Category Archives: Gene therapy

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

DUBLIN--(BUSINESS WIRE)--The "Global Gene Therapy Market Outlook and Projections, 2019-2027" report has been added to ResearchAndMarkets.com's offering.

Incidences of cancer are increasing, and the local governing bodies are taking required initiatives to handle the problem, by development of new healing and preventive gene therapeutics.

According to the World Bank, more than 2,300 clinical trials on gene therapy were carried out in 2017. This led to attainment of higher information about the potential applications and working of gene therapies. Besides, gene therapy is becoming a significant sector in bioscience industry research and can be produced on a commercial-scale, which is projected to further expand its application range. Yescarta - axicabtagene ciloleucel are the most recently approved gene therapeutics available in the global market that treats large B-cell lymphoma.

The global gene therapy market is estimated to grow on the back of rising healthcare expenditure with increasing demand for efficient disease treating practices coupled with growing technological developments and discoveries. The World Bank reported a rise in the global current health expenditure (% GDP) from 9.453% in 2011 to 10.023% in 2016.

Increasing incidences of chronic oncogenic diseases such as cancer with an estimated new cases of 18.1 million in 2018 as per the International Agency for Research on Cancer (IARC), is anticipated to display a rapid growth in application of gene therapy technologies in the upcoming years. Additionally, increasing application of gene therapy products for the treatment of various cardiovascular and blood disorders is also expected to back the rampant growth in the upcoming years.

Moreover, government initiatives to eliminate chronic diseases is anticipated to aid the growth in upcoming years. For instance, the World Health Organization (WHO) launched an initiative to eliminate hepatitis completely by 2023. Furthermore, experiments concerning gene therapy technologies in order to explore the benefits for various medical applications is another factor expected to propel the market growth.

Rising geriatric population across the globe holds immense opportunities for gene therapy products in the upcoming years. According to the World Bank, the population aged 65 and above, increased from 7.64% in 2010 to 8.93% of the global population in 2018. Moreover, change in climatic conditions and increase in sedentary lifestyles has led to drastic demographic changes in developed and developing countries, resulting in growing number of disease cases associated with aging. This aspect is attributed to contribute considerably to the market growth and thereby is expected to increase the adoption of gene therapy products across the globe.

The patient pool suffering from diabetes is expanding with growing aging population. The International Diabetes Federation reported that approximately 425 million adults (20-79 years) were living with diabetes in 2017, which is estimated to increase by 2045 to 629 million. Application of gene therapy in patients suffering with diabetes, wherein replacement of a single gene is expected to restore the function of beta cells, which secrete insulin and regulate the blood glucose level of the body is also envisaged to boost the market significantly, during the forthcoming decade.

Key Topics Covered

Introduction

Market Ecosystem

Global Gene Therapy Market Outlook

Industry Analysis

Market Dynamics

Company Profiles of Top 5 Players

For more information about this report visit https://www.researchandmarkets.com/r/ptfbs8

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Global Gene Therapy Market Outlook and Projections, 2019-2027, Featuring Profiles of the Top 5 Players: Novartis, Amgen, Orchard Therapeutics, Kite...

INDIANAPOLIS (WTHR) Four-month-old Anthony Schmitz has spent his entire life on a ventilator in intensive care at Riley Hospital for Children. But Wednesday he received a gene therapy infusion that might save and change his life.

Zolgensma is a prescription gene therapy that costs $2.1 million for the one-time dose.

The drug has proven effective in treating children with spinal muscular atrophy (SMA) under the age of two.

Indiana Medicaid first rejected the treatment for Schmitz because he was on a ventilator but gave approval on appeal.

"Early diagnosis is key and don't give up, said Louise Johnson, Schmitzs mother. It's not a death sentence, so just keep fighting. It's a baby. Keep fighting."

"I think this was really a group decision that said, 'Yeah, medically this made sense for this child. So, the cost kind of fell by the wayside, said Dr. Larry Walsh, Riley Children's Health Pediatric Neurologist.

