IndieBio’s therapeutics company Intrinsic Medicine to list on NASDAQ next year

Intrinsic Medicine is developing a new drug based on a sugar found in human milk to treat Gut-Brain Axis (GBA) and inflammatory diseases. Source: Intrinsic Medicine

In a post entitled, “Intrinsic Medicine and Phoenix Biotech Acquisition Corp. Announce Merger Agreement to Create Public Company Leveraging Human Milk Biology to Treat Gut-Brain Axis Disorders”, IndieBio’s Intrinsic Medicine (SF09 2019), a therapeutics company using the science of human milk to treat inflammatory disorders, announced that it has entered into a definitive business combination agreement with Phoenix Biotech Acquisition Corp. The agreement includes plans to list Intrinsic Medicine’s common stock on the Nasdaq Capital Market under the ticker symbol “INRX ”in 2023.

Intrinsic Medicine is leveraging human milk oligosaccharides (HMOs), an abundant solid component of human milk, to shift the composition of the gut microbiome, boost the microbiome’s production of helpful metabolites, and modulate the immune system. In a therapeutic context, HMO-based drugs have a favorable toxicity and tolerability profile, making them a promising candidate for patients who may otherwise be affected by the side effects and toxicities of other drugs.

According to the press release, Intrinsic Medicine’s merger with Phoenix Biotech Acquisition Corp. enables Intrinsic to advance its lead compound OM002, initiate a Phase 2b clinical study, initiate chronic toxicology studies, and advance the compound OM001 into the clinic.

“This milestone marks an important moment for Intrinsic,” said Intrinsic CEO Alexander Martinez. “With this commitment from PBAX, we will challenge the status quo to deliver a differentiated class of microbiome and immune-modulating medicines with the potential to provide true relief to individuals suffering from GBA disorders.”

Ceragen: Growing a Sustainable Future through Probiotics for Plants

Ceragen produces probiotics for plants that help crops grow faster and bigger.  Their unique discovery platform allows Ceragen to identify the ideal microbial consortia for each crop type, including crops like tomatoes and lettuce.

Watch Ceragen present at IndieBio NY Class 3 Demo Day

We spoke to CEO Danielle Rose about the importance of producing high quality produce and her passion for commercializing research discoveries.

What is sustainable intensification and why is it important?

The majority of the world’s population does not have access to sufficient vegetables to actually meet a healthy diet. Also, in terms of climate change, it’s getting harder and harder to continue producing foods. So we’re having to clear more land, and just keep expanding our agricultural practices. 

What we really need to be doing—and what people are starting to do—is something called sustainable intensification, or producing more food from less land. This means that there is more land available for things like reforestation, and really not having to have that negative impact, like clearing the land that we have traditionally had to have with agriculture.

What makes you feel so passionate about commercializing basic research findings? 

​​There are researchers making all of these amazing discoveries all the time that never really make it to market because that process isn’t something taught to a lot of scientific people. We don’t get taught market discovery in school; we don’t get taught how to do basic business, how to see an idea and be like, hey, this can solve a real world problem that I think people would actually pay money to solve—we can get this out into the real world and make something of it. 

I think that’s a real shame, because there’s a lot of amazing research that just sits and doesn’t make the positive impact that it could! This is really a waste of resources and detrimental to society as a whole.

How did you help identify a market opportunity for plant probiotics?

I connected with some professors at the University of Waterloo who are researching plant growth-promoting microbes, since I was an area I was interested in. I started to help them do market discovery, since I had gained some business experience in the previous year, when I had worked on a startup that I started with a friend. 

One of the things that we had determined was, wow, we have this amazing market opportunity here with these microbial products! And the ability to not only make a social impact, where we help increase fresh vegetable production, so that people have a more sustainable, better opportunity to access the sort of fresh vegetables, but also to increase the environmental sustainability of agriculture by increasing the amount of food that we can produce from the same amount of land.

How do Ceragen products help produce more food?

Ceragen is developing microbial products that help plants in a number of ways. These microbes that we’re combining into basically consortiums, or groups, of microbes to help the plant offer benefits, like nitrogen fixation, helping the plants absorb phosphorus, promoting growth, as well as regulating stress. 

How we do that is to take known plant growth-promoting microbes that we have isolated from environmental samples, and test them in all these different plants, to figure out which ones work best under which circumstances in which plants. We combine those together into products that help plants basically increase yields by enabling them to use nutrients better, reducing the amount of fertilizer that is used, as well as promoting growth and the amount of fruit that these products are yielding—or in the case of leafy greens, the amount of vegetation and the size of the lettuce and how fast it gets to market.

Our first product, Ceragen Accelerate, is for use in tomato crops. And we’ve seen anywhere upwards of 20% yield increases in tomatoes in our tests. We are currently in commercial trials for that product, and we have 3 commercial pilots ongoing with greenhouse tomato growers.

What is the mission of Ceragen?

Our mission is to help growers sustainably increase crop yields so that they can generate more revenue from their farms as well as produce more food to help feed our growing population.

I think the concept of the microbiome is pretty new in the agricultural space, all things considered in agriculture. So this is an area where a lot of people have paid attention to in the past and it’s only really started to gain traction in the last little while. So I think that the newness of the problem is something that we do have to face and also, you know, there have been some products that have been used before. That didn’t necessarily live up to the claims that they made. So having really good testing data, having really good validity on the function of our products, is something that we’ve been really striving towards.

Prellis Biologics raises $14.5M series B for lab-grown lymph node organoids

The TechCrunch post,  “Prellis Biologics raises $14.5M, debuts a ‘human immune system’ in a dish’” reports that the series B round for Prellis Biologics (IBSF05 2017) was led by Celesta Capital and existing investor Khosla Ventures. SOSV IndieBio also invested in the round, as it did all Prellis’ prior rounds. The article notes Prellis recently launched a lab-grown human lymph node, called EXIS (external immune system), which mimics the response of the human immune system and will be used in developing new drugs. 

On the benefits of the Prellis lymph node organoid, founder and CEO Melanie Matheu says “By creating this immune system in a dish, we can actually test if those therapeutics are going to elicit an immune response before it goes into a human. Our company’s edge is that [EXIS] is out of the box fully human.”

Spira take first place in Tata Consultancy Service TCS Pitch for Purpose 2021

The Forbes article “Startup uses genetically engineered algae to create pigments, protein, and more” reports that Spira (SOSV RebelBio 03) co-founder and CEO Elliot Roth won the TCS Pitch for Purpose competition for using the algae spirulina—sourced from small farms via fair-trade practices—to make carbon-negative dyes. More than 200 entrepreneurs from across the U.S. participated in the competition, which featured startups leveraging technology to address social issues.

Spira pays algae farmers a living wage and helps them improve operations. Spira turns their algae into carbon-negative pigments to approximately 1,000 food and cosmetics companies.

Huue founder explains fermentation process behind the startups’ sustainable dyes

In  “Where I work: The greener route to indigo blue,” a first-person account in the journal Nature, Tammy Hsu, CSO and co-founder of the SOSV startup Huue (IBSF08 2019) describes the motivation and science behind their earth-friendly dyes. 

In the article she states, “Indigo dye, for example, is usually made from petroleum-derived aniline in a high-temperature process that involves formaldehyde and cyanide. Globally, around 20% of industrial water pollution comes from fabric dyeing. I want to make dyes using microbial fermentation instead. At Huue … we look at how dye molecules are made in nature. We study the biochemical pathways, then program Escherichia coli bacteria to make our dye in the same way. Instead of using toxic chemicals, we feed the microbes and they make the dye.”

Michroma takes fungal food colors platform to pilot scale

Food Navigator takes a deep dive into the world of natural food dyes in “Michroma takes fungal food colors platform to pilot scale to produce pH-stable, heat-stable natural red.” Michroma (IBSF09 2019), a startup building a production platform for natural food colors from fungi, has advanced to pilot-scale production of a heat-stable vibrant red colorant it claims can give synthetic dyes a serious run for their money when it comes to performance and sustainability.

Sequential Skin raises $1.65 million seed round

Yahoo! News published news that  Sequential Skin raised US $1.65M in oversubscribed seed round to revolutionise skin health with their novel skin microbiome testing kit

Sequential Skin (SOSV IBNY02 2021) provides personalized skincare by using advanced genetic sequencing technology to analyze how genes, skin microbiome, and the environment interact and affect an individual’s skin.

Led by Metaplanet and joined by Scrum Ventures, SOSV, Genedant, and angel investor Ben Holmes, the press release explains “the funding will significantly boost their IP portfolio, using their novel patch-based, skin analysis, to develop further tools to understand how your genetics, epigenetics, and skin microbiome, affect health and disease.”

