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Pharming Group: A Potential Genzyme In The Making

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  8. [verwijderd] 18 februari 2015 21:33

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    Ligt het aan mij of denkt de schrijver dat bruto winst netto is ? Want met 50 miljoen aan omzet gaat Pharming niet winstgevend worden, al denkt zijn tabel er anders over.
  9. [verwijderd] 18 februari 2015 21:35

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    Pharming Group: A Potential Genzyme In The Making
    Feb. 17, 2015 2:29 PM ET | About: Pharming Group NV (PHGUF), Includes: BAX, DYAX, SHPG, SLXP, SNY
    Subscribers to SA PRO had an early look at this article. Learn more about PRO »
    Disclosure: The author is long PHGUF. (More...)
    Summary

    The potential of Pharming’s recently FDA-approved product in HAE attack treatment (Ruconest) is only about to unfold and could quickly capture a significant share of the $400 million US market.
    Pharming’s multiple partnering deals on major markets (EU, US & China) could provide large and diversified opportunities for growth.
    In the long-term, Pharming’s technology allows for development of multiple cost effective and therapeutically safer products on an industrial scale, with very high margins thanks to the orphan drug model.
    With a current market cap of $175 million there appears to be a good opportunity in Pharming’s pipeline and business deals for value creation on both short and long-term.
    Pharming Group (OTC:PHGUF) -- listed on Euronext Amsterdam under ticker 'PHARM' -- is a little known Dutch specialized biotech developing a leading technological platform with great potential. Based on this platform (Transgenic Product Technology Platform), Pharming has developed Ruconest -- a recombinant protein drug for the treatment of Hereditary Angioedema ('HAE') -- which was approved in July 2014 by the FDA for the treatment of HAE attacks and recorded its first US sales in November 2014. Ruconest is also commercialized in Europe since 2010.

    Ruconest -- partnered with Salix (NASDAQ:SLXP) in North America -- is currently in a phase 2b trial in the US for preventive (prophylactic) treatment of HAE, an extension on Ruconest's FDA-approved indication of HAE attack treatment. Pharming and Salix have also stated their intention to start in 2015 a phase 2 trial of Ruconest for the treatment of acute pancreatitis, a potentially deadly inflammation leading to more than 300.000 hospital admissions in the US each year -- a high burden disease with a therapeutic need currently unmet.

    Total market size for HAE treatments from actual product sales is estimated to come close to $800 million per year in the US alone -- $400 million for HAE acute attack treatment and $400 million for prophylactic HAE treatment with only a few competitors on the market.

    With an effective start of Ruconest sales in the US in 4Q-2014, Pharming seems ready to see royalty revenue streams improve considerably in the coming years, yet the company's valuation has been declining since US approval of Ruconest -- creating an interesting buying opportunity for investors seeking high growth, long-term stocks.

    Pharming's business model

    Pharming's business model is simple in concept but very sophisticated in practice. It is the result of 25 years of pioneering research from Pharming -- the company taking its name directly from the process it helped create and develop: genetic pharming.

    "(Genetic) pharming" refers to the use of genetic engineering to insert genes that code for useful pharmaceutical products into host animals (or plants) that would otherwise not express those genes. Typically, the products of pharming are recombinant proteins or their metabolic products. Recombinant proteins are most commonly produced using bacteria or yeast in a bioreactor, but pharming offers the advantage to the producer that it does not require expensive infrastructure, and production capacity can be quickly scaled to meet demand, at greatly reduced cost (adapted from Wikipedia).

    Developing this process, however, has not been a walkover for Pharming. Although the Dutch company -- a spin-off of American company GenPharm Inc -- made worldwide news in the early 90's following the breeding of Herman the Bull, the very first transgenic bovine, it had to wait almost 20 years to see its first commercial product approved (Ruconest). In the 90's, a breeding program established around Herman produced several calves, which all inherited the bull's modified genes and were able to produce human recombinant proteins (lactoferrin) in their milk. This was a revolution then and it still is the main technological approach of Pharming today -- although instead of cattle which is expensive to breed and raise, Pharming chose to focus on rabbits as a source of transgenic animals.

