UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of report (Date of earliest event reported): January 11, 2021
Bellerophon Therapeutics, Inc. | ||
(Exact Name of Registrant as Specified in Charter)
| Delaware | 001-36845 | 47-3116175 | ||||||
| (State or Other Jurisdiction of Incorporation) | (Commission File Number) | (IRS Employer Identification No.) | ||||||
184 Liberty Corner Road, Suite 302 Warren, New Jersey | 7059 | ||||
| (Address of Principal Executive Offices) | (Zip Code) | ||||
Registrant’s telephone number, including area code: (908) 574-4770
| (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 (see General Instruction A.2. below):
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
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).
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) | Name of each exchange on which registered | ||||||
| Common Stock, $0.01 par value per share | BLPH | The Nasdaq Capital Market | ||||||
| o | Emerging growth company | |||||||
| o | 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.
Bellerophon Therapeutics, Inc. has prepared an investor presentation to be presented to members of the investment community, a copy which is attached to this Current Report on Form 8-K as Exhibit 99.1.
In accordance with General Instruction B.2 on Form 8-K, the information set forth in this Item 7.01 and the investor presentation attached to this report as Exhibit 99.1 is “furnished” and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section, nor shall such information be deemed incorporated by reference in any filing under the Securities Exchange Act of 1934, as amended, or the Securities Act of 1933, as amended.
The investor presentation attached hereto as Exhibit 99.1 contains certain statements that may be deemed to be “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. In some cases, these forward-looking statements can be identified by the use of forward-looking terminology, including the terms “believes,” “estimates,” “continues,” “contemplates,” “potential,” “predicts,” “projects,” “targets,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “approximately” or, in each case, their negative or other variations thereon or comparable terminology, although not all forward-looking statements contain these words.
By their nature, forward-looking statements involve risks and uncertainties because they relate to events, competitive dynamics, and healthcare, regulatory and scientific developments and depend on the economic circumstances that may or may not occur in the future or may occur on longer or shorter timelines than anticipated. Although we believe that we have a reasonable basis for each forward-looking statement contained in the presentation, we caution you that forward-looking statements are not guarantees of future performance and that our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate may differ materially from the forward-looking statements contained in the presentation as a result of, among other factors, the factors referenced in the “Risk Factors” section of our Annual Report on Form 10-K filed with the Securities and Exchange Commission on April 6. 2020, and the “Risk Factors” sections of our Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission on May 11, 2020, August 5, 2020 and November 5, 2020, respectively. In addition, even if our results of operations, financial condition and liquidity, and the development of the industry in which we operate are consistent with the forward-looking statements contained in the presentation, they may not be predictive of results or developments in future periods. Any forward-looking statements that we make in the presentation speak only as of the date of such statement, and we undertake no obligation to update such statements to reflect events or circumstances after the date of the presentation, except as required by law.
You should read carefully our “Cautionary Note Regarding Forward-Looking Statements” and the factors described in the “Risk Factors” sections of our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q to better understand the risks and uncertainties inherent in our business.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits:
Exhibit No. | Description | |||||||
2
SIGNATURES
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.
