LyrArc Article Gist
Novartis is taking a new approach to drug research and drug discovery. The old one which was popular in the drug industry was to go directly for blockbuster drugs for large numbers of users, with a long time in the research pipeline because the area of research was largely an unknown. This was costly and becoming less and less productive. Dan Vasella who heads Novartis, is taking a different approach which comes from his understanding of medical science as a physician, in an industry run by accountants, lawyers and business people. This is to go after wellknown molecular pathways identified by Dr Fishman at Harvard in his research, and do this by taking on problems in diseases that afflict small numbers of people. These drugs have some established medical science to work with, and the research work takes a shorter period. Once the drug proves its effectiveness in one illness, it is tested for other illnesses that afflict a large number of people but which shares some of the same underlying phenomena that cause the disease in the two situations. Dr Vasella stumbled on this approach after the development of the drug Gleevec by Novartis. Gleevec was originally approved for a rare blood cancer, but has now shown to be effective against six other dieases. Gleevec brought 3.7 billion in revenues in 2008 for Novartis. In 2002 Vasella made a bold move to discard the old drug development model. The basis of this approach was to go after new drugs that were desperately needed and where the genetics of the illness were well understood. Whereas pursuing rare dieases is considered foolhardy by most drug company leaders, Vasella's idea is to use the common genetic underlying arrangements for that drug to go after other diseases that would be good prospects for the now proven drug. The known genetics makes it possible to complete the research in a shorter time. In 2009 Novartis has 93 drug candidates in the pipeline, 40% more than 3 years ago and 80% of Novartis' drugs last year made it from early testing to late stage development. This was a 60% improvement over 2005. The new approach fits the current regulatory climate, with regulators concerned more about safety, and Medicare and Medicaid and other payor less willing to pay for treatment with modest benefits or with uncertain outcomes. The approach had to be executed in terms of organization and staffing. Vasella moved the R&D global research operation from Basel to Cambridge, Massachusetts, and spent $4 billion on the move. He recruited a renowed researcher and cardiologist at Harvard University, Dr Mark Fishman, who had done research on the genetic mutations in the cardiovascular systems, to run the center and set the new direction for global research. Fishman convinced Vasella that medical research should focus on a small number of molecular pathways- the complex suquences of interactions among chemicals, proteins, and larger cell structures in the body that are behind all illnesses. Says Fishman, there are 24,000 genes in the genome, but only a few dozen pathways conserved through evolution. Fishman's theory is that you find all the links in a pathway and then locate the signals that can turn the genes on or off to develop medicines for illnesses. Bercause disease after disease share a common pathway, the knowledge gathered can then be applied across that region with more accuracy and directly, to address a range of illnesses. Fishman's approach means marketing and sales no longer make the decisions. There is a new method for doing things. Fishman focusses on clinical data and insists that commercial analysis comes after sufficient clinical data. A major restructuring in 2007 led to shedding 1260 sales and marketing jobs, as clinical science now takes precedence and medically trained scientists take senior leadership positions. The new approach is being used for a drug developed for Muckle-Wells syndrome. Computer simulations are shortening the time to late stage trials. The drug has applications for Type 2 diabetes and severe arthritis. The whole process will take many years, as its a sea change for the industry and for Novartis, a fresh approach when the approach used by the pharmaceutical industry for so long is failing. An oral drug treatment for multiple sclerosis is being developed along these lines. Afinitor. approved by the FDA for kidney cancer in March shows potential in six other diseases, including lymphoma where Afintor shrank tumors by 50% in one third of the patients in a trial. ...

