ProQR Therapeutics NV NL0010872495

Analisten , rapporten etc

1. NielsjeB 30 maart 2018 15:48

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   PlayBall10 schreef op 1 maart 2018 09:35:

   Leerink: 4Q Recap: All Eyes Set on Pompe/Fabry Updates in 2Q/3Q; PT to $22 / Outperform
   

   Thanks voor de rapporten. Deze gaat over Amicus, was het rapport van Leerink een update? Meen me te herinneren dat ze pas al een rapport uitbrachten.
2. PlayBall10 30 maart 2018 16:49

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   Helaas. Het laatste wat ik van Leerink heb is van 14 februari.
3. nmgn 1 april 2018 21:29

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   quote:

   PlayBall10 schreef op 30 maart 2018 15:40:

   ir.proqr.com/static-files/6a5fbdf0-1f...
   
   ProQR's Annual Magazine 2017
   
   We started ProQR Therapeutics five years ago to find a treatment for cystic fibrosis. Since then we have made great strides and we are now using our innovative RNA approach to develop treatments for rare genetic diseases including cystic fibrosis, debilitating skin diseases and genetic blindness disorders.
   
   In this Annual Magazine we highlight our quest to impact the lives of patients and their loved ones. Patients like Beatrice and her family who we interviewed on their struggle with the blinding disease Leber’s congenital amaurosis.
   You will also meet some key ProQRians;
   Dr. Peter Adamson (Senior Vice President Ophthalmology) and his hope that QR-110 will show restored vision in Leber’s congenital amaurosis patients in an ongoing clinical trial.
   Bart Klein (Senior Vice President Technology Development) on the promise of the novel RNA editing technology that was discovered at ProQRbullosa.
   The newest member of our Scientific Advisory Board Dr. Ted Dryja (professor of ophthalmology and former Head of Research at Novartis) talks about his motivation to stop or reverse genetic eye diseases.
   
   This year’s magazine is dedicated to our dear friend and co-founder, Henri Termeer, who unexpectedly passed away last year. His passion for patients with rare genetic diseases continues to inspire us as we progress on the path he helped us to define.
   
   Read our Annual Magazine 2017
   If you are interested in reading our complete Annual Report 2017, please follow this link. ( ir.proqr.com/static-files/6a5fbdf0-1f... )
   
   Yours sincerely,
   
   Daniel de Boer
   Chief Executive Officer at ProQR
   
   
   ProQR Therapeutics
   t: +31 88 166 7000
   e: info@proqr.com | w: www.proqr.com
   Zernikedreef 9, 2333 CK Leiden, the Netherlands
   
   

   Ze doen nogal uitspraken over de axiomer technologie zeg.....
4. Tom3 2 april 2018 11:01

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   Het jaaroverzicht (zoals hier gepubliceerd door Frenky-Tornado) vond ik ook nog op Seeking Alpha:
   
   seekingalpha.com/pr/17087161-proqr-an...
   
   Het is dus niet zo dat men niet aan de weg timmert, alleen nu moet men nog aantonen dat er geld verdiend kan worden. Zo`n deal over de verdere ontwikkeling van het CF medicijn met een partner zou het fonds op korte termijn vleugels kunnen geven. Maar tja, hoe realistisch is dat?
5. Tom3 2 april 2018 23:56

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   Slechte dag in de VS met veel omzet en een 4% daling. Vertex lijkt me niet een natuurlijke kandidaat om een CF deal te sluiten met PRoQR omdat ze al een deal hebben met Moderna. Omdat men hierover sedert 2016 muisstil is geweest, weten we natuurlijk niet of Moderna`s aanpak werkt, zo niet dan komt PRoQR natuurlijk weer in beeld. Beetje vreemd natuurlijk van PRoQR om een deskundige van Vertex in te huren, dubbelspion?
   
   pharmaphorum.com/news/vertex-help-90-...
   
   www.investopedia.com/news/12-growth-s...
   
   
6. [verwijderd] 3 april 2018 13:51

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   ProQR to Present at Two Upcoming Conferences
   
   ir.proqr.com/news-releases/news-relea...
7. [verwijderd] 25 juni 2018 11:51

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   lifesci.bluematrix.com/sellside/Email...
   
