Next Safety’s Pulmonary Delivery Platform (PDP) painlessly delivers medications through the lungs into the blood stream. Potentially, it is a powerful new way to treat and monitor many diseases and chronic medical conditions and to provide doctors with a new alternative to traditional treatments. In addition, PDP devices could integrate with broadband technology, directly linking health care professionals and patient using cell phones, computers, and other means. The Company has demonstrated prototypes at various stages throughout product cycle. For example, the miniaturization of the nicotine delivery device has reached a small 106 gram product (less than 4 oz.). After complete miniaturization (e.g., utilizing a single chip ASIC solution etc.), the device will be far more powerful and much smaller.
Why Pulmonary Delivery?
The surface area of human adult lungs is similar to that of a small apartment, between 550 and 1,100 square feet. The primary role of the lung is the exchange of oxygen and carbon dioxide. Gas exchange occurs in the roughly 300 million alveoli, which are spherical outcroppings at the end of approximately 20 branches of conducting airways. The lungs provide the most direct route of entry for medications into the bloodstream. Once in the bloodstream, medications gain access to all parts of the body including the brain. For psychoactive substances such as nicotine, pulmonary delivery has long been recognized as the most efficient route of delivery. Pulmonary drug delivery has been limited to this point, due to an absence of technology that allows this route to be utilized.
INHALATION MARKET
According to the latest World Health Organization estimates (2007), currently 300 million people suffer from asthma and 210 million suffer from chronic obstructive pulmonary disorder -COPD. Asthma is the most common chronic disease among children and the leading cause of hospitalization. The prevalence of asthma increased 75% from 1980-1994; asthma rates in children under age five increased more than 160% during that time period. Three million people died from COPD in 2005. Fatalities are projected to increase by more than 30% in the next ten years. The disease is poised to become the third leading cause of death worldwide by 2020.
The value of the inhaled drug market has been estimated at $18.5 billion globally for 2006. As can be seen from the chart below, asthma and COPD represent the largest market segment, 65%, of the inhaled drug market worldwide. The chart also illustrates the many market opportunities for inhaled drugs. The world market for asthma drugs is expected to exceed $21.94 billion by 2010 with the US market accounting for approximately half of the global total.
FIGURE 1: Current Market for Inhaled Drugs
In terms of revenue, the asthma and COPD therapeutics area historically ranks as the 6th largest single source of sales revenue for the pharmaceutical industry. The entire respiratory market is the 4th largest therapeutic area by sales and generated nearly $32.4 billion globally in 2005. Sales have grown steadily in the US and account for approximately 54% of global respiratory sales. The rise in the incidences of asthma and COPD combined with the possibilities of delivering many other medications through inhalation create a significant market opportunity. In addition, as pipelines weaken and many blockbuster drugs are coming off patent, the pharmaceutical companies are scrambling for new sources of revenue.
SUPERIOR TECHNOLOGY
The value of Next Safety’s pulmonary drug delivery platform (PDP) derives from the simplicity of its design and its ability to incorporate a wide set of highly desirable and customizable features. Next Safety’s PDP devices deliver medications that can be suspended or dissolved in liquid. Almost all medicines given intravenously fit this description. Next Safety’s PDP targets both currently marketed treatments as well as new drugs in development. Moreover, the PDP provides a clearly superior alternative for the efficient delivery of drugs which cannot be administered orally or intravenously.
DRUG “COCKTAILS”
Certain disease states are optimally treated by multiple medications. A severe asthmatic may take a short acting bronchodilator, a long acting bronchodilator, and an inhaled steroid. Currently, this requires multiple inhalers. Today, a two month old receives four vaccinations at a two-month well child visit; including, a DPT, hepatitis B, haemophilus influenza, and a streptococcus pneumonia vaccine. This requires four individual injections. The PDP provides the means of painlessly delivering medicines sequentially or all-but-simultaneously by varying, on a breath-by-breath basis, the drug(s) being delivered.
REVOLUTIONARY TECHNOLOGY
Imagine an asthma device that not only delivers medicine but also automatically monitors nitric oxide levels or pulmonary function. The PDP could send this information to a caretaker or a healthcare provider through instant messaging. The asthma device can also include an “emergency button,” which when depressed increases the dose while emergency services are contacted. In theory, the combination of the PDP with insulin, glucometer technology and simple programmable logic represents an artificial pancreas.