LyrArc Article Gist
A whole range of issues can be seen in the debt crises in developing countries. The margin for error shrinks with poor governance, lack of honest assessment and transparency for finances, wars and conflicts within or outside the countries, living beyond their means, lack of focus on development, infrastructure that is unproductive or unaffordable including some Belt and Road Initiative infrastructure at higher interest rates. Countries that are dependent on overseas remittances, tourism, that were hit hard by the pandemic have seen their finances further weakened reducing the margin for error even more to the point that the smallest tipping point can lead to huge crises. Once the finances are weak all it takes is an external tipping point that creates serious crisis. The war in Ukraine with shortages of wheat, fertilizer and skyrocketing oil prices acted as that tipping point. Because this was a major blow the crises have a level of magnitude that is more than a payments crisis. One sees this in South Asia in Sri Lanka and Pakistan, and in the Middle East for countries such as Egypt and Tunisia shown in this WSJ report. It is now not simply a crisis but a crisis of great magnitude because in the case of Sri Lanka and Pakistan this WSJ report says that both countries foreign exchange reserves have dwindled to the point where they can pay for only one or two months of imports according to central bank data, analysts and IMF. This crisis has affected countries that were seeing steady foreign investment such as Turkey for decades, then a sharp falloff in foreign investment with a change in the climate for foreign investment. The crisis has taken the form of high inflation, significant depreciation of currency that makes imports costlier so that shrinking revenues from loss of remittances, tourism, or other sources will now have less value in supporting import needs. Lack of a credible path can delay setting a path out of the crisis. The $1.5 billion fuel and electricity subsidy made by the prime minister of Pakistan in late February was done without IMF approval leading to the IMF program having to be renegotiated. Lack of national political and cultural consensus on a solution simply makes it that much more difficult to find the way through it. In this regard South Korea was able to tackle the 1997 financial payments crisis effectively because of a national consensus. The situation in Egypt- Egypt has borrowed $20 billion from the IMF since 2016., placing it second to Argentina in aid from IMF since 1980's.  In 2020 and 2021 Egypt' government spent more than 40% of its revenue servicing its debt, and is forecast to do the same in 2022. The situation in Tunisia- A shortage of sugar, flour, and other critical supplies, and government delaying wage payments to civil servants. The government got $400 million in financing last month from the World Bank and hopes to secure a lifeline from the IMF. Compared to the period between the 2 World Wars the two bright spots are China and India where lessons of the past of civil wars, religious or political conflict, and poor governance, lack of knowledge of how the western countries industrialized and modernized, was replaced with the conviction that drives patient effort, courage in the face of adversity, honesty, and humility to learn including from western countries that have forged their own path through the same difficult road. The most difficult experiences have offered lessons which were learned- for South Korea the Korean War and invasion from the north, China the civil war and Japanese invasion, for India the partition of India and million of refugees. Stagnation from stumbled efforts also taught lessons, the Great Leap Forward in China, the License Raj with corruption in India.       ...

LyrArc Article Gist
This report in the Hindusthan Times on president Trump's 25% steel tariff on steel imports focuses on the trade deficit with China of $375 billion in 2017. It shows the trade deficit for the month of February 2018 citing data from China as growing rapidly in 2018 over the prior year by 45%, even as imports went up only by 6.3%. In looking at coverage in the U.S. on this topic many of the reports in the Washington Post and the New York Times were critical of the tariff without mentioning the size of the trade surplus of China. Hardly any reports mentioned the growth by 45% in the February 2018 trade surplus of China with the U.S. over the prior year.  This report cites a tweet by president Trump that China was asked to come up with a plan to reduce its trade surplus by $1 billion in 2018, only 0.27% of the trade surplus, which looks strange as this would do little to change the trading relationship except that it puts pressure on China to change the direction of the surplus that is growing because of the strengthening dollar and the growth in the U.S.  This suggests that even with the 25% steel tariff America's basic problem of the imbalance in trading relationship with China will continue.  The headlines critical of Trump for starting a trade war therefore look strange in this context and show how little this subject is understood or debated with facts. Even today textbook economics principles are cited after two decades of hollowing out of industry in the midwestern U.S. and in Ontario, Canada. This led to public sentiment shift electing a liberal Justin Trudeau in Canada, and an outsider real estate businessman Donald Trump in the U.S.  For Democrats in the U.S. the support of marginal additional gains in trade with president Obama's push for another free trade agreement in the TPP may have cost them theiir working class base and the election.   ...

LyrArc Article Gist
A reminder from a veteran of investing about the enthusiasm and euphoria of Mr. Market, the term Benjamin Graham, author of the Intelligent Investor, used to describe the collective emotions of the people in the market during times of overoptimism when prices of shares have overextended and are overpriced. Graham warned of Mr Market in 1945, 1959, and in 1971, each time the market swooned and faltered. Zweig of the WSJ, points out data from Robert Shiller of Yale, the price/earnings ratio of the S&P 500 index jumping from 13.1 to 15.5 since March 2009, in 3 months. Ofcourse, this required aspecial disposition. Being well read and immersed in literature, mathematics and philosophy, helps to view things "from the standpoint of eternity, rather than day to day." And having a sense of detachment, a "certain aloofness," and "unruffled serenity." Graham mentions his internal equipment, his "embracing stoicism as a gospel sent to him from heaven." So Zweig again reminds investors on behalf of Graham as it were, and cautions about the mood swings ocurring lately from despair to a sudden optimism, which he describes as an insecure and desperate need to believe that things have taken a new turn when on closer examination things have only been papered over. Actually when one looks closely the credit tightening has eased by resolute action from the Fed and the Treasury and the Obama administration. But the underlying problem behind toxic mortgage securities remains at large. Private equity is being relied on to fix this problem in agovernment private partnership but no sigificant dent has been made in the toxic securities. Banks have made profits for one quarter, the outlook has improved and bank stock prices got a boost, but underlying problems remain. The loss in GDP this first quarter of 2009 compared to the prior year is 6% which is much better than the the 15-16 % drop in Germany and Japan, and 21% in Mexico. And the steep drops in unemployment are moderating. But large numbers of foreclosures continue with no dent in this in sight. And stimulus expenditures are only slowly trickling through, see the link to this. And the situation can only be described as improving but fragile....

