Aventis Spins Off Gene Therapy, Returns p53 Commercial Rights To Introgen

Aventis is reducing its direct involvement in gene therapy research with a spin off of its Gencell division and return of responsibility for worldwide development of p53 gene products to Texas biotech firm Introgen.

The company announced April 2 that it will spin off Gencell into a new entity focused on gene therapy research and development. Aventis will retain a minority investment in the new company that will seek external shareholders.

Formed in 1994 by Rhone-Poulenc Rorer, Gencell was established as a gene therapy division that would seek external collaborations within a network of academic institutions. Gencell became part of Aventis Pharma in 1998 with the merger of RPR and Hoechst Marion Roussel.

Since the merger, Aventis has been focusing its early research efforts on the development of small molecules for the treatment of various diseases and the Gencell division has not received adequate resources for its projects.

Aventis has over 50 small molecule projects ongoing and in June 2000, the company announced a $450 mil. research collaboration with Millennium Pharmaceuticals for small molecule discovery in the area of inflammatory diseases (¹ (Also see "Abbott/Millennium Metabolic Disease Deal Aims For 4-5 Drugs In 10 Years" - Pink Sheet, 19 Mar, 2001.)).

Aventis will continue to serve as a development and marketing partner for Gencell's lead product NV1-FGF, which is being developed for the prevention of leg amputation in patients with severe peripheral artery obstructive disease. NV1-FGF is expected to enter Phase II this fall and come to market in 2006.

The product consists of the fibroblast growth factor gene inserted into a plasmid DNA, which is then injected into the muscle in saline solution. FGF promotes growth of new blood vessels to replace obstructed arteries. Aventis estimates that 200,000 people in Europe and the U.S. face leg amputation due to PAOD annually.

The next most advanced Gencell project is its thymidine kinase immunotherapy, which is being studied preclinically for cancer and will be developed with an external partner.

Gencell is also developing genes for coronary artery disease, such as VEGF-b, and plans to discover other genes with anti-angiogenic properties.

The company plans to reduce its involvement in the field of adenoviral vectors; Aventis indicated that adenoviral vectors have re-administration problems. Gencell plans to focus primarily on non-viral vectors, like plasmids. Gencell's TK-immunotherapy, however, uses an adenovirus vector.

Gencell will be headed by Aventis' Senior VP- Drug Innovation & Approval-France Francois Meyer, currently also worldwide head of Gencell.

The company will be based in the Paris region, separate from Aventis' Vitry R&D site. However, Gencell will continue to run its production facility there. An initial public offering will be considered after the company is established, towards the end of 2001.

Aventis also pulled back from its development agreement with Introgen for p53 gene therapy products. Again, Aventis indicated that p53 research had suffered from internal competition for resources.

Instead, Aventis will invest $20 mil. in Introgen, upping its equity in the Austin, Texas-based company from 18% to close to 25%. Introgen will also receive a 5% equity stake in Gencell. The Introgen collaboration with Aventis (RPR) began in 1994.

The investment will allow Introgen to commercialize INGN 201, an adenoviral-based p53 gene therapy for head and neck cancer. The product is currently in Phase III trials in the U.S. and Europe that are expected to be completed in 2003. Introgen plans to file a BLA for the product in 2004.

Introgen plans to build a North American sales force of oncology specialists numbering between 50 and 70 who will be recruited six to nine months pre-launch.

INGN 201 is in development for other cancers including: bladder; recurrent glioblastoma; non-small cell lung; ovarian and breast; prostate and lung cancer. Introgen's NSCLC trial of INGN 201 was the subject of a letter from Rep. Waxman (D-Calif.) citing lax oversight by the National Institutes of Health of gene therapies (² (Also see "Aventis/Introgen Adenoviral Gene Therapy In Phase III For Head/Neck Cancer" - Pink Sheet, 28 Feb, 2000.)).