WIDE ARRAY OF APPLICATIONS
The following list is intended to illustrate how current medication classes might exploit the PDP.
1. Antibiotics
Non-invasive systemic delivery of antibiotics currently available only by intravenous (IV) delivery has an immediate market. Patients suffering from osteomyelitis, endocarditis, or complicated wound infections are currently treated for weeks with IV therapy. Long term IV access is associated with life threatening complications including line infections and line-induced thrombosis. Next Safety’s device could provide a non-invasive route for these same medicines.
Treating patients who have chronic lung disease with antibiotics is another frequently encountered problem in medicine. Patients with Cystic Fibrosis spend weeks in the hospital to treat their lung infections. An inhaled form of tobramycin is currently used to treat some bacteria successfully. The PDP could be used to deliver essentially any IV antibiotic directly to the lungs non-invasively.
The PDP has the potential to significantly benefit the treatment of tuberculosis. Isoniazid, while effective against TB, has highly toxic liver side effects. Delivering isoniazid directly to the lungs may allow a decrease in the total dose without compromising efficacy. The PDP would also provide a user-friendly route for streptomycin to treat TB. Although streptomycin is effective, the fact that it can only be given intravenously limits its use for treating TB.
2. Analgesics
The delivery of narcotics and benzodiazepines may be improved by the PDP because it would allow the use of these medicines in a home hospice setting. Moreover, in environments where IV access is troublesome, such as a battlefield or the scene of an accident, the PDP would be valuable because IV analgesic delivery is rare, if available at all.
Also, breakthrough treatments for migraine headaches and other episodic pain conditions can be developed by the rapid delivery of small amounts of medications. Immediate and relatively long lasting pain relief may be possible.
3. Anti-emetics
The last thing someone with nausea wants to do is put something in his or her mouth. Rectal delivery is not popular either. Drugs such as Phenergen or Zofran for anti-nausea would have significant benefits via pulmonary delivery by stopping nausea almost immediately (in sharp contrast to current approaches).
4. Pulmonary specific vasodilators
Flolan or prostacyclin is a constant infusion used for the treatment of primary pulmonary hypertension. Although an inhaled form was developed, it is not used because it is not practical with current nebulizer technology. It is therefore delivered intravenously, which necessitates continuous IV access. Side effects of continuous IV access and sudden changes in dosing are often life threatening. Bosentan is another common pulmonary vasodilator that is associated with serious liver toxicity. The PDP could simplify the delivery of these medicines and reduce side effects by delivering them directly where they need to act – namely, into pulmonary circulation.
5. Nicotine Replacement
In typical use, none of the current nicotine replacement therapy formulations achieves nicotine levels like those seen during typical smoking, leading to the idea that higher doses may be needed. The PDP delivers nicotine with higher efficacy than a cigarette while producing the same psychopharmacologic effect as smoking. This can eliminate the pharmacologic need for tobacco, eliminating the morbidity and mortality associated with cigarette smoking.
6. Vaccines
The current recommended vaccine schedule concentrates administration in the first year of life. Infants are routinely administered four injections at one office visit. This not only causes pain for the patient, but stress for the parents as well. Next Safety’s pulmonary delivery platform has the potential to deliver vaccines non-invasively.
7. Obesity
Obesity is becoming a global epidemic with adult obesity rates almost quadrupling in the last 25 years. Inhaled nicotine could be the most effective and safe drug to treat obesity. Obesity is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD. Obesity is also associated with an increased risk of morbidity and mortality, causing some 2.6 million deaths worldwide each year. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. The social stigma of obesity impacts a person’s mental health. Nearly half those responding to a Yale University online survey said they would be willing to give up a year of their life rather than be fat, and 15 percent said they would trim a decade off their lives for a thinner waistline.
Inhaled nicotine may provide a new tool in the battle against the obesity epidemic that afflicts millions worldwide. It has been identified as an appetite suppressant in animal models, and nicotine withdrawal has been associated with weight gain in humans. Nicotine delivered in cigarette smoke has also previously been recognized as a digestive aid. A pure clean form of nicotine has the potential to be used in this manner as well.
