Programs
Oncology programs
CriPec®-based nanomedicines are designed to unlock the therapeutic potential of new and existing cancer modalities.
CPC634
Product description
CPC634, our lead development candidate, entraps docetaxel (brand name Taxotere®), a clinically validated chemotherapy, as its therapeutic payload. Current docetaxel-containing products are extensively used to treat patients suffering from a number of different cancers types but are associated with clinically severe side effects. CPC634 has been designed to overcome the drawbacks of this conventional therapy by reducing the systemic exposure, increasing the tumour uptake and improving the safety profile.
Confirmatory study
A confirmatory study testing CPC634 in metastatic castration-resistant prostate cancer is planned for 2020. This study will compare CPC634 to Taxotere® and aim for registration via the 505(B)(2) / Hybrid 10(3) routes in the USA and Europe respectively. This approach has been supported by the FDA and European regulatory authorities.
Phase 2 study
CPC634 is under investigation in a Phase 2 clinical study, CINOVA, in patients with platinum-resistant ovarian cancer, an area of high unmet medical need. The primary objective of the trial will be to determine the response rate to CPC634 monotherapy, as measured by RECIST, a standard, unbiased method for assessing whether a tumour shrinks, grows, or stays the same. The clinical study is ongoing in eight centres across the UK, Belgium and the Netherlands.
Phase 1 studies
Results from the Phase 1 NAPOLY open-label, safety and pharmacokinetic study of CPC634 in patients with solid tumours showed a good safety and tolerability profile. Compared to Taxotere®, CPC634 demonstrated unique safety and tolerability, including a substantial reduction in neutropenia (low white blood cell count) and alopecia (hair loss).
Find out more at Clinical Trials website
CPC634 has also been evaluated in two investigator-initiated Phase 1 trials:
In the cross-over design CriTax study, CPC634 was shown to have a 4-fold higher accumulation in the tumour than Taxotere® after one cycle. A reduced impact on neutrophil counts was also observed, confirming, as the NAPOLY trial did, the reduced incidence and severity of neutropenia compared to Taxotere®.
In the Piccolo trial, the pharmacokinetics and tumour accumulation of a microdose of zirconium-labeled CPC634 were assessed by PET-scan. This demonstrated proof of principle for the approach as a means to monitor the biodistribution of CPC634 and other CriPec® nanomedicines in patients.
Find out more at Clinical Trials website
Prolonged circulation of CPC634 versus Taxotere®
Mode of action
CPC634 exhibits prolonged circulation in the blood stream, with limited exposure of the entrapped docetaxel, allowing it to passively target tumours. The drug nanoparticles are small enough to pass through the tumour’s “leaky” vasculature, but too large to move across the endothelial cells that line healthy blood vessels, a phenomenon known as enhanced permeability and retention (EPR). This means that CPC634 can concentrate its cytotoxic payload selectively inside tumours while sparing normal tissues, thereby overcoming the disadvantages associated with standard docetaxel therapies.
Clinical proof of increased tumour uptake
This has been confirmed in the Phase 1 CriTax study, which demonstrated significantly enhanced accumulation of CPC634 in the tumours when compared to equimolar doses of conventional Taxotere®.
Manufacturing
CPC634 is manufactured to cGMP standards using a straightforward and scalable two-step procedure. The process is also highly controllable, unlike that for many other nanoparticle drugs, such as liposomes. This results in a lower cost of goods compared to other nanoparticle drugs.
Development of a freeze-dried formulation for commercialisation is ongoing.
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Netherlands
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 784127.