SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
PURSUANT TO SECTION 13 OR 15(d)
OF THE SECURITIES EXCHANGE ACT OF 1934
Date of Report (Date of earliest event reported):
(Exact name of registrant as specified in its charter)
|(State or other jurisdiction
|(Commission File Number)||(IRS Employer|
(Address of principal executive offices, including zip code)
Registrant’s telephone number, including area code: (
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
|Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)|
|Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)|
|Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))|
|Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))|
Securities registered pursuant to Section 12(b) of the Act
|Title of each class||Trading Symbol(s)||Name of each exchange on which registered|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check
mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting
standards provided pursuant to Section 13(a) of the Exchange Act.
Item 7.01. Regulation FD Disclosure.
A copy of a slide presentation that Orchestra BioMed Holdings, Inc. (the “Company”) uses at investor and industry conferences and presentations is attached to this Current Report on Form 8-K (“Current Report”) as Exhibit 99.1 and is incorporated herein solely for purposes of this Item 7.01 disclosure. Additionally, the Company has posted the slide presentation on its website at https://investors.orchestrabiomed.com under the Investor Relations section.
The information in Item 7.01 of this Current Report, including Exhibit 99.1 attached hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of such section. The information in Item 7.01 of this Current Report, including Exhibit 99.1, shall not be incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, regardless of any incorporation by reference language in any such filing.
Item 8.01 Other Events.
The Company considers its exposure to Silicon Valley Bank (“SVB”) as de minimis, given that less than one percent of its total cash, cash equivalents and marketable securities are held at SVB.
Item 9.01. Financial Statements and Exhibits.
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|ORCHESTRA BIOMED HOLDINGS, INC.|
|By:||/s/ David P. Hochman|
|Name:||David P. Hochman|
|Title:||Chief Executive Officer|
Date: March 13, 2023
Bringing medical inn vation to life Orchestra BioMed Corporate Presentation Q1 2023
Forward - Looking Statements 2 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 - party information has not been independently verified. Orchestra BioMed makes no representation or warranty, expressed or implied, as to the accuracy or completeness of such information. This presentation contains forward - looking statements within the meaning of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including, without limitation, statements relating to our expected financial runway, the potential safety and efficacy of our product candidates, the timing of our planned pivotal trials, expected market sizes for our product candidates, the ability of our partnerships to accelerate clinical development, and our estimated future financial performance and financial position. These statements are often identified by the use of words such as “anticipate,” “believe,” “can,” “continue,” “could,” “estimate,” “expect,” “intend,” “likely,” “may,” “might,” “objective,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “to be,” “will,” “would,” or the negative or plural of these words, or similar expressions or variations, although not all forward - looking statements contain these words. We cannot assure you that the events and circumstances reflected in the forward - looking statements will be achieved or occur and actual results could differ materially from those expressed or implied by these forward - looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those identified herein, and those identified under the heading “Risk Factors — Risks Related to Orchestra’s Business and New Orchestra Following the Business Combination” in the definitive proxy statement/prospectus of Health Sciences Acquisitions Corporation 2 (Orchestra BioMed’s predecessor) filed with the U.S. Securities and Exchange Commission pursuant to Rule 424(b)(3) on December 16, 2022 and in our other filings with the SEC. These risks are not exhaustive. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward - looking statements. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date hereof and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain, and investors are cautioned not to unduly rely upon these statements. Except as required by law, we undertake no obligation to update any forward - looking statements to reflect events or circumstances after the date of such statements.
Orchestra BioMed Executive Summary Strategic collaboration Double - digit revenue share Strong balance sheet and outstanding investors Partnership - enabled business model designed to accelerate innovation to patients, drive strong partner and shareholder value and yield exceptional future profitability Statistically significant double - blind, randomized preliminary trial efficacy data Plan to initiate pivotal trial H2 2023 Strategic collaboration Double - digit revenue share Strong 3 - year multi - center preliminary trial safety and efficacy data Plan to initiate pivotal trial H1 2023 3 ĂĐŬĞĂƚ Ed Ρ ƚĂƌŐĞƚƐ хΨ ϭϬ ĂŶŶƵĂů ŚǇƉĞƌƚĞŶƐŝŽŶ ŵĂƌŬĞƚƐ &ŝƌŵǁĂƌĞ ƵƉŐƌĂĚĞ ƚŽ ĞǆŝƐƚŝŶŐ ƉĂĐĞŵĂŬĞƌ Virtue® SAB targets >$3B annual artery disease markets Protected sirolimus delivery, non - coated balloon
