Modified absorption - more convenient treatment regimens
LVT derivatives improve absorption across membranes because they have altered physicochemical properties when compared with
their parent compounds. Clavis Pharma has also shown that, compared with parent compounds, which can often only be administered
by injection, LVT-derived drugs may be absorbed by the oral, dermal and inhalation routes. Indeed, in animal models, LVT drugs
have successfully been administered by the following routes: intravenous, intraperitoneal, intracerebral, intratumoural, oral,
dermal (topical) and by inhalation. Clinical studies will be required to see if it is practicable to administer LVT drugs
by these routes in man.
Pharmacokinetic profile - improved efficacy and safety profile
An important aim of drug therapy is to maintain an effective but non-toxic concentration (the 'therapeutic window') for a
sustained period. Too high a concentration of drug may be toxic while a concentration that is too low may be ineffective.
The ideal drug remains in a target tissue or cell within the therapeutic window for a prolonged time, thereby reducing the
need for frequent administrations (as illustrated in the figure below). Clavis Pharma has demonstrated, for elacytarabine and CP-4126, that LVT can give sustained cellular levels of the active agent, causing prolonged inhibition of DNA synthesis (and thereby
inhibiting cell division), when compared with the parent molecules. Thus, there is reason to believe that LVT-based drugs
may allow effective treatment with less frequent dosing.
Increased cellular uptake - improved efficacy
Drugs that need to enter cells to reach their targets are often entering the cell through tightly controlled transport mechanisms
within the cellular membrane that are specific to the class of compunds in question. Sometimes the level of drug flow through
such transport mechanisms - influx - limits the amount of drug transported into a cell and limits efficacy of the drug. LVT
derivatives have shown cellular uptake that overcome insufficient transport into cells. Thus, multi-fold increases in cellular
uptake have been demonstrated with Clavis Pharma's anti-cancer and anti-viral compounds.
Resistance - improved efficacy
Resistance, or lack of sensitivity to a drug developing over time, may be due to a number of factors including decreased
cellular uptake of the drug into the cell (influx), increased transport out of the cell (efflux), imbalance between activation
and inactivation of a particular drug, and competition for the target of the compound. LVT products have been shown to circumvent
several such resistance mechanisms.
Metabolism and excretion - improved efficacy and reduced toxicity
Metabolism refers to the biochemical modification of a drug within the body. A transformation is often required for a drug
to achieve its active state. Yet other chemical modifications may transform a drug to its inactive state. Clavis Pharma has
demonstrated increased activation and reduced deactivation for several LVT derivatives when compared to their parent compounds.
Clavis Pharma has demonstrated that LVT derivatives can have an effect on additional molecular mechanisms, potentially giving them increased efficacy when compared with the parent drug.