Company Presentation I January 2022Bellerophon Therapeutics

Bellerophon Therapeutics Overview | January 20222 Forward Looking StatementsThispresentationcontainsforward-lookingstatementsthatinvolvesubstantialrisksanduncertainties.Allstatements,otherthanstatementsofhistoricalfacts,containedinthispresentation,includingstatementsregardingourstrategy,futureoperations,futurefinancialposition,futurerevenues,projectedcosts,prospects,plansandobjectivesofmanagement,areforward-lookingstatements.Thewordsanticipate,believe,estimate,expect,intend,may,plan,predict,project,target,potential,will,would,could,should,continue,andsimilarexpressionsareintendedtoidentifyforward-lookingstatements,althoughnotallforward-lookingstatementscontaintheseidentifyingwords.Wemaynotactuallyachievetheplans,intentionsorexpectationsdisclosedinourforward-lookingstatements,andyoushouldnotplaceunduerelianceonourforward-lookingstatements.Actualresultsoreventscoulddiffermateriallyfromtheplans,intentionsandexpectationsdisclosedintheforward-lookingstatementswemakeduetoanumberofimportantfactors,includingrisksanduncertaintiesrelatingto:INOpulsenotprovingtobeaneffectivetreatmentforCOVID-19orapprovedformarketingbytheFDA,thetimingandoutcomesofourongoingandexpectedclinicaltrialsforourproductcandidates;ourabilitytosuccessfullydevelop,commercializeandmarketanyofourproductcandidates;ourabilitytoobtain,maintainandenforceintellectualpropertyrights;competition;ourrelianceonthirdparties;ourabilitytoobtainnecessaryfinancing;andthoseriskfactorsdiscussedintheRiskFactorssectionandelsewhereinourmostrecentForm10-KandotherperiodicfilingswemakewiththeSEC.Allforward-lookingstatementscontainedinthispresentationreflectourcurrentviewswithrespecttofutureevents.Weassumenoobligation,exceptasrequiredbyapplicablelaw,toupdateanyforward-lookingstatementspublicly,ortoupdatethereasonswhyactualresultscoulddiffermateriallyfromthoseanticipatedintheforward-lookingstatements,evenifnewinformationbecomesavailableinthefuture.

Bellerophon Therapeutics Overview | January 20223 Bellerophon Therapeutics (BLPH)1. As of Sept 30, 2021; 2. Fully diluted Late-stage biotherapeutics company developing inhaled nitric oxide (iNO) therapies to address significant unmet need in serious cardiopulmonary disordersINOpulse inhaled nitric oxide (iNO) for chronic use‒Targeted, pulsatile NO delivered via proprietary, portable, user-friendly device‒Inhalational delivery to well ventilated areas of the lung overcomes drawbacks of systemic vasodilators‒Positive results from multiple Phase 2 studies support mechanism of actionBroad market opportunity in multiple cardiopulmonary disorders‒Fibrotic interstitial lung disease (fILD) represents a broad underserved population >200K patients‒Potential $1Bn+ markets in follow-on indications of pulmonary hypertension (PH) associated with sarcoidosis & chronic obstructive pulmonary disease (COPD) ‒IP protection up to 2039 before extensionsSimplified de-risked regulatory pathway ‒NO approved for use in neonates (Ikaria); ability to leverage existing NDA‒FDA agreement on MVPA primary endpoint in fILDPhase 3 REBUILD trialHighly experienced leadership team and solid financials‒Unrestricted cash & equivalents $28.7 M1; no debt1; 12.1 million shares outstanding1,2

Bellerophon Therapeutics Overview | January 20224 Highly Experienced Leadership Team with Expertise in Respiratory & Rare DiseasesMartin DekkerVP, Device Engineering & ManufacturingNaseem Amin, M.D.Chairman of the Board of DirectorsNicholas LacconaPrincipal Financial & Accounting Officer Peter FernandesPrincipal Executive Officer; Chief Regulatory & Safety OfficerParag Shah, Ph.D.VP, Business Operations Edwin Parsley, D.O.Acting Chief Medical Officer

Bellerophon Therapeutics Overview | January 20225 INOpulsedevelopment pipelineAddressing Unmet Needs in Multiple Cardiopulmonary Diseases IndicationPhase 1Phase 2Phase 3Current StatusfILDFibrotic InterstitialLung Disease at risk of Pulmonary HypertensionREBUILD trial recruitingUnderpinned by positive Phase 2 acute hemodynamic trial (2020) & Phase 2 chronic trial (2019)PH-SARCPulmonary Hypertension associated with SarcoidosisAcute hemodynamic study completedPositive study results reported end-2021Phase 2 chronic use trial to be designedPH-COPDPulmonary Hypertension associated with COPDPhase 2b readyMultiple phase 2 studies completedPhase 2b trial design finalized

