Scientists Flex — Patients Keep Waiting

In 2007, Pfizer discontinued Exubera, an insulin inhaler that was about the height of a bowling pin, after shelling $2.8 bn to buy it. Exubera was a scientific feat but became the protagonist for business case studies. Exubera required significant teaching time, didn’t allow for dose selection, required minutes of preparation and was not discrete. Despite its inhaled route of administration, it still required patients to inject a basal level of insulin. It became the symbol of the disconnect between scientists and patients; between hypothesis and quality of life. In reality, pharmaceutical development is and was littered with Exuberas but inhalers are not white tablets nor transparent liquids; inhalers are accessible to ridicule by the common public.

When we started DNALite Therapeutics we were tired of seeing all the Exuberas in the gastrointestinal space. Our initial target was a rare inherited form of colorectal cancer. Patients in this space get their entire colon and rectum removed in their youth as a prophylactic measure. This is followed with a lifetime surveillance for small intestinal polyps, frequent hospital visits, and overall reduction in quality of life. As it happened, the incumbents in this space were flexing their muscles on who can best hit one pathway out of several that are defected. Furthermore, there is definitive evidence for these drugs inducing mucosal injury which may lend itself to increased mutagenesis in epithelial cells that already have their checks and balances compromised.

Similarly, the inflammatory bowel disease (IBD) space is littered with anti-TNF drugs competing on who can marginally beat Infliximab, a revolutionary biologic that suppresses immune response. However, Infliximab and its competitors have been only moderately successful in healing the mucus. 75% of Crohn’s patients still get parts of their colon removed. We now need to move beyond just managing inflammation and towards a complete therapy. This means looking beyond the sexiness of hot science topics. The gut microbiome’s role in IBD, for instance, has seduced the imagination and flirtation of scientists. However, the gut microbiome could easily be a moving target due to the versatile nature of human diet and bacteria themselves.

We created DNALite to not be a microbiome company or a CRISPR company or an immunotherapy company. Instead, we are committed to hitting diseases at their core in the simplest (“Lite”) manner. For intestinal diseases, this meant creating the first delivery technology that could effectively release DNA or other biologics into the intestinal stem cells. Intestinal stem cells are responsible for the upkeep of your intestinal lining but are heavily protected by physical barriers. They are known to drive cancers of the intestine and might be ultimately responsible for defective protection barriers in IBDs. We are placing our bets on the body’s front-line generals that have been neglected for too long.