Cross-Over Thinking

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Imaginatively applying ideas from one discipline to a completely different area is often the source of innovation and entrepreneurial success.

In the Israeli life sciences industry, a good success story that was inspired by an external source is the Given Imaging camera capsule. The breakthrough medical device was invented by a scientist whose expertise was in developing video cameras that were placed on the tip of missiles. When Gabriel Iddan heard from a medical colleague about the difficulties gastroenterologists had pinpointing lesions in the spaghetti-like interior of the small intestine, he came up with idea of mounting a tiny camera onto pill and having patients swallow it. The result was a camera that broadcasts images back to a computer, much like a satellite in outer space, as it winds its way through the digestive tract.

And just as ideas can bring interesting results when they move into the life sciences, so too when they migrate outside.

Recently, an Israeli life scientist achieved international success in the world of art when he created a series of photographs drawn from the insights, reflections and experience that he had garnered during more than 30 years working in research labs.

Eran Gilat is a neurobiologist who has published extensively in journals such as Brain Research and Circulation. His hobby and passion for many years has been photography.

A few years ago he decided to do a photographic project that he called “Life Sciences” where the subject matter is biological tissue.

The result has been crowds lining up to see his photographs in recent exhibits in New York, London and Israel.

What makes Gilat’s “Life Science” series unique is not that the photographs are taken by a scientist or even that the images display biomedical content, but the incisive philosophical reflection that the photos offer. (His site, still under construction, is here.)

Gilat’s “Life Science” photographs generally document artifacts comprising some form of tissue, organ or dead animal that is juxtaposed beside antique medical instruments and other objects, including food and naked bodies. Impeccably lit, the radically juxtaposed artifacts are laid out in a surprisingly orderly way – as though some kind of inexplicable medical experiment is about to take place.

Gilat’s photography hobby moved him into the art world, and he joins a long line of scientists or entrepreneurs who have strong interests outside their chosen field. Craig Venter comes to mind, with his love of yachting. So does Sir Chris Evans and his infatuation with cars. Entrepreneurs often expand their interests or seek new challenges. What are others in biotech circles?

Bernard Dichek

The Israel-US Connection

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The Israeli and American biotechnology industries are quite closely intertwined, with collaborations ubiquitous in academia, the clinic and in the financial community.

What seems to makes the interplay successful is that there is no fixed pattern- players on both sides change roles according to various needs and opportunities. For instance, the U.S. seems to be a bigger draw for academic studies in this relationship, but when it comes to clinical or industrial work or finance, companies will simply go where the best deal is.

A good example is Prolor Biotech, a developer of therapeutic proteins that owes its origins to the almost de rigueur custom of Israeli life science Ph.D.’s doing post-docs at American institutions. Dr. Fuad Fares did so in the late ’90s when he joined a research team investigating fertility hormones at Washington University in St. Louis. The team developed a technology – a short, naturally occurring amino acid sequence known as CTP – that could increase the life span of hormonal injections used to promote pregnancy. Merck & Co. eventually licensed CTP in order to develop Elonva, a hormonal injection that requires a once-a-week dosage compared to the once-a-day dosage of the non-CTP version.

Dr. Fares returned to Israel in 2001 and established a start-up in a business incubator, looking for additional therapeutic protein applications for CTP. In 2005 he was joined by Dr. Avri Havron and Shai Novik, veterans of both the US and Israeli biotech industries. They accelerated development by raising funds in the US, first from investment angels and then later through an IPO on the over the counter (OTC) exchange in New York because, “At the time (2007) the Tel Aviv capital markets lacked experience in the life sciences and we didn’t think we could get funding in Israel,” says Novik.

But by 2010 things had changed. The Tel Aviv Stock Exchange (TASE) had become more interested in the life sciences, and more than 50 biomeds were traded locally. Prolor did a dual listing on the TASE, joining Teva Pharmaceuticals, Protalix, and other biopharma companies with public shareholders on both sides of the ocean.

The trans-Atlantic give-and-take is also evident in the way that the company does its R&D and clinical development. Prolor now has four CTP-enhanced proteins in its pipeline, including a growth hormone product that is about to enter Phase 3. Yet the company was able to do all this with a very small in-house staff of about 25 employees.

That’s because the company does “early stage R&D in-house here in Israel, and then sub-contracts the preclinical and clinical work to outside providers all around the world,” says Novik, noting that the company does its protein manufacturing in Massachusetts and toxicology studies in Michigan.

Novik sums it up this way: “We run our company the American way, but by being located in Israel we have lower cost structures than comparable companies in the U.S., and we are able to draw from a great pool of local talent. Also, we are able to get state support, apply to binational funds and thereby maximize our assets.”