   Page 1
   § Key Considerations for the Potential of ProQR’s QR-110 Program—Which We View Favorably.
   Some key questions that should be asked in assessing the potential of ProQR’s QR-110 program for LCA10
   (and frankly, many gene therapies) are as follows: 1) how is the target gene ultimately related to disease?, 2)
   is the therapy reaching the target tissue and is dosing sufficient?, 3) is protein expression achieving therapeutic
   thresholds?, 4) is the protein functional and fulfilling its endogenous role?, and 5) will this ultimately translate
   into functional improvements? While answering each question with certainty isn’t possible, we’ve become
   quite comfortable with the answers we’re seeing from the existing preclinical data with QR-110. Our answers
   are as follows:
   1) How is CEP290 ultimately related to LCA10? LCA10 is caused by the absence of functional
   CEP290 protein—most commonly due to the p.Cys998X mutation in the CEP290 gene, which creates
   a cryptic splice site on intron 26 of the pre-mRNA that ultimately causes abnormal splicing and
   inclusion of an mRNA segment encoding a premature termination codon. The end product is
   truncated, non-functional CEP290 protein product or degradation of mRNA prior to translation. This
   is problematic due to the role of CEP290 in the formation and stabilization of cilia within
   photoreceptor cells (rods and cones, responsible for phototransduction), as cilia connect the inner and
   outer segments of photoreceptors to facilitate the phototransduction cascade. Thus, we’re comfortable
   with CEP290 as an appropriate target for LCA10, and view ciliary function as a critical component to
   consider for improved functional outcomes.
   2) Is QR-110 reaching the target tissue and is dosing sufficient? Given that one of the constant
   hurdles surrounding the use of RNA oligonucleotide therapies is penetrating the appropriate
   tissue/cell type, we appreciate ProQR’s approach that focuses on local delivery. In the case of QR110,
   the drug is introduced via intravitreal injection, which provides high drug concentrations
   surrounding the retinal tissue locally. These injections are commonly performed by ophthalmologists
   with therapies like Roche’s (Swiss: ROG.VX) Lucentis (ranibizumab) for wet age-related macular
   degeneration. Furthermore, ProQR has validated uptake of QR-110 by photoreceptor cells using optic
   cups and in animal models. Optic cups are a useful surrogate considering this model uses fibroblasts
   from LCA10 patients, which are subsequently re-programmed into induced-pluripotent stem cells and
   differentiated into human retinal tissue. For dosing, the Company extrapolated from the effective drug
   concentrations in the medium of the optic cups to the therapeutic amount required in the vitreous,
   along with pharmacokinetic data from non-human primates and rabbits to inform dosing frequency.
   3) Is CEP290 expression achieving therapeutic thresholds? In the case of LCA10, the therapeutic
   threshold for CEP290 protein expression is thought to be ~50%, which makes sense given that
   individuals who are heterozygous carriers of a mutated allele are not affected by disease. In a preclinical
   model using homozygous p.Cys998X mutated fibroblasts, cells treated with 25nM QR-110 show
   CEP290 protein expression that is in-line with a normal control line (~100%), while levels achieved
   in compound heterozygous fibroblasts are also therapeutic (>50%). The discrepancy is due to the fact
   that compound heterozygous cells have two disease alleles, only one of which contains the targeted
   p.Cys998X mutation. These data give us optimism as to the potential for QR-110 treatment to drive
   a therapeutic benefit in CEP290 protein expression.
   4) Will increases in CEP290 protein translate into functional improvements? In the case of LCA10,
   while production of functional CEP290 protein is important, it is also critically important that these
   changes translate into enhanced formation and stabilization of cilia. The Company assessed this metric
   in the optic cup model using the homozygous p.Cys998X mutated cell line, and results were favorable,
   showing statistically significant increases in the proportion of ciliated cells and the length of cilia.
   June 22, 2018
   
   zie link voor hele rapport!
8. [verwijderd] 2 juli 2018 16:53

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   ProQR Therapeutics N.V.
   
   PRQR: Price: $7.30; Market Cap (M): $233
   Rating: Buy; Price Target: $20.00
   
   Andrew S. Fein
   
   Li Wang Watsek
   
   Corporate Refocus May Begin Yielding Catalysts; Reit Buy and $20 PT
   
   
   
   Skin and ophthalmic disease focus should begin to yield catalysts. With last week’s announcement of initiation of the WINGS study, a Phase 1/2 trial of QR-313 in recessive dystrophic epidermolysis bullosa (DEB), PRQR continues to transition itself into a RNA repair company focusing on rare disease, rather than a cystic fibrosis (CF) company that utilizes a novel RNA technology. As we alluded to in our previous note (March 1, 2018) the shift towards DEB, Leber’s congenital amaurosis 10 (LCA 10) and Usher syndrome 2A (USH2), in our opinion, allows PRQR to maximize its technology while targeting diseases in which it can: (1) more readily reach the target tissue; and (2) be able to directly measure if the target protein has achieved sufficient expression levels to yield a functional outcome. We believe that with the interim data readouts for both DEB and LCA 10, as well as initiation of a clinical trial in USH2 all planned for 2H18, PRQR is poised to validate its RNA technology and we reiterate our Buy rating and, using an updated valuation methodology, arrive at a $20 PT.
   
   WINGS trial is the first in human topical gene-therapy approach for “butterfly wings.” DEB is a dermatological condition caused by mutations in the COL7A1 gene encoding for type VII collagen (C7) protein which is responsible for anchoring the layers of skin together. Mutations in COL7A1 result in blistering and areas of missing skin from simple every-day friction of the skin surface. Affected patients are often referred to as Butterfly Children, because their skin is as fragile as a Butterfly’s wings, thus the aptly named trial name, WINGS. QR-313 is an antisense RNA oligonucleotide, formulated in a topical solution that functions via exon-skipping and is specifically designed to treat cases of DEB caused by a mutation in exon 73 of the COL7A1 gene. Preclinical studies with QR-313 demonstrated high degrees of exon-skipping in both fibroblast cell lines as well as human skin equivalent models. In both cases, QR-313 generated a greater than 70% efficiency of exon-skipping and collagen expression was detected in 70-100% of dermis or epidermis samples tested. We view the preliminary data as particularly strong and also note that although other ex vivo gene therapy approaches are being developed, this approach using a topical carbomer-based hydrogel which should provide several advantages including: (1) consistency with current treatment protocols; (2) a non-invasive approach; and (3) rapid therapeutic intervention, with no need to remove biopsies for treatment. We are not alone in our opinion of QR-313 as earlier this month (June 12, 2018) PRQR received an award of up to $5 million in co-funding through partnerships with the non-for profit organizations, EB Research Partnership (EBRP) and EB Medical Research Foundation (EBMRF), which we view as a vote of confidence on QR-313’s prospect. Briefly, these foundations will match funding generated by PRQR up to $5M. In our opinion, perhaps even more relevant than the financial support is the validation that these foundations provide to the PRQR platform. Note that earlier this year (Feb 2018) the Foundation Fighting Blindness also entered into a similar partnership to develop QR-421a for USH2, with a milestone-based co-funding of up to $7.5 M.
   
