and expression.

China Immunotech Biotech of Beijing completed a $6.5 million Series A financing, led by Jianxin Capital with Grower Venture Capital and Huacheng Group participating. Founded in March 2018, China Immunotech is developing TCR-T and CAR-T products that target hematological tumors, solid tumors and virus-related diseases. It has two unique technology platforms, STAR-T and TCR-T. The STAR-T platform uses a proprietary structure of antigen receptor complexes. The company believes the platform provides multi-targeted molecules with better efficacy, fewer side effects and easier development than traditional CAR-T products.

Chengdu's HitGen has signed a licensing agreement to develop a novel class of drugs for Kaken, a Japanese (TK: 4521) specialty pharma. HitGen has already used its large library of small molecule and macrocyclic compounds to identify potential candidates. Few details were released, but Kaken is known to be concentrating its R&D on inflammation/immunology (dermatitis, rheumatoid arthritis and osteoarthritis), pain relief and fungal infections. One year ago, the two companies formed a similar collaboration, presumably for other targets. HitGen will receive an upfront payment and be eligible to receive preclinical and clinical milestones.

Suzhou Ascentage Pharma (HK: 6855) announced approvals for three clinical studies of APG-2575, a novel Bcl-2 inhibitor, two in the US and one in China. APG-2575 is an oral drug designed to treat several hematologic malignancies by blocking Bcl-2 to restore the normal apoptosis process in cancer cells. According to Ascentage, the candidate is the first China-made Bcl-2 inhibitor to start clinical trials. In its Phase I clinical studies, APG-2575 did not exhibit any dose-limiting toxicity or tumor lysis syndrome (which is commonly associated with other Bcl-2 inhibitors).

Denovo Biopharma, a San Diego-Beijing precision medicine company, has discovered a novel genetic biomarker for depression that it intends to use with DB104, a triple dopamine, serotonin and norepinephrine reuptake inhibitor. The company made the discovery using its proprietary biomarker discovery platform. Denovo licensed DB104 from Albany Molecular Research. Bristol-Myers Squibb (NYSE:BMY) returned the candidate to Albany after two Phase IIb clinical trials in treatment-resistant depression. The biomarker is one of four DeNovo biomarkers aimed at psychiatric use.

I-Mab (NASDAQ:IMAB), a Shanghai clinical-stage biopharma, has started to develop TJM2 (TJ003234) to treat cytokine release syndrome in severe cases of COVID-19. TJM2 is an I-Mab-discovered neutralizing antibody that binds human granulocyte-macrophage colony stimulating factor (GM-CSF), an important cytokine that plays a critical role in acute and chronic inflammation. By binding GM-CSF, TJM2 prevents downstream signaling and target cell activation, inhibiting other inflammatory responses. I-Mab intends to start clinical trials in the US and expand to countries especially hard-hit by COVID-19.

Mesoblast (NSDQ: MESO; ASX: MSB), an Australia-based regenerative medicine company, announced plans to start trials of remestemcel-L, its allogeneic mesenchymal stem cell (MSC) product candidate, in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19. The trial will be conducted in the US, Australia, China and Europe. ARDS is the principal cause of death in COVID-19 patients. In a small China trial, allogeneic MSCs cured or significantly improved all seven patients with severe COVID-19 pneumonia.

Ascletis (HK: 1672), a Hangzhou biopharma, reported that an initial group of 11 COVID-19 patients all recovered after being treated with a combination Ganovo and Ritonavir therapy. Ascletis's Ganovo, the first approved direct-acting anti-viral agent developed by a China company, was launched in 2018 to treat hepatitis C. Ritonavir is a generic anti-retroviral that is used in AIDS/HIV combination therapies. The small clinical trial was led by Dr. Hongyi Chen, the director of the Ninth Hospital of Nanchang.

Disclosure: None

Original Post

Editor's Note: The summary bullets for this article were chosen by Seeking Alpha editors.

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Week In Review: Nanjing Legend Files To Stage IPO In The U.S. - Seeking Alpha

Gibbon ape leukemia virus (GALV) can infect a wide variety of cells but fails to infect most cells derived from laboratory mice. Transduction of human hematopoietic stem cells with GALV retroviral vectors is more efficient than with amphotropic vectors. In this study, a Moloney murine leukemia virus-gibbon ape leukemia virus (MoMLV-GALV) vector was constructed by replacing the natural env gene of the full-length Moloney MLV genome with the GALV env gene. To monitor viral transmission by green fluorescent protein (GFP) expression, internal ribosomal entry site-enhanced GFP (IRES-EGFP) was positioned between the GALV env gene and the 3 untranslated region (3 UTR) to obtain pMoMLV-GALV-EGFP. The MoMLV-GALV-EGFP vector was able to replicate with high titer in TE671 human rhabdomyosarcoma cells and U-87 human glioma cells. To evaluate the potential of the MoMLV-GALV vector as a therapeutic agent, the gene for the fusogenic envelope G glycoprotein of vesicular stomatitis virus (VSV-G) was incorporated into the vector. Infection with the resulting MoMLV-GALV-VSV-G vector resulted in lysis of the U-87 cells due to syncytium formation. Syncytium formation was also observed in the transfected human prostate cancer cell line LNCaP after extended cultivation of cells. In addition, we deleted the GALV env gene from the MoMLV-GALV-VSV-G vector to improve viral genome stability. This MoMLV-VSV-G vector is also replication competent and induces syncytium formation in 293T, HT1080, TE671 and U-87 cells. These results suggest that replication of the MoMLV-GALV-VSV-G vector or MoMLV-VSV-G vector may directly lead to cytotoxicity. Therefore, the vectors developed in this study are potentially useful tools for cancer gene therapy.

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Construction of a replication-competent retroviral vector for expression of the VSV-G envelope glycoprotein for cancer gene therapy. - Physician's...

HOUSTON--(BUSINESS WIRE)--Kuur Therapeutics today announced the launch of its new business in partnership with Baylor College of Medicine and Baylors Center for Cell and Gene Therapy. Houston-based Kuur Therapeutics will advance the work of its predecessor, Cell Medica, to develop anti-cancer therapies using its innovative chimeric antigen receptor natural killer T cell (CAR-NKT) therapy platform.

IP Group, Baylor College of Medicine and Schroeder Adveq are investing to support two phase 1 studies: GINAKIT 2 (autologous CAR-NKT cells in neuroblastoma) and ANCHOR (allogeneic CAR-NKT cells in CD19 malignancy). The ongoing GINAKIT2 study is now enrolling patients at the third dose level and the ANCHOR study IND has recently been approved by the FDA, with first patient treatment expected in 1H 2020. The funding will also support the preclinical development of an allogeneic CAR-NKT product for treatment of hepatocellular carcinoma, ahead of an IND submission anticipated in 1H 2021.

In conjunction with the new investment, Kevin S Boyle, Sr, was named CEO of Kuur, succeeding Chris Nowers. Mr Boyle joined Cell Medica as CFO in February 2018. Kevin previously held senior finance roles at both NASDAQ-listed and private equity backed companies. He is an accomplished capital markets professional, having raised over $2.0 billion in equity and debt capital.

Kuurs novel CAR-NKT platform is a next-generation technology of engineered immune cells with enhanced functions for the treatment of hematological and solid tumors. It utilizes the unique properties of NKT cells, a specialized type of innate lymphocyte, which shares properties with both T and NK cells. This platform, developed in the laboratory of Baylor Principal Investigator Leonid Metelitsa, is exclusively licensed to Kuur by its partner and collaborator, Baylor College of Medicine.

Annalisa Jenkins, Chair of Kuurs Board, said: We are fortunate to have Kevin step up to the role of CEO. He will act as a change agent, leading the company during a crucial period for our clinical trials and working to secure the additional capital required to progress our two lead CAR-NKT products through the clinic.

