Transgene SA has announced that new pre-clinical data for two of its programs - TG4010 and TG3003 - were presented at the Annual Meeting of the American Association for Cancer Research (AACR) in Philadelphia, PA USA.

New pre-clinical data support potential combinations of TG4010 and immune checkpoint inhibitors Immune checkpoints constitute a pool of inhibitory pathways that are essential for preserving tolerance to self and controlling the extent and breadth of normal immune responses to prevent collateral tissue damage. Tumors can corrupt some of these checkpoint inhibitors to escape immune-surveillance and proliferate. Immune checkpoint inhibitors (ICIs) targeting CTLA4 and PD-1 represent a major advance in treating several forms of cancer. Transgene has conducted pre-clinical experiments to evaluate the combination of MVA (modified vaccinia, Ankara strain) viruses - including its TG4010 MUC1 targeted cancer immunotherapy - with ICIs in different tumor models. The combination of MVA with anti-CTLA4 resulted in prolonged overall survival in a lung metastasis tumor model. More importantly, the combination of TG4010 and anti PD-1 showed an additive effect on the control of tumor growth in a MUC1-positive tumor model. Further studies evaluating combinations with ICIs and Transgene's immunotherapy candidates are ongoing.

Data with TG3003 anti-CD115 monoclonal antibody support biological activity and differentiated mode of action CD115 is the cell surface receptor for CSF-1 and is an important anti-cancer target. TG3003 is a humanized monoclonal antibody targeting CD115. Data were presented from pre-clinical proof-of-concept experiments with TG3003, supporting its mechanism of action and immune-modulatory properties. Based on its distinct mode of binding to CD115, Transgene's antibody works as a modulator rather than as a blocker of CD115. This differentiates TG3003 from other anti-CD115 antibodies in several important ways. Firstly, TG3003 does not increase the level of serum CSF1 and thus may have a better safety profile than other anti- CD115 monoclonal antibodies currently in development. Secondly, in the data presented, TG3003 was shown to decrease the number of immune-suppressive M2-type tumor- associated macrophages, which are often associated with a poor prognosis in cancer patients. Importantly, TG3003 did not eliminate immune-stimulating M1-type macrophages, thus preserving these immune-stimulatory antigen-presenting cells.

A third poster reviewing the clinical experience with Transgene's MVA platform was also presented.

Copies of these posters can be found on Transgene's website in the "Our Pipeline/Publications" section at http://www.transgene.fr/?page_id=10487#TG1050.

"The new pre-clinical data presented at AACR support our plans to initiate clinical trials evaluating TG4010 in combination with immune checkpoint inhibitors" said Nathalie Adda, MD, Chief Medical Officer. "To explore the full potential of TG4010 to treat non-small cell lung cancer, we plan to develop TG4010 not only in combination with traditional chemotherapy but also with novel immunotherapies, particularly the promising class of immune checkpoint inhibitors."

"The new data with TG3003 that we have presented further differentiate this antibody from other anti-CD115 antibodies in development" said Eric Quéméneur, Executive Vice President and Vice President, Research & Development. "We now have a strong pre-clinical package for this product, entirely designed at Transgene. This is an important achievement that supports advancing TG3003 towards the clinic."

About TG4010:

TG4010, a novel MUC1 targeting immunotherapy, is in development for the treatment of metastatic NSCLC in combination with first-line chemotherapy. TG4010 is a recombinant vaccinia virus of the Ankara strain (MVA) expressing the coding sequences of the MUC1 antigen and of the cytokine, Interleukin-2 (IL2). In healthy cells, the MUC1 protein is normally found on the surface of epithelial cells in many types of tissue and works to protect these cells. In tumor cells, several modifications of MUC1 can occur: over expression, hypo- glycosylation and changes in cellular localization. These changes transform the MUC1 protein into a highly immunogenic tumor associated antigen (TAA) and make it an attractive target for cancer immunotherapy. Thus, the strategy is to induce MUC1 antigen expression in a non-tumor environment, i.e., where the immune system is fully functional, in order to induce both innate and MUC1 specific adaptive immunity. In addition to NSCLC, the MUC1 TAA is expressed in many other solid tumor types, such as lung, breast, colorectal, kidney and prostate cancers.

About TG3003:

TG3003 is a humanized monoclonal antibody that was discovered and is being developed by Transgene. TG3003 is directed against human CD115, the CSF-1 cell-surface receptor expressed by all types of myeloid cells, including macrophages. The tumor microenvironment often contains high numbers of M2-type macrophages, often associated with a poor prognosis. M2-macrophages can dampen anti-tumor immune responses, promote tumor growth and metastasis, while M1-macrophages are generally associated with a good prognosis. TG3003 has been shown to inhibit the formation of M2-macrophages and to favor the generation of M1-macrophages and dendritic cells, which play a key role in stimulating the immune response against cancer. TG3003 has also been shown to target another type of myeloid cell, osteoclasts, which are responsible for metastasis-induced bone degradation and pain in cancer patients. TG3003 is currently in pre-clinical development.