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, is a new drug modality. It incorporates docetaxel (brand name Taxotere®), a clinically validated chemotherapy, as its therapeutic payload. Current docetaxel-containing products are extensively used to treat a number of different cancers but have been shown to have limited efficacy, and prolonged use increases the incidence of side effects. CPC634 has been designed with the aim of overcoming the drawbacks of this conventional therapy.
Phase 2 study
CPC634 is in a Phase 2 clinical research study to examine its therapeutic efficacy in the treatment of 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 as measured by RECIST, a standard unbiased method for assessing whether a tumour shrinks, stays the same, or gets bigger, with CPC634 monotherapy. The clinical study will be conducted in 10 centres across the UK, Belgium, Netherlands, and Spain.
Phase 1 study
Results from the Phase 1 NAPOLY open-label, safety and pharmacokinetic study of CPC634 in patients with solid tumours showed that the drug is safe and well tolerated at all the therapeutic dose levels tested. Compared to Taxotere®, CPC634 demonstrated unique safety and tolerability including significantly less, and in some cases no, neutropenia (low white blood cell count) and alopecia (hair loss).
Mode of action
CPC634 exhibits prolonged circulation in the blood stream, allowing it to passively target tumours. The drug nanoparticles are small enough to pass through the tumour’s “leaky” vasculature but are too large to move across the endothelial cells that line healthy blood vessels, a phenomenon that is also 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.
Preliminary data from an ongoing Phase 1 tumour-accumulation study also indicate significant enhanced accumulation of CPC634 in the tumours as compared to equimolar doses of conventional Taxotere®.
Assessing the distribution of CPC634 in vivo
The biological fate of CriPec®-based candidates can be tracked in vivo by directly combining an imaging agent, such as a fluorescent dye, a NIR label, and/or a PET radiotracer, to the CriPec® candidate.
CPC205 is the radiolabelled derivative of CPC634 i.e. 89Zr-CPC634 that is being used in combination with PET imaging, as a tool to examine drug distribution across the body. It also measures non-invasively its tumour uptake and therefore evaluates the suitability of CPC634 as a targeted treatment option for individual patients. This approach will provide the necessary data to determine if CPC205 has the potential to yield a companion diagnostic for CPC634 nanomedicine.
CPC879
Product description
CPC879 is the first CriPec®-oligonucleotide being developed by Cristal Therapeutics. CriPec®-oligonucleotides are CriPec®-based nanoparticles that incorporate therapeutic oligonucleotides such as siRNA and antisense RNA which are able to regulate the expression of genes.
CriPec®-oligonucleotides are designed to overcome the major shortcomings of current oligonucleotide therapies which include poor biodistribution, ineffective tissue targeting, and inappropriate cellular processing, due to endosomal uptake and subsequent lysosomal degradation. CriPec®-oligonucleotides aim to precisely and effectively target the right subcellular compartment in the diseased tissue. Accumulation of CriPec®-siRNA in tumour cells in vitro and in vivo.
Accumulation of CriPec®-siRNA in tumour cells in vitro and in vivo
In vitro studies with double labeled CriPec®-siRNA demonstrate uptake of CriPec®-siRNA in human prostate cancer tumour cells shortly after the start of exposure.
Accumulation of CriPec®-siRNA in a human prostate cancer, PC3 cell model in vitro. PC3 cells were exposed to Cy5.5 labeled CriPec® Rho3B labelled siRNA directed to AHA1 (Activator of HSP90 ATPase) which is involved in the maturation, stabilisation/degradation and function of oncogenic proteins. After 1 h, the medium was removed and cells were washed with warm PBS. Confocal imaging showed presence in the cells of CriPec® (A) as well as siRNA (B).
Upon intravenous injection, CriPec®-siRNA showed a long circulation time and good accumulation in tumour tissue in a prostate cancer (PC3) in vivo model.
siRNA levels in blood (A) and tumour tissue (B) upon intravenous injection in the PC3 in vivo model.
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