Zolgensma replaces the function of the missing or nonworking SMN1 gene with a new, working copy of a human SMN gene.

Without treatment, Anthony's life expectancy was about two years.

"No mom wants to bury their child, said Johnson, who is from Evansville. So, I just want to see him grow up with his brothers."

Schmitz received the treatment Wednesday morning.

The infusion took just over an hour. But it will be weeks, if not months, before doctors know if the medicine is working for him.

"Even if we can make some smaller difference where we do help his respiratory function, where he doesn't need to be on a ventilator - things like that - that would be a tremendous win I think for he and his family, said Dr. Walsh.

"The future is unknown, so I'm still nervous, said Johnson. But I'm more excited. I can't wait."

Indiana adopted newborn screening for SMA in 2018.

Schmitz is now part of a handful of babies to receive gene therapy infusion at Riley for the rare, progressive genetic disease.

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Local infant receives $2.1 million gene therapy infusion after initial Medicaid rejection - WTHR

In the presence of Federal Councillor Alain Berset and other distinguished guests, Novartis inaugurated a new manufacturing facility for cell and gene therapies at Stein, Switzerland on November 28th.

Our site in Stein is vital for new launches of solid and liquid drugs, said Steffen Lang, Global Head of Novartis Technical Operations and member of the Novartis Executive Committee. "The construction of the new manufacturing facility is another investment in the production of breakthrough cell-based therapies that can potentially change the lives of patients.

In addition to manufacturing areas for novel CAR-T cell therapies, the new building also hosts the production of innovative, difficult-to-manufacture solid dosage forms such as tablets and capsules. In September 2019, the first clinical production of a cell and gene therapy batchwas successfully completed.

Unlike conventional drug production, cell and gene therapy asks for the manufacture of a personal dose for each patient. For this purpose, patients who have already undergone various therapies have a small amount of their own blood cells taken, which are then sent to Stein. "Here we enrich part of the white blood cells, the T cells, and genetically modify them so that they can recognize and fight the cancer cells in the patient's blood," says Dorothea Ledergerber, project manager of the Stein plant for cell and gene therapies. The altered cells are then sent back to hospital and administered to the patient by infusion. Novartis is doing pioneering work here: "We have the unique opportunity to offer patients for whom there have been no other therapeutic options a totally new perspective by using these novel CAR-T cell therapies," says Dorothea Ledergerber.

Read more in German

This release wasfirst publishedby Novartis.

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Novartis opens facility for innovative cell and gene therapies in Switzerland - Science Business

The U.S. Food and Drug Administration (FDA) has lifted the clinical hold on a Phase 1/2 trial designed to test the gene therapy candidate PR001 in patients with type 2 Gaucher disease.

The team atPrevail Therapeutics expects to initiate patient dosing in the first half of 2020.

Prevail was awaiting a decision by the FDA to test higher doses of PR001 than initially planned. This request was supported by preclinical evidence of greater efficacy with no safety issues at such dosages. The investigational new drug (IND) application of PR001, an essential step to opening a clinical study, had first been accepted in June 2019.

PR001 uses a modified, harmless version of an adeno-associated virus (AAV9) to deliver a fully working version of the GBA1 gene to nerve cells. Mutations in this gene cause Gaucher disease by producing a defective enzyme called beta-glucocerebrosidase, which leads to the accumulation of fatty molecules inside cells.

In type 2 Gaucher disease, called acute infantile neuronopathic Gaucher disease, these toxic fatty molecules build up in the patients brain from early infancy, resulting in neurological symptoms.

By restoring production of normal beta-glucocerebrosidase in affected brain cells, a single dose of PR001 is intended to ease Gaucher symptoms and modify disease course.

Work in mice and monkeys showed that PR001 now being developed in collaboration with Lonza Pharma & Biotech is well-tolerated, leads to the production of a functional enzyme in nerve cells, reduces the accumulation of fatty molecules, and improves motor function.