    Recombinant human proteins produced in the milk of transgenic rabbits offer several clear competitive advantages over traditional methods of harvesting for human proteins. First, as previously stated, breeding a rabbit stock is quick -- as with the popular expression -- and doesn't require expensive infrastructure. Second, recombinant proteins, while generally demonstrating similar efficacy results as plasma-derived proteins, carry a much lower risk of disease transmission due to their "ex-human" method of production and are therefore often considered to be a better therapeutic option than plasma-derived proteins.

    Human recombinant proteins are used to treat diseases that result from a patient's own inability to naturally produce some essential proteins -- e.g. Factor VIII in the well-know case of Hemophilia-A. In the case treated by Ruconest, this disease is Hereditary Angioedema and it is caused by a low level or lack of a protein called C1 esterase inhibitor. Ruconest is a "recombinant human C1 esterase inhibitor" which provides a causal treatment with an excellent efficacy and safety profile to HAE patients. Like HAE and Hemophilia, some diseases which affect a very small percentage of the world's population typically require treatments that follow an "orphan drug" pricing model -- extremely high selling prices compensating for a tiny target population.

    Pharming's product platform works to address this specific type of need in a well-defined development process that can be summarized as follow :

    1 - identify a human protein that could provide an effective causal treatment for any type of genetic disorder
    2 - design a "founder" transgenic animal (rabbit) in which the protein can be produced
    3 - breed transgenic animals to provide target production level
    4 - harvest and purify recombinant proteins in animals' milk
    5 - obtain regulatory approval for the new drug substance
    6 - package and commercialize approved products on the market
  11. [verwijderd] 18 februari 2015 21:41

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    quote:

    surveyor schreef op 18 februari 2015 21:37:

    Expected price 72$ = 67 eurocent..!!
    Gebaseerd op 20x winst, uit Table 2, volgens mij neemt hij de omzet die Pharming krijgt - cashburn e.d als netto winst. Maar zit er wel een 100% winstmarge op Ruconest? Dan ga ik ook wel konijnen melken!

    Afijn misschien zit ik te slapen, maar ik zie nergens productiekosten.
  12. [verwijderd] 18 februari 2015 21:48

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    Om het in enig perspectief te plaatsen: wie is Logribel Biostocks?

    "I am an individual investor with a passion for biotechnology and stocks. I only pick stocks with a high and long-term potential and make investment choices based on deep analysis of their fundamentals."

    Het is zijn 2e artikel en hij heeft 24 volgers.
  13. forum rang 10 DeZwarteRidder 18 februari 2015 21:51

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    Een zeer komisch artikel: deze meneer denkt dat hij de toekomst over 5 jaar kan voorspellen......!!!

    Afgezien daarvan is hij nog wat 'vergeten': hij is namelijk de productiekosten vergeten....!! In ieder geval heeft hij alle kosten veel te laag ingeschat, maar ja hij weet natuurlijk niet dat De Vries een gat in z'n hand heeft.

    Bij een bruto omzet van 190 miljoen dollar schat ik de productiekosten op minstens 30 tot 50 miljoen USD en dat betekent dat Pharming over 5 jaar gewoon nog steeds verlies maakt.

    Conclusie: op het eerste gezicht een positief artikel, maar in werkelijkheid zeer negatief, zelfs inclusief Ruconest als preventiemiddel.
  14. [verwijderd] 18 februari 2015 21:52

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    quote:

    Beur schreef op 18 februari 2015 21:48:

    Wie is Logribel Biostocks?

    "I am an individual investor with a passion for biotechnology and stocks. I only pick stocks with a high and long-term potential and make investment choices based on deep analysis of their fundamentals."

