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Archive for the ‘Gene therapy’ Category

Citing pandemic, Sarepta defers much-anticipated DMD gene therapy PhIII, will head to regulators after 10-person study – Endpoints News

Saturday, November 7th, 2020

Roger Perlmutter has a few more moves to make before he exits the top job in Merck R&D.

The pharma giant is buying VelosBio for $2.75 billion in cash, grabbing a promising ROR1 antibody drug conjugate that is now in Phase I and Phase II studies for hematologic malignancies and solid tumors.

Perlmutter, who will leave at the end of the year after building Keytruda into a monster drug franchise, clearly likes the data hes seen from the biotech. And the oncology group sees plenty of opportunities for the rest of the pipeline at VelosBio, which raised a crossover round of $137 million just a few months ago in an apparent move toward an IPO.

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Citing pandemic, Sarepta defers much-anticipated DMD gene therapy PhIII, will head to regulators after 10-person study - Endpoints News

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Ocugen Provides Business Update and Third Quarter 2020 Financial ResultsFirst Gene Therapy Candidate OCU400 On Track to Enter the Clinic in 2021 -…

Saturday, November 7th, 2020

MALVERN, Pa., Nov. 06, 2020 (GLOBE NEWSWIRE) --Ocugen, Inc.. (NASDAQ: OCGN), a biopharmaceutical company focused on discovering, developing and commercializing transformative therapies to cure blindness diseases, today reported third quarter 2020 financial results along with a general business update.

I am proud of the advancements we have made this quarter in developing our modifier gene therapy and novel biologic product candidates. We remain on-track to achieve multiple near and mid-term milestones with a plan to initiate four Phase 1/2a trials during 2021 and 2022. Additionally, I am pleased that we have raised approximately $28million of gross proceeds in 2020, which have extended our cash runway for continued development of our product candidates, said Dr. Shankar Musunuri, Chairman, Chief Executive Officer and Co-Founder of Ocugen.

Business Highlights:

Third Quarter 2020 Financial Results:

About Ocugen, Inc.

Ocugen, Inc. is a biopharmaceutical company focused on discovering, developing, and commercializing transformative therapies to cure blindness diseases. Our breakthrough modifier gene therapy platform has the potential to treat multiple retinal diseases with one drug one to many and our novel biologic product candidate aims to offer better therapy to patients with underserved diseases such as wet age-related macular degeneration, diabetic macular edema, and diabetic retinopathy. For more information, please visit http://www.ocugen.com.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, which are subject to risks and uncertainties. We may, in some cases, use terms such as predicts, believes, potential, proposed, continue, estimates, anticipates, expects, plans, intends, may, could, might, will, should or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from our current expectations. These and other risks and uncertainties are more fully described in our periodic filings with the Securities and Exchange Commission (the SEC), including the risk factors described in the section entitled Risk Factors in the quarterly and annual reports that we file with the SEC. Any forward-looking statements that we make in this press release speak only as of the date of this press release. Except as required by law, we assume no obligation to update forward-looking statements contained in this press release whether as a result of new information, future events or otherwise, after the date of this press release.

Corporate Contact:Ocugen, Inc.Sanjay SubramanianChief Financial OfficerIR@Ocugen.com

Media Contact:LaVoieHealthScienceKatie Gallagherkgallagher@lavoiehealthscience.com+1 617-792-3937

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Roadmap to Market for Cell and Gene Therapies, Upcoming Webinar Hosted by Xtalks – PR Web

Saturday, November 7th, 2020

Is your team confident in handling the complicated logistics that come with cell and gene trials?

TORONTO (PRWEB) November 06, 2020

Nothing is standard about the study design, study conduct or the regulatory process in cell and gene therapy trials. Every cell and gene therapy is different due to the specific characteristics of each product, with a complicated regulatory approval process and unique therapeutic challenges.

Do you have confidence in your trials endpoints? Are you pursuing an accelerated pathway or special designation? Will you need to plan for a centralized site model or remote monitoring? Is your team confident in handling the complicated logistics that come with cell and gene trials?

In this webinar, participants will learn an end-to-end approach to bringing a cell and gene therapy to market. You will receive advice from experts responsible for supporting over 100 advanced cell and gene therapy programs. They will share each step of this process covering the planning, execution, submission and post-marketing for trials in the US and EU. The information provided will help participants determine their next step in the development of their cell and gene therapy product.

Join Ewan Campbell, Advanced Therapy & Biotech Director, Veristat; Kevin Hennegan, Senior Regulatory Strategist, Veristat; and Rachel Smith, Project Director, Veristat in a live webinar on Friday, November 20, 2020 at 11am EST (4pm GMT/UK).

For more information, or to register for this event, visit Roadmap to Market for Cell and Gene Therapies.

ABOUT XTALKS

Xtalks, powered by Honeycomb Worldwide Inc., is a leading provider of educational webinars to the global life science, food and medical device community. Every year, thousands of industry practitioners (from life science, food and medical device companies, private & academic research institutions, healthcare centers, etc.) turn to Xtalks for access to quality content. Xtalks helps Life Science professionals stay current with industry developments, trends and regulations. Xtalks webinars also provide perspectives on key issues from top industry thought leaders and service providers.

To learn more about Xtalks visit http://xtalks.comFor information about hosting a webinar visit http://xtalks.com/why-host-a-webinar/

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Accelerate Cell and Gene Therapy Development and Increase Manufacturing Capacity with Higher Titer LV and AAV Transfection Platforms – BioProcess…

Saturday, November 7th, 2020

This webcast features:Leisha Kopp, Applications Scientist, Mirus Bio

Cell and gene therapies show unparalleled promise to improve the human condition by eradicating cancer and rectifying genetic disorders. However, low viral titers and capacity constraints in viral vector manufacturing processes can dramatically hinder the progress of these transformative therapies.

TheTransIT-VirusGEN Transfection Reagent from Mirus Bio offers a simplified, cost-effective workflow for recombinant lentivirus (LV) and adenoassociated virus (AAV) generation.TransIT-VirusGEN Transfection Reagent is also effective in both adherent and suspension HEK 293derived cell types, making it the superior reagent choice for most large-scale production platforms. In addition, Mirus developed LV and AAV enhancers to increase functional virus titers two to three fold over previously optimized conditions and offer up to 10-fold titer improvements over polyethylenimine (PEI)-based formulations.

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Homology Medicines Announces Upcoming Oral Presentation on pheNIX Gene Therapy Clinical Trial for Adults with PKU – GlobeNewswire

Saturday, November 7th, 2020

Homology Webcast / Conference Call Scheduled for Friday, November 6 at 4:30 p.m. ET

BEDFORD, Mass., Nov. 05, 2020 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the upcoming oral presentation of data from the dose-escalation portion of the Companys ongoing Phase 1/2 pheNIX gene therapy clinical trial with HMI-102 for adults with phenylketonuria (PKU), the worlds first PKU gene therapy clinical trial. The data will be presented by pheNIX principal investigator Olaf Bodamer, M.D., Ph.D., FACMG, FAAP, Park Gerald Chair in Genetics & Genomics and Associate Chief of Genetics & Genomics at Boston Childrens Hospital, a premier center for metabolic disorders and the first site to enroll a patient in the pheNIX trial. The pheNIX trial results will be featured at the virtual New England Consortium of Metabolic Programs (NECMP) annual meeting, which is focused on new research in metabolic disorders, including PKU, on Friday, November 6. NECMP includes metabolic clinics, healthcare providers, patient organizations and others dedicated to increasing knowledge of metabolic disorders and improving delivery of healthcare to patients.

We are pleased that additional data from our pheNIX trial, the first-ever gene therapy trial for PKU, will be shared for the first time by a respected leader in the field of metabolic disorders and directly with the PKU community as part of a featured, peer-reviewed scientific session, stated Gabe Cohn, M.D., Chief Medical Officer of Homology Medicines. The oral presentation by Dr. Bodamer will include data from three dose cohorts in the dose-escalation phase of our pheNIX trial, the results of which are informing the upcoming expansion phase of our study.

