South Koreas Ministry of Food and Drug Safety said today that it has approved the countrys first gene therapy for osteoarthritis, the lead product candidate of a Maryland-based regenerative medicine company.

Invossa-K Inj. was developed by Maryland-based TissueGene, whose Korean licensee, Kolon Life Sciences, won approval for the injectable treatment. According to the company, Invossa is a first-in-class cell-mediated gene therapy designed to treat moderate (Kellgren and Lawrence grade 3) knee osteoarthritis through regeneration of cartilage.

Invossa uses allogeneic human cartilage cells engineered to express transforming growth factor TGF-1. TissueGenes platform technology involves transducing the cells with a retroviral vector engineered to express TGF-1 at a specific therapeutic level and duration of time.

The modified cell lines are further selected and screened for cellular expression characteristics intended to minimize patient immune response to the injected cellsthen mixed with unmodified cells to create cartilage regeneration via Invossa, as well as bone, disc, and nerve regeneration through the companys other product candidates.

Invossa is designed for a single injection directly into the knee joint, allowing the cells to induce repair and regeneration of tissue by secreting therapeutic growth factors. The gene therapyincluded in GENs recent roundup of Top Trends in Tissue Engineeringis an alternative to surgery for arthritis patients, according to Kolon.

Kolon has said injection of Invossa has been shown in Phase III trials in Korea to ease the symptoms of about 84% of patientswhile 88% of U.S. patients treated with the gene therapy in Phase 2 trials reported improved symptoms for up to two years.

Invossa is being assessed in a Phase III trial in the U.S. after TissueGene and the FDA came to agreement on a Special Protocol Assessment (SPA) for the study. The company is seeking agency approval for the gene therapy as the first disease-modifying osteoarthritis drug (DMOAD).

Kolon has also inked an exclusive licensing and development agreement with Mitsubishi Tanabe Pharma to market the drug in Japan. Under that deal, Mitsubishi Tanabe agreed to pay approximately $24 million upfront plus up to $410 million in payments tied to achieving development, regulatory, and commercial milestones, plus double-digit sales royalties.

In Korea, Mundipharma plans to market and distribute Invossa to general and semiprivate hospitals, while Kolon focuses on general practitioners, under an agreement announced April 11.

With the Korean drug ministrys approval, Invossa became the 29th South Koreandeveloped novel therapy approved by the countrys drug regulatory agencyand one of only four cell gene therapies to have ever been approved globally. The others were approved to treat immunodeficiency diseases, genetic disorders, and cancer.

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South Korea OKs First-in-Class Gene Therapy for Osteoarthritis - Genetic Engineering & Biotechnology News

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FDA Moves On Novartis Gene Therapy May Be Good For Kite Pharma Barron's A Food And Drug Administration panel is expected to meet tomorrow to discuss Novartis's (NVS) experimental gene therapy drug, a move that could be good news for Kite Pharma (KITE), according to Canaccord Genuity. Illustration: Getty Images/iStockphoto. FDA Decision on Novartis Gene Therapy Drug Could Benefit Kite PharmaTheStreet.com all 77 news articles »

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FDA Moves On Novartis Gene Therapy May Be Good For Kite Pharma - Barron's

(Reuters) - The U.S. Food and Drug Administration will ask a panel of advisors to focus on the safety of Novartis AG's experimental gene therapy drug when it meets to review the product on Wednesday.

The keenly anticipated preliminary review of the leukemia treatment, posted on the FDA's website on Monday, comes two days ahead of the advisory panel meeting, which will discuss the drug and vote on whether the benefits exceed the risks.

If approved, the drug, tisagenlecleucel, would be the first gene therapy to be approved in the United States. The FDA is not obliged to follow the recommendations of its advisors but typically does so.

The panel's decision could have significant implications not only for Novartis but for companies making similar drugs, including Kite Pharma Inc. Juno Therapeutics Inc and bluebird bio Inc.

The drugs use a new technology known as CAR-T, or chimeric antigen receptor T-cell therapy, which harnesses the body's own immune cells to recognize and attack malignant cells.

If approved they are expected to cost up to $500,000 and generate billions of dollars for their developers. Success would also help advance a cancer-fighting technique that scientists have been trying to perfect for decades.

Novartis is applying for approval in the first instance to treat B-cell acute lymphoblastic leukemia (ALL), the most common type of childhood cancer in the United States.

A clinical trial showed that 83 percent of patients who had relapsed or failed chemotherapy achieved complete or partial remission three months post infusion. Patients with ALL who fail chemotherapy typically have only a 16 to 30 percent chance of survival.

The FDA said it is not asking the panel to focus on whether the drug works, as it successfully met the main goal of the clinical trial. The panel will be asked only to focus on the short-term and long-term safety risks.

About half the patients experienced a serious complication known as cytokine release syndrome (CRS) which occurs when the body's immune system goes into overdrive. Doctors were able to manage the condition and it caused no patient deaths.

The FDA also raised concerns that the drug may cause secondary malignancies to occur and said long-term safety monitoring may be needed to address this concern.

Novartis is also testing its drug in diffuse large b-cell Lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, as is Kite. Part of the competitive landscape will include which company is best able to manufacture its drugs efficiently and reliably.

Reporting by Toni Clarke in Washington; Editing by Nick Zieminski

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FDA panel to focus on safety of Novartis gene therapy drug - Reuters

Kolon Life Science filed for a Biologics License Application (BLA) for Invossa-K Inj. with MFDS in August 2016 based on efficacy results from its Phase III clinical trials conducted at 12 major university hospitals in Korea. Invossa-K Inj. will be manufactured by Kolon Life Science, and marketed by Mundipharma and Kolon Pharmaceuticals for the Korean market.

"We are excited to launch the world's first cell and gene therapy for knee osteoarthritis and potentially the world's first disease-modifying osteoarthritis drug (DMOAD)," stated Mr. Woosok Lee, CEO of TissueGene. "This approval is the first critical step towards a global launch for this innovative, novel cell and gene therapy technology that will address one of the most pressing unmet medical need affecting millions of people suffering from osteoarthritis worldwide."

Invossa is a first-in-class cell and gene therapy drug designed to conveniently and effectively treat osteoarthritis of the knee through a single intra-articular injection. Clinical trials completed in Korea and on-going in the US have demonstrated pain relief, increased mobility, and potentially game-changing improvements in joint structure offering substantial relief and convenience for osteoarthritis patients who would otherwise be in need of surgery.

Through its national US Phase III clinical trials, TissueGene will be using the results to seek a DMOAD designation for Invossa from the US Food and Drug Administration (FDA), potentially making Invossa the first and only cell and gene therapy for osteoarthritis of the knee.

In November last year, Kolon Life Science signed a license agreement with Mitsubishi Tanabe Pharmaceutical Corporation, and Mitsubishi Tanabe Pharma is proceeding with the preparation of clinical trials through its exclusive development and commercialization rights in Japan.

TissueGene, Inc. TissueGene, Inc., is a Maryland-based regenerative medicine company specializing in cell and gene therapy. TissueGene's lead product is Invossa, an allogeneic, cell and gene therapy for osteoarthritis of the knee that is preparing for Phase III clinical trials in the US pursuant to a Special Protocol Assessment (SPA) agreement reached with the U.S. Food and Drug Administration. Information about the trials can be found at the NIH registry, ww.clinicaltrials.gov. For additional information about TissueGene, Inc., please visit http://www.tissuegene.com.

Kolon Life Science Kolon Life Science has been developing innovative cell and gene therapies including Invossa K Inj., the world's first cell-mediated gene therapy for osteoarthritis, since its founding in 2000. In addition to its biopharmaceuticals business, the company is also engaged in the business of providing active pharmaceuticals ingredients (API), eco-chemicals including antimicrobials for personal-care and industrial applications, as well as water-treatment solutions. For more information, please visit http://www.kolonls.co.kr/eng

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SOURCE TissueGene, Inc.

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Korea Approves the World's First Cell and Gene Therapy for Knee Osteoarthritis - PR Newswire (press release)

Breathing in a New Gene Therapy to treat Pulmonary Hypertension

Newswise (New York, NY July 12, 2017) Mount Sinai has partnered with Theragene Pharmaceuticals, Inc. to advance a novel airway-delivered gene therapy for treating pulmonary hypertension (PH), a form of high blood pressure in blood vessels in the lungs that is linked to heart failure. If the therapy succeeds in human clinical trials, it will provide patients for the first time with a way to reverse the damage caused by PH.