    Haha zat jij ook al te kijken? Geen zinnige link mee te maken. Wellicht gewoon een buitenlander die Roth`s adviezen er op na leest? Al is Tigenix ook wel iets wat hier vaker langs komt.
  15. forum rang 10 voda 18 februari 2015 21:57

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    quote:

    Authentiek schreef op 18 februari 2015 21:35:

    ...
    6 - package and commercialize approved products on the market
    De rest in vele stukken....

    Illustration of TPTP development and manufacturing process with Ruconest (source : Pharming)

    Pharming's current therapeutic approach to treating genetic-disorder induced diseases differs from traditional "experimental" biotech R&D processes in the way that Pharming's products mainly consist of improved formulations of well-established efficient treatments (plasma-derived proteins), some of which have been used for decades -- a significant advantage when trying to reach clinical endpoints in regulatory trials.

    Ruconest in HAE treatment

    Ruconest is a recombinant human C1 esterase inhibitor and it is the first of Pharming's products to be approved and sold in the US. The drug is partnered for marketing and distribution with Salix in the US, and has been distributed since 2010 in Europe -- where it has regulatory exclusivity until the end of 2025 -- by Swedish Orphan Biovitrum (SOBI). Following FDA approval in July 2014, the drug is now being sold effectively in the US since November 2014.

    Ruconest is approved for the treatment of angioedema attacks in patients with Hereditary Angioedema. HAE is a rare blood disorder that causes episodic attacks of swelling that may affect various parts of the body -- including the face and upper airways, in which case it could be potentially deadly. As there exists no cure for this disease, patients must resort to causal treatments which they will need to take for their entire lives.

    On HAE market and competing companies, I recommend reading this excellent SA article -- Dyax And ViroPharma: An Overview Of HAE Space -- which covered extensively the subject at time of writing (2012). Building upon this research, major updates on HAE approved drugs and market shares in the US according to latest available numbers are shown below in Table 1.

    - Table 1: HAE-approved drugs and sales in the US by 2015

    Company
    Drug
    Approved indication (US)
    Sales (2013)
    Shire (NASDAQ:SHPG)*
    Cinryze
    prophylaxis only
    $400 million
    Shire
    Firazyr
    acute attacks in adults only (18y+)
    $235 million
    Dyax (NASDAQ:DYAX)
    Kalbitor
    acute attacks in adolescents and adults
    $40 million
    CSL Behring
    Berinert
    acute attacks in adolescents and adults (face, abdomen & throat only)
    not disclosed
    Salix / Pharming
    Ruconest
    acute attacks in adolescents and adults (except laryngeal attacks)
    N/A
    * NB: at time of publication of LifeSci Advisor's research article on SA (2012), Cinryze was owned by ViroPharma. The company was later acquired by Shire for total price of $4.2 billion. Cinryze was ViroPharma's only marketed product and main value-driver.

    Of the whole HAE treatment market, $400 million are generated solely by prophylactic treatment (for which Cinryze is the only US approved product to this date) and it is estimated that approximately the same sales numbers are generated by all acute attack treatments combined (between $300 and $400 million annually) -- it is the second segment that Pharming is currently entering with Ruconest.

    Ruconest is well-positioned to capture a significant share of the acute attack market, owing to the drug's numerous competitive advantages:

    Safety profile

    - Ruconest is the only approved recombinant C1INH HAE treatment (not produced in human blood) with a very favourable safety profile;

    - Berinert (plasma-derived C1INH) is known to cause potential blood clots and like all plasma-derived products (including Cinryze) it carries a potential risk of passing on human viruses;

    - Kalbitor must be administered under monitoring by healthcare professionals for potential risks of anaphylaxis;

    - Ruconest can cause severe allergic reactions to patients with preexisting rabbit allergy but all other side effects are generally mild and uncommon and none of the thromboembolic events associated with pdC1INH have been reported in Ruconest.