Enable new growth opportunities Outsource development Minimize P&L dilution 4 Orchestra BioMed’s Partnership - enabled Model Benefits All Development Strategic Partners Commercialization Improve patient lives Accelerate development Leverage expertise & resources ^ĞĐƵƌĞ ƐƵďƐƚĂŶƚŝĂů ůŽŶŐ Ͳ ƚĞƌŵ ƌŽǇĂůƚŝĞƐKƵƚƐŽƵƌĐĞ ĐŽŵŵĞƌĐŝĂůŝǌĂƚŝŽŶ DƵůƚŝƉůĞ ƉŝƉĞůŝŶĞ ŽƉƉŽƌƚƵŶŝƚŝĞƐ Shared Benefits
Avi Fischer, M.D. SVP, Medical Affairs & Innovation J.C. Simeon SVP, Quality Inessa R. Wheeler VP, Marketing Bob Laughner VP, Regulatory Affairs Stephen A. Zielinski VP, Product Dev., Bioelectronic Therapies Ziv Belsky VP, Research, Bioelectronic Therapies Juan Lorenzo VP, Product Dev., Focal Therapies Highly Accomplished Executive Team & Board Executive Team: >250 Years of Experience, ~25 Avg Industry Years, >100 Product Approvals & >600 Authored Patents David Hochman Chairman, CEO, Co - Founder Darren R. Sherman President, COO, Director, Co - Founder Michael Kaswan Chief Financial Officer George Papandreou, Ph.D. GM & SVP, Focal Therapies ,ĂŶƐ Ͳ WĞƚĞƌ ^ƚŽůů͕ D͕͘͘ WŚ͘͘ ŚŝĞĨ ůŝŶŝĐĂů KĨĨŝĐĞƌ 5 Eric S. Fain, M.D. Board Member Eric A. Rose, M.D. Board Member Pamela Connealy Board Member Geoffrey W. Smith Board Member Jason Aryeh Board Member Yuval Mika, Ph.D. GM & CTO, Bioelectronic Therapies
Product Platforms Target Indications Preclinical Clinical Feasibility Clinical Pivotal Partner Study Sponsor Next Milestones & Expected Timing 6 BackBeat Cardiac Neuromodulation Therapy (CNT Ρ ) Hypertension (HTN) (pacing patients; HTN+P) Global Pivotal Study Start H2 2023 High - Risk HTN (non - pacing patients) ROFN Will Seek to Leverage Data from HTN+P 2 CNT - HF Heart Failure Acute Clinical Data 2023 Potential Chronic Study Start 2024 Virtue® Sirolimus AngioInfusion Ρ Balloon (SAB) Coronary In - Stent Restenosis (ISR) FDA Breakthrough 3 US Pivotal Study Start H1 2023 Japan Pivotal Study Start H1 2024 Coronary Small Vessel (SV) 1 FDA Breakthrough 4 Japan Pivotal Study Start H1 2024 US Pivotal Study Start 2024 Below - the - Knee (BTK) 1 FDA Breakthrough 5 Global BTK Study Start 2024/2025 SirolimusEFR Ρ / Urethral Strictures & BPH Preclinical Development Milestones Microporous Balloon Osteoarthritis 2023/2024 Advancing a High - Impact Pipeline 6 1 Plan to leverage existing coronary ISR data to support potential Pivotal Study, although there have only been limited discussions with the FDA or a comparable foreign regulator in this regard. 2 Will seek to leverage data from HTN+P pilot and pivotal trials to support clinical and regulatory development for High - Risk HTN indication given that age and other demographic factors of the target population are expected to be similar, the type of hypertension treated will likely be isolated systolic hypertension which is predominant in the HTN+P population, and other co - morbidities are also expected to be common to both target populations. However, there have been no discussions with the FDA or a comparable foreign regulator in this regard. 3 Virtue SAB has received Breakthrough Device Designation for the balloon dilatation of the stenotic portion (up to 26 mm length) of a stented coronary artery (in - stent restenosis (ISR)) that is 2.25 to 4.0 mm in diameter, for the purpose of improving lumen diameter; 4 Virtue SAB has received Breakthrough Device Designation for the balloon dilatation of the de novo stenotic portion (up to 26mm in lesion length) of a native coronary artery of 2.0 mm to 2.5 mm in diameter (small coronary arteries), for the purpose of improving lumen diameter; 5 Virtue SAB has received Breakthrough Device Designation for the balloon dilatation of the stenotic portion (up to 18 mm length) of an infrapopliteal artery (P - 3 segment or distal, below the knee, with reference vessel diameter (RVD) 2.25 - 4.0 mm), for the purpose of improving lumen diameter. All references to clinical study initiations for HTN+P, Coronary ISR and Coronary SV indications are based on ongoing interactions with US FDA regarding IDE approvals or Japan PMDA regarding CTN approvals, which are required to start clinical studies. With respect to BackBeat CNT for HTN, Orchestra and Medtronic have had initial interactions with the FDA regarding IDE approval and expect to continue interactions regarding clinical trial design and submission requirements ahead of submitting documentation for approval in the second half of 2023. A pre - CTN discussion with the PMDA is planned for December 2022 with submission for CTN approval anticipated in the second half of 2023. With respect to Virtue SAB for Coronary ISR, Orchestra has been working on IDE approval with the FDA under the breakthrough designation program to define all of the elements necessary for IDE approval and Orchestra expects to complete the agreed upon work and submit documentation for approval in Q1 of 2023. Orchestra and Terumo have had initial interactions with the PMDA and expect to submit for CTN approval for Coronary ISR and SV studies in the second half of 2023. FDA and PMDA responses are expected approximately 30 days following formal submissions; clinical study enrollment is expected to begin approximately 6 - 8 weeks after regulatory approvals; study enrollment timelines are currently estimated to be 12 - 18 months for all referenced studies although actual study enrollment timeframes may be longer; final primary endpoint results for all studies are at 12 months from enrollment with the exception of Japan Coronary ISR & SV studies, which are expected to be at 6 months from enrollment.
