Three men walk into a bar – an African-American, a Hispanic and a Jew. Which of the three is most likely to die of kidney failure? This isn’t a joke, but a question that a new field of 21st century medicine is attempting to answer and confront. [For the answer, scan to the end of this article.]

Since the advent of the Human Genome project, akin to searching in a crystal ball scientists have been gazing into our genes, trying to understand which diseases might afflict us, by considering our ancestry. As has long been suspected, no one cure fits all. A specific combination of drugs to cure breast cancer may succeed for one woman, while the same cocktail may fail in another.

This is because each of us is an individual with unique genes, different diets, environments, habits and behaviors. All these factors influence disease development, progression and ultimately how we will respond to the medicine we may have to take.

A recent conference in Israel covering this topic of personalized or translational medicine addressed some of the challenges in the field, highlighting the country’s success stories and discussing ways in which Israel, a world leader in biotech innovation, can help to advance this new trend in science.

Shai Yarkoni, CEO of Bio-Negev, a biotech tech transfer venture in southern Israel, and also chairman of the Life Sciences advisory council of the Israel Export and International Cooperation Institute, was among the featured guests at the June conference. The Personalized Medicine World Conference (PMWC) Israel, held in Herzliya on June 20 and 21 was the first of its kind in Israel, spurred by a similar conference earlier this year in the US. The PMWC Israel was put together by Silicom Ventures and the Advantest/Oncotest-TEVA business unit of Teva Pharmaceuticals.

There’s certainly a lot of hype around the new buzzwords ‘personalized medicine,’ and Yarkoni was only too happy to make some sense of what’s happening in Israel.

What makes medicine personal?

Like the new ‘clean technology’ brand, Yarkoni says the term ‘personalized medicine’ is now used for marketing purposes, to raise money and attract attention. However, “it’s clear that personalized medicine as a whole is coming to fruition in this decade,” he tells ISRAEL21c.

Hope for delivering personalized medicine around the world started as early as the 1980s and ’90s, reaching a peak in the area of antibodies, the only science in the field that has fulfilled expectations in personalized medicine, he says. In 1997, sales of antibody-related drugs reached $250 million. By 2007, sales had skyrocketed to $30 billion, with most activity in the US and Europe. “This is the only area in personalized medicine where the research and the early stage research have matured to real industry,” Yarkoni states.

Today, there are two successful antibody drugs driving the market: Herceptin to treat breast cancer, and Erbitux to treat colorectal and now head and neck cancers. Ironically, the early stage development of the blockbuster cancer drug Erbitux traces its roots to Israel at the Weizmann Institute and researchers Prof. Michael Sela, Dr. Esther Hurwitz and Dr. Esther Aboud-Pirak. Royalties from the research behind the drug were settled in court, and the company involved was linked to the Martha Stewart scandal.

This is part of the problem, says Yarkoni, who explains that while Israeli science may be very good at innovation, overall there is a problem in getting the innovation financed, getting it off the ground and transforming it into working companies.

Still, there is a chance that Israel could catch the next wave in personalized medicine, specifically with stem cells, through companies like Pluristem and SCTyx which treat autoimmune disorders, or Gamida Cell, which is combating blood cancer, he says. One additional company is BrainStorm, a stem cell company that’s developing a solution for Parkinson’s.

Yarkoni says: “We face a repeated story with the stem cells as we do with the antibodies. That’s where we fall behind; unable to move from a great idea and research to the next stage of a sustainable business model.”

Seeking sustainable business models for biotech

Through his Bio-Negev fund and networks in Europe and the US, Yarkoni is working to build sustainable biotech companies in Israel, where, he says, biotech start-ups tend to either sell out to bigger firms or fade away. “The main issue is that personalized medicine is still in its infancy. Because of that we can maintain a leadership position,” he declares.

He claims that while one of Israel’s personalized medicine biotech companies in oncology is quite successful, it’s not innovative. He’s referring to the diagnostic firm Oncotest (now Aventest), that analyzes blood samples to provide a genetic profile of a specific cell. The company is owned by the pharma giant Teva Pharmaceuticals.

Another company that brands itself as personalized medicine, Israel’s Rosetta Genomics, is not really personalized medicine, according to Yarkoni. Applying microRNA for therapeutics and diagnostics he says that it doesn’t actually deal with any issues that are ‘personal.’ Shares in the company have recently plummeted.

Yarkoni suggests that those interested in knowing more about the market potential in Israel and where its strengths lie, look to multi-disciplinary research, the hallmark of good personalized medicine. “Israel is perhaps the most advanced country in making combinations,” he states, meaning that Israelis combine math with chemistry, physics, genetic research, biology and pharmaceuticals. “All the biggest universities in Israel have good research brewing in this direction and the start-up factory in Israel is in very much a leading position,” he asserts.

