Category Archives: Gene therapy

Manufacturing issues and a scarcity of new commercial products leave predictions that 10-20 cell and gene therapy approvals each year by 2025 somewhat fanciful, says Dark Horse Consulting.

In his plenary address at the Phacilitate conference yesterday, Anthony Davies, founder of cell and gene therapy specialist firm Dark Horse Consulting, reflected on the difficulties the sector has faced since the high of 2017 when three products achieved US Food and Drug Administration (FDA) approval: Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel), and gene therapy Luxturna (voretigene neparvovec).

A few years ago, I introduced this evening by saying: Finally the field has had the year that weve been saying we are going to have for years. That was a great year, he told the packed room in Miami, Florida.

Dark Horses Anthony Davies opened the Phacilitate conference in Miami, Florida

The CAR-T therapies Kymriah and Yescarta gave hope to patients who previously could measure their life expectancy in a small number of months, while gene therapy Luxturna offered hope to children whose ophthalmic deterioration was a statistical certainty, he added.

With these breakthroughs, positivity was high and in January 2019 then FDA Commissioner Scott Gottlieb predicted in an agency statement that there will be upwards of 200 regenerative medicine IND submissions from 2020, and by 2025 the agency will be approving 10 to 20 cell and gene therapy products a year.

I think 200 INDs is doable this year, but INDs do not cure patients, Davies said. And I think if weve struggled with getting three commercial approvals in the years after that first year when three commercial approvals were made, so getting 10-20 in five years from now is going to be extremely challenging.

Since that breakthrough year, the industry has been hot by bad news and a lack of commercial products. Novartis/AveXis Zolgensma (onasemnogene abeparvovec) and bluebirds Zynteglo (autologous CD34+ cells encoding A-T87Q-globin gene) were approved by the FDA last year, while Takedas allogeneic cell therapy Alofisel (darvadstrocel) has been approved to a certain extent in Europe.

While Davies described the approval of Zolgensma, at a cost of $2.1 million, as groundbreaking, he noted it has been overshadowed by a scandal involving data falsification during the approval process.

He also noted that Zynteglos success has been muted by multiple manufacturing problems which has delayed launch.

Meanwhile, pioneer product Kymriah continues to suffer from manufacturing difficulties, and Novartis seems to be struggling with fixing them, Davies suggested.

At JP Morgan [Healthcare Conference] it was announced that for 10% of patients no shipment of drug is made, and for a very significant minority of patients shipment is made with out-of-spec product for which Novartis cannot charge, he told the conference

He added that at the investor conference last week, Novartis CEO Vasant Narasimhan said that they had made great process in identifying the manufacturing issues and were negotiating their resolution with the FDA.

This was exactly the same statement he made at JP Morgan the year before that.

But despite the slowdown in commercialization and industrys challenges, Davies said there remains a lot to be positive about.

Everything that I said reflects the extreme difficulty in bringing this class of therapeutics to market. If these therapeutics were easy to develop,p they would have been developed. If diseases were easy to cure, we wouldnt need new therapeutics.

Let us just use these good pieces of news and these bad pieces of news as inspiration, lets continually remind ourselves that what we do is one of the hardest things in science or medicine at this time.

Davies was not alone in his views.

Speaking Wednesday, Robert Preti, CEO of Hitachi Chem Advanced Therapeutic Solutions, admitted the industry is behind where he thought it would be when he began his career 37 years ago, but said he was not too worried.

I want to commend this industry on what we have achieved for patients, he said, noting the difficulty in developing and making these therapies. He also highlighted that with over 1,000 regenerative therapies in development, problems will eventually be ironed out and cell and gene therapies will make the widespread impact intended.

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FDA cell and gene therapy forecast 'unlikely' - Bioprocess Insider - BioProcess Insider

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy faster and better than how its currently done.

What we saw differently here is not just the obvious that theres such a outsized level of demand for the amount of supply but we also saw the need to create an entire ecosystem for gene therapy players, Alex Karnal, partner and managing director at Deerfield, told Endpoints News. This is the first time theyre gonna have a place where they can call home.