   Although this is a small MAD trial, we expect WINGS to provide significant insight into both safety and tolerability, as well as preliminary proof of concept. The WINGS trial is a randomized, double-blind, placebo-controlled Phase 1/2 trial investigating the safety and efficacy of QR-313 in recessive DEB (exon 73 mutations) patients. Per its protocol, the study consists of 2 cohorts. In the first cohort, 8 patients will receive topical QR-313 or placebo, 2 to 3 times a week for 4 weeks, with a follow-up period of 8 weeks after the treatment period. A second cohort of 8 patients will then be studied after the interim analysis of the first cohort, expected 2H18, is completed. Aside from the requisite safety and tolerability evaluations, management proposes to collect skin biopsies and measure the degree of exon skipping and thus production of collagen VII protein mediated by QR-313, which we view as a hard and more objective biomarker for efficacy. Additional secondary endpoints include parameters that we believe may be particularly useful in determining the potential clinical utility of this treatment, namely time to wound healing, delay before forming new blisters and skin strength. Although it remains unclear, precisely how much collagen VII will be required to make the patients asymptomatic, we are encouraged by the preliminary data that generated a large number of cells expressing collagen VII after treatment with QR-313. We believe positive responses in these endpoints could be strong candidates for PRQR to propose in future discussions with the regulators in the design of possible registrational trials. According to management, the proof of mechanism (exon skipping) will be available in 2H18 with preliminary proof of concept and wound healing data available in 2019.
   
   Continue to await data from ophthalmic programs in 2H18 as well. Per management, Interim data from the open-label Phase 1/2 for QR-110 in LCA10 remains on tap to have a 6-month interim readout before year-end. As a reminder, LCA 10 is caused by a point mutation in the CEP290 gene that results in production of a non-functional CEP290 protein and loss of photo transduction in both rods and cone cells. QR-110 is an RNA oligonucleotide designed to target the mutation and restore normal message and therefore CEP290 protein. Additionally, a third Phase 1/2 trial for QR-421a in USH2 is scheduled to begin in 2H18. Mutations in the USH2A gene coding for the Usher protein are known to result in a loss of functional protein. QR-421a is targeting mutations within exon 13 of USH2 that cause this disorder and preclinical data have thus far shown complete exon skipping that generates a smaller yet functional USH2 message.
   
   (...)
   
   
9. [verwijderd] 2 juli 2018 16:54

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   (vervolg...)
   
   Market models and revenue assumptions. We have updated our model to reflect the recent reprioritization of ProQR’s pipeline. We have added value to the following three programs: QR-110 in LCA10, QR-313 in DEB-exon73 and QR-421a in Usher syndrome-exon13. Meanwhile, we project the commercial launch of QR-010 in cystic fibrosis to be delayed to 2023 with a reduced probability of success to 15%.
   
   We model for US and EU commercial launch of QR-110 in LCA10 in 2023 with a probability of success of 30%, which is based on the historical success rate of a Phase 1/2 trial (~20%) and our favorable view of the program. We project 2,277 LCA10 cases in 2023, based on an estimated existing case of 2,000 in the beginning of 2018, an occurrence of LCA at 2.5 per 100,000 people, an estimated percentage of LCA10 among all LCA at 20%, an estimated number of newborns at 9,000,000 (US + EU) and 0.7% population growth rate. Our estimated annual cost of QR-110 of $200,000 is derived from the average price of orphan drugs for diseases in <10,000 patients ($150,000~$250,000), while considering the Luxturna’s (Spark, ONCE; not rated) price ($850,000, one-time treatment). We model for a peak penetration of 70% considering the lack of alternative therapies for this patient population.
   
   We model for US and EU commercial launch of QR-313 in DEB-exon73 in 2023 with a probability of success of 30%, which is based on the historical success rate of a Phase 1/2 trial (~20%) and our favorable view of the program. We project 2,288 cases of DEB-exon73 in 2023, based on an estimated existing case of 2,000 in the beginning of 2018, an occurrence of DEB at 0.7 per 100,000 people, an estimated percentage of DEB-exon73 among all DEB at 80%, an estimated number of newborns at 9,000,000 (US + EU) and 0.7% population growth rate. Our estimated annual cost of QR-313 of $200,000 is derived from the average price of orphan drugs for diseases in <10,000 patients ($150,000~$250,000). We model for a peak penetration of 40% considering potential competitive drugs.
   
   We model for US and EU commercial launch of QR-421a in Usher syndrome-exon13 in 2024 with a probability of success of 30%, which is based on the historical success rate of a Phase 1/2 trial (~20%) and our favorable view of the program. We project 17,512 cases of DEB-exon73 in 2024, based on an estimated existing case of 16,000 in the beginning of 2018, an occurrence of DEB at 3.3 per 100,000 people, an estimated percentage of exon13-related Usher syndrome of 70%, an estimated number of newborns at 9,000,000 (US + EU) and 0.7% population growth rate. Our estimated annual cost of QR-421a of $100,000 is derived from the average price of orphan drug for diseases in >10,000 patients ($50,000~$150,000). We model for a peak penetration of 70% for lack of alternative therapies for this population.
   
