BB&T Israel Correspondent
BB&T Contributing Editor

TEL AVIV — Israel has an abundance of emerging and innovative medical device companies. Its life science industry is young, growing and exuberant and currently exceeds 745 companies, 53% of which are in the medical device sector (see Chart 1). About 60 new life science companies are added each year, driven both by the innovative spirit of the Israeli culture and the large ratio of physicians with an innovative turn of mind.

Exports by Israel’s life science sector increased by 26% during the first quarter of 2007, fueled by exports to India, Ukraine and China, compared to the same period last year. The bulk of the increase was attributed to medical instruments. Many of these new companies are incorporated within incubators organized by the country’s universities, hospitals and research centers and being pushed out to commercialization by technology transfer efforts, and increasing coordination of those efforts.

Various other factors are driving the sector. The life science companies are attracting increased investment from venture groups, with $369 million raised in 2006, up from $284 million in 2005. Also, many companies have turned to the Tel Aviv Stock Exchange (TASE) to raise capital. The TASE index is up 21% this year, reaching an all-time high on June 17.

About 5,000 people attended the Biomed Israel 2007 conference in early July at the David Intercontinental Hotel, double the prior year’s attendance, and the conference was titled “Bio-pharma & Medical Devices,” thus emphasizing not only the country’s efforts in biopharmaceuticals but also the growing role of its device sector. (Chart 2, p. 10, indicates the stages of development for Israel’s developmental companies, ranging from earliest stage to revenue-producing.)

ITTN rolled out

Each of Israel’s dozen universities and leading research institutes has its own for-profit technology transfer office, company or commercialization arm, and these Israeli TT units will now be represented by the Israel Technology Transfer Organization (ITTN), launched at Biomed Israel. ITTN is a not-for-profit organization that will highlight the efforts of the TT organizations which are inherently attractive. Year 2006 patent royalties from Israel, in toto, were more than $100 million annually, most earned by the Weizmann Institute of Science (Rehovot) and the Hebrew University of Jerusalem, from about $1 billion in annual product sales.

The TT company of the Hebrew Unviersity is named Yissum (Hebrew for “application”) with its role of safeguarding one-third of Israel’s academic research, about half of the biomedical investigations.

Yissum and the Weizmann Institute rank among the top 15 TTs in the world, surpassing Harvard and the Massachusettws Institute of Technology, despite having research budgets less than one-sixth their size.

Heading Yissum is Nava Swersky Sofer. At the conference, Sofer told Biomedical Business & Technology that the TT effort is “a large responsibility and a great opportunity.” The Hebrew University produces more than 100 new inventions each year that are owned by Yissum, twice the industry standard per research budget dollar. “Education and research excellence are key to Israel’s future,” Sofer said. “Technology transfer provides a unique opportunity to help the university use its own resources to assist itself, and the nation.”

Another major Israeli group working on tech transfer is Hadasit, of the Hadassah Medical Organization (HMO). It is about to take up residence on the Hebrew University-Hadasssah Ein Karem campus where Israel’s first fully-dedicated biomedical technology park, BioPark, is being built.

Stuart Bernstein, VP marketing and business development for Hadasit, told BB&T, “HMO has long been known for its cutting-edge clinical innovation, but scientific progress during this past year has been astounding. Hadassah is a microcosm of Israel’s life science industry, with a solid academic R&D, patent-protected entrepreneurial base, poised to exponentially catalyze healthcare.

In 2006, Hadasit introduced a revolutionary business model to commercialize early technology developments. Hadasit Bio-Holdings, Hadasit’s subsidiary, was created as an entity to take nine HMO start-ups into a public offering. HBL raised NIS 43 million ($10 million) on the Tel Aviv Stock exchange, based on the promise of its technologies.

Implanted devices abound

The core of Biomed Israel was the broad array of technologies on view in its exhibition areas, with a growing presence in implantable device systems.

• Atria Medical (Caesarea/Dover, Delaware) is focusing on minimally invasive devices for the treatment of congestive heart failure. Its pressure decompression device is designed to reduce elevated left atrium and pulmonary venous pressures below where pulmonary congestion and edema occur. It operates on the same principle as a pressure relief valve. It is implanted between the left and right atria, creating an orifice similar to an atrial septal defect, thereby allowing blood flow from the left to the right atrium and preventing pressure buildup beyond a certain threshold. It is expected to improve the physical capabilities of congestive heart failure patients and to significantly reduce their hospitalization. The company is conducting animal trials using percutaneous insertion of the device.

• BetaStim (Caesarea) is developing a minimally invasive implantable neurostimulator to treat obesity and Type II diabetes. It utilizes the placement of electrodes at sites on a subject’s duodenum which are activated to increase blood insulin levels.