This gene therapy technique comes from the research of Roger J. Hajjar, MD, Professor of Medicine and Director of the Cardiovascular Research Center at the Icahn School of Medicine at Mount Sinai, and has been proven effective in rodent and pig animal models. PH is a deadly disease that disproportionately affects young adults and women; 58 percent of cases are found in young adults and 72 percent are women. There is currently no effective cure for PH, and about 50 percent of people who are diagnosed will die from the disease within five years.

PH is a rare (15-50 cases per million people), rapidly progressing disease that occurs when blood pressure is too high in vessels leading from the heart to the lungs. The high pressure is caused by abnormal remodeling of the lung blood vessels, characterized by a proliferation of smooth muscle cells and a thickening and narrowing of these vessels, and can lead to failure of the right ventricle of the heart and premature death. Abnormalities in calcium cycling within the vascular cells play a key role in the pathophysiology of pulmonary hypertension, along with deficiencies in the sarcoplasmic reticulum calcium ATPase pump (SERCA2a) protein which regulates intracellular calcium within these vascular cells and prevents them from proliferating within the vessel wall. Downregulation of SERCA2a leads to the proliferative remodeling of the vasculature. This gene therapy, delivered via an inhaled aerosolized spray, aims to increase the expression of SERCA2a protein, and has been shown in rodents and pigs to improve heart and lung function, as well as reduce and even reverse cellular changes caused by PH.

This is a devastating disease, and our work in collaboration with many laboratories across the country has allowed us to identify a specific molecular target and use gene therapy to improve cardiovascular and lung parameters in experimental models of PH. We look forward to starting first-in-human studies using this approach in affected patients, said Dr. Hajjar, the senior author of the studies, highlighting that clinical trials will be underway in the next two years.It may take several years before a product is commercially available for PH patients.

We are excited about the potential for SERCA2a gene therapy as a new modality in treating this serious disease, said Jon Berglin, Chief Executive Officer of Theragene Pharmaceuticals, Inc. We look forward to develop and advance this promising product into the clinic.

This represents another critical advancement in a potentially transformative therapeutic breakthrough by Mount Sinai scientists, demonstrating our commitment to improving health outcomes. We are thrilled to be working with Theragene Pharmaceuticals, and continue to strengthen our expertise in partnering health care innovations with industry, said Erik Lium, PhD, Senior Vice President of Mount Sinai Innovation Partners, the commercialization arm of the Icahn School of Medicine at Mount Sinai.

About Mount Sinai Innovation Partners (MSIP)MSIP is responsible for driving the real-world application and commercialization of Mount Sinai discoveries and the development of research partnerships with industry. The aim is to translate these innovations into healthcare products and services that benefit patients and society. MSIP is responsible for the full spectrum of commercialization activities required to bring the Icahn School of Medicine and the Mount Sinai Health Systems inventions to life. These activities include evaluating, patenting, marketing and licensing new technologies, engaging commercial and non-profit relationships for sponsored research, material transfer and confidentiality, as well as fostering an ecosystem of entrepreneurship within our research and health system communities. For more information, visit http://www.ip.mountsinai.org.

About Theragene Pharmaceuticals, Inc.Theragene is a biopharmaceutical company developing cutting-edge science for the treatment of debilitating diseases. The Companys diverse portfolio consists of preclinical and clinical oncology and cardiology platforms utilizing next generation gene therapy and immunotherapy methods.

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Breathing in a New Gene Therapy to Treat Pulmonary Hypertension - Newswise (press release)

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Gene therapy in hemophilia advances with big drops in patient bleeding rates - STAT

PHILADELPHIA When doctors saw the report on Bill Ludwigs bone-marrow biopsy, they thought it was a mistake and ordered the test repeated. But the results came back the same: His lethal leukemia had been wiped out by an experimental treatment never used in humans.

We were hoping for a little improvement, remembers the 72-year-old retired New Jersey corrections officer, who had battled the disease for a decade. He and his oncologist both broke down when she delivered the good news in 2010. Nobody was hoping for zero cancer.

The pioneering therapy with Ludwig and a few other adults at the University of Pennsylvania hospital paved the way for clinical trials with children. Six-year-old Emily Whitehead, who was near death, became the first pediatric recipient in 2012. Like Ludwig, she remains cancer-free.

Such results are why the treatment is on track to become the first gene therapy approved by the Food and Drug Administration. An FDA advisory committee will decide Wednesday whether to recommend approval of the approach, which uses patients own genetically altered immune cells to fight blood cancers.

If the panel gives the nod, the agency probably will follow suit by the end of September. That would open the latest chapter in immunotherapy a true living drug, says Penn scientist Carl June, who led its development.

The CAR T-cell treatment, manufactured by the drug company Novartis, initially would be available only for the small number of children and young adults whose leukemia doesnt respond to standard care. Those patients typically have a grim prognosis, but in the pivotal trial testing the therapy in almost a dozen countries, 83 percent of patients went into remission. A year later, two-thirds remained so.

And childhood leukemia is just the start for a field that has attracted intense interest in academia and industry. Kite Pharma of Santa Monica, Calif., has applied for FDA approval for aggressive non-Hodgkin lymphoma, and a similar Novartis application is close behind. Researchers also are exploring CAR T-cell therapys use for multiple myeloma and chronic lymphocytic leukemia, the disease that afflicted Ludwig. Theyre also tackling a far more difficult challenge using the therapy for solid tumors in the lungs or brain, for example.

The excitement among doctors and researchers is palpable. Were saving patients who three or four years ago we were at our wits end trying to keep alive, said Stephen Schuster, the Penn oncologist who is leading a Novartis lymphoma study. Both the study and a Kite trial have shown that the treatment can put about one-third of adults with advanced disease those who have exhausted all options into remission.

Yet along with the enthusiasm come pressing questions about safety, cost and the complexity of the procedure.

It involves extracting white blood cells called T cells the foot soldiers of the immune system from a patients blood, freezing and sending them to Novartiss sprawling manufacturing plant in Morris Plains, N.J. There, a crippled HIV fragment is used to genetically modify the T cells so they can find and attack the cancer. The cells then are refrozen and sent back to be infused into the patient.

Once inside the persons body, the T-cell army multiplies astronomically.

Novartis hasnt disclosed the price for its therapy, but analysts are predicting $300,000 to $600,000 for a one-time infusion. Brad Loncar, whose index fund focuses on cancer immunotherapy treatment, hopes the cost doesnt prompt a backlash. CAR-T is not the EpiPen, he said. This is truly pushing the envelope and at the cutting edge of science.

The biggest concerns, however, center on safety. The revved-up immune system becomes a potent cancer-fighting agent but also a dangerous threat to the patient. Serious side effects abound, raising concerns about broad use.

Treating patients safely is the heart of the rollout, said Stephan Grupp of the Childrens Hospital of Philadephia, who as director of its Cancer Immunotherapy Program led early pediatric studies as well as Novartiss global trial. The efficacy takes care of itself, but safety takes a lot of attention.

One of the most common side effects is called cytokine release syndrome, which causes high fever and flulike symptoms that in some cases can be so dangerous that the patient ends up in intensive care. The other major worry is neurotoxicity, which can result in temporary confusion or potentially fatal brain swelling. Juno Therapeutics, a biotech firm in Seattle, had to shut down one of its CAR T-cell programs because five patients died of brain swelling. Novartis has not seen brain swelling in its trials, company officials said.

To try to ensure patient safety, Novartis isnt planning a typical product rollout, with a drug pushed as widely and aggressively as possible. The company instead will designate 30to 35 medical centers to administer the treatment. Many of them took part in the clinical trial, and all have gotten extensive training by Grupp and others.

Grupp said he and his staff learned about the side effects of CAR T-cell therapy and what to do about them through terrifying experience that began five years ago with Emily Whitehead.

The young girl, who had relapsed twice on conventional treatments for acute lymphoblastic leukemia, was in grave condition. Grupp suggested to her parents that she become the first child to get the experimental therapy.