Just how big is the demand? Days ago John Chiminski, whos leading Catalent in bulking up its own gene therapy unit, told an Endpoints audience that the number of projects in the pipeline is expected to surge from 300 today to 1,100 by 2026 translating to a volume of 2.5 million to 4 million liters of viral vectors needed. Thats up from 300,000 liters now.

Deerfield is building its new Center for Breakthrough Medicines at a former GlaxoSmithKline campus at King of Prussia, PA, now run by The Discovery Labs. Spanning 680,000 square feet, the site will consist of somewhere between 75 to 100 suites spread around 26 interconnected buildings.

Starting from an old lab space with much of the equipment still intact means the center can hit the ground running, with the site expected to be partially functional by the end of this year and fully up and running in 2021. And doing so on the outskirts of Philadelphia where some of the earliest work in cell and gene therapy were done by pioneers such as Carl June and Jim Wilson on a sprawling 1.6 million square feet complex designed to other biotech startups should make it appealing to the 2,000 scientists, manufacturing experts, technicians and support staff Deerfield plans to recruit.

With Tony Khoury, a key consultant for AveXis, on board as a director and Paragon Bio founder Marco Chacn as chair at the Discovery Labs, Karnal feels confident about casting a wide net and training a whole cohort of cell and gene therapy specialists on site. In fact, Deerfield has seen considerable interest in the 24 hours theyve announced the project.

Which is good, because the King of Prussia site is only step 1. Deerfield is plotting three more across the US.

Its not just about expanding capacity or even having the first end-to-end production facility. According to Karnal, they will invest in optimizing the process of producing viral vectors from the most common AAV to lentivirus to both address the potency and yield.

The tragedy in the marketplace is that the purification processes are still in their infancy; were only getting yields that are 10 to 20% on average from a good run, he said. You start with 10 to the X viruses but then after you purify it you lose 70 to 80% of that batch, thats just thats like liquid gold being wasted.

The hope is to double the current numbers.

Most of the initial setup will be geared towards gene therapy one out of 26 buildings will be reserved for cell therapy but Karnal said they can keep it flexible for customers needs, regardless of company location, target tissues, or delivery methods. Each suite can produce around 8 to 12 batches every year, and companies will have the option to take one whole building for themselves. The total number of customers will depend on all those variables.

Generally speaking a batch is pretty consistently priced, whats not consistent is how many patients you can serve, he said.

A number of other companies, both drugmakers and contractors, are rushing to serve the same, ever-expanding patient pool. Novartis and Pfizer have committed $500 million and $600 million on their own production capabilities, respectively, and then theres the CDMOs like Catalent and Thermo Fisher, which have grown their gene therapy teams through billion-dollar acquisitions of Paragon and Brammer Bio. Biotechs big and small are jumping into the game; Pittsburgh-based Krystal Biotech has just broken ground on a second commercial facility in Findley Township near Ohio.

We want all the players in the marketplace to make it and be wildly successful because the reality of it is even with us and everybody that exists today, the demand far exceeds the supply still, Karnal said.

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Deerfield vaults to the top of cell and gene therapy CDMO game with $1.1B facility at Philadelphia's newest biopharma hub - Endpoints News

MIAMI--(BUSINESS WIRE)--Anemocyte, an innovative Italian company working in the field of cell and gene therapies, with special focus on plasmid production and non-viral gene modification approaches, attends Phacilitate Leaders World (Miami, 21-24 January 2020), a leading event for companies, professionals and investors working in the Advanced Therapy sector.Phacilitate Leaders World is an opportunity to take stock of this sector, which is in constant evolution, states Marco Ferrari, CEO of Anemocyte. We need to anticipate market demands and offer innovative, effective solutions and strategies".Anemocyte is a key player and the first ever Biotech Manufacturing Organization (BMO) operating in the Life Science sector: Anemocyte helps CGT developers to articulate initial ideas, perform clinical trials and engage in commercial production. The BMO also develops technological platform strategies for innovative R&D, HQ and GMP processes.

