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Where biotech and high-tech meet
Author  Gali Weinreb

Executives in Israel for the MIXiii conference tell "Globes" about the future of medicine.

From Globs

2014 is positioned to go down in history as one of the stormiest years for biomed. The Nasdaq Biotechnology Index has risen sharply, by tens of percentage points, since the beginning of the year - a process that opened the door to dozens of IPOs - but has recently lost ground.

Pfizer is in talks to acquire AstraZeneca for more than $100 billion, the pharmaceutical and biotech companies continue to launch groundbreaking products, and the field of medical technology is in the throes of a revolution.

Senior industry executives from around the world who participated in the MIXiii Israel Innovation Conference (which combined the Israel Advanced Technology Industries annual international biomed conference with a high-tech conference for the first time), spoke to “Globes” about the latest breakthroughs, gave forecasts for the future, and explained what brought them to Israel.

According to Pitango Venture Capital General Partner and MIXiii Biomed Co-Chair Ruti Alon, “The forecast in the field of biomed is fundamentally complicated, due to of the interaction between political trends, such as globalization and different modes of distribution that bring Western diseases to new countries, and technological trends, such as genomics.

“In light of this, we can expect continued pressure to lower prices, significant changes in marketing systems, broader use of Internet, and the continued rise in prominence of the consumer as a factor in decision making. In Israel, there is a deep understanding of what is required to develop HealthIT products, that will connect the medical community.”

DFJ Tel Aviv Venture Partners General Partner and MIXiii Biomed Co-Chair Dr. Benny Zeevi said: “I believe the transitions from hospital care to remote care, from general care to personalized care, from treatment-based care to more preventive care, and higher patient involvement in treatment, will translate into a more pleasant patient experience, and greater commitment to maintaining therapeutic regimes as a result.”

”More holistic diagnosis and care”

Boehringer Ingelheim (BI) seems to be one of the less familiar among the 20 big companies, but only because it is not publicly traded. The company has 50,000 employees, and invests 20% of its revenue in R&D, with an emphasis on internal R&D.

The company has, in the past, been in talks to acquire an Israeli company, and has recently established a branch in Israel, headed by Orna Fiat Steinberger. The branch is responsible for running the company’s clinical trials in Israel.

The company was established 129 years ago. It was founded by, and is managed still today, by the Boehringer family, and Ingelheim is the German city in which the company was founded. Today, the company has a rich pipeline of products. Chief Medical Officer Prof. Klaus Dugi points in particular to the new cancer drug Volasertib, a small molecule inhibitor that prevents cancer cells from dividing by attacking the PKL1 protein. The company is testing the product for leukemia treatment, and is currently in Phase II clinical trials.

According to Dugi, the most significant scientific breakthrough of recent years is the recognition of the role that the mix of live organisms living in and on our bodies has in causing and preventing illness. “Today, using genome sequencing technology, we can know precisely what the genomes of our intestinal bacteria are. These genes, which are not exactly part of our bodies, apparently affect not only diseases of the intestine, but others as well. This knowledge can lead to entirely different medical diagnoses and treatments from those we know today - more holistic diagnosis and care.”

Dugi claims that the patent cliff troubles the industry, but not BI, and it is likely to be less problematic for the industry in the future. “In a world where most newly approved products are biological, which are harder to duplicate, it is possible that patent expiry will be regarded differently, and less seriously, in the future.”

The real industry crisis is not an R&D crisis, in his opinion is, but rather a budget crisis - governments are unable to maintain the health budgets necessary to create significant continued growth in biotech and pharmaceuticals, and drugs will soon need to prove that they save not only lives and suffering, but also money (as is the case for medical devices today). In order to do this, it will be necessary to improve existing patient monitoring data systems, and to match the best treatment to each patient.

Fiat Steinberger says that: “The fact that BI is a private company allows it to invest in R&D without thinking about how the analysts will look at the bottom line next quarter, or even next year, and, therefore, we have many long-term plans.” The company has 90 research projects, and it classifies ten products (in eight categories) as “pre-launch,” which means they are either in advanced Phase II with good results in previous trials, post-Phase III, or they have already been approved.

BI also has a venture capital fund that seeks out biomed companies to invest in, including companies in early stages of development that are not yet suitable for traditional venture capital funds. In 2014, the fund invested in a company called Metabomed, which at the same time received investments from the Merck Serono incubator in Yavne, from the Pontifax fund, and from the Technion technology transfer company. The company deals in treatments based on cancer metabolism - treatment through the resources that the cancer consumes.