• Minimally Invasive Mastopexy (MIM; Kiryat Shemona) is developing a breast lift device that is implanted by a minimally invasive procedure for use on sagging (ptosis) breasts that are caused by aging and accelerated by pregnancy and nursing. MIM expects to replace the existing breast mastoplexy (lifting) procedure and achieve better symmetry and reduced scarring. The company has completed the design, production and sterilization of its first product which is now undergoing lab tests (loads, fatigue, moments), biocompatibility and animal safety tests. MIM is preparing an application for the Helsinki committee which it plans to submit later this year.

• BioControl Medical (Yehud) is developing implantable devices for the treatment of autonomic disorders. It is conducting a multi-center, open-label clinical study in Europe, Israel and Australia of its CardioFit system for the treatment of congestive heart failure. Early data show that the CardioFit system is safe to implant in patients. It is an electrical stimulator system designed to improve heart function through the controlled stimulation of the vagus nerve. Preclinical and preliminary clinical data demonstrate that vagus nerve stimulation has a therapeutic role in treating heart failure by reducing the heart rate and ventricular volumes in addition to restoring regular rhythm.

CardioFit also has been found to provide the same benefit when used simultaneously with other existing medical therapies. It is estimated that approximately 1.2% to 2% of the global population and as many as 10% of individuals 65 years and older suffer from heart failure, a serious condition defined by the inability of the heart to provide adequate output to the body. Causes of heart failure include hypertension, ischemic heart disease and valvular disease.

• StimPulse (Herzliya) uses electrical stimulation applied to the alimentary tract for controlling obesity. The electrodes and sensors are implanted by a minimally invasive procedure over the peritoneum without penetrating the abdominal cavity. When food is ingested, the sensors stimulate the receptors that communicate to the brain that the stomach is full.

• InnovaGraft Biologics (Yehud/Stillwater, Minnesota) is developing porcine derived collagen for use in tissue repair as a surgical mesh or in micronized form. Potential applications include, wound healing, aesthetic, spine surgery hernia and rotator cuff repair. The xenograft is remodeled by the body into native tissue. It can be produced as a crosslinked or non-crosslinked matrix, depending on the clinical use and the required specifications. It has sites for rapid and specific cell attachment and for binding cell-secreted products such as signaling molecules that stimulate and direct tissue regeneration. The dermal matrix contains collagen, elastin, hyaluronan, fibronectin and blood vessel channels that can be used by the body as it repairs itself. InnovaGraft’s wound healing products and hernia repair are 510K submission ready.

• Multigene Vascular Systems (MGVS; Haifa) develops autologous somatic cell therapy products for use in treating vascular-related disorders. It utilizes multiple genes in conjunction with the patient’s own endothelial and smooth muscle cells. Its MultiGeneAngio cell therapy-based product is for use in patients with peripheral artery disease secondary to blocked arteries in the legs. It is injected intra-arterially at the site of blockage. The cells are isolated from a short vein segment stripped from the patient’s arm under local anesthesia, then gene modified by the transfer of angiogenic genes into these cells.

MultiGeneGraft is a long-lasting, biosynthetic vascular graft lined with the patient’s own endothelial cells and modified to provide improved biocompatibility. It serves as a prosthetic conduit in patients with peripheral artery disease that are undergoing bypass surgery or as an access site for patients with renal disease who require hemodialysis.

Surgical devices

• Virtual Ports (M. P. Misgav) is developing the EndoGrab internal organ retracting device for use during laparoscopic procedures. Internally anchored, it is a hands-free retracting device. It is introduced at the start of surgery and attached to organs that require retraction and then to the internal wall, thereby exposing the operative field. Currently, conventional technique employs the use of hand-held retractors and additional auxiliary personnel for manipulating them, resulting in increased surgical costs and incidence of scarring. The device has FDA approval.

The company also is in the process of applying for FDA approval of EndoClear, a device for cleaning the laparoscope’s camera lens while inside the abdominal cavity that is used to guide the surgeon’s actions. EndoClear is a stand-alone cleaning station that is inserted along with the camera in the cavity.

• Ovalum (Rehovot) is focusing on the minimally invasive cardiology and interventional radiology fields. Its CiTop guidewire system was developed for treating total occlusions of coronary and peripheral arteries that today require bypass surgery or amputation of the lower limb.

The product uses shape memory alloy technology and a wave-like motion of the guidewire tip for navigation through the vasculature. Its variable guidewire stiffness technology allows the operator to control the actual stiffness at the wire tip with no need to exchange wires, a feature that is needed for penetrating highly calcified occlusions.

• Optiscope Technologies (Katzrin) s developing a disposable rigid endoscope which would eliminate the danger of cross contamination. The innovation in optical technology comes from Russia and enables the production of optical parts for rigid endoscopes that provide similar or better viewing quality at a cost low enough to make them disposable. Rigid endoscopes are used in multiple medical fields, including urology, stomatology, gynecology, and ophthalmology.

Diagnostics and monitoring

#8226; Pocared Diagnostics (Petach Tikvah) is developing a point-of-care in vitro diagnostics system for on-site analysis of human fluids for real-time detection and identification of antibiotic sensitivity to pathogenic bacteria. These systems are based upon its selective spectrum technology. The company’s is about two years away from introducing its first commercial product.

