BBI Contributing Editor

Israel continues to be a hotbed for innovations in medical technology and biopharmaceuticals. Its universities, research institutes and hospitals have organizations that have created a seemingly unending array of new startups or incubators based on their technologies, many of which receive funding from Israel's established venture capital community and from the Israeli government. These institutions also actively seek to outlicense their technologies.

Additionally, Matimop (Tel Aviv), known as the Israeli Industry Center for R&D, is a gatekeeper for many of the early stage companies that are seeking corporate partners, licensees or acquirers. Similarly, Mor Research Applications (Petach Tikva) serves as a technology transfer organization. The mission of the Israel-U.S. Binational Industrial Research and Development foundation (Bird-f) is to stimulate, promote and provide financial support strategic partnerships between U.S. and Israeli companies.

Israel is the leader in medical device patents per capita and is the fourth in the world in biotechnology patents per capita, after Japan, Germany and the UK. Medical device companies represent more than 54% of the estimated 466 life sciences companies in Israel. Half of Israel's life sciences companies are under five years old, yet 41% generate revenues. Funds for Is-rael's many emerging medical product companies have become more available, and are increasingly supplied by foreign sources due to the prospect of an enduring peace with its neighbors.

According to the Israel Venture Capital Research Center, $1.46 billion was raised from local and foreign venture investors in 2004 by 428 high-tech Israeli companies, of which 22% were in the life sciences. This was an increase of 45% from the $1 billion raised in 2003. Israel exported $936 million in medical and surgical equipment in 2003 as reported by the Israel Export Institute, a rise of 80% from 2002.

The Israeli government actively pursues investments in its development stage companies as exemplified by the Israel Life Sciences Roadshow 2005 that featured medical device and biotechnology companies and toured four northeastern U.S. states.

Bio-Tech Israel 2005 was held in Tel Aviv in late May and featured more than 75 Israeli companies and support organizations for its life science industry. A sampling of Israel's emerging medical technology companies in a diverse range of specialities is featured below.

Obstetric and fertility products

Barnev (Netanya) is developing the computerized labor management (CLM) system for monitoring labor. It is based on proprietary ultrasound technology. Signals from disposable sensors located at the maternal cervix and fetal head provide objective, continuous and accurate cervix dilatation and fetal head descent data, reducing the need for frequent vaginal examinations.

By automating the examination process, the CLM system provides the labor team with accurate, real-time information that is needed to make a more informed decision. This includes a timely determination of fetal distress, identification of inadequate progress of labor and an assessment of a quickly developing labor process. The CLM system recently received marketing approval in Europe.

ReproMed (Kiryat Shemona) is developing a sperm preparation device that selects the most suitable sperm for in vitro fertilization (IVF) and intrauterine insemination (IUI). It is based on the sperm thermotaxis discovery of researchers at the Weizmann Institute (Rechovot) and the Reproductive Genetics Institute (Chicago) who have demonstrated that mammalian spermatozoa can sense small temperature differences and respond to the temperature gradient by swimming towards the warmer temperature. The distinct characteristic of this phenomenon is that only capacitated sperm cells, namely cells that acquire a state of readiness for fertilizing the egg, are responsive to the temperature gradient.

Vascular therapy

FlowMedic (Caesarea) is developing a family of medical and consumer devices for the non-invasive treatment of various circulatory disorders of the lower limbs, such as deep vein thrombosis, peripheral arterial disease and related clinical conditions such as critical limb ischemia and intermittent claudication. The products are characterized by their light weight, portability and ease-of-use for treatment both at home and in the hospital. The proprietary technology increases circulation in the lower extremities by rapidly applying and releasing pressure to the lower limbs, resulting in more effective blood flow to the limbs. Clinical studies are being conducted to quantify the efficacy of this therapy.

Wound care

EnzySurge (Shoham) utilizes enzymes to debride wounds and accelerate the healing process for chronic ulcerated wounds, thereby reducing the treatment and hospitalization costs. The company's device, which is in clinical trials, continuously supplies the wound site with enzyme-containing solutions for selectively removing necrotic tissue and infective agents for enhancing the effectiveness of other treatment measures. EnzySurge was founded by Ramot, a Tel Aviv University organization that sponsors the creation of new companies.

Orthopedic devices

Impliant (Ramat Poleg) is developing posterior motion-preserving spinal implants. Its TOPS System is a mobile posterior implant that is designed to treat leg/back pain. It stabilizes but does not fuse the affected vertebral level to alleviate pain stemming from degenerative facet arthrosis, spondylolisthesis and spinal stenosis. Surgeons perform a decompression, place four pedicle screws, and connect the TOPS device. It is designed to re-create near-normal motion.

