Daily Archives: August 22, 2021

Dublin, Aug. 20, 2021 (GLOBE NEWSWIRE) -- The "Gene Therapy - Technologies, Markets & Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors.

Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression. Gene editing technologies such as CRISPR-Cas9 and CAR-T cell therapies are also included. Gene therapy can now be combined with antisense techniques such as RNA interference (RNAi), further increasing the therapeutic applications.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2016, over 2050 clinical trials were completed, were ongoing, or had been approved worldwide. A breakdown of these trials is shown according to the geographical areas and applications.

Since the death of Jesse Gelsinger in the US following a gene therapy treatment, the FDA has further tightened the regulatory control on gene therapy. A further setback was the reports of leukemia following the use of retroviral vectors in successful gene therapy for adenosine deaminase deficiency. Several clinical trials were put on hold and many have resumed now. Four gene medicines have been approved by the FDA. The report also discusses the adverse effects of various vectors, safety regulations and ethical aspects of gene therapy including gene editing and germline gene therapy.

The markets for gene therapy have been difficult to estimate as there only a few approved gene therapy products Gene therapy markets are estimated for the years 2020-2030. The estimates are based on the epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright. The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

The voluminous literature on gene therapy was reviewed and selected 750 references are appended in the bibliography. The references are constantly updated. The text is supplemented with 79 tables and 25 figures.

Profiles of 202 companies involved in developing gene therapy are presented along with 266 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold in 2 decades. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report.

Benefits of this report

Story continues

Up-to-date on-stop information on gene therapy with 79 tables and 25 figures

Evaluation of gene therapy technologies

750 selected references from the literature

Estimates of gene therapy markets from 2020-2030

Profiles of 202 companies involved and collaborations in this area

Who should read this report?

Biotechnology companies developing gene therapy

Academic institutions doing research in gene therapy

Drug delivery companies

Pharmaceutical companies interested in gene therapy

Gene therapy companies

Venture capital and investment companies

Key Topics Covered:

Executive Summary

1. Introduction

2. Gene Therapy Technologies

3. Clinical Applications of Gene Therapy

4. Gene Therapy of Genetic Disorders

5. Gene Therapy of Cancer

6. Gene Therapy of Neurological Disorders

7. Gene Therapy of Cardiovascular Disorders

8. Gene therapy of viral infections

9. Research, Development and Future of Gene Therapy

10. Regulatory, Safety, Ethical Patent Issues of Gene Therapy

11. Markets for Gene Therapy

12. Companies involved in Gene Therapy

13. References

For more information about this report visit https://www.researchandmarkets.com/r/v69ou

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Global Gene Therapy Technologies, Markets & Competitive Landscape Report 2021 with Profiles of 202 Companies and 266 Collaborations in this Area -...

Heidi Marsh, 46, of Seattle, tested positive for the PALB2 mutation after her mother a breast cancer and pancreatic cancer patient was found to have it. She said her own doctor was unaware of the gene.

My OB-GYN was aware of my moms history and never suggested genetic testing, Ms. Marsh said. She never heard of it. I educated her. The oncologist she sent me to did not suggest surgery.

But Seattle Cancer Care Alliance, a partner of Fred Hutchinson Cancer Research Center, where Ms. Marshs mother had been an oncology nurse, did know about the gene mutation. The group immediately put together a team that included a surgical oncologist, a pancreatic cancer specialist, a geneticist, a nutritionist and a social worker.

This has been life-changing, said Ms. Marsh, who had her fallopian tubes removed in April. (She was told most ovarian cancer first occurs in the tubes. She plans to remove her ovaries after menopause.)

She will have breast monitoring with alternating mammograms and breast M.R.I.s every six months. She has already had an endoscopic ultrasound to look at her pancreas.

She has found a Facebook group, PALB2 Warriors, to be helpful. Because she has a background in health care she was a phlebotomist she says she looks further than individual postings, to studies that are placebo-controlled and peer-reviewed for information. But when it comes to personal stories of experience with prophylactic mastectomies and reconstruction, she says that is invaluable.

