MENLO PARK, Calif., Oct. 24, 2019 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc.,(Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today announced that the first patient was dosed in the third cohort (n=9) of the ongoing OPTIC phase 1 clinical trial for ADVM-022 for the treatment of neovascular or wet age-related macular degeneration (wet AMD). Patients in this cohort are receiving a single intravitreal injection of gene therapy candidate ADVM-022 at a dose of 2 x 10 ^11 vg/eye.

We are excited to report dosing the first patient in the third cohort of OPTIC. This expansion of OPTIC will generate important clinical data to support the further development of ADVM-022, said Aaron Osborne, MBBS, chief medical officer of Adverum. Based on the recently presented data from the first cohort of OPTIC, which demonstrated a sustained response to a single injection of ADVM-022 out to a median of 34 weeks, with no patient in the first cohort requiring anti-VEGF rescue therapy, we believe that ADVM-022 has the potential to be a transformative treatment option for patients with wet AMD.

Dante Pieramici, M.D., co-director of the California Retina Research Foundation, Managing Partner of The California Retina Consultants and investigator in the OPTIC trial, said, An intravitreal gene therapy that can significantly reduce the number of injections required to maintain vision would be welcomed by patients with wet AMD as well as their caregivers and physicians. Im encouraged by the recently presented clinical data from the first cohort of the OPTIC trial showing that the therapy was safe and well tolerated with no rescue injections required in patients who previously required frequent anti-VEGF injections to control their wet AMD.

About the OPTIC Phase 1 Trial of ADVM-022 in Wet AMDThe multi-center, open-label, phase 1 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 (n=6) patients received ADVM-022 at a dose of 2 x 10^11 vg/eye. In the third cohort (n=9), patients are receiving ADVM-022 at a dose of 2 x 10^11 vg/eye and in the fourth cohort (n=9), patients will receive ADVM-022 at a dose of 6 x 10^11 vg/eye. Patients in the first and second cohorts received prophylactic oral steroids, while patients in the third and fourth cohorts will receive prophylactic steroid eye drops. The primary endpoint of the trial is the safety and tolerability of ADVM-022 after a single IVT administration. Secondary endpoints include change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST) and macular volume, as well as mean number of anti-VEGF rescue injections and percentage of patients needing anti-VEGF rescue injections. Each patient enrolled in the study will be followed for a total of two years.

Eight leading retinal centers acrossthe United Statesare 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, reduce the burden of frequent anti-VEGF injections, optimize patient compliance, and to 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 Adverum Biotechnologies, Inc.Adverum 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 for advancing ADVM-022; the potential benefits of ADVM-022: the expected timing of submitting an IND for diabetic retinopathy, 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 August 8, 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 BiotechnologiesVice President, Investor Relations and Corporate Communicationsmlacy@adverum.com1-650-304-3892

Media:Cherilyn Cecchini, M.D.Account Supervisorccecchini@lifescipublicrelations.com1-646-876-5196

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Adverum Biotechnologies Doses First Patient in Third Cohort of OPTIC Phase 1 Clinical Trial of ADVM-022 Intravitreal Gene Therapy for Wet AMDPatients...

Novartis raised its earnings forecast for the third time this year as its new gene therapy got off to a strong start in its first quarter of reported sales.

Earnings excluding some items are expected to increase by a mid- to high-teens percentage this year, the Basel, Switzerland-based company said. Novartis in July forecast a low double-digit to mid-teens percentage rise.

The focus is on gene therapy Zolgensma as the company discloses the first quarterly sales of the product that costs $2.1 million. The treatment exceeded analysts estimates despite concerns over coverage barriers.

Piqray, a breast cancer drug, is also in the spotlight with Novartis counting on the medicine to become one of its next growth drivers. The drug beat sales estimates.

Investors are looking for an update on an investigation into problematic data involving Zolgensma. The company has faced criticism that it should have told regulators about the data irregularities before the drugs approval in May.