We are pleased to now have an active IND for PR001 for the nGD [neuronopathic Gaucher disease] indication and look forward to initiating a Phase 1/2 clinical trial in the first half of 2020, Asa Abeliovich, MD, PhD, Prevails founder and CEO, said in a press release.

Patients with nGD have the most severe form of Gaucher disease and a significant unmet need for therapies to treat their neurological manifestations. We believe PR001 has tremendous potential, he added.

In addition, the company plans to initiate another Phase 1/2 study in people with type 3 Gaucher later this year. Patients with this type also experience neurological symptoms, but they are milder and progress slower than those seen in patients with type 2 Gaucher.

Prevail is also developing PR001 for GBA1 mutation-related Parkinsons disease. Mutations in the GBA1 gene are one of the most common genetic risk factors for Parkinsons. A Phase 1/2 clinical trial (NCT04127578), called PROPEL, is currently recruiting participants with Parkinsons to test PR001 administered directly into the cerebrospinal fluid (the liquid surrounding the brain and spinal cord).

With over three years of experience in the medical communications business, Catarina holds a BSc. in Biomedical Sciences and a MSc. in Neurosciences. Apart from writing, she has been involved in patient-oriented translational and clinical research.

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Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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Type 2 Gaucher Trial of PR001 Gene Therapy Has Hold Lifted by FDA - Gaucher Disease News

Cellular engineering promises new treatments for cancer and other maladies. But most manufacturing processes propel the cost of these so-called living drugs into the stratosphere, far beyond reach of most people who need them.

A technology patented at the University of California, Riverside, and recently licensed to startup Basilard BioTech could bring these prices back down to earth.

The technology, developed by Masa Rao, an associate professor of mechanical engineering in the Marlon and Rosemary Bourns College of Engineering, minimizes damage to the cell in the manufacturing process. This enables both high gene delivery efficiency and cellular viability, a feat that most other approaches cannot match.

Basilard spun out of Raos laboratory earlier this year. The company has obtained an exclusive license to commercialize the technology, which they have branded SoloPore. Basilard is seeking to develop it as a disruptive new platform for engineering ex vivo cell and gene therapies for cancer specifically, as well as genetic disorders and degenerative diseases more broadly.

Basilards SoloPore technology is a differentiated solution that provides greater scalability, safety, efficiency, and versatility than prevailing gene delivery methods, said Basilard CEO Brynley Lee. This will allow us to reduce manufacturing cost, and therefore, bring these revolutionary therapies to more of those in need.

Basilard is raising seed capital and working to build a commercial prototype. The young company is the first biotech instrumentation company to emerge from UC Riversides EPIC entrepreneurship incubator, which guides innovators through the commercialization and entrepreneurial process and helps connect them with investors.

Within the span of less than a year, weve gone from a purely academic effort to the formation of a startup thats on the cusp securing its first venture capital funding, Rao said. UC Riversides Office of Technology Partnerships has been instrumental in this rapid ascent.

Weve worked hard for the past three years to accelerate technology translation and commercialization with entrepreneurial programs that have mentored more than 220 entrepreneurs and 120 startups in the Inland Empire since October 2016, said Rosibel Ochoa, associate vice chancellor for technology partnerships. Basilards quick rise is a sign that we are building a healthy entrepreneurial ecosystem that supports the growth of startups in our region.

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Putting gene therapy in reach - University of California

January 9, 2020, London, UK and Philadelphia, USA - Ori Biotech Ltd (Ori), an innovator in Cell and Gene Therapy (CGT) manufacturing, today announced that they successfully closed a $9.4M (7M) seed round which will be used to bring their innovative manufacturing platform to market. The Ori platform will deliver scalable solutions to flexibly address the critical clinical and commercial manufacturing needs of CGT developers.

