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Davos-Klosters, Switzerland, 24 January 2015 – In a world of geopolitical unrest and economic sluggishness, developments in science offer needed bright spots on the horizon for 2015. Leaders of scientific institutions and Nobel laureates discussed the global outlook for science in the coming years in a session at the 45th World Economic Forum Annual Meeting. They identified big data, brain science, physics and epidemiology as some of the fastest changing fields of research.

“Dealing with data is really becoming a central object of study for science,” said Jean-Pierre Bourguignon, President, European Research Council, Belgium. For example, the complexity of the human brain demands sophisticated computational tools to understand how neurons interact and stimulate cognition. Big data has offered scientists new tools for exploring this complexity.

The result represents tremendous opportunities for scientific breakthroughs. “This is an amazing century for the life sciences,” said Francis S. Collins, Director, National Institutes of Health, USA. Increasingly, the major frontiers in science – from the origins of the universe to neuroscience – require interdisciplinary and international approaches. The genome project represents one example of this collaboration by bringing together engineers, computational scientists, biologists and others.

How can such interdisciplinary projects be encouraged in the future? Innovative funding models can encourage partnerships, and technology facilitates data-sharing. However, scientists often face difficulties securing funding for fundamental research.

One challenge is the long timeframe for basic research. “Scientific research works on a longer cycle than the election cycle,” said Konstantin Novoselov, Research Fellow, Mesoscopic Physics Research Group, University of Manchester, United Kingdom. “We have to fight for the money from the people who don’t get the benefits.”

Collaboration has expedited results and improved research in areas such as vaccines for Ebola, for example, as well as projects such as CERN’s complex of particle accelerators in studying astrophysics. “Some of these big databases that we are starting to assemble are opening knowledge about the world to people everywhere,” said France A. Córdova, Director, National Science Foundation (NSF), USA.

Scientists cautioned that breakthroughs in research are not enough to change societies. Research must be complemented by smart public policy and public action. One of the areas in which progress has been lacking involves global action to address climate change.

“We in science are doing a lousy job in communicating the extent of the risks we are facing,” said Mario Molina, Professor, Centro Mario Molina, Mexico. Social scientists can play a role in understanding political and behavioural obstacles that have thwarted efforts to address climate change.

“Science is this great tool for predicting knowledge,” said Brian Schmidt, Professor, Australian National University, Australia, “but it’s not guaranteed to come up with solutions fast enough.”

“In today’s economy, when having both parents in the workforce is an economic necessity for many families, we need affordable, high-quality childcare more than ever. It’s not a nice-to-have — it’s a must-have. So it’s time we stop treating childcare as a side issue, or as a women’s issue, and treat it like the national economic priority that it is for all of us.”
– President Obama, State of the Union Address, January 20, 2015

Helping working Americans meet the needs of their jobs and their families is a key part of the President’s plan to bolster and expand the middle class. Access to high-quality child care and early education not only promotes a child’s development, but it also helps support parents who are struggling to balance work and family obligations. A safe, nurturing environment that enriches children’s development is critical to working families and is one of the best investments we can make in our economy. Yet today, a year of child care costs higher than a year of in-state tuition at most colleges – putting a significant strain on parents.

Ensuring that children have access to high quality and affordable early childhood programs can help children prepare for school and succeed in later life while strengthening parents’ ability to go to work, advance their career, and increase their earning potential. Research shows that money spent on young children is an effective investment, yielding benefits immediately to parents and for many decades to come for the children. For example, the President’s Council of Economic Advisors’ report on the Economics of Early Childhood indicate that investments in high-quality early education generate economic returns of over $8 for every $1 spent.

Today, President Obama outlined his plan to make affordable, quality child care available to every working and middle-class family with young children. His plan includes:

Making a landmark investment in the Child Care and Development Fund that helps every eligible family with young children afford high-quality child care.
Tripling the maximum child care tax credit to $3,000 per young child.
Creating a new innovation fund to help states design programs that better serve families that face unique challenges in finding quality care, such as those in rural areas or working non-traditional hours.
Two years ago, the President called for a continuum of high-quality early learning for America’s children – including support for children and their parents beginning prenatally with evidence-based home visitation for young children and new and expecting parents and continuing through high-quality preschool for America’s 4-year olds. Over the past two years, the federal government, states, philanthropists, and business leaders have invested nearly $3 billion in high-quality preschool and early education. Today’s announcement builds on these continuing efforts to make high-quality early education and child care available for all. These investments to expand and strengthen child care and early education programs complement the Administration’s other efforts to help working families, including offering workers the opportunity to earn paid sick and family leave, a higher minimum wage, and equal pay for women.

NEW INVESTMENTS IN CHILD CARE AFFORDABILITY, QUALITY, AND AVAILABILITY

Parents who work in low-wage jobs can face real difficulties affording quality child care – in 2013, the average cost of full-time care for an infant at a child care center was about $10,000 per year – higher than the average cost of in-state tuition at a public 4-year college – and much higher in some locations. Without help, many families can face the untenable choice of not working or leaving their children in unsafe, unstable, or poor quality child care arrangements. Affordable, quality childcare can help parents so they can go to work to support their family.

Learning begins at birth, and the earliest years of a child’s life are those most critical for building foundational cognitive skills, social and emotional skills, and patterns of engagement in school and learning. Studies show that children who attend high-quality early learning programs – including high-quality child care – are more likely to do well in school, find good jobs, have fewer interactions with the justice system, and have greater earnings as adults than those who don’t. Increasing the supply of high-quality, affordable child care can help parents balance work and family responsibilities while also investing in young children.

That’s why this year the President proposes unprecedented investments in making quality child care affordable and available for working families by:

Expanding access to child care assistance for all eligible families with children under four years of age, within ten years. The federal Child Care and Development Fund (CCDF) helps low- and moderate-income families with the cost of child care and increases the availability and quality of that care. States contribute matching resources for a portion of the CCDF funding they receive. But currently, federal and state funding for child care assistance falls well short of the need, and only a small share of young children receive federally-funded child care subsidies. The President’s proposal will ensure that all low- and moderate-income families (those with incomes below 200 percent of the poverty line, or approximately $40,000 for a family of three) with children age three and under have access to a subsidy to pay for quality child care so they can work or attend school or job training. By 2025, this investment will expand access to high-quality care to more than 1 million additional young children, reaching a total of more than 2.6 million children served monthly through the child care subsidy system. To qualify for this funding, states will be required to develop sound plans for how they will build the supply of quality care for infants and toddlers and ensure that the subsidies they provide (when combined with reasonable copayments families can afford) will cover the cost of quality care.

Cutting taxes for families paying child care with a credit of up to $3,000 per child. The President’s tax proposal would streamline child care tax benefits and triple the maximum child care tax credit for middle class families with young children, increasing it to $3,000 per child. The President’s child care tax proposals would benefit 5.1 million families, helping them cover child care costs for 6.7 million children (including 3.5 million children under five), through the following reforms:

Triple the maximum Child and Dependent Care Tax Credit (CDCTC) for families with children under five, increasing it to $3,000 per child. Families with young children face the highest child care costs. Under the President’s proposal, they could claim a 50 percent credit for up to $6,000 of expenses per child under five.