Using stem cells to regenerate tissue

Over the past decade, Takeda Pharmaceuticals has gone from being a Japanese pharmaceutical company to being a global giant, competing head to head with the biggest global players. The company’s Israel office is headed by Arie Kramer. Following its acquisitions of US company Millennium Pharmaceuticals, which is developing a cancer treatment, and veteran European pharmaceutical company Nycomed, Takeda has become one of the most significant global powers in the pharmaceutical industry.

Despite the acquisitions, Takeda, like all the major pharmaceutical companies, has been forced to contend with the patent cliff: the expiry of patents on leading products, while R&D fails to produce new products at the expected rate.

“The patent cliff troubles the pharmaceutical companies and the investors,” said Takeda Head of R&D Tetsuyuki Maruyama, who was tasked with finding a solution to the problem, and has succeeded in doing so.

“It seems that the worst is behind us,” he says, “And I believe that the industry has learned from it: to place less emphasis on bestselling drugs, and to vary the product offering.

“A decade ago, large pharmaceutical companies avoided anything ‘difficult,’ like cancer, or rare diseases. The smaller companies proved that these are attractive markets, and now the big companies are scurrying to close the gap. We believe that this will happen also for the brain, so as larger companies leave this field, we focus on it.”

What are the developments that are likely to have the most significant impacts on the future of medicine?

“I believe in a combination of drugs and antibodies, where the antibodies lead the drugs directly to specific targets. Our company has such a product that should reach the market soon, after having waited for years for the right combination.

“Using such technology, together with products that use the immune system to treat cancer, I believe that the medical world will actually reach a cure for cancer, and I am not the only one who believes this.

“Another exciting technological development is the bacTRAP platform, which we loved so much that we bought the company that developed it. This is technology that allows us to look at changes in gene expression in specific cells in tissue that has many different kinds of cells, where each one expresses genes a little differently.

“Using this focus, we can develop far more accurate drugs. This is true for many areas, but most of all the brain, which has a mix of cells. I believe that the field of regenerative medicine, using stem cells to regenerate sick tissue, will lead to breakthroughs.”

Maruyama notes that Takeda owns a group called New Frontiers Science Team, which seeks technologies in advanced development stages and whose representatives were at the conference as well.

What are the most interesting products in your pipeline?

“We just now launched our first cancer drug based on a combination of antibodies and drugs. We are waiting on the launch of a new drug to treat Crohn’s disease and irritable bowel syndrome, which is most effective for patients for whom existing treatments don’t work. We are focusing on the digestive system.”

“Israel has an ideal mix”

Becton Dickinson (BD) is a medical device supplier that deals in a broad range of products, including hospital lab equipment. The company specializes in cheap medical equipment that is manufactured in large quantities.

“I have been with the company for 11 years,” said BD Director of Business Development Al Lauritano, “First, I headed the life science new business incubator in North Carolina, and I have basically held the same job ever since, only the job has grown.”

Incubator? That must have been revolutionary, at the time.

“We had an incubator from 1998 to 2008, into which we accepted mostly companies from academic institutions, but it wasn’t so successful. The business model was that after our initial investment, more investors were meant to join in, financial institutions, but, in order to attract such investors, the companies were forced to change their business models in directions that interested us less, as strategic investors. So we didn’t get what we wanted out of them.

“We never really shut the incubator down, but we became very picky. In the beginning of this year we decided to establish a ‘virtual incubator.’ We won’t host the companies, instead, we will support them wherever they are. We won’t only invest money - we will also send our people. That way, we will be able to get to know the companies well.”

In the coming year, BD will announce its first incubator company. “This is one of the reasons I am in Israel” says Lauritano.

“We believe that Israel has an ideal mix of entrepreneurs, technology, financing, and operational infrastructure, including the support of the chief scientist. In April, we announced our participation in a collaborative project between the chief scientist and the international corporations. This summer, we will put out a call for opportunities in Israel,” says Lauritano, who worked at Israeli company D-Pharm in the past.

Lauritano is particularly interested in combinations of information technologies in daily medical products. “Therefore, it makes sense for us that the conference brings high-tech and biotech together,” he says. He notes that many BD products are in competitive markets, where the product is manufactured by the millions (syringes and catheters, for example).

“How can we bring added value to such a product? Adding information technology in or around it is one method. We see that hospitals need to improve their workflows, in order to prevent mistakes in drug administration and to make sure that patients follow through on the treatments that are prescribed to them. So we want as much information as possible to be entered into medical records automatically from our medical devices.”