Bernard Dichek

Can a Hollywood horror movie influence drug development?

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Warner Brothers has begun a publicity campaign for a new calamity film, called Contagion, scheduled to be released in the U.S. on Sept. 9. Directed by Steven Soderbergh, and made with cooperation from the Center for Disease Control and Prevention, the film is about a deadly flu pandemic in which millions die.

With an all-star cast that includes Matt Damon, Kate Winslet, Gwyneth Paltrow and Elliot Gould, movie industry analysts are expecting Contagion to draw big crowds and earn Warner Bothers a profit on the $60 million it invested in the film.

But is it possible that this scary movie could also have a financial impact on the dozen or so biotech companies that are currently scrambling to develop a universal flu vaccine? Could the increased public awareness actually help cash-strapped researchers raise the funds they need to accelerate R&D programs?

The answer could be yes, if the stock-market experience of BiondVax Pharmaceuticals is an indication of investor interest.

BiondVax is one of the leading contenders in the race to find a universal flu vaccine, with its platform technology recently completing a successful Phase II trial. The company’s stock price has fluctuated dramatically over the years, often in an apparent response to the perceived public threat of a catastrophic global flu outbreak.

The company’s share price on the Tel Aviv Stock Exchange spiked most sharply in 2009 at the time of the swine flu outbreak, going overnight from about 2 shekels a share to 7.

BiondVax’s universal flu vaccine candidate attempts to overcome the limitation of current flu vaccines, which are strain specific and target proteins (hemagglutinin) on the surface of the influenza virus. As the hemagglutinin protein changes when the virus mutates, flu vaccines have to be constantly reformulated.

BiondVax’s platform technology breaks new ground because it targets conserved areas of the influenza virus, which are common to all strains. The technology has been shown in laboratory tests to provide protection against all known strains of flu, including swine flu and avian flu.

The company is planning another Phase II trial for its vaccine enhancer product to begin by the end of this year with results expected in early 2012. Following that, a third Phase II trial is planned for late 2012, with the Phase III trial expected in 2013. Launch of the flu vaccine enhancer product could potentially be as early as 2014.

The company had expected to wait for the completion of its vaccine enhancer product, which is based on the same technology as its universal flu vaccine product, before attempting to raise the funds needed for the more extensive trials required for the universal product.

But that was before Contagion was produced.

Bernard Dichek

Israeli Biotech Merges With Devices

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Israeli Companies Like CollPlant Apply Sophisticated Biotechnologies to Device Industry

The Israeli life sciences industry has shifted its focus from drugs to devices even though many of the underlying technologies have more in common with bio-pharma than with bio-med.

Israeli researchers made their mark on the global scene early, through several blockbuster biopharmaceuticals, including the cancer drug Doxil, (invented at the Hebrew University) and multiple sclerosis drugs like beta-interferon (commercialized by Serono) and copaxone (commercialized by Teva Pharmaceuticals).

Until about 15 years ago, VC investment, and the R&D talent that accompanied it, was drawn to developing biopharmaceuticals, while the medical devices sector was very much the poor cousin of the life sciences industry.

But in recent years, investors, seeking faster regulatory approval and a quicker return on their investment, have funneled a majority of their cash into the medical device sector. During the past decade nearly two-thirds of VC investment has been in medical devices, with about a third in biopharma, a reversal of the American trend.

About 400 companies, 57% of the total number of the country’s life science companies, according to the Israel Life Science Industry trade association, are now classified as medical device companies.

Yet, at a scientific or industrial level, sometimes the distinction between biotech and medical device is blurry. Often, it’s just a matter of how the FDA categorizes a product.

A good example is CollPlant, a developer of recombinant collagen products, and the innovator of a platform technology that is in many ways more sophisticated than those used in the development of many drugs. Because collagen is a structural protein without biological activity, the FDA recognizes collagen as a medical device.

CollPlant’s platform technology, however, involves the use of a very advanced type of genetic engineering: the human collagen is produced in tobacco plants through a transgenic process involving the insertion of five different human genes.

The technology is believed to be the first protein product derived from such a large number of genes (EPO by comparison involves only a single gene) and earned its inventor, Professor Oded Shoseyov, a company co-founder and CSO, the prestigious Hebrew University of Jerusalem Kay Award for Innovation.

As CollPlant’s collagen is grown in and extracted from plants, it offers clear safety advantages over conventional collagen products that are either derived from animals or human cadavers. In addition, because CollPlant’s collagen remains human in content, it is believed to be more easily integrated into the body and less likely to be rejected, thereby speeding up the healing process when used as a wound dressing, bone void filler or for the repair of other tissues.

