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Gene Therapy's Big Comeback

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  1. [verwijderd] 26 maart 2014 15:36
    www.forbes.com/sites/matthewherper/20...

    Gene Therapy's Big Comeback
    This story appears in the April 14, 2014 issue of Forbes.
    Comment Now
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    Bluebird Bio’s Nick Leschly (Photo: Jason Grow/Forbes)

    Elliott Sigal earned a reputation at Bristol-Myers Squibb BMY +3.04% as one of the drug industry’s best research chiefs. His bets on risky technologies like cancer immunotherapy and new types of diabetes drugs helped Bristol turn from a laggard into a growth stock. But there was one technology he wouldn’t touch: gene therapy, which tries to use engineered viruses to defeat disease at the DNA level. “I was burned on it myself 20 years ago,” he says. “When they told me gene therapy was back, I couldn’t believe it.”

    So what’s Sigal doing now? As a venture partner at New Enterprise Associates, he just took his first board seat–at a gene therapy company, Philadelphia’s Spark Therapeutics, which raised $50 million last October from the Children’s Hospital of Philadelphia and hopes to launch a treatment for a genetic form of blindness in as little as two years.

    Spark is far from alone. The once abandoned gene therapy field has become a hotbed, with 11 different companies raising at least $618 million from venture capitalists and the public markets since the beginning of 2013, and one more, AGTC, plans a $50 million initial public offering soon. Top venture capital firms are among their backers, and some of the industry’s top talent is being attracted to what was once seen as a lost cause. The iShares Nasdaq Biotechnology Index is up 65% in 12 months.

    “It’s no longer a theory. There’s data showing the real impact on patients that this kind of therapy can have,” says Nick Leschly, the chief executive of Bluebird Bio, a firm in Cambridge, Mass. that’s backed by Third Rock Ventures and ran a $116 million IPO in June.

    Even a few years ago Leschly’s statement would have drawn guffaws. Gene therapy was an obvious idea. If defective genes cause disease, why not replace them? Genetically modified viruses do just that, inserting their DNA into our cells. (This is normally how viruses reproduce.)

    After Francis Collins, now head of the National Institutes of Health, found the gene for the lung disease cystic fibrosis, a decade of work by many groups found the engineered viruses just couldn’t get into the lung.

    A lack of efficacy in gene therapy wasn’t the worst problem. In 1999 Jesse Gelsinger, a teenager with a genetic liver disease, died when the adenovirus carrying a corrective gene made him very, very sick. Investor money dried up.

    But a small group of scientists kept the field alive. One of them was Kathy High of the Children’s Hospital of Philadelphia. She thought gene therapy researchers had been making two mistakes: using a virus that might make the patient very sick (the adenovirus) and not carefully picking the diseases they would treat. “People were choosing targets based on high unmet medical need and the size of the market, not based on the scientific evidence that gene therapy would impact the disease,” she says.

    High decided to use not adenovirus but another, apparently harmless virus, called adeno-associated virus (AAV), which seems to piggyback on adenovirus infections in the wild. The gene therapist’s modified AAV sneaks little pieces of DNA into patients’ cells. That piece of DNA can contain a gene that makes a healthy version of a defective protein in a particular patient.

    To further boost her odds, High focused her early work on eye disease. The inside of the eye, and also, amazingly, the brain, is walled off from the immune system, unlike the lungs or skin. That makes a gene therapy far more likely to work, because existing antibodies won’t treat it as an invader.

    In adults and children who had gone blind because of a bad version of a gene called RPE65, High’s approach yielded amazing results. In one trial 12 patients, 5 of them kids, had dramatic improvements in their sight. The children were able to move from Braille classrooms to sighted ones. A late-stage study that could result in the treatment’s ?approval is ongoing.

    zie vervolg...
  2. [verwijderd] 26 maart 2014 15:36
    vervolg;

    Bluebird has another rare disease in its near-term sights: adrenoleukodystrophy, better known as the disease featured in the movie Lorenzo’s Oil . In the disorder a malfunction of the gates that transport fats into and out of cells causes buildups of fatty acids throughout the body, including in the brain. Instead of injecting the virus into the body, in Bluebird’s approach cells (in this case, bone marrow stem cells) are removed and treated with another virus, lentivirus. Unlike AAV, lentivirus inserts the genes permanently into the cell’s DNA-containing chromosomes. These stem cells are reinjected; Bluebird is running a phase III trial in 15 patients and aims to get its treatment on the market in the next several years.

