Pharma-Planta

Prof. Julian Ma, Prof. Rainer Fischer, Fraunhofer IME, Aachen Dr. Julia Boyle, University of Surrey Clinical Research Centre, Guildford Prof. Maurice Moloney, Rothamsted Research, Harpenden

http://www.pharma-planta.net

The Pharma-Planta Project

Recombinant Pharmaceuticals from Plants for Human Health

A public consortium comprising 28 Academic Institutes and 3 Small/medium companies. Funding period 2004 2009. 12M Euros of EU public funding.
http://www.pharma-planta.net

Global access to medicine

In 2009, 23M infants worldwide were not reached by routine immunization services
1.7M children under the age of 5 died from vaccine-preventable diseases in 2008 (WHO Global Immunisation Data; 2010)

The drive for the Pharma-Planta project comes from the need to produce modern medicines economically and in sufficient quantities to meet global demand.

Molecular Farming

An unprecedented opportunity to produce valuable medicines affordably and on a massive scale.

The challenge of making approved pharmaceuticals from plants

Good manufacturing practice (GMP) is part of a quality system covering the manufacture and testing of pharmaceuticals. GMP regulations require (by law) that drug manufacturers ensure their products are safe, pure and effective.

Manufacturing processes must be clearly defined, controlled and consistent.

GMP regulations are designed to minimize or eliminate contamination and errors. This protects the consumer from products that are dangerous or ineffective.

Manufacture of monoclonal antibodies

Mammalian cells current industry standard.
Cell culture. A highly controlled and defined, sterile process High-tech and expensive Limited scalability

Plants
Cultivation of whole plants A variable biological system Non-sterile Low-tech and inexpensive Massive scalability

Pharma-Planta Primary Objective

To move beyond proof of concept and develop candidate products for clinical evaluation in Phase I human trials
Monoclonal antibodies against two major diseases:
HIV (passive immunization and microbicidal use) Rabies (passive immunization)

Scaled-up production

Greenhouse

26 d

29 d

33 d

Scaled-up production

41 d

44 d

Harvested tobacco

Downstream processing

Disruption

Filtration

Filtered tobacco extract

Greenhouse Production of rAb 2G12 in Tobacco

Cultivation

transgenic tobacco plants

cultivated for 45 days in greenhouse

Harvesting

leaves chopped and

shredded in 250-kg batches

GMP

downstream processing using a

custom process, >5 g of pure antibody

Toxicology Clinical trial

product non toxic in rabbits phase I trial in humans

A Phase I study of P2G12 as a vaginal microbicide

Double-blind, placebo controlled, first in woman Dose escalation: 7, 14 and 28 mg

Objectives:
Evaluate safety: clinical safety tests, local reactions, adverse events Evaluate P2G12 concentration in blood and vaginal secretions

Phase I P2G12 safety trial

Study schedule

Dosing
7 mg, 28th June 2011. 3 subjects (2x P2G22, 1x placebo) 14 mg, 19th July 2011. 3 subjects (2x P2G12, 1x placebo)

28 mg, 30th August 2011.

5 subjects (4x P2G12, 1x placebo) Preliminary results 17th October 2011

The Significance of Monoclonal Antibodies

www.Pharma-Planta.net

The Significance of Monoclonal Antibodies

Major products in biotechnology and clinical care
Injectable, topical and oral applications Licensed products already available for: Cancers (avastin, herceptin) Infectious disease (Synagis) Chronic diseases (infliximab, rituximab) Many pipeline products Typical costs 10-15,000 /patient/yr

Summary
Pharma-Planta consortium. a publicly funded academic

A unique plant biotechnology manufacturing facility in Aachen, Germany. The GMP monoclonal antibody drug product from plants has been approved in UK. -derived Mab. Opening the potential of plants to manufacture a range of drugs for the developed and developing world. Our thanks to the European Union Framework 6 Programme funding this work. for