Optics in in Cardiology April 21, 2018 I did it for the - PowerPoint PPT Presentation

Optics in in Cardiology April 21, 2018 I did it for the patients>>: My journey from academia to industry and back to academia Dr. James Müller Brigham and Womens ’ Hospital Boston, MA

Conflict of Interest CEO, SpectraWAVE, Inc, which is building a combination OCT-Spectroscopy Catheter

Zurich University Heritage and Optics In In Cardiology Photoelectric effect PTCA 1921 Nobel Prize in Physics

Dr. Paul Müller 1915- 2015

The Problem -- Vulnerable Plaques and Patients +1.2 Million Heart Attacks Per Year in US and Complicate Stenting Lipid-core Plaques 5

Introduction of the “Vulnerable Plaque” concept Muller, Tofler, Stone Circulation, 1989

A “Vulnerable” Nuclear Weapon

1800 "Vulnerable Plaque" and 1600 "Case-Crossover" Citations per year (Google Scholar) 1400 1200 = 14,221 Vulnerable Plaque 1000 Case Cross-over = 6,259 800 600 VP, 1989 400 Case-crossover , Maclure, Mittleman, 1990 200 0 1985 1990 1995 2000 2005 2010 2012

Other Applications of the Case-Crossover Method Exposure Outcome Result Odds Ratio Air Pollution Mortality from 1.1 COPD in Barcelona Anger MI in Stockholm 9.0 Air Pollution Mortality in Seoul 1.02 Air Pollution Mortality in 1.05 Philadelphia Benzodiazepine Auto accident 1.6 (not for SSRI) Family Quarrel Childhood 2.6 accident

Diffuse Reflectance NIR Spectroscopy to Identify Chemical Composition of Unknown Substances 1.0 0.8 absorbance Absorbance Cholesteryl Oleate Cholesteryl Oleate Cholesterol Cholesterol 0.6 Collagen Collagen 0.4 Cholesteryl Linoleate Cholesteryl Linoleate 0.2 1100 1200 1300 1400 1500 1600 1700 1800 1900 wavelength Spectroscopy in 1998

Chemogram Findings in a Coronary Autopsy Specimen: Comparision with Histology 40 mm 36 mm 20 26 mm 14 mm

NIRS to differentiate patients with two different types of plaques Lumen Lumen Lipid-Rich Plaque Fibrotic / Calcified Plaque 15

NIRS and IVUS Combined Catheter NIRS Mirrors Fiber Optics Catheter Core Tip Sheath IVUS Transducer Composition Structure NIRS Image (Chemogram) IVUS Image Confidential 16

Intravascular Coronary Diagnostics Using Light and Sound to Image Coronary Arteries 1999 2008 2010 2012 FDA Approval Founded by FDA Approval Commercial Spectroscopy used to Dual modality Dr. James Muller Launch image coronary arteries Spectroscopy/IVUS Catheter TVC Insight Catheter • Single Use TVC Imaging System • Laser • Dual Modality • Computer with • Spectroscopy – lipid core plaque • IVUS – plaque structure algorithms • Pull-back and Rotation (PBR) Device 17

Courtesy Dr. Ryan Madder, TCT 2012

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Investor Update 2014

The Myth of the “Vulnerable Plaque” Transitioning From a Focus on Individual Lesions to Atherosclerotic Disease Burden for Coronary Artery Disease Risk Assessment Armin Arbab-Zadeh, MD, PHD,* Valentin Fuster, MD, PHD: JACC 2015 Requiem for the ‘vulnerable plaque’ Peter Libby and Gerard Pasterkamp, EHJ, March 2015 The Vulnerable Plaque Hype-pothesis Steve Nissen, MD, CRT Meeting

Soon, the Data will Speak

Identification of Vulnerable Patients by NIRS Schuurman, Oemrawsingh et al EHJ, 2018

The Lipid-rich Plaque (LRP) Study Dr. Ron Waksman, PI Results TCT Sept, 2018 PI, Europe, Dr. Carlo Di Mario 1500 PCI patients Max 4 mm LCBI with ACS or SA >250 for 100% FU with NIRS-IVUS imaging of 2 or more vessels 2 year MACE from a new lesion at patient and coronary Max 4 mm LCBI segment level ≤ 250 for 50% FU 25

PROSPECT 2 Study PROSPECT / ABSORB RCT Dr. David Erlinge, Dr. Gregg Stone 900 ACS Patients Undergoing PCI “PROSPECT 2” “ABSORB” 600 Patients 180 pts > 70% Plaque Burden,Non-Flow -Limiting BVS Scaffold GDMT Only BVS Scaffold + GDMT 90 Patients 90 Patients NIRS/IVUS LCP No LCP LCP No LCP Predicts MACE Assess Treatment Effect in Sub-set with LCP

