Current Programmes

Scheduled for clinical trials

Incanthera’s current pipeline is oncology focussed, where drug development leverages novel targeting strategies with known anti-cancer modes of action.

ICT01-2588 has been developed by the research group of Prof. Laurence Patterson at Institute Cancer Therapeutics, University of Bradford.

ICT01-2588 is a novel vascular disrupting agent (VDA) and drug delivery platform that comprises a colchicine derivative “warhead” linked to a stable peptide chain by a spacer designed to be cleaved by MMP14, an enzyme over-expressed in many human cancers. In the laboratory, ICT2588 achieves tumor selective delivery of the VDA leading to reduced tumor blood flow and tumor shrinkage without significant toxicity.

ICT2588 is a peptide-conjugate of azademethylcolchicine (aza-d-colch), with the peptide sequence rationalised to be specifically cleaved by membrane-type-1 MMP (MT1-MMP; MMP-14). The Incanthera strategy is not, however, to inhibit the MMPs, as was attempted with agents such as marimastat. Rather, Incanthera are looking to exploit the functional activity of MT1-MMP to hydrolyse a peptide-conjugated agent and release a potent VDA directly into the tumor.

In the preclinical development, ICT01-2588 showed very promising efficacy and PK profile in xenograft models. Administrated in combination with another standard of care drug ICT01-2588 achieved clinical cure in 60% of treated animals. ICT01-2588 is due to begin Phase 1 clinical trial, starting 2016.

1 in 2

patients survive cancer for ten or more years (CRUK)

24%-50%

Cancer survival in the UK has doubled in the last forty years

  1. Gill, G. Loadman, P.M. Shnyder, S. Cooper, P. Atkinson, J. Goreti, R. Patterson, L.H. Falconer, R.A. The Tumour-Targeted Prodrug ICT2588 Demontrates Therapeutic Activity Against Solid Tumors and Reduced Potential For Cardiovascular Toxicity. Molecular Pharmaceutica (2014)
  2. Atkinson, J.M. Falconer R.A. Edwards D.R. Pennington C.J. Siller C.S. Shnyder S.D. Bibby M.C. Patterson, L.H. Loadman P.M. Gill J. H. Development of the Novel Tumor-Targeted Vascular Disrupting Agent Activated by Memrane-Type Matrix Metalloproteinases. Cancer Research (2010)
  3. Ansari, C. Tikhomirov G.A. Su, H.H. Falconer, R.A. Loadman, P.M. Gill, J.H. Rosalinda, C. Florette, K.H. Ling Tong, Lenkov, O.D. Felsher, D.W. Rao J. Daldrup-Link H.E. Development of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy. Cancer Therapy (2013)
  4. MMP-14 mRNA expression and proteolytic activity. Eur J Cancer 43, 1764-1771 (2007)
  5. Markovic, D.S., et al. Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci U S A 106, 12530-12535 (2009)
  6. Kanthou, C. & Tozer, G.M. Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int J Exp Pathol 90, 284-294 (2009)
  7. Lippert, J.W., 3rd. Vascular disrupting agents. Bioorg Med Chem 15, 605-615 (2007)
  8. Davis, P.D., et al. ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature. Cancer Res 62, 7247-7253 (2002)
  9. Tozer, G.M., Kanthou, C. & Baguley, B.C. Disrupting tumour blood vessels. Nat Rev Cancer 5, 423-435 (2005)
  10. Hinnen, P. & Eskens, F.A. Vascular disrupting agents in clinical development. Br J Cancer 96, 1159-1165 (2007)
  11. van Heeckeren, W.J., et al. Promise of new vascular-disrupting agents balanced with cardiac toxicity: is it time for oncologists to get to know their cardiologists? J Clin Oncol 24, 1485- 1488 (2006)

ICT01-2588 has been developed by the research group of Prof. Laurence Patterson at Institute Cancer Therapeutics, University of Bradford.

ICT01-2588 is a novel vascular disrupting agent (VDA) and drug delivery platform that comprises a colchicine derivative “warhead” linked to a stable peptide chain by a spacer designed to be cleaved by MMP14, an enzyme over-expressed in many human cancers. In the laboratory, ICT2588 achieves tumor selective delivery of the VDA leading to reduced tumor blood flow and tumor shrinkage without significant toxicity.