• Labonnet (Zemach) specializes in optimizing DNA/RNA quantification and is based on real-time PCR. It is developing Kineret, a software solution enhancing the accuracy of real-time PCR test results that facilitates standardized and optimized evidence-based decision making. The company received the grand prize of the Eighth Danish Biotechnology forum and the BIZTEC’05 pre-seed venture competition organized by the Technion — Israel Institute of Technology (Haifa).

• Cheetah Medical (Ra’anana/Indianapolis, Indiana) markets the NICOM non-invasive cardiac output and thoracic fluid content monitors for hospital and outpatient applications including ICU hemodynamic monitoring, heart failure management and exercise cardiac output. Cheetah’s family of monitors are based on Bioreactance, a new technology platform which builds on frequency modulation in addition to impedance measurements.

• Cardiatec (M.P. Misgav) has developed a device that measures and assesses endothelial function using pulse wave measurement technology together with proprietary algorithms and can be used to diagnose the health of arteries. It combines two primary endothelial dysfunction measures — pulse wave transit time and amplitude. It is a noninvasive and easy to use device, similar to taking a blood pressure reading. Initial experimental results are very promising. Endothelial dysfunction is widely becoming recognized as an abnormality present during the initial stages of coronary artery disease.

Clinical trials are being conducted in Israel on healthy patients and patients with arterial problems to determine its value as a screening method for determining people at risk of cardiovascular disease.

Drug delivery systems

• SoluBest (Ness Ziona) is developing Solumer enabling nanotechnology, a proprietary platform that is based on the “custom wrapping” of active compounds with polymers, creating stable nanoparticle delivery that has a significantly increased surface area and volume, thereby increasing a drug’s bioavailability. This simple and cost-effective process is being used for insoluble and poorly soluble drugs, as validated in its lead product, SoluFeno, a nano-generic cholesterol lowering drug that possesses increased absorption, has completed exploratory pilot trials and is progressing towards a pilot trial in the U.S.

• CapsuTech (Nazareth) develops new entities for drug targeting. It uses nano-encapsulation of drugs for controlled drug release, improved stability and reduced degradation upon exposure to heat or light, as well as protection against oxidation and enzymatic hydrolysis.

CapsuTech’s technology is a generic platform for drug targeting. The chemical nature, size and properties of CapsuTech’s polymers can be rationally designed and manipulated according to the specific need.

• Aespira (Omer Industrial Park) specializes in pulmonary drug delivery via a novel dry powder inhaler. It utilizes the patient’s own intake breath to drive a mechanism by which micronized particles enter into the airflow, ensuring that the dose is well synchronized with the breath.

• Elcam Medical (BarAm/Hackensack, New Jersey) produces precision injection-molded disposable medical devices and provides stopcocks and manifolds for U.S. and European OEM markets. Elcam’s Auto-Injector line of disposable and semi-disposable prefilled syringes and vials has been developed in cooperation with Dali Medical Devices (Rishon Le’tzion)

And more...

The variety of technologies exhibited at the conference was shown further in its range from the highest of high-tech instrumentation for brain stimulation to new consumer skin care offerings.

• Brainsway (Jerusalem) is marketing Deep TMS, a transcranial magnetic stimulation system. It is a non-invasive device that applies brief magnetic pulses to the brain for treatment of neurological and psychopathological disorders. The pulses induce an electric field in the underlying brain tissue. In principle, any brain-related disorder that is associated with pathological activity of specific brain sites may be treated by this method. The company’s initial focus is on the treatment of major depression. Clinical trials on healthy volunteers were conducted and the technology was shown to be safe and have the ability to stimulate deep brain regions.

• Fertiligent (Migdal Ha’emek) is developing intelligent artificial insemination devices. Its initial product, IQI, is an intrauterine insemination device that enables in vivo and real-time sperm improvement. The slow release (several hours) of sperm into the uterine cavity extends the “window of opportunity” for ovum fertilization and prevents the loss of sperm by blocking the cervical cavity.

The device is composed of a disposable sperm-adjusted pump, a patented real-time sperm strainer and a catheter.

• FAH Solutions (Tel Aviv) has developed the LiftUp bed which can transfer a patient from a reclining to a standing position. The bed is for institutional and home use. It addresses the problem of falls by the elderly which are the leading cause of injury deaths among people over 65 years old. The product will be sold initially to nursing homes in Germany and the U.S.

Other products being developed to improve the day-to-day living conditions for the elderly are a wheelchair that can transfer a patient to an upright position and the “Joy Bath” all-in-one bathing device that is designed to a allow the transition from standing to sitting to a prostate position and back again to a standing position.

• NanoVibronics (Nesher) is using surface acoustic waves in a consumer, battery-operated handheld device that is being developed for use on skin to achieve a smooth and youthful complexion. Nanovibronix has expanded its surface acoustic platform to include pain and wound therapy as well as treatment of skin disorders.