BB&T Contributing Editor

TEL AVIV, Israel — This country's national life science and technology conference, Biomed Israel, held here in late May, drew 6,000 attendees from around the globe that were treated to an extensive program of company presentations and exhibits.

The Israeli life science industry is young, growing and exuberant. According to Israel Life Science Industry (ILSI; Herzliya), a non-profit organization and the conference's main sponsor, there are about 900 life science companies in Israel, of which 72.5% were founded during the last decade and 23.7% of them are revenue-generating.

Medical devices account for 53% of Israel's life sciences industry. Their product offerings are in over 20 areas, the leading ones being cardiology, gynecology, oncology, neurology and neurodegenerative disease, ophthalmology and orthopedics. A smaller number of companies focus on medical fields such as endocrinology, wound management and infectious diseases. See Table 7.

On a per-capita basis, Israel is in first place in the total number of granted patents in the medical device area and ranks seventh in the absolute number of patents. Israel is ranked second in the number of papers in leading life science publications per 100,000 inhabitants.

Exhibitors at Biomed Israel included several countries and U.S. states that are seeking to attract Israeli companies to open branch offices or create joint ventures. Indeed, many Israeli companies already have facilities in the U.S., while retaining research and development activities in Israel. For example, BioLineRx (Jerusalem), Israel's leading drug development company, recently announced the establishment of operations in Rockville, Maryland.

Many of the emerging med-tech companies featured below are housed within one of Israel's many groups of incubators. Their initial funding often is only $500,000, provided by Israel's Office of the Chief Scientist. Also present were the technology transfer organizations which are affiliated with the country's universities and research institutes.

Cardiovascular therapies

ArioMedica (Tel Aviv) is developing ARIO (Apparatus for Removing Intra-luminal Occlusions), a minimally invasive, disposable atherectomy device with a powerful cutting head for excising and removing all types of plaque from both partially and totally occluded peripheral arteries. The device's high excision moment of the cutting head enables removal of all plaque types (calcified, fibrotic or fatty). It employs three positioning balloons for steering and stabilizing the cutting head and an imaging guide wire for obtaining a cross-sectional view to distinguish between the artery and plaque.

The company has tested in pigs a prototype of the ARIO device and is seeking additional funding before entering human trials.

Cardiogal (Omer) is developing a non-invasive cardiac monitor for continuous evaluation of hemodynamic and cardiac functions that are performed on patients with cardiac failure or following an open heart procedure. This information is currently gathered by an invasive catheterization procedure using a Swan-Ganz catheter which has risks of complications.

Cardiogal's product obtains information using multiple ultrasound transducers that are placed over the anterior chest wall in a similar manner to the use of ECG monitoring leads. Based on standard Doppler and tissue Doppler techniques, it uses well validated measurements to assess cardiac function and body fluid status. Measurements are taken automatically and the procedure can be performed by a nurse.

BioControl Medical (Yehud) is developing CardioFit, an implantable device for treating heart conditions through the use of unidirectional vagus nerve stimulation. It is currently in clinical trials in Europe, Australia and Israel. BioControl's technology targets electrical stimulation at selected nerves in a manner that mimics natural physiological activity and minimizes non-related side effects. The Cardiofit system is intended as a therapeutic treatment for class II-!V heart failure patients with left ventricular dysfunction who have failed to achieve symptom relief from standard pharmacological management.

CorAssist Cardiovascular (Herzliya Pituach) is a preclinical-stage device company that is focused on the treatment of diastolic heart failure by directly enhancing the elastic characteristics of the left ventricle wall. ImCardia, the company's first product, is an elastic self-expanding device that is attached to the external left ventricle surface of the heart through an off-pump procedure.

The device assists diastolic function through reduction of filling pressures, and does not require an external power source. It applies outward expansion force on the ventricular wall to enlarge left ventricular and diastolic volume.

ImCardia MIS is a second-generation and minimally invasive version of the ImCardia device that allows for smaller incisions, less patient trauma and faster recovery. The device can be delivered by a left thoracotomy or by a laparoscopic approach.