| BELLEROPHON THERAPEUTICS, INC. | ||||||||||||||||||||
| Date: January 11, 2021 | By: | /s/ Fabian Tenenbaum | ||||||||||||||||||
| Name: Fabian Tenenbaum Title: Chief Executive Officer | ||||||||||||||||||||
3
2021 Company Presentation I Company Presentation I January 2021 Bellerophon Therapeutics
2021 Company Presentation I 2 This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make due to a number of important factors, including risks and uncertainties relating to: INOpulse® not proving to be an effective treatment for COVID-19 or approved for marketing by the FDA, the timing and outcomes of our ongoing and expected clinical trials for our product candidates; our ability to successfully develop, commercialize and market any of our product candidates; our ability to obtain, maintain and enforce intellectual property rights; competition; our reliance on third parties; our ability to obtain necessary financing; and those risk factors discussed in the “Risk Factors” section and elsewhere in our most recent Form 10-K and other periodic filings we make with the SEC. All forward-looking statements contained in this presentation reflect our current views with respect to future events. We assume no obligation, except as required by applicable law, to update any forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Forward Looking Statements
2021 Company Presentation I • Focused on developing inhaled nitric oxide (iNO) based therapies for management of serious cardiopulmonary and infectious diseases • Portable, lightweight delivery system (INOpulse®) allows for chronic home use • Simplified regulatory approval pathway via existing nitric oxide NDA • Company spun-off from Ikaria Clinical-Stage Biotherapeutics Company 3 Bellerophon Therapeutics (BLPH) Company Profile • Multiple late stage programs in respiratory diseases including fibrotic ILD, and pulmonary hypertension • Novel targeted vasodilation provides potential for first approved therapy in multiple indications Novel Therapy Addressing Unmet Medical Needs • Cash & Equivalents: $54.0 M(1) • No Debt(1) • Fully Diluted Shares Outstanding = 12.2 million Financial Summary 1. As of September 30, 2020
2021 Company Presentation I Jonathan Peacock Chairman 10 years experience as CFO at Amgen and Novartis Pharma Fabian Tenenbaum Chief Executive Officer 15 years of executive-level experience in finance, BD and operations Wassim Fares, M.D., MSc Chief Medical Officer 20 years experience in clinical research specializing in cardio-pulmonary diseases Peter Fernandes Chief Regulatory & Safety Officer 25 years experience in global regulatory affairs specializing in respiratory products Assaf Korner Chief Financial Officer 18 years of financial experience in medical device and life science companies Parag Shah, Ph.D. VP, Business Operations 15 years experience in pharmaceutical product development Amy Edmonds VP, Clinical Operations & Administration 20 years experience global clinical operations and training Martin Dekker VP, Device Engineering & Manufacturing 17 years experience in new product development and launch 4 Highly Experienced Leadership Team
2021 Company Presentation I PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 NDA Key Milestones fILD Fibrotic Interstitial Lung Disease at risk of Pulmonary Hypertension Phase 2 Hemodynamic Trial Completed Positive results in Feb 2020 Phase 2 Chronic Trial Complete Positive Cohort 1 results in Jan 2019 Positive Cohort 2 results in Dec 2019 Phase 3 REBUILD Trial First patient enrolled in November 2020 PH-COPD/SARC Pulmonary Hypertension associated with COPD/SARC PH-SARC Phase 2 hemodynamic results expected 2021 PH-COPD Multiple Phase 2 studies completed Phase 2b trial design finalized COVID-19 COVID-19 & Infectious Lung Diseases COVID-19 180 patients treated via EAP Phase 3 COViNOX trial initiated in July 2020; trial halted based on interim analysis 5 Development Pipeline
2021 Company Presentation I Nitric Oxide Portable pulsatile iNO delivery system Novel drug-device combination therapy with multiple mechanisms of action Well-established vasodilator approved for acute treatment of persistent pulmonary hypertension in hospitals Proprietary algorithm ensures accurate dosing independent of patient’s breath rate and tidal volume Targeted pulmonary vasodilation Ventilation/Perfusion (V/Q) matching Improved oxygen saturation Antiviral potential Broad spectrum antiviral that plays a key role in viral replication Portable stand-alone system allows for out-patient treatment 6 INOpulse Delivery System Overview Portable Delivery System Allows Chronic iNO Therapy Wound Healing Promotor Antifungal Antiviral Antibacterial Immuno-modulator Vasodilator NO