8. Asthma
Small particulates in high concentrations aggravate asthma, particularly in pediatric asthmatics. High ground level ozone concentrations are directly correlated to asthma and asthma attacks in pediatric patients (California EPA study, 3,562 students in six schools over ten years). Globally, there are approximately 600 million estimated cases of asthma.
SAFETY
We believe that Next Safety’s scientists and physicians have uncovered the basic mechanisms that allow the diameter of droplets containing medications to be controlled at never before seen levels of precision.
The PDP incorporates several important elements. Each droplet is individually made and is injected into an air stream with controls that ensure that the size of the droplet is in a specific size range. The energy requirement is dependent on a number of factors including the viscosity of the fluid, vapor pressure and rate requirement of the drug being delivered, and the temperature, humidity and flow rate of incoming air. Mass flow of the drug can be controlled to within picograms per minute. In most designs the device also incorporates highly advanced air filtration (e.g., 10 -6 efficiency @ 0.1 micron particle size).
Next Safety’s breakthrough provides extremely high efficacy and precision with inherently low risk. The injection of drugs into a large volume air stream improves control and accuracy. More importantly, it provides high efficacy, high efficiency and reduces risk. Delivering drugs with maximum dilution ensures extremely low variations in desired mass flow, thereby preventing the delivery of bursts of highly concentrated doses.
Next Safety’s drug delivery method achieves many broad improvements in efficacy, efficiency and risk reduction:
Lower risk and higher efficacy than other pulmonary products. Asthmatics that currently use nebulizers or metered dose inhalers to deliver bronchial dilators and steroids can inhale the drugs while under normal respiration utilizing the Next Safety devices - achieving far greater precision and a major increase in confidence of the dosage received. This capability is extremely important for pediatric asthma patients. More advanced device designs include feedback from nitrous oxide or pulmonary output measurements, independently or together, to adjust dosages, or if above certain preset levels and rates of change, contact 911 (location via triangulation) resulting in a lower risk of a fatal asthma attacks and far fewer visits to emergency rooms.
Reduced risk for the delivery of nicotine or tobacco substitutes. Other methods for delivering nicotine or other tobacco substitutes contain some element of risk - either because of very low efficacy and poor controls (most substitutes allow the patient to overdose in an attempt to achieve nicotine blood profiles similar to cigarettes). The NSI devices are intrinsically precise and allow accurate dosing while allowing the pulmonary delivery of “clean” nicotine versus the “dirty” nicotine in tobacco contaminated by 4000 harmful chemicals.
Higher efficacy and efficiency resulting in lower risk than many drugs prescribed orally. Patient outcomes using even established drugs may vary because of widely different patient diets and genetics. This is particularly true when viewed on a global basis. Many drugs delivered orally have a very low efficiency; high quantities of the drug must be taken to achieve and sustain specific blood levels. This low efficiency has enormous implications for treatments where systemic side effects are already a problem. By delivering drugs with a pulmonary method that has very high efficiency, it is possible that these long-term systemic side effects can be substantially eliminated.
Other risks inherent to oral delivery are the potential for a very low percentage of patients to have catastrophic side effects that create significant, and in most cases, unknown risks for drug companies. Importantly, it is not only diet but also severe allergic reactions to the drug that can be detected at low dosage levels which highlights the powerful capability the Company’s methods have relative to the oral delivery of certain drugs. Next Safety’s devices can deliver precise doses over a long period of time (e.g., ten or even thirty minutes) where dosing can begin or pulse at low or peak levels and only sustain the prescribed average dose when vital measured conditions meet preset levels. This capability is impossible with oral medicines because of the delivery technique and the lack of an ability to achieve near immediate blood concentrations necessary for meaningful measurements.
Market expansion for existing intravenous (IV) drugs. The potential to provide analgesics such as opiates (possibly in lower amounts when combined with nicotine) utilizing the Company’s methods, eliminating the need for IV access, is significant for hospice care in developed countries and enormous for less developed countries where IV access is typically not available.