OrthoMechanics (Teradion Industrial Zone) has developed AnchorShaft technology for use in a new generation of orthopedic implants, initially for fixation of large bone fractures and thereafter for joint prostheses. The technology enables the use of high-power blades (anchors) to expand from within a solid nail, screw or prosthesis in order to improve fixation and stabilization in a healing fracture or artificial joint. The anchors expand into the relevant bone segment to provide rigidity. The company's first product will be available in 2006. Unlike earlier attempts at internally locking nails which had lost much of their strength to accommodate complex mechanisms, the AnchorShaft has similar strength to a standard nail.

Disc-O-Tech Medical Technologies (Herzliya) markets in the U.S. its Fixion intramedullary nails that do not require interlocking screws for fracture fixation and the Sky Bone Expander system, a polymeric device used as a bone tamp for fracture reduction or for creation of a void in cancellous bone. The company markets in Europe its B-Twin Expandable Spinal System for use in lumbar spinal fusion procedures. It is introduced into the prepared intervertebral space in a reduced configuration of 5 mm diameter and is expanded to 15 mm after positioning within the intervertebral space.

Imaging technologies

BioScan Technologies (Yokneam) combines laser and ultrasound technologies in one device for use in diagnosing and treating cardiovascular diseases. Its first product, Light-Wire, is a 0.3 mm imaging guidewire that is used as a regular coronary guidewire and provides reconstructed images of a vessel's internal structure during cardiac catheterization intervention (PTCA), atherectomy or stent placement. By using a laser to generate ultrasound within a fiber optic, BioScan reduces the size of its ultrasound probe to that of an optic fiber. Light-Wire is used in coronary arteries to provide diagnostic information such as location, quantity and type of atherosclerotic plaque. Its use in cardiovascular procedures include angioplasty and treatment of restenosis plaque. It also can be used to facilitate deployment of stents and assess treatment results.

TopSpin Medical (Lod) has developed a novel technology for local high-resolution MR imaging using a miniature hand-held probe incorporating all magnetic field sources and eliminating the need for external magnets and a costly MRI scanner. This technology extends the tissue characterization capabilities of MRI to a new range of clinical applications, such as the detection and staging of cancer in the prostate and colon, as well as for intravascular imaging. Use of TopSpin's MRI catheter during cardiac catheterization will enable interventional cardiologists to guide therapy to vulnerable plaques and potentially reduce cardiac event rates.

V-Target Technologies (Tirat HaCarmel) has developed a nuclear medicine imaging technology that provides high resolution reconstructions and greater sensitivity. Based on its BroadView imaging platform, V-Target's technology generates images that enable the detection of abnormalities as small as a few millimeters in size and with efficiency greater than that of conventional Gamma/SPECT cameras currently in use. This new imaging capability can improve diagnostic testing, surgical guidance and treatment monitoring for a wide variety of indications. The company's first products are a miniature transrectal camera for early detection of prostate cancer and a very high-speed cardiac functional camera.

Navigation and robotic systems

Mazor Surgical Technologies (Caesarea) has developed the SmartAssist surgical guidance platform that is based on miniature robotic technology and provides optimal assistance in the intra-operative guidance of surgical tools. Its first product, the SpineAssist navigation device, is designed to facilitate pedicle screw placement during spine fusion surgery. It is inserted into the spine using a small incision and clamped to the vertebra. Prior to surgery, software is used to link preoperative CT data with intra-operative fluoroscopy images, enabling the device to pinpoint the angle and trajectory of the screw placement. The surgery is performed with minimum intervention, thereby reducing trauma, accelerating recovery and decreasing overall treatment costs.

Tactile Technologies (Zichron Yaakov) has developed the implant location system (ILS), a disposable micro-robot for improved accuracy of dental implant procedures. The FDA has given market clearance for its 3-D surgery planning and implant locator software. The company plans to market its software package in the U.S. while conducting clinical trials on its integrated micro-robot in the U.S. and Europe. Its system utilizes tactile bone-sensing technology to provide a mechanical image of the bone contour without removing any gum tissue. The sensor uses a matrix of ultra-thin micro-needles inserted through the gum until contact is made with bone. The bone contours are measured using miniature position encoders and digital signal processing electronics.

Diagnostic equipment and tests

Itamar Medical (Caesarea) markets a line of products for diagnosing sleep apnea that use the peripheral artery tone (PAT) signal as a non-invasive window to the autonomic nervous system. Its Endo2000 unit provides an objective assessment of endothelial function by measuring the PAT signal response to reactive hyperemia. The Watch-PAT 100 is a home-care device for diagnosing sleep apnea disorders. The company has developed unique signal processing algorithms for using arterial peripheral arterial tonometry in various clinical applications for understanding and managing cardiovascular, respiratory and nervous system disorders.

