Orchestra Biomed Holdings, Inc. · NASDAQ:OBIO
Orchestra Biomed — Investor Day (June 2024)
56 slides from Orchestra Biomed's investor day presentation, Jun 11, 2024
Slide 1: AVIM Therapy R&D Day
Bringing medical inn vation to life Orchestra BioMed AVIM Therapy R&D DAY June 11, 2024
Slide 2: Disclaimer and forward-looking statements
2 | Orchestra BioMed R&D Day 2024 This presentation has been prepared for informational purposes only from information supplied by Orchestra BioMed Holdings, Inc., referred to herein as “we,” “our,” “Orchestra BioMed,” and “the Company,” and from third-party sources indicated herein. Such third-part
Slide 3: Agenda and Speakers
Agenda and Speakers 3 | Orchestra BioMed R&D Day 2024 Introduction and Orchestra BioMed Overview, David Hochman Unmet Hypertension Treatment Need in Older High-Risk Patients, David Kandzari, M.D. Evidence Supporting AVIM Therapy Mechanism of Action, Vivek Reddy, M.D. Clinical Data from the MODERATO
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 Targets >$10B annual hypertension markets Statistically significant efficacy data from double-blind, randomized pilot study BACKBEAT global pivotal study now enrolling Lead Program Atrioventricular Interval Modulation (AVIM) Therapy Strategic collaboration Pipelin
Slide 6: Orchestra BioMed's Partnership-Enabled Model Benefits All
Orchestra BioMed Development Commercialization Shared Benefits Strategic Partners Innovation Secure substantial long-term royalties Outsource commercialization Enable multiple pipeline opportunities Improve patient lives Accelerate development Leverage expertise & resources Enable new growth opportu
Slide 7: A Renaissance is Happening Now
A revival or renewed interest in something; learning from the past to create something better for the future Art Architecture Science Music Device innovation? Renaissance (n): A Renaissance is Happening Now… This Photo by Unknown Author is licensed under CC BY-SA
Slide 8: The Renaissance of Orchestra
The Renaissance of Orchestra ŽƌĐŚۼƐƚƌĂ Ancient Greece: the circular space in front of the stage where the chorus performed Orchestra Renaissance Italy: a group of musicians performing a composition with pre-specified instrumentation 8 | Orchestra BioMed R&D Day 2024 The chorus in Classical Greek dra
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 Orchestra BioMed 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 11 | Orchestra BioMed R&D Day 2024 AVIM Therapy Virtue® SAB Our large, established target markets, built on foundational technologies introduced 50+ years ago, are experiencing a RENAISSANCE, enhancing the opportunity for our innovati
Slide 12: Medtronic Strategic Collaboration for AVIM Therapy
Developed BackBeat CNT (AVIM therapy) from concept stage; owns all related IP Conducted all prior development and the MODERATO I & II clinical studies Partnered with Medtronic for global regulatory approval and commercialization Sponsor for the BACKBEAT Global Pivotal Study $500 - $1,600 revenue sha
Slide 13: Large Global Opportunity for Treating Hypertension in Target Populations
*Total addressable market in 2025 based on company estimates; 1Company estimates based on published sources, including National Inpatient Survey (NIS) and National Health and Nutrition Examination Survey (NHANES); Definition: Hypertension (HTN) Annual Global Opportunity Large Global Opportunity for
Slide 14: 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 15: Hypertension is a Common and Serious Global Health Problem