ICT2588 is a peptide-conjugate of azademethylcolchicine (aza-d-colch), with the peptide sequence rationalised to be specifically cleaved by membrane-type-1 MMP (MT1-MMP; MMP-14). The Incanthera strategy is not, however, to inhibit the MMPs, as was attempted with agents such as marimastat. Rather, Incanthera are looking to exploit the functional activity of MT1-MMP to hydrolyse a peptide-conjugated agent and release a potent VDA directly into the tumor.

In the preclinical development, ICT01-2588 showed very promising efficacy and PK profile in xenograft models. Administrated in combination with another standard of care drug ICT01-2588 achieved clinical cure in 60% of treated animals. ICT01-2588 is due to begin Phase 1 clinical trial, starting 2016.

1 in 2

patients survive cancer for ten or more years (CRUK)

24%-50%

Cancer survival in the UK has doubled in the last forty years

  1. Gill, G. Loadman, P.M. Shnyder, S. Cooper, P. Atkinson, J. Goreti, R. Patterson, L.H. Falconer, R.A. The Tumour-Targeted Prodrug ICT2588 Demontrates Therapeutic Activity Against Solid Tumors and Reduced Potential For Cardiovascular Toxicity. Molecular Pharmaceutica (2014)
  2. Atkinson, J.M. Falconer R.A. Edwards D.R. Pennington C.J. Siller C.S. Shnyder S.D. Bibby M.C. Patterson, L.H. Loadman P.M. Gill J. H. Development of the Novel Tumor-Targeted Vascular Disrupting Agent Activated by Memrane-Type Matrix Metalloproteinases. Cancer Research (2010)
  3. Ansari, C. Tikhomirov G.A. Su, H.H. Falconer, R.A. Loadman, P.M. Gill, J.H. Rosalinda, C. Florette, K.H. Ling Tong, Lenkov, O.D. Felsher, D.W. Rao J. Daldrup-Link H.E. Development of Novel Tumor-Targeted Theranostic Nanoparticles Activated by Membrane-Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy. Cancer Therapy (2013)
  4. MMP-14 mRNA expression and proteolytic activity. Eur J Cancer 43, 1764-1771 (2007)
  5. Markovic, D.S., et al. Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci U S A 106, 12530-12535 (2009)
  6. Kanthou, C. & Tozer, G.M. Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int J Exp Pathol 90, 284-294 (2009)
  7. Lippert, J.W., 3rd. Vascular disrupting agents. Bioorg Med Chem 15, 605-615 (2007)
  8. Davis, P.D., et al. ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature. Cancer Res 62, 7247-7253 (2002)
  9. Tozer, G.M., Kanthou, C. & Baguley, B.C. Disrupting tumour blood vessels. Nat Rev Cancer 5, 423-435 (2005)
  10. Hinnen, P. & Eskens, F.A. Vascular disrupting agents in clinical development. Br J Cancer 96, 1159-1165 (2007)
  11. van Heeckeren, W.J., et al. Promise of new vascular-disrupting agents balanced with cardiac toxicity: is it time for oncologists to get to know their cardiologists? J Clin Oncol 24, 1485- 1488 (2006)

ICT03-Es5 is a potent bioreductive anticancer agent activated by the enzyme DTD which is overexpressed in many solid tumors including: breast; colon; liver; bladder; stomach; the central nervous system (CNS); lung tumours and in melanomas Expression of DTD is increased up to 80-fold in primary non-small cell lung cancer (NSCLC) when compared with normal lung and up to 400-fold in NSCLC compared with small cell lung cancer (SCLC) cell lines. 

DTD is also known to activate quinone-based pro-drugs and this has been proposed as an approach for selectively targeting cancer cells that express DTD.

ICT03-Es5 is a DNA cross-linking agent and has been designed to overcome limitations associated with previously proposed bioreductive agents including, stability, solubility, poor efficacy and unsuitable clinical regimes.

In preclinical development ICT03-Es5 showed promising efficacy and an improved PK profile.

ICT03-Es5 is currently undergoing preclinical development and a Phase 1 trial is anticipated to begin in 2017.