Shares in the company have climbed about 15 per cent this year, in line with a gain of about 15 per cent for a Bloomberg index of European pharma companies. Bloomberg

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Novartis raises earnings forecast as new gene therapy gets off to strong start - The Irish Times

KENDALLVILLE Eighteen-month-old Omarion Jordan plays with his toys in his Kendallville home under the watchful eye of his mother, Kristin Simpson, and the family dog. Hes wiggly and active, with no hint of the rare genetic disease that could have taken his life before age 2.

Omarion has a rare genetic disorder called severe combined immunodeficiency syndrome, SCID for short and better known as the bubble boy disease made famous in a 1976 television movie starring John Travolta as well as an episode of the 1990s sitcom Seinfeld. The disease affecting 40 to 100 American newborns each year makes them extremely vulnerable to infections, which left untreated, kills most children before they turn two.

Simpson said SCID is caused by a random gene mutation on the maternal side. She said, she has no family history that would indicate the disease was ever present in other family members.

Omarion was born normally, but began to have skin infection symptoms before he was 3-months-old, she said. Doctors thought he had an extreme case of eczema or cradle cap.

Simpson said everything changed when Omarion got his 3-month vaccinations.

He had a bad reaction. He had no immune system to react with the vaccine, she said. He was covered in a green, pus-like substance.

Simpson took Omarion to the emergency room twice, but was sent home. She then made an appointment with her pediatrician, not knowing then that it would be months before she saw her apartment again.

The pediatrician sent us right to the hospital, Simpson said. It was 1 weeks to clear the infection. I had to drop everything. I never came back (to the apartment) after that morning.

Doctors sent Omarion and his mother on a four-hour ambulance ride to Cincinnati Childrens Hospital for tests. There, Simpson learned that the standard treatment for SCID was a bone marrow transplant. When a two-month search for a bone marrow match came up empty, doctors suggested another route.

There was a trial at St. Jude (Childrens Hospital) for gene therapy and we were given the option, Simpson said. We were flown to St. Judes on a private jet.

The experimental gene therapy used Omarions own bone marrow, altered to correct the missing gene. The altered bone marrow is transplanted back into Omarions body, carried by an HIV virus with all the harmful cells removed.

Its like a car, Simpson said. They take out the harmful elements and use the virus as a carrier for the altered gene.

Experimental gene therapy comes with both reward and risk. The treatment could be a breakthrough cure for Omarion and other children affected by the gene mutation.

The risks include developing leukemia, which has happened to some patients in the small trial group, other unknown side effects and the enormous financial cost. Treatment costs run into the millions of dollars.

Gene therapies, while breaking new ground in fighting tough-to-cure ailments, are a cutting edge field of medicine, but also an exceptionally expense one. For example, a gene therapy drug called Zolgensma is the most expensive drug ever approved in the United States, according to a Bloomberg Businessweek story about Omarion and the rise of gene therapies. A one-time infusion costs $2.1 million.

Omarions case has received national media attention, including the story from Bloomberg Businessweek, which published a story June 5 about the balance of rapidly progressing gene therapy and its high cost, and other outlets including NBC News, WebMD.com and CNN Health.

Simpson is grateful that St. Judes Children Hospital, the worlds leader in the treatment of childhood diseases, has picked up the entire tab for Omarions treatment.

Simpson said that at St. Jude, she and her mother were the only family members allowed inside Omarions isolation room. Everyone else was fully masked and gowned. They were in the isolation room for months.

Omarion received his bone marrow transplant Dec. 20, 2018, and finally left the hospital in April. Omarion will have checkups every three months for the foreseeable future and an annual checkup for the rest of his life.

Today hes healthy, thanks to a cutting-edge gene therapy treatment, and a walking miracle.

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Gene therapy gives "miracle boy" a second chance at life - KPCnews.com

Let's play a game of word association. I'll go first.

