Orchestra Biomed Holdings, Inc. · NASDAQ:OBIO
Orchestra Biomed — Investor Day (June 2024)
57 slides from Orchestra Biomed's investor day presentation, Jun 11, 2024
Slide 1: Orchestra BioMed AVIM Therapy R&D Day
Orchestra BioMed AVIM Therapy R&D DAY June 11, 2024 Bringing medical inn vation to life
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation has been prepared for informational purposes only from information assurance, a prediction, or a definitive statement of fact or probability. Actual events supplied by Orchestra BioMed Holdings, Inc., referred to herein as “we,” “our,” and circumstances a
Slide 3: Agenda and Speakers
Agenda and Speakers Agenda Presenters Introduction and Orchestra BioMed Overview, David Hochman Unmet Hypertension Treatment Need in Older High-Risk Patients, David Kandzari, M.D. David Hochman David Kandzari, M.D. Vivek Reddy, M.D. CEO, Chairman, Founder BACKBEAT Study Co-PI, BACKBEAT Study Advisor
Slide 4: Orchestra BioMed Overview
Orchestra BioMed Overview David Hochman Chief Executive Officer, Founder Chairman, Orchestra BioMed 4 | Orchestra BioMed R&D Day 2024
Slide 5: Orchestra BioMed Executive Overview
Orchestra BioMed Executive Overview Partnership-enabled business model designed to: Accelerate innovation to patients & yield exceptional future profitability Lead Program Pipeline Program Atrioventricular Interval Modulation Virtue® Sirolimus AngioInfusion (AVIM) Therapy Balloon (SAB) Targets >$10B
Slide 6: Orchestra BioMed's Partnership-Enabled Model Benefits All
Orchestra BioMed’s Partnership-Enabled Model Benefits All Orchestra BioMed Shared Benefits Strategic Partners Development Innovation Commercialization Secure substantial Improve Enable new growth long-term royalties patient lives opportunities Outsource Accelerate Outsource commercialization develop
Slide 7: A Renaissance is Happening Now…
A Renaissance is Happening Now… Renaissance (n): A revival or renewed interest in something; learning from the past to create something better for the future Art Architecture Science Music Device innovation? This Photo by Unknown Author is licensed under CC BY-SA
Slide 8: The Renaissance of Orchestra
The Renaissance of Orchestra orchḗstra Orchestra Ancient Greece: the circular space in front of the Renaissance Italy: a group of musicians performing stage where the chorus performed a composition with pre-specified instrumentation The chorus in Claudio Monteverdi (1567-1643) Classical Greek The “F
Slide 9: An Orchestra Succeeds Through Collaboration
An Orchestra Succeeds Through Collaboration What more miraculous creation of mankind is there than the symphony orchestra — a hundred musicians collaborating flawlessly in the creation of a single sonority from moment to moment… We tend to take for granted the skill and sensitivity of such a perform
Slide 10: Our Symphony is Orchestra BioMed
Orchestra BioMed Our Symphony is 10 | Orchestra BioMed R&D Day 2024
Slide 11: The Current Renaissance in Cardiac Pacing and Balloon Angioplasty
The Current Renaissance in Cardiac Pacing and Balloon Angioplasty Our large, established target markets, built on foundational technologies introduced 50+ years ago, are experiencing a RENAISSANCE, enhancing the opportunity for our innovative technologies AVIM Therapy Virtue® SAB 1st pacemaker impla
Slide 12: Existing Body of Clinical Data Supporting Efficacy and Safety
Existing Body of Clinical Data Supporting Efficacy and Safety 2012 2016 2019 2021 2022 2023 Feasibility Study in MODERATO I - First MODERATO II – Pilot Study MODERATO II Strategic Initiation of the Canine HTN Model In-Human Implant Study Prospective, multi-center, Two-year and partnership with BACKB
Slide 13: AVIM Therapy Strategic Collaboration with Medtronic
AVIM Therapy Strategic Collaboration with Medtronic Developed BackBeat CNT (AVIM therapy) from Global market leader in cardiac pacing therapy: >$1.5B in concept stage; owns all related IP annual revenues Conducted all prior development and Pivotal trial utilizing premium commercial devices the MODER