In the future, the company intends to help healthy people as well, “For example, diabetics, who are at the forefront of the population that monitors and manages its health regularly, every single day. Why shouldn’t all the healthy people, or people with chronic diseases, monitor themselves in such a manner in order to maintain optimal health? Our goal is to make a business of this.”

What is the most interesting product you have launched in the past two years?

“We surprised the industry this year when we announced that were opening a generic drug department. We have always had syringes that added value to drugs, and now, instead of selling them only to companies, we will incorporate generic drugs ourselves.”

Published by Globes [online], Israel business news - www.globes-online.com - on May 26, 2014

© Copyright of Globes Publisher Itonut (1983) Ltd. 2014

 Taken from Globes - Where biotech and high-tech meet

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A Comprehensive Guide to Israel’s Biotech Industry
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Its 180 biotech companies – each built on a combination of academic excellence, a highly-skilled workforce, cutting-edge technological inventiveness and entrepreneurial daring – are creating therapeutic products, diagnostic tools and revolutionary drug-delivery techniques benefiting people all over the world. Tailor-made for IsraelBiotechnology, the science which applies breakthroughs in molecular biology and immunochemistry to diagnosis and therapy, was born in the late 1970s. In many ways, it is tailor-made for Israel, being rooted in innovation and perseverance; a highly educated workforce; the lessons of military service; intimate links between researchers and entrepreneurs; and US capital and markets and, particularly, the US 1985 free trade agreement with Israel.Innovation and perseverance: A small country with a population of only seven million and few natural resources, Israel’s economy is necessarily one of innovation and perseverance. Demanding conditions – first in agriculture, then in defense and from there throughout its economy – set the stage for dramatic economic growth, as Israel transformed itself from a developing to a developed nation, and from an economy based on agriculture to one based on knowledge.A highly educated workforce: With seven world-class universities, Israel is one of the most highly educated countries on the globe. Almost a quarter of its workforce has university degrees, and 12 percent of these have advanced degrees. Among the 750,000 people who immigrated to Israel from the Former Soviet Union between 1989 and 1991 were hundreds of highly skilled engineers. 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This was when chemist Chaim Weizmann, later to be the country’s first president, developed a process that produced acetone from the bacterium Clostridium acetobutylicum. It took almost six more decades, however, until the modern Israeli biotechnology industry was born, on the heels of the high-tech boom. While Israeli biotechnology embraces the whole biotech sphere – from animal vaccines and diagnostics to plant tissue culture, bioreactors, seeds, diagnostics and biopesticides – its emphasis is firmly on medical agents, diagnostics and cell- and tissue-therapies. Some 60 percent of Israeli biotech focuses on human therapeutics, including drug discovery, cell therapy and genetics. 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INNOVATION NATION
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The deal marked Broadcom’s ninth Israeli acquisition.A few weeks later Facebook snapped up its first Israeli company, Snaptu, which had launched a Facebook mobile app a few weeks earlier, for a reported $70m. And rumours were growing in techie circles that Conduit, a start-up based in Rehovot that creates browser platforms for toolbars, is negotiating a $1bn deal, possibly with Google or Microsoft, that would be the biggest sale of an Israeli internet firm so far.For the past 40 years, since ECI Telecom put down roots there, an enclave along Israel’s coastal plain – which became known as Silicon Wadi (the Arabic word for valley) – has become a hotspot of computing, surveillance, videogames, transport and other innovations. This hi-tech oasis, largely concentrated in Tel Aviv and smaller cities, is now home to companies such as Microsoft, Google, and many other household names, making it an important part of Israel’s economy. Intel’s latest microprocessor was developed at its new $110m R&D centre in Haifa, and Intel Israel has been responsible for developing the Pentium and Centrino chips which power most PCs around the world. According to official figures, Israel’s hi-tech industries, which include the software, medical, electronic and advanced mechanical sectors, made up about 15% of the country’s $200bn GDP in 2009, and 40% of its exports.It’s not hard to see how this situation came about. The modern-day State of Israel is a small country in the desert, constantly at war with its neighbours and with little in the way of natural resources. It has arguably had to live off its wits since its founding in 1948, becoming a pioneer in the field of desalination and a leading exporter of defence products. Toss in the influence of the Israeli Army Intelligence Corps’ technology units, world- class academic institutions such as the Technion in Haifa and the Weizmann Institute of Science in Rehovot, and the shared Jewish experience of moving from place to place and starting afresh, and you can see where the nation’s resourcefulness stems from.But although Israel has the largest number of start-ups in the world in relation to its population – and is second only to the US in total – a growing number of successful