Biolex Therapeutics Facility Expansion, Pittsboro, North Carolina, USA

Biolex Therapeutics is a biotech company involved in the development and commercialisation of complex proteins and monoclonal antibodies that have not been amenable to production using traditional methodology or are very expensive to produce using traditional methods. The company has a unique patented method called the LEX System that uses Lemna (a plant source) as a transgenic host in the manufacture of therapeutic peptides.

The Lemna-based LEX technology was obtained as part of the acquisition of the French biotech company LemnaGene in July 2005.

Biolex is working on the development of its own pipeline of products as well as supporting the programmes of strategic partners. One of the lead product candidates is Locteron, which is under joint development with OctoPlus. Biolex also has a multi-protein strategic alliance with Centocor and collaborations with other biotech companies including Medarex. The Biolex facility is based in the Research Triangle region of North Carolina.

LOCTERON

Locteron is a controlled release formulation of recombinant human alfa interferon that completed Phase I clinical trials in 2005 and has recently reported some results of Phase 2a trials. The Phase 2a randomised study, which is known as SELECT-1 (Safety and Efficacy of Locteron: European Clinical Trial-1), will seek to evaluate a range of up to four doses of Locteron given every two weeks in combination with the antiviral drug ribavirin, in treatment-naive hepatitis C patients with the geneotype-1 variant of the virus.

The 32 patients on the trial were treated with the combination therapy for 12 weeks and results were obtained in the middle of 2007. The results of the trial were presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The results showed a significant dose response and also that patients suffered far fewer side effects than other pegylated interferon systems.

Biolex and OctoPlus have planned to start SELECT-2, a Phase 2b trial of Locteron, in 2008. The 12-week Phase 2b trial results will be used as the basis for dose selection in the Phase 3 development programme.

Alfa interferon is a protein used to treat infectious diseases, such as Hepatitis C and B, and certain cancers. The product, called LocteronT, is a combination of OctoPlus' proprietary biodegradable PolyActiveT drug delivery technology with Biolex' BLX-883, a recombinant alfa interferon produced using LEX SystemT.

LocteronT is designed to be more convenient for patients than the currently used pegylated alfa interferon, as it can be administered every two weeks.

THE LEX SYSTEM

The LEX System is a system of technologies that gives Biolex the ability to develop a therapeutic protein from the primary amino acid sequence through a scale-up of purified cGMP product suitable for clinical trials and commercial supply. The system couples the natural characteristics of the small green aquatic plant, Lemna, with advanced genetic engineering and protein recovery methods.

The system is ideal for the production and development of hard-to-make proteins (such as peptides and cytokines) and monoclonal antibodies. Peptides produced with LEX include multimeric proteins, alfa interferon and other cytokines, and monoclonal antibodies.

In May 2007 Biolex announced an agreement with Genmab (antibody development) to evaluate the LEX system as a manufacturing system for antibodies developed with Unibody technology.

BIOLEX GMP FACILITY

In 2005 Biolex undertook the expansion of its Good Manufacturing Practice (GMP) biomanufacturing facility in Pittsboro, North Carolina. The facility, which was first opened on 27 September 2004, required further expansion. This was due to the increase in the number of collaborations with larger pharmaceutical concerns to develop peptide therapeutics and also its own increased product pipeline.

In 2004 Biolex had formed four top-tier corporate collaborations for ten proteins including Bayer HealthCare (two proteins), Centocor Inc (six proteins), and Debiopharm S.A. The facility employed 45 personnel when it first opened – the Phase 2 expansion doubled that number to 90 and also doubled the production capacity.

DESIGN AND CONSTRUCTION

The facility was designed and constructed between March and August 2005. Over this five month period the facility was constructed in a modular fashion using a 50 year old converted brick built textile mill as the building to house the manufacturing and processing equipment.

The floor space of the phase two expansion is 7,500ft² (giving a total of around 13,000ft²) and the project required an estimated investment of $3.6m. The next stage of expansion will take place according to the commercialisation of Locteron and other drugs in the pipeline and will probably require 50,000ft² of space.

The construction project was awarded to O'Neal Inc on a design-build basis. The design was carried out by O'Neal Engineering Inc; the construction was carried out by O’Neal Constructors LLC and the validation by O’Neal Inc. Because of the use of an older building, the simplicity of the design and the use of modular systems for the processing equipment, the phase two expansion was completed, validated to full GMP standards (August 2005) and in use for producing APIs (Active Pharmaceutical Ingredients) by the end of October 2005. The process of bringing a new plant on-line might usually take two to three years.

The reduction in time with the Biolex expansion will allow capital to be invested later in the clinical development pipeline, potentially avoiding capital investment risk. The equipment suppliers for the new facility included Controlled Environments, PureFlow, Advantage Engineering and Covington.

Equipment installed included media preparation suite, cleanroom, temperature controlled storage facilities, simple modular constructed environmental chambers for plant growth (adapted from agricultural equipment) and a downstream processing and purification train.

The requirement for upstream process and utility equipment was minimised because of the use of the genetically stable Lemna plant, which just requires salts, carbon dioxide and light for peptide expression. There was also no requirement for many stainless steel vessels with CIP and SIP systems as well as WFI and steam clean systems.

The use of the transgenic Lemna meant that the project involved mostly architectural changes to the building, HVAC installation and electrical design and construction. Many of the utility systems were bought off the shelf, which also saved money. The modular design saved a lot of time and brought down costs.