1 in 13

men are likely to develop lung cancer in their lifetime

3 in 20

lung cancers are non-small cell lung cancers

  1. Danson, S., Ward, T.H., Butler, J., Ranson, M. DT-diaphorase: a target for new anticancer drugs. Cancer Treatment Reviews 30, 437-449 (2004)
  2. Timothy H. Ward, Sarah Danson, Alan T. McGown, Malcolm Ranson, Nic A. Coe, Gordon C. Jayson, Jeff Cummings, Robert H.J Hargreaves and john Butler. Preclinical Evaluation of the Pharmacodynamic Properties od 2,5 – Diaziridinyl-3-Hydroxymethyl-6-Methyl-1,4-Benzoquinone, Clin Cancer Res 11: 2695-2701 (2005)
  3. Siegel, D., Yan, C., Ross, D. NAD(P)H: quinone oxireductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones. Biochemical Pharmacology 83, 1033-1040 (2012)
  4. Danson, S., Johnson, P., Ward, T.H., Dawson, M., Denney, O., Dickinson, G., Aarons, L. Watson, A., Jowle, D., Cummings, J., Robson, L., Halbert, G., Dive, C., Ranson, M., Phase I pharmacokinetic and pharmacodynamics study of the bioreductive drug RH1. Annals of Oncology, (2011)

ICT03-Es5 is a potent bioreductive anticancer agent activated by the enzyme DTD which is overexpressed in many solid tumors including: breast; colon; liver; bladder; stomach; the central nervous system (CNS); lung tumours and in melanomas Expression of DTD is increased up to 80-fold in primary non-small cell lung cancer (NSCLC) when compared with normal lung and up to 400-fold in NSCLC compared with small cell lung cancer (SCLC) cell lines. 

DTD is also known to activate quinone-based pro-drugs and this has been proposed as an approach for selectively targeting cancer cells that express DTD.

ICT03-Es5 is a DNA cross-linking agent and has been designed to overcome limitations associated with previously proposed bioreductive agents including, stability, solubility, poor efficacy and unsuitable clinical regimes.

In preclinical development ICT03-Es5 showed promising efficacy and an improved PK profile.

ICT03-Es5 is currently undergoing preclinical development and a Phase 1 trial is anticipated to begin in 2017.

1 in 13

men are likely to develop lung cancer in their lifetime

3 in 20

lung cancers are non-small cell lung cancers

  1. Danson, S., Ward, T.H., Butler, J., Ranson, M. DT-diaphorase: a target for new anticancer drugs. Cancer Treatment Reviews 30, 437-449 (2004)
  2. Timothy H. Ward, Sarah Danson, Alan T. McGown, Malcolm Ranson, Nic A. Coe, Gordon C. Jayson, Jeff Cummings, Robert H.J Hargreaves and john Butler. Preclinical Evaluation of the Pharmacodynamic Properties od 2,5 – Diaziridinyl-3-Hydroxymethyl-6-Methyl-1,4-Benzoquinone, Clin Cancer Res 11: 2695-2701 (2005)
  3. Siegel, D., Yan, C., Ross, D. NAD(P)H: quinone oxireductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones. Biochemical Pharmacology 83, 1033-1040 (2012)
  4. Danson, S., Johnson, P., Ward, T.H., Dawson, M., Denney, O., Dickinson, G., Aarons, L. Watson, A., Jowle, D., Cummings, J., Robson, L., Halbert, G., Dive, C., Ranson, M., Phase I pharmacokinetic and pharmacodynamics study of the bioreductive drug RH1. Annals of Oncology, (2011)

ICT04-CYP has been developed by the research group of Prof. Laurence Patterson at Institute Cancer Therapeutics, University of Bradford.

ICT04-CYP focuses upon targeting colorectal cancer using CYP2W1, a catabolic enzyme, to converted prodrug to ultrapotent chemotoxins based upon the class of natural compounds known as the duocarmicins. Results to date show promising prospects for this new class of drug, demonstrating successful delivery of ultrapotent agents with acceptable toxicity profiles.

ICT04-CYP is in the late discovery stage and will enter preclinical development in 2016.