This was not remotely on my radar screen, she said. In one sense I feel empowered. But I also feel like I am waiting for the other shoe to drop, that cancer will be inevitable.

But mostly, she is thankful that she knows about PALB2 and the risks involved.

Its an alarm clock and a wake-up call, she said. You can do something about it if you choose.

Continue reading here:
This Breast Cancer Gene Is Less Well Known, but Nearly as Dangerous - The New York Times

For a long time, gene and cell therapies were a treatment option for the future. Now, the pace of development is moving at breakneck speed, with a number of firsts and $14.1billion in financing collected over the initial half of the year.

The Alliance for Regenerative Medicine has documented the acceleration on all fronts in a new report looking at the first half of 2021.

Most notably was Intellias demonstration of CRISPR gene-editing in humans through phase 1 data for patients with transthyretin (ATTR) amyloidosis. But thats not all for regenerative medicine, which includes cell and gene therapies, gene editing and tissue-based therapies.

Companies developing these therapies have collected $14.1 billion in the first half alone, which is 71% of what was raised during all of 2020. The alliance called this surge the strongest half on record. 2020 already broke financing records, with $20 billion, and the report suggests 2021 could exceed that total.

RELATED:Intellia hits a 'home run' with gene-editing results, setting up entire field for a grand slam

Cell-based immuno-oncology has for the first time surpassed gene therapy in financing, notching $6.6 billion compared to $6.4 billion, respectively. The broader category of cell therapy, including stem cell treatments for Parkinson's disease, meanwhilepicked up $1.1 billion.

Gene therapies and gene-modified cell therapy products are on track to notch the highest annual number of regulatory approvals. Three have already been approved. Bluebird bios Skysona nabbed an EU nod for the rare neuromuscular disease cerebral adrenoleukodystrophy. Bristol Myers Squibb and bluebirds multiple myeloma CAR-T drug Abecma was cleared by the FDA in late March. And Bristol Myers long-awaited CAR-T liso-cel, now called Breyanzi, was approved in February.

Waiting in the regulatory queue in the U.S. and EU isJohnson & Johnson and Legend Bios cilta-cel in multiple myeloma, which will compete with Abecma. Other companies have approvals pending around the world.

Even with these approvals, however, cell and gene therapies face hurdles once they are cleared for the market. Bluebird bio, for instance, has pulled back from European markets after failing to reach a consensus on pricing for the one-time treatment Zynteglo.

RELATED: With the pricing situation 'untenable' in Europe, bluebird will wind down its operations in the 'broken' market

The pipeline is nevertheless filled to the brim with new therapies. The report counted 1,320 industry-sponsored trials underway worldwide, including 158 that are in phase 3. Academic and other research is responsible for an additional 1,328 non-industry trialsincluding 85 late-stage studies.

Indications run the gamut of diseases, but are mostly concentrated in oncology for the industry-sponsored trials, followed by central nervous system (CNS) disorders and rare genetic diseases. Academic research similarly focuses on oncology, followed by infectious diseases and CNS.

CAR-T therapies, which take a patients own cells and power them up to fight cancer before being returned to the body, have been particularly dominate in R&D. Abecma is one example, but the J&J-Legend cilta-cel showed some promising data in June, with a 98% overall response rate in multiple myeloma. The therapy is currently being reviewed by EU and U.S. regulators, with a decision expected later this year.

RELATED:ASCO: J&J's anti-BCMA CAR-T pads its case ahead of speedy review and Bristol Myers showdown

More readouts are expected from Precision BioSciences and CRISPR Therapeutics, which are working on separate BCMA-targeted CAR-T therapies.

The alliance counts 566 companies as developing regenerative medicines and advanced therapies in the U.S. and 588 industry-sponsored trials with U.S. sites.

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Regenerative medicine nears banner year with $14.1B cash infusion, regulatory milestones and a well-stocked pipeline - FierceBiotech

DALLAS Aug. 21, 2021 A first-in-kind kidney cancer drug developed from laboratory and translational studies conducted at UTSouthwestern Medical Center received approval from the Food and Drug Administration, providing a new treatment for patients with familial kidney cancer.