Cell Therapy

What words spring to mind? CRISPR? Medicine? Genetic disorders? Cancer? Gene therapy?

What about green tea? Unlikely, I imagine.

But in a new study published today in Science Advances, researchers from East China Normal University have created an elegant system for activating genetically edited cells using green tea.1Realizing the promise of cell therapiesEngineered cell therapies, deemed the "next frontier" in modern medicine, contain specific cellular material that triggers a desired effect in vitro or in vivo. Such therapies are in development in laboratories across the globe for an array of different conditions, including acute myocardial infarction (heart attack), brain cancer, breast cancer, diabetes and liver diseases. They offer a novel avenue of therapeutics for patients suffering from diseases for which treatment options are limited.For their efficacious and safe use in the clinic, scientists need to be able to regulate the activity of these cells in vivo. Essentially, they require a "remote control". This has proven a major barrier for the delivery of cell therapies to patients. Initial work in this field has adopted antibiotics such as doxycycline or tetracycline as remote-control triggers for gene expression in the cells. However, regular use of antibiotics may result in antibiotic resistance and other adverse side effects.So, what alternatives exist?Haifeng Ye, Professor at East China Normal University, says "Ideal trigger molecules for clinical biomedical applications would be natural, non-toxic, highly soluble, inexpensive, and perhaps even beneficial to health."Previous studies have reported that remote control switches can be activated through the use of food or cosmetic preservatives, vanillic acid, benzoate and phloretin for example. These molecules do not naturally occur in food however, and the safety implications of their long-term use is not well known.A green solution?Nothing beats a good cup of tea. It is the second most popular beverage on the planet (following water) and can be found in the household cupboards of 80% of Americans. Tea is available in a variety of forms, including but not limited to black tea, oolong tea, white tea and green tea. A plethora of research studies have documented the numerous health benefits of green tea consumption, including anticarcinogenic, anti-inflammatory, antimicrobial, and antioxidant effects.The components of green tea most heavily researched with regards to health are the polyphenols, of which the most pertinent are flavonoids, and the most pertinent flavonoids are the catechins.2Post green-tea consumption, the tea catechins and phenolic acids undergo metabolic processing to form the antioxidant protocatechuic acid (PCA). In their latest study, Ye and team have utilized this antioxidant as a "remote control" for activating gene switches in cells. "PCA is a major tea catechin compound produced by humans following green tea consumption that has powerful antioxidant activity. Therefore, in this study, we showed the use of protocatechuic acid (we call it PCA), a metabolite after tea drinking, as a trigger molecule," Ye told Technology Networks.PCA-inducible gene switchesIn the study, the scientists engineered PCA-inducible gene switches in mammalian cells. Initially, they explored the potential for using PCA to monitor cell-based long-term therapies in vivo by integrating the genetic switch into HEK-293 cells and found that the cell line demonstrated reversible and tunable induction kinetics, which the authors regard as "excellent switching performance". This was characterized by negligible basal expression and nonsaturating increases in the transgene output over the course of a 15-day trial.Next, they microencapsulated and implanted the HEK cells into mice. Ye tells us, "The alginate-poly (L-lysine)-alginate-based encapsulation technology was used in our study for cell therapy. This clinically validated implant technology enables the free diffusion of metabolites, nutrients and proteins of lower molecular weights (<72 kDa) across the biocompatible capsule membrane while shielding their cellular content from physical contact with the hosts immune system. The implant technology has been successfully validated in human clinical trials and the performance of the material is continuously improved for clinical applications."The researchers found that, regardless of delivery method (intraperitoneal, oral intake from water, or oral intake from concentrated green tea), PCA could control the secretion of a reporter protein, SEAP, in a dose-dependent manner.Making CRISPR more crisp?CRISPR gene-editing shows promise in revolutionizing personalized medicine. A notable key issue