Synthon Biopharmaceuticals Reports Positive Early Results With Its Second Generation HER2-Antibody-Drug Conjugate

Best-in-Class potential with improved therapeutic index compared to other armed antibodies

Synthon Biopharmaceuticals, a subsidiary of specialty pharma company Synthon, has reported promising results with its lead program of antibody-drug conjugates (ADCs). In pre-clinical xenograft studies using patient-derived breast cancer and non-small-cell lung cancer material, Synthon has reported complete tumor remission. Toxicity experiments conducted to-date have revealed Best-in-Class potential with a greatly improved therapeutic index compared to other armed antibodies, due to an impressive safety profile. The company has also opened a state-of-the-art GMP facility in Nijmegen for the production of ADCs up to phase III clinical trials and early launches.

ADCs are a new type of targeted therapy that combines a specific anti-cancer antibody or antibody fragment linked to a potent anti-cancer therapeutic. The aim for this class of therapy is to combine better tumor penetration and killing properties with lower side effects for cancer patients. 

Dr. Marco Timmers, chief scientific officer at Synthon Biopharmaceuticals said: "Synthon's first ADC program incorporates the HER2-binding antibody trastuzumab. The primary objective is to develop a broad therapeutic spectrum by targeting tumors that over-express HER2, such as metastatic breast cancer and non-small-cell lung cancer.  As a result of our unique linker-drug technology, this ADC program is delivering on its promise and giving us exciting preclinical results with the opportunity to become a Best-in-Class therapy."

In several xenograft models, including primary human breast cancer and non-small-cell lung cancer xenografts, Synthon's HER2-ADC dosed alone induced complete tumor remission, whereas with the antibody alone there was no effect. Toxicity studies conducted to-date have revealed that clinically effective doses are not likely to show serious side-effects since the difference between effective and toxic doses, the so-called therapeutic index, has been improved with at least one order of magnitude compared to competitor ADC technologies.

Synthon's proprietary ADC linker-drug technology is based on duocarmycin analogs. The differentiating design of Synthon's linker connecting the antibody to the duocarmycin drug, leads to high stability in circulation and also induces efficient release of the cytotoxin in the tumor cell. A key feature of Synthon's duocarmycin technology involves disruption of the DNA of (solid) tumor cells at any phase of the cellular cycle unlike many other ADCs which only attack tumor cells in a mitotic state. Another feature of duocarmycins is that these cytotoxins can also be effective against tumor cells that are multi-drug resistant. 

With the newly opened GMP facility available, Synthon will enter its drug candidate into clinical trials in 2014. Dr. Timmers added: "We strongly believe that advancing this second generation ADC technology will lead to a new class of effective, targeted medicines in oncology. Our GMP plant will also accelerate future patient access to oncology products based on this pioneering technology."

In addition to its ADC directed against HER2, Synthon is currently developing two other ADC programs for multiple indications in oncology. Depending on the indication, projects will be progressed independently until registration or will be co-developed/licensed out at an appropriate (pre-)clinical stage. Synthon also offers its linker-drug technology and manufacturing capabilities to external partners for conjugation to their own proprietary monoclonal antibodies.

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Drinking Age Laws Allowing Lower Drinking Ages Can Have An Impact On Later Drinking Patterns

Lower minimum legal drinking age (MLDA) laws have been associated with short-term effects such as a greater number of traffic fatalities and teen suicides. A new study has investigated the long-term and persistent linkages between permissive MLDA laws and specific drinking behaviors such as average alcohol consumption, frequency of drinking, patterns of binge drinking, and moderate drinking. Findings support an association with problematic drinking behaviors that persist into later adulthood, such as more frequent binge episodes.

Results will be published in the March 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Drinking age laws have been very effective in reducing alcohol related problems," said Andrew D. Plunk, post-doctoral research fellow at Washington University School of Medicine in St. Louis as well as corresponding author for the study. "Many researchers have studied the laws and there is quite a bit of evidence supporting their positive impact, especially for reducing alcohol consumption and traffic fatalities for those under the age of 21."

"Alcohol is the leading substance of abuse among youth in the United States," added Ralph Hingson, director of the Division of Epidemiology and Prevention Research at NIAAA. "Underage persons frequently binge drink, averaging six drinks per occasion five times per month."

