The hot innovations of Biotech Israel 2004 week

How do you extend the life of oranges? What new crowns are being developed for children's teeth? Who developed a cholesterol medicine from an edible plant? All the answers and many more will be presented at the exhibition of the hottest solutions and innovations in the field of biotechnology, nanotechnology, medicine, biology and medical devices. Entrance to the exhibition is free. Includes two conferences: 1. Development of tools, technologies, medicines and vaccines 2. Economic business conference. Lectures, sessions and panels. David Intercontinental Hotel

In the third Israeli biotechnology week - Biotech 2004, which opened this morning in Tel Aviv, over 80 biotechnology companies from Israel and about 12 from abroad, researchers and academics and representatives of some of the world's largest venture capital funds in the field of biotechnology took part, who will come to take a close look at the largest concentration of the startup -The biotechnological noses that can be found under one roof

According to the data of the Ministry of Industry and Trade regarding the progress of the industry in the last decade, it appears that the number of Israeli companies in the field of biotechnology in relation to the population is 5 times higher than the corresponding number relatively in the USA or the UK. Israel is even among the prominent countries in the relative share of professional publications in the fields of life sciences, in the number of senior academics in the field, and it receives a high score based on other criteria that first and foremost testify to the "Jewish garden" that stands behind innovative inventions and developments in this field as well.

Biotechnology companies from 12 countries will take part in the "Biotech Israel 2004" week, which will be held between May 4-6 at the David Intercontinental Hotel in Tel Aviv. Among the international companies, coming from the USA, Canada, Belgium, Norway, Germany, England, Japan and India, you can find Novartis, FMC BioPolymer AS/NovaMatrix, keyNeurotek and the Tata concern. Foreign investment companies, such as Invest UK and local funds specializing in biotech, have also confirmed their arrival. In addition, more than 80 Israeli companies have already confirmed their participation, including Teva, Paramus, General Biotechnology, Hadassit, Ehrlich & Partners, Kesselman et Kesselman, Biological Industries, IBM, Applision and more. The incubators NGT from Nazareth, Mashgav from the Galilee, A.T. from Ashkelon, Gabish from Kibbutz Galil-Yim and Granot Initiatives from Emek Hefer will promote about 30 startups in the field of biotechnology. The entire event already stands out today, despite the situation, as the largest biotechnology event in Israel.

A smart processor for heart failure patients

Problems with heart function currently affect tens of millions of people worldwide. In a significant number of cases, this is a problem of lack of synchronization in the action of the heart's ventricles and especially in the dysfunction of the left ventricle. The start-up company AI Semi is developing a unique solution to the problem: the Spike processor, an innovative artificial intelligence processor, the need for energy at the lowest level and performing a medical procedure known as CRT - Cardiac Resynchronization Therapy. AI Semi will take part next month in the "Biotech Israel 2004" week events, which will be held between May 4-6, at the David Intercontinental Hotel in Tel Aviv. As part of the event, the company will be revealed to the public for the first time and will present its working model.

The Spike processor, which will work closely with the microcontroller of a two-ventricular pacemaker, which is implanted in the patient's chest, will process data coming from electrodes and physiological sensors that are sensitive to the mechanical activity of the heart chambers. The processor will automatically and continuously learn the optimal pacing intervals that will restore the synchronization between the left and right ventricles, which is necessary for the efficient operation of the heart and thus increase the heart's capacity.

The use of AI Semi's solution will improve the patients' quality of life, improve the performance of the circulatory system, slow down the rate of disease development and even allow the heart to self-rehabilitate in a process that is at the center of several clinical studies (the reverse remodeling process).

Behind the development is a team of experts in the fields of artificial neural networks, heart experts, processor design experts, biologists and others. According to the CEO of AI Semi, Dr. Rami Rom, the company presented the new processor to several companies from the USA and Europe with the aim of integrating the Spike processor into their pacemaker devices. Dr. Ran Ginosar, chairman of the company's board of directors, expects the realization of AI Semi's technology in the future in additional implanted medical control systems that require learning and self-adjustment capabilities and ultra-low power supplies.

The AI ​​Semi company is a subsidiary of the Garnot incubator, located in the Garnot industrial park, in the north of Emek Hafer. The incubator mainly deals with the development of medical devices and information technologies. Hamma has a number of subsidiaries operating outside of Hamma, which have raised funds and sell their products.

