SwanBio Therapeutics Appoints Alison Lawton to Board of Directors – BioSpace

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Alison brings significant experience in guiding companies through all stages of drug development and ultimately to commercialization, which are key areas of expertise that will benefit us as we advance toward becoming a clinical-stage gene therapy company, said Tom Anderson, Chief Executive Officer of SwanBio. We are honored to add Alison to our Board of Directors, to support our goal of bringing life-changing treatments to people living with devastating neurological conditions.

I am delighted to join the team at SwanBio at this inflection point in their development as they progress their gene therapy product candidates for patients with neurological diseases, said Ms. Lawton. I look forward to working with the SwanBio team as they advance their programs into the clinic and expand on their platform to help the many patients who remain in need of new treatment options.

Ms. Lawton has more than 30 years of experience in the biopharma industry, most recently serving as the Chief Executive Officer, President and Member of the Board of Directors of Kaleido Biosciences from 2017 to 2020. Prior to joining Kaleido, she was Chief Operating Officer at Aura Biosciences, and previously held the same role at X4 Pharmaceuticals and OvaScience. Ms. Lawton spent more than 20 years at Genzyme Corporation and subsequently at Sanofi, following its acquisition of Genzyme. She served as Senior Vice President and General Manager of Sanofi Biosurgery, a $750 million business that included surgical, orthopedics, cell therapy and regenerative medicine franchises. Earlier, as SVP of Global Market Access for Genzyme, Ms. Lawton led global functional organizations, including regulatory affairs, quality systems, public policy, health outcomes and strategic pricing, product safety and risk management. Additionally, Ms. Lawton worked for seven years at Warner-Lambert/Parke-Davis in the U.K. She previously served two terms as the industry representative on the Food & Drug Administrations Cell & Gene Therapy Advisory Committee and as Chairman of the Board of the Regulatory Affairs Professional Society (RAPS). She is currently an independent Director of ProQR Therapeutics, X4 Pharmaceuticals, Aeglea Biotherapeutics and Magenta Therapeutics. Ms. Lawton earned her Bachelor of Science degree in Pharmacology from Kings College London.

About SwanBio Therapeutics

SwanBio Therapeutics is a gene therapy company that aims to bring life-changing treatments to people with devastating, genetically defined neurological conditions. SwanBio is advancing a pipeline of AAV-based gene therapies, designed to be delivered intrathecally, that can address targets within both the central and peripheral nervous systems. This approach has the potential to be applied broadly across three disease classifications spastic paraplegias, monogenic neuropathies and polygenic neuropathies. SwanBios lead program is being advanced toward clinical development for the treatment of adrenomyeloneuropathy (AMN). For more information, visit SwanBioTx.com.

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SwanBio Therapeutics Appoints Alison Lawton to Board of Directors - BioSpace

Liquid Biopsy Promising in Children With Vascular Malformations – On the Pulse

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Ezra Anpo (right), here with his sister Aria, participated in a research study investigating a liquid biopsy approach to providing a genetic diagnosis in children with lymphatic malformations.

Doctors at Seattle Childrens are investigating whether a simple liquid biopsy containing a small amount of fluid from a patient may someday provide an easier route to a genetic diagnosis in children with vascular or lymphatic malformations.

The work is a collaborative effort led by Dr. James Bennett, a clinical geneticist and co-director of the molecular diagnostic laboratory at Seattle Childrens and Dr. Jonathan Perkins, an otolaryngologist and director of the Seattle Childrens Vascular Anomalies Program. Liquid biopsy offers an alternative to the more invasive surgical biopsies required when a genetic, or molecular diagnosis, is needed to help guide a patients treatment.

We can now provide a specific genetic diagnosis for a lot of vascular malformations, Bennett said. Thats important for families for a variety of reasons with one being its just extremely healing and powerful to know the reason why your child has these differences.

Bennett adds that many of the genetic causes behind vascular malformations are in the same pathways involved in different adult cancers. Several drugs approved for cancer target these pathways by calming down overactive cell growth. A number of these drugs are already being tested in clinical trials for children with vascular malformations, but a genetic diagnosis is needed to determine if a child is a candidate for these studies.

A liquid biopsy offers a fast pass to get a specific molecular diagnosis without necessarily having to do a surgery on a child, Bennett said. If we can convert our research into a clinical grade test, we have the opportunity to potentially make a lot more kids eligible for the clinical trials investigating new drugs to treat vascular malformations.

Dr. James Bennett (left) and Dr. Jonathan Perkins (right) of Seattle Childrens.

Lymphatic malformations occur in about 1 in every 4,000 births when the tubes that carry lymph fluid throughout the body form abnormally. Most often, lymphatic malformations are in the head and neck, sometimes forming large fluid filled cysts. The vessels inside the cysts may shed their DNA into the surrounding fluid.

Bennett was interested in identifying alternative ways to make a genetic diagnosis in patients with vascular malformations without the need for surgery, and Perkins hypothesized that a little fluid taken directly from the cyst could provide enough DNA from the malformation to hunt for any genetic mutations.

When you take a fluid sample from a patient and you spin all the cells in a centrifuge, the cells go to the bottom and you get this layer of liquid on top, Bennett said. It turns out theres tiny little molecules of DNA, called cell-free DNA, that float around in that liquid. Its called cell-free because the DNA is not inside a cell. We can then analyze this cell-free DNA for mutations present in the patients malformation using genetic tests.

A paper published in Genetics in Medicine by Bennett, Perkins and others from Seattle Childrens Center for Clinical and Translational Research and Center for Developmental Biology and Regenerative Medicine used the liquid biopsy approach to identify genetic mutations in the cyst fluid cell-free DNA in patients with lymphatic malformations.

First, they tested the approach using a bank of vascular malformation patient tissue samples stored at Seattle Childrens in which the genetic diagnosis was already known. Liquid biopsy of cyst fluid cell-free DNA identified the previously known mutations in all seven lymphatic malformation samples. Prospective testing of cyst fluid cell-free DNA in lymphatic malformation patients who had never undergone surgery identified a genetic cause in four out of five of those enrolled in the study. The liquid biopsy did not find genetic mutations in the plasma from patients with lymphatic malformations but did find mutations in plasma from blood samples taken from patients with other types of vascular malformations.

This gives us the first proof of principle that we can detect genetic mutations using a liquid biopsy of cyst fluid from children with lymphatic malformations, Bennett said. This is significant because the procedure to draw the fluid from the cyst is much less invasive and complicated than surgically removing the tissue needed in the operating room.

Ezra was born with an extensive lymphatic malformation in his neck. His parents sought out Dr. Perkins for his expertise in treating vascular anomalies such as his.

Today, Ezra Anpo, 2, zooms around the room chasing his older sister. The fact he is living a normal childhood means everything to his parents, Chelsea Gillis and Hideki Anpo.

When Gillis was 20 weeks pregnant with Ezra, an ultrasound showed a concerning lymphatic malformation near his neck. The malformation continued to grow and at 28 weeks pregnant, his parents received a referral to see Perkins.

Ezra has a lymphatic malformation thats more extensive than most, said Perkins. Its location near the back of his tongue means that any significant inflammation could block his airway and send him to the hospital or into surgery.

On January 9, 2019, Ezra was born at the University of Washington Medical Center and was transferred immediately to Seattle Childrens Neonatal Intensive Care Unit (NICU). The team in the NICU stabilized Ezras breathing and supported his feeding while Seattle Childrens vascular anomalies care team determined a longer-term treatment plan.

Given the growing number of options available, Perkins wanted Ezra to undergo genetic testing to confirm his diagnosis and help guide his treatment. However, the standard approach of taking a biopsy from the malformation during a surgery also put Ezra at high risk of damaging his airway. If the airway became compromised, he would need a tracheostomy to breathe.

Ezra with his parents in Seattle Childrens NICU.

There was a lot of concern about doing any type of surgery that could cause an inflammatory reaction, which would most likely result in a tracheotomy, Gillis said. Both dad and I were adamant that we wanted to do everything possible to avoid a tracheostomy.

Perkins told the family about the liquid biopsy approach in development. Since he would only need to draw fluid from the cyst using a needle, it offered a significantly less invasive, and less complicated way to confirm Ezras genetic diagnosis.

The family agreed to move forward with the experimental test. Perkins took the fluid from Ezras cyst during a procedure to place a gastrostomy tube.

Shortly after, the family and Perkins had answers from the liquid biopsy: Ezra had a mutation in a gene called PIK3CA. Starting treatment with an immunosuppressant drug could provide initial benefit until he was old enough to potentially enroll in a clinical trial of a therapy that targets his mutation.

For now, the results of Ezras test are for research use only, though Bennett is hoping to develop a clinically available option in the near future.

Earlier this year, Bennett received a $2.5 million, five-year Research Project Grant (R01) grant from the National Institutes of Health to continue studying the use of cell-free DNA in larger numbers of patients with vascular malformations. Another area Bennett is excited to explore is whether the liquid biopsy could serve as a biomarker for patients receiving medication therapy.

Once a child is on a drug targeted to a specific mutation and youre trying to figure out if the drug is helping or not, you could potentially use this test to look for trends in the mutated DNA over time, he said. If levels of this DNA are trending down, it could indicate a drug is working.

As part of the research study, the liquid biopsy provided a genetic diagnosis for Ezra in a less invasive way than the standard surgical biopsy used to obtain a sample for genetic testing.

A precision diagnostic test developed by Seattle Childrens is already widely used in patient care. It is the only genetic testing panel certified for clinical use with vascular malformations at a childrens hospital.

The Vascular Anomalies Sequencing Panel, or VANseq, tests for mutations in 44 genes known to cause vascular anomalies. Doctors can use results from VANseq to make treatment decisions or help qualify patients for clinical trials. The advanced test currently accepts blood, saliva or tissue specimens obtained from the patient, but Bennett believes their research is on path to add testing with cell-free DNA to the clinical test.

There are labs doing clinical grade testing with cell-free DNA, mostly for cancer, Bennett said. We have more work to do to before the cell-free test for vascular anomalies is ready for clinical use, but Im confident well get there.

Beyond diagnostics, Seattle Childrens has long led advances to improve care for children with vascular anomalies. A collaborative team of physician-scientists work together to bring innovations such as glue embolization and facial mapping to the nearly 2,000 children the program sees each year.

With two clinical trials investigating the use of targeted therapies for vascular malformations already open at Seattle Childrens, Perkins sees an opportunity to move the field forward yet again.

Its completely shifting the paradigm of treatment of vascular malformations from surgery to medical therapy, Perkins said. We can get to the root of whats causing the malformation and using that information, develop new treatments that hopefully will be significantly more effective than what weve had to offer before.

Ezra celebrated his second birthday earlier this month.

The collaborative model embraced by Perkins, Bennett and the vascular anomalies team has helped Ezras parents feel supported through their sons hospitalization and ongoing care.

Im thankful because we took a good path with Ezra, Anpo said. The part I appreciate most is that it was a team effort. We were involved in the decision making and I felt like we got the information we needed from his whole medical team to guide us to the right decision.

Perkins estimates if Ezra had needed a tracheostomy, he would have had a much longer hospital stay upfront and then likely needed several trips to the operating room in his first two years of life. His mother is grateful they were given the option to avoid surgery and get a genetic diagnosis through the research study.

We are very appreciative that Dr. Perkins listened to us and really took our overall goals into account when making decisions about our sons care, she said. Were so fortunate. We havent needed any major surgeries, and Ezra is thriving. Hes fully oral besides his meds, his breathing is great and hes developing normally. Hes so full of life.

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Ixaka (formerly Rexgenero) Launches as an Integrated Cell and Gene Therapy Company – Business Wire

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LONDON--(BUSINESS WIRE)--Ixaka Ltd, an integrated cell and gene therapy company focused on the natural power of the body to cure disease, launches today. The Companys shareholders have funded the business with over 40 million in financing.

Previously Rexgenero Ltd, a UK-based company pioneering the development of cell therapies to treat serious diseases such as cancer and chronic limb-threatening ischaemia (CLTI), the launch of Ixaka follows integration of its nanoparticle gene therapy business in France and a shareholder restructuring.

The new business will continue to develop Ixakas proprietary technologies concentrated multi-cell therapies (MCTs) and targeted nanoparticle (TNP) therapeutics. Ixakas technologies enhance the naturally therapeutic power of cells by targeting curative cells at the site of disease, or by directly modifying cells within the body to improve disease targeting and boost their restorative function.

Joe Dupere, CEO of Ixaka, commented: Ixakas broad offering of integrated cell and gene therapy capabilities, encompassing cell-based products and an innovative in vivo gene delivery platform, provides a strong foundation for our ambitions to become a leader in cell and gene therapies. Our focus is now on accelerating progress to help realise the potential for durable and curative cell and gene therapies. By exploring multiple therapies across oncology and cardiovascular, genetic, neurological and autoimmune diseases, we are well positioned to bring life-changing treatments to multiple patient populations with critical unmet needs.

REX-001, Ixakas lead MCT product, is an autologous cell-based product in clinical development for the treatment of CLTI. REX-001 is currently being evaluated in the pivotal Phase III SALAMANDER clinical trial at multiple sites across Europe.

Ixakas polymeric nanoparticle platform can be used to perform genetic modifications directly inside a patients body. The platform enables in vivo targeting and transduction of T cells, and is currently being applied to generate chimeric antigen receptor (CAR) T-cell therapies in vivo for haematological malignancies. Modifications of the components will allow the technology to target a broad range of serious diseases, including cancers and genetic, neurological and autoimmune diseases.