Founded by Dr. Farlan Veraitch and Prof. Chris Mason in 2015, Ori has designed a bespoke platform to specifically address the unique requirements of the new generation of personalised, living medicines. The investor syndicate is comprised of some of the UKs leading venture investors including Amadeus Capital Partners, Delin Ventures, Kindred Capital and a London-based family office, alongside a group of angel investors who have supported the company since inception.

Jason C. Foster, newly appointed CEO of Ori Biotech said: The successful financing underscores the potential of the Ori platform to fully automate cell and gene therapy manufacturing to increase throughput, improve quality and decrease costs. We look forward to collaborating with best-in-class suppliers, service providers and therapeutics developers to create next generation manufacturing solutions. We appreciate the support from our investors, and I am honored to join a company that has the potential to positively impact millions of lives by enabling patient access to these lifesaving treatments.

Hundreds of clinical trials and a few recently marketed products have shown the revolutionary potential of CGTs. But this potential will never be realised unless we can remove the current bottleneck around scalable manufacturing. Ori Biotech has developed an innovative platform technology to facilitate scalable manufacturing that could eventually enable millions of patients to get access to the next generation of personalised medicines, commented Dr Alan Barge, ex-Head of Oncology at AstraZeneca, Venture Partner at Delin Ventures and Non-Executive Director of Ori Biotech.

Dr Farlan Veraitch, Co-Founder and Chief Scientific Officer of Ori Biotech added, The challenges of providing high throughput, high quality and cost-effective CGT manufacturing are well documented in the industry and in publications by global regulatory authorities like the US FDA. By pioneering a completely novel hardware and software platform approach, we can help the CGT industry accelerate the delivery of these transformative therapies to patients in need.

Ori Biotech at JP Morgan Healthcare Conference, San Francisco

The Ori Biotech team will be at the 38th Annual J.P. Morgan Healthcare Conference on 13-16 January 2020 in San Francisco, California.

Please get in touch if you would like to set up a meeting, details below

About Ori Biotech

Ori Biotech is a London- and Philadelphia-based CGT manufacturing technology company. Ori has developed a proprietary, flexible manufacturing platform that closes, automates and standardises manufacturing allowing therapeutics developers to further develop and bring their products from pre-clinical process development to commercial scale manufacturing.

The mission of the Ori platform is to fully automate CGT manufacturing to increase throughput, improve quality and decrease costs in order to enable patient access to this new generation of lifesaving treatments. Founded by Dr. Farlan Veraitch and Prof. Chris Mason in 2015, the Company has brought together a seasoned Board and executive management team with over 80 years of pharmaceutical, cell therapy and venture building experience including CEO Jason C. Foster (Indivior) and CBO Jason Jones (Miltenyi Biotec) alongside industry-leading expert advisors like Bruce Levine and Anthony Davies.

For more information, contact:

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Ori Biotech announces a $9.4M seed round to advance innovation in Cell and Gene Therapy manufacturing - BioSpace

DetailsCategory: DNA RNA and CellsPublished on Sunday, 12 January 2020 11:53Hits: 94

- The round was led by Vida Ventures, a next generation life science venture firm with industry-leading experience in cell and gene therapy

- The financing will be used to expand clinical & manufacturing development to deliver clinical data for patients with multiple solid tumor types

SOUTH SAN FRANCISCO, CA, USA I January 10, 2020 I PACT Pharma, in pursuit of its vision to eradicate solid tumors using transformational, first-in-class fully personalized NeoTCR-T cell therapies, today announced that it has closed an oversubscribed $75 million Series C financing. This round, led by Vida Ventures, a next generation life science venture firm with industry-leading experience in the cell and gene therapy, also included current investors of PACT.