home-grown companies are being gobbled up by larger foreign names.In selling out to US giants, Provigent – named by Ernst & Young as Israel’s most promising start-up for 2010 – and Snaptu are simply following in their peers’ footsteps. Only last April, Google paid $25m for start-up LabPixies, a leading developer of personalised web gadgets. Five months later it bought Quiksee for an estimated $10m. Founded in 2007, Quiksee produces location-based online tour technology, enabling users to create interactive 3D walkthroughs from simple video clips. The technology is regarded as the missing link in Google’s Street View service (used by Google Maps and Google Earth), which allows users to view images of streets around the world.Even in the depths of a global recession, 63 Israeli companies were acquired or merged in 2010 – a decline of 22% from the previous five-year average of 82 deals – according to the Israel Venture Capital Research Center (IVC). From 2009 to 2010, the size of the average deal fell 15%, from $37m to $32m. VC-backed deals (26) totaled $1.25bn, down from $1.54bn (28) in 2009.Three of last year’s M&A deals exceeded $200m and two were in the $100m-$200m range. The top 10 amounted to $1.4bn, 69% of the year’s total. The leading deals were 3M’s acquisition of Attenti, estimated at $230m; Mellanox’s $218m purchase of Voltaire, a Ra’anana-based provider of scale-out data-centre fabrics; and the $213m acquisition of network processer-maker Wintegra by PMC-Sierra, which already has a presence in Israel.Tel Aviv-based Attenti is a leading supplier of remote people- monitoring technologies, used to keep tabs on people awaiting trial or on probation, and by healthcare staff to assist in the care of elderly patients. The company’s CEO, Yoav Reisman, says: “3M’s culture of innovation fits well with our own, and its research-and-development capabilities and global reach will help accelerate the growth of our business.”Saul Singer, co-author of Start-Up Nation: The Story of Israel’s Economic Miracle, points out that no matter how hi-tech their products, the founders of Israeli businesses are entrepreneurs. When they reach the stage of scaling a company up, they become bored, preferring to move on to their next idea. “It’s not a bad thing,” he says. “Look at the career of an entrepreneur who is productive and able to build a few start-ups, then compare that productivity to someone who remains in the same company”.In his view, the pace of change over the next 20 years is likely to be greater than that of the past 50. “We don’t know what will happen, and in that situation it’s preferable to be in a start-up economy where there is much more flexibility. Start-ups are much better equipped to deal with rapid change as opposed to big companies and that makes them more valuable.”One problem is that Israel is a young nation with little experience of developing world-beating companies of its own. According to Todd Dollinger – chief executive of The Trendlines Group, which invests in and develops innovation-based businesses in the life sciences, cleantech, IT, security and other markets – few managers have “grown up” in large enterprises, meaning they lack the skills to engineer a company’s expansion. “Israelis who develop real skills in the sales and business- development realms do so while outside Israel – in the US, the UK and elsewhere,” he notes. “When they come back to Israel after succeeding abroad, they don’t stay in business development, they seem to move on to new ventures and their skills are lost.”A more serious hindrance is the lack of capital. Mindful of the rewards of a hi-tech culture – namely jobs, profits, investment opportunities and knowledge – governments in the 80s and 90s hatched Israel’s incubator system and various seed-funding mechanisms. Yet even at their peak, Israeli venture-capital funds were unable to offer large investments and following the global capital-market downturn, they struggled to raise cash. As a result, Israeli companies turned to foreign sources, which in many cases entailed basing their headquarters and senior management in the funder’s city. This has been exacerbated recently by a change in the R&D law – a cap on the penalty paid by companies if their operations are moved abroad. Dollinger adds: “The government’s insufficient support for education is a potential disaster. It’s bad for the country in every conceivable way.”“In general, start-ups can go two ways,” says Michael Eisenberg, a partner in Benchmark Israel II, a Herzliya-based fund that specialising in seed, start-up, and early-stage investments in ICT companies. “Either they sell or go public, otherwise the investors can’t get their money back. It’s about making money for the investors.“In Israel there is an issue about companies selling early and not going all the way to becoming a large company. A few reasons can be attributable to that: there has been some short- termism from fund managers looking for quick exits. There is a sea change and the trend is now for there to be larger, venture- capital backed companies, which is exactly what is needed, and the entrepreneurs are dreaming bigger, which will help the venture environment and lead to greater opportunities.”The financial crisis of 2008, which severely impacted institutional investors, was the major impediment to raising new funds. In 2009, only $234m was raised by Israeli VC funds and $200m of that was raised by just one of them, Sequoia Israel. In spite of improved macroeconomic conditions, Israeli VC funds were unable to attract new capital in 2010. Capital-raising trends in Israel generally correlate with trends in the US, which experienced a 50% reduction from 2009 levels.Last year, the government announced an incentive programme for Israeli institutions