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In first-of-its-kind initiative, <keyword id="6356172" type="ORGANIZATION" weightage="80" keywordseo="Maharashtra-government">Maharashtra Government</keyword> is planning to introduce Key Result Areas (KRAs) for state’s bureaucrats to assess their performance, just like the private sector. 
 Maharashtra Chief Minister <keyword id="6355042" type="PERSON" weightage="80" keywordseo="Devendra-Fadnavis">Devendra Fadnavis</keyword> wants to give a corporate look to his government and ensure that top bureaucrats complete their projects on time. 
The Chief Minister wants to show that he means business and has told the babus that if targets are not met on time, it would reflect adversely on their Annual Confidential Records (ACRs) that determine their promotion and career progression. 
 
"We have a lot of projects and it's important that they are implemented in a time-bound manner. It will benefit more people if projects are completed within deadline, which is why we have set KRAs," he said. 
 
Economic Times had an access to the KRAs, which were finalised after Fadnavis held one-on-one meetings with the bureaucrats concerned. 
Another round to fine-tune KRAs to scheduled for May 27. 
 
State government officials said the government was also planning to shunt erring bureaucrats, if they failed miserably to meet their targets. 
 
Meanwhile, the Maharashtra CM said the babus received KRAs with enthusiasm and some even suggested that the current targets could be easily met. 
 
ET reported that the state government had set different targets for different departments. The housing department, for instance, has been set a target of building two lakh affordable houses every year in Mumbai. The home department has been given a task of taking Maharashtra's dismal conviction rate from about 13% to 50%. 
 
(Image: Indiatimes)

Now even babus will have to achieve KRAs for promotion

<div class="KonaFilter image-container display-table"><div><div class="image on-image">ReutersPharmaceutical companies have tried and failed to develop a drug that targets common mutations in the KRAS gene for three decades.</div></div></div><ul class="summary-list"><li>Pharmaceutical companies long wanted to develop a drug that would target KRAS, a common gene mutation seen in <a href="https://www.businessinsider.com/what-causes-cancer-food-products-that-increase-your-cancer-risk-2018-3">cancers</a>. But every effort so far has failed.</li><li>The pharmaceutical company <a href="https://www.amgen.com/">Amgen</a> and biotech <a href="https://www.mirati.com/">Mirati</a> are backing two new drugs that are raising those hopes again, though it's still early days.</li><li>If these experimental products are successful, they could rake in billions in sales and help patients with few treatment options. </li></ul>The pharmaceutical industry has spent 30 years and wasted billions of dollars chasing a type of cancer drug in a quest that some have declared impossible.Today, though, it's back, with two drugmakers racing to see if theirs is the winning approach. Though it's early days still, their focus and potential has the industry abuzz. There is "huge enthusiasm for figuring out how to drug that pathway," SVB Leerink analyst Andy Berens told Business Insider. He called this and another cancer-fighting approach "probably the silver bullet," adding that it "would be a tremendous victory for biotech and <a href="https://www.businessinsider.com/novartis-jay-bradner-on-cancer-drug-development-future-2019-1">oncology</a>, if it works."Behind all this is the KRAS gene, which works in the body as a traffic light that signals the go-ahead for cells to grow and change. Mutations in the gene, though, could turn cells cancerous - and give them the green light to grow explosively.Read: <a href="https://www.businessinsider.com/pfizer-strategy-in-cancer-drug-development-sales-2019-1">Pfizer has a new strategy for fighting cancer that could generate $5 billion a year. We got a look inside.</a>Indeed, KRAS mutations are common, seen in <a href="https://www.sciencedirect.com/science/article/pii/S0959804918308414">lung</a>, pancreatic and colorectal cancers, among others. Stopping that mechanism has been the aim of scientists for a long time, but their <a href="https://www.wsj.com/articles/SB10001424052970203764804577059841672541590">lack of success</a> has led many to think that it is "undruggable." One of those companies is also leading the renewed focus on KRAS: the $23 billion pharmaceutical company Amgen. Amgen has started testing its drug, AMG 510, in humans in a early-stage research trial, and initial results - expected this summer at a prominent <a href="https://meetings.asco.org/am/attend-meeting">cancer-research meeting </a>- are hotly awaited.If the drug is promising, Wall Street expects sales of at least $1 billion or $2 billion a year. The $2.5 billion biotech <a href="https://www.mirati.com/">Mirati Therapeutics</a> is also racing to develop its own <a href="https://www.mirati.com/mrtx849/">KRAS-targeting drug</a>, and its shares have surged nearly 65% since the start of the year, when Amgen began talking up the potential of AMG 510. Mirati hasn't yet tested its product in humans but isn't far behind, analysts say.<h2>A discovery made from a 'library' of new potential drugs</h2>Amgen believes that AMG 510 works in a unique way that makes it more powerful, and thus could set it apart from other, failed drug development efforts. The experimental drug came out of a <a href="http://carmot-therapeutics.us/2014/01/14/carmot-enters-into-collaboration-with-amgen/">collaboration</a> that the pharmaceutical company had with the Berkeley, California-based biotech Carmot Therapeutics, developing "libraries" of new molecules that could one day be new drugs. The companies focused that effort on a specific mutation, KRASG12C. Amgen estimates that it is a relatively common mutation, making up about 12% of all KRAS mutations across different types of "solid tumor" cancers. Amgen is interested in studying the drug in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817724/">lung cancer</a> and likely in colorectal cancer, as well as other solid tumors.What excited the company about AMG 510 was way it behaved with the protein, doing a type of dance that opened up a flap in the molecule and exposed a deep pocket.That pocket lets the drug get in, where it should be able to keep a firm hold and prevent KRAS from giving that "green light," explained Dr. PK Morrow, Amgen global product general manager and team lead for AMG 510.<h2>Potential in lung and colorectal cancers</h2>If it works, it could be an option for patients with <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329017/">non-small cell lung cancer,</a> the most common type, for example, as a second or third treatment option where "the options are often quite limited," Morrow said. "This has been a program that has created within our company such a sense of true excitement and gratification for being able to develop something that has the potential to help patients in such grievous need," Morrow told Business Insider. AMG 510 also has potential as a combination, Amgen believes, and is being studied in animal research with another Amgen drug, Vectibix, something that could potentially be used in colorectal cancer. But, like with all drug development, there's no guarantee that these results will be as promising in humans. And being able to block the KRAS pathway, meanwhile, "doesn't necessarily mean it'll translate to the tumor dying and patients having improved outcomes," SVB Leerink's Berens said. <ul class="read-more-links"><li>Read more:</li><li><a href="https://www.businessinsider.com/avexis-sma-gene-therapy-manufacturing-drove-9-billion-novartis-deal-2019-3">The top scientist at AveXis told us the 'unique' strength that powered its $9 billion sale to Novartis, and it could shape the future of gene therapy</a></li><li><a href="https://www.businessinsider.com/spark-bluebird-avexis-executives-on-safety-for-gene-therapy-companies-2019-3">Billions of dollars are pouring into gene-therapy startups. Top execs at 3 companies described the biggest challenge the new field faces.</a></li><li><a href="https://www.businessinsider.com/how-much-money-do-doctors-make-gender-pay-gap-doximity-study-2019-3">Here's how much money doctors across the US make, for doing everything from brain surgery to treating kids and people with cancer</a></li><li><a href="https://www.businessinsider.com/biogen-aducanumab-failure-alzheimers-cure-or-treatment-clinical-trial-cause-2019-3">Big Pharma has tried and failed to cure Alzheimer's more than 200 times. The latest $18 billion flop leaves scientists hunting for a new path forward.</a></li></ul> <div class="margin-top"> <h3>NOW WATCH: <a href="https://www.businessinsider.com/shaq-financial-advice-for-nba-players-money-personal-finance-investing-tips-million-savings-contract-2017-11">Shaq is joining the board of Papa John's - here's his simple piece of advice for NBA players who don't want to lose their millions</a></h3> <div> </div> </div>

A $23 billion drugmaker and a $2 billion biotech upstart are racing to develop a type of 'silver bullet' drug for aggressive cancers that has eluded their industry for 30 years

It’s the appraisal season and most of us will either going in for our performance review discussions or are already over with it. But before you get your letters, ensure you have followed a few basic rules to get the best of the <keyword id="6370334" type="UNKNOWN" weightage="20" keywordseo="appraisals">appraisals</keyword>. BI India gives you check-list of the things that should be done before their appraisals are done. 
	 