A total of $15.4 billion was raised in the first half of 2020 for the development of cell and gene therapies, with 1,078 regenerative medicine and advanced therapy clinical trials ongoing worldwide1.

References1. https://alliancerm.org/sector-report/h1-2020-report/

ENDS

About Ixaka

Ixaka is a cell and gene therapy company focused on using the natural powers of the body to cure disease.

Ixakas proprietary technologies enhance the naturally therapeutic power of cells by increasing the presence of curative cells at the site of disease, or by directly modifying cells within the body to improve disease targeting and boost their restorative effect.

Ixakas technologies concentrated multi-cell therapies and nanoparticle therapeutics demonstrate potential for the treatment of a broad range of serious diseases across oncology, cardiovascular, neurological and ocular diseases, and genetic disorders.

Ixaka has offices in London, UK with R&D and manufacturing operations in Seville, Spain and Paris, France and additional manufacturing capability in Frankfurt, Germany.

For more information, please visit http://www.ixaka.com

Connect with us: Twitter: https://twitter.com/ixaka_Ltd; LinkedIn: https://www.linkedin.com/company/ixaka-limited/

About Ixakas multi-cell therapies

Multi-cell therapies (MCT) are derived from natural tissue extracts which are selected for the most active cells, removing components (such as red blood cells and platelets) that potentially reduce the activity of therapeutic cells. Our first MCT is REX-001, which is currently in a multi-site Phase 3 clinical trial for chronic limb-threatening ischemia (CLTI).

Ixakas REX-001 MCT consists of a combination of progenitor cells and immune cells (lymphocytes, monocytes and granulocytes) which are selected and concentrated from a patients own bone marrow and administered directly to the site of occluded blood vessels in the lower leg. Locally administered REX-001 acts to regenerate blood vessels (through both direct and indirect paracrine mechanisms), modulate immune responses, improve blood flow, improve tissue oxygenation, and promote wound healing. These effects lead to a significant improvement in clinical outcomes and quality of life through complete ulcer healing and alleviation of chronic ischemic rest pain.

About Ixakas in vivo gene delivery technology

Ixakas targeted nanoparticle (TNP) therapeutic is a platform which enables therapeutic cells to be targeted and genetic modifications to be performed directly inside the body. The first application is in the generation of chimeric antigen receptor (CAR) T-cell therapies for haematological malignancies. Modifications of the components however allows the technology to target a broad range of therapeutic cells for the treatment of many serious diseases including cancers, genetic disorders, neurological, autoimmune and ocular diseases.

The TNP in vivo gene delivery approach enables targeting of specific cells and expression of the gene of interest directly in the patient. The technology is also targeted and controllable offering potentially improved efficacy and safety. Generation of enhanced therapeutic cells through genetic modification inside the body also enables more standardized manufacturing which is less expensive as it does not require costly dedicated manufacturing sites needed to expand cells before use (as is required for ex vivo cell therapies).

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Ixaka (formerly Rexgenero) Launches as an Integrated Cell and Gene Therapy Company - Business Wire

After years of potential, cell and gene therapy is ready for the pharmaceutical mainstream – PMLiVE

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The argument for continued investment

C> is a high potential and maturing sector, and is an already crowded environment, playing host to numerous start-ups and now, through M&A, recognised big pharma firms. Much like the rush to find a COVID-19 vaccine that dominates headlines worldwide, not every company involved will be able to succeed.

But finnCaps finnLife watch list of 50 leading AIM-listed biotech companies demonstrates that there is room for numerous companies to contribute to, and profit from, C>. Examining three entirely different approaches to CAR-T therapy, it is possible to see just how much space there is for this exciting sector, therefore displaying the case for continued investment.

Innovative CAR-T therapy demonstrates the depth of C> potential

CAR-T therapy in its existing form is a relatively new and specialised approach at treating cancer. It takes T cells from a patients bloodstream and genetically modifies them in a laboratory. These T cells are then injected back into the bloodstream with the aim of targeting and killing cancer cells.

While it has been shown to be an effective treatment, there are risks and side effects. One is the two-step autologous process (the slow time it takes for cell expansion sometimes as long as two weeks) while another is cytokine release syndrome (CRS), which occurs when cytokine molecules are inadvertently released, but too quickly to target just the tumours and instead target healthy cells.

The next generation of CAR-T treatments shows that there is space for a multitude of start-ups to be active in the C> space as they all help find varied solutions to these problems without negating the effectiveness of CAR-T.

One example is Horizon Delivery, a company that is developing its CYAD-02 project, which will help transport T cells more effectively to the tumour via the use of SMARTvector products.

The product underwent its first phase 1 trial test in January 2020 with a patient who was suffering from acute myeloid leukaemia. Horizon Delivery is also an industry leader in CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) screenings, meaning they can identify key genes or genetic sequences that draw out specific functions of a cell type from thousands of potential variants.

In a cancer context, this means they can route out and exclusively eliminate problematic cells that may have shown signs theyd resist a future cancer treatment.

Another example is Maxcyte, a global cell- based therapies and life sciences company that is developing its CARMA process, where a patients peripheral blood mononuclear cells (PBMCs) are removed and modified. The modified cells can then be used to target an array of different cancers.

Currently the company is conducting a phase 1 trial for advanced ovarian cancer in a dose escalation trial that will treat four separate cohorts the fourth of which was administered in March 2020.

Another example which shows the versatility of new CAR-T innovation is provided by Oxford Biomedica, a gene and cell therapy company specialising in the development of gene-based medicines.

Rather than a contained project or platform, its contribution to CAR-T is through a contract manufacturing development organisation. Collaborating with pharma companies, Oxford Biomedica uses its infrastructure to produce other companies licensed products, including Novartis Kymriah treatment (alongside other undisclosed CAR-T-related products).

With fast-moving innovation finally allowing multiple C> treatments to gain regulatory approval, along with a huge pipeline of upcoming therapies and an influx of funding and M&A activity, investing in C> no longer entails taking a bet on potential the future is finally here.

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After years of potential, cell and gene therapy is ready for the pharmaceutical mainstream - PMLiVE

ScaleReady Launches With the Mission to Revolutionize T Cell Therapy Manufacturing – Business Wire

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ST. PAUL, Minn. & LAKE ZURICH, Ill.--(BUSINESS WIRE)--ScaleReady, a joint venture between Bio-Techne (NASDAQ: TECH), Fresenius Kabi, and Wilson Wolf, launches today. The new company brings together proven tools and technologies for cell culture, cell activation, gene editing, and cell processing from its founding partners.

ScaleReady provides leading therapeutic developers with the most simple, scalable, and versatile manufacturing platform in the industry, enhancing the prospects of success for cell and gene therapy organizations. The new company will accelerate innovation in cell and gene therapy manufacturing, building on the R&D pipelines of its founding partners and through global technology partnerships with industry and academic leaders.

ScaleReadys mission is to accelerate the groundbreaking advances in cell and gene therapy by satisfying the longstanding need for a truly scalable, cost-effective and practical manufacturing platform, said Adam Bryan, General Manager of ScaleReady. Its exciting to see the commitment that our industry-leading partners have made to this mission. Their dedication to combine resources, expertise and decades of experience, position us to make a meaningful contribution to this industry now and in the future through rapid advancement of platform technologies that lead the industry to greater efficiency, practicality and simplicity.

Through this partnership, ScaleReady provides sales, marketing, and application support for tools and technologies used in cell and gene therapy manufacturing worldwide. Wilson Wolfs G-Rex cell culture technology, Fresenius Kabis Lovo and upcoming Cue cell processing systems, and Bio-Technes range of GMP proteins, reagents, media, and gene editing technologies, are all part of the ScaleReady manufacturing platform.

With this venture, Wilson Wolf is adding tremendous wherewithal in our quest to provide the field of cell and gene therapy with a disruptive manufacturing platform that cost-effectively accelerates the delivery of potential life-saving therapies to a wide segment of society, said John Wilson, Chief Executive Officer of Wilson Wolf. Our G-Rex technology is uniquely positioned to address the scale limitation issues facing the industry. Our partners at Bio-Techne and Fresenius Kabi share our common purpose and bring complementary technologies that will accelerate our work.

With cell and gene therapies showing great potential for a wide range of diseases, the need for reliable and consistent raw material supply has never been more important. At Bio-Techne, we recently opened a new large-scale GMP reagent facility, increasing manufacturing capacity for animal-free raw materials, including E. coli-derived recombinant proteins, to ensure sustainable supply for future needs, said David Eansor, President Protein Sciences Segment, at Bio-Techne.

Dean Gregory, President Global Commercial Operations, Transfusion Medicine and Cell Therapies at Fresenius Kabi added, Cell therapies hold promise for patients and are a major area of focus for Fresenius Kabi. Through the partnership represented by ScaleReady, we will be able to make a greater contribution to this field at an accelerated pace. We are thrilled to share our expertise in automated cell processing and closed-system development to this important collaboration.

ScaleReady is owned equally by the three partners Bio-Techne, Fresenius Kabi, and Wilson Wolf. Separately, the three companies do business globally and have combined revenues of more than $7 billion. No other financial terms were disclosed at this time.

About ScaleReady

ScaleReady is bringing the future of cell and gene therapies to life with the most powerful and versatile manufacturing platform in the industry. ScaleReady delivers rapid expansion of T-cells at scalereducing complexity and cost, while providing superior repeatability and cell quality. Founded in 2020, ScaleReady is a joint venture between Bio-Techne, Fresenius Kabi and Wilson Wolf that brings together tools and technologies for cell culture, cell activation, gene editing and cell processing from each founding partner. Learn more at http://www.scaleready.com.

About Bio-Techne

Bio-Techne Corporation (NASDAQ: TECH) is a global life sciences company providing innovative tools and bioactive reagents for the research and clinical diagnostic communities. Bio-Techne products assist scientific investigations into biological processes and the nature and progress of specific diseases. They aid in drug discovery efforts and provide the means for accurate clinical tests and diagnoses. With thousands of products in its portfolio, Bio-Techne generated approximately $739 million in net sales in fiscal 2020 and has over 2,300 employees worldwide. For more information on Bio-Techne and its brands, please visit http://www.bio-techne.com.

About Fresenius Kabi

Fresenius Kabi (www.fresenius-kabi.com/us) is a global health care company that specializes in medicines and technologies for infusion, transfusion and clinical nutrition. The companys products and services are used to help care for critically and chronically ill patients. The companys U.S. headquarters is in Lake Zurich, Illinois. The companys global headquarters is in Bad Homburg, Germany. Fresenius Kabi is part of Fresenius SE(ETR: FRE), a global health care group with more than 305,000 employees in more than 100 countries, and annual sales exceeding $30 billion.

About Wilson Wolf

Based in St. Paul, Minnesota, Wilson Wolf (www.wilsonwolf.com) was founded in 1998 to pioneer the development of innovative cell culture technologies and has created patented products and protocols for numerous applications including monoclonal antibody production, corneal transplants, porcine heart valve testing, mesenchymal cell production, and islet transplants for type 1 diabetes. Over the last 5 years, its G-Rex product line has experienced an average annual sales growth rate of nearly 100%.

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ScaleReady Launches With the Mission to Revolutionize T Cell Therapy Manufacturing - Business Wire

DNA-editing method shows promise to treat mouse model of progeria – National Human Genome Research Institute

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Researchers have successfully used a DNA-editing technique to extend the lifespan of mice with the genetic variation associated with progeria, a rare genetic disease that causes extreme premature aging in children and can significantly shorten their life expectancy. The study was published in the journal Nature, and was a collaboration between the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health; Broad Institute of Harvard and MIT, Boston; and the Vanderbilt University Medical Center, Nashville, Tennessee.

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Base editing for progeria treatmentProgeria is caused by a mutation in the nuclear lamin Agene in which one DNA base C is changed to a T. Researchers used the base editing method, which substitutes a single DNA letter for another without damaging the DNA, to reverse that change. Credit: Ernesto Del Aguila, NHGRI.

DNA is made up of four chemical bases A, C, G and T. Progeria, which is also known as Hutchinson-Gilford progeria syndrome, is caused by a mutation in the nuclear lamin A(LMNA) gene in which one DNA base C is changed to a T. This change increases the production of the toxic protein progerin, which causes the rapid aging process.

Approximately 1 in 4 million children are diagnosed with progeria within the first two years of birth, and virtually all of these children develop health issues in childhood and adolescence that are normally associated with old age, including cardiovascular disease (heart attacks and strokes), hair loss, skeletal problems, subcutaneous fat loss and hardened skin.

For this study, researchers used a breakthrough DNA-editing technique called base editing, which substitutes a single DNA letter for another without damaging the DNA, to study how changing this mutation might affect progeria-like symptoms in mice.

"The toll of this devastating illness on affected children and their families cannot be overstated," said Francis S. Collins, M.D., Ph.D., a senior investigator in NHGRI's Medical Genomics and Metabolic Genetics Branch, NIH director and a corresponding author on the paper. "The fact that a single specific mutation causes the disease in nearly all affected children made us realize that we might have tools to fix the root cause. These tools could only be developed thanks to long-term investments in basic genomics research.

The toll of this devastating illness on affected children and their families cannot be overstated.The fact that a single specific mutation causes the disease in nearly all affected children made us realize that we might have tools to fix the root cause. These tools could only be developed thanks to long-term investments in basic genomics research.