to invest in domestic VC funds that is expected to increase investment by $220m in 2011-12. According to IVC CEO Koby Simana, the situation is critical. “Without improvement, it threatens the survival of numerous Israeli hi-tech companies that cannot raise needed capital.Moreover, VC funds will not be able to finance new companies or, in some cases, support their existing portfolio companies.”Looking ahead, IVC is cautiously optimistic about capital- raising, based on a positive outlook for the local economy and government steps to stimulate investment. “However, most of the impact of the government plan will only be felt in 2012,” says Simana, “since local VC funds must first raise substantial amounts – 60% of the total capital of each fund – from foreign investors. It’s a real challenge for Israeli VC funds.” Many hi-tech companies that have not managed to raise capital face a threat to their very survival, he warns.Yoram Tietz, managing partner of Ernst & Young Israel, points out that Israel’s main assets are human capital and innovation – and says that without more investment, the country risks losing its crucial innovative edge. Faced with such a crisis, the Ministry of Finance and the Ministry of Industry and Trade have intervened, introducing a programme called the Competitive Advantage National Plan. Yuval Wollman, an adviser to the finance minister, explains: “Given that this is the growth engine of the Israeli economy, we thought that it would be wiser, strategically speaking, to capitalise on the advantages that we still have, examine the weaknesses and see what measures should be taken.”The ministries concluded that potentially innovative companies were being starved of capital from the Israeli market. At the moment it is common to exit start-ups early, with entrepreneurs aiming their initial public offerings at the US or agreeing mergers and acquisitions with large American companies. The government’s idea is to encourage companies to have their IPO in Israel so that they contribute to the economic ecosystem.The measures also include encouraging minorities, such as the Arab and ultra-orthodox Jewish communities, to join the hi-tech workforce through the higher education system. In addition, a fund is being established that will match government funding to private capital, facilitiating the transition of ideas from academic institutions to industry.To address the dramatic decline in the capital raised from local pension and provident funds (institutional investing domestically is only 0.2%, compared with 2% abroad), the government has allocated approximately $55m as a way of participating in the investment risk of Israeli institutional investors.And with seed-stage companies short of cash – raising only $39m in 2009, down 56% on the previous year – the government will allow investment in an R&D-focused company to be reported as an expense on day one, deductable against income from all sources over a three-year period.In addition, there will be tax incentives for large Israeli tech companies, such as the security specialist Check Point, to buy local start-ups, creating sub-industries within the Israeli market.Alan Feld, founder of Vintage Investment Partners, is convinced that the industry will get back on its feet, given time. His firm, which manages around $460m, has a database of more than 3,500 Israeli tech companies and tracks 90% of funds related to the sector on a quarterly basis. “We probably have the most active database of what’s happening out there,” he says.According to Feld, the decline in the amount invested in Israel between 2008 and 2009 is not dramatically different to what happened in the US in that period. While the drop in the amount invested was approximately 40%, the drop in the number of venture deals was only about 10%. Funds are investing in a far more capital-efficient way, he notes. In addition, venture funds have raised the bar by looking for better quality companies and being much more careful about how they invest. “We view that as being good for the industry as well. So, despite the drop in dollar terms, what’s more important is the number of deals done, which indicates a healthy level of activity.”A dramatic increase in angel investing, along with an increase in the number of venture funds returning to seed investing, also bodes well for the industry, and Feld believes that $600m-$900m will be raised by venture-capital funds this year – not far off the average raised after the crash of 2001. “We anticipate committing to at least three funds in 2011,” he says.As far as Singer is concerned, Israeli tech has huge opportunities for growth. “The ecosystem that has developed with American companies has barely begun with the same kind of companies in Europe, Latin America and Asia,” he says. “Siemens, Deutsche Telecom and Samsung are in Israel, but so many other companies outside the US are not. Why shouldn’t these other regions gain the same advantage as US companies have by injecting themselves with Israeli innovation?”There is considerable room for US firms already in Israel to increase their involvement, says Singer, and for those that are not in Israel yet. As well as exporting technological innovations, the country is making a name for itself in the field of innovative business models. In recent years two of its more conspicuous successes have been Better Place, which provides electric- vehicle networks and services internationally, and food company Strauss-Elite, whose coffee division operates in 12 countries (including Brazil, where it merged with a domestic operator to form the nation’s second-largest coffee manufacturer).It may be down now – but if history is anything to go by, Israel is far from out. 
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