John Gill, PhD, is the Director of Research at Audion Therapeutics, a small biotech startup split between research activities at LabCentral in Kendall Square and its headquarters in Amsterdam. Gill leads Audion’s drug discovery and regenerative biology program for sensorineural hearing loss, managing lead compound identification, in vitro pharmacology, and cellular assay screening. Prior to heading research at Audion, Gill completed a postdoc at Harvard Medical School and was subsequently on the faculty before returning to industry to translate his experience and expertise into human therapeutics. Gill spoke to Synapse about his multiple transitions between industry and academia and the path forward for Audion as it moves a new-in-class research program into clinical trials supported by partnerships with Eli Lilly and the European Union.
Audion: Discovering new drugs for age-related hearing loss
“We refer to this as a corporate partnership model as opposed to a standard series of VC-backed funding. The alliance with Eli Lilly provides not only access to some of their molecules but also expertise in how to bring a drug candidate from a startup-sized company all the way to a product in the clinic.”
SYNAPSE: Tell us about how Audion was founded and the problem it set out to solve.
GILL: Audion was founded by three people, Rolf Jan Rutten, Helmuth van Es, and Albert Edge, who came together to develop technology that came out of Albert Edge’s laboratory at Massachusetts Eye & Ear Infirmary. They were interested in a therapeutic approach to treat hearing loss by enhancing a part of the cochlea known as the organ of Corti. Over one’s lifetime, the ciliated hair cell receptors that transduce sounds within the inner ear gradually lose the ability to function properly due to normal aging or damage from noise. The hair cells that transduce sound within the organ of Corti are surrounded by cells called supporting cells. During development, lateral inhibition prevents the supporting cells from differentiating into receptor cells - it’s similar to the retina where cells become organized similarly to allow the discrimination of fine visual contrast points. With regard to hearing, the discrimination occurs with the frequency of sound waves along the organ of Corti in the ear. Frequencies are able to be exquisitely separated in a refined fashion by the spacing between the receptor cells. As cells die, they leave a blank space in between them that no longer contains active receptor cells. Our goal is to stimulate supporting cells in the spaces between the receptors to convert into replacement hair cells.
SYNAPSE: What is the timeline for clinical trials of Audion’s therapeutic?
GILL: We’ve been developing our program with Eli Lilly for a couple of years and we hope to begin clinical trials next year. Our clinical development program is largely supported by a grant backed by the European Union, which involves clinical investigators and research institutions in five countries and this includes Eli Lilly.
SYNAPSE: Does the relationship with Albert Edge’s lab still continue, and how does it work in practice regarding the intellectual property coming out of his lab?
GILL: Audion has licensed technology from Mass Eye & Ear that was developed by Albert’s group. Albert remains a founder of Audion, but there is no current relationship with his research group.
SYNAPSE: Were the other two founders, Rolf Jan Rutten and Helmuth van Es, in Albert's lab?
GILL: No, they were in Amsterdam, and previously were business colleagues with Albert. There was earlier industry expertise between the founders in areas performing stem cell regeneration work. To have that type of industry experience, take it back into academia, and then use that expertise to start biotech companies is similar to my background as well.
Gill’s Path to Audion: Back-and-forth between industry and academia
“When starting graduate school, I thought, 'This will be great - I’ll just get my ticket punched and go back into industry right away.' But it’s really not that easy. Graduate school basically unscrewed my head and rethreaded it back on, and I saw things much differently.”
SYNAPSE: What did you do in industry before graduate school and how did that lead you to do a PhD?
GILL: After my undergraduate studies in molecular biology, I went immediately into industry as a laboratory technician. Technically, I was a “production operator” working midnight shifts at a biotech company where we were taking recombinant DNA, putting it into E. coli, growing up the bacteria in giant stainless steel tanks, purifying overexpressed human proteins, and putting them into vials for clinical trials. I saw that from an early age of 22, right out of college.
I continued at a couple of different biotech companies for the next 10 years until I decided to go back to graduate school and pursue my PhD at the University of Colorado in Boulder. At that point, I was working at a biotech company that was developing recombinant fertility hormones for reproductive assistance. The work got me interested in reproductive sciences and reproductive endocrinology, which is what I went to graduate school for. I studied the developmental biology of how the brain differentiates between males and females, specifically the cellular differentiation of neuronal subtypes in response to different hormonal signals throughout development. That’s where my expertise grew regarding how to differentiate specific cells within the inner ear.
SYNAPSE: How did you decide what lab to go to for a postdoc?
GILL: My PhD thesis was pretty successful in the reproductive sciences. As a result, scientists from Massachusetts General Hospital and Brigham and Women’s Hospital who were working on the specific pathways that I had developed the models for in my graduate training invited me to come work with them here in 2006. I decided to give it a try, and I’ve been here ever since.
SYNAPSE: Given that you had industry experience right out of college and then returned to academia for graduate school and a postdoc, did you know the entire time that you eventually wanted to end up back in industry?