Respiratory medication

Israel's "Baby's-breath" Co., Ltd. will reveal, as part of the Biotech 2004 exhibition, a development intended for inhalation treatments (medications taken by inhalation) for children. The company, which entered the market last year with the development of a tent called "Child-Hood" intended for babies suffering from respiratory problems such as asthma and bronchitis, is entering the market this year with another development in the field, which complements the existing product and opens up new markets for it.

In inhalation treatments, a nebulizer is used to inject the medicine into the respiratory tract. The nebulizer turns the liquid medicine into a fine spray of macaroni drops. All the nebulizers on the market only work upwards, when the compressor is placed on the floor and the mask is installed on the patient's face.

The new nebulizer integrates with the Child-Hood (inhalation tent) and completes it into one system that gives medicine to babies in a spray. This nebulizer is much cheaper than the ultrasonic nebulizer that worked with the system until now and makes it an attractive system for both the home and the hospitals.

The "Baby's Breath" company, which came out of the heat of initiatives, started its activity two and a half years ago by developing a solution to the problem of administering drugs in the respiratory tract to babies. About 30% of babies in the western world need medical treatment given by inhalation. Until the development of the "Baby's Breath" device, inhalation treatments for babies were given with the help of a mask. The mask must be attached to the face tightly - something that creates a natural resistance in babies that does not allow the treatment to be completed and impairs its effectiveness. The "Child-Hood" developed by "Baby's Breath" provided a solution that makes it possible to care for babies without creating resistance, even while sleeping. Tests done show that the effectiveness of the treatment with the help of the tent is high and guarantees the same results as those obtained in the mask inhalation treatment for an adult.

The idea for development was suggested by a pediatrician specializing in lung diseases from Ziv Hospital in Safed. "We came across this problem when we saw the problems the parents and the medical staff encounter when providing treatment with the existing equipment and we decided to find a solution to the problem" says Dr. Israel Amirav.
Assaf Halamish, the director of the company and himself an engineer with extensive experience in development: "We developed the first product within the Yozemot-Granot technology incubator and today, two and a half years after the start of development, we are producing both products. We have passed the CE tests and in a few months we will also receive FDA approval. There is interest from distributors in several regions of the world. We are in negotiations with the Teva company that is interested in marketing the products in Israel. The products will be sold both to private consumers through pharmacies and to hospitals.

The company "Baby-breath" is a portfolio company of Yozemot-Granot incubator, located in the Garnot industrial park, in the north of Emek Hefer. The incubator mainly deals with the development of medical devices and information technologies. Hamma has a number of subsidiaries operating outside of Hamma, which have raised funds and sell their products.

Crushing stones

The Sialo-Lite company will present, as part of the exhibition, an innovative medical device it has developed, designed to crush stones in the salivary glands with minimal harm to the patient being treated. The system can also be used to treat Temporomandibular Joint Syndrome, a condition of jaw joint erosion, manifested by symptoms of headaches, pain in the facial area and limited ability to open the mouth.

The unique technology of Sialo Lite simplifies the process of stone removal and treatment
In TMJ, in that the entire treatment process is done under local anesthesia only, while reducing the damage to the facial nerves and the tissues surrounding the treated area. The procedure is performed without leaving external scars for the patient and at a much lower cost than the cost of surgery, which is the accepted treatment today.

Sialo Light, which currently operates within the technology incubator "Ashkelon Knowledge Industries", was founded in 2003 by Prof. Oded Nahalieli, Head of the Oral and Maxillofacial Department at the Brazilian Hospital, Ashkelon, a world-renowned expert in the field of oral and maxillofacial surgery and the inventor of an endoscope and stent for oral and maxillofacial uses.

According to Prof. Nahalieli, over a percent of the world's population suffers from the problem of stones in the salivary glands, which in many cases manifests itself in repeated pain and swelling. In addition, close to 11 million, in the US alone, suffer from TMJ problems every year, with at least one percent of them needing surgery.

"The currently accepted techniques for these patients involve invasive surgery, under general anesthesia, which requires a prolonged recovery period of 5-7 days of hospitalization. The process developed by Sialo Lite is based on combining a medical laser device with an endoscopic system to gently crush the stone inside the salivary duct and treat the worn tissue (in the case of TMJ). The system consists of permanent parts and disposable parts."

Photo Caption - sialo3.jpg: Diagram of the oral cavity and salivary glands.
DNA tests in the field

The start-up company "Sensis", a subsidiary of "Gabish", will unveil a tiny device (length 16 cm, width 9 cm, thickness 7 cm), which is used to identify DNA sequences. One of the first applications for the device is in DNA testing processes in the field for military and police uses. It can also be used for food testing and determining gene sequences for research and medical purposes.

