Archive for the ‘Gene Therapy Research’ Category
Atamyo Therapeutics Announces First Patient Dosed with ATA-100 Gene Therapy in LGMD-R9 Clinical Trial – Business Wire
EVRY, France--(BUSINESS WIRE)--Atamyo Therapeutics, a biotechnology company focused on the development of new-generation gene therapies targeting neuromuscular diseases, today announced the dosing with ATA-100 of a first patient in a phase 1/2 clinical study in FRKP-related limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9).
This is an exciting milestone for our company but most importantly, if this clinical trial is successful, it could have a life-changing impact for patients affected by LGMD-R9, said Stephane Degove, Chief Executive Officer and Co-Founder of Atamyo Therapeutics.
This clinical trial (EudraCT 2021-004276-33, NCT05224505) is a multicenter, Phase 1/2 study evaluating safety, pharmacodynamic, efficacy, and immunogenicity of intravenous ATA-100, a single-dose Adeno-Associated Virus (AAV) vector carrying the human FKRP transgene.
This study will consist of 2 phases: an open-label dose escalation phase (Stage 1) and a double-blind placebo controlled, randomized phase (Stage 2).
LGMD-R9 is a severe progressive and debilitating disease with no approved treatment, said Pr. John Vissing, Director of the Copenhagen Neuromuscular Center at the National Hospital, Rigshospitalet, in Copenhagen, where the first patient was dosed, and principal investigator of this trial. This experimental treatment represents a new hope for the patients. It is a great motivation to know that the work we are doing here has the potential to make a life-changing difference.
After the first patient dosed in Copenhagen, we are now expecting recruitments at the two other approved clinical sites (Paris, FR, and Newcastle, UK) to complete enrollment of the dose escalation phase (Stage 1) of the study. For Stage 2 (after dose selection), we plan to open additional clinical sites in Europe and in the United States, said Dr. Sophie Olivier, Chief Medical Officer of Atamyo.
About the LGMD-R9 program ATA-100
ATA-100 is a one-time gene replacement therapy for LGMD-R9/2I based on the research of Dr. Isabelle Richard, who heads the Progressive Muscular Dystrophies Laboratory at Genethon (UMR 951 INSERM/Genethon/UEVE). ATA-100 has been awarded Orphan Drug Designation status by the U.S. Food and Drug Administration and the European Medicines Agency.
LGMD2I/R9 is a rare genetic disease caused by mutations in the gene that produces fukutin-related protein (FKRP). It affects an estimated 5,000 people in the US and Europe. Symptoms appear around late childhood or early adulthood. Patients suffer from progressive muscular weakness leading to loss of ambulation. They also are prone to respiratory impairment and myocardial dysfunction. There are currently no curative treatments for LGMDR9.
About Atamyo Therapeutics
Atamyo Therapeutics is a clinical-stage biopharma focused on the development of a new generation of effective and safe gene therapies for neuromuscular diseases. A spin-off of gene therapy pioneer Genethon, Atamyo leverages unique expertise in AAV-based gene therapy and muscular dystrophies from the Progressive Muscular Dystrophies Laboratory at Genethon. Atamyos most advanced programs address different forms of limb-girdle muscular dystrophies (LGMD). The name of the company is derived from two words: Celtic Atao which means Always or Forever and Myo which is the Greek root for muscle. Atamyo conveys the spirit of its commitment to improve the life of patients affected by neuromuscular diseases with life-long efficient treatments. For more information visit http://www.atamyo.com
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Atamyo Therapeutics Announces First Patient Dosed with ATA-100 Gene Therapy in LGMD-R9 Clinical Trial - Business Wire
Why Philly ranks #2 among best cell and gene therapy hubs in the US – Technical.ly
Theres a handful of reasons why the Philadelphia region has been (perhaps unfortunately) dubbed Cellicon Valley in the last few years, and a new report from the Chamber of Commerce for Greater Philadelphia and economic consulting firm Econsult Solutions has IDd them all.
In the report, which looked at 14 large cell and gene therapy hubs in the US, Philadelphia ranked as the runner up, just behind Boston, as the top spot for research and innovation in this space. Other metro areas such as New York and San Francisco scored the third and fourth spots on the list. The report shouts out early local work, including the first FDA-approved gene (Luxturna) and cell (Kymriah) therapies developed here at Spark Therapeutics and the University of Pennsylvania, respectively.
The Philadelphia region is increasingly attracting new and expanding cell and gene therapy companies because it checks all the boxes, but its the regions research infrastructure as defined by NIH-funded cell and gene therapy research and its large number of research institutions that give it the edge, said Claire Marrazzo Greenwood, executive director and CEO of Council for Growth and SVP of economic competitiveness for the Chamber, in a statement.
The study compared cell and gene therapy hubs for their research infrastructure, human capital, innovation output, commercial activity and value proposition. Heres why Philly ranked high:
Because Philly is home to four Tier 1 universities, 93 higher ed institutions, and tons of hospitals and research institutions, it scored second in research infrastructure. The region scored first for most National Health Institute funding, and the report said 302 gene or cell therapy patents had been approved in the last decade. In 2021, the region was home to 15,400 jobs in pharmaceutical manufacturing, and it pulled in $4.2 billion in venture capital funding since 2018.
The talent coming from the high number of universities and colleges and more than 450,000 students in the region also ranked the region high for human capital. Of this, a whopping 54% stay in the region. R&D jobs in the field have also increased more than 100% in the last five years.
Philadelphia also scored high for its innovation output, meaning the region produces a large amount of intellectual property in the cell and gene therapy space. As the birthplace of the industry, the report says, the region is currently home to 302 granted patent and 130 clinical trials now underway.
The large amount of attention cell and gene therapy has gotten from investors in the last four years also ranked the region high in commercial activity. Within the past few years, two local cell and gene therapy companies Passage Bio and Cabaletta Bio have also completed IPOs, raising more than $260 million combined. Cell and gene therapy companies also make up a significant portion of Phillys commercial real estate, leasing about 12 million square feet, with about 9 million planned in construction projects.
And Philadelphias value proposition, or cost to do business, helped the region rank so highly, the report said. The region attracts families and talent with cultural institutions, culinary scene and schools. Plus, life sciences office space rentals (averaging about $58 per square foot) were very affordable next to cities like San Francisco (at $78 per square foot).
Greater Philadelphia is an extremely livable region, boasting some of the worlds best museums, top-notch restaurants, and large open spaces at a comparatively affordable price, Econsult said in its summary.
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Why Philly ranks #2 among best cell and gene therapy hubs in the US - Technical.ly
Gene Therapy Cell Culture Media Market Research Report is Likely to grow at a higher CAGR during the Forecast Period The Colby Echo News – The Colby…
Gene Therapy Cell Culture Media Market Research ReportThe global Gene Therapy Cell Culture Media industry research report provides an in-depth and methodical assessment of regional and global markets, as well as the most current service and product innovations and the global markets predicted size. The Gene Therapy Cell Culture Media research does a complete market analysis to find the major suppliers by integrating all relevant products and services in order to understand the roles of the top industry players in the Gene Therapy Cell Culture Media segment. The global Gene Therapy Cell Culture Media market also provides a thorough analysis of cutting-edge competitor research and new industry advancements, as well as market dynamics, challenges, restrictions, and opportunities, in order to give precise insights and the latest scenarios for appropriate judgments.
The gene therapy cell culture media market was valued at 152.67 million in 2019 and is expected to record a CAGR of 10.87% during the forecast period, 20202029.
Get FREE PDF Sample Copy of the Report @ https://straitsresearch.com/report/gene-therapy-cell-culture-media-market/request-sample
This report centers about the top players in global Gene Therapy Cell Culture Media marketplace:Lonza, HiMedia, GE Healthcare, FUJIFILM Irvine Scientific, R&D Systems, Inc. (Bio-Techne), Thermo Fisher Scientific and Sartorius AG.
This research study contains a SWOT analysis, significant trends, and a financial evaluation of the Gene Therapy Cell Culture Media and the global markets major competitors. Additionally, the Gene Therapy Cell Culture Media study provides a complete perspective of the Gene Therapy Cell Culture Media market and assists organizations in generating sales by providing a better knowledge of the leading competitors growth plans and competitive environment. This report includes a deep investigation of PEST and the industrys overall dynamics during the anticipated term. The research includes essential results as well as highlights of guidance and significant industry changes in the Gene Therapy Cell Culture Media industry, supporting market leaders in developing new tactics to increase income.
Top key industry segmentsBy Type: Lysogeny Broth, Chemically defined media, Serum free media, Specialty media, Stem cell media, Custom media, OthersBy End User: Pharmaceutical & Biotechnology companies, Academic institutions, Research laboratories, Others
The global Gene Therapy Cell Culture Media study also looks at industry trends, size, cost structure, revenue, potential, market share, drivers, opportunities, competitive environment, market challenges, and market forecast. This study also includes a complete and general review of the Gene Therapy Cell Culture Media industry, as well as in-depth industry variables that affect market growth. In addition to supply chain characteristics, key players current market conditions, and a generally discussed market pricing study, the Gene Therapy Cell Culture Media research contains insights on supply chain features, key players recent market situations, and a widely talked market price study. Aside from the acceptance rate, the global Gene Therapy Cell Culture Media market study shows the entire quantity of technical progress produced in recent years. It does a complete study of the Gene Therapy Cell Culture Media market using SWOT analysis.
Key Points Covered in the Report:
Reasons to Purchase this Report:
The Gene Therapy Cell Culture Media market analysis covers many of the important device developments that are now being used in the global sector. The end-user is primarily concerned with the production of global Gene Therapy Cell Culture Media market items, and market prices reflect this. Global Gene Therapy Cell Culture Media market operators, including regional and global companies, place work orders with global Gene Therapy Cell Culture Media market manufacturers. As a consequence, demand numbers for the global Gene Therapy Cell Culture Media market are derived from the perspective of end-users, based on their orders.
About Us:StraitsResearch is a leading research and intelligence organization, specializing in research, analytics, and advisory services along with providing business insights & research reports.Contact Us:Email: sales@straitsresearch.comTel: +1 6464807505, +44 203 318 2846
Sanofi partners with Scribe to gain gene editing tools for cell therapy work – BioPharma Dive
Sanofi will partner with the Californian biotechnology company Scribe Therapeutics in a deal that extends its exploration of new ways to build cancer cell therapies.
Under a partnership announced Tuesday, Sanofi will pay Scribe $25 million upfront to gain access to the five-year-old startups gene editing technology. The pharmaceutical company is also promising more than $1 billion in additional payments based on unspecified development and commercial milestones, although that money may never be paid out.
In return, Sanofi gets non-exclusive rights to use Scribes CRISPR-based gene editing technology to develop cancer treatments constructed from modified natural killer, or NK, cells. A type of immune defender, NK cells have drawn increasing interest from cancer drugmakers looking for alternatives to the T cells used in CAR-T treatments for leukemia, lymphoma and multiple myeloma.
This collaboration with Scribe complements our robust research efforts across the NK cell therapy spectrum and offers our scientists unique access to engineered CRISPR-based technologies as they strive to deliver off-the-shelf NK cell therapies and novel combination approaches that improve upon the first generation of cell therapies, said Frank Nestle, Sanofis head of research and chief scientific officer, in a statement.
Sanofi missed the first wave of cancer cell therapy development, which companies like Novartis, Gilead and, more recently, Bristol Myers Squibb have led. But it appears interested in making up ground with bets on newer technologies.
In November 2020, Sanofi bought Kiadis Pharma and its pipeline of donor-derived NK cell therapies. Five months later, the company acquired Tidal Therapeutics, which was attempting to use messenger RNA to reprogram immune cells in the body to attack cancers.
While a much smaller financial commitment, the partnership with Scribe could help Sanofi better develop NK cells therapies. Scribes gene editing technology relies on the CRISPR framework pioneered by its cofounder Jennifer Doudna, but the company has developed its own DNA-cutting enzymes, too.
Scribe raised $100 million in a Series B round last spring and in March hired ex-Barclays banker David Parrot as its chief financial officer. In an interview with CFO Dive, Parrot said he had been brought on to help eventually launch an initial public offering, but noted the company would focus first on inking partnerships as public markets remain cool to IPOs.
The deal with Sanofi is the second Scribe has disclosed publicly. Its also working with Biogen on a research collaboration focused on ALS and another undisclosed disease.
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Sanofi partners with Scribe to gain gene editing tools for cell therapy work - BioPharma Dive
BioMarin Resubmits Biologics License Application (BLA) for Valoctocogene Roxaparvovec AAV Gene Therapy for Severe Hemophilia A to the FDA – PR…
BLA Includes Substantial Body of Data from Pivotal Phase 3 and Ongoing Phase 1/2 Studies
If Approved, Would Be 1st Gene Therapy in U.S. for Treatment of Severe Hemophilia A
SAN RAFAEL, Calif., Sept. 29, 2022 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) announced today that the Company resubmitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for its investigational AAV gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A. The resubmission incorporates the Company's response to the FDA Complete Response (CR) Letter for valoctocogene roxaparvovec gene therapy issued on August 18, 2020, and subsequent feedback, including two-year outcomes from the global GENEr8-1 Phase 3 study and supportive data from five years of follow-up from the ongoing Phase 1/2 dose escalation study.
BioMarin anticipates an FDA response by the end of October on whether the BLA resubmission is complete and acceptable for review. Typically, BLA resubmissions are followed by a six-month review procedure. However, the Company anticipates three additional months of review may be necessary based on the number of data read-outs that will emerge during the procedure. If approved, valoctocogene roxaparvovec would be the first commercially-available gene therapy in the U.S. for the treatment of severe hemophilia A.
The FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to valoctocogene roxaparvovec in March 2021. RMAT is an expedited program intended to facilitate development and review of regenerative medicine therapies, such as valoctocogene roxaparvovec, that are expected to address an unmet medical need in patients with serious conditions. The RMAT designation is complementary to Breakthrough Therapy Designation, which the Company received for valoctocogene roxaparvovec in 2017.
In addition to the RMAT Designation and Breakthrough Therapy Designation, BioMarin's valoctocogene roxaparvovec also received orphan drug designation from the EMA and FDA for the treatment of severe hemophilia A. Orphan drug designation is reserved for medicines treating rare, life-threatening or chronically debilitating diseases. The European Commission (EC) granted conditional marketing authorization to valoctocogene roxaparvovec gene therapy under the brand name ROCTAVIAN on August 24, 2022 and endorsed the recommendation from the European Medicines Agency (EMA) to maintain orphan drug designation, thereby granting a 10-year period of market exclusivity in the European Union.
"We are pleased to reach this point in the development program for valoctocogene roxaparvovec and look forward to working with the FDA with the goal of bringing a potentially transformative therapy to people with severe hemophilia A in the United States," said Hank Fuchs, M.D., President of Worldwide Research and Development at BioMarin. "This large and robust data set provided in this BLA resubmission shows an encouraging efficacy profile. We remain committed to sharing these data with the public, along with even longer-term data generated through our ongoing clinical trials and any post-approval studies, to further our understanding of AAV gene therapy in severe hemophilia A and of gene therapies more broadly."
The resubmission includes a substantial body of data from the valoctocogene roxaparvovec clinical development program, the most extensively studied gene therapy for severe hemophilia A, including two-year outcomes from the global GENEr8-1 Phase 3 study. The GENEr8-1 Phase 3 study demonstrated stable and durable bleed control, including a reduction in the mean annualized bleeding rate (ABR) and the mean annualized Factor VIII infusion rate. In addition, the data package included supportive evidence from five years of follow-up from the 6e13 vg/kg dose cohort in the ongoing Phase 1/2 dose escalation study. The resubmission alsoincludesaproposedlong-term extension studyfollowingall clinicaltrialparticipantsfor up to 15years, as well astwo post-approval registry studies.
Robust Clinical Program
BioMarin has multiple clinical studies underway in its comprehensive gene therapy program for the treatment of severe hemophilia A. In addition to the global Phase 3 study GENEr8-1 and the ongoing Phase 1/2 dose escalation study, the Company is also conducting a Phase 3, single arm, open-label study to evaluate the efficacy and safety of valoctocogene roxaparvovec at a dose of 6e13 vg/kg with prophylactic corticosteroids in people with severe hemophilia A (Study 270-303). Also ongoing are a Phase 1/2 Study with the 6e13 vg/kg dose of valoctocogene roxaparvovec in people with severe hemophilia A with pre-existing AAV5 antibodies (Study 270-203) and a Phase 1/2 Study with the 6e13 vg/kg dose of valoctocogene roxaparvovec in people with severe hemophilia A with active or prior Factor VIII inhibitors (Study 270-205).
Safety Summary
Overall, to date, a single 6e13 vg/kg dose of valoctocogene roxaparvovec has been well tolerated with no delayed-onset treatment related adverse events. The most common adverse events (AE) associated with valoctocogene roxaparvovec have occurred early and included transient infusion associated reactions and mild to moderate rise in liver enzymes with no long-lasting clinical sequelae. Alanine aminotransferase (ALT) elevation, a laboratory test of liver function, has remained the most common adverse drug reaction. Other adverse reactions have included aspartate aminotransferase (AST) elevation (101 participants, 63%), nausea (55 participants, 34%), headache (54 participants, 34%), and fatigue (44 participants, 28%). No participants have developed inhibitors to Factor VIII, thromboembolic events or malignancy associated with valoctocogene roxaparvovec.
About Hemophilia A
People living with hemophilia A lack sufficient functioning Factor VIII protein to help their blood clot and are at risk for painful and/or potentially life-threatening bleeds from even modest injuries. Additionally, people with the most severe form of hemophilia A (Factor VIII levels <1%) often experience painful, spontaneous bleeds into their muscles or joints. Individuals with the most severe form of hemophilia A make up approximately 50 percent of the hemophilia A population. People with hemophilia A with moderate (Factor VIII 1-5%) or mild (Factor VIII 5-40%) disease show a much-reduced propensity to bleed. Individuals with severe hemophilia A are treated with a prophylactic regimen of intravenous Factor VIII infusions administered 2-3 times per week (100-150 infusions per year) or a bispecific monoclonal antibody that mimics the activity of Factor VIII administered 1-4 times per month (12-48 injections or shots per year). Despite these regimens, many people continue to experience breakthrough bleeds, resulting in progressive and debilitating joint damage, which can have a major impact on their quality of life.
Hemophilia A, also called Factor VIII deficiency or classic hemophilia, is an X-linked genetic disorder caused by missing or defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a new mutation that was not inherited. Approximately 1 in 10,000 people have hemophilia A.
About BioMarin
BioMarin is a global biotechnology company that develops and commercializes innovative therapies for people with serious and life-threatening genetic diseases and medical conditions. The Company selects product candidates for diseases and conditions that represent a significant unmet medical need, have well-understood biology and provide an opportunity to be first-to-market or offer a significant benefit over existing products. The Company's portfolio consists of eight commercial products and multiple clinical and preclinical product candidates for the treatment of various diseases. For additional information, please visitwww.biomarin.com.
Forward-Looking Statements
This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: BioMarin anticipating an FDA response by the end of October on whether the BLA resubmission is complete and acceptable for review, BioMarin's expectations regarding the duration of the review procedure, valoctocogene roxaparvovec being the first commercially-available gene therapy in the U.S. for the treatment of severe hemophilia A, if approved, BioMarin's commitment to sharing longer-term data generated through its ongoing clinical trials and any post-approval studies. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: the results and timing of current and planned preclinical studies and clinical trials of valoctocogene roxaparvovec; additional data from the continuation of the clinical trials of valoctocogene roxaparvovec, any potential adverse events observed in the continuing monitoring of the participants in the clinical trials; the content and timing of decisions by the FDA and other regulatory authorities, including decisions to grant additional marketing registrations based on an EMA license; the content and timing of decisions by local and central ethics committees regarding the clinical trials; our ability to successfully manufacture valoctocogene roxaparvovec for the clinical trials and commercially; and those and those factors detailed in BioMarin's filings with the Securities and Exchange Commission (SEC), including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.
BioMarin is a registered trademark of BioMarin Pharmaceutical Inc and ROCTAVIAN is a trademark of BioMarin Pharmaceutical Inc.
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Viral Vector Manufacturing, Non-Viral Vector Manufacturing and Gene Therapy Manufacturing Market by Scale of Operation, Type of Vector, Application…
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INTRODUCTION With the increasing number of cell and gene therapies being developed and launched for a wide range of therapeutic areas, these modalities are on their way to become one of the highest valued markets in the biopharmaceutical domain.