	Authentic performance discussions 
	 <keyword id="891494" type="PERSON" weightage="20" keywordseo="V-Suresh">V Suresh</keyword>, executive vice president and chief sales officer, <keyword id="218117" type="COMPANY" weightage="20" keywordseo="Naukri-com">Naukri.com</keyword> said that an employee must ensure that he has had authentic performance review discussions before the appraisals processes get over. “He should ensure that he has got an honest feedback from his supervisors and reporting manager about his performance,” he noted. 
	 
	Give honest feedback 
	 
	Not only is it important to get an authentic feedback for your work, it is equally important to share your feedback about the work environment constructively. An employee must talk about factors that affect his productivity. “Also, one must talk about his achievements as most often than not, reporting managers tend to forget an individual employees’ achievements as they are managing a team,” said Suresh. 
	 
	Market yourself well 
	 
	During an appraisal discussion, it is important to clearly mention the extra initiatives you have taken up during the year. “An employee is expected to do extra work apart from fulfilling his KRAs,” pointed out Suresh. Hence, take notes of all that you have done in the past year and bring them to your manager’s notice. 
	 
	Sync aspirations 
	 
	It is important to sync your professional goals with those of the organisation. Talk about what you want to do in the organisation and how you want to see your growth in the company. Do SWOT analyses of yourself, which will also help you understand what your goals are. Thus, you can clearly explain to the management on how you want to grow i 
	 
	Set realistic expectations 
	 
	In an appraisal, it is always best to set realistic expectations. Evaluate your work and accordingly set expectations and talk about them. It is important to remember that appraisals is not just given on the basis of on an individual’s performance but also on how the vertical and the company have performed overall. 
	 
	Representational Image

5 ways to derive the best results from your appraisal process

If you are a bit conscious about the global fashion industry you know how fast forward it is. Prior to six months, even before the season commences, the style is ready. That’s how it works everywhere. The runway trend of October will trickle down to the manufacturers in a month. And by March, the <keyword id="118206" type="PERSON" weightage="20" keywordseo="chanel">Chanel</keyword> sling bag that won loud applause at <keyword id="6355838" type="COMPANY" weightage="20" keywordseo="New-York">New York</keyword> in autumn will be sold at the retail outlets of <keyword id="6354539" type="COMPANY" weightage="20" keywordseo="Dubai">Dubai</keyword>. 
 
But did you ever wonder who are the brains behind the fashion at shows and stores? Where do these designers get ideas from? The designers conceptualize and design but there must be someone who ideates the outline. 
 
Meet trendsetter called WGSN or the World Global Style Network. With 350 plus staffs, and 14 offices including one in India, WGSN is the world’s leading trendsetter in fashion. 
 
The subscriber based business of WGSN has 70,000 members who are directly dependent on it for fashion trend alerts. Amongst the KRAs of WGSN are streamlining the patterns, colours, motifs of the season. So, the designers, colourists, merchandiser, all WGSN subscribers get to know about every aspect of fashion much ahead of time. 
 
The work culture of WGSN is also quite ahead of time. If you check with the senior editors of the company, you would know that for them its already the spring of 2018 when jute-soled espadrilles might be in style. 
 
Not only designers, WGSN’s major chunk of clientele also includes big brands in fashion. While the customers depend on blogs and magazines for fashion updates, brands rely on WGSN for similar reasons. 
 We chatted with Anupreet <keyword id="359486" type="PERSON" weightage="20" keywordseo="Bhui">Bhui</keyword>, Senior Editor, Street Style WGSN in India and this is what she has to say about Indian fashion. 
 
“More and more urban Indian youth is travelling, socially aware and well connected with antennas picking up trends all across the globe. Having said that, there is also an influx of foreign brands rapidly expanding in retail in the Indian domestic market. All these factors have actually enabled to shrink the gap and help align global trends increasingly with the Indian taste and style.” 
 
Fashion forecast for India 
“While Men’s silhouettes and fits move towards keeping in step with international trends, women explore styles that are definitely in tune with global trends but dialing down in terms of skin exposure,” Bhui told Business Insider. 
 
“India is a prints market with already a rich heritage of patterns and designs. The consumers love their prints that are alive. Floral, geometric leaning more towards a happier colour mix are mostly a preference. Indian consumers love colour. Saturated and bright hues always win with women,” she said.

Here's the secret company who decides what will be in fashion every
season

<ul class="summary-list"><li>A wildfire in Slovenia has set off many unexploded WW1-era ordnances, per reports.</li><li>There have been more than 500 detonations of unexploded ordnances, according to local media.</li></ul>The summer's <a href="https://www.insider.com/photos-show-how-people-are-dealing-with-european-heatwave-2022-7">unusually hot temperatures</a> have led to several wildfires across Europe and, according to <a href="https://www.vice.com/en/article/4axwe3/wildfires-are-setting-off-100-year-old-bombs-on-wwi-battlefields]">Vice World News,</a> they are setting off unexploded World War 1 bombs in the process.A wildfire in the southwest Kras region of Slovenia, which officials told <a href="https://www.vice.com/en/article/4axwe3/wildfires-are-setting-off-100-year-old-bombs-on-wwi-battlefields">The Washington Post</a> was the biggest since the country's independence in 1991, has destroyed more than 8,000 acres of farmland.It's also led to the explosion of countless WWI-era bombs, which had laid dormant for more than 100 years, per reports.<div type="image" title="A large wildfire burns near the village of Novelo in the Karst region of Slovenia." height="3000" width="3999" msid="93254407" hostid="261" sizebytes="2154992"></div>Darko Zonjič, the commander of Slovenia's explosive ordnance disposal unit, <a href="https://slovenia.postsen.com/news/15706/Already-14-tons-of-unexploded-ordnance-were-removed-from-the-Karst.html">told Slovenian media</a> that they've stopped counting the number of detonations of these historic ordnances because there have been so many. Officials are now only taking note of explosions taking place near roads, Zonjič said.It is estimated that, as of Thursday, there had been more than 500 detonations, according to local media.The unexploded ordnances, mostly underground, explode when they overheat due to the extreme rising of temperatures as a result of the fires.An incident on July 22 saw the heat from the raging fire set off an unexploded WWI-era bomb, launching shrapnel at nearby firefighters, per <a href="https://www.total-slovenia-news.com/news/10319-kras-fire-latest">local media.</a> Nobody was injured.Igor Boh, the deputy commander of the state explosive ordnance disposal unit, told Insider that six members of the team were present at the scene of the fire. They were directing firefighters on how to avoid accidents due to explosions, he said."The EOD State Unit was successful in this, as there were no injuries or casualties among the firefighters," Boh said.The unit has so far removed 821 pieces of explosive remnants of war, weighing 4,630 lbs, according to Boh.The danger of the fire setting off further unexploded bombs remains an issue and people are warned against walking on the land near the wildfire, said Slovenia's defense minister Marjan Šarec, according to local media.The site of the wildfire was where the Battles of the Isonzo, a series of 12 battles between the Austro-Hungarian and Italian armies in WWI, took place. More than 200,000 people died there between 1915 and 1917.Leftover unexploded ordnances cause problems for countries for a long time after the wars come to an end, as is the case in Slovenia, <a href="https://taskandpurpose.com/news/this-world-war-i-battlefield-slovenia-fire-unexploded-ordnance/">Task &amp; Purpose reported.</a>Guy Momper, a bomb clearance specialist, <a href="https://www.reuters.com/article/us-ww1-century-bombs/a-century-on-from-ww1-100-years-of-work-remains-to-clear-munitions-idUSKCN1N40TS">told Reuters</a> that it could take more than 100 years to clear all WWI-era munitions from former European battlefields.

