Fighting Fear – the Entrepreneur’s Enemy

How often have you heard someone say “I thought of this 10 years ago” when they see a new product on the market? Assuming they really did think of it 10 years ago, then why didn’t they do it? According to Mir Imran, an entrepreneur and venture capitalist, what holds most people back in any entrepreneurial endeavor is fear. How do you get the funds? What if it doesn’t work? There are many hurdles on the road to building companies, and one must navigate those carefully to be successful.

Over his career of more than 35 years, Imran has been involved in more than two dozen start-up healthcare and medical companies. In this interview, he gives his insights into what makes a successful entrepreneur.

What’s the key to success as an entrepreneur?

In any endeavor, fearlessness is crucial. It is important to recognize the difference between fearlessness and recklessness. Recklessness comes from arrogance, but fearlessness comes from confidence in your abilities and a well thought out approach. When I began my career in my twenties, I had many fears. But as I matured and gained more experience, I learned to understand and overcome my fears, and as a result, I had more confidence in my abilities.

How did your entrepreneurial adventure begin?

My background is in engineering, mechanical science and medicine. I started my career in the late 1970s when I co-founded a medical company to develop the first implantable defibrillator. Today, defibrillators are routinely used in cardiology for the treatment of arrhythmia, and the technology has been implanted in a couple of million people worldwide.

Since then, I’ve started around two dozen companies, mostly in different chronic disease areas. About 15 of my companies have been acquired by large corporations. Most of my colleagues started one or two companies, made some money, and then started playing golf or became venture capitalists. I find golf incredibly boring…

So you are still working on start-ups?

Right. I am fascinated by innovation. How does innovation work? How does creativity work? I’ve read a whole host of books on the subject – you’ll find thousands if you search for them, but none of them teach you how to innovate. Most books talk about how people innovated in the past, or they discuss the character and personality traits of innovators. But most innovators are not introspective, and don’t spend much time trying to figure out how they innovate – they are just so happy they did. And most innovators have just one or two big ideas in their life.

I was intrigued by this process, and I thought if I could do it once then why couldn’t I keep doing it? And so I did. I now have more than 400 patents in the US and around 1500 worldwide. For example, I do much of my best work through my R&D lab and incubator, InCube Labs, where we pursue major unmet medical needs. One of InCube’s portfolio companies is Rani Therapeutics, where we are working on an oral method for delivering biologics, which is something of a holy grail in pharma development. Going after these big problems is what motivates me.

What inspired you to tackle this challenge?

The spark of inspiration came to me about five years ago during a conversation with an executive at a large pharmaceutical company, who told me about an oral biotherapeutic company that they had invested in that had just shut down. I’m always interested in failure – failure indicates unsolved problems – so I asked what had happened. He told me that over the last 40 years there have been hundreds of attempts made at solving the problems associated with delivering biologics orally. Although a few groups have achieved some minor successes, most have failed, and the advances made haven’t really led to practical approaches.

After that conversation I started to think more about the topic. If all attempts so far have failed, it’s obviously a really juicy problem – meaning that the solution could have a profound impact on the market and most importantly, for patients. With that in mind, I started working to understand the problem more deeply and came up with a completely new approach for solving it.

What progress have you made in the search for this ‘holy grail’?

I’d already done a fair amount of work in the gastrointestinal (GI) tract area with other research projects, so I knew the biology and physiology. I came to the conclusion that biologics can only be delivered by injection. But I also knew that intestines do not have pain receptors, unlike the skin; you can poke needles into your intestines all day long and you won’t feel a thing. I imagined an orally-administered pill that would travel into the intestine and then inject the drug. The patient would be oblivious to the process, gaining the benefit of an injected drug without the pain associated with needles.

It’s not as easy as it sounds and there were many challenges. First of all, we had to make the capsule pass through the stomach intact, so we developed a pH-sensitive protein that preserved the pill. In the intestine, the pH begins to rise and the outer shell dissolves.

The next challenge was figuring out how to inject the drug.  Rather than a traditional metal needle, we made micro-needles out of sugar. The drug is inside the needle in solid form, and the needles are fully inserted into the intestinal wall.

For any injection, you need a force. We created a small polymer balloon that inflates itself using carbon dioxide that’s produced by an internal chemical reaction. The two chemicals are allowed to mix together to initiate the self-inflating reaction once the outer shell dissolves. As the balloon inflates, it pushes the needles into the intestinal wall.  Because the intestinal wall is designed for absorption of nutrients, it is highly vascularised so when the sugar needle is inserted it dissolves in less than a minute. Once the needles are injected, the balloon collapses, the CO2 is absorbed in the tissue and the patient passes out the balloon, which by now has the consistency of a tomato skin.

The concept is simple but it’s taken us years to figure out all the details. We have done hundreds of pre-clinical experiments with excellent results. We’re now in discussion with several big companies and recently announced an initial collaboration with Novartis to begin feasibility studies. As for commercial manufacturing, we’ve been paying a lot of attention to the scalability of the design from the outset; we’ve already set up a small pilot line as a starting point.

Not all projects are a success; how do you cope with failure?

While I have had many successes, I have certainly not been immune to failure. But those failures never devastate me. I try to understand and learn from them. I believe that failures can make you a better problem solver, innovator and entrepreneur.

In science, research projects typically fail at the exploratory phase – and that happens before we form companies. That said, companies clearly still fail. The trick is to learn valuable lessons from any failure. In my early days, after four or five successful companies, I had a failure. I had set up a biomaterials company; the business model was to out-license the materials we were creating to other companies. After a couple of years, I realized that medical device companies were not as open to licensing fees, and that it was a horrible business model. There was nothing wrong with the materials we had created and we actually used them later ourselves, but the business model was flawed and not scalable. I shut the company down, and learnt a very valuable lesson about business model choice.

Another failure I experienced was in the early 1990s, when I came across a material with really interesting shape-memory/super-elastic properties. I was so enamored by the technology that I decided to set up a company. I talked to a cardiologist about developing an electrically steerable guide wire. The cardiologist said it was an amazing idea, so I went ahead with the start up.

A few years later, I had developed a product and went back to a larger group of cardiologists. They asked me, “Why on earth have you created this product? We already have guide wires that will allow us to navigate the vascular anatomy.” In fact, they weren’t interested in complicated electrical steering. It was a real wakeup call. I shut down the project but I actually did make the company a success. Most importantly, it was probably the best lesson I’ve learned in my entire career: don’t fall in love with a technology – focus on the problem. In other words, don’t start with a technology and then look for a problem to solve; instead, start with the problem – take the time to understand it inside and out – and then let the problem tell you how it wants to be solved.

Any final words of advice for would-be entrepreneurs?

As I tell many aspiring entrepreneurs, you must select your problems carefully. You must make sure they are worthy of being solved. Is a new solution really needed? Will the new solution be an incremental or substantial improvement over existing solutions? And as you develop the solution, you need to keep asking what attributes of the solution make it worthy of commercialization. If you can tackle these points, you’ll have the makings of a successful company.