New Data Opens Potential for Patient Stratification for CriPec® Nanomedicines in Cancer and Other Indications via Non-Invasive Imaging

Maastricht, The Netherlands, 4 May 2022 – Cristal Therapeutics, a Dutch pharmaceutical company developing tailored nanomedicines for the treatment of cancer and other diseases with high unmet patient need, today announced the publication of the results of the clinical PICCOLO study in the peer-reviewed journal, Advanced Materials¹.

This first-of-its-kind study², part funded by an EU Horizon 2020 and a Health Holland grant, applied radiolabelling and PET-imaging to non-invasively track CriPec^® nanomedicines in patients with solid tumours over time.

The data showed that a diagnostic dose of CriPec^® nanomedicine radiolabelled with zirconium-89 (⁸⁹Zr-CPC634) was reliably predictive for the behaviour of a therapeutic dose and provides a powerful tool to non-invasively monitor the biological journey, including tumour uptake. This opens up the potential of using this approach to stratify patients without exposing them to therapeutic dose levels and thus possible side effects.

In the study, undertaken in close collaboration with researchers from Amsterdam University Medical Centre (location VUmc), radiolabelled CriPec^® was followed by positron emission tomography / computed tomography (PET/CT) imaging in seven patients with solid tumours. A therapeutic dose as well as a diagnostic dose were administered, and pharmacokinetics and tumour uptake were assessed for both. Extended blood residence and substantial tumour uptake were observed and were in fact found to be comparable for both dose levels. These findings are significant as they provide further evidence for the long circulation and substantial tumour uptake of CriPec^® nanomedicines in patients, as was previously observed in other clinical studies^2,3. They further support the potential for superior therapeutic performance of CriPec^® nanomedicines.

In addition, the ability to monitor CriPec^® nanoparticles in patients also provides Cristal Therapeutics with detailed information for use in its rational design process to engineer CriPec^® nanomedicines for superior therapeutic performance and to stratify patients for precision medicine-based approaches.

Dr Cristianne Rijcken, PharmD PhD, founder and CSO of Cristal Therapeutics said:

“Despite the many advances in the nanomedicine field, the heterogeneity of tumours, both inter- and intra-patient, remains a major challenge. The non-invasive, diagnostic approach validated in this unique study provides valuable insight into the behaviour of CriPec^® nanomedicines and gives Cristal Therapeutics a powerful tool to further enhance the rational design of our nanomedicines with the goal of stratifying patients for safer, more targeted anticancer treatments in the future.”

Cristal Therapeutics is progressing a robust pipeline of nanoparticle therapeutic candidates which are rationally designed to target specific tissues, cells and intracellular components throughout the body. Its strategy is to partner its technology platforms and CriPec^® based therapeutic products to maximise the potential for advancing new medicines in areas of high unmet need.

Representatives from Cristal Therapeutics will be attending the BIO International Convention in San Diego 13-16 June 2022 – please contact info@cristaltherapeutics.com.

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About the PICCOLO study

In the PICCOLO clinical study, a docetaxel-entrapping polymeric nanoparticle was radiolabelled with zirconium-89 (⁸⁹Zr-CPC634) and positron emission tomography / computed tomography (PET/CT) imaging was performed in seven patients with solid tumours of various origins with two different doses of CPC634: an on-treatment (containing 60 mg m^-2 docetaxel) and a diagnostic (1-2 mg docetaxel) dose (NCT03712423). Pharmacokinetic half-life for ⁸⁹Zr-CPC634 was mean 97.0 ±14.4 hours on-treatment, and 62.4 ±12.9 hours for the diagnostic dose (p = 0.003). At these doses accumulation was observed in 46% and 41% of tumour lesions with a median accumulation in positive lesions 96 hours post-injection of 4.94 and 4.45%IA kg^-1 (p = 0.91), respectively.

About Cristal Therapeutics

Cristal Therapeutics applies three distinct and interconnected technologies together with biologic insights to improve the therapeutic profile of our partners’ programs in development. Based on over 10 years of real-world experience, the Company’s CliCr^®, CriPec^® and CriVac^® technologies provide superior conjugation, enhance target specificity and engender highly selective immune responses, thereby increasing efficacy and reducing toxicity. Cristal Therapeutics aims to be the partner of choice for overcoming challenges and enabling the full potential of nanomedicines, bio-conjugates and vaccines, among a broad range of therapeutic areas, tuned to modality and indication.

Find out more: www.cristaltherapeutics.com

References

1. PET-CT imaging of polymeric nanoparticle tumour accumulation in patients, Miedema et al, Advanced Materials 2022, https://onlinelibrary.wiley.com/doi/10.1002/adma.202201043
2. PET Study With [89Zr]-Df-CriPec® Docetaxel - Full Text View - ClinicalTrials.gov
3. A phase I dose-escalation and pharmacokinetic study of a nanoparticle with entrapped docetaxel (CPC634) in patients with advanced solid tumours, Atrafi et al, Journal Controlled Release 2020, https://www.sciencedirect.com/science/article/pii/S0168365920303540?via%3Dihub

Intratumoural comparison of nanoparticle entrapped docetaxel with conventional docetaxel in patients with solid tumours, van Eerden et al, Clinical Cancer Research 2020, https://aacrjournals.org/clincancerres/article/26/14/3537/9960/Intratumoral-Comparison-of-Nanoparticle-Entrapped