New York, Sept. 29, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Viral Vector Manufacturing, Non-Viral Vector Manufacturing and Gene Therapy Manufacturing Market by Scale of Operation, Type of Vector, Application Area, Therapeutic Area, and Geographical Regions : Industry Trends and Global Forecasts, 2022-2035" - https://www.reportlinker.com/p06323417/?utm_source=GNW In fact, in 2021, cell and gene therapy developers raised capital worth more than USD 20 billion, registering an increase of 19% from the amount raised in 2020 (~USD 17 billion). It is worth highlighting that, in February 2022, the USFDA approved second CAR-T therapy, CARVYKTI, developed by Johnson and Johnson, which can be used for the treatment of relapsed or refractory multiple myeloma. Additionally, close to 1,500 clinical trials are being conducted, globally, for the evaluation of cell and gene therapies. Over time, it has been observed that the clinical success of these therapies relies on the design and type of gene delivery vector used (in therapy development and / or administration). At present, several innovator companies are actively engaged in the development / production of viral vectors and / or non-viral vectors for cell and gene therapies. In this context, it is worth mentioning that, over the past few years, multiple viral vector and non-viral vector based vaccine candidates have been developed against COVID-19 (caused by novel coronavirus, SARS-CoV-2) and oncological disorders; this is indicative of lucrative opportunities for companies that have the required capabilities to manufacture vectors and gene therapies.
The viral and non-viral vector manufacturing landscape features a mix of industry players (well-established companies, mid-sized firms and start-ups / small companies), as well as several academic institutes. It is worth highlighting that several companies that have the required capabilities and facilities to manufacturing vectors for both in-house requirements and offer contract services (primarily to ensure the optimum use of their resources and open up additional revenue generation opportunities) have emerged in this domain. Further, in order to produce more effective and affordable vectors, several stakeholders are integrating various novel technologies; these technologies are likely to improve the scalability and quality of the resultant therapy. In addition, this industry has also witnessed a significant increase in the partnership and expansion activities over the past few years, with several companies having been acquired by the larger firms. Given the growing demand for interventions that require genetic modification, the vector and gene therapy manufacturing market is poised to witness substantial growth in the foreseen future.
SCOPE OF THE REPORTThe Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market (5th Edition) by Scale of Operation (Preclinical, Clinical and Commercial), Type of Vector (AAV Vector, Adenoviral Vector, Lentiviral Vector, Retroviral Vector, Plasmid DNA and Others), Application Area (Gene Therapy, Cell Therapy and Vaccine), Therapeutic Area (Oncological Disorders, Rare Disorders, Neurological Disorders, Sensory Disorders, Metabolic Disorders, Musco-skeletal Disorders, Blood Disorders, Immunological Diseases, and Others), and Geographical Regions (North America, Europe, Asia Pacific, MENA, Latin America and Rest of the World): Industry Trends and Global Forecasts, 2022-2035 report features an extensive study of the rapidly growing market of vector and gene therapy manufacturing, focusing on contract manufacturers, as well as companies having in-house manufacturing facilities. The study presents an in-depth analysis of the various firms / organizations that are engaged in this domain, across different regions of the globe. Amongst other elements, the report includes:An overview of the current status of the market with respect to the players engaged (both industry and non-industry) in the manufacturing of viral, non-viral and other novel types of vectors and gene therapies. It features information on the year of establishment, company size, location of headquarters, type of product manufactured (vector and gene therapy / cell therapy / vaccine), location of manufacturing facilities, type of manufacturers (in-house and contract services), scale of operation (preclinical, clinical and commercial), type of vector manufactured (AAV, adenoviral, lentiviral, retroviral, plasmid DNA and others) and application area (gene therapy, cell therapy, vaccine and others).An analysis of the technologies offered / developed by the companies enagaged in this domain, based on the type of technology (viral vector related platform, non-viral vector related platform and others), type of manufacturer (vector manufacturing, gene delivery, product manufacturing, transduction / transfection, vector packaging and other), scale of operation (preclinical, clinical and commercial), type of vector involved (AAV, adenoviral, lentiviral, retroviral, non-viral and other viral vectors), application area (gene therapy, cell therapy, vcaccine and others). It also highlights the most prominent players within this domain, in terms of number of technologies.A region-wise, company competitiveness analysis, highlighting key players engaged in the manufacturing of vectors and gene therapies, across key geographical areas, featuring a four-dimensional bubble representation, taking into consideration supplier strength (based on experience in this field), manufacturing strength (type of product manufactured, number of manufacturing facilites and number of application areas), service strength (scale of operation, number of vectors manufactured and geographical reach) and company size (small, mid-sized and large).Elaborate profiles of key players based in North America, Europe and Asia-Pacific (shortlisted based on proprietary criterion). Each profile features an overview of the company / organization, its financial performance (if available), information related to its manufacturing facilities, vector manufacturing technology and an informed future outlook.Tabulated profiles of the other key players headquartered in different regions across the globe (shortlisted based on proprietary criterion). Each profile features an overview of the company, its financial performance (if available), information related to its manufacturing capabilities, and an informed future outlook.An analysis of partnerships and collaborations established in this domain since 2015; it includes details of deals that were / are focused on the manufacturing of vectors, which were analyzed on the basis of year of partnership, type of partnership (manufacturing agreement, product / technology licensing, product development, merger / acqusition, research and development agreement, process development / optimization, service alliance, production asset / facility acquisition, supply agreement and others), scale of operation (preclinical, clinical and commercial), type of vector involved (AAV, adenoviral, lentiviral, retroviral, plasmid and others), region and most active players (in terms of number of partnerships).An analysis of the expansions related to viral vector and non-viral vector manufacturing, which have been undertaken since 2015, based on several parameters, such as year of expansion, type of expansion (new facility / plant establishment, facility expansion, technology installation / expansion, capacity expansion, service expansion and others), type of vector (AAV, adenoviral, lentiviral, retroviral, plasmid and others), application area (gene therapy, cell therapy, vaccine and others) and geographical location of the expansion.An analysis evaluating the potential strategic partners (comparing vector based therapy developers and vector purification product developers) for vector and gene therapy product manufacturers, based on several parameters, such as developer strength, product strength, type of vector, therapeutic area, pipeline strength (preclinical and clinical).An overview of other viral / non-viral gene delivery approaches that are currently being researched for the development of therapies involving genetic modification.An in-depth analysis of viral vector and plasmid DNA manufacturers, featuring three schematic representations, a three dimensional grid analysis, representing the distribution of vector manufacturers (on the basis of type of vector) across various scales of operation and type of manufacturer (in-house operations and contract manufacturing services), a heat map of viral vector and plasmid DNA manufacturers based on the type of vector (AAV, adenoviral vector, lentiviral vector, retroviral vector and plasmid DNA) and type of organization (industry (small, mid-sized and large) and non-industry), and a schematic world map representation, highlighting the headquarters and geographical location of key vector manufacturing hubs.An analysis of the various factors that are likely to influence the pricing of vectors, featuring different models / approaches that may be adopted by product developers / manufacturers in order to decide the prices of proprietary vectors.An estimate of the overall, installed vector manufacturing capacity of industry players based on the information available in the public domain, and insights generated via both secondary and primary research. The analysis also highlights the distribution of the global capacity by company size (small, mid-sized and large), scale of operation (clinical and commercial), type of vector (viral vector and plasmid DNA) and region (North America, Europe, Asia Pacific and the rest of the world).An informed estimate of the annual demand for viral and non-viral vectors, taking into account the marketed gene-based therapies and clinical studies evaluating vector-based therapies; the analysis also takes into consideration various relevant parameters, such as target patient population, dosing frequency and dose strength.A discussion on the factors driving the market and various challenges associated with the vector production process.A qualitative analysis, highlighting the five competitive forces prevalent in this domain, including threats for new entrants, bargaining power of drug developers, bargaining power of vector and gene therapy manufacturers, threats of substitute technologies and rivalry among existing competitors.
One of the key objectives of this report was to evaluate the current market size and the future opportunity associated with the vector and gene therapy manufacturing market, over the coming decade. Based on various parameters, such as the likely increase in number of clinical studies, anticipated growth in target patient population, existing price variations across different types of vectors, and the anticipated success of gene therapy products (considering both approved and late-stage clinical candidates), we have provided an informed estimate of the likely evolution of the market in the short to mid-term and long term, for the period 2022-2035. In order to provide a detailed future outlook, our projections have been segmented on the basis of scale of operation (preclinical, clinical and commercial), type of vector (AAV vector, adenoviral vector, lentiviral vector, retroviral vector, plasmid DNA and others), application area (gene therapy, cell therapy and vaccine), therapeutic area (oncological disorders, rare disorders, neurological disorders, sensory disorders, metabolic disorders, musco-skeletal disorders, blood disorders, immunological diseases, and others) and geographical region (North America, Europe, Asia Pacific, MENA, Latin America and rest of the world). In order to account for future uncertainties and to add robustness to our model, we have provided three forecast scenarios, namely conservative, base and optimistic scenarios, representing different tracks of the industrys growth.
The research, analysis and insights presented in this report are backed by a deep understanding of key insights generated from both secondary and primary research. For the purpose of the study, we invited over 300 stakeholders to participate in a survey to solicit their opinions on upcoming opportunities and challenges that must be considered for a more inclusive growth. The opinions and insights presented in this study were also influenced by discussions held with senior stakeholders in the industry. The report features detailed transcripts of interviews held with the following industry and non-industry players:Menzo Havenga (Chief Executive Officer and President, Batavia Biosciences)Nicole Faust (Chief Executive Officer & Chief Scientific Officer, CEVEC Pharmaceuticals)Cedric Szpirer (Former Executive & Scientific Director, Delphi Genetics)Olivier Boisteau, (Co-Founder / President, Clean Cells), Laurent Ciavatti (Former Business Development Manager, Clean Cells) and Xavier Leclerc (Head of Gene Therapy, Clean Cells)Alain Lamproye (Former President of Biopharma Business Unit, Novasep)Joost van den Berg (Former Director, Amsterdam BioTherapeutics Unit)Bakhos A Tannous (Director, MGH Viral Vector Development Facility, Massachusetts General Hospital)Eduard Ayuso, DVM, PhD (Scientific Director, Translational Vector Core, University of Nantes)Colin Lee Novick (Managing Director, CJ Partners)Semyon Rubinchik (Scientific Director, ACGT)Astrid Brammer (Senior Manager Business Development, Richter-Helm)Marco Schmeer (Project Manager, Plasmid Factory) and Tatjana Buchholz (Former Marketing Manager, Plasmid Factory)Brain M Dattilo (Business Development Manager, Waisman Biomanufacturing)Beatrice Araud (ATMP Key Account Manager, EFS-West Biotherapy)Nicolas Grandchamp (R&D Leader, GEG Tech)Graldine Gurin-Peyrou (Director of Marketing and Technical Support, Polypus Transfection)Naiara Tejados, Head of Marketing and Technology Development, VIVEBiotech)Jeffery Hung (Independent Consultant)
All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.
RESEARCH METHODOLOGYThe data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market may evolve across different regions and technology segments. Wherever possible, the available data has been checked for accuracy from multiple sources of information.
The secondary sources of information include:Annual reportsInvestor presentationsSEC filingsIndustry databasesNews releases from company websitesGovernment policy documentsIndustry analysts views
While the focus has been on forecasting the market over the period 2022-2035, the report also provides our independent view on various technological and non-commercial trends emerging in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant market gathered from various secondary and primary sources of information.
KEY QUESTIONS ANSWEREDWho are the leading players (contract service providers and in-house manufacturers) engaged in the development of vectors and gene therapies?Which regions are the current manufacturing hubs for vectors and gene therapies?Which type of vector related technologies are presently offered / being developed by the stakeholders engaged in this domain?Which companies are likely to partner with viral and non-viral vector contract manufacturing service providers?Which partnership models are commonly adopted by stakeholders engaged in this industry?What type of expansion initiatives are being undertaken by players in this domain?What are the various emerging viral and non-viral vectors used by players for the manufacturing of genetically modified therapies?What are the strengths and threats for the stakeholders engaged in this industry?What is the current, global demand for viral and non-viral vector, and gene therapies?How is the current and future market opportunity likely to be distributed across key market segments?
CHAPTER OUTLINES
Chapter 2 is an executive summary of the insights captured in our research. It offers a high-level view on the likely evolution of the vector and gene therapy manufacturing market in the short to mid-term, and long term.
Chapter 3 is a general introduction to the various types of viral and non-viral vectors. It includes a detailed discussion on the design, manufacturing requirements, advantages, limitations and applications of the currently available gene delivery vehicles. The chapter also features the clinical and approved pipeline of genetically modified therapies. Further, it includes a review of the latest trends and innovations in the contemporary vector manufacturing market.
Chapter 4 provides a detailed overview of close to 150 companies, featuring both contract service providers and in-house manufacturers that are actively involved in the production of viral vectors and / or gene therapies utilizing viral vectors. The chapter provides details on the year of establishment, company size, location of headquarters, type of product manufactured (vector and gene therapy / cell therapy / vaccine), location of manufacturing facilities, type of manufacturer (in-house and contract services), scale of operation (preclinical, clinical and commercial), type of vector manufactured (AAV, adenoviral, lentiviral, retroviral, plasmid DNA and others) and application area (gene therapy, cell therapy, vaccine and others).
Chapter 5 provides an overview of close to 70 industry players that are actively involved in the production of plasmid DNA and other non-viral vectors and / or gene therapies utilizing non-viral vectors. The chapter provides details on the the year of establishment, company size, location of headquarters, type of product manufactured (vector and gene therapy / cell therapy / vaccine), location of plasmid DNA manufacturing facilities, type of manufacturer (in-house and contract services), scale of operation (preclinical, clinical and commercial) and application area (gene therapy, cell therapy, vaccine and others).
Chapter 6 provides an overview of close to 90 non-industry players (academia and research institutes) that are actively involved in the production of vectors (both viral and non-viral) and / or gene therapies. The chapter provides details on the year of establishment, type of manufacturer (in-house and contract services), scale of operation (preclinical, clinical and commercial), location of headquarters, type of vector manufactured (AAV, adenoviral, lentiviral, retroviral, plasmid DNA and others) and application area (gene therapy, cell therapy, vaccine and others).
Chapter 7 features an in-depth analysis of the technologies offered / developed by the companies engaged in this domain, based on the type of technology (viral vector and non-viral vector related platform), purpose of technology (vector manufacturing, gene delivery, product manufacturing, transduction / transfection, vector packaging and other), scale of operation (preclinical, clinical and commerical), type of vector involved (AAV, adenoviral, lentiviral, retroviral, non-viral and other viral vectors), application area (gene therapy, cell therapy, vaccine and others) and leading technology providers.
Chapter 8 presents a detailed competitiveness analysis of vector manufacturers across key geographical areas, featuring a four-dimensional bubble representation, taking into consideration supplier strength (based on its experience in this field), manufacturing strength (type of product manufactured, number of manufacturing facilities and number of application area), service strength (scale of operation, number of vectors manufactured and geographical reach) and company size (small, mid-sized and large).
Chapter 9 features detailed profiles of some of the key players that have the capability to manufacture viral vectors / plasmid DNA in North America. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience and an informed future outlook.
Chapter 10 features detailed profiles of some of the key players that have the capability to manufacture viral vectors / plasmid DNA in Europe. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience and an informed future outlook.
Chapter 11 features detailed profiles of some of the key players that have the capability to manufacture viral vectors / plasmid DNA in Asia-Pacific. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience and an informed future outlook.
Chapter 12 features tabulated profiles of the other key players that have the capability to manufacture viral vectors / plasmid DNA. Each profile features an overview of the company, its financial performance (if available), information related to its manufacturing capabilities, and an informed future outlook.
Chapter 13 features in-depth analysis and discussion of the various partnerships inked between the players in this market, during the period, 2015-2022, covering analysis based on parameters such as year of partnership, type of partnership(manufacturing agreement, product / technology licensing, product development, merger / acquisition, research and development agreement, process development / optimization, service alliance, production asset / facility acquisition, supply agreement and others), scale of operation (preclinical, clinical and commercial) and type of vector (AAV, adenoviral, lentiviral, retroviral, plasmid and others) most active players (in terms of number of partnerships).
Chapter 14 features an elaborate discussion and analysis of the various expansions that have been undertaken, since 2015. Further, the expansion activities in this domain have been analyzed on the basis of year of expansion, type of expansion (new facility / plant establishment, facility expansion, technology installation / expansion, capacity expansion, service expansion and others), geographical location of the facility, type of vector (AAV, adenoviral, lentiviral, retroviral, plasmid and others) and application area (gene therapy, cell therapy, vaccine and others).
Chapter 15 highlights potential strategic partners (vector based therapy developers and vector purification product developers) for vector and gene therapy product manufacturers, based on several parameters, such as developer strength, product strength, type of vector, therapeutic area, pipeline strength (clinical and preclinical). The analysis aims to provide the necessary inputs to the product developers, enabling them to make the right decisions to collaborate with industry stakeholders with relatively more initiatives in the domain.
Chapter 16 provides detailed information on other viral / non-viral vectors. These include alphavirus vectors, Bifidobacterium longum vectors, Listeria monocytogenes vectors, myxoma virus based vectors, Sendai virus based vectors, self-complementary vectors (improved versions of AAV), minicircle DNA and Sleeping Beauty transposon vectors (non-viral gene delivery approach) and chimeric vectors, that are currently being utilized by pharmaceutical players to develop gene therapies, T-cell therapies and certain vaccines, as well. This chapter presents overview on all the aforementioned types of vectors, along with examples of companies that use them in their proprietary products. It also includes examples of companies that are utilizing specific technology platforms for the development / manufacturing of some of these novel vectors.
Chapter 17 presents a collection of key insights derived from the study. It includes a grid analysis, highlighting the distribution of viral vectors and plasmid DNA manufacturers on the basis of their scale of operation and type of manufacturer (fulfilling in-house requirement / contract service provider). In addition, it consists of a heat map of viral vector and plasmid DNA manufacturers based on the type of vector (AAV, adenoviral vector, lentiviral vector, retroviral vector and plasmid DNA) and type of organization (industry (small, mid-sized and large) and non-industry). The chapter also consists of six world map representations of manufacturers of viral / non-viral vectors (AAV, adenoviral, lentiviral, retroviral vectors, and plasmid DNA), depicting the most active geographies in terms of the presence of the organizations. Furthermore, we have provided a schematic world map representation to highlight the geographical locations of key vector manufacturing hubs across different continents.
Chapter 18 highlights our views on the various factors that may be taken into consideration while pricing viral vectors / plasmid DNA. It features discussions on different pricing models / approaches that manufacturers may choose to adopt to decide the prices of their proprietary products.Chapter 19 features an informed analysis of the overall installed capacity of the vectors and gene therapy manufacturers. The analysis is based on meticulously collected data (via both secondary and primary research) on reported capacities of various small, mid-sized and large companies, distributed across their respective facilities. The results of this analysis were used to establish an informed opinion on the vector production capabilities of the organizations by company size (small, mid-sized and large), scale of operation (clinical and commercial), type of vector (viral vector and plasmid DNA) and region (North America, Europe, Asia Pacific and the rest of the world).
Chapter 20 features an informed estimate of the annual demand for viral and non-viral vectors, taking into account the marketed gene-based therapies and clinical studies evaluating vector-based therapies. This section offers an opinion on the required scale of supply (in terms of vector manufacturing services) in this market. For the purpose of estimating the current clinical demand, we considered the active clinical studies of different types of vector-based therapies that have been registered till date. The data was analyzed on the basis of various parameters, such as number of annual clinical doses, trial location, and the enrolled patient population across different geographies. Further, in order to estimate the commercial demand, we considered the marketed vector-based therapies, based on various parameters, such as target patient population, dosing frequency and dose strength.
Chapter 21 presents a comprehensive market forecast analysis, highlighting the likely growth of vector and gene therapy manufacturing market till the year 2030. We have segmented the financial opportunity on the basis of type of vector (AAV vector, adenoviral vector, lentiviral vector, retroviral vector, plasmid DNA and others), application area (gene therapy, cell therapy and vaccine), therapeutic area (oncological disorders, rare disorders, neurological disorders, sensory disorders, metabolic disorders, musco-skeletal disorders, blood disorders, immunological diseases, and others), scale of operation (preclinical, clinical and commercial) and geography (North America, Europe, Asia Pacific, MENA, Latin America and rest of the world). Due to the uncertain nature of the market, we have presented three different growth tracks outlined as the conservative, base and optimistic scenarios.
Chapter 22 highlights the qualitative analysis on the five competitive forces prevalent in this domain, including threats for new entrants, bargaining power of drug developers, bargaining power of vector and gene therapy manufacturers, threats of substitute technologies and rivalry among existing competitors.
Chapter 23 provides details on the various factors associated with popular viral vectors and plasmid DNA that act as market drivers and the various challenges associated with the production process. This information has been validated by soliciting the opinions of several industry stakeholders active in this domain.
