Author: Jun Axup

Liberum: Automating Protein Production

Posted on by Jun Axup

When we think of synthetic biology, we often think of synthetic DNA. However, the purpose of the DNA is often to make protein. Today we can order DNA overnight for cheap, but producing protein takes at least two weeks of lab work with various instruments and techniques. Liberum aims to free researchers from the tedious task of turning DNA into protein and make experiments faster and cheaper. I chatted with Liberum’s CEO, Aidan Tinafar.

How important is protein for biological research and production?

When most people hear the word protein, they immediately think of food. Proteins are far more than food. They are used as therapeutics, industrial catalysts, biomedical research tools, materials for manufacturing and additives in consumer goods just to name a few. Insulin is a protein. Chymosin, the enzyme that enables cheesemaking is a protein. Silk is two proteins combined.

Imagine if you could come up with a type of material that you could design with vastly diverse physical and chemical properties for a whole host of applications. Ideally, you would want this material to have three properties. First, you would want to be able to make the material from a small set of inputs that are readily available. Second, you would want to be able to control the properties of the material in a tunable or programmable fashion. And third, you would want the production process to be sustainable and capable of being integrated into pre-existing environmentally-friendly modes of production. Protein is that type of material.

Proteins are strings of building blocks called amino acids that are folded and held together such that they enable certain functions. Combinatorial combinations of 20 amino acids give rise to all the breathtaking diversity we see in nature. The type and order of amino acids are generally encoded within the DNA of an organism. A single cell such as an E. coli bacterium requires a couple thousand different proteins to carry out its biological activity. These proteins can act individually or in concert as networks.

One way to take advantage of proteins is to piggyback on an existing living organism. For example, we can use yeast to make beer without having to deal with its proteins on a granular level. We can also benefit from extracts, secretions or purified proteins from organisms found in nature.

In the 70s, we began gaining a grasp on being able to mix and match these wild-type proteins between organisms through somatic fusions and recombinant technologies. During the same decade, chemical synthesis of a complete gene was demonstrated for the first time. Shortly after, in the 80s, polymerase chain reaction (PCR) was invented allowing us to make billions of identical copies of these chemically derived sequences. Together, these technologies enable us to go from a digital DNA sequence stored on a computer to a designer protein within weeks. At Liberum, we significantly speed up this process, so that we can create better products faster.

These breakthroughs have already brought about the synthetic biology revolution with a total market size worth hundreds of billions of dollars and rapidly growing. For example, the size of the recombinant therapeutics market alone is now over 100 billion dollars. There are two factors that have hidden this revolution in plain sight. Firstly, cultural taboos surrounding genetically modified organisms (GMOs) have incentivized many to categorize these products as natural rather than engineered ones. More importantly, the wide range of applications of these technologies make the market appear highly fragmented. End products include anything from extracts and purified proteins to small molecules, cell lines and other goods and services that use these as intermediates. While apps of the internet revolution came to most through their screens, proteins that lead the synthetic biology revolution touch people’s lives in so many ways that make them hard to categorize as a single class. Massive shifts are often harder to observe.

What are the bottlenecks in creating protein today and how is your technology solving those bottlenecks?

Making protein using biology is hard. For every idea, for every iteration, you have to re-engineer the genetics of living cells, grow them, break them open and purify. This process is very hands-on. You need to keep coming back to it over a week or two. The process also requires expertise and expensive equipment that take up a lot of space. Even if you outsource the work to a contract research organization, you are still bound by similar timelines, plus the duration of shipping. Liberum speeds up and automates the protein manufacturing process in a miniaturized device without having the need to re-engineer any living cells. We do it all in a cell-free system that contains the same powerful enzymatic machinery used by cells.

Now you may wonder, why can we not chemically synthesize these proteins; what is so special about using biology to accomplish protein manufacturing? The problem with chemical synthesis of proteins is really two-fold. First, the error rate for state-of-the-art chemical amino acid incorporation hovers around 1%. This means that for an average bacterial protein of 320 amino acids in length, only about 4% of the final mixture would contain the correct sequence. More importantly, proper folding of amino acid chains into functioning proteins tends to be trickier in chemical systems. A system that more closely resembles biological conditions, such as a cell-free protein expression system, can avoid these problems.

Technical challenges of making proteins aside, there is a deeper conceptual issue at play. We can certainly make a protein of a specific function starting from a working DNA blueprint, but designing that blueprint is far from trivial. While rational and modular protein designs can be highly informative, they are rarely strictly prescriptive. One often needs to screen sizable libraries of designs to optimize for a specific function. Even if we take wild-type sequences from organisms in nature, there is still room for validation and screening of homologues. Unless and until we have computational means that can predictably design for functionality in silico, protein prototyping remains an indispensable tool for protein engineering.

