Alveair: General Product Information

Alveair™ is an inhaled insulin delivery system which has the potential to provide patients with diabetes a “needle-less” alternative to current insulin injections. The technology uses a generic hand-held device that delivers inhaled insulin with the same units as conventionally injected insulin, making it possible for the direct substitution of injectable insulin.

The device is capable of delivering any amount between 0.2 to 200 units in one single dose administration. The median mass diameter (MMD) of the vaporized droplet size is 1.9 um (microns). All steps in the administration of Alveair™ insulin exactly follow the current clinical practice of insulin injection, including packaging, storage, dosing steps and dosages. The only difference is that humans inhale Alveair insulin, with no need to use a needle.

Alveair™ offers the major competitive advantages of efficacy, "cleanliness," reliable glucodynamic profiles, and extremely low manufacturing costs which will be only a fraction of the leading technology. These advantages will enable a pharmaceutical company to develop a leading product without significant investment in sophisticated insulin manufacturing and biological facilities.

Efficacy & Bioavailability

Based on its pre-clinical data, Alveair™ achieves insulin bioavailability of intravenous injections of analog insulin. Multiple experiments were performed comparing Alveair™ to intravenous and subcutaneous injections in two different animal models, rats and guinea pigs. Alveair™ demonstrated delayed insulin peak and better AUC (area under the curve) compared to intravenous insulin. Alveair™ insulin peaked slowly over many hours, whereas Aspar i.v. peaked around 15 minutes. The data variations were minimal and its glucodynamic profiles were uniform. Alveair™ also showed superior efficacy and bioavailability, equaling or surpassing both subcutaneous and intravenous injections of analog insulin, such as Aspar.

Alveair™ insulin bioavailability is the highest of any insulin in the current reported literature, with close to 100% bioavailability. The current leading inhaled insulin technology is approximately one tenth of the efficacy and 15% of the bioavailability of an injection. Its glucose-lowering action is relatively short-lived. Alveair™’s bioavailability, as mentioned above, is close to 100% of the injection and has a longer duration of action.

Coremed’s first human trial yielded positive results with significant efficacy using low sub-unit dosage and without any adverse effect and respiratory irritation.

Safety

Of utmost importance in the development of pulmonary insulin is the issue of safety and tolerability. The lungs are exquisitely sensitive to particles, whether they are inert or biologically inactive. Any residues, including insulin itself, can be potentially harmful to the lungs. Based on its animal studies, Alveair has been found to be extremely clean, leaving "no residue." Safety and tolerability of inhaled insulin technologies depend on:

• The physical characteristics of the formulation
• Insulin dosage
•  Insulin concentration
• Location of drug deposition
• Recipients

With respect to these factors, Alveair™ is substantially different from current leading inhaled insulin technologies. Because of this, it is poised to minimize potential adverse reactions including immune responses.

Key advantages of Alveair ™ include:

• It is completely aqueous soluble.
• It is vaporized before inhalation.
• It has been demonstrated, in pre-clinical trials, to have excellent efficacy in the upper airway when delivered intra-nasally or intra-tracheally.
• It uses the lowest insulin concentration and dosage (on the order of sub-units, compared to the requirement of 250-500 units/ml concentration in some of the leading inhaled insulin formulations)
• Its insulin protein structure is closer to the naive molecules.
• It is made of GRAS ingredients.
• It has very low residue.

Thus, not only does Alveair™ have the potential to replace insulin injections in many clinical conditions; it also can lower insulin’s side-effect profile.