LIBERATE Clinical Study Background, Study Overview, Device Description, Patient Selection

Summary Physicians’ efforts to help their severe emphysema patients are hampered by a lack of good therapeutic tools Pulmonx produces minimally invasive medical devices to expand treatment options for emphysema patients These have been available for many years in Europe Multiple randomized trials have already been completed and have helped identify which patients are most likely to benefit Based on this clinical experience, there is a US pivotal study of the Pulmonx Zephyr® EBV recruiting in your area

Emphysema The core issue in advanced emphysema is reduced elasticity, leading to gas trapping and lung hyperinflation Healthy Lung Lung with Emphysema Emphysema causes air sacs (called alveoli) to deteriorate and lose elasticity, making breathing difficult. Oxygen exchange is reduced in the alveoli Air gets trapped in the alveoli, causing the diseased lung region to expand The diseased region compresses the healthier region, and breathing is even more difficult.  Tissue is elastic with large surface area Tissue destruction reduces elasticity and gas exchange Breathing is easy; Lung expands and contracts normally Diseased region compresses healthier region, making breathing difficult

The Burden of Emphysema Creates a downward spiral of deconditioning and lung function decline that results in death 6 Million people in Europe and the US suffer from emphysema; 1.5M of these are severe or very severe 4th leading cause of death worldwide Costs the US healthcare system >$30B in direct expense annually

Limited Treatment Options Today Medical Management Stop smoking Medication/inhalers to help breathing Supplemental oxygen Pulmonary rehabilitation Lung Volume Reduction Surgery Remove diseased part of lung Lung Transplant Replace diseased lung

Summary of Treatment Options in Severe Emphysema High New Solutions Needed Medical Management %FEV1 improvement: 3.9% (vs. MCID of 15%) Safety Lung Volume Reduction Surgery 30 day mortality rate: 5% Extended hospitalization: 59% NETT: 30 days mortality rate: 16% BeLieVeR-HIFi: FEV1 with MM 3.9% vs 24.8% with valves, 2 deaths but none related to valves Low Effectiveness High

New Options Pulmonx developed the Zephyr® Endobronchial Valve (EBV) System for bronchoscopic lung volume reduction More than 60 clinical articles have been published to-date1 Approved in Europe in 2003 and over 9,000 patients treated outside of the USA Supplements but does not replace ongoing medical management by their physician The EBV system is available as an investigational device through the LIBERATE clinical study in the USA 1Data on file at Pulmonx

Bronchoscopic Lung Volume Reduction (BLVR) with Zephyr® EBV Minimally invasive, investigational implant reduces the volume of the diseased part of the lung Allows the healthy part of the lung to expand and function efficiently

What is the LIBERATE study device? The Zephyr® EBV System consists of: Endobronchial Valve (EBV) Valve Loading system Delivery Catheter (EDC)

The Zephyr® EBV Flexible frame Designed to seal against target lung airway and prevent tissue ingrowth One-way valve Designed to close when breathing in and open when breathing out

What is the study procedure? A bronchoscope is inserted through the nose or mouth and into the lungs The Zephyr® EBV is delivered through the bronchoscope If needed, the EBV may also be removed through the bronchoscope

Lung Volume Reduction with EBVs The Zephyr® EBV allows air and secretions to pass out through the valve but not back in, resulting in lung volume reduction In turn, the healthy part of the lung expands again and takes part in the exchange of oxygen and carbon dioxide

Zephyr® EBV Implantation A standard procedure will typically place 3-4 EBVs in the target lung area

What is collateral ventilation? Collateral ventilation is like a backdoor for airflow between lobes in the lungs If there is low collateral ventilation, the EBVs will keep air from entering the diseased area, reducing lung volume. If there is collateral ventilation, air can enter the diseased area from behind the EBVs and lung volume will not reduce. The Chartis® System can assess this prior to implanting the EBVs into the lung.

Chartis® System for Collateral Ventilation Assessment The Chartis® System consists of: Console for measuring flow and pressure Balloon catheter Similar to the EBV, the low pressure balloon catheter is delivered through a bronchoscope

Procedure Summary

Patient Selection Informed by Prior Clinical Experience VENT RCT All Valve Patients VENT RCT Patients with Low Collateral Ventilation (subgroup) BeLieVeR-HIFi RCT Patients with Low Collateral Ventilation Change in FEV1% vs Medical Control Change in FEV1% vs Medical Control Change in FEV1% vs Medical Control MCID MCID MCID Information from these studies is intended for scientific educational purposes only. References to published literature are available at request. Caution: Safety and effectiveness of the EBV Zephyr® Valve have not been established.