    These treatments won’t be cheap. The first gene therapy ever to clear a regulator was approved in Europe in 2012 by the Nasdaq-listed firm uniQure. Reports pegged the price at $1 million; CEO Joern Aldag disputes that any price has yet been set. The treatment is not yet on the market. But that kind of pricing power–beyond even the norm of $300,000 per patient per year and up for rare-disease drugs–is enticing more and more companies to enter the field.

    One of the hottest areas is already one of the biggest markets for expensive biotech drugs: hemophilia A and B, the genetic diseases that cause the blood not to clot properly, potentially leading patients to bleed to death.

    “Gene therapy for hemophilia A possibly could be our biggest product,” says Jean-Jacques Bienaime, chief executive of rare-disease specialist Biomarin, which forecasts revenue of at least $650 million this year.

    Bienaime says his company estimates there are 50,000 type A hemophiliacs in territories where it markets drugs and who are receiving hemophilia medicine; that would be his addressable market. A company called Dimension Therapeutics is competing with Biomarin; Spark, Dimension and hemophilia expert Baxter International BAX +1.55% are chasing hemophilia B.

    The promise of the technology has some venture capitalists pushing far beyond rare genetic diseases. San Diego’s Celladon, which raised $51 million in an IPO earlier this year, is aiming to treat heart diseases like advanced heart failure, in which the heart muscle becomes too weak to function.

    Mark Levin, the former chief executive of Millennium Pharmaceuticals and founder of Third Rock Ventures, is now serving as interim chief executive of a company named Voyager Therapeutics, which aims to treat Parkinson’s disease. Patients now get a drug to raise dopamine levels, but it eventually stops working; Voyager’s gene therapy would cause the brain itself to produce more dopamine.

    “It is really exciting to see how rapidly science and medicine are changing to make a big difference for patients,” Levin says.

    The viruses used in gene therapy have also joined the war on cancer. Novartis NVS -0.02%, Bluebird and Juno Therapeutics, which raised $120 million in venture capital last year, are all working on cells genetically engineered to hunt down tumors. Early results in blood cancer show dramatic reductions in the number of cancer cells in patients who had few other options.

    And biotech researchers are dreaming of doing far more. Even viruses like lentivirus, which write DNA directly into a cell’s chromosome, can make only limited additions to the patient’s genes. They’re like adding an ingredient to life’s recipe book. But what if you need to change the recipe?

    Recently, researchers have been working with a series of proteins, originally found in the immune systems of bacteria, that allow them to cut DNA in specific places and splice it back together. This technology, called CRISPR/Cas9, might be deliverable to cells using gene therapy. Editas Medicine was launched in November with $43 million in capital by Flagship Ventures, Polaris Partners and Third Rock to turn that dream into a reality.