The study follows another recent milestone for progeria research, as the U.S. Food and Drug Administration approved the first treatment for progeria in November 2020, a drug called lonafarnib. The drug therapy provides some life extension, but it is not a cure. The DNA-editing method may provide an additional and even more dramatic treatment option in the future.

David Liu, Ph.D., and his lab at the Broad Institute developed the base-editing method in 2016, funded in part by NHGRI.

"CRISPR editing, while revolutionary, cannot yet make precise DNA changes in many kinds of cells," said Dr. Liu, a senior author on the paper. "The base-editing technique we've developed is like a find-and-replace function in a word processor. It is extremely efficient in converting one base pair to another, which we believed would be powerful in treating a disease like progeria.

To test the effectiveness of their base-editing method, the team initially collaborated with the Progeria Research Foundation to obtain connective tissue cells from progeria patients. The team used the base editor on theLMNAgene within the patients cells in a laboratory setting. The treatment fixed the mutation in 90% of the cells.

The Progeria Research Foundation was thrilled to collaborate on this seminal study with Dr. Collinss group at the NIH and Dr. Lius group at Broad Institute, said Leslie Gordon, M.D., Ph.D., a co-author and medical director of The Progeria Research Foundation, which partially funded the study. These study results present an exciting new pathway for investigation into new treatments and the cure for children with progeria.

Following this success, the researchers tested the gene-editing technique by delivering a single intravenous injection of the DNA-editing mix into nearly a dozen mice with the progeria-causing mutation soon after birth. The gene editor successfully restored the normal DNA sequence of theLMNAgene in a significant percentage of cells in various organs, including the heart and aorta.

Many of the mice cell types still maintained the corrected DNA sequence six months after the treatment. In the aorta, the results were even better than expected, as the edited cells seemed to have replaced those that carried the progeria mutation and dropped out from early deterioration. Most dramatically, the treated mice's lifespan increased from seven months to almost 1.5 years. The average normal lifespan of the mice used in the study is two years.

As a physician-scientist, its incredibly exciting to think that an idea youve been working on in the laboratory might actually have therapeutic benefit, said Jonathan D. Brown, M.D., assistant professor of medicine in the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. Ultimately our goal will be to try to develop this for humans, but there are additional key questions that we need to first address in these model systems.

Funding for the study was supported in part by NHGRI, the NIH Common Fund, the National Institute of Allergy and Infectious Diseases, the National Institute of Biomedical Imaging and Engineering, the National Institute of General Medical Sciences, the National Heart, Lung and Blood Institute and the National Center for Advancing Translational Sciences.

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DNA-editing method shows promise to treat mouse model of progeria - National Human Genome Research Institute

New Study Provides Personalized Breast Cancer Risk Information for Women with ATM Gene Mutations – GlobeNewswire

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Figure 1

Remaining Lifetime Risk for ATM PV Carriers

SALT LAKE CITY, Dec. 11, 2020 (GLOBE NEWSWIRE) -- In a spotlight poster discussion at the 2020 San Antonio Breast Cancer Symposium (SABCS), Myriad Genetics (NASDAQ: MYGN), a global leader in molecular diagnostics and precision medicine, today presented a new study that shows how its myRisk Hereditary Cancer and riskScore tests can better inform individualized clinical screening and prevention strategies for women at risk of developing breast cancer. The new Myriad study highlights how riskScore, a proprietary tool used to evaluate a womans risk of developing breast cancer, can accurately provide breast cancer risk information into a personalized assessment model for women carrying a pathogenic variant (PV) in the ATM gene.

This new study will enable a highly personalized risk calculation for patients who carry mutations in the ATM gene, said Nicole Lambert, president of Myriad Genetic Laboratories. As a result, women carrying gene mutations will be able to make more informed choices about how to manage their risk; if increased surveillance is sufficient or if they would consider surgical options.

Myriads riskScore test combines data from 20 years of genome-wide association studies with a validated algorithm that uses personal and family history. riskScore is performed in conjunction with Myriads myRisk Hereditary Cancer test, where myRisk identifies people who carry specific cancer-linked genetic mutations.

Asummary of the study is below. Follow Myriad on Twitter via @myriadgenetics and keep up to date with SABCS meeting news and updates by using the #SACBS20 hashtag.

riskScore Poster at SABCS Title: Development of a breast cancer risk assessment model for ATM mutation carriers incorporating Tyrer-Cuzick and a polygenic risk score Program Number: PD10-09 Session Title: Spotlight Poster Discussion 10 This study highlights the development of a comprehensive breast cancer risk model for ATM PV carriers incorporating an 86-variant PRS, along with family history and clinical information captured by Tyrer-Cuzick (a tool used to calculate the risk of breast cancer). The study found that with ATM PV carriers (N=216), a comprehensive model allowed for differentiation of carriers into low, moderate, and high breast cancer risk categories (See figure 1 below).

To view Figure 1. Remaining Lifetime Risk for ATM PV Carriers, please visit the following link:https://www.globenewswire.com/NewsRoom/AttachmentNg/d77da35a-714a-41f4-8a8a-dd79a79dc644

AboutriskScore riskScore is a clinically validated personalized medicine tool that enhances Myriads myRisk Hereditary Cancer test. riskScore helps to further predict a womens lifetime risk of developing breast cancer using clinical risk factors and genetic markers throughout the genome. The test incorporates data from more than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was prospectively validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a personal history and family history algorithm, the Tyrer-Cuzick model, to provide an individualized breast cancer risk assessment. Myriad is committed to advancing the validation of risk-assessment tools and making them available to all women, regardless of ancestry.

About Myriad myRisk Hereditary Cancer The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 35 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

About Myriad Genetics Myriad Genetics Inc., is a leading personalized medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on three strategic imperatives: transitioning and expanding its hereditary cancer testing markets, diversifying its product portfolio through the introduction of new products and increasing the revenue contribution from international markets. For more information on how Myriad is making a difference, please visit the Company's website:www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, Vectra, Prequel, Foresight, GeneSight, riskScore and Prolaris are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor Statement This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the Company building ATM status into a clinically validated risk assessment tool that will create a more comprehensive, highly personalized report for patients seeking to understand their risk of developing breast cancer; and the Companys strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties associated with COVID-19, including its possible effects on our operations and the demand for our products and services; our ability to efficiently and flexibly manage our business amid uncertainties related to COVID-19; the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decisions in Mayo Collab. Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012), Assn for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), and Alice Corp. v. CLS Bank Intl, 573 U.S. 208 (2014); risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2020, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

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New Study Provides Personalized Breast Cancer Risk Information for Women with ATM Gene Mutations - GlobeNewswire

They thought their gene therapy failed. Instead, it spawned a medical mystery – Endpoints News

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Jos-Alain Sahel was on a rare vacation in Portugal in the spring of 2018 when his phone rang with grim news: The gene therapy he had worked on for a decade, a potential cure for a rare form of blindness, had failed in a pivotal trial.

In the first minute, I was very disappointed, Sahel says. I said, well OK, its not working.

A failed trial in drug development is crushing but not unexpected, a tradeoff of doing business in biology. You examine the full data, go back to the drawing board and either abandon the effort or tweak and try again. Sahel, founder of four companies and the longtime head of the Vision Institute of Paris, was used to the process. But this time, when the full data came, he was bewildered.

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They thought their gene therapy failed. Instead, it spawned a medical mystery - Endpoints News

CRISPR/Cas9 Gene-Editing Therapy CTX001 for Severe Hemoglobinopathies Accepted for Plenary Presentation at the 62nd American Society of Hematology…

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ZUG, Switzerland and CAMBRIDGE, Mass. and BOSTON, Nov. 04, 2020 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced data in seven patients from two ongoing Phase 1/2 clinical trials of the investigational CRISPR/Cas9 gene-editing therapy CTX001 in severe hemoglobinopathies has been accepted for an oral presentation during the Plenary Scientific Session at the annual ASH Meeting and Exposition, which will take place virtually from December 5-8, 2020. Haydar Frangoul, M.D., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute, HCA Healthcares TriStar Centennial Medical Center, will deliver the presentation on behalf of all the authors on December 6, 2020.

An abstract posted online today includes data from five patients with three months to 15 months of follow-up after CTX001 infusion in the ongoing Phase 1/2 CLIMB-111 trial in transfusion-dependent beta thalassemia (TDT) and data from two patients with three months and 12 months of follow-up in the ongoing Phase 1/2 CLIMB-121 trial in severe sickle cell disease (SCD). Additional data will be presented at ASH, including longer-duration follow-up data for the patients included in the abstract and data for additional patients with greater than three months of follow-up.

CTX001 is being investigated in these two ongoing clinical trials as a potential one-time curative therapy for patients suffering from TDT and severe SCD.

The accepted abstract is now available on the ASH conference website.

About CTX001CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patients hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and reduce painful and debilitating sickle crises for SCD patients.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA). CTX001 has also been granted Orphan Drug Designation from the European Commission for both TDT and SCD, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for SCD.

CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex. Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About CLIMB-111The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About the Gene-Editing Process in These TrialsPatients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patients cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of CTX001 on multiple measures of disease and for safety.

About the CRISPR-Vertex CollaborationCRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. CRISPR Therapeutics and Vertex will jointly develop and commercialize CTX001 and equally share all research and development costs and profits worldwide.

About CRISPR TherapeuticsCRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR Therapeutics Forward-Looking StatementThis press release may contain a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, as well as statements regarding CRISPR Therapeutics expectations about any or all of the following: (i) the status of clinical trials (including, without limitation, the expected timing of data releases) related to product candidates under development by CRISPR Therapeutics and its collaborators, including expectations regarding the data and plans to present data at the annual ASH meeting and exposition; (ii) the expected benefits of CRISPR Therapeutics collaborations; and (iii) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words believes, anticipates, plans, expects and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the potential for initial and preliminary data from any clinical trial and initial data from a limited number of patients (as is the case with CTX001 at this time) not to be indicative of final trial results; the potential that CTX001 clinical trial results may not be favorable; the potential impacts due to the coronavirus pandemic, such as the timing and progress of clinical trials; that future competitive or other market factors may adversely affect the commercial potential for CTX001; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics most recent annual report on Form 10-K, quarterly report on Form 10-Q, and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at http://www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

CRISPR THERAPEUTICS word mark and design logo and CTX001 are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.

About VertexVertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 11 consecutive years on Science magazine's Top Employers list and a best place to work for LGBTQ equality by the Human Rights Campaign. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Vertex Special Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding the expectations and plans to present data at the annual ASH meeting and exposition, the development, including expected timeline for development, and potential benefits of CTX001, our plans and expectations for our clinical trials and clinical trial sites, and the status of our clinical trials of our product candidates under development by us and our collaborators, including activities at the clinical trial sites and potential outcomes. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs, including its programs with its collaborators, may not support registration or further development of its compounds due to safety, efficacy or other reasons, and other risks listed under Risk Factors in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission and available through the company's website at http://www.vrtx.com. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

CRISPR Therapeutics Investor Contact:Susan Kim, +1 617-307-7503susan.kim@crisprtx.com

CRISPR Therapeutics Media Contact:Rachel EidesWCG on behalf of CRISPR+1 617-337-4167reides@wcgworld.com

Vertex Pharmaceuticals IncorporatedInvestors:Michael Partridge, +1 617-341-6108orZach Barber, +1 617-341-6470orBrenda Eustace, +1 617-341-6187

Media:mediainfo@vrtx.comorU.S.: +1 617-341-6992orHeather Nichols: +1 617-839-3607orInternational: +44 20 3204 5275

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CRISPR/Cas9 Gene-Editing Therapy CTX001 for Severe Hemoglobinopathies Accepted for Plenary Presentation at the 62nd American Society of Hematology...

Orgenesis CEO talks disruption: ‘We are the Uber of the cell and gene therapy space’ – BioPharma-Reporter.com

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Maryland, US headquartered company, Orgenesis, is championing a model that aims to bring down those costs it works with partner hospitals throughout the commercialization process.

The companys CGT platform, consisting of a pipeline of licensed cell and gene therapies, scientific expertise, customised processing systems, and an ecosystem of healthcare providers and research institutes, is designed to provide a pathway for groundbreaking autologous therapies to become commercially available on an industrial scale and at prices accessible to large populations.

Orgenesis business model is one focused on decentralization, enabling precision medicines to be prepared on-site at hospitals. In this way, we can really expedite cell and gene therapy development, said Orgenesis CEO, Vered Caplan.

With operations in the US, Europe, Israel and South Korea, Orgenesis has now created an international network of point of care (POCare) centers to serve patients directly in the hospital setting.

Beyond the US, we have POCare centers in many countries in Europe such as Greece, the Netherlands, Belgium, Slovenia, Italy and Spain; we also have centers in Israel, in Korea and in India and we will be starting up soon in Dubai,said the CEO.

The goal is to make gene and cell therapies feasible for large numbers of patients, said Caplan. We used to work as a contract development and manufacturing organization (CDMO) but we sold that business to Catalent at the beginning of the year.

The centralized processing and supply chain model only served to create a frustrating working environment, with plenty of constraints, said the Orgenesis lead.

