BIP Endotracheal Tube (ETT)

To prevent device related healthcare associated infections: Bactiguard’s mission To prevent device related healthcare associated infections: Reduce healthcare cost Reduce the use of antibiotics – to prevent spread of multi-resistant bacteria Save lives

Consequences of VAP Ventilator associated pneumonia, caused by endotracheal tubes The relative risk of VAP in a ventilated patient is up to 25 %1-3 VAP adds a estimated cost of more than $40,000 to a typical hospital admission 30-50% The mortality is between 30–50% 4-5. BIP ETT is a new product and the clinical data is limited. I will guide you through why we belive that BIP ETT will have great potential to reduce VAP and the clinical data we have availble right now. 1. Ibrahim EH et al. Chest. 2001;120(2):555-561. 2. Craven DE et al. Infect. 1996;11(1):32-53. 3. Rello J et al. Chest. 2002;122(6):2115-2121. 4. Kollef MH et al. Chest. 2005; 128 (6): 3854-3862. 5. Stijn Blot et al. Critcal Care Medicine, March (2014) 42:3

Bacteria causing VAP and longer stay Early onset <4 days Community acquired bacteria Late onset >4 days Antibiotic – resistant nosocomial organisms (gram negative, aerobes) If the symptoms start before 4 days it is probably a community acquired bacteria If it starts after 4 days it is probably a nosocomial infection by antibiotic-resistent organisms, often gram negative aerobes. Some authors use the cut off point 2 days, and some use 4 days. VAP is associated with increasing the number of days the patients’ needs to stay in the ICU. Studies show that patients ventilated more than 5 days, stay up to 22 days in the ICU and in the hospital in general up to 25 days longer.

Reduce micro aspiration (=subglottic secretion drainage) VAP Prevention Keep the head of the patient’s bed raised Check the patient’s ability to breathe on his or her own Hand hygiene Clean the inside of the patient’s mouth on a regular basis. Reduce micro aspiration (=subglottic secretion drainage) Limit bacterial colonization So what can be done to prevent VAP. These are common guidelines to prevent it: To keep the patients head high. Extubate if possible Hand hygiene; if the health care professional touches the ETT, bacteria can move down the tube. Routine cleaning of patients mouth. Reduce micro aspiration, meaning removing fluid or mucose that is stuck above the cuff. This is usually done through a suction lumen, a feature that Bactiguard offers through the BIP ETT Evac – Evac being short for evacuation lumen. This feature is often also called subglottic secretion drainage. Another important way is to limit bacterial growth and biofilm formation – which we are adressing with our coating.

Prevention of microbial adhesion and biofilm formation Our mechanism of action Microbes adhere and multiply. When enough have developed, they form a biofilm. Uncoated surface Less microbes adhere to and colonize on the surface, preventing biofilm formation and subsequent infection. Bactiguard coated surface

How does it work? The galvanic effect – effective and safe Bactiguard coated surface Bactiguard coated surface Release of substances, such as silver ions, chlorhexidine or antibiotics, killing microbes. Short effect due to release Potential harm to tissue Releasing coatings The Bactiguard Infection Protection (BIP) technology is based on applying an extremely thin noble metal coating, consisting of gold, silver and palladium, to medical devices. The Bactiguard® coating is firmly bound to the surface of the device and reduces the adhesion and growth of microbes. The three noble metals in the Bactiguard coating – gold, silver and palladium, cause a galvanic effect which leads to a micro current that prevent the bacteria to adhere to the surface. The solution is unique. As opposed to coating technologies, which depend on the release of toxic substances e.g. silver ions or antibiotics, the Bactiguard coating is non-toxic and non-pharmacologic. To date, more than130 million Bactiguard® coated urinary catheters have been sold for patient use, with no reported adverse events related to the coating. The noble metals Au, Ag and Pd cause a galvanic effect when in contact with fluid. The micro current on the surface create an unfavorable environment for microbial adhesion. No toxic release of antimicrobial agents Tissuefriendly Biocompatible

BIP ETT Evac- A dual approach to VAP prevention Bactiguard coating preventing infections through less microbial adhesion Subglottic secretion drainage (SSD) Reducing VAP by 67%2 Reducing VAP by 50%1 The solution – A dual approach with BIP Endotracheal Tube Evac It has been specifically designed to reduce ventilator associated pneumonia (VAP). It combines the known VAP reducing feature of subglottic secretion drainage with the clinically proven ability to reduce microbial adhesion and prevention of biofilm formation of the Bactiguard noble metal alloy coating. It is still to be proven in clinical studies what the reduction of the combination of these two features can bring, but I think you can agree with me it looks very promising. 1 Haas CF et al. Respir Care. 2014; Jun; 59(6):933-52 2 Tincu R et al. Poster Euroanasthesia June (2015) 32

In vitro data BIP ETT Average % reduction The table shows In vitro data for 5 relevant bacterial strains and their reduction compared to uncoated ETT. 1. Data on file

Clinical evidence, BIP ETT Bucharest Clinical Emergency Hospital, University of Medicine and Pharmacy “Carol Davila”, Critical Care Toxicology Unit, Bucharest, Romania Clinical evidence, BIP ETT Tincu et al. 2015 (Poster, Euroanasthesia 2015) No of patients 100 Patient type Come due to drug poisoning Design Prospective, randomized, controlled, independent, cross-over Site Bucharest, Rumania Primary outcome VAP rates, length of stay Other outcomes Microbiological findings, Antibiotic use 67% “ ~70% less antibiotics per VAP case (p=0.05)” 50 patients randomized into either standard or BIP group

BIP ETT Evac features Approved for 30 day use For oral intubation High volume, low pressure cuff PVC with Bactiguard coating on both inside and outside Reduces bacterial growth in vitro by >90%1 Tissue friendly and safe for patient use The BIP ETT Evac is approved for oral intubation up to 30 days. It is available in the most commonly used sizes from 6Fr to 9Fr. It has a high volume, low pressure cuff – I will come back to this in a couple of slides. ’ The tube itself is made out of PVC with Bactiguard coating on both inside and outside, which has proved to reduce bacterial adhesion by over 90% in vitro. The tube is also proven to be perfectly safe for patient use. 1. Data on file

BIP ETT features Approved for 30 day use For both oral/nasal intubation High volume, low pressure cuff PVC with Bactiguard coating on both inside and outside Reduces bacterial growth in vitro by >90%1 Tissue friendly and safe for patient use The BIP ETT is approved for use up to 30 days and available in a broad range of sizes, from pediatric 3Fr up to 10Fr. It can be used for wither oral or nasal intubation and has a high volume, low pressure cuff. The tube itself is made out of PVC with Bactiguard coating on both inside and outside, which has proved to reduce bacterial adhesion by over 90% in vitro. The tube is also proven to be perfectly safe for patient use. 1. Data on file

Bactiguard Infection Protection Effective prevention of healthcare associated infections, through reduction of microbial adherence and growth to medical devices. Reduces the need for antibiotics, and can so limit the spread of multiresistant bacteria. The Bactiguard coating is proven to be a tissue friendly and safe technology. To summarize our offer: - Effective prevention of healthcare associated infections, through reduction of microbial adherence and growth to medical devices. - Reduces the need for antibiotics, and can so limit the spread of multiresistant bacteria. - The Bactiguard coating is proven to be a tissue friendly and safe technology.