Biology-Centric Hypothesis

To maximize the benefits of our technology, we work with industry collaborators or academics to build a disease hypothesis that is "biology-centric".

A biology-centric approach is very different from the traditional approach which is "drug format-centric".  The traditional approach in a large pharmaceutical company says, well, I have one hundred chemists in my therapeutic area so what disease-associated target can I interdict with a small molecule, and then let's develop that small molecule plus a series of back-up molecules?  The traditional approach in a biotechnology company says, well, I have antibody engineering expertise so what extracellular target can I interdict with an antibody, and then let's develop that antibody and test it in multiple clinical trials across multiple indications?  The traditional approach is reductionist and benefits in a fairly narrow way from the continually increasing disease knowledge base as generated across industry and academia.

In taking a biology-centric approach we ask a much broader set of questions and can operationalize a much broader disease understanding.  For example:

• Which tissues, cells and/or organelles are to be targeted?
• Which of protein, DNA and/or RNA are driving disease pathogenesis?
• Which molecular pathways?
• Which spatial and/or temporal relationships between the bad actors?
• What combination of activation, inhibition, modulation, and/or targeting can be imagined to treat the disease?
• What optimal set of functional agents of whichever formats (small molecule, antibody, antibody fragment, peptide, oligonucleotide, etc.) to bring to bear?
• What stoichiometries or numerical relationships between these elements?

The hypothesis is then translated into a single multi-format medicine in which we can modulate several different underlying mechanisms in parallel.  Many biological mechanisms exist that (i) have been screened by biotechnology and pharmaceutical companies, (ii) have produced candidate drug molecules that have the desired bioactivity, but (iii) where the molecules failed at some development stage (usually for reasons of bioavailability, toxicology or insufficient efficacy as single agents).  Given our ability to work with broad stoichiometry (the ratio of two drugs for instance can be anywhere from1:1 to 1:>1,000), targeted distribution, tailored kinetics of release, and enhanced biocompatibility, the druggability demands on the bioactive drugs are much reduced.  What this means is that there are thousands of 'almost-drugs' out there that can modulate hundreds of useful disease mechanisms and that are sufficiently druggable for use with our approach.  These pipeline molecules can be used directly, and if desired, combined with marketed drug moieties.

In summary, we have a very practical approach that can be rapidly implemented to create multi-functional drugs with the best chance of combating the given disease.

In many cases, pharmaceutical companies are interested in large disease populations.  The applicability of our technology to that end is very clear.  Our potential can be grander and may change or may contribute to changing how disease is treated in the future.  Today a disease is classified according to a broad brush stroke.  Each large disease can be broken down into smaller disease sub-sets based on varying levels of contribution of the different underlying mechanisms.  For example, 80%+ of patients with a disease such as Rheumatoid Arthritis can be encompassed within five or six sub-groups.  Today, one drug is used to treat all of these, but realistically shows benefit only in a minority.  Our approach allows us to start with the dominant drug on the market and to put it on our biopolymer scaffold and have its efficacy enhanced and/or safety improved through bringing additional mechanisms and different stoichiometries and/or different temporal release characteristics and using different variations for the different sub-groups.  This may sound complicated but it is actually a nice drug life cycle management strategy for existing large market drugs.  There is potential beyond this to personalized medicine, but that is for the more distant future (not for feasibility reasons, but predominantly financial).  For example, we can apply the same approach for an individual patient's specific, personal disease biology.  With the advent of our technology, for the first time, this has become feasible and with the hypothesis outlined and the drug moieties selected, synthesis of the new multi-factorial medicine can proceed at a rapid pace.