    Administration mode and restrictions:

    - Ruconest is approved for self-injection (IV) by HAE patients after proper training;

    - Firazyr (subcutaneous) and Berinert (IV) are also approved for self-injection but Kalbitor isn't;

    - Kalbitor and Firazyr can be administered with no restriction on the site of the attack, but Firazyr is not approved for patients under 18 years old;

    - Due to the limited number of patients with laryngeal attacks treated in Ruconest's clinical trials, effectiveness could not be established in HAE patients with laryngeal attacks (which is one of the most uncommon but deadliest type of attacks) but Ruconest can be administered to adolescent and adult patients alike;

    - Berinert is only approved for attacks occurring to the face, abdomen or throat of the patient.
  16. forum rang 10 voda 18 februari 2015 21:57

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    Dosing:

    - Most patients can be treated with only one vial of Ruconest (under 84kg);

    - Berinert requires 3 to 4 vials at equal weight;

    - Firazyr could require 1, 2 or 3 doses depending on initial reaction to treatment.

    (sources : drugs websites and UpToDate)

    Clinical profile:

    In addition to good efficacy results, Ruconest's main clinical advantages over competing treatments are summarized in the table below:

    (click to enlarge)
    Ruconest Clinical Profile

    (source : Pharming)

    In terms of revenues from Ruconest US sales, Pharming is entitled to receive a tiered supply payment of between 30% of net sales up to $100 million (per year) and 40% of net sales greater than $750 million (with progressively higher percentages for sales numbers comprised between $100 and $750 million) plus additional potential milestone payments totaling $45 million. (source : pages 13/14 of Santarus 10-K form ; NB : Santarus was acquired in 2013 by Salix)

    Therefore, a reasonable market share in HAE attack treatments of 25% -- given its competitive advantages -- in a $400 million US market could generate around $30 million in revenues for Pharming in the coming years.

    In the meantime, European sales from Ruconest are expected to reach EUR 3 million in 2014 (from around EUR 1 million in 2013) and this number is expected to grow steadily in the next years as more reimbursement authorizations are obtained, SOBI's sales territories are expanded and Pharming is starting direct commercialization of Ruconest in key European territories (Germany, Netherlands and Austria) in 2015.

    Beyond Ruconest's current indication, Pharming and Salix currently have two ongoing phase 2 clinical trials seeking potential extensions to children for HAE attacks in Europe and for preventive treatment of HAE (prophylaxis) in the US. Both of these trials have estimated completion dates set before the end of 2015.

    Recently, Pharming announced the treatment of the first patient in its ongoing HAE prophylaxis trial, about two months after launching the trial. This trial follows a small phase 2 exploratory trial conducted by Pharming in 25 patients during 2009/2010 to evaluate the safety and prophylactic effect of weekly administrations of Ruconest. The trial results showed good efficacy for prophylactic treatment with an average of 50% reduction in HAE attacks in treated patients (in line with Cinryze's efficacy results). With this previous proof of efficacy, it is therefore reasonably safe to assume that the ongoing trial (designed according to FDA's requirements) will be a success in prophylaxis.

    At current trial pace and assuming successful clinical results, it is estimated that Ruconest could enter the US market for prophylaxis around 2019 -- and this could be a real value driver for Pharming as competition is very limited (to Cinryze only) and there are reasons to believe that Ruconest could capture a significant market share in this $400 million market.

    Other pipeline developments and partnering deals

    Pharming's territorial views for Ruconest sales extend well beyond Europe and US markets and the company has already concluded a number of specific partnering deals targeting China, South Korea, South Asian countries and Turkey among others. The exact regulatory progression of Ruconest's marketing in each of these countries is hard to determine precisely -- Pharming itself has only limited information as all regulatory details are dealt with by partners -- but in the long term, all of these opportunities could accrue to generate steady revenue streams for Pharming.

