Pharmaceutical Industry and Life Sciences

There is practically no industry that is as intimately connected to the content world of intellectual property as the biomedical industry. Whether in the development of new drugs or generic drugs, whether in the design of medical devices and medical equipment – in all these areas patent protection has a critical role in the development and marketing processes.

In principle, patent laws are organized separately by each country. However, the TRIPS Agreement established a set of rules to which policies of the signatory countries must adhere. These rules mainly ensure a minimum standard of intellectual property protection in general and patents in the pharmaceutical market in particular

Pharmaceutical Drug Development, R&D and Intellectual Property –  Worldwide Outlook

Pharmaceutical R&D companies are completely dependent on suitable protection of intellectual property rights. Without this, it is doubtful whether they would invest the substantial resources required for the process or take upon themselves the inherent risks. At the end of the day, the time and costs involved in the research and development (R&D) process in pharmaceutical industry innovation are especially high. On average, the research and development process, including drug licensing, takes approximately 12-15 years, and the costs are estimated at approximately 900 million dollars.

In addition, out of every 5000 selected molecules, on average only 5 are examined in clinical trials, and only one of them becomes an approved drug for treating patients. In fact, less than 20% of the drugs that reach the stage of trials on human subjects receive regulatory approval at the end of the process.

In addition, on average, only three out of every 10 prescription drugs available for treatment produce income equal to the average costs of R&D. Without patent protection, 65% of existing drugs on the market today would not have been developed at all.

At the opposite end of the spectrum, the business model of generic drug companies is based on patent expiration and the possibility of producing similar or identical drugs.

Between these two branches of the worldwide pharmaceutical industry – the innovative ethical companies (that produce original drugs) and the generic companies – difficult economic, legal and political struggles take place, mainly surrounding issues of patent regulation.

While the innovative pharmaceutical companies seek to lengthen the duration of patent life as much as possible, the generic companies seek to decrease it. Since the cost of generic drug development is relatively inexpensive, these drugs are sold at cheaper prices, approximately 30-50% of the original drug price. After two years of activity, generic drugs control approximately 70% of the market for the particular drug.

Patent Expiration

This struggle is sharper in light of what has been defined as the moment of truth for the original pharmaceutical companies. In the coming years, the moment they have feared will arrive – the moment when the patent expires. A series of patents that protect important original drugs will expire and the original companies do not have sufficient R&D pipelines of new patents. Experts estimate that many pharmaceutical companies will seek out business partnerships or mergers that can ensure their continued survival in a market in which more and more companies are producing generic alternatives sold at prices that are lower by tens of percentage points.

The Global Pharmaceutical Market

The global pharmaceutical market is estimated at approximately 850 billion dollars. The main players in this market are the United States (responsible for 50% of all the existing drugs in the world) and also Western European countries (mainly Switzerland, Germany and England), Japan and Israel, which is very dominant in the field of generic drugs (mainly due to the Teva company).

The scope of prescription drug sales in the U.S. alone in 2014 was 374 billion dollars. New drugs that have come on the market in the past year yielded aggregate revenues of approximately 20.4 billion dollars, out of which 11 billion were in sales of SOVALDI, a medicine for treatment of hepatitis manufactured by the Gilead company, and approximately 2.6 billion dollars in sales of the breakthrough drug Tecfidera produced by Biogen.

The numbers in Israel are also large. In December 2014, the Israel Pharmaceutical Committee authorized the addition of 320 million ILS to the government “basket” of medications and technologies, which is estimated at 6 billion ILS per year and is considered advanced and comprehensive by worldwide criteria. The main portion of the additions to the basket were in the field of treatment for hepatitis and breakthrough drugs for cancer treatment (Opdivo, Imbruvica).

It is no secret that the health market moves big money and that life sciences and biotechnology companies demonstrate unprecedented performance alongside exceptional growth rates and profitability. The constant questions are whether this can continue, what are the risks to investors, to companies and to patients, and whether the stocks are cheap or expensive?

It is in fact becoming clear that the traditional business model of pharmaceutical companies is changing. After the large companies – that manufacture approximately 70% of pharmaceutical drugs in the world – saw their market value skyrocket, they are now under huge pressure and the prediction is that by 2020 the traditional model will cease working and will change – from use of drugs by the wider population to use of drugs adapted to a particular user based on his or her genetic profile, and thus medications will be adapted to smaller populations of users. The economic significance is that the income from each new drug will significantly decrease and the economic feasibility of developing new drugs will be dubious.