    Still, laboratory success doesn’t ensure financial success. “We may be taking a really simplistic view that if you’re able to come close to treating grievous illness, the pricing and getting paid and developing a valid business model will take care of itself,” says Kevin Bitterman of Polaris, who is serving as Editas’ interim president. “The goal very simply is to leverage this technology to develop a new class of therapeutics against genetic disorders.” Eager investors, take note.
  3. [verwijderd] 31 maart 2014 15:49
    Dank dank Ivet. Ook hier zie je weer dat er een bias is richting USA onderzoek. Gkybera/uniQure was dec eerste en wordt wel genoemd, maar hun pijplijn niet. En vooral de USa initatieven krijgen de aandacht. Daarin zit ook Hemofilie B en de gen-casette die is gebruikt was van uniQure. Maar goed de wereld is transparant & rechtvaardig dus ooit krijgt uniQure de credits! Het enige war ze voor moeten oppassen is da ze niet in IP sfeer iets over het hoofd (hebben) gezien...
  4. [verwijderd] 31 maart 2014 15:57
    Overigens heeft BiogenIdec net registratie verkregen voor de eersts profylactische behandeling (Alprolix) waarmee wekelijkse infusies nodig zijn. Ook daar zie je dat de uniQure propositie een stuk aantrekkelijker is.
  5. harrysnel 24 september 2014 01:20
    "Biogen shoulders into gene therapy amid a second honeymoon for the field

    As researchers and investors toast renewed optimism for a new generation of gene therapies, biotech bellwether Biogen Idec ($BIIB) is deepening its commitment to the space, another sign of life for the resurgent field.

    The Big Biotech has hired Olivier Danos, most recently of Kadmon Pharmaceuticals, to serve as senior vice president in charge of its growing gene therapy operation, a position that reports to R&D chief Douglas Williams. Danos' job is to oversee Biogen's efforts to identify and develop new methods for gene transfer and genomic engineering, ferreting out potential deals across all of the company's therapeutic areas.

    ....

    But while Biogen may have some catching up to do, its history of moving swiftly on its key interests suggests a serious commitment to come. And though the company isn't disclosing any near-term disease targets in its new focus on gene therapy, Biogen's longtime devotion to hemophilia would make that indication a natural starting point. As programs at Dimension and elsewhere have demonstrated, monogenic forms of the rare bleeding disease have the potential to be cured by one-time treatments, and Biogen, which has mounted a multibillion-dollar effort to develop new therapies for hemophilia, has the expertise to scale up quickly.

    And analysts say the move may be a prelude to a deal. As Piper Jaffray's Joshua Schimmer and Jerry Yang pointed out in a note to investors, as many as 7 gene therapies for hemophilia could enter the clinic by next year, and Biogen's competitors in the space have already snatched up rights to some of the most promising candidates. Getting serious about gene therapy could be Biogen's first step to taking action on an external program, the two write.

    Whatever the result of Biogen's honed focus, Danos, who previously ran the gene therapy arm of University College London, believes the biotech has the right capital, intellectual and monetary, to stage some major advances in the expanding field."
    www.fiercebiotech.com/story/biogen-sh...

    UniQure en University College London:

    "uniQure moved its hemophilia B AAV5 candidate toward the start of a Phase I/II clinical trial, slated to begin late in the second half of 2014. This trial will complement the ongoing trial conducted by uniQure’s partners St. Jude’s Children Research Hospital and University College of London by testing the same transgene in patients at higher doses compared to the partner-sponsored trial..."
    www.uniqure.com/news/201/182/uniQure-...

  6. harrysnel 24 september 2014 16:46
    quote:

    Prof. Dollar schreef op 24 september 2014 11:18:

    Bedankt, Harry! ;-)
    Wat is je eigen duiding van het verhaal in de context van uniQure?
    Als belegger in UniQure vind ik het positief dat Biogen serieus werk gaat maken van gen therapie. Toch een signaal dat ook big farma kansen ziet op dit terrein. Van behandelen naar genezen, het is weliswaar nog toekomstmuziek maar deze nieuwe focus op gen therapie bij Biogen geeft m.i. een positief signaal af. Biogen heeft bovendien al therapieën voor hemofilie A en B op de markt.
    www.biogenidec.com/research_product_p...

    UniQure heeft hemofilie B al gepartnerd met Chiesi. Kijk je naar de pipeline dan zie je dat er bij UniQure 6 preklinische programma's lopen waarvan hemofilie A specifiek genoemd wordt.
    www.uniqure.com/pipeline/clinical-pip...