Make the full credit available to most middle-class families. Under current law, almost no families qualify for the maximum CDCTC. The President’s proposal would make the maximum credit – for young children, older children, and elderly or disabled dependents – available to families with incomes up to $120,000, meaning that most middle-class families could easily determine how much help they can get.

Eliminate complex child care flexible spending accounts and reinvest the savings in the improved CDCTC. The President’s proposal would replace the current system of complex and duplicative incentives with one generous and simple child care tax benefit.

Improving the quality of child care. Last year Congress acted on a bipartisan basis to pass child care legislation that includes much-needed reforms to improve the quality and safety in child care settings, including requiring training for providers to prevent sudden infant death syndrome, instituting annual inspections of child care facilities, and comprehensive background checks of all providers. This proposal would provide the resources to help states implement those important reforms and support the expansion of access to quality child care programs staffed by early educators that can provide developmentally appropriate services that promote the healthy development and school readiness of young children

Promoting Innovation in the Child Care Subsidy System. The President will also invest $100 million in new competitive grants to states, territories, tribes and communities to develop, implement and evaluate models of providing child care to address the unmet needs for families who face unique challenges to securing child care. These pilots could be used to develop promising practices for families in rural communities or have children with disabilities, parents who work non-traditional hours, and other families who struggle to find and use high-quality child care.

A COMPREHENSIVE EARLY EDUCATION AGENDA

In addition to the historic investment in helping every low-income and middle-class family afford child care, the President’s FY16 budget will make critical investments to expand access to high-quality early education, including:

Providing Preschool for All: In his 2013 State of the Union, the Obama Administration announced a proposal to provide high-quality preschool to every American child and the FY 2016 Budget will continue to support this historic public investment in early education and in the future of America’s children. This $75 billion partnership with states would extend federal funds to expand high-quality preschool to reach all low- and moderate-income four-year-olds from families at or below 200% of poverty. The proposal, financed through an increase in tobacco taxes which will discourage youth smoking and save lives, also encourages states to broaden participation to reach additional middle-income families and to expand the availability of full-day kindergarten. In December 2014, the President and Vice President hosted the White House Summit on Early Childhood Education, highlighting over $1 billion in investments dedicated to early childhood education and development, including new efforts to expand preschool across 18 states and in over 200 high-need communities, reaching an additional 33,000 children.

Supporting Infants and Toddlers through Early Head Start-Child Care Partnerships: This Administration has more than doubled the number of infants and toddlers in Early Head Start and, in 2014, created the new Early Head Start-Child Care Partnerships program – an effort to provide quality care to tens of thousands of additional infants and toddlers through a partnership between Early Head Start and child care providers that meet the highest standards of quality to serve children from birth through age three. The Obama Administration has invested $500 million to support communities and proposes additional funding as they improve and expand comprehensive early care and education through the Early Head Start-Child Care Partnerships program, reaching over 30,000 infants and toddlers this year.

Increasing the duration of Head Start to a full school day and year. Head Start is a key element of the Administration’s efforts to help all children meet their full potential. The Obama Administration has already taken dramatic steps to raise the bar on Head Start quality, including requiring low-performing programs to compete for continued funding, and is revising performance standards to reflect the best available science on early learning and development. The President’s Budget includes a new proposal to further increase the impact of Head Start – while also helping the working parents of Head Start children – by providing enough resources to make sure all children in Head Start benefit from a full school day and full school year (at least six hours a day, 170 days a year), which research shows leads to better outcomes for young children.

Investing in Voluntary, Evidence-Based Home Visiting: Established in 2010, the Maternal, Infant and Early Childhood Home Visiting program builds on research showing that home visits by a nurse, social worker, or other professional during pregnancy and in the earliest years of life has benefits to parents and to children. These programs have been shown to significantly improve maternal and child health, development, and learning. These effects have proven to be long-lasting, with one study showing improved language and math abilities at age 12. Additionally, these programs have led to increases in parental employment and reductions in child maltreatment. To date it has supported more than 1.4 million visits in over 700 communities. The President’s Budget would ensure the program does not end when funding is scheduled to expire in March 2015 and expand the program to reach additional families and communities. This proposal is also supported by the increased tobacco tax.

The EU has acted decisively since the early stages of the current Ebola crisis and is today announcing its latest actions in the field of research. Support to research is part of the EU’s response, together with humanitarian aid, expertise, international coordination and longer-term development assistance.

The European Commission is today announcing eight research projects into Ebola that will be funded with a total of €215 million. These projects will develop in particular vaccines and rapid diagnostics tests, which are key to overcoming the current Ebola crisis. In parallel, another project is now on site in Guinea to monitor the ongoing Ebola crisis with the aim to improve preparedness and planning, operational effectiveness of future interventions in case of similar outbreaks or pandemics.

The eight projects working on vaccine and diagnostics are run under the new Ebola+ programme of the Innovative Medicines Initiative (IMI) and funded jointly by the European Commission and the European pharmaceutical industry. €114 million come from Horizon 2020, the EU’s research funding programme, and the remaining €101 million from the pharmaceutical companies involved in the projects[1]. The announcement comes shortly before the start of the World Economic Forum in Davos, where the Ebola crisis is expected to feature high on the agenda.

European Commissioner for Research, Science and Innovation Carlos Moedas said: “There is no vaccine or treatment against Ebola as yet, so we must urgently step up our efforts in Ebola research. With this funding from Horizon 2020 and our industry partners, we are speeding up the development of an Ebola vaccine as well as rapid diagnostic tests to aid heroic health workers. These are the tools we need to defeat Ebola once and for all.”

The projects include partners from around the world (mainly Europe, Africa, and north America) and address the following aspects (see Annex for more details). The topics are among the key priorities set out by the World Health Organization in the current Ebola crisis:

Development of Ebola vaccines (3 projects)
There are currently no licensed vaccines for Ebola. Three projects will advance the development of such vaccines by assessing the safety and efficacy of different vaccine candidates.

Scaling up vaccine manufacture (1 project)
Ebola vaccines can be manufactured in facilities with a higher biosafety rating. This project will establish a platform capable of rapidly producing sufficient quantities of the vaccine, while adhering to stringent quality and safety requirements.
Compliance with vaccine regimens (1 project)
For a vaccine to have a real impact on an outbreak, high levels of vaccination coverage are essential. In addition, for lasting protection, two doses of the vaccine may be needed. The project will raise awareness of vaccination campaigns and aim to secure patient compliance for vaccines that require two doses.

Rapid diagnostic tests (3 projects)
There is currently no fast, reliable test to determine if someone has Ebola or not. Three projects will pave the way for rapid diagnostic tests capable of delivering reliable results in as little as 15 minutes.

In addition to these, the Miracle project (Mobile Laboratory Capacity for the Rapid Assessment of CBRN Threats Located within and outside the EU) has developed a “Biological scenario” which closely mimics the current Ebola crisis situation and its rapid spread in West Africa, and how it can be addressed. This scenario is currently being implemented in real life operational conditions: An in-field laboratory in the immediate vicinity of an Ebola treatment centre located in the outskirt of Nzere Kore, Guinea, close to the borders of Liberia, Ivory Coast and Sierra Leone. In addition to helping identify Ebola patients quickly, this laboratory will also support new clinical research into one of the most promising drugs for the treatment of Ebola patients. Lessons learned from this deployment will also help refine the analysis of gaps, technological or logistical improvements and missing technologies for mobile laboratories.