PlasmidsAnemocyte is the leading Italian producer of gene therapy plasmids. The brand-new Plasmid Manufacturing Unit dedicated to producing plasmids for viral vectors is equipped with state-of-the-art laboratories and facilities. The company improved the production capacity (tripled the output since 2018): "In a market where production wait times are extremely long, Anemocyte is able to respond to requests quickly and with the highest quality standards, states Stefano Baila, Director of Operations and Business Development at Anemocyte. Anemocyte is a dynamic market player equipped with cutting-edge technologies and over ten years of expertise producing recombinant proteins; experience that it now exploits to produce plasmids our core business. We are able to intercept market needs and offer punctual, effective and qualitatively competitive results.

Non-viral: excellence in genetic modificationFollowing a strategic agreement with MaxCyte. Inc., Anemocyte is now a centre of excellence for electroporation technology and can support non-viral gene modification projects requiring both process development and GMP production.The ability to modify cells genetically has exponentially increased the clinical use of cell-based medicines. Non-viral gene modification is an emerging trend in the delivery of nucleic acids to cells thanks to its reliability, safety and affordability. Electroporation technology is at the forefront of non-viral gene transfer for ex-vivo cell modifications.The construction of a global non-viral gene transfer hub will see product developers exploit Anemocytes experience and MaxCytes technology.

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Anemocyte Brings Italian Excellence in the Cell and Gene Therapy Sector to Phacilitate Leaders World 2020 in Miami - Business Wire

REDWOOD CITY, Calif., Jan. 28, 2020 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today announced the presentation of 24-week data from the second cohort of patients (n=6; 2 x 1011 vg/eye) as well as an update from the first cohort of patients (n=6; 6 x 1011 vg/eye) in the OPTIC Phase1 clinical trial of ADVM-022 intravitreal gene therapy in wet AMD at the Angiogenesis, Exudation, and Degeneration 2020 Meeting.

Adverum plans to issue a press release relating to the presentation and post the presentation on Adverums website at http://www.adverum.com in the Investors section under the Events and Presentations page at the beginning of the data presentation at Angiogenesis.

KOL Event Details:In addition, Adverum will host an event with expert retinal specialists to discuss the OPTIC data presented at Angiogenesis and the potential opportunity for ADVM-022. The discussion will be held on Sunday, February 9, 2020 beginning at 10:00 am EST. The event will be webcast live from Adverums website at http://www.adverum.com in the Investors section under the Events and Presentations page. A replay of the webcast will be archived and available for replay following the event.

About Adverum BiotechnologiesAdverum Biotechnologies (Nasdaq: ADVM) is a clinical-stage gene therapy company targeting unmet medical needs in serious ocular and rare diseases. Adverum is evaluating its novel gene therapy candidate, ADVM-022, as a one-time, intravitreal injection for the treatment of its lead indication, wet age-related macular degeneration. For more information, please visit http://www.adverum.com.

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Adverum Biotechnologies to Present Additional Data from the OPTIC Phase 1 Trial with ADVM-022 Intravitreal Gene Therapy in Wet AMD at the...

The FDA has published their industry guidance on the topic of long term follow up (LTFU) post gene therapy. Please see a link to the full guidance below. In summary, they are stipulating that a good proportion of these therapies will require LTFU of up to fifteen years.

This presents significant challenge to manufacturers given that patients will, in that stretch of time, have multiple changes to their care settings and life circumstances. In addition to this, and if these therapies live up to their promise, treated patients will potentially become chronically well and keen to disengage from their previous disease state and their healthcare professionals.

This is a significant challenge but achievable! We have already shared our experienced thinking on this topic and a link to our article is provided below. Our recommendations focus on putting the patient at the centre of a solution and wrapping a, digitally enabled, registry solution around thoughtful patient and healthcare professional engagement.

Please read our full thinking below:

http://edition.pagesuite-professional.co.uk/html5/reader/production/default.aspx?pubname=&edid=5cf08b2f-f3d9-435a-8255-ef07542eb9a3&pnum=31

https://www.fda.gov/media/113768/download

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OPEN Health's response to the FDA's guidance on long term follow up post gene therapy - PMLiVE

Krystal Biotech and Foghorn Therapeutics are beginning 2020 with significant expansion projects.