Slide 14: Large Global Opportunity for Treating Hypertension in Target Populations
Large Global Opportunity for Treating Hypertension in Target Populations HTN + Pacemaker High Risk HTN 750,000 patients 2,400,000 patients ~70% of pacemaker patients1 ~0.2% of HTN patients Annual Global >$2 Billion* Opportunity >$8 Billion* Same patients, device implant, and Older patients with unco
Slide 15: The Unmet Treatment Need for Hypertension in Older High-Risk Patients
The Unmet Treatment Need for Hypertension in Older High-Risk Patients David Kandzari, M.D., FACC, FSCAI Chief, Piedmont Heart Institute and Cardiovascular Services Chief Scientific Officer, Piedmont Healthcare Director, Interventional Cardiology, Piedmont Heart Institute Co-principal investigator of
Slide 16: Hypertension is a Common and Serious Global Health Problem
Hypertension is a Common and Serious Global Health Problem1 Hypertension (HTN) is the leading risk factor for death globally, and a significant portion of U.S. adults with HTN remain uncontrolled ~120 million (48%) of U.S. adults have HTN ~25 million (21%) are ~95 million (79%) are prescribed lifest
Slide 17: Modest Reductions in Blood Pressure Have Significant Clinical Benefit
Modest Reductions in Blood Pressure (BP) Have Significant Clinical Benefit Reductions as low as 5mmHg in office systolic blood pressure (oSBP) substantially decrease the Relative Risk (%) of common cardiovascular conditions Ischemic Heart Major CV Disease Stroke Heart Failure CV Disease 0 Disease Re
Slide 18: Challenges with Pharmacotherapy for Hypertension
Challenges with Pharmacotherapy for Hypertension While pharmacologic therapy is often effective, many patients experience insufficient BP control1 Patient compliance is particularly difficult in HTN HTN is the “silent killer,” and most patients are asymptomatic Medications often have significant sid
Slide 19: The Nature of Hypertension Changes with Age
The Nature of Hypertension Changes with Age Due to arterial stiffening, older patients have higher prevalence of ISH leading to substantially greater risk of CV complications (CAD, CHF, stroke, mortality)1 Variation of SBP & DBP with age ISH is the predominant hypertension subtype in patients over 6
Slide 20: Older Patients with Hypertension Frequently Have Significant Comorbidities
Older Patients with Hypertension Frequently Have Significant Comorbidities1 ACS/MI Heart Failure Stroke AFib Common comorbidities in older hypertensive patients TAVR Diabetes Kidney CAD/PAD Cardiac Disease Arrhythmia 1Company estimates based on published sources; Definitions: Acute coronary syndrome
Slide 21: Hypertensive Patients with Pacemakers: An Older, Higher Risk Population
Hypertensive Patients with Pacemakers: An Older, Higher Risk Population in Need of Better Treatment Options1 73 years average age Frequent additional comorbidities: atherosclerosis, hyperlipidemia, diabetes mellitus, and chronic kidney disease 70% of patients with pacemakers also have HTN HTN + PPM
Slide 22: Compelling Opportunity to Evaluate AVIM Therapy
Compelling Opportunity to Evaluate AVIM Therapy BACKBEAT IDE Pivotal study: currently enrolling Evaluating a novel investigational hypertension therapy that takes advantage of existing pacemaker Same device implant and treating physicians No additional daily compliance requirements for patients Pilo
Slide 23: Evidence in Support of AVIM Therapy Mechanism of Action
Evidence in Support of AVIM Therapy Mechanism of Action Vivek Reddy, M.D. Director, Cardiac Arrhythmia Services at Mount Sinai Hospital Director, Electrophysiology at Mount Sinai Health System Professor of Medicine, The Icahn School of Medicine at Mount Sinai BACKBEAT Study Clinical Steering Committ
Slide 24: AVIM Therapy Summary
