CriPec docetaxel

CriPec® docetaxel is our lead candidate in development for treatment of solid tumours. Current docetaxel-containing products often have limited efficacy, and prolongation of survival comes with a high incidence of adverse reactions. This imposes major limitations on the current therapy. CriPec docetaxel overcomes the drawbacks of these conventional docetaxel therapies. CriPec docetaxel has successfully passed the various nonclinical efficacy and safety studies. A clinical phase I study was started in Q2, 2015.

Outcome nonclinical package

The therapeutic and competitive value of CriPec docetaxel is compelling as demonstrated in the various nonclinical studies:

  • Improved efficacy compared to Taxotere
  • Controllable and sustained drug blood levels, absence of high peak levels
  • Improved disposition and increased accumulation at the targeted tumour
  • Enhanced tolerability profile compared to Taxotere, allowing higher dosages

Preclinical efficacy

CriPec docetaxel has demonstrated superiority against Taxotere in multiple tumour xenograft models.

preclinical efficacy of CriPec docetaxel

Enhanced anti-tumour activity of CriPec docetaxel versus Taxotere in a subcutaneous xenograft model of breast cancer (MDA-MB-231) in mice. Left: CriPec docetaxel and Taxotere were administered at the same dose. Right: CriPec docetaxel and Taxotere were administered at equitoxic dose.

Tumour accumulation

The superior efficacy as observed in the tumour xenograft models is the result of the enhanced and sustained exposure to CriPec docetaxel. The docetaxel concentrations is approximately 20-fold higher upon CriPec docetaxel than observed after treatment with Taxotere (equal dose) or even approximately 40-fold in case of an equitoxic dose.

tumour accumulation

Docetaxel tumour concentration following a single administration of either CriPec docetaxel or Taxotere to a xenograft breast cancer model (MDA-MB-231) in mice. Left: CriPec docetaxel and Taxotere were given at equimolar dose. Right: CriPec docetaxel and Taxotere were administered at equitoxic dose.

Preclinical pharmacokinetics

The prolonged systemic circulation of CriPec docetaxel was clearly demonstrated upon evaluation of the pharmacokinetic profile when compared to Taxotere. The CriPec nanoparticles had a very small volume of distribution, while Taxotere was rapidly removed from the circulation, illustrating the completely different disposition over the body. This sustained systemic exposure with an approximate half-life of 16 hours in rats is known to all CriPec nanoparticles: the entrapped drug does not affect the pharmacokinetic profile of the nanoparticles, solely the used linker determines how much of the drugs is released in time. In addition, the PK profile is linear over a wide range of doses.

prolonged systemic circulation of CriPec docetaxel