Hingson said that persons under 21 who binge frequently are more likely to engage in a variety of behaviors that place themselves and others at risk: driving after drinking, riding with drinking drivers, never wearing safety belts, carrying weapons, having unplanned and unprotected sex, and illicit drug use. "Frequent bingers are also more likely to be injured in physical fights and suicide attempts," he said. "Furthermore, human brain development continues into the third decade of life, raising concern that heavy adolescent alcohol misuse may produce cognitive deficits and impairment in memory and attention. Finally, numerous studies have linked binge drinking to poorer academic performance."

Hingson explained that, in 1984, when less than half the states had a minimum legal drinking age of 21, the U.S. Congress passed legislation to withhold highway construction funds from states that did not raise the legal drinking age to 21. By 1988, it became illegal to sell alcohol to persons under age 21 in all states. "A review of 49 studies published in peer-reviewed scientific journals found that, when the legal drinking age was lowered in many states during the 1970s and early 1980s, there was a 10 percent increase in average alcohol-related traffic crashes in the states that lowered the age, whereas in states that raised the drinking age, there was a 16 percent decline in alcohol-related traffic crashes," he said. "Much less is known about the effects of raising the legal drinking age on persons older than 21."

"Our research is different for a few reasons," said Plunk. "First, most studies have focused on the immediate or short-term impact of MLDA laws on drinking, whether the outcome is drinking behavior or traffic fatalities. Second, while there has been some prior research on the long-term impact of MLDA laws on binge drinking, to my knowledge we are the first to look at the impact on both binge drinking and non-heavy drinking, that is, more moderate drinking that didn't cross the binge threshold. Third, we were specifically interested in looking at how the effects of these laws might have been different based on whether or not an individual attended college, which previous research on the long-term impact of the laws didn't do."

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The Effects Of Binge Drinking On The Liver

Alcoholic liver disease (ALD) is characterized by a fatty liver, hepatitis, fibrosis, and cirrhosis. Binge drinking is on the rise worldwide, and is particularly common in the U.S. A review of studies addressing the effects of binge drinking on the liver underscores the complex interactions among various immune, signaling pathways, epigenetic, and metabolic responses of the liver to binge drinking.

Results will be published in the April 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"The liver is the main metabolic site in the body," said Shivendra D. Shukla, Margaret Proctor Mulligan Professor at the University of Missouri, School of Medicine as well as corresponding author for the study. "It is involved in nutrient and drug metabolism and disposition, and in the production of a myriad of agents needed for the physiological functions of organs such as the heart, kidney, blood vessels, and brain. ALD-affected liver chemicals can also influence immunity, cardiovascular health, and coagulation. Thus, ALD can have a 'domino effect' on many organs."

"The liver is also the major organ for alcohol metabolism, and as such, is the first line of defense against excessive alcohol consumption," added Samir Zakhari, senior vice president in the Office of Science at Distilled Spirits Council of the United States. "The effects of binge drinking on the liver depend on whether binge drinking is superimposed on chronic heavy drinking, or is done on an empty stomach especially after a period of fasting or starvation."

"Binge abuse is on the rise globally," said Shukla. "For example, about 43 percent of college students have reported at least one binge episode during the previous months. It is therefore necessary to fully understand its consequences at molecular levels. This is the first review that highlights the molecular pharmacology of binge drinking and how this may offer insight into binge-induced injury and its wider implications."

Some of the review's key themes are:

• Binge consumption of alcohol is implicated in the pathophysiology of ALD. New studies from both experimental animals and humans indicate that binge drinking has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute levels of alcohol.
• "Chronic alcohol consumption renders the liver highly susceptible to binge-induced liver damage," said Shukla. "Binge-induced liver injury impacts other organs as well, a view rather poorly appreciated by the public."
• Binge drinking alters the levels of several cellular components and dramatically amplifies liver injury in the chronically alcohol-exposed liver.

"This review, the first of its kind, emphasizes the importance of molecular and epigenetic mechanisms in binge-induced liver injury," said Shukla. "This review also sets the stage for additional investigations in this field. The cross-organ implications of binge-induced liver damage must be explored."

"Binge drinking influences all the mechanisms mentioned above, but can also cause mitochondrial damage, which may result in cell death and disturbances in bioenergetics," added Zakhari. "Therefore, people should not binge drink, especially on an empty stomach, and if they are chronic heavy drinkers, binge drinking will exacerbate liver injury, especially if comorbid conditions such as obesity, Hepatitis C, or HIV infection exist."