Pittsburgh-based Krystal, a gene therapy company developing medicines to treat rare diseases, broke ground this week on its second commercial gene therapy facility in Findlay Township, Penn. The new 100,000 square-foot facility, called ASTRA, will have the capacity to produce commercial gene therapy medicines to treat patients suffering from debilitating rare diseases. The facility is being designed as a state-of-the-art cGMP manufacturing facility that will allow the in-house incorporation of raw material preparation, excipient manufacturing, testing, packaging, labeling and distribution, fully-integrating all components of the supply chain from starting materials to patient experience, the company said in an announcement.

Krystal said the ASTRA facility will initially be used as a commercial back up facility for B-VEC, previously known as KB103, which is being developed for the treatment of dystrophic epidermolysis bullosa, a rare and devastating skin disorder, and expand to produce investigational and commercial material for our pipeline products. When the site is fully operational, it will have the potential to create around 200 new jobs when at full capacity.

Krish S. Krishnan, chairman and chief executive officer atKrystal, said biologics manufacturing is a complex science and is a competitive advantage forKrystal Biotech.

We are very excited to announce the creation of ASTRA which will be a global resource for production of gene therapies with the potential to bring new treatments to rare disease patients around the world. The success with our first GMP facility, Ancoris, gives us the experience and confidence to have ASTRA be functionally ready in time for the anticipated launch of our lead therapeutic, B-VEC, Krishnan said in a statement.

In Massachusetts, Foghorn Therapeutics, launched by Flagship Pioneering in 2018, is undertaking an expansion of its headquarters, nearly tripling the space. In a brief report, the Boston Business Journal said the Foghorn headquarters will include biology labs, chemistry labs, open-space offices, huddle rooms, conference rooms and an employee cafe. The additional space provides the company with significant room for growth, but Foghorn has no specific timeline for that growth, a company spokesperson told the Journal.

"There is no specific timeframe for filling the new office to capacity but Foghorn has grown rapidly since its inception and we are regularly adding talented individuals to help us achieve our mission, the spokesperson said, according to the Journal.

Foghorns goal is to develop drugs that work in the chromatin regulatory system, which orchestrates the movement of molecules that turn genes on and off, the company said. Using its Gene Traffic Control platform, Foghorn is focusing on sarcoma, as well as prostate cancer and non-small cell lung cancer. The chromatin process has possible applications in autism, schizophrenia and some rare neurological diseases. The company is currently pre-clinical but said it is rapidly advancing more than 10 programs.

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Krystal, Foghorn Undertake Expansions that Will Lead to New Hires - BioSpace

LONGMONT, Colo. A few months ago, 2-year-old Maisie Forest was finally able to sit up on her own for the first time. Her development has been delayed by a rare genetic disorder called Spinal Muscular Atrophy, but last August, she received a groundbreaking treatment for the condition.

"It's a miracle drug," said Maisie's mother, Ciji Green. "It's not the cure, but we're talking about a disease that had no treatments four years ago," she added.

The "miracle drug" Green is referring to Zolgensma, a gene therapy for Spinal Muscular Atrophy made by Novartis-owned AveXis. On Tuesday, AveXis cut the ribbon on a new facility in Longmont where it will soon produce Zolgensma.

"Zolgensma is this first product weve had approved by the FDA for the treatment of kids with Spinal Muscular Atrophy," said AveXis President David Lennon.

The FDA approval came last May, just in time for Maisie to receive the treatment. But her mother still had to fight for the insurance company to pay for it. At $2.1 million per dose, Zolgensma is the most expensive drug or treatment ever made. Lennon said Novartis has invested half a billion dollars in the production of Zolgensma.

For Green, the cost is well worth the changes she's already seen in her daughter. Speaking to employees at the AveXis ribbon cutting, she called them heroes.

"To all of you it may just be a treatment, but to my family and so many others, its so much more," said Green.

AveXis says the same platform they used to produce Zolgensma might be applied to other therapies for other diseases in the future. The company is looking at developing treatments for Rett Syndrome, Friedreichs Ataxia, and an inherited form of Amyotrophic Lateral Sclerosis, or ALS.

"There are actually thousands of these kinds of diseases. Usually they impact a few hundred kids or adults every year, but altogether there are potentially millions of patients who have genetic diseases around the world," said Lennon.