Chapter 24 presents insights from the survey conducted on over 300 stakeholders involved in the development of different types of gene therapy vectors. The participants, who were primarily Director / CXO level representatives of their respective companies, helped us develop a deeper understanding on the nature of their services and the associated commercial potential.
Chapter 25 summarizes the entire report, highlighting various facts related to contemporary market trend and the likely evolution of the viral vector, non-viral vector and gene therapy manufacturing market.
Chapter 26 is a collection of transcripts of the interviews conducted with representatives from renowned organizations that are engaged in the vector and gene therapy manufacturing domain. In this study, we spoke to Menzo Havenga (Chief Executive Officer and President, Batavia Biosciences), Nicole Faust (Chief Executive Officer & Chief Scientific Officer, CEVEC Pharmaceuticals), Cedric Szpirer (Former Executive & Scientific Director, Delphi Genetics), Olivier Boisteau, (Co-Founder / President, Clean Cells), Laurent Ciavatti (Former Business Development Manager, Clean Cells) and Xavier Leclerc (Head of Gene Therapy, Clean Cells), Alain Lamproye (Former President of Biopharma Business Unit, Novasep), Joost van den Berg (Former Director, Amsterdam BioTherapeutics Unit), Bakhos A Tannous (Director, MGH Viral Vector Development Facility, Massachusetts General Hospital), Eduard Ayuso, DVM, PhD (Scientific Director, Translational Vector Core, University of Nantes), Colin Lee Novick (Managing Director, CJ Partners), Semyon Rubinchik (Scientific Director, ACGT), Astrid Brammer (Senior Manager Business Development, Richter-Helm), Marco Schmeer (Project Manager, Plasmid Factory) and Tatjana Buchholz (Former Marketing Manager, Plasmid Factory), Brain M Dattilo (Business Development Manager, Waisman Biomanufacturing), Beatrice Araud (ATMP Key Account Manager, EFS-West Biotherapy), Nicolas Grandchamp (R&D Leader, GEG Tech), Graldine Gurin-Peyrou (Director of Marketing and Technical Support, Polypus Transfection), Naiara Tejados, Head of Marketing and Technology Development, VIVEBiotech) and Jeffery Hung (Independent Consultant)
Chapter 27 is an appendix, which provides tabulated data and numbers for all the figures in the report.
Chapter 28 is an appendix that provides the list of companies and organizations that have been mentioned in the report.Read the full report: https://www.reportlinker.com/p06323417/?utm_source=GNW
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Viral Vector Manufacturing, Non-Viral Vector Manufacturing and Gene Therapy Manufacturing Market by Scale of Operation, Type of Vector, Application...
The Future of AAV Gene Therapy Is Scalable – BioProcess Insider
Ryan Cawood, chief scientific officer, WuXi Advanced Therapies.
Cawood began by noting that WuXi Advanced Therapies supports clients throughout their journeys toward developing cell and gene therapies. With the acquisition of the UK-based contract research organization (CRO) Oxgene and its adenoassociated virus (AAV) and lentivirus platforms (known as the TESSA and XLenti platforms/technologies, respectively), WuXi Advanced Therapies now can scale processes up to good manufacturing practice (GMP) manufacturing through to commercial supply.
After describing the work that takes place in different company locations, Cawood focused on the TESSA technology, which provides a plasmid-free alternative for large-scale clinical manufacturing. Most AAV manufacturing is based on plasmid transfection. Not only are such processes expensive, but transfection can occur only at a certain cell density. Adenovirus can be used to manufacture AAV, and such processes are easy to scale up. However, they yield as much adenovirus as AAV, creating major downstream purification issues and raising product-contamination concerns. The goal of the TESSA technology is to use an adenoviral vector to manufacture AAV without contaminating the preparation. In the early phase of the adenoviral life cycle, genes in the AAV helper plasmid are expressed by cells to manufacture both AAV and adenovirus. But in late phases of the cycle, those genes induce cells to make unwanted adenovirus. The TESSA technology is designed to close down all of those late genes.
Cawood described how TESSA technology regulates the promoter that drives expression of structural proteins. The adenovirus titer is determined by the promoter that it represses, so the more the virus tries to make itself, the more it cripples itself. WuXi Advanced Therapies is working on different models of the technology and now has made TESSA rep-cap genes for all of the main serotypes that people work with. Production titers for one particular construct yielded 1 1012 gc/mL. TESSA rep-cap 1, 2, 4, and 5 showed significant improvements in productivity per cell in a suspension-based process for all the serotypes that the company has worked on generally 10-fold more than what is produced using a plasmid system. He also described how data from a cell line developed at WuXi AppTec showed improvement in packaging efficiencies.
Cawood noted that the US Food and Drug Administration (FDA) is increasing pressure on manufacturers to ensure absence of residual contaminants and confirm efficacy. WuXi Advanced Therapies has tested a number of different serotypes and compared the ability of those AAV particles to infect cells with AAVs made from the plasmid process. He illustrated work showing that in some cases, the particles were >10-fold more infectious when produced by TESSA technology than when induced by the plasmid-based process. In an example of scaling up the TESSA technology for AAV6 to 50 L, every cell in the population contained the adenoviral DNA after three days. Around 3% of the particles were able to infect a cell compared with 0.5%0.7% with the plasmid system. Before any purification, 66% of full particles were obtained in the bioreactor. Following purification, the number came to about 102%, and using analytical ultracentrifugation yielded 94.4% full capsids of pure AAV. In an example of scaling up the technology for AAV2, the yields were lower than in the bioreactor but still 20 higher than what was produced by the plasmid-based equivalent. In an alternative model, the company introduced the AAV genome into the chromosome of an HEK293 cell line. The cells were infected with just one TESSA vector, after which AAV was removed with purification.
Other examples illustrated how the technology increased AAV particle yields for all serotypes tested. It increased particle infectivity for a number of the serotypes, is safe and efficient, and removes dependency on transfection. It allows for a number of different operations in bioreactors that simply cant be done in a transfection-based process.
Cawood concluded by noting that the company provides materials that clients can access through evaluation in their own laboratories. WuXi Advanced Therapies also can construct specific TESSA vectors for clients.
Find More OnlineWatch the complete presentation online at https://bioprocessintl.com/sponsored-content/the-future-of-aav-gene-therapy-is-scalable.
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The Future of AAV Gene Therapy Is Scalable - BioProcess Insider
5 Life Science Companies Drive Innovation in Lone Star Bio – BioSpace
A single star may adorn the Texas state flag but the life sciences ecosystem is comprised of a galaxy of brightly shining companies such as FUJIFILM Diosynth Biotechnologies, Taysha Gene Therapies and Veravas developing innovative new medicines, diagnostics and medical devices.
The growth of the quickly rising Lone Star Bio life sciences hub is fueled by financial support from the state government in the form of the multi-billion dollar Cancer Prevention Research Institute of Texas fund and the drug discovery research coming out of the states universities. Baylor College of Medicine and Texas A&M headline the list of academic powerhouses.
Thats where it all begins. Most research that results in drug discovery generally starts at universities, said Andrew Strong, a partner at Houston-based Hogan Lovells, a legal firm representing biotech clients across Texas and the United States, in an interview with BioSpace.
Barry Burgdorf, also an attorney with Hogan Lovells, echoed Strongs statement. There is a ton of great IP spinning out of the universities, he said. That research is fueling a number of startups across the state, as well as legacy pharma companies that are licensing the developmental programs. That, in turn, is strengthening the ecosystem, Burgdorf noted.
Although the slowing economy is reducing expenditures of venture capital, Burgdorf and Strong agreed that in Texas, there has been no slowdown of new technologies being developed in the universities.
Texas is still very focused on growth [and] recruiting companies, Burgdorf said.
Real estate prices are also attractive to companies hoping to set up shop in Texas, especially when compared to other major U.S. hubs such as Boston and San Francisco.
Lower Cost Real Estate
The per-square-foot cost for space in the Boston area is approximately $95.57, according to Pete Briskman, executive managing director and co-lead for JLLs Mid-Atlantic life sciences practice. In the Bay Area, the per-square-foot cost is $82.41. This compares to $22 per square foot In Houston. Briskman said the difference is critical to companies as it can help them build out space and hire new employees.
He said companies used to have a mantra that the real estate costs were less significant than the science. When it comes to a place like Texas where a company is saving tens of millions of dollars, however, it becomes a real consideration.
Strong agreed with that assessment. He relayed that the CEO of a Boston area biotech told him real estate needs were taking up seven percent of its annual budget. The money can go much farther in Texas, he said.
Strong pointed to the August decision of Cellipont Bioservices to relocate to Texas from San Diego. Cellipont, a cell therapy contract development and manufacturing organization, plans to build a 76,000-square-foot facility in the state.
Strong was the founding chief executive officer of Kalon Biotherapeutics, a startup biotech spun out of the A&M system. He sold the company to FUJIFILM.
Strong pointed to the significant investments FUJIFILM has made. Those expenses are having a positive ripple effect across the region. For every one of the 1,000 FUJIFILM jobs in Texas with a salary of more than $80,000, six additional jobs have been created because of these investments, he said.
FUJIFILMs Ever-Expanding Footprint
Since its 2014 arrival in Texas, FUJIFILM Diosynth Biotechnologies (FDB)s contract manufacturing operations in College Station have rapidly expanded and changed the landscape of the ecosystem across the Brazos Valley region. The Japan-based company has invested hundreds of millions of dollars into its facility, expanding its offerings to bolster the development of gene therapies. The College Station facility has become the largest single-use CDMO production campus in the United States.
In 2019, FUJIFILM established anew Gene Therapy Innovation Center. One year later, the federal government selected the College Station facility to support COVID-19 vaccine candidate manufacturing at its Flexible Biomanufacturing Facility.
In December 2021, FUJIFILM announced another investment to expand its services in Texas and in June, it provided additional finances to expand its continuous processing technologies.
Gerry Farrell, chief operating officer at FDB Texas, told BioSpace thecompany's expansions within Texas have been supported by a strong partnership with state and local governments, as well as the universities.
Tayshas Gene Therapies for Rare and Orphan Diseases
Dallas-based Taysha started the year with disappointing news from its experimental gene therapy for Sandhoff and Tay-Sachs diseases, two forms of GM2 gangliosidosis. A patient treated with TSHA-101, a bicistronic vector, died. However, the patient did not succumb to complications from the gene therapy. They died after contracting a hospital-acquired methicillin-resistant staphylococcus aureus (MRSA) infection while being treated for COVID-19.
Although the death was related to the infection, the independent review board determined a review of the data was warranted.
In addition to TSHA-101, Taysha is also developing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system in both rare and large patient populations. In its quarterly financial report issued in August, the companyhighlighted positive momentum with its gene therapy for giant axonal neuropathy.
Taysha received orphan drug and rare pediatric disease designations from the FDA and orphan drug designation from the European Commission for TSHA-120, an AAV9 gene therapy. Data showed GAN patients treated with TSHA-120 have seen durable improvement and recoverability of sensory nerve amplitude potential (SNAP), a definitive clinical endpoint, the company noted in its announcement.
Taysha is also developing a gene therapy for Rett Syndrome. TSHA-102 is the first-and-only gene therapy in clinical development for Rett. It has also received orphan drug and rare pediatric disease designations from the FDA and has been granted orphan drug designation from the European Commission.
Veravas Antibody Detection Platform
Based in Austin, Veravas launched in 2017. The company has developed the VeraPrep Antibody Detection Platform. The platform uses proprietary magnetic beads to pre-analytically clean samples to remove problematic heterophilic and autoantibody interference, according to the company. The clean sample allows for better capture and measurement of targeted IgA, IgG and IgM immunoglobulins.
During the COVID-19 pandemic, Veravas used its platform to develop an antibody test for SARS-CoV-2.
Baylor Genetics' Pandemic Contributions
A pioneer in genetic testing, Houston-based Baylor Genetics offers a range of diagnostic sequencing and analysis. The company provides a full spectrum of cost-effective, genetic testing it claims leads to clinically relevant solutions.
Baylor offers whole exome and genome sequencing services that provide data for point mutations, insertions and deletions. Oncology testing can find mutation panels through next-generation sequencing.
The company also provides prenatal diagnostics, molecular diagnostics and cytogenetics.
During the height of the COVID-19 pandemic, Baylor launched a combination test for the SARS-CoV-2 virus, as well as influenza A and B.
Asuragen
Also based in Austin, molecular diagnostics company Asuragen, a Bio-Techne brand, provides streamlined solutions for genetics, oncology, controls and companion diagnostic needs.
One of Asuragens products is AmplideX, a genetic test for Fragile X syndrome, whichcauses mild to severe intellectual disability and is associated with autism spectrum disorder.
Beyond Fragile X, Asuragen offers a chronic myeloid leukemia monitoring kit.
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5 Life Science Companies Drive Innovation in Lone Star Bio - BioSpace
NeuroVoices: Emma Ciafaloni, MD, on the Vast Expansion of Innovative Approaches to Duchenne Muscular Dystrophy – Neurology Live
Duchenne muscular dystrophy (DMD) was first described by the French neurologist Guillaume Benjamin Amand Duchenne in the 1860s, though it took until 1986 for researchers to identify a particular gene flaw that leads to the condition. The identification of the dystrophin gene by Louis Kunkel and Jerry Louis opened the door for disease-modifying therapies such as exon-skipping, stop codon readthrough, gene therapy, and CRISPR/cas9 mediated gene editing that focus in on dystrophin restoration.
Currently, there are 4 drugs approved in the United States for mutations amenable to skipping of exons 51, 53, and 45, which are applicable to about 30% of patients total with DMD. Each of these were approved through the accelerated approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases. At the recently concluded 2022 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) annual meeting, September 21-24, in Nashville, Tennessee, Emma Ciafaloni, MD, gave the Reiner Lecture to a crowd of a few hundred clinicians, highlighting new treatments for DMD.
In her talk, she summarized the expanding pipeline of agents for DMD, how each differs mechanistically, and whether any are more advantageous than another. Ciafaloni, a professor of neurology and pediatrics at the University of Rochester Medical Center, also discussed how to translate new treatments from trials to clinics, the need to improve clinical trial design and process, and how researchers can build on previous successes. Prior to her presentation, as part of a new NeuroVoices, Ciafaloni provided commentary on several topics regarding the DMD pipeline, including the differences and advantages each approach brings, as well as ways to overcome complexities with conducting clinical trials.
Emma Ciafaloni, MD: The exciting research development in the field of Duchenne muscular dystrophy is extraordinary. Many years after understanding the pathophysiology of Duchennewhich the gene wasnt discovered until the late 1980sall that knowledge is finally paying off and opening a window on therapeutic strategies that have to do with disease-modifying gene editing. There are many different approaches now, some like exon skipping, which are already used in the clinics. Some are different stages of development, such as gene therapy in phase three trials. I would be surprised if we didnt have a gene therapy drug in the clinic in the near future. And then CRISPR, which has not been used yet in humans, but has made major milestones and proof of concept in animal models that are highly promising. These are all strategies that are advancing very rapidly, I think that the field is moving much faster than in the past because of the collaboration between pharma and academia, and the patients and the families. There are many clinical trials in Duchenne, and it's a very exciting time.
Also, there has never been a time before in muscular dystrophies in general, not just Duchenne, where there were so many different, new ideas, as well as old ideas that finally started working in humans. The second part of my talk briefly covered other treatments, ideas and strategies that are not directed to restoration of dystrophin. They're not genetic treatments, but they work more on the downstream pathology of muscle degeneration into Duchenne, like the fibrosis, inflammation, and regeneration. There are some interesting drugs out there, probably a few that are going to be approved soon. We're looking at probably a multifactorial type of treatment, it may be a combination treatment. It's never been a richer time in terms of treatments for Duchenne. Also, it's exciting because some of the lessons learn, for example, with the genetic treatments, are extremely helpful for the larger field of neuromuscular diseases and even neurology. The learning has been fantastic.
With spinal muscular atrophy leading the way, we're moving into more muscle-based diseases [with gene therapy], but the lessons learned are still very valuable. Additionally, we have seen this collaboration between different sponsors, pharmaceuticals, and academias to share the learning, because that's just going to help move things faster and better and in a safer way. That is a positive phenomenon that is unprecedented, and it's helping to accelerate the science in a safe and effective way.
There are still many questions that remain. All these genetic modification approaches have been exon skipping, or gene therapy replacement. They don't replace the full-length dystrophin because it's a very large gene. It's a biologically modified type of dystrophin, so there is no doubt that it will have a profound benefit, but I think that there is plenty of room for improvement. Obviously, gene therapy is not approved yet, so remains to be seen in terms of clinical improvement. But even in the exon skipping, I think that we're going to see much more exciting next generation, exon-skipping that people are currently working on very hard on. The field of science and medicine always evolves. What we have now is only going to be much better down the road in a few years. I have no doubt, and the community of Duchenne is working very hard to make even the drugs that we have now, better.
Sometimes, for the more general neurologist or certainly for the general public, it's important to remember that when we talk about Duchenne muscular dystrophy, or many of our neuromuscular diseases that we discuss here at AANEM, these are also rare diseases. The definition from the FDA for a rare disease is less than 200,000 total patients in the United States. For Duchenne, for example, we're talking about maybe around 12,000 patients. This is not [multiple sclerosis], or Parkinson disease or Alzheimer disease. There are challenges in clinical trial designs that are unique, and they need to be understood. Some of the accelerated approval for some of these drugs is part of that challenge and difference. For example, especially with the genetic approach, some of these genetic approaches like exon skipping, only target a specific mutation in maybe 10% to 13% of patients. Now you're taking a subgroup of an ultra-rare disease that is only 10% of that population. Then you need to run clinical trials that are going to have a chance to prove a difference, and so, you restrict the inclusion criteria to a specific age. Then you're really challenged to find enough patients to do well in a placebo-controlled trial. It's important to keep that in mind that there is plenty of room for improvement in making our rare disease clinical trial design more effective, less time consuming for patients, and improving the approval path.
I also want to say that in Duchenne, the amount of data that has been produced in the past several years in terms of motor endpoints, natural history, the six-minute walk test, the North Star [Ambulatory Assessment], etc. These outcome measure prospective cohorts have been incredibly invaluable. This is just to recognize the incredible amount of work that researchers and families and patients have done in the past several years that is helping the field immensely. We are at a different time, its an exhilarating, exciting time. I think that the community of rare diseases like Duchenne have been incredibly, hard-working in a good, cohesive way to advance the field forward, which is very refreshing.
Transcript edited for clarity. Click here for more NeuroVoices.
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NeuroVoices: Emma Ciafaloni, MD, on the Vast Expansion of Innovative Approaches to Duchenne Muscular Dystrophy - Neurology Live
NeuShen Therapeutics Closes Pre-A Financing with ~$20M – BioSpace
SHANGHAI, Sept. 29, 2022 /PRNewswire/ -- NeuShen Therapeutics, Inc., a biotechnology company focusing on developing innovative treatments for central nervous system (CNS) disorders with dual platforms of AAV-based gene therapy and small molecule discovery, announced today the closure of ~$20 million Series pre-A financing led by LAPAM, a China based venture capital. NeuShen was founded by a group of industrial executives who have extensive global experiences in central nervous system (CNS) drug development. The new capital will be used to expand the team and catalyze in-house CNS drug discovery in both the US and China.
"The successful completion of this fundraising is a testimony to our team's ability to accomplish CNS drug development and jump starts our discovery engine to build a pipeline with AAV-based gene therapy and small molecule programs," said Joan Shen, M.D., Ph.D., chief executive officer and founder of NeuShen. "CNS disease is an area with huge unmet needs. Our company has had a very clear goal from Day 1, which is to develop novel therapies to relieve the burdens of patients with CNS disorders. In the past few months, we have developed an achievable R&D strategy and built-up a substantial core team with experienced CNS drug hunters. Significant progress has been made in building the internal small molecule pipeline and new AAV gene therapy programs. In addition, multiple collaborations and partnerships have been discussed and established."
CNS disorders are increasingly recognized as major causes of death and disability worldwide while the diagnosis and treatments have largely lagged. Urgent measures are needed to tackle the growing challenges. "Bringing breakthroughs and learnings from other disease targets such as ophthalmology, oncology and hematology, we believe AAV-based gene therapy represents a new opportunity in the treatment of CNS disorders. My colleagues and I at Horae Gene Therapy Center are looking forward to working with Neushen to explore these treatment opportunities. The experiences of NeuShen team in neurosciences will be critical to make this happen," noted Dr. Guangping Gao, Professor, Director, Horae Gene Therapy Center, UMass Chan Medical School. The collaborations between NeuShen and UMass are currently in discussion, which will include multiple projects in CNS gene therapy.
"We are very excited to partner with NeuShen from the beginning. Lapam Capital has a strong commitment to healthcare, and we believe the CNS therapeutic area will attract more investment, considering the huge unmet needs and scientific advancements in the field. We highly value Dr. Joan Shen and her management team for their expertise. Lampam Capital is confident with NeuShen's ability to be a top player in developing innovative therapies for CNS diseases," said Mr. Zhihua Yu, Managing Director of Lapam Capital.