LyrArc Article Gist
Americans loaded up with debt may be turning to older thriftier ways of an earlier generation. This this will affect consumer spending, have an impact on Chinese exports, and on the Japanese economy which is dependent on China for growth. Some argue that there is a culture of consumer spending that runs through recent American history. Even after one boom was over the stock boom was replaced by a housing boom, each boom and easy credit offering free spending and borrowing lifestyles. Is it going to change now? But it could be that a point has been reached where the finances of households and of the nation's credit system can only go so far, and culture won't matter if banks tighten up credit. There is a limit for the Fed to act to lower rates, and household debt has reached highly serious proportions. The savings rate went from one tenth of income in 1984, to 5% in 1994, to slightly negative in 2008. Today for those who borrowed against their homes in 2003-2007, 34 million households or one third of the US households, savings rate was negative 13% in 2006 June. Thhis came down to 7% in end of 2007, according to Moody's Economy.com, which suggests that the cutback in consumer spending from this group of people had already begun. What will this mean for consumer spending in the USA? It means that even though the top fifth of American earners who generate half of all consumer spending according to Barclay's Capital, will continue spending though a bit more carefully than before. The rest of the American people will be cutting back, especially the one third of the nation that is heavily in debt, and the unemployed if job numbers aren't that good. Which could be why Goldman Sachs predicts that Japan is already in recession using the Japanese definintion of decline in output, and China may be slowing down more significantly than is understood because of the poor data that is coming out of China. The Chinese economic activity too chaotic to accurately measure, and with large time lags before what is actually happening is detected and quantified correctly. ...

LyrArc Article Gist
Government data show that the German GDP declined by 0.5% in the thrid quarter after declining 0.4% in the second quarter. IMF predicts GDP decline of 0.8% in 2009. Germany's recession look like the worst in Europe except for the UK which has many of the same problems as the US economy. Germany's housing market has seen prices grow by almost zero in the last 10 years and German consumers are not in debt so Germany felt fairly immune to the troubles facing the US and the UK and Spain. But Germany is a big exporter and it has become more dependent on exports in the last 10 years. Exports account for 41% of GDP and CHina sucked up alot of machinery exports from Germany and China is in the midst of a drastic slowdown. In fact for the first time China is seeing a decline in monthly electricity output. And China's GDP growth rate may go from 12% to the range of somewhere around 6% in 2009, considering that Chinese export factories are closing down as the USA its main export market is seeing a rapid slowdown. Its already reached 9% and the slowdown is just beginning as the US market is also at the beginning of its slowdown. As the US market declines further in 2009 China's export factories will face a further decline in orders. Comparing the US at 10%, Japan at 20% and Germany at 41% of GDP one can see how heavily dependent the Germans have become on exports, especially with Asia's booming economies sucking up German exports. New orders for German goods declined by 18% from their peak in November 2007. And this is just the beginnning. So German unemployment is expected to increase. Its true that German banks invested heavily in mortgage related securities and other risky assets abroad, and the international financial crisis has led to a bailout fund of 500 billion euros setup by the German government. But Bundesbank figures show that what is causing the drastic contraction is the drop in investment spending as loan demand has dropped. ...

LyrArc Article Gist
Volkswagen restructuring in Western Europe. Note the price pressures in global markets and high import taxes in growth markets like Russia, China and India. This puts more pressure for restructuring Western European auto manufacturing.

LyrArc Article Gist
Fitch Ratings reports that 10 of the largest U.S. money market funds have combined assets of $755 billion, and as of May 2011, half of these assets are in instruments issued by European banks. These assets have been held for 5 years. In the event of a crisis it is feared that the funds will withdraw from the European market. Money market fund holdings for the ten largest funds show that no European bank has more than 7% of its short term funding from these money market funds, according to Fitch. A combined withdrawal would affect global credit markets.