I said, Surely, this has been tried on kids somewhere else in the world, recalled her father, Thomas Whitehead of Philipsburg, Pa. But Steve said, Nope, some adults got it, but that was a different kind of leukemia.

After getting the therapy, Emilys fever soared, her blood pressure plummeted, and she ended up in a coma and on a ventilator for two weeks in the hospitals intensive care unit. Convinced his patient would not survive another day, a frantic Grupp got rushed lab results that suggested a surge of interleukin 6 was causing her immune system to relentlessly hammer her body. Doctors decided to give Emily an immunosuppressant drug called tocilizumab.

She was dramatically better within hours. She woke up the next day, her 7th birthday. Tests showed her cancer was gone.

The approval of CAR T-cell therapy would represent the second big immunotherapy advance in less than a decade. In 2011, the FDA cleared the first agent in a new class of drugs called checkpoint inhibitors. It has approved four more since then.

There are big differences between the two approaches. The checkpoint inhibitors are targeted at solid tumors, such as advanced melanoma, lung and bladder cancer, while CAR-T cell therapy has been aimed at blood disorders. And although checkpoint inhibitors are off the shelf, with every patient getting the same drug, the other is customized to an individual. Many immunotherapy experts think the greatest progress against cancer will occur when researchers figure out how to combine the approaches.

For the Penn team, the CAR T-cell story goes back decades, starting at the then-National Naval Medical Center in Bethesda, where June and a postdoc fellow named Bruce Levine worked on new HIV treatments. In the process, they figured out a way to turbocharge T cells to make them more powerful and plentiful.

The pair moved to Philadelphia in 1999 and dove into cancer research. Two years later, Junes wife died of ovarian cancer, something he has credited as spurring him to work even harder in the field. In the years that followed, researchers across the country, including at Memorial Sloan Kettering Cancer Center in New York and Fred Hutchinson Cancer Research Center in Seattle racked up an array of tantalizing discoveries involving T cells.

Fast-forward to 2010, when Ludwig, who lives in Bridgeton, N.J. became Penns first patient to receive CAR T-cell therapy. Two other men got the treatment not long after. One is still in remission; the other relapsed and died.

But after those three patients, the Penn researchers ran out of money for more treatments. To try to raise interest and funding, they decided to publish the results of their work. The article that appeared in the New England Journal of Medicine in August 2011 created a firestorm, June said one that brought them new resources. David Porter, a Penn oncologist working with June, was on vacation in western Maryland and had to stop at a Kohls to buy a dress shirt for the immediate TV interviews.

The pediatric trial opened the following spring with Whitehead. Six months later, Penn licensed its technology to Novartis in exchange for financial support, which included a new cell-manufacturing facility on campus.

With FDA approval seeming imminent, the researchers who were so instrumental in the therapys development and testing are almost giddy. Grupp is especially pleased that the advance will be available first to children. Usually everything is developed first for adults, he noted recently, and children are an afterthought.

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First gene therapy 'a true living drug' on the cusp of FDA approval - Washington Post

A new method efficiently transfers genes into cells, then activates them with light. This could lead to gene therapies for cancers

Mineko Kengaku, Tatsuya Murakami, and their colleagues from Kyoto Universitys Institute for Integrated Cell-Material Sciences (iCeMS) have developed a new method that modifies the surface of nanorods, making them more efficient in transporting cancer-killing genes into cells.

The method involves coating gold nanorods, which produce heat when exposed to a near-infrared laser, with the lipids oleate and DOTAP. The lipids enhance the nanorods' ability to interact with and penetrate cells.

The team also developed a gene carrier, known as a plasmid vector, which includes a heat shock protein that is activated in response to heat.

First, the vector was bound to the enhanced green fluorescent protein (EGFP) gene, and then transferred into mammalian cells by the lipid-coated gold nanorods. Exposing cells to near-infrared laser for ten seconds heated up the gold nanorods, turning on the EGFP gene. Surrounding, non-targeted cells showed little to no EGFP expression.

A protein called TRAIL was then added to the plasmid vector. TRAIL induces cell death in cancer cell lines. Infrared illumination of cells transfected by TRAIL-carrying nanorods led to a high cell death rate in surrounding cancer cells.

The lipid-coated gold nanorods could potentially help with molecular cancer therapies.

This new system provides a unique opportunity for site-directed, light-inducible transgene expression in mammalian cells by a near-infrared laser, with minimal phototoxicity, conclude the researchers in their study published in the journal Scientific Reports.

This article has been republished frommaterialsprovided by Kyoto University. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference

Nakatsuji, H., Kawabata, G. K., Kurisu, J., Imahori, H., Murakami, T., & Kengaku, M. (2017). Surface chemistry for cytosolic gene delivery and photothermal transgene expression by gold nanorods. Scientific reports, 7(1), 4694.

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Breakthrough Nanorod Tech Could Deliver Gene Therapy Directly to Cancer Cells - Technology Networks

After rattling investors with early signs of an immune reaction in a couple of cases as well as an unexpected infusion for a suspected knee bleed, Spark Therapeutics $ONCE says that its early Phase I/II study for its hemophilia B gene therapy is staying on track, slashing the rate of annual infusions and the bleed rate among the 10 patients on the pioneering therapy SPK-9001.

The annual infusion rate has new dropped 99%, down to a mean of 1 compared to 67.5 ahead of treatment. Five of the 10 are now past the one-year mark since their treatment, with no bleeding issues. The group of 10 posted an average bleed rate of 0.4 compared to 11.1 ahead of once-and-done therapy.

Singling out the first patient, whos now past the 18-month mark, researchers say hes had zero bleeds with no Factor IX infusions. Both cases of elevated liver enzymes indicating an immune response to the delivery vector were resolved with steroids and neither have had bleeds or the need for infusions.

Spark has now accumulated close to 10 years of patient responses to its therapy, an important first step in laying out the potential for gene therapy to end hemophilia.

The latest update arrived at a scientific conference in Berlin marked by the dramatic showdown between Shire and its rival Roche, which fielded more newly contested boasts about its would-be hemophilia blockbuster emicizumab. Alnylam and Sanofi also stepped up with a promising look at the latest Phase II data on their RNAi approach underscoring some significant gains in the field for a variety of new approaches to the rare blood disorder.

We continue to be encouraged by the SPK-9001 clinical trial results observed to date, with all participants having discontinued routine infusions of factor IX concentrates, said Katherine A. High, M.D., president and chief scientific officer at Spark Therapeutics. The growing body of data showing a sustained response is a promising sign for this investigational hemophilia B gene therapy program.

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Pioneering gene therapy patients stay on track, boosting Spark's ... - Endpoints News

July 11, 2017 06:30 ET | Source: uniQure N.V.

LEXINGTON, Mass. and AMSTERDAM, the Netherlands, July 11, 2017 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ:QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today presented new clinical data demonstrating that the presence of pre-existing anti-AAV5 neutralizing antibodies (NABs) does not predict the potential efficacy of AAV5-mediated gene transfer in patients with hemophilia B. Clinically meaningful factor IX (FIX) activity levels from the ongoing Phase I-II trial of AMT-060 were observed at NAB titers up to 1:341, determined as corresponding up to the 90th percentile of a healthy control population. NABs were quantified in the blood sera of these patients using a highly sensitive assay. These clinical data were presented today in a poster presentation at the 26th Biennial Congress of theInternational Society on Thrombosis and Hemostasis(ISTH), taking place this week in Berlin, Germany.

The presence of pre-existing NABs to adeno-associated virus (AAV) vectors has long posed a critical challenge for the clinical application of gene therapies, as patients who currently screen positive for NABs are generally excluded from treatment. Researchers from uniQure recently presented data in non-human primates suggesting that AAV5 could successfully mediate gene transfer in the presence of NABs at levels as high as 1:1031.