To reinforce EU efforts to help fight Ebola in rural communities of Guinea, under the leadership of the Commission, the European Centre for Disease Prevention and Control is deploying in the next few days four teams of French-speaking epidemiologists to support surveillance and response at community level.

Background
The European Commission has already mobilised €24.4 million from Horizon 2020, the EU’s framework programme for research and innovation, that will fund five projects ranging from large-scale clinical trials to tests of existing and new Ebola compound treatments (IP/14/1194).

It also worked with the industry partners within IMI to launch the Ebola+ programme, a multi-million euro programme on Ebola and related diseases such as Marburg haemorrhagic fever, in November 2014 (IP/14/1462). The eight projects announced today were selected following the first call for proposals under this programme.

IMI is a partnership between the EU and the European pharmaceutical industry, represented by the European Federation of Pharmaceutical Industries and Associations (EFPIA), to speed up the development of medicines. IMI was launched in 2007 and had a budget of €2 billion in its first phase until 2013. IMI2 has a budget of €3.3 billion for the period 2014-2024. Half of the funding comes from the EU, the other half from large companies, mostly from the pharmaceutical sector. These do not receive any EU funding, but contribute to the projects ‘in kind’, for example by donating their researchers’ time or providing access to research facilities or resources.

The EU is also helping to fight infectious diseases in sub-Saharan Africa, including Ebola, within the European and Developing Countries Clinical Trials Partnership programme (EDCTP2). This partnership works with a budget of €2 billion over the next ten years, with nearly €700 million coming from Horizon2020 (IP/14/2273).

The Miracle project operates with a budget of €1.4 million, co-funded by the Security research programme of the European Commission. The project is coordinated by the Universite Catholique de Louvain and runs from 1 December 2013 to 31 May 2015.

GENEVA/DAKAR/CONAKRY/FREETOWN/MONROVIA, – UNICEF is helping governments and communities restart stalled immunizations amid a surge in measles cases in Ebola-affected countries, where health systems are overwhelmed and tens of thousands of children are left vulnerable to deadly diseases.

“Measles is a major killer of children that can easily be stopped through a safe and effective vaccine,” said Manuel Fontaine, UNICEF Regional Director for West and Central Africa. “But immunization rates have dropped significantly, further threatening children’s lives.”

In Guinea, where a measles outbreak was declared in early 2014 – prior to Ebola – the number of confirmed measles cases increased almost fourfold, from 59 between January and December 2013 to 215 for the same period in 2014, according to WHO. In Sierra Leone, the figure tripled from 13 to 39 over the same period.

In Liberia, which had reported no measles in 2013, four cases have been confirmed in Lofa County, one of the areas hardest hit by Ebola.

The increase in cases of measles – a highly contagious disease – is of particular concern as a drop in immunization coverage rates has left children vulnerable at a time when measles transmission traditionally peaks in West Africa, between December and March.

Health systems are overstretched by efforts to manage the Ebola crisis, and people are avoiding health facilities for fear of contracting Ebola. As a result, preliminary figures clearly show that vaccine coverage rates have fallen sharply this year.

In Liberia, for example, government data shows that monthly measles immunization coverage against target dropped from 71 per cent in May 2014, to 55 per cent in October, with only about 50 per cent of health facilities reporting.

While vaccination campaigns that involve large crowds have been put on hold, UNICEF and partners are intensifying carefully guided routine immunizations to rapidly reduce the number of unimmunized children.

In Guinea, UNICEF is supporting activities to step up routine vaccinations, whose initial phase, in late November and early December 2014, covered communities that had not had any Ebola cases for 42 days.

In response to the cases in Liberia, UNICEF, the Ministry of Health and other partners, including WHO, are conducting periodic intensification of routine immunization (PIRI) to vaccinate children under the age of 5 and provide them with vitamin A supplementation. This was completed in eight counties, is under way in four, and is set to begin in the other three.

As vaccinators venture out to provide lifesaving vaccines, which in many cases are long overdue, they also help with the control of the Ebola outbreak. In compliance with infection prevention and control (IPC) procedures and WHO guidelines on immunization in the context of an Ebola outbreak, UNICEF is providing not only vaccines, but also kits that include gloves and infrared thermometers for vaccinators. Vaccinators are being trained on infection prevention and control measures, supervision during immunization activities, and on how to conduct outreach sessions in areas which have not reported an Ebola case for 42 days.

Breaking the cycle of Ebola transmission and improving health services, including vaccinations, must go hand in hand in order to defeat the virus and to prevent large-scale child deaths.

UNICEF is playing a major role in the response, promoting behaviour that can help stop transmission, setting up Community Care Centres – where patients can be supported by their families and communities, with a referral system for any complicated cases – and providing essential supplies. It is also helping train community health workers, providing psychosocial support to Ebola-affected children and ensuring access to the clean water and waste management systems that are essential to preventing new infections.

“The best way we can help children is by stopping Ebola, while at the same time strengthening health systems,” said Fontaine. “We need to restore faith in the health system and offer communities regular opportunities for their children to get the vaccines they need to stay healthy.”

“Vaccinators and other health workers who are in the frontline need to feel protected so they can deliver life-saving interventions in the context of Ebola,” Fontaine added.

About UNICEF
UNICEF promotes the rights and wellbeing of every child, in everything we do. Together with our partners, we work in 190 countries and territories to translate that commitment into practical action, focusing special effort on reaching the most vulnerable and excluded children, to the benefit of all children, everywhere. For more information about UNICEF and its work visit: www.unicef.org

Dublin, Ireland and Bedminster, NJ – Shire plc (LSE: SHP, NASDAQ: SHPG) and NPS Pharmaceuticals, Inc. (NASDAQ: NPSP) today announced that the companies have entered into a merger agreement pursuant to which Shire will acquire all the outstanding shares of NPS Pharma for $46.00 per share in cash, for a total consideration of approximately $5.2 billion. Shire will accelerate the growth of NPS Pharma’s innovative portfolio through its market expertise in gastrointestinal (GI) disorders, core capabilities in rare disease patient management, and global footprint. The transaction has been approved unanimously by the Boards of Directors of both Shire and NPS Pharma.

NPS Pharma is a rare disease-focused biopharmaceutical company and its first product, GATTEX®/REVESTIVE® (teduglutide [rDNA origin]) for injection, is approved in the United States and Europe1 to treat adults with short bowel syndrome (SBS) who are dependent on parenteral support. NPS Pharma also has a registration phase product, NATPARA®/NATPAR® (rhPTH -83) for the treatment of hypoparathyroidism (HPT).

The $46.00 per share price in the transaction represents a 51% premium to NPS Pharma’s unaffected share price of $30.47 on December 16, 2014.

1In Europe, Revestive is indicated for the treatment of adult patients with short bowel syndrome who should be stable following a period of intestinal adaptation after surgery.