FDA approval of belzutifan culminates a 25-year journey at UTSW from gene discovery to a first-in-class drug.

Mercks belzutifan grew out of the discovery at UTSouthwestern of a protein, HIF-2, that is key to fuel the growth of kidney and other cancers. HIF-2 was discovered by Steven McKnight, Ph.D., Professor of Biochemistry.

This is an exciting milestone for patients with inherited forms of kidney cancer who are in need of more effective therapies, said David Russell, Ph.D., Vice Provost and Dean of Research, and Professor of Molecular Genetics, who collaborated in the early stages of the research.

The drug, once called PT2977, was developed based on a backbone discovered by UTSW researchers, with further drug development efforts conducted by a spinoff company named Peloton Therapeutics, which was launched on the UTSW campus and eventually acquired by Merck.

Drs. McKnight and Russell first identified HIF-2 in the 1990s.

HIF-2 was considered undruggable for many years until two more UTSW scientists at the time Richard Bruick, Ph.D., Professor of Biochemistry, and Kevin Gardner, Ph.D., Professor of Biophysics, who also directs a structural biology center at the City University of New York did the structural and biochemical work showing that the HIF-2 molecule contains a pocket that is potentially druggable. The two scientists then identified multiple compounds that fit into this pocket and inhibited the activity of HIF-2.

The history of belzutifans development demonstrates the value of cross-disciplinary collaborations at academic medical centers and how that can translate to new treatments for diseases, said Dr. Russell. It also underscores the value of investing in basic science discoveries at the core of advancements in medicine.

In 2011, several researchers spun off Peloton Therapeutics, and by 2019, when Merck acquired the company, at least three HIF-2 agents were under investigation.

James Brugarolas, M.D., Ph.D., Director of the UTSW Kidney Cancer Program

James Brugarolas, M.D., Ph.D., Director of the Kidney Cancer Program at UTSouthwesterns Harold C. Simmons Comprehensive Cancer Center, showed that the drug was effective against kidney cancer.

With funding from a prestigious National Cancer Institute SPORE award, they showed in a publication inNaturein 2016 that the drug was able to inhibit HIF-2in human kidney tumors transplanted into mice and stop their growth.

This and other studies led to the first clinical trial of PT2385, a precursor to PT2977, which became belzutifan. The trial, which was led by the UTSW Kidney Cancer Program, showed that the drug was well-tolerated and active.

The approval of belzutifan represents a new paradigm in the treatment of kidney cancer, said Dr. Brugarolas, Professor of Internal Medicine. By exclusively targeting HIF-2, which is essential for kidney cancers but dispensable for normal processes, belzutifan specifically disables cancer cells while sparing normal cells. Belzutifan is the best-tolerated kidney cancer drug today and one suitable for patients with familial kidney cancer. It is a testament to the prowess of designer drugs and carefully chosen targets of which it is a prime example.

1997UTSouthwestern biochemist Steven McKnight, Ph.D., and molecular geneticist David Russell, Ph.D., report the discovery of the HIF-2 gene, which they call EPAS1. The team shows that HIF-2 binds to another protein, HIF-1. The HIF-2 partner functions like a pair of tweezers to grab DNA. HIF-2 binds DNA at specific places to initiate the production of other proteins such as VEGF, which support kidney cancer growth.

2003The laboratories of Richard Bruick, Ph.D., and Kevin Gardner, Ph.D., uncover aspects of the atomic blueprint of HIF-2. They show how HIF-2 docks with HIF-1 to assemble into a functional HIF-2 complex. They identify a cavity within the HIF-2 protein, hypothesizing that it may offer a foothold for a drug. Working with UTSouthwesterns High-Throughput Screening laboratory, Drs. Bruick and Gardner develop a test to identify chemicals among 200,000 drug-like molecules that bind to the HIF-2 cavity, preventing HIF-2 binding to HIF-1. By interfering with HIF-2 binding to HIF-1, these compounds block HIF-2 action. The most promising chemicals undergo a refinement process by medicinal chemists at UTSouthwestern.