"Dr. Shen has assembled a pre-eminent group of scientists, clinicians and drug developers to build a global biotech developing novel medicines for unmet needs in CNS therapeutic areas. TTM Capital are excited to support Neushen to build its multi-modality pipelines to help patients worldwide," said Ms. Lilly Zhang, founding and managing partner at TTM Capital.
About NeuShen Therapeutics
NeuShen Therapeutics is a biotechnology company focusing on innovative drug research and development to address CNS disorders, applying dual research platforms, including AAV-based gene therapy and small molecule discovery. With operations both in Shanghai, China and Boston, MA, NeuShen has a world-class team and is honored to be advised by an outstanding Board of Directors and Scientific Advisory Board.
About Lapam Capital
Headquartered in Beijing, Lapam Capital is a leading healthcare venture capital firm in China. Lapam is currently managing five RMB funds and one USD fund, with more than 10 billion RMB under management. Lapam Capital focuses on investments in early to middle stage fast-growing companies that have innovative pharmaceuticals and medical devices. It has invested in about 60 biopharmaceutical companies and 10 medical device companies to date, including Betta Pharma, RemeGen Co. Ltd., Clover Biopharmaceuticals, Yahong Meditech, Stemirna Therapeutics, Binhui Biotech, ImmuneOnco Biopharmaceuticals, Biostar Pharmaceuticals, Aibo Medical Robot Co. Ltd. and many other companies with great potential. Lapam Capital has a professional investment team with more than 20 years' international and domestic biopharmaceutical industry R&D and management experience and can provide comprehensive value-added supports for the invested companies.
About TTM Capital
TTM Capital is an investment firm that specializes in China and worldwide healthcare industry. We focus on early and growth stage companies including pharmaceutical, biotech and medical technology sub-sectors.
TTM Capital's team consists of experienced global vision investment professionals with extensive industry experience, who work together to achieve superior and consistent returns for the firm's investors. We are committed to accumulating industry experience over time, with the aim to develop an ecosystem of expertise to create transformative healthcare businesses.
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NeuShen Therapeutics Closes Pre-A Financing with ~$20M - BioSpace
Epigenetic therapy promotes spinal cord regeneration in mice following injury – RegMedNet
Presently, there are no effective therapies for spinal cord damage. Physical therapy can help patients regain some movement, but the outcomes are heavily limited in severe cases due to the inability of spinal neurons to repair organically after injury.
However, in a study published in the journal PLOS Biology, Simone Di Giovanni and his research team at Imperial College London (United Kingdom) have looked to change this roadblock. The team displayed how weekly treatments that contain an epigenetic activator can help the regeneration of motor and sensory neurons in the spinal cord, when administered to mice 12 weeks after a serious injury.
Using a small molecule known asTTK21, theresearchers were able to trigger genetic programming that stimulates axon regeneration in neurons. TTK21 affects gene epigenetics via activating the CBP/p300 family of coactivator proteins.
TTK21 therapy was investigated in micemodels where the specimen had experiencedsevere spinal cord damage. The mice were raised in an enriching environment that allowed them to be physically active, as is recommended for human patients.
The treatment started 12 weeks after the severe spinal cord damage and lasted 10 weeks. Researchers discovered numerous improvements following TTK21 therapy when compared to the control treatment. Increased neuron sprouting in the spinal cord was the most noticeable effect. The researchers additionally found that motor axon retraction above the site of injury stopped and sensory axon development sharply increased. These changes were most likely caused by the observed increase in gene expression associated with regeneration. The next stage will be to further increase these effects to stimulate the regenerated axons to reconnect with the rest of the nervous system, so that the mice regain the capability to may move freely again.
Di Giovanni goes on to emphasize, This work shows that a drug called TTK21 that is administered systemically once/week after a chronic spinal cord injury in animals can promote neuronal regrowth and an increase in synapses that are needed for neuronal transmission. This is important because chronic spinal cord injury is a condition without a cure where neuronal regrowth and repair fail. We are now exploring the combination of this drug with strategies that bridge the spinal cord gap such as biomaterials as possible avenues to improve disability in spinal cord injury patients.
Press release:https://www.eurekalert.org/news-releases/964425
See more here:
Epigenetic therapy promotes spinal cord regeneration in mice following injury - RegMedNet
Pittsburgh Project to Pave Way for Technology to Revolutionize Treatment of Fatal Brain Diseases – timesobserver.com
PITTSBURGH A collaborative group of neuroscientists from the University of Pittsburgh School of Medicine and Carnegie Mellon University received a $6.8 million grant from the National Institutes of Health Brain Research Through Advancing Innovative Neurotechologies (BRAIN) Initiative to create an ultra-high resolution molecular atlas of the brain and develop brain cell type-specific strategies for effective and precise gene delivery.
The research will leverage genetic information resolved with single-cell precision to establish a comprehensive database of cell types and neural circuits comprising the brains cognitive and reward systems. In combination with ultra-high-resolution magnetic resonance imaging (MRI), the researchers intend to build brain atlases of marmosets and macaque monkeys and make them available to other neuroscientists across the world, free of charge.
This award enables cross-disciplinary collaboration between experts in neural imaging, gene therapy, machine learning, and molecular biology to advance our understanding of single-cell level organization of the brains essential systems, said project principal investigator Dr. William Stauffer, assistant professor of neurobiology at Pitt. We hope this unmatched degree of precision will eventually pave the way for the development of effective and precise gene editing technologies that might revolutionize treatment of previously fatal diseases, such as Alzheimers or Parkinsons.
The recently launched BioForge Initiative, backed by Pitt Senior Vice Chancellor for the Health Sciences, Dr. Anantha Shekhar, will be used to advance the wide-scale production and commercialization of the gene delivery vectors identified with the grant support.
We are excited that the services of a state-of-the-art biomanufacturing facility will soon be available in Pittsburgh to help make the lofty goal of delivering new and improved medical treatments for brain disorders a reality, said Shekhar. It feels very special to participate in a program that will not only bring life-saving treatments to our patients but also facilitate the dissemination of Pitt-developed technologies to research labs around the world and take a big step toward creating products with economic impact on the region.
The BRAIN Initiative was announced in 2013 to deepen understanding of the inner workings of the human mind and over the years has grown to prioritize the expansion of molecular cell-type profiling and data analysis, enabling genetic and non-genetic access to cell types across multiple species. The multi-year NIH grant was awarded as part of the Armamentarium for Precision Brain Cell Access, a large-scale NIH BRAIN Initiative project.
Delivery technologies for specific brain cell types are revolutionizing experimental neuroscience by allowing researchers to probe the cells and circuits underlying complex behaviors, said Dr. John Ngai, director of the NIH BRAIN Initiative. An expanded toolkit of precision brain cell access tools supported by the first phase of the Armamentarium project could ultimately inform cell- and circuit-specific therapies for human patients, for example, those with epilepsy, neurodevelopmental diseases, or mood disorders.
Projects like the one led by Stauffer, who is interested in defining how different cell types contribute to behavior, as well as investigating cell type-specific disease processes, are essential to the Initiatives mission. Stauffer and his close collaborators, Leah Byrne, Ph.D., assistant professor of ophthalmology at Pitt, and Andreas Pfenning, Ph.D., assistant professor of computational biology at CMU, were awarded a BRAIN Initiative grant in 2018 to begin defining the molecular profiles of different neuron types.
Even a small piece of brain tissue contains dozens of different subtypes of neurons, each performing different functions during different behaviors, said Pfenning, who is a part of CMUs Neuroscience Institute. The ability to target these populations using viruses could accelerate basic research and also pave the way for targeted therapeutics.
Pfennings group will use custom-made machine learning models and evolutionary theory to identify sequences that are most likely to label subpopulations of neurons. His laboratory will also test the ability of those sequences to target specific cell types in the mouse brain.
Further building on the molecular profiling data, scientists at Pitts Brain Institute intend to identify cell type-specific drivers of gene expression in the forebrain and the frontal lobe and develop ready-to-use, specific and efficient gene delivery vectors, including adeno-associated viruses (AAVs). To develop novel AAVs, they will use scAAVengr, the single cell AAV engineering pipeline developed by Byrne. The team will combine scAAVengr-optimized AAV viral shells with newly identified cell type-specific enhancers, and the combination of these elements will generate viral vectors capable of delivering highly efficient and cell type-specific gene therapies. Afonso Silva, Ph.D., professor of neurobiology who holds an endowed chair in translational neuroimaging at Pitt and also a member of the Brain Institute, joins Stauffer, Byrne and Pfenning on the project team. The Silva lab will create an ultra-high resolution MRI atlas of the rhesus monkey brain. That MRI-based atlas will provide the framework for detailing how viral vector expression is controlled in a brain-wide fashion.
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The FNIH Announces New Research Initiative to Identify More Precise Treatment Strategies for Patients Suffering from Heart Failure – PR Newswire
NORTH BETHESDA, Md., Sept. 29, 2022 /PRNewswire/ -- The Foundation for the National Institutes of Health (FNIH) and the National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) are launching a new partnership to investigate the syndrome of heart failure with preserved ejection fraction (HFpEF). Developing precision treatment strategies for HFpEF is more critical than ever, as the world's population continues to live longer, resulting in an increase in HFpEF cases. Utilizing cutting edge technologies, including digital measurements and artificial intelligence analytic methods, the Accelerating Medicines Partnership Heart Failure (AMP HF) Program is designed to find novel proteins or genes that could mitigate this disease when altered by therapeutics.
"We know that treatments that target the biological changes that drive disease are often most effective, but the challenge faced by researchers is finding the right targets," said Lawrence A. Tabak, D.D.S., Ph.D., who is performing the duties of the NIH director. "AMP Heart Failure aims to improve the odds of hitting the mark earlier and faster."
Although compelling progress has been made in the treatment of many forms of heart disease, death due to heart failure continues to rise nationally. The AMP HF Program aims to alter the landscape of heart failure treatment, improving the outlook for millions of patients around the world.
"The promise of precision treatments for heart failure is that we will have the opportunity to diagnose individuals much earlier and intervene, changing the course of this disease," said NHLBI Director Dr. Gary H. Gibbons. "The AMP Heart Failure program -- and the high caliber of the partnership at its core -- will help us better understand and treat this common syndrome with the goal of ultimately benefitting millions."
In the United States, heart failure directly contributes to about 45% of all cardiovascular disease deaths.1 HFpEF is a common form of heart failure in which the ejection fractionthe percentage of blood ejected from the left ventricle with each heartbeatis within the normal range. HFpEF is difficult to detect, because the left ventricle appears to be functioning normally, and is often deadly, with a five-year survival rate of just 35-40%. In addition to a high risk for mortality, patients with HFpEF live with declining quality of life and poor capacity to perform tasks of daily living.
The AMP HF Program, a public-private partnership facilitated by the FNIH, will advance our understanding of heart failure with preserved ejection fraction using two complementary and integrated research components: analyzing existing HFpEF datasets, sourced from public and private sector funded studies, and initiating a new clinical trial to confirm retrospective findings in an observational cohort with a goal to develop a framework for new precision treatments.
"HFpEF is clearly a major cause of heart failure hospitalizations and diminished quality of life for older patients. Up until now, developing effective therapeutic strategies to identify and treat HFpEF has eluded us. Through AMP HF, we will harness the valuable perspectives and expertise that collaborations bring to biomedical research, paving the way for a more hopeful outlook," said Dr. Julie Gerberding, Chief Executive Officer at the FNIH.
"Roughly half of all heart failure patients suffer from HFpEF. Understanding what it is, when it happens, and how to treat it remains the single largest unmet need in cardiovascular health.2 The AMP HF Program aims to close this gap in understanding, and ultimately improve the lives of patients everywhere," said Dr. Norman Stockbridge, Director of the Division of Cardiology and Nephrology at the Office of Cardiology, Hematology, Endocrinology and Nephrology at the U.S. Food and Drug Administration (FDA).
AMP Heart Failure is the latest initiative to emerge from the AMP Program, a set of public-private collaborations that coalesce the collective knowledge of the NIH, the U.S. FDA, the biotech and pharmaceutical industry, and patient organizations to speed drug development across different diseases. AMP HF brings together the resources of 8 partner organizations spanning the public and private sectors, with combined commitments totaling over $37 million. The FNIH will provide project management for the effort over the next 5 years.
NIH Institutes and Centers involved include:National Heart, Lung, and Blood Institute
Private partners include:American Society of Echocardiography (ASE)Bayer USCytokinetics, Inc.Ionis Pharmaceuticals, Inc.Novartis AGUltromics
Support also provided by the American Heart Association
For more information about the program, click here. To read what our partners and supporters are saying about the program, click here.
About the Accelerating Medicines Partnership Program: AMP Heart Failure joins other AMP programs expediting discovery around Alzheimer's disease, Parkinson's disease, Schizophrenia, Rheumatoid Arthritis and Lupus, Type II Diabetes, Common Metabolic Diseases, Autoimmune and Immune-Mediated Diseases, and the Bespoke Gene Therapy Consortium, all coordinated by the FNIH since the 2014 launch of the large-scale initiative. The AMP partnerships use cutting-edge scientific approaches to bring new medicines to patients by enhancing validation of novel, clinically relevant therapeutic targets and biomarkers. To learn more about AMP, visithttps://fnih.org/AMP.
About the Foundation for the National Institutes of Health: The Foundation for the National Institutes of Health creates and manages alliances with public and private institutions to support the NIH, the world's premier medical research agency. FNIH works with its partners to accelerate biomedical advances and therapies targeting diseases in the United States and across the globe. The FNIH organizes and administers research projects; supports education and training of new researchers; and holds educational events focused on areas of unmet medical need worldwide. Established by Congress in 1990, the FNIH is a not-for-profit 501(c)(3) charitable organization. For additional information about the FNIH, please visit https://fnih.org.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visithttps://www.nih.gov/.
ACCELERATING MEDICINES PARTNERSHIP and AMP are registered service marks of the U.S. Department of Health and Human Services.
CONTACT:Katherine Thompson[emailprotected]
SOURCE Foundation For The National Institutes of Health, Inc.
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The FNIH Announces New Research Initiative to Identify More Precise Treatment Strategies for Patients Suffering from Heart Failure - PR Newswire
Healthcare Contract Research Outsourcing Market to Reach the Value of US$ 63.09 Bn by 2028 – Digital Journal
Healthcare Contract Research Outsourcing Market: Introduction
According to the report, the global healthcare contract research outsourcing market was valued at US$ 38.04 Bn in 2020 and is projected to expand at a CAGR of 6.6% from 2021 to 2028. A contract research organization (CRO) is a company that provides clinical trial management services for the pharmaceutical, biotech, and medical device companies.
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The different types of CRO services are regulatory affairs, site selection & activation, recruitment support, clinical monitoring, data management, trial logistics, pharmacovigilance, biostatistics, medical writing, and project management.
Broad and Expanding Product Pipeline: Key Driver
Rise in demand for new drug and novel therapies for treatment of life-threatening diseases such as cancer & immunological disorders and evolving research & development process have led to an increase in the number of compounds in pipeline in the last decade.
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According to the Congressional Budget Office (CBO), in 2019, there was an increase of 60% of new drugs approved for sale compared to that in 2018.
In the past few years, development of biosimilar products, cellular therapy, and immune-biological has contributed toward the advancing pipeline and need of stringent clinical trials. This drives the global healthcare contract research outsourcing market.
Funding for Emerging Healthcare Companies: Major Driver
Increase in funding for small to mid-sized pharmaceutical, biotechnology, and medical devices companies has induced large companies to opt for CRO services with focus on niche market. Currently, expenditure in the biotechnology sector is the highest due to recent advancements in research on monoclonal antibodies, immunotherapy, gene therapy, and cancer vaccines. Small pharmaceutical companies focus on advancement in product development through CRO services due to rise in demand for innovative products and patent expiration.
The need to improve adoption and value proposition in the market has induced medical devices companies to outsource clinical trial services.
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Clinical Trial Services Segment to Dominate Global Market
The clinical trial services segment is expected to dominate the global market during the forecast period. Optimization of R&D costs and shorter drug development timeline resulting from outsourcing of clinical trial services to CROs are likely to contribute to the segments large market share in the near future. However, the segment is projected to lose market share to regulatory services and clinical data management & biometrics segments by 2028 due to stringent regulatory guidelines.
North America to Lead Healthcare Contract Research Outsourcing Market
In terms of region, the global healthcare contract research outsourcing market has been segmented into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. North America accounted for a major share of 46.59% of the global market in 2020. The market in the region is estimated to reach US$ 27.19 Bn in 2028, expanding at a CAGR of 5.6% from 2021 to 2028. This can be attributed to the presence of world renowned research experts in CNS, rare disease, oncology, immunology, and stem cells, advanced infrastructure of clinical research sites, and effective government incentive programs.
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Key Players in Global Market
Major players operating in the global healthcare contract research outsourcing market include Syneos Health, PAREXEL International, ICON plc, PRA Health Sciences, Inc., Charles River, Laboratory Corporation of America Holdings (Covance), IQVIA, Medpace, and Pharmaceutical Product Development, LLC.
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BMS: Platforms are pivotal to pandemic speed – BioProcess Insider – BioProcess Insider
Only companies that have strong platforms will be able to meet specific timelines, says Bristol-Myers Squibbs Jim Xu.
As COVID-19 transitions into an endemic, delegates at Biotech Week Boston discussed the challenges concerning the upstream process development process. Jianlin (Jim) Xu, scientific director, biologics development at BMS, explained told a packed room that monoclonal antibodies (mAbs) are difficult to produce with complex glycosylation profile, process related impurities, and amino acid oxidation.
Xu also outlined other challenges, which included bioreactor operation scalability, upstream processes lasting over a month for one run from vial thaw to harvest, competitive development of similar mAb products in the industry, and the length of time it takes to create stable monoclonal CHO lines with desirable characteristics.
To solve said challenges, Xu maintained that a strong platform is the number one solution, and that a robust platform can help a firm meet particular timelines. He said that a platform approach has numerous benefits, from decreasing costs, shortening development timelines, and making it possible to have a robust production process from clinical supply through to commercial use.
Xu claimed that in order to develop upstream platform technology, the individual and/or company must be able to demonstrate the benefit and proof-of-concept of an upstream technology in the first instance. Additionally, he told delegates that the technology should be successfully applied to various mAb products, and this will provide a good starting point for future mAb manufacture process development.
In other platform related news at Biotech Week Boston, PerkinElmer launched its Cellaca PLX system, saying that it is the cell analysis solution to streamline cell and gene therapy research and production.
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BMS: Platforms are pivotal to pandemic speed - BioProcess Insider - BioProcess Insider
Biopharmaceutical Contract Manufacturing Market by Type of Service Offered, Type of Biologic Manufactured, Type of Expression System Used, Scale of…
ReportLinker
INTRODUCTION Over the last few decades, the development landscape of small molecule drugs has been significantly impacted by various biotechnology breakthroughs. Further, with the advent of novel technologies, biologics have made a significant impact in the pharmaceutical domain, delivering ground-breaking treatment for a myriad of disease indications, including immunological, oncological and rare disorders.
New York, Sept. 29, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Biopharmaceutical Contract Manufacturing Market by Type of Service Offered, Type of Biologic Manufactured, Type of Expression System Used, Scale of Operation, Company Size, and Key Geographical Regions : Industry Trends and Global Forecasts, 2022 2035" - https://www.reportlinker.com/p06323412/?utm_source=GNW In this context, it is worth highlighting those 14 biopharmaceutical products (including cell therapies, gene therapies, monoclonal antibodies and recombinant proteins) were approved in the US alone, in 2021. Further, promising results from ongoing clinical research initiatives have encouraged various government and private firms to make significant investments in this domain. For instance, in 2021, a sum of over USD 70 billion was invested in the cell and gene therapy domain. However, manufacturing of biologics is fraught with various challenges. Some of the key concerns of contemporary innovators include rate of attrition of pipeline drugs / therapies, prolonged development timelines, current facility limitations, regulatory and compliance-related issues, and inconsistencies related to quality attributes of the final product. Therefore, therapy developers are actively exploring avenues that enable them to overcome the existing challenges. Amongst other alternatives, outsourcing has emerged as a lucrative option for biologic drug developers.
Currently, a significant number of players engaged in the biopharmaceutical domain prefer to outsource various operations to contract service providers. In fact, currently over 275 companies claim to offer contract manufacturing services for biologic therapeutics, in compliance with the regulatory standards. It is also worth highlighting that biopharmaceutical contract manufacturers are actively trying to consolidate their presence in this field by entering into strategic alliances in order to meet the indubitably rising demand for biologics. For this purpose, substantial expansions, and mergers and acquisitions have been reported in this market, as service providers strive to become one-stop-shops, to cater to the diverse needs of their clientele. With outsourcing being increasingly accepted as a viable and beneficial business model within this field, we anticipate the biopharmaceutical contract manufacturing market to grow at a commendable pace in the coming years.