    In bovenstaande artikel staat:
    "..And analysts say the move may be a prelude to a deal. As Piper Jaffray's Joshua Schimmer and Jerry Yang pointed out in a note to investors, as many as 7 gene therapies for hemophilia could enter the clinic by next year.."

    Als Biogen deal sluit met UniQure voor hemofilie A zou dat natuurlijk zeer positief zijn. Wellicht kent de nieuwe man die bij Biogen leiding gaat geven aan de afdeling gen therapie de mogelijkheden die UniQure biedt goed vanuit zijn tijd bij University College Londen. Dan kan UniQure streepje voor hebben.

    NB: Zeer speculatieve interpretatie/fantasietje mijnerzijds maar je vroeg naar mijn mening:).

    Edit: het past ook bij de strategie van UniQure om de "orphan" indicaties (waar nog geen afdoende middel op de markt is) zelf te doen (Glybera) en juist een partner te zoeken voor de "grote" indicaties waar al producten/concurrenten op de markt zijn.
  7. [verwijderd] 21 januari 2015 00:59

    finance.yahoo.com/news/why-drug-prici...

    Why Drug Pricing Could Bring Volatility To The Biotech Sector This Year
    Benzinga
    By Kyle Dennis 2 hours ago

    ?
    ?
    ?
    ?

    Over the last two years, biotechnology companies have been on the forefront of technological breakthroughs. The emergence of gene therapy and personalized medicine have begun to show that many drugs have the potential to be curative instead of therapeutic.

    Bringing a drug through all the stages of clinical trials is not only extremely expensive, but not probable. However, if a drug does make it to the market, it has the potential to be incredibly profitable.

    This dynamic has made drug pricing very important to investors.

    There was much debate over Gilead Sciences, Inc. (NASDAQ: GILD)'s pricing of its HCV drug Sovaldi, which costs about $1,000 per pill. Without any competition, Gilead had the most successful drug launch in history.

    Related Link: 10 Biotech Stories You Might've Missed Last Week

    Another example is Uniqure NV (NASDAQ: QURE), which set its price tag at $1.4 million for its gene therapy treatment Glybera.
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    Growing competition, pricing push back from payers like Express Scripts Holding Company (NASDAQ: ESRX), or new regulatory measures could be something to watch. A change in this pricing dynamic could quickly cause a revaluation of biotech stocks.

    Bluebird bio Inc (NASDAQ: BLUE) CEO Nick Leschly spoke at the J.P. Morgan Healthcare Conference about the pricing issues. Given Bluebird has the potential to produce curative therapies, pricing could be set quite high, as well.

    For curative therapies, Leschly proposed the best solution could be a "pay for performance" structure.

    For now, drug pricing and biotech valuations remain high, but this will be a topic to keep an eye on as Johnson & Johnson (NYSE: JNJ), Bristol-Myers Squibb (NYSE: BMY), Pfizer (NYSE: PFE), AbbVie (NYSE: ABBV), and Eli Lilly (NYSE: LLY) give guidance over the next month.

  8. [verwijderd] 16 maart 2015 19:35
    het enige bedrijf op de Nasdaq dat een gentherapy-produkt op de markt heeft naast diens pijplijn lijkt te worden afgeserveerd!

    Het enige westerse bedrijf dat bewijs heeft geleverd, na plm 40 jaar R&D, dat gentherapy mogelijk is wordt gewaardeerd als een outsider in het miljardencircus!

    Zelfs PRQR doet het beter (gemeten aan marktcap), wat m.i. vnl getuigd van je PR goed aanwenden (en dat is meer dan persberichten alleen).
  9. Prof. Dollar 16 maart 2015 19:48
    Geduld is een schone zaak.

    Eind deze maand kan uniQure met de kwartaalcijfers (Q4/2014) komen. De cijfers zullen niet rooskleurig zijn; andere bedrijven hebben meer in kas.

    MAAR... er ligt op datzelfde moment veel in het verschiet: uitgifte nieuwe stukken (kasgeld), (bevestiging) uitrol Glybera, nieuwe markttoetreding Glybera (bijvoorbeeld UK), partnership Congestive Heart Failure (zal ook geld opleveren). Afijn, je kent het rijtje.