7 BackBeat Cardiac Neuromodulation Therapy (CNT Ρ )
BackBeat CNT Ρ Overview 1 Company estimates based on published sources, including National Inpatient Survey (NIS) and National Health and Nutrition Examination Survey 8 (NHANES); 2 Kalaras et al. Journal of the American Heart Association. ahajournals.org/doi/10.1161/JAHA.120.020492; 3 Burkhoff. MODERATO II Study 2 - Year Results TCT 2021;. Definitions: Ambulatory Systolic Blood Pressure (aSBP) and Office Systolic Blood Pressure (oSBP) Opportunity • Hypertension is #1 comorbidity in pacemaker population affecting over 70% of patients 1 • Older population at increased risk for major events & challenges with drug compliance Innovation • Bioelectronic therapy designed to substantially & persistently lower blood pressure • Compatible with standard pacemaker device & leverages existing treatment paradigm • Compelling clinical data from double - blind randomized study : significant 8.1 mmHg net reduction in 24 - Hr aSBP at 6 months & 17.5 mmHg reduction in oSBP at 2 years 2,3 Collaboration with • Global pacemaker leader providing technology and development/clinical/regulatory support for Orchestra BioMed - sponsored global pivotal trial • Following regulatory approval, Medtronic has exclusive global rights to commercialization in the pacemaker - indicated patient population with double - digit revenue sharing for Orchestra BioMed of BackBeat CNT - enabled pacemaker sales
Large Global Opportunity for Treating Hypertension in Target Populations *Total addressable market in 2025 based on company estimates; 1 Company estimates based on published sources, including National Inpatient Survey (NIS) and National Health and Nutrition Examination Survey (NHANES); 2 Known and well - characterized population, multiple references available; Definition: Hypertension (HTN) 9 >$10 Billion Potential Annual Global Market Opportunity* >3.1 M Addressable HTN Patients HTN + Pacemaker • Over 70% of pacemaker patients have HTN 1 • Older, co - morbid population at increased risk of major events 2 High Risk HTN (Non - pacemaker) • Older patients with isolated systolic hypertension (ISH) and comorbidities 750,000 patients >$2 Billion Annual Global Opportunity 2,400,000 patients >$8 Billion HTN + Pacemaker High Risk HTN
• Bioelectronic therapy designed to leverage standard rhythm management device procedures (dual - chamber pacemaker) - Same implant procedure and lead positions - Large trained physician pool - Same target patient population - Leverageable existing reimbursement • Mechanism of action - Designed to substantially reduce blood pressure by reducing preload through programmed pacing with short AV delays - Designed to maintain reduction by modulating sympathetic tone and reducing afterload through programmed variable pressure patterns Designed to Substantially Lower BP & Maintain Reduction BackBeat CNT Ρ 10 Designed to Substantially and Persistently Lower Blood Pressure 1. Reducing Preload Lowers BP 2 . Modulating Sympathetic Tone & Reducing Afterload Maintains Reduction in BP SBP (mmHg) Time (s) 155 150 145 140 135 130 0 50 100. 150 200 250 300