We realized very quickly that we couldnt really ramp up to large scale relying on that kind of centralized model, particularly for autologous products, which represent most of the market today. It takes six months to train someone to work in a high-grade cleanroom there is a lot of work and expense involved in that and there is a limited number of patients that can be treated in such cleanrooms the utilization rate is very low - it [centralized processing and supply] is a very inefficient and costly way to supply and to develop medicine there is so much manual work involved, she told BioPharma-Reporter.

The company had been working for a number of years, investing a huge amount of effort in developing a range of automation solutions to supplant those manual processes, as well as building its mobile CGT processing labs and units (OMPULs), she said.

We had been fielding so many requests from hospitals that wanted to collaborate with us, asking us to make or scale up their CAR-T and other therapies. We realized that in order to get this done, we needed to take a decentralized approach and that we needed to provide a solution, not only for one hospital, but for every hospital that wanted these type of therapies; and we saw that such a model brings down the price of the therapy tremendously.

A hospital gives Orgenesis a license to work on the therapy, on the processing; production of the final product is automated and supplied via an on-site point-of-care processing unit. Orgenesis then sets about democratizing the treatment,making it available to any hospital in its POCare network.

The company says the final customized, automated processing system it has developed, with the integrated specific therapy, solves a variety of processing and cost hurdles. It results in a lower required grade of cleanroom, it simplifies facility management requirements, it enables multi-batch processing per cleanroom, which means reduced technical staffing. Moreover, the localized processing eliminates the many logistical difficulties associated with traditional, centralized manufacturing and transport.

Overall, it is said to provide faster turnaround, increased safety, and improved quality control management on-site.

Hospitals really want to supply CGTs, while patients are reading about such treatments and making inquiries of healthcare providers, she added.

Ours is really a combined licensing and service model.

We are like Uber. If you have a car, you want to make some extra revenue, you call up Uber and it gives you the network, the technology and all the operating procedures to be a taxi driver. That is very much what we do in terms of hospitals we give them the ability to be biotech companies, because this is not the standard thing they do, they dont want to take responsibility for cell and gene therapy it is too much for them. They want to treat patients, but they want to have that local supply, so we give them the technology and the capabilities to do that. We give them regulatory support for clinical trials, we give them CRO support, we give them a network - so they can function and do what they need to do, which is to undertake research and treat patients.

Orgenesis intends to leverage its network of regional partners to advance the development and commercialization of its therapeutic pipeline. Towards this end, it said its partners have committed to funding the clinical programs. In turn, the company typically grants its partners geographic rights in exchange for future royalties, and a partnership with Orgenesis to support the supply of the targeted therapies. Through this model, Orgenesis has already signed contracts, which it expect to generate over US$40M in revenue over the next three years, if fully realized.

On the therapeutic front, Orgenesis is focused on several key verticals, including immuno-oncology, anti-viral, and metabolic/auto-immune diseases.

It recently acquired Koligo Therapeutics, with the aim of leveraging Koligos 3D-V bioprinting technology across its POCare Platform. That technology, which utilizes 3D bioprinting and vascularization with autologous cells to create biodegradable and shelf-stable three-dimensional cell and tissue implants, is being developed for diabetes and pancreatitis, with longer term applications for neural, liver, and other cell/tissue transplants.

In February this year, Orgenesis announced that it has entered into a collaboration agreement with the John Hopkins University to utilize the POCare platform to develop and supply a variety of CGTs including cell-based immunotherapy technologies.

And the University of California, Davis (UC Davis) joined its POCare network in January. The collaboration will involve the scale up and integration of UC Davis lentiviral vector process.

Today we are very much in validation mode. Most of the therapies in this space, and the ones we have licensed from the hospitals I think we have about 25 today are all at different stages of clinical development. Some have been used to treat patients but that has all been done under hospital exception.

When we adopt a therapy into the network, we run it through the entire R&D, formal clinical and regulatory processes as [our goal] is a harmonized process, to have the same standard [in our closed systems] at our [POCare] centers, whether that is in Germany or Korea, said the CEO.

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Orgenesis CEO talks disruption: 'We are the Uber of the cell and gene therapy space' - BioPharma-Reporter.com

Further Research Required to Find Biomarkers for Urothelial Cancer – Targeted Oncology

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Petros Grivas, MD, PhD, discusses the phase 3 KEYNOTE-045 trial and the association between gene expression signatures and pembrolizumab in patients with advanced urothelial cancer.

Petros Grivas, MD, PhD, physician, Seattle Cancer Care Alliance; associate professor, Department of Medicine, Division of Oncology, and clinical director, Genitourinary Cancers Program, University of Washington School of Medicine; and associate member, Clinical Research Division, Fred Hutchinson Cancer Center, discusses the phase 3 KEYNOTE-045 trial and the association between gene expression signatures and pembrolizumab (Keytruda) in patients with advanced urothelial cancer.

All the patients receiving pembrolizumab on the KEYNOTE-045 trial appeared to benefit in terms of progression-free survival and overall survival, according to Grivas. There are no biomarkers with clinical utility that can guide selection of which patients should get pembrolizumab or not, based on the data presented the 2020 European Society for Medical Oncology. Therefore, these data show no impact on practice when using pembrolizumab to treat patients with platinum-refractory disease.

Grivas says that the utilization of pembrolizumab based on potential biomarkers needs to be researched further to evaluate the clinical advantage of gene expression signatures. At the moment, patients with platinum-refractory advanced urothelial cancer are all treated able to be treated with pembrolizumab.

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Further Research Required to Find Biomarkers for Urothelial Cancer - Targeted Oncology

Tetra Therapeutics Announces Positive Topline Results from Phase 2 Study of BPN14770 in Patients with Fragile X Syndrome – BioSpace

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Nov. 2, 2020 13:00 UTC

Study shows significant cognitive improvement in domains related to language and caregivers reported improved language and daily functioning

Lead drug candidate continues to be safe and well-tolerated

GRAND RAPIDS, Mich.--(BUSINESS WIRE)-- Tetra Therapeutics, a wholly owned subsidiary of Shionogi & Co. Ltd., today announced positive topline results from its Phase 2 exploratory study in adult patients with Fragile X Syndrome (FXS). The study evaluated its lead candidate, BPN14770, a first-in-class phosphodiesterase4D (PDE4D) allosteric inhibitor. In this single-center, randomized, placebo-controlled, two-way crossover study, BPN14770 demonstrated excellent safety as well as benefits on cognitive function and behavior in 30 patients with FXS.

BPN14770 is a novel therapeutic agent that selectively inhibits phosphodiesterase4D (PDE4D). In preclinical studies, BPN14770 promoted the maturation of connections between neurons, which is impaired in patients with FXS, the most common genetic form of Autism.

We are very excited about the results of this study, said Mark Gurney PhD, Founder and Chief Executive Officer of Tetra. In addition to being safe and well tolerated, treatment with BPN14770 led to significant cognitive improvement, specifically in the language domains, and we also saw a clinically meaningful benefit in overall daily functioning. These findings validate our approach to treating this disease through a mechanism that addresses a core deficit in the disorder. On behalf of the entire Tetra team, I want to sincerely thank the patients, families and investigators who participated in this study as well as the FRAXA Research Foundation, for their assistance in this study.

The Phase 2 clinical trial was a randomized, placebo-controlled, two-way crossover study. Each period was 12 weeks in duration with no washout between periods. The study enrolled 30 adult male subjects age 18-41 years with FXS due to >200 CGG repeats in the FMR1 gene. Subjects received daily oral doses of 25 mg twice a day of BPN14770 or placebo. Parents/caregivers and physician raters were blinded to treatment. Study enrollment occurred between July 9, 2018 and July 31, 2020. All subjects completed both treatment periods, although carryover effects limited the primary statistical analysis to Period 1. The following results, therefore, describe the outcomes for patients who received BPN14770 during Period 1, compared to those who received placebo.

Cognitive assessments using the NIH-Toolbox revealed significant benefit in Oral Reading Recognition (LSMean Difference +2.80, p=0.0157), Picture Vocabulary (+5.79, p=0.0342), and Cognition Crystallized Composite Score (+5.29, p=0.0018). Parent/Caregiver ratings using 100 point Visual Analog Scales revealed benefit that was judged to be clinically significant in Language (LSMean Difference +14.04, p=0.0051) and Daily Functioning (+14.53, p=0.0017). The benefit of BPN14770 was maintained up to 12 weeks after the crossover from drug to placebo. BPN14770 was very well tolerated in the Phase 2 trial with few adverse events.

These results offer hope for Fragile X Syndrome patients and their parents said Dr. Elizabeth Berry-Kravis, pediatric neurologist, Rush University Medical Center, and principal investigator. The preponderance of clinical outcome measures were in favor of the drug. These included performance-based as well as parent and physician-rated scales which suggests a meaningful impact on the global FXS disease process. I find it exciting that we have a drug that potentially addresses a core deficit in FXS, a decrease in cAMP, that has been documented in patients as well as in the fly and mouse models of the disorder.

About the Phase 2 Trial

The Phase 2 clinical trial was a randomized, placebo-controlled, two-way crossover study in 30 adult male patients with FXS, ages 18-45, to assess the safety and efficacy of BPN14770. The study was conducted at Rush University Medical Center, Chicago, Illinois by principal investigator Elizabeth M. Berry-Kravis, M.D., Ph.D. with financial support from the FRAXA Research Foundation. Additional information is available through clinicaltrials.gov (Identifier: NCT03569631).

About BPN14770

BPN14770 is a novel therapeutic agent that selectively inhibits phosphodiesterase-4D (PDE4D) to increase the levels of cAMP, a key signaling molecule, in brain. In preclinical models, BPN14770 promotes the maturation of connections between neurons, which is impaired in patients with Fragile X Syndrome, an indication for which BPN14770 has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA). This unique mechanism of action has the potential to improve cognitive and memory function in devastating CNS disorders, including FXS, Alzheimer's disease and other dementias, learning/developmental disabilities and schizophrenia. BPN14770 currently is approved for investigational use only by the FDA.

About Tetra Therapeutics

Tetra Therapeutics, a wholly owned subsidiary of Shionogi & Co., Ltd., is a clinical stage biotechnology company developing a portfolio of therapeutic products that will bring clarity of thought to people suffering from Fragile X syndrome, Alzheimers disease, traumatic brain injury, and other brain disorders. Tetra uses structure-guided drug design to discover mechanistically novel, allosteric inhibitors of the phosphodiesterase 4 (PDE4) enzymes, a family of enzymes that play key roles in memory formation, learning, neuroinflammation, and traumatic brain injury. Tetra Therapeutics is headquartered in Grand Rapids, Michigan. For more information, please visit the companys website at http://www.tetratherapeutics.com.

About Shionogi

Shionogi & Co., Ltd. is a major Japanese research-driven pharmaceutical company dedicated to bringing benefits to patients based on its corporate philosophy of supplying the best possible medicine to protect the health and wellbeing of the patients we serve. The company currently markets products in several therapeutic areas including anti-infectives, pain, cardiovascular diseases, and gastroenterology. The Shionogi pipeline is focused on infectious disease, pain, CNS, and oncology. For more information on Shionogi & Co., Ltd., visit https://www.shionogi.com/global/en/.

Forward Looking Statement

This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also, for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, unavailability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise.

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Fortress Biotech Announces Oral and Poster Data Presentations at the 62nd American Society of Hematology (ASH) Annual Meeting – GlobeNewswire

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NEW YORK, Nov. 04, 2020 (GLOBE NEWSWIRE) -- Fortress Biotech, Inc. (NASDAQ: FBIO) (Fortress), an innovative revenue-generating company focused on acquiring, developing and commercializing or monetizing promising biopharmaceutical products and product candidates cost-effectively, today announced that data from two of its clinical programs have been accepted for presentation at the 62nd American Society of Hematology (ASH) Annual Meeting, which is being held virtually from December 5 8, 2020.

Phase 2 data on Caelum Biosciences (Caelum) CAEL-101 for the treatment of relapsed or refractory amyloid light chain AL amyloidosis will be presented by the Cleveland Clinic during oral and poster sessions. CAEL-101, which is being developed in a collaboration between Caelum, a company founded by Fortress, and Alexion Pharmaceuticals, Inc., recently progressed into Phase 3 development. In addition, interim Phase 1/2 data on Mustang Bios (Mustang) MB-106, a CD20-targeted, autologous chimeric antigen receptor (CAR) T cell therapy for patients with relapsed or refractory B-cell non-Hodgkin lymphomas, will be presented by Mustangs research partner Fred Hutchinson Cancer Research Center (Fred Hutch) during a poster session.

Lindsay A. Rosenwald, M.D., Fortress Chairman, President and Chief Executive Officer, said, We are looking forward to data from two of our clinical programs being presented in oral and poster sessions at the ASH Annual Meeting. CAEL-101 and MB-106 are important product candidates that are poised to fill the urgent need for new treatment options and make a meaningful difference for patients.