Bellerophon Therapeutics Overview | January 20226 Portable Delivery System Allows Chronic iNO TherapyNitric Oxide is a well-established vasodilator being developed for ambulatory setting1. SoRelle, R.; Circulation, 1998, 2365-2366; 2. Furchgott, Ignarro, Murad 1998 Nobel Prize in Physiology or Medicine 1998; 3. Subject was enrolled in PAH201 study in 2012 and transitioned to INOpulse Delivery System in 2016.Nitric OxideMolecule of the Year 19921Nobel Prize for discovering itssignaling role2Approved for use in 1999 for persistent pulmonary hypertension in neonatesContinuous flow iNOdelivery system for acute administrationCommercially established for 20+ yearsPortable pulsatile iNOdelivery system for use in chronic in-home setting376 patients treated to date in PH trials; average duration of ~10 months eachAdditional 368 patients treated as part of COVID-19 related clinical trialCumulative subject exposure 300+ years; longest subject treatment 8+ years3Hospital based acute therapyAmbulatory chronic therapy NO

Bellerophon Therapeutics Overview | January 20227 Significant quality improvements achieved following introduction in 2016INOpulse Delivery System performance in clinical trial setting95% improvement achieved in 2021 compared to 2016 across the INOpulse Device, Cannula and CartridgeActive continuous improvement process ongoing; additional trend reduction expected during course of the REBUILD trial Delivery System data represents both the INOpulse Device and CannulaREBUILD patients receive:Two INOpulse Devices upon enrollmentOne INOpulse Cannula for every two weeks of useOne re-fillable INOpulse Cartridge per day of use

Bellerophon Therapeutics Overview | January 20228 Preventing Ventilation/Perfusion Mismatch is Critical in PH BaselineGeneralized vasodilation Reverses protective hypoxic vasoconstriction responseResults in ventilation / perfusion (V/Q) mismatch and worsened systemic oxygenationTargeted vasodilation of only well ventilatedalveoliSynergistic with hypoxic vasoconstriction responsePrevents V/Q mismatch, improves systemic oxygenation, improves PHSignificant lung disease results in alveolar hypoxiaTriggers protective hypoxic vasoconstriction responsePrevents systemic oxygen desaturation but increases pulmonary pressure resulting in PH Systemic therapies NormoxicHypoxic NormoxicHypoxic NormoxicHypoxic

Bellerophon Therapeutics Overview | January 20229 A broad category of diffuse lung diseases with significant unmet needFibrotic Interstitial Lung Disease (fILD) Normal IPFCharacterized by variable amounts of inflammation and fibrosis of lung air sacsIdiopathic Pulmonary Fibrosis (IPF) is the most commonly diagnosedand most serious fILDPatients often require supplemental oxygen (O2) to maintain O2saturationSeverely impaired quality of life and limitations on activities of daily livingPrognosis and survival significantly worse for patients with associated pulmonary hypertension (PH)

Bellerophon Therapeutics Overview | January 202210 Pulmonary Hypertension (PH) associated with fILDSignificantly Reduces SurvivalRivera-Lebron, Advances in Pulmonary Hypertension, 2013, 12:127-134; Tyvaso (inhaled Treprostinil) recently approved to improve 6MWD in PH-ILD Pulmonary Hypertension as Predictor of Survival in IPFof IPF patients exhibit PH symptoms at rest increase in risk of death with PH-IPF vs. IPF aloneapproved therapies to improve physical function or quality of life~40%3x0

Bellerophon Therapeutics Overview | January 202211 Acute Phase 2 Data Showed Immediate Benefit of INOpulse on Vasodilation and Ventilation/Perfusion MatchingINOpulse Demonstrates Targeted Vasodilation in fILDSupporting the Mechanism of ActionHaijanet al., ATS 2017, Poster Presentation Targeted vasodilation to better ventilated areas of lung Significant correlation between ventilation/vasodilation matching

