Corporate Backgrounder

Our Company

Concentric Medical, Inc., headquartered in Mountain View, CA, is a medical device company focused on the design, development and commercialization of products for restoring blood flow in patients who are experiencing an ischemic stroke.

Our lead products, the Merci Retrievers^®, the Merci^® Balloon Guide Catheters and the Merci^® Microcatheters collectively comprise the Merci Retrieval System^®. The Merci Retriever was cleared by the FDA in 2004. It is the leading mechanical thrombectomy device on the market for patients experiencing ischemic stroke. Merci® expands the window of time for clinical intervention in patients that otherwise may not have been eligible to receive treatment.

In addition to clot retrieval, the Merci Retrieval System is also cleared for use in the retrieval of foreign bodies misplaced during interventional radiological procedures in the neuro, peripheral and coronary vasculature.

Concentric Medical is the global leader in mechanical clot retrieval in stroke patients, with over 10,000 patients treated to date globally. The Merci Retrieval System has been used in more than 500 hospitals worldwide. As a pioneer in the field of mechanical thrombectomy, Concentric Medical strives everyday to discover new solutions for ischemic stroke intervention.

Concentric Medical employs more than 100 professionals worldwide who work hand-in-hand with physicians and hospitals to help implement stroke programs and create awareness of stroke throughout their community.

The Stroke Market

Stroke is a Healthcare Priority

Acute ischemic stroke is a devastating diagnosis with limited interventional options. There is a continuous need for patient awareness about the urgency of stroke, as well as a need for infrastructure improvement for most stroke markets in order to provide important options to patients. According to the American Heart Association, each year over 795,000 new or recurrent strokes occur in the United States which translates to one every 40 seconds. Stroke is the third leading cause of death and a leading cause of disability in the United States with an expected 2009 cost of $68.9 billion.¹ In 2005 (the most recent data available) stroke accounted for approximately one of every seventeen deaths in the United States.

Understanding Stroke

There are two types of stroke: ischemic and hemorrhagic. Ischemic strokes are more common and make up approximately 87% of strokes.¹ They are typically caused by a blocked artery that limits or completely deprives the brain of essential blood and oxygen. Patients may survive an ischemic stroke although many are left with functional disability that may include permanent impairment of movement, speech, sensation, memory or reasoning. The level of disability will depend upon the blood vessel involved, the area of the brain affected, and the length of time that the brain was left without oxygen. Approximately 30-50% of ischemic strokes are considered large vessel strokes Large vessels supply a greater amount of blood and large vessel strokes affect a greater area of the brain.²

The other type of stroke, hemorrhagic stroke, occurs when a blood vessel ruptures or bursts. Hemorrhagic strokes occur less frequently, but have a higher mortality or death rate.

While approximately 75% of strokes occur in people over the age of 65, a stroke can happen at any age. Risk factors for stroke include increased age, diabetes, cardiovascular disease and obesity.

Options in Stroke Care

Current Treatment for Acute Ischemic Stroke (AIS)

Currently, the only FDA-approved pharmaceutical treatment for ischemic stroke is intravenous tissue plasminogen activator, or IV t-PA. IV t-PA has a very narrow time window during which it can be administered - 0-3 hours from the onset of stroke symptoms. Since the efficacy of IV t-PA was demonstrated in the pivotal National Institute of Neurological Disorders and Stroke (NINDS) trial in 1995, there has been little progress in additional acute stroke drug development and the use of IV t-PA remains low. The national average utilization of IV t-PA is approximately 2-5% and is primarily due to the limited 3-hour time window and contraindications for certain patients.^5-6 IV t-PA has also been shown to be less effective in large vessel strokes where the clot burden can be quite large.³

Mechanical Thrombectomy

The need for additional options for patients led to the development of mechanical thrombectomy as an intervention option for acute ischemic stroke. Mechanical thrombectomy offers acute stroke patients an expanded time window for intervention, and a chance for restored blood flow with published positive outcomes1. In 2004, the FDA cleared Concentric Medical's innovative Merci Retriever for patients who are ineligible for IV t-PA or fail to respond to IV t-PA. The device may be used for patients who are beyond the 3-hour time window for IV t-PA.