About Sequential Skin’s mission, the company’s CSO and co-founder Dr. Albert Dashi said, “Our scope is to provide science to people and empower them with the right tools and knowledge so they make the right decision for the future of their skin health and well-being.”

SOSV’s Perfect Day raises $350 million, reaches $1.5 billion valuation

The Wall Street Journal broke an exclusive on Perfect Day’s big fund raise and planned IPO. Perfect Day launched in Cork, Ireland in 2014 as part of SOSV’s now retired Rebel Bio program, and SOSV was its first investor. From the Wall Street Journal story:

“Perfect Day Inc. raised $350 million in a late-stage funding round, valuing the non-animal dairy startup at roughly $1.5 billion and setting the stage for an initial public offering.

“Singapore’s Temasek and Canada Pension Plan Investment Board led the Series D funding round for the California company, co-founders Ryan Pandya and Perumal Gandhi told The Wall Street Journal. Other investors include Walt Disney Co. Executive Chairman Robert Iger.

“Since its founding in 2014, Perfect Day, which uses fermentation technology to produce animal-free dairy proteins and counts actor Leonardo DiCaprio as an adviser, has raised $750 million.”

Congrats to @animalbiome for closing their Series A led by @Cargill!

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.

Sequential Skin: the First Truly Personalized Skin Care

Sequential Skin uses their unique at-home test to provide the world’s first truly personalized skin care. Their test considers both the human genetics and the skin microbiome to generate a report tailored to the individual. Years of research have indicated that the skin microbiome, and specifically the diversity (how many different types of microorganisms), are correlated with skin health, and further that microbiome diversity is influenced by a number of genetic and environmental factors

After using the Sequential Skin test, customers receive a personalized skin care regimen, including a face mask containing all the ingredients necessary for personalized optimal skin health.

Watch Sequential Skin at IndieBio New York Class Two Demo Day

We spoke with Sequential Skin CEO Oliver Worsley to gain insight into his technology and motivation in building his startup.

How did you recognize a need for Sequential Skin’s technology?

One of our key insights was recognizing that most skin tests are clinical, so they require a swab or saliva test. We want to revolutionize that. We bring a patch that is simple to use and isn’t associated with a hospital or clinic to customers, to enable that information in a really simple way.  

Our other insight was due to being based in Singapore, the heart of Asia which is very multicultural, and seeing there is a hugely underrepresented group of people around the world that don’t have the important health information about their genetics and skin microbiome. Because of the decreasing costs of sequencing, we are finally at a point where we can collect this information in a cost-effective way, using technology to improve skin health for anyone.

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

Sequential Skin has so far used a B2B model, where we help companies validate their new skincare products, improving skin microbiome claims. Speaking at conferences has initiated connections with many companies in this space and showcased what we are doing. They then approached us to ask us to test the effects of their products on the skin microbiome. 

Though B2B isn’t the entire vision of sequential skin, it’s been really useful for us to use the kit with the individuals working with the companies to test their products. It’s been a good way to both bring revenue and refine the technology. We are lucky to have that.

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

There is no other company looking at both human genetics and the skin microbiome for the purposes of skin care or skin health. That alone makes Sequential Skin standout from others in this space. The expertise of our team, having 3 Ph.D. scientists in genetics and the microbiome, has been really key for us as well. 

We have also been very lucky in terms of timing: the skincare industry is shifting to more personalized care, and we are hoping to ride that wave to help these customers in that space. 

What have you found most rewarding about entrepreneurship?

During the pandemic, we had a lot of time. We couldn’t go into the lab—that forced us to be at home, sharing these reports with friends and family and ensuring the science we are communicating is useful for consumers. We put a lot of attention on customer experience, and it’s been really rewarding.

Above all though, it’s most rewarding when customers come back and say, “I have been using this product. It’s really amazing and I really feel the difference in the quality of my skin. This really changes things.” I had a customer reach out the other day saying, “the products you gave me, I am still using them.” This is a year later! What’s most rewarding is to see the science being used for the intended translation and the whole process working really nicely. 

How do you predict that skin health will change in the next 10 years? How will this affect the broader medical field?

We talk about this a lot within the Sequential Skin team. Did you know 70% of consultation can be done in a telemedicine way? And it’s estimated that after this pandemic, 30% of these consultations will take place in some sort of tele-arena. We see that being accelerated in 10 years, to the point where everything can be done at home. 

Imagine: you have a kit that arrived. You perform the test and then your doctor is on the call with you. Everything is prescribed and treated through that tele-system. In this future, you wouldn’t have to go and wait in long waiting queues to see a doctor, and you don’t have the risk of being exposed to something else in the clinic or the hospital. I think everything will be completely remote. So, we are building this at-home test and refining the process to make it as simple as possible. I think that is here to stay. 

Microbiomes are generally the forgotten organ. But in the future, everything is going to be targeted around the microbiome, whether it’s to treat neurological or skin conditions; instead of using generic and often systemic drugs, the microbiome will be the focus of targeted therapeutics.

Busting Top Manufacturing Myths at Unexpected Biotech

The future is in fermentation, but what does that mean to benchtop scientists who want to produce consumer or therapeutic products at industrial scale? During the IndieBio-produced event, Unexpected Biotech, IndieBio NY Managing Director Stephen Chambers spoke with Stuart Wilkinson, Co-Founder and Technology Director of BioBrew. The conversation broke down several myths of startup scale up.

See the future of biotech at IndieBio Demo Days!

Myth 1: There is no such thing as a universal best microbial fermenter.

Question: What is the best microbial system to produce biological products via fermentation?

Answer: There isn’t one ‘ideal’ system.

Instead, the best microbial host for recombinant expression must be decided for each use case. “Being locked into a certain host system because of familiarity with it is the wrong approach,” says Wilkinson. 

All hosts have strengths and weaknesses: for example, bacteria grow quickly but are susceptible to phage infection, especially at the industrial scale. Slower growing hosts like filamentous fungi require more time to ferment but also more time to develop the ideal production strain. Startups should consider expression levels and determine the titers that they want to produce. 

Myth 2: Scale up is much more complicated than most people appreciate.

“Microtiter plates are great for screening and high throughput experiments, but not really representative of industrial scale,” says Wilkinson. “Industrial food biotech and yeast systems are 100,000-500,000 liters; microtiter plates have very little in common in the process or dynamics that mimic those systems.”

If one’s aspiration is to go from a microtiter plate to industrial scale, the best strategy is to use a downscaling system. Rather than going upward in incremental steps, decide the aspirational scale. This will help define the physical/chemical parameters that are the constraints, and incremental experiments can be planned backwards for a pilot scale, lab scale, and (“if you’re capable and clever enough,” says Wilkinson), the microtiter scale.

Downscaling helps ward off the glass ceilings that many startups see when upscaling: technical problems that they can’t break through that can be amplified into potentially big problems when reaching industrial scale.

Myth 3: Downstream processing is more than an afterthought.

When people start to design strain and process combinations, it’s often strain engineering first, then fermentation, and then downstream processing to collect the product. “You’ve really got to look at this more holistically and think of the entire process as one,” says Wilkinson.

Myth 4: The ‘scale-up savior syndrome.’

Many startups assume that equipment and processes will be more efficient at higher scale. Wilkinson says, “ultimately, if your strain and process don’t work at a lab scale, it’s highly unlikely it will work at industrial scale.”

Think of scale-up as the opportunity to fine-tune and optimize processes, rather than solve problems. Have a line-of-sight techno-economic viability at the lab and pilot scale before considering demonstration and industrial scale. 

Ultimately, “this goes back to the modeling,” says Wilkinson. Bring in the cost of goods at the scale you aim to produce. This provides a baseline and if your theoretical practice fails to meet the breakpoint, you can expect challenges ahead. “Models are fantastic, and I wouldn’t do any work without strong models,” says WIlkinson, “but models are only as strong as the assumptions you make and the data you plug into those models. There’s no substitute for real-world data.”

Find more insights from the IndieBio-produced event, Unexpected Biotech

AsimicA: Raising the Bar for All Biofermentation

In May 2020, a McKinsey report found that the global bioeconomy is slated to become a $4 trillion gold rush as synthetic biology’s promise to make high-quality, sustainable products gains traction. These products range from food to textiles to medicines, and biofermentation is the manufacturing process that makes all of it instead of having to extract them as natural resources. Today, we sit down with Nik Mushnikov, CEO and co-founder of AsimicA, whose technology promises to solve the bane of biomanufacturing: low yields that formerly could not compete with traditional manufacturing methods. Using his invention, dubbed “microbial stem cells,” Nik thinks he can achieve multi-fold yield increases in product, and keep the bioreactors running longer.

