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 in many countries 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 strategy, 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:

Currently there is no known 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.

Traditional supplemental oxygen sources:

traditional oxygen delivery systems such as tanks and large concentrators

Traditional supplemental oxygen sources:

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 directly into an electrical 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 anticipated to be significantly smaller, lighter, quieter, more energy efficient, and less expensive than units and systems 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, drug delivery units and even a next generation portable artificial lung.

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 to the FDA. 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 cleared by the FDA. Not for Sale. Anticipated commercial launch Q3 2019

We have developed with our research partner, Separation Design Group, a patented portable oxygen concentrator (POC), the X-PLO2R, that delivers 95% pure oxygen to patients 24 hours a day, 7 days a week. The X-PLO2R is designed to replace metal oxygen tanks and heavier concentrator devices.

Our conversations with patients and physicians showed that not only is portability a desired feature in POCs, but so is cost.  Besides being lightweight and efficient, the patented X-PLO2R will include our proprietary ModulAir™ Technology.  Expected to be the first modular POC in the world, the X-PLO2R will have a base model that can later be upgraded to a higher oxygen producing POC to match increased supplemental oxygen prescription requirements, eliminating the need in many cases of having to purchase a whole new larger concentrator.

X-PLO2R will be both portable, increasing the mobility of people suffering from COPD and price efficient, costing less than tanks over the duration of the disease.

Finally, our ModulAir technology allows us the ability to provide users with convenient user-replaceable oxygen sieve cartridges. Over time, the zeolite material contained in the oxygen cartridge becomes less productive requiring repair or replacement. Like a toner cartridge on a printer, we have designed our patented cartridges to be easily replaced by the user. No more having to return your POC to a distributor or manufacturer to replace the oxygen sieve cartridge.  We simply mail a replacement to your door. This is all part of our goal of making a better POC for our customers.

X-PLO2R™ Adapt™ oxygen concentrator

The next product to follow the X-PLOR is expected to be the X-PLOR Adapt™ oxygen concentrator.  The Adapt will be a portable hybrid of a traditional “At Home” oxygen concentrator and portable oxygen concentrator producing both continuous and pulse dose oxygen flow.   Our early design and development efforts reflect a truly portable continuous flow concentrator that will be used by a wide range of patients, both mobile and mobility challenged/restricted.

Not for sale. Anticipated commercial launch Q4 2020

Portable Artificial Lung

Background:

There are two types of ECMO (Extracorporeal Membrane Oxygenation) VA (venous-artery) and VV (venous-venous).  VV ECMO is typically used for respiratory bypass while VA is used for cardiac bypass. It has been shown that in situations where a patient’s lungs are no longer functioning properly VV ECMO has been used to bridge the gap between surgery and transplant.  VV ECMO has also been shown to produce positive results when used to provide rest to a patient’s lungs after, for example, an inhalation injury such as smoke, extreme heat, or chemical. A truly portable lung assist device has been the goal of extracorporeal oxygenation researchers for many years. Advances have been made in hollow gas permeable membrane fibers and blood pumping mechanisms have been perfected to a point where cell shearing is no longer an issue. Making the device truly lightweight and portable requires a novel new oxygen source, oxygenation and carbon dioxide removal such that power cords, oxygen tanks and long hoses are no longer needed.

Product in Development:

The wearable and lightweight device that is being conceived and developed by Belluscura and our research partner, Separation Design Group, is anticipated to be used by patients who have experienced lung failure or an acute respiratory exacerbation distress event and require extracorporeal oxygenation and carbon dioxide removal while waiting for lung transplant or other remedial procedure. Other uses would include coronary bypass and other situations where blood is required to be oxygenated without assistance of the lungs.

Other uses include carbon dioxide removal from the blood for patients with compromised lung function. High concentrations of carbon dioxide have been shown to reduce infection fighting ability. Also, after certain surgical procedures it may be beneficial to reduce the work load on the lungs.

Ultimately, the goal would be to prolong the lives of people suffering from COPD by providing them supplemental oxygen and then, eventually, as the disease unfortunately progresses, a portable artificial lung.



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 have 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



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

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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