The authors stress the importance of additional molecular investigations into the binge effects of alcohol for a better understanding of ALD. They also suggest that future research address the development of therapeutic strategies to control binge drinking.

"Our review highlights the effects of ALD on multiple molecules that in turn have effects on various organs," said Shukla. "We hope this will encourage research and development of newer approaches and tools to control and ameliorate binge-induced health effects."

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Alcohol's Effects On Normal Sleep Reviewed

Sleep is supported by natural cycles of activity in the brain and consists of two basic states: rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Typically, people begin the sleep cycle with NREM sleep followed by a very short period of REM sleep, then continue with more NREM sleep and more REM sleep, this 90 minute cycle continuing through the night. A review of all known scientific studies on the impact of drinking on nocturnal sleep has clarified that alcohol shortens the time it takes to fall asleep, increases deep sleep, and reduces REM sleep.

Results will be published in the April 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"This review has for the first time consolidated all the available literature on the immediate effects of alcohol on the sleep of healthy individuals," said Irshaad Ebrahim, medical director at The London Sleep Centre as well as corresponding author for the study.

"Certainly a mythology seems to have developed around the impact of alcohol on sleep," added Chris Idzikowski, director of the Edinburgh Sleep Centre. "It is a good time to review the research as the mythology seems to be flourishing more rapidly than the research itself. Also, our understanding of sleep has accelerated in the past 30 years, which has meant that some of the initial interpretations need to be revisited."

Some of the review's key themes are:

• At all dosages, alcohol causes a reduction in sleep onset latency, a more consolidated first half sleep, and an increase in sleep disruption in the second half of sleep.
  "This review confirms that the immediate and short-term impact of alcohol is to reduce the time it takes to fall asleep," said Ebrahim. "In addition, the higher the dose, the greater the impact on increasing deep sleep. This effect on the first half of sleep may be partly the reason some people with insomnia use alcohol as a sleep aid. However, the effect of consolidating sleep in the first half of the night is offset by having more disrupted sleep in the second half of the night."
• The majority of studies, across alcohol dose, age, and gender, confirm an increase in slow-wave sleep (SWS) in the first half of the night. SWS, often referred to as deep sleep, consists of stages 3 and 4 of NREM. During SWS, the body repairs and regenerates tissues, builds bone and muscle, and appears to strengthen the immune system. Alcohol's impact on SWS in the first half of the night appears to be more robust than its effect on REM sleep.
  "SWS or deep sleep generally promotes rest and restoration," said Ebrahim. "However, when alcohol increases SWS, this may also increase vulnerability to certain sleep problems such as sleepwalking or sleep apnoea in those who are predisposed."
• Alcohol's effects on REM sleep in the first half of sleep appear to be dose related. Low and moderate doses show no clear effects on REM sleep in the first half of the night, whereas at high doses, REM sleep reduction in the first part of sleep is significant. Total night REM sleep percent is decreased in the majority of studies at moderate and high doses.
  "Dreams generally occur in the REM stage of sleep," said Ebrahim. "During REM sleep the brain is more active, and may be regarded as 'defragmenting the drive.' REM sleep is also important because it can influence memory and serve restorative functions. Conversely, lack of REM sleep can have a detrimental effect on concentration, motor skills, and memory. REM sleep typically accounts for 20 to 25 percent of the sleep period."
• The onset of the first REM sleep period is significantly delayed at all doses and appears to be the most recognizable effect of alcohol on REM sleep, followed by a reduction in total night REM sleep.

"One consequence of a delayed onset of the first REM sleep would be less restful sleep," said Idzikowski. "The first REM episode is often delayed in stressful environments. There is also a linkage with depression."

Ebrahim agreed. "One hypothesis is that alcohol acts like medications that are used for depression and anxiety," he added. "Studies on patients with depression have identified that untreated patients had excessive REM sleep, particularly in the early part of the night, and that antidepressant medication suppressed REM sleep. Alcohol acts like antidepressants, reducing REM sleep particularly in the first part of the night. This impact of alcohol on REM sleep may explain the mood elevation and anxiety reduction associated with alcohol use."

"This review really helps to clarify findings to date as they apply to normal individuals," said Idzikowski. "The high attrition rate from 153 to 20 published studies that were examined enables us to know the real state of play regarding the impact of alcohol on normal volunteers. Whilst some of the studies were rejected on methodological grounds, many were rejected because they were on physically or mentally disordered individuals."