Ok first off, what is a biofactory, and why is everybody talking about them?

Microbial biofactories are basically reactions in which we use microbes (like a bacteria or yeasts) to make the product we want. This was a solution when the product itself was biological, like insulin, and we didn’t know how to engineer a synthetic process that is smarter than a living cell.

Now with genetic engineering, biofermentation is becoming more popular as we are learning how to make other products that aren’t even biological in nature. For example, we used to make plastics with petrochemicals because it was cheaper and more efficient, but the synthetic biology field is learning they can engineer microbes to make specialized plastics.

Wow, so do you think that biofermentation will be used to make everything?

I think petrochemical or chemical synthesis is still more efficient, but it comes with problems like relying on oil as a feedstock and toxic pollutants as a byproduct.

Microbes, on the other hand, have the potential to produce any chemical compound in a sustainable manner, using renewable resources, if you can engineer it correctly. If you factor in the externalities, I think that traditional chemical synthesis is starting to lose its edge, especially when it comes to specialized products.

Why isn’t everyone using biofermentation right now?

Microbial biofactories can’t operate non-stop. As they divide, every generation becomes less productive and you have to restart the entire batch. Every restart is expensive in terms of expensive, specialized labor and downtime. We’re talking several days. Economically this doesn’t fare well, and we need to find ways of making them more efficient and more productive.

People have tried ways to make the microbes live longer or more resistant, but evolutionary genetics eventually catches up and drives the population to become sickly and unproductive. The solutions in the past have been… lackluster.

So I guess that’s where you come in! How are you solving this problem of low yields?

Instead of trying to make the microbes live longer, we found a way to repopulate and replenish biofactories with a fresh generation of microbes during the batch. We’re doing it using our innovation of “Microbial Stem Cells.”

In our bodies, our stem cells essentially replenish the cells in our tissues so that they stay functional for decades, much longer than individual functional cells can live.

Our idea is similar to that — microbial stem cells are constantly replenishing the fraction of productive microbes in the bioreactor. It is a way to bring up new young and strong “workers” to the factory, so to speak. We’ve published mathematical models that show that this replenishment strategy would result in a 2–4 fold higher number of productive microbes in the bioreactor, which translates to higher productivity per reactor, and longer batch runs.

The effect that microbial stem cells can provide on bioreactor productivity can significantly increase the profitability of bio-manufacturing.

How did you come upon this insight? Was this always something you engineered with biofermentation in mind?

I was always very intrigued by the potential of biofactories for manufacturing all sorts of chemicals: pharmaceuticals, fuels, advanced materials, and so on. And I wanted to be involved in designing new strategies for bio-manufacturing using microbes.

When I started my PhD, I had a couple of projects, focused on increasing yields of microbial fermentation. The idea of realizing stem-cell-like behavior in industrial strains of microbes came out from previous fundamental research insights made by my advisor, Dr. Grant Bowman. He was studying a phenomenon of asymmetric cell division in some unique bacterial species. Sometimes their cell division diagram resembles the division of stem cells. Certainly, these species are not applicable to the industry. And molecular mechanisms underlying their asymmetry are way too complex to just copy them.

What we’ve done is that we identified a minimal set of key components that can induce asymmetric division in other species. We borrowed them from several different bacteria and transferred them into E. coli, and our Nature Chemical Biology paper demonstrated that we can indeed induce asymmetric cell division and program differentiation in different cell types.

What kind of products are you able to make and is there any limit to what yields you can increase?

We just got results last week that we are able to make several products from pharma, food, and the cosmetics industries. These are just proof of principle experiments to demonstrate how versatile our platform is. We’re thinking of experimenting with fuels next which are highly toxic products for microbes to make — again, just to flex how broadly applicable our “microbial stem cell” technology is.

Everyone who does biofermentation is dealing with the exhaustion of microbes, and I don’t think there is a better solution than ours to improve yields and lengthen batch reactor runs.

So the sky is the limit in terms of products, but what about the cells? Are you limited to E. Coli?

That is a very good point. Of course, not all biofactories are using E. coli cells as their workhorse. We see a fairly straightforward way to transfer out technology to other species of bacteria. We’re already working with Bacillus subtilis, which is what most of our industrial partners are using. Transferring our ideas to eukaryotic microbes, yeast, and fungi, would be a more R&D extensive project but we’re confident we can get there.

How does a potential partner incorporate their technology into their existing manufacturing process?

Biotech companies won’t need to change much in their manufacturing processes. What we do is a strain engineering service, which changes how the culture of cells in the bioreactor behaves, enabling microbial stem cell properties. But it doesn’t change the production process itself. Simply speaking, our partners would do the same things they were used to, but their strains after AsimicA modified them would have higher productivity.

Why did you study microbiology?

I started to learn about the broad potential of microbes back in high school and my interest kept growing throughout college. Each microbiology course taught me that the potential of microorganisms is unlimited. My first research project was in yeast genetics. I’ve learned some methods and practices of working with microbes, but the research scope was rather fundamental and driven by the needs of clinical biology, whereas I was more interested in applied microbiology.

I finally found The Bowman Lab in Wyoming to do my PhD, where my interests were more aligned with applied bio. There, I could perform my research studies, keeping in mind that we’re creating new tools, new technologies that can be directly applied to the industry. That research dynamic is closer to my heart, and launching AsimicA where I can take the application to industry has been one of the most rewarding experiences I’ve ever had.

What good would this do for the world?

The world needs cleaner economics. Humanity is facing existential challenges, and although we are getting closer to solving those challenges we still have a long way to go and perhaps what will move the needle the most is to change the way we make things — using renewable resources, reducing pollutants, and dropping down our emissions. Our technology can facilitate biofermentation in becoming the primary method for the production of the vast majority of chemicals. Just imagine how much dirty production we can push out if we can increase yields by 2–4 fold across the entire industry. That’s what I think AsimicA could do for the world and that’s the future that I want to help build for us.

Cybele Microbiome: Skincare Through Precision Prebiotics

Nearly half of society has some sort of skin sensitivity. Cybele Microbiome is the company behind a new direct-to-consumer skincare brand. Cybele’s unique products trigger the natural skin biome to secrete skin restoration compounds. Today I sat down with Cybele’s CEO and Founder, Nicole Scott PhD. Nicole is a geneticist who became fascinated with the interaction of skincare products and the skin biome. Cybele was born when Nicole discovered how to gain precision control of microbes through the use of functionalized prebiotics. She thinks of cosmetic ingredients as first and foremost “food for the microbiome.”

Q. During IndieBio, you ran a small pilot study with your skin serum formulation and got some exciting early results. Tell us about what was seen?

Just two weeks into the study, I got a bunch of excited phone calls, because many of our volunteers were noticing the results right away. We provided the photos to a dermatologist who is highly experienced in reading skin conditions on photos, and he confirmed there’s notable decreases in scaliness, flakiness, hyperpigmentation, papular eczema, eczema, psoriasis, and even a decrease in a precancerous lesion. We knew that one of our long-chain ceramides is a known anti-melanoma compound– but these early results after just 2 weeks have us floored.

Q. Your prebiotic ingredients trigger the skin biome to create only long chain ceramides and no short chain ceramides. Why is that so important?

There are huge differences in the bioactive function of short chain and long chain ceramides. The long chains are the good ones. The short chains actually harm your skin, competing with, and fighting against, the good ceramides. Your typical skin care products that advertise ceramides don’t make this distinction, and can be doing as much bad as good.

Q. As a direct-to-consumer company, how does your hero product evolve over time into additional products and SKUs?

From skin serum we can round out that product line with moisturizers, toners, and eye creams.

But we aren’t a one trick pony. What is also really exciting is that we can get your skin biome to make hyaluronic acid — the most common ingredient in anti-aging cosmetics. These advances come from our platform to identify and formulate new prebiotics for other uses. This allows us to create a suite of related and complementary products. We also will customer’s skin biome assessments and input to help craft the additional products.

Q. How do you manufacture the prebiotic ingredients, and how does this affect Cybele’s margins in the early years of the company?

Our prebiotics are the output of fermentation. At small scale, we can purchase our prebiotics. They are not expensive. As we scale up, we can use any standard contract manufacturing organization to produce them for us — so no capex needs to go into ingredient manufacturing.

Ceramides are normally expensive to add to skincare products — and every bit added to a formulation hurts margins. In our case, not only is our product more effective, but we aren’t paying for ceramides. The skin biome makes them. So we have a much higher margin — estimated at 88% for our serum product.

