Applications for San Francisco (Batch 12) extended through September 15th, 2021!

June 4, 2021
By Yi Fu
BrickBuilt Therapeutics: the First Oral Microbiome Therapeutics

BrickBuilt Therapeutics is the first company targeting the microbiome via live biotherapeutic products to treat oral diseases. They are replacing conventional therapies—surgery or broad spectrum antibiotics—with bacterial strains isolated and formulated specifically to treat oral diseases. BrickBuilt’s first preclinical candidate microbial drug targets periodontitis, or gum disease. This targeted treatment will not only create a more effective way to eliminate gum disease, but also has the possibility of reducing other related severe conditions, such as cardiovascular disease and preterm birth.

Watch BrickBuilt at IndieBio New York Class Two Demo Day

We spoke with BrickBuilt Co-founder & CEO Brian Klein to gain insight into his technology and motivation in building his startup.

Why did you start BrickBuilt?

I have been in the oral microbiome space for almost 15 years, during which I saw several gut microbiome companies launch. Then the microbiome therapeutics industry started to move to the skin. But the mouth is actually the easiest to access, and one of the places in the body with the most disease prevalence. There was no company trying to make therapeutics for oral diseases, and this drove me crazy. 

We need someone to push this forward and no one else was doing it. Importantly, not a current gut or skin focused company can or is going to treat oral diseases; they lack the expertises, microbes, drives and fundings to do so. Additionally, the big players in the probiotics or nutriceutical space don’t have the correct microbes to enter the field either. This is why BrickBuilt is perfectly placed to act: we’re dedicated to oral health and we have the expertise as well as the niche-specific microbes to get the job done.

How did you develop your go-to-market strategy?

Having the microbial library and being able to go on the clinical side as well as partner with people on the consumer side is really important to me. When you look at companies developing microbiome drugs, they frequently mention their enormous libraries and proprietary sequencing data. This is great because microbial libraries and sequencing data are important as you need those things to make drugs. 

However,  if you have a library of 50 different Clostridium scindens, why let 49 sit idle in a freezer because you only picked 1 to go to the clinic with? Why would you not use a different one for potentially an over-the-counter product or developing an enzyme therapy with a partner? That’s why we want to have a useful library and use it both on the clinical side and through partnerships for more consumer and over-the-counter applications, not directly from us but via partners.

We decided to focus first on the clinical route to provide better therapeutics. In the dental space, and for gum disease specifically, a patient could have a surgery, take antibiotics, or both. It’s generally not a good idea for something like gum disease to be treated with a broad spectrum antimicrobial. And surgery alone will not rid the patient of the microbes causing the gum disease in the first place. So, we want to fill that space. 

To do so, we have to go through clinical trials to prove it is safe and efficacious. We have made amazing strides during the IndieBio program toward this. First, we sequenced and closed the genome of our lead microbial candidate, which tells us what the strain is and what it could do. Second, we’ve completed in silico and in vitro antimicrobial resistance profiling. We’ve learned that our lead strain is susceptible to most common antibiotics, an important safety requirement. Lastly, we have begun sourcing healthy donors from around the world and isolating microbes from their saliva to derive other beneficial strains for use in therapeutics. 

What do you think is your key differentiator comparing to others that are in that space?

This is my favorite part because there are no other microbial therapeutics companies focused on the mouth. That’s the first differentiator.

Additionally, even though our team is small, we have a ridiculous amount of experience working with these anaerobic and microaerophilic microbes in the oral niche, an understanding of how you isolate and screen for these microbes, and how to invade microbial communities. People need to realize that “microbiome” as a term is not that old. So, we have been in it from the relative beginning. 

Dr. Esther Miller, our first scientist, has been working on different food-related microbiomes and how to invade those systems. That’s a relatively novel thing: how can I get a good bug into a disease system and track that? 

The understanding of the anaerobic and microaerophilic side of things is extremely important and not very common. If you go to pharma ‘A’ or ‘B’ and say, “Hey! How many anaerobic chambers do you have? Can you create high-throughput libraries and screen them?”—you’re likely to get a blank stare equating to a ‘no.’ It’s a highly trained skill and there just aren’t many people who specialize in it. 

What is the most rewarding thing about your entrepreneurship?

The most rewarding thing has been bringing the initial team together. Esther, who is a highly qualified scientist, came onboard because she believes the work to be both interesting and impactful for the world. 

Our advisor, Dr. Ian Needleman, the former head of British Perio, was driven to join us because of the importance for patients. In fact, he was specifically motivated because we are not just going to try another antibiotic, but instead finding a truly novel solution. 

Being able to move from a concept to potential patient impact, and then pulling people together around the idea, is one of the super rewarding things about entrepreneurship. 

How do you predict that oral health will change in the next 10 years? 

I’m really happy to see phase II and phase III clinical trials from a lot of gut and skin microbiome therapeutics companies coming forward. I think we may see approved treatments for C. difficile infections within the next two years. 

When it comes to oral health and oral medical devices, I think that we are at this amazing time where within 5 to 10 years, I envision dental health being more fully developed and connected to general healthcare. Especially now that we know these oral diseases, like gum disease, have broad reaching systemic effects, like preterm birth, type II diabetes, and Alzheimers. And the same will go for cavities and oral cancer. 

As we are developing our drugs, the dental and medical establishments will start to say, “okay, you can prescribe these things for oral diseases.” And people will acknowledge that the oral diseases will affect the outcome of the rest of the whole body problems. Treating oral diseases is treating half of the world population with acute oral diseases as well as preventing diseases among the world’s entire population. Because when you take all oral diseases combined with diseases like arthritis and diabetes, you end up covering almost everyone on the planet.