In a poster presentation at the ISTH meeting, a re-analysis was described of pre-gene transfer screening samples from the 10 patients who have been treated in the ongoing Phase I/II trial of AMT-060 for hemophilia B. The patients had tested negative for preexisting anti-AAV5 NAbs using a green fluorescent proteinbased (GFP) assay before receiving treatment. These samples were later re-assessed using a highly sensitive luciferase-based (LUC) NAB assay. Anti-AAV5 NABs were detected retrospectively in three patients who had been treated with the low dose (5x1012 gc/kg) of AMT-060. However, all three patients presented increases in FIX expression and, especially, the patient with the highest NAB level (titer 1:341) had the highest FIX-activity (steady-state FIX 6.8% of normal; latest FIX measurement 10.7% of normal) among all five patients treated in the low-dose cohort. None of the three patients who tested positive for NAB titers, experienced over time elevations in liver enzymes post gene transfer, FIX activity loss, or clinically relevant T-cell responses to the capsid.

These clinical data show that hemophilia B patients presenting with neutralizing antibodies may be considered eligible for AAV5-mediated gene transfer, stated Matthew Kapusta, chief executive officer at uniQure. This development potentially expands the applicability of AAV5 gene therapies to nearly all hemophilia B patients. We believe these factors contribute to making AAV5 a potential best-in-class vector for delivering gene therapies more effectively and safely to a greater portion of patients in need of treatment.

About uniQure uniQure is delivering on the promise of gene therapy single treatments with potentially curative results. We are leveraging our modular and validated technology platform to rapidly advance a pipeline of proprietary and partnered gene therapies to treat patients with hemophilia, Huntingtons disease and cardiovascular diseases. http://www.uniQure.com

uniQure Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. These forward-looking statements include, but are not limited to, statements regarding the development of our gene therapy product candidates, including the future development of AMT-060, the success of our collaborations and the risk of cessation, delay or lack of success of any of our ongoing or planned clinical studies and/or development of our product candidates. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, risks associated with corporate reorganizations and strategic shifts, collaboration arrangements, our and our collaborators clinical development activities, regulatory oversight, product commercialization and intellectual property claims, as well as the risks, uncertainties and other factors described under the heading "Risk Factors" in uniQures 2016 Annual Report on Form 10-K filed on March 15, 2017. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future.

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uniQure Presents New Clinical Data in Hemophilia B Patients Demonstrating Therapeutic Efficacy of AAV5 Gene ... - GlobeNewswire (press release)

DUBLIN--(BUSINESS WIRE)--Research and Markets has announced the addition of Jain PharmaBiotech's new report "Gene Therapy - Technologies, Markets and Companies" to their offering.

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression.

The markets for gene therapy are difficult to estimate as there is only one approved gene therapy product and it is marketed in China since 2004. Gene therapy markets are estimated for the years 2016-2026. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright. The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

The voluminous literature on gene therapy was reviewed and selected 750 references are appended in the bibliography. The references are constantly updated. The text is supplemented with 76 tables and 21 figures.

Profiles of 189 companies involved in developing gene therapy are presented along with 240 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report. John Wiley & Sons published the book in 2000 and from 2001 to 2003, updated versions of these companies (approximately 160 at mid-2003) were available on Wiley's web site. Since that free service was discontinued and the rights reverted to the author, this report remains the only authorized continuously updated version on gene therapy companies.

Key Topics Covered:

Part I: Technologies & Markets

Executive Summary

1. Introduction

2. Gene Therapy Technologies

3. Clinical Applications of Gene Therapy

4. Gene Therapy of Genetic Disorders

5. Gene Therapy of Cancer

6. Gene Therapy of Neurological Disorders

7. Gene Therapy of Cardiovascular Disorders

8. Gene therapy of viral infections

9. Research, Development and Future of Gene Therapy

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

11. Markets for Gene Therapy

12. References

Part II: Companies

13. Companies involved in Gene Therapy

For more information about this report visit https://www.researchandmarkets.com/research/466r2h/gene_therapy

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Gene Therapy 2016-2026 - Technologies, Markets and Companies Report 2017 - Profiles of 189 Companies with 240 ... - Business Wire (press release)

Shire has submitted a request to the US Food and Drug Administration to test its investigational factor VIII (FVIII) gene therapy SHP654 in patients with the bleeding disorder haemophilia A.

SHP654 (also known as BAX 888) aims to protect haemophilia A patients against bleeds through the delivery of a long-term, constant level of factor expression, the firm noted.

Shires gene therapy programme for haemophilia A uses a recombinant adeno-associated virus serotype 8 (rAAV8) vector that selectively targets the liver.

It involves the delivery of a functional copy of FVIII to the bodys liver to enable its own production of FVIII, rather than relying on a factor-based treatment.

The Investigational New Drug submission is based on the results of preclinical and phase I studies showing the potential utility of its candidate, the firm noted.

If Shire gets a green light for human testing it intends to study SHP654 in a global multi-center trial evaluating safety and examining the doses required to boost factor VIII activity levels and affect haemophilic bleeding.

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Shire applies to test haemophilia A gene therapy in humans ... - PharmaTimes

The ruckus over the CRISPR gene-editing system hides a dark reality: its high cost may make it unaffordable and questions remain whether most insurance companies will pay for it.

The cost isnt coming down, said Mark Trusheim, director of the Massachusetts Institute of TechnologysNEW Drug Development Paradigms, a think tank working on the problem of how we will pay for expensive new drugs. Companies will say, We are developing these medicines, just pay us; insurers will say, We cant afford it.

Editas Medicineplans to use CRISPR-Cas9 to treat various diseases, including Leber congenital amaurosisBut in itsannual report, Editas noted significant uncertainty on whether payers would cover the treatment. In fact, a handful of insurance companieshave issued policy documents that exclude gene therapy from coverage, a move that experts say establishes policy against paying for CRISPR-based therapeutics.

Companies will charge whatever the market will bear, [said Tania Bubela, a law and policy expert]. Im not even sure that many of these gene therapies will work, and not all medicine is worth the price. But if these technologies become broadly used, especially in altering T cells for cancer, payers wont meet the demands of steep prices, and Bubela predicts that the system implodes under its own weight.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Who will pay for CRISPR?

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CRISPR's high costs may limit development of gene therapy drugs - Genetic Literacy Project

The conference will take place in London on the 11th - 13th September. Early registration is rewarded so visit the event website for the latest early bird rates or email enquire@iqpc.co.uk to find out more.

With cell and gene manufacturing activity on the rise, the race towards commercialisation of cell and gene products has already begun. Where technology innovations are pathing the way towards the development of these products, challenges surrounding scale up and closed system processing highlight areas that need focus so that cell and gene therapy products can be produced on an industrial scale. Pharma IQ will be addressing the key barriers and opportunities in enhancing the development of cell and gene therapies, with the focus on how manufacturing processes can be improved ready for the market boom!

About Pharma IQ

Pharma IQ has 100k+ members and is an international online community focusing on providing pharmaceutical professionals with knowledge, information and articles. Pharma IQ is dedicated to creating a learning environment for sharing ideas, best practices and solutions within the pharmaceutical community. To learn more visit http://www.cellgenemanufacturing.iqpc.co.uk , or call us at +44(0)207-036-1300

Media Contact: Rumina Akther, Trainee Marketing Manager, IQPC: rumina.akther@iqpc.co.uk or call +44(0)207-036-1300

Press are invited to attend this important industry summit, if you would like to a complimentary press pass please email Rumina Akther on rumina.akther@iqpc.co.uk

SOURCE Pharma IQ

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Pharma IQ: Cell & Gene Therapy Manufacturing Summit - PR Newswire (press release)

news

This latest funding round attracts two prominent new investors; Brian Kennedy and Sir Brian Souter.

Ryboquin Limited, a Scottish Borders based pharmaceutical company, announces that it has closed a 1.8m equity fund raising to accelerate product development in gene therapy.

In addition to support from existing shareholders, including Borders business angel group, TRI Capital and the Scottish Investment Bank (the investment arm of Scottish Enterprise), funding has also been provided by Brian Kennedy, the highly successful Scottish entrepreneur and Sir Brian Souter, the founder and Chairman of Stagecoach. Brian Kennedy will also join the Board.

Founded in 2013, Ryboquin is a privately held, pharmaceutical company focused on commercialising patented intellectual property in the area of delivering gene therapy primarily in the field of human cancer medicine. Ryboquin is in partnership with Nanogenics to promote the targeted nucleic acid delivery system LipTide.

The funds being raised will be used to further scientific development as well as providing funding for corporate expansion.