Q. Tell us about your team.

Our team includes James Lamoureux — a microbiologist that received his PhD with Dr. David Low at UC Santa Barbara — and Hui-Ling Seow, who helped develop and carry out the marketing strategy for a HR platform Epic Quest Games, and Liz De Ruyter, who lead the Amazon On-Campus Store, launching products like PuraVida, Red Bull and Aveeno at UC San Diego. We are currently expanding the team by actively recruiting a Chief Marketing Officer right now.


Microgenesis: Restoring the Fertility Biome

Through the development of a simple swab-based test combined with personalized nutraceutical solutions, Microgenesis is helping women facing fertility challenges forge a path to pregnancy and motherhood.  Building off their impressive initial patient results in Latin America and Spain, the team just landed (literally!) in the US to begin offering their infertility solution to the American market.  I wanted to dig a little deeper into Microgenesis’ offerings, upcoming clinical trials, and their future plans.  Here are excerpts from my conversation with co-founder and CEO/CSO, Dr. Gabriela Gutierrez.

Pae Wu: Gaby, your team really caught our attention with your impressive clinical data from Argentina that predated IndieBio.  Out of 287 women that had previously failed at least 4 IVF procedures, 75% of them got pregnant within 6 months!  

Tell us, what are you most proud of accomplishing during this pandemic edition of IndieBio?   

Gabriela Gutiérrez: During IndieBio we studied 15 alpha testers that are at the beginning of their fertility journey and 14 of them are already pregnant!

PW: What motivates you to tackle such a tough challenge?    

GG: Yes, we have worked with the hardest cases of infertility.  I have spent 15 years helping women that already failed IVF treatments. Women that are desperate and looking for a test that can help them to understand the real problem and how to fix it. We intend to replace the painful classic fertility journey of women by focusing on women’s health. 

PW: But you’re not solely working with women who are undergoing IVF, is that right?  

GG: Because we can anticipate the real problem using our test we can treat the patients before they start IVF.  We also work with women who are just starting their fertility journey and couples. 

PW: What’s the customer journey like?  Is this a one-size-fits-all solution?

GG: We send the woman a non-invasive test and we guide her through nutraceutical recommendations that improve her fertility potential while preventing inflammatory diseases.  

Our test is able to identify 64 different infertile biome phenotypes and we have developed 53 different treatment combinations to provide the right solution for every woman.

PW: There are so many fertility tests on the market today – traditional tests through ob-gyns, and newer direct-to-consumer options.  How does Microgenesis’ solution differ?  

GG: The traditional test is based on the evaluation of 5 hormone indicators of ovary function. This information is oriented to determine if a woman with low ovarian reserve/function should go for assisted reproduction. Our test brings information about the real problem and it is actionable. Our fundamental insight is that infertility is associated with an intestinal condition which also can affect ovary function. 

There is no other test in the market oriented to study intestinal microbiome disbalances affecting fertility.  We focus on women’s health, we restore key components to treat inflammation and the reproductive senescence associated, and we get women pregnant during the process.

PW: You’re now in the Bay Area!  Welcome to the US – what’s on slate for Microgenesis here?    

GG: In the next 3-4 months, we will focus on our Seed round to go to the US market next year. 

We have launched our alpha test in the Bay Area with women who are asking about their fertility potential.  We will send them the sample kit with a swab and lancet for a blood drop test.  They can send us the samples to our CLIA lab in Oakland.  They will receive the report by e-mail and we can send them nutraceuticals and customized probiotics for a 90-day treatment based on the results [and] we will work with them through conception and pregnancy. Please refer potential customers to

We also will repeat our proof-of-concept with 86 infertile couples and 20 fertile couples in a clinical trial at Wayne State University with Professor Gil Mor, the chairman of the Clinical Research Center at Wayne State University and president of the American Society of Reproductive Immunology. I have been a member of this society since the last 15 years. 

PW: For your alpha test, you are poised to bring in early users and ship your product — who are you partnering with to make this happen? 

GG: Our partner in the CLIA lab is Renegade Bio, our partner in digital marketing is Bullmetrix, our supplier of probiotics is Sacco System, and the supplier of our customized private label nutraceuticals is Equinox. 

PW: You talk a lot about a couple’s fertility, not just a woman’s.        

GG: We are planning to study male partners during the clinical study at Wayne State.  We know that the markers we hunt for in our test can impact fertility potential in women, and they can also be exchanged by fluids. So we want to test the expression of these markers and restore missing key components of the fertility biome in a male partner, too.  

We also have a scientific collaboration with a pediatric gastroenterologist that will run our study with autistic and celiac infants.  We intend to track the expression of our markers in the family and prevent early onset of diseases associated with microbiome disbalances like autoimmunity.

Check out Microgenesis at IndieBio’s (virtual) Demo Day on 28 October!  Register here for the two-day event (27-28 October 2020).  

Brightcure: Reviving, Restoring, and Replenishing a Woman’s Intimate Microbiome.

Brightcure is a company dedicated to improving women’s health. We asked Brightcure CEO Chiara Heide questions about the first product, a bioactive cream that promotes a healthy microbiome in a woman’s urogenital tract. 

Watch and read an abbreviated version of the conversation below.

Your personal story lends a lot of motivation. Will you please share it?

I personally suffered from chronic urinary tract infections, caused by harmful bacteria that enter the bladder and cause an infection. However, I’m not alone; every second woman worldwide suffers from these infections, and many are my friends and family.

I was super frustrated with the treatment situation because urinary tract infections are basically treated by antibiotics. There aren’t validated alternatives available and antibiotic resistance is now much more common. What that means is that many women experience a vicious cycle, to constantly contract infections and subsequently constantly take antibiotics. 

This is not a sustainable solution; it’s bad for the immune system and the natural microbiota. Antibiotics destroy the microbiome of your vaginal flora, and create many side effects, including making it more likely to get another infection because you don’t have the good bacteria in your intimate area anymore. Because of my frustration with this situation, I used my scientific background to look into new solutions. 

Tell us about Brightcure’s unique solution.

It’s very exciting: we basically found a good bacterium and we can use a good actor to fight the bad bacteria. Our bacterium is one that naturally exists on some healthy individuals and animals and can also be found in nature. There is nothing externally introduced.

This bacterium specifically fights the bad bacteria, but it does not affect the good bacteria of the urogenital tract, so it’s perfect for the intimate care area, because it balances your vaginal flora.

By fighting these bad bacteria, it gives the good bacteria room to colonize the vaginal area. This is what balances and promotes the good bacteria in the intimate area.

Is there risk of resistance developing to this solution?

There have been decades of research conducted with this bacteria and there is no associated risk with it. There has been extensive animal research around it and also testing in different human cells, and it has been in no way negative at all. 

This good bacterial strain basically eats the bad bacteria that cause these recurrent urinary tract infections. These normally travel from the rectum to infect the vaginal area. Our strain sees and kills bad bacteria, but it does not affect the good bacteria, those like Lactobacillus that promote vaginal flora. It is very targeted. 

How will women have access to Brightcure’s cream?

We are using this bacterium in our cream. It will be an intimate cream sold as a cosmetic cream that women apply externally to their intimate area; our bacterium is in that cream.

The cream will be sold as a cosmetic, making it a consumer product that women can easily access. We have a newsletter on our website to get the latest updates on our product development and our product itself. We also have a list where you can sign up for pre-launch notification if you are really keen on the product. We’ll have the product ready next year (2021).

We aim to destigmatize the conversation around intimate health. The community aspect is really important for me, because there’s not enough awareness around UTIs and the stress levels around chronic infection. It has a huge impact on women’s life.

To make the claim specifically around preventing UTIs, we will be partnering with clinicians and healthcare providers for rigorous clinical studies. These will allow us to make more specific claims about efficacy in the future.

How does this cream promote a healthy intimate microbiome? 

By fighting these bad bacteria, it gives the good bacteria room to colonize the vaginal area. This is what balances and promotes the good bacteria in the intimate area.

How will Brightcure change women’s intimate health in the future?

I hope to create a huge supportive Brightcure community, who uses our products. I hope we can reduce their suffering and bring back happiness to their everyday life with less stress. I hope we raise awareness for UTI and UTI patients because it has a major impact on a woman’s life, as well as how important the vaginal flora is to boost one’s immune system.

Learn more about Brightcure and all of IndieBio New York Class 1 companies at Demo Day.

The MicroBiome is a Drug Factory

At IndieBio, our perspective on gut bacteria is informed not just by the companies we’ve invested in that do human microbiome science, but by all the companies in our portfolio who work with bacteria and biomes in diverse sectors from the Future of Food to the Future of Energy to Biomaterials to Agriculture.

