Crucell
Wikipedia 🌐 NONE
In 1993 [Introgene], [Crucell]'s predecessor, was established as a spin-off of Leiden University. The company formed a partnership with Genzyme to collaborate on its vector technology and viral-based products. In 1999 the company founded [Galapagos Genomics (renamed by 2005 to Galapagos NV )] as a joint venture together with [Tibotec]. In 2000 [Introgene] acquired U-Bisys to form [Crucell].
In 2006, [Crucell] and Swiss Berna Biotech; Swedish SBL Vaccines and US-based Berna Products joined forces to become the sixth largest vaccine company worldwide, with their own clinical programs.[citation needed]
On 7 January 2009 [Crucell] released a press release saying Crucell and Wyeth were in discussion on a merger of the two companies. On 26 January 2009 Crucell released another press release saying the discussions on a combination of Crucell and Wyeth was discontinued due to Pfizer's acquisition of Wyeth.[citation needed]
In September 2009 Johnson & Johnson bought 18% stake in [Crucell] for €302 million in order to collaborate on the development of a flu vaccine.[1] This followed Crucell's discovery of CR6261, a potent human antibody that neutralizes a broad range of influenza A viruses. J&J acquired the rest of the company in October 2010, taking its stake to over 95% by February 2011[2][3] and delisting the company from stock exchanges two months later.[4]
After the takeover by Johnson & Johnson in 2011, Crucell was assigned to Janssen Pharmaceuticals division. In 2014, the subsidiary was renamed from [Crucell] to Janssen Vaccines.[5][6]
[...]
EVIDENCE TIMELINE
2000 (Oct 24) - WSJ : "Crucell's IPO Will Launch On Nasdaq, Dutch Markets"
By James M. Dorsey / Oct. 24, 2000 at 12:01 am ET
https://www.wsj.com/articles/SB972331765625409215?mod=Searchresults_pos1&page=1
2000-10-24-wsj-crucell-ipo-launch.pdf
2000-10-24-wsj-crucell-ipo-launch-img-1.jpg
Crucell NV, undeterred by choppy markets and faltering biotech IPOs, is going ahead this week with the flotation of eight million shares on the Nasdaq and Amsterdam stock markets.
The Dutch biopharmaceutical company, formed by a merger in June of IntroGene BV [see IntroGene] and U-Bisys BV, believes its initial public offering will attract enough investors. U-Bisys was established by the University of Utrecht and the Dutch city's academic hospital.
"We believe that we have sufficient alliances and licensing agreements with major pharmaceutical companies and ... a number of medicines already in the pipeline that there is no reason to postpone going public. The feedback from the roadshows is very positive," said Crucell Vice President Annemarie Haverhals.
Leiden-based Crucell is one of many biotech companies looking for equity financing. The list of IPO candidates in the coming months includes Italian cancer-drug developer Novuspharma, Danish antibody specialist Genmab, Israel's SHL Telemedicine and Britain's Gene Medic. German group Schering AG and Spanish food company Puleva said recently that they would seek separate listings for their biotech units. And Swiss investment firm International BM Biomedicine Holdings AG has announced plans to list in Switzerland in the next six to 12 months.
"It's a difficult market; it takes courage to list," said Geert-Jan Hoppers, an analyst with Dutch investment bank Effectenbank Stroeve NV, noting that recent biotech offerings haven't fared well.
Terrence Norchi, a fund manager at SSB Citi Asset Management, said, "Volatility is part of the game. It does not mean anything about the long term. Unless there is something fundamentally wrong with the company, it's not a concern to me."
Meanwhile, market conditions have been tough. Shares in Dutch biotech firm IsoTis NV have fallen almost 25% from their IPO price of 10 euros earlier this month. Last week, Swiss-based BB Biotech AG said it received requests for only 162,204 shares for its IPO of 250,000 shares during the subscription period.
"The fact that Crucell nonetheless is going to market indicates sufficient self-confidence that they can conclude this exercise successfully," said Willem Burger, manager of the small-cap Orange European NM Fund in the Netherlands.