Changes in the United States Intellectual Property Regime

In the past, the United States was one of the most developed and most liberal countries in all matters connected to approving patents, but since 2010 and until today, following a series of Supreme Court decisions that occurred one after another, the situation has changed completely.

One of the most recent decisions of the United States Supreme Court held that it is not possible to register patents on human genes, but it is possible to register patents on genes that have undergone manipulation, on methods for isolating genes, or on innovative applications that are derived from genetic research. “The DNA sequence is a product of nature and therefore a patent cannot be registered for it simply because the genes in it were isolated in a laboratory. However, the product of genetic manipulation is something that does not exist in nature and therefore it can be defined as an invention that can be protected in the framework of intellectual property laws,” wrote Justice Clarence Thomas in the court decision.

The judges’ ruling cancelled patents held by Myriad Genetics regarding two genes related to the development of breast and ovarian cancer. At the center of the case was the question of whether genes isolated in the company laboratories were a “product of nature” or a “human invention.” The case began in 2009 and over its course the company claimed that they should be able to keep their patents, while the American Civil Liberties Union (ACLU) and the medical Association for Molecular Pathology claimed that the matter would thwart the advancement of research and would not make it possible to lower prices for genetic testing.

This court decision joined a previous U.S. Supreme Court decision in another case that held that the laws of nature cannot be patented and therefore inventions that are an expression of the laws of nature are an act of thought and are not entitled to patent protection.

There is no doubt that this most recent court decision will shape the nature of research and medical testing in the future. It has created great consternation and called into question many technological developments. Biomedical research industry entities even warned throughout the case that a sweeping prohibition on registering patents in genetic research would put research that had already begun at risk and prevent the development of advanced disease treatments. In an opinion presented to the Supreme Court, the Obama government advised reaching a compromise in which existing patents in the field of synthetic molecules (complementary DNA) would receive protection under the intellectual property laws. Some even thought that Congress would intervene and pass legislation, but that did not happen. Instead a book of guidelines from the U.S. Patent and Trade Office (USPTO) was published, which did not untangle the problem and in fact increased the uncertainty. Only recently has a public body been appointed that has held a number of discussions, studied the problem in depth and published a new book of guidelines that is slightly clearer. However in many different areas, especially in all matters concerned with diagnostic methods, the situation is still bleak.

The Pharmaceutical Industry and Intellectual Property in Israel

As a result of the changes in the biomedical field worldwide, multi-national pharmaceutical companies are trying to associate with research companies, universities, laboratories, clinics, hospitals and even drug distributors in order to identify new trends and technologies and to develop effective products for the public.

In fact, this process is already active in Israel and we are witnessing large global pharmaceutical corporations, such as Roche and Novartis, as well as the Israeli company Teva, partnering in research on drug development with academic researchers, while investing in small pharma and biotech companies.

Israel has great potential to attract investment in research and development of biomedical products, as well as to conduct clinical studies. Until recently this potential was not sufficiently realized due to a series of legal and regulatory problems in the field of intellectual property protections for pharmaceutical drugs and other bureaucratic difficulties.

Following entrance into the OECD, Israel began implementing changes, adjustments and corrections that were intended to provide suitable protection of intellectual property rights for pharmaceutical drugs in accordance with the accepted standards for the organization’s member countries. These changes are still in the process of legislation and their main importance relates to extending the validity of patents, an area in which Israel lags behind the West. What follows is a brief survey of the existing situation and the changes that Israel is planning to make in this area that are intended to improve protections for intellectual property rights for pharmaceutical drugs.

Extending Patent Validity

In principle, the issue of extending patent validity in Israel is quite complicated, cumbersome and laden with gaps and uncertainty that has still not been addressed in local rulings. Likewise, the system for extending validity in Israel is not balanced and clearly tends toward the interests of the local generic industry over those of the ethical companies (the innovative companies that produce original drugs).

The entire topic of extending patent validity in Israel is integrated in the framework of amendments to the patent law of February 1998. For a number of years, a bill has been before the Israeli parliament (Knesset) that would regulate the subject; to date the bill has not yet passed. However, by means of article 64 of the patent law, it is possible to extend the period of patent protection in the area of drugs and medical equipment under certain conditions. The matter derives inter alia from increasing international pressure on Israel to raise and adjust the level of protection Israel provides for intellectual property rights.