Early Popularization

A decade ago, the microbiome was a novel curiosity. The public learned that there was anywhere from 3 to 5 pounds of bacteria inside our bodies. Each was around one or two microns long — a tenth the size of cells. The number of them was astounding: estimated at 100 trillion. Exactly how they survived inside our bodies, without being attacked by our immune system, was unknown. Western diets (and overly-sanitary conditions) were eliminating our gut diversity; westerners had lost a third of their microbiome diversity, and flora diversity was correlated with health — across all animals, and all conditions. Probiotic drinks showed up on every store shelf, and soon after came the prebiotic supplements that gut bacteria feed on — oligosaccharides, fructans, and galactans.

A New Metaphor Emerges

Society grew to appreciate how the microbiome was important to health. Early research showed the gut was the source of 90% of our serotonin, and 60% of our oxytocin. That state of your gut was directly connected to the state of your mind. For awhile, the gut was often characterized as our “second brain.”

It’s time to upgrade that metaphor. Yes, the biome acts on our brain — but it acts on just about every other part of our body, too. The microbiome is more like a drug factory. It’s the “invisible organ” of the body that interacts with 70% of our immune system, generating our circadian rhythms, and turning our genes on and off.

When we say “drugs,” we’re using the term a little loosely to make the point. They’re naturally made. And in many species of bacteria, their output might not be quite a drug, but it’s a bioactive compound that acts on a pathway elsewhere in the body, either as a primary metabolite or a secondary metabolite. In this sense, the line between a drug and a bioactive compound is virtually indistinguishable, as the definition of a drug is anything with physiological effects. Traditionally, what we meant by “drugs” was that they were made outside the body and then put into the body. Arguably, most of this definition holds, as the bacteria are not of our body, even if they are inside it.

The Drug Factory’s “Top Sellers”

To list all the drugs made by bacteria in our bodies would take far too long. But here’s a short, starter list — solely for the purpose of illustrating the point that the microbiome has widespread impact on the body, for both better and worse:

  • Histamines, both pro and anti-inflammatories
  • Beta-glucuronidase / hormones / estrogen & estrogen cancers
  • Short-chain fatty-acids / histone chrotonylation / HDAC2 / gene regulation
  • 5-HT biosynthesis / Enterochromaffin cells / Serotonin, brain neurotransmitter
  • Chylomicrons / energy-rich triacylglycerol
  • Tyramine / blood pressure & hypertension
  • Microcins that block salmonella
  • Oxalate / protein transporter SLC26A6 / prevents kidney stones
  • Zonulin / haptoglobin 2 / atherosclerosis
  • Glutamate & cytokines / Vagus nerve / Oxytocin
  • Tryptophan & tryptophan antibiotics
  • Glucagon Peptide 2 / GLP2R / bone and neuroprotection
  • Butyrate / Insulin Sensitivity / Diabetes & Obesity
  • Deoxycholate / fat reduction
  • A-tocopherol / Vitamin E / free radical scavengers
  • G-aminobutyric acid / neurotransmitter / muscle tone
  • Cholate / FXR transcription factor / antimicrobial peptides
  • P-aminobenzoate / Folate / blood cell creation
  • Eicosatetraenoic acid / Endocannabinoids anandamide and 2-AG
  • Commendamide / GPR132/G2A / prevents autoimmune disease

All of the above are from the gut, but the gut isn’t the only place we have bacteria. A skin bacteria, staphylococcus epidermis, fights skin cancers — producing 6-HAP, which inhibits melanoma and lymphoma tumor cells.

Other Mechanisms of Action

Making drugs outright is only one way the bacteria in our gut do their work. Another way is that they chop free bioactive peptides or small molecules from longer chain proteins. A lot of what we eat is digested by hydrochloric acid and protease actions into basic building blocks. But food proteins also contain certain biochemical strings that, if chopped correctly, are then biologically active.

The microbiome also interferes with medical drugs. 80% of our current medical drugs are metabolized in the liver, but 20% of the drugs on the market are metabolized by gut bacteria. Since some people have different flora than others, these drugs tend not to work as intended for certain people. For instance, the emerging market of Anti-PD-1 checkpoint blockade immunotherapy has only a 10% success rate. It’s still a matter of debate just how to get that rate up, but many of the solutions being researched involve first transplanting necessary microbiota into the patient. About 50 medical drugs are now understood to be codependent on gut bacteria populations.

The Birth of Microbiome Therapeutics

The race to translate this research into commercial therapies is well under way. There are at least 6 drugs in development to treat cancers, from solid tumors to mucositis, with one candidate already in Phase II. There are three drugs in development for obesity, and five in development for diabetes, with one at Phase II. Fourteen drugs are being developed for Crohn’s and ulcerative colitis, with one of each at Phase II. There are drugs for lactose intolerance, for dental caries, for repeated urinary tract infections, for celiac disease, and several skin diseases, with one in Phase III for acne. Revenue out of this market is expected to begin in 2021 and reach $10 billion by 2024, continuing to go up steadily in the decade beyond.

We view the acceleration of this pipeline as proof of its market potential, but not necessarily as evidence that science has strong command and control over gut bacteria and all they interact with.

Finely-Tuned Control (and Effects)

To gain precise command over the drug factory, a variety of tools and competencies are needed. Science teams with these expertises are what IndieBio looks for and what drives our investments.

  • Daily Fluctuation Tracking. Most microbiome research today uses single-shot samples of patients’ stool samples. But disease states tend to correlate with dramatic, short-term swings in the species population. For researchers to model these correlations, they desperately need a low-cost assay to track population swings. When such a tool is available, we believe it will be widely used — by all manner of researchers, even those who don’t currently factor in microbiome effects. It will also become a common biomarker in clinical trials, and then be required as a companion with microbiome therapeutics.
  • Personalization. Because everybody’s microbiome is unique, and because the bacteria interact with each other, off-the-shelf probiotics are likely to work for some people, and not for others — or, to avoid undesired side effects, they have to be dosed at numbers that are too low to have much impact at all. Companies that built trust with consumers making personalized probiotic services will be able to grow into more and more effective blends.
  • Setting You Up for Life. An infant’s microbiome fluctuates continuously in the first three years, but then largely stabilizes (with the exceptions around the disease-states described here, when health and the microbiome both swing together). There are two significant opportunities in this space. First, how to help an infant’s microbiome, from the first weeks to the first years, and second, how to optimize the biome around that stabilization transition —for a lifelong impact. In the US today, 32% of babies are born by caesarian section,
  • Shared Metabolites. Bacteria by themselves are not the same as bacteria in a biome. A biome is an ecosystem; the bacteria interact, regulate each other, and the metabolites from some bacteria become the feed for others, in a chain reaction. For this reason, transplanting and colonizing individual strains is often ineffective. It’s not enough to formulate a strain in a synbiotic that combines the probiotic with a prebiotic — as soon as that hits the gut, other bacteria may suppress it. Companies that have worked out the interactions within a consortia of bacteria have a much better technology platform.
  • Variants Within a Species. Most news about microbiome-health correlations is based on research looking at relative species populations. People with more of strain X have less of health condition Y, and so forth. But there is still a great deal of genetic variation within a species. Think about all the humans on the planet for a moment — we are all one species, but our DNA (and our health) varies meaningfully. Some of the best microbiome research investigates these differences; cohorts of people with the same species, but some have variants of that species — and dramatically different health functions as a result.
  • Precision editing. Rational design of the bacteria genome is seemingly inevitable. Researchers today are busy editing microbiota as a way of understanding what the edits do — attacking it node by node. The challenge this path faces is that bacteria have ways of sharing their DNA, so precision edits could spread around a microbiome in unintended ways. One approach at a solution is to make the edits in the bacterium chromosome, not in the plasmid. But this has had mixed results.
  • Culturing the Unculturable. 99% of the bacteria found in the wild have been unculturable in the lab; they grow in unusual conditions. A less extreme version of this occurs in the human gut, where some bacteria that have been identified as beneficial have unconventional properties and are particularly hard to colonize. Researchers who have developed expertise in culturing them have an advantage over researchers who’ve merely identified them.

At IndieBio, we are always looking for the next great microbiome company. We don’t just invest in startups — we help create them, often working with post-docs and principal investigators to build a team and transform them into scientist-entrepreneurs. To learn more, visit

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The Most Incredible Technology You’ve Never Seen

Guest post By Bryan Johnson, founder of Kernel, OS Fund, and Braintree

Saving the world (or some subset of people in it) is in vogue among the world’s wealthiest.