Transaction highlights
Excellent strategic fit; strengthens Shire’s focus on rare diseases while leveraging industry-leading GI commercial capabilities and global footprint
Shire anticipates enhanced revenue and earnings growth profile
Adds innovative product portfolio with multiple growth catalysts:
GATTEX/REVESTIVE (teduglutide [rDNA origin]) with growing sales for the treatment of adults with SBS, a rare GI condition
NATPARA/NATPAR (rhPTH -83), if approved, would be the only bioengineered hormone replacement therapy for use in the treatment of HPT, a rare endocrine disease

Shire expects transaction to be accretive to Non GAAP EPS from 2016 onward
Acquisition to be effected by a tender offer and funded from Shire’s cash resources, as well as existing and new bank facilities

Shire’s Chief Executive Officer, Flemming Ornskov, MD, MPH, commented:
“The acquisition of NPS Pharma is a significant step in advancing Shire’s strategy to become a leading biotechnology company. With our global strength and expertise in both rare diseases and GI, Shire is uniquely positioned to drive the continued success of GATTEX/REVESTIVE, and, if approved, commercialize NPS Pharma’s pipeline compound NATPARA/NATPAR.
“We look forward to accelerating the growth of the NPS Pharma portfolio based on our proven track record of maximizing value from acquired assets and commercial execution. The NPS Pharma organization will be a welcome addition to Shire as we continue to help transform the lives of patients with rare diseases.”

Francois Nader, MD, President, Chief Executive Officer and Director of NPS Pharma, stated:
“Shire shares NPS Pharma’s commitment to patients with rare diseases. We believe that joining our two companies will drive value for shareholders and ensure we continue to transform the lives of patients with short bowel syndrome, hypoparathyroidism, and autosomal dominant hypocalcemia worldwide. I am confident that this transaction will accelerate our ambition of creating a world where every person living with a rare disease has a therapy.

I would like to thank all of our employees for their continued outstanding contributions and steadfast commitment to the patients we serve.”

Information on NPS Pharma
NPS Pharma is a commercial-stage rare disease-focused biopharmaceutical company, whose first product, GATTEX (teduglutide [rDNA origin]) for injection, has been launched in the U.S. to treat adults with short bowel syndrome (SBS). NPS Pharma is in the process of launching the product in Europe under the trade name REVESTIVE. NPS Pharma’s second product rhPTH -83 (NATPARA in the U.S. / NATPAR in Europe) is currently under review in the U.S. and Europe for the treatment for hypoparathyroidism (HPT). NPS Pharma has an ongoing Phase 2a study evaluating its lead pipeline candidate NPSP795 for the treatment of adults with autosomal dominant hypocalcemia. NPS Pharma has an operational presence in the U.S., Canada, Europe, Latin America and Japan. The value of NPS Pharma’s gross assets were $282.2 million with net assets totaling $130.9 million as of September 30, 2014. NPS Pharma’s losses before tax for the three and nine month periods ending September 30, 2014 were $1.9 million and $6.2 million, respectively.

Information on GATTEX/REVESTIVE
In the United States, GATTEX (teduglutide [rDNA origin]) for injection is approved for the long-term treatment of adults with short bowel syndrome (SBS) who need parenteral support. GATTEX is the first analog of GLP-2 approved to treat SBS, a disease which may require patients to get their nutrition intravenously through a central line.

SBS is a condition in which a large portion of the intestine has been removed by surgery. As a result, people can’t absorb enough nutrients or fluids from food and liquids to maintain good health. It can also be caused by disease or injury that prevents the small intestine from functioning properly despite normal length. To make up for the inadequate absorption, intravenous (IV) feeding (parenteral support) may be prescribed to help the patient stay healthy.

In the U.S., approximately 6,000-7,000 SBS patients are dependent on parenteral support with a similar prevalence in Europe.2

GATTEX has received orphan drug designation from the U.S. Food and Drug Administration (FDA) and was approved in December 2012. GATTEX generated sales of $67.9 million in the nine months ending September 30, 2014.
In Europe, REVESTIVE has been launched in Germany and Sweden.

Information on NATPARA/NATPAR
NATPARA/NATPAR, NPS Pharma’s parathyroid hormone (rhPTH -83) for the treatment of hypoparathyroidism (HPT), a rare endocrine disorder characterized by insufficient levels of parathyroid hormone (PTH), is currently under review in the U.S. with an FDA Prescription Drug User Fee Act (PDUFA) action date for the Biologics License Application (BLA) on January 24, 2015. In Europe, the European Medicines Agency (EMA) has validated and initiated its review of NPS Pharma’s marketing authorization application (MAA) for NATPAR.

HPT is a rare condition in which the parathyroid glands fail to produce sufficient amounts of PTH or where PTH lacks biologic activity. PTH plays a central role in a variety of critical physiological functions in the body. In patients with HPT, insufficient levels of PTH lead to many physiological abnormalities, including low serum calcium and an inability to convert native vitamin D into its active state to properly absorb dietary calcium.

In the U.S., approximately 75,000 patients are diagnosed with HPT with 41,000 having moderate to severe disease with a similar prevalence in EU5 (France, Germany, United Kingdom, Italy and Spain).3

Acute symptoms of HPT are largely due to low serum calcium and range from muscle pain and tingling, to lack of focus or ability to concentrate, and anxiety and depression. In extreme cases, life-threatening events, such as arrhythmias and seizures, may occur. In the absence of an approved parathyroid replacement therapy, the standard approach focuses on using large doses of calcium and active vitamin D to increase calcium levels in the blood and reduce the severity of symptoms. However, balancing the administration of large doses of calcium and vitamin D is challenging due to calcium fluctuations and the long-term use of this regimen may lead to serious complications. In addition, calcium and vitamin D do not correct the abnormal bone metabolism due to PTH deficiency or enable the activation of vitamin D.

2NA HPEN Patient Registry. Oley Foundation. 1994
3Powers et al., Prev. and Incid. of HPT in the USA, large cohort study, DOI 10.1002/jbmr.2004, (2013)

Additional value from NPS Pharma’s licenced products and pipeline
NPS Pharma currently has several successful partnerships in place. Amgen markets cinacalcet HCl as Sensipar® in the U.S. and as Mimpara® in the EU; Janssen Pharmaceuticals markets tapentadol as Nucynta® in the U.S.; and Kyowa Hakko Kirin markets cinacalcet HCI as Regpara® in Japan, Hong Kong, Malaysia, Macau, Singapore, and Taiwan.

NPS Pharma earned royalty revenues of $123.8 million for 2013 and $89.5 million for the first nine months ending September 30, 2014.

NPS Pharma is developing teduglutide as a treatment for pediatric SBS. NPS Pharma is currently conducting a global study for teduglutide in pediatric patients with SBS who are dependent on parenteral support.

NPS Pharma is also investigating NPSP795, a small molecule antagonist of the calcium-sensing receptor, which is believed to play a role in the distribution of PTH -83 throughout the body by antagonizing calcium-sensing receptors on the parathyroid gland to trigger a release of the body’s stores of PTH -83. NPSP795 is in development as a treatment for autosomal dominant hypocalcemia (ADH). There is no approved therapy for this ultra-rare, life-long genetic disorder that affects both adults and children.

Following the above transactions, Dr. Gillis holds 674 ADSs. One ADS is equal to three ordinary shares of 5 pence each in the Company.

Financial benefit to Shire
The acquisition of NPS Pharma is expected to enhance Shire’s revenue and earnings growth profile. Shire expects the transaction to be accretive to Non GAAP EPS from 2016 onward.