MODERATO II Double - Blind, Randomized Results ĂĐŬĞĂƚ Ed Ρ ƐŚŽǁĞĚ ĞŶĐŽƵƌĂŐŝŶŐ ƌĞƐƵůƚƐ ŝŶ DKZdK //͕ Ă ƉƌŽƐƉĞĐƚŝǀĞ͕ ŵƵůƚŝ Ͳ ĐĞŶƚĞƌ͕ ƌĂŶĚŽŵŝǌĞĚ͕ ;ĂĐŬĞĂƚ Ed н DĞĚŝĐĂů dŚĞƌĂƉǇ ǀƐ͘ ŽŶƚŝŶƵĞĚ DĞĚŝĐĂů dŚĞƌĂƉǇͿ͕ ĚŽƵďůĞ Ͳ ďůŝŶĚ͕ƉŝůŽƚ ƐƚƵĚǇ ŽĨ ƉĂĐĞŵĂŬĞƌ ƉĂƚŝĞŶƚƐ ǁŝƚŚ ƉĞƌƐŝƐƚĞŶƚ ŚǇƉĞƌƚĞŶƐŝŽŶ 1 Kalaras et al. Journal of the American Heart Association. 2021;10:e020492 ahajournals.org/doi/10.1161/JAHA.120.020492 ; 2 Burkhoff MODERATO II Study 2 - Year Results TCT 2021; 3 24 - Hr aSBP Control (n=19),1 control patient could not be measured despite repeat measurement (patient had extremely high blood pressure); Definitions: Major Adverse Cardiac Events (MACE) included death, heart failure, clinically significant arrhythmias (i.e., persistent or increased atrial fibrillation, serious ventricular arrhythmias), myocardial infarction, stroke and renal failure in treatment group calculated per patient, Office Systolic Blood Pressure (oSBP), Ambulatory Systolic Blood Pressure (aSBP) 11 Significant Reduction in aSBP 24 Hours a Day - 11.1 mmHg in 24 - Hour aSBP at 6 months - 17.5 mmHg in oSBP at 2 years 0% MACE vs. 9.5% in control group at 6 months 85% of patients with reduction in aSBP oSBP 6 Months 24 Months ^ŝŐŶŝĨŝĐĂŶƚ ZĞĚƵĐƚŝŽŶ ŝŶ Ϯϰ Ͳ ,ƌĂ^W ĂŶĚ Ž^W ϭ͕Ϯ aSBP 6 Months 0 - 5 - 10 - 15 - 20 - 3.1 P = 0.17 Ͳ ϭϭ͘ϭ W ф Ϭ͘ϬϬϭ - 12.4 P < 0.001 - 0.1 P = 0.94 - 17.5 P < 0.01 Δ - 12.3 p = 0.02 Δ - 8.1 p = 0.01 Δ in BP (mmHg) 150 145 140 135 130 125 120 115 110 ϬϬ͗ϬϬ Ϭϭ͗ϬϬ ϬϮ͗ϬϬ Ϭϯ͗ϬϬ Ϭϰ͗ϬϬ Ϭϱ͗ϬϬ Ϭϲ͗ϬϬ Ϭϳ͗ϬϬ Ϭϴ͗ϬϬ Ϭϵ͗ϬϬ ϭϬ͗ϬϬ ϭϭ͗ϬϬ ϭϮ͗ϬϬ ϭϯ͗ϬϬ ϭϰ͗ϬϬ ϭϱ͗ϬϬ ϭϲ͗ϬϬ ϭϳ͗ϬϬ ϭϴ͗ϬϬ ϭϵ͗ϬϬ ϮϬ͗ϬϬ Ϯϭ͗ϬϬ ϮϮ͗ϬϬ Ϯϯ͗ϬϬ 24 - Hr aSBP (mmHg) P < 0.01 for all times of day Control (n=20) 3 BackBeat CNT (n=26) Pre - activation (n=26) 6 months (n=26) 6 Month Mean Pre - activation Mean
ĂĐŬĞĂƚ Ed Ρ DĞĚƚƌŽŶŝĐ ŽůůĂďŽƌĂƚŝŽŶ • Medtronic is the global leader in pacemakers - >$1.5 billion annual pacemaker revenues 1 • Key Terms: (Hypertension + Pacemaker population) - Orchestra BioMed drives and finances development as sponsor of global pivotal trial - Medtronic provides certain development/clinical/regulatory resources funded by Orchestra to support integration into a Medtronic pacemaker and execution of the pivotal trial - Medtronic has exclusive global rights for commercialization upon regulatory approval - Orchestra is expected to receive between $500 and $1,600 per BackBeat CNT enabled device sold based on a formula of the higher of (1) a fixed dollar amount per device (amount varies materially on a country - by - country basis) or (2) a percentage of sales. - BackBeat CNT enabled devices expected to be sold under existing reimbursement codes . - Medtronic has a right of first negotiation to expand its global rights to BackBeat CNT for the treatment of HTN patients not indicated for a pacemaker • $50 million equity investment in Orchestra BioMed 12 Aligned with Global Market Leader in Pacemakers and Device - based Hypertension Treatment 1 Based on MDTs consolidated financial results for the fiscal year ended April 29, 2022