Paul Murray, Executive Chairman, Ryboquin, says:

The support from existing shareholders and the investment by Brian Kennedy and Sir Brian Souter, two esteemed leaders and hugely successful businessmen, is testimony to the potential of Ryboquin and to the work we are undertaking in the field of cancer gene therapy drug development.

We also welcome Brian Kennedy to the Board and look forward to his contribution as we seek to grow the business both organically and by acquisition.

Brian Kennedy says:

I am delighted to be part of Ryboquin and to be working with the team that could make great progress in the treatment of cancer and other diseases.

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Ryboquin raises 1.8m for drug development in gene therapy - Drug Target Review

Boston Business Journal

After raising $50M, virtual gene therapy startup LogicBio sets up ... Boston Business Journal LogicBio Therapeutics becomes the latest local entrant to the field of gene therapy, a method of inserting healthy genes into cells to replace missing or faulty ... and more »

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After raising $50M, virtual gene therapy startup LogicBio sets up ... - Boston Business Journal

Xconomy Boston

Gene therapy offers the potential for a long-lasting, if not permanent, treatment for an inherited disease, but cells that divide rapidly, such as those in the liver, present a thorny problem. Because of how they insert themselves in the cells, some forms of gene therapy get diluted as the cells divide.

Its a particular problem in growing children. Cambridge, MA-based LogicBio says it has developed a workaround by combining gene editing with gene therapy. The firm has raised $45 million in additional capital to help bring this technology into human testing, and it is moving from California to the LabCentral shared incubator space in Cambridges Kendall Square.

LogicBio calls its technology GeneRide. The company says its approach can transfer genetic material to specific sites to repair a faulty genetic sequence. The companys focus is metabolic disorders that affect the liver in children. Published research shows that metabolic disorders of the liver can progress to injury affecting other organs. In rare cases, the severity of the disease requires a pediatric liver transplant.

If GeneRide works as the company envisions, the gene therapy would offer a one-time treatment that avoids side effects.

London-based Arix Bioscience (LSE: ARIX) led the Series B round of investment, which was joined by new investors OrbiMed, Edmond De Rothschild Investment Partners, Pontifax, and SBI Japan-Israel Innovation Fund. Earlier investor OrbiMed Israel Partners also joined in the latest investment. In total, LogicBio says it has raised approximately $50 million in financing to date.

Gene therapy remains largely experimental. UniQure (NASDAQ: QURE) received the Western worlds first gene therapy approval in 2012 for alipogene tiparovec (Glybera), a treatment for a rare metabolic disorder. But earlier this year, the company, split between the Netherlands and Lexington, MA, announced it would not seek renewal of its conditional approval, set to expire in October. Patient demand for the drug was limited and the company did not expect that to change.

The first U.S. approval could come soon. Philadelphia-based Spark Therapeutics (NASDAQ: ONCE) is awaiting an FDA decision on a gene therapy for an inherited form of blindness. Cambridge-based Bluebird Bio (NASDAQ: BLUE) last week released early data from a Phase 3 study in patients with beta-thalassemia, a rare blood disorder.

The technologies underlying LogicBios approach were developed at Stanford University by company co-founders Mark Kay, Adi Barzel, and Leszek Lisowski. In addition to its Cambridge site, the company also has scientists in Tel Aviv, Israel.

Frank Vinluan is editor of Xconomy Raleigh-Durham, based in Research Triangle Park. You can reach him at fvinluan [at] xconomy.com

Link:

LogicBio Lands $45M for Gene Therapies in Rare Pediatric Diseases - Xconomy

Inherent Complexity

The inherent complexity of viral vector-based products, due to their physical size, formulation, and the fact that they often utilize a combined drug targeting/delivery vehicle function, makes their physical and biological characterization highly challenging from a regulatory perspective. Consequently, a fallback approach is adopted where the product is defined by the manufacturing process. This approach then makes the introduction of potentially product-impacting process changes difficult to implement and by default, the process becomes locked down within the early stages of development, severely restricting the scope for process improvement and scale up.

Classical process scale up tends to be via a vertical approach, with a focus on increasing the size of single operations (such as fermentation vessels) while keeping similar labor levels, subsequently achieving reduction in cost. This approach is valid if the process is well understood and amenable to linear scale up. The reality is that a large number of the key operations in the production of viral vectors are neither well characterized nor easily scaled. Lack of time and analytical tools will eventually direct developers to take a more horizontal approach to process scale up.

It seems likely that scale up will be based on limited vertical scale up, with multiple and overlapping production streams, potentially exploiting options around the adoption of closed single-use production systems to maximize outputs from production facilities. While this may not be the most efficient approach with regard to labor and facility costs and end-product testing, it is likely to be the only realistic option for many product development groups.

It is inevitable that some process changes will need to be introduced, for example, the requirement to replace purification of vectors by ultracentrifugation, as these processes are perceived as not only being unscalable, but also as highly operator-dependent with regard to yield and purity. The challenge becomes how engineers replace this type of operation. From a regulatory perspective, the key is an understanding of the critical quality attributes (CQAs) that impact product safety, purity, and potency; the critical process parameters (CPPs) required to control them; and the availability of the tools to measure CPPs.

This approach then, in theory, will allow process development groups to develop strategies for introducing and verifying the impact of desired process changes. However, the successful process development of these legacy processes will be dependent on the availability of suitable in-process and final-product assays. There is a clear regulatory, as well as operational, need for drug developers to invest in the analytical tools required to achieve greater understanding of AAV vectors and the processes used to make them for the products to receive commercial licensing.

The production of vectors through transient production routes entails a complex materials supply chain. At the front end is the supply of plasmid DNA constructs used to generate the vectors; clearly the quantities required will not only increase proportionally with the increased scale of vector manufacturing, but also, the associated quality requirements will be increased, moving from materials made to traceable standards to those made to GMP-grade standards (Figure 2). For early-phase development, non-GMP-grade plasmids may be used for the production of material for proof-of principle clinical studies. However, this may not be the case for commercial vectors, where GMP-grade plasmids may be required. One consequence of this will be the potential need for manufacturers to align with suppliers that have large-scale GMP capabilities to ensure the timely and secure delivery of plasmid supplies to support late clinical and commercial production.

At the end of the supply chain is the production of the viral vector drug product. For early-stage development, relatively little focus is given to either the product formulation or the filling process. There is often good reason for this, as material for such development studies is in very short supply, with all available material often directed into clinical studies to demonstrate product efficacy.

The result of this is that the basic formulations used in early-stage development are carried forward into late-stage trials, with the products 0.2-m filtered and hand filled into glass vials and stored at 80C.

Future development activities in the AAV field will need to be focused on identifying formulations that provide long-term stability, potentially moving to +28C storage, and generating meaningful stability data. Fully defining the drug product manufacturing process will also ensure the retention of product titers and activity throughout the manufacturing process, including activities such as inspection and labeling.

In conclusion, we are in exciting times with a number of these potentially life-changing products coming through to clinic. However, if we are to bring these products efficiently to the market, developers will need to adopt pragmatic and informed solutions for the manufacturing challenges that lie ahead.

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Manufacturing of AAV Vectors for Gene Therapy - Genetic Engineering & Biotechnology News

U.K. firm NightstaRx raised $45 million in a Series C financing round to support continued clinical development of its pipeline of retinal gene therapies, including a pending Phase III study with lead candidate NSR-REP1 for treating choroideremia. The new funds will also be used to support an ongoing Phase I/II study with NSR-RPGR in patients with X-linked retinitis pigmentosa (RP), and a proposed Phase I/II trial with a gene therapy product targeting an inherited form of macular dystrophy. Nightstar projects starting the macular dystrophy clinical trial during late 2018.

Investors in the Series C round included Nightstars existing investors Syncona and New Enterprise Associates (NEA) and new investors Wellington Management Company and Redmile Group. As an original investor in Nightstar, our goal from day one was to build a global gene therapy leader with the capability of developing multiple programs for inherited retinal diseases, commented Chris Hollowood, Ph.D., chairman of the board of Nightstar and chief investment officer of Syncona, which is funded by The Wellcome Trust. We welcome Wellington Management and Redmile Group as investors and look forward to working with them and NEA to fulfill Nightstars potential.