Webcast/Conference Call The NECMP annual meeting is for members of the Consortium. Homology will host a conference call and webcast following the meeting on Friday, November 6 at 4:30 p.m. ET. The webcast will be accessible on Homologys website in the Investors section, and the webcast replay will be available on the website for 90 days following the presentation. To access using the conference call line, dial (866) 244-8091 (U.S./Canada toll-free) or (602) 563-8623, with Conference ID 7394503.

About HMI-102HMI-102 is an investigational gene therapy in clinical development for the treatment of phenylketonuria (PKU) in adults. HMI-102 is designed to encode the PAH gene, which is mutated in people with PKU, delivered via the liver-tropic AAVHSC15 vector. Homology has received Fast Track Designation and orphan drug designation for HMI-102 from the U.S. Food and Drug Administration (FDA), and orphan drug designation from the European Medicines Agency (EMA).

About Phenylketonuria (PKU)PKU is a rare inborn error of metabolism caused by a mutation in thePAHgene. PKU results in a loss of function of the enzyme phenylalanine hydroxylase, which is responsible for the metabolism of phenylalanine (Phe), an amino acid obtained exclusively from the diet. If left untreated, toxic levels of Phe can accumulate in the blood and result in progressive and severe neurological impairment. Currently, there are no treatment options for PKU that target the underlying genetic cause of the disease. According to the National PKU Alliance, PKU affects nearly 16,500 people in the U.S. with approximately 350 newborns diagnosed each year. The worldwide prevalence of PKU is estimated to be 50,000 people.

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

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; plans and timing for the release of clinical data from the Phase 1/2 pheNIX trial; our position as a leader in the development of genetic medicines; and our participation in upcoming presentations and conferences. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the capabilities of our manufacturing facility; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs as a result of operating as a public company. These and other important factors discussed under the caption Risk Factors in our Quarterly Report on Form 10-Q for the quarterly period endedJune 30, 2020and our other filings with theSECcould cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Company ContactsTheresa McNeely Chief Communications Officer and Patient Advocate tmcneely@homologymedicines.com781-301-7277

Media Contact: Cara Mayfield Senior Director, Patient Advocacy and Corporate Communications cmayfield@homologymedicines.com781-691-3510

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Homology Medicines Announces Upcoming Oral Presentation on pheNIX Gene Therapy Clinical Trial for Adults with PKU - GlobeNewswire

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CRISPR, Vertex show CRISPR/Cas9 gene-editing therapy works in more patients – FierceBiotech

Saturday, November 7th, 2020

CRISPR Therapeutics and Vertex have presented updated data on their CRISPR/Cas9 gene-editing therapy in sickle cell disease and beta thalassemia, showing patients continue to benefit from the drug. Yet, hemoglobin levels fell in two of the seven patients in the latest update, raising early questions about the durability of CTX001.

One year ago, CRISPR and Vertex linked CTX001 to improvements in two hemoglobinopathy patients. The results were a milestone for gene editing, but CTX001 needs to build on the early success if it is to emerge as a viable rival to bluebird bios LentiGlobin gene therapy, which is now set to be submitted for FDA approval in late 2022.

The LentiGlobin delays create an opportunity for CTX001. The question is whether CRISPR and Vertex can take it. Ahead of the American Society of Hematology's (ASH's) annual meeting, the partners shared new data that shed light on the potential prospects of CTX001.

Fetal hemoglobin levels rose in all seven patients after administration of CTX001 and have remained elevated for up to 15 months of follow-up. The five beta thalassemia patients last needed packed red blood cells in the first month or two after receiving CTX001, having previously more than 10 units a year, and neither of the sickle cell patients have suffered vaso-occlusive crises since being treated.

There are potential points of concern in the data, though, particularly given the likelihood of CTX001 facing competition. Hemoglobin fell from 12.5 to 11.6 in one beta thalassemia patient between the fifth and sixth months. The drop followed a decrease from 12.9 to 12.5 between the fourth and fifth months.

Investigators also tracked a decline in hemoglobin levels in one of the sickle cell patients. Levels fell from 11.8 to 10.3 between month nine and month 12.

The declines happened in two of the three patients with the longest follow-up, raising the question of whether similar trends will play out in other subjects in the coming months. Those concerns are countered by data on the first beta thalassemia patient, whose hemoglobin level is higher than ever 15 months after treatment with CTX001.

Safety is another concern. In an update earlier this year, CRISPR and Vertex revealed they had seen seven serious adverse events across three patients, suggesting bluebirds LentiGlobin may have the edge in terms of safety. The ASH update discussed a new patient who suffered four serious adverse events that may be related to CTX001.

Such details could matter, given CTX001 is still likely to cede a head start to LentiGlobin. Yet, CRISPR sees CTX001 as a best-in-class treatment and, with bluebird stumbling, thinks the drug is well placed to capture a sizable slice of the market.

CRSP has mentioned they are working on bridging the development timeline gap (~1-2 yrs now) w/ BLUE, and they expect BLUE's earlier launch and investment in developing+educating the mkt could benefit CRSP w/o loss of a bolus of pts, analysts at Jefferies wrote in a note to investors.

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Researchers Explore Respiratory Impact of Novel Therapies in SMA – AJMC.com Managed Markets Network

Saturday, November 7th, 2020

Short-term pulmonary outcomes of these medications are published and longitudinal monitoring is active, they wrote. Most studies have demonstrated favorable responses in overall muscle strength compared to natural history, but the pulmonary outcomes vary.

Studies included in the review revolved around 3 recently approved treatments:

Nusinersen

Although nusinersen has demonstrated efficacy on respiratory muscle function, the effect varies by SMA subtype, according to the researchers. They cited a study that found the treatment had little impact on patients with SMA1 A and B and had better response in patients with SMA1 C when it came to ventilatory and thoracoabdominal patterns.

Onasemnogene abeparvovec-xioi

In the pivotal phase 1 START trial for the gene therapy, survival data was striking, with an event-free survival of 100% without need for permanent ventilation at 20 months compared with the 8% event-free survival in natural history studies. Throughout the study, 83% (n = 10) of patients required at least 1 hospitalization for respiratory illness with increased length of noninvasive ventilation support, although no hospitalizations surpassed 8 days. Patients in the study had 1.4 respiratory-related hospitalizations per year, with a mean length of stay of 6.7 days.

According to the researchers, the study data suggest that overall pulmonary morbidity and consequent healthcare utilization may have decreased, but some patients may still require escalation of respiratory support during illnesses.

Other data, coming from the phase 3 STRIVE trial, the ongoing SPR1NT study, and real-world experience with the treatment in 3 tertiary centers in Ohio, have made the case for improved respiratory and nutritional outcomes with the gene therapy as researchers await long-term data.

Risdiplam

In the multicenter FIREFISH trial, 90% of the 21 patients were alive without permanent ventilation and rarely required hospitalized after 12 months of treatment. After 23 months, 81% were alive without permanent ventilation. All patients were able to swallow safely and most (95%) were able to be fed orally or with supplemental gastrostomy feeds.

Promising data have also emerged from the SUNFISH and JEWELFISH trials, both of which included patients with varying subtypes of SMA. The researchers also highlighted the RAINBOWFISH study, which is actively recruiting patients with SMA type 1. According to the researchers, the results of the study could be transforming to those with a neonatal diagnosis of SMA type 1.

Looking forward

Looking toward the future, the researchers of the review noted that monitoring of short- and long-term outcomes is still critical, as its still too early to determine sustained improvement in pulmonary outcomes. They add that currently available data come from a limited number of patients and emphasize the need for more multicenter trials to better validate the impact of novel treatments.

Reference

Paul G, Gushue C, Kotha K, Shell R. The respiratory impact of novel therapies for spinal muscular atrophy. Pediatr Pulmonol. Published online October 24, 2020. doi:10.1002/ppul.25135

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Orchard Therapeutics’ gene therapy Strimvelis linked to a leukemia case – FiercePharma

Tuesday, November 3rd, 2020

The potential of gene therapies as cures for some hard-to-treat genetic diseases can be very attractive. But one such product is now suspected of causing a serious safety problem.