The Board would also like to thank Chris for his exceptional leadership during a transition period that has resulted in a company on the right path forward for its investors, with a focus on its important collaborations.

Kevin S Boyle, Sr, Kuurs CEO, said: I am excited to lead Kuur Therapeutics at such a pivotal moment. We are making final preparations to take our off-the-shelf program into the clinic and believe the allogeneic approach holds huge promise for unlocking the potential of CAR therapies for large patient populations. Compared with patient-specific autologous CAR products, it is immediately available for treatment and less expensive to manufacture.

Leonid S. Metelitsa, BCM Principal Investigator, said: My goal is to make a difference in the lives of cancer patients, especially children, and Im excited to be working with the Kuur team to make this goal a reality. I believe that the NKT-cell platform technology, developed in my laboratory and progressed to first-in-human clinical testing in close collaboration with colleagues at BCM and Texas Childrens Hospital, offers a unique route to next-generation off-the-shelf CAR therapies for a broad range of malignancies.

- ENDS -

Notes to Editors

About Kuur Therapeutics

Kuur Therapeutics, headquartered in Houston, is a clinical-stage biotechnology company focused on transforming the treatment of solid and hematological cancers by developing next generation chimeric antigen receptor-natural killer T cell (CAR-NKT) therapies. Developing a portfolio of primarily allogeneic therapies, the companys revolutionary platform spanning both hematological and solid tumors is being created in partnership with Baylor College of Medicine and Baylors Center for Cell and Gene Therapy.

For further information, please visit http://www.kuurtx.com. Follow Kuur Therapeutics on LinkedIn

About Kuurs CAR-NKT cell technology

One of the challenges with allogeneic therapies is that infusing a patient with donor-derived lymphocytes can induce graft versus host disease (GvHD), a potentially life-threatening condition in which the infused cells recognize the patients tissues as foreign. The NKT cells used in Cell Medicas CAR-NKT platform have an invariant T cell receptor (iTCR) that does not distinguish between self- and non-self tissues, making them unlikely to induce GvHD when given to another person. Kuurs CAR-NKT cells are also engineered to secrete IL-15, to prolong persistence and enhance anti-tumor activity.

Baylor has previously reported evidence of clinical activity and a good safety profile in neuroblastoma patients treated at low dose levels of autologous CAR-NKT cells at the 2019 American Society for Gene and Cell Therapy conference.

About Baylor College of Medicine

Baylor College of Medicine (www.bcm.edu) in Houston is recognized as a premier academic health sciences center and is known for excellence in education, research and patient care. It is the only private medical school in the greater southwest and is ranked 16th among medical schools for research and 5th for primary care by U.S. News & World Report. Baylor is listed 21st among all U.S. medical schools for National Institutes of Health funding and number one in Texas. Located in the Texas Medical Center, Baylor has affiliations with seven teaching hospitals and jointly owns and operates Baylor St. Lukes Medical Center, part of CHI St. Lukes Health. Currently, Baylor trains more than 3,000 medical, graduate, nurse anesthesia, physician assistant and orthotics students, as well as residents and post-doctoral fellows.

Follow Baylor College of Medicine on Facebook (http://www.facebook.com/BaylorCollegeOfMedicine) and Twitter (http://twitter.com/BCMHouston).

About the Baylor College of Medicine Center for Cell and Gene Therapy

The Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital in Houston, Texas is led by Helen E Heslop, MD, DSc (Hon), Director and Malcolm K Brenner, MD, PhD, Founding Director. The Center for Cell and Gene Therapy provides an infrastructure to rapidly translate novel cell and gene therapy protocols from the laboratory to the clinic. The comprehensive approach of the center brings a wide variety of scientists and clinicians together to develop strategies for the treatment of cancer, HIV and cardiovascular disease. Patient facilities include the adult stem cell transplant unit at Houston Methodist Hospital and the pediatric stem cell transplant unit at Texas Children's Hospital.

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Kuur Therapeutics Launches to Develop and Commercialize Off-the-shelf CAR-NKT Cell Therapies Targeting Hematological and Solid Tumors - Business Wire

These more resilient microbes are generally less susceptible to the chemical onslaught of ethanol and soap. But vigorous scrubbing with soap and water can still expunge these microbes from the skin, which is partly why hand-washing is more effective than sanitizer. Alcohol-based sanitizer is a good backup when soap and water are not accessible.

In an age of robotic surgery and gene therapy, it is all the more wondrous that a bit of soap in water, an ancient and fundamentally unaltered recipe, remains one of our most valuable medical interventions. Throughout the course of a day, we pick up all sorts of viruses and microorganisms from the objects and people in the environment. When we absentmindedly touch our eyes, nose and mouth a habit, one study suggests, that recurs as often as every two and a half minutes we offer potentially dangerous microbes a portal to our internal organs.

As a foundation of everyday hygiene, hand-washing was broadly adopted relatively recently. In the 1840s Dr. Ignaz Semmelweis, a Hungarian physician, discovered that if doctors washed their hands, far fewer women died after childbirth. At the time, microbes were not widely recognized as vectors of disease, and many doctors ridiculed the notion that a lack of personal cleanliness could be responsible for their patients deaths. Ostracized by his colleagues, Dr. Semmelweis was eventually committed to an asylum, where he was severely beaten by guards and died from infected wounds.

Florence Nightingale, the English nurse and statistician, also promoted hand-washing in the mid-1800s, but it was not until the 1980s that the Centers for Disease Control and Prevention issued the worlds first nationally endorsed hand hygiene guidelines.

Washing with soap and water is one of the key public health practices that can significantly slow the rate of a pandemic and limit the number of infections, preventing a disastrous overburdening of hospitals and clinics. But the technique works only if everyone washes their hands frequently and thoroughly: Work up a good lather, scrub your palms and the back of your hands, interlace your fingers, rub your fingertips against your palms, and twist a soapy fist around your thumbs.

Or as the Canadian health officer Bonnie Henry said recently, Wash your hands like youve been chopping jalapeos and you need to change your contacts. Even people who are relatively young and healthy should regularly wash their hands, especially during a pandemic, because they can spread the disease to those who are more vulnerable.

Soap is more than a personal protectant; when used properly, it becomes part of a communal safety net. At the molecular level, soap works by breaking things apart, but at the level of society, it helps hold everything together. Remember this the next time you have the impulse to bypass the sink: Other peoples lives are in your hands.

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Why Soap Works - The New York Times

K.L. always knew he might be completely blind before reaching adulthood.

Even as a child he realized something was wrong with his eyes. Although he could see enough to navigate the world in daytime, as soon as the sun set so did his eyesight. Going out with friends was impossible at night. Eventually the world looked as if he was seeing through a large tunnel, focusing on only a tiny fraction at a time.

K.Ls condition didnt have a cure. His family, and he himself, were well aware. I was struggling deeply with what I thought my life would become, he said, but then my mum spotted the trial in a newsletter.

This month, K.L. became one of the first patients to receive a new experimental gene therapy for children with a severe form of inherited vision loss. The treatment, currently not yet named, targets young men who are susceptible to a particularly vicious genetic disorder that gradually destroys the light-sensing portion of their eyes.

Within a month following a single injection, my vision was beginning to return in the treated eye. The sharpness and depth of colors I was slowly beginning to see were so clear and attractive, said K.L.

The trial, a first-in-human case for X-linked Retinitis Pigmentosa (RP), was led by Dr. Robert MacLaren at the University of Oxford but spanned multiple centers including the Bascom Palmer Eye Institute in Miami, which previously championed Luxterna, the first FDA-approved gene therapy for a type of inherited blindness. The results are some of the first targeting a particularly difficult gene prone to mutation in humans. Amazingly, despite some inflammation in early stages, the therapy provided massive improvements in eyesight as early as two weeks following treatment.