BackBeat CNT Ρ Pivotal Trial Design 13 Current anticipated trial design: • Randomization of ~650 - 750 patients with uncontrolled HTN despite medical therapy who are indicated for a dual - chamber pacemaker • Inclusion and exclusion criteria for enrollment in the BackBeat CNT Pivotal Study will be similar to the criteria used in the MODERATO II study • Patients will be randomized 1:1 in a double - blinded manner to either active treatment with the BackBeat CNT - with continued antihypertensive drug treatment or to standard pacing - only with continued antihypertensive drug therapies • Anticipated primary efficacy and safety endpoints: - Efficacy endpoint: Superiority of treatment as compared to control based on mean change in 24 - hour aSBP at 3 months post randomization - Safety endpoint: Non - inferiority between the treatment and control groups comparing Major Adverse Cardiovascular Events (MACE) at 12 months post randomization • Enroll patients across ~80 study sites planned for United States, Europe and, potentially, Japan
ϭϰ Virtue® Sirolimus AngioInfusion Ρ Balloon (SAB)
Virtue® SAB Overview 1 Total addressable market is 2025 market data based on company estimates; ; 2 von Birgelen et al. JACC Vol. 59, No. 15, 2012 April 10, 2012:1350 – 61; Virtue SAB has received Breakthrough Device Designation for: 3 The balloon dilatation of the stenotic portion (up to 26 mm length) of a stented coronary artery (in - stent restenosis (ISR)) that is 2.25 to 4.0 mm in diameter, for the purpose of improving lumen diameter; 4 The balloon dilation of the de novo stenotic portion (up to 26mm in lesion length) of a native coronary artery 15 of 2.0 mm to 2.5 mm in diameter (small coronary arteries), for the purpose of improving lumen diameter; 5 The balloon dilatation of the stenotic portion (up to 18 mm length) of an infrapopliteal artery (P - 3 segment or distal, below the knee, with reference vessel diameter (RVD) 2.25 - 4.0 mm), for the purpose of improving lumen diameter. Opportunity • Significant need for “leave nothing behind” treatment for coronary and peripheral indications representing an > $3B global market opportunity 1 • Drug - eluting stents (DES) carry risks of long - term restenosis and late thrombosis; require extended dual antiplatelet therapy; not effective/approved for select patients/lesions Innovation • Highly - differentiated, non - coated drug/device combination product candidate designed to enable angioplasty with protected delivery of extended release sirolimus • Compelling clinical results in multi - center coronary ISR clinical trial with 3 - year follow - up 2 • FDA Breakthrough Device Designation received for indications in coronary ISR 3 , coronary SV 4 and BTK 5 Partnership with • Global commercial leader with >$2.5B annual interventional cardiology revenue responsible for commercializing Virtue SAB as flagship therapeutic offering • Collaboration driving multi - indication pivotal trial program starting with coronary ISR • Orchestra BioMed to receive double - digit royalties and per unit drug payments