Friday, Orchard Therapeutics said its Strimvelis treatment, approved by European authorities in 2016 to treatthe rare inherited condition ADA-SCID, has been linked to a patients leukemia.

Preliminary findings suggest this diagnosis may be attributable to an insertional event related to treatment with Strimvelis, the company said. Its now investigating whether theres indeed a causal relationship.

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Since its 2016 EU approvalwhen it was owned by original developer GlaxoSmithKlineonly 16 patients have been treated with Stimvelis. The patient who developed leukemia had apparently been treated under a GSK compassionate use program in 2016.

No more patients will get the therapy before the investigation is complete, Orchard said. The drug was never approved in the U.S.

ADA-SCIDis a condition marked by a mutation in the gene making the adenosine deaminase (ADA) enzyme, which is essential for maintaining normal white blood cells. ADA-SCID patients, with a dysfunctional immune system, have less than two years to live without effective intervention.

RELATED:Orchard licenses gene therapy tech from GSK

Strimvelis, originally developed by GSK and bought by Orchard in 2018, offers an option for patients who cant find a matched stem cell donor. It works by editing the patients own hematopoietic stem cells with the functional ADA gene. The cells arethen transferred back into the patient's bone marrow to mature and produce the normal ADA protein.

The therapy uses a gammaretrovirus as the vector to carry the gene. Problem is, retrovirus can incorporate their own genetic information into the human genome, causing unintended changes that can give rise to cancer. It is a known risk factor of gammaretroviral vector-based gene therapy and has been described as one of the important potential risks for Strimvelis in its EU approval.

Besides Strimvelis, Orchard is also developing OTL-101, which uses a lentivirus to insert a functional copy of the ADA gene into a patients cells. The drug is currently undergoing a registrational trial and has won breakthrough and orphan drug designations from the FDA.

All the gene therapy candidates in Orchards pipeline use lentiviral vectors that have been specifically designed to avoid insertional oncogenesis after administration, Orchard said, adding that no dangerous gene insertion has been reported around lentiviral vector-based stem cell gene therapy in any indication.

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Gene therapy may be able to restore vision – Genetic Literacy Project

Tuesday, November 3rd, 2020

In a normal eye, opsins are expressed by the rod and cone photoreceptors in the retina. When activated by light, the photoreceptors pulse and send a signal through other retinal neurons, the optic nerve, and on to neurons in the brain.

A variety of common eye diseases, including age-related macular degeneration and retinitis pigmentosa, damage the photoreceptors, impairing vision. But while the photoreceptors may no longer fully function, other retinal neurons (bipolar cells) remain intact. The team identified a way for bipolar cells to take on some of the work of damaged photoreceptors.

The beauty of our strategy is its simplicity, said Samarendra Mohanty, PhD, Nanoscope founder and corresponding author of a report on the mouse study that appears today in Nature Gene Therapy. Bipolar cells are downstream from the photoreceptors, so when the MCO1 opsin gene is added to bipolar cells in a retina with nonfunctioning photoreceptors, light sensitivity is restored.

The strategy could overcome challenges plagued by other approaches to retinal regeneration, according to the researchers. Gene replacement therapy has thus far worked principally in rare diseases that leave photoreceptors intact.

Under a best-case scenario, the therapy could help patients achieve 20/60 vision, according to the researchers; however, no one knows how the restored vision will compare to normal vision.

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Avantor Discusses Cell & Gene Therapy Production Trends Through the Lens of COVID-19 – PRNewswire

Tuesday, November 3rd, 2020

Avantor executives joined other industry leaders at virtual Cell & Gene Therapy Bioprocessing & Commercialization Conference

Panels discussed critical topics including process efficiency and scaling solutions

RADNOR, Pa., Nov. 2, 2020 /PRNewswire/ --Executives from Avantor Inc. (NYSE: AVTR), a leading global provider of mission-critical products and services to customers in the life sciences, advanced technologies and applied materials industries, recently provided expert insight at the Cell & Gene Therapy Bioprocessing & Commercialization Virtual Conference. Cell and gene therapy (C>) are two of the most revolutionary applications driving the biopharmaceutical industry.

In separate panel discussions with other global industry leaders, Dr. Ger Brophy, EVP, Biopharma Production at Avantor and Claudia Berrn, SVP, Business Development and Commercial Operations at Avantor, each addressed novel considerations and challenges facing the biopharmaceutical industry, including the impact of COVID-19. They highlighted innovation to help drive the creation and commercialization of life-changing, personalized C> treatments.

In a panel on the evolution of C> and the path toward scalability and manufacturability of these treatments, Dr. Brophy gave his perspective on this growing need for the bioprocessing industry.

"Genuine progress is being made in the long-standing battle to effectively treat and control disease, and cell & gene therapies will only continue to unlock new frontiers in medicine," said Dr. Brophy. "We're beginning to see more clearly the issues that need to be addressed, and know that if products are to scale and become more accessible to patients worldwide, there needs to be efficiency in operations. There is an absolute requirement for automation, both to reduce variability and to generate process efficiencies. At Avantor, we are ready to make the essential materials and technologies available to companies leading the charge and treating patients. Innovation and agility are central to how we're partnering with the industry to resolve these issues."

On a separate panel, Ms. Berrn highlighted how the industry is navigating the challenges and impact of the global pandemic, from the fragmentation of supply chains to clinical trial disruption.

"In this critical moment for the industry and the world, it is more important than ever for leaders in the cell & gene therapy community to come together to strategize and share ideas," said Ms. Berrn. "Avantor is actively working with the world's leading pharmaceutical and biotechnology companies to accelerate the production of novel treatments. Collectively, our goal is to mitigate any challenges in the process of taking a groundbreaking treatment from its initial scientific discovery to delivery in treating patients."

Avantor provides products for biopharma production workflows, including cell and gene therapy offering. Search 'Avantor biopharma' in your browser.

About AvantorAvantor, a Fortune 500 company, is a leading global provider of mission-critical products and services to customers in the biopharma, healthcare, education & government, and advanced technologies & applied materials industries. Our portfolio is used in virtually every stage of the most important research, development and production activities in the industries we serve. One of our greatest strengths comes from having a global infrastructure that is strategically located to support the needs of our customers. Our global footprint enables us to serve more than 225,000 customer locations and gives us extensive access to research laboratories and scientists in more than 180 countries.We set science in motion to create a better world. For information, visit avantorsciences.com and find us on LinkedIn, Twitter and Facebook.

Robert DonohoeSenior Director, Corporate CommunicationsAvantorM: 484-688-4730[emailprotected]

Source: Avantor and Financial News

SOURCE Avantor and Financial News

http://avantorsciences.com

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Euro Convergence: Early consultation critical in overcoming gene therapy hurdles – Regulatory Focus

Tuesday, November 3rd, 2020

When it comes to advancing gene therapy products in the United States and Europe, the key is early consultation with regulators and identification of potential problems, experts said at the Euro Convergence 2020 virtual meeting.

It is better to do it earlier and establish a collaborative and educational approach to discussions, advised Mridula Shukla, director of global regulatory affairs at Arcutis Biotherapeutics in Palo Alto, Calif. Patrick Celis, PhD, head of the scientific secretariat of the Committee for Advanced Therapies at the European Medicines Agency (EMA), echoed that advice.

Please talk to EMA and National Authorities early and frequently so that we can help you as much as possible to get these innovative products to the patients as soon as possible, Celis said.

There are currently more than 10 gene therapy products approved globally and momentum has been building in this area since around 2015, Shukla said.

Gene therapy seems to have potential as it offers the possibility of an actual cure instead of chronic treatment for rare diseases, hereditary diseases and cancer, Shukla said.

Despite the promise of the therapies, more than half of gene therapy clinical trials are in phase 1. Shukla said this is due to a combination of factors including the complexity of the therapies, the rare indications, the high price of the therapies and reimbursement issues, unique manufacturing and supply chain challenges and controversies surrounding the ethnics of the techniques.

