Intact Advancing Drug Delivery for Gastrointestinal Diseases:
An Interview with Sidhartha Sinha of Intact Therapeutics
What is the need Intact Therapeutics seeks to address?
Our initial focus is on ulcerative colitis, a form of inflammatory bowel disease that affects millions of people worldwide. Treatment for this condition varies quite a bit, from oral, to injectable, to topical therapies. Oral and injectable approaches can certainly be effective, but since they often involve the use of immunosuppressive drugs they can have serious side effects. For many patients, a topical approach is preferable because it allows for improved delivery of the drug to that actual site of disease and reduces systemic side effects. Unfortunately, topical therapies delivered via an enema are difficult for patients to retain, and suppositories only extend a few centimeters into the colon so the treatment frequently does not treat the entire diseased area, which typically involves the rectum/sigmoid or left side of the colon.
When we were investigating the problem, I encountered a patient who had been on oral steroids for distal ulcerative colitis for more than 50 years. That's a very long time to be on steroids, and he had experienced all sorts of negative side effects from the therapy. I asked why he wasn’t using a topical treatment since all of his disease could have been treated topically and he said, ‘I've tried it many times; I just can't hold it in.’
"The idea was to develop a formulation that would be liquid at room temperature.... But at body temperature, [it] would turn into a gel."
What key insight was most important to guiding the design of your solution?
Our insight was to create an approach for delivering topical therapy that would not only improve the amount of medication that gets to the inflamed area, but also make it easier to retain. The simple idea was to develop a formulation that would be liquid at room temperature, allowing it to travel far into the colon like a regular enema. But at body temperature, which is several degrees warmer, the formulation would turn into a gel to help it adhere to the colon wall and make it easier to retain.
How does your solution work?
Our solution uses safe, biocompatible ingredients to topically deliver approved drug therapies to patients suffering from ulcerative colitis. The formulation, which is currently delivered via a conventional enema bottle, includes polymers that are liquid at room temperature but transition to a viscous gel with mucoadhesive properties at body temperature to keep the medication in contact with the inflamed areas.
At what stage of development is the solution?
We've done several animal studies in a couple of different disease models. And we completed a preliminary human study where we assessed several factors, including preference in healthy human subjects for our formulation versus a standard liquid enema. That study investigated ease of retention, the presence of any adverse side effects, and whether our formula would travel as far as the liquid enema. Every single patient found it easier to retain Intact’s formulation than a traditional enema, and we also validated that it gets as far into the colon as the liquid enema.
More recently, we got IRB approval to test our formulation with an active, approved therapeutic called mesalamine, a well-established drug used to treat ulcerative colitis, in patients with left-sided ulcerative colitis. We have tested it in two human patients with ulcerative colitis so far, with good results in terms healing the colon and also being easier to use.
What are your plans for the future?
Our initial plan is to focus on providing a better way to deliver mesalamine to get more efficacious results. We are also evaluating opportunities to partner with other entities to co-develop new therapies that can potentially benefit from our drug delivery approach. In addition, we have plans to improve the actual delivery device used to administer an enema to make the experience more acceptable to patients.
Tell us about a major obstacle you encountered and how you overcame it.
From a personal perspective, it has been a challenge to balance my ‘day job’ as a physician and faculty member at Stanford with keeping the project moving. Luckily, we’ve been able to bring on partners and collaborators to fill key roles. Ravi Pamnani, another Biodesign Innovation Fellowship alum, has been instrumental as our CEO and co-founder. And we’ve been working with a number of consultants to help us with the formulation work, as well as with other activities that require specialized expertise such as our regulatory and intellectual property strategies.
How did your Biodesign training help you advance the project?
During my time in the Innovation Fellowship, I remember it was Rich Popp [Stanford Biodesign’s Director of Ethics & Policy] who said, ‘It can easily take 5-10-plus years to get an idea into patient care. So you really have to think about how many shots on goal you have in your career and pick the right ideas to pursue.’
That statement solidified in my mind how important it is to choose the right need, and then really validate it before you commit to taking the project forward. This emphasis on needs identification and validation is the way I approach everything I do in research as well.
"If you feel like you’ve found a solution to a compelling patient need, don’t let anything stop you."
Reflecting on your experience, what advice do you have for other health technology innovators?
Don’t underestimate the importance of collaboration. For me that has been critical. I had an idea, the clinical expertise, and the Biodesign training, but I had never worked on a pharmaceutical product. I had never developed a platform for delivering drugs. And I did not have a background in biomaterials or polymer chemistry. But the project was still doable. The key is to identify the most important risks and figure out who you need to collaborate with to help you address them. If you feel like you’ve found a solution to a compelling patient need, don’t let anything stop you.
Sid Sinha is Intact Therapeutics’ Founder and Scientific Advisor. Ravi Pamnani is the company’s CEO and co-founder. Both completed the Biodesign Innovation Fellowship in 2010-11. To learn more about the technology, visit the Intact Therapeutics website.
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