Possible Outcome of LRP Study: Risk that a 30 mm coronary segment with a given 4 mm Max LCBI will LCBI 974 produce a MACE event in 3 years. Estimate only. Dr. Jim Muller, Infraredx, Inc., March, 2015 35 (34%) 30 3-Year Event Rate (%) 25 LCBI 68 20 Prospect 1 (17%) 15 Event Rate 10 5 0 0 100 200 300 400 500 600 700 800 900 1000 Max 4mm LCBI Distribution of LCBI from COLOR: (21.3%) (15%) (16.2%) (16.3%) (13%) (7.6%) (5%) (3.1%) (1.3%) (1.3%) No. of Evaluable Patients (1000): 213 150 162 163 130 76 50 31 13 13 Estimate of Evaluable Events (116): 4 5 8 18 27 21 15 10 4 4

Medical Medical Failure Success Ardian The Early Promised Financial Connor Land Success Medical Early Infraredx? Financial (Definite early Failure financial failure, medical outcome pending )

Return to Academic Medical Center

SpectraWAVE -- Combined OCT-Spectroscopy system + = OCT-S LUMEN Spectroscopy OCT Provides: Suspected • Accurate measurements Automated identification Vulnerable plaque • Fibrous cap thickness of cholesterol plaque Lipid • Stent apposition • Thrombus • Dissection • Vasa vasorum Uemura et al, Acta Cardiologia Sinica, 2014; Fard A, and Tearney GJ; Opt Express, 2013 SpectraWAVE, Inc.

The Search for Vulnerable Plaque and Patient – A Long and Winding Road Academia Industry Academia Treatment Trials 2018 & Patient Care SpectraWAVE, Inc OCT-NIRS 2017 Prediction Trials Start 2014 NIRS-IVUS Vulnerable Plaque NIRS 2010 Concept, 1989 2008 Circadian Rhythm of MI, 1985 Triggers of CV Events Gill Heart, KY, 1987 1998 Infraredx, Inc Founded 33

Features of Academia and Industry Academia Industry Positive Positive Patient care encourages research Focused drive to commercialization and wide use of a product Teaching and research focus Funding less difficult than in academia Negative Negative For start-up, constant Difficult to stay funded need to raise funds Pressure to see patients quickly Assumed to be pitching for commercial reason

Prevention of Nuclear War – A Long and Winding Road Nuclear Activism Cardiology Only Nuclear Activism Co-Founder NKaUS Physicians for Prevention of Nuclear War 2018 ICAN Wins Nobel Peace Prize International Physicians 2017 for Prevention of Nuclear War Wins Nobel Peace Prize 1985 Dr. Jerome Co-Founder Frank book IPPNW,1980 On Nukes US USSR Health Cooperation 1972 Summit Exchange Student Mtg To Moscow 1967 35

Ambassador Ri of the United Nations – Responsible for DPRK Relations with the United States 14 April 2018

The International Campaign to Abolish Nuclear Weapons (ICAN) is a coalition of non-governmental organizations in one hundred countries promoting adherence to and implementation of the United Nations nuclear weapon ban treaty. This landmark global agreement was adopted in New York on 7 July 2017 . Awarded the 2017 Nobel Peace Prize Annual Meeting, 22 April, 2018 Geneva, Switzerland

Erasmus Medical Center Clinical Trial Colleagues Harvard Medical School Ton van der Steen, Ph.D David Erlinge, MD Patrick Serruys, MD Eugene Braunwald, MD Gregg Stone, MD Evelyn Regar, MD Calum MacRae, MD, Ph.D John Ambrose, MD Gijs van Soest, Ph.D Jim Kirshenbaum, MD Rob Wilensky MD Rohit Oemrawsingh, MD John Parrish, MD Jim Goldstein MD Yoshinobu Onuma, MD Farouc Jaffer, MD Ron Waksman, MD Jurgen Ligthart Sam Goldhaber, MD Sergio Waxman, MD Eric BoersmaPh.D Gary Tearney, MD, Ph.D Takashi Akasaka, MD Brett Bouma, Ph. D Yasunori Ueda, MD InfraReDx/Nipro Inc Peter Stone, MD Carlo DiMario,MD Geoffrey Tofler, MD Sean Madden, Ph.D Bob McNeil Ph.D Francesco Prati, MD Stephan Willich, MD Steve Sum, Ph.D Bill Priest Antonio Columbo, MD Murray Mittleman, MD Michael Hendricks, MS Bill Holland Gary Mintz MD Malcom MacLure, Ph.D Priti Shah Bill Marquard Akiko Maehara, MD Kevin Croce, MD Jay Caplan Ken Jones Lorenz Rabe, MD Ron Blankstein, MD Craig Gardner, Ph.D Jack Gill, PhD Wolfgang Koenig, MD Tom Brady, MD Ed Hull, Ph.D Sano San Renu Virmani, MD Ahmed Tawakol, MD Ujihara San Ryan Madder, MD James Ware, Ph.D