Lennon said AveXis chose Longmont for its production facility in part because of the infrastructure already in place. The building at 4000 Nelson Rd. was previously occupied by pharmaceutical companies AstraZeneca and Amgen. He said the available talent was also a factor.

AveXis retained most of the employees from the previous tenants. With new hires, the Longmont facility currently has a staff of around 300 employees and expects to grow to 400 by the end of 2020.

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Gene therapy company begins operations in Longmont - The Denver Channel

Ultragenyx Pharmaceutical saw its shares jump around 27% in trading Friday after announcing positive top-line data out of its gene therapy trial.

Its a small number, just three patients that form part of a third cohort for the phase 1/2 study, as well as another small test but a longer-term look from the second cohort.

In cohort three testing the biotechs drug DTX301, an adeno-associated virus gene therapy for the treatment of ornithine transcarbamylase (OTC) deficiency, there were two confirmed female responders as well a third potential male responder who requires longer-term follow-up to confirm response status.

The Art of Recognizing Clinical Supply Risk Factors and Applying Proactive Measures to Avoid Study Delays and Disruptions

No two studies are the same and each clinical supply project carries unique risks. But what characteristics are most likely to raise a flag that issues are ahead? Are there certain types of clinical sponsors and studies that are at greater risk of experiencing supply challenges? And how do clinical sponsors know what is important to focus on and what is not? Join us for this webinar as we attempt to answer these questions.

Meanwhile, in cohort two, one female patient saw a new response after a year. The biotech added that the two previously disclosed responders in cohort one and two also remain clinically and metabolically stable at 104 and 78 weeks, respectively. Across all nine patients dosed in the study, up to six patients have demonstrated a response, it said in a statement.

RELATED: BIO: In conversation with Emil Kakkis, Ultragenyx CEO

OTC deficiency is a rare X-linked genetic disorder characterized by complete or partial lack of the enzyme OTC. Excess ammonia, which is a neurotoxin, travels to the central nervous system through the blood,

According to the National Organization for Rare Disorders, the severity and age of onset of OTC deficiency vary from person to person, even within the same family. A severe form of the disorder affects some infants, typically males, shortly after birth (neonatal period). A milder form of the disorder affects some children later in infancy. Both males and females may develop symptoms of OTC deficiency during childhood. Most carrier females are healthy, but may be prone to severe headaches following protein intake.

Analysts at Jefferies said the data looked better than expected and could be a positive spark to help turn the stock heading into 2020 events. It certainly did in the immediate term, with the biotechs shares up by 27% in mid-morning trading Friday.

We are encouraged to see a more uniform response at the higher doses including three female responders. To date, three patients in the study have discontinued alternate pathway medication and liberalized their diets while remaining clinically and metabolically stable, said Eric Crombez, M.D., chief medical officer of the Ultragenyx Gene Therapy development unit.

We are moving to prophylactic steroid use in the next cohort as we believe this could further enhance the level and consistency of expression that we have demonstrated so far.

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Ultragenyx shares jump on 'better than expected' gene therapy data - FierceBiotech

BOSTON Helen Obando, a shy slip of a girl, lay curled in a hospital bed in June waiting for a bag of stem cells from her bone marrow, modified by gene therapy, to start dripping into her chest.

The hope was that the treatment would cure her of sickle cell disease, an inherited blood disorder that can cause excruciating pain, organ damage and early death.

Helen, who at 16 was the youngest person ever to undergo the therapy, was sound asleep for the big moment.

It was a critical moment in medical science.

For more than a half-century, scientists have known the cause of sickle cell disease: A single mutation in a gene turns red blood cells into rigid crescent or sickle shapes instead of soft discs. These misshapen cells get stuck in veins and arteries, blocking the flow of blood that carries life-giving oxygen to the body and causing the diseases horrifying hallmark: episodes of agony that begin in babyhood.

Millions of people globally, a vast majority of them Africans, suffer from sickle cell disease. Researchers have worked for decades on improving treatment and finding a cure, but experts said the effort has been hindered by chronic underfunding, in part because most of the estimated 100,000 people in the United States who have the disease are African American, often poor or of modest means.

