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€ 0,12 > € 0,22 Koersdoel omhoog

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Vandaag weer gekwakkel op de beurs en pharming,,,,,,,,,,, ja............................. geen stap naar omhoog...... kan ook niet, er is geen reden voor.
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US MARKETS
02 december 21:50

AEX: Elke terugval is koopkans.

De AEX heeft na twee weken van twijfel de eerste (korte) weerstandslijn

kunnen nemen rond 393, en kan nu de lange top-lijn testen 407- 413.

Zo'n lijn werkt in de praktijk als een magneet.

Na het tikken van de lijn mag een tijdje neutrale topvorming

worden verwacht (2014).

KBC SECURITIES
Pharming lijkt voor het eerst in jaren weer aantrekkelijk voor beleggers.
Dat stelt KBC Securities. De Belgische bank verhoogde zijn advies voor het aandeel Pharming
van hold naar buy. KBC wees op de verbetering van de zwakke financiële positie van het biotechnologiebedrijf. Pharming is volgens de bank nu zeker in staat om de periode tot de volgende mijlpaalbetaling in verband met Ruconest te overbruggen. Volgens KBC is er een grote kans dat Ruconest in de Verenigde Staten tot de markt wordt toegelaten en dat partner Santarus in staat
zal zijn om de unieke eigenschappen van het product te benutten. KBC verhoogde het koersdoel
naar € 0,22. Hoogste koers 2013 07 jan € 0,32. Dinsdag 03 dec in de plus naar € 0,15.

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Berdientje schreef op 3 december 2013 08:51:

Dat bericht van KBC = van 7 november, zet dat dan er tenminste boven.
Ze hebben van zichzelf niet in de gaten hoe vervelend ze wel niet worden op een forum.
Het zit tegen misleiding aan,dit gepush.
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Hoopmazzel schreef op 3 december 2013 09:08:

[...]

Ze hebben van zichzelf niet in de gaten hoe vervelend ze wel niet worden op een forum.
Het zit tegen misleiding aan,dit gepush.
Die Laurenzo pusht kinderlijk graag zijn eigen draadjes steeds omhoog met allerlei tig keer herhaalde non-info :D Ach ja, IEX Pharming heh......
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coeffie schreef op 3 december 2013 10:17:

morgen allen
mogge coeffie ,koffie?
coeffie
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jurpsy @ 02-12-2013 13:36:50 (http://www.ErikErik.com / Pharming)
Efficient methods for producing TAs expressing RPs have been developed over the past 20 years. TAs offer opportunities to significantly reduce costs in producing mAb and human RPs with post-translational modifications that closely match those of human proteins.
Until recently, the main reasons behind the reluctance to produce RPs using TAs in developing countries included a lack of developed laws regulating the use of TAs, strict ethical standards, and protests in the public against the use of animals as bioreactors.
However, the situation has begun to change. Detailed regulations to accompany the use of TAs for the production of RPs have been developed. The establishment of two manufacturing productions of RPs in the milk of TAs approved by regulatory agencies in the USA and EU has removed many issues related to the organization of production, while the expiration of patents on many biological preparations has increased competition between manufacturers, forcing companies to search for the most economically efficient technological models of production. Thus, it is very likely that in the near future the use of TAs in the biotechnology and food industries will expand.
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jurpsy @ 02-12-2013 19:30:24 (http://www.ErikErik.com / Pharming)
We have acquired rights to Ruconest under license and supply agreements with Pharming. Ruconest is a recombinant version of the human protein C1 esterase inhibitor, which is produced using proprietary transgenic technology. In November 2012, we announced positive top-line results from the phase III clinical study to evaluate the safety and efficacy of Ruconest for the treatment of acute attacks of angioedema
in patients with HAE. In June 2013, our BLA seeking approval to market Ruconest for this indication was accepted for review by the FDA.

Pursuant to the Prescription Drug User Fee Act guidelines, or PDUFA, we expect that the FDA will complete its review or otherwise respond to the BLA by April 16, 2014.
We currently are exploring clinical and regulatory strategies to evaluate Ruconest for the treatment of acute pancreatitis and for HAE prophylaxis. For HAE prophylaxis, Pharming submitted under its investigational new drug application a protocol to the FDA with a request for a special protocol assessment, or SPA. The FDA has indicated that modifications to the protocol are needed before proceeding with the study and further discussions will be required in order for the protocol to be approved pursuant to the SPA process. We and Pharming are evaluating next steps to move the program forward.

""""For acute pancreatitis, we have a meeting scheduled with the FDA later in November 2013 to discuss the study design."""""....