Large Opportunity for Leave Nothing Behind Solution 16 >$3 Billion Annual Global CAD & PAD Market Opportunity * ƌƚĞƌǇ ĚŝƐĞĂƐĞ ŝƐ ƚŚĞ ƉƌŝŵĂƌǇ ĐĂƵƐĞ ŽĨ ĚĞĂƚŚ ǁŽƌůĚǁŝĚĞ >ĂƌŐĞ ŵĂƚƵƌĞ ŵĂƌŬĞƚ ǁŝƚŚ ƐŝŐŶŝĨŝĐĂŶƚ ƵŶŵĞƚ ŶĞĞĚ Ʌ ^ƵďŽƉƚŝŵĂů ƚƌĞĂƚŵĞŶƚƐ ĨŽƌ ĐŽƌŽŶĂƌǇ /^Z͕ ĐŽƌŽŶĂƌǇ ^s ĚĞ ŶŽǀŽ ĂŶĚ d< ĞƐŝŐŶĞĚ ƚŽ ůĞǀĞƌĂŐĞ ĞǆŝƐƚŝŶŐ ƚƌĞĂƚŵĞŶƚ ƉĂƌĂĚŝŐŵ Θ ĞƐƚĂďůŝƐŚĞĚ ƚĞĐŚŶŽůŽŐŝĞƐ͗ ƐŝƌŽůŝŵƵƐ ĂŶĚ ďĂůůŽŽŶ ĂŶŐŝŽƉůĂƐƚǇ >3.2M Addressable CAD & PAD Patients (2025 Estimate) ~2,000,000 patients >$1.8 Billion Annual Global Opportunity ~1,250,000 patients >$1.2 Billion ŽƌŽŶĂƌǇ Peripheral *Total addressable market in 2025 based on company estimates; Definitions: Coronary Artery Disease (CAD), Peripheral Artery Disease (PAD), In - stent Restenosis (ISR), Small Vessel (SV, ≤2.5mm), High bleeding Risk De Novo (>2.5mm), Below - the - Knee (BTK, Rutherford 3 - 6, w/out severe comorbidities).
Virtue® SAB ŶŐŝŽ/ŶĨƵƐŝŽŶ Ρ ĂůůŽŽŶ ĚĞƐŝŐŶĞĚ ƚŽ ĞŶĂďůĞ ĂŶŐŝŽƉůĂƐƚǇ ǁŝƚŚ ƉƌŽƚĞĐƚĞĚ ĚƌƵŐ ĚĞůŝǀĞƌǇ ƚŽ ĚŝůĂƚĞ ǀĞƐƐĞů͕ ƚŽ ĐŽŶƐŝƐƚĞŶƚůǇ ĚĞůŝǀĞƌ ŝŶƚĞŶĚĞĚ ĚŽƐĞ ĂŶĚ ƚŽ ůĞĂǀĞ ŶŽ ŵĞƚĂů ďĞŚŝŶĚ Designed to Enable Angioplasty with Protected Sirolimus Delivery while Leaving No Metal Behind 17 1 Granada et al. EuroIntervention 2016;12:740 - 747 WƌĞĐŝƐĞ ĚŽƐĞ ƉƌŽƚĞĐƚĞĚ ŝŶ ĚŽƐĞ ƵŶŝƚ Inflated to deliver dose through micropores ^ŝƌŽůŝŵƵƐ&Z Ρ &ŽƌŵƵůĂƚŝŽŶ ƉƌŽǀŝĚĞĚ ĞǆƚĞŶĚĞĚ ĨŽĐĂů ƌĞůĞĂƐĞ ŽĨ ƚŚĞƌĂƉĞƵƚŝĐ ůĞǀĞůƐ ŽĨ ƐŝƌŽůŝŵƵƐ ƚŚƌŽƵŐŚ ĐƌŝƚŝĐĂů ŚĞĂůŝŶŐ ƉĞƌŝŽĚ ; у ϯϬ ĚĂǇƐͿ ϭ 1000 ϭϬϬ ϭϬ 1 0.1 0.01 Ϭ͘ϬϬϭ 0.0001 ^ŝƌŽůŝŵƵƐ dŝƐƐƵĞ ŽŶĐĞŶƚƌĂƚŝŽŶ ;ŶŐͬŵŐͿ Required Therapeutic Concentration > 1ng/mg >ƵŶŐ͕ ůŝǀĞƌ Θ ŬŝĚŶĞǇ ďĞůŽǁ ůĞǀĞů ŽĨ ĂƐƐĂǇ ƋƵĂŶƚŝĨŝĐĂƚŝŽŶ ; Ϭ͘ϭ ŶŐͬŵŐͿ ŝŶ ф ϭ ǁĞĞŬ 0 5 10 ϮϬ 25 ϯϬ Coronary Distal Kidney Liver Lun g ϭϱ dŝŵĞ ;ĂǇƐͿ N = 753 porcine coronary artery segments Protected Delivery/No Drug Coating • No drug loss in transit • No time limits on delivery • No drug coating particulates
ŽŵƉĞůůŝŶŐ ^Z dƌŝĂů ZĞƐƵůƚƐ ŝŶ ŽƌŽŶĂƌǇ /^Z WĂƚŝĞŶƚƐ 1 Verheye et al. JACC Cardiovasc Interv 2017 Oct 23;10(20):2029 - 2037. DOI: 10.1016/j.jcin.2017.06.021. 2 Granada 3 - Year Clinical Results TCT 2018. 3 - Year SABRE Trial Clinical Report on file. Definitions: Target lesion failure (TLF), late lumen loss (LLL), target lesion revascularization (TLR) and Myocardial Infarction (MI). ϭϴ Virtue® SAB preliminarily demonstrated encouraging safety and efficacy results in patients with coronary in - stent restenosis (ISR) in prospective, multi - center SABRE Trial 1 Ϭ͘ϭϮ ŵŵ >>> Ăƚ ϲ Ͳ ŵŽŶƚŚƐ 2.8% Target Lesion Failure at 1 year 0% New TLR between 1 to 3 years Preliminarily Demonstrated Safety with Low Event Rates Out to 3 Years 2 WƌĞůŝŵŝŶĂƌǇ ĨĨŝĐĂĐǇZĞƐƵůƚƐ ^ŚŽǁĞĚ >Žǁ Ϭ͘ϭϮ ŵŵ >ĂƚĞ >ŽƐƐ 1 RVD reported using Internormal values; 2 Trial primary performance endpoint; 3 Trial secondary performance endpoint (binary restenosis = >50% lumen diameter stenosis). 