There is guidance from the US Food and Drug Administration (FDA) to assist developers. In July 2018, FDA issued draft guidance on Human Gene Therapy for Rare Diseases, which was finalized in January 2020. The document offers advice on some common manufacturing challenges, including encouraging companies to establish critical process parameters (CPP) early on and establish and qualify a potency assay prior to conducting clinical trials.

The FDA recommends communication with its Office of Tissues and Advanced Therapies early in product development, even before submission of an investigational new drug (IND) application. The agency also offers an Initial Targeted Engagement for Regulatory Advice on CBER Products (INTERACT) meeting, which can be used to discuss specific product issues, Shukla said.

Overall, the recommended approach is to front-load as much development as possible, preferably prior to Phase 1, and to hold early interactions and frequent interactions with FDA or EMA, Shukla said.

In the US, there are also multiple options for expedited review of products, including:

These expedited processes are similar to programs available for advanced therapy medicinal products (ATMPs) in Europe, such as the priority medicines (PRIME) scheme, which offers early consultation and the potential for accelerated assessment.

Since 2009, the EMA has approved 17 ATMPs, of which 10 are gene therapy products, Celis said.

The common issues that come up with ATMP applications include a lack of experience with commercial manufacturing processes, finding a relevant potency assay, ensuring product consistency and challenges with consistent starting materials, according to Celis. Other problems that can lead to delays in authorization include a lack of randomization in trial design, an indication that doesnt reflect the patients in the trial, and limited data on safety and durability of response.

The nature of gene therapies and the small number of patients in clinical trials mean that sponsors often have difficulty showing long-term safety and efficacy in a robust patient population. While regulators dont expect the same level of data as with other traditional medicines, there is a need for early planning of post-authorization studies, Celis said.

The EMA is asking for a detailed post-authorization plan that can include follow-up of patients in the clinical trials, post-marketing trials, and post-authorization registry-based studies.

If a sponsor is using a registry, Celis said it is better to go with an established disease registry and to contact the registry early to find out what data is collected. Additionally, registries may not be a good basis for safety reporting, Celis said.

There are support mechanisms in place for ATMP developers including scientific advice, a meeting with the EMAs Innovation Task Force, and the PRIME program for medicines addressing unmet needs.

We can help, Celis said. Make sure that you make best use of what we can do.

For sponsors looking to market gene therapies globally, Celis said that the EMA and FDA are in frequent contact and are seeing many of the same issues as they review products. He encouraged developers to make use of this interaction between European and US regulators either formally, through parallel scientific advice, or informally.

Euro Convergence 2020

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ELEVECTA for AAV gene therapy vector production – Bioprocess Insider – BioProcess Insider

Tuesday, November 3rd, 2020

Pharmaceutical companies with gene therapies in their pipeline need to establish scalable production processes that can keep up with the increasing demand in terms of volume, quality and robustness, says CEVEC.

Gene therapies are seen as one of the most promising approach to treat life-threatening diseases with no therapeutic options and high medical needs. In addition, gene therapies are now advancing also into indications with larger numbers of patients, including Alzheimers and Parkinsons, thereby dramatically increasing the demand for viral vectors. As a result, pharmaceutical companies with gene therapies in their pipeline need to establish scalable production processes that can keep up with the increasing demand in terms of volume, quality and robustness.

CEVEC Pharmaceuticals, a German biotechnology company focusing on viral vector technologies, has developed and commercially launched ELEVECTA, a unique technology that enables fully scalable AAV manufacturing providing unprecedented process robustness and consistency in vector yield and quality.

One of the major bottlenecks in AAV vector production is volumes. Standard technologies have proven to be very hard or impossible to scale, as they are often based on adherent cell lines or require transient transfections or helper viruses.

While suspension cell lines are getting more and more common now, most processes still rely on transient transfection to bring the different AAV genes into the producer cells. The typical transient transfection process is complex and requires three different GMP-grade plasmids driving up the production costs. This is where ELEVECTA stableAAV producer cell lines come into play.

Figure 1: ELEVECTA, a revolutionary technology that enables fully scalable, stable viral vector manufacturing with unprecedented process robustness and consistency in vector yield and quality.

Based on a stable human suspension cell line, ELEVECTA enables full scalability in all types and formats of suspension bioreactors, from laboratory to commercial scale. ELEVECTA Producer Cell Lines reach titers of 1*1014 vg/l and more during a typical single-use suspension bioreactor run. CEVEC has now successfully scaled-up from 15 ml to 50 L bioreactors in a single step without any productivity loss, demonstrating the scalability and robustness of the process.

ELEVECTA Producer Cells contain all components required for AAV stably integrated into the cell. There is no need for cGMP plasmids, special transfection reagents and difficult-to-scale-up transfection protocols. Just one cell line which, after propagation and expansion to the desired cell titers, produces AAV vectors at high yields a process that resembles well-established production methods for recombinant proteins and monoclonal antibodies.

Figure 2: Cryo TEM picture from AAV particles derived from ELEVECTA Producer Cell Lines. The viral particles display an approximate size of 22 nm. Full particles are indicated by a black arrow, empty particles by a white arrow

AAV vectors can have different surface structures, so called serotypes, which in nature allow the virus to target specific cells in a body. For gene therapy applications viral serotypes can further be engineered to improve their tissue-specificity and safety. Every ELEVECTA producer cell line is custom-made and employs a specific natural or engineered capsid gene and the therapeutic gene of interest.

With this newly introduced technology, CEVEC is the leading technology provider for stable AAV producer cell lines. Its inherent scalability, process robustness and consistency in yield and quality provide the features that are needed to pave the way for the success of modern gene therapies in a broad range of indications.

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Novartis Expands Presence in Gene Therapy With Acquisition – Yahoo Finance

Tuesday, November 3rd, 2020

- By Barry Cohen

Novartis AG (NYSE:NVS) is expanding its gene therapy footprint by acquiring a venture capital-backed company focusing on treating vision loss that can lead to blindness.

The Swiss pharmaceutical giant will pay shareholders of Vedere Bio $150 million upfront, which could be boosted by $130 million more if the Cambridge, Massachusetts-based company's programs achieve several development milestones.

Novartis has made huge strides aimed at beefing up its gene therapy program. In 2018, the company bought AveXis for $8.7 billion, inheriting its spinal muscular atrophy therapy Zolgensma, and this year established partnerships with Dyno Therapeutics and Sangamo Therapeutics Inc. (NASDAQ:SGMO).

Vedere is trying to take naturally occurring, light-sensing proteins and use a special gene therapy method to inject them into a certain part of the eye. Once there, they will be sent to retinal cells that are still healthy to help improve the vision of patients, according to an article in BioPharma Dive.

Novartis thinks this approach has much broader uses. The company said the proteins, in conjunction with Vedere's delivery tools, could "vastly expand" the number of treatable patients with vision loss from photoreceptor death.

Investors should keep in mind that the Vedere treatments are still in the pre-clinical stage so a great deal of development still needs to be done. Working with the acquisition's scientists, Novartis is preparing to promptly begin human testing.

There could be an even bigger population the Vedere platform could address, beyond inherited eye disorders. That would be a new way to treat geographic atrophy, one of the more advanced forms of an age-related vision loss called dry age-related macular degeneration. The American Academy of Ophthalmology notes an estimated 15 million people in North America have AMD, the vast majority with the dry form.

Story continues

Following the close of the deal, Vedere Bio II will operate as a wholly independent entity from Novartis and Vedere Bio.

Novartis decided to get out of one area of the eye-care business when it spun off Alcon Inc. (NYSE:ALC) last year. The company said it wanted to concentrate on treating diseases of the eye, not eye-care products.

Novartis' eye drugs include Xidra, treating dry eye disease, and Beovu, which was recently approved for the wet form of AMD. Its third eye drug and the biggest producer is Lucentis, which had sales of $515 million in the third quarter. Xidra and Beovu combined to bring in revenue of about $151 million. Novartis' biggest competitor is the Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) drug Eylea, a multibillion-dollar annual seller.

The Novartis faithful are hoping for better days ahead. At about $90, the company's shares are pretty much where they were five years ago. On the plus side, its dividend yields nearly 4%.

