Antibodies

The notion of using antibodies as a therapeutic has been the nirvana of drug developers. Bianca Ogden, portfolio manager of the Platinum International Health Care Fund, explains what the science involves and what companies such as Immunogen and Roche are developing using their antibody technology expertise. 

Antibodies are produced by our immune system.  They identify and neutralise pathogens.  In drug therapy antibodies are engineered to attack disease targets instead.  Drug developers like them for their high target specificity.

In the 70s, the structure of antibodies was discovered.  Scientists progressively refined their understanding and began to grow monoclonal antibodies in petri dishes.  In the 80s, humanisation techniques became available removing the potential side effect that murine antibodies exhibited.  By the mid-80s, the first monoclonal antibody was approved and by the late 90s, the antibodies that dominate the top 10 global drugs today were approved.

Today, six out of the top 10 global drugs are antibody therapies generating almost $46 billion in sales last year.  The excitement around this drug class is set to continue, as pharma companies stock up on antibody drugs and technology.  However, more importantly we are about to enter stage two of antibody therapy with the approval of Antibody Drug Conjugates (ADC) and the emergence of more potent antibody molecules or fragments thereof (e.g. nanobodies).

ADCs combine the specificity of the antibody world with the cell killing ability of the anti-cancer small molecule world.  The antibody carries a potent chemical drug and essentially functions like a ‘guided missile’ delivering the payload right to where it belongs, inside a tumour.  The idea is to spare healthy cells, while the cancerous cells get the full impact of the cancer drug.

The linker between antibody and drug is a crucial aspect of this ‘partnership’ and has represented a stumbling block in the past.  Stability was a problem and often the chemical was released too early, seldom reaching the actual tumour.  Ideally the antibody binds to a target on the surface of the tumour cell, the target-antibody complex gets internalised and only then, is the chemical be released.

Immunogen, one of our antibody holdings, is an ADC company that developed a successful linker technology and earlier this year got its first ADC, Kadycla, approved for advanced breast cancer.  Kadycla is the ADC version of Roche’s breast cancer antibody Herceptin.  While Herceptin binds to Her2 and stops cancer cells from growing, Kadycla goes one step further:  once inside the cell it releases its toxin and kills the cells.  Herceptin now has some serious competition!  No surprise that Roche has licensed Kadycla (and developed it) to again increase the standard of care for breast cancer.

Immunogen has a pipeline of ADCs and has alliances with a number of pharma companies.  Kadycla is the first success for Immunogen and we see it as a confirmation that the linker technology does work.

We believe that antibodies as well as antibody-like proteins have a very bright future.  Companies with strong antibody technology expertise will be in demand in years to come.

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