ADVERTISEMENT FEATURE Oxford BioMedica www.oxfordbiomedica.co.uk Oxford BioMedica, a leader in gene and cell therapies With its unique LentiVector platform and expanding state-of-the-art manufacturing facilities, Oxford BioMedica has established itself as the partner of choice for companies developing advanced therapy medicinal products.

A newfound confidence has entered the fields of gene and cell therapy, and biopharmaceutical company Oxford BioMedica has had an impor- tant role in the development of these transfor- mative therapeutic areas. The company, based in Oxford, has 20 years of experience in develop- ing lentivirus-based vectors, and its pioneering platform technologies underpin the design, development and manufacture of a portfolio of gene- and cell-based medicines. Its expanding manufacturing capabilities, in-house know-how and intellectual property (IP) have attracted the attention of leading players in the field, with the company recently entering into a major collabo- ration with to develop chimeric antigen receptor (CAR) T cell therapeutics. Oxford BioMedica has been building its gene- and cell-therapy platform since 1995, when it was spun out of the University of Oxford’s Department of Biochemistry by Alan and Susan Kingsman. An initial public offering on the Alternative Investment Market followed a year later, with a move to the main in 2001. With a growing research program and devel- opment pipeline, Oxford BioMedica has been continuously expanding—thanks to a substan- tial increase in size in 2014, the company now has almost 150 employees. Oxford BioMedica boasts its own world-class Centre of Excellence in process development and manufacturing ser- vices for lentiviral vectors, coupled with a totally integrated supply chain. The approach to gene and cell therapy taken by Oxford BioMedica is based on lentiviruses as a vector for delivering genes. Lentiviruses have the ability to infect nondividing as well as mitoti- Figure 1: Oxford BioMedica's lentiviral vector platform. The platform consists of 'stripped-down' cally active cells, making them one of the most lentiviruses expressing therapeutic genes of interest. Shown is the company's ProSavin/OXB-102 efficient cell-transformation tools available. treatment for Parkinson's disease, which requires the engineering of three genes into the lentiviral They are nontoxic, cause no adverse immune vector and delivery into specific areas of the brain to boost dopamine levels. reactions and have the capacity to carry large or multiple genes within a single vector. on HIV-1, with both featuring key safety features Vector manufacture and www.nature.com/biopharmadealmakers Delivering genes via a single injection of a for clinical applications (Fig 1). process development lentiviral vector has the potential to achieve Using the platform, Oxford BioMedica is able Oxford BioMedica’s move into manufacturing and permanent therapeutic benefits. Oxford to deliver genetic material efficiently and stably process development has been an important BioMedica scientists were the first to directly for both gene therapy and gene knockdown strategic decision for the company—one that administer a lentiviral vector to patients in using RNA interference. The platform has grew out of a necessity to find more cost-effective trials for their ProSavin Parkinson’s disease advantages for delivering genes to nondividing ways to manufacture its products. The company’s treatment. To date over 56 patients have been cells in localized areas such as the brain or eye, state-of-the-art facilities in Oxford now provide a treated with Oxford BioMedica’s LentiVector- as well as for ex vivo stem cell or T cell therapies full range of services, from preclinical to good

dealmakers based products. for which researchers want permanent genetic manufacturing practice (GMP) manufacture for The LentiVector platform offers one of the modification of dividing cells. A patented late-stage clinical development and market sup- most advanced gene delivery technologies technology has recently been added to the ply. Facilities are multipurpose and suitable for in the field, developed using the company’s platform, the Translation Repression in vector all phases of clinical studies and meet all current third-generation minimal lentiviral vector. The Production (TRiP) system, which allows the US and EU GMP standards. But as Alex Lewis, platform uses two systems—one based on company to increase vector yields and improve director of corporate activities and strategy,

biopharma equine infectious anemia virus and the other vector particle purity. stressed, “What we can offer is much more than