4 Data is based on per protocol population criteria revised to be consistent with proposed Virtue ISR - US pivotal study population. ǀĞŶƚ ZĂƚĞƐ ;йͿ TLR d>& 10% 9% 8% 7% 6% 5% 4% 3% 2% 1% 0% 30 days 1 - year 3 - years 0% 0% 0% 0% 0% Cardiac Death TV - MI Ϭ й 0% Ϯ͘ϴ й 2.8% 2.8% Ϯ͘ϴ й 5.6% 4
Virtue® SAB Terumo Partnership dĞƌƵŵŽ ŝƐ Ă ŐůŽďĂů ůĞĂĚĞƌ ǁŝƚŚ хΨ Ϯ͘ϱ ďŝůůŝŽŶ ĂŶŶƵĂů ŝŶƚĞƌǀĞŶƚŝŽŶĂů ĐĂƌĚŝŽůŽŐǇ ƌĞǀĞŶƵĞƐ ϭ sŝƌƚƵĞ ^ ƉŽƐŝƚŝŽŶĞĚ ƚŽ ďĞĐŽŵĞ dĞƌƵŵŽ ͛ Ɛ ĨůĂŐƐŚŝƉ ƚŚĞƌĂƉĞƵƚŝĐ ŽĨĨĞƌŝŶŐ ǁŝƚŚ ƉŽƚĞŶƚŝĂů ƚŽ ĚƌŝǀĞ ƐŝŐŶŝĨŝĐĂŶƚ ĨƵƚƵƌĞ ŐƌŽǁƚŚ <ĞǇ dĞƌŵƐ͗ Ψ ϯϬ ŵŝůůŝŽŶ ƵƉĨƌŽŶƚ ĂŶĚ ƉŽƚĞŶƚŝĂů ĨƵƚƵƌĞ ĐůŝŶŝĐĂů ĂŶĚ ƌĞŐƵůĂƚŽƌǇ ŵŝůĞƐƚŽŶĞƐ Ψ ϱ ŵŝůůŝŽŶ ĞƋƵŝƚǇ ŝŶǀĞƐƚŵĞŶƚ ŝŶ KƌĐŚĞƐƚƌĂ ŝŽDĞĚ dĞƌƵŵŽ ƌĞƐƉŽŶƐŝďůĞ ĨŽƌ ĐůŝŶŝĐĂů ĂŶĚ ƌĞŐƵůĂƚŽƌǇ ĞǆƉĞŶƐĞƐ͕ ĞǆĐůƵĚŝŶŐ sŝƌƚƵĞ /^Z Ͳ h^ ƐƚƵĚǇ ǁŚŝĐŚ KƌĐŚĞƐƚƌĂ ŝŽDĞĚ ŝƐ ƐƉŽŶƐŽƌŝŶŐ dĞƌƵŵŽ ƌĞƐƉŽŶƐŝďůĞ ĨŽƌ ĚĞǀŝĐĞ ƐƵƉƉůǇ ĐŚĂŝŶ ĂŶĚ ĐŽŵŵĞƌĐŝĂůŝǌĂƚŝŽŶ ĞǆƉĞŶƐĞƐ KƌĐŚĞƐƚƌĂ ŝŽDĞĚ ƌĞĐĞŝǀĞƐ ϭϬ Ͳ ϭϱ й ƌŽǇĂůƚǇ W>h^ ƉĞƌ ƵŶŝƚ ƉĂǇŵĞŶƚƐ ĨŽƌ ^ŝƌŽůŝŵƵƐ&Z Ρ ĂƐ ĞǆĐůƵƐŝǀĞ ƐƵƉƉůŝĞƌ KƌĐŚĞƐƚƌĂ ŝŽDĞĚ ƌĞƚĂŝŶƐ ƌŝŐŚƚƐ ƚŽ sŝƌƚƵĞ ^ ŝŶ Ăůů ĐůŝŶŝĐĂů ĂƉƉůŝĐĂƚŝŽŶƐ ŽƵƚƐŝĚĞ ŽĨ ǀĂƐĐƵůĂƌ ŝŶĚŝĐĂƚŝŽŶƐ 19 DƵůƚŝŶĂƚŝŽŶĂů DĂƌŬĞƚ >ĞĂĚĞƌ WƌŽǀŝĚĞƐ 'ůŽďĂů ŽŵŵĞƌĐŝĂů ZĞĂĐŚ ĂŶĚ >ŽŶŐ Ͳ dĞƌŵ ůŝŐŶŵĞŶƚ 1 Based on Terumo’s consolidated financial results for the fiscal year ended March 31, 2022
sŝƌƚƵĞΠ ^ ʹ ŽƌŽŶĂƌǇ /^Z h^ WŝǀŽƚĂů dƌŝĂů 20 Double - blind, multi - center, prospective, randomized controlled study in patients with single - layer coronary ISR Virtue® SAB N=200 Z Primary Endpoint Target Lesion Failure (CD, TV - MI and TLR) at 12 months ^ƚĂƚŝƐƚŝĐĂů ƐƐƵŵƉƚŝŽŶ ϵϬ й ƉŽǁĞƌĞĚ ĨŽƌ ƐƵƉĞƌŝŽƌŝƚǇ sŝƌƚƵĞ ^ d>& ч ϭϵ й ǀƐ͘ W d>& ш ϯϬ й Success Considerations Virtue SAB: 2.8% TLF at 12 months in SABRE trial per protocol population PBA: 33 - 46% TLF at 12 months in coronary ISR published studies ϭϮ DŽŶƚŚ WƌŝŵĂƌǇ ŶĚƉŽŝŶƚ 12 - 18 Months Enrollment Key Inclusion RVD 2.5 to 4.0 mm, <30% DS (vs. RVD 2.5 to 3.5, <40% DS SABRE 1 Trial) PBA N=100 WƌŽƐƉĞĐƚŝǀĞ͕ ƐŝŶŐůĞ Ͳ Ăƌŵ͕ ĐŽŶƚƌŽůůĞĚ ƐƚƵĚǇ ŝŶ ƉĂƚŝĞŶƚƐ ǁŝƚŚ ĚŽƵďůĞ Ͳ ůĂǇĞƌ ĐŽƌŽŶĂƌǇ /^Z Virtue® SAB N=100 <ĞǇ /ŶĐůƵƐŝŽŶ Zs Ϯ͘ϱ ƚŽ ϰ͘Ϭ ŵŵ͕ ф ϯϬ й ^ ;ǀƐ͘ Zs Ϯ͘ϱ ƚŽ ϯ͘ϱ ͕ ф ϰϬ й ^ ^Z ϭ dƌŝĂůͿ Primary Endpoint Target Lesion Failure (CD, TV - MI and TLR) at 12 months ϭ sĞƌŚĞǇĞ ^͘ : ĂƌĚŝŽǀĂƐĐ /ŶƚĞƌǀ͘ ϮϬϭϳ ͖ ϭϬ ͗ ϮϬϮϵ Ͳ ϯϳ ͘ ĞĨŝŶŝƚŝŽŶƐ͗ ŽƌŽŶĂƌǇ /Ŷ Ͳ ƐƚĞŶƚ ZĞƐƚĞŶŽƐŝƐ ;/^ZͿ͕ ŝĂŵĞƚĞƌ ^ƚĞŶŽƐŝƐ ;^Ϳ͕ WůĂŝŶ ĂůůŽŽŶ ŶŐŝŽƉůĂƐƚǇ ;WͿ͘ ZĞǀŝƐĞĚ ƉĞƌ ƉƌŽƚŽĐŽů ĂŶĂůǇƐŝƐ ƐĞƚ ŵĞĞƚƐ ƚŚĞ ĐƌŝƚĞƌŝĂ ŽĨ ƚŚĞ ƉƌŽƉŽƐĞĚ /Ŷ Ͳ ^ƚĞŶƚ ZĞƐƚĞŶŽƐŝƐ / ƐƚƵĚǇ ƉŽƉƵůĂƚŝŽŶ͘ Randomized Study Arm to Support Regulatory Approval: Single - Layer Coronary ISR Non - Randomized Study Arm: Double - Layer Coronary ISR Study Objective Provide additional clinical data in support of use in double - layer Coronary ISR without confounding TLF performance results in single - layer Coronary ISR
