Small
Treatment for cancer (IPP-204106)

ImmuPharma has filed appropriate patents on the composition of matter relating to the peptides covering a large variety of Nucant structures in IPP-204106. Manufacturing processes transferable to large scale production have also been successfully developed. The company is also researching other areas including psoriasis, wound healing and diabetic retinopathy.

Background

According to the GLOBOCAN 2008 database from the WHO’s International Agency for Research on Cancer, almost 13 million new cancer cases were diagnosed in 2008 around the world, equivalent to more than 180 people per 100,000.  More than 7 million people died because of cancer in 2008.The United States National Cancer Institute estimates that in 2011, more than 1.5 million people were expected to be diagnosed with cancer and more than half a million die per year in the US alone. Based on rates from 2006-2008 according to the American Cancer Society, approximately 45% of men and women are diagnosed with cancer at some point.

ImmuPharma’s cancer treatment compound 

IPP-204106 has a dual mechanism of action, acting both in preventing angiogenesis as well as proliferation.

Data on ImmuPharma’s anti-cancer nucleolin antagonist (‘Nucant’) peptide programme, IPP-204106, have been obtained confirming the ability of the compounds to effectively control and stop the growth of a large panel of human cancer cell lines both ‘in vitro’ and ‘in vivo’. Collectively the studies comprised breast cancer, prostate cancer, melanoma, glioblastoma, leukaemia, colon cancer and pancreatic cancer cell lines.

The schedule of administration was typically 10 injections over two weeks at doses in the range of 1 mg/kg body weight. ‘In vivo’ studies showed that the majority of tumours were completely eradicated and survival time increased without additional treatment.

ImmuPharma has filed appropriate patents on the composition of matter relating to the peptides covering a large variety of Nucant structures. Manufacturing processes transferable to large scale production have also been successfully developed.

In addition to cancer indications, ImmuPharma believes that Nucants could have use in other areas such as psoriasis, wound healing and diabetic retinopathy and these are currently under investigation in research programmes conducted by the CNRS teams and ImmuPharma. Due to the considerable progress made, ImmuPharma has initiated the regulatory studies necessary for the development program of IPP-204106, and ImmuPharma has been awarded grants of over €1m from the French national research agencies.

In May 2010, ImmuPharma received an Investigational New Drug (IND) approval from the French authorities (Agence Française de Sécurité Sanitaire des Produits de Santé), to start testing IPP-204106 in a Phase I/IIa study in cancer patients.

Patients suffering from a range of cancers have been dosed already and the study is underway in three centres in France (two in Paris and one in Dijon). The clinical trial is a dose escalating open label study in patients with at least one treatment failure according to standard regulatory guidelines. The study was designed to show safety and tolerability and assess the maximum tolerated dose. Patients are dosed with an initial dose of 40 mg/sqm or 1 mg/kg and if stabilisation or improvement occurs, then patients continue treatment for an additional four sessions. The patients dosed have been suffering from breast cancer, lung cancer or bladder cancer and all with metastasis. No serious drug-related adverse events have so far been reported and a number of patients have already been rated as having stabilised disease.

Featured research

In May 2011, IPP-204106 (also referred to as N6L) was chosen to feature on the front cover of ‘Cancer Research’, a prestigious medical journal of the American Association for Cancer Research. The article was entitled ‘A Simple Approach to Cancer Therapy Afforded by Multivalent Pseudopeptides That Target Cell-Surface Nucleoproteins’, and was authored by a number of researchers working at or with the CNRS, the research institution with which ImmuPharma is collaborating.

The key findings of this study are that the compound (referred to in the paper as ‘N6L’): 

  • inhibits growth of several tumour cell lines, xenograft models and blocks angiogenesis 
  • rapidly localizes selectively in tumour tissue
  • promotes apoptosis (the death of cells, a key approach in the treatment of cancer)
  • has a novel mechanism of action, acting on nucleophosmin and nucleolin

How ImmuPharma’s IPP-204106 works in cancer treatment 

Nucants are pseudopeptides, which selectively bind to the nucleolin expressed at the surface of the cells. Located in the nucleus of normal cells where it is protected, nucleolin is much more abundant (often 30 times more) at the surface of the cells which are proliferating as well as on the surface of active endothelial cells where it can be a target for antagonist peptides.

Cell surface expressed nucleolin is also a receptor for many growth factors and plays a key role in angiogenesis. Numerous papers have been published demonstrating the role of nucleolin in stabilization of mRNAs (among them Bcl2 mRNA targeted by Taxol derivatives and gastrin mRNA involved in pancreatic cancer) in the nucleus. This stabilization is required for protein synthesis and therefore cell proliferation. Blocking nucleolin destabilizes mRNAs and prevents proliferation. Nucants and IPP-204106 in particular have therefore both anti-angiogenic and anti-proliferative properties. Anti-angiogenesis alone has been a target in the pharmaceutical industry for cancer, so has inhibition of proliferation. ImmuPharma’s Nucant programme targets both approaches and this dual mechanism makes it particularly effective. 

Click here to download the publication in Cancer Research.

Click here to download a scientific paper published on IPP-204-106 (reffered to as N6L)