Jeff Bezos has a rocket company, Blue Origin. Bezos believes our future is extraterrestrial, and his rocket company exists because he thinks the price for getting anything off this rock is too damn high.

Bezos is not alone. Elon Musk is also building huge, reusable rockets. He wants to see humans fly to Mars, initially on a lark but eventually for forever.

This type of long-term thinking about the future of our species coupled with serious investment is important. But Bezos and Musk (and most other investors) are missing the most significant — and smallest — technological opportunity to save humanity.

No one has captured this tech blindspot better than my friend and Ginkgo Bioworks Co-Founder Jason Kelly. He did it by showing an image like this:

“What’s the most advanced piece of technology you see on this desk?,” Kelly asked his audience. The correct answer is in green.

A $4 houseplant is one of the most astonishing objects ever assembled. It’s a biodegradable, carbon-capturing, self-replicating, solar-powered work of art. Have you ever bought an electronic gadget that even comes close?

The mind-bending fact that a common shrub is more advanced than the latest MacBook Pro is overlooked by almost everyone. We fail to see it for a simple reason: the coolest parts of a plant can’t be seen. Not with the naked eye, at least.

It’s at the molecular level that plants fix CO2, soak up sunlight and churn out nutrients that we can eat. Way down at the level of atoms and molecules, the most mundane living objects are doing things that our best engineers can only dream of.

Small solutions to big problems

Humanity faces enormous, imminent challenges. The way we use energy is poisoning the planet, we are on track to use up many of our most important non-renewable resources, and we are ill prepared for the next inevitable global pandemic. And that’s just a small sampling of the challenges we see coming; there are dozens more around corners we can’t see around.

Major advances in deep tech – the marriage of hard sciences and emerging technology –  is going to be critical if humanity is to survive these challenges and thrive, but most of the money in the world is maintained or managed by people who do not have formal scientific training. For example, just 5% of the Forbes richest 400 people have formal scientific training. Most therefore invest in things they’re familiar with, like real estate, software and finance.

I founded OS Fund to support the scientists entrepreneurs bringing deep tech to market; leveraging hard sciences and technology to rewrite the basic operating systems of our world. Atoms, molecules, genes and proteins can be designed like never before. The biological world has already demonstrated what’s possible on this scale — if we’re going to aim big as a species, it’s time we think small.

At OS Fund, we don’t invest in particular problems. Instead of trying to solve energy or climate change or the spread of disease, we invest in the foundational technology that could be applied to solve all problems. In the same way that early computer companies like Intel, Apple and Microsoft helped spawn the modern era of computing, we aim to do the same thing with atoms, molecules, organisms and complex systems.

The scientists at Ginkgo Bioworks, one of the first companies in the OS Fund ecosystem, are charting their way by designing bacteria that puff out perfume, crops that fertilize themselves, gut microbes to make medicine, and much more. With three highly automated foundries up and running, the company is poised to upset almost every industry you can think of.

Arzeda, another OS Fund company, is using computers to design new genetically-encoded nanomachines, otherwise known as proteins. Although most of us know proteins only as food, these intricate biological objects actually do almost all the work needed to keep cells alive. Designing new proteins from scratch will let humanity play by biology’s rules, meaning we can design our way to better food, fuels and chemicals in the greenest way possible.

Another OS Fund company rewriting our world is NuMat, where they’re  arranging atoms in MOFs (metal organic frameworks) to create the most powerful sponges you’ve never heard of. NuMat works at the intersection of high-performance computing, chemistry, and hardware systems to design and manufacture materials that can filter non-renewable material like xenon out of thin air.

But wait, I can hear you thinking, isn’t AI going to eliminate the need for this kind of innovation?

That may be the grandest challenge of them all. How are we as a species going to thrive in a world where artificial intelligence can do more even than our best minds? The answer again requires innovation at the molecular level.

I started Kernel, a neuroenhancement company, personally investing $100M, to help ensure that humans and AI evolve together. We are working at the bleeding edge of neuroscience, solid-state quantum devices, materials science, and photonics to develop the science and brain interface products to allow people to bring their brains “online,” and use that data to radically improve themselves. Radical human cognitive improvement is a requirement if humanity is going to thrive in the future we are barrelling toward. We are a few tools away from an evolutionary leap; what’s on the other side of it is beyond what we can possibly imagine.

Investing in huge rockets, brain interfaces and tiny molecules isn’t actually that different. Developing a green global economy and exploring beyond our pale blue dot are complementary — not competing — visions of the future. It’s time investments in our future here on Earth get the attention and scale afforded those focused on our future in the cosmos.

Oralta: pioneering oral care through the microbiome

Americans spend over 40 billion dollars every year taking care of their oral health, yet conditions like bad breath, gum disease, and tooth decay are incredibly common. Oralta is looking to change the paradigm of oral health by going beyond the symptom based treatment of today’s products. They’re doing this by targeting the oral microbiome, restoring balance between communities of good bacteria.

I sat down with Kishore Nannapaneni, Oralta’s CEO, to learn more about how Oralta is changing oral health.

How did you become interested in microbiome science?

My first job was as a plant scientist at DuPont Pioneer when they acquired Danisco and Genencor. These were both biotech companies working with bacteria, but DuPont didn’t have a bioinformatics staff, and I was put in charge of handling it. This was my first introduction to bacteria and fungi. I loved working with them. They’re much simpler organisms. Their genes have all been annotated, so it’s easy to work with and you can see the results really fast. It’s not like plants where the genomes have not been sequenced, and you can never completely sequence them. There’s a lot of uncertainties with the plant genomes because they’re large,  have a lot of repeats, and a lot of transplants. The relative simplicity of working with bacteria made them incredibly interesting models to work with..

How did you go from working on the microbiome at DuPont to thinking about starting Oralta? And how did you and the team get together?

While I was working at DuPont, Denisco called and said they had started getting their own bioinformatics faculty. I couldn’t continue working with microbial bioinformatics anymore. I’d have to go back to my plant bioinformatics. So, I was looking for a job in microbial bioinformatics and was then hired at Bayer Crop Science where I met Patrick. I never had any problems with my teeth. Patrick, on the other hand, has had a lot of cavities, and he would complain about how he hated going to the dentist. Then, an idea came to us. We were identifying which  bacteria helps plants grow better and helps them fight fungal diseases. Why can’t we do the same for the oral space? Because of the fact that I have good oral hygiene and somebody else doesn’t means that there is a good microbiome and a bad microbiome. If we could identify the bacteria in the good microbiome and put them in people with bad oral health, then we would be able to restore their oral health.

How did that idea become a company and what product are you focused on currently?

Our first product is for bad breath, and the reason we are going for bad breath first is because we can see efficacy in just two weeks. We have a unique formulation formatted as a chewable tablet. People can take it once in the morning and once in the evening after brushing their teeth, and the bad breath levels will drop really significantly in just two weeks. This is an easy way to go directly to the market and make a name for ourselves. We have plans to develop other products in the very near future for other common oral conditions.

What lessons did you learn transitioning into scientific entrepreneurship at IndieBio?

The biggest thing for me at IndieBio was the pace. You’re always working really hard, your peers are working very hard, and IndieBio has been very helpful in pushing us to reach our weekly milestones at a rapid pace. This was the most important thing for me apart from all the connections made through IndieBio and the workshops. For me, the most important thing is that IndieBio sets the pace, and it’s up to you to actually take it beyond the program and work with the same passion and pace.

How do you think success is for Oralta a company can change the dental and oral care industry?

At this point, most other oral hygiene routines are only addressing the symptoms. For example, if you’re brushing your teeth, then you’re only reducing the biofilm and by the evening it grows back. It’s the same thing with mouthwashes, mint, and gum. They’re not addressing the root cause of oral diseases like tooth decay, gum disease, and bad breath. We are addressing the problem at the root. We’re trying to rebalance the oral microbiome from a diseased state to a healthy state. In the case of a bad breath, it’s caused by a bacteria releasing volatile sulfur compounds. Our chewable tablets will replace the odor-causing bacteria and replenish the mouth with good bacteria.

What are the big milestones that as a company you are looking to hit in the near future?

Our first product for bad breath is coming out in November 2018, and our second product for gum disease is coming out in Q2 of 2019. Lastly, our third product for tooth decay is coming in Q2 of 2019. Simultaneously, we are building an Oralta AI platform where we will be sequencing thousands of diseased and healthy microbiomes, which we will feed to a platform. The platform will then design the new generation of probiotics and therapeutics.