ϮϬϮϯ Ͳ ŶƚŝĐŝƉĂƚĞĚ DŝůĞƐƚŽŶĞƐ Virtue SAB – Coronary ISR sŝƌƚƵĞ /^Z Ͳ h^ & / ƉƉƌŽǀĂů ϭ Ɛƚ Wƚ͘ ŶƌŽůůŵĞŶƚ H1 2023 , Ϯ ϮϬϮϯ 21 BackBeat CNT – HTN + Pacemaker • FDA IDE Approval • 1 st Pt. Enrollment Ed Ͳ ,& ĐƵƚĞ ůŝŶŝĐĂů ZĞƐƵůƚƐ sŝƌƚƵĞ ^ ʹ ŽƌŽŶĂƌǇ /^Z :ĂƉĂŶ WD dE ƉƉƌŽǀĂů ϭ sŝƌƚƵĞ ^ ʹ ŽƌŽŶĂƌǇ ^s :ĂƉĂŶ WD dE ƉƉƌŽǀĂů ϭ ^ŝƌŽůŝŵƵƐ&Z WƌĞĐůŝŶŝĐĂů &ĞĂƐŝďŝůŝƚǇ ZĞƐƵůƚƐ Ϯ 1 Timing estimated and subject to Terumo execution since Terumo controls development of Virtue SAB for SV indication and for ISR in Japan 2 Assumes focus on a device/drug combination balloon - based solution targeting indication such as urethral strictures or BPH ĂĐŬĞĂƚ Ed ͬ Ed Ͳ ,& sŝƌƚƵĞ ^ ^ŝƌŽůŝŵƵƐ&Z
22 dǁŽ WƌŽŐƌĂŵƐ dĂƌŐĞƚŝŶŐ >ĂƌŐĞ DĂƌŬĞƚƐ ^ƵƉƉŽƌƚĞĚ ďǇ WƌŽŵŝƐŝŶŐ dƌŝĂů ĂƚĂ ŶƚĞƌŝŶŐ WŝǀŽƚĂů dƌŝĂůƐ – BackBeat CNT Ρ • >$10 billion annual market • Randomized, controlled study shows efficacy potential • Collaboration with – Virtue® SAB • ∼ $3 billion annual market • 3 - year pilot study results show potential safety & efficacy • Partnered with Strong Balance Sheet and Committed Strategic and Financial Investors Bringing Medical Inn vations to Life Through Partnerships WĂƌƚŶĞƌƐŚŝƉ Ͳ ŶĂďůĞĚ ƵƐŝŶĞƐƐ DŽĚĞů Θ ĐĐŽŵƉůŝƐŚĞĚ >ĞĂĚĞƌƐŚŝƉ dĞĂŵ – Designed to accelerate innovation to patients, enable pipeline expansion and drive strong partner and shareholder value ± ,ŝŐŚůǇ ĞǆƉĞƌŝĞŶĐĞĚ ƚĞĂŵ ǁŝƚŚ ƉƌŽǀĞŶ ƚƌĂĐŬ ƌĞĐŽƌĚ ŽĨ ŝŶŶŽǀĂƚŝŽŶ ĂŶĚ ĞǆĞĐƵƚŝŽŶ
Partnership - Enabled Business Model Ϯϯ
Significant Barriers Prevent Innovation From Reaching Patients 24 Startups often struggle for resources to reach commercial value inflection >ĂƌŐĞ ĐŽŵƉĂŶŝĞƐ ͛ ĐŽŶƐƚƌĂŝŶĞĚ ZΘ ďƵĚŐĞƚƐ ůŝŵŝƚ ŝŶŶŽǀĂƚŝŽŶ Θ ĂĐƋƵŝƐŝƚŝŽŶƐ Increasing burden of cost, time, and work to bring medical innovation to patients Product Development ŽŵŵĞƌĐŝĂůŝǌĂƚŝŽŶ 1 Pitchbook – Analysis of 430 companies since 2015 that completed at least Series B financing 2 SVB Healthcare Report 2019 3 Capital IQ ǀŐ Ψ ϲϬ D ĨƵŶĚŝŶŐ ŶĞĞĚĞĚ͕ ϴϱ й ŽĨ ĂĐƋƵŝƐŝƚŝŽŶƐ ƌĞƋƵŝƌĞĚ ĐŽŵŵĞƌĐŝĂů ƚƌĂĐƚŝŽŶ ϭ Avg 7% of revenue spent on R&D by top 20 med device vs. 20% in pharma 2,3
Orchestra BioMed Can Accelerate Innovation to Patients 25 ZŝƐŬ Ͳ ZĞǁĂƌĚ ^ŚĂƌŝŶŐ WĂƌƚŶĞƌƐŚŝƉƐ ĂŶ KǀĞƌĐŽŵĞ ƚŚĞ ĂƌƌŝĞƌƐ ƚŽ /ŶŶŽǀĂƚŝŽŶ
26 ^ĞůĞĐƚŝŶŐ KƉƚŝŵĂů KƉƉŽƌƚƵŶŝƚŝĞƐ Develop for Partnership WƌĞ Ͳ ƉĂƌƚŶĞƌĞĚ ĐƋƵŝƐŝƚŝŽŶƐ Key Pipeline Criteria Large Market with Unmet Needs Large market, significant unmet needs, established distribution channels Potential for High Impact Designed to improve standard of care, fit existing treatment paradigm, disrupt market dynamics Favorable for Partnering Significant differentiation, attractive economics for partnership, durable IP protection Innovation Royalty - based R&D Programs
Orchestrating Inn ǀĂƚŝŽŶ 27 ƌĞĂƚĞĚ WŝƉĞůŝŶĞ͕ WŝŽŶĞĞƌĞĚ ƵƐŝŶĞƐƐ DŽĚĞů ĂŶĚ ƐƚĂďůŝƐŚĞĚ WĂƌƚŶĞƌƐŚŝƉƐ Combined, our leadership team has zĞĂƌƐ ŽĨ ĞǆƉĞƌŝĞŶĐĞ Average years of experience each New product approvals/clearances Authored patents ϮϱϬ н 25 ϭϬϬ н 600+ ĐĐŽŵƉůŝƐŚĞĚ >ĞĂĚĞƌƐŚŝƉ dĞĂŵ