The disease also affects people with southern European, Middle Eastern or Asian backgrounds, or those who are Hispanic, like Helen.

This is the story of two quests for a sickle cell cure one by the Obando family and one by a determined scientist at Boston Childrens Hospital, Dr. Stuart Orkin, 73, who has labored against the disease since he was a medical resident in the 1970s.

Like many others affected by sickle cell, the Obando family faced a double whammy: not one but two children with the disease, Helen and her older sister, Haylee Obando. They lived with one hope for a cure, a dangerous and sometimes fatal bone marrow transplant usually reserved for those with a healthy sibling as a match. But then they heard about a potential breakthrough: a complex procedure to flip a genetic switch so the body produces healthy blood.

Scientists have been experimenting with gene therapy for two decades, with mixed success. And it will be years before they know if this new procedure is effective in the long term. But if it is, sickle cell disease could be the first common genetic disorder to be cured by manipulating human DNA.

Four weeks after the infusion of stem cells, Helen was strong enough to be discharged. At home, in Lawrence, Massachusetts, on a sofa with her mother by her side, she put a hand over her eyes and started to sob. She and her family wondered: Would it work? Was her suffering really over?

A Familys Nightmare

Sheila Cintron, 35, and Byron Obando, 40, met when she was in the eighth grade and he was a high school senior. They fell in love. Haylee, their first child, was born in 2001, when Cintron was 17.

When a newborn screening test showed that Haylee had the disease, her father asked, Whats sickle cell?

They soon found out.

As the family gathered for her first birthday party, Haylee started screaming inconsolably. They rushed her to the hospital. It was the first of many pain crises.

Doctors warned the parents that if they had another baby, the odds were 1 in 4 that the child would have sickle cell, too. But they decided to take the chance.

Less than two years later, Helen was born. As bad as Haylees disease was, Helens was much worse. When she was 9 months old, a severe blockage of blood flow in her pelvis destroyed bone. At age 2, her spleen, which helps fight bacterial infections, became dangerously enlarged because of blocked blood flow. Doctors surgically removed the organ.

After Helen was born, her parents decided not to have any more children. But four years later, Cintron discovered she was pregnant again.

But they were lucky. Their third child, Ryan Obando, did not inherit the sickle cell mutation.

As Ryan grew up, Helens health worsened. When he was 9, Helens doctors suggested a drastic solution: If Ryan was a match for her, he might be able to cure her by giving her some of his bone marrow, though there would also be major risks for her, including death from severe infections or serious damage to organs if his immune system attacked her body.

As it turned out, Ryan matched not Helen but Haylee.

The transplant succeeded, but her parents asked themselves how they could stand by while one daughter was cured and the sicker one continued to suffer.

There was only one way to get a sibling donor for Helen: have another baby. In 2017, the couple embarked on another grueling medical journey.

Obando had a vasectomy, so doctors had to surgically extract his sperm from his testicles. Cintron had 75 eggs removed from her ovaries and fertilized with her husbands sperm. The result was more than 30 embryos.

Not a single embryo was both free of the sickle cell gene and a match for Helen.

So the family decided to move to Mesa, Arizona, from Lawrence, where the cold, which set off pain crises, kept Helen indoors all winter. The family had already sold their house when they heard that doctors at Boston Childrens were working on sickle cell gene therapy.

Cintron approached Dr. Erica Esrick, a principal investigator for the trial. But the trial wasnt yet open to children.

Figuring Out the Science

Nothing had prepared Orkin for the suffering he witnessed in his 30s as a medical resident in the pediatric hematology ward at Boston Childrens. It was the 1970s, and the beds were filled with children who had sickle cell crying in pain.

Orkin knew there was a solution to the puzzle of sickle cell, at least in theory: Fetuses make hemoglobin the oxygen-carrying molecules in blood cells with a different gene. Blood cells filled with fetal hemoglobin do not sickle. But the fetal gene is turned off after a baby is born, and an adult hemoglobin gene takes over. If the adult gene is mutated, red cells sickle.

Researchers had to figure out how to switch hemoglobin production to the fetal form. No one knew how to do that.