The availability of the Merci Retriever offers physicians and patients options for stroke intervention and creates a departure from the historic method of caring for stroke patients. This tiny corkscrew shaped device works by wrapping around the clot and trapping it. The clot is then retrieved and removed from the body. The Merci Retriever has repeatedly shown the ability to restore blood flow in the larger vessels of the brain by removing blood clots. Over 10,000 patients worldwide have undergone this procedure and it has been performed at over 500 hospitals.

The Merci Retriever

In August 2004, Concentric Medical, Inc. received FDA clearance for the Merci Retriever for patients who are ineligible for IV t-PA or fail to respond to IV t-PA. This device offers physicians and patients options for stroke intervention and creates a departure from the historically limited methods of caring for acute ischemic stroke patients.

The Merci Retriever has repeatedly been shown to restore blood flow in the large vessels of the brain through the removal of blood clots. Over 10,000 patients worldwide have undergone this procedure and it has been performed at over 500 hospitals worldwide.

The system is a tiny corkscrew shaped nitinol wire that is inserted into the femoral artery and threaded to the intracranial vessels in a similar fashion to other neuro endovascular procedures. The device works by wrapping around the clot and trapping it. A balloon guide catheter temporarily occludes blood flow as the physician aspirates the clot through the catheter. The clot is retrieved and removed from the body.

The Merci Retrieval System® is continually evolving based on emerging technology and physician feedback. Our newest retriever, the V-Series, is our most efficient retriever yet.

Clinical Effectiveness

The Multi MERCI trial reported that the device restored blood flow to the brain 68% of the time, when used with adjunctive therapy such as intra-arterial lytic. Of the patients who had blood flow restored, 49% were functionally independent at 90-day follow up.⁴

Stroke Management with the Merci Retrieval System

Stroke is a type of cardiovascular disease that affects the arteries leading to and within the brain. A stroke occurs when a blood vessel in or around the brain either becomes blocked (ischemic) or ruptures (hemorrhagic). When a stroke occurs, the area of the brain supplied by the affected blood vessel fails to work properly, and in some cases, that part of the brain dies. Depending on the severity of the stroke and the part of the brain affected, severe disability or death can occur. Rapid medical intervention to restore blood flow is critical to minimizing long term disability and/or death.

The Merci Retrieval System from Concentric Medical is a novel, minimally invasive, catheter-based system comprised of three products: the Merci Retriever, the Merci Balloon Guide Catheter and the Merci Microcatheter. The Merci Retrieval System is designed to remove clots and restore blood flow in the neurovasculature, thereby offering hope for ischemic stroke patients who otherwise might have had limited options available to them. The procedure operates through a widely accepted mode of delivery, where the arterial system is accessed through the femoral artery in the groin. The device is then navigated through the body to the brain using standard endovascular techniques.

The FDA granted clearance after reviewing patient data obtained in a clinical study at 25 medical centers in the United States. The MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial evaluated the device in 141 patients who were ineligible for intervention with the drug Intravenous Tissue Plasminogen Activator, or IV t-PA, which can only be used within the first three hours of stroke onset.

A subsequent study, the Multi MERCI Trial, utilized another generation of retrievers in a multinational trial. The trial evaluated the device in 164 patients, of which 131 were initially treated with the Merci L5 Retriever. Additionally, in contrast with the MERCI Trial, patients administered IV t-PA were also enrolled.

The Merci Retriever is used in conjunction with the Merci Microcatheter and the Merci Balloon Guide Catheter, and employs standard endovascular techniques. Once the location of the clot has been identified through angiography, the Merci Balloon Guide Catheter is inserted through a small incision in the femoral artery in the groin. Under x-ray guidance, the Merci Balloon Guide Catheter is maneuvered up to the carotid artery in the neck; a guidewire and the Merci Microcatheter are deployed through the Merci Balloon Guide Catheter and then placed just beyond the clot. The physician then deploys the Merci Retriever to engage and ensnare the clot. Once the clot is captured, the Merci Balloon Guide Catheter is inflated to temporarily arrest forward flow while the clot is being withdrawn. The clot is pulled into the Merci Balloon Guide Catheter and completely out of the body, at which point the balloon is deflated and blood flow is restored.