   Valuation and risks to achievement of target price. Our price target of $20/share is based on an equally-weighted composite of: (a) $20.8/share, as a 25x multiple of taxed and diluted FY28 EPS of $11.5 discounted back to FY18 at 30% (in line with the expected PE multiple and discount rate of an early development-stage biotechnology company); and (b) an NPV of $18.8/share (discounted cash flow analysis using a 20% discount rate and 2.0% growth rate, in line with the expected discount and growth parameters of an early development-stage biotechnology company). Risks to our investment thesis and target price include: (1) failure in clinical studies; (2) failure to secure regulatory approval; and (3) smaller than anticipated commercial opportunity due to market size, competition, and pricing.
   
   Andrew S. Fein
   212-356-0546
   afein@hcwresearch.com
   
   Li Wang Watsek
   212-356-0513
   lwatsek@hcwresearch.com
10. [verwijderd] 9 augustus 2018 16:59

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    ProQR Therapeutics N.V. (PRQR)
    Rating: Buy
    Andrew S. Fein
    212-356-0546
    afein@hcwresearch.com
    Li Wang Watsek
    212-356-0513
    lwatsek@hcwresearch.com
    Alicia Yin, Ph.D.
    646-975-6983
    ayin@hcwresearch.com
    2Q18 Update
    Stock Data 08/08/2018
    Price $7.45
    Exchange NASDAQ
    Price Target $20.00
    52-Week High $7.50
    52-Week Low $2.75
    Enterprise Value (M) $199.8
    Market Cap (M) $238
    Public Market Float (M) 15.5
    Shares Outstanding (M) 31.9
    3 Month Avg Volume 90,391
    Short Interest (M) 0.13
    Balance Sheet Metrics
    Cash (M) $38.2
    Total Debt (M) $0.0
    Total Cash/Share $1.20
    EPS Diluted
    Full Year - Dec 2017A 2018E 2019E
    1Q (0.50) (0.34)A --
    2Q (0.54) (0.27)A --
    3Q (0.42) (0.39) --
    4Q (0.49) (0.53) --
    FY (1.94) (1.52) (2.15)
    Revenue ($M) Diluted
    Full Year - Dec 2017A 2018E 2019E
    1Q 0.4 0.5A --
    2Q 0.3 1.1A --
    3Q 0.3 0.3 --
    4Q 0.6 0.6 --
    FY 1.7 2.6 2.7
    8
    7
    6
    5
    4
    3
    2
    AUG-17 DEC-17 APR-18 AUG-18
    1.5
    1
    0.5
    0
    Vol. (mil) Price
    Skin and ophthalmic indications remain the focus for PRQR.
    During 2Q18, PRQR initiated a Phase 1/2 trial of QR-313 in recessive
    dystrophic epidermolysis bullosa (DEB), as well as continued enrollment
    in the open-label Phase 1/2 for QR-110 in Leber’s congenital amaurosis
    10 (LCA 10) and evaluated and designed a Phase 1/2 trial in Usher
    syndrome 2A (USH2), expected to initiate in 2H18. We look forward
    to the on-time execution that will lead to interim readouts for both
    the DEB and LCA 10 programs. With respect to the WINGS study
    in DEB, this approach which uses a topical carbomer-based hydrogel
    should provide several advantages including: (1) consistency with
    current treatment protocols; (2) a non-invasive approach; and (3)
    rapid therapeutic intervention, with no need to remove biopsies for
    treatment. Aside from the requisite safety and tolerability evaluations,
    management proposes to collect skin biopsies and measure the degree
    of exon skipping and thus production of collagen VII protein mediated
    by QR-313, which we view as a hard and more objective biomarker
    for efficacy. Additional secondary endpoints include parameters that
    we believe may be particularly useful in determining the potential
    clinical utility of this treatment, namely time to wound healing, delay
    before forming new blisters and skin strength. Although it remains
    unclear, precisely how much collagen VII will be required to make the
    patients asymptomatic, we are encouraged by the preliminary data
    that generated many cells expressing collagen VII after treatment with
    QR-313. Interim proof of mechanism (exon skipping) will be available in
    2H18 and preliminary proof of concept and wound healing data available
    in 2019. LCA 10 is caused by a point mutation in the CEP290 gene
    that results in production of a non-functional CEP290 protein and loss
    of photo transduction in both rods and cone cells. QR-110 is an RNA
    oligonucleotide designed to target the mutation and restore normal
    message and therefore CEP290 protein. With respect to QR-421a in
    USH2 we are still awaiting trial design but have a high degree of
    confidence that Dr. David Rodman will design a trial that will rapidly
    guide the development of this program. We anticipate a productive
    and data-rich 2H18 that will better delineate the PRQR strategy and
    development pathway.
    (continued on next page)
    For definitions and the distribution of analyst ratings, analyst certifications, and other disclosures, please refer to pages 4 - 5 of this report.
    Competitive landscape as PRQR continues development. With respect to DEB, and according to the dystrophic
    epidermolysis bullosa research association, there are several companies aside from PRQR that are developing therapies to
    treat this indication. From our perspective, two of the most competitive products are provided by gene therapy companies and
    both appear to be at a similar state of development as QR-313. The first is a topical gene therapy agent called KB103 being
    developed by Krystal pharmaceuticals (KRYS; not rated). KB103 is a replication-deficient, non-integrating viral vector virus
    modified to make the collagen VII (COL7) protein formulated as a gel and applied topically to wounds and is being evaluated
    in an ongoing Phase 1/2 trial. Secondly, Fibrocell Science (FCSC; Buy; Pantginis) is currently recruiting for a Phase 1/2 trial
    in DEB evaluating the safety of its lead compound, FCX-007. FCX-007 is a is a genetically-modified autologous fibroblast that
    encodes the gene for COL7. The trial will evaluate type VII collagen expression and the presence of anchoring fibrils resulting
    from FCX-007, as well as evidence of wound healing. Spark Therapeutics (ONCE; not rated) developed the first RPE65 gene
    therapy approved by the FDA for treatment of LCA-10 and in our opinion has set the early bar for safety and efficacy in LCA-10.
    With respect to USH2, we note that Editas (EDIT; not rated) is in early preliminary studies examining a construct that generates
    a human Ush2a protein that lacks Exon 13.
    2Q in numbers. The company reported revenues of $0.5M for the quarter. Net loss was $8.6M, or $0.27/share. The company
    ended the quarter with $38.24M in cash and cash equivalents.
    Valuation and risks. Our price target of $20/share is based on an equally-weighted composite of: (a) $21.3/share, as a 25x
    multiple of taxed and diluted FY28 EPS of $11.7 discounted back to FY18 at 30% (in line with the expected PE multiple and
    discount rate of an early development-stage biotechnology company); and (b) an NPV of $21.3/ share (discounted cash flow
    analysis using a 20% discount rate and 2.0% growth rate, in line with the expected discount and growth parameters of an
    early development-stage biotechnology company). Risks to our investment thesis and target price include: (1) failure in clinical
    studies; (2) failure to secure regulatory approval; and (3) smaller than anticipated commercial opportunity due to market size,
    competition, and pricing.
    ProQR Therapeutics N.V. August 9, 2018
    H.C. WAINWRIGHT & CO. EQUITY RESEARCH
11. [verwijderd] 9 augustus 2018 17:07

