ANTUREC Pharmaceuticals
ANTUREC's research has the aim to improve cancer outcome by therapy with new recombinant and targeted drugs.
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ANTURECNew Progress
The ANTUREC Pharmaceuticals team has made the following progress:
1. Manufacturer´s authorization for tTF-NGR renewed: 2021-05-17
2. Phase III study in patients with sarcomas approved by:
- Paul-Ehrlich-Institute: 2021-09-17
- Ethical Board: 2021-10-15
3. First patient on phase III study: 2021-11-12
Our Mission
ANTUREC's mission embraces research and development in the area of new targeted recombinant drugs against cancer and the translation of promising compounds from the laboratory to the clinic. ANTURECs first ANti TUmor RECombinant pharmaceutical – the fusion protein tTF-NGR – is in clinical phase II/III studies in oncology. In addition to the clinical lead structure tTF-NGR, ANTUREC follows active preclinical programs on other targeted proteins.
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Our Company
ANTUREC is a privately owned pharmaceutical company devoted to anticancer drug development. The company was founded in 2020 by Wolfgang E. Berdel, Christian Schwöppe, and Ari Bizimis.
ANTUREC's CEOs are Wolfgang E. Berdel and Ari Bizimis, Christian Schwöppe is CSO of the company. Below, you can find each CV as a PDF.
Science
By targeting tissue factor to tumor vasculature we aim to selectively occlude tumor vessels and induce tumor infarction. Our target is aminopeptidase N (CD13) located on cells of the tumor vasculature and some tumor cells, but absent from most mature blood vessels. We have designed and studied truncated tissue factor (tTF) with a C- terminal GNGRAHA peptide (tTF-NGR) binding to CD13 and causing tumor vascular thrombosis with subsequent tumor infarction.
In our clinical studies we combine tTF-NGR with cytotoxic drugs. When tTF-NGR is given at the time of high intratumoral cytotoxic drug levels, the tumor vessels will be occluded resulting in tumor-entrapped drugs. By this mechanism, the antitumor activity of cyctotoxic drugs can be significantly enhanced. Vice versa, the activity of tTF-NGR is increased by the apoptotic action of the cytotoxic drugs on tumor cells and tumor endothelial cells through upregulation of phosphatidylserine. This principle is tested in a first randomized clinical study in soft tissue sarcoma.
As tTF-NGR targets the tumor vasculature, which is similar in different tumor types, the principle of entrapping tumor therapeutics by tTF-NGR induced vascular occlusion, if successful in the active trial, can be generalized as a treatment modality for multiple vascularized tumor entities.
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ANTUREC - Resources
ANTURECRelated Publications
This list includes preclinical studies, clinical phase I studies, information on "Good Manufacturing Practice" (GMP) guidelines and information on the tTF-NGR working group of the university hospital Muenster.
The list was last updated on Feb. 2, 2021.
Preclinical Studies
- Kessler, T.; et al. Inhibition of tumor growth by RGD peptide-directed delivery of truncated tissue factor to the tumor vasculature. Clin Cancer Res. 2005, 11, 6317-6324. doi:10.1158/1078-0432.CCR-05-0389.
- Persigehl, T.; et al. Antiangiogenic tumor treatment: early noninvasive monitoring with USPIO-enhanced MR imaging in mice. Radiology. 2007, 244, 449–456. doi: 10.1148/radiol.2442060371.
- Persigehl, T.; et al. Prediction of antiangiogenic treatment efficacy by iron oxide enhanced parametric magnetic resonance imaging. Investig Radiol. 2007, 42, 791–796. doi: 10.1097/RLI.0b013e3180d5cbd9.
- Kessler, T.; et al. Generation of fusion proteins for selective occlusion of tumor vessels. Curr Drug Discov Technol. 2008, 5, 1–8. DOI: 10.2174/157016308783769487.
- Bieker, R.; et al. Infarction of tumor vessels by NGR-peptide directed targeting of tissue factor. Experimental results and first-in-man experience. Blood. 2009, 113, 5019–5027. DOI: 10.1182/blood-2008-04-150318.
- Schwöppe, C.; et al. Tissue-factor fusion proteins induce occlusion of tumor vessels. Thromb Res. 2010, 125, S143–S150. DOI: 10.1016/S0049-3848(10)70033-5.