Both Ebrahim and Idzikowski hope this review will help readers understand that short-term alcohol use only gives the impression of improving sleep, and it should not be used as a sleep aid.

"In sum," said Idzikowski, "alcohol on the whole is not useful for improving a whole night's sleep. Sleep may be deeper to start with, but then becomes disrupted. Additionally, that deeper sleep will probably promote snoring and poorer breathing. So, one shouldn't expect better sleep with alcohol."

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Teenagers Avoid Early Alcohol Misuse Through Personality Management

Personality-targeted interventions delivered by trained teachers and school staff decrease alcohol misuse in at-risk teens and delay their classmates' alcohol uptake.

In a study published in the very first issue of the new journal JAMA Psychiatry, researchers from Sainte-Justine University Hospital Center, University of Montreal and King's College London have shown that personality-targeted school interventions delivered to high risk adolescents manage to reduce and postpone problem drinking, which is responsible for 9% of the deaths in young people between the ages of 15 and 29 in developed countries. Furthermore, by delaying alcohol uptake in at-risk youth, low-risk youth apparently gain group immunity due to reduced drinking within their social network.

"Two factors determine problem drinking: personality and peer pressure," explains Dr. Patricia Conrod, the study's first author, who supports the assumption that approaching at-risk youth from the angle of mental health rather than information on the dangers of alcohol is more effective at preventing early-onset alcohol misuse. "Teaching young people how to better manage their personality traits or vulnerabilities helps them make the right decisions in given situations," she explained, "whether it is a matter of overcoming their fears, managing thoughts that make them very emotional, controlling their compulsions, analyzing objectively the intentions of others or improving their self-perception."

The researcher conducted a two-year study called Adventure in which high-school school staff in London, England, were trained to intervene with their ninth grade students (median age of 13.7 years) in order to determine whether their intervention could reduce or postpone the participants' misuse of alcohol in the long term. The development of consumption patterns was measured by observing the drinking rates, problem drinking rates, binge drinking rates, and growth in binge-drinking rates. In addition, the study also attempted to examine a possible group ("herd") immunity effect associated with these interventions.

Participating schools were divided into two groups (control and intervention). The "intervention" school group conducted the intervention at the beginning of the study, whereas the "control" school group benefited from the program and training later on. Out of the total sample, 1,210 students were identified as being more at risk of developing future alcohol dependence after having filled out a personality questionnaire. They presented at least one of the following personality profiles: "anxiety-sensitivity," "hopelessness," "impulsivity" or "sensation-seeking." Trained school facilitators met these students during two brief personalized group sessions and asked them, based on their personality profile, to describe their reactions to various real-life scenarios and try to react to them in a different way.

"The advantage of this approach is that it is easy to implement as opposed to community-based approaches. Teachers can be trained to implement the program and closely adhere to its objectives very effectively, especially since only two interventions are required," explained Dr. Conrod.

A similar study is now under way in 32 high schools in Montreal, Canada. The study is also adding a component that analyses youth styles of thinking. Schools interested in taking part in the program can visit the project's website here.

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Five-Minute' Blood Cancer Injection Cuts Treatment Time By Two Hours

A new injection for blood cancer patients trialled at Southampton's teaching hospitals can deliver a two-hour dose of drugs in around five minutes.

Patients diagnosed with follicular non-Hodgkin lymphoma (NHL), a disease that attacks one specific type of infection-fighting cell, previously had rituximab administered via an intravenous drip.

Around 4,000 people, mainly in their 60s, are diagnosed with the condition in the UK every year and the majority of them will receive the drug, which targets and destroys specific proteins on the surface of cancerous cells, alongside chemotherapy to help eliminate all signs of the lymphoma and induce remission.

At the moment, most sufferers receive both treatments via a drip in a four-hour session once every three weeks. When the six-month course of chemotherapy ends, patients often require a further two years of rituximab given over two hours once every eight weeks.

Results of the multi-centre international study, presented at the annual meeting of the American Society of Hematology in Atlanta, showed that giving the drug by a quick injection under the skin was as safe and effective as the conventional intravenous treatment.

Dr Andrew Davies, a consultant in medical oncology at Southampton General Hospital and study lead, said: "This is a new formulation of a drug we are very familiar with and have been using for many years and the study demonstrates injection is equivalent to the intravenous drip method.