Founded in 2014 by researchers at the University of Oxford, Nightstar is developing a pipeline of one-time potentially curative treatments for rare inherited retinal diseases. Lead candidate NSR-REP1 is an adeno-associated virus (AAV) vector-based gene therapy in development for treating choroideremia, a rare X-linked inherited retinal dystrophy for which there are currently no disease-modifying therapies. The AAV vector is administered by injection under the retina, using standard surgical procedures performed under local anesthetic. Nightstar says a Phase I/II study carried out by the University of Oxford confirmed long-term benefits of the treatment including vision improvement or stabilization.

The firms AAV-vector-based NSR-RPGR gene therapy for X-linked RP is designed to deliver a normal copy of the RP GTPase regulator (RPGR) gene, which Nightstar says is mutated in more than 70% of cases of X-linked RP. The procedure similarly involves injecting the gene-carrying vector under the retina. The ongoing Phase I/II study with NSR-RPGR was started in March.

Nightstar has ongoing collaborations with the University of Oxford, the Bascom Palmer Eye Institute, and the Institute for Ophthalmic Research, Tbingen University Hospital. In February, the firm inked a collaboration with Netherlands-based Preceyes to develop a subretinal drug delivery technology based on the latters high-precision robotic device for ocular surgery.

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NightstaRx Raises $45M to Fund Phase III Study with Retinal ... - Genetic Engineering & Biotechnology News (blog)

Author's note: The following consists of excerpts from my 45-page May 30 report on bluebird bio (NASDAQ:BLUE), Kite Pharma (NASDAQ:KITE), and Juno Therapeutics (NASDAQ:JUNO). The focus in this submission is BLUE. Please check out my Seeking Alpha profile for important information. Global Gene Therapy Market

The gene therapy market is gaining popularity in the global medical community. The advent of advanced techniques for gene transfer has enabled the use of gene therapy for various new applications. Although it is still at an infant stage, its promise has led to a range of bullish estimates. Market research firm BCC Research forecasts the global market for DNA vaccines to grow at a 54.8% CAGR to $2.7 bln by 2019, while two other observers - Roots Analysis and Research and Markets - predict the gene therapy market as a whole to reach ~$11 bln by 2025. Another report from market intelligence firm Transparency Market Research forecasts that the global stem cell market will grow at a CAGR of > 20% in the next few years and said there is a rich pipeline of more than 500 cell and gene therapy products, which will drive significant capacity as the pipeline matures and progresses to commercial supply.

Key factors driving market growth include demand for novel and efficient therapies to treat cancers and other indications with high unmet needs. Other market drivers include completion of the human genome project, rising incidence and prevalence of cancers and other critical diseases, and the prospective launch of gene therapies in major global markets.

Most gene therapy products are in the pre-clinical or clinical research stage. To-date, there are only five marketed drugs, namely Glybera, Neovasculogen, Gendicine, Rexin-G, and Oncorine. However, these products constitute very little revenue for the gene therapy market. Most revenue for the gene therapy market is generated from products used in clinical trials.

Need for gene therapy: It is estimated that approximately 5% of the global population suffers from a rare disease, and half of the global population affected by rare diseases are children, making rare disease treatment a concern for children across the globe. There are about 7,000 known rare diseases that comprise the most complex healthcare challenges for researchers and health professionals - with most being difficult to diagnose due to heterogeneity in disease epidemiology.

Rare diseases that affect 200,000 people in the US (as per the FDA definition) and a similar percentage in Europe are typically genetic in nature and, thus, present a significant unmet need for potential regimes in the market.

As per World Health Organization, 80% of rare diseases are caused due to genetic abnormality and are inherited for generations. Approximately 5% of the rare diseases have a treatment, and most of the current therapeutic approaches include gene therapy and cell therapy. A significant gap between demand and supply of rare disease drugs is expected to create a massive opportunity for manufacturers and researchers in the area of rare disease treatment.

How Does Gene Therapy Work?

Advances in biotechnology have brought gene therapy to the forefront of medical research. The prelude to successful gene therapy, the efficient transfer and expression of a variety of human gene into target cells, has already been accomplished in several systems.

Gene therapy may be defined as the introduction of genetic material into defective cells for a therapeutic purpose. While gene therapy holds great potential as an effective means for selective targeting and treatment of disease, the field has seen relatively slow progress in the development of effective clinical protocols. Although identifying genetic factors that cause a physiological defect is straightforward, successful targeted correction techniques are proving continually elusive. Hence, safe methods have been devised to do this (using several viral and no-viral vectors). Two main approaches have emerged in-vivo modification and ex-vivo modification. Retrovirus, adenovirus, adeno-associated virus are suitable for gene therapeutic approaches; these are based on permanent expression of the therapeutic gene. Non-viral vectors are far less efficient than viral vectors, but they have advantages due to their low immunogenicity and large capacity for therapeutic DNA.

Viral Vectors: These are virus-based vectors. Examples include retrovirus vector, adeno virus vector system, adeno associated virus vector, and herpes simplex virus. Extensive research is being conducted on the various viral vectors used in gene delivery. Non-viral vectors: Examples of non-viral vector systems include pure DNA constructs, lipoplexes, DNA molecular conjugates, and human artificial chromosomes. Owing to the following advantages, non-viral vectors have gained significant importance in the past few years as they are less immune-toxic, there is risk-free repeat administration and relative ease of large-scale production.

A major disadvantage is that the corrected gene needs to be unloaded into the target cell, and the vector has to be made to reach the required treatment site.

Gene therapy has transitioned from the conceptual, technology-driven, laboratory research, to clinical trial stages for a wide variety of diseases. In addition to curing genetic disorders such as Hemophilia, Chronic Granulomatous Disorder, and Severe Combined Immune Deficiency (ADA-SCID), it is also being tested to cure acquired diseases such as cancer, neurodegenerative diseases, influenza, and hepatitis.

Gene therapy is not limited to any particular disease. It is proving to be a promising treatment for rare diseases such as X-linked adrenoleukodystrophy. The therapy has proved effective in research conducted for the following diseases:

Fat Metabolism Disorder: Gene therapy is used to correct rare genetic diseases caused due to lipoprotein lipase deficiency. This deficiency leads to fat molecules clogging the bloodstream. An adeno-associated virus vector is used to deliver the corrected copy of the LPL to the muscle cells. This corrected copy prevents excess accumulation of fat in the blood by breaking down the fat molecules. In 2012, the EU approved Glybera, the first viral gene therapy treatment for LPLD, manufactured by uniQure (NASDAQ:QURE). Glybera is likely to be approved for the American market by 2018.

Adenosine Deaminase Deficiency: Gene therapy has successfully been used to treat another inherited immune disorder - ADA deficiency. More importantly, none of the patients undergoing this treatment developed any other disorder. The retroviral vector is used in multiple small trials to deliver the functional copy of the ADA gene. Primarily, all the patients involved in these trials did not require any injection of ADA enzyme as their immune functions had immensely improved.

Severe Combined Immune Deficiency: A lot of documented work is already available regarding treating this immunodeficiency with gene therapy; however, clinical trials have not shown promising results. The viral vectors used during the trials triggered leukemia in patients. Since then, focus of the research and trials has been on preparing new vectors that are safe and do not cause cancer.

Hemophilia: Patients with hemophilia suffer excessive blood loss as the blood clotting protein (Factor IX) is absent. Researchers have successfully inserted the missing gene in the liver cells using an adeno-associated viral vector. After undergoing this treatment, patients experienced less bleeding as their body was able to create some of the Factor IX protein.

Cystic Fibrosis (CF): CF is a chronic lung disease caused due to a faulty CFTR gene. Genes are injected into cells using a virus. Recent studies also include testing the cationic liposome (a fatty container) to deliver DNA to the faulty CFTR gene, thus making the use of the non-viral gene carrier more successful. Phase II trials using this therapy were published in early 2015, which promised a novel therapeutic approach to CF.

-thalassemia: Clinical trials on gene therapy for -thalassemia (the faulty beta-globin gene, which codes for an oxygen-carrying protein in RBC) can be tracked back to 2007. Blood stem cells were taken from the patients bone marrow, and a retrovirus was used to transfer a working copy of the faulty gene. The modified stem cells were re-injected into the body to supply functional red blood cells. This treatment, once conducted, lasted over seven years, with the patient not undergoing blood transfusion during this time.

