6060 Spine Road  Boulder CO 80301 303-350-3060  www.aktiv-dry.com

1. The PuffHaler Dry Powder Delivery System AKTIV-DRY 6060 Spine Road  Boulder CO 80301 303-350-3060  www.aktiv-dry.com • Fundamental Principle • The PuffHaler is a revolutionary active dry powder inhaler (DPI) that has been developed in the laboratories of Aktiv-Dry. The PuffHaler utilizes gas expansion through a tetra-foliate pressure release valve (seen below) to provide the dispersive energy to break particles up into the necessary size range for pulmonary delivery. Operation The PuffHaler has been designed for both adults and small children. The aerosol is dispersed out of a blister into a 200 cc reservoir by simply squeezing a bulb until the valve pops open. This aerosol reservoir, with attached mask for children and mouthpiece for adults, is removed from the rest of the PuffHaler and provided to the patient. This gives adults the opportunity to inhale the dose in a single-breath and children can use multiple inhalations. Side View Top View The aerosolization energy provided by the air expansion through the pressure release valve has been investigated. The diagram below shows the peak flow rate released from the PuffHalerTM over 100 manual actuations, with the dashed lines representing a design criterion of +/- 20% of the mean. The mean peak flow rate was 75 +/- 4 LPM and all of the actuations fell within the desired range. PuffHaler, the low-cost alternative for your drug delivery needs

2. PuffHaler, the low-cost alternative for your drug delivery needs Cost The PuffHaler has been designed to meet the demands of mass vaccination campaigns in developing countries. As such, we have paid extra close attention to cost. By designing an energy source that is reusable, we have been able to drive down our cost per dose for the device to a mere $0.10 US (adjusted for inflation). Live Virus Vaccine Delivery and Replication Tests with the PuffHaler The PuffHaler has also proven successful in vivo. We have shown dose-dependent deposition and replication of live-virus measles powder in the lungs of cotton rats during tests by Dr. Kevin Kisich at the National Jewish Medical Research Center. Cotton rats were vaccinated via inhalation of dry-powder measles vaccine from the PuffHaler device. RNA was extracted from the lungs at increasing intervals and assessed for the number of nucleoprotein RNA copies (y axis). Error bars represent standard deviation of 4-5 samples. The dose delivery was assessed within 5 minutes of administration, and the administered vaccine viral mRNA accounts for the initial signal detected at time 0. The administered vaccine viral mRNA subsided to nearly undetectable copies after 1 day. Between 3 and 7 days the mRNA signal increased rapidly due to viral replication in the cells of the lungs. The number of copies detected continued to increase until approximately the 7th day after inoculation, and then decreased to a small signal after 28 days. Plaque neutralization measurements confirmed generation of a neutralizing immune response. • Summary of Some Dry Powder Advantages over Liquid Vaccines • Powders inherently more stable than liquids • Less vaccine wastage • No line current or batteries required • Lower risk of disease transmission • More difficult to contaminate • No water or reconstitution needed, so easier to carry • No skin puncture or contact with blood • No re-use of needles Photographs taken by Unicef (left) and PATH (right) that depict the difficult transport of vaccines.