Although primarily designed for safety and not to comprehensively study efficacy, the trail still offers hope to 1 in 4,000 people around the world battling gradual, unstoppable vision loss. But it also signals that gene therapy is rapidly coming of age for other neural degenerative problemsperhaps faster than previously anticipated.

It is becoming more apparent to us that novel genetic therapies, when working, lead to a clear improvement in neuronal function, which holds great hope for a variety of other degenerative conditions that have a genetic basis, said MacLaren.

K.L. is one of 80,000 or so people in the US with RP, a genetic condition that slowly eats away at the light-sensing portion of the eyes. RP can be due to one of tens of different mutations in genes that control how light receptors in the eyes develop. RP never had a treatment or a curethe only option for people with the condition is to learn to navigate it without severely disrupting their lives.

In late 2017, everything changed. Luxturna, a gene therapy for inherited RP, was approved by the FDA. The treatment, a synthetic version of a healthy gene, was delivered directly into patients eyesoften young boysto replace a faulty version that eats away at the back of their eyes, the retina.

The retina is a delicate, wispy sheet of tissue that contains elements sensitive to light. In RP, two light-sensing proteins in the retina begin dying out as early as infancy, wiping out a persons peripheral vision and night vision. Most are legally, if not biologically, blind by their early 20s.

Luxturna came as a galvanizing shot to RP sufferers, yet it had severe limitations. A large portion of RP cases are caused by a particularly complex and volatile gene, dubbed RPGR, prone to mutations and other rearrangements. Even as a miracle cure, Luxturna could only tackle a small subset of patients with RPabout 1,000that had a very specific mutation relying on Vitamin A chemical processing.

In other words, for K.L. and other RP suffers, Luxturna offered hope, but not relief.

K.L.s treatment took a direct stab at RPGR, which sits on the X chromosome.

Stay with me. We all know that biological females are generally dubbed XX and males XY. Biological females usually have two copies of the X chromosome, whereas males only have one copy.

This means that biological males are far more susceptible than females to contracting X-linked RP. If anything goes wrong with their single copy, unlike females, they dont have a healthy backup to save the day. Unfortunately, the RPGR gene also happens to be quite temperamental and prone to genetic shifts that cause disease. It makes the gene a terrible test subject in the lab, where it tends to be unstable and difficult to work with.

After years of wrangling in animal models, however, the Oxford team was able to increase its stability and fidelity, so much so that when given to animal models with retinal disease, the stabilized, healthy version was able to restore visual properties.

In their first human trial, 18 patients with confirmed RPGR gene mutations and severe eyesight problems were separated into 6 groups, with each receiving a different dose of the therapy.

Similar to Luxturna, the healthy gene was packaged inside a virus carrier to deliver it into retinal cells in a simple injection surgery. To combat potential side effects of inflammation, which scientists previously found with similar treatments, the patients were given steroid pills to combat inflammation in the eyes.

Only one eye of each patient was treated in an effort to compare to the other, non-treated one. K.L., for example, opted to go for the one with poorer vision, thinking there was nothing to lose.

The speed of my conditions degeneration was unknown, so I had no choice but to apply and do whatever I could to hopefully help others in the future, as well as myself, he said.

Although the three patients receiving low-dose treatment didnt see notable results, others did.

Within a month, said K.L., my visual field exploded and I could see so much more at once than ever before in that eye. Before long, the eye was undoubtedly better than the untreated eye.

The improvements lasted at least six months, and only those who received the highest doses of the virus had minimal signs of inflammation, suggesting that the treatment is relatively safe.

Overall, seven patients gained back significant functionality in their eyesnot just night vision, as with Luxturna, but also their visual fields and clarity. Whats more, in some patients the outer regions of the retina also seemed to kick back into gear, regenerating their functionality even without direct treatment.

We are delighted with the early results of this clinical trial for a degenerative eye disease, said MacLaren. With X-linked RP, the goal is to slow or stop degeneration of the eyes, and despite somewhat inconsistent results between people, the therapy seems overall beneficial.

The results will next be validated in a broader population. Since performing the therapy, the Bascom Palmer team has further treated nine patients using the optimized dose determined from the trial, though outcomes have not yet been published.

For K.L., however, the trial has already revamped his life for the better.

The results have been nothing short of astonishing and life changing for me, I really hope this trial is approved and they can treat what once was my better eye, said K.L.

Image Credit: Free-Photos from Pixabay

Link:

Gene Therapy Is Successfully Treating a Common Form of Inherited Blindness - Singularity Hub

Cell and gene therapy manufacturers need staff with laboratory skills and GMP know-how, according to an expert from Texas A&M.

Cell and gene therapies attract a lot of attention. In recent years products like Yescarta, Kymriah and Zolgensma and the debate about their prices $373,000, $475,000 and $2.1m respectively have dominated the headlines.

In industry circles the focus has shifted to the manufacture of such therapies. Developers are working to ensure there are sufficient vectors, or to make production systems more cost efficient.

Ex-military personnel could be a good fit for the cell and gene therapy industry. Image: iStock/ChrisSuperseal

But biopharma should not forget its staff.

Even automated lines need skilled operators says Jenny Ligon, assistant director of workforce development at Texas A&Ms National Center for Therapeutics Manufacturing (NCTM).

For cell and gene therapy, technicians need to have a better understanding of molecular biology and even immunology and virology.

She told us: The reality is we just need more people with practical laboratory experience. In general, upstream manufacturing technicians seem to be in high demand, so those individuals with experience with good cell culture technique will be highly marketable.

With gene and cell therapy taking off, there will be an even larger demand for those with experience in mammalian cell culture.

Adaptability is key. Ligon told us: By and large, there arent any new unit operations in cell and gene therapy manufacturing, however, because of the novelty of this field, manufacturing processes are still evolving.

Staff training is dictated by resources. Large biopharma firms have systems in place to ensure staff have the right skills, but small companies may find it more difficult.

Many gene and cell therapy companies are still in start-up mode, Ligon said. For them, the critical need for technicians is an understanding of cGMP manufacturing processes as many of them may only be familiar with bench-scale manufacturing.

Fortunately, there is support according to Ligon, who cited a Texas A&M course funded by the National Institute for Innovation in Manufacturing Biopharmaeuticals (NIIMBL) as an example.

The course was developed by BTEC through NIIMBL funding and remains the only hands-on short course focused on vector manufacturing.NCTM will be offering the course beginning in the latter half of 2020.

Cell and gene therapy firms also struggle to find staff according to Ligon, who says competition for skilled employees will have negative consequences.

Current cell and gene therapy roles are being filled with those workers who have been in traditional biomanufacturing for several years, which will create a tremendous gap in positions for traditional manufacturers, confirming the demand for more trained workers, period.

Ligon suggests ex-military personnel could be a good fit for the cell and gene therapy industry.

Im still a strong advocate for former service members to fill many of the future jobs in this industry, given their strong sense of responsibility, dedication to accomplishing a mission, ability to innovate and identify solutions to challenging and demanding work environments, attention to detail, and understanding of following protocol and doing it right the first time.

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Staff: Cell gene therapy sector needs reinforcements - Bioprocess Insider - BioProcess Insider

A large biotech is partnering with a firm developing cell and gene therapies on treatments for neurological diseases like Alzheimers and Parkinsons.

Cambridge, Massachusetts-based Biogen said Thursday afternoon after markets closed that it had partnered with Brisbane, California-based Sangamo Therapeutics in a deal that could be worth up to $2.7 billion. The partnership will initially focus on two preclinical Sangamo gene therapy candidates ST-501 for tauopathies such as Alzheimers and ST-502 for synucleinopathies like Parkinsons disease, plus an undisclosed neuromuscular target. It also includes exclusive rights for up to nine other undisclosed neurological targets.