Details of the presentations are as follows:

CAEL-101 Oral Presentation:

Title: Safety, Tolerability and Efficacy of CAEL-101 in AL Amyloidosis Patients Treated on a Phase 2, Open-Label, Dose Selection Study to Evaluate the Safety and Tolerability of CAEL-101 in Patients with AL AmyloidosisSession: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation; Novel Approaches for Relapsed/Refractory Myeloma and AmyloidosisAbstract: 729Date and Time: Monday, December 7, 2020, 5:45 p.m. ETPresenter: Jason Valent, M.D., Clinical Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Staff Department of Hematology and Oncology, Director Multiple Myeloma Program, Taussig Cancer Institute, Co-Director Amyloidosis CenterCleveland Clinic

CAEL-101 Poster Presentation:

Title: CAEL-101 Is Well-Tolerated in AL Amyloidosis Patients Receiving Concomitant Cyclophosphamide-Bortezomib-Dexamethasone (CyborD): A Phase 2 Dose-Finding Study (NCT04304144)Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II Abstract: 2277Date and Time: Sunday, December 6, 2020, 10:00 a.m. - 6:30 p.m. ETPresenter: Jason Valent, M.D., Clinical Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Staff Department of Hematology and Oncology, Director Multiple Myeloma Program, Taussig Cancer Institute, Co-Director Amyloidosis CenterCleveland Clinic

MB-106 Poster Presentation:

Title: Third Generation CD20 Targeted CAR T-Cell Therapy (MB-106) for Treatment of Patients with Relapsed/Refractory B-Cell Non-Hodgkin LymphomaSession: 704. Immunotherapies: Poster IAbstract: 1443Date and Time: Saturday, December 5, 2020, 10:00 a.m. - 6:30 p.m. ETPresenter: Mazyar Shadman, M.D., M.P.H., Associate Professor, Clinical Research Division, Fred Hutch, Seattle, WA

For more information, please visit the 62nd ASH Annual Meeting and Exposition website at https://www.hematology.org/meetings/annual-meeting/abstracts.

About CAEL-101 (Light Chain Fibril-reactive Monoclonal Antibody for AL Amyloidosis)CAEL-101 is a first-in-class monoclonal antibody (mAb) designed to improve organ function by reducing or eliminating amyloid deposits in the tissues and organs of patients with AL amyloidosis. The antibody is designed to bind to misfolded light chain protein and amyloid and shows binding to both kappa and lambda subtypes. In a Phase 1a/1b study, CAEL-101 demonstrated improved organ function, including cardiac and renal function, in 27 patients with relapsed and refractory AL amyloidosis who had previously not had an organ response to standard of care therapy. CAEL-101 has received Orphan Drug Designation from both the U.S. Food and Drug Administration and European Medicine Agency as a therapy for patients with AL amyloidosis.

About Caelum BiosciencesCaelum Biosciences, Inc. (Caelum) is a clinical-stage biotechnology company developing treatments for rare and life-threatening diseases. Caelums lead asset, CAEL-101, is a novel antibody for the treatment of patients with amyloid light chain (AL) amyloidosis. In 2019, Caelum entered a collaboration agreement with Alexion under which Alexion acquired a minority equity interest in Caelum and an exclusive option to acquire the remaining equity in the company based on Phase 3 CAEL-101 data. Caelum was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visitwww.caelumbio.com.

About MB-106 (CD20-targeted CAR T Cell Therapy)CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustangs research partner, Fred Hutchinson Cancer Research Center (Fred Hutch), in the laboratory of Oliver Press, M.D., Ph.D., and Brian Till, M.D., in the Clinical Research Division and exclusively licensed to Mustang Bio in 2017. MB-106 has been optimized as a third-generation CAR derived from a fully human antibody and is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in B-cell non-Hodgkin lymphoma patients. Additional information on the trial can be found at http://www.clinicaltrials.gov using the identifier NCT03277729.

About Mustang BioMustang Bio, Inc. is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for X-linked severe combined immunodeficiency (XSCID), also known as bubble boy disease. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission (SEC). Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

About Fortress Biotech Fortress Biotech, Inc. (Fortress) is an innovative biopharmaceutical company that was ranked number 10 in Deloittes 2019 Technology Fast 500, an annual ranking of the fastest-growing North American companies in the technology, media, telecommunications, life sciences and energy tech sectors, based on percentage of fiscal year revenue growth over a three-year period. Fortress is focused on acquiring, developing and commercializing high-potential marketed and development-stage drugs and drug candidates. The company has five marketed prescription pharmaceutical products and over 25 programs in development at Fortress, at its majority-owned and majority-controlled partners and at partners it founded and in which it holds significant minority ownership positions. Such product candidates span six large-market areas, including oncology, rare diseases and gene therapy, which allow it to create value for shareholders. Fortress advances its diversified pipeline through a streamlined operating structure that fosters efficient drug development. The Fortress model is driven by a world-class business development team that is focused on leveraging its significant biopharmaceutical industry expertise to further expand the companys portfolio of product opportunities. Fortress has established partnerships with some of the worlds leading academic research institutions and biopharmaceutical companies to maximize each opportunity to its full potential, including Alexion Pharmaceuticals, Inc., AstraZeneca, City of Hope, Fred Hutchinson Cancer Research Center, InvaGen Pharmaceuticals Inc. (a subsidiary of Cipla Limited), St. Jude Childrens Research Hospital and Nationwide Childrens Hospital. For more information, visit http://www.fortressbiotech.com.

Forward-Looking StatementsThis press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended. As used below and throughout this press release, the words we, us and our may refer to Fortress individually or together with one or more partner companies, as dictated by context. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; uncertainties relating to preclinical and clinical testing; risks relating to the timing of starting and completing clinical trials; our dependence on third-party suppliers; risks relating to the COVID-19 outbreak and its potential impact on our employees and consultants ability to complete work in a timely manner and on our ability to obtain additional financing on favorable terms or at all; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. The information contained herein is intended to be reviewed in its totality, and any stipulations, conditions or provisos that apply to a given piece of information in one part of this press release should be read as applying mutatis mutandis to every other instance of such information appearing herein.

Company Contacts:Jaclyn Jaffe and William BegienFortress Biotech, Inc.(781) 652-4500ir@fortressbiotech.com

Investor Relations Contact:Daniel FerryLifeSci Advisors, LLC(617) 430-7576daniel@lifesciadvisors.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

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Lynparza approved in the EU as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer | Small Molecules | News…

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DetailsCategory: Small MoleculesPublished on Thursday, 05 November 2020 11:36Hits: 152

Patients treated with Lynparza and bevacizumab lived without disease progression for a median of 37.2 months vs. 17.7 months with bevacizumab alone

One in two women with advanced ovarian cancer has an HRD-positive tumour

LONDON, UK I November 5, 2020 I AstraZeneca and MSDs Lynparza (olaparib) has been approved in the European Union (EU) for the 1st-line maintenance treatment with bevacizumab of patients with homologous recombination deficient (HRD)-positive advanced ovarian cancer.

Ovarian cancer is the fifth most common cause of cancer death in the EU and the five-year survival rate is approximately 45%, due partly because women are often diagnosed with advanced disease (Stage III or IV).1-3

The approval by the European Commission was based on a biomarker subgroup analysis of the PAOLA-1 Phase III trial which showed Lynparza, in combination with bevacizumab maintenance treatment, demonstrated a substantial progression-free survival (PFS) improvement versus bevacizumab alone for patients with HRD-positive advanced ovarian cancer. It follows the recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency in September 2020.

Isabelle Ray-Coquard, principal investigator of the PAOLA-1 Phase III trial and medical oncologist, Centre Lon Brard and President of the GINECO group, Paris, France, said: For women with advanced ovarian cancer, the goal of 1st-line treatment is to delay disease progression for as long as possible with the intent of achieving long-term remission. Unfortunately, once a patients cancer recurs, it historically has been incurable. Lynparza together with bevacizumab has demonstrated an impressive median progression-free survival benefit of more than three years and is poised to become the standard of care for eligible patients with HRD-positive tumours in the EU.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: Half of all newly diagnosed patients with advanced ovarian cancer have HRD-positive tumours. Women treated with Lynparza in combination with bevacizumab in the PAOLA-1 Phase III trial lived progression free for a median of more than three years, showing that HRD testing should be an essential component of clinical diagnosis. HRD status can help physicians select a personalised 1st-line treatment regimen for patients to substantially delay relapse in this devastating disease.

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: Biomarker testing has rapidly enhanced our understanding of how PARP inhibition can help target this disease. The EU approval reinforces that HRD-positive tumours represent a distinct subset of advanced ovarian cancer and HRD testing is critical for women in this setting.

The PAOLA-1 Phase III trial showed thatLynparza,in combination with bevacizumab maintenance treatment, reduced the risk of disease progression or death by 67% (based on a hazard ratio of 0.33; 95% confidence interval 0.25-0.45). The addition ofLynparzaimproved PFS to a median of 37.2 months versus 17.7 with bevacizumab alone in patients with HRD-positive advanced ovarian cancer. The data from the PAOLA-1 trial was published inThe New England Journal of Medicinein 2019.

Further results recently presented at the European Society for Medical Oncology Virtual Congress 2020 showed a statistically significant improvement in the key secondary endpoint of the time to second disease progression (PFS2). Lynparza with bevacizumab provided benefit beyond first disease progression, improving PFS2 to a median of 50.3 months versus 35.3 with bevacizumab alone.

The full EU indication is for Lynparza in combination with bevacizumab for the maintenance treatment of adult patients with advanced (FIGO Stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of 1st-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with HRD positive status defined by either a breast cancer susceptibility gene 1/2 (BRCA1/2) mutation and/or genomic instability.

Lynparzain combination with bevacizumab isapproved in the USand in several other countries as a 1st-line maintenance treatment for patients with HRD-positive advanced ovarian cancer and is currently under regulatory review in other countries around the world.

Financial considerations

Following this approval for Lynparza in the EU, AstraZeneca will receive a regulatory milestone payment from MSD of $25m, anticipated to be booked as collaboration revenue during the fourth quarter of 2020.

Ovarian cancer

In 2018, there were nearly 68,000 new cases of ovarian cancer diagnosed in the EU and around 45,000 deaths.3Approximately 50% of ovarian cancers are HRD-positive including BRCA1/2 mutation.4,5Approximately 15% of ovarian cancers have a BRCA1/2 mutation.6 The primary aim of 1st-line treatment is to delay disease progression for as long as possible with the intent to achieve long-term remission.7-9

Homologous recombination deficiency

HRD, which defines a subgroup of ovarian cancer, encompasses a wide range of genetic abnormalities, including BRCA mutations and beyond. As with BRCA gene mutations, HRD interferes with normal cell DNA repair mechanisms and confers sensitivity to PARP inhibitors including Lynparza.10

PAOLA-1

PAOLA-1 is a double-blinded Phase III trial testing the efficacy and safety ofLynparzaadded to standard-of-care bevacizumab versus bevacizumab alone, as a 1st-line maintenance treatment for newly diagnosed advanced FIGO Stage III-IV high-grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab.AstraZeneca and MSD announced in August 2019 that the trial met its primary endpoint of PFS in the overall trial population.

Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in the US as a 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm and/or genomic instability). Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. It is also approved in the US, the EU and several other countries for the treatment of germline BRCAm metastatic pancreatic cancer. Lynparza is approved in the US for homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (BRCAm and other HRR gene mutations). Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 30,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

The AstraZeneca and MSD strategic oncology collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the worlds first PARP inhibitor, and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio ofnew medicines that has the potential to transform patients lives and the Companys future. With seven new medicines launched between 2014 and 2020, and a broad pipelineof small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

References

1. EuroHealth. (2018). Ovarian Cancer: The Silent Killer. Available at: https://eurohealth.ie/policy-brief-women-and-ovarian-cancer-in-the-eu-2018/ [Accessed October 2020].

2. ECIS. (2020).Estimates of cancer incidence and mortality in 2020, for all cancer sites. Available here [Accessed October 2020].

3. The World Health Organization. IARC. Globocan. (2018). Available at: http://gco.iarc.fr/ [Accessed October 2020].

4. Moschetta et al. (2016). BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Annals of Oncology, 27(8), pp.1449-1455.

5. Bonadio et al. (2018). Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics, 73(Suppl 1): e450s.

6. Ramus. (2009). The Contribution of BRCA1 and BRCA2 to Ovarian Cancer. Molecular Oncology, 3(2), pp.138150.

7. Raja et al. (2012). Optimal first-line treatment in ovarian cancer. Annals on Oncology. 23 Suppl 10, x118-127.

8. NHS Choices, Ovarian Cancer Available at: https://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed October 2020].

9. Ledermann et al. (2013). Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 24, pp.vi24-vi32.

10. Moore, K. (2018). Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine, 379(26), pp.2495-2505.

SOURCE: AstraZeneca

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IBCN 2020: Improving Immune Checkpoint Inhibitor Therapy In Cancer – UroToday

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(UroToday.com)Application of immune checkpoint inhibitor (ICI) therapy has seen significant progress in the last few years. Agents targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1 have shown activity in locally advanced and metastatic urothelial carcinoma in the first- and second-line setting.1,2 However, a significant proportion of patients still perform poorly after receiving these therapies as their disease progresses rapidly.

In his keynote presentation at the 2020International Bladder Cancer Network (IBCN) Annual Meeting, Dr. Dan Theodorescu challenged the audience to seek alternative approaches to tackle this problem. He suggested that this may be addressed by either discovery of new therapies, or using novel modalities to enhance the effect of current ICI therapies. His research group has, more recently, focused on the latter approach.

While the idea of combination therapy has been successfully applied for chemotherapeutic regimens, an existing problem is that agnostic drug combinations could result in the need for far too many dual-drug clinical trials that would just not be feasible in the current environment. He, therefore, pointed out that an urgent need, therefore, is to rationally choose drugs that would be potentially optimal combinations with immune checkpoint inhibitors. The underlying goal of his groups current investigations is to identify molecular pathways that allow cancer growth while on ICI, and identify drugs that can target such pathways to enhance ICI response (Figure 1). His group has employed functional genomics to identify such lethal combinations.