1Hypertension Cascade: Hypertension Prevalence, Treatment and Control Estimates Among US Adults Aged 18 Years and Older Applying the Criteria From the American College of Cardiology and American Heart Association’s 2017 Hypertension Guideline—NHANES 2017–2020. CDC. May 12, 2023. https://millionheart
Slide 16: Modest Reductions in Blood Pressure Have Significant Clinical Benefit
Modest Reductions in Blood Pressure (BP) Have Significant Clinical Benefit 16 | Orchestra BioMed R&D Day 2024 1 Blood Pressure Lowering Treatment Trialists' Collaboration. Lancet. 2021;397(10285):1625-36. 2Ettehad D, et al. Lancet. 2016;387(10022):957-67. -10 -13 -13 -8 -5 -20 -27 -28 -17 -13 -30 -2
Slide 17: Challenges with Pharmacotherapy for Hypertension
While pharmacologic therapy is often effective, many patients experience insufficient BP control1 Challenges with Pharmacotherapy for Hypertension Patient compliance is particularly difficult in HTN HTN is the “silent killer,” and most patients are asymptomatic Medications often have significant sid
Slide 18: 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 The Nature of Hypertension Changes with Age 1Lilly L, 2021, Wolters Kluwer; Franklin SS, J Clin Hypertens. 2006;8:444-449; Definitions: NH
Slide 19: Older Patients with Hypertension Frequently Have Significant Comorbidities
Older Patients with Hypertension Frequently Have Significant Comorbidities1 19 | Orchestra BioMed R&D Day 2024 Common comorbidities in older hypertensive patients Stroke TAVR CAD/PAD Heart Failure AFib Diabetes Kidney Disease ACS/MI 1Company estimates based on published sources; Definitions: Acute c
Slide 20: Hypertensive Patients with Pacemakers: An Older, Higher Risk Population
Hypertensive Patients with Pacemakers: An Older, Higher Risk Population in Need of Better Treatment Options1 20 70% of patients with pacemakers also have HTN 73 years average age Frequent additional comorbidities: atherosclerosis, hyperlipidemia, diabetes mellitus, and chronic kidney disease More li
Slide 21: Compelling Opportunity to Evaluate AVIM Therapy
Compelling Opportunity to Evaluate AVIM Therapy 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 BACKBEAT IDE Pivotal study: currently enrolling Pilo
Slide 22: Evidence in Support of AVIM Therapy Mechanism of Action
22 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 Comm
Slide 23: 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 deactivated, as needed Com
Slide 24: Novel AVIM Therapy Mechanism of Action
Novel AVIM Therapy Mechanism of Action Designed to Substantially and Persistently Reduce Blood Pressure 24 | Orchestra BioMed R&D Day 2024 AVIM therapy uses a dual-chamber pacemaker to deliver programmed sequences of short AV intervals interspersed with longer AV intervals designed to reduce blood p
Slide 25: Emerging Role of Conduction System Pacing in Cardiac Pacing Therapy
Emerging Role of Conduction System Pacing in Cardiac Pacing Therapy 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 physiologic contractions, al
Slide 26: Invasive Pressure Volume Loop Study Shows Favorable Acute Hemodynamics
Invasive Pressure Volume (PV) Loop Study Shows Favorable Acute Hemodynamics from AVIM Therapy1 Data on file with Orchestra BioMed. 1Kuck, Hemodynamics Effects of AVIM Therapy, THT’24. Definitions: EDV (end-diastolic volume), ESV (end-systolic volume), LVP (left ventricular pressure). 26 Decreases sy
Slide 27: AVIM Therapy Reduces Systolic Blood Pressure
AVIM Therapy Reduces Systolic Blood Pressure1 1 27 Kuck, Hemodynamics Effects of AVIM Therapy, THT’24. Significant reduction in SBP with AVIM therapy and no significant difference between right ventricular (RV) and conduction system pacing (CSP) lead placement -25.0 -20.0 -15.0 -10.0 -5.0 0.0 AV Pac
Slide 28: AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics
AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics1 1 28 Kuck, Hemodynamics Effects of AVIM Therapy, THT’24. Significant reductions in EDV, PED & ESV N=16 *P < 0.05 (compared to baseline); no significant difference between AVIM RV & AVIM CSP -7.0 -6.0 -5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0 2.0 AV
Slide 29: AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics
AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics1 1Kuck, Hemodynamics Effects of AVIM Therapy, THT’24; Definitions: Ea (arterial elastance) (Ees (end-systolic elastance, which is a measure of contractility) 29 Reduction in total peripheral resistance (Ea) & no change in contractility (Ees
Slide 30: AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics
AVIM Therapy has a Favorable Impact on Cardiac Hemodynamics1 1 30 Kuck, Hemodynamics Effects of AVIM Therapy, THT’24. Significant reduction in stroke work (SW) without significant reduction in stroke volume (SV) N=16 *P < 0.05 (compared to baseline); no significant difference between AVIM RV & AVIM
Slide 31: 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 AVIM therapy on cardiac hemodynamics,
Slide 32: Clinical Data: MODERATO I & II Pilot Studies
Clinical Data 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 MODERATO I & II Pilot Studies 32
Slide 33: MODERATO I: Significant Reduction in 24-Hour aSBP and oSBP
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 months activation Primary safety & e
Slide 34: MODERATO I: Safety Data at 24 Months
MODERATO I: Safety Data at 24 Months 85 80 75 70 HR (bpm) Pre-act 24 months Heart Rate * Ejection Fraction EF (%) Pre-act 24 months 65.0 60.0 55.0 50.0 45.0 40.0 * P<0.05 Pre-act 24 months EDV (%) 130 110 90 70 50 End Diastolic Volume * Pre-act 24 months ESV (ml) 50.0 45.0 40.0 35.0 30.0 25.0 20.0 E
Slide 35: MODERATO II Study Design
Daytime aSBP шϭϯϬŵŵ,ŐΘ oSBP шϭϰϬŵŵ,Ő Continue Med Therapy Continue Med Therapy + AVIM Withdraw No Pacemaker with AVIM implant ĂLJƚŝŵĞĂWшϭϮϱŵŵ,ŐΛtĞĞŬϯ 30-day Run-In (RI) Phase Standard Pacing only (AVIM OFF) 6 Month Follow-Up Post-Randomization (PR) Randomization Prospective, multi-center,
Slide 36: MODERATO II: Patient Demographics
No significant differences between groups at baseline Control (n=21) AVIM Therapy (n=26) p-value 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 Fibrillation 6 (28.6%) 5 (19.2%) 0.505
Slide 37: Significant Reduction in 24-Hr aSBP and oSBP
Significant Reduction in 24-Hr aSBP and oSBP1,2 Control (n=20)3 AVIM Therapy (n=26) -11.1 mmHg in 24-Hour aSBP at 6 months -17.5 mmHg in oSBP at 2 years 0% MACE vs. 14.3% in control group at 6 months 85% of patients with reduction in aSBP 6 Months 24 Months aSBP oSBP 6 Months 0 -5 -10 -15 -20 -11.1
Slide 38: 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 -4.0 N=15 ȴ aSBP (mmHg) -1.0 N=15 -2.1 N=13+ -16.1 N =22o -12.0 N=23 -9.5 N=23 -15.2 ±10.7 P<0.01 -8.0 ± 10.0 P= 0.02 -7.4 ± 9.6 P=0.03 +1 Day +1 Months +6 Months Control BackBeat CNT +
Slide 39: MODERATO II: Significant Reduction in 24-hour aSBP
MODERATO II: Significant Reduction in 24-hour aSBP1 1Burkhoff MODERATO II Study 2-Year Results TCT 2021. aSBP (mmHg) P < 0.01 for all times of day 00:00 01:00 02:00 03:00 04:00 05:00 06:00 07:00 08:00 09:00 10:00 11:00 12:00 13;00 14:00 15:00 16:00 17:00 18:00 19:00 20:00 21:00 22:00 23:00 150 145 1
Slide 40: MODERATO II: High Overall Response Rate to AVIM Therapy
MODERATO II: High Overall Response Rate to AVIM Therapy1 1 40 Kalarus et al. Journal of the Am Heart Assoc. 2021;10:e020492 ahajournals.org/doi/10.1161/JAHA.120.020492. AVIM (n=26) Control (n=19) Isolated Systolic Hypertension (ISH) 88.5% 71.4% % with Reduction in aSBP 85% 53% % with > 5 mmHg Reduct