Wildfires are setting off hundreds of unexploded bombs on WWI battlefields, endangering firefighters

<div class="KonaFilter image-container display-table"><div><div class="image on-image">ArvinasThe biotech Arvinas focuses on targeted protein technology. Started by a founder of the field, it was the first to begin testing the tech in a research trial in humans.</div></div></div><ul class="summary-list"><li>A new technology could revolutionize how everything from Alzheimer's disease to autoimmune diseases and cancer are treated.</li><li>Cancer has become an early focus for the technology, called targeted protein degradation or PROTAC, because there are many well-known drivers of cancer that modern medicine hasn't been able to reach. </li><li>At least $1 billion has been invested in the space by big pharmaceutical companies like <a href="https://www.novartis.com/stories/discovery/novartis-and-uc-berkeley-take-undruggable-proteins-new-collaboration">Novartis</a> and <a href="https://www.kymeratx.com/2018/04/04/kymera-therapeutics-announces-discovery-collaboration-gsk-advance-new-treatment-modality/">GlaxoSmithKline</a> and biotech startups alike, one expert estimates. </li><li><a href="https://www.businessinsider.com/?hprecirc-bullet">Visit Business Insider's home page for more stories.</a></li></ul>An experimental technology that's been under development for almost two decades could upend treatment for conditions ranging from Alzheimer's to lung diseases. First, it's coming for cancer. Called targeted protein degradation or PROTAC, the tech is promising because it gives scientists new tools to destroy disease-causing agents, clearing them from the body. In cancer, that could put targets so elusive they've been dubbed "undruggable" and even the "Holy Grail" within reach. Cancer will be a crucial testing ground for targeted protein degradation, which has only recently been tried in humans. There aren't yet any treatments based on the technique, though <a href="https://www.scientificamerican.com/article/new-thalidomide-like-therapy-hijacks-cells-trash-disposal-system/">one decades-old drug</a> used to treat cancer was recently discovered to work in a similar way. Roughly 30 companies are investing in the technology, including big pharmaceutical firms like <a href="https://www.novartis.com/stories/discovery/novartis-and-uc-berkeley-take-undruggable-proteins-new-collaboration">Novartis</a>, <a href="https://www.kymeratx.com/2018/04/04/kymera-therapeutics-announces-discovery-collaboration-gsk-advance-new-treatment-modality/">GlaxoSmithKline</a>, <a href="https://www.roche.com/research_and_development/what_we_are_working_on/oncology/aacr_2016/molecular_targeted_therapy.htm">Roche,</a> and <a href="https://www.boehringer-ingelheim.com/press-release/boehringer-ingelheim-and-university-dundee-collaborate">Boehringer Ingelheim</a> and biotech upstarts. Excitement runs so high because the tech could vanquish the traditional limitations of making new drugs, opening up new possibilities, experts say."I would say that it is unlimited. And thats why I think there's so much interest in this field, is that it can be applied to so many different exciting proteins that heretofore have not been druggable," <a href="http://crewslab.yale.edu/people/craig-crews-biosketch/">Craig Crews</a>, the Yale professor who pioneered the field, told Business Insider. Cancer "is the first one out of the gate," he said. Not all the deals and rounds of funding around the cutting-edge field have been disclosed, so it's hard to say exactly how much is being invested.All told, the area has attracted "easily over a billion dollars," estimated <a href="http://arvinas.com/team/randy-teel-ph-d/">Randy Teel,</a> vice president of corporate development at protein-degradation-focused biotech Arvinas. Crews founded Arvinas and serves as chief scientific advisor. Read more: <a href="https://www.businessinsider.com/new-medicine-tech-backed-by-novartis-johnson-and-johnson-has-big-potential-2019-4">Pharma giants Novartis and J&amp;J are putting their might behind 2 new technologies that could transform how we treat cancer and obesity</a><h2>Zooming in on cancer</h2><div class="KonaFilter image-container display-table"><div><div class="image on-image">Arvinas</div></div></div><a href="https://www.businessinsider.com/amgen-and-mirati-cancer-drug-push-despite-kras-failures-2019-4">KRAS</a>. Myc. Beta-catenin.In cancer, these are notorious names, just a few of many well-known drivers of cancer. But they have also long been <a href="https://www.businessinsider.com/amgen-and-mirati-cancer-drug-push-despite-kras-failures-2019-4">unreachable</a> by modern medicine. Protein degradation could change that, in the process transforming the way that cancer is treated. Most medicines that you take work in a similar way against disease. Imagine a light switch on a wall. A drug for high blood pressure, for instance, would switch "off" the bodily mechanisms driving the condition. In cancer, similarly, a drug might suppress proteins known to cause the disease. But that switch model sets a high bar for potential new drugs. The approach doesn't always work fully, and there's plenty that scientists haven't been able to reach, in cancer and beyond. "Therefore, why don't you just eliminate the switch, and rip out the wiring altogether?" Yale's Crews explains.Targeted protein