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Immutep Announces New Interim Results In Phase I/II Chemoimmunotherapy Trial In Breast Cancer

New results confirm that ImmuFact IMP321 doubles clinical response rate

Orsay, France, October 6, 2009, Immutep S.A. announced today interim results from the first three cohorts of its ongoing Phase I/II chemoimmunotherapy clinical trial in metastatic breast carcinoma. The new results confirm the clinical response rate of 50 percent with IMP321 associated with paclitaxel compared to 25 percent with paclitaxel alone.

Chemoimmunotherapy is a new approach to the treatment of cancer. Chemotherapy drugs induce tumour cell apoptosis and cause modulation of the immunological environment combined with a burst of tumour antigen release. The resulting T cell immune response contributes to the regression of the tumour and, importantly, may seek out and destroy metastases. However, this initial immune response needs to be sustained and amplified by a T-cell booster that is non-toxic and can be given repeatedly, such as ImmuFact IMP321.

IMP321 is a first-in-class immunopotentiator that agonizes MHC class II molecules thereby stimulating antigen-presenting cells, such as dendritic cells and monocytes, leading to markedly improved cytotoxic CD8 T cells responses against tumours.

The design of the study is a multi-centre open-label fixed dose-escalation trial. One of the lead centre's main Principal Investigators, Maya Gutierrez, is coordinating the team carrying out the trial at the René Huguenin Cancer Centre, Saint Cloud, near Paris.

Patients receive 6 cycles of low-dose weekly paclitaxel as first line chemotherapy plus bi-weekly IMP321 administered the day after the paclitaxel to make a total of 12 injections of IMP321 over 24 weeks. Three dose levels of IMP321 are being studied in four cohorts. The new interim results are based on tumour regression under RECIST criteria in the first three cohorts of 24 patients out of the total of 30 compared to the historical control group which is the weekly paclitaxel arm of a recent randomised phase III study (N. Engl. J. Med. 2007; 357:2666-76). The improvement is highly statistically significant with a p-value of 0.006.

In addition, immuno-monitoring confirmed that IMP321 is a potent agonist of the anti-cancer cellular immune response. Both the primary target cells (monocytes, dendritic cells) and secondary target cells (CD8 effector memory T cells) were found to be expanded/activated for several months.

"Such sequential chemo- and then non-toxic immunotherapeutic combos may be a way to improve the response rate and/or consolidate or stabilize the partial tumour responses obtained with chemotherapy alone," said Dr Maya Gutierrez, Principal Investigator of this Phase I trial. "We are very pleased to be testing this innovative therapeutic approach at our Institute."

"With only a few patients left to analyse and a p-value of 0.006, we are expecting to secure the results required to go forward to a pivotal trial," said Frédéric Triebel, Scientific & Medical Director of Immutep. "We believe that this form of chemo-immunotherapy should be applicable to many chemotherapies. It is now being tested in the USA in association with gemcitabine in pancreatic cancer".

"The next steps are a Phase IIb pivotal trial leading to Conditional Marketing Authorisation in Europe and further trials in other cancers and with other chemotherapies" added John Hawken, CEO.

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Metastatic Breast Cancer and Chemoimmunotherapy Metastatic breast cancer remains incurable. The failure of current approaches is generally attributed to the outgrowth of breast tumour cells that are inherently resistant to standard treatments. Manipulating the immune system to recognize and eradicate breast tumour cells is a highly attractive alternative approach to disease management Active immunization offers multiple theoretical advantages over all other therapies, including low toxicity. The sustained antitumour effect due to immunological memory would obviate the requirement for prolonged, repetitive cycles of therapy.

The objective of chemoimmunotherapy is to amplify natural pre-existing T cell responses specific for any known or unknown tumour antigen and to recruit and amplify new tumour-specific T cell responses resulting from the use of cytotoxic drugs. The direct cytolytic effect of some cytotoxic drugs, such as paclitaxel, can enhance antigen presentation by inducing tumour cell apoptosis. This mechanism of therapeutic synergy has been shown with cyclophosphamide, doxorubicin, or paclitaxel when given with dendritic cell-based vaccines. Until 8 years ago, it was thought that the T cell depletion caused by chemotherapy would make immunotherapy ineffective. However it has now been shown that, on the contrary, the vigorous T cell repopulation following depletion can be directed against the tumour.

Soluble LAG-3 protein is a prognostic factor in breast cancer ImmuFact IMP321 is closely related to the soluble form of the LAG-3 (Lymphocyte Activation Gene-3) protein which is a prognostic indicator for survival in breast cancers expressing oestrogen or progesterone receptors. This was shown is a study carried out by researchers at the René Huguenin Cancer Centre and Pr. Frédéric Triebel when he was at the Pharmacy Faculty of University Paris 11. These results paved the way for the current clinical trial. (Immutep Press Release No 6, April 2006)

Centre René Huguenin de Lutte contre le Cancer The René Huguenin Centre for the Fight against Cancer is a comprehensive cancer centre that treats more than 3,000 new cases of cancer each year, with more than 2,000 new cases of breast cancer. It has a medical staff of 66 practitioners. Besides participation in therapeutic trials, the Centre has developed special expertise in the field of tumorigenesis and pharmacogenetics of breast cancers. Professor Jean-Nicolas Munck is the Directeur-Général of the Centre.

Immutep S.A. Immutep S.A. is a biopharmaceutical company developing immunostimulatory factors for the treatment of cancer and chronic infectious diseases and immunomodulatory therapeutic antibodies for the treatment of cancer or autoimmune disease. The Company's technologies are based on the LAG-3 immune control mechanism that mediates T cell immune responses.

ImmuFact(R) - T cell Immunostimulatory Factors for amplifying the T cell response The lead product, ImmuFact(R) IMP321, is a highly potent T cell immunostimulatory factor. It is a soluble form of LAG-3 that binds, with high affinity, to MHC class II molecules expressed by dendritic cells (DC) and monocytes. This binding leads to DC maturation, migration to the lymph nodes and enhanced cross-presentation of antigens to T cells. As a result, strong and sustained anti-tumour or anti-viral cytotoxic T cell responses are obtained.

ImmuFact(R) - Clinical Development More than 600 s.c. injections of IMP321 have been administered to date in Europe and the USA at doses up to 30 mg with no clinically significant drug-related adverse events. A Phase I trial in metastatic renal cell carcinoma with IMP321 alone has been completed. Four Phase I/II clinical trials are in progress: in metastatic breast cancer combining IMP321 with weekly paclitaxel in a chemoimmunotherapy protocol (, in pancreatic cancer combining IMP321 with gemcitabine in chemoimmunotherapy (, a disease-free melanoma study with IMP321 as a therapeutic vaccine adjuvant to peptide antigens and a lympho-depletive/adoptive transfer metastatic melanoma study.

For further information, please contact: Andrew Lloyd & Associates Andrew Lloyd / Neil Hunter Tel: +44 1273 675100>

Posted: October 2009