AVIM Therapy Summary* Programmable and adjustable device-based HTN therapy designed to be delivered via dual-chamber pacemaker Integrated for use with Medtronic Astra or Azure MRI-compatible pacemakers Leverages previously completed or already indicated procedure Can be activated, adjusted or deacti
Slide 25: Novel AVIM Therapy Mechanism of Action
Novel AVIM Therapy Mechanism of Action Designed to Substantially and Persistently Reduce Blood Pressure AVIM therapy uses a dual-chamber pacemaker to deliver programmed sequences of short AV intervals Designed to Substantially Lower Blood Pressure (BP) interspersed with longer AV intervals designed
Slide 26: Emerging Role of Conduction System Pacing in Cardiac Pacing Therapy
Emerging Role of Conduction System Pacing in Cardiac Pacing Therapy Left Bundle Branch Area Cardiac rhythm market rapidly adopting CSP via left bundle branch area pacing (LBBAP) LBBAP is a pacing approach that taps into the heart's natural electrical system, helping ensure pacing closely mimics phys
Slide 27: Invasive Pressure Volume Loop Study Shows Favorable Acute Hemodynamics
Invasive Pressure Volume (PV) Loop Study Shows Favorable Acute Hemodynamics from AVIM Therapy1 Decreases intra-cardiac volume & pressure AVIM – CSP Lead Location (↓ EDV, ↓ ESV, & ↓ SBP) 200 180 Baseline TPR↓ AVIM CSP 160 SBP↓ LV Pressure (mmHg) 140 Decreases total peripheral resistance 120 ESV↓ (↓ T
Slide 28: AVIM Therapy Reduces Systolic Blood Pressure
AVIM Therapy Reduces Systolic Blood Pressure1 Significant Reduction in SBP AV Pacing AVIM RV AVIM CSP 0.0 Significant reduction in SBP with AVIM therapy -5.0 -1.6 ± 3 and no significant (-2%) difference between right ∆ SBP (mmHg) -10.0 ventricular (RV) and -17.1 ± 2.5 conduction system -15.0 (-12%)
Slide 29: AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics
AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics1 Significant reductions in EDV, PED & ESV Change in End-Diastolic Volume Change in End-Diastolic Pressure Change in End-Systolic Volume (EDV) (PED) (ESV) AV Pacing AVIM RV AVIM CSP AV Pacing AVIM RV AVIM CSP AV Pacing AVIM RV AVIM CSP 0.0 2
Slide 30: AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics
AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics1 Reduction in total peripheral resistance (Ea) & no change in contractility (Ees) Change in Effective Arterial Elastance Change in Contractility (Ea) (Ees) AV Pacing AVIM RV AVIM CSP AV Pacing AVIM RV AVIM CSP 0.150 0.20 0.10 0.100 ∆ Ees (m
Slide 31: AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics
AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics1 Significant reduction in stroke work (SW) without significant reduction in stroke volume (SV) Change in SW Change in SV AV Pacing AVIM RV AVIM CSP AV Pacing AVIM RV AVIM CSP 0 0.0 -1.7 ± 3.6 -1.7 ± 3.8 -1.0 -500 (-2%) (-3%) -42 ± 452 -2.0
Slide 32: AVIM Mechanism of Action Highlights
AVIM Mechanism of Action Highlights AVIM therapy is designed to use a dual- chamber pacemaker to deliver programmed sequences of short AV intervals interspersed with longer AV intervals to reduce blood pressure Preliminary data support the mechanism of action and demonstrated a favorable impact of A
Slide 33: Clinical Data: MODERATO I & II Pilot Studies
Clinical Data MODERATO I & II Pilot Studies Vivek Reddy, M.D. Director, Cardiac Arrhythmia Services at Mount Sinai Hospital Director, Electrophysiology at Mount Sinai Health System Professor of Medicine, The Icahn School of Medicine at Mount Sinai BACKBEAT study Clinical Steering Committee Member 33
Slide 34: MODERATO I Study Design & Results
MODERATO I Study Design & Results Prospective, single-arm study of 27 patients with persistent hypertension (office systolic blood pressure (oSBP) > 150mmHg) despite 2 or more anti-hypertensive medications & an indication for pacemaker - 1-month run-in to account for Hawthorne effect, followed by 3
Slide 35: MODERATO I: Safety Data at 24 Months
