BioWorld International Correspondent
PARIS Transgene SA, which already has five products in clinical development, mostly for the treatment of cancer, is hoping to initiate clinical trials of a new therapeutic gene this year and aims to have its first product on the market by 2006, the company’s CEO, Gilles Bélanger, told a conference in Paris last week.
He added that the Strasbourg-based gene therapy company had sufficient cash to fund its activities up to the beginning of 2005, by when “it will have the support of very strong trial results to go back to the financial markets.”
Bélanger also said he would be leaving Transgene in July to join another unit in the BioMérieux-Pierre Fabre group, Transgene’s controlling shareholder. He will be succeeded by Jean-François Carmier, who was Transgene’s vice president of pharmaceutical development between 1996 and 2001 and has just rejoined the company as deputy CEO.
Bélanger, who replaced former CEO Bernard Gilly in November 2000, maintained that he had accomplished his mission, which was to put Transgene onto a sounder strategic and financial footing. The company is now focused primarily on cancer and, to a lesser extent, muscular dystrophy (Duchenne’s disease), while it has reduced the number of gene therapy vectors under development from five to three adenovirus, pox virus and nonviral and has spun off its cardiovascular activities into a separate unit within the group.
Of the five products Transgene has in clinical development, four are for the treatment of cancer (two in Phase II and two in Phase I) and the fifth is for Duchenne’s disease (in Phase I trials). The two products in Phase II are anticancer vaccines that carry specific tumor antigens. They both use the highly attenuated MVA pox virus as a vector and carry interleukin-2 (IL-2) to enhance the immune system response, but one, MVA-HPV-IL2, delivers a gene coding for the HPV antigen while the other, MVA-Muc1-IL2, delivers a gene coding for the tumor antigen Muc1. Each is in two separate Phase II trials in different indications.
MVA-HPV-IL2 is being developed for the treatment of cervical and vulva cancer, as well as for cervical and anal/genital neoplasias. Phase II trials in the indications of cervical cancer and vulvar intraepithelial neoplasia (VIN 3) started in October and December 2001, respectively, while a trial in cervical intraepithelial neoplasia (CIN 2-3) is due to get under way shortly. Final results are expected in 2003.
As regards the MVA-Muc1-IL2 vaccine, Phase II trials in the indications of breast and lung cancer started in January, while Phase II trials in prostate and renal cancer are due to begin in the first and second quarters of this year, respectively. The product’s potential therapeutic targets also include pancreatic, gastrointestinal and other cancers. The various trials involve patients at different stages of disease and different administration protocols (monotherapy in varying doses, combination chemotherapy). The results of the first three trials are due to be fully evaluated by the last quarter of 2003, and the renal cancer trial by the first quarter of 2004.
Transgene also is developing two nonspecific immunotherapies for cancer involving the delivery of IL-2 and interferon-gamma via the E1-E3-CMV adenovirus vector. They are being developed for the treatment of solid primary or metastatic tumors open to intra-tumoral injection (such as renal, lung, breast, gastrointestinal, head and neck cancers and melanoma). One delivers IL-2 (Ad-IL2) and the other interferon g (Ad-IFNg).
A Phase I trial of Ad-IL2 started in June 2001 in the indication of solid tumors and melanoma and will be completed next September. After that, Transgene plans to focus development of the product on combination chemotherapy for melanoma and soft sarcoma tissues. In the case of Ad- IFNg, a Phase I trial started in January in cutaneous T-cell lymphoma and also is due to run until September. Further development will be in the same therapeutic area.
Transgene Research Director Serge Braun said the company was continuing to look for new therapeutic genes with different mechanisms of action against cancer. A particularly promising one in preclinical development was the FCU1 cytotoxic gene, he said, adding that the company was due to decide this year whether to take it into clinical development. Before the end of 2002, Transgene also plans to select another gene for development, which will be an angiostatic gene that destroys tumors by preventing the formation of blood vessels.
Bélanger explained that the company’s business strategy was to take drug candidates as far as Phase II and then enter partnerships with pharmaceutical companies that would partially or totally fund Phase III trials and take charge of their regulatory filings and commercialization. He told BioWorld International that the first agreement would not be signed before 2003, because Phase II trial results would be in by then and the company would be in a stronger bargaining position.
Although it intensified its clinical development program in 2001, Transgene managed to reduce its operating expenses to EUR25.6 million (US$22.3 million) last year from EUR29.4 million (US$25.6 million) in 2000, so its annual burn rate declined from EUR21.7 million to EUR17.3 million. The reduction in costs enabled it to cut its annual loss marginally to EUR21.9 million in 2001 from EUR22.5 million in 2000, despite a sharp drop in revenues from EUR4.7 million to EUR1.3 million.
Thanks to a rights offering completed in May 2001, which netted the company EUR60.6 million, Transgene had cash in hand of EUR71.8 million as of Dec. 31.