MeltDose® Technology Platform

The company’s proprietary MeltDose technology enables the formulation and drug delivery attributes of the Envarsus® product candidate. MeltDose enhances the bioavailability of compounds with low water solubility, supporting the creation of improved versions of marketed drugs. MeltDose has been validated in clinical studies and received regulatory acceptance through the FDA approval of Fenoglide for sale in the United States.

The fundamental limiting factor for oral absorption of drugs with low water solubility is the transfer of drug substance particles to dissolved molecules that can penetrate the epithelium of the gastrointestinal tract and enter into the bloodstream.

The majority of conventional drug delivery technologies aimed at increasing bioavailability of compounds with low water-solubility rely on reduction of the particle size of the drug substance – thereby increasing the surface area available for the dissolution process.

Veloxis believes that the company’s proprietary MeltDose technology provides a novel drug formulation technology that produces improved bioavailability of compounds with low water-solubility by solubilising them and incorporating the drug substance into a melted vehicle which is then sprayed onto a carrier. The result of this process is a granulate.

The drug substances are solubilised in low-melting vehicles such as PEG, poloxamers or lipids; all of which are so-called GRAS (generally recognised as safe). This process can be conducted under controlled atmosphere (nitrogen) in order to avoid degradation processes such as oxidation. The solubilised drug in this melted vehicle is transformed into solid particles by being sprayed under controlled conditions onto an inert carrier in a fluid bed. From the resulting granulate, known as a solid solution or solid dispersion, tablets can be manufactured by way of direct compression.

Potential clinical benefits of the company's proprietary MeltDose technology

Veloxis believes that the MeltDose technology, which forms the basis of the Envarsus® product candidate, may offer several meaningful clinical benefits, including but not limited to:

  • Decreased intra-individual variability: Veloxis believes that by enhancing bioavailability, variability can be reduced leading to improved efficacy/side-effect profiles of compounds with a narrow therapeutic index. In some cases, the therapeutic window is very narrow and minimal variability is mandatory. Veloxis believes that reduction in the intra-subject variability will improve the efficacy and reduce the number of adverse events. Furthermore, a decrease in variability may reduce the number of individual titrations and/or the need for control visits by the patient to the physician.
  • Reduction in peak-to-trough ratio: Drugs often exhibit high peak (Cmax) and low trough (Cmin) plasma levels that may severely affect the clinical profile of the drug. This is particularly problematic since severe side effects may be induced at high Cmax values, and lack of clinical effect may occur at low trough levels. A solution to this pharmacokinetic profile problem may be the development of a sustained release formulation such as the Company’s MeltDose technology allowing a beneficial combination of an increase in bioavailability and a controlled or modified release plasma profile.
  • Reduction of administration frequency: In order to improve compliance, it may be beneficial to reduce daily dosing frequency, for example, from two times a day to once daily. This may be achieved by a sustained release formulation, and as described above, Veloxis believes that the company’s proprietary MeltDose technology may solve this problem as it combines an increase in bioavailability with a sustained- or modified-release profile. Compliance continues to be a clinical problem, even in the transplant setting. Recent research has indicated that 28% of patients are non-compliant to some degree and that noncompliance contributes to 20% of late rejections and 16% of graft losses. Other publications have indicated that 36% of graft losses result from noncompliance. Veloxis believes that a simplified dosing regimen, such as once-daily dosing with Envarsus® will improve patient compliance and lead to better transplant outcomes.

Through the development of Envarsus®, the company’s proprietary MeltDose technology has shown the ability to create a product candidate with a once-daily administration schedule compared with the twice-daily administration schedule of the currently marketed drug, Prograf.