MODERATO I: Safety Data at 24 Months Significant Reduction in End-Diastolic Volume & Heart Rate with No Significant Change in Ejection Fraction (EF)1 Heart Rate End Diastolic Volume 85 130 EDV (%) 110 HR (bpm) 80 * * 90 75 70 70 50 Pre-act 24 months Pre-act 24 months * P<0.05 End Systolic Volume Eje
Slide 36: MODERATO II Study Design
MODERATO II Study Design1 Prospective, multi-center, double-blind study investigating the efficacy of AVIM therapy in patients with persistent hypertension and an indication for pacemaker Primary safety & efficacy assessed at 6 months post AVIM activation; continued follow-up to 2 years 6 Month Foll
Slide 37: MODERATO II: Patient Demographics
MODERATO II: Patient Demographics No significant differences between groups at baseline Control AVIM Therapy p-value (n=21) (n=26) Age 74.9 ± 8.5 73.2± 9.0 0.518 Gender 15 M / 6 F 15 M / 11F 0.375 LVEF (%) 58.4±4.9 59.8±6.3 0.414 Medical History Diabetes 9 (42.9%) 12 (46.2%) 0.999 Prior Atrial Fibri
Slide 38: MODERATO II Randomized, Double-Blind Results
MODERATO II Randomized, Double-Blind Results -11.1 mmHg Significant Reduction in 24-Hr aSBP and oSBP1,2 in 24-Hour aSBP at 6 months aSBP oSBP 1 day 6 Months 6 Months 24 Months 0 AVIM therapy showed -3.1 -0.1 0% P =0.17 encouraging results in -5 -1.5 P = 0.5 P = 0.94 MACE vs. 14.3% in control MODERAT
Slide 39: MODERATO II: Significant aSBP Reduction in ISH Patients
MODERATO II: Significant aSBP Reduction in ISH Patients 7.4 mmHg reduction in aSBP at 6 Months compared to control Reduction in 24-Hr aSBP in ISH Patients +1 Day +1 Months +6 Months -4.0 N=15 -1.0 -2.1 N=15 -9.5 Δ aSBP (mmHg) N=13+ N=23 -12.0 N=23 -16.1 -7.4 N =22o ± 9.6 -8.0 P=0.03 ± 10.0 P= 0.02 C
Slide 40: MODERATO II: Significant Reduction in 24-hour aSBP
MODERATO II: Significant Reduction in 24-hour aSBP1 Paired average 24-hour aSBP profile after 6 months of AVIM therapy demonstrate reduction in SBP with preservation of normal daily blood pressure variations 150 145 140 aSBP (mmHg) 135 130 125 120 115 Pre-activation (n=26) 6 months (n=26) 110 P < 0.
Slide 41: MODERATO II: High Overall Response Rate to AVIM Therapy
MODERATO II: High Overall Response Rate to AVIM Therapy1 6 Months Post-Randomization AVIM Control (n=26) (n=19) Isolated Systolic Hypertension (ISH) 88.5% 71.4% % with Reduction in aSBP 85% 53% % with > 5 mmHg Reduction in aSBP 65% 42% % with > 10 mmHg Reduction in aSBP 54% 21% 41 | Orchestra BioMed
Slide 42: MODERATO II: Chronic, Non-Invasive PV Loop Data
MODERATO II: Chronic, Non-Invasive PV Loop Data Show Favorable Effects on Cardiac Remodeling1 AVIM Therapy affects adverse remodeling Unfavorable remodeling in control patients after 6 Favorable reverse remodeling 6 months after crossover to months resulted in increases in ESV, EDV, & ESP AVIM thera
Slide 43: MODERATO II: Long-Term SBP Reduction with AVIM Therapy
MODERATO II: Long-Term SBP Reduction with AVIM Therapy AVIM therapy demonstrated sustained, long-term reduction in 24-Hr aSBP Significant Reduction in 24-Hr aSBP and oSBP1,2,3 Long-term blood pressure from aSBP -8.9 mmHg oSBP in 24-Hour aSBP from a follow-up study of 16 patients from MODERATO II* 0
Slide 44: AVIM Clinical Results Summary
AVIM Clinical Results Summary AVIM therapy resulted in: Significant reduction in mean aSBP & oSBP at 6 months, in a group where 88.5% were ISH patients 85% overall response rate to treatment with AVIM therapy 54% experiencing > 10mmHg reduction in aSBP at 6 months Significant reduction in oSBP & aSB
Slide 45: Rationale and Design of the BACKBEAT Global Pivotal Study
Rationale and Design of the BACKBEAT Global Pivotal Study David Kandzari, M.D., FACC, FSCAI Chief, Piedmont Heart Institute and Cardiovascular Services Chief Scientific Officer, Piedmont Healthcare Director, Interventional Cardiology, Piedmont Heart Institute Co-principal investigator for the BACKBE
Slide 46: Novel Design for a Device-Based Therapy