Biological Signal Processing (Tel Aviv) is a pioneer in the field of high frequency ECG. It recently received FDA clearance for marketing its HyperQ System, a PC-based ECG device that records, analyzes and displays both conventional and high-frequency ECG for the detection of myocardial ischemia. The system uses proprietary signal acquisition and processing algorithms and offers a user-friendly interface, numeric readout of the results and graphs that demonstrate changes in the high-frequency components of the QRS complex. A 1,000-patient study showed that critical changes in certain high-frequency components of the QRS complex are consistently present with acute myocardial ischemia and are reversed by reperfusion. Other products under development are the HyperQ rest monitor, a patient monitoring product for bedside and perioperative implementation, and the HyperQ check-up system, a periodic rest ECG check-up device.

Nexense (Yavne) has created a biosensor platform that is based on the discovery of direct digital measurement (DDM) and is able to measure in real time and with molecular precision parameters such as temperature, acceleration, pressure distance and weight, in addition to pulse and respiratory rates, body movements and blood flow. This non-contact and non-radiating biosensor is in the final stages of product integration and customization of monitoring applications, and is targeted at the expanding home health market.

Diagnostic Technologies (Haifa) is developing a diagnostic test on blood for the early detection of high-risk pregnancies based on genomics and proteomics. The company uses newly identified placental genes and proteins to detect abnormal pregnancy development related to pre-eclampsia, pre-term delivery and intrauterine growth restriction. Its marker for pregnancy complications is placental protein 13 (PP-13) that is incorporated into an en-zyme immunoassay kit which detects abnormal first and second trimester PP-13 levels. It is used to predict risk before complications develop in pregnancy.

Tissue and organ preservation

Core Dynamics (Nes Ziona) has developed cryopreservation processes and technologies enabling the freezing and freeze drying of blood cells, as well as the freezing and long-term storage of organs and tissues for transplantation. The long-term storage of blood cells should reduce seasonal supply shortages and improve safety by allowing the use of pathogen inactivation technologies. The company's products are in various stages of development, with its first entry, expected this month, to be cryopreserved osteochondral grafts for the repair of knee cartilage injuries. Two blood cryopreservation products are being developed, a frozen blood unit that contains no toxic cryoprotective agents that need to be washed out prior to use, and a freeze dried blood unit that can be stored at room temperature and is ready for transfusion upon the addition of distilled water.

Artificial organs

Nicast (Caesarea) is a nanotech company operating in the field of tissue engineering and im-plantable biomaterials. Nicast has developed a broad IP portfolio and unique know-how, focused on the fabrication and use of nanometric-scale polymer mat-rices. Its matrices mimic biological tissue and therefore allow the creation of artificial replacement tissue. The proprietary technology is based on electrocapillary spinning of polymers. Nicast products are targeted at the fields of interventional cardiology and cardiovascular surgery. As a building block toward the cardiovascular applications, its initial product is a 6 mm multilayered vascular graft made from polymer nanofibers to facilitate high performance vascular access in end-stage renal disease patients. The product will allow access and be self-sealing following needle punctures. Combined with Nicast's endoluminal matrix morphology, it also promotes endothelialization of the graft. Clinical trials in Europe are planned for early 2006.

Endoscopic procedures

superDimension (Herzliya) is developing minimally invasive devices for the diagnosis and treatment of lung diseases via interactive real-time guidance of endoscopic tools. Its superDimension/Bronchus system extends the use of bronchoscopes by enabling pulmonologists to navigate into the lungs' periphery. It employs a disposable and flexible catheter that has a 360 degree steering capability which allows it to maneuver through the small bronchial branches and reach lung locations that are beyond the endoscope's vision. Currently, an estimated 65% of diagnostic bronchoscopies in the lung's periphery fail to reach the target and must be repeated or replaced with more invasive approaches, such as CT-guided percutabeous needle biopsy or surgical biopsy.

MediGus (Omer) has developed the SRS system, an endoscopic device for the treatment of gastroesophageal reflux disease (GERD). It combines in a single instrument a video flexible gastroscope, a surgical stapler and ultrasonic sights for alignment. It is used to perform an anterior fundoplication procedure, a standard operation used to treat GERD. The core technology used for the SRS system has potential applications in the fields of gynecology and gastroenterology.

ETView (Zichron Yaakov) is addressing the challenges of difficult intubations which can result in damage to the larynx, broken teeth, poor brain oxygenation and, in extreme cases, death. The company is developing an endotracheal tube with an embedded video camera at its tip to view and monitor the upper airways and trachea during intubation of a sedated and artificially respired patient.

Endogun Medical Systems (Kiryat Shimona) is developing the EndoFast family of devices used to attach or reinforce tissues by fastening or supporting them with ribbons, bands or strips of flexible material. EndoFast connects tissues and the body's internal organs with ribbons using small darts (anchors) that are pushed by the device into the tissue. By employing expertise in bio-engineering design, Endogun has produced devices for use in minimally invasive and laparoscopic procedures. The company plans to soon enter clinical trials with a urogynecology product.

No Comments