Mr. Burger said Crucell's IPO would be considered a success if the company manages to keep its issue price within the expected range of 17 euros to 20.50 euros. A midrange price would will value the company at 653.9 million euros ($549.8 million). The IPO is due to close on Thursday.
Crucell has said it needs 150 million euros to support further development of drugs in its pipeline. The eight million IPO shares amount to 25% of Crucell's equity.
Goldman Sachs International is Crucell's global coordinator and bookbuilder while ING Barings and UBS Warburg are co-managers.
The first of Crucell's two technologies is IntroGene's PER.C6 -- a platform for the development of drugs based exclusively on human cells -- which has already been licensed to Merck & Co., GlaxoWellcome PLC, Novartis AG, Aventis Pharmaceutical Products Inc. and Pfizer Inc. The second is U-BiSys's M'Ab'stract, a technology that aims to recreate the human immune system in a tube in order to identify healthy and sick tissues and select the antibodies needed to repair unhealthy tissue.
"Both these technologies will produce medicines that have less side effects because they do not contain any elements alien to the human body. We already have enough licensing agreements to create a revenue stream and a pipeline full of medicines that are likely to hit the market in about five years," Mrs. Haverhals said.
Before their merger, IntroGene and U-BiSys had obtained a total of 50 million euros in venture capital from Atlas Venture, Advent International and Alta Partners in the U.S., Threeeye in Britain, ABN Amro NV in the Netherlands and GIMB in Belgium.
2004 (Jan 08) - NYTimes : "Difficult Flu Season Appears To Have Reached Its Peak, Doctor Says"
By Lawrence K. Altman and Andrew Pollack / Jan. 8, 2004
2004-01-08-nytimes-ciom-difficult-flu-season-appears-to-have-reached-its-peak-doctor-says.pdf
2004-01-08-nytimes-ciom-difficult-flu-season-appears-to-have-reached-its-peak-doctor-says-img-1.jpg
The influenza season, which got off to an unusually early start, appears to have reached its peak in this country, an official with the Centers for Disease Control and Prevention said yesterday.
But it is too early to know whether the number of influenza cases will decline sharply or stay at a plateau for another few weeks, the official, Dr. Stephen M. Ostroff, said.
Dr. Ostroff also said it was still too early to know whether a second wave would occur later in the winter. ''We are at the peak right now nationally, but not every region sees their peak activity at the same time,'' he said in a telephone interview from the centers' headquarters in Atlanta.
''So it certainly appears that there are some areas where they have already peaked, some regions that have not quite hit their peak yet and some that are in the midst of their peak now,'' Dr. Ostroff said.
He also said: ''We have had indications from the states that felt the impact earliest, like Texas and Colorado, that the amount of influenza activity has backed off considerably. The way that I read our monitoring systems, this is what we see when we have hit the peak of a season.''
But influenza is notoriously unpredictable.
''We have seen spikes go up and come right back down again within a week or two, while in other years there has been a zigzag pattern where the peak stays up for weeks,'' Dr. Ostroff said.
The agency monitors influenza activity in a number of ways. One is a statistical calculation based on the number of deaths from pneumonia and influenza in 122 cities. By that measure, influenza exceeded the statistical threshold for a seasonal epidemic, for the first time, the week that ended Dec. 27. The calculation shows that the number of deaths from pneumonia and influenza have exceeded the usual number for recent weeks. But it will take a few more weeks to determine how many there will be.
At this point, Dr. Ostroff said, ''there is no reason to believe that this season should be significantly dissimilar from other influenza seasons.''
The duration of the peak period could be a crucial determinant in the severity of this season's epidemic. In some seasons, a second wave of influenza occurs, often in late February or March, although Dr. Ostroff said he had seen no hint of a second wave.
Because of the holiday period, the agency will not release data from the period since Dec. 27 until today.
On average, influenza causes about 36,000 deaths in the United States each year.
This season, the vast majority of influenza has been caused by a new variant of the virus known as the Fujian strain, which this year's vaccine was not developed to combat. Officials believe, however, that there is some cross-protection. The strain seems to have hit young children hard. The C.D.C. earlier reported 42 deaths in children from influenza this season. According to one statistical model, about 92 deaths in children occur a year on average in this country.