Aurora is an elastic device that is implanted inside the left ventricle in a minimally invasive or percutaneous procedure. It applies direct internal expansion forces distributed on the left ventricle wall and the septum to improve diastolic function.

Aesthetic devices and implants

Applisonix (Rehovot) is developing innovative ultrasonic devices for the aesthetic market. The first application is for long-term hair removal for use by professionals, to be followed by a product for the consumer market. The devices are powered by Impresa, the company's proprietary ultrasonic hair removal technology that is applicable to all skin tones, hair colors and body areas.

The Impresa technology utilizes hair and skin characteristics to make the hair serve as an accurate and efficient ultrasonic waveguide. An ultrasonic head is used to focus the acoustic energy directly into the hair shaft which channels the acoustic energy to the hair root, where the energy is converted into heat. The surrounding skin is not affected.

The company's initial commercial product will be the Selectif device for use by professionals. It can complement currently available laser and intense pulse light (IPL) treatments used by aesthetic professionals to achieve a high level of accuracy. The device requires only minimal training.

Aesthetics Point operates within the Ashkelon Technology Incubator (ATI ; Ashkelon), a subsidiary of Biomedix Incubator Ltd. (Ramat Gan) which trades on the Tel Aviv Stock Exchange. It is developing an implant for aesthetic facial wrinkle treatment. The product is a dynamic miniature stent that can expand and maintain its new configuration underneath the skin for facial skin-shape procedures.

The implant is made from biodegradable materials. It is released from a trocar and automatically retracts to the unloaded extended shape, stretching the adjacent tissue and wrinkled skin.

CollPlant (Rehovot) has developed Type I recombinant human collagen that is derived from transgenic tobacco plants. It is based on the expression of five different genes required for the synthesis of recombinant collagen in plant compartments.

CollPlant will initially be a bulk supplier of medical-grade collagen and will transition into collaborative relationships for producing collagen-based end products. Ultimately, it plans to produce in-house new products addressing unmet needs.

The company announced at the conference a new program to develop an elastin-like fibrin protein having strong mechanical and elastic properties for orthopedic applications. It will be modeled after resilin that is used by fleas to jump to great heights.

CollPlant's technologies have been licensed from Yissum, the technology transfer company for Hebrew University (Jerusalem).

Diagnostics and monitoring

Professor Aaron Palmon from the faculty of dental medicine at Hebrew University described a saliva-based device for the detection of low levels of biomarkers. The disposable device clears from saliva in a single pass amylase which constitutes about 60% of salivary proteins. Studies indicate that saliva may be useful for detecting various cancers, heart disease, diabetes and periodontal disease. The technology is available for licensing from Yissum.

EarlySense (Ramat Gan/Dedham, Massachusetts) is the developer of signal-processing technology designed to advance proactive healthcare and enable better patient outcomes. The Institute for Healthcare Improvement (Cambridge, Massachusetts) has estimated that 2.5 million people are unnecessarily harmed in hospitals in the U.S. each year.

EverOn, the company's lead product, recently received FDA clearance and will be launched this year for use in hospital wards. It is a continuous and contact-free patient monitoring system that identifies early warning signs of patient deterioration, allowing for early intervention by medical professionals. It measures the heart and respiration rates as well as bed entries and exits.

The device displays real time vital signs and corresponding trend lines, providing early notification for the medical team of any significant increase or decrease in heart and respiration rates. This aids medical professionals in predicting the likelihood of deterioration in a patient's health.

Orthopedic, neurological, surgical implants

Orthogon Technologies (Ofakim) has entered into a collaboration with Smith & Nephew's orthopedic unit (Memphis, Tennessee) to develop a magnetically actuated intramedullary nail for fracture fixation and limb elongation of the femur and tibia. External manipulation of the nail is used with a magnetic coil for force induction.

This collaboration is partly funded by a grant from Israel's Bird Foundation (Binational Industrial Research and Development; Tel Aviv). The technology can potentially be used as a cosmetic procedure for limb lengthening to achieve greater height. It also is believed to have application for treating non-union fractures by applying internal axial vibration through the intramedullary nail.

