Product Pipeline

RESPIRATORY

Background:

Over 250 million people worldwide suffer from Chronic Obstructive Pulmonary Disease (COPD) and is now the third leading cause of death.1 COPD hospitalizations are projected to be an epidemic over the next 15 years with the global cost of COPD estimated to rise from $2.1tr (USD) in 2010 to $4.8tr by 2030.2,3 In the US alone, costs of COPD are estimated to rise from $32bn in 2014 to $49bn by 2020.4

With this incredible financial burden facing global healthcare, acute and disruptive policies and therapeutic interventions aimed at reducing the burden of COPD need to be developed and implemented as soon as possible. Any disease-management strategies, including new and cost-effective technologies, that can efficiently manage and alleviate COPD burden in the community can potentially slow the escalating cost of this disease.

Technology:

There is no cure for COPD. Those with severe COPD are typically prescribed supplemental oxygen to alleviate their symptoms and improve their quality of life. Supplemental oxygen is usually provided either in the form of an oxygen tank, a/k/a cylinder, or via an oxygen concentrator.

Oxygen cylinders have been around for many years. An oxygen supplier or other medical supplies provider typically delivers the tanks to a patient based on their level of oxygen usage and prescription. A major problem with oxygen cylinders is that they have a finite supply of oxygen with many smaller ones lasting only a few hours while larger ones are very difficult for patients to carry, especially those suffering from later stage COPD. In addition, oxygen cylinders cannot be taken on aircraft.

Oxygen concentrators, on the other hand, generate concentrated oxygen from ordinary air which is typically 20% oxygen, 79% nitrogen and 1% argon and other trace gases. A concentrator generates 85-95% concentrated oxygen through an adsorption process involving a material called a zeolite that removes the nitrogen. Portable oxygen concentrators run on batteries (or can be plugged in directly to an outlet) and will keep generating concentrated oxygen as long as the battery has a charge. The portable oxygen market has seen tremendous growth the past few years with an estimated global market size of $1.4bn, growing rapidly to $2.4bn by 2024.5

Belluscura researched the portable oxygen market and concluded that new technology could improve the quality and efficiency of oxygen concentrators while also reducing the cost to the patient or caregiver. Since that initial research, Belluscura has exclusively licensed, acquired or filed 13 patents and applications in the field of concentrated oxygen generation. Some of the technology has won national awards for innovation.

Products in the Pipeline:

The technology Belluscura is developing and licensing is allowing the company to develop oxygen concentrators that are significantly smaller, lighter, quieter, more energy efficient, and less expensive than units currently available on the market. Moreover, these attributes along with additional innovations allow us to create an oxygen platform technology beyond the prescription portable oxygen market to include smaller stationary units than currently available, recreational and industrial units, wound care units and drug delivery units.

Belluscura’s pipeline oxygen concentrators are considered Class II prescription products that must receive Food and Drug Administration (FDA) clearance through what is known as a 510(k) application. The purpose of a 510(k) submission is to demonstrate that a device is “substantially equivalent” in safety and efficacy to a predicate device (one that has been cleared by the FDA or marketed before 1976). The 510(k) applicant compares the subject and predicate devices, explaining why any differences between them should be acceptable. Human data is not required for an oxygen concentrator 510(k) submission.

By comparison, a Premarket Approval (PMA) is used to demonstrate to the FDA that a new or modified device is safe and effective. This standard is higher than is required for 510(k) submissions. Much like a new drug, human use data from a formal clinical study is almost always required in addition to laboratory studies.

Belluscura’s oxygen concentrators will be lightweight, quiet, energy efficient, have easy consumer replaceable filter cartridges, and be modular allowing a patient to upgrade their concentrator over time as their prescription changes.

X-PLO2R™ portable oxygen concentrator


Not for Sale. Anticipated commercial launch Q2 2019

X-PLO2R™ stationary oxygen concentrator


Not for sale. Anticipated commercial launch Q2 2020



WOUND CARE

Background

Nearly 15% of Medicare beneficiaries in the United States had at least one type of wound or infection.6 The cost, for example, to treat pressure ulcers, i.e., bed sores, alone cost anywhere from $3.8bn - $22bn per year.7 The entire wound care market size is estimated to be at least $25.5bn.8 Recent studies of chronic wound care has shown that topical transdermal oxygen can help to improve the healing of chronic wounds.9

Additionally, ozone, an inorganic molecule with the chemical formula O3 is a powerful oxidant that when dissolved in water has been found to be an effective bactericidal agent against biofilms.10 It has also been shown to have anti-inflammatory effects11, improve the healing of wounds,12 and even have anti-tumor effects,13 Ozone, for example, has long been used to disinfect drinking water, swimming pools, laundry systems and waste water.