Dit heeft dus afgelopen weken ( week) plaats gevonden...
jurpsy @ 02-12-2013 19:14:06 (http://www.ErikErik.com / Pharming)
Morgen dan? .......

Therapeutic Rationale for Ruconest® in Acute Pancreatitis
• Acute pancreatitis is associated with the activation of the complement cascade and the contact (kallikrein-kinin) system
• C1INH inhibits the complement system
– Anti-inflammatory benefits
• C1INH also inhibits contact system proteases involved in the kallikrein
- kinin pathway
– Reduced vascular permeability
• Literature reports of clinical benefit seen with C1INH in patients with acute pancreatitis and/or vascular leak syndrome
• Limited number of therapies in development for acute pancreatitis underscores opportunity


""""" Plan to request pre-IND meeting with FDA with goal of initiating exploratory/proof-of-concept study"""" in late 2013 """"""
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jurpsy @ 02-12-2013 19:48:00 (http://www.ErikErik.com / Pharming)
License Agreement and Supply Agreement with Pharming:

Under our license agreement with Pharming entered into in September 2010,
- we paid Pharming a $5.0 million milestone in July 2013 as a result of the FDA acceptance for review of the BLA seeking approval of Ruconest for the treatment of acute attacks of angioedema in patients with HAE.

-We may be required to pay Pharming a $20.0 million milestone:
*upon the earlier of first commercial sale of Ruconest in the U.S.
or
*90 days following receipt of FDA approval.

In addition, we will be required to pay certain one-time performance milestones if we achieve certain aggregate net sales levels of Ruconest.

The amount of each such milestone payment varies upon the level of net sales of Ruconest.
-a $20.0 million milestone if calendar year net sales exceed $300.0 million
and
-a $25.0 million milestone if calendar year net sales exceed $500.0 million.

As consideration for the licenses and rights granted under the license agreement, and as compensation for the commercial supply of Ruconest by Pharming pursuant to our supply
agreement, we will pay Pharming a tiered supply price, based on a percentage of net sales of Ruconest, subject to reduction in certain events, as follows:

-30% of net sales less than or equal to $100.0 million,
-32% of net sales greater than $100.0 million but less than or equal to $250.0 million,
-34% of net sales greater than $250.0 million but less than or equal to $500.0 million,
-37% of net sales greater than $500.0 million but less than or equal to $750.0 million,
- 40% of net sales greater than $750.0 million.
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jurpsy @ 01-12-2013 19:19:25 (http://www.ErikErik.com / Pharming)
Running head: Recombinant C1-INH in Cerebral Ischemia
Recombinant C1-inhibitor in Brain Ischemic Injury
Author’s names: GESUETE Raffaella1*, BD; STORINI Claudio1*, PhD; FANTIN Alessandro1, BD;
STRAVALACI Matteo1, BD; ZANIER Elisa R. 1, MD; ORSINI Franca1, BD; VIETSCH Helene2,
PhD; MANNESSE M. L. Maurice2, PhD; ZIERE Bertjan2, PhD; GOBBI Marco1, PhD and DE
SIMONI Maria Grazia1, PhD
* These two authors contributed equally to the work
1Mario Negri Institute, 20156 Milan, Italy; 2Pharming Technologies B.V., 2333 CN Leiden, The
Netherlands
Corresponding author: Maria Grazia DE SIMONI
Head of Laboratory of Inflammation and Nervous System Diseases, Mario Negri Institute
via G. La Masa, 19; 20156 Milan ITALY
tel: +39 02 390 14 505
fax: +39 02 354 6277
email: desimoni@marionegri.it

Statement of conflict of interest: Helene Vietsch, Maurice Mannesse and Bertjan Ziere are employees
of Pharming Technologies B.V.

ABSTRACT

Objective. C1-inhibitor(C1-INH) is an endogenous inhibitor of complement and kinin systems. We
have explored the efficacy and the therapeutic window of the recently available recombinant human
(rh)C1-INH on ischemic brain injury and investigated its mechanism of action in comparison with that
of plasma-derived (pd)C1-INH.
Methods. rhC1-INH was administered intravenously to C57Bl/6 mice undergoing transient or
permanent ischemia and its protective effects were evaluated by measuring infarct volume and
neurodegeneration. The binding profiles of rhC1-INH and pdC1-INH were assessed in vitro using
surface plasmon resonance. Their localization in the ischemic brain tissue was determined by
immunohistochemistry and confocal analysis. The functional consequences of rhC1-INH and pdC1-
INH administration on complement activation were analysed by ELISA on plasma samples.
Results. rhC1-INH markedly reduced cerebral damage when administered up to 18h after transient
ischemia and up to 6h after permanent ischemia, thus showing a surprisingly wide therapeutic window.
In vitro rhC1-INH bound mannose binding lectin (MBL), a key protein in the lectin complement
pathway, with high affinity, whereas pdC1-INH, which has a different glycosylation pattern, did not. In
the ischemic brain rhC1-INH was confined to cerebral vessels where it colocalized with MBL, while
pdC1-INH diffused into the brain parenchyma. In addition rhC1-INH was more active than pdC1-INH
in inhibiting MBL-induced complement activation.
Interpretation. rhC1-INH showed a surprisingly wider time-window of efficacy compared to the
corresponding plasmatic protein. We propose that the superiority of rhC1-INH is due to its selective
binding to MBL, which emerged as a novel target for stroke treatment...............
jurpsy @ 01-12-2013 18:47:25 (http://www.ErikErik.com / Pharming)

