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CODIC

COmmercializing first-in-class dCTPase Inhibitors for treatment of hematological Cancers

Total Cost €

EC-Contrib. €

Partnership

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CODIC project word cloud

Explore the words cloud of the CODIC project. It provides you a very rough idea of what is the project "CODIC" about.

explore cancer patients chemistry therapies medical validate compounds profit agency commercialization plan clinicians synergistically therapy combination throughput agencies ip house assay start screening company pharmacokinetic nucleoside license ab inhibitor induces science holds discuss mu dividing hits revealed selective vitro erc protein direction sirna potent market clinical viability vivo prepare screen owns 10 1 inhibitors grant attract oxcia plays model strategy tool inhibit investments bodies purified rights cells shows secure preclinical ic50 65 dna death nm medicinal analogues rnai genetic cytidine degradation translational apoptosis repair anti drug gt enzymatic regulatory treatment perform commercial dctpase nontransformed replication trials th1217 effort business impd cell networks exclusive toxicity foundation

Project "CODIC" data sheet

The following table provides information about the project.

Coordinator	KAROLINSKA INSTITUTET Organization address address: Nobels Vag 5 city: STOCKHOLM postcode: 17177 website: www.ki.se contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Sweden [SE]
Total cost	150˙000 €
EC max contribution	150˙000 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2015-PoC
Funding Scheme	ERC-POC
Starting year	2016
Duration (year-month-day)	from 2016-01-01 to 2017-06-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	KAROLINSKA INSTITUTET KAROLINSKA INSTITUTET Organization address address: Nobels Vag 5 city: STOCKHOLM postcode: 17177 website: www.ki.se contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SE (STOCKHOLM)	coordinator	94˙738.00
2	OXCIA AB OXCIA AB Organization address address: FOGDEVRETEN 2A city: SOLNA postcode: 171 65 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	SE (SOLNA)	participant	55˙262.00

Map

Project objective

In our ERC grant GEnetic NEtworks as a tool for anti-CAncer Drug Development we used siRNA screening and genetic networks to identify dCTPase being involved in DNA repair and replication. Further studies revealed that dCTPase plays a role in the degradation of nucleoside analogues used in cancer treatment. We then used an RNAi approach to validate dCTPase as a target to improve nucleoside analogue therapy. The dCTPase protein was purified and we set up an enzymatic high-throughput assay to screen >65,000 compounds, which generated hits that inhibit dCTPase (IC50~1-10μM). Using in house medicinal chemistry we developed TH1217, a low nM potent and selective dCTPase inhibitor with favourable pharmacokinetic properties. TH1217 synergistically induces apoptosis and cell death in combination with cytidine analogue treatment in cancer cells in vitro and in vivo, but shows no increased toxicity in nontransformed dividing cells. Here, we want to explore the commercial potential of the dCTPase inhibitors identified in the ERC grant. In this programme, we will, with the company Oxcia AB, establish the viability of the business programme using technical analysis, develop a business strategy and direction, specifically secure IP, perform market analysis, develop a business plan, manage preclinical development and prepare for clinical trials in collaboration with clinicians and regulatory bodies, IMPD application to Medical Products Agency and identify and discuss with potential commercialization partners and funding agencies to support cost of clinical trials. We have a non-profit foundation that owns our IP rights in an effort to secure long term support for translational science aimed at bringing new therapies to patients. In our planned business model, we start a new company that holds an exclusive license to the IP from the foundation which is used to develop the overall business programme and attract investments.

Publications

List of publications.
year	authors and title	journal	last update
2016	Sabin Llona-Minguez, Andreas HÃ¶glund, Sylvain A. Jacques, Lars Johansson, JosÃ© Manuel CalderÃ³n-MontaÃ±o, Magnus Claesson, Olga Loseva, Nicholas C. K. Valerie, Thomas LundbÃ¤ck, Javier Piedrafita, Giovanni Maga, Emmanuele Crespan, Laurent Meijer, EstefanÃa Burgos MorÃ³n, Pawel Baranczewski, Ann-Louise HagbjÃ¶rk, Richard Svensson, Elisee Wiita, Ingrid AlmlÃ¶f, Torkild Visnes, Fredrik Jeppsson, Kristmundur Sigmundsson, Annika Jenmalm Jensen, Per Artursson, Ann-Sofie Jemth, PÃ¥l Stenmark, Ulrika Warpman Berglund, Martin Scobie, Thomas Helleday Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1 published pages: 1140-1148, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.5b01741	Journal of Medicinal Chemistry 59/3	2019-07-26

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