Combined with proceeds from previous financings, PACT will use the Series C proceeds to expand the scope of its clinical plan to investigate NeoTCR-T cell products targeting multiple neoantigens for a spectrum of solid tumor types. In addition to clinical expansion, PACT will open in 2020 a next-gen GMP manufacturing facility in South San Francisco to support the end-to-end production and supply chain for the engineering of personalized neoantigen-targeted autologous T cells. Under the direction of industry veteran Tim Moore, President and Chief Technology Officer, PACT will leverage the new in-house manufacturing facility to automate manufacturing and analytic processes to reduce cycle time and manufacturing costs.

"PACT has grown from company launch to opening its first-in-kind clinical trial in two years. Our progress has been exhilarating and the support from our existing investors has made that progress possible," said Alex Franzusoff, PhD, Chief Executive Officer of PACT Pharma. "As we look to the next stage of our development and expansion of our clinical programs, we are excited to have interest from a new group of prominent investors who both understand the potential of NeoTCR-T cell therapy and have direct experience in the space. Vida Ventures stood out as a partner of choice, given their depth of operational experience in research, clinical development and manufacturing in cell therapy as well as their proven ability to guide companies like Kite and Allogene across key stages of development.

As part of the Series C financing, Helen S. Kim, Managing Director at Vida Ventures, will join the Company's Board of Directors. Ms. Kim brings over 25 years of biotechnology leadership experience and serves on the boards of Assembly Biosciences, Applied Molecular Transport, A2 Biotherapeutics and Exicure, Inc.

"Our investment in PACT Pharma represents our goal to fund scientific advances by embracing cutting edge innovation with the potential to make a meaningful difference in the lives of patients," said Kim. "PACT has developed a pioneering platform of personalized designer T cells with the potential to target some of the most elusive solid cancers facing society today."

ABOUT PACT Pharma

PACT Pharma is an independent, privately funded clinical stage company, based inSouth San Francisco, California, developing transformational personalized neoTCR-T cell therapies for the eradication of solid tumors and is now enrolling patients in its first-in-human Phase 1 clinical studies at several key academic centers of the CIRM-funded Alpha Clinic network, inCalifornia.

PACT Pharma's distinguised co-founders,David Baltimore(Nobel Laureate),Antoni Ribas,Jim Heath,Terry RosenandJuan Jaen launched the company in early 2017. The company is backed by GV (formerly Google Ventures), Canaan, Casdin Capital, Droia, Foresite Capital, Invus Opportunities, Pontifax and Wu Capital and is supported by investment from AbbVie Ventures and Taiho Ventures. PACT Pharma's technology is designed to individually program tumor-exclusive targeting into each patient's own immune system cells to eradicate their own cancer. The process, which is currently in Phase 1 clinical testing, involves taking a biopsy of a person's cancer tissue to assess the tumor-exclusive mutations with predictive algorithms, then to biologically verify the optimal targets by capturing T cells from blood that already recognize the mutations. Using the T cell receptor information from the captured T cells, together with proprietary, cutting edge, (non-viral) precision genome engineering technologies, fresh patient T cells are edited in one step to craft tumor-specific neoTCR-P1 cells. These private designer T cells have been shown to immediately kill mutation-expressing tumors in pre-clinical studies, and to create a deep reservoir of 'ready-to-go' neoTCR-P1 cells with the potential for long term persistence to prevent future cancer recurrence. These developments offer PACT exceptional prospects to leverage the potential of ideal tumor targets and biologically verified neoTCRs into clinical development of neoTCR-T adoptive cell therapies.

SOURCE: PACT Pharma

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PACT Pharma Raises $75M in Oversubscribed Series C Financing to Develop Fully Personalized NeoTCR-T Cell Therapies for Patients with Cancer | DNA RNA...

--44 week median follow up for patients (n=6)----Zero anti-VEGF rescue injections required following intravitreal ADVM-022; First patient has reached 52-weeks post treatment----Vision remains stable and anatomical improvements maintained--

MENLO PARK, Calif., Jan. 11, 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 clinical data for the first cohort of patients (n=6) in the OPTIC phase 1 clinical trial of ADVM-022, the companys intravitreal injection gene therapy, in treatment-experienced patients with wet age-related macular degeneration (wet AMD). The data are being presented today by Charles C. Wykoff M.D., Ph.D., director of research, Retina Consultants of Houston, at the Atlantic Coast Retina Club Macula 20/20 Annual Meeting inNew York, NY.