Despite the stock being stuck in neutral, Wall Street seems to think Novartis is a good investment, with three recent buy ratings and just one hold. Analysts give it an average target price of more than $106, according to TipRanks

UBS analyst Laura Sutcliffe last month upgraded the stock to buy from hold, calling its valuation "compelling." She thinks new products in the pipeline will boost the company's annual earnings growth to a healthy 9%.

Disclosure: The author has no positions in any of the stocks mentioned in this article.

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Retinal Disorders Treatment Market: Advancements in Gene-therapy and Stem-cell Therapy to Bolster Market Growth – BioSpace

Tuesday, November 3rd, 2020

Retinal Disorders Treatment Market: Introduction

According to the report, the global retinal disorders treatment market was valued at US$ 9.18 Bn in 2019 and is projected to expand at a CAGR of ~7% from 2020 to 2030. Macular degeneration is of two types: wet age-related macular degeneration and dry age-related macular degeneration. Diabetic retinopathy is one of the common diabetic eye disorders characterized by damaged blood vessels in the retina. Damaged blood vessels and nerves lead to vision impairment, blurring of vision, and eye hemorrhage. If left untreated, it could lead to retinal detachment and blindness. In terms of indication, the global retinal disorders treatment market has been classified into macular degeneration, diabetic retinopathy, diabetic macular edema, and others. The macular degeneration segment has been bifurcated into dry macular degeneration and wet macular degeneration. Based on therapeutic class, the global retinal disorders treatment market has been categorized into anti-VEGF agents and others. In terms of dosage form, the global retinal disorders treatment market has been divided into gels, eye solutions, capsules & tablets, eye drops, and ointments.

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Based on distribution channel, the global retinal disorders treatment market has been segregated into hospital pharmacies, retail pharmacies, and online sales. Rise in prevalence of retinal disorders due to increase in geriatric patient population boosts the growth of the global retinal disorders treatment market. The U.S. dominated the global retinal disorders treatment market in 2019, and the trend is anticipated to continue during the forecast period. Well-established healthcare infrastructure and early adoption of advanced technologies are the factors expected to fuel the growth of the market in the region. Moreover, rise in prevalence of various types of retinal disorder leads to increase in demand for treatment.

China is likely to be a highly lucrative market for retinal disorders treatment during the forecast period. Diagnosis and treatment rates have increased due to a rise in disposable income and health awareness. This has led to an increase in the adoption of macular degeneration drugs

Rise in Prevalence of Retinal Disorders Due to Increase in Geriatric Patient Population to Drive Global Market

Age is a prominent risk factor for age-related macular degeneration. The risk of developing advanced age-related macular degeneration increases from 2% in people aged between 50 and 59 to nearly 30% for those over 75. The prevalence of other retinal disorders was 93 million people with diabetic retinopathy, 21 million people diabetic macular edema and 28 million people with vision-threatening diabetic retinopathy. Increase in R&D activities, rise in the number of patients suffering from diseases, and rapid expansion of healthcare and biopharmaceutical industries in developed and developing countries are projected to boost advancements in therapies in the AMD treatment market during the forecast period. For instance, Lucentis and Eylea accounted for 2.8% of total pharmaceutical sales in Canada in 2017.

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Macular Degeneration to Dominate Global Market

In terms of indication, the global retinal disorders treatment market has been divided into macular degeneration, diabetic retinopathy, diabetic macular edema, and others. Macular degeneration has been bifurcated into dry macular degeneration and wet macular degeneration. The macular degeneration segment dominated the market in terms of revenue in 2019. The rise in prevalence of macular degeneration is anticipated to drive the segment during the forecast period. For instance, the number of people living with macular degeneration is expected to reach 196 million globally by 2020 and increase to 288 million by 2040.

Anti-VEGF Agents to be Main Therapeutic Class

Based on therapeutic class, the global retinal disorders treatment market has been categorized into anti-VEGF agents and others. The anti-VEGF agents dominated the global retinal disorders treatment market in 2019. Major market products such as Avastin and Eylea are included in the anti-VEGF drug class. Increase in demand for these products in the treatment of retinal disorders and strong product pipeline are likely to drive the segment. However, the others segment, which includes anti-inflammatory drugs, is projected to expand at the highest CAGR from 2020 to 2030. The increase in the use of anti-inflammatory drugs for pain relief is anticipated to augment the segment.

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Eye Solutions to be Preferred Dosage Form

In terms of dosage form, the global retinal disorders treatment market has been divided into gels, eye solutions, capsules & tablets, eye drops, and ointments. The eye solutions segment dominated the global retinal disorders treatment market in 2019. However, the eye drops segment is expected to expand at the highest CAGR during the forecast period. The segment is likely to grow at a rapid pace due to increase in demand for eye drops for treatment of retinal diseases in emerging countries such have China, India, and Brazil.

Retail Pharmacies to Emerge as Major Distribution Channel

Based on distribution channel, the global retinal disorders treatment market has been segregated into hospital pharmacies, retail pharmacies, and online sales. The retail pharmacies segment dominated the market in terms of revenue in 2019 due to wide network, ease of access, and diverse product offerings, including prescription and OTC ophthalmic drugs. However, the shift toward the use of electronic payment modes is projected to boost the growth of the online sale segment during the forecast period.

U.S. to Dominate Global Market

The global retinal disorders treatment market has been segmented into five major regions/country: the U.S., Europe, China, Russia, and Rest of the World. The U.S. dominated the global market in 2019, followed by Europe. The U.S. accounted for a major share of the global retinal disorders treatment market in 2019. Well-developed healthcare infrastructure, high healthcare expenditure, and adoption of branded drugs to treat retinal disorder disorders are the key factors attributed to the countrys significant share of the global market.

The retinal disorders treatment market in China is anticipated to expand at a high CAGR from 2020 to 2030. There have been significant unmet medical needs in the region. Furthermore, healthcare expenditure is increasing in developing markets. Key players are making investments to establish their operations in China. This, in turn, is projected to augment the market in the country.

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Competition Landscape

Regeneron Pharmaceuticals, Inc., F. Hoffmann-La Roche Ltd., and Novartis AG are the three major companies operating in the global retinal disorders treatment market. The global retinal disorders treatment market is fragmented in terms of number of players. Key players in the global market include Allergan plc, Bayer AG, F. Hoffmann-La Roche Ltd., Graybug Vision, Inc., Kubota Pharmaceutical Holdings Co., Ltd., Novartis AG, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Santen Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Company Limited. New product development through robust R&D activities and mergers & acquisitions are key strategies adopted by these players to gain a competitive advantage in the global retinal disorders treatment market.

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Decibel Therapeutics Announces Exclusive Licensing Agreements for Hearing Loss Gene Therapy Technology | DNA RNA and Cells | News Channels -…

Tuesday, November 3rd, 2020

DetailsCategory: DNA RNA and CellsPublished on Monday, 02 November 2020 14:44Hits: 321

BOSTON, MA, USA I November 02, 2020 IDecibel Therapeutics, a clinical-stage biotechnology company developing novel restorative gene therapeutics to treat hearing loss and balance disorders, today announced exclusive license agreements with the University of Florida (UF) and the University of California, San Francisco (UCSF) for an adeno-associated virus (AAV) gene therapy technology designed to restore hearing to individuals with profound, congenital hearing loss caused by mutations in the otoferlin gene.

Otoferlin is a protein present in the inner hair cells of the cochlea that is critical for the communication between sensory cells of the inner ear and the auditory nerve by regulating release of neurotransmitters. People born with biallelic mutations in the otoferlin gene have profound hearing loss because this signal between the ear and the brain is lost. Decibel aims to restore functional otoferlin using gene therapy. A principal challenge is the size of the otoferlin gene, which is too large for the packaging capacity of AAV vectors. To overcome this challenge, Dr. William Hauswirth (UF), Dr. Omar Akil (UCSF), and collaborators employed a dual-vector approach to deliver the gene in two separate AAV vectors. This approach resulted in expression of the complete otoferlin gene, restored the signaling connection between the ear and the brain, and rescued normal hearing in a deaf, otoferlin-deficient mouse model.1

The dual-AAV gene therapy approach has shown significant promise in preclinical research as a method to deliver a large gene to the ear, said William Hauswirth, Ph.D., Professor of Ophthalmology at University of Florida. We were able to cure deafness in a mouse model and look forward to the potential of this technology in the development of a gene therapy to restore hearing in human patients.

