Intro

For first-time CEOs who’ve recently made the transition from academia to entrepreneurship, building a successful biotech startup goes well beyond realizing their first rounds of funding.

Their new role necessitates striking a balance between advancing the science they’ve painstakingly developed and building a company framework that’s capable of successfully shepherding that science through the discovery and development process and beyond.

Iviva Medical Founder and CEO Harald Ott knows this all too well. He stands at the helm of a company that’s pioneering organ engineering and regenerative medicine technology. Founded in 2013, the company is a spin-out of the Harvard Stem Cell Institute and is focused on developing a solution for end-stage kidney disease.

Theoria Creative spoke with Dr. Ott, who is also a Thoracic Surgeon at Massachusetts General Brigham in Boston and Associate Professor of Surgery at Harvard Medical School, and Brock Reeve, Iviva Investor and Executive Advisor and the Founder of Eos BioInnovation, an incubator and investment firm for early-stage regenerative medicine companies. Together, we discussed their thoughts on transitioning from academia to building a successful biotech startup, the challenges of communicating novel biotechnology ideas to investors, and the excitement they share for early-stage organ engineering and regenerative medicine.

What it takes to build a successful early-stage biotech startup

Q: Brock, what attracted you to Iviva, given that it’s an early-stage bioengineering company?

Brock Reeve: Well, the fact that it was early stage was attractive. The scientific and clinical problem we’re trying to solve is, I think, the next stage of regenerative medicine therapies. People have already done individual cells and tissues. The next stage is at the organ level.

I’ve known Harald for a long time and really respect his work. I think he came up with a very interesting way to solve that problem. Practical, interesting, and unproven admittedly, so it’s risky, and it’s early, but it’s also exciting. Being part of and being able to build something coming out of work that I’ve known the foundations of for a while was just an exciting and fun opportunity.

Q: What does a first-time CEO need for you to consider working with them?

BR: In terms of building a successful company, there are really three key points they need to bring together.

A good idea: a solution that the market or clinic wants and that is meaningful for patients.

The right people: the people aren’t just the CEO or CSO, right? They need to manage a multidisciplinary team of engineers, biologists, material scientists, et cetera and understand enough of those different worlds to bring them together and have the credibility to lead them. They also need a willingness to roll up their sleeves and fix things when they go wrong. I remember walking into the office at one point, and Harald was fixing the dishwasher.

The right approach to solving the scientific problem: a lot of the original science plan won’t materialize, so they need strength of purpose, flexibility around how to get there, and the ability to know when to switch gears. Part of the challenge is not giving up too soon.

Building a successful startup, particularly a technology based one like Iviva, is really a series of de-risking experiments. You need to de-risk the technology, de-risk the market approach, get more data as you go along, and always be looking for questions – what will show that this won’t work? As you get those big questions out of the way, you’re on the path to building a successful solution.

Making the transition from academia to biotech startup

Q: Harald, what made you decide to make the transition from researcher and surgeon to entrepreneur?

Harald Ott: I’ve always been excited about driving technology to patients and focused on translating results to improve patients’ lives. I think what it takes right now, in this phase of the project, is a more serious commitment, and so this was the right time.

Seeing the transition from a very early seed project to something more mature and to see the science still in this very early phase is exciting and really requires a multidisciplinary team to solve. This made it a very attractive opportunity for me. Brock really helped mentor me on both the academic side and the entrepreneurial side. He helped me build the company from early proof-of-concept to a much more functional stage. The team size is bigger, we have our own facilities and equipment, and we are able to execute the experiments that are required to develop a biologic device.

Same as above – (rephrase) and move this to the relevant question above. And let’s eliminate this section.

Q: Brock, what advice would you give to scientists looking to spin out of academia and start their own companies?

BR: Particularly in academia, one thing is not to do it too early, because in academia, the motivations and the way to judge success are very different. You publish a paper about an idea, and it may be successful, but the question is, ultimately, will this work in hundreds of thousands of people? There are differences in terms of the scale of the experiments and some of the initial de-risking questions.

There’s also a question about what motivates you as the academic scientist. Do you want to work in the lab on fundamental technology questions or are you interested in translating the big technology question into practical applications? Academics don’t necessarily have training in how to do that and are unaware of some of the risks and steps they need to take to build something that will actually work in people at scale.

Q: What unexpected challenges have you faced starting Iviva?

HO: When you’re working in academia, you’re exposed to very similar challenges. You have to manage a multidisciplinary team, you live in an ecosystem, you’re under stress to raise funding for your projects and meet deadlines, and so on.

What you realize once you’re in business, is that you’re on your own. In an academic institution, you’re used to somebody else managing the infrastructure. Somebody else works . If you’re in an institution, it’s mostly negotiating for resources and finding ways to get what you need.

In an entrepreneurial environment you need to build it on your own, which has been an extremely educational experience. You’re not only building the technology; you’re also building a project that people are committed to and the plans to house the project all the way through from early technology development and ultimately to manufacturing for the first clinical trial.

BR: Another way to think about it is that the entrepreneur’s job is to maximize the use of scarce resources, whether that’s people or money, and that’s also somewhat true on the academic side. In a company, if you get delayed, you get punished pretty severely by investors or the market. It’s a different way of your feet being held to the fire, which also affects mindset and behavior.

Pitching a novel technology to investors

Q: What are some of the challenges you face when communicating your novel technology to investors?

HO: One of the major challenges is that we’re trying something very new. It’s a new form of curative therapy for chronic disease by leveraging, at the same time, a lot of components that already exist. In many ways, our technology stands on the shoulders of other technologies and other developments in biology, stem cell biology, additive manufacturing, transplantation, and so on.

So, it’s communicating the fact that it’s novel, explaining what it is, and communicating that it’s not just an idea but that there’s a very concrete plan on how to de-risk it and get it into people.

BR: Investors see all the technical risks. There are many elements that you have to pull together. Will they all work?

Many investors to date have been either medical device investors that tend to be mechanical, so they understand that, or they ‘re investors in individual therapies, individual drugs, or individual cells, and they understand that.

Combining cells and materials in a three-dimensional structure to replace organ-level function hasn’t been accomplished yet. No investor has done it before, so it makes them nervous, they have to be willing to take a risk.

Getting an engineered organ into the patient

Q: Given that organ engineering is still early, what challenges need to be overcome in the field to get these units prescribed?

HO: We’re trying to reassemble functioning biologic tissues. We call them organ therapeutics, tissues that fulfill higher-level functions and that are made out of cells. We are not trying to rebuild the kidney. We’re trying to build a biologic dialysis machine that can be implanted.

Sourcing the various components, understanding the systems biology of every one of those components that we’re trying to rebuild, and then assembling those components in a functional way as a living structure, is basically what we’re trying to do.

Various aspects have their own sets of challenges. One being material blood interaction and the fact that living structures need to renew themselves and develop some stability and homeostasis. We also have to, in all reality, simplify the architecture of tissue because we don’t want to rebuild human organs but to fulfill specific functions.

I think the research challenges are defining the functional targets, then sourcing the components that enable these functions, and then assembling them in the correct way as a three-dimensional structure.

Then there is a set of very unique challenges around the fact that we’re trying to manufacture living things. Simply the fact that this is relatively unchartered ground in terms of how to manufacture, how to distribute, and so on makes this challenging.

Additional Information

This interview has been edited for length and clarity.
View our work with Iviva Medical here.