degradation aims to do just that, tossing disease-causing proteins into the trash cans that naturally exist within our cells. Obvious targets for that process are mutations in special proteins called transcription factors, because they are known to cause cancer. Drugs that employ targeted protein degradation could get rid of the mutated proteins.Working there "would be an awesome way to treat many different diseases. This has been borne out many times," <a href="https://www.linkedin.com/in/john-tallarico-chemicalbiology/">John Tallarico</a>, site head of the chemical biology and therapeutics department at Novartis Institutes for BioMedical Research, told Business Insider. Scientists haven't been able to affect this process with chemically-made pills. So drug companies have been increasingly looking to more complex medicines. <div class="KonaFilter image-container display-table"><div><div class="image on-image">Yutong Yuan/Business Insider</div></div></div>Among the startups researching protein degradation are <a href="https://www.kymeratx.com/">Kymera</a>, which has raised $95 million from investors like <a href="https://atlasventure.com/">Atlas Venture</a>, Pfizer Ventures, Amgen Ventures and Lilly Ventures; <a href="http://www.vividion.com/">Vividion Therapeutics</a>, which is valued at $295 million, and <a href="https://www.nurixtx.com/">Nurix</a>, valued at $227 million.Novartis's Tallarico tells an illustrative story about why so many are betting on protein degradation. Five years ago, Novartis scientists came up with a list of around 20 targets that they wanted to develop drugs for. At the time, he figured that it would take a decade just to develop a drug for one of the 20 targets. Yet just five years later, thanks to the advent of protein degradation technology, he says Novartis might be able to find drugs for all 20.The jury is still out on whether this approach will work, with drugs only beginning to get tested in humans. "Could this perhaps provide a therapeutic solution for these aggressive cancers? There is exciting potential, but time will tell," said <a href="https://secure-web.cisco.com/1A-Qzo-y-znwb2JQvYEbOuu6kU1dsLpnzn9xghzdFoy5MeHs3CDuhLOriPEH1QKL-FczGusMemBzIgwiQxSGf3T-KvthfjlP-wZETJ5BwEqJlK6Zmt3LlMej_sXxgYK1XB48CjudyYby6oVnrDPsDoO3UPAcdaGau9s-cxvRcDi4ignaXkWe2wbCPT4OafN5fTUn5wtEWo7bUAzyqDSFf2UM7nDHTwMjkfmP4gAsO9l-JOwhOteS9FIXTlRfRX9EvPTvxn1aiSgJsIG2SEENfrjmrrNDrDyvVuMDz36CbxWaq-RQvRml10Av0vg5A3VzcWHS-KFjJMCWF4lnclYxYM7_JOcw2ma7mD0PUH3H6KLIe-FKgCVV5Pv4i_fuVFKCE1s8oqHmFttz7evQ2gzqVTw9XGa7F_OEuzuJvm9RsN--kxm3tRr2ktlMDSP_CXO2z4rq5yRIgbO5fqW3qUeBgh4gmEivNFpWUecBckTsu-AE/https%3A%2F%2Fwww.cancer.org%2Fresearch%2Facs-researchers%2Flynne-elmore-bio.html" target="_blank" rel="noopener" data-saferedirecturl="https://www.google.com/url?q=https://secure-web.cisco.com/1A-Qzo-y-znwb2JQvYEbOuu6kU1dsLpnzn9xghzdFoy5MeHs3CDuhLOriPEH1QKL-FczGusMemBzIgwiQxSGf3T-KvthfjlP-wZETJ5BwEqJlK6Zmt3LlMej_sXxgYK1XB48CjudyYby6oVnrDPsDoO3UPAcdaGau9s-cxvRcDi4ignaXkWe2wbCPT4OafN5fTUn5wtEWo7bUAzyqDSFf2UM7nDHTwMjkfmP4gAsO9l-JOwhOteS9FIXTlRfRX9EvPTvxn1aiSgJsIG2SEENfrjmrrNDrDyvVuMDz36CbxWaq-RQvRml10Av0vg5A3VzcWHS-KFjJMCWF4lnclYxYM7_JOcw2ma7mD0PUH3H6KLIe-FKgCVV5Pv4i_fuVFKCE1s8oqHmFttz7evQ2gzqVTw9XGa7F_OEuzuJvm9RsN--kxm3tRr2ktlMDSP_CXO2z4rq5yRIgbO5fqW3qUeBgh4gmEivNFpWUecBckTsu-AE/https%253A%252F%252Fwww.cancer.org%252Fresearch%252Facs-researchers%252Flynne-elmore-bio.html&amp;source=gmail&amp;ust=1557319059197000&amp;usg=AFQjCNEdHPztoF46oNheZkkS2NyBinpazQ">Lynne Elmore,</a> who is director of the Translational Cancer Research program at the American Cancer Society and has a doctorate in pathology. The cancer nonprofit recently awarded Crews a prestigious ACS Research Professorship.<h2>Why a startup founded with this tech didn't start with 'undruggables'</h2>Founded in 2013 to focus on protein degrader development, Connecticut-based biotech Arvinas is the first to test it out in humans, to treat prostate cancer.You might think, then, that the biotech is focused on cancer mutations that medicine traditionally hasn't been able to touch. Those "undruggable" targets include KRAS, Myc, and Beta-catenin.But instead, Arvinas sidestepped them, at least in the beginning. Venturing out on into uncharted territory would have been too risky for initial tests of the technology, two top leaders explained to Business Insider.Instead, Arvinas' drugs are focused on the androgen and estrogen receptors, two well-established places where a signaling process gone awry can lead to cancer.For the company, there was "some temptation to go after the undruggables" first, said <a href="http://arvinas.com/team/ian-taylor/">Ian Taylor,</a> the biotech's chief scientific officer. But these are "clinically validated by drugs that have been working for a long time. These targets have been validated for decades." And "because the industry has never been able to effectively inhibit [undruggables], we don't really know what will happen when we destroy the protein," Teel said. "But obviously we are all excited to find out."The biotech probably won't say which of those more challenging targets it's working on publicly until next year, Teel said. <div class="margin-top"> <h3>NOW WATCH: <a href="https://www.businessinsider.com/game-of-thrones-dragons-fly-real-life-2019-5">Why the 'Game of Thrones' dragons wouldn't fly in real life</a></h3> <div> </div> </div>