Figure 1: Using functional genomics to identify rational combinations with ICI.

He elaborated on the technique for the construction of such functional genomic druggable libraries, wherein gene targets of drugs used in clinical trials for bladder cancer were identified, and five shRNAs per gene were constructed as part of a lentiviral library that were used to infect murine bladder cancer cells. The best performing shRNAs were selected as models for inhibiting the respective pathways and used to test in combination with ICI therapy. Using this approach, and in combination with anti PD-1 therapies, tumors that were resistant to the latter therapy were profiled using next-generation sequencing to identify pathways of ICI escape (Figure 2).

Figure 2: Identifying synthetic lethal combinations with anti PD-1

These investigations identified DDR2 and CCL2 alterations as key escape mechanisms. The DDR2 gene encodes for discoidin domain-containing receptor 2, a receptor tyrosine kinase that can be targeted by dasatinib.3 His group, therefore, proceeded to characterize DDR2 alterations in the context of ICI therapy in bladder cancer.4 Their analysis of published bladder cancer genomic profiling data indicated that patients with high DDR2 were associated with worse survival in four independent cohorts. When bladder cancer cells were transduced with DDR2 shRNAs in vitro, this resulted in appropriate reduction in protein levels (Figure 3). In the presence of anti PID-1, there was a significant reduction in subcutaneous tumor growth in syngeneic mice with bladder tumors that also stably expressed shDDR2, indicating a synergistic response. A similar response was also observed in melanoma and breast cancer in vivo models.

Figure 3: Effect of DDR2 depletion on anti PD-1 response.

RNA from mice bearing shControl and shDDR2-transduced bladder tumors treated with antiPD-1 were analyzed using RNAseq followed by gene set enrichment analysis. This revealed a strong immune response in the shDDR2 tumors treated with anti-PD-1 when compared with controls. Cytometry by time-of-flight analysis of these tumors revealed increased CD8+ T cell infiltration into shDDR2 tumors treated with anti-PD-1, which was not seen in the spleen. These observations suggested a strong T cell presence following the treatment of shDDR2-treated tumors with anti-PD-1.

To further evaluate the efficacy of targeting DDR2, the combination of dasatinib and anti-PD-1 was tested. Whereas therapeutic blockade of PD-1 or DDR2 alone had little or no effect on murine bladder tumors, treatment with the combination of dasatinib and anti-PD-1 showed a significant reduction in tumor burden (Figure 4). Similar results were seen within vivo colon cancer and sarcoma models.

Figure 4: Effect of dasatinib on PD-1 response.

Similar studies of synthetic lethal combinations of anti-PD-1 with CCL2 inhibitors are now underway in Dr. Theodorescus lab. Unpublished data from his group indicates that the combination of CCL2 depletion with anti-PD-1 has a significant effect in metastatic melanoma. The data indicate there may be potential benefits in considering triple-drug combinations that target DDR2, CCL2 and PD-1.

In closing, Dr. Theodorescu highlighted recent developing results from a Phase II trial of sitravatinib, a multi-receptor tyrosine kinase inhibitor in combination with nivolumab that is indicating encouraging clinical activity in checkpoint inhibitor nave, platinum-experienced patients with advanced or metastatic urothelial carcinoma.5 The combination with data generated from his lab and early trial results suggest that there is merit in the addition of targeted therapeutics with ICI for treatment of advanced bladder cancer.

Presented by: Dan Theodorescu, MD, Ph.D., Director of the Cedar-Sinai Cancer Center, Phase ONE Distinguished Endowed Chair in Cancer Research, Professor of the Departments of Surgery, Pathology and Laboratory Medicine, Cedars-Sinai Health System, Los Angeles, CA, USA.

References:1. Powles T, et al. Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: Updated results from a phase 1/2 open-label study. JAMA Oncol 2017;3(9):e172411.2. Sharma P, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol 2017;18(3):312-322.3. Carafoli F, Hohenester E. Collagen recognition and transmembrane signalling by discoidin domain receptors. Biochim Biophys Acta 2013;183:2187-94.4. Tu MM, et al. Targeting DDR2 enhances tumor response to anti-PD-1 immunotherapy. Sci Adv 2019;5(2):eaav2437.5. Msaouel P, et al. 705MO Sitravatinib (sitra) in combination with nivolumab (nivo) demonstrates clinical activity in checkpoint inhibitor (CPI) nave, platinum-experienced patients (pts) with advanced or metastatic urothelial carcinoma (UC). Annals Oncol 2020;31(4):S556.

Written by:Anirban P. Mitra, MD, Ph.D., Urologic Oncology Fellow, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Twitter: @APMitra, with Ashish M. Kamat, MD, MBBS, President of IBCN and IBCG, Endowed Professor, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Twitter:@UroDocAsh,at the International Bladder Cancer Network (IBCN) Annual Meeting, #IBCN2020, October 17, 2020.

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IBCN 2020: IBCN 2020: Molecular Correlates of Cisplatin-Based Chemotherapy Response In Muscle-Invasive Blad… – UroToday

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(UroToday.com) While cisplatin-based chemotherapy is a mainstay for neoadjuvant and adjuvant treatment of patients with muscle-invasive bladder cancer (MIBC), and none of the reported biomarkers for predicting response have been implemented in the clinic thus far.

Dr. Ann Taber presented data from researchers at the Aarhus University Hospital, Denmark, where they performed comprehensive genomic, transcriptomic, epigenomic, and proteomic analysis of 300 MIBC patients treated with cisplatin-based chemotherapy to identify molecular changes associated with treatment response. Based on mutational signatures, they identified two patient groups: those characterized by mutations in a tri-nucleotide signature 5 context (SBS5) that are related to ERCC2 mutations, and those related to APOBEC mutations.

Expression data identified the basal/squamous gene expression subtype to be associated with poor cisplatin-based treatment response. Immune cell infiltration and high PD-1 protein expression was also significantly associated with treatment response; they identified a unique subset that corresponds to an immune desert, which was associated with poor treatment response (Figure 1).

Figure 1: Association of immune cell infiltration and cisplatin-based treatment response.

The authors then assigned patients to high and low genomic instability groups based on SBS5 mutations, indels, allelic imbalance and BRCA2 mutation status. Patients with high genomic instability had a response rate of 71% versus 49% for patients with low genomic instability (p = 0.007). Through further integration, they identified a group of patients with a very high response rate (80%) characterized by high genomic instability and non-basal/squamous gene expression subtype and a group of patients with a very low response rate (25%) characterized by low genomic instability and basal/squamous gene expression subtype (p<0.001, Figure 2).

Figure 2: Patient subclassification based on genomic instability and basal/squamous gene expression subtype.

The results highlight several molecular correlates of chemotherapy response. These findings are now the basis of a new clinical trial for the treatment of metastatic bladder cancer following radical cystectomy.1

Presented by: Ann Taber, Ph.D., Department of Molecular Medicine (MOMA), Aarhus University Hospital, Denmark.

Written by:Anirban P. Mitra, MD, Ph.D., Urologic Oncology Fellow, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Twitter: @APMitra, with Ashish M. Kamat, MD, MBBS, President of IBCN and IBCG, Endowed Professor, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Twitter:@UroDocAsh,at the International Bladder Cancer Network (IBCN) Annual Meeting, #IBCN2020, October 17, 2020.

References:1. Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy (TOMBOLA). ClinicalTrials.gov identifier NCT04138628.

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Biogen pushes further into eye gene therapy with new deal – BioPharma Dive

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Dive Brief:

Biogen is at a crossroads, awaiting a regulatory decision on the Alzheimer's drug aducanumab by early March that will have wide-ranging implications for the biotech's future.

But while aducanumab's fate hangs in the balance, Biogen has been stocking up on other early-stage assets, aiming to diversify its portfolio beyond risky neuroscience bets. Company executives in 2019 said they were putting more emphasis on ophthalmology and immunology, for instance, and that same year, the company spent $800 million on an acquisition of the eye gene therapy company Nightstar Therapeutics.

ViGeneron offers a novel technology for harnessing adeno-associated virus vectors to treat eye disease. Its vgAAV vectors are designed to get around some of the limits of the standard gene therapy delivery tools and target a variety of different cell types. The two companies noted the technology's potential to more efficiently transduce retinal cells via eye injections, which in theory could lead to more potent treatments.

The company is still fairly new, however, having being spun off in 2017 by Ludwig-Maximilians University in Munich. Its investors include WuXi AppTec and Sequoia Capital China. None of its experimental treatments, led by a gene therapy for retinitis pigmentosa, are in human testing.

The deal is another bet by Biogen on genetic medicine. Earlier this year, the biotech formed a gene editing alliance with Sangamo Therapeutics that could be worth billions of dollars.

Still, investors at the moment are most focused on aducanumab. The roller coaster ride for the drug began in March 2019, when the drug appeared to have failed two clinical trials. Seven months later, however, the company said a further analysis showed significant benefits for a high dose in one clinical trial, and the Food and Drug Administration agreed to review the medicine.

In November 2020, the FDA convened a panel of outside experts, whose review was overwhelmingly negative. Panelists criticized the agency for being too optimistic about Biogen's data and voted near-unanimously against approving the drug.

The committee's vote isn't binding for the FDA, though the agency typically follows its advice. Regulators are due to make their final decision on aducanumab by March 7.

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Biogen pushes further into eye gene therapy with new deal - BioPharma Dive

NeuBase Therapeutics Appoints Dr. Kia Motesharei Chief Business and Strategy Officer – GlobeNewswire

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PITTSBURGH, May 25, 2021 (GLOBE NEWSWIRE) -- NeuBase Therapeutics, Inc. (Nasdaq: NBSE) ("NeuBase" or the "Company"), a biotechnology company accelerating the genetic revolution using a new class of precision genetic medicines, today announced the appointment of Kia Motesharei, Ph.D., as Chief Business and Strategy Officer, effective May 24, 2021. Dr. Motesharei has more than 20 years of experience in business development, licensing and transactions, alliance management and strategy in the biotechnology and pharmaceutical industry.

Kia has successfully completed more than 100 deals, with particular expertise in scaling the output of platform biotechnology companies through partnerships to maximize shareholder value, with several drugs on market now as a direct result of his activities. Kia also has expertise in our programmatic areas including in neurology, oncology and rare diseases, said Dietrich A. Stephan, Ph.D., Founder, CEO and Chairman of NeuBase. We are excited to welcome Kia to the NeuBase team, as we evaluate potential partnership opportunities and expand our therapeutic pipeline, leveraging the broad capabilities of our PATrOLTM platform for precision genetic medicines.

Genetic mutations are the fundamental drivers of all diseases, rare and common, so NeuBases ability to specifically modulate mutated DNA and RNA can unlock a whole new class of medicines for diseases that currently have few treatment options, said Dr. Motesharei. I look forward to utilizing partnership strategies to expand the breadth of what we have the potential to accomplish with this technology to benefit patients around the world.

Most recently, Dr. Motesharei was Senior Vice President, Business Development & Corporate Strategy at Akcea Therapeutics, a late-stage development and commercial biopharmaceutical company focused on rare diseases, where he led and executed the regional partnership of Akceas marketed products Tegsedi and Waylivra with Sobi in Europe and the Middle East. Prior to Akcea, Dr. Motesharei headed Global Licensing & Business Development, Neurology & Immunology (N&I) at EMD Serono, the biopharmaceutical business of Merck KGaA. He was a core member of the N&I Franchise Leadership Team that executed the overall strategy of the $1.8 billion franchise, including product and pipeline development, partnering, regulatory and commercial and marketing decisions. He managed the global licensing team responsible for search and evaluation and transactions across the entire R&D spectrum for the immunology, neurology, allergy, fertility, medical device and global health franchises. Previously, Dr. Motesharei was a member of the management team and investor relations team at Dyax Corporation, a pharmaceutical company focused on development and commercialization of novel biotherapeutics for prevention of hereditary angioedema. He led the business development, alliance management and competitive intelligence functions covering Dyaxs phage display platform as well as pipeline products including Kalbitor and DX-2930 (now approved as Takhzyro) that contributed to its approximately $6.5 billion acquisition by Shire. Earlier in his career, he held a series of leadership positions at Genfit Corporation, ActivX Biosciences and Lion Bioscience. He currently serves on the board of Ariana Pharma. Dr. Motesharei received a Ph.D. in organic chemistry from the UCLA and a B.A. in chemistry from Colorado College. He completed his postdoctoral training as an NIH fellow at The Scripps Research Institute.

About NeuBase TherapeuticsNeuBase is accelerating the genetic revolution by developing a new class of precision genetic medicines which can be designed to increase, decrease, or change gene function, as appropriate, to resolve genetic defects that drive disease. NeuBases targeted PATrOL therapies are centered around its proprietary drug scaffold to address genetic diseases at the DNA or RNA level by combining the highly targeted approach of traditional genetic therapies with the broad organ distribution capabilities of small molecules. With an initial focus on silencing disease-causing mutations in debilitating neurological, neuromuscular and oncologic disorders, NeuBase is committed to redefining medicine for the millions of patients with both common and rare conditions. To learn more, visit http://www.neubasetherapeutics.com.