    Here's an overview of Pharming's worldwide distribution partners for Ruconest:

    (click to enlarge)
  17. forum rang 10 voda 18 februari 2015 21:58

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    (source : Pharming)

    One of these partnering deals is of particular interest: in 2013, Pharming and the Shanghai Institute of Pharmaceutical Industry (SIPI) established a strategic collaboration deal, in which Pharming gained access to China's market and SIPI acquired the right to co-develop and market products based on Pharming's technology platform. This includes an exclusive license for SIPI to market Ruconest in China but the deal extends well beyond Ruconest:

    Under the terms of the agreement, Pharming will transfer the Pharming technology platform and manufacturing know-how to SIPI, such that joint global development for new products will take place at SIPI's facilities in Shanghai and benefit from both the cost advantages of the Pharming platform and the competitive development and manufacturing costs structures at SIPI. The first projects to be jointly developed at SIPI will be C1-inhibitor (conestat alfa) and Factor VIII. Under the agreement, SIPI will fund preclinical and manufacturing development. (...) SIPI will have commercialisation rights for the Chinese market for all new products developed; Pharming will retain global rights ex-China. (...) For every product developed by and manufactured, SIPI will pay Pharming a number of clinical and regulatory milestones. SIPI will supply Pharming on a cost plus basis for world- wide commercialisation. Pharming will pay SIPI 4% royalties on global sales (ex-China) and SIPI will pay Pharming 4% royalties on sales in China. Until the technology transfer is completed and a Chinese marketing authorisation for SIPI produced conestat alfa has been granted, Pharming will supply SIPI with Ruconest® as an import drug for China, at a cost plus basis and 4% royalties and SIPI will pay Pharming a €0.3 million milestone upon receipt of a Ruconest® import license for China.

    (source : Pharming)

    Pharming and SIPI have chosen to focus on two first projects: taking Ruconest to market approval in China and developing recombinant human Factor VIII (rhFVIII) for the treatment of Hemophilia-A based on Pharming's technology platform. According to the company, the global rhFVIII market was worth over US$4 billion in 2011 with 90% of sales in the developed markets and very high unmet medical needs in the developing markets, such as China -- a worldwide rhFVIII market estimated to grow to US$6.5 billion in 2020.

    Meanwhile, in the US, Pharming and Salix have already agreed to investigate Ruconest's anti-inflammatory properties in the treatment of acute pancreatitis and are expected to start a phase 2 clinical trial in 2015. Acute pancreatitis is a sudden inflammation of the pancreas that can have severe complications and high mortality despite treatment. In the US, acute pancreatitis is estimated to cause around 300.000 hospital admissions each year, generating over $2 billion of admission costs. Acute pancreatitis has currently no effective targeted treatment and disease management consists mainly of supportive care with fluid resuscitation, pain control, and nutritional support. This is a large unmet need with a high market potential, but of course clinical efficacy needs to be demonstrated first.

    Finally, in 2014, Pharming acquired some interesting product leads through the buy-out of a small private French transgenic rabbit model service company (TRM). Product leads consist of transgenic "founder rabbits" which, in Pharming's technology platform, are the very first step in designing new products (see details above). Potential developments from this acquisition include treatments for Pompe's disease, Fabry's disease, Gaucher's disease, Haemophilia-A and Haemophilia-B. While all these are long-term prospects, it is interesting to note that Pharming contributed, many years ago, to the development of Genzyme's (now Sanofi's) blockbuster product Cerezyme for the treatment of Pompe disease that generated $914 million of sales in 2013 -- another lucrative market in which Pharming has experience and the potential to develop an effective, competitive product.

    Other ongoing developments also include ongoing preclinical research -- exclusively led, financed and managed by third parties including the US Army -- about Ruconest's promising effects in Ischemia/Reperfusion Injury (IRI) prevention in organ transplants, delayed graft function and hemorrhagic shock (see also here).

    Pharming's current pipeline can be summarized as follows -- product leads described above do not yet appear in this pipeline as Pharming has to officially announce its strategic decisions on which products it will choose to develop first:

    (click to enlarge)
  18. forum rang 10 voda 18 februari 2015 21:58

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    (source : Pharming ; NB: since end of 2014, status of Ruconest in prophylaxis of HAE should also display "clinical phase" instead of pre-clinical)

    A turning point in Pharming's history

    A look at Pharming's long-term chart clearly shows that, with more than 25 years of existence, the company has gone through rough patches in its history. Established as an independent company in 1995, Pharming went public in 1998 at a price of 30 florins (EUR 13.61) per share. In the early 2000's, Pharming was a flourishing company which had signed important deals to co-develop drugs for HAE with Baxter (NYSE:BAX) and Pompe disease with Genzyme, among others.

