From Preclinical Data to the Manufacture of a Clinical Batch

Within medac CDMO, we have successfully completed the NaDiNa project, whose main objective was to develop a formulation, establish a manufacturing process, and prepare a prototype of a novel anticancer drug up to the stage enabling its clinical evaluation. The project was carried out in close collaboration with the Faculty of Medicine of Palacký University in Olomouc (UPOL) and was financially supported by the Technology Agency of the Czech Republic (TAČR).

The NaDiNa Medicinal Product
The NaDiNa drug candidate is an anticancer agent based on a nanotechnology formulation of the copper salt of diethyldithiocarbamate (CuET), utilizing albumin as a carrier. The product was developed by UPOL scientists for intravenous administration and targeted treatment of solid tumors and hematological malignancies. Its mechanism of action lies in the specific binding of CuET to the protein NPL4, which induces proteotoxic stress and leads to cancer cell death. The results of this long-term research were published in the prestigious scientific journal Nature (December 14, 2017; Vol. 552, Issue 7684, pp. 194–199).

Project Progress and Results
The project had two main directions. Our company focused on the Process development of the dosage form under GMP conditions, while UPOL conducted the preclinical testing of the drug.

The development led by the Institute of Molecular and Translational Medicine (IMTM) at the UPOL Faculty of Medicine included optimization of the nanoparticle formulation and stability tests in infusion solutions. As part of the preclinical studies, pharmacokinetics, toxicity, and efficacy were evaluated in tumor in vivo models. In addition, a GLP-certified method for the determination of CuET in biological material was developed.

In vitro experimental data confirm the selective cytotoxic effect against tumor cells, including cells resistant to conventional chemotherapy. The drug thus represents a promising candidate for further preclinical and clinical development in oncology. Another significant achievement is the granting of several national patents covering the preparation of albumin–CuET nanoparticles, including protection in the United States.

Among the most important outputs on the part of oncomed are not only the development of the formulation and the optimization of the manufacturing process of the drug, but above all the production of a clinical batch of CuET, including complete documentation enabling its use for Phase I clinical trials. An integral part of the project was also the development and implementation of analytical methods necessary for testing the manufactured batch, as well as the preparation of manufacturing and technical documentation ensuring reproducible production and its use in further clinical development and contract manufacturing.

Official Approval
The project was successfully defended on July 8, 2025, as part of the final opposition procedure, and subsequently approved for closure by the TAČR Presidium on August 7, 2025.

“The official evaluation by the Technology Agency of the Czech Republic confirmed that the project achieved results corresponding to its defined objectives and created a solid foundation for further clinical development of the drug and its potential use in practice,” said Radek Fialka, Commercial Director at medac CDMO.

Conclusion
The implementation of the project has demonstrated our ability to effectively connect academic research with industrial manufacturing and deliver results with significant potential for the further advancement of modern medicine.

Complete list of publications and sources cited in Annex 15 – Loffelmann (European Journal of Medicinal Chemistry, 2023). All are listed, including DOI/links:

References – Loffelmann et al., EJMECH 2023
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Annex 17 – Patent (US 11,766,404 B2) has its own bibliography, the official application is available here: https://patents.google.com/patent/US11766404B2

From patent US 11,766,404 B2 (Annex 17) – complete list:
Patent citations
• US20170143729A1
• US20190337106A1
• WO2017207317A1
• WO2018202283A1
• EP3402581A1
• CN110293998A

Non-patent literature
1. Skrott Z. et al. Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4. Nature 552 (2017): 194–199. https://doi.org/10.1038/nature25016
2. Cvek B. Diethyldithiocarbamate complex with copper: the mechanism of action in cancer cells. Mini-Rev Med Chem 12 (2012): 1184–1192. https://doi.org/10.2174/138955712802762068
3. Liu P. et al. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer stem-like cells. Br J Cancer 107 (2012): 1488–1497. https://doi.org/10.1038/bjc.2012.442
4. Kanellis D.C. et al. Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET. Cell Death Differ (2023). https://doi.org/10.1038/s41418-023-01167-4
5. Majera D. et al. Targeting the NPL4 adaptor of p97/VCP segregase by disulfiram as an emerging cancer vulnerability evokes replication stress and DNA damage while silencing the ATR pathway. Cells 9 (2020): 469. https://doi.org/10.3390/cells9020469
6. Kaul L. et al. The revival of dithiocarbamates: from pesticides to innovative medical treatments. iScience 24 (2021). https://doi.org/10.1016/j.isci.2021.102092