The AAV-mediated gene therapy technology is jointly owned by UF and UCSF, and Decibel has secured exclusive licenses to the rights of the two universities in the intellectual property. The technology has been incorporated as a key component of Decibels lead gene therapy program, DB-OTO, for treatment of individuals lacking otoferlin.

Decibels precision gene therapeutic, DB-OTO, also incorporates proprietary, cell-specific regulatory control that restricts expression of the human otoferlin sequence to hair cells of the inner ear, thereby avoiding off-target expression. Decibel is developing DB-OTO in collaboration with Regeneron Pharmaceuticals.

There is a significant unmet need for therapeutics that can restore hearing in individuals with congenital, profound hearing loss. We believe AAV-mediated gene therapy is a modality well-suited to the ear, which could potentially have a major impact for patients, said Laurence Reid, Ph.D., Chief Executive Officer of Decibel. These important agreements support our goal to further advance our lead developmental gene therapy program, DB-OTO.

Terms of the agreement have not been disclosed.

1Akil et al. (2019) Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1817537116

About Decibel Therapeutics

Decibel Therapeutics is a clinical-stage biotechnology company focused on developing treatments that restore functional hair cells within the inner ear to treat disorders of hearing and balance. Leveraging industry-leading single-cell genomics capabilities and proprietary gene therapy technologies, Decibel has established the worlds first comprehensive research, discovery and drug development platform aimed at restoring hearing and balance function. Decibels pipeline, including its lead gene therapy program (DB-OTO) to treat congenital monogenic deafness and its ototoxicity prevention program, is designed to deliver on our vision of a world in which the privileges of hearing and balance are available to all. For more information about Decibel Therapeutics, please visit http://www.decibeltx.com or follow @DecibelTx.

SOURCE: Decibel Therapeutics

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Novartis buys a new gene therapy for vision loss, and this is one preclinical venture that didn’t come cheap – Endpoints News

Tuesday, November 3rd, 2020

Big Pharma execs usually dont just fade away. Sometimes, they jump to the money side of the biotech business, like Chris Viehbacher and Olivier Brandicourt. Some stick with a batch of mentoring board seats. Joe Jimenez not only plans to do both, hes also going biotech entrepreneur and starting his own play in style.

A week ago, Jimenez and his close partner Mark Fishman, who got to know each other well during their respective time as CEO and early-stage NIBR chief at Novartis, filed papers with the SEC noting that their Aditum Bio Fund I had raised the $133,040,000 they had targeted more than a year ago.

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Sloan Kettering Institute, Bluebird Bio in court trial over gene therapy deal – Crain’s Chicago Business

Tuesday, November 3rd, 2020

Then, Girondi claimed, Sloan Kettering mothballed his work to favor Bluebird, whose chief executivehad a prior business relationship with the cancer center's boss.

Girondis rage has been fueled by Bluebirds trajectory since then: its thalassemia treatment was approved last year by the European Union and at $1.8 million per patient will be among the most expensive.

In my neighborhood, theyd have gotten ball batted for similar behavior, said Girondi, a self-described former street tough from the South Side of Chicago whosbeen using such talk to describe his adversaries for years.

Now, Girondi is finally getting his day in court. Having survived years of legal challenges, which have portrayed his case as absurd and Girondi himself as erratic and ill-tempered, his trial began on Thursday.Errant is seeking hundreds of millions of dollars in damages, according to court filings.

The trial promises a rare glimpse into the not uncommonly messy marriage of medical researchers and for-profit companies, and it will showcase a slew of revealingdocuments and emails that have emerged in the court file, including one that Girondis lawyers described in court as the smoking gun.

Written in June 2010 by Nick Leschly, then interim president of Genetix Pharmaceuticals, which was renamed Bluebird Bio a few months later, the emailsaid:Pat Girondineed to shut him down.

The recipient of the email, another Genetix executive, responded by saying they need to be nice, suck up, etc. to Girondi, so they can review valuable data from a Sloan Kettering scientist with whom Errant was collaborating.

Both Sloan Kettering and Bluebird deny Errants allegations.

Sloan Kettering is vigorously defending itself in court, said Jorge Lopez, executive vice president and general counsel for Memorial Sloan Kettering Cancer Center, in a statement. We also disagree with EGTs characterizations of the case and of the Courts rulings. He declined further comment.

In court filings, Sloan Kettering has argued that Girondis company, called EGT for short,wasnt tricked but rather was short of money and repeatedly failed to meet obligations outlined in its deal.

The evidence shows that EGTs case is the fantasy of a defunct company and its founder that refuse to accept responsibility for their own failure, an attorney for Sloan Kettering Institute wrotein a July 8, 2019 filing.

Bluebirds attorney, Jeffrey Eilender, said the court record has disproved Errantsclaim of a conspiracy between Sloan Kettering Institute, referred to as SKI in court filings, and Bluebird, as well as an allegation that Bluebird gleaned secrets from Girondis company.

None of the evidence relied upon by EGT shows a material issue as to the ultimate fact: none suggests in any way that there was an agreement between Bluebird and SKI to defraud EGT, Bluebirds lawyers wrotein a July 8, 2019 court filing. In fact, EGT does not even explain how or why the facts it cites are relevant here (they are not); it just throws everything at the wall to see if it sticks.

As for Leschlys email saying that Girondi needed to be shut down, Eilender said it referred to Girondi,not the company. Why? Because with all due respect to Mr. Girondi, hes a nudnik, Eilender told the court at January 2019 hearing, explaining Girondi had becomea nuisance.

Leschly wasnt available for an interview, but he has previously expressed his opinions about Girondi and his firm.

Errant is toothless and the guy behind it is completely insane, truly, Leschly wrote in a 2012 email to an investment analyst.

Thalassemia is an inherited blood disorder in which the body doesnt produce enough hemoglobin, the substance in red blood cells that carriesoxygen. Moderate and severe, or beta,cases require frequent blood transfusions and can result in early death.

In 1992, Rocco Girondi was diagnosed with a more severe form of the blood disorder. He was two years old. The next year, Girondi retired from what he describes as a lucrative trading career to devote himself to finding a cure.

Girondi, 62, isnt your typical biotech entrepreneur. A high school dropout, he was listed as one of America's most eligible bachelors in Playgirl magazine in 1988 and appeared on the Oprah Winfrey Show in an episode on male chauvinists. (A copy of the show wasnt readily available; Girondi said he had defended both a mans and a woman's right to work, but believed one should stay home if they have children).A 1987 article about him in Chicago Magazine is entitled Fonzie Gets Rich. He left Chicago decades ago for Italy, where he occasionally performs in concert, playing blues and rock andthe occasional Italian ballad. But hestill speaks in the blunt, sometimes salty, manner of the Chicago neighborhood where he grew up.

He had some money at a time when few others showed interest in gene therapy. By 2000, Girondi began providing financial support to researchers at Sloan Kettering, including Dr. Michel Sadelain, who had brought thalassemia under control in mice, according to Errants complaint. Those researchers had developed a method to replace defective genes in thalassemia patients with a healthy copy. The plan used a modified virus known as a vector to deliver the genetic material into the cells.

At that time, gene therapy was relatively new and scarred by missteps, including a patient who had died after undergoing treatment. In 2005, Sloan Kettering granted a license to develop Sadelains potential gene therapy treatment to the only interested party, Errant Gene Therapeutics, according to the complaint.

Progress was slow and hampered by delays, according to Girondi and his lawyers. But by 2010, Errant had manufactured enough of the medicine to start clinical trials, his lawyers say in court papers.

Girondi said the relationship between his company and Sloan Kettering changedsoon after Craig Thompsons hiring as president and chief executive officer of Memorial Sloan Kettering Medical Centerwas announced in August 2010. By that fall, he said it was clear his company was on the outs.

It ended very strangely, Girondi said. I think thats the best way to say it.

