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.

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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

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

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

XconomyBoston

Solid Biosciences is slashing its workforce, including two top executives, in order to devote the companys remaining resources to its experimental gene therapy for Duchenne muscular dystrophy.

The corporate restructuring announced Thursday comes two months after the FDA placed a hold on the study after safety problems emerged that were linked to the gene therapy, SGT-001. Cambridge, MA-based Solid Bio (NASDAQ: SLDB) says going forward it will focus on how to address the clinical hold and resume testing. With the corporate changes, Solid Bio says it has enough cash to last into next year. At the end of the third quarter of 2019, the company reported cash and other holdings totaling $105.7 million.

Following the announcement, Solid Bios stock price slid more than 17 percent to $3.66 per share in pre-market trading.

Solid Bio has been developing SGT-001 as a way to potentially address the genetic defect underpinning Duchenne. Patients who have the inherited disease dont make enough of the muscle protein dystrophin. The Solid Bio gene therapy uses an engineered virus to deliver genetic material intended to restore dystrophin production. But the company had also previously disclosed theres a chance that the dosing requirements of the gene therapy could increase the risk of side effects related to the virus used in the treatment.

The complications reported in the November clinical hold included an immune system reaction, a decrease in red blood cells, kidney injury, and blood circulation difficulties. Those problems are similar to ones cited in the FDAs 2018 clinical hold on tests of SGT-001. Months later, the agency allowed the study to resume but with additional safety measures.

Solid Bios board approved the corporate restructuring on Tuesday, according to a securities filing. In the first quarter of this year, the company expects to record a $2.1 million charge related to the layoffs, which will cut about one third of its workforce. Last years annual report states that the company had 111 full-time employees as of Dec. 31, 2018. Those leaving Solid Bio include Alvaro Amorrortu, the companys chief operating officer, and Jorge Quiroz, its chief medical officer. But both will continue to advise Solid Bio under consulting agreements.

Photo by Flickr user reynermedia via a Creative Commons license

Frank Vinluan is an Xconomy editor based in Research Triangle Park. You can reach him at fvinluan [[at]] xconomy.com.

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Solid Bio Restructures to Get Halted Gene Therapy Study Back on Track - Xconomy

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