    However, with heavy operational expenses and not enough revenues, Pharming was on the brink of bankruptcy and had to gain protection from its creditors until the end of 2002. This was the first major blow in the company's development plans, as Pharming had no other choice than to sell its stake in its recombinant Pompe disease treatment to Genzyme -- a drug that Genzyme took all the way to commercialization and that became the blockbuster Cerezyme.

    In the following years, Pharming chose to concentrate on its HAE asset, taking it through clinical trials in Europe on its own and partnering with a US company (Santarus, later bought by Salix) to get FDA approval. Unfortunately, the need for financing conducted Pharming to very heavy stock dilution -- in 2008, the company had approximately 100 million shares and this number had shot up to 900 million by 2012. To this date and following a 1:10 reverse split, Pharming has approximately 400 million shares on the market.

    This excruciating ordeal for historical shareholders should now be a thing of the past though, as Pharming's CEO, Sijmen de Vries, declared in a September 2014 interview (in Dutch) that "a capital increase to survive is not needed" anymore. Therefore, after years of research and equity burning, normalization might have finally come for Pharming as 2014 should be the first in a series of cash flow positive years for the company, owing to significant milestones received from its partners and expected recurring profits from US and European sales of Ruconest.

    Key events and milestones

    Ruconest's first sales numbers in the US are obviously one of the main potential catalysts for 2015. One should not expect to see significant numbers from 2014 sales however, as the product was only sold for two months in Q4-2014 (from November) and more than a few months' time should be expected to see sales take off.

    On the clinical front, results from Ruconest's current phase 2 trial for HAE prophylactic treatment are expected in 4Q-2015 or early 2016. Before the end of 2015, Pharming and Salix are also expected to announce the launch of a phase 2 clinical trial for Ruconest in acute pancreatitis treatment.

    With no specific schedule, news of market extensions and/or clinical progress could be announced through one of Pharming's partners outside of Europe, such as market authorization for Ruconest in Turkey or in South-Asia as well as clinical progress from SIPI's China developments.

    Potential risks and financials

    With only one product commercialized, Pharming's mid-term future strongly depends on Ruconest sales picking up in the US and in Europe. If sales are deemed disappointing by investors, Pharming's market cap could stagnate or decline over the next months and years.

    Like many developing-stage biotechs, Pharming's current market cap partially depends on valuations attributed to early or mid-stage assets in ongoing clinical trials. Should any clinical trial fail to reach its endpoints, Pharming's valuation could be negatively affected. However, I estimate that Pharming's current valuation is mainly based on its marketed product Ruconest, thus limiting exposure to potential clinical failures at the current market cap.

    With EUR 23.8 million in cash at the end of Q3-2014, excluding a $20 million milestone received in Q4-2014 from its partner Salix, Pharming's cash reserves should be sufficient to fund commercial and R&D activities for several years (FY 2013 operating costs were app. EUR 13 million and total net loss was app. EUR 15 million) -- at least 2 to 3 years at current cash burn and not accounting for any increase in revenues.

    Conclusion and valuation model

    My valuation model is based on 2020 projected sales of Ruconest in two already approved markets (HAE attack treatment in Europe and in the US) and assumes conservative probability of success for Ruconest's extension in HAE prophylaxis in the US (75% despite proven efficacy in a previous study).

    Ruconest's market share in the US for HAE attacks is estimated to reach 25% by 2020 -- due to competitive advantages listed above -- and European sales are estimated to grow at an annual rate of 25% owing to opening of new markets and direct commercialization efforts by Pharming -- 2020 sales of $10 million compared to $3.4 million in 2014 with a mean royalty rate of 35% coming from direct sales and SOBI distribution depending on market.

