The Problem.
This inherent limitation has two consequences:
- The therapeutic potential of even well absorbed drugs is often not maximised
- New and existing lipophilic or highly complex molecules require bio-enabling delivery approaches to address solubility and permeability limitations simultaneously
The Solution.
The TRx approach offers new opportunities in oral drug delivery for existing drugs and future ‘beyond the-rule-of-5’ molecules:
- Well absorbed drugs can be highly targeted towards specific cells and tissues to best leverage their pharmacology
- Size and specificity of more complex molecules no longer problematic for sufficient absorption
We believe TRx technology has the potential to disrupt the design and development of existing and future small molecule-based therapies, as demonstrated by our emerging data.
Targeted Delivery Across Three Tiers.
1. Absorption
- Utilise unexploited uptake channels solving historic limitations in drug absorption using existing human biology
- High drug load into chylomicrons prior to systemic distribution
2. Transport
- Avoidance of first pass metabolism and sustained metabolic protection
- Priming of key immune cells followed wider drug distribution commencing with lung and brain
3. Targeting
- On top of increased systemic absorption chylomicrons enhance uptake in tumors and brain
- New opportunities exist to generate regulatory immune cells with systemic reach
Targeting Delivery to the Brain.
In this example, the pharmacokinetics post oral delivery have been evaluated in both plasma and brain.
- TRx technology has successfully increased drug uptake in the brain for a molecule that is not usually centrally penetrant
- This creates the possibility to consider the use of drug pharmacology in the brain that has not been previously accessible
Pre-clinical CNS biodistribution data supported further pharmacodynamic evaluation to evaluate the potential for innovative anti-inflammatory action.
Corresponding Increase in Efficacy.
Brain levels of inflammatory cytokines were measured post LPS-stimulation:
- Increases in brain drug exposure data are matched by significant reductions in the production of inflammatory cytokines in response to LPS challenge
- Reduction in cytokines is only achieved in TRx drug presentations, demonstrating our ability to optimise both pharmacokinetics and pharmacodynamics simultaneously
Significant validation of TRx technology in neuroinflammation and our ability to innovatively leverage novel and unexploited pharmacology in the brain.