US 20130244941A1

United States

Patent Application Publication (10) Pub. No.: US 2013/0244941 A1

Mannesse et al. (43) Pub. Date: Sep. 19, 2013

The main results of this study are the folloWing:

1. the half life of rhC1INH in mouse plasma is about 3 hours
(at a dose of 15 U/mouse). The good correlation betWeen
antigen and functional activity indicates that the recombinant
protein circulates in plasma in its active form only; it is
possible that tissue distribution contributed to the reduction of
plasma levels.
2. rhC1INH, at the dose of 15 U/mouse-pre is very effective in
reducing the ischemic volume (reduction of 69%).
3. rhC1INH at the dose of 15 U/mouse is able to clearly
reduce the number of degenerating neurons in the hippocam
pus as assessed by Fluoro-Jade staining thus indicating that
the reduction in ischemic volume is due to sparing of neurons.
4. rhC1INH is similarly effective in reducing ischemic vol
ume When given at the beginning (-pre), at the end of the
ischemic period (-post, i.e. at reperfusion) or 1 hour after the
onset of ischemia (1 h-post, i.e. 30 min from beginning of
reperfusion). Thus rhC1INH has a Wider time-WindoW of
e?icacy than pdC1INH (that is no more effective When given
1 h after ischemia).
5. the neuroprotective effect of rhC1INH-pre dose is long
lasting, as shoWed by neuronal counting performed 7 days
after the beginning of ischemia.
6. rhC1INH, induced a slight improvement of general and
focal de?cits assessed 48 hours after ischemia. This ?nding is
similar to What observed With pdC1INH. In order to evaluate
the effect of rhC1INH on long-term behavioral outcome, We
analyZed mouse behavior by open ?eld test. Seven days after
ischemia the rearing behavior shoWs a signi?cantly loWer
score in the ischemic compared to naive mice. This decrease
is not present in rhC1INH treated mice Whose score is not
different from control mice.
7. rhC1INH is able to counteract the activation/recruitment of
microglia/macrophages in ischemic mice brain as assessed
both at early (48 h) and at late (7 days) time points. These cells
are an index of the in?ammatory response of the brain tissue.
8. The strong astrocytic response elicited by ischemia at 48 h
is dampened by rhC1INH. The astrocytic activation is mark
edly decreased at 7 days in both experimental groups and no
difference betWeen saline- and rhC1INH-treated mice could
be observed.
jurpsy @ 01-12-2013 18:44:24 (http://www.ErikErik.com / Pharming)
3. Conclusions
[0092] The present data shoW that rhC1INH at the dose of
15 U/mouse is similarly effective in reducing the ischemic
volume When given at the beginning (-pre) or at the end of
ischemic period (-post, i.e. at reperfusion). More importantly
the inhibitor is able to exert its neuroprotective effects also
When injected 1 hour after the onset of ischemia (1 h-post).
Furthermore, the protective action of rhC1INH is still present
7 days after ischemia. These results are in sharp contrast With
plasma derived hC1INH Which When injected 1 hour after
ischemia has nearly completely lost the ability to exert neu
roprotective effects (see FIG. 2).
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jurpsy @ 01-12-2013 20:50:39 (http://www.ErikErik.com / Pharming)
DIFFERENT FORMS OF HAE PROPHYLAXIS

Murat Bas, Ulrich Straßen
Technical University Munich, Munich, Germany

Several forms for prophylactic treatment of HAE are possible. We have used in our angioedema center three forms of prophylaxis: 1. Short term prophylaxis before surgery, 2. Long term prophylaxis and 3. On demand prophylaxis. We used for the three prophylaxis forms following drugs: Icatibant in short term prophylaxis and on demand prophylaxis, C1 inhibitor concentrates in all prophylaxis forms. All prophylaxis treatment forms were successful.