Besides occurring naturally from lightning or the sun’s UV rays, ozone is typically produced for industrial or medical uses through what is known as the corona discharge method where an electric current, i.e., a spark, flows from an electrode with a high potential into air. The spark splits some oxygen molecules (O2) into two oxygen atoms (O) which then bond to nearby oxygen molecules to form ozone (O3).

Technology

Belluscura’s oxygen generation patent portfolio includes numerous descriptions, disclosures and claims to oxygen concentrator wound care treatment devices and methods. Belluscura’s small, lightweight, battery-operated and quiet design, with patented user-replaceable filter cartridges, makes it an ideal product that can be used multiple times unlike disposable chemical based topical oxygen units. This, we believe, would be ideal where, for example, a physician's’ office rents out a unit multiple times during a year. Moreover, we believe that a portable design with a micro compressor can deliver more concentrated oxygen at a higher pressure than low pressure chemical designs.

Typical ozone generators utilize ambient air to generate ozone. Whereas, typical air is 20% oxygen, 79% nitrogen and 1% argon, connecting the 96% pure oxygen from an oxygen concentrator to the generator significantly increases the productivity and efficiency of the system. Prototypes have been built for potential clinical and home use to deliver topical oxygen or ozone to wounds.

Products in the Pipeline:

Portable low-pressure topical oxygen

 

Not for sale. Anticipated launch 2020.

Improved Ozone Generator


Not for sale. Exploring commercial opportunities.



Drug Delivery

Background

For purposes of Belluscura’s oxygen generation technology, we have been evaluating two drug delivery applications: (1) bronchial applications and (2) topical wound care. Numerous studies have shown that aerosol therapy can be achieved with patients receiving noninvasive positive pressure ventilation (NIPPV), for example, CPAP or BiPAP devices.14 Patients with acute or acute-on-chronic respiratory failure who receive NIPPV often require inhaled bronchodilators for relief of airway obstruction. One option is to remove the patient from NIPPV and administer bronchodilators by pressurized metered-dose inhaler (pMDI) and holding chamber or nebulizer as patients can tolerate brief periods of discontinuation that are needed for providing such treatments. The preferable option, however, is to continue NIPPV without interruption, especially in hypoxemic or acutely dyspneic patients.15

Another source of aerosol delivery of medication is through a nebulizer. Hypoxemia during nebulization with air-driven nebulizers can easily be prevented by simple addition of oxygen source to the air inlet of available nebulizers as mentioned above, since oxygen has to be given to children in severe attacks of asthma not only before and after but also during treatment with ß2-agonist. This is important in preventing continued deaths occurring from asthma.16

Examples of topical antimicrobials used in the treatment of chronic wounds include antiseptics and antibiotics. Antiseptics are disinfectants that can be used on intact skin and some open wounds to kill or inhibit microorganisms. They often have multiple microbial targets, a broad antimicrobial spectrum, and residual anti-infective activity but are often toxic to host tissues (eg, fibroblasts, keratinocytes, and possibly leukocytes)17. Antibiotics are chemicals produced either naturally (by a microorganism) or synthetically that in dilute solution inhibit or kill other microorganisms. They usually act on one specific cell target, have a narrower spectrum of activity, are relatively nontoxic, and are more susceptible to losing their effectiveness to bacterial resistance.18

Technology

In addition to Belluscura’s patented and patent pending oxygen generating technology, we have filed patent applications on various drug delivery mechanisms relating to oxygen concentrator units. For example, there are numerous embodiments disclosed in the patents and patent applications describing a method of delivering medication via the consumer replaceable sieve cartridges. It is contemplated in the intellectual property that a user of an oxygen concentrator practicing Belluscura’s patents could receive bronchial medication via the nasal cannula or medication such as an antiseptic or antibiotic through a cannula to the wound site.