Prior Clinical Experience: Safety (VENT study) Major Complication Composite (MCC) (Primary Safety Endpoint) 0 – 194 Days Control % (n / N) Zephyr® EBV % (n / N) MCCs 1.2% (1 / 87) 6.1% (13 / 214) Death 0.0% (0 / 87) 2.8% (6 / 214) Empyema 0.0% (0 / 214) Massive hemoptysis 0.5% (1 / 214) Distal pneumonia -- 1.4% (3 / 214) Pneumothorax or prolonged air leak Respiratory failure > 24 hours 1.9% (4 / 214) Information from these studies is intended for scientific educational purposes only. References to published literature are available at request. Caution: Safety and effectiveness of the EBV Zephyr® Valve have not been established.

The LIBERATE Study US FDA Investigational Device Exempt (IDE) Study Purpose of Study To determine the safety and effectiveness of bronchoscopic lung volume reduction using the Zephyr® EBV for treatment of emphysema Key Endpoints Primary: Proportion of treated patients achieving a clinically significant improvement in FEV1 % compared to control patients Secondary: Improvements in lung function measures, shortness of breath, and quality of life Safety: Frequency of adverse events or complications in study participants who receive the EBV

Who is eligible for study treatment? Screening Eligibility for participation: Age 40 to 75 years BMI <35 kg/m2 Non-smoking for > 4 months Spirometry (FEV1 >15% <45% pred) Completed a pulmonary rehabilitation program in the last 6 months – Or willing to complete prior to study enrollment CT scan (heterogeneous emphysema via thin slice HRCT) Body plethysmography (RV >175% pred) Assessment of collateral ventilation using the Pulmonx Chartis® System Note: This list is not comprehensive; full set of requirements are in the Informed Consent Document General test descriptions “lung function tests, blood test”

What happens on procedure day? The procedure is performed in bronch suite/operating room Final eligibility is determined by air flow evaluation Chartis® assessment of collateral ventilation The patient is randomly assigned to Treatment or Control Zephyr® EBVs are placed if assigned to Treatment The total procedure time is approximately 1 hour Patients receiving the EBV treatment will stay overnight in the hospital for 5 nights

How long will my patient be in the study? Study participants in the Treatment group Post-procedure: 5-night hospital stay Daily phone call for 10 days post-discharge In-clinic visits scheduled – 7 days post-discharge 30 days and 45 days post-procedure 3, 6, 9, and 12 months post-procedure 2, 3, 4 and 5 years post-procedure Total study participation will be approximately 5 ½ years

How long will my patient be in the study? Study participants in the Control group Post-procedure: Discharged on the day of procedure In-clinic visits scheduled 45 days post-procedure 3, 6, 9, 12 months post-procedure Total study participation will be approximately 1 ½ years Patient can cross over to treatment group at 12 months

Post-Procedure Clinic Visits Each visit involves medical tests which will vary by timepoint, including: Physical exam, medical review, blood gases Lung function testing Imaging such as high resolution CT scan and x-rays Quality of Life surveys and daily diary symptoms questionnaire

Please Consider Referring Qualifying Patients for This Study Prior clinical experience informs study design Zephyr® EBV technology used since 2003 in Europe to treat over 9,000 patients Recent RCT shows the Chartis® system helps select patients most likely to benefit Key parameters for referral for evaluation: Age 40 to 75 years BMI <35 kg/m2 Non-smoking for > 4 months Spirometry (FEV1 >15% <45% pred) Completed a pulmonary rehabilitation program in the last 6 months – Or willing to complete prior to study enrollment Body plethysmography (RV >175% pred) Additional criteria will be evaluated at treatment site

https://pulmonx.com/liberate-endobronchial-valve-study/ Questions/Comments Who do I contact if I have eligible patients? Pulmonx Call Center 1-888-248-LUNG (1-888-248-5864) Or Find your nearest Study Site https://pulmonx.com/liberate-endobronchial-valve-study/