- Dreischalück, J.; et al. Vascular infarction by subcutaneous application of tissue factor targeted to tumor vessels with NGR-peptides: activity and toxicity profile. Int J Oncol. 2010, 37, 1389–1397. DOI: 10.3892/ijo_00000790.
- Von Maltzahn, G.; et al. Nanoparticles that communicate in vivo to amplify tumour targeting. Nat Mater. 2011, 10, 545–552. DOI: 10.1038/nmat3049.
- Schwöppe, C.; et al. Using native gel electrophoresis or isoelectric focusing as experimental “clock” for the (iso)aspartate formation of tTF-NGR fusion proteins. Biomacromol. Mass Spectrom. 2012, 2, 285–293.
- Schwöppe, C.; et al. Anticancer therapy by tumor vessel infarction with polyethylene glycol conjugated retargeted tissue factor. J Med Chem. 2013, 56, 2337–2347. DOI: 10.1021/jm301669z.
- Persigehl, T.; et al. Non-invasive monitoring of tumor-vessel infarction by retargeted truncated tissue factor tTF-NGR using multi-modal imaging. Angiogenesis. 2014, 17, 235–246. doi: 10.1007/s10456-013-9391-4.
- Brand, C.; et al. Low-energy ultrasound treatment improves regional tumor vessel infarction by retargeted tissue factor. J Ultrasound Med. 2015, 34, 1227–1236. DOI: 10.7863/ultra.34.7.1227.
- Brand, C.; et al. Tumor growth inhibition via occlusion of tumor vasculature induced by N-terminally PEGylated retargeted tissue factor tTF-NGR. Mol Pharm. 2015, 12, 3749–3758. DOI: 10.1021/acs.molpharmaceut.5b00508.
- Brand, C.; et al. NG2 proteoglycan as a pericyte target for anticancer therapy by tumor vessel infarction with retargeted tissue factor. Oncotarget. 2016, 7, 6774-6789. doi: 10.18632/oncotarget.12559.
- Stucke-Ring, J.; et al. Combinatorial effects of doxorubicin and retargeted tissue factor by intratumoral entrapment of doxorubicin and proapoptotic increase of tumor vascular infarction. Oncotarget. 2016, 7, 82458–82472. DOI: 10.18632/oncotarget.12559.
- Schmidt, L.H.; et al. Potential therapeutic impact of CD13 expression in non-small cell lung cancer. PLoS ONE. 2017, 12, e0177146. DOI: 10.1371/journal.pone.0177146.
- Schmidt, L.H.; et al. CD13 as target for tissue factor induced tumor vascular infarction in small cell lung cancer. Lung Cancer. 2017, 113, 121–127. DOI: 10.1016/j.lungcan.2017.09.013.
- Kessler, T.; et al. Aminopeptidase N (CD13): Expression, prognostic impact, and use as therapeutic target for tissue factor induced tumor vascular infarction in soft tissue sarcoma. Transl Oncol. 2018, 11, 1271–1282. DOI: 10.1016/j.tranon.2018.08.004.
- Höink, A.; et al. Gadofosveset-enhanced MRI as simple surrogate parameter for real-time evaluation of the initial tumour vessel infarction by retargeted tissue factor tTF-NGR. Oncol Lett. 2019, 17, 270–280. DOI: 10.3892/ol.2018.9638.
- Brand, C.; et al. Radiation synergizes with antitumor activity of CD13-targeted tissue factor in a HT1080 xenograft model of human soft tissue sarcoma. PLoS ONE. 2020, 15, e0229271. DOI: 10.1371/journal.pone.0229271.
Clinical Phase I Studies
- Gerwing, M.; et al. The beginning of the end for conventional RECIST—novel therapies require novel imaging approaches. Nat Rev Clin Oncol. 2019, 16, 442–458. DOI: 10.1038/s41571-019-0169-5.
- Schliemann, C.; et al. First-in-class CD13-targeted tissue factor tTF-NGR in patients with recurrent or refractory malignant tumors: results of a phase I dose-escalation study. Cancers. 2020, 12, 1488. DOI: 10.3390/cancers12061488.
- Berdel, W.E.; et al. Animal safety, toxicology, and pharmacokinetic studies according to the ICH S9 guideline for a novel fusion protein tTF-NGR targeting procoagulatory activity into tumor vasculature: are results predictive for humans? Cancers. 2020, 12, 3536. doi:10.3390/cancers12123536.