The innovative "Sensis" device, which uses a laser beam passing through an electrophoresis system (running samples in an electric field), performs automatic analysis of nucleic acids (DNA). "The equipment that exists today and is used for similar purposes is expensive and requires a lot of expertise in operating it," says Dr. Iris Geffen, CEO of Sensis. "Sequencing (the act of identifying DNA sequences) is usually done in special laboratory units, in universities, hospitals and industry. The uniqueness of our device is its minimal size, in the fact that it is not sensitive to shaking and that its price is significantly lower than the systems used today. Beyond that, it is multi-purpose and suitable both for DNA sequencing and for identifying unique segments for various purposes."

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Photo caption: "Dr., what is my DNA?". The innovative Sensis device

Protects fruits

The Frigal start-up project, which operates as part of Migl/Gabish in the Galilee, will be unveiled at the Biotechnology Exhibition 2004. The project includes a line of natural oils that are sprayed on fruits, designed to protect, preserve and extend the shelf life of the fruits. The protective layer extends the shelf life of the sprayed fruits - even in extremely high humidity and temperature conditions. Beyond that, the oils also protect the fruit from pests. According to the company, the Israeli development will be a natural alternative to pesticides and chemical preservatives that are currently used in the industry. The global market for fruit protection and life preservation products reaches over 32 billion dollars a year.

To date, the company has identified oils that can protect strawberries, tangerines, peaches, nectarines and pears - fruits that are particularly sensitive to harmful fungi. The guiding line in finding the solution, the company says, is to avoid side effects, such as smell, taste, or shape change and the ability to extend the shelf life of the treated fruit.

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Fruits treated with Frigel oils, versus control groups
Photo Caption: Freegel strawberry and just a strawberry
Mini capsules for medicine

The start-up "NutraLease" (NutraLease) will reveal new carriers (nano-encapsulation) of hard to dissolve drugs. The carriers developed by "Nutra Liz" allow the dissolution, transport and absorption of health supplements by the digestive system. The company's solutions are already on the market and are integrated, for example, in "Canola Active" oil, produced by the "Olive Tree" company, which is enriched with a unique mixture of natural substances capable of reducing the chance of getting heart diseases.

"The development of a medicine includes the synthesis of the active substance and the addition of substances whose function is to make the medicine water-soluble, so that its absorption in the body is optimally possible and the passage through the various cell membranes is easy," explains the founder of the company, Prof. Nissim Garti, who serves as the head of the Institute of Applied Chemistry at the university Hebrew and a world expert in emulsion technology. "In recent years, an effort has been made to change the approach and switch to drugs based on peptides and/or based on macromolecules that are not necessarily water soluble. "Gluing" inactive substances to increase solubility is an expensive operation, sometimes complicated and sometimes results in the neutralization of the active groups."

At "Nutra Liz" they developed the Nano-Sized Self-assembled Liquids (NSSL), which are an advanced generation of nanoemulsions. The nanodroplets are able to dissolve considerable amounts of molecules with limited solubility and transfer them directly to the digestive system and from there to the blood system. "There are currently no liquid systems capable of dissolving active substances such as: lycopene, phytosterols, Voltaren, vitamins, etc.," says Prof. Garthy. "On the other hand, there is a high demand from the health authorities for the ability to absorb and protect these substances in a liquid state. Therefore, it is expected that many transparent products in the field of food, cosmetics and pharmaceuticals will occupy a significant part of the market in the future".

Crowns for children

Urident, which develops unique dental products, will present its first industrial product - ready-made crowns for children's primary and permanent teeth. The uniqueness in the development: the crowns are the color of the tooth and do not contain allergenic (sensitizing) substances.

According to Dr. Uri Zilberman, the inventor and development manager of "Uri-Dent", it is a cast crown, the color of the tooth, made with a complex technique of injecting a plastic material with properties close to those of metal. The new crowns will replace the stainless steel crowns that are currently used to restore teeth that suffer extensive destruction due to caries, or due to developmental problems. "Ori-Dent" crowns are more aesthetic compared to stainless steel crowns and they do not contain sensitizing substances, which have the potential for future health damage. "The time has come to also solve the last important aesthetic problem that still exists in pediatric medicine," says Dr. Zilberman.

According to Dr. Zilberman, the new product is the fruit of over two years of research. The invention is protected by a registered patent registered in the USA in July 2003 and submitted for registration and approval in the rest of the world. During 2003, a comprehensive anthropometric study was also carried out, in order to adapt the shape and size of the crowns to today's population and to produce new crowns in sizes suitable for children today. Dr. Zilberman is a globally renowned researcher, an expert in pediatric dentistry and a PhD in anthropology (doing theoretical and applied research at the Hebrew University of Jerusalem) who serves as the head of the Pediatric Dentistry Unit at the "Barzilai Medical Center" in Ashkelon.