Novel Design for a Device-Based Therapy Global, pivotal randomized, controlled, double-blind study in which all patients: Receive Medtronic dual-chamber pacemaker implant Have the investigational RAMware downloaded to their device Undergo follow-up testing with AVIM therapy ON and OFF Are managed by
Slide 47: BACKBEAT Study Target Population
BACKBEAT Study Target Population Patients Indicated for a Dual-Chamber Pacemaker Who Also Have Uncontrolled Hypertension Despite Use of Antihypertensive Medications Eligibility: recently received de novo implant of a dual-chamber pacemaker system (including leads) All patients are indicated for a du
Slide 48: Co-Principal Investigators and Clinical Steering Committee Members
Clinical Steering Committee Members Steering Committee Members Co-Principal Investigators Andrea M Russo Vivek Reddy Béla Merkely Charles Love Electrophysiology Electrophysiology Electrophysiology Electrophysiology David Kandzari Felix Mahfoud JoAnn Lindenfeld Raymond Townsend Interv. Cardiology, HT
Slide 49: Approximately 50% of Patients Will be Enrolled Outside of the US
Approximately 50% of Patients Will be Enrolled Outside of the US Study will randomize approximately 500 patients across ~80 study sites Participating countries include: Belgium Spain Czech Republic Switzerland Germany The Netherlands Hungary UK Poland US 49 | Orchestra BioMed R&D Day 2024
Slide 50: BACKBEAT Study Design
BACKBEAT Study Design Top-Line Results Enrollment/ Blinded Study Screening Eligibility Assessment Phase and Regulatory Randomization 12 months Activities Treatment: AVIM therapy + medical therapy Primary Follow-up Patients who have been at 3M at 12M AVIM therapy Potential implanted with a Eligibilit
Slide 51: Key Inclusion and Exclusion Criteria
Key Inclusion and Exclusion Criteria Inclusion Exclusion Recently received a Medtronic Astra/Azure dual Presence of conditions that limit effective chamber pacemaker delivery of AVIM therapy (i.e., permanent or significant atrial fibrillation, severe valvular On a stable anti-HTN treatment regimen o
Slide 52: Set-Up Procedure Determines Enrollment and Randomization
Set-Up Procedure Determines Enrollment and Randomization ≥ 5 mmHg reduction is required to proceed to randomization phase AVIM RAMware downloaded onto previously implanted pacemaker in all patients Response to AVIM therapy activation assessed acutely: Observe blood pressure reduction Determine stabi
Slide 53: Double Blind Phase: Primary Endpoints
Double Blind Phase: Primary Endpoints Primary Efficacy Endpoint: Between group difference in the change of mean 24-hour ambulatory systolic blood pressure (aSBP) at 3 months post- randomization aSBP is the gold-standard measurement of blood pressure 3 months is the standard duration to demonstrate e
Slide 54: Double-Blind Follow-up Through 12-Months to Collect Additional Data
Double-Blind Follow-up Through 12-Months to Collect Additional Data Hypertension Adverse Events Medications Between-group difference in: Between group comparison: Between group comparison: Mean Change of 24-hour aSBP Freedom from the composite Reduction in anti- immediately after cardiovascular adve
Slide 55: Key Takeaways and Q&A
Key Takeaways and Q&A 55 | Orchestra BioMed R&D Day 2024
Slide 56: Key Takeaways
Key Takeaways Hypertension is the leading risk factor for death & most common comorbidity in patients with pacemakers globally AVIM therapy is an investigational, programmable & adjustable treatment developed by Orchestra BioMed AVIM therapy is designed to have an immediate, substantial, & persisten
Slide 57: Q&A
Q&A Moderator David Hochman Darren Sherman Avi Fischer, M.D. David Kandzari, M.D. Vivek Reddy, M.D. CEO, Chairman, Founder COO, President, Founder SVP, Medical Affairs BACKBEAT Study Co-PI, BACKBEAT Study Advisor, Orchestra BioMed Orchestra BioMed and Innovation Piedmont Heart Institute Mount Sinai