2010Peloton Therapeutics is founded by UTSW researchers to develop the HIF-2 blocking chemicals into drugs. Peloton scientists create libraries of related compounds, ultimately identifying PT2385 and PT2977 to test in humans. A related drug, PT2399, is identified for laboratory work.

2016Dr. James Brugarolas validates HIF-2 as a target in kidney cancer. In experiments incorporating more than 250 mice transplanted with human kidney tumors, researchers show that PT2399 blocks HIF-2 while not affecting related proteins, is active against 50% of human kidney tumors, and has more activity and is better tolerated than sunitinib (the most commonly used drug for renal cancer treatment at the time).

2018Dr. Kevin Courtney reports the results of a phase 1 clinical trial testing PT2385 in humans. The trial represents the first-in-human study of a first-in-class inhibitor of HIF-2. The trial, which involves 51 patients, shows that PT2385 is safe, well tolerated, and active against ccRCC in humans. More than 50 percent of patients see their cancer regress or stabilize. A patient of Dr. Brugarolas sees benefit for more than a year despite prior progression on seven drugs.

2019U.S. drug manufacturer Merck acquires Peloton Therapeutics for $1.05 billion, with an additional $1.15 billion contingent on sales and regulatory milestones.

2020Through studies of tumor biopsy samples from patients who participated in the Phase 1 clinical trial, Drs. Courtney, Brugarolas, and Ivan Pedrosa, M.D., Ph.D., report the identification of drug resistance mutations in patients, establishing HIF-2 as the first-known core dependency of kidney cancer.

Dr. Brugarolas holds The Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D. Dr. McKnight holds the Distinguished Chair in Basic Biomedical Research. Dr. Pedrosa holds the Jack Reynolds, M.D., Chair in Radiology. Dr. Russell holds the Eugene McDermott Distinguished Chair in Molecular Genetics. Disclosures: UTSouthwestern and some of its researchers will receive financial compensation, through prior agreements with Peloton, based on belzutifans FDA approval.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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FDA approval of belzutifan culminates 25-year journey at UTSW from gene discovery to a first-in-class drug - UT Southwestern

A rare disease is, by its very nature, rare. The CDC defines a rare disease as a condition that affects fewer than 200,000 people in the United States, or no more than one out of every 2,000 people in Europe.1 And yet, rare diseaseswhich frequently have a genetic componentaffect many: there may be as many 7,000 different types of rare diseases, impacting 25 to 30 million people in the United States, according to the National Center for Advancing Translational Sciences.2 Often, rare diseases lack treatments, leaving patients with little hope.

An ambitious new project, called Accelerating Research and Development for Advanced Therapies (ARDAT), is working to change that. This five-year endeavor through the Innovative Medicines Initiative (IMI), "the world's biggest private-public partnership in the life sciences," is seeking to better understand ways of treating rare diseases through something called advanced therapy medicinal products (ATMPs), such as cell and gene therapies.

Led by Pfizer and University of Sheffield, ARDAT is a consortium made up of more than 30 academic, nonprofit, and private organizations from Europe and the United States that is collaborating to work with regulators and share research and data. The goal is ultimately to improve our understanding of ATMPs, which may helpbring more effective medicines to patients with rare diseases. Gene therapy is one of the new transformative frontiers of medicine, says Greg LaRosa, who is the projects lead at Pfizer, where he serves as Vice President, Head of Scientific Research in the Rare Disease Research Unit.

By collaborating with so many other experienced partners, James Eshelby, Vice President of Global Public-Private Partnerships with Pfizer, hopes researchers will be able to gain a deeper understanding, faster, about this new class of drugs that are advancing toward the marketplace. The project being conducted as a public-private partnership is much more robust than it would be if we were all making separate efforts, he says. Theres a shared hope that findings from ARDAT will also lead to a deeper understanding of ATMPS that may translate into advanced therapies for other diseases.

When a person has a genetic disease, doctors have insights into what the defect is. We know what the cellular activity the gene and the protein product from that gene is responsible for performing, and often we really understand why the people have this disease, says LaRosa. Gene therapy allows them to essentially replace that mutated gene with the correct gene.