Hereditary Blindness: Currently, gene therapy is being tested to treat degenerative form of inherited blindness, where patients lose light-sensing cells in their eyes over time. Experimental data suggests that the animal models of a mouse, rat, and dog show slow or even reverse vision loss using gene therapy. The most important advantage associated with gene therapy for eye disorders is that AAV (adeno-associated virus) cannot shift from the eye to other body parts and hence does not cause an immune reaction.

Parkinson's Disease: Patients with Parkinson's disease lose the ability to control their movement as their brain cells stop producing the dopamine molecule used for signaling. A small group of patients showed improved muscle control when a small area of their brain was treated with a retroviral vector that contained dopamine-producing genes.

This is because cancer genetics is a novel treatment method, marked by high R&D costs. The therapy targets diseases with high unmet needs; this has been the driving force behind academic research laboratories, small biotech firms, and large pharmaceutical companies. The therapy is of short-duration treatment or mostly one-time treatment customized to individuals and often in small patient populations.

bluebird bio (BLUE) is a clinical-stage biotechnology company that focuses on developing transformative gene therapies for severe genetic diseases and cancer. Its product candidates include Lenti-D, which is in Phase II/III clinical studies for the treatment of cerebral adrenoleukodystrophy - a rare hereditary neurological disorder - and LentiGlobin, which is in four clinical studies for the treatment of transfusion-dependent beta-thalassemia and severe sickle cell disease. The companys lead product candidate is bb2121, a chimeric antigen receptor (CAR) T cell receptor (TCR) product candidate that is in Phase I trial for the treatment of relapsed/refractory multiple myeloma.

The company's gene therapy platform is based on viral vectors that utilize a non-replicating version of the Human Immunodeficiency Virus Type 1 (HIV-1). Its lentiviral vectors are used to introduce a functional copy of a gene to the patient's own isolated hematopoietic stem cells (HSCs) in the case of its LentiGlobin and Lenti-D product candidates, or the patient's own isolated white blood cells, which include T cells, in the case of its bb2121 product candidate.

BLUE has a strategic collaboration with Celgene Corporation (NASDAQ:CELG) to discover, develop, and commercialize disease-altering gene therapies in oncology; with Kite Pharma (KITE) to develop and commercialize second generation T cell receptor product candidates against an antigen related to certain cancers associated with the human papilloma virus; and with Medigene (Germany) for the research and development of (TCR) product candidates directed against approximately four antigens for the treatment of cancer indications. Founded in 1992 and headquartered in Cambridge, Massachusetts, the company was formerly known as Genetix Pharmaceuticals and later changed its name to bluebird bio (Incorporated) in September 2010.

With its lentiviral-based gene therapies, T cell immunotherapy expertise, and gene-editing capabilities, BLUE has built an integrated product platform with broad potential application for severe genetic diseases and cancer. BLUE's approach to gene therapy is based on viral vectors that utilize the Human Immunodeficiency Virus Type 1 or HIV-1. The HIV-1 vector is stripped off all the components that allow it to self-replicate and infect additional cells. HIV-1 is part of the lentivirus family of viruses. The vectors are used to introduce a modified copy of a gene from the patients own blood stem cells called hematopoietic stem cells (HSC), which reside in the patient's bone marrow. HSCs divide cells that allow for sustained expression of the modified gene.

Lenti-D

bluebird is developing the Lenti-D product candidate to treat patients with cerebral adrenoleukodystrophy.

Adrenoleukodystrophy is a rare X-linked, metabolic disorder caused by mutations in the ABCD1 gene, which results in a deficiency in adrenoleukodystrophy protein, or ALDP, and subsequent accumulation of very long-chain fatty acids. Symptoms of CALD usually occur in early childhood and progress rapidly if untreated, leading to severe loss of neurological function and eventual death.

Completed non-interventional retrospective study (the ALD-101 Study)

CALD is a rare disease, and data on the natural history of the disease, as well as the efficacy and safety profile of allogeneic HSCT, is limited in scientific literature. To properly design clinical studies of Lenti-D and interpret the efficacy and safety results thereof, at the recommendation of the FDA, bluebird performed a non-interventional retrospective data collection study to assess the natural course of the disease in CALD patients that were left untreated in comparison with the efficacy and safety data obtained from patients that received allogeneic HSCT.

For this study, data was collected from four US sites and one French site on a total of 137 subjects, 72 of whom were untreated, and 65 were treated with allogeneic HSCT.

Starbeam Study (ALD-102) - Phase II/III clinical study in subjects with CALD

The company is currently conducting a Phase II/III clinical study of Lenti-D product candidate in the US, referred to as the Starbeam Study (ALD-102), to examine the safety and efficacy of Lenti-D product candidate in subjects with CALD. The study was fully enrolled in May 2015; however, in December 2016, the company amended the protocol for this study to enroll up to an additional eight subjects in an effort to enable the first manufacture of Lenti-D product candidate in Europe and the subsequent treatment of subjects in Europe, and to bolster the overall clinical data package for potential future regulatory filings in the US and Europe. It intended to begin treating the additional patients in early 2017.

The ALD-103 (observational) study

bluebird is also conducting the ALD-103 study, an observational study of subjects with CALD treated by allogeneic HSCT. This study is ongoing and is designed to collect efficacy and safety outcomes data in subjects who have undergone allogeneic HSCT over a period that is contemporary with the Starbeam study.

Lentiglobin Product

Transfusion-dependent -thalassemia (TDT)

-thalassemia is a rare hereditary blood disorder caused by a mutation in the -globin gene, resulting in the production of defective red blood cells, or RBCs. Genetic mutations cause the absence or reduced production of beta chains of hemoglobin, or -globin, preventing the proper formation of hemoglobin A, which normally accounts for more than 95% of the hemoglobin in the blood of adults.

Limitations of current treatment options

In geographies where treatment is available, patients with TDT receive chronic blood transfusion regimens. These regimens consist of regular infusions with units of packed RBC, or pRBC, usually every three to five weeks, to maintain hemoglobin levels and control symptoms of the disease.

The only potentially curative therapy for -thalassemia today is allogeneic HSCT. However, complications of allogeneic HSCT include risk of engraftment failure in unrelated human-leukocyte-antigen, or HLA, matched patients, risk of life-threatening infection, and risk of GVHD - a common complication in which donor immune cells (white blood cells in the graft) recognize the cells of the recipient (the host) as foreign and attack them. As a result of these challenges, allogeneic HSCT can lead to significantly high mortality rates, particularly in patients treated with cells from a donor who is not a matched sibling and in older patients. Overall, TDT remains a devastating disease with an unmet medical need.

The Northstar Study (HGB-204) Phase I/II clinical study in subjects with TDT

The Northstar study is a single-dose, open-label, non-randomized, multi-site Phase I/II clinical study in the US, Australia, and Thailand to evaluate the safety and efficacy of the LentiGlobin product candidate in increasing hemoglobin production and eliminating or reducing transfusion dependence following treatment. In March 2014, the first subject with TDT was treated in this study, and, in May 2016, the study was fully enrolled.

The study enrolled 18 adults and adolescents. To be eligible for enrollment, subjects had to be between 12 and 35 years of age, with a diagnosis of TDT, and received at least 100 mL/kg/year of pRBCs or more than or equal to eight transfusions of pRBCs per year in each of the two years preceding enrollment.

Efficacy will be evaluated primarily by the production of 2.0 g/dL of hemoglobin A containing A-T87Q-globin for the six-month period between 18 and 24 months, post transplants. Exploratory efficacy endpoints include RBC transfusion requirements (measured in milliliters per kilogram) per month and per year, post transplants.

The HGB-205 study Phase I/II clinical study in subjects with TDT or with severe SCD

bluebird is conducting the HGB-205 study, a Phase I/II clinical study, in France to study the safety and efficacy of its LentiGlobin product candidate in the treatment of subjects with TDT and of subjects with severe SCD. In December 2013, the company said that the first subject with TDT had been treated in this study; in October 2014, bluebird declared that the first subject with severe SCD had been treated in this study. By February 2017, the study had been fully enrolled.

bluebird is conducting HGB-206 multi-site Phase I clinical study in the US to evaluate the safety and efficacy of its LentiGlobin product candidate for the treatment of subjects with severe SCD. In October 2016, the company amended the protocol of its HGB-206 study to expand enrollment and incorporate several process changes, including updated drug product manufacturing process. Enrollment had begun under this amended protocol, and in February 2017, the company treated the first subject under this amended protocol.