Biogen will pay Sangamo $350 million upfront, which includes a license fee and equity investment, while Sangamo will be eligible for up to $2.37 billion in milestone payments, plus royalties.

Shares of Sangamo were up more than 28% on the Nasdaq after markets opened Friday. The company had also announced its fourth quarter and full year 2019 financial results. Biogens shares were down 2.6%.

Sangamo had reached out to multiple companies in a competitive process. While declining to say how many companies the biotech had spoken to, Sangamo head of corporate strategy Stephane Boissel said in a phone interview that it had put together multiple term sheets.

Its a combination of economics, but also the expertise of that partner in that particular field, Boissel said, referring to why the company had chosen Biogen. Biogen, in the pharma world, is probably the best franchise when it comes to neurology.

Adrian Woolfson, Sangamos executive vice president for research and development, said in the same call that it was also because of an appreciation for Biogens enthusiasm and energy.

I think its fair to say we had a very good chemistry with them at a personal level when we went to meet with them in Boston, and we seemed to get along very well, Woolfson said.

Sangamo has existing partnerships with a number of other firms, including Pfizer and Gilead Sciences.

Biogens moves into Alzheimers disease have not been without controversy. The company plans to file for Food and Drug Administration approval of aducanumab, a monoclonal antibody targeting the amyloid beta protein that has long dominated Alzheimers research. The company initially halted the Phase III development program for the drug when it was predicted to fail, but revived it when a post-hoc analysis indicated potential efficacy. Investors have remained skeptical.

Still, that did not come up in the minds of Sangamos executives, Boissel said. While emphasizing that he could not compare the two companies approaches, Woolfson added that gene therapies are potentially better ways to address neurological diseases like Alzheimers because they can switch off genes completely rather than being limited to taking out specific proteins, as monoclonal antibodies are.

ST-501 targets tau, another protein that has been researched as a potential therapeutic target in Alzheimers. ST-501 and ST-502 use adeno-associated viral vectors to deliver zinc finger protein transcription factors (ZFP-TFs), a form of gene therapy that Sangamo said in its quarterly earnings presentation is ideally suited to neurological disorders due to its ability to up- or down-regulate gene expression.

Boissel did not disclose specific timelines for ST-501 and ST-502, but noted that the next steps in their development will be preclinical studies to enable them to enter the clinic.

Photo: John Tlumacki, The Boston Globe, via Getty Images

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Biogen teams up with Sangamo in gene therapy deal worth up to $2.7B - MedCity News

GRENOBLE, France and RESEARCH TRIANGLE PARK, N.C., March 02, 2020 (GLOBE NEWSWIRE) -- CYTOO, a leading drug discovery company on muscle disorders, today announced that it has entered into a research collaboration aimed at selecting a gene therapy candidate for a rare muscle disorder withAsklepios BioPharmaceutical, Inc.(AskBio), a clinical-stage, fully integrated adeno-associated virus (AAV) gene therapy company. Under the terms of the agreement, AskBio and CYTOO will work together to develop an AAV-based screening platform derived from patient cells. The goal of the collaboration is to screen and select a preclinical candidate capable of restoring a healthy phenotype from patient cells culturedin vitro.

CYTOO has developed a muscle-on-a-plate platform using patients primary cells, called MyoScreen. MyoScreen is anin vitrosystem in which skeletal muscle cells mimic the physiology, contractile and metabolic functions of human musclein vivoand allow infection by AAV-based gene therapy vectors targeting muscle.

Dr. Philippe Moullier, Chief Scientific Officer, AskBio Europe, said, As a leader in the gene therapy space, the ability to quickly and efficiently screen potential therapeutic candidates will be invaluable. The expertise provided by CYTOO and the MyoScreen platform will potentially give us a better understanding of how those candidates perform in patient cells and improve efficiency throughout the R&D process.

Luc Selig, CYTOOs CEO, added, Gene therapy for muscle disorders is becoming a reality for patients and their families, and we are proud that AskBio has chosen our expertise to investigate a potential new treatment. We have developed MyoScreen as a laboratory model of patient-derived muscle that can be used to screen gene therapy candidates and QC clinical and commercial batches.

The financial terms of the agreement were not disclosed.

About CYTOOCYTOO is a preclinical-stage drug discovery company addressing muscular disorders (NMDs, muscle waste, muscle disuse, metabolic ageing). The company has developed MyoScreen, a versatile and high-throughput muscle-on-a-plate R&D platform, from patient-derived myotubes, that can be used to model any muscle disorder and screen any type of therapeutic candidate. The platform is open to partnering with biotech and pharmaceutical companies and has been the starting point of CYTOOs internal drug discovery program on Duchenne Muscular Dystrophy. Among partners of CYTOO: Daiichi Sankyo, Pfizer, Axcella. CYTOO has offices in Grenoble, France and Bethesda, MD, USA.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process called Pro10 and an extensive AAV capsid and promoter library. Based in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. AskBio maintains a portfolio of clinical programs across a range of neurodegenerative and neuromuscular indications with a current clinical pipeline that includes therapeutics for Pompe disease, limb-girdle muscular dystrophy type 2i/R9 and congestive heart failure, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). Learn more atwww.askbio.comor follow us onLinkedIn.

Media Contacts:

FP2COMFlorence Portejoiefportejoie@fp2com.frMob: + 33 (0)6 07 76 82 83

AskBioRobin FastenauVice President, Communicationsrfastenau@askbio.com+1 984 275 2705

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CYTOO and AskBio Enter Research Agreement to Screen Gene Therapy Candidates for Rare Muscle Disorder - Yahoo Finance

The growing prevalence of cell and gene therapies in both the clinical and the commercial side of the biopharmaceutical industry is leading to increased demand for viral vectors, with companies within the contract manufacturing sector building their capacity to meet clients needs.

BioPharma-Reporter (BPR) spoke to Colin MacKay (CM), CEO of viral vector manufacturer Symbiosis, about how companies in this sector are addressing the rising demand, how the lack of capacity is affecting the industry, and what are the other challenges that manufacturers face.

MacKay told us that the demand needs to be addressed with improved technical expertise, but the industry is learning experientially on how to deal with these new technologies.

Moreover, he explained how adding capacity has to come concurrently with ensuring compliance to regulations, and how the inherent biological nature of these products, and the sensitivity and complexity of their production systems, needs to be put under the spotlight.

BPR: What are the current challenges in viral vector manufacturing?

CM: The positive regulatory climate with regards to the approval of viral vector-based biopharmaceuticals is further fueling focused investment across the industry in drugs of this nature. In essence, the technology has been vindicated in a commercial setting. Although point-of-use pricing remains a contentious talking point, regulatory, technical and commercial tail-winds are driving the industry to adapt in many ways, and to do so quickly.With respect to manufacturing, for example, there is strong demand for both drug substance and drug product manufacturing, while CMOs like Symbiosis continue to invest in additional manufacturing capacity in direct response to that demand. With high demand, and relatively smaller supply, the foundation is laid for the value of strategic relationships to be realized and to gain prioritized access to manufacturing capacity, for example, while the commercial successes of those CMOs is providing relatively easier access to both internal and external financial resources to further grow overall manufacturing capacity.

Challenges include balancing supply versus demand for a growing business while ensuring that the competitive strengths that come from short lead-times to access manufacturing slots, for example, is positioned to support the accelerated development timeframes which drug developing client companies are working to.

BPR: How have the demands of the cell and gene therapies development market evolved during the past year?

CM: The successes of cell and gene therapy products being approved for market and their breathtakingly positive therapeutic impact on patients has, I believe, driven the market to evolve quickly. The overarching commercial driver in our industry to take investors dollars and to develop innovative and profitable new medicines is undiminished, and indeed has been amplified in niche sectors, such as cell and gene therapies.