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    ProQR Therapeutics N.V.
    
    PRQR: Price: $7.45; Market Cap (M): $238
    Rating: Buy; Price Target: $20.00
    
    Andrew S. Fein
    Li Wang Watsek
    Alicia Yin, Ph.D.
    
    2Q18 Update
    
    Skin and ophthalmic indications remain the focus for PRQR. During 2Q18, PRQR initiated a Phase 1/2 trial of QR-313 in recessive dystrophic epidermolysis bullosa (DEB), as well as continued enrollment in the open-label Phase 1/2 for QR-110 in Leber’s congenital amaurosis 10 (LCA 10) and evaluated and designed a Phase 1/2 trial in Usher syndrome 2A (USH2), expected to initiate in 2H18. We look forward to the on-time execution that will lead to interim readouts for both the DEB and LCA 10 programs. With respect to the WINGS study in DEB, this approach which uses a topical carbomer-based hydrogel should provide several advantages including: (1) consistency with current treatment protocols; (2) a non-invasive approach; and (3) rapid therapeutic intervention, with no need to remove biopsies for treatment. Aside from the requisite safety and tolerability evaluations, management proposes to collect skin biopsies and measure the degree of exon skipping and thus production of collagen VII protein mediated by QR-313, which we view as a hard and more objective biomarker for efficacy. Additional secondary endpoints include parameters that we believe may be particularly useful in determining the potential clinical utility of this treatment, namely time to wound healing, delay before forming new blisters and skin strength. Although it remains unclear, precisely how much collagen VII will be required to make the patients asymptomatic, we are encouraged by the preliminary data that generated many cells expressing collagen VII after treatment with QR-313. Interim proof of mechanism (exon skipping) will be available in 2H18 and preliminary proof of concept and wound healing data available in 2019. LCA 10 is caused by a point mutation in the CEP290 gene that results in production of a non-functional CEP290 protein and loss of photo transduction in both rods and cone cells. QR-110 is an RNA oligonucleotide designed to target the mutation and restore normal message and therefore CEP290 protein. With respect to QR-421a in USH2 we are still awaiting trial design but have a high degree of confidence that Dr. David Rodman will design a trial that will rapidly guide the development of this program. We anticipate a productive and data-rich 2H18 that will better delineate the PRQR strategy and development pathway.
    
    Competitive landscape as PRQR continues development. With respect to DEB, and according to the dystrophic epidermolysis bullosa research association, there are several companies aside from PRQR that are developing therapies to treat this indication. From our perspective, two of the most competitive products are provided by gene therapy companies and both appear to be at a similar state of development as QR-313. The first is a topical gene therapy agent called KB103 being developed by Krystal pharmaceuticals (KRYS; not rated). KB103 is a replication-deficient, non-integrating viral vector virus modified to make the collagen VII (COL7) protein formulated as a gel and applied topically to wounds and is being evaluated in an ongoing Phase 1/2 trial. Secondly, Fibrocell Science (FCSC; Buy; Pantginis) is currently recruiting for a Phase 1/2 trial in DEB evaluating the safety of its lead compound, FCX-007. FCX-007 is a is a genetically-modified autologous fibroblast that encodes the gene for COL7. The trial will evaluate type VII collagen expression and the presence of anchoring fibrils resulting from FCX-007, as well as evidence of wound healing. Spark Therapeutics (ONCE; not rated) developed the first RPE65 gene therapy approved by the FDA for treatment of LCA-10 and in our opinion has set the early bar for safety and efficacy in LCA-10. With respect to USH2, we note that Editas (EDIT; not rated) is in early preliminary studies examining a construct that generates a human Ush2a protein that lacks Exon 13.
    
