The invention is the result of many years of research in the fields of chemical synthesis and preclinical development of platinum derivatives, carried out in collaboration with Christian Kowol and Bernhard Keppler from the University of Vienna's Institute of Inorganic Chemistry within the framework of the "Translational Cancer Therapy Research" cluster.
Using a new strategy, they managed to produce a new active agent known as "Albuplatin". In preclinical models, this shows itself to be much more efficacious and to have fewer side effects than the platinum therapeutics that have been in use for decades.
The spin-off company "P4 Therapeutics" (P4T) was set up in the Spring of 2019 to carry out further clinical development. The team comprises Heffeter, Kowol, Berger and Keppler, as well as Otto Kanzler and company CEO, Nadine S. Sommerfeld. Only a few months after it was set up, the new spin-off managed to attract a pharmaceutical company to partner it. Since then, the partners are collaborating closely on further development of Albuplatin.
Biomarkers will play a major role in P4T's ongoing research and development activities, as will trials with combination therapies, with particular attention on immunotherapeutics.
Albuplatin introduced as a "Trojan horse"
Using an innovative strategy, the initially inactive "prodrug" Albuplatin is deliberately enriched in the tumour tissue, where it is selectively activated by the specific metabolic characteristics of the tumour.
The essentially well-tolerated agent Albuplatin binds to the albumin protein in the blood, so that it is further deactivated. Minimal interaction is therefore expected with healthy tissues and organs. At the same time, albumin is used as a means of transport to the tumour. It serves as an important supplier of nutrients to many types of cancer and is specifically broken down in the tumour tissue to produce energy. The endogenous protein therefore acts as a natural, bio-degradable nanotransporter.
Because it binds to albumin, Albuplatin is introduced unnoticed into the tumour cells, like a Trojan horse, and only releases the active agent once it is in situ, when the albumin is broken down. This results in targeted killing of the cancer cells.
"This strategy enables us to significantly increase the activity of the drug, while at the same time minimising the side-effects," says biologist Petra Heffeter.The use of platinum-based drugs is not without its drawbacks: "Because of a lack of selectivity and poor tolerability, they often cause severe side effects, which greatly impair patients' quality of life," explains Heffeter. It is therefore essential to develop new platinum-based therapeutics with improved pharmacokinetics and greater tumour selectivity but this has long been a huge challenge for cancer researchers.
A priority-establishing patent application was filed with the European Patent Office in 2015. In 2017, national applications were filed in the USA, Europe, Canada, Australia, Israel, Japan, China, Mexico, India and Singapore.
Petra Heffeter studied biology at the University of Vienna. She completed her studies at the end of 2003 with a masters thesis, which she wrote at the Institute of Cancer Research (IKF). Immediately afterwards, she started her PhD course, also at the Institute of Cancer Research, qualifying in October 2008. In parallel to this, she did a postgraduate course in toxicology at MedUni Vienna, successfully completing this in 2008 with her paper entitled "Impact of Common Resistance Mechanisms on the Anticancer Activity of Three Novel Chemotherapeutics". She has completed several research placements abroad. Since 2016, she has worked as Assistant Professor at the Institute of Cancer Research. Her work has won numerous prizes: in 2016 she received the City of Vienna Promotion Prize and the Otto Kraupp Habilitation Prize, in 2014, the INiTS award and the RIZ Genius award and, in 2011, the City of Vienna Fund Research Development Prize for innovative interdisciplinary cancer research.
After completing his degree in biology and German studies, Walter Berger worked for three years as a project manager at Hoechst Austria. His interest in science prompted him to return to research and to write his doctoral thesis at the Institute of Cancer Research. Following a research placement at the University of Cambridge, he gained his postdoctoral qualification at the University of Vienna in 2001 on the topic of treatment-resistance in oncology. In 2010, Berger became Deputy Head of MedUni Vienna's Institute of Cancer Research. In November 2013, he was appointed Professor of Applied and Experimental Oncology at MedUni Vienna’s Institute of Cancer Research. In addition to this, the cancer research is an active member of the Comprehensive Cancer Center of MedUni Vienna and Vienna General Hospital.