Related to the acquisition, Shire anticipates that it will realize operating synergies beginning in 2016 and growing substantially thereafter. Shire anticipates synergies approximating 25-35% of the Street’s consensus forecast of NPS Pharma’s standalone future operating cost base from 2017 onward.
Shire also expects that the transaction will deliver ROIC in excess of its weighted average cost of capital.

Financing
Shire has secured an $850 million fully underwritten short-term bank facility, which, in addition to Shire’s cash and cash equivalents and its existing $2.1 billion five-year revolving credit facility, is available to finance the transaction and pay related fees and expenses. Shire plans to refinance the short-term bank facility through new debt issuances in due course.

Closing
The acquisition is structured as an all-cash tender offer for all of the outstanding shares of NPS Pharma at a price of $46.00 per share followed by a merger in which each remaining untendered share of NPS Pharma common stock would be converted into the same $46.00 cash per share consideration as in the tender offer.

The closing of the transaction is subject to customary conditions, including the tender of a majority of the outstanding NPS Pharma shares and the receipt of Hart-Scott-Rodino clearance. Pending such closing conditions, it is anticipated that the transaction will close in the first quarter of 2015.

Citigroup Global Markets Limited and Lazard are acting as joint financial advisors to Shire. Goldman, Sachs & Co. and Leerink Partners LLC are acting as financial advisors to NPS Pharma. Davis Polk & Wardwell LLP and Slaughter & May are acting as legal advisors to Shire and Skadden, Arps, Slate, Meagher & Flom LLP is acting as legal advisor to NPS Pharma.

PROVIDENCE, R.I. – Rhode Island Primary Care Physicians Corporation (RIPCPC) and UnitedHealthcare have launched an accountable care organization (ACO) to improve the care coordination and provide enhanced health services for more than 15,000 Rhode Island residents enrolled in UnitedHealthcare’s employer-sponsored health plans.

RIPCPC has been dedicated to improving patient outcomes since 1994. The state’s largest independent practice association has a track record of developing innovative approaches to health care delivery that foster improved quality, enhanced patient satisfaction and reduced cost.

This new ACO will help continue shifting Rhode Island’s health care system to one that rewards quality and value rather than the volume of procedures performed. The practice’s 130 primary care physicians will manage all aspects of patients’ care, providing the right care in the right place at the right time. Physicians in the ACO will receive regular patient updates, enabling the care providers to monitor the care patients are receiving, and enhancing RIPCPC’s patient-management capabilities.

RIPCPC’s care providers will be eligible to receive payment incentives based on evidence-based measures such as hospital readmission rates, disease management and prevention, patient safety and care delivery, as well as total cost savings and patient satisfaction.

“We have long partnered with UnitedHealthcare to apply our expertise in health care innovation and patient-centered programs to improve the health of its plan participants and the broader Rhode Island community,” said Al Puerini, M.D., president and CEO, RIPCPC. “Together, we can continue to increase patient engagement to achieve better health outcomes and improve patient satisfaction, while reducing the overall cost of care.”

UnitedHealthcare employer-sponsored plan participants who currently receive care from RIPCPC-affiliated care providers will not have to do anything differently to receive the benefits of this new ACO that include enhanced care coordination and follow-up care.

“Our collaborative relationship with RIPCPC has helped improve the quality of care for our plan participants for many years while reducing health care costs,” said Stephen Farrell, CEO, UnitedHealthcare of New England. “We have piloted programs to help people better manage chronic illness and enhanced the effectiveness of personal health tracking devices to improve their health. We look forward to expanding ways we can help our plan participants live healthier lives.”

Care providers nationwide are showing strong interest in a shift to value-based care. UnitedHealthcare’s physician and hospital reimbursements that are tied to accountable care programs, centers of excellence and performance-based arrangements have nearly tripled in the last three years to $36 billion. The company projects this reimbursement will reach $65 billion by 2018. For more information about UnitedHealthcare’s accountable care organization initiatives, visit www.AccountableCareAnswers.com.

UnitedHealthcare serves more than 280,000 people in Rhode Island with a care provider network of 13 hospitals and more than 3,500 physicians statewide.

About Rhode Island Primary Care Physicians Corporation (RIPCPC)
Rhode Island Primary Care, Rhode Island’s largest IPA, was formed in 1994 to provide a venue for the smaller and independent practices to work together with the ultimate goal of improving quality of care for their patients. Its 130 primary care physicians act as primary care providers for more than 200,000 patients throughout the state of Rhode Island and also have an affiliation with more than 200 specialty-care member physicians. RIPCPC has transformed more than 50 practices into Patient-Centered Medical Homes, meeting the National Committee for Quality Assurance’s rigorous criteria. There are now more than 20 nurse care managers working in their member practices, following their most complex patients, promoting wellness and working with the RIPCPC champion physicians to focus on quality improvement.

About UnitedHealthcare
UnitedHealthcare is dedicated to helping people nationwide live healthier lives by simplifying the health care experience, meeting consumer health and wellness needs, and sustaining trusted relationships with care providers. The company offers the full spectrum of health benefit programs for individuals, employers, military service members, retirees and their families,and Medicare and Medicaid beneficiaries, and contracts directly with more than 800,000 physicians and care professionals, and 6,000 hospitals and other care facilities nationwide. Globally, UnitedHealthcare serves 45 million people in health benefits and is one of the businesses of UnitedHealth Group (NYSE: UNH), a diversified Fortune 50 health and well-being company. For more information, visit UnitedHealthcare at www.uhc.com or follow @myUHC on Twitter.

A report released by the Department of Health and Human Services today provides the first detailed analysis of enrollment in the Marketplaces for the first month of the 2015 open enrollment period. About 87 percent of people who selected health insurance plans through HealthCare.gov for coverage beginning Jan. 1, 2015 were determined eligible for financial assistance to lower their monthly premiums, compared to 80 percent of enrollees who selected plans over a similar period last year. In addition, more than 4 million people in both the state and federal Marketplaces signed up for the first time or reenrolled in coverage for 2015 during the first month of open enrollment. That includes more than 3.4 million people who selected a plan in the 37 states that are using the HealthCare.gov platform for 2015, and more than 600,000 consumers who selected plans in the 14 states that are operating their own Marketplace platform for 2015.

Today’s report includes data through December 15 for the 37 states using the HealthCare.gov platform, and through December 13 for 12 states and the District of Columbia that are using their own Marketplace platforms. Data for California are through December 14. Data for automatic reenrollments are not yet available in the vast majority of states, so today’s report does not fully capture the number of people who selected plans leading up to the deadline for Jan. 1, 2015 coverage. In particular, the automatic reenrollment process for the 37 states using the HealthCare.gov platform began on December 16 and was completed for the vast majority of consumers on December 18.

HHS also released a Weekly Enrollment Snapshot that captures more recent enrollment activity in the 37 states using the HealthCare.gov platform. The Weekly Snapshot shows that from November 15 to December 26, nearly 6.5 million consumers selected a plan or were automatically reenrolled.
“We’re pleased that nationwide, millions of people signed up for Marketplace coverage starting January 1. The vast majority were able to lower their costs even further by getting tax credits, making a difference in the bottom lines of so many families,” HHS Secretary Sylvia M. Burwell said. “Interest in the Marketplace has been strong during the first month of open enrollment. We still have a ways to go and a lot of work to do before February 15, but this is an encouraging start.”