Sadelain didnt respond to messages seeking comment.

Thompson, 67, had previously worked at the University of Pennsylvania, where he had been director of the Abramson Cancer Center. He also co-founded a company called Agios Pharmaceuticals in 2007with the goal of unlocking a new field of discovery in cellular metabolism.

Agiosreceived an infusion of $33 million from several venture capital firms in 2008 including Third Rock Ventures, where Leschly the future Bluebird CEO -- was a partner. Leschly also served as Agioss interim chief business officer,according to a 2010 Bluebird press release. A few months later, when Thompson began his job at Sloan Kettering, he was listed as being on Agioss scientific advisory board.

In September, 2010, Sloan Kettering asked Errant for physical possession of the vector to complete a study which it said was necessary to move forward with clinical trials, according to Errants lawyers. Errant delivered the vector and never got it back, the lawyers said.

Sloan Kettering said in court documents that by 2010, Errant had defaulted on its obligations, and that following arbitration and a new deal the following year, all rights granted to Errant in the 2005 deal reverted to Sloan Kettering.

Thompson started his job at Sloan Kettering in November, 2010. That same month,Sloan Ketteringmet with Bluebird and gave them a technical demonstration on Errants vector, sharing confidential information that served as a preludeto a more formal agreement the next year, according to Errants lawyers.

In November 2010, Bluebirds board of directors in 2010 weighedthe pros and cons of collaborating withSloan Kettering, according to Errants court filings. Among the positives? Eliminates the most threatening competitor, according to thepresentation, which is part of the court record.

Andrew Maslow, a former Sloan Kettering executive, said in an interview thathe made the decision to pursue a collaboration with Bluebird, not Thompson. One reason was the improving landscape for gene therapy, and another was Bluebirds capabilities, he said.

These guys are the real thing. They are totally capable, he said. They were just the opposite of Pat.

While Errant squabbled with Sloan Kettering, Bluebird continued to move toward commercialization of its treatment.

Bluebirds treatment for transfusion-dependent thalassemia patients, Zynteglo, was approved by the European Union last year, and the company plans to apply for U.S. approval in 2021. But thats just the beginning. The gene therapy is also intended foruseas a treatment for sickle cell disease(SCD). It could ultimately generate $1 billion a year in annual sales, according to Bloomberg Intelligence.

These therapies have the potential to transform the lives of patients with thalassemia and SCD,said Marc Engelsgjerd, a biotech analyst at Bloomberg Intelligence, who called the treatments groundbeaking.

Leschly, for one, has already benefited. He has pocketed roughly $78 million from stock sales since the company went public in 2013, according to data compiled by Bloomberg. Girondi and Sadelain have been left to contemplate what might have been.

We could have gotten an incredible product and a Nobel Prize, Sadelain said, in a May 2015 phone call that Girondi recorded, also part of the court file. And right now, we have nothing.

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Precision Medicines That Are Tailored and Off-the-Rack – Genetic Engineering & Biotechnology News

Tuesday, November 3rd, 2020

Precision medicines, such as cell therapies, remain expensive to manufacture and hard to access by patients. For example, Kymriah, the first chimeric antigen receptor (CAR) T-cell treatment approved in the United States, can have price tags as high as $475,000. Unfortunately, precision medicines are expensive to develop and manufacture, and the costs are ultimately borne by taxpayers and patients, according to The State of Personalized/Precision Medicine a report issued last year by GlobalData.

Today, companies are developing new models to lower the costs of manufacturing and bring drugs to more patients. Among them are companies developing new business models and services, innovative equipment for on-site manufacturing in hospitals, and improved formulation technology.

A key challenge for companies is scaling up the delivery of precision medicines, notes Janel Firestein, partner and life sciences industry leader at Clarkston Consulting. Companies supplying precision medicines are harvesting material for patients in a hospital or clinic, and then freezing or shipping it fresh to a contract manufacturing organization (CMO), contract development and manufacturing organization (CDMO), or other manufacturing entity.

What were seeing with a lot of our clients leveraging contract manufacturers is theyre contracting for specific slots, she says. They have x number of slots per week or month, and the scalability of that is hard.

Precision medicines are manufactured in small batches in accordance with genetic, environmental, and lifestyle factors, that is, for patients in subpopulations that meet certain well-defined criteria. (The subset of precision medicines known as personalized medicines are even more specific; that is, they are developed uniquely for each individual patient.) If a patient doesnt pass prescreening at the scheduled time, Firestein warns, the manufacturing slot for the patients treatment is lost unless the manufacturer can find another eligible patient.

Conversely, if the company is working across multiple CMOs in different countries, it needs to schedule slots in a predictable way. You need to know which slots are open, Firestein points out. You need to leverage automation and artificial intelligence to give a manufacturing view to physicians at the patient hub, so they know which dates are available and can ensure the patients cells are viable upon receipt at the manufacturing plant.

Orgenesis is among the companies turning to localization to deliver precision medicines to patients. The companys CEO and director, Vered Caplan, is a serial entrepreneur and among the top 20 inspirational leaders in advanced medicine listed in The Medicine Makers Power List 2020. Caplan has developed a point-of-care business model for hospitals that combines technological and biological development with a business strategy.

We see that centralized processing is very costly, she explains. It can be a solution for companies working in clinical trials, butonce you get to marketit is not feasible for large numbers of patients.

The companys Cell & Gene Therapy Biotech Platform incorporates the following elements: POCare Therapeutics, a pipeline of licensed cell and gene therapies (CGTs); POCare Technologies, a suite of proprietary and in-licensed technologies; and POCare Network, a collaborative, international ecosystem of research institutes and hospitals. This platform, the company asserts, is about decentralization, enabling precision medicines to be prepared on-site at hospitals.

The platform automates the production of precision medicines by validating closed box processes to reduce cleanroom footprints once the product gets to market. Caplan works to develop and commercialize drugs that can be licensed for use by hospitals in the Orgenesis network.

What we do is offer a low-cost supply platform with processing and regulatory solutions that are validated in a harmonized fashion, she details. Essentially, we take responsibility for R&D. Our hospitals are partners, and because were working in a network, the economic burden isnt high, and we can supply the therapy at a reasonable cost.

The Orgenesis approach doesnt follow the usual approach, which involves a hospital research center licensing its drug to a pharmaceutical company, which then pays the center for clinical trials. Instead, Orgenesis works in partnership with a partner hospital throughout the commercialization process. Production of the final product is automated and supplied via an on-site point-of-care processing unitreducing the complex logistics involved in transporting cells.

Fujifilm Diosynth Biotechnologies, a global CDMO, is developing a new platform to streamline the development of adeno-associated viruses (AAVs) for gene therapies. There are three methods to make AAVs, says Steve Pincus, PhD, the companys head of science and innovation. Two of the methods use viral vectors, and a third uses plasmids.

People using the latter need a source of cells and plasmids, he notes. Unfortunately, there are few licensable cell lines and few plasmid manufacturers. Consequently, as Pincus points out, If you want to manufacture your GMP plasmids at one of these, you have to wait 6 to 12 months to get in the queue.

Fujifilm wanted to tackle these problems, so it decided to license five different Rep-Cap plasmids, an adenovirus helper plasmid, and a human embryonic kidney 293 (HEK293) cell line for AAV production by plasmid transfection from Oxford Genetics. Pincus explains that by licensing these technologies, the company means to offer an HEK293 master cell bank that is well characterized and stocks GMP-grade Rep-Cap and helper plasmids, so that people can come and use those readily available reagents without having to wait 6 to 12 months, and so that the clients pay only for what they need.

To support the production of AAVs, Pincus and his team are developing specialized upstream and downstream processes. They are also developing in-process analytics for common problems in the AAV manufacturing space, such as measuring empty and full virus capsids.

Earlier this year, on September 8, Lonza announced that in a project at Sheba Medical Center in Israel, the first cancer patient received a CAR T-cell therapy that had been manufactured using the companys Cocoon platform. Cocoon is another model for distributed manufacturinga closed, automated piece of equipment for manufacturing cell therapies at the scale of a single patient, with a custom cassette that incorporates all the media, agents, and other consumables.