    2Q in numbers. The company reported revenues of $0.5M for the quarter. Net loss was $8.6M, or $0.27/share. The company ended the quarter with $38.24M in cash and cash equivalents.
    
    Valuation and risks. Our price target of $20/share is based on an equally-weighted composite of: (a) $21.3/share, as a 25x multiple of taxed and diluted FY28 EPS of $11.7 discounted back to FY18 at 30% (in line with the expected PE multiple and discount rate of an early development-stage biotechnology company); and (b) an NPV of $21.3/ share (discounted cash flow analysis using a 20% discount rate and 2.0% growth rate, in line with the expected discount and growth parameters of an early development-stage biotechnology company). Risks to our investment thesis and target price include: (1) failure in clinical studies; (2) failure to secure regulatory approval; and (3) smaller than anticipated commercial opportunity due to market size, competition, and pricing.
    
    Andrew S. Fein
    212-356-0546
    afein@hcwresearch.com
12. MZ 12 augustus 2018 15:26

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    Wainwright dus verlaagd van price target 40$ (1 maart 2018) naar 20$?
13. nmgn 13 augustus 2018 18:13

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    in het rapport van 1 maart gaven ze al aan dat bij doorzetten van de strategie de focus op Cf minder zou zijn en er dus een aanpassing van het doel zou komen. in mijn ogen wel terecht. 40 euro is nu niet reëel.
    
14. [verwijderd] 13 augustus 2018 23:42

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    Al die koersdoelen zijn ter vermaak... ik neem ze niet serieus meer na 29 jaar!
    
    Onderbouwing is belangrijker...maar ook dat blijft vaak binnen de lijntjes.
    
    Ik weet koersdoelen die indien de mitsen en maaren zijn gepasseerd tot wel 80-100$ reiken omdat ze niet genoemde targets in het verlengde zien.
    
    Voor vele beleggers lijkt het alsof ProQR met gerommel id marge bezig is, maar m.i. kan de huidige marktcap binnen enkele jaren de omzet zijn...of nog beter: winst hoop ik zelf.
15. [verwijderd] 5 september 2018 10:21

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    ProQR Announces Positive Interim Results from Phase 1/2 Clinical Trial of QR-110 in LCA10 Patients, and Plans to Start a Phase 2/3 Pivotal Trial
    
    QR-110 demonstrated rapid and sustained improvement in vision in the majority of subjects, as measured by visual acuity and mobility course
    QR-110 was well-tolerated with no serious adverse events
    A Phase 2/3 pivotal trial is expected to start in the first half of 2019
    Management to host a conference call today at 8:15 a.m. ET
    LEIDEN, Netherlands & CAMBRIDGE, Mass., Sept. 05, 2018 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq:PRQR), a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, today announced results from a planned interim analysis of its Phase 1/2 trial of QR-110 in patients with Leber’s congenital amaurosis 10 (LCA10) due to the p.Cys998X mutation in the CEP290 gene. LCA10 typically leads to childhood blindness and has no available treatment options. In the trial, QR-110 demonstrated rapid and sustained improvement in vision in patients with LCA10, as measured by visual acuity and the mobility course performance, as well as being well-tolerated with no serious adverse events recorded. Results from this interim analysis were presented earlier today at the Retinal Degeneration 2018 meeting in Killarney, Ireland, by principal investigator Artur Cideciyan, Ph.D., research professor of ophthalmology at the Scheie Eye Institute, University of Pennsylvania.
    
    “The results of this interim analysis are encouraging and met our decision criteria to stop enrollment in this study and progress to a pivotal Phase 2/3 trial,” said David Rodman, M.D., executive vice president of research and development of ProQR. “We observed a clinically meaningful improvement in vision in the treated eye as measured by both mechanistic and potential registration endpoints. Consistent with predictions based on our patient derived optic-cup models, improvement in visual function was observed as early as two months after treatment and was maximal and stable by three months and thereafter. We are very grateful to the study participants, their caregivers, and the investigators and their staff for the support in the development of QR-110 in this trial.”
    Thaddeus P. Dryja, M.D., professor of ophthalmology at Harvard Medical School and Massachusetts Eye and Ear and member of the National Academy of Sciences, commented, “These results are the first human data to evaluate the clinical utility of RNA-based therapeutics in a human photoreceptor disease, particularly one with a severe unmet medical need. While a confirmatory trial will be required to establish the full potential of QR-110 in LCA10, these results suggest that therapeutic oligonucleotides have the potential to be broadly applicable to a wide spectrum of inherited retinal disorders.”
    Based on the emerging findings from the Phase 1/2 trial, the Company agreed with the FDA to submit a protocol to progress to a pivotal Phase 2/3 trial. In light thereof, the originally planned interim analysis at six months treatment was accelerated to the point when eight patients had reached three months of treatment. Given comparable activity was observed in the first two dose levels, the trial did not escalate up to the high dose and trial enrollment has stopped, in anticipation of the start of a Phase 2/3 trial.
    Results from the interim analysis
    
    Efficacy data: Approximately 60% of subjects showed a clinically meaningful response in visual acuity and mobility course endpoints at three months of treatment and there was general concordance across the endpoints. Efficacy signals were observed within two months with maximal benefits seen within two to three months post treatment initiation. A secondary analysis assessing all available data demonstrated that observed effects on efficacy were durable beyond three months.
    