A copy of the presentation is available on the Adverum corporate website under Events and Presentations in the Investors section, available here.

In October 2019, Adverum presented data from the first cohort in OPTIC at a median 34-week time point (28-44 week range). Today, additional data for the first cohort are being presented, including efficacy and safety data, with a median follow up of 44 weeks at a range of 40-52 weeks, and included:

As of December 1, 2019, ADVM-022 continues to be well-tolerated in the first cohort with no drug-related or procedure-related serious adverse events (SAEs), no drug-related systemic adverse events and no adverse events meeting the criteria for dose-limiting toxicities (DLTs). Low-grade inflammation was reported in all six patients and was generally mild to moderate and responsive to steroid eye drops. One ocular SAE, a retinal detachment, that was not related to ADVM-022 or the administration procedure was reported.

OPTIC Phase 1 Clinical Trial Data from Cohort 1 (n=6)

1 Best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) (i.e., sight charts) 2 Central retinal thickness (CRT), also referred to as central subfield thickness (CST) assessed using Optical Coherence Tomography (OCT) imaging and measured by an independent Central Reading Center3 BCVA and CST values for patient with retinal detachment (unrelated to study treatment) used last observations prior to detachment 4 This event was deemed unrelated to ADVM-022 or any study procedure

These longer-term follow-up data demonstrate that patients in this first cohort of OPTIC are achieving sustained benefits from ADVM-022, a one-time intravitreal therapy, and have not required any anti-VEGF rescue injections through a median of 44 weeks while demonstrating impressive anatomic improvements, said Charles C. Wykoff M.D., Ph.D., director of research, Retina Consultants of Houston and associate professor of clinical ophthalmology, Blanton Eye Institute, Houston Methodist Hospital and Weill Cornell Medical College, Houston Texas. With a median follow-up period of 44 weeks, ADVM022 continues to control wet AMD disease activity in all 6 patients and the low-grade intraocular inflammation appears manageable with steroid eyedrops. Based on the data to date, ADVM-022 has the potential to be a meaningful and potentially transformative treatment for patients with wet AMD.

Aaron Osborne, MBBS, chief medical officer of Adverum, added, These new clinical data are promising as they continue to support the safety, efficacy, and durable clinical profile of ADVM-022 and this therapys potential to change the treatment paradigm for patients with wet AMD. Anti-VEGF injections, the current standard of care, carry a significant treatment burden and real-world outcomes data suggest that vision outcomes are suboptimal due to undertreatment. In the first cohort of OPTIC, we continue to see stable vision and anatomical improvements being maintained out to a median of 44 weeks after a single ADVM-022 injection in these difficult-to-treat patients who previously required frequent anti-VEGF injections. We look forward to presenting longer-term data from the first cohort and 24-week data from the second cohort of OPTIC on February 8 at the Angiogenesis, Exudation, and Degeneration 2020 symposium.

About the OPTIC Phase 1 Trial of ADVM-022 in Wet AMDThe multi-center, open-label, Phase 1, dose-escalation trial is designed to assess the safety and tolerability of a single intravitreal (IVT) administration of ADVM-022 in patients with wet AMD who are responsive to anti-vascular endothelial growth factor (VEGF) treatment. In the first cohort, patients (n=6) received ADVM-022 at a dose of 6 x 10^11 vg/eye and in the second cohort, patients (n=6) received ADVM-022 at a dose of 2 x 10^11 vg/eye. In the third cohort (n=9), patients also are receiving a dose of 2 x 10^11 vg/eye and in the fourth cohort (n=9), patients will receive a dose of 6x10^11 vg/eye. Patients in the third and fourth cohorts will receive prophylactic steroid eye drops instead of oral steroids which were used in the first and second cohorts. The primary endpoint of the trial is the safety and tolerability of ADVM-022 after a single IVT administration. Secondary endpoints include changes in best-corrected visual acuity (BCVA), measurement of central retinal thickness (CRT), as well as mean number of anti-VEGF rescue injections and percentage of patients needing anti-VEGF rescue injections. Each patient enrolled will be followed for a total of two years.

