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North American Neuromodulation Society Meeting 2012
Harnessing the Inflammatory Reflex: Using Neuromodulation as a Novel Approach to
Treat Chronic Inflammatory Diseases
R Zitnik, Y Levine, M Faltys, T Arnold
SetPoint Medical Corporation, Valencia, California
112/7/12
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North American Neuromodulation Society Meeting 2012
Rheumatoid ArthritisInflammatory Bowel Disease: Crohn’s and Ulcerative Colitis
Psoriasis, Ankylosing Spondylitis, Psoriatic Arthritis, Lupus
Inflammatory Disorders Have Significant Morbidity and Mortality- Medical Need Remains High
• Common disorders- up to 2% of population• Affects young and middle aged adults• Severe, “life-impacting” symptoms• Systemic inflammation associated with highly elevated
cardiovascular mortality risk
212/7/12
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North American Neuromodulation Society Meeting 2012
Current Drugs and Biologics are an Important Advance- Yet Have Major Drawbacks
• Lack of efficacy in 1/3 (RA) to 2/3 (Crohn’s)• Rare but serious safety issues: Infection, TB, CHF, cancer risk,
MS, PML, hypercholesterolemia• $30 billion in annual sales with per patient cost of $25-35K/year
312/7/12
Goal is to improve the treatment of these diseases using neuromodulation
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North American Neuromodulation Society Meeting 2012
CNS Regulates the Immune System via the “Inflammatory Reflex”
• Afferent vagus and CNS sense inflammatory mediators (should this read: CNS senses inflammation via the afferent vagus)
• Efferent vagus signals resident T cells and macrophages in the spleen and GI tract
• Pro-inflammatory cytokine production reduced• Circulating immune cells traversing the spleen
are altered: • Reduced capacity to express inflammatory
mediators and adhesion molecules as cells move into diseased tissue
412/7/12
Tracey, Cell 2012
Rosas-Ballina, Science 2011
In inflammatory diseases, activity of pathway is
decreased
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North American Neuromodulation Society Meeting 2012
Stimulating this Reflex Using Neuromodulation will Reduce Inflammation and Improve Clinical Disease
Andersson U, Tracey K.
Ann Rev Immunol 2012; 30:313
Rheumatoid Arthritis Inflammatory Bowel Disease
512/7/12
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North American Neuromodulation Society Meeting 2012
VNS Lead for Rodent Inflammation Models
612/7/12
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North American Neuromodulation Society Meeting 2012
•Bolder BioPATH, Inc.•n=4/Normal Controls•n=12/disease control•n=9/ stimulation group•*p≤0.05 t-test to Disease Controls
Joint Swelling Was Reduced in Standard Collagen-Induced Arthritis Model
712/7/12
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North American Neuromodulation Society Meeting 2012
•Bolder BioPATH, Inc.•n=12/disease control•n=9/ stimulation group•*p≤0.05 t-test to Disease Controls
*
**
*
Importantly, Structural Damage to the Joint was Also Reduced
812/7/12
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North American Neuromodulation Society Meeting 2012
Clinical Study of Neuromodulation in Rheumatoid Arthritis
“Methotrexate Failure” Population•Active RA despite treatment with first line agent methotrexate•Patients would otherwise have been candidates for a TNF antagonistStandard RA clinical endpoints:•DAS28 (Tender and Swollen Joint score, CRP, Patient VAS)•ACR 20/50/70 Response Rate•EULAR Response and Remission RateCommercially purchased VNS devices were used for the study
912/7/12
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North American Neuromodulation Society Meeting 2012
Individual Patient DAS Scores Show Rapid and Marked Improvement in 6 of the 8 Subjects
1012/7/12
EULAR Remission
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North American Neuromodulation Society Meeting 2012
Clinical Response Rates are Comparable to Those Seen with Biologics
1112/7/12 1112/7/12
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North American Neuromodulation Society Meeting 2012
Future Studies Will Utilize SetPoint’s Proprietary Neuromodulation Platform
MicroRegulator Pod
Patient Charger Prescription Pad
Surgical Implant
1212/7/12
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North American Neuromodulation Society Meeting 2012
Summary and Conclusions
• Inflammatory diseases are a $30B market with significant unmet need• Using neuromodulation to drive the inflammatory reflex has a sound
biological foundation: Use in clinic is supported by strong preclinical evidence
• This is the first demonstration that an implantable neuromodulation device improves clinical manifestations of RA:• Significant and clinically meaningful improvement in signs and symptoms • Response rates were comparable to those with current biologic agents• Further larger controlled studies in RA and other chronic inflammatory
diseases are warranted.
• Our microregulator offers significant advantages over current vagal nerve stimulation devices
SetPoint intends to offer a novel therapy that will significantly increases patient QOL, while bending per-patient cost curves down by more than 60%
1312/7/12