SCOPE OF THE REPORTThe Biopharmaceutical Contract Manufacturing Market by Type of Service(s) Offered (API, FDF), Type of Biologic Manufactured (Antibodies, Cell Therapies, Vaccines and Other Biologics), Type of Expression System Used (Mammalian, Microbial and Others), Scale of Operation (Preclinical / Clinical and Commercial), Company Size (Small, Mid-sized, and Large and Very Large), and Key Geographical Regions (North America, Europe, Asia-Pacific, Latin America and MENA): Industry Trends and Global Forecasts, 2022 2035 report features an extensive study of the current market landscape and the likely future potential associated with the biopharmaceutical contract manufacturing market, over the next decade.
The study also includes a detailed analysis of key drivers and trends within this evolving market.
Amongst other elements, the report features:
A detailed overview of the overall landscape of companies engaged in offering contract manufacturing services for biologics, including a detailed analysis based on several relevant parameters, such as year of establishment, company size (based on number of employees), location of headquarters, type of service(s) offered (API and FDF manufacturing), type of biologic manufactured (ADCs, antibodies, biosimilars, cell therapies, gene therapies, nucleic acids / oligonucleotides, plasmid DNA / viral vectors, proteins / peptides, vaccines and others), scale of operation (preclinical, clinical and commercial), type of expression system used (mammalian, microbial and others), type of bioreactor used (single use, stainless steel and others) and mode of operation of bioreactor (batch, fed batch and perfusion / continuous).A detailed landscape of the biopharmaceutical manufacturing facilities established across the key geographical regions (North America, Europe, Asia-Pacific and Rest of the World), highlighting the manufacturing hubs for biologics.Elaborate profiles of key industry players based in North America, Europe and Asia-Pacific that offer contract manufacturing services for biologics. Each profile features a brief overview of the company, details related to its biologic-related service portfolio, manufacturing facilities, recent developments, and an informed future outlook.A detailed discussion on the key enablers in this domain, including certain niche product classes, such as antibody drug conjugates (ADCs), bispecific antibodies, cell therapies, gene therapies and viral vectors, which are likely to have a significant impact on the growth of the contract services market.A case study on the growing global biosimilars market, highlighting the associated opportunities for biopharmaceutical CMOs and CDMOs.A case study comparing the key characteristics of small and large molecule drugs, along with details on the various steps involved in their respective manufacturing processes.A detailed discussion on the benefits and challenges associated with in-house manufacturing, featuring a brief overview of the various parameters that a drug / therapy developer may need to take into consideration while deciding whether to manufacture its products in-house or outsource the production operations.A qualitative analysis, highlighting various factors that need to be taken into consideration by biopharmaceutical developers while deciding whether to manufacture their respective products in-house or engage the services of a CMO.A review of the various biopharmaceutical-focused manufacturing initiatives undertaken by top 10 big pharma players (shortlisted on the basis of 2021 revenues), highlighting trends across various parameters, such as number of initiatives, year of initiative, purpose of initiative, type of initiative, scale of operation and type of biologic manufactured.An analysis of the recent collaborations within the biopharmaceutical contract manufacturing industry, based on several relevant parameters, such as year of partnership, type of partnership, type of biologic manufactured, therapeutic area, most active players (in terms of number of deals inked) and regional distribution of partnership activity that have taken place in this domain, during the period 2015-2022.A detailed analysis of the various mergers and acquisitions that have taken place within this domain, during the period 2015-2022, based on several relevant parameters, such as year of agreement, type of deal, geographical location of companies, type of acquisition, type of biologic manufactured and key value drivers.A detailed review of expansion initiatives undertaken by biopharmaceutical contract manufacturers, during the period 2016-2022, along with information on several relevant parameters, such as year of expansion, purpose of expansion, type of biologic manufactured and location of expanded facility.An analysis of the recent developments within the biopharmaceutical contract manufacturing industry, highlighting information on the funding investments made during the period 2016-2022, along with information on the technology advancements related to biomanufacturing.An estimate of the overall, installed capacity for the manufacturing of biopharmaceuticals, based on information reported by various industry stakeholders in the public domain, highlighting the distribution of the available capacity, based on size of manufacturer (small, mid-sized and large and very large), scale of operation (preclinical, clinical and commercial), type of expression system used (mammalian, microbial and others) and geography (North America, Europe, Asia-Pacific and Rest of the World).An informed estimate of the annual demand for biologics, taking into account the top 20 biologics, based on various relevant parameters, such as target patient population, dosing frequency and dose strength of the abovementioned products.A company size-wise, detailed analysis of the total cost of ownership for biopharmaceuticals contract manufacturing organizations, during the period 2022-2042.A case study on the virtual business model concept, along with its role in the overall biopharmaceutical industry. It also features a discussion on the advantages and risks / challenges associated with outsourcing operations from virtual service providers.A discussion on affiliated trends, key drivers and challenges, under an elaborate SWOT framework, which are likely to impact the industrys evolution, including a Harvey ball analysis, highlighting the relative effect of each SWOT parameter on the overall biopharmaceutical industry.A survey analysis featuring inputs solicited from various experts who are directly / indirectly involved in providing contract manufacturing services to biopharmaceutical developers.
One of the key objectives of the report was to estimate the existing market size and estimate the future size of biopharmaceutical contract manufacturing market. We have provided informed estimates on the evolution of the market, over the period 2022-2035. Our year-wise projections of the current and future opportunity have further been segmented on the basis of [A] type of service(s) offered (API, FDF), [B] type of biologic manufactured (antibodies, cell therapies, vaccines and other biologics), [C] type of expression system used (mammalian, microbial and others), [D] scale of operation (preclinical / clinical and commercial), [E] company size (small, mid-sized, and large and very large), and [F] key geographical regions (North America, Europe, Asia-Pacific, Latin America and MENA).
In order to account for future uncertainties associated with some of the key parameters and to add robustness to our forecast model, we have provided three market forecast scenarios, portraying the conservative, base and optimistic tracks of the markets evolution.
All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.
KEY QUESTIONS ANSWEREDWho are the key players engaged in offering contract manufacturing services for biopharmaceuticals?What are the different partnerships and expansion initiatives undertaken by biopharmaceutical contract manufacturers in the recent past?Which regions represent the current key contract manufacturing hubs for biopharmaceuticals?What is the current, installed capacity for contract manufacturing of biopharmaceuticals?What is the current, global demand for biologics? How is the demand for such candidates likely to evolve in the foreseen future?What percentage of the biopharmaceuticals manufacturing operations are presently outsourced?What factors should be taken into consideration while deciding whether the manufacturing operations for biopharmaceuticals should be kept in-house or outsourced?How is the current and future opportunity likely to be distributed across key market segments?
CHAPTER OUTLINES
Chapter 2 is an executive summary of key insights captured during our research. It offers a high-level view on the current state of biopharmaceutical contract manufacturing market and its likely evolution in the short to mid-term and long-term.
Chapter 3 provides a general introduction to biopharmaceuticals and biopharmaceutical manufacturing processes. The chapter also includes an overview of the various expression systems used for the development of different types of biotherapeutic products. It features a brief overview of contract manufacturing, along with a detailed discussion on the need for outsourcing within the biopharmaceutical industry. Furthermore, it provides information on the challenges faced by players currently engaged in this domain.
Chapter 4 provides a detailed assessment of the current market landscape of companies engaged in offering contract manufacturing services for biologics, including a detailed analysis based on several relevant parameters, such as year of establishment, company size (based on number of employees), location of headquarters, type of service(s) offered (API and FDF manufacturing), type of biologic manufactured (ADCs, antibodies, biosimilars, cell therapies, gene therapies, nucleic acids / oligonucleotides, plasmid DNA / viral vectors, proteins / peptides, vaccines and others), scale of operation (preclinical, clinical and commercial), type of expression system used (mammalian, microbial and others), type of bioreactor used (single use, stainless steel and others) and mode of operation of bioreactor (batch, fed batch and perfusion / continuous).
Chapter 5 provides a detailed landscape of the biopharmaceutical manufacturing facilities established across the key geographical regions (North America, Europe, Asia-Pacific and Rest of the World), highlighting the manufacturing hubs for biologics.
Chapter 6 provides elaborate profiles of key industry players based in North America that offer contract manufacturing services for biologics. Each profile features a brief overview of the company, details related to its biologic-related service portfolio, manufacturing facilities, recent developments, and an informed future outlook.
Chapter 7 provides elaborate profiles of key industry players based in Europe that offer contract manufacturing services for biologics. Each profile features a brief overview of the company, details related to its biologic-related service portfolio, manufacturing facilities, recent developments, and an informed future outlook.
Chapter 8 provides elaborate profiles of key industry players based in Asia-Pacific that offer contract manufacturing services for biologics. Each profile features a brief overview of the company, details related to its biologic-related service portfolio, manufacturing facilities, recent developments, and an informed future outlook.Chapter 9 provides a detailed discussion on the key enablers in this domain, including certain niche product classes, such as antibody drug conjugates (ADCs), bispecific antibodies, cell therapies, gene therapies and viral vectors, which are likely to have a significant impact on the growth of the contract services market.
Chapter 10 presents a case study on the growing global biosimilars market, highlighting the associated opportunities for biopharmaceutical CMOs and CDMOs.
Chapter 11 presents a case study comparing the key characteristics of small and large molecule drugs, along with details on the various steps involved in their respective manufacturing processes.
Chapter 12 provides a detailed discussion on the benefits and challenges associated with in-house manufacturing, featuring a brief overview of the various parameters that a drug / therapy developer may need to take into consideration while deciding whether to manufacture its products in-house or outsource the production operations.Chapter 13 presents a qualitative analysis, highlighting various factors that need to be taken into consideration by biopharmaceutical developers while deciding whether to manufacture their respective products in-house or engage the services of a CMO.
Chapter 14 provides a review of the various biopharmaceutical-focused manufacturing initiatives undertaken by top 10 big pharma players (shortlisted on the basis of 2021 revenues), highlighting trends across various parameters, such as number of initiatives, year of initiative, purpose of initiative, type of initiative, scale of operation and type of biologic manufactured.
Chapter 15 presents an analysis of the recent collaborations within the biopharmaceutical contract manufacturing industry, based on several relevant parameters, such as year of partnership, type of partnership, type of biologic manufactured, therapeutic area, most active players (in terms of number of deals inked) and regional distribution of partnership activity that have taken place in this domain, during the period 2015-2022.
Chapter 16 provides a detailed analysis of the various mergers and acquisitions that have taken place within this domain, during the period 2015-2022, based on several relevant parameters, such as year of agreement, type of deal, geographical location of companies, type of acquisition, type of biologic manufactured and key value drivers.
Chapter 17 presents a detailed review of expansion initiatives undertaken by biopharmaceutical contract manufacturers, during the period 2016-2022, along with information on several relevant parameters, such as year of expansion, purpose of expansion, type of biologic manufactured and location of expanded facility.
Chapter 18 presents an analysis of the recent developments within the biopharmaceutical contract manufacturing industry, highlighting information on the funding investments made during the period 2016-2022, along with information on the technology advancements related to biomanufacturing.
Chapter 19 provides an estimate of the overall, installed capacity for the manufacturing of biopharmaceuticals, based on information reported by various industry stakeholders in the public domain, highlighting the distribution of the available capacity, based on size of manufacturer (small, mid-sized, and large and very large), scale of operation (preclinical, clinical and commercial), type of expression system used (mammalian, microbial and others) and geography (North America, Europe, Asia-Pacific and Rest of the World).
Chapter 20 presents an informed estimate of the annual demand for biologics, taking into account the top 20 biologics, based on various relevant parameters, such as target patient population, dosing frequency and dose strength of the abovementioned products.
Chapter 21 presents a company size-wise, detailed analysis of the total cost of ownership for biopharmaceuticals contract manufacturing organizations, during the period 2022-2042.
Chapter 22 presents an insightful market forecast analysis, highlighting the future potential of biopharmaceutical contract manufacturing market till 2035. We have segmented the market on the basis of type of service(s) offered (API, FDF), type of biologic manufactured (antibodies, cell therapies, vaccines and other biologics), type of expression system used (mammalian, microbial and others), scale of operation (preclinical / clinical and commercial) , company size (small, mid-sized, and large and very large), and key geographical regions (North America, Europe, Asia-Pacific, Latin America and MENA).
Chapter 23 presents a case study on the virtual business model concept, along with its role in the overall biopharmaceutical industry. It also features a discussion on the advantages and risks / challenges associated with outsourcing operations from virtual service providers.
Chapter 24 provides a discussion on affiliated trends, key drivers and challenges, under an elaborate SWOT framework, which are likely to impact the industrys evolution, including a Harvey ball analysis, highlighting the relative effect of each SWOT parameter on the overall biopharmaceutical industry.
Chapter 25 features an elaborate discussion on the future opportunities / trends within the biopharmaceutical contract manufacturing market that are likely to influence the growth of this domain over the coming years.
Chapter 26 provides a survey analysis featuring inputs solicited from various experts who are directly / indirectly involved in providing contract manufacturing services to biopharmaceutical developers.
Chapter 27 is a summary of the entire report. It provides the key takeaways and presents our independent opinion of the biopharmaceutical contract manufacturing market, based on the research and analysis described in the previous chapters.
Chapter 28 is a collection of transcripts of interviews conducted with various stakeholders in the industry.
Chapter 29 is an appendix, which provides tabulated data and numbers for all the figures provided in the report.
Chapter 30 is an appendix, which provides the list of companies and organizations mentioned in the report.Read the full report: https://www.reportlinker.com/p06323412/?utm_source=GNW
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Biopharmaceutical Contract Manufacturing Market by Type of Service Offered, Type of Biologic Manufactured, Type of Expression System Used, Scale of...
Emerging Therapies for Huntington’s Disease Focus on N-T | BTT – Dove Medical Press
Introduction
Huntingtons disease (HD) is an autosomal dominant neurodegenerative disorder with an estimated prevalence of up to 9 per 100,000 in the USA, Canada, Oceania, and Western Europe.1,2 HD is caused by a CAG (cytosine, adenine, and guanine) repeat expansion in exon 1 of the Huntingtin (HTT) gene, resulting in the translation of a mutant Huntingtin protein harboring a toxic polyglutamine (polyQ) stretch at its amino (N) terminus. Gene carriers with repeats between 36 and 39 CAG show incomplete penetrance, while repeats of 40 and more triplets lead to fully penetrant disease. The age of onset is inversely correlated with the CAG repeat length, with an average age of onset of 3544 years. HD is characterized by motor, cognitive and psychiatric symptoms and is ultimately fatal, with a median survival of 1518 years after onset. About 510% of HD patients show disease onset before 20 years of age, in which case it is called juvenile HD. Juvenile HD has a different clinical presentation compared to adult onset HD, characterized by symptoms such as severe mental retardation, speech and language delay, as well as more pronounced motor and cerebellar symptoms and overall more rapid disease progression.3
Apart from the inherited CAG length, several genetic modifiers have been identified that are associated with age of onset. Many of these modifiers point towards an important role for somatic instability: the process in which the CAG repeat within cells expands over time. Within the HTT locus, a strong genetic modifier is whether or not a CAA (cytosine, adenine, and adenine) interruption is present at the 3 end of the CAG repeat. Similar to CAG triplets, CAA encodes for glutamine, thus resulting in the same polyQ stretch. Nonetheless, alleles that lack this CAA interruption were found to be more prone to somatic expansion and showed decreased age of onset, while the presence of an additional CAA interruption was found to delay both somatic expansion and age of onset.4,5 Moreover, many of the identified trans-acting genetic modifiers, such as FANCD2 And FANCI Associated Nuclease 1 (FAN1) and MutL Homolog 1 (MLH1), are involved in DNA mismatch repair and influence somatic instability of the CAG repeat.5,6
Although HD was initially thought to be mainly a protein toxic gain-of-function disorder, it is likely that protein loss-of-function also plays a role, as reviewed elsewhere,710 and there is increasing evidence for the involvement of other disease mechanisms, such as repeat-associated non-AUG dependent (RAN) translation and RNA toxic gain-of-function, also reviewed previously.1113 Still, little is known regarding the relative contribution of each of these pathogenic mechanisms to the disease (Figure 1).
Figure 1 Schematic overview of the molecular pathogenesis of HD.
HTT is known to be essential for embryonic development, as demonstrated by the fact that knockout mice are embryonically lethal, and also appears to play a role in later stages of development and life, as reviewed by Kaemmerer and Grondin.10 There is, however, no clear consensus on the level of wild type HTT (wtHTT) that is required for its normal function, as this is likely to depend on many factors, including age and tissue/brain region. wtHTT is involved in many important cellular processes, including endocytosis and vesicular trafficking, cell division, autophagy and transcriptional regulation (reviewed by Saudou and Humbert)9 which may all be impacted by a loss of wtHTT function in HD.
Compelling evidence for the involvement of RNA-mediated toxicity was provided by Sun et al, who found that even in the absence of translation, there was still repeat-length dependent toxicity of 5 HTT mRNA as well as full-length HTT.14 RNA toxic gain-of-function is caused by the interaction between RNA-binding proteins (RBPs), such as Muscleblind like splicing regulator 1 (MBNL1) and Pre-mRNA processing factor 8 (PRPF8), and the secondary structure formed by the expanded CAG repeat in the mRNA, affecting the splicing of a range of transcripts.15,16 This interaction appears to be dependent on the purity of the CAG repeat (ie, the absence of CAA interruptions), as Mbnl1 was found to be recruited to nuclear foci in the novel BAC-CAG mouse model, which has an uninterrupted repeat, but not in the BACHD model, which harbors an interrupted repeat.17
Finally, the presence of the expanded CAG repeat has also been shown to induce repeat-associated non-AUG dependent (RAN) translation, which leads to the production of homopolymers other than polyQ that may also negatively impact cell function. RAN translation products have been detected in the affected brain regions of patients, as well as in N171-82Q mice and a C. elegans model.18,19 However, the actual contribution of RAN translation products to HD is not clear, as, for example, no RAN toxicity was observed in HD140Q knock-in mice.20
The expanded polyQ-containing mutant HTT (mHTT) protein has been shown to interact aberrantly with a variety of proteins, including transcriptional regulators such as RNA polymerase II subunit A (POLR2A), Tumor protein p53, Mouse double minute 2 (MDM2), CREB-binding protein (CBP) and Heat shock protein 70 (HSP70), cell cycle regulators like Ras homolog enriched in brain (Rheb) and mammalian target of rapamycin (mTOR), and cytoskeleton proteins such as actin and neurofilament light (NF-L). These aberrant interactions result in a complex and widespread molecular pathology, affecting many essential processes in the cell, including DNA damage repair, transcriptional regulation, mitochondrial function and apoptosis.2125 Importantly, premature polyadenylation of the pre-mRNA as well as proteolytic cleavage of HTT protein lead to the production of a variety of HTT fragments, and there is ample evidence that such fragments, especially the short N-terminal species, are more toxic than the full-length mHTT protein.2635 In order to make tailored therapeutics towards the short toxic fragments, a good understanding of the mechanisms leading to their formation is needed. In this review, we therefore focus on how toxic N-terminal HTT protein species are produced and how they are linked to toxicity, as well as on therapeutic strategies that are capable of reducing these fragments.
N-terminal HTT protein fragments are mainly produced through two distinct processes: proteolytic cleavage and premature polyadenylation (see Figure 2 and Table 1).
Table 1 Overview of Proteolytic Cleavage Sites
Figure 2 Schematic overview of production of N-terminal HTT protein. (A) Regular splicing, overview of the resulting mRNA and full-length protein and the identified proteolytic cleavage sites. (B) Alternative splicing and premature polyadenylation and resulting transcript. (C) Resulting protein species and propensity for nuclear entry, aggregation and toxicity.