Scientists are working on cancer treatments that attack the disease's 'Holy Grail.' Big pharma and biotechs have already invested more than $1 billion.

<div class="KonaFilter image-container display-table"><div><div class="image on-image">Hollis Johnson/Business Insider</div></div></div>Hello,Welcome to Dispensed, our weekly newsletter recapping all the big healthcare stories that kept our team busy this week. For those who are new to the newsletter, I'm <a href="https://www.businessinsider.com/author/lydia-ramsey">Lydia Ramsey</a>, a senior reporter here on the team. I'm curious to hear what you all think of <a href="https://www.businessinsider.com/insulin-diabetes-program-from-cigna-express-scripts-offers-25-price-2019-4">Cigna and Express Scripts' program that caps a 30-day supply of insulin</a> at $25 for patients. How many plans will pick this up? How many patients will this impact? I guess time will tell. It'll also be interesting to see how the healthcare industry taps into Alexa now that Amazon's <a href="https://www.businessinsider.com/amazons-alexa-adds-healthcare-skills-2019-4">voice assistant is HIPAA compliant</a>. Would you want to set up an appointment or give your doctor an update via the Echo Dot in your living room?One thing to keep an eye on: the FDA is holding a hearing about cannabis next month. One day, it <a href="https://www.businessinsider.com/are-cbd-cannabis-foods-drinks-legal-maybe-fda-2019-4">might be legal</a> to make foods and drinks with certain levels of the cannabis extract CBD, at least according to <a href="https://www.businessinsider.com/are-cbd-cannabis-foods-drinks-legal-maybe-fda-2019-4">a recent note</a> from outgoing FDA Commissioner Scott Gottlieb.New to our newsletter? You can <a href="http://newsletter.businessinsider.com/join/4np/health-insider&amp;hash=f4e91136c13f3c40c496d77bc7347502">subscribe here</a>.<a href="https://www.businessinsider.com/author/erin-brodwin">Erin Brodwin</a> had the story on the newest test out using the Helix DNA kit. It looks at risk of some of the same conditions 23andMe looks at, but includes genetic counseling and requires a doctor's sign-off. Here's what you need to know about it. <h3><a href="https://www.businessinsider.com/helix-new-genetics-dna-health-test-breast-cancer-cholesterol-2019-3">A Silicon Valley startup just launched a DNA-based health test that could be a big competitor to 23andMe</a></h3><ul><li>On Tuesday, DNA testing startup Helix launched a new test that looks at your risk of diseases like breast cancer, colon cancer, and high cholesterol.</li><li>You can buy the test online for $260, but it must be approved by a physician.</li><li>Helix partnered with clinical diagnostics company PerkinElmer to create the test, which includes genetics counseling.</li><li>The test also uses a type of sequencing that some experts say all DNA-based health tests should use.</li></ul>I had the scoop on venture-backed health insurer Bright Health's 2019 enrollment and revenue expectations. Those numbers, and the company's 2018 results based on regulatory filings, suggest that the insurer is managing to double its footprint every year (its first year offering plans was 2017). So far, it's been holding losses steady. <h3><a href="https://www.businessinsider.com/bright-health-insurance-startup-financial-results-aca-medicare-advantage-2019-3">We got a look at the 2019 plans for venture-backed health-insurance startup Bright Health, which says it doubled its membership again</a></h3><ul><li>Bright Health, the Minneapolis-based health-insurance startup that provides health plans for individuals and families and to seniors, made $145 million in gross revenue in 2018, its second year offering health plans.</li><li>According to state filings, Bright lost $17.5 million in 2018, the same as in 2017. At the same time, it doubled its membership base to more than 24,000 from 12,000.</li><li>Bright Health CEO Bob Sheehy told Business Insider the company expected to jump to about $400 million in revenue for 2019 and had signed on more than 60,000 members.</li></ul>And if you need a recap of how all the health insurance startups fared in 2018 and what's ahead for 2019 and 2020, I've got you covered.<div class="KonaFilter image-container display-table"><div><div class="image on-image">Bright Health; Alex Wong/Getty; Clover Health; Oscar Health; Shayanne Gal/Business InsiderBright Health CEO Bob Sheehy, Devoted Health co-founder and executive chairman Todd Park, Clover Health CEO Vivek Garipalli, and Oscar Health CEO Mario Schlosser.</div></div></div><h3><a href="https://www.businessinsider.com/health-insurance-startups-clover-oscar-bright-devoted-annual-results-projections-2019-4">Health-insurance startups like Oscar Health and Clover Health have raked in $1.3 billion in the past year. We took a look at their financials, which show how hard it is to get a foothold in the industry.</a></h3><ul><li>Startups have attracted massive funding in the past few years to build new kinds of health-insurance plans - with the help of technology.</li><li>In the past year, four companies in particular - Oscar Health, Devoted Health, Bright Health, and Clover Health - brought in a combined $1.3 billion in funding.</li></ul><a href="https://www.businessinsider.com/author/emma-court">Emma Court</a> has the story of the race to successfully develop a cancer drug targeting the KRAS mutation. <h3><a href="https://www.businessinsider.com/amgen-and-mirati-cancer-drug-push-despite-kras-failures-2019-4">A $23 billion drugmaker and a $2 billion biotech upstart are racing to develop a type of 'silver bullet' drug for aggressive cancers that has eluded their industry for 30 years</a></h3><ul><li>Pharmaceutical companies long wanted to develop a drug that would target KRAS, a common gene mutation seen in cancers. But every effort so far has failed.</li><li>The pharmaceutical company Amgen and biotech Mirati are backing two new drugs that are raising those hopes again, though it's still early days.</li><li>If these experimental products are successful, they could rake in billions in sales and help patients with few treatment options. </li></ul>Emma also chatted with the top scientist at AveXis, which Novartis acquired last year. He broke down why the Swiss pharma giant was so interested in the gene-therapy maker.<h3><a href="https://www.businessinsider.com/avexis-sma-gene-therapy-manufacturing-drove-9-billion-novartis-deal-2019-3">The top scientist at AveXis told us it got sold to Novartis for $9 billion because of this 'unique' strength that could shape the future of gene therapy</a></h3><ul><li>The biotech AveXis develops cutting-edge "gene therapy" products that could be powerful and long-lasting medical treatments.</li><li>Swiss drug giant Novartis bought the biotech for $9 billion last year in part because AveXis had figured out how to actually make gene therapies at a big-enough scale, AveXis Chief Scientific Officer Brian Kaspar told Business Insider.</li><li>Manufacturing has emerged as a huge challenge for the booming industry because these products are so new and complex.</li></ul>And for those just catching up on Thursday's lawsuit - Emma broke down the significance of the dispute between Amgen and Novartis over their new migraine drug, Aimovig. <h3><a href="https://www.businessinsider.com/novartis-amgen-aimovig-migraine-lawsuit-shows-future-of-cgrp-drugs-2019-4">2 drug giants are feuding over a highly successful new migraine drug, and court documents reveal how profitable the $10 billion market could be</a></h3><ul><li>Two drugmakers, Amgen and Novartis, have worked together for years on a new type of cutting-edge migraine drug, Aimovig.</li><li>Now they're involved in a bitter fight. Amgen is trying to get out of the collaboration, while Novartis is suing Amgen to keep it in place.</li><li>Aimovig costs roughly $7,000 a year and was the first of a new category of migraine drugs to get to market. The lawsuit provides a window into how successful it has been and how much Novartis stands to lose in the disagreement. </li></ul>Out on the West Coast, Erin took a look at a startup coming out of Y Combinator that wants to crack the male birth control market. <h3><a href="https://www.businessinsider.com/male-birth-control-startup-backed-y-combinator-your-choice-therapeutics-2019-4">A Berkeley-stacked startup backed by Silicon Valley's top tech hub is developing male birth control that experts call promising</a></h3><ul><li>A new startup called Your Choice Therapeutics aims to bring the first hormone-free male and female birth control drug to market.</li><li>The company debuted at a recent demo day hosted by Silicon Valley tech hub Y Combinator.</li><li>Stacked with researchers from UC Berkeley, the startup has published several basic studies in top-notch <keyword id="41551" type="ENTERTAINMENT" weightage="100" keywordseo="science">science</keyword> journals.</li><li>Still, the field of male birth control is a tough nut to crack, and the company faces challenges.</li></ul>For those eager to hear what comes out of the PBM grilling next week in the Senate, we'll be following along. Find <a href="https://twitter.com/emmarcourt">Emma</a> and <a href="https://twitter.com/lydiaramsey125">me</a> on Twitter, where I'm sure we'll post some live updates.In the meantime, be sure to send tips, thoughts, and ideas for how you'd use now-HIPAA-compliant Alexa to lramsey@businessinsider.com, or you can find the whole healthcare team at healthcare@businessinsider.com. - Lydia <div class="margin-top"> <h3>NOW WATCH: <a href="https://www.businessinsider.com/new-york-city-cockroaches-rats-mice-exterminator-places-avoid-infestation-2019-3">Your apartment location can affect how cockroaches, rats, and mice get in. A New York City exterminator told us the places he'd never live.</a></h3> <div> </div> </div>

Dispensed: Venture-backed insurance startup Bright Health's 2018 results, a dispute between 2 drug giants, and the quest for a male birth control drug

It is a huge challenge to get excellent professionals managers to leave large companies and join startups. Good people are needed by a startup but they won’t join easily. Such managers are generally poor risk takers and only when they see stability in a company and they see other professional managers making this leap of faith do they agree to make a change. 
 