Detailed findings for HealthCare.gov states through December 15:
More than 3.4 million people selected a plan through December 15 in the 37 states that are using the HealthCare.gov platform for 2015, including Oregon and Nevada. Of those:
87 percent selected a plan with financial assistance compared to 80 percent in the early months of the first open enrollment period.
33 percent were under 35 years of age compared to 29 percent in the early months of the first open enrollment period.
Nearly 1 million consumers selected a plan in the three days leading up to December 15. That is almost one third (28 percent) of total plan selections from November 15 through December 15.
Of the 3.4 million plan selections, 48 percent (1.6 million) reenrolled in a Marketplace plan and 52 percent (1.8 million) signed up for the first time.
The most recent Weekly Enrollment Snapshot with data available through December 26 can be found here.
Detailed findings for the 14 states using state based Marketplace enrollment platforms:
More than 600,000 consumers selected plans in the 14 states that are operating their own Marketplace platform for 2015. That includes:
161,752 Marketplace plan selections in two states reporting only data for new consumers (California and New York);
153,011 Marketplace plan selections in seven states reporting data on new consumers and consumers actively reenrolling in Marketplace coverage (Colorado, District of Columbia, Hawaii, Maryland, Massachusetts, Minnesota, and Rhode Island); and
318,075 Marketplace plan selections in five states reporting data on new enrollees, consumers actively reenrolling in Marketplace coverage, and automatic reenrollees (Connecticut, Idaho, Kentucky, Vermont, and Washington).

The information contained in this report provides the most systematic summary of enrollment-related activity in the Marketplaces to date. Data for the various metrics are counted using comparable definitions for data elements across states and Marketplace types. But because many states extended their plan selection deadlines for January 1 coverage, the report does not include the full count of consumers who will have selected coverage that begins Jan. 1, 2015.

Open Enrollment in the Marketplace runs from Nov. 15, 2014, through Feb. 15, 2015. Consumers should visit HealthCare.gov to review and compare health plan options. Consumers shopping for health insurance coverage should sign up by Jan. 15, 2015, in order to have coverage effective on Feb. 1, 2015. If consumers who were automatically reenrolled decide in the coming weeks that a better plan exists for their families, they can make that change at any time before the end of open enrollment on February 15.

Consumers can find local help at: Localhelp.healthcare.gov/. Or call the Federally-facilitated Marketplace Call Center at 1-800-318-2596. TTY users should call 1-855- 889-4325. Translation services are available. The call is free.

Department of Health and Human Services’ Secretary Sylvia M. Burwell announced today that HHS is collaborating with the nation’s largest pharmacies to encourage enrollment through the Health Insurance Marketplace at thousands of locations across the country. Ahold USA Companies, Bi-Lo Holdings, CVS Health, H-E-B, Kroger, Rite Aid, Walgreens and Walmart are playing an important role in providing information about the Health Insurance Marketplace to people across the country.

“Pharmacies and pharmacists are a trusted source of information for consumers who have health related questions, and they can provide information directly to consumers looking for quality and affordable health coverage on the Health Insurance Marketplace,” Secretary Burwell said. “These collaborations are integral to getting information directly to consumers from trusted health care providers in their communities.”

Pharmacists have been trained to answer basic questions about the Marketplace, and they know where to direct customers for enrollment assistance through HealthCare.gov, the call center, or through local in-person assistance. Special brochures, signage, circular advertisements, and other marketing materials have been and will be on display in many stores, providing consumers with information on health insurance and how to get enrolled. Many pharmacies have webpages dedicated to the Affordable Care Act and health insurance information. Pharmacy-based enrollment events are planned across the country and some pharmacies will have assisters available in stores to help enroll customers.

Among the activities taking place at pharmacies across the country:

Ahold USA
Ahold USA retail brands include Stop & Shop, Giant of Maryland and GIANT/MARTIN’S, which operate more than 560 pharmacies in nearly 770 supermarkets in the Northeast and mid-Atlantic. All pharmacists have received information regarding open enrollment and how to direct customers to resources for enrollment assistance. Links to HealthCare.gov are available on pharmacy webpages.In addition, Giant pharmacies in Maryland and Stop & Shop pharmacies in New York are partnering with State-Based Marketplace exchanges to further assist customers.

Bi-Lo Holdings, LLC
At Bi-Lo Holdings properties, BI-LO, Harveys and Winn-Dixie, all pharmacists are notified of the Medicare.gov website on the Bi-Lo Holdings portal, as well as of the Healthcare.gov website, and a number of the pharmacists have iPads which are used by the pharmacists to provide instant access of the plan options for interested patients. The pharmacy locations were chosen based on patient age and economic demographics.
Additionally, representatives of insurance plans are present in over 200 BI-LO and Winn Dixie stores in South Carolina and in Florida to discuss prescription program options under ACA, and health seminars are being scheduled with insurers in their offsite facilities to discuss medical conditions, as well as Affordable Care Act prescription plan options.

CVS Health
CVS Health is partnering with numerous health insurers offering coverage on the Marketplace to conduct more than 5,300 health insurance education events in CVS/pharmacy stores across the country between November 2014 and February 2015, providing customers the opportunity to have one-on-one conversations with insurance experts about the options available to them on the Marketplace. Consumers can find a schedule of in-store Marketplace information events with health plans at CVS.com/MarketplaceEvents. The outreach campaign also involves in-store brochure displays. CVS/pharmacy stores across the country will have free educational brochures, provided by CVS/pharmacy and numerous health plans, on hand for customers, including Spanish-language materials in select locations. Customers can also access online Marketplace insurance information and tools at CVS.com/insurance and in Spanish at CVS.com/seguro.
CVS/pharmacy offers an in-store option to pay monthly insurance bill using cash or a credit or debit card. Bill Pay at CVS/pharmacyis a service aimed at making it easier for newly-insured people, including those who may not have a checking account, to maintain their health insurance by providing a convenient method of paying their monthly insurance bill at any of the 7,800 CVS/pharmacy locations across the U.S. CVS/pharmacy is the first national retail pharmacy to offer this service. Members of health plans that participate in Bill Pay at CVS/pharmacy will receive their monthly premium bills featuring a customer-specific barcode and instructions on how it may be used to pay their premium. CVS will simply scan the barcode and collect the member’s desired payment without any additional fee for this service.
CVS Health is also partnering with State-Based Marketplaces. For example, the New York State Department of Health and CVS/pharmacy have partnered to educate and promote the many health insurance options available to New Yorkers through the NYSOH Marketplace, as part of the multi-pronged outreach campaign. CVS/pharmacy has similar partnerships with Covered California and MNSure.

H-E-B
H-E-B are holding education and enrollment efforts during the winter season in many of its stores/pharmacies and provide educational materials and signage to customers to promote access. Each of these stores are host insurance agents approximately two days per week in addition to ongoing patient interaction about the Affordable Care Act with their Pharmacy Teams. H-E-B is also providing open enrollment information at diabetes, cholesterol and blood pressure screening events in all its pharmacies. H-E-B is also active in administering immunizations and uses those opportunities to educate customers on the Affordable Care Act.