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manufacturing services alone.” Oxford BioMedica testing that is important but the problem solving OXB-102, a more potent second-generation is a platform- and product-development partner and strong scientific and analytical skills that we therapy for Parkinson’s disease that the com- that offers technical expertise, vector-related IP can offer to solve technical issues as they arise.” pany believes could have greater efficacy. The and in-house manufacturing, process develop- The company also offers partners its wealth of company expects clinical trials to start in 2016. ment and analytical services, as well as 20 years regulatory experience and a successful track Another central nervous system therapy— of experience. record in bringing new gene-based products into MoNuDin, for the treatment of motor neuron dis- The company is continuing to develop its clinical development. “We can get from concept ease—is in preclinical development. The therapy manufacturing capabilities, applying its technical to the clinic in under 24 months because the uses LentiVector technology to deliver a neuro- expertise and good business practices to regulators are already familiar with our platform,” protective gene to cells affected by the disease. provide even more cost-effective production. Lewis said. In addition to its LentiVector platform, the In 2013, the company received a £7.1 million Using its LentiVector platform, Oxford company has exclusive rights to IP regarding (US$11.4 million) award (including a £5.3 million BioMedica is also developing its own pipeline the 5T4 antigen, a unique protein expressed by (US$8.5 million) loan) from the UK government’s in a number of areas, including ophthalmology. tumors and thought to be involved in metastasis. Advanced Manufacturing Supply Chain Initiative RetinoStat, a gene-based treatment for wet Because the antigen is found in most common to support the development of its Centre of age-related macular degeneration (wet AMD), solid tumors but only at low levels in healthy Excellence for the specialist manufacture was developed as part of the company’s first tissue, it is a valuable anticancer target. Oxford of gene-based therapies. The company is multiproduct alliance with Sanofi in 2009. Wet BioMedica is using the target to develop TroVax developing its manufacturing capability and is in AMD is responsible for 90% of cases of severe (MVA-5T4), a therapeutic vaccine that stimulates the process of expanding its facilities in Oxford vision loss associated with AMD, with up to the immune system to destroy 5T4 antigen– to bring on additional capacity to maintain its 4.5 million patients worldwide. A single injection expressing cancerous cells. The vaccine is based position as a world leader in the manufacture of of RetinoStat delivers two genes directly to the on a modified vaccinia virus Ankara (MVA) vector advanced therapy medicinal products. retina. They encode for two antiangiogenic pro- encoding the 5T4 antigen. Oxford BioMedica has teins, which can prevent the formation of new identified a biomarker that predicts treatment Pipeline partnering aberrant and leaky blood vessels that disrupt the benefit using a simple blood test. Clinical trials In 2014, Oxford BioMedica and Novartis retina and cause loss of sight. Oxford BioMedica are under way in colorectal cancer, ovarian can- extended an initial 2013 collaboration agree- has demonstrated clear proof of concept in stan- cer and mesothelioma, and two of the trials will ment to develop and commercialize oncology dard animal models, and a phase 1 trial has also report results over the next 12 months. therapies using the LentiVector platform. Oxford been completed. In 2014, Oxford BioMedica also initiated its BioMedica will manufacture lentiviral vectors In 2014, Oxford BioMedica granted Sanofi a own in-house CAR T cell program (CAR–T 5T4) required for the production of the Novartis T cell development and commercialization license for using both the LentiVector and 5T4 technology therapeutic CTL019. Pilot clinical trials of this two further ophthalmology products that treat platforms. The product is based on the modifica- CAR T cell therapy have shown significant poten- rare genetic conditions that cause sight loss: tion of a patient’s own T cells, which are engi- tial in treating patients with forms of acute and StarGen, a gene-based therapy for the treatment neered using a lentiviral vector to express an chronic lymphocytic leukemia. Data showed that of Stargardt disease, which causes the degen- antibody against 5T4. These engineered cells 90% of patients with relapsed/refractory acute eration of photoreceptors, and UshStat, a gene are infused into the patient, where they multiply lymphoblastic leukemia experienced complete therapy for Usher syndrome type 1B, the most to form an army of CAR T cells that recognize and sustained remission over 2 years. common form of deaf-blindness. The company the 5T4 antigen and trigger an immune response Oxford BioMedica’s CTO, James Miskin, said is also at the preclinical stage with several that kills the cancer cells. The program is cur- the deal is a validation of the company’s excellent other ocular treatments including EncorStat, rently in preclinical development. According to reputation. “When Novartis looked around the for the prevention of corneal graft rejection, and Mitrophanous, “It’s an exciting field and one with world for a partner able to manufacture lentiviral Glaucoma-GT, for lowering intraocular pressure, huge potential—given Oxford BioMedica’s tech- vectors for their CTL019 program at a high qual- which is being developed in conjunction with the nology platforms, we feel we could progress with ity, they chose us,” he said. Oxford BioMedica Mayo Clinic in the US. the project really fast.” has granted Novartis a nonexclusive license to Oxford BioMedica is further developing As one of the few companies developing its background IP and an exclusive license to its ProSavin, a therapy for advanced Parkinson’s gene and cell therapies to have lasted for two IP for the worldwide development and commer- disease. The disease is caused by progressive decades, Oxford BioMedica is confident that cialization of all CAR T cell products arising from damage to parts of the brain that leads to invol- its products and manufacturing processes will the collaboration. untary shaking and affects an estimated 10 mil- soon be improving the lives of patients with www.nature.com/biopharmadealmakers

Oxford BioMedica’s preferred business model lion individuals worldwide. ProSavin is a lentiviral debilitating and life-threatening diseases. The is to build mutually beneficial, long-lasting vector–based gene therapy that can restore local company hopes to have a global role in the relationships. In addition to its partnership dopamine production in patients with advanced growth and expansion of the sector, through both with Novartis, Oxford BioMedica is working Parkinson’s disease. its own pipeline and strategic partnerships that with GlaxoSmithKline, Immune Design, Sanofi CSO Kyriacos Mitrophanous explained, exploit its LentiVector platform and associated and Pfizer, and it is keen to develop new “ProSavin was the first ever lentiviral vec- know-how. collaborations. tor–based gene therapy product administered

The company offers licenses under its directly in vivo, and we were very pleased with dealmakers LentiVector platform IP, but partnering with the trial’s positive outcome showing the therapy CONTACT DETAILS Oxford BioMedica provides access to much more to be safe and providing significant improve- Peter Nolan, Chief Business Officer through the company’s integrated teams of sci- ments in patients’ motor function.” In 2014, Oxford BioMedica entists and engineers. Lewis explained, “I think Oxford BioMedica was awarded a £2.2 million Oxford, United Kingdom that is why companies come to us—they realize (US$3.7 million) grant from the UK’s innova- Tel: + 44 (0) 1865 783000

it isn’t just the manufacturing and associated tion agency for further clinical development of Email: [email protected] biopharma

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