2021 Company Presentation I 7 INOpulse Delivery System Lightweight, Portable and User Friendly Alarm Cannula Key & ConnectorDrug & Battery Indicators Power Oxygen Sources Easy engagement with drug cartridge Intuitive and simple user interface Tri-lumen cannula allows direct connection with oxygen Lightweight portable design allows ease of transport 01 02 03 04
2021 Company Presentation I 8 INOpulse Provides a Unique and Differentiating Mechanism of Action Baseline Hypoxic pulmonary vasoconstriction prevents oxygen desaturation Systemic Vasodilators Systemic vasodilators can reverse hypoxic vasoconstriction leading to ventilation/perfusion (V/Q) mismatch and arterial O2 desaturation INOpulse Providing iNO early in the inspiratory phase allows for targeted vasodilation of only the well ventilated alveoli thereby preventing V/Q mismatch and O2 desaturation
2021 Company Presentation I 9 Fibrotic Interstitial Lung Disease (fILD) A Significant Unmet Medical Need Normal IPF • Fibrotic Interstitial Lung Disease (fILD) is a broad category of diffuse lung diseases characterized by variable amounts of inflammation and fibrosis • Idiopathic Pulmonary Fibrosis (IPF) is the largest and most serious of these diseases • Patients with fILD have thickening and scarring of the air sacs in the lungs, and often require supplemental oxygen to maintain adequate oxygen saturation
2021 Company Presentation I 10 Pulmonary Hypertension (PH) associated with fILD Significantly Reduces Survival Pulmonary Hypertension as Predictor of Survival in IPF • Approximately 40% of IPF patients exhibit symptoms of pulmonary hypertension at rest • Prognosis and survival are significantly worse for patients with pulmonary hypertension • PH-IPF associated with 3-fold increase in risk of death compared to IPF alone • No approved therapy for treating PH in these patients • INOpulse has the potential to provide targeted vasodilation while avoiding concerns of V/Q mismatch which have prevented current PAH systemic vasodilators to be approved for this unmet medical need Rivera-Lebron, Advances in Pulmonary Hypertension, 2013
2021 Company Presentation I Source: LEK report (2018) 11 fILD Market Opportunity in the US 0 500 1,000 1,500 2,000 2,500 3,000 2017 2022E IPF branded drug sales (2017) Millions of USD ~3,000 Estimated Penetration: ~24,000 in US Based on: LTOT penetration of 70-75% Physician adoption rate of 35-60% PH-fILD: ~84,000 in US Estimated patient population with PH at rest (35-40%) Represents intermediate/high risk of PH by echo fILD Patient Population: ~226,000 in US Patients would be eligible for INOpulse therapy regardless of verified PH ~44% are IPF (~100,000 in US) 2,100 KOL feedback supports high unmet medical need in fILD Pricing assessment supported by current IPF and PAH therapies priced at $100-200k/year $2B+ US Market Opportunity ~2,100
2021 Company Presentation I Targeted Vasodilation Ventilation/Vasodilation Matching 12 Phase 2: INOpulse Demonstrates Targeted Vasodilation in fILD Acute Phase Data Showed Immediate Benefit of INOpulse on Vasodilation and Hemodynamics • Significant correlation between ventilation and vasodilation, demonstrating selective vasodilation to better ventilated areas of the lung (p=0.009) • Consistent and clinically meaningful reduction of 14% in systolic pulmonary arterial pressure (sPAP) • Clinically meaningful improvement oxygen desaturation of 28.5% and SpO2 nadir of 5.5%
2021 Company Presentation I 13 Phase 2: INOpulse Demonstrates Acute Hemodynamic Benefit in fILD Clinically and statistically meaningful cardiopulmonary improvement on iNO30 w/ cont. benefit on dose escalation Pulmonary hemodynamics measured via right heart catheterization at baseline and following each sequential iNO dose p=0.02 p=0.03 p=0.01 mean Pulmonary Arterial Pressure (mPAP) Baseline mPAP: 34.7 mmHg Average reduction of 4 mmHg p<0.01 p<0.01 p=0.01 p<0.01 Pulmonary Vascular Resistance (PVR) Baseline PVR: 583 dyne×sec/cm5 Average reduction of 125 dyne×sec/cm5 • p-value based on Wilcoxon Rank Test • Bar graphs are median values at each assessment for all available study participants • Oxygen saturation remained stable and iNO was well-tolerated with no safety concerns across doses • Data based on 9 fILD study participants