The Northstar-2 Study (HGB-207) Phase III study in subjects with TDT and a non-0/0 genotype

The Northstar-2 study is an ongoing single-dose, open-label, non-randomized, international, multi-site Phase III clinical study to evaluate the safety and efficacy of the LentiGlobin product candidate to treat subjects with TDT and non-0/0 genotype. Approximately 23 subjects will be enrolled in the study, consisting of at least 15 adolescent and adult subjects between 12 and 50 years of age at enrollment and at least eight pediatric subjects less than 12 years of age at enrollment. In December 2016, the first subject had received treatment with the LentiGlobin product candidate.

The planned Northstar-3 Study (HGB-212) Phase III Study for TDT in subjects with TDT and a 0/ 0 genotype

The company plans the initiation of HGB-212, a Phase III clinical study of LentiGlobin in patients with TDT and the 0/0 genotype in 2H FY2017.

bluebird expects to enroll up to 15 adult, adolescent, and pediatric subjects. The company anticipates that the primary endpoint of the Northstar-3 study will be transfusion reduction, which is defined as a demonstration of a reduction in the volume of pRBC transfusion requirements in the post-treatment time period of 12-24 months, compared with the average annual transfusion requirement in the 24 months prior to enrollment.

Sickle Cell Disease

SCD is an inherited disease that is caused by a mutation in the -globin gene; this results in sickle-shaped red blood cells. The disease is characterized by anemia, vaso-occlusive crisis, infections, stroke, overall poor quality of life, and, sometimes, early death. Where adequate medical care is available, common treatments for patients with SCD largely revolves around the management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Given the limitations of these treatments, there is no effective long-term treatment. The only advanced therapy for SCD is allogeneic hematopoietic stem cell transplantation (HSCT). Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, graft-versus-host disease, and opportunistic infections - particularly in patients who undergo non-sibling-matched allogeneic HSCT.

In March 2017, bluebird announced the Publication of the Case Study on the First Patient with Severe Sickle Cell Disease Treated with Gene Therapy in The New England Journal of Medicine. Patient 1204, a male patient with S/S genotype, was enrolled in May 2014 at 13 years of age into the HGB-205 clinical study. The patient underwent a regular transfusion regimen for four years prior to this study. Over 15 months since transplant, no SCD-related clinical events or hospitalizations occurred - contrasting favorably with the period before the patient began regular transfusions. All medications were discontinued, including pain medication.

The successful outcome in Patient 1204 demonstrates the promise of treatment with LentiGlobin gene therapy in patients with severe SCD and serves as a guide to optimize outcomes in future patients.

Celgene Collaboration

In March 2013, BLUE entered into a strategic collaboration with Celgene to advance gene therapy in oncology (cancer), which was amended and restated in June 2015, and amended again in February 2016. The multi-year research and development collaboration focused on applying BLUEs expertise in gene therapy technology to CAR T cell-based therapies, to target and destroy cancer cells. The collaboration now focuses exclusively on anti- B-cell maturation antigen BCMA product candidates for a new three-year term.

Under the terms of the Amended Collaboration Agreement, for up to two product candidates selected for development under the collaboration, BLUE is responsible for conducting and funding all research and development activities performed up through completion of the initial Phase I clinical study of such a product candidate.

In February 2016, Celgene exercised its option to obtain an exclusive worldwide license to develop and commercialize bb2121, the first product candidate under the Amended Collaboration Agreement, and paid the associated ($10 million) option fee. BLUE will share equally in all costs related to developing, commercializing, and manufacturing the product candidate within the US, if it elects to co-develop and co-promote bb2121 with Celgene. In case BLUE does not exercise its option to co-develop and co-promote bb2121, it will receive an additional fee (of $10 million).

Summary

All three names in my May 30, 2017, (45-page) report are from the same space, and I highly recommend taking a look at the entire report before making an investment decision. It is available on request.

This industry is in its infancy - most trials are only in Phase I or Phase II. The companies do not have earnings yet, and that makes them difficult to value today. In my opinion, the upside here is significant, but you may have to hold on to these names for a few years in order to realize that upside, because today an argument can be made that the stocks have gotten a little bit ahead of themselves.

I am keeping my Buy recommendation on Juno (unchanged), and I am keeping my Hold recommendation on Kite (unchanged). There are currently seven institutions (each) with stakes of at least 250 million dollars in BLUE. There are nine institutions (each) with stakes of at least 175 million dollars in KITE. With JUNO, the institutional ownership is much lower - many institutions probably got shaken out following deaths on the Juno trials last year. In my opinion, the market over-reacted to those deaths. In fact, the shares have already bounced significantly since the low from last year following that market over-reaction (and insiders bought $500,000 worth of Juno shares recently).

I went in and out of KITE twice in the last couple of years and locked in gains of 35% both times. I most recently exited KITE at $87 a share on March 13.

The 52-week high on BLUE is $124, and the all-time high is $194.

There are 8,000,000 shares short, and that is more than 10X the average daily volume.

My recommendation is to allocate 3% portfolio weight to this industry: 1.5% to BLUE, 0.75% to KITE, and 0.75% to JUNO.

I remember an analyst (many years ago) on CNBC defending his Sell recommendation on Amazon (NASDAQ:AMZN). It was trading at $100/share at the time. He defended the Sell rating by saying it loses money on every book it sells. AMZN recently hit $1,000 today. The lesson here is do not be afraid to invest in names with multi-billion market caps that are without EPS today. With KITE, BLUE, and JUNO, you must look out 3-5 years.

Sources

Why bluebird bio Stock Surged 20.7% Higher in January

Risks - Mayo Clinic

bluebird bio Reports First Quarter 2017 Financial Results and Recent Operational Progress

bluebird bio Announces Publication of Case Study on First Patient with Severe Sickle Cell Disease Treated with Gene Therapy in The New England Journal of Medicine

Annual Report 10-K

Quarterly Report 10-Q

Press Release | Investor Relations | Bluebird Bio

Kite Pharma Posts Q1 Loss, Reveals CAR-T Patient Death

SHAREHOLDER ALERT: Bronstein, Gewirtz & Grossman, LLC Announces Investigation of Kite Pharma, Inc. (KITE)

KITE INVESTOR ALERT: Faruqi & Faruqi, LLP Encourages Investors Who Suffered Losses Exceeding $100,000 Investing In Kite Pharma, Inc. To Contact The Firm

SHAREHOLDER ALERT: Levi & Korsinsky, LLP Announces the Commencement of an Investigation Involving Possible Securities Fraud Violations by the Board of Directors of Kite Pharma, Inc.

Kite Investors See An Uncomfortable Parallel With Juno

Kite Pharma: History In The Making?

Kite Pharma: Still Time To Get In Ahead Of Lead Oncology Treatment Approval

Here's What's Dragging Kite Pharma Inc. Down Today -- The Motley Fool

Global Gene Therapy Market to Reach US$316 Million by 2015, According to a New Report by Global Industry Analysts, Inc.

Gene Therapy Market information, Current Trends Analysis, Major Players and Forecast 2024

Gene Therapies Market will generate $204m in 2020

Cancer Gene Therapy Market size to exceed $4.3bn by 2024

Could gene therapy become biotech's growth driver in 2017?

Cell Therapy 2016 - Year in Review (part 1)

Cancer Gene Therapy Market Size, Share, Industry Report 2024

Gene Therapy Market information, Current Trends Analysis, Major Players and Forecast 2024

Gene Therapy Clinical Trials Worldwide

Human Gene Therapy (PDF)

Aranca Report - GENE THERAPY: Advanced Treatments for a New Era

International Journal Of Pharma Sciences and Research (IJPSR) - Gene therapy: Current status and future perspectives Gene Therapy Institute for Clinical and Economic Review

Read more here:

Biotech Gene Therapy Names Juno, Kite, And bluebird bio Still Have Room To Run - Seeking Alpha