"In the near future, patients will be able to benefit from shorter, more convenient and potentially less complicated hospital visits, which will greatly reduce administration time for NHL patients and ease the capacity burden in busy chemotherapy day units."

Dr Davies, who is also a Cancer Research UK senior lecturer at the University of Southampton, added: "There is a high degree of patient preference and satisfaction with this new formulation of rituximab in Southampton and we hope to see it rolled out nationwide very soon."

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Effect Of Taking Smaller Bites Outweighs Tendency To Eat More When Distracted

Smaller bites reduce food intake even during distracted eating

Eating while distracted generally makes people eat more without being aware of it, but reducing bite sizes may be able to counter this effect, according to new research published January 23 in the open access journal PLOS ONE by Dieuwerke Bolhuis and colleagues from Wageningen University, Netherlands.

Previous studies have shown that taking smaller bites helps people eat less. Other research has also shown that people tend to eat larger meals if eating while distracted. In this new study, the authors assessed whether taking smaller bites or sips of food affected meal size if eaters were distracted during their meal. Participants in the study were given a meal of soup as they watched a 15 minute animation film. Two groups ate in pre-measured volumes of either 'small' or 'large' sips, and the rest were allowed to take sips of whatever size they liked. All participants could eat as much as they wanted, and were later asked to estimate how much they had eaten.

The authors found that people who ate pre-specified 'small' bites of food consumed about 30% less soup for their meal than those in the other two groups. The latter two groups also under-estimated how much they had eaten. Across all three groups, distractions during the meal led to a general increase in food intake, but even when distracted, people who ate pre-specified small sips of soup consumed less food than the others. According to the researchers, their results suggest that reducing sip or bite sizes during a meal may help those trying to lower their food intake, even if they are eating while distracted. 

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Sugar And Calories Cut In Soft Drinks, UK

Leading soft drinks brands Lucozade and Ribena will reduce the amount of sugar and calories in their products by up to 10 per cent as part of the Government's drive to curb obesity levels, Public Health Minister Anna Soubry announced this week.

Speaking at the Food and Drink Federation's 'Delivering Healthy Growth' stakeholder event, the minister unveiled the latest brands to sign up to the Responsibility Deal's calorie reduction pledge. Ribena ready to drink and Lucozade Energy will reduce the amount of sugar and calories by up to 10 per cent; AG Barr, who produce IrnBru, will reduce the calorific content across their portfolio of drinks by five per cent; and J2O will launch two flavours in a new slim-line can which will represent a 10 per cent calorie reduction compared with their standard 275mL bottle.

The Public Health Responsibility Deal aims to tap into the potential for businesses and other influential organisations to make a significant contribution to improving public health by helping us to create this environment.

England has some of the highest obesity rates in the developed world with 60  per cent of adults and one third of 10 and 11 year olds being overweight or obese. The Government's Obesity Call to Action outlined that consuming too many calories is at the heart of the problem and through initiatives like the Responsibility Deal Calorie Reduction pledge concerted action is needed.

Other pledges announced include:

Co-operative Food will look at controlling calories through a variety of measures, including establishing calorie guidelines and target levels in popular product lines; and

Burtons Biscuits Company will offer more portion control packs and will be reviewing its recipes to reduce calories where possible within its portfolio.

Public Health Minister Anna Soubry said:

"Being overweight and not eating well is bad for our health. To reverse the rising tide of obesity we have challenged the nation to reduce our calorie intake by five billion calories a day. On average that's just 100 calories less a day per person.

"Today's announcement will cut the calories and sugar by up to 10 per cent in leading brands like Lucozade and Ribena. Through the Responsibility Deal we are already achieving real progress in helping people reduce the calories and salt in their diet. Overall, more than 480 companies including many leading high street brands have signed up to the Responsibility Deal.

"All of the major supermarkets have now committed to removing artificial trans fats, and over 70 per cent of fast food and takeaway meals sold on the high street have calories clearly labelled, but more needs to be done.

"We are encouraged by the extra businesses which have signed up today but I want to see even more progress.  All in the food industry have a part to play and I now expect companies which are not yet taking action to come forward and make pledges."


Chair of the Responsibility Deal Food Network Dr Susan Jebb said:

"I'm pleased to see the soft drinks manufacturers, like GSK, AG Barr and Britvic join Coca-Cola and PepsiCo to make some very real commitments to help consumers  cut down on their calories as they take control of their weight."