Kroger
Marketplace materials have been placed in all stores and pharmacy associates are available to assist customers with questions about the Health Insurance Marketplace. Kroger maintains a Health Insurance Marketplace landing page on its website to assist customers and provide a destination for them to review and enroll in Marketplace plans. Kroger is also providing open enrollment information on its health assessment kiosks installed in every pharmacy, which offer free screenings of key health vitals, like blood pressure, weight, BMI, and more.​

Rite Aid
Since Nov. 15 and through Feb. 15, 2015, Rite Aid has made independent, licensed insurance agents available to customers through a dedicated, toll free number. Agents are able to provide free consultations and answer customer questions on the Affordable Care Act. The agents are also able to help customers compare health care plans based on individual needs, and will be able to advise customers on Medicaid eligibility in applicable states. Customers are able to enroll in a plan over the phone if they choose. All Rite Aid stores have brochures with information on the Affordable Care Act and information is also offered on www.riteaid.com/affordablecare.

Walgreens
Walgreens is helping to educate consumers about the Health Insurance Marketplace through various channels, including national digital advertising, the Walgreens website (walgreens.com/healthinsurance) and in-store materials across all of its more than 8,200 locations nationwide.
Walgreens stores in select states will also have more customized consumer education efforts that include specially trained health and wellness guides, as well as flyers, automated print-outs and other materials available in both Spanish and English languages. The health and wellness guides, stationed in select stores, have been trained to answer questions and provide Marketplace-related information to customers.
Walgreens is providing informational materials to customers without insurance coverage for their prescriptions, and is also distributing materials through its Wellness Tour buses, which are planned to run through the end of the month, as many of these customers may be eligible for health insurance offered through the Marketplace.
The company is again working with GoHealth, a web-based, licensed insurance broker that can answer questions, offer one-on-one assistance, and provide access to the Marketplace for customers looking to enroll in or shop for health insurance.

Walmart
Since 2005, Walmart has hosted agents from individual insurers in stores to answer questions and enroll customers in specific healthcare plans. This year, in an effort to bring transparency and simplicity to the changing health insurance market, Walmart launched Healthcare Begins Here, an in-store program designed to educate customers on health insurance options. In addition to providing information on www.walmart.com, pharmacists will also provide assistance in verifying enrollment and will be available to help answer questions about the new insurance plans. Simple, easy to understand educational materials will be available for customers in English and Spanish languages at all pharmacies.

Stockholm, Sweden – 19 December 2014 – GE Healthcare has signed one of the largest and most complete cyclotron and radiochemistry system agreements in the world with Stockholm County Council and Karolinska University Hospital, Sweden. GE Healthcare will be building a complete tracer production facility center for the hospital that will significantly expand its capacity to manufacture PET tracers, a fundamental element in PET scanning that is most commonly used in the diagnosis and assessment of cancer. With the new center the hospital will achieve three to four times higher PET tracer production capacity compared to today, and it will support the development of new tracers.

The production facility will give the physicians and patients at Karolinska University Hospital readily available access to all commonly used PET tracers in clinical practice. The main area of application of the produced tracers is cancer treatment – by injecting a small amount of PET tracer into a patient followed by a PET scan, potential ‘hot spots’ can be revealed, the parts in the patient’s body where the distribution of tracers can be used for the assessment of metabolic activity associated with cancer.

“The wider availability of PET imaging technology and its benefits for early diagnosis and staging of diseases has grown the interest and demand for new PET tracers. We are entering a new era in molecular medicine with targeted tracers for specific diseases and personalized treatment pathways. The new centre at Karolinska will help them improve patient care,” said Karl Blight, General Manager, GE Healthcare, Northern Europe.
Besides cancer, the tracers can be used in the mapping and treatment of cardiovascular and neurological diseases, and they have an increasingly important role especially in Alzheimer’s, dementia and brain research.

The new tracer center includes two PETtrace 800 Series Cyclotron systems (for cyclotron production), 20 hot cells supporting radiation safety for personnel when they are using the equipment and fully automated and easily programmable TRACERlab* FX series chemistry synthesizers that will enable the hospital to monitor the tracer production remotely. The agreement also includes a FASTlab* Platform for multi-tracer production that makes the production of different tracers on the same hardware possible.

Karolinska University Hospital will also receive a broad range of technical trainings over the entire contract period and resources for joint innovation projects. The contract is signed to cover delivery, installation and qualification of the equipment, warranty and service contracts for three years, with an option to be extended by further two two year periods.

*Trademark of General Electric Company
Uppsala is home to the global headquarters of GE Healthcare’s cyclotron unit, where cyclotrons are developed, manufactured and serviced by more than 100 employees. In addition, GE Healthcare Life Sciences has around 1200 employees in Uppsala, of which over 450 people are working with production and research & development. It is a center of expertise in protein science and creates technology that pharmaceutical companies can use in the production of biopharmaceuticals, such as insulin, antibodies and vaccines.

About GE Healthcare
GE Healthcare provides transformational medical technologies and services to meet the demand for increased access, enhanced quality and more affordable healthcare around the world. GE (NYSE: GE) works on things that matter – great people and technologies taking on tough challenges. From medical imaging, software & IT, patient monitoring and diagnostics to drug discovery, biopharmaceutical manufacturing technologies and performance improvement solutions, GE Healthcare helps medical professionals deliver great healthcare to their patients. For more information about GE Healthcare, visit our website at www.gehealthcare.com.

Health and Human Services Secretary Sylvia M. Burwell today announced $36.3 million in Affordable Care Act funding to 1,113 health centers in all 50 states, the District of Columbia, and seven U.S. Territories to recognize health center quality improvement achievements and invest in ongoing quality improvement activities. The health centers receiving awards today are proven leaders in areas such as chronic disease management, preventive care and the use of Electronic Health Records (EHRs) to report quality data.

“This funding rewards health centers that have a proven track record in clinical quality improvement, which translates to better patient care, and it allows them to expand and improve their systems and infrastructure to bring the highest quality primary care services to the communities they serve,” said Secretary Burwell. “With these funds, health centers in all 50 states will continue to provide access to high quality, comprehensive primary and preventive health care to the patients that need it the most.”

Health centers receiving these funds are being recognized for high levels of quality performance in one or more of the following four categories.

Health center quality leaders received awards if they were among the top 30 percent of all health centers that achieved the best overall clinical outcomes, demonstrating their ability to focus on quality in all aspects of their clinical operations; 361 health centers received funding in this category for approximately $11.2 million dollars.

National quality leaders received awards for exceeding national clinical benchmarks (Healthy People 2020 objectives and health center national averages) for chronic disease management, preventive care, and perinatal/prenatal care, demonstrating the critical role that health centers play in promoting higher quality health care nationwide; 57 health centers received funding in this category for approximately $2.5 million dollars.
Clinical quality improvers received awards if they demonstrated at least a 10 percent improvement in clinical quality measures between 2012 and 2013, showing a significant improvement in the health of the patients they serve; 1,058 health centers received funding in this category for approximately $17.7 million dollars.

Electronic Health Record reporters received funding if they used EHRs to report clinical quality measure data on all of their patients, a key transformational step in driving quality improvement for all health center patients across the nation; 332 health centers received funding in this category for approximately $4.9 million dollars.