    Visual acuity: In the majority of patients, there was a substantive ov erall improvement in best corrected visual acuity (BCVA) as assessed by the Berkeley Rudimentary Vision Test (BRVT) and the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart. At three months of treatment, the mean improvement (and standard error of mean, SEM) was -0.67 LogMAR (SEM 0.32) with 62.5% of subjects showing an improvement of greater than -0.3 LogMAR from baseline, which is considered clinically meaningful. The mean change in the contralateral eye was 0.02 LogMAR (SEM 0.05).
    
    Mobility course: Effects on visual acuity correlated with effects on mobility. In the majority of patients there was a substantive overall improvement in functional visual performance as assessed using a series of mobility courses at increasing difficulty and multiple light intensities. At three months of treatment, the mean improvement in navigating the mobility course was 2.6 levels (SEM 1.2) with 57.1% of subjects improving by more than 2.0 levels, which is regarded as clinically meaningful. The mean change in the contralateral eye was 1.36 (SEM 1.04).
    
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16. [verwijderd] 5 september 2018 10:23

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    Full field stimulus test (FST): Improvements in visual function were supported by a meaningful increase in the ability to detect flashes of red or blue light as determined by the FST. After three months of treatment mean improvement in red light sensitivity was -0.74 log Cd/m2 (SEM 0.35) and improvement in blue light sensitivity was -0.91 log Cd/m2 (SEM 0.38).
    Ocular Instability (OCI): Additionally, the majority of patients improved on nystagmus (involuntary eye movements in low vision patients), with a mean change of log -0.14 mm (SEM 0.08) in OCI.
    
    Safety: Out of the 10 subjects dosed in the study, one subject has received all four doses and three have received three doses, representing a combined total of more than 1,500 treatment days. So far QR-110 was well tolerated with no serious adverse events related to treatment or procedure. All data and safety monitoring committee (DSMC) reviews were completed with no restrictions on further dose escalation or pediatric dosing.
    Start of Phase 2/3 pivotal “ILLUMINATE” trial
    The Company has agreed with the FDA to submit a protocol to start a Phase 2/3 trial that could serve as the sole registration trial, to be called "ILLUMINATE". The preliminary design for “ILLUMINATE” is a double-blind, controlled, 12-month study. The trial is expected to initially enroll 30-40 patients with LCA10 due to one or two copies of the p.Cys998X mutation and could be adaptively repowered. The primary endpoints in this trial are expected to include the mobility course and visual acuity, among others. The trial is expected to be conducted at centers in North America and select European countries. Pending completing discussions on the design of the study with the FDA in 2018, the trial is expected to start in the first half of 2019. In parallel to the pivotal Phase 2/3 trial, the Company plans to start a trial in patients <6 years old.
    Conference call
    Management will discuss the data during a webcasted conference call today at 8:15 a.m. ET. The live webcast can be accessed here. The dial-in details for the call are +1-877-407-3982 or +1-201-493-6780 (international), conference ID: 13682382.
    An archive of the webcast (available for 30 days) can be accessed here.
    About the PQ-110-001 Phase 1/2 trial
    A total of 12 patients were screened, of which 10 subjects were dosed, have been in the trial for at least one month and are included in the interim analysis. All 10 patients were enrolled in either the 80 µg dose cohort (160 µg loading dose) or 160 µg dose cohort (320 µg loading dose) in the treated eye, with the other eye remaining untreated. Based on the safety profile the DSMC approved further dose escalation if needed. However, given indications of comparable activity in the first two dose groups, the decision was made to defer further dose escalation. Enrollment has been completed and patients in the trial will complete the 12-month treatment and observation period and subsequently will have the option to participate in “INSIGHT”, an open-label extension study including the possibility of receiving treatment in the second eye.
    PQ-110-001 is an open-label trial that has been designed to enroll children (age 6 - 17 years) and adults (= 18 years) who have LCA10 due to one or two copies of the p.Cys998X mutation in the CEP290 gene. Patients are receiving four intravitreal injections of QR-110 into one eye; one injection every three months. The trial is being conducted at three specialized centers with significant expertise in genetic retinal disease: the University of Iowa, Iowa City, Iowa, U.S., the Scheie Eye Institute at the University of Pennsylvania, Philadelphia, U.S., and the Ghent University Hospital, Ghent, Belgium.
    The primary objectives of the PQ-110-001 trial are safety and tolerability. Secondary objectives include pharmacokinetics, as well as restoration/improvement of visual function and retinal structure through ophthalmic endpoints, such as visual acuity (BCVA), mobility course, full field stimulus testing (FST), ocular instability (OCI), optical coherence tomography (OCT), and pupillary light reflex (PLR). Changes in quality of life in the trial subjects are also being evaluated.
    
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17. [verwijderd] 5 september 2018 10:26

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    About QR-110 Full field stimulus test (FST)[/b]: Improvements in visual function were supported by a meaningful increase in the ability to detect flashes of red or blue light as determined by the FST. After three months of treatment mean improvement in red light sensitivity was -0.74 log Cd/m2 (SEM 0.35) and improvement in blue light sensitivity was -0.91 log Cd/m2 (SEM 0.38).
    Ocular Instability (OCI): Additionally, the majority of patients improved on nystagmus (involuntary eye movements in low vision patients), with a mean change of log -0.14 mm (SEM 0.08) in OCI.
    