Product Pipeline

Molecular sieve beds seeded with medications


Not for sale. Exploring potential drug delivery partners



Level of Consciousness / Sleep Monitor

Background

The type of anesthesia a patient receives is dependent on the type of surgery being performed, as well as specific patient needs. The anesthesiology professional will select a specific type of anesthesia in consultation with the patient and surgical team. Local anesthesia is usually used to numb a specific region of the body, while regional anesthesia, such as epidural delivery of an anesthetic compound, targets multiple nerve clusters (American Society of Anesthesiologists, 1994). General anesthesia is usually used to induce a lack of consciousness and awareness and loss of sensation during large and extensive procedures. Typically, general anesthesia includes the use of paralytic agents to prevent voluntary and involuntary movements in response to surgical manipulation. With this type of anesthesia, it is very important for an anesthesiology professional to monitor a patient’s level of consciousness in order to control and stabilize the patient’s bodily functions (American Society of Anesthesiologists, 2005).

The goal of the anesthesiology professional – a specialty that includes anesthesiologists, nurse anesthetists and anesthesiology technicians – is to administer the exact dose of anesthetic to ensure a loss of consciousness that is sufficient for surgery to progress while allowing a rapid return to consciousness when the procedure is complete. In preparing a patient for general anesthesia, the anesthesiology professional conducts a pre-operative evaluation to determine the appropriate anesthetic as well as to assess the extent of intraoperative monitoring the patient will require. The amount of anesthetic used to medicate a patient is usually based on the patient’s body weight.

Anesthesia awareness (AA) is an uncommon but serious event that occurs when a patient under general anesthesia stays conscious or becomes conscious during surgery due to delivery of an inadequate amount of anesthetic. Such an experience may be extremely traumatic for the patient, who may feel pressure or pain from the surgery, may hear conversations, or may feel unable to breathe. The condition is exacerbated when the patient is unable to communicate, particularly when movement is inhibited by delivery of a paralytic or muscle relaxant. The most traumatic case of anesthesia awareness is full consciousness during surgery, whereby the patient experiences pain and explicit recall of intraoperative events; some patients experiencing extreme cases compare it to torture. About half of those who endure anesthesia awareness complain about mental distress following surgery, a problem that sometimes manifests itself as post-traumatic stress disorder (PTSD).19, 20 The trauma may be so profound it can dissuade sufferers from ever undergoing surgery again. In severe cases, patients have described having flashbacks and panic attacks triggered by the smell of rubbing alcohol, the sound of metal on metal (reminding them of surgical instruments), or media images of people wearing surgical scrubs.

The incidence of AA in the United States is believed to be 20,000 to 40,000 cases per year, which represents 0.1% to 0.2% of all patients undergoing general anesthesia.20 Awareness claims formed 2% of all malpractice claims from 1990 to 2001, including 56 claims for recall under general anesthesia and nine claims for awake paralysis.

"The most traumatic cause of anesthesia awareness is full consciousness during surgery, whereby the patient experiences pain and explicit recall."

Each day in the U.S., many thousands of patients undergo surgical procedures that require general anesthesia. The sheer number of procedures, coupled with the increasing sophistication of surgical techniques, makes the use of advanced anesthesia technology especially important in optimizing patient safety and surgical outcomes. In addition to keeping anesthesia professionals advised of the patient’s vital signs, the LOC monitor provides important information about the adequacy of anesthetic depth in the form of electrical activity in the brain.

Using EEG signals to measure LOC provides an accurate depiction of a patient’s response to anesthesia. This is because cells in the brain communicate with each other by producing electrical signals; electroencephalography is the measurement of the electrical activity of the brain. An added advantage of analyzing EEG signals to monitor LOC is that it can facilitate the titration of anesthetic and sedative drugs, thereby helping to minimize the potential risk of under-medicating — or the more common occurrence of over-medicating — a patient.

Technology

The SNAP II™ LOC monitor, developed by Everest Medical and later acquired and sold by Stryker Corporation, was designed to meet these surgical needs and provide anesthesia professionals with an efficient and reliable tool to enhance the clinical judgment of a patient’s LOC and return to consciousness. Used in over 250,000 procedures, the SNAP II™ monitor is intended to supplement the multiple modalities traditionally used to assess LOC, including the observation of clinical signs, anesthetic agent analysis, and conventional monitoring of hemodynamic and respiratory systems.

The SNAP II™ LOC monitor utilizes a unique, patented algorithm and database system that collects high- and low-frequency EEG signals and compares them to other patients that have undergone surgery. The device uses the information provided by the algorithm and historical database to determine a probability projection of a patient’s LOC. Simultaneously, the algorithm reduces signal contamination by eliminating EEG bands (beta waves as low as 20 Hz and up to 50 Hz) that are prone to electrical interference.

