Scaling is a familiar challenge for any biotech company. From moving from benchtop assays to large scale fermenters, to demonstrating business model sustainability or establishing a market niche, a number of obstacles stand in the way of transforming scientifically proven concepts into profitable products. This is especially true for companies in the microbiome engineering space, a relatively new area of innovation that faces unique scaling challenges compared to other biotech or pharma companies.
Most biotech companies that use microbes as their core platform leverage microbial fermentation to produce proteins of interest: food ingredients, fragrances, fine materials and chemicals, or biomedically relevant molecules such as insulin. In all cases the end result is the same: a protein purified en masse from a microbial culture. Microbiome engineering companies, on the other hand, provide something unique: an engineered microbe that is itself introduced, alive, into an environment, such as the human gut or skin, where it (hopefully) elicits a desired effect without negatively impacting the natural microbial community or human host.
Travis Whitfill, co-founder and Executive Director of Advanced Technology of Azitra, which engineers microbes to treat a variety of skin conditions, has seen his company navigate several scaling challenges on its way to bringing microbiome-based therapeutics to the clinic — something that no microbiome company has achieved quite yet (though several, including Azitra as well as Finch Therapeutics, and Synlogic, have products currently or recently in clinical trials).
“It’s definitely never too early to start thinking about scaling,” Whitfill says. “There are a lot of challenges, especially in this field, that need to be addressed early on.” From his experiences with Azitra, Whitfill sees three major considerations entrepreneurs in the microbiome space should be thinking about right now: product formulation and manufacturing, building out your team, and fundraising.
Manufacture: a unique challenge for microbiome engineering companies
One of the most important questions a young microbe company can ask is whether to scale up internally and build out your own production of your own microbes, or do you outsource the process and if so, to who? Scaling up the production of therapeutic microbes is a young and nascent process, so not many companies are able to do that efficiently yet. In Azitra’s case, the company was fortunate to find a European partner willing and able to manufacture their microbes, eliminating potentially years of trial and error building the process in-house.
Part of the manufacture equation also includes being aware of different regulatory bodies, especially if you sell products in one (or more) country but produce them in a different country. Regulatory agencies like the FDA are open and willing to help, even (and perhaps especially) early on. In general, Whitfill says, regulatory issues are more straightforward to navigate than many other scaling challenges, especially if you begin interacting with regulatory agencies early.
Product formulation is one such challenge that is a bigger beast than regulation, especially when compared to traditional drug development. Consider this: unlike traditional pharmaceuticals, microbial-based therapeutics are living organisms, so a company must figure out how to keep their microbes alive while also considering things like product stability and shelf life.
“I wish we had started on our product formulation issues a year sooner,” says Whitfill with a rueful laugh, adding that fortunately that decision (or lack thereof) didn’t really harm the company in the long run. “End-product formulation, product positioning, thinking about market segmentation and how [your product] fits with other products in the market, and what’s going to be approved in the market by the time [your drug] gets there are all considerations that can’t be considered too early.”
And why is considering such things important? The answer is simple: pharma companies will take you much more seriously when it comes time for them to look at your data and consider a partnership.
Build the right team, build your company
Though Whitfill believes manufacture and product formulation are the biggest challenges facing any microbiome company today, they weren’t actually the biggest challenge for Azitra, in his opinion. Instead, he says, the harder to surmount challenge has been building the right team. And while missing or questionable science and unfounded claims keep many post-docs or young professionals away from companies in the microbiome space, this hasn’t been the case for Azitra. Instead, the company’s location (Connecticut, though the company now has a second location in Montreal) has made it difficult to entice people to relocate. But the company is flexible — several people work remotely, so relocation isn’t a deal breaker if you want to be part of the team (depending, of course, on your specific role).
Image source: Azitra
It also takes time to build a diverse team, not just in terms of background and expertise but also in terms of gender and ethnicity, which altogether give any company a better shot at scaling success. Richard Andrews joined the company as CEO in the fall of 2017 and has played an instrumental role in the company’s growth during the past two years.
“For a while, we were just one or two people, but now we have a team of 15 or 20 people, and we’re rapidly growing. We have a molecular biologist in-house, a protein expert in-house, a number of microbiologists — all of these components are critical to the development of a product [like ours] that touches so many different fields, from synthetic biology to dermatology to immunology. It takes a team that’s very diverse in terms of scientific background, and that’s, that’s what’s great about our team,” says Whitfill, adding that “we’re pretty balanced in terms of gender, and ethnicity is also relatively diverse — that’s something that I’m really proud of.”
Yet when asked which single piece of advice Whitfill would give to anyone aiming to start a microbiome engineering company, he responds with this:
“Think carefully about how you fundraise.”
It’s a difficult space to fundraise in, he says, because of the hype surrounding the field and the microbiome companies that haven’t worked out despite lofty promises. But there are a few firms that do focus on the microbiome space (such as Seventure Partners in France) and others that invest only in the microbiome — so it becomes incredibly important to make sure you partner with the right investors.
“It’s really important to [take capital] at the right time, and take the right capital from the right investors. Investors don’t just provide money, but they provide a lot of other resources. So the type of investor, the type of investment, and your strategy for [fundraising] are all really important,” emphasizes Whitfill, who is a partner at Bios Partners and has a heavy focus on VC funding.
It can be extremely difficult to forge ahead in a field rife with skepticism and companies built upon the shifting sands of fake science and hype. Companies like Azitra are demonstrating what real microbiome science can do for the future of human healthcare, and for Whitfill, the people his company’s technology affects are what help him to continue pushing ahead, despite all the skepticism.
“What drives me and keep me going is getting letters from patients, and parents, especially. It reminds us of why we’re doing this. We’re not just making another beauty product; [we’re] making a difference and solving real, major problems.”1