    Ruconest in HAE prophylaxis treatment in the US -- expected to reach market around 2019 at current trial pace -- is estimated to grab around 20% of market share by 2020 as competition is limited to Cinryze only. The total size of the HAE prophylaxis market is based on $400 million FY 2013 sales of Cinryze -- although it is estimated that only a portion of HAE patients are currently treated and this market could be growing further in the coming years.

    According to this risk-adjusted NPV valuation model and considering 2020 royalty revenues (EU + US) of $51.50 million, I estimate the current fair value of Pharming to be at approximately $300 million (or app. $0.720 per share). This represents a 70% upside on the share price at time of writing (app. $0.420 or EUR 0.370).

    As of now, valuations for Ruconest's additional indications (outside of HAE prophylaxis) are not specifically forecast as Pharming has yet to prove significant clinical efficacy and define further strategic options. However, potential for these promising developing assets is included in a 20x multiple of 2020 net profits in the company's valuation model.

    See Table 2 below for summary of my valuation model's main assumptions (rNPV at 12.5% discount).

    - Table 2: summary of rNVP valuation model of Pharming

    (click to enlarge)
  19. forum rang 10 voda 18 februari 2015 21:59

    • voda

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    In the short term, Ruconest sales numbers will need to be closely watched during 2015 as this will be the main value-driver behind Pharming's valuation. Before the end of the year, Pharming's ongoing clinical trials in Ruconest's HAE extensions (pediatric use in Europe and prophylaxis in the US) could provide additional catalysts for the stock.

    In the long term, Pharming appears well-equipped to target multiple indications in niche "orphan drug" markets with an effective product platform -- a business model that has made Genzyme one of the world's largest biotechs before it was taken over by Sanofi (NYSE:SNY) in 2011 for $20 billion -- starting with the full deployment of Ruconest's potential in HAE and further indications.

    Editor's Note: This article covers one or more stocks trading at less than $1 per share and/or with less than a $100 million market cap. Please be aware of the risks associated with these stocks.
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Accsys Technologies 23 10.770
ACCSYS TECHNOLOGIES PLC 218 11.686
Ackermans & van Haaren 1 192
ADMA Biologics 1 34
Adomos 1 126
AdUX 2 457
Adyen 14 17.764
Aedifica 3 923
Aegon 3.258 322.957
AFC Ajax 538 7.088
Affimed NV 2 6.297
ageas 5.844 109.896
Agfa-Gevaert 14 2.051
Ahold 3.538 74.343
Air France - KLM 1.025 35.219
AIRBUS 1 12
Airspray 511 1.258
Akka Technologies 1 18
AkzoNobel 467 13.046
Alfen 16 25.012
Allfunds Group 4 1.510
Almunda Professionals (vh Novisource) 651 4.251
Alpha Pro Tech 1 17
Alphabet Inc. 1 406
Altice 106 51.198
Alumexx ((Voorheen Phelix (voorheen Inverko)) 8.486 114.826
AM 228 684
Amarin Corporation 1 133
Amerikaanse aandelen 3.837 243.502
AMG 971 134.000
AMS 3 73
Amsterdam Commodities 305 6.734
AMT Holding 199 7.047
Anavex Life Sciences Corp 2 491
Antonov 22.632 153.605
Aperam 92 15.027
Apollo Alternative Assets 1 17
Apple 5 384
Arcadis 252 8.787
Arcelor Mittal 2.034 320.848
Archos 1 1
Arcona Property Fund 1 286
arGEN-X 17 10.332
Aroundtown SA 1 220
Arrowhead Research 5 9.747
Ascencio 1 28
ASIT biotech 2 697
ASMI 4.108 39.443
ASML 1.766 108.719
ASR Nederland 21 4.502
ATAI Life Sciences 1 7
Atenor Group 1 521
Athlon Group 121 176
Atrium European Real Estate 2 199
Auplata 1 55
Avantium 32 13.690
Axsome Therapeutics 1 177
Azelis Group 1 66
Azerion 7 3.410