Investor Hub Answers, page-3

There are a huge number of commercial solubility/penetration enhancers available commercially. We are never asked to compare/contrast our TPM versus specific ones (including TPGS) by potential licensees. I know TPGS has been a focus of shareholders in the past given we both share a Vitamin E backbone, but it doesn't come up in discussions with potential partners.

There are a couple of reasons for this. Firstly, we aren't an excipient supplier. If we were, and our business model was solely the sale of TPM as a raw ingredient, we'd have to compare/contrast TPM with a whole range of different formulation excipients. In that scenario, TPM would just be another tool in every formulators toolbox that is brought out for specific formulations/drugs. Our primary aim is to develop and license drug products. It is the attributes of the products that determine their commerciality and subseqent licensing. We just use TPM to help build the attributes that are commercially attractive, as it also provides for patent protection, which is a key commercial ingredient. There is no scenario where a product shows increased absorption, good stability, good toxicity, patent protection, has human clinical trial data, and a potentical licensee says "now can you do all that work with other excipients to see if they're different/better than TPM". They just focus on the product, not each of the components that are inside it.

On the technical side, TPM and TPGS would be complementary in a formulator's toolbox. TPM is more lipophilic than TPGS, and so would potentially be more beneficial for certain actives/dosage forms (and vice versa). TPM is predominantly made of Vitamin E, whereas the bulk of TPGS is a surfactant. Because of the surfactant, most formulation labs/pharma companies won't consider TPGS for injectable dosage forms, as they're concerned by possibly allergic reactions. It's increased hydophilicity means that it doesn't work particularly well in topical/transdermal products (outer layer of skin is lipid) as a penetration enhancer. TPM works across all dosage forms.

There are very likely certain drugs that are more appropriate for TPGS than TPM (and vice versa). We obviously focus on the development of drug products that we know TPM will add specific value to, so it's never an issue.

The one further piece we have is the biological activity of tocopheryl phosphate itself that lend itself to certain applications. TPM has anti-inflammatory/anti-erythema p no roperties for the skin (in addition to its ability to increase absorption). This is why Ashland sells over 10 tonnes per year into the personal care industry (as Vital-ET). TPGS is just standard tocopherol, so doesn't have any of the enhanced tocopheryl phospate activity. TPM also produces anti-inflammatory effects orally, which have potential benefits to a range of cardiovascular endpoints. TPGS, and other routine bioavailability enhancers, do not. This is particularly interesting when looking at drugs that may have cardiovascular endpoints. CBD is an example. Research is now showing that CBD can reduce TNF-alpha and interleukin-6 (pro-inflammatory cytokines), which would have potential benefits for certain cardiovascular/inflammatory conditions. We have shown that TPM reduces the same inflammatory cytokines. So, we could potentially increase the absorption of CBD for greater therapeutic effect, while the excipient itself adds some addition value. This is not something associated with standard excipients.