GILL: It was a big decision to leave industry and go back to the University of Colorado for graduate school. It required going from a fairly stable paycheck back to grad school wages and eating free pizza when you can get it. That was difficult, but I was very dedicated to the science at that point. I knew that I didn’t have the skills, expertise, or training to develop my career much further than I had achieved already - I was a senior scientist with a bachelor’s degree at that point. Since I couldn’t advance much further or diversify into the many elements within biotech, I knew that if I wanted to keep advancing the science and gain some research experience, I had to pursue an advanced degree.
When starting graduate school, I thought, “This will be great - I’ll just get my ticket punched and go back into industry right away.” But it’s really not that easy. Graduate school basically unscrewed my head and rethreaded it back on, and I saw things much differently. With this new scientific point of view, my training was now guided by the normal tracks in graduate school that take you into an academic route. So to answer your question honestly, when I first began my graduate studies, I really did want to get back into industry and the startup world as quickly as I could, as I felt that the challenges that were there would be approached with diverse topics from the scientific, business, entrepreneurial realms. At the time, I thought a pure academic route would be somewhat more limiting.
But of course, things change and what happened is that I was invited to continue studies in wonderful institutions here in Boston, and how can you pass up that opportunity? The science and the brainpower here is so fantastic that to work with such amazing scientists is great, and I continued to grow both scientifically and creatively. But at the same time, they’re still trying to track you into grant writing and starting your own lab. I ended up getting on the faculty at Harvard Medical School and had a junior faculty position there with a small group of people - mostly undergrads, but it felt like a team. Though being a professor in the Harvard system was very difficult and the funding was not forthcoming, so I looked at my options to go back into industry. It wasn’t an easy transition despite the 10 years of biotech experience under my belt - somebody took the time to look at the breadth of my experience and background as well as academic training, and saw that I would be a good match to grow this interesting startup.
SYNAPSE: How did you find out about Audion Therapeutics?
GILL: Audion was the first company I worked with after Harvard Medical School, but it was not the first one I applied to! I had a difficult time trying to find positions outside of academia. Of course, I thought that maybe I could take junior faculty positions in other parts of the country, but I knew it was going to be a hard road ahead, so I thought that there had to be something in the Boston or Cambridge area. Since the biotech scene was growing leaps and bounds here, I was fortunately able to find the Audion team and we saw eye-to-eye on how to make this approach a go. They needed somebody here who was going to be on-site who had the managerial and scientific experience as well as having the entrepreneurial spirit and “can-do” attitude to really make a go of this.
Directing Audion’s research program
“They needed somebody here who was going to be on-site who had the managerial and scientific experience as well as having the entrepreneurial spirit and 'can-do' attitude to really make a go of this”.
SYNAPSE: How large is your staff at LabCentral, and what goes into your decision of whether or not to hire someone?
GILL: Right now we have 2 people here at LabCentral. Regarding hiring for Audion, we’re mostly looking for people who can get the job done. It doesn’t necessarily mean you’re going to have a background in hearing research or expertise in any one specific technical area. Mostly what we’re looking for are forward-thinking individuals with a ‘self-starter’ attitude - those are the people I try to surround myself with in this business. I also look for people who are trainable and are okay with making mistakes (and not making them again).
SYNAPSE: How does the trans-continental partnership of Audion’s leadership team play out in practice? What challenges are presented given that you and a small LabCentral team are here in Cambridge while the two founders are based in the Netherlands?
GILL: A lot of it is through electronic communication - we primarily work through Skype and teleconferencing. We also make concerted efforts to keep communication at a high level through teleconferences with our external partners and contract research organizations around the world.
SYNAPSE: What are the key milestones or indicators that tell you when a drug candidate is ready for a Phase I clinical trial?
GILL: In order to get to approval for a clinical study, we need to run a toxicology program that sufficiently demonstrates the safety of the product, as is required by regulatory agencies. We also need to show that we can manufacture the clinical trial material in a way that is consistent with all the quality requirements. This is what we are currently working on.
Navigating the ups and downs of the startup world
“Perseverance and patience are crucial personal qualities. Having the right mentoring team is also important.”
SYNAPSE: What words of advice do have for graduate students or postdocs who are considering a possible career in the biotech industry?
GILL: Perseverance and patience are crucial personal qualities. Having the right mentoring team is also important - you want to seek out the people who have made the mistakes before so that you might be able to learn from some of theirs. Keep asking questions, and know that there may be moments of frustration throughout the long, hard hours in the laboratory. It’s also essential to know how to communicate what you’ve discovered in the lab to others effectively.
SYNAPSE: What do you do when the science isn’t working? If you’ve hit a rough patch or have results that you don’t want to see, how do you report that back to the founders, investors, and board of directors?
GILL: As straightforwardly as you can. Everyone in this business understands that setbacks in scientific research are part of the game. I believe that experience helps problem-solve, but it also helps to have some creativity to get around the setbacks and progress. To just go and say that there’s a problem without crafting a potential work-around is not only coming empty-handed to your team, but it’s also dumping the problem onto them. It’s also important to be able to communicate potential solutions to possible pitfalls and setbacks to your funders and others during any type of proposal.
The work and successes that we’re having right now at Audion largely come from our efforts to keep it very straightforward and simple. We’re very focused right now on one particular indication and if the luck continues, we can get some additional information from tests in humans.