Patients with short term prophylaxis were treated with icatibant or C1 INH 30-60 minutes pre surgery, 2 hours post-surgery and 12 h post-surgery. In long surgeries with more than 2 h or large blood-loss an additional application of icatibant or C1 INH was given. Long term prophylaxis was possible with Ruconest, Berinert and Cynrize. We have used all three C1 INH options in long term prophylaxis. Patients get 2 times in the week the C1 INH concentrates for 12 weeks. Our results demonstrate here a significant reduction of angioedema attacks.
jurpsy @ 01-12-2013 20:45:19 (http://www.ErikErik.com / Pharming)
Background: Hereditary Angioedema (HAE) is a rare disease with estimated prevalence of 1:10000 to 1:50000 individuals. According to this incidence, Latin America should have up to 57,000 HAE patients. In order to evaluate LA situation regarding HAE diagnosis and therapy, we developed a registry of confirmed cases. Methods: The 1st Latin American Meeting on HAE took place on June 2nd, 2012 and the delegates representing LA countries collected HAE data. Clinical data and access to therapy was evaluated. Results: The following countries participated: Panama, Paraguay, Uruguay, Chile, Peru, El Salvador, Costa Rica, Colombia, Mexico, Brazil and Argentina. The last 4 countries presented data from 20, 34, 276 and 227 cases, respectively. Only 15 HAE patients were identified in the other countries. Difficult access to therapy was detected and fresh frozen plasma is still the therapeutic resource to treat the patients. Conclusions: Deficient identification of HAE patients as well as knowledge about the disease was identified. The access to laboratorial diagnosis and therapy is restricted in allcountries, with more profound problems regarding drugs and assistance for HAE attacks.The authors propose a plan to action including registry of identified cases, educative programs, laboratorial support with reference centers, and access to prophylactic and attack treatment.
jurpsy @ 01-12-2013 20:40:19 (http://www.ErikErik.com / Pharming)
RUCONEST IN ROUTINE CLINICAL PRACTICE: UK EXPERIENCE
A.L. Manson, J. Dempster, S. Grigoriadou, M.S. Buckland, Hilary J. Longhurst

Department of Immunology, Barts Health NHS Trust, London E1 2ES, UK

Conestat alfa (Ruconest) is a recombinant human C1 inhibitor protein (C1INH) that is extracted from the milk of transgenic rabbits. It was licensed in Europe for the treatment of acute attacks of hereditary angiodema (HAE) in 2010. Here we describe our experiences treating the first 11 adult patients who have received Ruconest outside a clinical trial setting in the UK. Nine patients had HAE type 1, one had HAE type 2 and one had acquired C1INH deficiency.
We have considered the prescription of Ruconest in preference to plasma-derived C1INH (pdC1INH), which is comparatively well established in routine clinical practice, in several clinical situations:- when patients prefer to avoid blood products, for heavier patients, when the licensed dose of Ruconest is more cost effective and for patients showing a sub-optimal response to 20 U/Kg of pdC1INH.
The majority of the patients self administered the drug at home and reported that having fewer vials to prepare was a benefit. Eight patients were treated with 4200 and three with 2100 units of Ruconest. Ruconest appeared effective and was well-tolerated by all patients, and six of the patients chose to continue to use it as their preferred treatment for acute attacks. Some patients reported a more rapid time to initial response and complete resolution of their symptoms following treatment with Ruconest compared to their usual pdC1INH. However, three patients experienced recurrent swellings following treatment with Ruconest:- Two patients with very frequent attacks (occurring more than twice weekly) treated with 4200 and 2100 units reported recurrences after 11 hours and 2 days respectively - these were treated successfully with pdC1INH; The third patient, who has acquired C1INH deficiency associated with mild C1INH resistance, had a recurrence at 7 hours after Ruconest that subsequently resolved with tranexamic acid.
Overall, Ruconest was effective and well-tolerated; it has the potential to improve outcomes in HAE
jip banaan!
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quote:

Beur schreef op 3 december 2013 09:14:

[...]Die Laurenzo pusht kinderlijk graag zijn eigen draadjes steeds omhoog met allerlei tig keer herhaalde non-info :D Ach ja, IEX Pharming heh......

Ja, en als je in z'n geschiedenis kijkt zie je dat hij alleen maar post in door hemzelf geopende draadjes. Wat een narcist haha!

groetjip
coeffie
0
Wanneer komt er weer een keer nieuws positief of negatief, het wordt wel weer een keer tijd he
Lordjord
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Het nieuws vandaag is dat we als bijna enige fonds in het groen staan.
Zou wel mooi zijn als we een hele dikke plus kunnen krijgen vandaag..
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