In tandem, technology platforms are being validated, meaning that multiple further drugs in companies pipelines are being accelerated down the previously ploughed furrow of those pioneering therapies which went first. That is fueling demand for all services which support the development of cell and gene therapies and the appetite of investors to finance the profitable growth of those service providers.

BPR: What is the main challenge that cell and gene developers face?

CM: The technical challenges of developing, and then robustly and reproducibly manufacturing cell and gene therapy products to GMP is a major challenge, principally due to the inherent biological nature of these products and the sensitivity and complexity of their production systems.

Access to manufacturing capacity, particularly amongst the bigger CMO players, is challenging clients and their drug development timeline planning.

BPR: How does the CMO industry assist developers in overcoming technical challenges?

CM: The experiential learning in the industry, with respect to the technical and GMP manufacture of both drug substance and drug product, continues to grow and that learning is being reflected back into overcoming the principal technical challenges the industry faces. Processes are being refined and optimized to improve yields and productivity, making the development of biopharmaceuticals faster and relatively more cost-effective.

BPR: How do you see the current lack of capacity in the CMO industry changing?

CM: My understanding is that access to manufacturing capacity, particularly amongst the bigger CMO players, is proving a challenge to customers and their ability to achieve their preferred drug development timelines. The industry is responding and investing significantly in building new capacity, and new drug (vector) substance manufacturing capacity.

The relatively smaller CMO players, such as ourselves, are strategically working hard to increase in-house manufacturing capacity while doing so in a measured way to ensure continued compliance in line with that growth, while investing in strategic relationships with existing clients to ensure they have access to our capacity to align with the increasing manufacturing requirement of their maturing products.

In tandem, we are adding new capacity output from our existing manufacturing infrastructure, allowing us to continue to add new, high-value, clients to our existing client portfolio who can use that growing capacity. Strategically, and competitively, Symbiosis is therefore well-positioned to provide sterile GMP manufacturing capacity to clients who are experiencing frustrations with the wider industry and its lack of manufacturing capacity and access to it on a short timeframe.

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Symbiosis on increased demand for viral vectors - BioPharma-Reporter.com

DetailsCategory: DNA RNA and CellsPublished on Tuesday, 03 March 2020 17:27Hits: 481

NEW YORK, NY, USA I March 02, 2020 I Prevail Therapeutics Inc. (Nasdaq: PRVL), a biotechnology company developing potentially disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted the Companys Investigational New Drug (IND) application for its experimental gene therapy program, PR006, for the treatment of frontotemporal dementia patients with GRN mutation (FTD-GRN), and that the Company may proceed with the initiation of its Phase 1/2 clinical trial.

PR006 is being developed as a potential one-time gene therapy for FTD-GRN, a progressive neurodegenerative disease caused by mutations in the GRN gene that reduce production of progranulin, a protein critical for lysosomal function, neuronal survival, and normal microglial activities. The progranulin deficiency leads to lysosomal dysfunction, ineffective protein degradation and recycling, neuroinflammation, and ultimately neurodegeneration and death, typically within three to ten years of diagnosis.

PR006 is designed to increase progranulin levels in the brains of FTD-GRN patients by delivering a healthy GRN gene using an AAV9 vector.

FTD-GRN is a serious and progressive neurodegenerative disease for which there are no approved treatments, said Asa Abeliovich, M.D., Ph.D., Founder and Chief Executive Officer of Prevail. Now that the PR006 IND is active, we look forward to advancing clinical development of PR006, which has the potential to positively impact the lives of patients by slowing or stopping the progression of this devastating disease.

The PROCLAIM Phase 1/2 clinical trial will investigate the safety and tolerability of PR006, and will also measure key biomarkers and exploratory efficacy endpoints in patients with FTD-GRN. The Company plans to begin dosing for PROCLAIM this year. We believe this makes PR006 the first gene therapy for FTD-GRN to enter clinical trials.

The FDA has granted Orphan Drug Designation for PR006 for the treatment of patients with FTD.

About Frontotemporal Dementia with a GRN MutationFrontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65, after Alzheimers disease. 50,000 to 60,000 people in the U.S. and 80,000 to 110,000 individuals in theEuropean Unionare affected byFTD. Frontotemporal dementia with a GRN mutation (FTD-GRN) represents 5-10% of all patients withFTD.FTDresults from the progressive degeneration of the frontal and temporal lobes of the brain, which control decision-making, behavior, emotion and language.In FTD-GRN patients, reduced levels of progranulin lead to age-dependent lysosomal dysfunction, neuroinflammation, and neurodegeneration. There are no approved treatments forFTDor FTD-GRN.

About Prevail TherapeuticsPrevail is a gene therapy company leveraging breakthroughs in human genetics with the goal of developing and commercializing disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases. The company is developing PR001 for patients with Parkinsons disease with aGBA1mutation (PD-GBA) and neuronopathic Gaucher disease; PR006 for patients with frontotemporal dementia withGRNmutation (FTD-GRN); and PR004 for patients with certain synucleinopathies.

Prevail was founded by Dr.Asa Abeliovichin 2017, through a collaborative effort withThe Silverstein Foundationfor Parkinsons with GBA and OrbiMed, and is headquartered inNewYork, NY.

SOURCE: Preavail Therapeutics

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Prevail Therapeutics Announces Investigational New Drug Application Active for PR006 for the Treatment of Frontotemporal Dementia with GRN Mutation |...

DUBLIN and TORONTO, March 3, 2020 /PRNewswire/ --Avectas, a cell engineering technology business,and CCRM, a leader in developing and commercializing cell and gene therapies, today announced they have entered into a collaboration to accelerate the translation of Avectas' non-viral cell engineering platform (Solupore) into the clinic.

Cell and gene therapies offer the potential to dramatically transform the treatment of diseases, including cancer, for millions of patients worldwide. However, a global viral vector shortfall could halt progress in the industry as very few CDMOs have the capabilities required to manufacture vectors that can deliver molecules to cells.

Avectas developed Solupore to address an urgent need for an efficient, non-viral cell engineering solution to facilitate therapeutic development in the areas of immuno-oncology and gene editing.Solupore is designed for use with mRNA, DNA, and proteins, including gene editing tools such as CRISPR. It achieves excellent engineering efficiencies for delivery of these payloads toprimary T cells and NK cells for immuno-oncology and gene editing applications.

Speaking today, Dr. Michael Maguire, CEO of Avectas, said: "We are delighted to partner with CCRMto leverage their deep experience in cell manufacturing processes to support the translation of our Solupore platform towards clinical applications." He continued: "Combining Avectas' novel cell engineering platform and CCRM's experience in the development of manufacturing processes for cell therapies will accelerate the transfer of the Solupore technology to our development partners."

Dr. Michael May, President and CEO of CCRM, said:"This collaboration demonstrates exactly how CCRM is able to support partners and the broader industry. It is evident there is a real need for a non-viral delivery platform to enable the manufacture of these lifesaving cellular therapies and we are eager to receive the Solupore platform and support the Avectas team in bringing this innovative platform to the clinic."

About Avectas

Avectasis a cell engineering technology business developingaunique delivery platform to enable the ex-vivo manufacture ofour partners' gene modified cell therapy products, which will retain high in-vivo functionality. Our vision is to be a leading non-viral cell engineering technology provider, integrated into manufacturing processes for multiple autologous and allogeneic therapies, commercialized through development and license agreements. For more information, please visit the Company's website at: http://www.avectas.com.

About CCRM

CCRM, a Canadian not-for-profit organization funded by the Government of Canada, the Province of Ontario, and leading academic and industry partners, supports the development of regenerative medicines and associated enabling technologies, with a specific focus on cell and gene therapy. A network of researchers, leading companies, strategic investors and entrepreneurs, CCRM accelerates the translation of scientific discovery into new companies and marketable products for patients, with specialized teams, funding, and infrastructure. CCRM is the commercialization partner of the Ontario Institute for Regenerative Medicine and the University of Toronto's Medicine by Design. CCRM is hosted by the University of Toronto. Visit us at http://www.ccrm.ca.