LyrArc Article Gist
Study showing the ineffectiveness of mammograms in correctly screening for cancer. The technology is not developed enough for correct detection. Many doctors are compensated on the basis of having all patients screened.

LyrArc Article Gist
Wealth for top 7% of U.S. households averaged $3.2 million in 2011, compared to $133,817 for the other 93% of the population. Third quarter 2013 household net worth is 615% of after tax income, up from 570% in 2012. The uneven distribution of household wealth and the gains from the stock market recovery going disproportionately to wealthier investors, does not provide strong enough underpinnings for robust consumer spending.

LyrArc Article Gist
Total payments if a payout is triggered on credit default swaps on Greece is $3.2 billion.

LyrArc Article Gist
The view of regional Fed presidents indicates that the Fed may take a pause from any further intervention in financial markets. QE 2 was launched at a time when the government was at a deadlock for any further stimulus, and a deflationary trend was setting in. In August of 2010 inflation was on a downward trajectory, from 2.8% to less than 2.2% in a few months. A New York Times article by Paul Krugman pointed out the dangers of deflation. Alan Blinder argued for the need for Fed action with the deadlock in government over further stimulus in another op-ed in the Wall Street Journal at the time. The political deadlock continues with pressure to cut federal spending to reduce the deficit, reducing the chances of government support, and leaving the Fed as the sole source of support. The Fed initiated QE 2 in Novemeber 2010 when consumer prices were up 1.1% from a year earlier, and far below the Fed's 2% goal. In April 2011 consumer prices were up 3.1% over the prior year. Current TIPS prices suggest investor expectations of inflation of 2.8% over 5 years. Another deflationary trend could lead the Fed to take some sort of action in the presence of a political deadlock for government action....

LyrArc Article Gist
As Indian pharmaceutical industry sees drug testing in India as an opportunity, conditions for obtaining the best results are being established by taking necessary steps. With ashortage of experienced people to run drug trials, Indian government has stepped up training, setting up partnerships with the U.S. FDA, Health Canada, the World Health Organization, and other similiar organizations, The emphasis should be on credible dat and the safety of subjects says A.K. Pradhan, India's Assistant Drug Controller. After the death of an infant in a Wyeth Pharmaceuticals drug testing effort, the Drug Controller of India though supportive of Wyeth has raised certain issues that Wyeth is addressing.

LyrArc Article Gist
The US housing market in 2022 with sharp increase in cash out refinancing and home equity financing. Total home equity increased 20% in the first quarter to $27.8 trillion, a record high, according to the Federal Reserve, the US central bank. About 60% of equity was withdrawn through cash out refinancing in 2021, according to mortgage data. Cash out refinancing simply adds the amount borrowed to the existing mortgage balance. The amount borrowed through such financing by homeowners adds to inflationary pressures with more cash borrowed on the house for home improvement projects, gardening projects, appliance spending and automobile purchases. The increase in the interest rates by the US Federal Reserve including the 0.75% increase in the rate announced on June 15 slows the amount of borrowing through cash out refinancing. The supply chain disruptions disrupted flow of goods at a time of high demand in 2021 following the lockdowns, and then the war in Ukraine added another layer of inflation from high gas prices. The combined effect with housing price pressures created the perfect storm in inflation the US is facing with the rest of the world. ...

LyrArc Article Gist
A 41 year old doctor, Vasant Narasimhan, is the new CEO of Novartis in Feb. 2018. Under Narasimhan R&D is expected to get prominence. His predecesor Mr. Jimenez's focus was on developing new prescription drugs. Dr. Narasimhan sees a shift to new technology, improving data science and digital capabilities to discover new medicines. This shift raises the possibility of a spinoff of the Alcon eyecare business and the Sandoz generics business.   Narasimhan joined Novartis in 2005 from consultancy Mckinsey & Co. and becoming head of R&D. He is expected to push a series of tech based initiatives including artificial intelligence to be used for new biomarkers showing effectiveness of treatment, new sensor technologies developed with Microsoft. This shift is a result of the earlier effort under previous CEO's to make up for the loss of patent protection on profitable drugs by diversifying into consumer healthcare. During the period under Jimenez Novartis share price performance was mediocre, rising 41% over 8 years. Its business is stagnant with a 1% increase in 2017 for revenues, the first increase in 3 years.   ...