Operating within InCube Labs, a multi-disciplinary life sciences R&D lab based in Silicon Valley, Rani Therapeutics is developing a novel approach for the oral delivery of large-molecule drugs such as basal insulin, which is currently delivered via injections. By replacing painful injections with a painless, easy-to-take pill, the technology has the potential to drastically improve the lives of millions of patients suffering from diabetes, osteoporosis, rheumatoid arthritis, multiple sclerosis, and many other chronic conditions.
The idea is that the pill allows biological drugs, such as proteins, that would otherwise be destroyed in the stomach and intestine, to be delivered orally. This means that patients don’t have to undergo painful injections. For diabetic patients, who must inject insulin daily, this could mean that they don’t need to worry about needles and painful injections. The pill protects the drug inside itself until it reaches the intestine, where needles made of sugar emerge from the pill and inject the drug directly into the wall of the intestine.
Medgadget had the opportunity to ask Mir Imran, Chairman and CEO of Rani Therapeutics, some questions about the technology. Mir Imran is a prolific inventor of medical devices and has founded more than 20 life sciences companies. Mir holds more than 300 issued patents and is perhaps most well-known for his pioneering contributions to the first FDA-approved Automatic Implantable Cardioverter Defibrillator.
See the technology in action here:
Conn Hastings, Medgadget: Please introduce yourself and tell us a little about how you got into medical technology in general.
Mir Imran, Rani Therapeutics: My passion is developing and commercializing medical innovations. I have been an entrepreneur for the past 35 years, and my focus has been on solving major unmet clinical needs. I have a background in engineering and medicine, but even from a very young age, I loved to solve problems and understand how things worked. As a child in Hyderabad, India, I often took apart anything I could get my hands on to see how it worked. My mother eventually started buying toys for me in pairs — one to play with, the other to break down. At 8 years old, I made toys of wood, string and glue, and sold them to classmates. As a teenager, I took radio repair classes. I built AM radios, fit them inside matchboxes and sold them to friends. I later left India for the US and attended Rutgers, where I earned a BS in electrical engineering in 1976. By the time I actually had started my formal engineering training, I had probably a dozen years of hands-on experience.
As a college student, I had an experience that would change the course of my life and led me to the work I do today. I had a summer job working at The Matheney School for Cerebral Palsy Children. They needed engineers to develop communication devices for quadriplegic CP children, so I built a machine for one severely afflicted girl. The unit translated her facial expressions using pre-recorded phrases, allowing her to communicate. The experience was incredibly moving, and it inspired me to pursue medicine. After three years of med school, I decided that I did not want to be a doctor and instead wanted to pursue the business of innovation.
Medgadget: What inspired you to design the Rani device?
Mir Imran: Understanding and trying to solve big problems in medicine is what motivates me. Sometimes I discover problems through my own experience or from friends, and in other cases, I learn about problems through other sources. In the case of Rani, I heard from a friend in the world of big pharma that pharma companies spent billions of dollars over the past 40 years trying to convert injectable drugs into pills. And despite that kind of investment of time and money, the attempts were largely unsuccessful. This sounded like a juicy problem. If a solution could be developed, it would affect millions of patients and would have a major impact on the pharma market.
Take insulin as an example. As a protein-based drug, it cannot be ingested, only injected. With my engineering and medical background, I thought about it from a different perspective. If the pill could protect the drug until it reaches the intestine, and then inject the biologic into the intestinal wall — which has no sharp pain receptors — we could achieve successful administration without pain or loss of efficacy. While previous attempts to convert injections into pills have relied exclusively on chemistry, Rani has approached this challenge with engineering. That is the breakthrough.
Medgadget: Put simply, how does the technology work? What triggers the drug release in the intestine?
Mir Imran: The Rani pill is essentially a mini swallowable auto-injector that delivers the drug directly into the highly vascular intestinal wall, allowing the drug to be absorbed quickly into the bloodstream. Figuring out how to trigger the injection was a challenge. The answer came to me when I reached for an Alka Seltzer after a spicy Indian dinner. The reaction created in my glass gave me the idea to inflate a balloon and inject the needle. So, the patient swallows the pill, and it protects the proteins from breaking down in the digestive tract. When it reaches the intestine, the balloon inflates, prompting needles made of bioabsorbable materials — such as sugar — to be injected in the intestinal wall.
Medgadget: Is positioning in the intestine crucial, or can the pill consistently and reliably deliver the same drug payload? Are there any safety issues – could the pill block the intestine?
Mir Imran: The intestine offers an ideal location for optimal drug absorption into the bloodstream, and its lack of pain receptors make the approach painless. After the drug is administered, the sugar needle dissolves and the balloon and any other ingestible materials pass through and exit the body, without risk of blockage.
Medgadget: What types of drugs can be delivered using the pills? What diseases could these pills be useful for?
Mir Imran: The pill was designed with biologic drugs in mind, such as basal insulin, adalimumab, Human Interferon, and human growth hormone, each a multi-billion dollar market. Patients might recognize brand names, such as Humira® and Avonex®; these are examples of injectable biologics. We have partnered with two of the largest pharma companies — Novartis and AstraZeneca – to test their molecules on our platform. We are also testing a number of off-patent biologics.
Medgadget: Getting people to take drugs consistently is a challenge. Do you think that this pill could substantially enhance patient compliance for diseases where injections are currently needed?
Mir Imran: Certainly. Fear of needles is a major issue for patient compliance, and I saw recent estimates that non-compliance incurs costs $290 billion per year in complications and related hospitalizations.
Hundreds of millions of patients rely on biologic drugs, including people with diabetes, multiple sclerosis, and rheumatoid arthritis. We are talking about patient compliance and outcomes on a massive scale.
Let’s look at a specific example: there’s a basal insulin drug, Sanofi’s Lantus, which has been the historical market leader. About a year ago, Novo Nordisk came out with Tresiba, which was a longer acting insulin. In this case, the drug delivery innovation was a formulation change, causing the insulin to release over 42 hours, which resulted in patients experiencing fewer low blood sugar events between meals. Patients responded very quickly and enthusiastically when drug delivery reduced the frequency of these painful injections. Tresiba is on the way to a billion dollars in revenue within a year of marketing.
Now, imagine eliminating injections all together and delivering the drug through the oral route. This technology could be a game changer for pharma companies that license our technology. Because the market shifts happen very rapidly, partners could end up owning the market very quickly. For patients, this could mean they no longer have to fear or dread the treatment plans designed to help them.
Link: Rani Therapeutics…