Use of Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements are distinguished by use of words such as "will," "would," "anticipate," "expect," "believe," "designed," "plan," or "intend," the negative of these terms, and similar references to future periods. These forward-looking statements include, among others, those related to Dr. Moteshareis leadership and development experience guiding the Company as it advances its preclinical portfolio and discovery and drug development platform and towards clinical trials and beliefs that Dr. Moteshareis ability will help the growth of the Company. These views involve risks and uncertainties that are difficult to predict and, accordingly, our actual results may differ materially from the results discussed in our forward-looking statements. Our forward-looking statements contained herein speak only as of the date of this press release. Factors or events that we cannot predict, including those risk factors contained in our filings with the U.S. Securities and Exchange Commission (the SEC), may cause our actual results to differ from those expressed in forward-looking statements. The Company may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements, and you should not place undue reliance on these forward-looking statements. Because such statements deal with future events and are based on the Company's current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of the Company could differ materially from those described in or implied by the statements in this press release, including: the Company's plans to develop and commercialize its product candidates; the timing of initiation of the Company's planned clinical trials; the risks that prior data will not be replicated in future studies; the timing of any planned investigational new drug application or new drug application; the Company's plans to research, develop and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of the Company's product candidates; the Company's commercialization, marketing and manufacturing capabilities and strategy; global health conditions, including the impact of COVID-19; the Company's ability to protect its intellectual property position; and the requirement for additional capital to continue to advance these product candidates, which may not be available on favorable terms or at all, as well as those risk factors contained in our filings with the SEC. Except as otherwise required by law, the Company disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

NeuBase Investor Contact:Dan FerryManaging DirectorLifeSci Advisors, LLCdaniel@lifesciadvisors.com OP: (617) 430-7576

NeuBase Media Contact:Jessica Yingling, Ph.D.Little Dog Communications Inc.(858) 344-8091jessica@litldog.com

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NeuBase Therapeutics Appoints Dr. Kia Motesharei Chief Business and Strategy Officer - GlobeNewswire

Haematological Indicators of Response to Erythropoietin Therapy in Chr | PGPM – Dove Medical Press

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Key Message

Chronic kidney disease (CKD) has a global prevalence of 816%, with serious morbidity and mortality.1 CKD is a direct risk factor for cardiovascular diseases, end-stage renal disease (ESRD)/CRF, and mortality.2 While replacement therapy with regular dialysis represents a temporary solution, renal transplantation is the permanent solution.3 Anaemia is one of the most important CRF complications, which develops early and worsens during the long-term progression of the disease.4 Coresh et al showed the association between lower Hb levels, the severity of anaemia and kidney function reduction.5 Erythropoietin (Epo), iron therapy, and continuous patient response monitoring provide a good tool for treating CKD-associated anaemia6 that helps to minimize transfusions and improve CKD patient survival.7 Although the response to rHuEpo is mostly good, resistance to Epo therapy among these cases ranges from 10% to 20%.8

Many factors may affect patients responses to replacement therapy with rHuEPO, including genetic factors, eg, ACE gene polymorphism that has an important impact on hematopoiesis. ACE gene is located at 17q23. It contains 26 exons and 25 introns.9 It has several single-nucleotide polymorphisms (SNPs). ACE G2350A (rs4343) SNP is located in exon 17 of the ACE gene and results in silent Thr 776 Thr (NP_000780.1) change. ACE gene SNPs may affect the patients response to Epo and could be useful genetic markers in assessing the required dose of Epo in such patients.10 ACE SNPs effect on CKD response to Epo therapy was evaluated with conflicting results. Varagunam et al reported a predictive role for it in determining Epo dosage in continuous ambulatory peritoneal dialysis English patients,11 while in another study in Korean HD patients, it was found to be associated with Epo resistance.10 ACE G2350A (RS4343) was selected for the present study based on a genome-wide-analysis study that reported the ACE G2350A (RS4343) is a good predictor of ACE activity12 due to the absence of wide genomic mapping in Arabian Countries, so our hypothesis that it may affect HD patients response to rHuEPO.

Although it was investigated concerning other clinical conditions, to the best of our knowledge, none of the international reports studied the effect of ACE G2350A (RS4343) gene polymorphisms on haematological markers of response to rHuEpo in CRF patients on HD. The current study aims to study the effect of ACE G2350A (RS4343) I/D gene polymorphisms on the response to rHuEpo, anaemia biomarkers, ACE content, inflammatory biomarkers, serum Epo and soluble Epo receptor (sEpoR) among CRF patients on HD.

Observational cross-sectional study.

Nephrology department and Biochemistry and molecular biology department, faculty of medicine, Cairo University.

Our cross-sectional study enrolled 256 CRF patients on HD for six months receiving rHuEpo therapy. They included 162 males and 103 females and aged 51.3 11.9 years. They were recruited from the nephrology unit, Internal Medicine Department, Cairo University, Cairo, Egypt, from April 2019 to June 2020. Matching 160 normal healthy control subjects were recruited from those accompanying outpatients and comprised 122 males and 38 females ageing 36.1 12.8 years (Table 1). Each participant had a five-minute interview to discuss the current studys objectives and aims before signing the informed consent and enrollment.

Table 1 General Characteristics and Laboratories of HD Patients versus Controls

Patients excluded from the study if age 18 years, acute renal failure, non-CKD-related anaemia, recent blood transfusion within the previous three months, a history of hepatitis B (HBV) or C (HCV) or HIV or other active acute or chronic infections, decompensated liver cirrhosis, pregnancy, and malignancy.

10 mL peripheral venous blood was collected on heparin. The recovered plasma by centrifugation (1000 x g for 10 min at 4 C) was aliquot stored at 40 C till used for assessment of ferritin, Transferrin (TF), soluble transferrin receptor (sTfR), EPO, sEpoR, ACE, and cytokines (IL-1, IL-6, and IL-10) content, iron workup (iron and total iron-binding capacity; TIBC). Iron (g/dL) and TIBC (g/dL) were assayed using colorimetric kits (Stanbio Laboratory, Boerne, TX, USA). Transferrin saturation (%) was calculated from iron and TIBC. Plasma proteins and cytokines were assayed using specific quantitative commercially available ELISA kits as instructed; ferritin in ng/mL and sTfR in nmol/L (Diagnostic Automation/Cortez Diagnostics Inc, CA, USA; cat#1601-16 and 3126-15), TF in mg/dL (Abcam, Cambridge, MA, USA, USA cat#ab187391), ACE in ng/mL and sEpoR in ng/mL (MyBioSource, Inc., San Diego, CA, USA; cat#MBS494753 and MBS702997), IL-1, IL-6, and IL-10 in pg/mL (RayBiotech, Inc., Peachtree Corners, GA, USA; cat# ELH-IL1b, ELH-IL6, and ELH-IL10), and Epo in mIU/mL (BioVision, Inc., Milpitas, CA, USA; cat# E4720-100). An aliquot of whole blood was also used to assess Hb, TLC count using a cell counter (Sysmex XT-4000i Automated Haematology Analyzer Lincolnshire, IL, USA). Hb level was measured in the 6th month three times, one week apart, the mean of these three readings was recorded. Half of the whole blood sample collected was used for genomic DNA extraction and real-time PCR analysis of ACE genes polymorphism.

Total DNA was isolated from whole blood mononuclear cells (MNC) using the extraction kit (Zymo Research, Irvine, CA, USA; cat# D302 Quick-DNA Microprep Kit) instructed. The DNA purity (A260/A280 ratio) and concentration were assessed spectrophotometrically (dual-wavelength Beckman, Spectrophotometer, USA). GAPDH house-keeping gene was assessed in all PCR reactions as an internal control and for DNA integrity. The extracted and purified DNA samples were stored at 80 C till used. ACE polymorphism genotyping and allelic discrimination was assessed using TaqMan Analysis. DNA was genotyped for ACE G/A at rs4343. PCRs were carried out in reaction volumes of 25 L containing 50 ng DNA, 10 L TaqMan Universal PCR Master Mix (Applied Biosystems, ThermoFisher Scientific Inc., Waltham, MA, USA) with the passive reference ROX (Perkin Elmer), 280 nmol/L of each primer and 200 nmol/L VIC-labeled probes for ACE G > A. Primers and minor groove binder probes were synthesized by Applied Biosystems. The primer sequence was forward: 5-GTGAGCTAAGGGCTGGA-3 and reverse: 5-CCAGCCCTCCCATGCCCATAA-3. PCR thermal cycler conditions included an initial incubation at 50 C for 2 minutes, 95 C for 10 minutes, followed by 35 cycles of 15 seconds at 92 C and 1 minute at 6062 C. Allele discrimination was accomplished by running endpoint detection using the StepOne and SDS 2.0 software. ACE AA = ACE Insertion/Insertion (I/I), ACE GA = ACE Insertion/Deletion (I/D) while ACE GG = ACE Deletion/Deletion (D/D).

Data were collected, tabulated, and analyzed using SPSS version 21 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp). Deviation of genotype frequencies of the studied group of patients from Hardy-Weinberg equilibrium (HWE) was assessed by Chi-squared test with one degree of freedom (df) using the Michael H. Courts (20052008) calculator.13 If P 0.05, then the population is in HWE. For categorical data like gender was presented as frequency and percentage. Scale data like age, haematological parameters were presented as mean Standard Error of Mean (SEM). ShapiroWilk test was applied to determine the distribution of data. Chi-square test/ Fischer exact test was applied to measure the difference among categories. Independent samples t-test was used to measure the mean difference across two categories. Levenes test was applied to ascertain equal variance among the groups. One-way ANOVA with LSD posthoc analysis was applied to determine the difference in scale data among more than two categories. Correlations between ACE level and haematological parameters were using Pearsons correlation coefficient. The stepwise regression test was used to determine the independent parameters that may affect Hb or Hct values. A p-value < 0.05 was considered significant.

The current study protocol was approved by the Bioethics Committee, Medical College, Cairo University (Approval Number CU III F 40 20) and conducted following the Helsinki declaration.

Comparing HD patients vs healthy controls showed significant differences in plasma potassium, urea, creatinine, iron, TIBC, % TF Saturation, TF, sTfR, Hb, Hct, TLC, platelets count IL-6, IL-10 and IL-1, EPO, ACE and sEpoR (Table 1).

The prevalence of ACE G2350A (rs4343) I/D genotype among HD patients and healthy controls showed that the I/D genotype is the most prevalent while the I/I genotype is the least one. ACE G2350A (rs4343) I/D genotype distribution showed a significant difference in the gene allele distribution between HD patients compared to normal controls: I/D (n = 174 vs 85), I/I (n = 41 vs 6) and D/D (n = 50 vs 69) (p = 0.001). D allele is the most prevalent one either in HD patients (0.52) or among the control group (0.7) (Table 2).

Table 2 Patients and Control Group ACE Rs4343 Genotype and Allele Distributions

The mean Hb was highest in D/D genotype patients (11.120.19), followed by I/I (11.110.2) n I/D (10.470.1).

The effect of ACE G2350A (rs4343) genotypes on different parameters among CRF patients was evaluated using one-way ANOVA; a significant difference between the three categories was found, F= 5.9, P=0.003. Differences were significant between I/I and I/D genotype (mean difference=.63, P = 0.012), D/D and I/D genotype (mean difference =.65, P = 0.005). no significant difference was noted between I/I and D/D (P=0.956) Table 3.

Table 3 Comparison of Hb & Serum Iron in Different HD Patient Genotypes of ACE Gene Rs4343

The mean serum iron was highest in I/D genotype patients (44.53 .87), followed by I/I (40.951.3 n DD (40.61.05). A one-way ANOVA found a significant difference between three categories, F= 4.062, P=0.018. Differences were significant between I/D and II (mean difference=3.58. P =0.045), I/D and D/D (mean difference=3.93, P =0.018). I/I and D/D had not shown a significant difference (P= 0.871) Table 3.

There were insignificant differences among patients with I/I, D/D, or I/D genotypes regarding TLC (Figure 1A) or the inflammatory biomarkers (IL-6, IL-10, and IL-1) (Figure 1B).

Figure 1 Comparison of WBC (A), IL6 & IL10 & IL1 (B) regarding the ACE G2350A (rs4343) genotypes. Data presented as mean SEM. Evaluated by ANOVA test followed by LSD as a post hoc.

Figure 2 Comparison of Transferrin Saturation or sTfR (soluble transferrin receptor) (A), TIBC (Total Iron Binding Capacity), ferritin, and Transferrin (B) regarding the ACE G2350A (rs4343) genotypes. Data presented as mean SEM. Evaluated by ANOVA test followed by LSD as a post hoc.

There were insignificant differences among patients with I/I, D/D, or I/D genotypes regarding % TF Saturation and sTfR (Figure 2A), TIBC, Ferritin, or TF level (Figure 2B).

Figure 3 Comparison of Epo (erythropoietin), ACE (angiotensin-converting enzyme) and sEpoR (Soluble erythropoietin receptors) regarding the ACE G2350A (rs4343) genotypes. Data presented as mean SEM. Evaluated by ANOVA test followed by LSD as a post hoc.

The effect of ACE G2350A (rs4343) genotypes on levels of ACE, EPO, and sEpoR levels was evaluated among CRF patients. Our results showed insignificant differences between patients with different genotypes in that regard (Figure 3).