    Safety: Out of the 10 subjects dosed in the study, one subject has received all four doses and three have received three doses, representing a combined total of more than 1,500 treatment days. So far QR-110 was well tolerated with no serious adverse events related to treatment or procedure. All data and safety monitoring committee (DSMC) reviews were completed with no restrictions on further dose escalation or pediatric dosing.
    Start of Phase 2/3 pivotal “ILLUMINATE” trial
    The Company has agreed with the FDA to submit a protocol to start a Phase 2/3 trial that could serve as the sole registration trial, to be called "ILLUMINATE". The preliminary design for “ILLUMINATE” is a double-blind, controlled, 12-month study. The trial is expected to initially enroll 30-40 patients with LCA10 due to one or two copies of the p.Cys998X mutation and could be adaptively repowered. The primary endpoints in this trial are expected to include the mobility course and visual acuity, among others. The trial is expected to be conducted at centers in North America and select European countries. Pending completing discussions on the design of the study with the FDA in 2018, the trial is expected to start in the first half of 2019. In parallel to the pivotal Phase 2/3 trial, the Company plans to start a trial in patients <6 years old.
    Conference call
    Management will discuss the data during a webcasted conference call today at 8:15 a.m. ET. The live webcast can be accessed here. The dial-in details for the call are +1-877-407-3982 or +1-201-493-6780 (international), conference ID: 13682382.
    An archive of the webcast (available for 30 days) can be accessed here.
    About the PQ-110-001 Phase 1/2 trial
    A total of 12 patients were screened, of which 10 subjects were dosed, have been in the trial for at least one month and are included in the interim analysis. All 10 patients were enrolled in either the 80 µg dose cohort (160 µg loading dose) or 160 µg dose cohort (320 µg loading dose) in the treated eye, with the other eye remaining untreated. Based on the safety profile the DSMC approved further dose escalation if needed. However, given indications of comparable activity in the first two dose groups, the decision was made to defer further dose escalation. Enrollment has been completed and patients in the trial will complete the 12-month treatment and observation period and subsequently will have the option to participate in “INSIGHT”, an open-label extension study including the possibility of receiving treatment in the second eye.
    PQ-110-001 is an open-label trial that has been designed to enroll children (age 6 - 17 years) and adults (= 18 years) who have LCA10 due to one or two copies of the p.Cys998X mutation in the CEP290 gene. Patients are receiving four intravitreal injections of QR-110 into one eye; one injection every three months. The trial is being conducted at three specialized centers with significant expertise in genetic retinal disease: the University of Iowa, Iowa City, Iowa, U.S., the Scheie Eye Institute at the University of Pennsylvania, Philadelphia, U.S., and the Ghent University Hospital, Ghent, Belgium.
    The primary objectives of the PQ-110-001 trial are safety and tolerability. Secondary objectives include pharmacokinetics, as well as restoration/improvement of visual function and retinal structure through ophthalmic endpoints, such as visual acuity (BCVA), mobility course, full field stimulus testing (FST), ocular instability (OCI), optical coherence tomography (OCT), and pupillary light reflex (PLR). Changes in quality of life in the trial subjects are also being evaluated. About QR-110
    QR-110 is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of Leber’s congenital amaurosis 10 due to the p.Cys998X mutation (also known as the c.2991+1655A>G mutation) in the CEP290 gene. The p.Cys998X mutation is a substitution of one nucleotide in the pre-mRNA that leads to aberrant splicing of the mRNA and non-functional CEP290 protein. QR-110 is designed to restore normal (wild-type) CEP290 mRNA leading to the production of normal CEP290 protein by binding to the mutated location in the pre-mRNA causing normal splicing of the pre-mRNA. QR-110 is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the United States and the European Union and received fast-track designation by the FDA.
    About Leber’s Congenital Amaurosis 10
    Leber’s congenital amaurosis (LCA) is the most common cause of blindness due to genetic disease in children and consists of a group of diseases of which LCA10 is the most frequent and one of the more severe forms. LCA10 is caused by mutations in the CEP290 gene, of which the p.Cys998X mutation is the most common. LCA10 leads to early loss of vision causing most people to lose their sight in the first few years of life. To date, there are no treatments approved or other products in clinical development that treat the underlying cause of the disease. Approximately 2,000 people in the Western world have LCA10 because of this mutation.
    
    
18. [verwijderd] 5 september 2018 10:26

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    About ProQR
    ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases such as Leber’s congenital amaurosis 10, dystrophic epidermolysis bullosa and cystic fibrosis. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind.
    *Since 2012*
    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. Such statements include those relating to QR-110 and the clinical development and therapeutic potential thereof, including our PQ-110-001 clinical trial of QR-110 and statements regarding release of clinical data, including that from our PQ-110-001 trial. 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. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors in our filings made with the Securities and Exchange Commission, including certain sections of our annual report filed on Form 20-F. 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, except as required by law.
    ProQR Therapeutics N.V.:
    Investor Contact:
    Smital Shah
    Chief Financial Officer
    T: +1 415 231 6431
    ir@proqr.com
    Media Contact:
    Sara Zelkovic
    LifeSci Public Relations
    T: +1 646 876 4933
    Sara@lifescipublicrelations.com
    
    
19. Dar-win 5 september 2018 10:35

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    Bedankt voor het posten Frenky, AB.
    
    Ben benieuwd wat de koers hier vanmiddag bij opening Nasdaq op gaat doen.
    
    Gr, Dar-win
20. [verwijderd] 5 september 2018 11:30

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    De koers zou hierop moeten stijgen, maar ja het blijft de beurs he.