2021 Company Presentation I Continuous Monitoring of Physical Activity Study participant wears actigraphy monitor on non- dominant arm Monitor continuously measures movement in acceleration units Movement is Categorized into Activity Intensity Levels Activity Intensity Example activities Sedentary (<100 counts/min) (< 1.5 METs) • Lying • Sitting • Computer work Light (100 -1951 counts/min) (1.6 - 3.0 METs) • Getting dressed • Bathing/showering • Light house cleaning Moderate (1952-5724 counts/min) (3.1 - 6.0 METs) • Walking • Ascending/descending stairs • Housework/yardwork Vigorous (>5724 counts/min) (> 6.0 METs) • Slow/fast running • Intense sport 14 Provides Profile of Daily Activity Study participants spend 74 minutes per day in moderate physical activity Study participants are unable to achieve vigorous activity levels MVPA is the sum of moderate and vigorous activity Continuous Physical Activity Monitoring (Actigraphy) Allows Objective Assessment of Daily Physical Activity
2021 Company Presentation I 15 Phase 2 Results Suggest Clinically Meaningful Benefit in MVPA (moderate to vigorous physical activity) • Study participants on INOpulse (iNO30 and iNO45) maintain activity levels while study participants on placebo deteriorate across activity parameters • Study participants on iNO45 maintain PRO scores (UCSD & SGRQ) while study participants on placebo deteriorate consistent with changes in activity levels • Physical activity levels maintained during open label extension with study participants transitioning from placebo to active demonstrating reversal from decline to maintenance • INOpulse targeted delivery maintains oxygen saturation during exercise • INOpulse was generally well-tolerated with no serious adverse events Phase 2 was designed as an exploratory study to identify optimal endpoints to progress into pivotal Phase 3 trial. Key findings include:
2021 Company Presentation I 16 Cohort 1 (n=41) iNO 30 n=23 Placebo n=18 Age – years (mean, SD) 68.6 (6.45) 65.8 (13.73) Male (n, %) 16 (69.6%) 13 (72.2%) Intermediate to High Probability of PH (n, %) 15 (65.2%) 14 (77.8%) Baseline DLCO – % predicted (mean, SD) 30.7 (11.4) 30.4 (10.2) Baseline FVC – % predicted (mean, SD) 56.3 (10.2) 59.9 (18.4) Cohort 2 (n=44) iNO 45 n=30 Placebo n=14 68.9 (9.95) 71.4 (5.14) 15 (50.0%) 10 (71.4%) 18 (60.0%) 9 (64.3%) 35.7 (14.2) 35.3 (7.9) 59.7 (15.9) 60.5 (15.1) Phase 2 Patient Demographics
2021 Company Presentation I 17 Analysis based on MMRM model to estimate therapeutic benefit through treatment period based on all available data as planned for pivotal Phase 3 study 20% benefit after 4 months of treatment p=0.02 Overall ActivityMVPA 7% benefit after 4 months of treatment Longitudinal Analysis Benefit on iNO in MVPA and Overall Activity • MMRM model based on change from Week 1 or Month 1; no baseline covariate • Data log-transformed for normality • Month 2 data based on pooled placebo and weeks 4-8 • Month 4 data based on months 2-4
2021 Company Presentation I 18 Study participants on INOpulse maintain activity levels while study participants on placebo deteriorate Study participants on INOpulse demonstrate 7.5 min/day (~10%) benefit over placebo after 2 months of treatment p=0.02 MVPA Month 4MVPA Month 2 Benefit increases to 14 min/day (~20%) after 4 months of treatment Benefit Observed in MVPA at Month 4 on iNO45 • p-value based on t-test on available data (exploratory endpoint; post-hoc analysis not adjusted for multiplicity) • Data points and error bars = mean and standard error • Month 2 analysis based on change from Week 1 to Week 8 and pooled placebo • Month 4 analysis based on change from Month 1 to Month 4 p=0.02
2021 Company Presentation I 19 Continued Benefit for Study Participants on Open Label Extension (OLE) Study participants transitioning from placebo to active demonstrate trend reversal from deterioration to maintenance • MVPA = moderate to vigorous physical activity • Change is based on Cohort 1 study participants with available data during blinded treatment and open label treatment (average 27 weeks of OLE) on all active doses Overall ActivityMVPA
2021 Company Presentation I 20 • Placebo corrected improvement of 4 points • Measures shortness of breath while study participants perform daily physical activity Increased score indicative of worsening UCSD SOBQ iNO45: UCSD Shortness of Breath Questionnaire (SOBQ) Indicates Benefit in Dyspnea • Data points and error bars = LS Mean and Standard Error • Longitudinal MMRM model includes baseline as covariate