In a step that might eventually reduce problems of the type experienced with the flu vaccine this year, Aventis, the world's leading manufacturer of flu vaccines, yesterday announced a move toward improving the way its vaccine is produced.
Aventis, which is owned by Aventis S.A., said it would team with Crucell, a Dutch biotechnology company, to produce flu vaccine in cultures of human cells, rather than in hen's eggs, as is done now. But the new vaccine will not even begin to be tested in people until 2005 and will not be approved for use for several years after that.
Current production requires millions of eggs and many months. That makes it hard to make new doses quickly when supply falls short, as happened this year. Also, the strains to be used in the vaccine have to be decided months in advance, in some cases before scientists know which strains will be prevalent that year.
Government officials have been encouraging the development of new techniques like cell culture, and other manufacturers besides Aventis, like Chiron and Baxter International, are also moving in that direction.
Michel DeWilde, executive vice president for research and development at Aventis's vaccines business, said in an interview that using of cell cultures could shave only about a month off the time it takes to produce a vaccine. That would not have been enough extra time to prevent the viral mismatch this year, Mr. DeWilde said, though it might in some years. Also, cell cultures might be more efficient at producing certain viral strains that do not grow well in eggs, he said.
2009 (Jan 08) - NYTimes (Deal Book) - "Wyeth in Talks to Buy Crucell"
2009-01-08-nytimes-wyeth-in-talks-to-buy-crucell.pdf
2009-01-08-nytimes-wyeth-in-talks-to-buy-crucell-img-1.jpg
January 8, 2009 7:08 am
Crucell confirmed Wednesday night that it was deal talks with Wyeth, shortly after reports surfaced that the United States drug maker was in discussions to buy the Dutch biopharmaceutical company for around 1 billion euros ($1.35 billion).
Crucell, which makes vaccines for a range of diseases including cholera and hepatitis B, said that it was “in friendly discussions with Wyeth that may lead to a combination of the two companies.” It cautioned that the talks were at a preliminary stage and that a deal may not come to fruition.
The statement followed a report in The Wall Street Journal that said a deal could materialize as early as next week.
Crucell had a market value of 760 million euros ($1.03 billion) at the close of trading yesterday. Its shares have surged as much as 42 percent Thursday.
Bloomberg News noted that Wyeth’s chief executive, Bernard Poussot, has focused the company’s research on vaccines, which are generally a dependable source of revenue for drug makers because they don’t lose patent protection and are often purchased by governments.
2009 (Jan 23) - NYTimes (Deal Book) - "Do Pfizer-Wyeth Talks Leave Crucell Out in the Cold?"
2009-01-23-nytimes-com-do-pfizer-wyeth-talks-leave-crucell-in-the-cold.pdf
2009-01-23-nytimes-com-do-pfizer-wyeth-talks-leave-crucell-in-the-cold-img-1.jpg
Reports that drug giant Pfizer is in talks to acquire rival Wyeth in a deal that could be worth more than $60 billion are having a treacherous effect on shares of Crucell, a Dutch biotech company.
Earlier this month, Crucell said it was in discussions to sell itself to Wyeth, although it described the talk as “preliminary.” At the time, analysts said the company would likely be sold for at least 1.3 billion euros ($1.7 billion).
Investors on Friday seemed to believe a Wyeth takeover of Crucell was now off the table because of the Pfizer talks.
Shares of Crucell, which develops vaccines against AIDS, rabies and Ebola, fell as much as 13 percent on Friday.
After Crucell’s talks with Wyeth were disclosed a few weeks ago, analysts speculated that a bidding war could erupt, with rival drug giants Sanofi-Aventis and Novartis emerging as potential acquirers.
If Wyeth drops out of the bidding, it could open the door for one of the other two potential bidders to come in.
Crucell has said it will provide an update on the Wyeth talks “in due course.”