The group of Michael Hayden first showed that HTT could be cleaved proteolytically by apopain (caspase-3) in a repeat-length dependent manner.36 This was confirmed in a follow-up study, in which they mapped one of the caspase-3 cleavage sites to D513 and another site C-terminally of amino acid (aa) 548. Furthermore, two caspase-1 cleavage sites were identified in the first 548 aa. In contrast to their previous work with truncated HTT, the authors found no repeat-length dependence of cleavage efficiency of full-length HTT.37 In a third study, the authors were able to map the second caspase-3 cleavage site to D552, and further identified a caspase-6 cleavage site at D586.38 More recently, Martin et al recently identified yet another caspase cleavage site at D572, which was shown to be cleaved by caspase-1 and caspase-2.39
Both full-length and N-terminal caspase-cleavage products of HTT were found to be substrates for cleavage by calpains.4042 Four calpain cleavage sites have been mapped, at aa 437, 465/469 and 536/54041 and between aa 63111,42 calpain cleavage efficiency appears to be positively correlated with repeat length.41,42 Furthermore, it was shown that calpain levels, and in particular the active form, were increased in the caudate of HD patients compared to controls.41
Next to caspase and calpain generated fragments, various other cleaved HTT products have been described. Lunkes et al identified two N-terminal HTT fragments, cp-A and cp-B, which appeared to be generated in transfected NG108 cells through cleavage by aspartic endopeptidases. The C-terminus of HTT cp-A fragment was mapped between aa 104114. N-terminal fragments with the same immunogenic properties were identified in nuclear inclusions in post mortem frontal cortex of HD patients.43
Similarly, Schilling et al identified an N-terminal fragment ending between aa 90115 in post mortem tissues from HD patients and N171-82Q mice, as well as in transfected HEK293 cells.44 Further investigation in a HEK293 cell model revealed that short, HTT cp-B-like fragments were efficiently processed to HTT cp-A-like fragments, while longer HTT fragments proved to be inefficient substrates. The C-terminus of the HTT cp-A-like fragments was mapped between aa 105 and 115124. Although similar in size to the fragment described by Lunkes et al, inhibition of aspartyl proteases did not affect the formation of the cp-A-like fragment, and the authors were unable to identify any protease that generates these HTT cp-A-like fragments, suggesting that i) the fragments are not the same or ii) that the cp-A-like fragment described by Schilling et al is the same fragment but generated by a novel protease, which may be cell-type dependent.45 Ratovitski et al identified two N-terminal fragments (HTT cp-1 and cp-2) in PC12 and HEK293 cells expressing full-length HTT with 21Q or 126153Q or a truncated N1212 HTT fragment with 15Q or 138Q.46 These fragments were similar in size to the previously described HTT cp-A and cp-B fragments but were not affected by inhibition of aspartic endopeptidases. In addition, they were not affected by deletion of aa 105114. In combination with the epitope mapping, this narrowed the C-terminus of the HTT cp-1 fragment down to between aa 90 and 105, shorter than the cp-A and cp-A-like fragments described by Lunkes et al43 and Schilling et al44,45 Based on the absence of identified proteases and on the fragment length, we speculate that the generation of these fragments could involve aberrant splicing (see Aberrant Splicing and Premature Polyadenylation), although this would require further investigation.
Finally, Landles et al showed fourteen different N-terminal HTT protein isoforms (fragments 114) in brain tissue from HdhQ150 KI mice, the three shortest of which (fragments 1214) were specific to mHTT.33 Some of these fragments could be linked to specific proteolytic cleavage events: fragment 7 terminated at a novel calpain cleavage site between aa 510654, fragment 8 appeared to correspond to the D586 caspase-6 cleavage product, fragment 9 was likely produced by cleavage at calpain site 536 and fragment 10 by caspase cleavage at D513. Lastly, fragment 13 was determined to correspond to HTT-ex1.
In summary, many different proteases have been found to act on mHTT and wtHTT, generating N-terminal and C-terminal HTT fragments. The availability of antibodies that can recognize these fragments, as well as the possibility to specifically inhibit certain proteases, have allowed mapping of various fragments, albeit with variable resolution. Nonetheless, for multiple fragments, the mechanisms of production remain to be identified.
Besides proteolytic cleavage, there are other mechanisms that lead to the generation of toxic N-terminal mHTT fragments. Sathasivam et al showed that incomplete splicing of intron 1 leads to the production of a short premature polyadenylated HTT-ex1 transcript in various HD mouse models and that this HTT-ex1 can be translated into a 90 aa N-terminal HTT-ex1 protein (based on 23Q). HTT-ex1 transcript was also found to be expressed in HD patient fibroblasts and cortex.47 In a follow-up study, Neueder et al confirmed that the HTT-ex1 transcript can be detected in patient-derived fibroblasts, as well as HD patient cerebellum, sensory motor cortex and hippocampus, with the highest expression levels measured in juvenile HD patient tissues.48 The HTT-ex1 transcript has also been detected by RNA-sequencing in various HD mouse models, including BACHD, BAC-CAG and HdhQ111.17 Both in vitro and in patient-derived tissues, the production of the HTT-ex1 transcript appears to be positively correlated with CAG repeat length, showing much higher expression in cells and tissues derived from juvenile HD patients.48,49
The current hypothesis is that HTT-ex1 formation is influenced by a combination of sequestration of spliceosome components such as U1 snRNP at the CAG repeat, leading to less efficient splicing of exon 1 to exon 2, and a reduced transcription rate, which leads to longer exposure of the cryptic polyA site in intron 1. Although the Bates group initially found evidence for the involvement of Serine and Arginine Rich Splicing Factor 6 (SRSF6) in HTT-ex1 formation,47,49 they later found that the silencing of Srsf6 in HD mouse models did not affect HTT-ex1 formation.50 It has therefore been hypothesized that multiple RNA-binding proteins may be involved in the missplicing of HTT-ex1.12 Regardless of the exact mechanisms involved, aberrant mHTT splicing is CAG repeat length dependent, suggesting that HTT-ex1 formation and associated toxicity would increase as somatic instability progresses in HD48 and that interventions targeting repeat expansion and HTT-ex1 may have therapeutic advantage.
Consistently accumulating evidence indicates that small N-terminal fragments containing extended polyQ tracts significantly contribute mHTT cellular mislocalization, aggregation and toxicity. Initial studies by the Ross group showed that transfection of N2a or HEK293 cells with full-length HTT with either 23Q or 82Q, or of truncated HTT N171-18Q or N63-18Q resulted in a diffuse cytoplasmic localization of the protein. In contrast, transfection with N171-82Q or N63-82Q led to more punctate labeling in both cytoplasm and nucleus, with the short N63-82Q construct showing the most prominent nuclear localization.51 The Hayden group found similar results, showing that N-terminal fragments of 427, 548 or more aa formed mainly perinuclear aggregates, while fragments up to 224 aa showed both cytoplasmic and nuclear aggregates. Furthermore, they found that pathogenicity depended both on repeat length and on fragment size.26,27
Barbaro et al found that, in Drosophila, shorter N-terminal fragments were more toxic and more prone to aggregate, with HTT-ex1 being by far the most toxic species.28 In mice, the R6/2 model that expresses only HTT-ex1 is by far the most swiftly progressing HD mouse model,52,53 while conditional suppression of HTT-ex1 has been shown to be neuroprotective.54 Recent in vitro studies by the Lashuel group confirm these results and further extend the findings by showing that the polyQ and Nt17 domains of HTT-ex1 synergistically modulate the aggregation propensity of HTT-ex1, with a key role of the Nt17 domain in regulating HTT-ex1 aggregation dynamics and subcellular localization and toxicity.34
There is conflicting evidence with regard to the pathogenicity of nuclear and cytoplasmic mHTT. Some groups have reported evidence that nuclear localization is required for toxicity. For example, the Greenberg group showed that adding a nuclear export signal to a N171 HTT fragment blocked its toxicity in transfected striatal neurons.55 In contrast, the Hayden group reported that neither the addition of a nuclear localization signal to a N548 HTT fragment nor the addition of a nuclear export signal to a N151 fragment altered the toxicity of those fragments, suggesting that both the nucleus and the cytoplasm are sites of HD toxicity.56 Trushina et al found that nuclear entry of mHTT only occurred after commitment of a cell to cell death. Therefore, the authors argue that nuclear mHTT localization may not be the primary event leading to toxicity.57
Intranuclear and neuropil aggregates have been observed in most HD animal models,17,30,31,5863 and the presence of aggregates containing N-terminal HTT fragments has also been confirmed in patient brains by multiple groups.40,64,65 However, various groups have shown that it is not the insoluble aggregates or inclusion bodies, but rather the soluble oligomers that are the more toxic species.6669 In fact, some groups have found evidence that the formation of intranuclear inclusions may be protective,55,70,71 as reviewed by Arrasate and Finkbeiner.72 Mechanistically, this may be explained by the fact that soluble mHTT-ex1 oligomers have more aberrant protein interactions than insoluble aggregates and inclusions.73 Importantly, the length of N-terminal protein species and the associated sequence context, as well as post-translational modifications, also appear to play an important role in the aggregation process.35,74,75 For more in-depth reviews on the role of post-translational modifications, we redirect elsewhere.76,77
Various approaches have been investigated to therapeutically lower the expression or reduce the toxicity of the mutant HTT protein. The proteolytic cleavage pathway can be targeted to reduce the formation of N-terminal mHTT protein species. Furthermore, the N-terminal part of the protein can be targeted to reduce aggregation and/or increase clearance of mHTT. Finally, mHTT can be targeted at the transcript or gene level. Here, we will focus on approaches that are able to target not only full-length HTT but also HTT-ex1 and other N-terminal mHTT species, considering their potential therapeutic advantage (see Table 2).
Table 2 Overview of Studies Targeting HTT Protein
Caspase inhibition has been shown to reduce the proteolytic cleavage of mHTT and to improve the HD phenotype in BACHD78 and HdhQ111 mice.79 These results are backed up by earlier studies, where mutation of caspase-6 cleavage sites slowed down disease progression in YAC128 mice.80 However, it is not clear to what extent the protective effects are due specifically to the reduction of N-terminal mHTT species, rather than a general protective effect of caspase inhibition, as caspase inhibition was also protective in R6/2 and malonate models of HD, which do not express caspase-cleavable mHTT.8183
Using a different approach, Evers et al showed that removal of the caspase-6 cleavage site by antisense oligonucleotide (ASO)-mediated skipping of (part of) exon 12 led to reduced levels of the N568 fragment in vitro and in vivo in wild type and YAC128 mice.84,85 Except for the absence of astrogliosis, no data are available regarding phenotypic effects of this ASO treatment.
None of these approaches have yet successfully been translated into the clinic, and although all may potentially decrease the formation of toxic mHTT fragments and have the potential of allele-specificity, mechanisms of RNA-associated toxicity would not be addressed.
Aptamers are single-stranded oligonucleotides that, through their tertiary structure, can interact with target molecules such as proteins. The Roy lab identified aptamers that bind specifically to mHTT with 51 or 103Q but not wtHTT with 20Q.86,87 The selected aptamers were shown to inhibit aggregation of recombinant mHTT-ex1 in cell-free assays and in yeast, as well as reducing oxidative stress and mitochondrial dysfunction.86 To our knowledge, this approach has not yet been tested in vivo.
Various antibodies have been expressed intracellularly as intrabodies to target the N-terminus of HTT. In vivo, such intrabodies are delivered using viral vectors. An excellent review on the use of intrabodies in various neurodegenerative diseases was written by Messer and Butler.88
Two groups of intrabodies have been tested most extensively (see Figure 3): those that bind to the N-terminus of HTT (VL12.3, scFv-C4) and those that recognize the proline-rich regions (PRRs) in HTT-ex1 (MW7, Happ1, Happ3, INT41). In addition, there is some literature about polyQ-binding intrabodies (MW1, MW2) and a more C-terminal intrabody derived from EM48 (scFv-EM48).
Figure 3 Anti-HTT Exon 1 intrabodies. (A) Antigens used to select the published anti-HTT intrabodies. (B) Specific binding identified by crystallography for scFvC4 and VL12.3.
Notes: Reproduced from Messer A, Butler DC. Optimizing intracellular antibodies (intrabodies/nanobodies) to treat neurodegenerative disorders. Neurobiol Dis. 2020;134(October 2019):104619. doi: 10.1016/j.nbd.2019.104619 under Creative Commons BY-NC-ND 4.0.88
Southwell et al showed that intrabodies that bind to the PRR, ie, MW7, Happ1 and Happ3, increase the turnover of mHTT-ex1 overexpressed in vitro. VL12.3, an intrabody that binds to the N-terminal 17 aa of HTT, did not affect turnover, but did increase the nuclear localization of mHTT-ex1.90 In vivo, the PRR-binding Happ1 was shown to be beneficial in five different HD mouse models. In contrast, VL12.3, while effective in a lentiviral HD model, was ineffective in YAC128 mice and had a detrimental effect in R6/2 mice.91 The authors later showed that the increased turnover mediated by the PRR-binding intrabodies is dependent on a calpain-chaperone-mediated autophagy-dependent mechanism and that this process is blocked by VL12.3,92 explaining the detrimental effects of VL12.3.
Although scFv-C4 also binds to the N-terminus of HTT,93 its predominant cytoplasmic localization appears to protect from the detrimental effects observed for VL12.3.89 The scFv-C4 intrabody was shown to have beneficial effects in various HD models, including in vitro models, Drosophila and different mouse models.9498
Two additional intrabodies have been investigated: scFv-EM48 and INT41. Like Happ1, scFv-EM48, which binds just C-terminally to the second PRR, was shown to increase turnover of mHTT, and improved motor function of N171-82Q mice.99 INT41, an intrabody that recognizes the same epitope as Happ1, but which has enhanced cytoplasmic solubility, was shown to improve cognitive function in female R6/2 mice.100
In addition to the increased turnover induced by some of the intrabodies, the endogenous cellular machinery can be harnessed specifically to target proteins for degradation, using engineered proteins, peptides or small molecules. These can direct the protein of interest to the ubiquitin proteasome system, the autophagy-lysosomal pathway or chaperone-mediated autophagy. These approaches and their specific application in the context of HD have been extensively reviewed by Jarosiska and Rdiger.101
Two such approaches specifically target the polyQ region. Bauer et al engineered a fusion molecule consisting of two copies of a polyQ-binding peptide (QBP1) and heat shock-cognate protein 70 (HSC70)-binding motifs to induce chaperone-mediated autophagy.102 Clift et al co-expressed a polyQ-binding antibody (3B5H10) with TRIM21 in an approach that they call Trim-Away, to target mHTT for proteasomal degradation.103 Additionally, Butler et al produced a fusion protein consisting of the scFv-C4 intrabody and a PEST motif to enhance proteasomal degradation of HTT-ex1.104
Several endogenous proteins have been described to enhance the turnover of mHTT, including Praja1 ubiquitin ligase,105 TBK1106 and Blm10/PA200.107 Induction or overexpression of such proteins may represent a therapeutic strategy, although, so far, this notion is only supported by experiments in cellular, Drosophila, and C. elegans models. Additionally, specificity for mHTT has not been shown for any of these three proteins.
Finally, a small molecule that can bind to mHTT-ex1, called GLYN122, has been identified recently. GLYN122 was shown to reduce mHTT-ex1 aggregation in PC12 cells, as well as reducing mHTT in cortex and striatum of R6/2 mice after intraperitoneal injection.108
Next to targeting the pathogenic protein species itself, the production of such proteins can also be inhibited by targeting the HTT mRNA. Many different approaches have been tested to this effect, including ASOs, siRNAs, shRNAs and miRNAs (Table 3). Again, we only focus on those strategies that target HTT-ex1. Broadly speaking, the HTT-ex1 mRNA targeting approaches can be divided into those that target the expanded CAG repeat, and those that target other regions of HTT-ex1. In addition, some other approaches have been described.
Table 3 Overview of Studies That Evaluated Therapeutic Approaches Targeting HTT at the RNA Level
Many studies have tested ASOs or RNAi agents to target the CAG repeat.109122 In general, CAG-targeting confers preference towards the expanded allele, as this allows for binding of multiple molecules per mRNA.111 Only a few studies included in vivo efficacy. Yu et al showed the efficacy of their siRNA in HdhQ150 mice.115 Monteys et al used transgenic mice expressing tagged full-length wtHTT and mHTT, showing preferential silencing of mHTT.118 Datson et al showed the efficacy of their CAG-targeting ASO in R6/2 and Q175 mice,120 an ASO that is now further developed by Vico Therapeutics. Kotowska-Zimmer et al have shown that artificial miRNAs targeting the CAG repeat specifically reduced mHTT in YAC128 mice.122
A number of strategies that target other regions of HTT-ex1 have been described as well.123137 This approach would be expected to lower both wtHTT and mHTT. With the exception of Boado et al and Kordasiewicz et al, who used ASOs, all of these studies utilized RNAi agents. Various groups have demonstrated efficacy of siRNA or shRNA in R6/1, R6/2 and AAV100Q mice.127130 uniQures miRNA therapy has shown target engagement in the widest range of HD animal models, including Hu128/21, Q175 and R6/2 mice, lentiviral rat model and transgenic HD minipigs,123,124,132134,136 as well as a favorable safety profile in toxicity studies in rats and non-human primates.137
A handful of studies described other approaches to HTT RNA-targeting. Rindt et al developed a method to induce trans-splicing, by which mHTT exon 1 is replaced with exogenous wtHTT exon 1 in the mRNA. Thus far, there is only in vitro proof of principle for this approach, and the efficiency is rather low, with 1015% of trans-splicing observed even after extensive optimization.138,139 Batra et al have developed an RNA-targeting Cas9 approach which targets the CAG repeat.140 For HD, there is only in vitro evidence for this approach so far, but a similar approach targeting a CUG (cytosine, uracil, and guanine) repeat was shown to be effective in vivo in myotonic dystrophy type 1 mouse models.141 This platform is being developed by Locanabio.
Finally, some small molecules have been described to bind to either HTT-ex1 or the CAG repeat, most notably furamidine, myricetin and a series of pyridocoumarin derivatives, reviewed elsewhere.12 These compounds have been described to inhibit translation of HTT. However, specificity of such compounds is generally low, thereby increasing the chance of unwanted off-target effects.
Finally, several approaches that target the HTT gene have been described (Table 4).
Table 4 Overview of Studies Targeting the HTT Gene
Transcription can be prevented using zinc finger proteins (ZFPs) targeting the expanded CAG repeat.142144 This approach shows allele-selectivity for the expanded repeat and is currently being developed for the clinic by Sangamo and Takeda. Further, CRISPR-Cas9 genome editing approaches have been developed to either knock out HTT by inducing mutations or excise the region containing the CAG repeat. Several groups have shown in vitro and in vivo proof of principle using single guide RNAs directed to HTT-ex1 to induce HTT knockout.145148 Further, using a double guide RNA approach, various groups have shown that it is possible to excise the region containing CAG repeat.149154 The size of this region differs based on the chosen guide RNAs, with the first report by Shin et al deleting a large 44 kb region,149 while the most precise excision was shown by Yang et al and Monteys et al, who deleted only the CAG repeat and small flanking regions.150,151
Several HTT lowering therapies are either already in clinical trials or are close to entering the clinic. These therapies include different therapeutic modalities and mechanisms of action, each with distinct potential efficacy and safety profiles. Only the approaches in clinical trials or performing IND-enabling studies are covered here.
Two of the most advanced programs, the Phase III trial with the non-allele-specific HTT exon 36-targeting ASO tominersen (Roche) and the phase I/II trials with the allele-specific mHTT-associated single nucleotide polymorphism (SNP)-targeting ASOs WVE-120101 and WVE-120102 (Wave Life Sciences) were halted in 2021, as reviewed elsewhere.155 Roche plans to design a new Phase II study with tominersen, for younger adult patients with lower disease burden (https://ir.ionispharma.com/news-releases/news-release-details/ionis-partner-evaluate-tominersen-huntingtons-disease-new-phase). Wave Life Sciences has now initiated a new trial with their novel product WVE-003, which targets another SNP and has improved chemistry (clinicaltrials.gov NCT05032196). These ASOs are administered repeatedly through intrathecal administration, which may explain some of the adverse events observed with tominersen, which was more pronounced in the cohort receiving more frequent administration.155 Neither drug is expected to affect HTT-ex1 formation or RNA-mediated toxicity.
Novartis and PTC Therapeutics both have initiated Phase 2 clinical trials for their splicing modulators Branaplam (NCT05111249) and PTC518 (NCT05358717). These small molecules induce the inclusion of a pseudoexon between HTT exons 49 and 50, which leads to a premature stop codon and subsequent nonsense-mediated decay.156,157 One of the main advantages is that these small molecules can be administered orally. Furthermore, the mechanism of action targets the pre-mRNA and is therefore quite upstream in the molecular pathology. However, this approach is not specific for the mutant allele and, as it targets a downstream exon, is also not expected to affect HTT-ex1 production or toxic RNA gain-of-function.
In a more indirect fashion, metformin has been shown to reduce translation of HTT through interacting with the MID1/PP2A/mTOR protein complex.158 Interestingly, the effect of metformin was found to be specific for mHTT and to also impact HTT-ex1 protein formation. The drug can be administered orally, and as it is already in clinical use for the treatment of diabetes, its safety profile has already been well established. Metformin is currently being tested for the treatment of HD in a phase III clinical trial to establish its potential as a treatment for HD (NCT04826692). Although it has been shown to reduce HTT levels, RNA-mediated toxicity is not expected to be targeted by its mechanism of action.