I think one thing that's fabulous about gene therapy is it's not just treating the symptom, it's attempting to treat the cause, says Eshelby. Its trying to get the body to do what it should have been doing in the first place.

One example of gene therapy that Pfizer has been studying, in collaboration with ARDAT partner Spark Therapeutics, targets a rare bleeding disorder called Hemophilia B. When a person has Hemophilia B, their body doesnt make enough Factor IX, which is a protein that helps with clotting. Because of that genetic mutation, their blood doesnt clot as quickly as it normally would, which puts them at a greater risk of bleeding excessively, from minor injuries, or even spontaneously.

In an ongoing Phase 3 clinical trial, scientists are placing the Factor IX gene into an AAV viral vector, which is used to deliver the gene to cells of the patient. The viruses are modified so they cannot replicate or cause disease. After receiving the potential therapy intravenously, the body should begin making Factor IX, helping the blood to clot.

With the currently available treatments for Hemophilia B, every few days patients need to receive intravenous medication that aids clotting. Whereas if a gene therapy treatment is successful and approved for this purpose, a single treatment could have long-lasting effects. It just really frees the patients up to live a more normal life, says LaRosa. It gives them something that could dramatically change the path they're on with their disease.

Because most advanced therapy medicinal products such as gene therapy are still being developed, theres much to learn about how and why these advanced medicines work, how long the effects will last and how to overcome barriers to developing medicines with the aim of obtaining regulatory approvals and getting them to patients as rapidly as they need them. Through ARDAT, which launched in late 2020, partners in the consortium are sharing data to collectively gain a deeper understanding of ATMPs. Data sets within single institutions are not as big as that which would be compiled under the ARDAT collaboration, says Eshelby. By sharing individual data sets, you have a better potential to get to data set sizes where you can undertake a more comprehensive analysis.

In addition, Eshelby says sharing knowledge has the potential to benefit other areas, including product development, research, communication and awareness campaigns and more. The partners have expertise in areas such as gene therapy, immunology, chemistry, engineering, biotechnology, drug safety, viral vector creation, and regulatory and clinical trials. They include organizations from 10 countriesas well asprominent universities, research institutes,and biotech firms,includingBayer, Sanofi, University of Oxford,and more.

Together, the partners of ARDAT seek to better understand ATMPs and build upon that knowledge, without having to reinvent the wheel at each individual organization. By working with regulatory agencies as well, LaRosa says theyre hoping to streamline the development path of these therapeutics to make them available faster and give people suffering from rare diseases an offering of hope. For some, that might mean they no longer have to receive intravenous treatments multiple times a week; for others, it could mean continuing to move about without the use of a wheelchair. For many, it could mean a better quality of life.

With many of these rare diseases, there's no treatment yet available, says LaRosa. So the goal of this collaboration is to try to fill those knowledge gaps in cell and gene therapyso we can get these potentially curative products into the clinic, and then to the patients that need them.

References:

1. National Institutes of Health. Public Health and Rare Diseases: Oxymoron No More https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases

2. National Center for Advancing Translational Sciences, FAQs About Rare Diseases https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases

About ARDAT

The ARDAT project is a precompetitive 25.5M,5 yearconsortium that brings together the leading expertise of 34 academic, nonprofit, and private organizations, with the shared goal of helping to standardize and accelerate development of Advanced Therapy Medicinal Products (ATMPs) and potentially helping to bring these transformative treatments to patients sooner. For more information on ARDAT, visitwww.ardat.org

TheIMIis Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients. IMI supports collaborative research projects and builds networks of patients, industrial and academic experts in order to boost pharmaceutical innovation in Europe. IMI is a joint undertaking between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). For further details please visit:http://imi.europa.eu/

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No [945473]. This Joint Undertaking receives support from the European Unions Horizon 2020 research and innovationprogrammeand EFPIA.

This communication reflects the views of the authors and neither the IMI nor the European Union, EFPIA or any other partners are liable for any use that may be made of the information contained herein.

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Through Public-Private Partnership, Scientists are Working to Better Understand Gene Therapy and How it Could Help Patients With Rare Diseases |...