“These funds reward and support those health centers that have taken steps to achieve the highest levels of clinical quality performance and improvement,” said Health and Resources Administration (HRSA) Administrator Mary K. Wakefield, Ph.D., R.N.
Nearly 1,300 HRSA-supported health centers operate more than 9,200 service delivery sites that provide care to nearly 22 million patients in every state, the District of Columbia, Puerto Rico, the U.S. Virgin Islands, and the Pacific Basin.

For a list of FY 2015 Quality Improvement Awards recipients, visit www.hrsa.gov/about/news/2014tables/qualityimprovement/.
To learn more about the Affordable Care Act and Community Health Centers, visit http://bphc.hrsa.gov/about/healthcenterfactsheet.pdf.
To learn more about HRSA’s Community Health Center Program, visit http://bphc.hrsa.gov/about/index.html.
To find a health center in your area, visit http://findahealthcenter.hrsa.gov.

First results from a small phase 1 trial published today in the New England Journal of Medicine show that a GSK/NIH Ebola candidate vaccine was well-tolerated and produced an immunological response in each of the 20 healthy adult volunteers in the USA who received it.

The candidate vaccine used in the trial conducted by the National Institutes of Health (NIH) was co-developed by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Okairos, a biotechnology company acquired by GSK in 2013. It uses a type of chimpanzee cold virus, known as chimpanzee adenovirus type 3 (ChAd3), as a carrier to deliver genetic material from two strains of the Ebola virus – the Sudan strain and the Zaire strain, which is responsible for the current Ebola outbreak in west Africa. GSK has been working with the NIH to accelerate development of both this bivalent version of the candidate vaccine and a monovalent version targeting only the Zaire strain in response to the current Ebola epidemic.

Commenting on the results, Dr Moncef Slaoui, Chairman of Global Vaccines at GSK said: “We are very encouraged by these positive first trial results showing this type of vaccine has an acceptable safety profile and can produce an immune response against Ebola in humans.

“Working with partners including the NIH, we’re doing all we can to advance development of a candidate vaccine in response to the Ebola crisis in west Africa.

“It’s important to remember that these data are the first piece in the jigsaw and we’re continuing to gather other important information. Over the coming weeks, we will see results from further phase 1 trials which will tell us more about the profile of the monovalent vaccine; most significantly results from a trial in Mali which is assessing its safety and immune response in west African populations.

“If the combined data from these trials are positive, the next phases of the clinical trial programme will begin in early 2015 to see whether the immune response we are seeing in phase 1 actually translates into providing people in affected countries with meaningful protection against Ebola.

“These phase 3 trials will involve the vaccination of thousands of volunteers, including frontline healthcare workers in affected countries, including Liberia and Sierra Leone, and possibly Guinea. If the candidate vaccine is able to protect these healthcare workers as we hope it will, it could significantly contribute to efforts to bring this epidemic under control.”

Next steps
Development of the vaccine candidate is progressing at an unprecedented rate, with further data from ongoing phase 1 trials in the USA, UK, Mali and Switzerland expected by the end of the year.

If trials are successful, the next phases of the clinical trial programme will begin in early 2015 which will involve the vaccination of thousands of frontline healthcare workers in the two of the affected countries – Sierra Leone and Liberia. Further safety studies will also be conducted in west African countries not affected by the current outbreak in adults and children.

GSK continues to work with the WHO, regulators and other stakeholders to determine possible solutions to accelerate the development of the Ebola candidate vaccine with the goal of trying to limit the further spread of the epidemic.

Its potential future use in mass vaccination campaigns will depend on whether WHO, regulators and other stakeholders are satisfied that the vaccine candidate provides protection against Ebola without causing significant side effects and how quickly large quantities of vaccine can be made.

GSK continue to actively explore with relevant organisations and partners all opportunities to accelerate the development of manufacturing at an industrial scale. Additionally, the company is looking at whether use of a booster vaccine may help provide longer-lasting protection.
GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.

Using a new imaging technique, National Institutes of Health researchers have found that the biological machinery that builds DNA can insert molecules into the DNA strand that are damaged as a result of environmental exposures. These damaged molecules trigger cell death that produces some human diseases, according to the researchers. The work, appearing online Nov. 17 in the journal Nature, provides a possible explanation for how one type of DNA damage may lead to cancer, diabetes, hypertension, cardiovascular and lung disease, and Alzheimer’s disease.

“Until this paper, no one had actually seen how the polymerase did it or understood the downstream implications.” Samuel Wilson, M.D.
Senior NIEHS researcher

Time-lapse crystallography was used by National Institute of Environmental Health Sciences (NIEHS) researchers to determine that DNA polymerase, the enzyme responsible for assembling the nucleotides or building blocks of DNA, incorporates nucleotides with a specific kind of damage into the DNA strand. Time-lapse crystallography is a technique that takes snapshots of biochemical reactions occurring in cells.

Samuel Wilson, M.D., senior NIEHS researcher on the team, explained that the damage is caused by oxidative stress, or the generation of free oxygen molecules, in response to environmental factors, such as ultraviolet exposure, diet, and chemical compounds in paints, plastics, and other consumer products. He said scientists suspected that the DNA polymerase was inserting nucleotides that were damaged by carrying an additional oxygen atom.

“When one of these oxidized nucleotides is placed into the DNA strand, it can’t pair with the opposing nucleotide as usual, which leaves a gap in the DNA,” Wilson said. “Until this paper, no one had actually seen how the polymerase did it or understood the downstream implications.”

DNA nucleotide damaged by oxidation
After the DNA polymerase (gray molecule in background) inserts a damaged nucleotide into DNA, the damaged nucleotide is unable to bond with its undamaged partner. As a result, the damaged nucleotide swings freely within the DNA, interfering with the repair function or causing double-strand breaks. These steps may ultimately lead to several human diseases. (Graphic courtesy of Bret Freudenthal)
Wilson and his colleagues saw the process in real time, by forming crystal complexes made of DNA, polymerase, and oxidized nucleotides, and capturing snapshots at different time points through time-lapse crystallography. The procedure not only uncovered the stages of nucleotide insertion, but indicated that the new DNA stopped the DNA repair machinery from sealing the gap. This fissure in the DNA prevented further DNA repair and replication, or caused an immediate double-strand break.

“The damaged nucleotide site is akin to a missing plank in a train track,” Wilson said. “When the engine hits it, the train jumps the track, and all of the box cars collide.”

Large numbers of these pileups and double-strand breaks are lethal to the cell, serving as a jumping off point for the development of disease. However, it can be a good thing if you are a researcher trying to destroy a cancer cell.

“One of the characteristics of cancer cells is that they tend to have more oxidative stress than normal cells,” said Bret Freudenthal, Ph.D., lead author of the paper and postdoctoral fellow in Wilson’s group. “Cancer cells address the issue by using an enzyme that removes oxidized nucleotides that otherwise would be inserted into the genome by DNA polymerases. Research performed by other groups determined if you inhibit this enzyme, you can preferentially kill cancer cells.”

Wilson and Freudenthal stressed that the quantities of oxidized nucleotides in the nucleotide pool are usually under tight control, but if they accumulate and start to outnumber undamaged nucleotides, the DNA polymerase adds more of them to the strand. Molecules that inhibit oxidation, known as antioxidants, reduce the level of oxidized nucleotides, and may help prevent some diseases.

NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit http://www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.