— Zachery Kouwe
2009-09-28-nytimes-com-johnson-johnson-invests-444-million-in-crucell.pdf
2009-09-28-nytimes-com-johnson-johnson-invests-444-million-in-crucell-img-1.jpg
Johnson & Johnson Invests $444 Million in Crucell
BY DEALBOOK SEPTEMBER 28, 2009 5:54 AM
September 28, 2009 5:54 am
Dutch biotechnology firm Crucell said on Monday Johnson & Johnson had bought 14.6 million new Crucell shares for 302 million euros ($443.5 million) as part of a flu vaccine development deal.
Crucell said the collaboration would focus on developing a universal “flu-mAb” product targeting all influenza A strains, including H1N1 strains that cause seasonal flu and the current pandemic flu along with the H5N1 or avian strain.
The newly issued shares represent about 18 percent of Crucell’s outstanding ordinary shares, Reuters reported. Both companies also agreed to development milestones and royalty payments based on the successful development and commercialization of products.
“A universal antibody or vaccine that protects against a broad range of strains would be an important advance” in helping to “control acute epidemic and pandemic outbreaks,” Paul Stoffels, global head of pharmaceuticals research and development at Johnson & Johnson, told Reuters.
The collaboration will also focus on development and commercialization of nonflu vaccines for the treatment and prevention of other infectious and noninfectious diseases.
As part of the deal, Crucell and Johnson & Johnson affiliate JHC Nederland agreed to a three-year standstill requiring Crucell’s consent for an increase of in JHC Nederland’s interest in Crucell and a three-month lockup on transfers of the shares.
The transaction will have an estimated dilutive impact of $0.02 to $0.04 on Johnson & Johnson’s 2009 adjusted earnings per share.
Go to Article from Reuters via The New York Times »
Go to Joint Press Release via PR Newswire »
2010-09-17-nytimes-johnson-johnson-bids-2-3-billion-for-crucell.pdf
2010-09-17-nytimes-johnson-johnson-bids-2-3-billion-for-crucell-img-1.jpg
Johnson & Johnson Mulling $2.3 Billion Crucell Bid
BY CHRIS V. NICHOLSON SEPTEMBER 17, 2010 5:54 AM
September 17, 2010 5:54 am
2
Johnson & Johnson, the American health products company, said Friday that it was in advanced talks to bid for the 82 percent of Crucell, a Dutch biopharmaceutical firm, that it does not already own, in what would be a 1.75 billion euro ($2.3 billion) deal.
The all-cash bid would give Crucell stakeholders 24.75 euros a share.
Johnson & Johnson would acquire a company known for its research, manufacture and marketing of vaccines and antibodies. It bought its initial stake in Crucell for 300 million euros last year.
Crucell shares rose 8.51 euros, or 54.19 percent, to 24.20 euros in Amsterdam on Friday, giving the company a market cap of nearly 2 billion euros.
Fabian Smeets, an analyst at Rabo Securities, said he thought the bid might go higher.
“Johnson & Johnson could add a couple euros,” Mr. Smeets said, citing Crucell’s 500 million euros in cash.
While other bidders may be in the wings, Crucell is bound by change-of-control clauses for certain products it makes and markets, including Quinvaxem, a vaccine against childhood diseases that it co-developed with Novartis and which is now a major revenue source for the Dutch company. Crucell could lose rights to the drug if it were sold to certain pharmaceutical competitors.
Should the deal go through, Johnson & Johnson would maintain Crucell’s management, staff levels and headquarters in Leiden, the Netherlands, the company said.
The expectation of such a limited restructuring in the event of a takeover is one reason why Crucell prefers Johnson & Johnson, Mr. Smeets said, adding that it would occupy a special place in a company that allows for entrepreneurship, unlike some other drug makers.
The last time Crucell was in play was just last year, but the bid from Wyeth fell through after it was taken over by Pfizer.