The risk of drugs being delivered incorrectly. This allows constant monitoring ensuring that drugs are being delivered appropriately. It can virtually lock out users so they cannot overdose even if they are trying to do it intentionally. The microprocessor allows for safety measures (”password”) to be implemented so only the intended patient can use it. It also has the potential to provide compliance and dosage data to prescribing physicians that has never been available before so physicians have better information to make medical decisions.
Enhanced credibility in launching new drugs. By utilizing methods and devices that have efficient, precise and repeatable control to deliver medications—such as Next Safety’s pulmonary drug delivery platform—it is much easier for drug companies to establish real numbers for efficacy and side effects during trials. This makes a new drug launch more defendable, by better defining efficacy and risk early in development. This could also speed the process for bringing certain drugs to market. Current trials are often dependent on relatively crude devices and delivery methods making them hugely time consuming, highly debated and sometimes meaningless.
COMPETITION
Through industry standard third party testing, Next Safety has demonstrated that its pulmonary drug delivery device (PDP) is technologically superior to currently marketed systems such as nebulizers and inhalers. The Company believes that the PDP provides a wide range of advantages over existing device platforms. These advantages offer benefits to patients, physicians, and third party payers. The advantages include:
· simultaneous multiple drug capability
· increased efficiency and efficacy
· greater dose control
· built-in overdosing control
· lower drug dose
· simplified patient use
· reduced side effects
· elimination of injections in certain cases
· treatment alternatives for under-treated populations
Aerosolization of a compound is the basic mechanism for inhaled drug delivery. Factors that can affect the quantity of inhaled particles reaching the lungs and their topographical distribution are the manner of inhalation, aerosol characteristics and subject characteristics. The main types of inhalation devices are metered-dose inhalers (MDIs), dry powder inhalers (DPIs) and nebulizers. The currently available inhalation devices are not very efficient in aerosol delivery and have several disadvantages.
Nebulizers: A nebulizer is a device that turns medication in solution or suspension into an aerosol mist that patients inhale through a facemask or mouthpiece. Nebulizers are used most frequently for young children, people who have trouble using metered-dose inhalers, and people who suffer from severe asthma. Unlike inhalers, nebulizers do not require deep breathing or coordination between taking a breath and pressing the pump to deliver the drug. Nebulizers are larger than inhalers and must be plugged into an electrical socket or powered by batteries. Delivery of a single dose of medication takes longer than inhalers, typically between 5 and 30 minutes. Nebulizers continuously produce a wide range of droplet sizes; as a result, they are inefficient and the dose is inaccurate. Other disadvantages of nebulizers include high cost and risk of bacterial contamination.
Metered-Dose Inhalers: By pushing down on a small, pressurized canister, a metered amount of aerosolized medication is released from the inhaler through the use of a chemical propellant, usually chlorofluorocarbon (CFCs). The medicine is then converted to a fine mist that is inhaled by the patient. While MDIs are portable, fast and easy to use, many patients have difficulty using a MDI properly. Problems with MDIs include failure to coordinate inhalation with actuation, inadequate breath-hold and inappropriately fast inspiratory flow. With incorrect breathing techniques, the medication is blocked by the tongue or the back of the throat and does not reach the lungs, which can create systemic side effects. Spacers, a holding chamber that is added to the mouthpiece, can increase the effectiveness but result in a bulkier product for the patient.
Metered-dose inhalers usually contain between 50 and 200 individual doses. Lack of a dose counter makes determining the number of doses remaining in a MDI problematic.
The CFC propellants used in metered-dose inhalers were phased out on December 31, 2008 due to concerns about the environment. CFCs were replaced by hydrofluoroalkane (HFA).
Dry Powder Inhalers (DPI): These inhalers do not use a chemical propellant to release the medication. They rely on a sharp inhalation from the user to deliver small granules of medication in measured doses. Dry powder inhalers are considered easier to use than metered-dose inhalers because there is no need for coordination between the hand and the breath. However, some types of these inhalers require a large amount of effort to inhale the medicine, and may be difficult to use with elderly patients, children and patients with reduced lung function. Spacers cannot be used with dry powder inhalers.
One of the biggest problems is loading and priming the DPI for use; this may be due to the fact that every DPI model in current use is different. A limitation of DPIs that have multi-dose powder reservoirs is ambient humidity, which can reduce the released dose.