Ischemic Stroke

Prior to FDA market clearance of the Merci Retrieval System, options for ischemic stroke intervention were limited. The only FDA-approved therapy for this indication is IV t-PA. IV t-PA remains under-utilized due to the fact that:
- It must be used within the first three hours of the stroke symptom onset, and
- It carries an increased risk of intracerebral hemorrhage.

Due to these limitations, fewer than five percent of stroke patients in the United States receive IV t-PA treatment.⁶

Along with the limitations of the use of IV t-PA, there are many other challenges in treating ischemic stroke. The approval of IV t-PA in 1996 increased the awareness level of stroke. National programs were started to educate people about the signs and symptoms of stroke and the need to consider it a medical emergency by acting quickly to dial 911. Studies performed years later still suggest that fewer than five percent of patients are treated in time. Getting patients and caregivers to recognize the symptoms of stroke, building community recognition of the need for stroke treatments and continued research into new alternatives will significantly impact stroke treatment and outcomes. The Merci Retrieval System extends the time window beyond three hours for ischemic stroke, which provides an opportunity for even more patients with ischemic stroke to be revascularized and the potential to dramatically decrease the morbidity and mortality associated with ischemic stroke.

Hemorrhagic Stroke

Hemorrhagic stroke accounts for about 13% of stroke cases.¹ It results from a weakened vessel that ruptures and bleeds into the surrounding brain. The blood then accumulates and compresses the surrounding brain tissue. This compressing of the brain tissue deprives parts of the brain of blood and oxygen. There are two types of hemorrhagic stroke:

Intracerebral hemorrhage is the most common type of hemorrhagic stroke and occurs when a diseased blood vessel within the brain bursts and allows blood to leak within the brain. This causes an increase in pressure within the brain, which causes damage to the surrounding brain cells. Hypertension is the primary cause of this condition. Other risk factors include alcohol and drug abuse, increased age, being male and being African American.

Subarachnoid hemorrhage occurs when a blood vessel just outside of the brain ruptures, causing the area of the skull surrounding the brain to rapidly fill with blood. It is usually caused when an aneurysm swells, weakens the vessel and ruptures. Risk factors include middle age, family history, smoking, excessive alcohol use, being female and being African American.

Approximately 30,000 people a year suffer from ruptured aneurysms, 10-15% of which die before reaching the hospital.¹ The most common treatments for aneurysms are surgical clipping and interventional coiling. Surgical clipping can involve craniotomy and extensive hospitalization. Interventional coiling is a less-invasive alternative to clipping.

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References
1. American Heart Association/ American Stroke Association, Disease and Stroke Statistics — 2009 Update
2. Smith WS, Tsao JW, Billings ME, Johnston SC, Hemphill JC 3rd, Bonovich DC, Dillon WP. Prognostic significance of angiographically confirmed large vessel intracranial occlusion in patients presenting with acute brain ischemia. Neurocrit Care. 2006;4(1):14-7
3. Saqqur M, Uchino K, Demchuk AM, Molina CA, Garami Z, Calleja S, Akhtar N, Orouk FO, Salam A, Shuaib A, Alexandrov AV; CLOTBUST Investigators. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke. 2007 Mar;38(3):948-54
4. Smith WS., Mechanical Thrombectomy for Acute Ischemic Stroke, Final Results of the Multi MERCI Trial. Stroke 2008; Apr;39(4):1205-1212.
5. Reed SD, Cramer SC, Blough DK, Meyer K, Jarvik JG. Treatment with tissue plasminogen activator and inpatient mortality rates for patients with ischemic stroke treated in community hospitals. Stroke. 2001;32:1932-1940.
6. Nilasena DS, Kreskowik TF, Wiblin RT, et al. Assessing patterns of tPA use in acute stroke [abstract]. Stroke. 2002;33:354

APM0300_D_4343, 2010-08