While it must always be the objective of every entrepreneur who is working towards building a big business on a national level to bring in strong professionals and gradually handover the operations of the company to such professionals, the timing of bringing in these professionals has to be right. The entrepreneur must outline his philosophy for the Human Resources function not just in words but also in deeds because this is what will set the management culture of the company. 
 
The human resource function of any company can make or break a company since the employees are ambassadors of the company and and your “face” in front of your customers. Therefore this function must have a strong leader and must have complete support of the entrepreneur. 
 
Some guiding human resources principles that the entrepreneur should consider establishing very early in the company’s journey are: 
 
• The company should rapidly move towards professional management and that not build a family run organisation. 
 
• Professional growth must be based on meritocracy and not based on relationships with the entrepreneur or some senior member of management or patronage 
 
• Any relationships between managers would need to be disclosed at the time of hiring and approved by the management committee of the company. It should also specified that two managers who are related would not be allowed to work in the same department. 
 
• Performance management must be done based on agreed and quantifiable key result areas for each manager 
 
• Salary increases would be based on achievement of results and not based on seniority and definitely not based on relationships. 
 
In large established companies, HR policies are followed by everyone because “everyone else” follows them and no one asks for any exceptions to be made. However in a new company, most new employees try and implement policies they have either seen in use elsewhere or want to get implemented for their own personal needs. 
 
The entrepreneur must make it clear to everyone that the company will implement policies for employees that the entrepreneur is willing to accept himself. He must take a decision to abide with the policies articulated by the Human Resources department of the company, and approved by the board, in their entirety so that there would no exceptions. 
 
1. He must start marking his attendance on the biometric finger print reader every morning and evening like he would expect all employees to do. 
 
2. Leave should be applied for in the standard company approved application form. This must apply to the entrepreneur as well. 
 
3. Ensure that no special discounts are offered to the entrepreneur that the other employees are not entitled to. Obviously, these can be graded based on seniority but the principle must be transparent for all to understand. 
 
4. If the entrepreneur calls for any samples to be given out as gifts, these should be duly authorised as is done for all other managers. 
 
5. All the expense claims of the entrepreneur must be approved by another board member as is the practice followed in the company. 
 
6. For gifts received by employees, some companies fix a limit beyond which all gifts need to be handed over to the Human Resources manager. These gifts are then given away to all staff members through a raffle either on the annual day or in a town hall meeting. 
 
Only when people start to see the entrepreneur following the companies’ policies will they start accepting these and started adhering to them. If the entrepreneur does not follow these policies then it will take a very short time before all management levels will start to build exceptions for themselves. 
 
Establishing the key result areas, quantifying these and getting the “buy in” from the respective managers is a big challenge the human resources function is confronted with in every new company. Getting people to sit down and make a commitment to accountable and measurable parameters was tough since most people did not want to be pinned down to a set of numbers they would be held accountable for. 
 
It can take several years and constant cajoling to get managers to start making this commitment for themselves based on which they would set similar KRA’s for their teams. This cannot be done though a directive because the entrepreneur is always worried about losing key managers and therefore he needs to constantly live on the edge of the razor! 
 
While it is important to professionalise a startup company quickly, handing over the reins of the company and stepping back should only be done by an entrepreneur when the organisation has built sufficient resilience to handle changes that a professional manager is bound to bring in for the long term good of the company. 
 
Good policies coupled with firm implementation could mean that your young company will need to keep hiring better and better people to keep upgrading your skill sets. This will also result in a higher than normal turnover in your management ranks but this is to be expected and must not be a reason for any concern. It is better to lose those employees who find it difficult to accept the company’s policies rather than allow them to develop arbitrary policies and norms for employees. Over a period of time, the management team will stabilise. 
 
In summary, motivation of human beings in a startup must be a fire from within. If someone else tries to light that fire under the employee, chances are that this fire of motivation will burn very briefly. 
 
(Image: Thinkstock)

These are few HR principles that every entrepreneur should consider while launching startup

