Project Summary Cystic Fibrosis is a genetic disorder that affects 30,000 patients in the USA with an average life span of 37 years and the majority (85%) of the mortality is a result of lung disease. Airway Clearance Therapies (ACT) are extensively used by patients for forceful mechanical clearance of mucus accumulated in airways using high pressure and high frequency vibrations. However, the use of ACTs is intrusive, painful, uncomfortable, and poses tremendous burden on patients who are required to perform ACTs daily for 1-2 hours. Without effective ACT, the mucus-plugged airways trap bacteria causing infections, inflammations, respiratory failures, and other complications. ACT is also used by patients with lung conditions where mucus clearance is necessary (e.g. bronchiectasis, COPD, Asthma). ACT works on the principle of vibrating the lungs to increase mucus mobility. Ideally, the therapy needs to be individualized and continuously adaptive for effective clearance. However, none of the current ACT devices and techniques, including chest physiotherapy, high-frequency chest compression, oscillation, and acoustic vibration therapies, are adaptive. The challenges with current ACT devices: 1. Brute-force approach: Patients have diverse airway geometry, mucus accretion levels, and obstruction locations. Optimal therapy requires input frequencies to match the resonant frequency of specific airways to target mucus clearance. Current ACT devices work on a set vibration pattern (Vest, oPEP, CPT) or a “feeling- based” subjective tweaking of input frequencies and airway location (Frequencer, VibraLung), often rendering them ineffective. 2. Subjective Assessment: None of the current devices measure lung function to provide a quantitative assessment of the airway obstruction or therapy progress putting the burden on the patient to determine treatment effectiveness. 3. Poor Quality of Life: As a result, patients perform uncomfortable ACT for long durations to see a positive effect, leading to poor adherence to ACT. Further, home ACTs are considered ineffective for a large segment of the patient population due to the lack of personalized treatment. Cognita Labs’s proposed solution, SonoHeal, will be the first device to adapt the treatment in real-time based on the patient’s lung status, such that the right airways are targeted for stimulation/vibration to reduce the reliance on patient’s guesswork as well as provide effective therapy by localizing airway clearance. SonoHeal will utilize Cognita’s patent-pending airway monitoring technology that measures airway obstruction in real- time. Combined with quantified lung response with mucus localization information, SonoHeal will algorithmically tune the right resonant frequency to target patient’s airways and promote effective mucus removal. In this proposal, Cognita’s team will bring years of airway modeling, device technologies and commercialization experience to conduct in-vitro experimentation on multiple lung models to show the feasibility and efficiency of the SonoHeal device in a lab setup.

PROJECT NARRATIVE Airway Clearance Therapies (ACT) are critical daily requirement for Cystic Fibrosis patients to remove mucus from the lungs and avoid infections and pulmonary exacerbations. Current ACT devices work on the principals of violently vibrating/shaking the lung which leads to ineffective, uncomfortable and long therapy times. Cognita’s SonoHeal will be the first closed- loop innovation that will listen to the lung response while adaptively changing acoustic vibrating pressure waves to target the resonant frequencies of the individual airways and provide most efficient and effective therapy.