Yarkoni points out that of 15 companies featured at the PMWC Israel conference, four were based on stem cells: “Gamida Cell has a stem cell treatment in Phase III clinical trials and in a year or two they will have a product in the market,” he says, adding, “We fall behind in technologies and areas where the world has moved forward to establish bigger companies, with more money and management. Israel is still very much a start-up nation in that respect.”

Computers that model cancer

Bernard Dichek, editor and founder of BioIsrael, Israel’s leading biotech news website in English, isn’t convinced that Israel is a leader in personalized medicine just yet.

Among the companies featured on the recent conference roster Dichek believes that Pluristem and Insightec, which ablates tumors using ultrasound and MRI, are good companies, “but I wouldn’t normally think of them as personalized medicine,” he tells ISRAEL21c. “Though as you can see, when something becomes trendy everybody wants to jump on the bandwagon, or gets placed there by people anxious to organize conferences.

“Personalized medicine has been talked about for years but there still isn’t really a critical mass of mature companies in the area. The fact that it’s a bit of a stretch for some of the companies in that list to be placed on it is perhaps an indication of this,” he suggests.

That said, this doesn’t mean that there isn’t any innovation coming from Israel. Dichek cities Optimata, with its predictive powers, as a “company that has the greatest potential for providing real, personalized medicine. The company is at the forefront because of both technology and insight.

“The technology is a sophisticated computer modeling system that uses algorithms to predict how each individual will respond to specific drugs and can therefore help doctors decide which drugs have the best chance of helping their patients,” he says.

With cancer, drug selection is a game-changer

“In the cancer arena drug selection can be a game-changer,” Dichek points out. “Doctors have no way of knowing how a patient will respond to a chemotherapy drug and by the time they find out if the drug is working the condition of the patient can be irreversible.

“In a landmark study conducted with Cancer UK, Optimata proved that its computerized system was much better than oncologists at predicting the right drug for breast cancer patients,” he adds.

“The insight – espoused by founder Zvia Agur more than a decade ago – was that many companies were betting on the wrong horse around the time that the mapping of the Human Genome was taking place, by assuming that it would be possible to treat diseases by identifying disease-causing genes. As is now generally accepted, 10 years after the genome was mapped, most diseases have multiple gene causes and consequently, treating patients through gene mapping is a very limited area,” Dichek explains.

“Optimata’s approach, on the other hand, which is based on mapping the physiological parameters of the patient, has proven itself and the company has received significant financial support from Teva Pharmaceuticals and is currently using its technology to help Teva test new cancer drug candidates.”

Optimata was represented at the PMWC Israel event. Dichek names Aposense as another company worthy of mention in the personalized medicine arena: “The company has a molecular imaging technology that can identify non-responders to drugs early on, especially cancer drugs. The company is only in Phase II clinical trials but is well-funded and recently went public on the Tel Aviv Stock Exchange,” he says.

A personal investment

Dr. David Sidransky, as an American physician and research scientist looking in from the outside, believes that Israeli personalized medicine holds great promise. Chairman of the personalized medicine oncology company Champions Biotechnology, Sidransky was profiled by TIME Magazine in 2001 as one of the top physicians in America for his work with cancer.

Champions, which has invested in Israeli research and has a branch in Israel, is an oncology company that takes a specific cancer tumor from a patient, grows it in a mouse lacking an immune system and tests various drug combinations to find the best one for the patient.

“Israel is receptive to personalized oncology,” says Sidransky who has recently licensed a technology from one of the local universities. He sees what he calls a “general acceptance by the Israeli population,” among consumers and institutions that personalized medicine should be a major focus.

Maybe it’s cultural? “Israel and the Jewish people in general will go to the ultimate out-of-the-box solutions to help themselves and their families. Health drives that desire,” says Sidransky who participated in the PMWC Israel as a keynote speaker.

Another of Israel’s strengths is the country’s much-touted entrepreneurial spirit: “I think there is a real push to do unique things [in Israel]. That drives a lot of small businesses,” he says. And then there’s human capital; brains. That’s another Israeli strength in the burgeoning field of personalized medicine. “It’s not hard to find doctors in any area contributing here.”

Accelerating science and Israel’s potential

Sidransky says that when it comes to diseases, breast cancers and ovarian cancers, which are major diseases in the Jewish population gene pool, have led to “watershed” research in other cancers.

Interested in bringing together companies and researchers working in the field of personalized medicine, Sidransky tells ISRAEL21c, “Personalized medicine is such a cool idea. How can we reduce this to practice? We need substantial interaction in the business and venture capital arena; to bring together the investment world with the scientists.”

Sidransky is not only dreaming of better treatments for patients today and in the future, but is also accelerating ways to make the most of the science and potential in Israel, by bringing together different worlds.

By the way, the answer to the question posed at the opening of this article: An African-American has a four times greater chance of dying of kidney failure. New research into identifying genetic biomarkers and finding a treatment for kidney failure based on genetics is being led by an Israeli team headed by Prof. Karl Skorecki, a nephrologist at Rambam Hospital, and a researcher at the Technion – Israel Institute of Science.

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