The main reasons for integrating the process of extending patent validity are as follows:

• Compensation to ethical companies for prolonged required regulatory processes prior to receiving market authorization, during which they are prevented from realizing any commercial benefit from their patent protected invention.
• The effective lifespan of drug patents is much shorter than the period recorded in law (20 years). The long required process for drug development and receiving market authorization leads to a situation in which the ethical pharmaceutical companies have only a relatively short period of time to market the drug.
• Balancing out the impact of the Bolar Exemption, the permission given to generic producers to conduct trials during the period of the original patent protection for the purpose of receiving market authorization for generic alternatives when the patent expires.

Calculation of the period of extension in Israel is not conducted independently, but rather is based on prior decisions. There is a clear and direct link (linking mechanism) for calculating the extension period for Israeli patents and patents in one of the 21 recognized countries. The extension decree can be valid for a period equal to the shortest of the extension periods given to the comparable patent in any country among the recognized countries, but not more than five years. The aforementioned calculation is cumbersome and puts excessive bureaucratic burden on ethical companies seeking to receive extension decrees.

The essential conditions for granting an extension decree in Israel are:

• The material, the production process or the use of it, the medication that includes the material, or the production process, or the medical equipment is an intrinsic part of the basic patent and the basic patent is valid.
• The medication is listed in the Israeli pharmaceutical registry.
• The product registration is the first registration confirming the use of the material in Israel for medical purposes.
• The basic patent or the material has not received a previous extension decree.
• Marketing authorization has been issued for the medication or medical device in the United States that is protected by a comparable patent – if the comparable patent validity was extended in the United States regarding the stated medication or medical device.

In the memorandum of understanding signed between the Israeli and American governments on February 18, 2010, the Israeli government committed to initiate and promote certain legislative changes in the instructions for patent extensions. On September 18, 2010, the Ministry of Justice published draft legislation to make a number of corrections in the instructions for patent extensions. Following are the main proposed points:

• Decreasing the number of recognized countries – the number of recognized countries that constitute the basis for calculating the duration of extension decrees in Israel will be decreased to about five countries in the European Union (France, Germany, Italy, Spain and Britain) and the United States.
• Setting official date targets in the matter of application claims to extend validity.
• Adding the option to submit a request for extending patent validity to patents that are still in the examination process.
• Adding a process for examining requests for extensions also in cases where the extension of validity has not yet been granted in recognized countries.

There is no doubt that improving the protection of intellectual property rights will accelerate the pace of registration of new medications in Israel and increase the competition among the different original medications for treatment of different kinds of illnesses. It is worth remembering that the cost to the economy of importing medications that are not registered in Israel is higher than the cost for medications that are registered in Israel and that are based on intellectual property rights. Moreover, the lack of registration of these medications in Israel prevents any possibility of generic competition or of lowering prices over time.

Clinical Studies

Regarding clinical studies, no fewer than one thousand clinical studies are conducted in Israel each year solely in the area of medications. The developed infrastructure in the hospitals, the heterogeneous population, the accessibility of information and the level of cooperation still attract pharmaceutical companies to Israel. Clinical studies bring approximately 350 million dollars into Israel each year, and in the last decade approximately 1,300 new medications were authorized in Israel.

Israel still attracts large companies and is perceived by the world as a center of innovation, but we cannot be complacent. There is an annual increase of 5-10% in the number of clinical studies conducted in Eastern Europe and Asia, and countries that were considered leaders in the field are actually experiencing a decrease, fighting to preserve their portion of the field. In order to ensure Israel’s continued advantage in this area, Israel must decrease bureaucratic barriers that create difficulties in the process of promoting clinical studies. The world is advancing and there is concern that Israel is standing still. If changes do not occur in the field, we will witness companies’ increasing preference for conducting clinical studies in Eastern Europe and the Far East.

Maximizing Israel’s Comparative Advantage in the Biomedical Field

Israel has impressive statistics that provide a significant comparative advantage in the field of biotechnology. The central basis for Israel’s comparative advantage is the potential human capital. Israel is in third place among OECD nations in percentage of academic degrees, with 47% of the relevant age group (age 25 to 64) in Israel holding an academic degree, compared to the average of 33% in OECD nations. A significant portion of these degrees are in subjects relevant to biotechnology: approximately 40% of doctorates completed in Israel are in the sciences, compared to an average of only 24% in the OECD.