<ul class="summary-list"><li>The business of developing new drugs faces two "existential challenges," Amgen's research chief David Reese told Business Insider in a recent interview.</li><li>Those are: How long it takes to take a drug from idea to approval, and the high failure rates for therapies that start human trials, said Reese. He took charge of the $130 billion biotech's research strategy in 2018.</li><li>"It has to change, therefore it will," Reese said on the low success rate of drugs, where about 8% that enter clinical testing are eventually approved. "Because, realistically, the only alternative is extinction."</li><li>In light of these problems, Amgen has recently narrowed its research focus, backing away from the areas of neuroscience, kidney disease, and bone health.</li><li>Instead, Amgen is investing in genetics, with a "triple threat" approach to understand disease and craft better treatments. "We want to load the dice," Reese said, on boosting success rates with this approach.</li><li><a href="https://www.businessinsider.com/?hprecirc-bullet">Visit Business Insider's homepage for more stories</a>.</li></ul>The drug industry is facing two existential challenges in developing new treatments, according to Amgen's top research exec: the process takes too long and the drugs fail too often.Roughly one in 10 drugs that enter clinical testing <a href="https://www.policymed.com/2014/12/a-tough-road-cost-to-develop-one-new-drug-is-26-billion-approval-rate-for-drugs-entering-clinical-de.html">eventually make it to market</a>, and those that do typically take <a href="https://www.nature.com/articles/nrd3078">12 to 14 years</a> to go from idea to approved drug. "We can't go on like that," David Reese, Amgen's executive vice president of research &amp; development, said in a recent interview with Business Insider.Reese is far from alone - these are well-recognized problems facing the industry. The biggest pharmas have seen returns on their research and development spending plummet over the past decade, from 10% in 2010 to 2% in 2019, <a href="https://www2.deloitte.com/us/en/pages/life-sciences-and-health-care/articles/measuring-return-from-pharmaceutical-innovation.html">according to Deloitte research</a>. The consultancy said it costs about $2 billion to bring a single drug to market."It has to change and therefore it will," Reese added on the low success rate of drug development. "Because realistically the only alternative is extinction."Never miss out on healthcare news. <a href="http://newsletter.businessinsider.com/join/health-insider">Subscribe to Dispensed</a>, our weekly newsletter on pharma, biotech, and healthcare.In response, the world's largest biotech has narrowed its research strategy under Reese, focusing in on three areas: cancer, heart disease, and inflammation.The California biotech is still selling some treatments for kidney disease, bone health, and brain disorders, and may also make deals to acquire new treatments in those areas. But it won't focus on finding new treatments in those areas in its own labs, Reese said. He said the company just doesn't have a strong enough understanding of the biology underlying those disease areas to make it worthwhile.<h2>'Loading the dice' with genetics</h2>To tackle the big R&amp;D challenges facing the drug industry, Amgen has been building up its expertise in genetics. "The use of genetic and allied technologies is really meant in many ways to address the success rate," Reese said. "We want to load the dice."The R&amp;D head called it a "triple threat" approach: building a foundation of genetic data, using biology to turn that data into targets for treatments and a better understanding of how diseases work, and then crafting drugs to target those areas using molecular engineering.While several large drugmakers are taking similar steps in genetics, Amgen's partnerships make it unique, Reese said. To build its genetic database, Amgen <a href="https://www.decode.com/amgen-to-acquire-decode-genetics-a-global-leader-in-human-genetics/">agreed to acquire deCODE Genetics</a> in 2012. Back then, the Icelandic company had sequenced about 3,000 whole genomes in total. Now, the subsidiary is sequencing more than 10,000 each month and has built a database of 1.5 million participants, Reese said.<h2>Amgen is using deals and partnerships to get access to more genetic data</h2>Two new partnerships inked in 2019 will add one million more genomes over the next few years: Amgen is one of four companies working with the UK government to sequence 500,000 participants. And the biotech also struck a <a href="https://wwwext.amgen.com/media/news-releases/2019/06/intermountain-healthcare-and-decode-genetics-launch-groundbreaking-dna-study-of-500000-people-to-find-new-links-between-genetics-and-disease/">deal with the Utah health system Intermountain Health</a> to provide another half a million genomes."At that point, we will largely have the scale we're interested in," Reese said.The next step is adding depth beyond genetics: large-scale studies of proteins and RNA molecules. deCODE is working with a Colorado-based protein specialist called SomaLogic to run experiments collecting massive amounts of protein measurements.One ongoing experiment, for instance, is collecting 5,000 protein measurements from 40,000 people, Reese said, totaling 200 million data points from that one effort.Traditional analytic tools won't be sufficient for this massive data effort, Reese said, inevitablly putting AI and machine learning in Amgen's future. While the big biotech has stayed out of gene therapy so far, Reese called it "inevitable" that Amgen will eventually enter the burgeoning space. He said he is waiting for when these one-time treatments show the ability to go beyond treating rare diseases."Gene therapy now tends to be very focused," he said. "Eventually, it will develop into platforms that are more widely applicable. For me, that's where I am probably going to likely make a move."<h2>Speeding up success </h2>While the moutain of genetic data accumulates and theoretically boosts Amgen's chances of success in drug development, Reese is also attempting to speed up the process.A few years ago, he led an effort at Amgen to map out in fine detail all the steps in taking a drug from an idea to a marketed product. The goal was to answer the question: what is the speed of drug R&amp;D? The end result was a playbook to shave as much time as possible off of the drug development process. Now, Reese said the California biotech has begun to do that. An Amgen spokesperson confirmed this is in place for one of its most valuable experimental drugs, AMG 510, which targets a mutation to a gene called KRAS that causes cancer. "In a number of our programs, we think we're probably on track to take up to three years out of that process," he said. "That's a lot. I think we can do better. So we're continuing to strive for, and iteratively learn, how we can reduce that cycle time going forward."<ul class="read-more-links"><li>Read more:</li><li><a href="https://www.businessinsider.com/amgen-and-mirati-cancer-drug-push-despite-kras-failures-2019-4">A $105 billion drugmaker and a $3 billion biotech upstart are racing to develop a type of 'silver bullet' drug for aggressive cancers that has eluded their industry for 30 years</a></li><li><a href="https://www.businessinsider.com/why-gsk-invested-300-million-in-23andme-genetic-drug-discovery-collaboration-2018-7">Why pharma giant GSK just made a $300 million bet on 23andMe's approach to finding new medicines</a></li><li><a href="https://www.businessinsider.com/bezos-startup-gilead-nash-liver-drugs-insitro-2019-4">A Jeff Bezos-backed startup just inked a deal with $84 billion biotech Gilead to make drugs for a troubling and increasingly common disease</a></li><li><a href="https://www.businessinsider.com/biggest-healthcare-and-biotech-developments-of-the-decade-2019-12">From Obamacare to cancer cures, here are the advances that defined the decade, according to top healthcare leaders who worked for Trump, Obama, and Bush</a></li></ul><a href="/intelligence/digital-health?IR=T&amp;itm_source=businessinsider&amp;itm_medium=ctgr_bii&amp;itm_term=ctgr_subscription&amp;itm_content=health&amp;itm_campaign=digital-health"></a>Featured Digital Health Articles: - <a href="/telehealth-industry-explained">Telehealth Industry: Benefits, Services &amp; Examples</a> - <a href="/value-based-care-pay-for-performance-healthcare-model">Value-Based Care Model: Pay-for-Performance Healthcare</a> - <a href="/senior-care-market-trends">Senior Care &amp; Assisted Living Market Trends</a> - <a href="/wearable-technology-healthcare-medical-devices">Smart Medical Devices: Wearable Tech in Healthcare</a> - <a href="/artificial-intelligence-healthcare">AI in Healthcare</a> - <a href="/remote-patient-monitoring-industry-explained">Remote Patient Monitoring Industry: Devices &amp; Market Trends</a>

The man in charge of discovering new drugs at the world's biggest biotech told us how Amgen's 'triple threat' genetics approach can overcome the industry's high failure rates