1 in 26

men are likely to develop bladder cancer in their lifetime

9 in 10

people with bladder cancer are over the age of 55

  1. Sheldrake HM, Travica S, Johansson I, Loadman PM, Sutherland M, Elsalem L, Illingworth N, Cresswell AJ, Reuillon T, Shnyder SD, MkrtchianS, Searcey M, Ingelman-Sundberg M, Patterson LH, Pors K. Reengineering of the duocarmycin structural architecture enables bioprecursor development targeting CYP1A1 and CYP2W1 for biological activity. J Med Chem. 2013 Aug 8;56(15):6273-7. doi: 10.1021/jm4000209. Epub 2013 Jul 26. PubMed PMID: 23844629.
  2. Travica S, Pors K, Loadman PM, Shnyder SD, Johansson I, Alandas MN, Sheldrake HM, Mkrtchian S, Patterson LH, Ingelman-Sundberg M. Colon cancer-specific cytochrome P450 2W1 converts duocarmycin analogues into potent tumor cytotoxins. Clin Cancer Res. 2013 Jun 1;19(11):2952-61. doi: 10.1158/1078-0432.CCR-13-0238. Epub 2013 Apr 15. PubMed PMID: 23589180.
  3. Sutherland M, Gill JH, Loadman PM, Laye JP, Sheldrake HM, Illingworth NA, Alandas MN, Cooper PA, Searcey M, Pors K, Shnyder SD, Patterson LH. Antitumor activity of a duocarmycin analogue rationalized to be metabolically activated by cytochrome P450 1A1 in human transitional cell carcinoma of the bladder. Mol Cancer Ther. 2013 Jan; 12(1):27-37. doi: 10.1158/1535-7163.MCT-12-0405. Epub 2012 Oct 1. PubMed PMID: 23033491.
  4. Pors K, Loadman PM, Shnyder SD, Sutherland M, Sheldrake HM, Guino M, Kiakos K, Hartley JA, Searcey M, Patterson LH. Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity. Chem Commun (Camb). 2011 Nov 28;47(44):12062-4. doi: 10.1039/c1cc15638a. Epub 2011 Oct 14. PubMed PMID: 22002321.

ICT04-CYP has been developed by the research group of Prof. Laurence Patterson at Institute Cancer Therapeutics, University of Bradford.

ICT04-CYP focuses upon targeting colorectal cancer using CYP2W1, a catabolic enzyme, to converted prodrug to ultrapotent chemotoxins based upon the class of natural compounds known as the duocarmicins. Results to date show promising prospects for this new class of drug, demonstrating successful delivery of ultrapotent agents with acceptable toxicity profiles.

ICT04-CYP is in the late discovery stage and will enter preclinical development in 2016.

1 in 26

men are likely to develop bladder cancer in their lifetime

9 in 10

people with bladder cancer are over the age of 55

  1. Sheldrake HM, Travica S, Johansson I, Loadman PM, Sutherland M, Elsalem L, Illingworth N, Cresswell AJ, Reuillon T, Shnyder SD, MkrtchianS, Searcey M, Ingelman-Sundberg M, Patterson LH, Pors K. Reengineering of the duocarmycin structural architecture enables bioprecursor development targeting CYP1A1 and CYP2W1 for biological activity. J Med Chem. 2013 Aug 8;56(15):6273-7. doi: 10.1021/jm4000209. Epub 2013 Jul 26. PubMed PMID: 23844629.
  2. Travica S, Pors K, Loadman PM, Shnyder SD, Johansson I, Alandas MN, Sheldrake HM, Mkrtchian S, Patterson LH, Ingelman-Sundberg M. Colon cancer-specific cytochrome P450 2W1 converts duocarmycin analogues into potent tumor cytotoxins. Clin Cancer Res. 2013 Jun 1;19(11):2952-61. doi: 10.1158/1078-0432.CCR-13-0238. Epub 2013 Apr 15. PubMed PMID: 23589180.
  3. Sutherland M, Gill JH, Loadman PM, Laye JP, Sheldrake HM, Illingworth NA, Alandas MN, Cooper PA, Searcey M, Pors K, Shnyder SD, Patterson LH. Antitumor activity of a duocarmycin analogue rationalized to be metabolically activated by cytochrome P450 1A1 in human transitional cell carcinoma of the bladder. Mol Cancer Ther. 2013 Jan; 12(1):27-37. doi: 10.1158/1535-7163.MCT-12-0405. Epub 2012 Oct 1. PubMed PMID: 23033491.
  4. Pors K, Loadman PM, Shnyder SD, Sutherland M, Sheldrake HM, Guino M, Kiakos K, Hartley JA, Searcey M, Patterson LH. Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity. Chem Commun (Camb). 2011 Nov 28;47(44):12062-4. doi: 10.1039/c1cc15638a. Epub 2011 Oct 14. PubMed PMID: 22002321.