BioMedica will receive $26 million up front under the collaboration and $16.5 million due to TroVax.

Sanofi-aventis is shaking up its clinical pipeline, reporting the close of 13 programs, giving rights to anticancer agent TroVax back to Oxford BioMedica, and also licensing four candidates from BioMedica.

The collaboration to exploit its LentiVector gene delivery technology in the development of gene-based ophthalmology treatments sent Oxford BioMedica’s share price up 21%. The agreement includes a $26 million up-front payment to Oxford BioMedica and additional funding of up to $24 million over three years.

With the initial sanofi-aventis payment included, the company’s pro forma net cash balance was £51 million as of year-end 2008, sufficient to support its operations until 2012, according to Oxford BioMedica’s CEO, John Dawson.

The ophthalmology collaboration initially covers four of Oxford BioMedica’s LentiVector-based products: RetinoStat® for wet age-related macular degeneration (AMD), StarGen™ against Startgardt disease, UshStat™ for Usher syndrome 1B, and EncorStat™ for corneal graft rejection. There are currently no existing treatments for Stargardt disease, Usher syndrome, or corneal graft rejection.

Under terms of the deal Oxford BioMedica will be responsible for continued preclinical and Phase I/II clinical development of the products. Sanofi-aventis has an exclusive option to worldwide development and commercialization. The companies aim to have all four products in Phase I/II development within three years. 

Stuart Naylor, Ph.D., Oxford BioMedica’s CSO, stressed that while the agreement initially covers four products, these will represent a springboard from which additional development projects may emerge.

In parallel to the ophthalmology agreement, sanofi-aventis passed all rights to the therapeutic cancer vaccine TroVax back to BioMedica, citing reprioritization of its portfolio. As a result, sanofi-aventis will pay Oxford BioMedica $16.5 million, which includes the settlement of previously committed development costs.

The original transaction covering TroVax was signed in March 2007 and had a total value of $744 million. The company reported receiving $39 million up front and a $9 million milestone fee. The firm would have received another $10 million related to the Phase III trial. The rest of the payments were to come from development and approval in other cancer indications.

TroVax is in clinical development for the treatment of renal, colorectal, and prostate cancer. In July 2008, the Data Safety Monitoring Board (DSMB) for the Phase III TRIST trial of TroVax in renal cancer recommended the study itself should continue but that further vaccinations should be discontinued as the trial would not meet its primary efficacy endpoint.

In October 2008, Oxford BioMedica reported cross-trial analysis of Phase I and Phase II trials of TroVax in colorectal, renal, and prostate cancer. The data suggested a significant association between the magnitude of the antibody response to the 5T4 tumor antigen targeted by TroVax and increased patient survival. Sanofi-aventis confirmed it will continue to support Oxford BioMedica at its forthcoming meeting with the FDA to assess the TRIST study results. If the FDA meeting is favorable, it will actively be looking to repartner TroVax, remarks Dawson.

In addition to handing TroVax back to Oxford BioMedica, sanofi-aventis separately confirmed shelving another 13 clinical-stage product candidates including four in Phase III, three in Phase II, and six Phase I compounds. The decision on four other candidates will be made within the next few months, pending trial results.

The sanofi-aventis portfolio now comprises 51 projects in clinical development (NMEs and vaccines), of which 21 are either in Phase III or have been submitted for regulatory approval.

The latest addition to sanofi-aventis’ resources, the LentiVector system, contains only the few viral components required for efficient gene delivery. Oxford BioMedica reports that its studies have confirmed that 20 minimal lentiviral vectors are able to deliver genes to a wide range of dividing and nondividing cells including neurons in the brain. The LentiVector system is already in Phase I/II trials as the basis of Oxford BioMedica’s gene-based Parkinson’s disease therapy, ProSavin, which delivers the genes for three enzymes required for dopamine synthesis directly into the brain.

The LentiVector technology is ideal for treating chronic diseases that require long-term therapeutic exposure, Dr. Naylor continued, and specific advantages include the system’s ability to target and efficiently deliver genes to nondividing cell types, which is particularly relevant for ophthalmology indications as well as for ProSavin’s delivery of dopamine into neuronal cells.

“Specific attributes of the LentiVector gene delivery system include its ability to promote stable gene expression over the long-term and the ability to deliver a fairly significant genetic cargo. There are also elegant means for restricting gene expression to a particular target site using genetic switches that are part of the development programs for our indications. Manufacturing has been developed on the back of the ProSavin program, and it is scalable and sufficient for commercial supply in all the indications we are pursuing.”

RetinoStat is designed to halt the aberrant blood vessel growth that causes AMD and proliferative diabetic retinopathy. The LentiVector product expresses angiostatin and endostatin genes and preferentially targets gene expression to the retinal pigment epithelial cells via the incorporation of a tissue-specific switch (VMD2). StarGen is designed to deliver a correct version of the ABCR gene, which is mutated Stargardt’s disease, leading to degeneration of photoreceptors in the retina.

UshStat is designed to deliver a corrected version of the myosin VIIA (MYO7A) gene, which is mutated in Usher syndrome IB, leading to progressive retinitis pigmentosa and congential hearing defects. EncorStat uses the same genetic payload as RetinoStat but differs in the way gene expression is controlled, so that it blocks vascularization and prevents graft rejection.

Other News from Sanofi-Aventis
Sanofi-Aventis to Acquire BiPar in Deal Valued at $500M (Apr. 15, 2009)
Sanofi-Aventis to Commercialize AEterna Zentaris’ Late-Stage BPH Drug in the U.S. (Mar. 6, 2009)
Oxford BioMedica to Obtain $250K to Support Gene Therapy for Stargardt Disease (Feb. 5, 2009) 
MIP to Develop Peptide-Selective Polymers for Sanofi-Aventis (Dec. 10, 2008)
ImmunoGen Obtains $4M Milestone from Sanofi-Aventis for Anticancer Compound (Oct. 28, 2008)

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