    En wellicht heeft QURE nog wat positief verrassends in petto.
  10. [verwijderd] 16 maart 2015 20:07
    mijn angst (als belegger) is dat bij deze lage waardering t.o.v. peers, UniQure de power mist om zelfstandig te blijven. Hoewel het fantastisch is als QURE vele mensen kan helpen met diens technologie, worden in de branche zelf doorgaans keiharde zakelijke gevechten gevoerd (buiten de belangen van de patienten zelf om).

    Op de beurs draait het niet om wetenschappelijke kansen of feiten, maar veelal gewoon om geld en marketing. Een mindere branchegenoot (qua kansen en technologie) kan QURE zomaar inlijven als het op beurswaardering aankomt. Ik kan alleen maar hopen dat het MT zich daar voldoende van bewust is (dat is echt niet elk branchegenoot gegeven).

    Ik vind het jammer dat UniQure de markt zo weinig voorziet van informatie en dat we dat zelf in de krochten van het internet moeten vinden. Beleggers kunnen dat ervaren als gemis aan transparantie.

    Vele peers stuiven QURE ver vooruit qua marktcap en dat is m.i. geen goed teken voor hoe je als beursgenoteerde onderneming in de markt ligt bij beleggers!
  11. [verwijderd] 16 maart 2015 21:05
    en aan het slot weer de gebruikelijke reset...altijd even tikkie terug.

    Ik mag hangen als die koers niet zwaar gemanipuleerd wordt! Niks geen normale vraag en aanbod mechanismen en/of vrije markt. Hier wordt 100% gespeeld.
  12. QLVT 16 maart 2015 21:25
    Bij de Nasdaq staat nu $26,97 om twee over negen ,dat zou mooi zijn maar denk niet dat het er morgen nog staat {QURE 1,73 +6,81%}
  13. [verwijderd] 16 maart 2015 21:29
    ik herken dit spelletje zo duidelijk vanuit de Crucell-tijd...we weten waar dat op uitliep.
    Aan het slot ff 40 cent teruggezet. (er staat een high van 25,90$ dus mogelijk 50 $cent)

    After hours 'vuurwerk' (met 546 stukjes 6,2% hoger...):

    uniQure N.V. (QURE)
    -NasdaqGS
    Watchlist
    25.40 Up 0.15(0.59%) 4:00PM EDT
    After Hours : 26.97 Up 1.57 (6.18%) 4:15PM EDT - Nasdaq Real Time Price

    Mar. 16, 2015 Market Close: $ 25.40
    Pre-Market Charts | After Hours Charts
    View most recent trades for the selected time period:
    After Hours Volume: After Hours High: After Hours Low:
    2,515 $ 26.97
    (16:02:04 PM) $ 25.40
    (16:01:21 PM)

    Trade Detail
    Most Active in the After-Hours
    After Hours Time (ET) After Hours Price After Hours Share Volume
    16:02 $ 26.97 High 546
    16:01 $ 25.40 Low 74
    16:01 $ 25.40 Low 100
    16:01 $ 25.40 Low 100
    16:01 $ 25.40 Low 100
    16:01 $ 25.40 Low 100
    16:01 $ 25.40 Low 100
    16:01 $ 25.40 Low 100
    16:00 $ 25.40 1,220
    16:00 $ 25.82 3
    16:00 $ 25.82 72

    Read more: www.nasdaq.com/symbol/qure/after-hour...
  14. [verwijderd] 16 maart 2015 22:44
    Beste Forumleden,
    Deel de zorg over onderwaardering en wil daar ook wel wat aan proberen te doen. Voor 1 ding ben ik echter niet zo bang en dat is dat QURE voor een appel en een ei wordt overgenomen. Daavoor is het belang van Gilde etc. te groot. Zonder hun medewerking krijg je QURE niet gekocht toch?
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