North America Neuromodulation Society I3 Session Creating a Device Around Headache Benjamin Pless, CEO Autonomic Technologies, Inc. North America Neuromodulation Society I3 Session Las Vegas, December 2012 Dec 6, 2012 Autonomic Technologies Not For Distribution

2007(March): The beginning Cleveland Clinic presentation to KPCB of autonomic patents to control a wide range of disorders Headache Vascular Cardiac Pulmonary Renal Dec 6, 2012 Autonomic Technologies Not For Distribution

SPG is a known therapeutic target to treat headache SPG interventions have a long history in the treatment of Migraine and Cluster Headache Anesthetic trans-nasal topical blocks Drug injection blocks Pulsed RF and ablative blocks Surgical procedures including gamma knife Acute interventions have been reported sometimes to provide weeks of sustained pain relief Local Anesthetic Topical Blocks Intranasal Approach Local Drug Injection Blocks Intranasal Infra-Zygomatic Supra-Zygomatic Palatine Ablative Blocks Radio Frequency Lesions Pulsed RF Lesions Gamma Knife Lesions Cryosurgical Lesions Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution Acute SPG Stimulation Early Proof of Concept research at the Cleveland Clinic by physician inventors demonstrating ability of stimulation to stop cluster headaches Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution Dec 6, 2012 Autonomic Technologies Not For Distribution

Sphenopalatine Ganglion (aka Pterygopalatine Ganglion) – a closer look R.L. Drake, Grays Anatomy for Students, 2005 Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution Dec 6, 2012 Autonomic Technologies Not For Distribution

ATI Product Considerations Good cosmesis majority of patients are women Minimally invasive implant Difficult surgery would reduce acceptability Simple and easy explant “no harm, no foul” lowers barriers to acceptance Dec 6, 2012 Autonomic Technologies Not For Distribution

Prior Neurostimulator Paradigm Dec 6, 2012 Autonomic Technologies Not For Distribution

Early ATI Product Concept Dec 6, 2012 Autonomic Technologies Not For Distribution

Patient Experiences of Tunneling Dec 6, 2012 Autonomic Technologies Not For Distribution

Surgical Retreat August 2008 ATI dissatisfaction with invasiveness of approach Included variety of Neurosurgeons ENTs Plastic surgeons CMF Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution Dec 6, 2012 Autonomic Technologies Not For Distribution

Gingival Buccal Approach to the SPG Adopted by ATI Developed by: Dr. Frank Papay, Cleveland Clinic, Cleveland Ohio Dec 6, 2012 Autonomic Technologies Not For Distribution

New ATI Neurostimulator Concept No battery Patient activated Stimulating probe neurostimulator Fixation bracket Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution Upper Lip Mucosa Incision The procedure begins by doing a submucosal injection of a vasoconstrictor and local anesthesic. An 1-2 cm incision is made approximately 3 to 5 mm superior to the mucogingival junction. Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution Mucosa Periosteal elevators are used to elevate the tissue in the subperiosteal plane. Dissect the tissue until the inferior aspect of the zygomaticomaxillary buttress area is exposed, also called the zygomatic process of the maxilla. Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution ATI introducer The proprietary ATI introducer is then inserted subperiosteally behind the zygomaticomaxillary buttress, and advanced on the posterior side of the maxillary sinus to the pterygopalatine fossa. Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution ATI neurostimulator The neurostimulator is then placed in the PPF either by using the introducer as a guide, and sliding the neurostimulator probe between the bone and introducer, or by removing the introducer and placing the neurostimulator probe into the dissection path created by the introducer. Dec 6, 2012 Autonomic Technologies Not For Distribution

ATI neurostimulator Implantation Neurostimulator lead in the pterygopalatine fossa stimulates the sphenopalatine ganglion (SPG) Neurostimulator lead within the pterygopalatine fossa Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies SPG Stimulator for Headache Implantable Neurostimulator Miniaturized Minimally invasive CE Marked Investigational use only in the US Simple therapy controls: on/off and up/down Wirelessly powers and controls Neurostimulator Rechargeable battery with USB connector for charging Wirelessly powers/activates Neurostimulator Patient control of stimulation and amplitude Headache Diary Pain level Autonomic symptoms Rescue medication use Wireless data transmission Use data Headache diary responses On-demand, patient-controlled therapy Dec 6, 2012 Autonomic Technologies Not For Distribution

Acute Response to SPG Stimulation Dec 6, 2012 Autonomic Technologies Not For Distribution

Special Thanks to Physician Collaborators Frank Papay Stew Tepper Ali Rezai Samer Narouz Mehdi Ansarinia Joseph Roberson Michael Stanton-Hicks Peter Goadsby Richard Lipton Jean Schoenen Rigmor Jensen Arne May Soren Hillerup Stephen Silberstein Miguel Lainez …and many more!!! Dec 6, 2012 Autonomic Technologies Not For Distribution

Autonomic Technologies Not For Distribution Thank You! Dec 6, 2012 Autonomic Technologies Not For Distribution