Eight leading retinal centers acrossthe United States(U.S.) are participating in the OPTIC Phase 1 trial for ADVM-022. For more information on the OPTIC Phase 1 clinical trial of ADVM-022 in wet AMD, please visithttps://clinicaltrials.gov/ct2/show/NCT03748784.

About ADVM-022 Gene TherapyADVM-022 utilizes a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. ADVM-022 is administered as a one-time intravitreal injection, designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections, optimize patient compliance and improve vision outcomes for wet AMD and diabetic retinopathy patients.

In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for ADVM-022 for the treatment of this disease.

Adverum is currently evaluating ADVM-022 in the OPTIC Study, a Phase 1 clinical trial in patients 50 years and older with wet AMD. Additionally, Adverum plans to submit an Investigational New Drug Application for ADVM-022 for the treatment of diabetic retinopathy to the U.S. Food and Drug Administration in the first half of 2020.

About Wet Age-related Macular Degeneration (Wet AMD)Age-related macular degeneration (AMD) is a progressive disease affecting the macula, the region of the retina at the back of the eye responsible for central vision. In patients with wet AMD, an aggressive form of AMD, abnormal blood vessels grow underneath and into the retina. These abnormal blood vessels leak fluid and blood into and beneath the retina, causing vision loss.

Wet AMD is a leading cause of vision loss in patients over 60 years of age, with a prevalence of approximately 1.2 million individuals in the U.S. and 3 million worldwide. The incidence of new cases of wet AMD in the U.S. is approximately 150,000 to 200,000 annually, and this number is expected to grow significantly as the countrys population ages.

The current standard-of-care therapy for wet AMD is anti-VEGF intravitreal injections. These are effective but typically require eye injections every 4-12 weeks in order to maintain vision. Compliance with this regimen can be difficult for patients, caregivers, and healthcare systems, leading to undertreatment and resulting in loss of vision.

About Adverum BiotechnologiesAdverum Biotechnologies (Nasdaq: ADVM) is a clinical-stage gene therapy company targeting unmet medical needs for 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

Forward-looking StatementsStatements contained in this press release regarding events or results that may occur in the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to statements regarding: Adverums plans to report additional clinical data for ADVM-022 from the OPTIC trial and to advance ADVM-022, including Adverums plans to submit an Investigational New Drug Application for ADVM-022 for the treatment of diabetic retinopathy to the U.S. Food and Drug Administration in the first half of 2020, and the potential benefits of ADVM-022, all of which are based on certain assumptions made by Adverum on current conditions, expected future developments and other factors Adverum believes are appropriate in the circumstances. Adverum may not achieve any of these in a timely manner, or at all, or otherwise carry out the intentions or meet the expectations disclosed in its forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include risks inherent to, without limitation: Adverums novel technology, which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; the results of early clinical trials not always being predictive of future results; the potential for future complications or side effects in connection with use of ADVM-022; obtaining regulatory approval for gene therapy product candidates; enrolling patients in clinical trials; reliance on third parties for conducting the OPTIC trial and vector production; and ability to fund operations through completion of the OPTIC trial and thereafter. Risks and uncertainties facing Adverum are described more fully in Adverums Form 10-Q filed with the SEC on November 7, 2019 under the heading Risk Factors. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Investor and Media Inquiries:

Investors:Myesha LacyAdverum Biotechnologies, Inc.mlacy@adverum.com1-650-304-3892

Media:Cherilyn Cecchini, M.D.LifeSci Communicationsccecchini@lifescicomms.com1-646-876-5196

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Adverum Biotechnologies Reports Additional Clinical Data from First Cohort of OPTIC Phase 1 Trial of ADVM-022 Intravitreal Gene Therapy for Wet AMD at...

