So much of the process of drug discovery revolves around answering questions: “what does this target do with respect to the indication”, “how (in)tractable is this target”, “how good are the models for this indication”. With all of the focus on results, we sometimes forget how important the art of storytelling is in the furtherance of science.
Many companies hold a science meeting either once a week, or once a month. If gives scientists a chance to practice their story-telling skills — translating ideas and results into terms that are more easily accessible and understood. And groups like BioToasters provide scientists with similar opportunities outside of their business.
I was reminded how important storytelling was at a recent meeting of the San Diego Entrepreneur’s Exchange when the Jonathan Lim, CEO of Ignyta Pharmaceuticals, gave an insightful and inspirational talk on the power of perseverance in the face of adversity. His company and an East Coast competitor had been in a race to be the first to bring to market a drug that targeted TRKA a protein which plays a key role in a number of types of cancer.
During the presentation, he shared some images which showed remarkable shrinkage of colorectal tumors over the course of a month.
In passing, he mentioned that one of their challenges had been to find enough patients to be able to carry out the clinical trial. In pancreatic cancer, I had seen similar challenges, with barely 4% enrollment of eligible patients in most trials.
All through the talk though something was bothering me. I’ve been interested in perineural invasion for many years. It’s a common co-morbidity found in 90% or more of pancreatic cancer patients. Tumour cells invade nearby nerve tissue causing extreme pain. It’s a difficult indication to treat, the standard of care is often not durable, and because it typically falls under the rubric of palliative care it’s often given short-shrift when it comes to research funding.
But even the briefest of scans of review articles on the subject will show that in a number of papers, perineural invasion has been shown to play a role in the progression of pancreatic cancer. As one paper declared in its title, “Perineural Invasion: More Than Pain”.
What had been puzzling me was this — TRKA plays a large role in perineural invasion. And some studies in mouse models of pancreatic cancer had demonstrated that inhibiting TRKA resulted in a reduction in tumor size and a reduction in pain. [1–7]
So given the role that TRKA played, and given the fact that 55,000 patients were going to be diagnosed with pancreatic cancer this year (of which at least 90% would have this condition); why then did they not approach the pancreatic cancer patient community and recruit from there?
I put the question to him after the talk and was surprised at the answer. The problem was that in the minds of investors, treating perineural invasion was not as compelling a story as treating colon cancer. By making cancer the focus of their trials they were able to find the investment they needed. The results of their trials (and the concomitant story) attracted the attention of Roche, and that was enough for a buy-out. And the resulting drug, Entrectinib is currently going through its Stage II/III trials for extra-cranial solid tumours. So I can’t really argue with success, and I’m hopeful that their work on Entrectinib and a Smoothened-inhibitor will bear fruit for them and may eventually help pancreatic cancer patients. A quick check of ClinicalTrials.gov confirmed that Ignyta was currently conducting a Phase II basket trial that included pancreatic cancer patients.
So a story can have a profound effect on a company’s financial future, but often the stories that we tell during drug discovery play just as important a role. Stories can inform, recruit and inspire colleagues, they can point the way towards unmet medical need, and more often than not, they can spur further investigation by uncovering unasked questions.
At Aspen, we’re always interested in these stories. We’re interested in the how’s and why’s of target selection, and everything from the point at which that decision is made, to the point at which a new drug-like molecule is brought to the clinic. That is, in part, why we’ve built Pipeline our pharmaceutical portfolio and project management application: to give you, our customers, better tools for telling stories.
Contact us to find out how you can participate in our early access program.
References
2. Watson JJ, Allen SJ, Dawbarn D. Targeting Nerve Growth Factor in Pain. BioDrugs. 2008;22: 349–359.