When you are talking about using the microbiome to design new therapeutics, how do you see this space of microbiome expanding in the future? Do you think it’s a new frontier of medicine?

There is an emerging body of evidence that suggests the role of the oral microbiome in systemic diseases like Alzheimer’s, oral cancer, cardiovascular disease, etc. This has already been established in the case of the gut microbiome. A lot of companies are already successful in the space where they’ve come up with therapeutics, and there’s an emerging body of evidence in the gut microbiome, the gut-brain access, etc. I think there is a great future for therapeutics in the microbiome space and specifically in the oral microbiome space. Our goal is to be the powerhouse of the oral microbiome space.

Watch Oralta pitch on IndieBio Demo Day, Tuesday Nov. 6th in San Francisco or via LiveStream. Register here!

Sun Genomics: Precision Probiotics Based on Your DNA

It all begins in the gut. We know that a balanced gut microbiome is key to a healthy (and happy) life. Probiotics, ingestible products that contain healthy bacteria and yeast, are available for people to buy and help with their digestive issues. But not all probiotics are created equal.

Sun Genomics found that an individual’s genome can help identify which probiotic strains are best for the person. By creating personalized probiotics, the company can eliminate the guesswork that’s involved with buying probiotics off the shelf and help people regain control of their health. We asked Sunny Jain, the company’s founder and CEO, more about their personalized probiotics:

How did you become interested in the gut microbiome?

SJ: I’ve studied Microbiology for a decade now and have always had interest in gut health. However, the real turning point was in early 2016. My son was suffering from a dysbiosis and when I went to the local grocery store to pick up a probiotic, I was faced with the realization that the consumer products on the shelf were utterly confusing. I had no idea what to choose between CFUs, strains, and the refrigerated section. So instead of picking up one probiotic, I grabbed tons off the shelf and began testing them in the lab.  My concerns were validated when the store-bought probiotics did not contain the strains listed on the bottle and failed to survive the gastric system. At that point, I custom formulated a probiotic for my son, alleviating his gut health issue. I realized that targeted probiotics were 8 times more specific and I could ensure they worked.

Sunny Jain
Sunny Jain

When did you decide to start a company, and where did your team get together?

SJ: I began the company by myself in 2016, but once I realized that I had an affordable solution for the world’s health issues, I began hiring key members of my team. We came together in a relatively auspicious way. For example, I connected with our bioinformatics hire, Thibaut Montagne, when he began following Sun Genomics’ Twitter Account.  We began building the team rapidly after Thibaut and all the pieces began to fall into place.

How does your technology work?

SJ: Sun Genomics uses next generation whole genome sequencing and a patented bioinformatics and data platform to process and analyze the DNA of its customers’ gut microbiome. We leverage existing data compiled by the Human Microbiome Project and American Gut Project and integrate that information into our existing technology. Our vast database of over 100,000 genomes allows our team of microbiome scientists to make calls related to not only bacterial strains but fungi, parasites, and viruses found in the gut microbiome, thereby allowing us to create custom probiotics for the end user.

What lessons did you learn transitioning from science to entrepreneurship at IndieBio?

SJ: IndieBio and its team challenged us to think bigger and innovate quicker. In order for me to share my findings with the world, I was going to have to move from just being a laboratorian to a entrepreneur. During our four months at IndieBio we experienced more growth than over the previous 14 months as a company. We developed and filed additional intellectual property, grew our customer base by 1000%, and hired several key employees to assist us with our growth.

How do you think your success as a company would change the healthcare industry?

SJ: At Sun Genomics we believe, as did Hippocrates, that “All Disease Begins in the Gut.” Billions of people worldwide suffer from disease states and chronic conditions that both Eastern and Western medicine have been unable to diagnose and treat. We believe the gut microbiome holds the key to alleviating some of these conditions including; arthritis, Chron’s, lupus, diabetes, IBD, IBS, colitis, obesity, and perhaps even certain types of cancers. As a microbiome health company, our vision is to not find really expensive solutions for only a few, but affordable solutions for billions of people.

What milestones are you aiming to hit in the near future?

SJ: Sun Genomics is experiencing unprecedented customer growth and soon will announce additional partnerships, publications, and commercialization milestones. We are well on our way to analyzing 10,000 microbiome profiles and becoming a leading contributor to microbiome science. We have developed core technology that is beyond probiotics. Come hear about our newest innovation at IndieBio Demo day on April 17th.

Watch Sun Genomics pitch on IndieBio Demo Day, Tuesday April 17th in San Francisco or via LiveStream. Register here!

Antibiotic Adjuvant: Transforming Antibiotic Use from Chaos into a Coordinated Campaign

Although doctors mean well by prescribing antibiotics, we can’t ignore the fact that antibiotic resistance as an effect of overuse has become an overwhelming problem in the healthcare industry and elsewhere. The situation can appear hopeless to some, but the team at Antibiotic Adjuvant sees it as a challenge they are willing to accept. They have developed software that works with the doctor at point-of-decision, along with the patient’s specific information and information about the facility itself, transforming antibiotic use from chaos into a coordinated, conscious campaign. Using the correct methods, antibiotic resistance therefore becomes preventable. We asked David Flores, the co-founder and CEO of Antibiotic Adjuvant, and Dr. Robert Yancey Jr, the company’s co-founder and Medical Director, to tell us more about their motivation and how it all works:

How did you become interested in healthcare?

DF: When I was a little boy, I wanted to be just like my father, a doctor. However, after being in the O.R. couple of times, I decided to study something else. The bug never seemed to fade on me though. While having another business, I found myself talking to doctors and doing apps in the healthcare space. After learning about this problem from Bob, our Medical Director, I just couldn’t believe how crazy it is that antibiotic resistance is growing so rampantly, and that no one seems able to control it—even though it is preventable!

RY: I have wanted to be a doctor since I was eight years old. It is a gift and a privilege to practice medicine. Infectious Diseases is by far the most interesting sub-specialty in medicine.  It is a little like being Sherlock Holmes. Seeing patients in the hospital getting substandard antibiotics so frequently made me think that there has to be a better way, and as a consequence, I have been working in the field of Antibiotic Stewardship for over 20 years.

When did you decide to start a company, and where did your team get together?

DF: Preventing the increase in antibiotic resistance is a very compelling problem that can be prevented by applying new technologies to existing systems. After doing couple of prototypes and getting good feedback from doctors and nurses, we decided it was time to tackle this problem. We started working in Gainesville, FL and relocated to San Francisco to improve our chances of making this idea a reality while doing IndieBio.

RY: I have been kicking this idea of how to codify algorithms for improved and coordinated antibiotic use for many years, after it became obvious that current methods of Antibiotic Stewardship were inadequate.

How does your technology work?

DF: We have created a software that reduces the time it takes a doctor to prescribe antibiotics, improves communications between pharmacists, doctors, and nurses; saves the hospital millions of dollars in unneeded procedures and loss of funding, and improves patient outcomes. We can do this by improving the way antibiotic stewardship programs are implemented in a health center. Our software uses input from the electronic medical records, lab reports, and other reports to provide personalized antibiotic recommendations for a particular patient and facility. We take into account the health center’s microbiome and create a coordinated antibiotic campaign to prevent antibiotic resistance from occurring in the first place. Since we are with the doctor at point-of-decision, we can affect virtually every patient in the facility and provide true comprehensive antibiotic stewardship.

RY: The basic premise is that given sufficient, easy to understand information, the busy physician will do the correct thing, especially if it is fast. In addition, modern analytics can help even the most knowledgeable physician make better decisions. The fields of Quality Assurance and Infection Prevention are enhanced by identifying and predicting all adverse events and infections in the facility, not just those with a positive culture, and their predisposing factors.  Administration can identify methods to reduce costs that were not visible before. Patients have better outcomes. Win-Win!

What lessons did you learn transitioning from science to entrepreneurship at IndieBio?

DF: The main difference I see between science and entrepreneurship is the market forces. In the market, you have to take into account the feasibility of the science but also the costs to create the product. The profit margins have to be healthy, and your customers must want to use your product. The market will reward companies that take these three pieces into account when commercializing a technology/idea.

RY: Saving lives and costs is a great product, but we have to demonstrate that we can execute. IndieBio has helped us execute in so many ways. They have pushed us to be the best we can be, not just an idea.

How do you think your success as a company would change the medical industry?

DF: We will fundamentally change the way antibiotic prescriptions are made in the world. In the future, people will be able to go to the hospital and not acquire an infection while receiving treatment because health centers will not have rampant antibiotic resistance as they do today.

RY: We will transform antibiotic use from chaos to a coordinated conscious campaign to minimize resistance and complications. More intelligent antibiotic use means a safer, more effective, less costly healthcare system.