According to estimates, one in nine children in Israel and in the world is treated with a steel crown, while there are cases where one child is treated with 8 crowns at the same time. About 120,000 metal crowns are sold annually in Israel. "When you take into account the same ratio of children to the population in developed countries, the global annual market is estimated at about 175 million dollars - and this is our target market."

According to Asher Weinstein, CEO of "Orient", after the start of sales in Israel, the company plans to introduce the product to the world market. The company expects to reach a sales turnover of approximately 4.7 million dollars in the fifth year of operation (not including sales of new products that are currently in initial development). The company is currently looking for a strategic partner with a global market setup for dental products, or an investor, to finance the company's business development and marketing activities.
Shortening the wait for tests

The "Biological Industries" company will unveil the BIOAMF-3, an innovative growth medium for growing amniotic fluid and placental cells for genetic analysis. The Israeli development significantly shortens the period of time that passes from the moment of the test to receiving the results. Chromosome tests help identify genetic defects in the fetus.

According to David Fiorentini, the scientific director at "Biological Industries", the time that passes until receiving a final result of the genetic analysis is of great importance both from an emotional point of view - the stress involved in waiting for the final result, and from a practical point of view - the need to terminate a pregnancy in case of finding a genetic defect. "Termination of a pregnancy in the second trimester is actually an abortion, so it is important to get a result as early as possible in order to facilitate the process," says Fiorentini.

Acupuncture for the purpose of pumping the amniotic fluid and the cells is done at week 16-20 of pregnancy. Usually 20-40 ml are drawn for the genetic diagnosis. The cells can be sown on glass, or suitable bottles, for the purpose of obtaining colonies, or cell culture. Since the cells are dividing, genetic diagnosis can be performed on these cells and thus any defect can be identified - a lack or excess of a chromosome, breaks in the chromosomes, or an excess of genetic material.

"The accepted process for genetic testing today lasts between 8-12 days," says Fiorentini. "We managed to shorten the time to 6-8 days, a figure that is of enormous significance to everyone who is waiting for the laboratory's answers. In addition, the substrate selectively encourages the growth of only the desired cells and not the cells that are not suitable for chromosomal analysis and even interfere with the growth of the desired cells."

In the last decade, a variety of products designed for the field of cellular genetics have been developed at "Biological Industries Israel Beit HaEmek". Among them, substrates for growing amniotic fluid cells and placental cysts and substrates for blood and bone marrow cell cultures for genetic analysis, which are sold with great success in Israel, Europe and Asia.
An old and annoying problem

The Israeli start-up Quantumix (QuantomiX) has solved an old and annoying problem in the field of life sciences - the fact that with the electron microscope, which with its development turned the world of science upside down and opened new horizons for research, it was not possible until now to examine wet samples. The company's blue-white development, which will be presented as part of the Biotech 2004 exhibition, changed the picture.

Quantumics has developed a disposable capsule, based on a thin membrane with a thickness of 100 nanometers, which originates from the semiconductor industry. The membrane is transparent to the electron beam of the microscope, but strong enough to maintain the pressure differences between the vacuum in the microscope and the wet sample being tested inside the capsule - whether it is solid or liquid.

According to the CEO and founder of Quantumics, Dr. Uri Zik, life science researchers have been waiting for about two decades for a real electron microscope image of a wet sample. "Until today, the researcher had to dry the samples and watch them, which could take days and changed the natural state of the sample. The capsule, which we developed, allows for the first time to see wet samples in their real state within a few minutes, is suitable for any scanning electron microscope and definitely changes and expands their performance", says Dr. Zik. "Our capsule opens up a new world for biologists and drug research, with fascinating applications in the field of pathology as well." One of the most immediate uses: the ability to measure the size of the fat particles in the blood. This ability led to cooperation with a number of leading research institutes, such as the Obesity Research Institute in Boston, where the latest experiments in technology were made.

Lower cholesterol

"Palsamed" will present the Pals, a natural ingredient that can be used as a basis for a natural medicine to lower cholesterol. The active ingredient was isolated and produced by the company from an edible plant, known in the traditional medicine of the Middle East and the Far East. The company even succeeded in proving, based on animal model experiments, that the cholesterol-lowering capabilities of the substance developed by "Falsmed" are similar to those of "Lipitor", a popular drug marketed by the Pfizer company for monitoring cholesterol levels.