View original content:http://www.prnewswire.com/news-releases/avectas-and-ccrm-announce-collaboration-to-accelerate-development-of-novel-technology-for-cell-therapies-301015122.html

SOURCE Avectas; CCRM

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Avectas and CCRM Announce Collaboration to Accelerate Development of Novel Technology for Cell Therapies - Yahoo Finance

NEW YORK, March 03, 2020 (GLOBE NEWSWIRE) --Prevail TherapeuticsInc. (Nasdaq: PRVL), a biotechnology company developing potentially disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases, provided an update today on the clinical advancement of its gene therapy program PR001 for patients with Parkinsons disease with GBA1 mutations (PD-GBA). Enrollment in the PR001 Phase 1/2 PROPEL clinical trial is progressing, patient dosing continues, and the Company is on track to report interim data on a subset of patients in the second half of 2020.

The Company will present on its clinical progress at the Cowen & Co. Annual Healthcare Conference in Boston today.

We believe the PROPEL trial makes PR001 the first potentially disease-modifying gene therapy for PD-GBA patients to enter clinical trials. Its ongoing progress brings us a step closer to new treatment options for patients living with PD-GBA, said Asa Abeliovich, M.D., Ph.D., Founder and Chief Executive Officer of Prevail. We are excited about the potential of PR001 to slow or stop disease progression for PD-GBA patients.

The PROPEL trial is a randomized, double-blind Phase 1/2 clinical trial evaluating the safety and tolerability of two escalating dose levels of PR001 in up to 16 patients with moderate-to-severe PD-GBA. The trial also evaluates the effect of PR001 on biomarkers of disease activity and on Parkinsons disease clinical efficacy measures. Full trial details are available at clinicaltrials.gov.

PR001 utilizes an AAV9 viral vector to deliver theGBA1gene to a patients cells, correcting the lysosomal enzyme deficiency caused by PD-GBA patients GBA1 mutations. GBA1encodes the lysosomal enzyme, beta-glucocerebrosidase, or GCase, which is required for the disposal and recycling of glycolipids. PD-GBA patients have a mutation in at least one chromosomal copy ofGBA1.

In addition to the PROPEL clinical trial for patients with PD-GBA, PR001 is also being developed for neuronopathic Gaucher disease, a devastating disorder that shares the same underlying genetic mechanism. In December 2019, the Company announced that its IND for PR001 for the treatment of neuronopathic Gaucher disease is active.

About PD-GBAParkinsons disease is a chronic, progressive neurodegenerative disorder that affects up to one million people in the United States and more than seven million people worldwide. PD-GBA affects 7% to 10% of the total Parkinsons disease population worldwide and an estimated 90,000 individuals in the United States alone. GBA1 encodes the lysosomal enzyme, beta-glucocerebrosidase, or GCase. Mutations in the GBA1 gene lead to a deficiency of GCase, resulting in lysosomal dysfunction in CNS cells, which we believe leads to the inflammation and neurodegeneration present in PD-GBA. GBA1 mutations impact the risk of developing Parkinsons disease as well as many other aspects of the disease course, including the severity, age of onset and rate of progression of disease and the likelihood of dementia. There are no treatments available that modify the progressive course or the underlying disease process of Parkinsons disease.

About Prevail TherapeuticsPrevail is a gene therapy company leveraging breakthroughs in human genetics with the goal of developing and commercializing disease-modifying AAV-based gene therapies for patients with neurodegenerative diseases. The company is developing PR001 for patients with Parkinsons disease with aGBA1mutation (PD-GBA) and neuronopathic Gaucher disease; PR006 for patients with frontotemporal dementia withGRNmutation (FTD-GRN); and PR004 for patients with certain synucleinopathies.

Prevail was founded by Dr.Asa Abeliovichin 2017, through a collaborative effort withThe Silverstein Foundationfor Parkinsons with GBA and OrbiMed, and is headquartered inNewYork, NY.

Forward-Looking Statements Related to PrevailStatements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Examples of these forward-looking statements include statements concerning Prevails ability to develop meaningful therapeutic advances for patients with neurodegenerative diseases, the continued progression of our PROPEL Phase 1/2 clinical trial, the continued dosing of patients and the expected timing for the delivery of interim data from a subset of patients from our PROPEL Phase 1/2 clinical trial. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Prevails novel approach to gene therapy makes it difficult to predict the time, cost and potential success of product candidate development or regulatory approval; Prevails gene therapy programs may not meet safety and efficacy levels needed to support ongoing clinical development or regulatory approval; the regulatory landscape for gene therapy is rigorous, complex, uncertain and subject to change; and the fact that gene therapies are novel, complex and difficult to manufacture. These and other risks are described more fully in Prevails filings with theSecurities and Exchange Commission(SEC), including the Risk Factors section of the Companys Quarterly Report on Form 10-Q for the period endedSeptember 30, 2019, filed with theSEConNovember 12, 2019, and its other documents subsequently filed with or furnished to theSEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Prevail undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Media Contact:Mary CarmichaelTen Bridge Communicationsmary@tenbridgecommunications.com617-413-3543

Investor Contact:investors@prevailtherapeutics.com

Excerpt from:

Prevail Therapeutics Provides Clinical Advancement Update on PR001 for the Treatment of Parkinson's Disease with GBA1 mutationsCompany Will Present at...

A University of Virginia biomedical engineering student is trying to tackle the worlds No. 1 cause of death on a genetic level.

Rita Anane-Wae, from Ghana by way of Glendale, Arizona, and a third-year biomedical engineering student, is using a 2019 Harrison Undergraduate Research grant to seek a genetic solution to atherosclerosis, or the build-up of plaque in ones arteries, which impedes blood flow.

There are cells that will try to fix this problem by covering them and basically pushing the plaque down to allow blood flow, she said. These cells will try to reduce that plaque so that there is correct blood flow. In very serious cases, the plaque can harden and break off. Once it breaks, it can get lodged somewhere and cause a stroke or a heart attack.

Created through a gift from the late David A. Harrison III and his family, the Harrison Undergraduate Research Awards fund outstanding undergraduate research projects. Selected by a faculty review committee, awardees receive as much as $4,000 apiece to pursue their research interests, under the direction of a faculty mentor.

Anane-Wae started working in a laboratory run by Mete Civelek, an assistant professor of biomedical engineering, as a second-year student.

Civelek had already altered her life. Anane-Wae came to UVA to be a chemical engineer. She met Civelek when she signed up as a first-year student for a program that offered faculty mentoring.

At the time I was a chemical engineering major with an interest in biomedical engineering, Anane-Wae said. After talking with him, he was able to assuage my fears about biomedical engineering.

Biomedical engineering is a relatively new field and as such, I did not believe there were many jobs out there, and my parents were worried for the same reason, she said. Mete has a chemical engineering undergrad degree and a masters and Ph.D. in biomedical engineering, so he was the perfect person for me to talk to. He explained the two fields in a unique way, unlike what I had read and seen on YouTube.

Honestly, I love biomedical engineering. When I switched into biomedical engineering, literally in my first class, I though Oh, my God, this is home. I am learning about anatomy, physiology, genes and cells, and it is still all really exciting for me.

Civelek also suggested Anane-Wae participate in the research trip to Uganda through the UVA Minority Health & Health Disparities International Research Training program to perform research on congestive heart failure. While in Uganda, Anane-Wae made rounds with a doctor at a local hospital and met a 17-year-old girl suffering from congestive heart failure.

Her legs were all swollen, Anane-Wae said. She had edema and her stomach was filled with fluid. I was looking at her and thinking, This girl cant lay down because of all the swelling and she cant even be at rest. And I was thinking, She is about my age and I am fortunate enough to be traveling the world and she is here stuck in this hospital bed.