There are no therapies that target HTT-ex1 exclusively, but some therapies target HTT-ex1 in addition to the full-length HTT. The most advanced is uniQures gene therapy AMT-130, which is currently being tested in phase I/II clinical trials (NCT04120493 and NCT05243017). AMT-130 is an AAV5-delivered miRNA which is administered through a one-time intrastriatal injection. This therapy is not allele-selective, and its effect on RNA-mediated toxicity has not yet been established.
Several other HTT-ex1 targeting candidates are close to entering clinical trials, including Galyan Bios HTT-ex1 binding small molecule GLYN122 and Vybions INT41 intrabody. These therapeutic candidates target the protein and are therefore not expected to impact RNA-mediated toxicity. According to the companies websites, both are performing IND-enabling studies, although their target date to enter the clinic is not clear (https://www.galyan.bio/pipeline, https://www.vybion.com/?page=product_pipeline).
Likewise, Vico Therapeutics received FDA orphan drug designation for their CAG-targeting ASO in July 2021 and is expected to start clinical trials soon (https://vicotx.com/pipeline/). Takeda and Sangamo are further developing their ZFP approach targeting the CAG repeat (https://www.sangamo.com/programs/). Both approaches preferentially target mHTT and as they act on the (pre-)mRNA and on transcription, respectively, these drug candidates may also have a beneficial effect on RNA-mediated toxicity.
Although all the approaches mentioned, as well as others in earlier phases of development, aim to reduce HTT levels, their mechanism of action is different and not all pathways related to HTT toxicity will be engaged. The relative contribution of each pathway is a matter of debate and is likely to depend on many factors, including age, tissue and cell type. Several of the described mechanisms of N-terminal HTT fragment production, including calpain cleavage and premature polyadenylation, have been shown to correlate with repeat length. This is also the case with HTT-ex1 formation through aberrant splicing. Therefore, it may be expected that as the repeat gets longer over time due to somatic instability, the contribution of these mechanisms will increase. Nonetheless, the broad molecular pathology of HD would likely benefit most from an intervention that acts as far upstream as possible, ie, on the DNA or the RNA level.
For an approach to be successful in disease modification, next to efficiency, adequate safety is key. Safety issues can arise from intrinsic characteristics of the therapeutic modality itself (eg, chemistry, properties of the therapeutic vector, and need of chronic administration), which are not covered in this review. The mechanism of action of the approach can also have different safety risks. Very specific approaches, with a well-understood mechanism, and with low to no interactions with other processes and molecules other than those related to HTT toxicity, would be preferred.
Multiple different approaches are running head-to-head. The small molecule splicing modulators are among the most elegant in terms of delivery, as these are capable of crossing the bloodbrain barrier and can therefore be administered orally. However, these small molecules are not specific for mHTT or even solely for HTT, and long-term studies are needed to determine the safety profile. Furthermore, these splicing modulators are expected to affect neither aberrant splicing of HTT-ex1 nor toxic RNA gain-of-function effects. ASOs and siRNAs have a less favorable distribution and need to be administered locally, although novel chemistries, such as peptide nucleic acids and di-siRNAs, have shown more promising biodistribution and may allow for systemic administration. These synthetic oligonucleotides are active for a limited amount of time, and therefore need to be readministered frequently. CAG-targeting ASOs are expected to not only reduce HTT and HTT-ex1 protein gain-of-function but also to alleviate RNA-mediated toxicity; however, non-specific effects on other genes containing CAG repeats may be difficult to overcome. Finally, the gene therapy approaches utilize AAVs to deliver their cargo. The current generation of AAVs is not sufficiently capable of crossing the bloodbrain barrier and therefore still needs to be administered locally, although efforts are ongoing to identify novel capsids that could be administered in a less invasive manner, eg, Goertsen et al.159 Because most cells that are targeted in HD are non-dividing, a more invasive route of administration is, however, less of an issue, as the therapy would only need to be administered once. uniQures miRNA-based strategy would reduce toxic protein gain-of-function, whereas Takeda and Sangamos ZFP approach targets DNA and thereby acts upstream of mHTT transcription, which would improve both toxic protein- and RNA gain-of-function; yet, as the mechanism of action of this approach involves direct targeting of the repeat, off-target effects may be an issue. Pre-clinically, gene editing approaches using CRISPR-Cas are being explored. However, long-term studies will need to show the safety profiles of such approaches.
To maximize therapeutic efficacy, future research will need to point out whether it may be advantageous to combine various therapeutic strategies with different modes of action. Further, it is likely that any therapeutic approach will benefit from as early intervention as possible. To this end, excellent safety profiles and good biomarkers of both safety and efficacy will be key.160
In summary, we have reviewed the production of N-terminal HTT protein fragments, their role in HD pathology, as well as therapeutic approaches to target these toxic species. Extensive research into HD continues to deepen our understanding of the broad molecular mechanisms leading to disease. With the increasing understanding of the pathological mechanisms associated with mHTT, several different therapeutic approaches are being developed, which will hopefully lead, in the near future, to halting or modification of this devastating disease.
We thank our uniQure colleagues who provided a critical review of the manuscript.
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
LB, ME and AV are employees of, and may own stock/options in, uniQure biopharma B.V. In addition, Dr Astrid Valls has a patent WO2021053018 issued to UNIQURE IP B.V. The authors report no other conflicts of interest in this work.
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Adverum to Present at the Inaugural Gilmartin Group Emerging Growth Company Showcase – GlobeNewswire
REDWOOD CITY, Calif., Aug. 26, 2022 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases, today announced that Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies, will present at the Gilmartin Group Inaugural Emerging Growth Company Showcase, being held on Wednesday, August 31, 2022.
Interested parties can access a live webcast of the presentation directly by following this link. An archived webcast of the presentation will be available under the Events and Presentations in the Investors section of Adverums website.
About Adverum Biotechnologies
Adverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases with the aspiration of developing functional cures for these diseases to restore vision and prevent blindness. Leveraging the research capabilities of its proprietary, intravitreal (IVT) platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. By overcoming the challenges associated with current treatment paradigms for these debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit http://www.adverum.com.
Forward-looking Statements
Statements 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. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including risks inherent to, without limitation: Adverums novel technology, which makes it difficult to predict the timing of commencement and completion of clinical trials; regulatory uncertainties; enrollment uncertainties; the results of early clinical trials not always being predictive of future clinical trials and results; and the potential for future complications or side effects in connection with use of Ixo-vec. Additional risks and uncertainties facing Adverum are set forth under the caption Risk Factors and elsewhere in Adverums Securities and Exchange Commission (SEC) filings and reports, including Adverums Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 filed with the SEC on August 11, 2022. 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.
Corporate & Investor Inquiries
Anand ReddiVice President, Head of Corporate Strategy, External Affairs and EngagementAdverum Biotechnologies, Inc.T: 650-649-1358E: areddi@adverum.com
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Adverum to Present at the Inaugural Gilmartin Group Emerging Growth Company Showcase - GlobeNewswire
Global Viral Vectors and Plasmid DNA Manufacturing Market (2022 to 2027) – Featuring Audentes Therapeutics, Batavia Biosciences and BioMarin…
DUBLIN, Aug. 26, 2022 /PRNewswire/ -- The "Global Viral Vectors and Plasmid DNA Manufacturing Market (2022-2027) by Product Type, Application, Geography, Competitive Analysis and the Impact of Covid-19 with Ansoff Analysis" report has been added to ResearchAndMarkets.com's offering.
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The Global Viral Vectors and Plasmid DNA Manufacturing Market is estimated to be USD 901.01 Mn in 2022 and is expected to reach USD 2752.97 Mn by 2027, growing at a CAGR of 25.03%.
Market dynamics are forces that impact the prices and behaviors of the Global Viral Vectors and Plasmid DNA Manufacturing Market stakeholders. These forces create pricing signals which result from the changes in the supply and demand curves for a given product or service. Forces of Market Dynamics may be related to macro-economic and micro-economic factors.
There are dynamic market forces other than price, demand, and supply. Human emotions can also drive decisions, influence the market, and create price signals. As the market dynamics impact the supply and demand curves, decision-makers aim to determine the best way to use various financial tools to stem various strategies for speeding the growth and reducing the risks.
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The report provides a detailed analysis of the competitors in the market. It covers the financial performance analysis for the publicly listed companies in the market. The report also offers detailed information on the companies' recent development and competitive scenario. Some of the companies covered in this report are Merck KGaA, Lonza, FUJIFILM Diosynth Biotechnologies, Thermo Fisher Scientific, Cobra Biologics, Catalent, etc.
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America (Argentina, Brazil, Canada, Chile, Colombia, Mexico, Peru, United States, Rest of Americas)
Europe (Austria, Belgium, Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Poland, Russia, Spain, Sweden, Switzerland, United Kingdom, Rest of Europe)
Middle-East and Africa (Egypt, Israel, Qatar, Saudi Arabia, South Africa, United Arab Emirates, Rest of MEA)
Asia-Pacific (Australia, Bangladesh, China, India, Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Thailand, Taiwan, Rest of Asia-Pacific)
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The report presents a detailed Ansoff matrix analysis for the Global Viral Vectors and Plasmid DNA Manufacturing Market. Ansoff Matrix, also known as Product/Market Expansion Grid, is a strategic tool used to design strategies for the growth of the company. The matrix can be used to evaluate approaches in four strategies viz. Market Development, Market Penetration, Product Development and Diversification.
The matrix is also used for risk analysis to understand the risk involved with each approach. The analyst analyses the using the Ansoff Matrix to provide the best approaches a company can take to improve its market position. Based on the SWOT analysis conducted on the industry and industry players, the analyst has devised suitable strategies for market growth.
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The report offers a comprehensive evaluation of the Global Viral Vectors and Plasmid DNA Manufacturing Market. The report includes in-depth qualitative analysis, verifiable data from authentic sources, and projections about market size. The projections are calculated using proven research methodologies.
The report has been compiled through extensive primary and secondary research. The primary research is done through interviews, surveys, and observation of renowned personnel in the industry.
The report includes an in-depth market analysis using Porter's 5 forces model and the Ansoff Matrix. In addition, the impact of Covid-19 on the market is also featured in the report.
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2 Research Methodology
3 Executive Summary
4 Market Dynamics4.1 Drivers4.1.1 Increasing Capacities by Manufacturers Owing to Rising Demand4.1.2 Rise in Prevalence of Cancer, Viral Infections, and Genetic Disorders4.1.3 Increase in Awareness Regarding Gene Therapies4.2 Restraints4.2.1 High Cost Associated with Gene Therapies4.2.2 Stringent Government Regulations4.3 Opportunities4.3.1 The Rise in the Development of Allogeneic and Autologous Cell Therapy4.3.2 Increase in Funding for R&D Activities Pertaining to Gene Therapy4.4 Challenges4.4.1 Involved Risks For Mutagenesis and Other Obstruction in Gene Therapy
5 Market Analysis5.1 Regulatory Scenario5.2 Porter's Five Forces Analysis5.3 Impact of COVID-195.4 Ansoff Matrix Analysis
6 Global Viral Vectors and Plasmid DNA Manufacturing Market, By Product Type6.1 Introduction6.2 Plasmid DNA6.3 Viral Vector6.4 Non-viral Vector
7 Global Viral Vectors and Plasmid DNA Manufacturing Market, By Application7.1 Introduction7.2 Cancer7.3 Genetic Disorder7.4 Infectious Disease7.5 Other Applications
8 Americas' Viral Vectors and Plasmid DNA Manufacturing Market8.1 Introduction8.2 Argentina8.3 Brazil8.4 Canada8.5 Chile8.6 Colombia8.7 Mexico8.8 Peru8.9 United States8.10 Rest of Americas
9 Europe's Viral Vectors and Plasmid DNA Manufacturing Market9.1 Introduction9.2 Austria9.3 Belgium9.4 Denmark9.5 Finland9.6 France9.7 Germany9.8 Italy9.9 Netherlands9.10 Norway9.11 Poland9.12 Russia9.13 Spain9.14 Sweden9.15 Switzerland9.16 United Kingdom9.17 Rest of Europe
10 Middle East and Africa's Viral Vectors and Plasmid DNA Manufacturing Market10.1 Introduction10.2 Egypt10.3 Israel10.4 Qatar10.5 Saudi Arabia10.6 South Africa10.7 United Arab Emirates10.8 Rest of MEA
11 APAC's Viral Vectors and Plasmid DNA Manufacturing Market11.1 Introduction11.2 Australia11.3 Bangladesh11.4 China11.5 India11.6 Indonesia11.7 Japan11.8 Malaysia11.9 Philippines11.10 Singapore11.11 South Korea11.12 Sri Lanka11.13 Thailand11.14 Taiwan11.15 Rest of Asia-Pacific
12 Competitive Landscape12.1 Competitive Quadrant12.2 Market Share Analysis12.3 Strategic Initiatives12.3.1 M&A and Investments12.3.2 Partnerships and Collaborations12.3.3 Product Developments and Improvements
13 Company Profiles 13.1 Audentes Therapeutics13.2 Batavia Biosciences13.3 BioMarin Pharmaceutical13.4 BioNTech IMFS13.5 Catalent13.6 Cobra Biologics13.7 FUJIFILM Diosynth Biotechnologies13.8 Genezen laboratories13.9 Lonza13.10 Merck KGaA13.11 Miltenyi Biotec13.12 RegenxBio13.13 SIRION Biotech 13.14 Takara Bio13.15 Thermo Fisher Scientific13.16 Virovek 13.17 Waisman Biomanufacturing13.18 Wuxi Biologics
14 Appendix
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Gene Therapy Market Research Report 2022 – ResearchAndMarkets.com – Business Wire
DUBLIN--(BUSINESS WIRE)--The "Gene Therapy Market by Type of Therapy, Type of Gene Delivery Method Used, Type of Vector Used, Target Therapeutic Areas, Route of Administration, and Key Geographical Regions: Industry Trends and Global Forecasts, 2022-2035" report has been added to ResearchAndMarkets.com's offering.
Gene Therapy Market (5th Edition) report features an extensive study of the current market landscape and the likely future potential associated with the gene therapy market, primarily focusing on gene augmentation-based therapies, oncolytic viral therapies, immunotherapies and gene editing therapies.
One of the key objectives of the report was to estimate the existing market size and the future opportunity associated with gene therapies, over the next decade. Based on multiple parameters, such as target patient population, likely adoption rates and expected pricing, we have provided informed estimates on the evolution of the market for the period 2022-2035.
Over the last two decades, there have been several breakthroughs related to the development of gene therapies. In 2020, LibmeldyT, an ex vivo gene therapy received approval for the treatment of metachromatic leukodystrophy. To provide more context, the treatment regimen of such therapies, encompassing gene replacement and gene-editing modalities, is aimed at correction of the mutated gene in patients using molecular carriers (viral and non-viral vectors).
Further, post the onset of the COVID-19 pandemic, there has been a steady increase in the investigational new drug (IND) applications filed for cell and gene therapies. In fact, in 2021, more than 200 gene therapies were being evaluated in phase II and III studies. Moreover, in 2022, six gene therapies are expected to receive the USFDA market approval. Promising results from ongoing clinical research initiatives have encouraged government and private firms to make investments to support therapy product development initiatives in this domain.
In 2021 alone, gene therapy developers raised around USD 9.5 billion in capital investments. Taking into consideration the continuous progress in this domain, gene therapies are anticipated to be used for the treatment of 1.1 million patients suffering from a myriad of disease indications, by 2035.
Presently, more than 250 companies are engaged in the development of various early and late-stage gene therapies, worldwide. In recent years, there has been a significant increase in the integration of novel technologies, such as gene modification, gene-editing, genome sequencing and manipulation technologies (molecular switches), in conjugation with gene delivery methods.
For instance, the CRISPR-Cas9 based gene-editing tool is one of the remarkable technological advancements, which enables the precise alteration of the transgene. It is worth mentioning that the new generation delivery platforms, including nanoparticles and hybrid vector systems, have been demonstrated to be capable of enabling effective and safe delivery of gene based therapeutics.
Further, a variety of consolidation efforts are currently ongoing in this industry. Such initiatives are primarily focused on expanding and strengthening the existing development efforts; this can be validated from the fact that 56% of the total acquisitions reported in the domain were focused on drug class consolidation.
Driven by the collective and consistent efforts of developers and the growing demand for a single dose of effective therapeutic, the gene therapy market is anticipated to witness significant growth in the foreseen future.
Key Questions Answered
Key Topics Covered:
1. PREFACE
2. EXECUTIVE SUMMARY
3. INTRODUCTION
3.1. Context and Background
3.2. Evolution of Gene Therapies
3.3. Classification of Gene Therapies
3.3.1. Somatic and Germline Gene Therapies
3.3.2. Ex Vivo and In Vivo Gene Therapies
3.4. Routes of Administration
3.5. Mechanism of Action
3.6. Overview of Gene Editing
3.6.1. Evolution of Genome Editing
3.6.2. Applications of Genome Editing
3.6.3. Available Genome Editing Techniques
3.7. Advantages and Disadvantages of Gene Therapies
3.7.1 Ethical and Social Concerns Related to Gene Therapies
3.7.2. Constraints and Challenges Related to Gene Therapies
3.7.3. Therapy Development Concerns
3.7.4. Manufacturing Concerns
3.7.5. Commercial Viability Concerns
4. GENE DELIVERY VECTORS
4.1. Chapter Overview
4.2. Viral and Non-Viral Methods of Gene Transfer
4.3. Viral Vectors for Genetically Modified Therapies
4.4. Types of Viral Vectors
4.5. Types of Non-Viral Vectors
5. REGULATORY LANDSCAPE AND REIMBURSEMENT SCENARIO
5.1. Chapter Overview
5.2. Regulatory Guidelines in North America
5.3. Regulatory Guidelines in Europe
5.4. Regulatory Guidelines in Asia-Pacific
5.5. Reimbursement Scenario
5.6. Commonly Offered Payment Models for Gene Therapies
6. MARKET OVERVIEW
6.1. Chapter Overview
6.2. Gene Therapy Market: Clinical and Commercial Pipeline
6.3. Gene Therapy Market: Early-Stage Pipeline
6.4. Gene Therapy Market: Special Drug Designations
6.5. Analysis by Phase of Development, Therapeutic Area and Type of Therapy (Grid Representation)
7. COMPETITIVE LANDSCAPE
7.1. Chapter Overview
7.2. Gene Therapy Market: List of Developers
7.3. Key Players: Analysis by Number of Pipeline Candidates
8. MARKETED GENE THERAPIES
8.1. Chapter Overview
8.2. Gendicine (Shenzhen Sibiono GeneTech)
8.3. Oncorine (Shanghai Sunway Biotech)
8.4. Rexin-G (Epeius Biotechnologies)
8.5. Neovasculgen (Human Stem Cells Institute)
8.6. Imlygic (Amgen)
8.7. Strimvelis (Orchard Therapeutics)
8.8. LuxturnaT (Spark Therapeutics)
8.9. ZolgensmaT (Novartis)
8.10. Collategene (AnGes)
8.11. ZyntelgoT (bluebird bio)
8.12. LibmeldyT (Orchard Therapeutics)
9. KEY COMMERCIALIZATION STRATEGIES
9.1. Chapter Overview
9.2. Successful Drug Launch Strategy: ROOTS Framework
9.3. Successful Drug Launch Strategy: Product Differentiation
9.4. Commonly Adopted Commercialization Strategies based on Phase of Development of Product
9.5. List of Currently Approved Gene Therapies
9.6. Key Commercialization Strategies Adopted by Gene Therapy Developers
9.6.1. Strategies Adopted Before Therapy Approval
9.6.1.1. Participation in Global Events
9.6.1.2. Collaboration with Stakeholders and Pharmaceutical Firms
9.6.1.3. Indication Expansion
9.6.2. Strategies Adopted During/Post Therapy Approval
9.6.2.1. Geographical Expansion
9.6.2.2. Participation in Global Events
9.6.2.3. Patience Assistance Programs
9.6.2.4. Awareness through Product Websites
9.6.2.5. Collaboration with Stakeholders and Pharmaceutical Firms
9.7. Concluding Remarks
10. LATE STAGE (PHASE II/III AND ABOVE) GENE THERAPIES
10.1. Chapter Overview
10.2. Lumevoq (GS010): Information on Dosage, Mechanism of Action, Clinical Trials and Clinical Trial Results
10.3. OTL-103
10.4. PTC-AADC
10.5. BMN 270
10.6. rAd-IFN/Syn3
10.7. beti-cel
10.8. eli-cel
10.9. lovo-cel
10.10. SRP-9001
10.11. EB-101
10.12. ProstAtak
10.13. D-Fi
Continued here:
Gene Therapy Market Research Report 2022 - ResearchAndMarkets.com - Business Wire
Health and Tech: The promise of gene therapy to cure cancers – Telangana Today
Published: Published Date - 09:21 PM, Wed - 10 August 22
Hyderabad: This concept may seem quite fictional and even futuristic. However, this is what geneticists worldwide through gene therapy are pursuing, while trying to find cure for a wide range of diseases that challenge modern medicine including cancers, heart diseases, diabetes, haemophilia, AIDS, genetic disorders, among others.
