Armed antibodies to fight cancer
The Philogen group is a specialist for therapies against cancer. Unlike other private companies, the Swiss-Italian firm has developed a rich pipeline of antibodies consisting of five different molecules being tested in 15 different clinical trials. The R&D facility in Zurich is run by Philogen subsidiary Philochem, which has specialised in many areas. One of them is the chemical modification of immunomolecules called ‘armed’ antibodies.
The development of antibody-drug conjugates has recently been receiving a lot of attention, and not only at Philochem, but in the whole biotech industry. With growing generic competition and a lack of new targets, many companies are looking for ways to make antibodies against known targets more efficient. Antibody-drug conjugates represent an interesting therapeutic approach that combines the desirable properties of monoclonal antibodies with the cell-killing activity of cytotoxic drugs, reducing systemic toxicity and increasing therapeutic benefit for patients. In this area, Philogen and its R&D subsidiary Philochem have demonstrated for the first time that a non-internalising vascular targeting ADC can be used to mediate strong anti-tumour activity in vivo. The scientists believe that bio-orthogonal reactions that modify proteins at specific sites using cleavable linkages are essential for the development of antibodydrug conjugates. Philochem has developed proprietary traceless site-specific linkage technologies to conjugate novel drugs to clinical-stage human monoclonal antibodies.
Phase III in planning
At present, Philogen has four anti-cancer antibody derivatives in clinical studies, as well as an antibody-derivative for the treatment of rheumatoid arthritis. Two registrational studies (one in Phase III and one in Phase II) are in planning. Since it was founded in 2006, Philochem has worked on the following methods for biotechnological product development:
– isolation of human monoclonal antibodies from large combinatorial libraries.
– development of armed antibodies (immuno-cytokines and antibody-drug conjugates).
– discovery and validation of vascular markers of pathology using a perfusion-based chemical proteomics approach.
– design, construction and screening of DNA-encoded chemical libraries of unprecedented quality and size.
Since its inception in 1996, the mother company Philogen has focused on the development of new biopharmaceuticals for the treatment of angiogenesis-related disorders. Angiogenesis – the formation of new blood vessels – is a characteristic feature of many severe pathologies such as cancer, rheumatoid arthritis and age-related macular degeneration.
The company and its founder Dario Neri have been pioneers in the isolation, engineering and clinical development of lead products capable of targeting angiogenesis in vivo. These technologies are integrated into drug discovery programs. The most promising candidate products are further developed in the Siena-based Philogen facilities. Here production according to GMP standards and clinical trials is conducted with the aim of developing superior products for the imaging and treatment of serious angiogenesis-related diseases.
Philogen and Philochem run three different collaborations with big pharma. Together with Pfizer Inc., Philochem is active in the field of target discovery. It assists Merck Serono in the search for biomarkers by generating monoclonal antibodies. And self-assembling chemical libraries are in the focus of a co-operation with MedImmune. Philogen is also in negotiations with other pharma partners to out-license its clinical-stage compounds.