In contrast to the fields of computer and information technology, in which there are indications of a trend of excess demand for personnel, in the biotechnology field there is a large reserve of skilled, academically-trained human capital. In the past decade the number of (second and third) degree recipients in fields relevant to biotechnology (biology, chemistry, biochemistry, engineering and agriculture) reached approximately 15,000. In contrast, the number of employees in biotechnology in Israel is relatives low – only approximately 6,500 people are employed in this field. Hence there is a high potential for human capital in the biotechnology field which offers a wide area for industry development. Israel’s comparative advantage is also expressed in academic excellence, which has important significance in these research fields. Israel is one of the world leaders, relative to its size, in publications in the life sciences, and Israeli universities rank highly in worldwide ranking indices.

Israel’s comparative advantage in biotechnology fields is not only in academics. It is also actualized in an impressive scope of activities of R&D companies in biotechnology fields. In Israel, there are currently approximately 260 operating companies focused on biotechnology fields; of them, 220 are Israeli companies and approximately 40 are foreign companies. Israel ranks fifth among OECD nations in the number of companies in the field relative to the GDP. For comparison, in the U.S., where the economy is 60 times larger than Israel in GDP, there are only 9 times more companies operating with a business focus on biotechnology fields, approximately 2,200. In addition, another approximately 4,000 companies operate in a range of fields in the U.S. that also include the biotechnology field.

In scope of investment in business R&D in biotechnology fields, Israel is also among the world leaders. The scope of annual investment in R&D in biotechnology fields is approximately 4 million dollars, and Israel is in fifth place worldwide in terms of investment in business R&D in biotechnology relative to GDP.

The integration of advantages in human capital, the relatively large number of companies dealing with development in this branch and the relatively high level of investment in R&D are bearing fruit, as expressed in the high percentage of patents in biotechnology held by Israeli companies. According to the OECD index of comparative advantage in the field of patents, which measures the percentage of patents in biotechnology fields in comparison to the overall percentage of patents from each country, Israel is in 9th place out of 33 OECD countries. Israel’s comparative advantage index stands at 1.5 in biotechnology fields, very close to the U.S. index of 1.6. Israel is in second place among OECD countries in the number of patents in biotechnology fields per dollar of GDP, following Denmark.

Medical Devices

The field of medical devices is a branch in constant growth in Israel. Only recently, the Israel Export Institute published statistics regarding Israeli exports for 2014. From the data it appears that in 2014, the scope of export of medical equipment from Israel increased by 11% over 2013, and totals approximately 2 billion dollars. The Export Institute estimates that the life sciences industry in Israel numbers approximately 1,100 companies, with 70% of them in the medical device field.

Jerusalem Biotech Cluster

In public media discourse, Jerusalem usually merits mention in political and religious contexts. This discourse is replete with emotions and tends to obscure the fact that the city is also a metropolitan economic and employment center. After all, Jerusalem is the largest city in Israel and contains several central economic-employment anchors that attract human resources and investment. One of the prominent anchors is the field of life sciences, which is considered the central economic growth engine of the capital city.

Jerusalem currently has a number of clear advantages in the field of life sciences. In the city, there are several institutions of higher education, medical centers and sites that concentrate significant activities in the field of biomed R&D. First and foremost, Hebrew University, the leader in the field of biotech in Israel, controlling 43% of research in the field, as well as the Hadassah University Medical Center and Shaare Zedek Medical Center, two leading medical centers of significant reputation. There are also three technology colleges in Jerusalem – the Jerusalem College of Engineering, the Jerusalem College of Technology (Machon Lev) and Hadassah College – as well as the Bezalel Academy of Design, whose graduates make an important contribution to designing medical products and devices.

Alongside all these, in Har Hotzvim and Atarot there are tens of pharma and biomed companies operating, including Teva, Rafa, Medinol, Omrix, Covidien, Sigma, Bio-Lab, and Fermentek. A total of 32,000 people are employed in the city in the medical and life sciences fields – 14% of the labor force in Jerusalem. We note that on the Ein Karem campus there is a dedicated area for biomed companies, operated in cooperation with the University and Hadassah. This is the Jerusalem Biotechnology Park which is currently operating with renewed momentum. All these aspects together constitute a unique advantage for Jerusalem in the biomedical field.