Bellerophon Therapeutics Overview | January 202212 Clinically and statistically meaningful cardiopulmonary improvement on iNO30 with statistically significant benefit in PVR on dose escalation to iNO45Acute Hemodynamic Benefit in fILDSupports Continuing iNO45 in Phase 2b/3Bar graphs are median values at each assessment for all available study participants; p-value based on Wilcoxon Rank Test (no correction for multiplicity); Oxygen saturation remained stable and iNOwas well-tolerated with no safety concerns across doses; Data based on 9 fILDstudy participants Baseline PVR: 583 dynesec/cm5Average reduction of 125 dynesec/cm5p=0.01p<0.01p<0.01 p<0.01Pulmonary Vascular Resistance (PVR) Pulmonary Vascular Resistance (PVR) p=0.01p=0.02p=0.03Baseline mPAP: 34.7 mmHgAverage reduction of 4 mmHg mean Pulmonary Arterial Pressure (mPAP)Pulmonary hemodynamics measured via right heart catheterization at baseline and following each sequential iNOdose

Bellerophon Therapeutics Overview | January 202213 Exploratory trial designed to identify optimal endpoints and dose for Phase 3 trialPhase 2 Development in fILDused to Select Primary Endpoint PHASE 2Chronic studyCohort 1: n=41iNO30 vs placebo (1:1) 2-month blinded treatmentCohort 2:n=44iNO45 vs placebo (2:1) 4-month blinded treatment Complete Cohort 1 study participants continuein open label extension (OLE) Complete Cohort 2 study participants continue in open label extension (OLE)Trial assessed multiple exploratory endpoints including actigraphy (continuous monitoring of daily physical activity) and patient reported outcomesBoth cohorts supported use of MVPA (moderate to vigorous physical activity) assessed by actigraphy as the optimal endpoint to progress into Phase 3FDA acceptance of the overall study design and MVPA as the primary endpoint for the Phase 3 registration study, with the validation of the MVPA endpoint by establishing meaningful changes in in PROsfILDdiagnosed in accordance with accepted guidelines and confirmed by high resolution CT (HRCT) scan; Forced vital capacity (FVC)of ≥ 40% predicted in the 6 months prior to screening; Needing supplemental oxygen defined as desaturation to ≤ 88% at rest or with exertion

Bellerophon Therapeutics Overview | January 202214 Phase 2 data supports use of MVPA measurement as primary endpoint for Phase 3 trial14.6 min/day decline in MVPA on placebo; 2.3 min/day decline in MVPA on iNO45 at month 412.3 min/day (~21%) difference in time spent in MVPA as compared to placebo10-20% change in actigraphy parameters estimated to be clinically relevant in diseased populations (fILD, COPD, heart failure)Similar trend seen in overall activityiNO45 group remained stable~6% placebo adjusted difference (89.4 counts/min)King et al., Annals of American Thoracic Society, article in press 2021, press 2021, https://doi.org/10.1513/AnnalsATS.202107-864OC; . Rivera-Lebron, Advances in Pulmonary Hypertension, 2013, 12:127-134; IPF Voice of Patient, FDA Meeting and Report, 2015; Hur, et al, 2019; Teylanet al., Chron Respir Dis., 2019, 16:1479973118816424; Demeyeret al., PLoSOne. 2016;11:e0154587; Shoemaker MJ, World Journal of Cardiovascular Diseases; 2012., 129-35 MVPA change from baseline (min/day)12.3min/daydifference vs. placebo (p=0.03) Moderate to vigorous physical activity (MVPA; min/day) maintained on iNO45 while placebo patients deteriorateMMRM analysis based on change from Month 1 to Month 4; data points and error bars = LS mean and standard error; p-value not adjusted for multiplicityTarget patient population has a median survival of 1.5 to 2 years and typically struggle to perform basic activities such as walking up stairs, showering, housework

Bellerophon Therapeutics Overview | January 202215 Outcomes measured by UCSD Shortness Of Breath Questionnaire (SOBQ) and St. Georges Respiratory Questionnaire (SGRQ) remained stable on iNO45 vs. deterioration on placebo MVPA Results Mirrored Closely by Patient Reported Outcomes Change from baseline (points)UCSD SOBQSGRQ totalSGRQ activitySGRQ impacts WorseBetter -6.05vs. placebo-3.75vs. placebo-5.84vs. placebo-6.30vs. placeboKing et al., Annals of American Thoracic Society, article in press 2021, https://doi.org/10.1513/AnnalsATS.202107-864OC 4 5 pointchange typically considered clinically meaningful MMRM analysis based on change from Baseline to Month 4; data points and error bars = LS mean and standard error