2021 Company Presentation I 21 • Placebo corrected improvement of 6 points • Measures psychological and social impact of the disease • Placebo corrected improvement of 6 points • Measures disturbances to study participants’ daily physical activity • Placebo corrected improvement of 4 points • Measures health status and quality of life Increased score indicative of worsening SGRQ Total SGRQ Activity SGRQ Impacts iNO45: St. George’s Respiratory Questionnaire (SGRQ) Indicates QOL Benefit in Multiple Measures • Data points and error bars = LS Mean and Standard Error • Longitudinal MMRM model includes baseline as covariate
2021 Company Presentation I 22 Phase 2 Safety Summary INOpulse was well-tolerated in Cohort 1 and Cohort 2 Cohort 1 (8 weeks) iNO 30 n=23 Placebo n=18 Study participants with Adverse Events 19 (82.6%) 15 (83.3%) Study participants with Serious Adverse Events 2 (8.7%) 2 (11.1%) Total Serious Adverse Events Reported 3 (0.13/study participant) 4 (0.22/study participant) Deaths 1 (4.3%) 0 • Incidence of SAEs was low in both active and placebo groups and all reported as unrelated to study drug • AEs were balanced and generally non-serious with no observable trends Cohort 2 (16 weeks) iNO 45 n=30 Placebo n=14 26 (86.7%) 9 (64.3%) 3 (10.0%) 3 (21.4%) 4 (0.14/study participant) 7 (0.5/study participant) 0 0
2021 Company Presentation I PHASE 2 PHASE 3 23 Double-blind placebo-controlled study will assess study participants with fibrotic interstitial lung disease at risk of associated pulmonary hypertension • Phase 2 Complete: Cohorts 1 and 2 suggest improvement in MVPA supported by other activity parameters and patient reported outcomes (Cohort 2) • Phase 3: Pivotal REBUILD initiated with first patient enrolled in November 2020 Complete Cohort 1 study participants continue on open label extension Complete Pivotal Phase 3 Trial Cohort 1: n=41 iNO30 vs placebo (1:1) 2-month blinded treatment Cohort 2: n=44 iNO45 vs placebo (2:1) 4-month blinded treatment REBUILD Trial: n=300 iNO45 vs placebo (1:1) 4-month blinded treatment Cohort 2 study participants continue on open label extension FDA agreement on pivotal Phase 3 REBUILD study with MVPA as primary endpoint Phase 2 Results Allow Immediate Transition into Pivotal Phase 3 Trial
2021 Company Presentation I An Orphan Unmet Medical Need Pulmonary Hypertension associated with Sarcoidosis (PH-Sarc) 24 Patients with associated PH have significantly reduced survival 1-year survival 3-year survival 5-year survival PH-Sarc 84% 74% 59% Sarc 100% 96% 96% Sarcoidosis is characterized by the growth of inflammatory cells (granulomas) most commonly in the lungs or lymphatic tissues Prevalence of sarcoidosis is estimated at 200,000 in the US with up to 30% with associated pulmonary hypertension Chest x-ray & CT of patient with PH-Sarc
2021 Company Presentation I 25 INOpulse MoA has the Potential to Provide Benefit to PH-Sarc Patients Inhaled nitric oxide has been shown to improve hemodynamics and exercise capacity in PH-Sarc Preston et al., Chest, 2001 Chronic Benefit on Exercise Capacity Acute Hemodynamic Benefit on iNO Parameter % Change mPAP -18 ± 4 PVR -31 ± 5 CO 12 ± 4 Systemic vasodilators exacerbate hypoxic vasoconstriction and cause hypoxemia No approved therapy for treating PH in these patients Phase 2 study designed to verify hemodynamic effect of INOpulse in PH-Sarc • Acute dose escalation study with right heart catheterization • Primary endpoint: change in mean PAP, PCWP, cardiac output and PVR • Study results expected in 2021
2021 Company Presentation I Andersen KH et al. Prevalence, Predictors and Survival in Pulmonary Hypertension Related to End-stage Chronic Obstructive Pulmonary Disease. Journal of Heart and Lung Transplantation 2012; 31: 373-380. 26 • Typically associated with smoking or exposure to other pollutants • Obstruction of the bronchioles and alveoli reduces the ability to get oxygen and ultimately leads to hypoxemia • Hypoxemia and inflammation contribute to development pulmonary hypertension mPAP < 25 mmHg mPAP ≥ 25 mmHg Survival years 5 Year Survival mPAP < 25 mmHg: 63% mPAP ≥ 25 mmHg: 37% Pulmonary Hypertension associated with Chronic Obstructive Pulmonary Disease (PH-COPD) Represents Large Unmet Medical Need COPD is a group of lung diseases characterized by progressive airflow obstruction and chronic airway inflammation Pulmonary hypertension predicts survival in COPD No approved therapy for treating PH in these patients