with CRISPR, however, is the "off target" effects that limit its specificity. In this study, the scientists used the PCA-responsive cells to perform more targeted CRISPR gene editing: "By applying newly-designed fusion-protein-based PCA-controlled gene switches to Pol III promoters, we created trigger-inducible expression systems for gRNAs to program PCA-mediated CRISPR/Cas9-activity," says Ye.Exploring diabetes treatment with PCA-induced cell therapyYe and colleagues next tested the potential of the PCA remote control system for treating experimental diabetes using a mouse model. Using the switch, they engineered two different cell lines: one that enabled PCA-inducible expression of the reporter protein SEAP and insulin, and the other producing a short variant of human glucagon-like peptide 1 and SEAP. Implantation of these cells into mouse models of type 1 diabetes and type 2 diabetes mellitus resulted in restored homeostatic fasting blood glucose concentrations and glucose tolerance upon PCA injection.Recognizing that the translation of research findings from mouse models to humans in the clinic can be problematic, the scientists then decided to explore the PCA remote control switch efficacy in non-human primate models of diabetes. In parallel to the treatment efficacy observed in the type 2 diabetic mice, daily oral administration of PCA rapidly increased the expression of glucagon-like peptide 1 and restored glucose homeostasis in diabetic monkeys.In terms of safety, blood biochemical analyses related to inflammatory responses found that white blood cell count, lymphocytes, monocytes, eosinophils, and basophils, did not increase at any point during the treatment when compared with pre-treatment.The study findings certainly excite the authors, "Although there have not yet been preclinical studies for the application of engineered cellbased therapies in humans, this first-in-monkey study demonstrates the feasibility of safely and successfully scaling up a treatment strategy by controlling microencapsulated engineered cells to release therapeutic outputs from animals such as mice to larger NHPs. Therefore, this study substantiates the medical utility of concepts developed in synthetic biology," they note in the discussion of the paper.How much tea is too much tea?Hypothetically, if this therapy was to reach the clinic, I ponder over the possibility of an individual consuming "too much" green tea, and how this might impact the therapy. Ye is quick to inform me that this would not be an issue, "Only custom prepared concentrated green tea can activated the implanted designer cells. The normal green tea drinks cannot activate the implanted cells because of low concentration," he says.The future looks greenThe study is comprehensive, assessing the PCA "switch" in a variety of cell lines and mammalian models with a variety of control measures in place.Thus, in which direction will this research go next? I ask Ye, who tells me, " We will next focus on solving the following limitations:(1) The PCAON-switch was stably integrated into [the] genome by a "Sleeping Beauty" transposon system. Due to a random integration, unwanted insertional mutagenesis might occur. We will next consider using gene editing tools, such as CRISPR, to enable facile and permanent integration of the switch into the targeted genomic sequences in human cells without insertional mutagenesis;(2) The chassis of the HEK-293 cells are easily handled, transfected, and compatible to the PCAON-switch. For translational applications, they must also be safe (no side effects) in humans. Hence, we will test the therapeutic efficiency of the PCAON-switch in autologous parental cells from patients own mesenchymal stem cells, which may provide immunocompatible and noncarcinogenic autologous or allogeneic cell sources;(3) The lifespan of the designer cells inside the alginate microcapsules is an imperative issue. To realize long-term cell therapy, we will further improve the encapsulation technology."Haifeng Ye, Professor at East China Normal University, was speaking with Molly Campbell, Science Writer, Technology Networks.References:1. A green teatriggered genetic control system for treating diabetes in mice and monkeys," by J. Yin; L. Yang; K. Dong; J. Jiang; S. Xue; Y. Xu; X. Wang; H. Ye at East China Normal University in Shanghai, China; L. Mou; Y. Lu at First Affiliated Hospital of Shenzhen University in Shenzhen, China.2. Reygaert. 2018. Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases. Biomed Research International. doi: 10.1155/2018/9105261.

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Green Tea Acts as a "Remote Control" To Switch on Cell Therapy - Technology Networks