Gene therapy involves altering the genes inside the cells of the human body, in order to treat or prevent the disease progression. Essentially, geneticists worldwide are exploring ways to utilise gene therapy to alter genetic composition of cells that are responsible for causing diseases and in the process find a long term cure for diseases. The potential to unlock the cure for a wide range of diseases has become a major driving force for researchers and pharma giants worldwide to focus their energies and resources on gene therapy.
So what exactly is gene and gene therapy?
The Gene Therapy Advisory and Evaluation Committee (GTAEC), which monitors clinical trials across India on gene therapies, defines Gene is the most basic and functional unit of heredity and inheritance and consists of a specific sequence of nucleotides in DNA or RNA located on chromosomes that encodes for specific proteins. The human genome comprises more than 20,000 genes. Gene therapy refers to the process of introduction, removal or change in content of an individuals genetic material with the goal of treating the disease and a possibility of achieving long term cure.
The genetic material that has to be introduced to the diseased cell is done through a vector, whch is usually a virus. Viruses are the preferred vectors or vehicles as they are adaptable and efficient in delivering genetic material, the GTAEC, said.
While worldwide major pharmaceutical companies are developing gene therapies for treatment of single gene defects like haemophilia and muscular dystrophy, the Department of Biotechnology (DBT), Government of India, Tata Memorial Hospital, Mumbai and IIT-Mumbai have collaborated to start clinical trials of gene therapy on cancer in India.
Gene therapy in cancer:
In the last few years, CAR- (Chimeric Antigen Receptor) T therapy, a form of gene therapy has emerged as a breakthrough treatment for cancer, especially for leukemia, lymphoma (cancer of the lymphatic system) and multiple myeloma or the cancer of the plasma cells.
The CAR-T cells are genetically engineered in a laboratory and they bind with the cancer cells and kill them. The therapy is available in a few cancer research centres (on clinical trials basis) in US and cost of treatment ranges anywhere from Rs 3 crore to Rs. 4 crore.
To reduce treatment costs, promote and support development CAR-T cell technology against cancers, for the first time in India, Biotechnology Industry Research Assistance Council (BIRAC), established by DBT, Tata Memorial Hospital and IIT Bombay, have launched clincal trials of CAR-T gene therapy to treat cancers. The CAR-T cells were designed and manufactured at Bioscience and Bioengineering (BSBE) department of IIT Bombay. The gene therapy study on cancers is in early phase clinical trials at Tata Memorial in Mumbai.
Regulation of gene therapy:
Realising the potential of gene therapies in treating complex diseases, the GOI is providing financial and even technical guidance to researchers through ICMR, DBT and DST. To ensure gene therapies are introduced in India and clinical trials for gene therapies are performed in an ethical, scientific and safe manner, the ICMR has also framed National Guidelines for Gene Therapy Product Development and Clinical Trials document.
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Health and Tech: The promise of gene therapy to cure cancers - Telangana Today
Stem Cell Therapy Global Market Report 2022: Rising Research and Development Spending, and Increasing Healthcare Expenditure Present Future…
DUBLIN, Aug. 10, 2022 /PRNewswire/ -- The "Stem Cell Therapy Global Market Opportunities And Strategies To 2031" report has been added to ResearchAndMarkets.com's offering.
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The global stem cell therapy market reached a value of nearly $4,019.6 million in 2021, having increased at a compound annual growth rate (CAGR) of 70.9% since 2016. The market is expected to grow from $4,019.6 million in 2021 to $10,600.2 million in 2026 at a rate of 21.4%. The market is then expected to grow at a CAGR of 11.4% from 2026 and reach $18,175.4 million in 2031.
Growth in the historic period in the stem cell therapy market resulted from rising prevalence of chronic diseases, a rise in funding from governments and private organizations, rapid growth in emerging markets, an increase in investments in cell and gene therapies, surge in healthcare expenditure, and an increase in pharmaceutical R&D expenditure. The market was restrained by low healthcare access in developing countries, limited reimbursements, and ethical concerns related to the use of embryonic stem cells in the research and development.
Going forward, increasing government support, rapid increase in the aging population, rising research and development spending, and increasing healthcare expenditure will drive market growth. Factors that could hinder the growth of the market in the future include high cost of stem cell therapy, stringent regulations imposed by regulators, and high cost of storage of stem cells.
The stem cell therapy market is segmented by type into allogeneic stem cell therapy and autologous stem cell therapy. The autologous stem cell therapy segment was the largest segment of the stem cell therapy market segmented by type, accounting for 100% of the total in 2021.
The stem cell therapy market is also segmented by cell source into adult stem cells, induced pluripotent stem cells, and embryonic stem cells. The induced pluripotent stem cells was the largest segment of the stem cell therapy market segmented by cell source, accounting for 77.2% of the total in 2021. Going forward, the adult stem cells segment is expected to be the fastest growing segment in the stem cell therapy market segmented by cell source, at a CAGR of 21.7% during 2021-2026.
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The stem cell therapy market is also segmented by application into musculoskeletal disorders and wounds & injuries, cancer, autoimmune disorders, and others. The cancer segment was the largest segment of the stem cell therapy market segmented by application, accounting for 49.7% of the total in 2021. Going forward, musculoskeletal disorders and wounds & injuries segment is expected to be the fastest growing segment in the stem cell therapy market segmented by application, at a CAGR of 22.1% during 2021-2026.
The stem cell therapy market is also segmented by end-users into hospitals and clinics, research centers, and others. The hospitals and clinics segment was the largest segment of the stem cell therapy market segmented by end-users, accounting for 66.0% of the total in 2021. Going forward, hospitals and clinics segment is expected to be the fastest growing segment in the stem cell therapy market segmented by end-users, at a CAGR of 22.0% during 2021-2026.
Scope:
Markets Covered:
By Type: Allogeneic Stem Cell Therapy; Autologous Stem Cell Therapy
By Cell Source: Adult Stem Cells; Induced Pluripotent Stem Cells; Embryonic Stem Cells
By Application: Musculoskeletal Disorders and Wounds & Injuries; Cancer; Autoimmune Disorders; Others
By End-Users: Hospitals And Clinics; Research Centers; Others
Key Topics Covered:
1. Stem Cell Therapy Market Executive Summary
2. Table of Contents
3. List of Figures
4. List of Tables
5. Report Structure
6. Introduction
7. Stem Cell Therapy Market Characteristics
8. Stem Cell Therapy Trends And Strategies
9. Impact Of Covid-19 On Stem Cell Therapy Market
10. Global Stem Cell Therapy Market Size And Growth
11. Global Stem Cell Therapy Market Segmentation
12. Stem Cell Therapy Market, Regional And Country Analysis
13. Asia-Pacific Stem Cell Therapy Market
14. Western Europe Stem Cell Therapy Market
15. Eastern Europe Stem Cell Therapy Market
16. North America Stem Cell Therapy Market
17. South America Stem Cell Therapy Market
18. Middle East Stem Cell Therapy Market
19. Africa Stem Cell Therapy Market
20. Stem Cell Therapy Global Market Competitive Landscape
21. Stem Cell Therapy Market Pipeline Analysis
22. Key Mergers And Acquisitions In The Stem Cell Therapy Market
23. Stem Cell Therapy Market Opportunities And Strategies
24. Stem Cell Therapy Market, Conclusions And Recommendations
25. Appendix
Companies Mentioned
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New research digs into the genetic drivers of heart failure, with an eye to precision treatments – STAT
When coronary arteries are blocked, starving the heart of blood, there are good medications and treatments to deploy, from statins to stents. Not so for heart failure, the leading factor involved in heart disease, the top cause of death worldwide.
Its whats on death certificates, said cardiologist Christine Seidman.
Seidman has long been interested in heart muscle disorders and their genetic drivers. She studies heart failure and other conditions that affect the myocardium the muscular tissue of the heart not the blood vessels where atherosclerosis and heart attacks come from, although their consequences are also felt in the myocardium, including heart failure.
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With her colleagues at Brigham and Womens Hospital and Harvard Medical School, she and a long list of international collaborators have been exploring the genetic underpinnings of heart failure. Based on experiments deploying a new technique called single-nucleus RNA sequencing on samples from heart patients, on Thursday they reported in Science their discovery of how genotypes change the way the heart functions.
Their work raises the possibility that some of the molecular pathways that lead to heart failure could be precisely targeted, in contrast to treating heart failure as a disease with only one final outcome.
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Were not there yet, but we certainly have the capacity to make small molecules to interfere with pathways that we think are deleterious to the heart in this setting, she said. To my mind, thats the way to drive precision therapeutics. We know the cause of heart failure. We intervene in a pathway that we know is activated. And for the first time, we have that information now from human samples, not from an experimental model.
Seidman talked with STAT about the research, including how snRNAseq solves the smoothie problem, and what it might mean for patients. The conversation has been edited for clarity and brevity.
What happens in heart failure?
The heart becomes misshapen in one of two ways. It either becomes hypertrophied, where the walls of heart muscle become thickened and the volume within the heart is diminished, in what we call hypertrophic cardiomyopathy. Or it becomes dilated, when the volume in the heart is expanded and the walls become stretched. I think of it as an overinflated balloon, and that is called dilated cardiomyopathy.
Hypertrophy and dilatation are known to cause the heart over time to have profoundly diminished functional capacity. And clinically, we call that heart failure, much more commonly arising from dilated cardiomyopathy.
What does it feel like to patients?
When we see patients clinically, theyre short of breath, they have fluid retention. When we look at their hearts, we see that the pump function is diminished. That has led to a hypothesis of heart failure as sort of the end stage of many different disorders, but eventually the heart walks down a final common pathway. Then you need a transplant or a left ventricular assist device, or youre going to die prematurely.
What can be done?
Heart failure is a truly devastating condition, and it can arise early in life, in middle age, and in older people. There is no treatment for it, no cure for it, except cardiac transplantation, of course, which provides a whole host of other problems.
How did you approach this problem?
One of the questions we wanted to answer is, are there signals that we can discern that say there are different pathways and there are molecules that are functioning in those pathways that ultimately converge for failure, but through different strategies of your heart?
We treat every patient with heart failure with diuretics. We give them a series of different medications to reduce the pressure against which the heart has to contract. Im clinically a cardiologist, but molecularly Im a geneticist, so it doesnt make sense. If your house is falling down because the bricks are sticking together or if its falling down because the roof leaks and the water is pooling, you do things differently.
Tell me how you used single-cell RNA sequencing to learn more.
Looking at RNA molecules gives us a snapshot of how much a gene is active or inactive at a particular time point. Until recently, we couldnt do that in the heart because the approach had been to take heart tissue, grind it all up, and look at the RNAs that are up or down. But that gives you what we call a smoothie: Its all the different component cells those strawberries, blueberries, bananas mixed together.
But theres a technology now called single-cell RNA sequencing. And that says, what are the RNAs that are up or down in the cardiomyocytes as compared to the smooth muscle cells, as compared to the fibroblasts, all of which are in the cells? You get a much more precise look at whats changing in a different cell type. And thats the approach that we use, because cardiomyocytes [the cells in the heart that make it contract] are very large. Theyre at least three times bigger than other cells. We cant capture the single cell it literally does not fit through the microfluidic device. And so we sequenced the nuclei, which is where the RNA emanates from.
What did you find?
There were some similarities, but what was remarkable was the degree of differences that we saw in cardiomyocytes, in endothelial cells, in fibroblasts. Theres a signature thats telling us I walked down this pathway as compared to a different one that caused the heart to fail, but through activation or lack of activation of different signals along the way.
And that to me is the excitement, because if we can say that, we can then go back and say, OK, what happens if we were to have tweaked the pathway in this genotype and a different pathway in a different genotype? Thats really what precision therapy could be about, and thats where we aim to get to.
Whats the next step?
It may be that several genotypes will have more similarities as compared to other genotypes. But understanding that, I think, will allow us to test in experimental models, largely in mice, but increasingly in cellular models of disease, in iPS [induced pluripotent stem] cells that we can now begin to use molecular technologies to silence a pathway and see what that does to the cardiomyocytes, or silence the fibroblast molecule and see what that does in that particular genotype.
To my mind, thats the way to drive precision therapeutics. We know the cause of heart failure. We intervene in a pathway that we know is activated. And for the first time, we have that information now from human samples, not from an experimental model.
What might this mean for patients?
If we knew that an intervention would make a difference thats where the experiments are we would intervene when we saw manifestations of disease. So the reason I can tell you with confidence that certain genes cause dilated cardiomyopathy is theres a long time between the onset of that expansion of the ventricle until you develop heart failure. So theres years for us to be able to stop it in its tracks or potentially revert the pathology, if we can do that.
What else can you say?
I would be foolish not to mention the genetic cause of dilated cardiomyopathy. Ultimately, if you know the genetic cause of dilated cardiomyopathy, this is where gene therapy may be the ultimate cure. Were not there yet, but we certainly have the capacity to make small molecules to interfere with pathways that we think are deleterious to the heart in this setting.
My colleagues have estimated that approximately 1 in 250 to 1 in 500 people may have an important genetic driver of heart muscle disease, cardiomyopathy. Thats a huge number, but not all of them will progress to heart failure, thank goodness. Around the world, there are 23 million people with heart failure. Its what ends up on most peoples death certificate. It is the most common cause of death.
Its a huge, huge burden. And there really is no cure for it except transplantation. We dont have a reparative capacity, so were going to have to know a cause and be able to intervene precisely for that cause.
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New research digs into the genetic drivers of heart failure, with an eye to precision treatments - STAT
Intracranial Therapeutic Delivery Market revenue will climb to US$ 4.2 Bn by the end of 2032 Persistence Market Research – GlobeNewswire
New York, Aug. 08, 2022 (GLOBE NEWSWIRE) -- The global intracranial therapeutic delivery market is currently valued at around US$ 1.6 Bn and is anticipated to progress at an impressive CAGR of 7.9% over the 2022-2032 study period.
Cell and gene therapies are at the forefront of innovation in treating severe diseases, such as cancer, as well as rare diseases, accounting for around 12 percent of the pharmaceutical industrys clinical pipeline. However, the growing focus on effective therapy has impacted positive financial grades for cell and gene therapy throughout the clinical and social spectrum; intracranial therapeutic administration has been gaining favor in the biopharma industry.
The progressive development of CRISPR and next-generation sequencing has led to a surge in the interest in gene therapy and cell treatment in the past few years. The manufacturing community for cell and gene therapies, including pharmaceutical companies, contract development and manufacturing organizations (CDMOs), and suppliers of lab supplies and equipment, are looking into ways to strengthen supply chains and address process bottlenecks.
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Sales footprint expansion, which has been gaining more and more traction among key participants, calls for the desired assistance, based on financial approvals and consolidated activities. Additionally, several clinical trials have been carried out in association with research institutes.
Key Takeaways from Market Study
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Rising prevalence of neurological disorders and increasing research activities for the development of regenerative medicine to drive market growth over the coming years, says an analyst of Persistence Market Research.
Market Competition
The therapeutic delivery for intracranial is a highly consolidated market with limited key manufacturers operating in the industry. A majority of market players are focused on offering a limited range of cell, gene, and enzyme replacement therapy used for neurological disorder indications.
To strengthen their position in the global market, key players are focusing on strategic approaches such as mergers and collaborations to improve their production capabilities and expand their portfolios in various clinical and research fields.
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Persistence Market Research offers a unique perspective and actionable insights on the intracranial therapeutic delivery market in its latest study, presenting a historical demand assessment of 2017 2021 and projections for 2022 2032.
The research study is based on the therapy (cell-based therapy, gene therapy, and enzyme replacement therapy) and indication (spinal muscular atrophy (SMA), multiple sclerosis, batten disease), and amyotrophic lateral sclerosis, across three key regions of the world considered in the taxonomy.
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Intracranial Therapeutic Delivery Market revenue will climb to US$ 4.2 Bn by the end of 2032 Persistence Market Research - GlobeNewswire
The Alliance for Regenerative Medicine Announces the Appointment of Timothy D. Hunt as Chief Executive Officer – GlobeNewswire
The Alliance for Regenerative Medicine Announces the Appointment of Timothy D. Hunt as Chief Executive Officer
WASHINGTON, D.C. August 10, 2022
The Alliance for Regenerative Medicine (ARM), the leading international advocacy organization representing the cell and gene therapy sector, today formally announced that its Board of Directors has appointed Timothy D. Hunt as the organizations next Chief Executive Officer. Hunt will succeed Janet Lynch Lambert, who announced in April her plan to step down as CEO and who served on the Boards Search Committee. Hunt will start at ARM on September 6.
We are excited to welcome Tim to the ARM team at such a pivotal moment for our sector, said Emile Nuwaysir, Chair of the ARM Board and Search Committee,and President and Chief Executive Officer of Ensoma, an in vivo genomic medicines company. Tims two decades of experience advocating for biotechnology companies, knowledge of the key issues facing the cell and gene therapy field, and expertise in leading teams make him the ideal choice to guide ARM in building the future of medicine. Tim has a deep philosophy of engagement with major stakeholders that will support ARM members and help bring cell and gene therapies into mainstream medical practice.
Hunt was most recently the Chief Culture and Corporate Affairs Officer at Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer. Prior to that, he was the Chief Corporate Affairs Officer at CRISPR gene-editing pioneer Editas Medicine, where he led the companys global policy and government affairs, bioethics, communications, market development and human resources initiatives. He also served in executive public affairs roles at Cubist Pharmaceuticals and Biogen.
Hunt was an Advisory Group member of the Value-Based Payments for Medical Products consortium at the Duke-Margolis Center for Health Policy. He also has been a member of the Board of Directors of the non-profit organization Life Science Cares and has chaired the Ethics Committee of the American Society of Gene and Cell Therapy (ASGCT). Hunt previously served as a member of ARMs Gene Editing Task Force and on the Biotechnology Innovation Organizations Gene Editing Working Group. He received a B.A. in history and philosophy from Boston College and a J.D. from the Columbus School of Law at the Catholic University of America.
I am honored to succeed Janet as Chief Executive Officer of the Alliance for Regenerative Medicine and for the tremendous opportunity to build upon her legacy of developing ARM into the leading sector advocate and resource for the industry, said Hunt. Cell and gene therapies are already transforming patients lives, and we are on the cusp of even more breakthroughs in both rare and prevalent diseases. Our mission is both urgent and clear: to engage all our major stakeholders to ensure the patients we serve have access to the durable and potentially curative therapies of the present and future.
Tim is an excellent choice to continue to grow and strengthen this amazing organization and help realize the potential of regenerative medicine, said Lambert, whose tenure includes doubling ARMs global membership to 425 members, strengthening the organizations advocacy in the US and Europe, and building the ARM team.
Cell and gene therapies to treat blood cancers, spinal muscular atrophy, and an inherited form of blindness are approved in the US and Europe. 2022 could be a record year for new gene therapy approvals for rare disease, and regulators in the US and Europe could approve the first such therapies for hemophilia and sickle cell disease in late 2022 and 2023. More than 2,400 regenerative medicine clinical trials 60% of which targeted prevalent diseases including diabetes and cardiovascular disease were active globally at the end of 2021. ARM is committed to working with stakeholders to ensure that patients benefit from this rapidly advancing pipeline of transformative therapies.
About The Alliance for Regenerative Medicine
The Alliance for Regenerative Medicine (ARM) is the leading international advocacy organisation dedicated to realizing the promise of advanced therapy medicinal products (ATMPs).ARMpromotes legislative, regulatory, reimbursement and manufacturing initiativesin Europe and internationally to advance this innovative and transformative sector, which includes cell therapies, gene therapies and tissue-engineered therapies.Early products to market have demonstrated profound, durable and potentially curative benefits that are already helping thousands of patients worldwide, many of whom have no other viable treatment options. Hundreds of additional product candidates contribute to a robust pipeline of potentially life-changing ATMPs.In its 12-year history,ARMhas become the global voice of the sector, representing the interests of 425+ members worldwide and 80+ members across 15 Europeancountries, including small and large companies, academic research institutions, major medical centres and patient groups.To learn more aboutARMor to become a member, visithttp://www.alliancerm.org.
Media inquiries
For more information or for media requests, please contact Stephen Majors, Senior Director of Public Affairs for ARM, atsmajors@alliancerm.org.
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The Alliance for Regenerative Medicine Announces the Appointment of Timothy D. Hunt as Chief Executive Officer - GlobeNewswire