–Chris V. Nicholson
2011
2011-02-09-johnson-johnson-deal-for-crucell-moves-forward.pdf
2011-02-09-johnson-johnson-deal-for-crucell-moves-forward-img-1.jpg
Johnson & Johnson Deal for Crucell Moves Forward
BY CHRIS V. NICHOLSON FEBRUARY 9, 2011 9:22 AM
February 9, 2011 9:22 am
Comment
Shareholders of the Dutch biotechnology company Crucell voted on Tuesday to change the company’s bylaws and the makeup of its supervisory board, two moves that will pave the way for Johnson & Johnson‘s 1.75 billion euro ($2.4 billion) takeover.
The vote amended Crucell’s articles of association, and allowed for Johnson & Johnson nominees to take positions on the board once its bid is finalized.
In December, Johnson & Johnson offered 24.75 euros for each Crucell share it did not already own. That offer expires Feb. 16. The company set the minimum acceptance level at 80 percent of Crucell shares.
In the meantime, Johnson & Johnson is requesting a favorable ruling from the Internal Revenue Service in tax matters related to the deal.
While the transaction has the support of Crucell management, and received the approval of the European Commission last month, some shareholders felt the bid was too low.
But Crucell’s announcement this week with its full-year results that it had to suspend shipments of a drug from a South Korean plant because of microbiological contamination took the wind out of shareholder resistance.
2012
2012-10-30-nytimes-com-scientists-move-closer-to-a-long-lasting-flu-vaccine.pdf
2012-10-30-nytimes-com-scientists-move-closer-to-a-long-lasting-flu-vaccine-img-1.jpf
Scientists Move Closer to a Lasting Flu Vaccine
By Carl Zimmer
Oct. 29, 2012
6 MIN READ
As this year’s flu season gathers steam, doctors and pharmacists have a fresh stock of vaccines to offer their patients. The vaccines usually provide strong protection against the virus, but only for a while. Vaccines for other diseases typically work for years or decades. With the flu, though, next fall it will be time to get another dose.
“In the history of vaccinology, it’s the only one we update year to year,” said Gary J. Nabel, the director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases.
That has been the case ever since the flu vaccine was introduced in the 1950s. But a flurry of recent studies on the virus has brought some hope for a change. Dr. Nabel and other flu experts foresee a time when seasonal flu shots are a thing of the past, replaced by long-lasting vaccines.
“That’s the goal: two shots when you’re young, and then boosters later in life. That’s where we’d like to go,” Dr. Nabel said. He predicted that scientists would reach that goal before long — “in our lifetime, for sure, unless you’re 90 years old,” he said.
Such a vaccine would be a great help in the fight against seasonal flu outbreaks, which kill an estimated 500,000 people a year. But in a review to be published in the journal Influenza and Other Respiratory Viruses, Sarah Gilbert of Oxford University argues that they could potentially have an even greater benefit.
Periodically, a radically new type of flu has evolved and rapidly spread around the world. A pandemic in 1918 is estimated to have killed 50 million people.
With current technology, scientists would not have a vaccine for a new pandemic strain until the outbreak was well under way. An effective universal flu vaccine would already be able to fight it.
“Universal vaccination with universal vaccines would put an end to the threat of global disaster that pandemic influenza can cause,” Dr. Gilbert wrote.
Vaccines work by enhancing the protection the immune system already provides. In the battle against the flu, two sets of immune cells do most of the work.
One set, called B cells, makes antibodies that can latch onto free-floating viruses. Burdened by these antibodies, the viruses cannot enter cells.
Once flu viruses get into cells, the body resorts to a second line of defense. Infected cells gather some of the virus proteins and stick them on their surface. Immune cells known as T cells crawl past, and if their receptors latch onto the virus proteins, they recognize that the cell is infected; the T cells then release molecules that rip open the cells and kill them.
This defense mechanism works fairly well, allowing many people to fight off the virus without ever feeling sick. But it also has a built-in flaw: The immune system has to encounter a particular kind of flu virus to develop an effective response against it.
It takes time for B cells to develop tightfitting antibodies. T cells also need time to adjust their biochemistry to make receptors that can lock quickly onto a particular flu protein. While the immune system educates itself, an unfamiliar flu virus can explode into full-blown disease.