The D allele is the most prevalent allele among patients in the current study (Table 2). Analysis of the genotype correlation in a recessive mode of inheritance of the risk of D allele between Non-DD (II+ID) vs (DD) was done using an independent t-test. Our results showed a significant difference between the two groups regarding iron status (43.9.7, 40.61.1, respectively, F: 6.946, t: 2.529, CI: 0.7019:5.8004, P=0.013) and Hb level (10.6.1, 11.1.19, respectively, F: 0.261, t: 2.308, CI: 0.9797:0.0776, P=0.013) (Table 4).

Table 4 Comparison of Different Parameters Between Non-DD (ID+II) and DD Genotype Among HD Patients

Using Pearsons correlation coefficient, the correlation between the ACE level and haematological parameters among HD patients showed a significant positive correlation between the ACE level and Epo (r: 0.244, P=0.0001) and a significant negative correlation between the ACE level and HCT (r: 0.131, P=0.033) (Table 5).

Table 5 Correlations Between ACE Level and Haematological Parameters Using Pearsons Correlation Coefficient

Linear regression analysis revealed that among all parameters tested, ACE G2350A (rs4343) (R.194, P=0.001), TLC (R 0.282, P=0.001), and sEpoR (R 0.312, P=0.024) were independent predictors of Hb level (Table 6). While the ACE content (R. 0.292, P= 0.017), TLC (R. 0.255, P=0.015), and iron (R 0.209, P=0.001) were independent predictors of the Hct level (Table 7).

Table 6 Hb Stepwise Regression Test

Table 7 HCT Stepwise Regression Test

The current study is the first report that studied the effect of ACE G2350A (rs4343) gene polymorphism on the haematological indicators of response to rHuEpo therapy. It is well-established that genetic factors play an essential role in determining the efficacy and response to drug treatment.14 Pharmacogenomics analyses such relationships towards the personalization of medicine. Our lab showed the importance of such an approach in predicting the patients response to different drug therapy.15,16

The present study showed that HD patients with the ACE G2350A (rs4343) D/D and I/I genotype respond better to rHuEpo therapy than those with the I/D genotype as evidenced by the higher Hb level among the former group. This higher Hb level among D/D and I/I genotypes were not related to iron level. Our results showed that patients with the I/D allele had higher iron than patients with each of the D/D and I/I genotypes, despite the lower Hb level of the I/D allele holders. The better Hb response was recently partially reasoned to higher plasma angiotensin II (Ang II) levels in D/D and I/D genotypes compared to the II genotype.17

Ang II is the main effector member of the renin-angiotensin system acting through the AT1 receptor and is generated from Ang. I by an ACE-induced proteolytic cleavage.18 The Renin-angiotensin system plays a vital role in hematopoiesis and other diseases.19,20 However, the exact mechanism by which ACE may affect erythropoiesis and Hb level is still not well elucidated. Among the other plausible explanations is ACE inhibition of Ang IIinduced Epo release and prevention of the induction of pluripotent hematopoietic stem cells.21 ACE directs stem cell differentiation to erythroid progenitors synthesis.22 ACE may affect the Ang II level, directly increasing erythroid progenitors in vitro proliferation.23

Savin et al showed that the ACE D/D genotype is associated with higher Hb levels.24 Patients with the D/D genotype were shown to require less Epo dose than the I/I genotype.11

In a study that included 112 ambulatory peritoneal dialysis patients, Sharples et al25 showed that the ACE DD genotype requires less rHuEpo than other ACE genotypes, I/I or I/D. This result seems to be in line with our conclusion, albeit we could not identify the exact ACE SNPs that Sharples and his colleagues had examined. Similarly, Hatano et al26 showed that HD patients with D/D-allele require low rHuEPO.

The ACE rs4646994 D/D genotype was associated with a poor response to rHuEpo in HD Korean patients, suggesting that it could be a useful genetic tool in predicting Epo requirement and responsiveness in HD patients.10 Kiss et al,27 working on Hungarian and Al-Radeef et al,28 working on Iraqi HD patients, reported that ACE polymorphism had a non-significant effect on the Hb level. These variations may arise from the exact SNPs tested; we explored the ACE G2350A (rs4343) effect while they examined rs1799752 and rs4646994, respectively. Also, the small sample size of these studies compared to ours might have affected their conclusions.

Our results showed a higher iron store among the heterozygous ID genotype than II or DD genotype patients assuming a heterozygous advantage for the ACE G2350A (rs4343) ID genotype among HD patients included in the present study.

Heterozygote advantage or overdominant refers to better fitness of heterozygous genotype patients over both homozygous. It firstly appeared in 1922 to maintain polymorphism stability.29 Major histocompatibility complex (MHC) gene represent one of the prominent examples for the heterozygote advantage, in which MHC heterozygotes genetic diversity is abundant. Heterozygote genotype patients have better recognition of pathogen antigen and resist infections effectively than homozygous.30,31 Heterozygote advantage provides a protective effect against malaria for the sickle-cell anaemia allele carriers.32

Recently, A genome-wide association study revealed that heterozygous individuals were significantly healthy-aged compared to other individuals with other genotypes. Moreover, in the same age group population, a 10-year higher survival was associated with individuals with higher heterozygosity rates; the association is more likely to be explained by heterozygote advantage.33 Previous observations noted heterozygous advantages on ACE genotype patients among cardiovascular diseases; because of high linkage disequilibrium (LD) between the polymorphisms, ACE haplotypes needed to be determined in different populations with different evolutionary histories search for additional ancestral breakpoints. The phenotypes complexity also includes the possibility of multiple interactions between genes or genes and environmental factors. The high frequency of I/D, ie, 56.61%, could be because of heterozygote advantages against the two homozygotes D/D and I/I in cardiovascular diseases9 and kidney diseases; individuals with I/D genotype have the least levels of ACE. The DD genotype has the highest levels, followed by I/I34 or having lower plasma ACE levels,35 although these studies may differ from our study in its design, ethnicity, and allele distributions.

A 287-bp insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene (17q22-q24, 26 exons, and 25 introns) in humans may control serum ACE levels. Many SNPs in linkage disequilibrium (LD) with the I/D polymorphism, including T5941C, A262T, T93C, T1237C, C4656T, and A11860G (rs 4343; exon 16),36,37 are known to influence serum ACE.38

Furthermore, rs1799752 is one of four SNPs that may be the most well-studied ACE SNP. It is an insertion/deletion of an Alu repetitive element in an ACE genes intron rather than a single nucleotide polymorphism.

ACE G2350A (rs4343) gene polymorphism is associated with increased ACE enzyme activity in physiological and pathological states.39 It increases ACE levels in subjects with a high-saturated-fat diet that enhances diet-dependent hypertension.40

Our data showed insignificant differences among the tested three ACE G2350A (rs4343) I/I, I/D, and D/D genotypes regarding the circulating ACE protein content. On the contrary, Mizuiri et al and Elshamaa et al demonstrated an opposite conclusion. ACE I/D genotype is associated with renal ACE gene expression in healthy Japanese subjects41 and plasma and tissue ACE levels.42 Nand et al showed D allele positively affects ACE serum level.43

Endogenous or rHuEpo binds to EPOr resulting in stimulation of erythropoiesis.44 sEpoR is generated from mRNA alternative splicing, and since it lacks the transmembrane domain, it is released into extracellular fluids. sEpoR buffers rHuEpo because of its high affinity to EPO; therefore, it acts as a potent antagonist to EPO, resulting in decreased response to rHuEpo treatment. sEpoR high level was correlated to a high need for rHuEpo dose.45,46

In the current work, there was an insignificant difference between ACE G2350A (rs4343) I/I, I/D, or D/D genotypes regarding plasma Epo and sEpoR content in the present study. This notion contradicts the finding of Al-Radeef et al, who showed that another rs1799752 I/D and D/D genotypes had a higher serum Epo level compared to the I/I genotype.28

Our patients were free of active infection, and the measured proinflammatory cytokine levels, IL-6, IL-1, and IL-10, were insignificant differences among the three ACE G2350A (rs4343) genotypes; I/I, I/D, or DD.

Increases in the inflammatory mediator, such as IL-6 and TNF-, lead to increases in the sEpoR level that would hinder erythropoiesis.46 sEpoR stabilizes proinflammatory cytokine ligand and modulates cytokine interaction to its membrane-bound receptor, leading to variation in its concentration.47 Inflammatory cytokines accompanying CRF and HD decrease rHuEpo efficacy. TNF-, IL-1, and IL-6 induce resistance against rHuEpo in erythroid progenitor cells reducing iron release from the reticuloendothelial system and decreasing Hb production.48,49 Betjes et al reported a lack of response to rHuEpo among CKD patients with cytomegalovirus infection mainly due to IFN- and TNF- production.50

Although our HD patients showed higher levels of % TF saturation and sTfR, TIBC, Ferritin, or TF, there were insignificant differences among patients with I/I, D/D, and I/D genotypes regarding these parameters.

Various tissues obtain their iron need via TF binding to its receptor, endocytosis of the complex, and iron download.51,52 The expression rate of the cell surface TF receptor is directly proportional to its iron need.53 The transmembrane glycoprotein TF receptor is formed of two disulfide-linked monomers; each polypeptide subunit comprises three major domains: a large C-terminal extracellular domain and a transmembrane and an N-terminal cytoplasmic domain. sTfR is the cleaved extracellular domain of the high-affinity iron-sensor TF receptor released soluble in extracellular fluids. Circulating levels of sTfR reflect the number of cells with receptors (erythropoietic activity) and the receptor density on cells (tissue iron status).54 Ferritin is used for diagnosing iron deficiency anaemia, but it could be falsely elevated in inflammation giving the erroneous impression of normal iron stores.55 sTfR is insensitive to inflammatory states and inflammatory biomarkers. It could detect anaemia even in subjects with the inflammatory condition; moreover, it could differentiate between anaemia due to iron deficiency or chronic diseases.56

Finally, we tested for independent factors that may affect the patients response to rHuEPO. Among all parameters tested, ACE protein level, TLC, and sEpoR were the independent predictors of Hb level. Simultaneously, ACE protein content, TLC, and iron are the independent predictors for the Hct level.

Previous works measured Hb level at the beginning, 3rd, and 6th months of treatment with rHuEpo [24, 28]. In the present study, we measured the Hb level after six months of the treatment with rHuEpo to allow more precision and avoid fluctuation of patient response to treatment. We took the mean of the three Hb levels in the 6th month. We could not retrieve accurate data considering the use of ACE inhibitors (ACEIs) or ARBs among our patients. We measured circulating ACE level as a protein rather than an activity that revealed insignificant differences among the three genotypes assessed to avoid any related confusion. We did not evaluate angiotensin II (Ang II) level in the current study and iron intake status, but we estimate Hct, iron, ferritin, TF, % TF saturation, sTfR, and TIBC. Many other ACE gene SNPs may affect the HD patients response to rHuEPOs as rs1799752, rs429, and rs4341 which may be in linkage disequilibrium with studied rs4343; however, the only studied here is the ACE G2350A (rs4343). These limitations of the current study are highly acknowledged and will be considered in our future studies.

Patients with either ACE G2350A (rs4343) I/I or D/D genotype showed better response to rHuEpo than those with I/D genotype. ACE protein content, TLC, and sEpoR may represent independent predictors for the HD patients response to rHuEPOs. Screening for ACE G2350A (rs4343) gene polymorphisms in the HD patients on HD before rHuEpo administration may predict patients response.

This project was funded by The Deanship for Scientific Research, Jouf University, Sakaka, Saudi Arabia (Grant # 40/345). The authors express their deepest thanks to Prof. Dr Dina Sabry (The Molecular Biology Lab, Faculty of Medicine, Cairo University, Cairo, Egypt) for facilitating the gene analysis and biochemical investigations.

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.

The authors stated that they have no conflicts of interest for this work.

1. Vianna HR, Soares CMBM, Tavares MS, Teixeira MM, Simoes AC. [Inflammation in chronic kidney disease: the role of cytokines]. Jornal Brasileiro de Nefrologia. 2011;33(3):351364. Portuguese. doi:10.1590/S0101-28002011000300012

2. Okada R, Wakai K, Naito M, et al. Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a Cross-Sectional Study. BMC Nephrol. 2012;13(1):2. doi:10.1186/1471-2369-13-2

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Thematic Research into the Global Regenerative Medicine in Pharma Market – Opportunities, Challenges, and Unmet Needs – ResearchAndMarkets.com -…

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DUBLIN--(BUSINESS WIRE)--The "Regenerative Medicine in Pharma - Thematic Research" report has been added to ResearchAndMarkets.com's offering.

Regenerative medicine is a multidisciplinary field that seeks to develop the science and tools that can help repair, augment, replace, or regenerate damaged or diseased human cells, tissues, genes, organs, or metabolic processes, to restore normal function. It may involve the transplantation of stem cells, progenitor cells, or tissue, stimulation of the body's own repair mechanisms, or the use of cells as delivery vehicles for therapeutic agents such as genes and cytokines.

It is widely anticipated that Gene therapy is the most valuable regenerative medicine sector however, this market is also expected to be slowed down by high cost of therapies, which may limit its accessibility.

Existing programs will facilitate the approval and development of regenerative medicines, however, a reimbursement system especially for curative therapies is warranted.

The publisher's Regenerative Medicine in Pharma report combines primary research from a cross-specialty panel of experts with in-house analyst expertise to provide an assessment of the development landscape.

Scope

Reasons to Buy

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

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Thematic Research into the Global Regenerative Medicine in Pharma Market - Opportunities, Challenges, and Unmet Needs - ResearchAndMarkets.com -...