When you look at the way cell therapies are manufactured, one of the costs is cleanroom space, says Matthew Hewitt, PhD, head of clinical development and personalized medicine at Lonza. A cleanroom suite graded class B for air quality is noticeably more expensive than one graded class C, and the size of the room also matters. If you move to a closed or functionally closed automated platform like the Cocoon that has integrated cell culture, then you can move to cheaper cleanroom space, Hewitt asserts. or you can increase the manufacturing density in your existing cleanroom to use the space more efficiently.

Hewitt divides CAR T-cell manufacturing into a seven-step process: 1) collecting a patient sample; 2) preparing the sample for manufacturing; 3) activating the cells; 4) modifying (transducing) the cells; 5) expanding cell populations as needed for dosing; 6) washing, harvesting, and formulating the cells; and 7) dosing the patient. According to Hewitt, the steps currently automated by Cocoon include activation, transduction, and washing/harvesting/formulation. Additional automation features, he says, will debut in the coming months. Later this year, the company will begin beta testing automatic magnetic cell separation. Next year, the company plans to incorporate automated sample preparation into the Cocoons cassette.

Speaking on the future of manufacturing for precision medicine, Hewitt says he sees a role for both distributed and centralized models. Lonzas centralized facility in Houston, TX, for example, can offer standardized and well-controlled conditions, as well as an experienced team, for process development and early-stage activities.

Once you get to later stages, he points out, manufacturing needs to be moved toward the point of care to mitigate any issues with logistics. He adds that as cell therapies become more common, building enough space to process patient therapies at a centralized facility becomes increasingly impractical. Even if your centralized location served 50,000 patients a year, he says, the logistics would be a heroic endeavor.

Gene and cell therapies dont have much going on in terms of formulation, says Maria Croyle, PhD, professor of molecular pharmaceutics and drug delivery at the University of Texas at Austin. The formulation side needs to catch up.

She argues that even though precision medicines are often formulated just by adding glycerol to the cells, preparing precision medicines to dose the patient is often a complex process. When I talk about these therapies to my students, she relates, I explain that you need to thaw them out and do complicated dilutions. Its not as simple as adding 5 mL to a flask.

Precision medicines are often stored on-site in ultra-low-temperature (80C) freezers, devices that are, Croyle notes, expensive to run. The costs are often passed onto the patient. In addition, preparing the medications often involves lengthy dilution processes. Any of these medications that arent used within a couple of hours must be discarded, pushing costs yet higher.

Although some companies are moving to freeze-drying as a way to preserve living viruses and cells, preserving a live virus can take 48 to 72 hours. I had no idea until I talked to industry how much freezer dryers were a power drain, she recalls. They use a lot of electricity for 72-plus hours, and thats added to the cost of the drug.

Croyle has developed a method for stabilizing live viruses inspired by the film Jurassic Park, which depicted the recovery of dinosaur DNA from amber. She has three patents on a peelable film, inspired by amber, into which gene therapy or vaccine products can be suspended and dried within hours. You can mix them by 8 am, peel them by 3 pm, and package them to be sent off, she asserts. Its very simple and space savingits just a flat envelope with a strip of film, and it can be used in a variety of ways.

Film-packaged doses, she says, can be rehydrated to produce nasal-sprayable vaccines or injectable gene therapy solutions, or they can be placed under the tongue and upper cheek, where dissolution of the film surface releases the vaccine, activating an immune response. To commercialize the technology, she has founded Jurata Thin Film. The company is named after a mythical Lithuanian goddess who lived in an amber castle under the sea.

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Precision Medicines That Are Tailored and Off-the-Rack - Genetic Engineering & Biotechnology News

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Analysis of Recent Cell and Gene Therapy Innovations: 2020 Competitive Landscape Report – CD-19 is the Most Common Target Antigen for Allogeneic CAR-T…

Tuesday, November 3rd, 2020

DUBLIN, Oct. 28, 2020 /PRNewswire/ -- The "Competitive Landscape Analysis of Recent Cell and Gene Therapy Innovations" report has been added to ResearchAndMarkets.com's offering.

This research identifies some of the key developments across CAR-T cell therapies and provides insights across technological, IP, and investment landscapes. The study also provides an analysis of the competitive landscape while highlighting the key growth opportunities within the CAR-T cell therapy platform.

Key Topics Covered:

1.0 Executive Summary1.1 Research Focus: Emerging Technologies Enabling chimeric antigen receptor (CAR) T-cell Therapies1.2 Analysis Framework: The Author's Core Value1.3 Research Methodology: Five Steps Toward Success1.4 Key Findings of Technology Breakthrough Driving Sepsis Diagnosis

2.0 Technology Snapshot2.1 Rising Pace of Cell and Gene Therapy Approvals2.2 Regulatory and Ethical Perspectives on Gene Therapy2.3 Rising Demand for Precision Medicine Strategies2.4 Manufacturing Continues to be the Key Bottle Neck2.5 II Generation Chimeric Antigen Receptors Likely to Dominate the Cell Therapy Landscape in the Future2.6 CD-19 is the Most Common Target Antigen for Allogeneic CAR-T Therapies

3.0 Emerging Patent Landscape3.1 Steady Increase in Patent Grants for CAR-T Cell Therapies3.2 University of Pennsylvania and Novartis Lead the Patent Landscape for CAR-T Cell Therapies3.3 China and the US Lead the Patent Landscape for CAR-T Cell Therapies3.4 Snapshot of Key Patent Grants: Novartis3.5 Snapshot of Key Patent Grants: Cellectis and BlueBird Bio

4.0 Analysis of the Investment Landscape4.1 Key M&A Trends Across the Global Life Sciences Sector4.2 Gene Therapy - Venture Capital Funding Assessment4.3 Gene Therapy - Big Pharma In-licensing Deals Assessment4.4 Strategic Insights: Cell Therapies and Gene Therapies, Viral Vector CMOS

5. Analysis of the Competitive Landscape5.1 Allogene Therapeutics5.2 Precision BioSciences Inc.5.3 CRISPR Therapeutics AG5.4 Cellectis S.A.5.5 Celyad5.6 Bristol-Myers Squibb (BMS)5.7 Gilead5.8 Novartis5.9 BlueBird Bio5.10 Summary of the Scoring Methodology5.11 Competitive Analysis of CAR-T Participants

6.0 CAR-T Cell Therapies: Growth Opportunity Universe6.1 Growth Opportunity: CAR-T for Solid tumors, 2020

7.0 Industry Influencers

For more information about this report visit https://www.researchandmarkets.com/r/dgf6f3

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

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Analysis of Recent Cell and Gene Therapy Innovations: 2020 Competitive Landscape Report - CD-19 is the Most Common Target Antigen for Allogeneic CAR-T...

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BRIEFNovasep and Handl sign gene therapy product development and manufacturing deal – The Pharma Letter

Tuesday, November 3rd, 2020

Belgian companies Novasep and Handl Therapeutics have signed an agreement for the development and manufacturing of an adeno associated virus (AAV)-based gene therapy drug candidate for the treatment of neurodegenerative diseases.

Handl is developing multiple therapeutic AAV-based programs in collaboration with the Katholieke Universiteit Leuven, with the Center for Applied Medical Research of the University of Navarra, Spain, and with the Biomedical Neuroscience Institute of the University of Chile. The company is currently conducting invesrigational new drug (IND)-enabling pre-clinical studies.

Under the terms of the agreement, Novasep will develop and manufacture AAV vectors designed for these programs and will supply drug substance and drug product to support Handl Therapeutics preclinical and clinical studies.

Michael Linden, co-founder and head of research and development at Handl, said: We are excited to engage with Novasep to develop GMP manufacture capabilities for our novel gene therapies and are happy to have identified an outstanding partner right on our doorstep here in Belgium.

Cedric Volanti, Novaseps president of biopharma solutions, said: This new agreement recognizes Novaseps expertise in the field of viral vectors and will contribute to the important development of the cell and gene therapy market in Belgium.

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BRIEFNovasep and Handl sign gene therapy product development and manufacturing deal - The Pharma Letter

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