"Incorporating high-frequency EEG signals makes the SNAP II™ a better predictor of a patient's return to consciousness."

Belluscura acquired an exclusive license to the Snap II LOC device including related trade secrets, know-how and patented technology in 2016, but decided not to launch the product due to its high manufacturing and retail cost of several thousand dollars.

After speaking with anesthesiologists and other physicians while reviewing the competitive landscape of the global anesthesia monitoring market (estimated to be $1.29bn. 21), Belluscura concluded that it could significantly improve healthcare by updating the Snap II. More specifically, by integrating the latest digital hardware technology and mobile app technology, we developed the Snap 3™. A next generation LOC platform that will cost an estimated 1/10th the cost of the Snap II and have potential application far beyond the original Snap II.

By moving an FDA cleared device to a significantly lower cost of hardware combined with a readily available display and processor such as a Samsung® or Apple® tablet, we open up the possibility of numerous new software applications being developed to utilize the Snap 3 EEG monitor.

Product Pipeline

Snap 3™ Level of Conscious Monitor

 

Not for Sale. Anticipated commercial launch 2020.

Snap III Postoperative Sleep Device

Not for Sale. Commercial Launch Anticipated 2019/2020.



1 World Health Organisation - Chronic Obstructive Pulmonary Disease (COPD) - 1 December 2017

2 Journal of Respiratory and Critical Care Medicine – February 2017

3 The Projected Epidemic of Chronic Obstructive Pulmonary Disease Hospitalizations over the Next Fifteen Years, Khakban, Amir et al, Am J Respir Crit Care Med Vol 195, Iss 3, pp 287–291, Feb 1, 2017

4 CDC reports annual financial cost of COPD to be $36 billion in the United States. CHEST July 2014

5 Global Market Insights: Oxygen Cylinders Market Size By Product, By Industry Analysis Report, Application Potential, Price Trends, and Competitive Market Share & Forecast, 2017 –2024

An Economic Evaluation of the Impact, Cost, and Medicare Policy Implications of Chronic Nonhealing Wounds, Nussbaum, Samuel et al, Value in Health 21 (2018) 27-32.

7 Id.

8 www.prnewswire.com/news-releases/global-wound-healing-market-to-reach-over-us-350-billion-by-2025-says-tmr-676809663.html

9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698133/

10 Activity of ozonated water and ozone against Staphylococcus aureus and Pseudomonas aeruginosa biofilms, Bialoszewski, Dariusz et al, Med Sci Monit, 2011; 17(11): BR 339-344

11 Anti-Inflammatory effects of ozonated water in an experimental mouse model, Azuma, Kazuo et al, Biomedical Reports 2: 671-674 2014

12 Effectiveness of a short-term treatment of oxygen-ozone therapy into healing in a posttraumatic wound, Agosti, Irene Degli et al, Case Reports in Medicine, Vol 2016, Article ID 9528572

13 The Safety and Anti-Tumor Effects of Ozonated Water in Vivo, Kuroda, Kohei et al, Int. J. Mol. Sci. 2015, 16, 25108-120.

14 Aerosol Therapy in Patients Receiving Noninvasive Positive Pressure Ventilation, Dhand, Rajiv, Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 25, No. 2 2012

15 id

16 Delivering Oxygen during Nebulization to Infants and Toddlers, Singh Tomar, RP, Med J Armed Forces India, 2004 Apr. 60(2) 179-80.

17 Topical Antimicrobial Therapy for Treating Chronic Wounds, Lipsky, Benjamin, Clinical Practice 15 November 2009

18 id

19 fn a Sebel, P. S., Bowdle, T. A., Ghoneim, M. M., Rampil, I. J., Padilla, R. E., Gan, T. J. et al. (2004). The incidence of awareness during
anesthesia: a multicenter United States study. Anesth. Analg., 99, 833-9, table.

20 fn B JCAHO (2004). Preventing, and managing the impact of, anesthesia awareness. JCAHO Sentinel Event Alert.

21 https://www.marketsandmarkets.com/Market-Reports/anesthesia-monitoring-devices-market-57663369.html?gclid=EAIaIQobChMI77PXj4O72AIVx7rACh0tMQkREAAYASAAEgLZovD_BwE