Her encounter with the girl became part inspiration to her and part reminder that congestive heart failure is not just for older patients.

I have a hard time accepting what I am capable of doing, Anane-Wae said. Being here, being in Uganda, working in the lab, it has taught me that I am basically capable of making change. I know what I am supposed to be doing with my time and my future and I know that doing it makes me happy and will make other people better.

In her lab work, Anane-Wae studies a specific gene melanoma inhibitor activity 3, or MIA3 that affects smooth muscle cells.

Smooth muscle cells are able to basically cover the plaque in that disease state, Anane-Wae said. We are running experiments to see how us modulating MIA3 affects the disease.

She said she and members of the research team in the lab also performed experiments knocking out the MIA3 gene from the cells, which led to a more serious disease state.

I think experiments like these are really important because we are not yet at the stage where we can do gene therapy on a person, Anane-Wae said. If you knock out specific genes, it will affect things that we dont understand yet.

Anane-Wae is working on a small section of a large field, but she thinks there is promise in the work she is doing.

The genome-wide association studies show that 161 different genes so far have been associated with coronary artery disease, she said. And we are studying just one. There is so much further that we have to go.

The path is really long, but we are trying to understand the mechanism by which one gene affects the disease and if we actually figure out that mechanism, we can try to apply it to the other genes and maybe understand the bigger picture.

Research can lead her down many blind alleys, which she understands. Anane-Wae is also very conscious of the law of unintended consequences, and how something that solves one problem can create other problems in the process.

We can say that about everything, she said. I think that is the way with all new development. You fix problems and new ones will arise, and then you fix those, too. So we can only do so much. But I think what I have learned is that I have found something about which I am passionate. I have found something that I enjoy and here at UVA, I have found a community of people who will help me develop my skills.

Included in that community, Anane-Wae cited Civelek and Redouane Aherrahrou, an American Heart Association Postdoctoral Fellow with whom she works.

Aherrahrou has known Anane-Wae since she joined the lab in 2018. When she first joined our lab, Rita knew only the fundamental lab skills and methods, he said. After a short amount of training, she learned rapidly and became very familiar with the cell culture techniques and appropriate lab handling. She performed the experiments independently. Her interactions with other lab members are both professional and friendly.

He described Anane-Wae as a diligent researcher, a gifted student, an inspiring person, and enjoyable to be around.

She has a great personality, is open to guidance and responds well to criticism, he said. She wants to apply to Ph.D. programs after she graduates, and I predict a great future in her career as a research scientist.

Civelek said he enjoys having Anane-Wae as part of his team.

She is hard-working, curious and eager to make a scientific impact, he said. I can see the joy in her face when she learns something new. She gets along well with everyone in the lab and is a role model to those who are junior to her. She has a bright future and I am very proud of her accomplishments.

Civelek said Anane-Wae was recently awarded a German Academic Exchange Research Internship in Science and Engineering, which is presented to only 300 students from the U.S. and Canada.

Redouane and Mete both have high standards for me and motivate me to do my very best, Anane-Wae said. They have instilled a confidence in me that I did not have prior to joining the lab, and they continuously push me to achieve great things. I am so fortunate to have these two individuals as mentors, in addition to all of the other members in the laboratory.

A Blue Ridge Scholarship recipient, Anane-Wae is member of the National Society of Black Engineers and the Society of Women Engineers. She also has received a Hugh Bache Scholarship.

Anane-Wae said she is looking at doing big things, such as gene therapy, but realizes that she has to take small steps at first, and that her friends in the lab will help her out when things go wrong.

She has also learned that research is a team effort, not a solo pursuit.

You cant do research by yourself, she said. You wont be able to get anything done. You will have to depend on other people and you have to be able to share what you have learned. You wont get anything done in any amount of time if you dont trust other people and work together.

More:

First-Year Lab Experience Gave This Student the Confidence to Aim for a Ph.D. - UVA Today

Protocol amendment being implemented for ongoing RESTORE-1 trial of VY-AADC (NBIb-1817) for Parkinsons disease; plan to initiate RESTORE-2 trial in 2H 2020

Update on VY-HTT01 for Huntingtons disease preclinical program expected in 2Q 2020

Strong financial position with ~$282M of cash at the end of 2019 and expected runway into mid-2022

CAMBRIDGE, Mass., March 03, 2020 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (VYGR), a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases, today reported its fourth quarter and full year 2019 financial results, program progress and corporate updates.

In 2019, we took important steps toward our vision of establishing Voyager as the leader in neurological gene therapy, including forming our strategic collaboration with Neurocrine Biosciences, expanding our partnership with AbbVie, and further progressing our wholly-owned and partnered programs, said Andre Turenne, President and CEO of Voyager. Turning to 2020, we are excited to continue this momentum across all programs. These initiatives include presenting longer-term data from the Parkinsons disease program, advancing our Huntingtons disease program, and further leveraging our novel capsid research and expertise in vector engineering and delivery toward additional pipeline programs.

Recent Corporate Highlights and Program Outlook

VY-AADC for Parkinsons Disease

VY-HTT01 for Huntingtons Disease

Early Pipeline and Platform

Corporate Updates

Anticipated Upcoming Milestones

VY-AADC for Parkinsons Disease:

VY-HTT01 for Huntingtons Disease:

Early Pipeline and Platform:

Fourth Quarter and Full Year 2019 Financial Results

Financial Guidance

Conference Call Information

Voyager will host a conference call and webcast today at 4:30 p.m. EST. The conference call may be accessed by dialing (877) 851-3834 for domestic callers, or +1 (631) 291-4595 for international callers. Please reference conference ID number 8461408 to join the call. The conference call will be webcast live from the Investors & Media section of Voyagers website at http://www.voyagertherapeutics.com and will be archived there following the call for 90 days.

About Voyager Therapeutics

Voyager Therapeutics is a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases. Voyager is committed to advancing the field of AAV gene therapy through innovation and investment in vector engineering and optimization, manufacturing, and dosing and delivery techniques. Voyagers wholly-owned and partnered pipeline focuses on severe neurological diseases for which effective new therapies are needed, including Parkinsons disease, Huntingtons disease, a monogenic form of ALS called SOD1, Friedreichs ataxia, Alzheimers disease, and other neurodegenerative diseases related to defective or excess aggregation of tau and alpha-synuclein proteins in the brain. Voyager has strategic collaborations with AbbVie and Neurocrine Biosciences. Founded by scientific and clinical leaders in the fields of AAV gene therapy, expressed RNA interference and neuroscience, Voyager is headquartered in Cambridge, Massachusetts. For more information, please visit http://www.voyagertherapeutics.com or follow @VoyagerTx on Twitter and LinkedIn.

