By Mir Imran, Chairman and Chief Executive Officer, Rani Therapeutics
Mir will be giving the Capstone Keynote at 23rd Annual Medical Technologies: A Frost & Sullivan Executive MindXchange
When I was a child growing up in India, I was fascinated by how things worked. To my mother’s dismay, I spent many of my childhood days taking my toys apart. I liked to see the inner workings, look at the different parts, and take note of how they came together to create something unique. I was always seeking to understand. After a few years of this, my mother made a very smart decision to buy me two of the same toy – one to play with and one to take apart. It seemed she understood the value of hands-on experiential learning and exploration much earlier than I did, and her vision led me to a lifetime of problem solving, engineering and research and development. For the last 35 years, I have pursued a career of developing and commercializing medical innovations. It has resulted in about 22 companies and 400+ patents, but the most important numbers for me are the millions of patients that have been positively affected by these innovations. With over one billion people suffering from one or more chronic diseases, there remains so much opportunity for innovation and that is the inspiration for my work.
Over the years, I have spent considerable time thinking about the process of innovation and evaluating what has led me to be successful in creating products and companies. It has taken me decades to truly understand how successful innovations are created. One important learning was a choice I made early in my career. I decided to pursue the most disruptive innovations and not chase incremental innovations. Many companies have been successful creating solutions that reflect incremental improvements over existing products. There is a place for incremental innovations, but my personal interest and motivation centers on solving the biggest problems and creating solutions that can truly disrupt patient outcomes.
In my work, I have collaborated with and mentored hundreds of entrepreneurs and they all ask a similar question…what advice do you have for aspiring innovators and entrepreneurs? My answer is always the same – go after the big problems. Start with understanding the problem from all facets. Once you truly understand the problem, the solution will reveal itself. If you pursue solutions too quickly without that fundamental understanding of the problem, you might miss the opportunity for a breakthrough.
I have seen this happen many times in my career. Earlier in my career, I was quicker to try to “solve” the problems. I would spend less time thinking through the problem, and more time dreaming up the solution to a problem that I did not fully understand. Experience, maturity and failures have taught me that you must take the time to appreciate the problem, look at it from all sides, enlist other opinions, and see what has been done before. Now I take the time to understand why better solutions do not exist, and digest the challenges that have come before when trying to solve a problem.
I went through this exercise over the last few years as I was developing one of InCube’s portfolio companies, Rani Therapeutics. Through discussions with pharma executives, I was introduced to a giant problem that has been plaguing the pharmaceutical world for decades…how to deliver biologic drugs (peptides, proteins and antibodies) orally? Over the past several decades, these biologic therapeutics have proven to be highly effective treatments for a number of common and chronic diseases such as arthritis, diabetes, multiple sclerosis, plaque psoriasis, Crohn’s disease, and ulcerative colitis, among others. Yet, despite their blockbuster success, the delivery of biologics is far from ideal as these drugs can only be delivered by injection. As a result, patients must endure painful and frequent injections, some as often as daily, which can have a dramatic impact on a patient’s quality of life.
This sounded like a worthy problem to solve and I started looking into it more deeply. After examining the problem, I understood why there were so many failed attempts at delivering biologics orally. Prior attempts failed primarily because pharmacological/chemical approaches did not protect the proteins from degradation and digestion in the GI tract.
When we founded Rani Therapeutics in 2012, we decided to take a completely new approach. I drew on my years of knowledge gathering and experience to understand the problem. My medical school background helped me understand how gastrointestinal physiology worked; my work in GI disorders informed me about the GI tract and its characteristics; my work in mechanical engineering and material science would help me devise a new “solution.” The solution wasn’t going to be a chemical one – we knew those didn’t work; instead it came in a mechanical form.
The solution became what we call the RaniPill™ — a “robotic” pill that delivers an intestinal injection without exposing the drug to the digestive enzymes. The patient takes what appears as an ordinary capsule, but is actually a sophisticated device which incorporates a number of innovations, enabling it to navigate through the stomach and enter the small intestine. This device goes through a transformation, positions itself and injects the drug into the intestinal wall.
We started with the premise that injecting the drug into the intestinal wall would be ideal because there are no sharp-pain receptors in the intestine, rendering the injection painless. In addition, the intestinal wall is highly vascularized which means that the drug once delivered will be quickly absorbed. With deep experience in engineering and material science, we designed the pill to ensure that the drug would stay protected within the pill until injected. To ensure safety of the RaniPill,™ we selected FDA approved injectable and ingestible materials that are either safely absorbed or easily passed out of the body.
One decision we made early on was to formulate the biologic drug with appropriate excipients, in solid form. This has two distinct advantages; first, we can maximize the amount of drug in a small volume and second, the drug in solid dry form has longer shelf-life than in liquid formulation. The next question was what kind of needle do we use for the injection? We decided to create tiny dissolvable needles which would contain the biologic drug. The idea was to deliver the dissolvable needle containing the solid drug into the intestinal wall. The drug would be released after the needle is injected and the needle is dissolved.
The next challenge was to figure out a way to develop enough force to deliver the needle into the intestinal wall. Initially, we considered levers and springs, but quickly ruled that out as no patient will want to swallow springs. We settled on the use of an inflatable balloon-like structure that would supply the force to deliver the needle. Balloon inflation happens when carbon dioxide is produced from a chemical reaction between citric acid and sodium bicarbonate that takes place inside the balloon, and this creates the pressure needed to inject the needle.
The balloon, including the needle and drug, are assembled in a cellulose capsule shell which is then coated with a pH-sensitive polymer that is designed to dissolve at a pH >6.5. This ensures that the capsule does not dissolve in the stomach where the pH is generally less than 5. Once the capsule goes past the duodenum, and the pH rises above 6.5, the outer shell dissolves, triggering the chemical reaction inside the balloon. The balloon then inflates and delivers the needle with the drug. Once the needle is delivered, all that is left is a deflated polymer, having the consistency of a bell pepper skin or tomato skin., We believe this approach will allow us to deliver biologics of any molecular weight regardless of its structure or properties. So not only small peptides and proteins but even therapeutic antibodies can easily be delivered with the RaniPill™.
An ingestible auto injector or “robotic” pill is a completely new concept in the industry. We have created an innovation that was only possible with a deep understanding of a very real and big problem. The solution revealed itself to me after years of research, and now it has the potential to radically improve the quality of life for millions of patients suffering from chronic diseases. It is this kind of work – the understanding of big problems – that has kept me engaged for decades. Every day I am learning. Every day I am problem solving. And just like that little boy in India years ago, every day I am seeking to understand.
Mir Imran is a prolific medical inventor, entrepreneur and investor, who has founded more than 20 life sciences companies and holds more than 400 patents. Many of Mir’s innovations have resulted in new standards of care, including the first FDA-approved Automatic Implantable Cardioverter Defibrillator. Rani Therapeutics was developed at InCube Labs, Mir’s multi-disciplinary life sciences R&D lab focused on developing breakthrough medical innovations in 2012. Mir named “Rani” after his mother. For more information, please visit: www.ranitherapeutics.com and www.incubelabs.com.