Pharmaceutical Backgrounder

The pressures are enormous on the health care sector, and on biotechnology and pharmaceutical companies in particular, to deliver better drugs.  Most drugs are incremental in their efficacy to the point that statisticians are the final arbiter as to whether a drug works.  This is unacceptable.  Drugs need to have a level of efficacy such that even a child can look at the data and say whether it works.

More efficacious drugs are faster and cheaper to develop, can be progressed and approved more rapidly by the FDA, have a clear and recognizable impact on the patient, and will be commercially differentiated.  Such drugs are more valuable and reimbursable (even for orphan populations as witnessed by Sanofi's recent acquisition of Genzyme for over $20 billion) and will in most cases be cost effective for the health system and the economy as a whole.

For pharma companies with their many patent expiries, accessing innovative new drugs through internal discovery, or more likely collaboration or acquisition, is now a matter of survival.

Today's drugs are composed of different basic substances such as proteins (e.g. injectable interferon), peptides (e.g. injectable insulin) or organic small molecules (essentially all orally available drugs such as ibuprofen and some injectable drugs such as the chemotherapy agent irinotecan).  These basic substances generally can be engineered to do only one thing, so today's drugs are largely uni-functional, a remnant of the lock-and-key approach of traditional drug discovery and development efforts.

However, most diseases are multi-factorial in that there are multiple underlying mechanisms contributing to the disease.  Recent research and clinical studies have shown that combining different drug formats into a single interconnected molecule can dramatically improve efficacy against the disease even in refractory patients, and surprisingly, in some cases can be many fold better than merely administering the drug substances at the same time in a co-formulation.

But current ways of implementing multifunctional drugs are clumsy.  For example, conjugating a small molecule to an antibody can increase efficacy for diseases like cancer, but the resulting medicine is limited in its ability to be modified without an increase in other liabilities such as clearance and toxicology.