Forward-Looking Statements

This 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 may, might, will, would, should, expect, plan, anticipate, believe, estimate, undoubtedly, project, intend, future, potential, or continue, and other similar expressions are intended to identify forward-looking statements. For example, all statements Voyager makes regarding the initiation, timing, progress, activities, goals and reporting of results of its preclinical programs and clinical trials and its research and development programs, the potential benefits, timing and future operation of the collaboration agreements with AbbVie and Neurocrine Biosciences, including any potential future payments thereunder, its ability to identify and attract parties to participate in research and development collaborations, its ability to advance its AAV-based gene therapies into, and successfully initiate, enroll and complete, clinical trials, the potential clinical utility of its product candidates, its ability to continue to develop its gene therapy platform, its ability to perform under existing collaborations including those with AbbVie and Neurocrine Biosciences, its ability to add new programs to its pipeline, the regulatory pathway of, and the timing or likelihood of its regulatory filings and approvals for, any of its product candidates, its ability to operate its research and development activities efficiently and effectively, the utility and value of Voyagers patent portfolio, and Voyagers anticipated financial results, including Voyagers available cash, cash equivalents and marketable debt securities, the receipt by Voyager of revenues or reimbursement payments from collaboration partners, Voyagers operating expenses, and Voyagers ability to fund its operating expenses with its current cash, cash equivalents and marketable debt securities though a stated time period are forward looking. All forward-looking statements are based on estimates and assumptions by Voyagers management that, although Voyager believes such forward-looking statements 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 Voyager expected. Such risks and uncertainties include, among others, those related to the initiation and conduct of preclinical studies and clinical trials; the availability of data from preclinical studies and clinical trials; the expectations for regulatory communications, submissions and approvals; the continued development of the gene therapy platform; Voyagers scientific approach and general development progress; the ability to attract and retain talented contractors and employees; the ability to create and protect intellectual property; the sufficiency of cash resources; the possibility or the timing of the exercise of development, commercialization, license and other options under collaborations; and the availability or commercial potential of Voyagers product candidates. These statements are also subject to a number of material risks and uncertainties that are described in Voyagers Annual Report on Form 10-K filed with the Securities and Exchange Commission, as updated by its subsequent filings with the Securities and Exchange Commission. All information in the press release is as of the date of this press release, and any forward-looking statement speaks only as of the date on which it was made. Voyager undertakes no obligation to publicly update or revise this information or any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Investors: Paul CoxVP, Investor Relations857-201-3463pcox@vygr.com

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Voyager Therapeutics Announces Fourth Quarter and Full Year 2019 Financial Results and Corporate Updates - Yahoo Finance

Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein.

A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell. The viruses are modified so they can't cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome.

The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient's cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein.

Researchers must overcome many technical challenges before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.

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How does gene therapy work? - Genetics Home Reference - NIH

The Center for Gene Therapy at Nationwide Childrens Hospital is working to develop childrens gene therapy treatments. Officials say the gene therapy research and clinical trials there are starting to attract companies to central Ohio.

Nationwide Childrens Hospital is in the forefront of curing several genetic childhood diseases, transforming Columbus into a major medical hub, several gene therapy experts say.

The hospital's Center for Gene Therapy at the Abigail Wexner Research Institute is working to develop treatments for children, which is attracting patients and companies to Ohio, according to officials at Nationwide Childrens and JobsOhio, the state's economic development organization.

The illnesses that were making use of in gene therapy are devastating illnesses, said Dr. Kevin Flanigan, the director of Nationwide Childrens Center for Gene Therapy. These are ones we know that children would be significantly impaired for life or die because of the disease.

Gene therapy involves altering the genes inside the patient's cells in an effort to treat or stop disease. It gives doctors the chance to treat many previously untreatable rare and genetic diseases.

Gene therapy is currently available primarily in a research setting, with only four gene therapy products approved by the U.S. Food and Drug Administration for sale in the United States. One of the four, Zolgensma, started as a clinical trial for spinal muscular atrophy at Nationwide Childrens in 2014.

The hospital is working on a handful of gene therapy treatments for various childhood diseases that affect muscle, motor or mental functions, Flanigan said.

Gene therapy presents a tremendous opportunity for our medical system, and Columbus has been a huge part of that growth thanks to the work being done at Nationwide Childrens Hospital, Edith Pfister, chairwoman of the American Society of Gene & Cell Therapys communications committee, said in an email.

The FDA approved Zolgensma, a one-time treatment that intravenously delivers the gene that is missing in children with spinal muscular atrophy, on May 24.

SMA is a progressive childhood neuromuscular disease that is caused by a mutation in a single gene that attacks nerve cells. It causes major physical limitations including the inability to breathe, swallow, talk or sit up. Children born with SMA typically die or need permanent breathing assistance by the time they turn 2 years old.

Donovan Weisgarber was diagnosed with SMA type 1 at Nationwide Childrens in November 2015 when he was 5 weeks old. His parents, Matt and Laura Weisgarber, decided to participate in a clinical trial at the hospital and Donovan received Zolgensma.

Before the treatment, Donovan was unable to swallow and had difficulty breathing. Today, the 4-year-old has doubled his life expectancy and is able to talk, sit up, roll over and hold his head up on his own. He also attends the Early Childhood Education and Family Center on Johnstown Road on the East Side, which offers services from the Franklin County Board of Developmental Disabilities.

(Gene therapy) has given us an opportunity that we otherwise wouldnt have to love Donovan and experience him, said Matt Weisgarber, 33, of the Northeast Side.

A lot of people hear Ohio and think flyover state, but now Columbus is going to be a hub of the most groundbreaking science known to mankind and thats a really cool thing, he said.

Boston Childrens Hospital and Childrens Hospital of Philadelphia also have impressive gene therapy centers, but Columbus sets itself apart from those East Coast cities, said Severina Kraner, JobsOhios health care director.

The cost to operate, manufacture and live in Ohio is cheaper than Boston and Philadelphia, putting Ohio in a position to win cell and gene therapy companies, she said.

People are being priced out of these coastal cities, Kraner said.

One of the companies who has committed to building in Columbus is Sarepta Therapeutics, a Massachusetts-based biopharmaceutical company. Sarepta signed an agreement with Nationwide Childrens in May 2019, giving the company the licensing to a gene therapy treatment that came out of hospital research for limb-girdle muscular dystrophies, a group of diseases that cause weakness and wasting of the muscles in the arms and legs.

Sarepta is scheduled to open an 85,000-square-foot Gene Therapy Center of Excellence near Nationwide Childrens Hospital in the fall to do early research for all the companys gene therapy programs. A team of about 30 employees from Sarepta is currently working at a facility at Easton Town Center.

The region has every ingredient needed for a thriving gene therapy cluster: a strong academic foundation, world-renowned research hospitals, and, now, industry investment, Louise Rodino-Klapac, Sareptas senior vice president of gene therapy, said in an email. All of these contribute to creating a pipeline of talented people who will accelerate scientific advances that help patients.

Nationwide Childrens recently also announced it will be expanding its gene therapy research by creating Andelyn BioSciences, a new for-profit subsidiary that will manufacture gene therapy products for the biotechnology and pharmaceutical industries.

Were hoping, and we have a vision, that Andelyn can help capitalize a biotechnology hub in central Ohio focused on developing and advancing gene therapies, said Dr. Dennis Durbin, Nationwide Childrens chief science officer.

Andelyn BioSciences will launch this summer and operate out of the Abigail Wexner Research Institute, 575 Children's Crossroad. Nationwide Children's is trying to secure a permanent location for Andelyn and is looking at land on Ohio State Universitys West Campus.

Gene therapy treatment, however, comes at a high price.

The manufacturer set the price of Zolgensma at more than $2.1 million. Insurers can pay $425,000 a year for five years for one treatment.

Insurance companies are used to regular installment payments, but the single-dose nature of gene therapies are adding a level of uncertainty to health insurance structures, Pfister said in an email. A one-time administration gene therapy costs less overall, but it occurs in one upfront payment.

Pfister said she is hopeful the cost of gene therapy will go down.

Currently, most of the FDA-approved gene and cell therapies are tailored for the specific patient, but theres an incredible amount of research going into standardizing the components and delivery mechanisms behind gene therapy, Pfister said in an email.

Dr. Jerry Mendell helped usher in the era of gene therapy at Nationwide Childrens when he came to the hospital in 2004.

Nationwide Childrens first gene therapy trial was in 2006 for duchenne muscular dystrophy, a rare, inherited, degenerative muscle disorder that almost exclusively affects boys.

Things have really changed significantly in the gene therapy world because of the contributions weve made here, and its been a very gratifying experience, said Mendell, the principal investigator in Nationwide Childrens Center for Gene Therapy.

mhenry@dispatch.com

@megankhenry

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Nationwide Childrens among hospitals leading the way in gene therapy - The Columbus Dispatch