Conclusion

The life sciences industry in Israel is taking great steps forward, but is still in the formative stages. We have indeed succeeded in becoming an attractive center of innovation, based on scientific excellence and entrepreneurial spirit, but there is still a long way to go to become a mature, sustainable industry.

Scientific breakthroughs in the field take place mostly in academia. In order for these discoveries to ripen into products, there is a need to bridge the gap between scientific discovery stage and the product development stage. The biotech industry is largely capable of developing scientific discoveries only into the first stages of product development, afterwards, and especially in the field of drug development, the biotech industry is dependent on the global pharmaceutical industry for continued development and commercialization of products on the market. In Israel, there is a lack of skills in the field of development and commercialization of medications, and sources of funding for expensive development processes, involving investments of hundreds of millions of dollars or more, are lacking. Other than Teva, there are no pharmaceutical companies capable of bringing products from initial development stages to market. Therefore, the lion’s share of the profits on final products does not stay in Israel, despite the fact that the initial discovery of the medication is “blue and white.”

Creating a mature, sustainable industry in Israel requires massive support from the government, Israeli and international financial bodies, and partnerships with international pharma companies. Only in this way can we create the infrastructure, environment and growth climate here for additional pharmaceutical companies that can leverage the life sciences industry to create significant income for the Israeli economy and bring about the growth of more companies in their wake.

National Digital Health Plan 

The Israeli government approved recently a National Digital Health plan, which, plans to create a digital database of the medical files of some 9 million residents and make them available to researchers and enterprises.

To promote the initiative, Israel will unify the existing database of the digital medical records it has collected over a period of 20 years – which holds the medical files of more than 98 percent of the population – to create a single database, in which one’s participation is optional, that will help attract researchers and industry leaders from across the globe, the Prime Minister’s office said Sunday.

Prime Minister Benjamin Netanyahu estimated the global digital health sector at some $6 trillion, calling the field “huge.” He speculated that Israel might be able to snag some 10% of this market potential, worth some $600 billion. “I think this is a conservative estimate,” he said. “And if we succeed, just like we succeeded in cybersecurity and in autonomous cars,” then Israel can expect a significant boost of new products.

Israel has medical records of close to 9 million people collected over the past 20 years, Netanyahu said. “This is a huge asset,” he said. “We want to make this available to researchers and developers and enterprises.” The aim is to boost the development of preventive medications as well as personalized, custom-made treatments. “Of course this depends on the consent of each and every person,” he said, adding that this new policy was a “global breakthrough,” and global companies have already expressed a huge interest in the initiative. “I’ve already met many of them. They all want to come here. Quite rightly, they see that this is a new direction.”

Israeli life science industry

Analysis of the data shows that although the Israeli life science industry is relatively young, it has been growing steadily in the past decade, experiencing a compounded annual growth (CAGR) of 10% from 2008 to 2017. Out of the 1,200 life science companies active to date, around 60% (720) were founded in the last decade. A closer look reveals that 31% (374) of the companies were established in the last five years. Four hundred and eighty companies were established prior to 2008, with the first one, Teva Pharmaceutical, founded in 1901.

Out of the 720 companies that were established in the past decade, 137 companies (19%) are revenue generating entities. Approximately 160 companies (22%) are at the seed stage, 187 (26%) are at preclinical stages and 137 (19%) are at clinical stages of development. A closer analysis of the companies established in the last decade reveals that 72 medical device, 15 biotechnology and 21 pharmaceutical companies are currently in the preclinical stage. Concurrently, 63 medical device, 19 biotechnology and 23 pharmaceutical companies are currently clinical stage companies.

Interesting to note is that the emergence of the health IT sector in recent years has changed the composition of the different sectors within the Israeli life sciences industry. While five years ago, the medical device sector accounted for the majority of the companies (60%), today this sector still leads, but accounts for only 41%, with 493 of the 1,200 companies. Health IT is the second largest sector, with 360 companies (30%), followed by biotech with 157 (13%), and finally pharma with 112 companies (9%).

Over 65% of the Israeli life sciences industry is composed of “tiny” companies with 1-10 employees. Altogether, this group employs an estimated 6% of the total 65,000 employed in the life science workforce. In comparison, the 119 “large companies” (10% of 1,200) with over 50 employees, employ around 52,400 individuals or 81% of the total life science workforce. In the case of the multi-national companies, the data includes only R&D professionals, and for domestic companies, only employees based in Israel.