Today’s flu vaccines protect people from the virus by letting them make antibodies in advance. The vaccine contains fragments from the tip of a protein on the surface of the virus, called hemagglutinin. B cells that encounter the vaccine fragments learn how to make antibodies against them. When vaccinated people become infected, the B cells can quickly unleash their antibodies against the viruses.
Unfortunately, a traditional flu vaccine can protect against only flu viruses with a matching hemagglutinin protein. If a virus evolves a different shape, the antibodies cannot latch on, and it escapes destruction.
Image
Credit...
Jacquelyn Martin/Associated Press
Influenza’s relentless evolution forces scientists to reconfigure the vaccine every year. A few months before flu season, they have to guess which strains will be dominant. Vaccine producers then combine protein fragments from those strains to create a new vaccine.
Scientists have long wondered whether they could escape this evolutionary cycle with a vaccine that could work against any type of influenza. This so-called universal flu vaccine would have to attack a part of the virus that changes little from year to year.
Dr. Gilbert and her colleagues at Oxford are trying to build a T cell-based vaccine that could find such a target. When T cells learn to recognize proteins from one kind of virus, the scientists have found, they can attack many other kinds. It appears that the flu proteins that infected cells select to put on display evolve very little.
The scientists are testing a vaccine that prepares T cells to mount a strong attack against flu viruses. They engineered a virus that can infect cells but cannot replicate. As a result, infected cells put proteins on display, but people who receive the vaccine do not get sick.
In a clinical trial reported this summer, the scientists found that people who received the vaccine developed a strong response from their T cells. “We can bring them up to much higher levels with a single injection,” said Dr. Gilbert, the lead author of the study.
Once the scientists had vaccinated 11 subjects, they exposed them to the flu. Meanwhile, they also exposed 11 unvaccinated volunteers. Two vaccinated people became ill, while five unvaccinated ones did.
While the Oxford researchers focus on T cell vaccines, others are developing vaccines that can generate antibodies that are effective against many flu viruses — or perhaps all of them.
The first hint that such antibodies exist emerged in 1993. Japanese researchers infected mice with the flu virus H1N1. They extracted antibodies from the mice and injected them into other mice. The animals that received the antibodies turned out to be protected against a different kind of flu, H2N2. In hindsight, that discovery was hugely important. But at the time no one made much of it.
“By and large, people just said, ‘This is an oddity — so what?’ ” said Ian Wilson of the Scripps Research Institute.
Scientists did not appreciate its importance for more than 15 years, until Dr. Wilson and other researchers began isolating the antibodies that provided this kind of broad protection and showed how they worked.
The new antibodies turn out to attack different parts of the flu virus from the ones produced by today’s vaccines. Today’s vaccines cause B cells to make antibodies that clamp onto a broad region of the tip of the hemagglutinin protein. Recently, Dr. Wilson and his colleagues discovered a new antibody with a slender tendril. It can snake into a groove in the hemagglutinin tip.
Dr. Wilson and his colleagues found that this tendriled antibody can attach to a wide range of flu viruses. The results hint that the groove — which flu viruses use to attach to host cells — cannot work if its shape changes much.
The antibody is also impressively powerful, the scientists found. They infected mice with a lethal dose of the flu and then, after three days, injected the new antibody into them. The antibody stopped the virus so effectively that the mice recovered.
The hemagglutinin groove is not the only promising target for antibodies. Dr. Wilson and other scientists are discovering antibodies that attack the base of the protein. Influenza viruses can be broadly categorized into three types — A, B and C. Until now, scientists have found only antibodies that attack different versions of influenza A. Dr. Wilson and colleagues at Scripps and the Crucell Vaccine Institute in the Netherlands recently found a stem-attacking antibody that blocks influenzas A and B.
“The whole field is invigorated,” Dr. Wilson said. “It’s a great time.”
Building on these discoveries, Dr. Nabel and other scientists have recently developed vaccines that generate some of the new antibodies in humans. Now they are trying to figure out how to get the body to make a lot of the antibodies.
“Once you have an antibody that has all the properties you desire, how do you coax the immune system to make that?” Dr. Nabel said. “That’s the classic problem in immunology.”