An abnormality in the SOD1 gene is linked to some inherited cases of amyotrophic lateral sclerosis (ALS). So could turning off the mutated gene halt the disease? An international research team led by the University of California San Diego School of Medicine showed the potential of that strategy in mice by using a gene therapy approach.

A one-time injection of a gene-silencing RNA delivered by an adeno-associated virus (AAV) vector into the spinal cord prevented the onset of ALS in presymptomatic mice, and it blocked disease progression in rodents that had already developed symptoms. The team reported the findings in the journal Nature Medicine.

The SOD1 gene codes for an enzyme called superoxide dismutase. Normally, the enzyme breaks down superoxide radicals that are produced during cell metabolism. But in ALS, SOD1 mutations can create misfolded SOD1 protein, as toxic oxygen molecules persist, leading to the death of motor neurons.

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The UC San Diego-led team postulated that a short hairpin RNA (shRNA)an artificial RNA molecule that can silence gene expressioncould be utilized to block the dysfunctional SOD1 gene.

Other researchers had tried delivering shRNA-bearing vectors into the blood via intravenous injection. In mouse models of ALS, disease progression was indeed slowed, but the approach only extended survival by about three months. In a more recent study, scientists used intrathecal injection into the cerebrospinal fluid, but the animals lived only two months longer despite being treated immediately after birth.

For the current study, the UCSD researchers injected the shRNA-containing AAV therapy into the spinal subpial space at cervical and lumbar spine levels.

The team observed impressive results. Remarkably, SOD1-mutated mice treated before disease onset never developed disabilities related to motor neuron functions when followed to an average age of 462 days. That means they didn't lose functions like grip strength ororientation reflexes. The control animals, by contrast,started showing symptomsat about 306 days and reached the end-stage of ALS about three months later.

Further analysis showed that the therapy suppressed the accumulation of misfolded SOD1 protein and almost completely preserved motor neuron cells.

In mice that had already entered the symptomatic stage, the injection also blocked disease progression and further motor neuron degeneration, the team reported.

At present, this therapeutic approach provides the most potent therapy ever demonstrated in mouse models of mutatedSOD1gene-linked ALS, the studys senior author, Martin Marsala of UCSD, said in a statement.

RELATED:Biogen's antisense ALS drug shows promise in early clinical trial

Several other strategies have been developed aimed at decreasing the production of mutated SOD1 protein. Swiss biotech Neurimmune has a recombinant antibody called -miSOD1, which the company developed based on memory B cells that are found in healthy elderly people and that protect against misfolded SOD1. In mouse models of ALS, the drug extended the animals lives by up to two months.

Antisense oligonucleotide therapy isanother potential modality for fighting neurodegenerative disease. Biogen recently showed its antisense drug tofersen (BIIB067) was well tolerated in ALS patients in a small phase 1 study. At its highest dose, the drug cutSOD1 protein levels in spinal fluid and the patients performed well on certain clinical function tests.

Marsala and colleagues now plan to run additional studies of their spinal subpial shRNA approach in a large animal model to determine the optimal, safe dosage of the treatment.

In addition, effective spinal cord delivery of AAV9 vector in adult animals suggests that the use of this new delivery method will likely be effective in treatment of other hereditary forms of ALS or other spinal neurodegenerative disorders that require spinal parenchymal delivery of therapeutic gene(s) or mutated-gene silencing machinery, such as in C9orf72 gene mutation-linked ALS or in some forms of lysosomal storage disease, Marsala said in the statement.

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Halting ALS with a gene therapy approach - FierceBiotech