Bellerophon Therapeutics Overview | January 202216 INOpulse was well-tolerated in Cohort 1 and Cohort 2 Phase 2 Safety SummaryIncidence of SAEs was low in both active and placebo groupsand all reported as unrelated to study drugAEs were balanced and generally non-serious with no observable trends Cohort 2 (16 weeks)iNO 45n=30Placebon=1426 (86.7%)9 (64.3%)3 (10.0%)3 (21.4%)4 (0.14/patient)7 (0.5/patient)00 Cohort 1 (8 weeks)iNO 30n=23Placebon=1819 (82.6%)15 (83.3%)2 (8.7%)2 (11.1%)3 (0.13/patient)4 (0.22/patient)1 (4.3%)0 Patients with Adverse EventsPatients with SeriousAdverse EventsTotal SeriousAdverse Events ReportedDeaths

Bellerophon Therapeutics Overview | January 202217 Data supported move to Phase 3 with MVPA as a primary endpointPhase 2 fILDKey TakeawaysObserved meaningful effects on key activity levels and patient recorded outcomes (PRO)INOpulse(iNO30 and iNO45) group maintain activity levels while placebo group deteriorates across activity parametersiNO45 group maintain PRO scores (UCSD & SGRQ) while placebo group deteriorates consistent with change in activity levelsPhysical activity levels maintained during OLE; patients switching from placebo to active demonstrated reversal in declineGenerally well-tolerated with no serious adverse events considered related to INOpulse Advanced into Phase 3 REBUILD study in fILD

Bellerophon Therapeutics Overview | January 202218 FDA agreement on study design with MVPA as the primary endpointPivotal Phase 3 Trial in fILDOpen label extensionpatients continue oniNO45 or switch from placebo to iNO45 Primary EndpointChange in MVPA assessed by ActigraphySafetyAdditional EndpointsChange in Overall Activity assessed by ActigraphyPatient Reported Outcomes (SGRQ, UCSD, PROMIS SF, PGIS/C)Time to Clinical Worsening 300patientsfILDpatients at risk for associated PH 4 months4 months 1:1 Pulsed iNO45 g/kgPlaceboFDA acceptance of the overall study design and MVPA as the primary endpoint for the Phase 3 registration study, with the validation of the MVPA endpoint established by its confirmation vs. PROs

Bellerophon Therapeutics Overview | January 202219 fILDRepresents a Significant Market Opportunity in the USand BeyondSource: LEK INOpulse Market Research Report (2018); addressable population includes PH-ILD, with the majority on LTOT (long-termoxygen therapy); physician adoption rate based on product profile prior to identifying MVPA as the primary endpoint in REBUILD Phase 3 trialAdditional growth potential in: fILDlow-risk of PHEx-US regions Pricing assessment supported by current IPF and PAH therapies ($100-200k/year) Estimated Penetration: ~24,000 in US Based on: LTOT penetration of 70-75% Physician adoption rate of 35-60% PH-fILD: ~84,000 in USEstimated patient population with PH at rest (35-40%)Represents intermediate/high risk of PH by echo fILDPatient Population: ~226,000 in USPatients would be eligible for INOpulse therapy regardless of verified PH~44% are IPF (~100,000 in US) 2,100 fILDwith intermediate/high risk of PH$2bn+US Market opportunity

Bellerophon Therapeutics Overview | January 202220 INOpulse Could Address Multiple Large Market Opportunities1. Huitema et al., NethHeart J, 2016, 24:390399; Nunes et al., Thorax, 2006, 61:6874; 2. Baughman et al., Annals ATS, 2016, 13:1244-1252; 3. Andersen KH et al. J Heart Lung Trans, 2012; 31:373-380; Oswald-Mammosseret al., Chest, 1995, 107:1193-1198; 4. Rivera-Lebron, Advances in Pulmonary Hypertension, 2013, 12:127-134LEK INOpulse Market Research Report (2018); 5. PH-COPD(COPD associated with pulmonary hypertension) COPD with PH reduces 5-year survival from 63% to 37%3 fILD(fibrotic interstitial lung disease at risk of pulmonary hypertension)PH-SARC(sarcoidosis associated with pulmonary hypertension)SARC with PH reduces 5-year survival from 96% to 59%1Significant Unmet NeedLarge Potential MarketfILDwith PH reduces 1-year survival from 28% to 5.5%5 approved therapy; no approved therapy to improve physical function or quality of life $2B+ market opportunity226,000 fILDin the US; 30-40% with associated PH41 approved therapies0 approved therapies0 200,000 Sarcprevalence in the US; up to 30% with associated PH2 $1B+ market opportunity 12.7 M diagnosed COPD in the U.S; ~27% with associated PH4 Multi-billion $market opportunity