Orkin needed ideas. Supported by the National Institutes of Health and Howard Hughes Medical Institute, he kept looking.

The breakthrough came in 2008. The cost of gene sequencing was plummeting, and scientists were finding millions of genetic signposts on human DNA, allowing them to home in on small genetic differences among individuals. Researchers started doing large-scale DNA scans of populations, looking for tiny but significant changes in genes. They asked: Was there a molecular switch that flipped cells from making fetal to adult hemoglobin? And if there was, could the switch be flipped back?

They found a promising lead: an unprepossessing gene called BCL11A.

In a lab experiment, researchers blocked this gene and discovered that the blood cells in petri dishes started making fetal instead of adult hemoglobin.

Next they tried blocking the gene in mice genetically engineered to have human hemoglobin and sickle cell disease. Again, it worked.

Patients came next, in the gene therapy trial at Boston Childrens that began in 2018.

The trial run by Dr. David Williams, an expert in the biology of blood-forming stem cells at Boston Childrens, and Esrick has a straightforward goal: Were going to reeducate the blood cells and make them think they are still in the fetus, Williams said.

Doctors gave adult patients a drug that loosened stem cells immature cells that can turn into red blood cells from the bone marrow, their normal home, so they floated free in the bloodstream. Then they extracted those stem cells from whole blood drawn from the patient.

The researchers used a disabled genetically engineered AIDS virus to carry information into the stem cells, flipping on the fetal hemoglobin gene and turning off the adult gene. Then they infused the treated stem cells into patients veins. From there, the treated cells migrated into the patients bone marrow, where they began making healthy blood cells.

With the success in adults, the Food and Drug Administration said Boston Childrens could move on to teenagers.

When her mother told her about the gene therapy trial, Helen was frightened. But the more she thought about it, the more she was ready to take the risk.

In the months after the gene therapy infusion at Boston Childrens, her symptoms disappeared.

Helen was scheduled for her six-month checkup Dec. 16. Helens total hemoglobin level was so high it was nearly normal a level she had never before achieved, even with blood transfusions. She had no signs of sickle cell disease.

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At 16, shes a pioneer in the fight to cure sickle cell disease at Boston Childrens - Boston.com

In 2018, Generation Bio broke cover with a $25 million series A, swiftly followed by a meatier $100 million second funding round.

Now, just before the J.P. Morgan Healthcare Conference, it has grabbed its biggest yet, a $110 million series C, as it looks to go all in for IND-enabling studies for its leading programs: liver-targeted therapies for hemophilia A and phenylketonuria.

In addition to the liver, Generation Bio is also working on potential treatments for diseases of skeletal muscle and the eye.

The Art of Recognizing Clinical Supply Risk Factors and Applying Proactive Measures to Avoid Study Delays and Disruptions

No two studies are the same and each clinical supply project carries unique risks. But what characteristics are most likely to raise a flag that issues are ahead? Are there certain types of clinical sponsors and studies that are at greater risk of experiencing supply challenges? And how do clinical sponsors know what is important to focus on and what is not? Join us for this webinar as we attempt to answer these questions.

The early-stage Cambridge, Massachusetts-based biotech saw its major round led by T. Rowe Price with help from Farallon, Wellington Management and existing investors Atlas Venture, Fidelity, Invus, Casdin, Deerfield, Foresite Capital and an entity associated with SVB Leerink.

Generation Bios platform is geared up to be gene therapy 2.0 and is designed to develop re-dosable, long-lasting, scalable gene therapies for severe diseases.

The company is developing gene therapies under the GeneWave banner that use closed-ended DNA rather than viruses to deliver therapeutic proteins, which could sidestep safety issues such as immune reactions

Our vision is to develop re-dosable, long-lasting gene therapies manufactured at a scale that leaves no patient or family behind, said Geoff McDonough, M.D., president and CEO of Generation Bio.

Since our founding we have had the support of high-quality investors who share our excitement about the potential of our platform to lead a new generation of gene therapy and about advancing our lead programs toward the clinic.

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Generation Bio grabs a $110M round to ramp up work on next-gen gene therapies - FierceBiotech