"Diseases resulting from excess cholesterol are among the most common causes of death in the Western world. In the US alone, close to 100 million adults suffer from excess cholesterol..." says Dr. Saif Abu Mouch, founder of the company "Falsmed" "The problem is that the drugs that exist today, designed to regulate cholesterol levels, have many side effects, including muscle pain , inflammation and destruction of muscles, liver function disorders and many other phenomena. And most importantly, high doses of statins are needed to reach the desired cholesterol level."

According to Dr. Jamal Mahajana, the company's chief scientist, the Israeli development of the Pals as a drug is expected to have a much easier approval process than was the case in the past, due to the change in FDA (American Drug Administration) policy and the facilitation of obtaining approval As far as herbal medicines are concerned. "The medical establishment is gradually opening up to the view of natural medicine according to which the totality of ingredients in a medicinal plant is responsible for its healing ability. The new approval route is much shorter than the usual investigational new drug (IND) procedure, which requires the definition of a new chemical entity."

Citrus fruit

At the exhibition, Citramed will unveil the ACPE (Active Citrus Peel Extract), a product based on citrus peel extract, capable of killing a wide variety of bacteria and fungi. The extract is watery and has a light citrus scent. The company estimates that the main uses for the development will be mainly in the cosmetics, food and pharmaceutical industries. Citramed, which specializes in the development and production of natural products, currently operates within the "Ashkelon Knowledge Industries" technology incubator.

Behind the technology are Dr. Uzi Afek and Zhanna Orenstein, researchers at the Volcanic Institute who developed a unique technology that makes it possible to restore the citrus fruit's natural defense system in an aqueous extract and enrich it with ingredients with antimicrobial properties. The discovery led to a unique compound - an extract based on only natural ingredients and produced in a unique biotechnological process and exclusive to Citramed.

According to Efrat Kat, CEO of Citramed, the development meets a growing demand from consumers to reduce the use of synthetic materials and switch to the use of natural materials, especially in consumer products such as food, cosmetics and health products. "In the field of cosmetics, the product will be used as a preservative for cosmetics and toiletries and as an addition to cosmetic products, in order to prevent the formation of infections in the users. In the food sector, the product will be used as a natural antimicrobial preservative, and in the medical market we intend to market it as a botanical drug with antibiotic activity."

According to the company's estimation, the scope of the relevant commercial market for the product currently stands at $5.5 billion per year.
The product, protected by a registered patent, is currently nearing the end of the phase of identification, evaluation and characterization of all the active ingredients.

XNUMXD studies

Whereas Academac, CambridgeSoft's representative in Israel, will reveal for the first time ChemOffice 2004, an educational research software package that builds molecular models in XNUMXD. The software comes with special viewing glasses that allow XNUMXD viewing of the created structures, and examining them from different directions.

Another uniqueness of ChemOffice is the ability to combine in one package all the software necessary for daily work in the laboratory, or in the classroom. Among the basic tools in the software stands out the possibility of drawing different molecular structures while automatically checking the drawn structure for correctness and the ability to identify and display a molecular structure by name. The application includes the automatic addition of hydrogen atoms to complete the molecule and the ability to rotate the molecule on each of the three axes.

The merger of the software with Microsoft's 'Office' software made it possible to design a familiar work environment and a common interface between the two, which is reflected mainly in the ability to combine documents, or document sections. Thus, for example, NoteBook, an electronic "notebook", allows to consolidate all the information accumulated during the day-to-day work and the integration of Merck's medical book that has been converted into an electronic format allows easy and simple information search. Once the requested information is found, it can be copied and transferred to any other document or database.

It seems that against the backdrop of disappointments from the software and communication markets of the investors, the direction is now shifting to biotech, and more precisely - to the medical devices market. A large number of large foreign companies operate local offices in Israel to locate technologies or occasionally send delegations to test products.
It seems that even though in many cases we still don't really see results, the belief in the field still exists.
True, the life sciences and biotechnology industry in Israel has a good chance of replicating the success of the high-tech industry in the fields of communications and software.

There is no reason, with the taking of the appropriate responsibility by the government and the arrival of the appropriate funds from the funds, why all those companies currently active in the biotech industry, will not succeed and some of them in a big way. Since this is a field that matures more slowly than the high-tech field, and requires more investments, it takes time for a complete cycle to go through and for you to see results in the field, and therefore currently see only a little of the existing potential. In order to promote the field of biotechnology in Israel, we must also understand that this cannot be done without the largest companies in the world and without the Israeli government directing the right resources in that direction.