2021 Company Presentation I Haijan et al., Int J of COPD, 2016 27 p<0.05* p<0.05* p<0.05* Change in 6MWD sPAP *Statistically significant compared to baseline Study participants completing 4 weeks on iNO 30 demonstrated: • Statistically significant increase in 6MWD at 2 weeks and 4 weeks (+50.7m) • Statistically and clinically significant decrease in sPAP at 4 weeks (-12.0 mmHg; 19.9% reduction) • sPAP increased to near baseline upon stopping treatment with iNO INOpulse targets delivery to well ventilated pulmonary vessels Chronic treatment with INOpulse provides statistically significant improvement in 6MWD and hemodynamics INOpulse Provides Targeted Delivery and Improves Hemodynamics and Exercise Capacity in PH-COPD Patients
2021 Company Presentation I 28 INOpulse for the Treatment of COVID-19 FDA granted emergency expanded access for pulsatile inhaled nitric oxide for treating COVID-19 • 180 patients treated at 18 hospitals across the US under emergency expanded access • Preliminary data demonstrated recovery rate of 73.0% and mortality rate of 6.3% at day 14 from treatment initiation • INOpulse was well-tolerated with no safety concerns related to the therapy COViNOX: Phase 3 randomized, placebo-controlled study initiated in July 2020 Independent data monitoring committee has completed pre-specified interim analysis based on first 100 patients • Interim Analysis: Study halted based on assessment of a single endpoint of respiratory failure or mortality; low event rate (10 total events) resulted in limited sample size for analysis • Next Steps: Completion of study procedures for remaining subjects and evaluation of full data set for all randomized subjects (close to 200); full data set includes multiple additional clinically important endpoints (e.g. change in clinical status, duration of hospitalization, etc.)
2021 Company Presentation I 29 INOpulse Intellectual Property Protection Orphan Drug designation for IPF provides exclusivity for 7 years (US) and up to 10 years (EU) Patent Status Expiration Description Method of NO administration US/EU: Issued Other Territories: Issued/Pending Jan 2027 Covers consistent delivery of prescribed dose independent of respiratory rate Breath Skipping & Pulse Volume Variation US: Issued Sept 2025 Covers skipping breaths or modifying pulse volume to ensure consistent dose independent of respiratory rate Method of Administering High Concentration NO US/EU: Pending Other Territories: Pending Mar 2033 Limits delivery rate of high concentration iNO to prevent safety concerns Optimized Pulse Shape US: Pending Oct 2035 Covers key parameters of pulse shape INOpulse Design US: Issued Apr 2028 Covers design of the INOpulse device Tip Purge US: Issued EU/Other Territories: Pending Apr 2033 Covers the use tip purge to ensure purity of iNO within the cannula Triple-Lumen Cannula US/ EU: Issued Other Territories: Pending Dec 2033 Covers accurate dose delivery and reduced NO2 formation Index valve US/EU: Issued Other Territories: Issued/Pending May 2029 Ensures other cartridges cannot be used with INOpulse Multiple provisional patent applications filed from 2017-2019 that can extend patent coverage into 2039
2021 Company Presentation I 1. As of September 30, 2020 30 Financial Summary Amount (in millions) Cash and Cash Equivalents $54.0 (1) Restricted Cash $0.4(1) Debt $0(1) Fully Diluted Shares Outstanding 12.2
2021 Company Presentation I Established iNO Therapeutic Benefit • Approved for acute treatment of persistent pulmonary hypertension in neonates • Positive results from multiple Phase 2 studies support INOpulse MoA and benefit Advanced Clinical Stage Product INOpulse technology focused on several large unmet orphan indications fILD PH-SARC / PH-COPD COVID-19 / Infectious Lung Diseases Successful Phase 2 Proof of Concept studies in fILD PH-Sarc: Phase 2 results expected in 2021 180 patients treated with INOpulse under expanded access Positive Phase 2 results for Cohorts 1 and 2 PH-COPD: Successful Phase 2 study completed FDA cleared Phase 3 placebo-controlled registrational study Pivotal Phase 3 REBUILD study initiated in 4Q 2020 with FDA agreement on primary endpoint PH-COPD: Phase 2b study design finalized in agreement w/ FDA Phase 3 COViNOX study initiated in July 2020; trial halted based on interim analysis Proprietary INOpulse Technology Strong IP protection on core programs through 2033 and ability to extend coverage into 2039 31 Investment Highlights
2021 Company Presentation I Investor Contacts Fabian Tenenbaum Chief Executive Officer BTInvestorRelations@bellerophon.com Brian Ritchie LifeSci Advisors britchie@lifesciadvisors.com 212-915-2578