Bellerophon Therapeutics Overview | January 202221 Dose-escalation study designed to verify acute hemodynamic effect of INOpulseBeyond fILD: Positive top-line Phase 2 data in PH-SarcoidosisAll 8 patients demonstrated decreases in mPAPand PVR across the doses of INOpulseutilized in the studyiNO45 dose median decrease of 20% (-54% to +22%) in PVR, compared to a median baseline PVR of 329 dynecmsec-5iNO125 dose (7 out of 8 patients) median decrease of 29% (-43% to -5%) in PVR p=0.02 vs. baseline and prior dose) mPAPdecreased by a median of 6-10% across the doses of iNO30 to iNO125, compared to median baseline of 37.2 mmHgGenerally well-tolerated No treatment-emergent adverse events or serious adverse eventsAcute hemodynamic data supports progressing to a chronic dosing Phase 2b study mPAPmean pulmonary arterial pressure; PVR pulmonary vascular resistance; p-value based on Wilcoxon Rank Test (no correction for multiplicity); range represents max and min values for each condition; data based on 8 PH-Sarcpatients; 7 of 8 patients escalated to dose of iNO125 Next steps: design multi-dose Phase 2b trial in chronic use in consultation with Scientific Advisors and FDA 20%+ reduction in PVR which is typicallyconsidered clinically meaningful 

Bellerophon Therapeutics Overview | January 202222 Pulmonary Vascular Resistance (PVR) mean Pulmonary Arterial Pressure (mPAP) INOpulse Demonstrates Acute Hemodynamic Improvement in PH-SarcBaseline mPAP: 37.2 mmHg Pulmonary hemodynamics measured via right heart catheterization at baseline and following each sequential iNOdoseClinically meaningful reduction in PVR on iNO45 with potentially increasedbenefit at highest dose of iNO125No treatment-emergent adverse events (TEAEs) or serious adverse events (TESAEs)Baseline values are median of the group; bar graphs are median values at each assessment for all available study participants; p-value based on Wilcoxon Rank Test between baseline and each dose and between dose and prior dose (no correction for multiplicity); Data based on 8 PH-Sarcpatients; 7 of 8 patients escalated to dose of iNO125Baseline PVR: 329 dynesec/cm5p=0.02 p=0.02p=0.02

Bellerophon Therapeutics Overview | January 202223 Delivery to well ventilated pulmonary vessels and ventilation/vasodilation matchingBeyond fILD: INOpulseProvides Targeted Delivery and Improves Hemodynamics and Exercise Capacity in PH-COPD PatientsPatients completing 4 weeks of chronic treatment on iNO30 demonstrated:Statistically significant increase in 6MWD at 2 weeks and 4 weeks (+50.7m) as compared to baselineStatistically and clinically significant decrease in sPAPat 4 weeks (-12.0 mmHg; 19.9% reduction)sPAPincreased to near baseline upon stopping treatment with iNOThe iNOtherapy was well tolerated with no related safety concernsPrimary concepts for Phase 2b trial design in agreement with FDAHaijanet al., Int J of COPD, 2016

Bellerophon Therapeutics Overview | January 202224 Compelling Investment Opportunity in Late Stage Biotherapeutics Company with Multiple High Value Indications1. As of Sept 30, 2021 Clinically validated approachNO is a proven, well-established vasodilator approved for acute use in persistent pulmonary hypertension in neonatesBeing developed for chronic administration to address multiple significant unmet and underserved needsClear development pathwayPhase 2a completed establishing V/Q matching and acute hemodynamicsPhase 3 initiated for lead program in fILD; PH- Sarcand PH-COPD are Phase 2b readySimplified, de-risked approval pathway with ability to leverage Ikarias existing NDALarge market opportunitiesTargeting $2Bn+ market in fILDPotential $1Bn+ markets in follow-on indications of PH-Sarcand PH-COPD IP protection through 2039Corporate profile Highly experienced team with expertise in rare and respiratory diseaseUnrestricted cash & equivalents of $28.7 M1, no debt    

Investor Contacts Bellerophon Investor RelationsBTInvestorRelations@bellerophon.comBrian Ritchie I LifeSci Advisorsbritchie@lifesciadvisors.com212-915-257