What milestones are you aiming to hit in the near future?

DF: We are aiming to arm skilled nursing facilities with tools to improve their antibiotic stewardship programs and then start doing a pilot in hospitals.

RY: Out first installation into a skilled nursing facility is underway, and we will reach at least 100 more facilities within 10 months. CMS requirements for Antibiotic Stewardship and Infection Control will drive our sales. Testing in acute care hospitals will begin in early 2019 with demonstration of financial and patient safety benefits within months after that. At that point, AA will add physicians’ offices to the campaign to monitor and control resistance in entire communities. It’s a big goal, but doable according to the CDC.

Watch Antibiotic Adjuvant pitch on IndieBio Demo Day, Tuesday, April 17th in San Francisco or via LiveStream. Register here!

Sugarlogix: Prebiotic Sugar for Your Gut Health

What if sugar was good for you? The consumption of excess sugar has led to health issues in humans, such as autoimmune diseases and IBD, that begin in the gut. Sugarlogix has found a way to create prebiotic sugars to fix this problem and make sugar that’s actually healthy for people to consume. Although there are plenty of probiotic solutions that add good bacteria to the gut, Sugarlogix’s prebiotic sugar is the missing link in actually nourishing those good bacteria. The company’s co-founder and CTO, Chaeyoung Shin, explained more:

Where did everyone on your team first meet?

CS: I’m from UC Berkeley, and that’s where our team got together. We were originally part of a large project funded by British Petroleum to make biofuels out of fermentation. Our co-founding team consists of two professors and two PhD graduate students including myself. After that project, we realized that, “Hey, we could use this technology to make something of higher value.” That’s when we decided to build a company.

So you started with biofuels, and now you’re focusing on sugars?

CS: Yes, but not just any sugar. Prebiotic sugars. These sugars naturally exist in human breastmilk, however they’re not really accounted for anywhere in the market right now. They are starting to make some products that look like it, but not much, because it is very expensive to recreate it outside of a human body. We have the technology to do that in a cost-effective and food-safe way. We brew the prebiotic sugars by using yeast fermentation. It’s just the bakery yeast that we normally use.

How did you become interested in science and biotech?

CS: That goes back a long way. I actually chose to be in the biofuels project during my PhD because I knew we had no way of going around biotechnology. Right now the current industry consists of a lot of chemical-based industries, but we know that these won’t last forever, and also they’re not environmentally friendly. Now in biology, the coolest things happen. Just look at our bodies, it’s amazing what biology can obtain. Improving our knowledge of biotechnology would enable us to mimic biology and use it to our benefit. So that’s how I became interested in that area and I decided to focus my PhD project on it.

Why is Sugarlogix’s technology needed right now, and what problem is it solving?

CS: We know that our current way of living is not the healthiest kind with conventional sugars. We’re exposed to a lot of fatty foods, and that’s why so many people experience gut discomfort. There’s been a huge increase in gut-related diseases, including irritable bowel syndrome and autoimmune diseases which are known to have direct relationships to gut health. One way to prevent that is to provide these types of prebiotics to the gut. In relationship to probiotics (the probiotics are the good gut bacteria), the probiotics are food for the good gut bacteria. Only by having those two components can the good gut bacteria really thrive in your gut. There are probiotic solutions out there, but not the prebiotic part. And by providing the other half, we would really be able to affect people’s gut health in a good way.

What would be the single biggest indicator that your company is succeeding?

CS: Thankfully a lot of people have done research on prebiotic sugars that exist in human breastmilk. It has been long been known as the holy grail of an infant formula ingredient. As long as new research doesn’t come out that proves otherwise, we have solid proof that our technology will benefit people’s gut health. In the long run, an indicator that we’re successful would be the fact that we’re making a lot of profit by selling these prebiotic sugars. The question is different in terms of a short term goal. We want to do a demonstration of a larger size than where we’re currently at. We are hoping to move up to a larger size fermenter to prove to our investors and customers that we can indeed manufacture this on a large scale.

What big lessons have you learned transitioning from science to entrepreneurship at IndieBio?

CS: I never envisioned myself going through this type of transition. I thought I was just going to be scientist. But now my role has dramatically changed, where I’m actively seeking out customers, and actively reaching out to suppliers and investors. For me personally, talking to investors and recruiting them is the toughest part about all this, because you have to sell yourself as well as the company, and it’s something I’m still getting comfortable with. At IndieBio, it’s been really fun to see all the gears of the company come together along with my partner Kulika Chomvong, who is running all the gears.

See Sugarlogix pitch at IndieBio Demo Day on September 14th in San Francisco or via Livestream! Register here.

Photo credit: Or Weizman

Improving Your Pet’s Digestive Health With Science: An Interview with Holly Ganz of AnimalBiome

It’s not uncommon for a pet dog or cat to have digestive issues, especially early in life. Instead of treating the root of the problem—an imbalance of good and bad bacteria in the gut—veterinarians commonly prescribe antibiotics. Without a true fix for the problem, pets can fall victim to a number of other health issues later in life as a result.

Animal Biome is harnessing the power of the microbiome to make targeted therapeutics for dogs and cats that are suffering from digestive issues. We asked the company’s CEO, Holly Ganz, a few questions:

Tell me about your background, how did you get interested in the biotech space?

Up until recently, I was an academic researcher working at UC Davis studying co-evolution between animals and microbes. I became interested in the biotech space after launching a citizen science project to study the microbiology of domestic cats. From this experience, I learned that digestive disorders are common in cats and that many of these kitties have an imbalance in the composition of bacteria in their gut. I found that chronic conditions like Irritable Bowel Disease cost pet owners thousands of dollars to diagnose and manage, and there is currently no cure. My goal is to rapidly translate what we are learning in our research to create solutions for pet owners.

“I found that chronic conditions like Irritable Bowel Disease cost pet owners thousands of dollars to diagnose and manage, and there is currently no cure.”

Holly Ganz, CEO

What problem are you working to solve with your company, AnimalBiome?

We estimate that about 10 million dogs and cats in the US suffer from digestive disorders. Based on our research, we have found that many digestive disorders are linked to low bacterial diversity in the gut. The current solutions to these disorders are expensive and they only address the symptoms, not the source of the problem. At AnimalBiome, we are using our assessment kit to allow pet owners to view their pet’s bacterial diversity, and we are developing solutions in the form of fecal transplant pills and cat- and dog-specific probiotic mixtures.

If you could only pick one thing to validate your reason for forming a startup, what would it be? In other words, what would be the single biggest indicator to you that you are doing the right thing?

Our customers and partner veterinarians are already telling us that we are doing the right thing. It is a certainty that microbiome data is going to be used to improve the health and wellness of both pets and their owners in the future, and we are striving to make that happen as soon as possible.

How do you think success can change your industry?

Our success can change the pet health industry by enabling pet owners and veterinarians to make data driven decisions about the care of their pets. The gut microbiome influences more than just digestion; it’s been linked to conditions such as allergies, diabetes and even depression. The more pet owners we have participating in our cause, the more successful we will be at addressing the underlying role of gut bacteria in a wide variety of disorders.

How is your team uniquely able to tackle this? What’s the expertise?

Our team of scientists has amassed the largest database in the world on the microbiome of the order Carnivora (dogs, cats, and their close relatives). We are researchers from UC Davis and UC Berkeley, who have published more than 30 papers and have extensive experience in both microbiology, computational biology and data analytics.

“Our team of scientists has amassed the largest database in the world on the microbiome of the order Carnivora (dogs, cats, and their close relatives).”

Holly Ganz, CEO

Any big lessons learned transitioning to startup entrepreneurship?

In academia, we have more freedom to pursue our own personal, intellectual interests, so long as we can find funding to do so. In the private sector you have to understand the market needs and focus your time on building your business to meet those needs.

What’s the biggest challenge you’ve encountered so far?

We’ve developed personal relationships with a number of our customers who have grieved the loss of their companion animal. Although we are currently able to diagnose low gut bacteria diversity, we do not yet have the amount of data necessary to provide tailored cures for their pets. The biggest challenge we’re currently facing is learning how to quickly spread our mission so we can provide solutions to ailing pets as soon as possible.

What are the big goals and milestones you’re looking to hit in the short term? Long term?

Our big goal in the short term is to hit 5,000 participants in DoggyBiome and KittyBiome. In the long term, our goal is to create tailored probiotics using isolates that we have identified from this database as being essential for animal health.

Check out the products in Animal Biome’s shop, and register for the IndieBio Demo Day LiveStream (Feb. 9th) to watch them pitch!