According to a 2018 IVC report, in 2017, Israeli life sciences companies raised $1.2 billion from VC funds in 135 investment deals, a 41% increase compared to $850 million raised in 137 deals during 2016. In 2017, funds received from the Israeli Innovation Authority reached approximately 135 million dollars. The most prominent Israeli venture capital firms active in the life science sector are Orbimed Israel, Pitango Venture Capital, TriVenture, Pontifax, Accelmed, Arkin Bio Ventures, and the latest two entrants, aMoon and Israel Biotech Fund. 2017 marks two record breaking exits: NeuroDerm was acquired by Mitsubishi Tanabe for $1.1 billion, and Valtech was acquired by Edwards Lifesciences for $1.0 billion with an upfront payment of $340 million. Other noteworthy events include Urogen’s public offering on the Nasdaq raising $58.2 million, and Redhill Biopharma raising $22.5 on the Nasdaq.

Leading Academic Researchers

Also noted is that Israeli universities are staffed with leading academic researchers, offering excellent curricula in engineering and science. Many students pursue advanced degrees that form the backbone of R&D in Israel’s life science companies. In 2016, approximately 8,020 students received academic degrees in life sciences related fields. Of those, 51% earned Bachelor’s degrees, 27% MSc. degrees and 22% MDs and PhDs. Despite this highly educated group, the Israeli industry suffers from a lack of large corporations that typically nurture management talent and serve as a conduit for personal and professional growth of industry leaders.

Areas of Focus of the Israeli Life Science Industry

The data indicate that the areas of focus of the Israeli life science industry are aligned with the current trends in the global life sciences industry. The most innovative and active therapeutics areas are still cancer, neurodegenerative diseases, fibrotic diseases and anti-inflammatory/immunomodulation. In general, we see biologics (e.g. antibodies, proteins, mRNA and cell therapy) taking the lead over the traditional small molecules.

Immunotherapies have produced remarkable results for many, but not for all, cancer patients. The future fight against cancer lies in developing novel therapeutics that are based on the unique characteristics of tumors and individual patients and that will help a larger number of cancer patients. Companies pursuing this challenge include BioLineRx, Kahr Medical, VBL Therapeutics, Compugen and more. A new trend involves the expansion of immunotherapy beyond checkpoint inhibitors. One example is a novel form of immunotherapy that is based on oncolytic viruses that preferentially infects and kills cancer cells.

Gene Therapy

Another burgeoning area is rare genetic diseases and gene therapy, with the first gene therapy approved by the FDA last year (for eye treatment). Innovative Israeli companies in this area include Eloxx Pharmaceuticals (treating rare diseases caused by premature termination codon nonsense mutations), LogicBio Therapeutics (treatment for a rare liver disease using gene editing), Emendo Biotherapeutics (gene editing using synthetic biology), SpliSense (antisense oligonucleotide based treatment for cystic fibrosis through splicing modulation) and Art Biosciences (mRNA based therapy).

Personalized Medicine

Personalized medicine tailored to the unique needs, genetic makeup and lifestyle of each patient will continue to be an important trend in healthcare. Among the growing numbers of Israeli companies developing such technologies are NevellusDx (cancer), Day two (metabolic) and Taliaz (neurology).

Artificial Intelligence

The computing power of artificial intelligent (AI) will drastically decrease the time scientists spend analyzing data, testing new molecules and predicting the relationships between biological mechanisms and disease symptoms. AI also has the potential to improve the diagnosis and treatment plans of patients. Israeli companies, such as MDClone, Zebra Medical and Ibex Medical Analytics develop AI-driven decision-support tools that help physicians deliver more efficient, metric-driven, objective and accurate diagnosis. 

Medical Devices

In the medical device arena, metabolic and ophthalmic diseases are two prevalent fields due to population aging and the obesity epidemic. Israeli scientists and medical engineers have come up with novel approaches to treat or halt disease progression. Diabesity is a modern epidemic and a deadly disease, the continuum of abnormal biology that ranges from mild insulin resistance to full-blown diabetes. People with metabolic diseases are more likely to be diagnosed with cancer, and tend to have risks factors for heart diseases or stroke. In addition, an extensive and advanced ophthalmic R&D community has emerged in Israel, leading to the establishment of several new and exciting companies in the fields of advanced diagnostics, corneal and retinal implants, surgical helmets, artificial vision and more, including companies such as OrCam Technologies, Nano Retina, EyeYon Medical, Visionix and BeyeOnics.