The RAD Biomed Incubator (Tel Aviv) this year granted its "outstanding project" award to Tavor, a company that is developing a prosthetic ligament for use as a replacement for anterior and posterior cruciate ligaments.

Brainsgate (Caesarea) is developing neurostimulation technology focused on the spheno-palatine ganglion (SPG), a natural organ that controls cerebral blood flow. By electrically stimulating the SPG, cerebral perfusion can be augmented in a natural, physiological way.

Brainsgate's device is a one-inch-long implant that is inserted into a patient's palate in a minimally invasive 15-minute procedure under local anesthesia. The implant is externally activated by a headset worn by the patient during the treatment session.

The company's efforts are directed at treating acute ischemic stroke (AIS) as the primary use of this technology. A pilot human trial for AIS is nearing completion and the company is planning a pivotal trial this year under FDA guidance and approval is anticipated in 2010.

NiTi Surgical Solutions (Netanya) is the process of commercializing a family of CE-marked and FDA-cleared disposable tissue closure devices, the CAR Series compression anastomosis ring-based devices, and the CAC Series compression anastomosis clip-based devices. The nitinol alloy-based surgical rings, clips and appliers are used to press together the ends of resected tissue for a tissue-sparing and uniform compression anastomosis, for facilitating a natural healing process, eliminating leakage, and reducing strictures and adhesions.

NiTi's devices are designed for the treatment of colorectal, gastric and upper gastrointestinal disease requiring surgical anastomosis. Surgical instruments were designed for side-to-end as well as endoluminal end-to-end and for other circular techniques.

Externally worn devices

Headway (M.P. Misgav) has developed Occiflex, a non-invasive medical device for use by patients that suffer chronic headaches and neck pain. It consists of a specialized head cradle that is adjusted to the patient's head and neck and moves the head gently along a pre-defined 3-D course set by the practitioner, a physician, physical therapist or pain specialist.

Treatment is done individually with a cradle that moves in 6 degrees of freedom and is controlled by a computer. Headway's products are focused on treating neck muscle dysfunction for use by physicians and caregivers and it is developing a personal device for home use.

Hadasit, the technology transfer company of Hadassah University Hospitals (both Jerusalem), jointly with Ramot, the technology transfer company of Tel Aviv University, demonstrated the LuboCollar for use by medical personnel to quickly and safely evacuate semiconscious and unconscious patients who can't breathe on their own. It simultaneously secures the spine and prevents suffocation. The LuboCollar was found to be safe and effective in preliminary clinical studies. It is meant to help patients suffering from trauma.

Innovent Medical Solutions (Jerusalem) is developing a non-invasive device for clearing airway secretions in ventilator-dependent patients to prevent ventilator associated pneumonia, a common critical care infectious complication. The device works on the principle of cough simulation. It has two components, a suction unit and a disposable valve that connects the suction unit in-line with the patients' ventilation circuit. The ventilator fills the patient's lungs with air.

At the point of peak inhalation, the valve momentarily stops airflow from the ventilator and switches the direction of airflow to the suction unit, which performs sudden exhalation. This rapid switch from inhalation to exhalation simulates a natural cough, clearing the patient's secretions.

Compared to treatment using invasive catheter suction, Innovent's device removes more secretions, is less traumatic and prevents the need for intubation. The company plans to conduct clinical trials on ICU patients in 2008 and to seek FDA clearance via a 510(k) submission.

Insulin delivery pump

NiliMEDIX (Haifa), a subsidiary of D. Medical Industries (Ramat Gan), plans to launch in Israel by the end of this year an insulin pump with a disposable cartridge. It is seeking a U.S. distribution partner.

The pump employs a passive system that has a control unit with a pressure sensor and pressure reader that calculates the time and duration for opening of the pump valve to release insulin that is kept under pressure. This is different from other insulin pumps, with the exception of the OmniPod insulin management system from Insulet (Bedford, Massachusetts), by its use of a DC motor with reduction gear and lead screw that pushes a piston to release insulin through an administration set.

NiliMEDIX's pump is lightweight and will be the smallest on the market. It will have a bubble detector, along with an occlusion and leakage alarm. It is claimed to have a low manufacturing cost due to its simple design.

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