"I hope we will now see others, including the out of home sector, taking a careful look at how they can build on this and come to the table with new commitments to encourage their customers choose smaller portions and swap to lower calorie options."

Director General of the Food and Drink Federation Melanie Leech said:

"We commend these businesses for joining existing pledge signatories in a shared commitment to support the calorie reduction challenge issued to the nation by ministers last year. Of the 31 pledge signatories, 15 are manufacturers, demonstrating our sector's willingness to engage and deliver improved public health outcomes under the Deal.

"On calorie reduction, and the other pledges already issued by the Food Network, we urge the Department of Health to continue its efforts to broaden engagement and bring in new companies to work with those of our members, and others, who have already made substantial commitments through the Responsibility Deal."  

The eight new drink and food manufacturers, supermarket and catering companies which have signed up today include GlaxoSmithKline, Co-Operative Food, Burtons Biscuits, AG Barr, Britvic, Dairy Crest Lexington Catering and CH&Co. They join the 23 companies including Mars and Tesco which have already pledged.

Further highlights from the commitments being made by companies:

GlaxoSmithKline: Targets set (including by end 2013) for the reduction of calorie and sugars content across GSK's drinks Lucozade Energy and Ribena ready to drink.

Co-operative Food: They will look at controlling calories through a variety of measures, including establishing calorie guidelines and target levels in popular product lines.

Burtons Biscuits: They will offer more portion control packs and will be reviewing its recipes to reduce calories where possible within its portfolio.

AG Barr: They will reduce the average calorific content per 100ml of their drinks' portfolio by 5% by 2016.

Britvic: They will develop a formal health and wellbeing strategy and increase their packaging mix to include smaller pack sizes. This year they will launch J2O in a new 250 ml slim-line can.

Dairy Crest: They will develop new products and broaden their range of exisiting products, to include lower calorie options and a range of portion sizes to suit customers. This includes developing cheese and spread products which contain less fat and fewer calories; and introduce single serve varities of products, where the size of the serving is fixed and the calorie content per serving controlled.

Lexington Catering (a small contract catering company)

They will reduce the number of calories by providing new menu choices, portion control, and education information at Point of Sale, on labels and menus, as well as through informative and trained staff.

CH & Co (contract catering company consisting of eight subsidiary companies, turnover £73m)

They will be working with suppliers to source low calorie new products and will reduce portion sizes (i.e. working with existing juice supplier to offer a smaller unit of sale, particularly for smoothies, reducing calorie content by 40%). 

In March 2012 we announced the first signatories to the calorie reduction pledge - in response to the Call to Action on Obesity published in October 2011. The pledge, developed through intensive work with business in the following months, focuses on reducing calories in products as well as encouraging and making it easier for people to make healthier choices.

Companies such as Asda, Coca-Cola GB, Mars, Tesco and Subway have already signed up.

About the Responsibility Deal:

The Public Health Responsibility Deal aims to tap into the potential for businesses and other influential organisations to make a significant contribution to improving public health by helping us to create this environment.

Since launching in 2011, the Responsibility Deal has worked with industry to achieve the following:

• over 70 per cent of the fast food and takeaway meals sold will have calories clearly labelled - almost 9,000 high street outlets by this year - with more companies signing up;
• all of the major supermarkets and 69 per cent of the retail market have committed to removing artificial trans fats - some 97 companies in all;
• over 70 per cent of the retail market and over half of the major high street and contract caterers are committed to further reductions in salt in over 80 categories of foods - such as bread, soups, cereals and pasta sauces;
• over 80 per cent of all alcoholic drinks on shelf will have clear labelling on units, NHS guidelines and pregnancy messages by the end of next year - with 92 companies signed up. [Early indications are that over 60 per cent of labels already carry this information].
• 23 leading food and drink companies, including Coca-cola, Mondelez International (formerly Kraft Foods UK), Nestle, Subway and the major retailers had already signed up to the calorie reduction pledge - making some strong commitments to cut and cap calories, as well as through promotional activity encouraging people to eat healthier foods.  The additional signatories bring the total to 31.
• 34 major alcohol companies have committed to removing a billion units from sale. The initiative, which includes major brands like Echo Falls, First Cape and Heineken will see a greater choice of lower strength alcohol products and smaller measures by 2015.

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