<div class="KonaFilter image-container display-table float_right"><div><div class="image">Bill Pugliano/Getty Images</div></div></div>Here's a big, juicy M&amp;A story to get the market excited on a Monday morning.
Pharmaceutical giant Pfizer has said in a new press release that it has approached UK pharmacuetical maker AstraZeneca about a $100 billion takeover offer, but that AstraZeneca so far has shown no interest in doing a deal.
Pfizer made the announcement in a press release, indicating that earlier discussions had ended in mid-January, and that Pfizer tried to engage in new discussions on April 26, but to no avail.
Shares of AstraZeneca are surging 15% this morning.
In the announcement, which you can read below, Pfizer says the deal would have benefits in terms of distribution brand, and improving the company's product portfolio.
Pfizer will hold a conference call later this morning to discuss the proposal.
--------------------------------------------------------------
Pfizer Inc. confirms that it previously submitted a preliminary, non-binding indication of interest to the board of directors of AstraZeneca in January 2014 regarding a possible merger transaction. After limited high-level discussions, AstraZeneca declined to pursue negotiations. The discussions were discontinued on 14 January 2014 and Pfizer then ceased to consider a possible transaction. In light of recent market developments, Pfizer contacted AstraZeneca on 26 April 2014 seeking to renew discussions in order to develop a proposal that could be recommended by both companies to their shareholders. AstraZeneca again declined to engage. Pfizer is currently considering its options with respect to AstraZeneca.
Pfizer's previous proposal made to the board of AstraZeneca on 5 January 2014 included a combination of cash and shares in the combined entity which represented an indicative value of £46.61 ($76.62)1 per AstraZeneca share and a substantial premium of approximately 30% to AstraZeneca's closing share price of £35.86 on 3 January 2014.
As in its previous proposal, Pfizer is considering a possible transaction in which AstraZeneca shareholders would receive a significant premium for their AstraZeneca shares, to be paid in a combination of cash and shares in the combined entity. Pfizer believes that a transaction, if proposed and consummated, would offer AstraZeneca shareholders a highly compelling opportunity to realise a significant premium to the undisturbed AstraZeneca share price as of 17 April 2014, which includes a substantial cash payment. AstraZeneca shareholders would become significant shareholders in the combined company and participate in significant value creation opportunities, including benefiting from the potential growth opportunities and operational and financial synergies that the combination of two complementary global pharmaceutical companies would be expected to generate. Pfizer is confident a combination is capable of being consummated. The transaction, if consummated, is expected to result in the combination of the two companies under a new U.K.-incorporated holding company. As a global corporation, Pfizer would expect the combined company to have management in both the United States and the United Kingdom, and to maintain head offices in New York and list its shares on the New York Stock Exchange.
The making of any firm offer by Pfizer would be subject to the following pre-conditions (which may be waived in whole or in part by Pfizer):
<ul id="yui_3_9_1_1_1398672260981_1523">
<li id="yui_3_9_1_1_1398672260981_1522" class="bwlistitemmargb">satisfactory completion of a customary due diligence review by Pfizer;</li>
<li class="bwlistitemmargb">unanimous recommendation by the directors of AstraZeneca to vote in favour of the combination; and</li>
<li class="bwlistitemmargb">the directors of AstraZeneca giving irrevocable undertakings to accept any offer in respect of their AstraZeneca shares.</li>
</ul>
Commenting on the possible transaction, Ian Read, Chairman and CEO of Pfizer, said:
"We have great respect for AstraZeneca and its proud heritage as an innovation-driven biopharmaceutical business with a rich science-based foundation in both the United Kingdom and Sweden. In addition, the United Kingdom has created attractive incentives for companies to manufacture products and maintain and protect intellectual property, and we have seen that capital and jobs have followed these types of incentives.
"We believe patients all over the globe would benefit from our shared commitment to R&amp;D, which is critical to the future success of the pharmaceutical industry, in the form of potential new therapies that help to fight some of the world's most feared diseases, such as cancer.
"The combination of Pfizer and AstraZeneca could further enhance the ability to create value for shareholders of both companies and bring an expanded portfolio of important treatments to patients. A potential combination with AstraZeneca aligns with Pfizer's current structure and fully supports its existing strategy to build world-class businesses. The combination would complement our two innovative businesses and our Global Established Pharmaceutical business, allowing us to maintain the flexibility for the potential future separation of our businesses whilst at the same time broadening our pipeline breadth and potential new product launches over coming years. We believe that a transaction would further strengthen our ability to generate strong and consistent cash flow, targeted for both investment in our business and return to shareholders, while at the same time offering an efficient operating structure and the anticipated realization of attractive synergies.
"As always, we continue to focus on value creation and will be disciplined in our approach to capital deployment. Pfizer has a proven track record of successful acquisitions and, if a transaction were consummated, would use its extensive integration experience to support a successful combination of the businesses and focus on delivering value to shareholders."
Pfizer believes the strategic, business and financial rationale for a transaction is compelling. Pfizer believes the possible combination would create a highly complementary mapping of products, pipeline and operating assets to Pfizer's new operating structure, providing additional critical mass to all business segments and strong cash flow through:
<ul id="yui_3_9_1_1_1398672260981_1596">
<li class="bwlistitemmargb">an industry-leading combined portfolio of molecularly targeted medicines for lung cancer, including novel agents for ALK, EGFR and KRas subtypes;</li>
<li class="bwlistitemmargb">strengthened presence in breast cancer, including the ongoing phase 3 trial which combines palbociclib with Faslodex for women with recurrent, metastatic hormone-sensitive disease;</li>
<li class="bwlistitemmargb">opportunities for greater depth in immuno-oncology, including the option to combine anti-PD-L1 with palbociclib, Xalkori or Inlyta for breast, lung and renal cancer respectively. Additionally, molecules targeting PD-L1, CTLA4 and 41BB offer attractive opportunities for combination immuno-oncology therapy in several cancer indications, including lung cancer and melanoma;</li>
<li class="bwlistitemmargb">a strong complementary portfolio of important cardiovascular medicines, such as Brilinta and Eliquis and promising development stage programs, such as bococizumab (PCSK9);</li>
<li class="bwlistitemmargb">a broad, innovative commercial offering of non-insulin anti-diabetic medicines that complements Pfizer's early-stage research initiatives and capabilities in diabetes;</li>
<li class="bwlistitemmargb">a Global Established Pharmaceutical business with integrated distribution capabilities, expanded reach to healthcare providers and a broad portfolio of market-leading products generating strong and consistent cash flow; and</li>
<li id="yui_3_9_1_1_1398672260981_1595" class="bwlistitemmargb">a strengthened global footprint and enhanced opportunities in developing markets.</li>
</ul>
The possible transaction is expected to be accretive to Pfizer's adjusted diluted earnings per share2 in the first full year following the combination3. In addition, Pfizer has a track record of realising operational synergies and delivering meaningful value accretion for shareholders in prior transactions of a similar type and scale. Pfizer believes that synergies would be achieved through the combination of the two companies' operations and that the combination would enable greater capital efficiency and a more efficient tax structure. In particular, the currently contemplated structure under a new U.K.-incorporated holding company would not subject AstraZeneca's non-U.S. profits to U.S. tax, which would be in the best interests of the combined company's shareholders.
The completion of a possible transaction is subject to the approval of Pfizer's shareholders and is expected to be a taxable event to Pfizer's shareholders.
Pfizer reserves the right to introduce other forms of consideration and/or vary the mix of consideration and waive in whole or in part any of the pre-conditions to making an offer.
Pfizer reserves the right to make an offer for AstraZeneca at any time for less than the equivalent of £46.61 ($76.62) for each AstraZeneca share:
(i) with the agreement or recommendation of the AstraZeneca board;
(ii) if a third party announces a firm intention to make an offer for AstraZeneca which, as at the date Pfizer announces a firm intention to make an offer for AstraZeneca, is valued at a lower price than the equivalent of £46.61 ($76.62) for each AstraZeneca share;
(iii) following the announcement by AstraZeneca of a whitewash transaction4 pursuant to the Code; or
(iv) in the event that any AstraZeneca dividend is declared, made or paid in excess of what is expected by the consensus analyst forecasted dividends of 53.6 pence5 per share due to be announced by AstraZeneca on 31 July 2014, a £ for £ adjustment reduction equal to the excess amount.
The deadline set by Rule 2.6(a) of the Code (the "Deadline") requires Pfizer either:
(i) to announce a firm intention to make an offer for AstraZeneca under Rule 2.7 of the Code; or
(ii) to announce that it does not intend to make an offer for AstraZeneca, in which case the announcement will be treated as a statement to which Rule 2.8 of the Code applies,
by not later than 5.00 pm on 26 May 2014, save where either:
(i) AstraZeneca and the Takeover Panel have consented to an extension of the Deadline; or
(ii) the Deadline does not apply, or ceases to apply, by virtue of Rule 2.6(b) (a firm intention to make an offer for AstraZeneca under Rule 2.7 of the Code being announced by an offeror (other than Pfizer) prior to the Deadline).
A copy of this announcement will be available on Pfizer's website at <a href="http://cts.businesswire.com/ct/CT?id=smartlink&amp;url=http%3A%2F%2Fwww.pfizer.com&amp;esheet=50851997&amp;newsitemid=20140427005064&amp;lan=en-US&amp;anchor=www.pfizer.com&amp;index=1&amp;md5=3c960644e31ebbe36e13d4fe9d054246" data-rapid_p="8">www.pfizer.com</a>.
Pfizer will hold an analyst and investor call in respect of this announcement today at 8:30 a.m. EDT (1:30 p.m. BST). A live and recorded webcast will be available from <a href="http://cts.businesswire.com/ct/CT?id=smartlink&amp;url=http%3A%2F%2Fwww.pfizer.com&amp;esheet=50851997&amp;newsitemid=20140427005064&amp;lan=en-US&amp;anchor=www.pfizer.com&amp;index=2&amp;md5=356e6c438ebab77444e3b68f9bb1ae8b" data-rapid_p="9">www.pfizer.com</a>.

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