Even more promising are the advantages of CollPlant’s recombinant collagen’s improved biofunctionality and enhanced physical properties such as tensile strength and extensibility: these qualities are enabling the company’s R&D team to design novel products not possible to be manufactured from animal-derived collagen.

With this goal in mind, CollPlant is co-developing orthopedics products with Pfizer as well as cardio products with Edwards Lifesciences. The company expects to find large untapped markets in Japan and China where consumers are reluctant to use animal-derived collagen products.

Financially, the company has received investments from leading life science VC funds and is now publicly traded on the Tel Aviv Stock Exchange.

The poor cousin has come of age.

Bernard Dichek

Israel and Stem Cells

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In the Israeli stem cell arena – contrary to what many expected – adult stem cells (ASCs) seem to be outdoing the embryonic ones (ESCs). Israeli researchers were among the pioneering developers of ESC technologies, due in part to relatively unrestricted government and societal support.

Unlike the US and many European countries, where political leaders opposed the use of human embryonic cells for research on the basis of Christian religious beliefs, in Israel, rabbinical authorities supported scientific exploration in this area for a positive reason, as well as for the lack of a negative one. Orthodox Jewish belief maintains that a human does not come into being until about 30 days after conception; there was a strong positive, since the same doctrine takes a very activist line about using every possible means to ‘save human lives.’

Consequently, Israel soon became the leading publisher of stem cell research per capita in the world (as reported in a 2006 German study by the Central Library of the Research Center Julich), and a national academic-industry consortium known as Bereshit (Genesis) was formed.

But despite a flurry of academic research, few ECS startups materialized. Currently only one company, Cell Cure Neurosciences, seems to be within reach of a clinical study. Cell Cure today is focused on an ESC product for age-related macular degeneration (AMD).

While the number of ESC technology-derived companies remains small, a substantial number of ASC companies have sprung up. Among them: Gamida Cell, with a Phase III trial underway for patients with blood cancers, such as leukemia and lymphoma, who cannot find a family-related matched bone marrow donor; Pluristem, preparing Phase II trials for placenta-derived stem cell products for the treatment of Peripheral Artery Disease and Critical Limb Ischemia; and TheraVitae with a product in a clinical trial for the treatment of angina pectoris.

Now, another ASC company is on the verge of a clinical trial: BrainStorm Cell Therapeutics, developer of an autologous technology that produces differentiated stem cell products, is about to begin a PhaseI/II study for Amyotrophic Lateral Sclerosis (ALS). The trial has garnered much attention, both because of its stem cell technology and as a consequence of the closely watched indication that is its initial target.

ALS is known to many as Lou Gehrig’s Disease, in reference to the famous American baseball player who was stricken at the height of his career in 1939 at age 36 and died two years later. The disease has completely frustrated researchers ever since, with no therapy being able to stop the almost certain and rapid deterioration that was also the fate of the protagonist in the American best-selling book, Tuesdays With Morrie.

BrainStorm has shown promising preclinical results with a technology that processes adult human mesenchymal stem cells derived from the patient’s own bone marrow. The treated stem cells are differentiated into astrocyte-like cells capable of releasing neurotrophic factors, including glial-derived neurotrophic factor (GDNF). The astrocyte-like cells are intended to be neuroprotective and have a positive impact on ALS as well as on other neurodegenerative conditions like Parkinson’s disease, multiple sclerosis and spinal cord injury.

BrainStorm’s trial will be the first differentiated stem cell human study in Israel, and only the second stem cell trial for ALS in the world, after the US-based Neuralstem clinical trial, using fetal neuronal stem cells, which began last year.

Although BrainStorm has yet to start its trial, it could actually finish ahead of the Neuralstem trial. The latter involves injection of stem cells into the spinal cord of the patient and the trial is moving ahead at a carefully monitored and measured pace. BrainStorm, with a relatively simpler and safer autologous technology involving injection into the muscles or spinal cord, could have preliminary results within 6 months of the start of its trial, scheduled to begin shortly.

It is still too early to say whether it will be an ASC or ESC technology that produces the first commercial product to reach the market; but researchers from both sectors agree that they all owe a fair amount to each other, as there has been a great deal of information sharing and cross-pollination of ideas. Despite the differing sources of the stem cells, many of the processes employ similar methods.

The pooling of Israel’s stem cell resources could gain an additional boost from an international source. According to a news report published earlier this year in the Globes financial daily, Roche Holding AG is about to fund the establishment of a new Israeli stem cell consortium. The consortium will be created in partnership with the local Pontifax VC fund and will based on the intellectual property rights of Israeli universities, in particular the research of Prof. Joseph Itskovitz-Eldor of the Technion Institute of Technology, and Prof. Nissim Benvenisty of the Hebrew University of Jerusalem.

Bernard Dichek