Slide 41: MODERATO II: Chronic Non-Invasive PV Loop Data Show Favorable Effects
MODERATO II: Chronic, Non-Invasive PV Loop Data Show Favorable Effects on Cardiac Remodeling1 AVIM Therapy affects adverse remodeling LV Volume(ml) Unfavorable remodeling in control patients after 6 months resulted in increases in ESV, EDV, & ESP Left Ventricle Pressure (mmHg) LV Volume(ml) Favorabl
Slide 42: MODERATO II: Long-Term SBP Reduction with AVIM Therapy
* -8.9 mmHg in 24-Hour aSBP from baseline at 3.6 years (±0.6) -12.5 mmHg in oSBP at 3.6 years (±0.6) 100% of patients with reduction in aSBP at 3.6 years (±0.6) Long-term blood pressure from a follow-up study of 16 patients from MODERATO II* 8 AVIM & 8 control patients who crossed-over to AVIM thera
Slide 43: 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 44: 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 45: 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 46: 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 All patients are indicated for a dual-chamber pacemaker Sinus node dysfunction & AV block patients are eligible Favorable risk/benefit
Slide 47: Clinical Steering Committee Members
Clinical Steering Committee Members Definitions: Interv (Interventional) Andrea M Russo Electrophysiology Andrea M Russo Electrophysiology David Kandzari Interv. Cardiology, HTN Co-Principal Investigators Steering Committee Members JoAnn Lindenfeld Advanced Heart Failure Felix Mahfoud Interv. Cardio
Slide 48: 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 Czech Republic Germany Hungary Poland Spain Switzerland The Netherlands UK US 48 | Orchestra BioMed R&D Day 2024
Slide 49: BACKBEAT Study Design
Patients who have been implanted with a Medtronic dual-chamber pacemaker and have uncontrolled hypertension despite medications* R Treatment: AVIM therapy + medical therapy Primary at 3M Control: Medical therapy Follow-up at 12M AVIM therapy download and set up Eligibility Assessment Screening Eligi
Slide 50: Key Inclusion and Exclusion Criteria
Recently received a Medtronic Astra/Azure dual chamber pacemaker On a stable anti-HTN treatment regimen of 1, 2 or 3 classes of anti-HTN drugs oSBP шϭϰϬŵŵ,ŐĂŶĚфϭϴϬŵŵ,Ő Average 24-Hour aSBP шϭϯϬŵŵ,ŐĂŶĚфϭϳϬ mmHg Key Inclusion and Exclusion Criteria Presence of conditions that limit effecti
Slide 51: Set-Up Procedure Determines Enrollment and Randomization
Set-Up Procedure Determines Enrollment and Randomization AVIM RAMware downloaded onto previously implanted pacemaker in all patients Response to AVIM therapy activation assessed acutely: Observe blood pressure reduction Determine stability of reduction Optimize therapy parameters for each patient ш
Slide 52: 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 Primary Safety Endpoint Freedom from unanticipated serious adverse device events at 3 months post-randomization Double Blind Phase: Primary Endpo
Slide 53: 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: Mean Change of 24-hour aSBP immediately after randomization Mean change in 24-hour ambulatory pulse pressure (aPP) Mean reduction of oSBP at 3 months post-randomiz
Slide 54: Key Takeaways and Q&A
Key Takeaways and Q&A 54 | Orchestra BioMed R&D Day 2024
Slide 55: 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 56: Q&A
Q&A David Hochman CEO, Chairman, Founder Orchestra BioMed David Kandzari, M.D. BACKBEAT Study Co-PI, Piedmont Heart Institute Vivek Reddy, M.D. BACKBEAT Study Advisor, Mount Sinai Hospital Darren Sherman COO, President, Founder Orchestra BioMed Avi Fischer, M.D. SVP, Medical Affairs and Innovation O