How might your company change the way we produce protein?

We want to enable protein manufacturing at small scale with minimal time and capital investment on the part of our customers. The key insight for our business model is that we have separated the fermentation process from the act of protein production. This allows us to operate as a utility company that delivers protein production capacity to our clients on-demand. Our device and cartridges are merely the last mile. The infrastructure we build to enable this capacity is where much of the value we provide will be generated.

Once our customers have ordered and amplified their template DNA, they can simply place it inside one of our cartridges and produce their desired protein with a push of a button. Having the capacity in their own labs will allow them to optimize the desired conditions. It also provides control and rapid turnaround to enable more bright ideas to see the light of day.

What lessons have you learned transitioning from scientist to entrepreneur during the IndieBio program?

Put the customer first. Science is just the tool we use to serve our customers and the community at large. The value of our company is a function of the value we create for our customers and other stakeholders in the community.

What does the next year look like for Liberum?

Rapid iteration cycles to loop in customer feedback has been in our company’s DNA from the very early days. Our goal over the next year is to build our infrastructure such that we can bring the power of cell-free protein expression to thousands of labs around the world at very affordable prices. We will continue to build upon enhancing user experience through further iterations of the device and cartridges. Our goal is to wrap up alpha and beta testing as soon as possible so that we can launch our product within the next year.

Ivy Natal: Turning Skin Cells into Eggs

Posted on by Jun Axup

The future of our species depends on procreation, but today the world is at an all-time high in infertility due to disease, stress, and the decision to delay having kids. But what if we can generate healthy egg and sperm from your skin cells? Ivy Natal is attempting just that using stem cell technologies and CRISPR. I talked with Ivy Natal cofounders, Colin Bortner and Jeff Hsu.

How did you get interested in the fertility field?

COLIN:

That definitely started with Jeff. We are pursuing a revolutionary solution to the problem of the fragility and scarcity of human eggs. Right now, many women can only have children using donor eggs, which has many challenges and obstacles, and donor eggs still don’t allow patients to have a genetic child.

Our solution pulls together different innovations in synthetic and molecular biology and genetics and genomics to solve this particular problem. Jeff became interested in the problem while working at a pre-implantation genetic diagnosis startup, which was his exposure to the application space, but the underlying approach stems from his interests during his PhD and postdoc research.

For me, when Jeff and I started talking about the idea, I was very excited by the potential for patients and for society as a whole. Women have always born a disproportionate share of the costs of having children, which has shaped society. Now, effective contraception has been a revolution in giving women the ability to choose to not have a child, but our company has the potential to provide women certainty in their ability to choose to have a child. It’s the flip side of the same coin.

The science of turning stem cells to eggs has so far only been demonstrated in mice. What bottlenecks do you see for making this possible in people? How do you plan to address those bottlenecks?

COLIN:

Yeah, as you say, this has only been done in mice. About four years ago, a team based in Japan published the landmark result in this area. They successfully differentiated stem cells into egg cells, and then they essentially completed IVF cycles with their mice, and those mice gave birth to fertile offspring.

For a couple of reasons we’re taking a different approach. The first is that a direct translation of the Japanese group’s approach to humans is a non-starter because that would require ovarian tissue from a human fetus. Ovarian tissue from a mouse fetus was a key component of their results. So, part of our motivation is solving that issue.

So this is a kind of bottleneck, which is legal and ethical but also technical. What we mean by technical is that we don’t have a great way to systematically answer the question: what is the mouse ovarian tissue doing to differentiate the stem cells into egg cells? If we could easily answer that question, we could just emulate whatever variables that matter and get the same results, and by extension we could do the same for humans.

Now, without getting too deep into the details, our approach works from the inside out instead of from the outside in. Essentially, we’re using different kinds of sequencing technologies to understand the internal state of egg cells, like which genes are being expressed, and then we’re using new tools to directly change the internal state of skin cells to match the internal state of egg cells, and in doing so transforming the skin cell into an egg cell. We’re still in the early stages of proving out this approach for egg cells, but it has worked with a bunch of other cell types.

The specific engineering challenges in our approach are discovering the genes to turn on or off in order to “reprogram” our skin cells into egg cells, and developing a “safe” tool to do the reprogramming, which eliminates any risk of genome changes. But here we have a huge advantage in that we can work systematically, using sequencing data and computational methods to discover targets and leveraging the synthetic biology ecosystem to do safe reprogramming.

We already have solutions in place for these challenges, and we are now applying them to a proof-of-concept of our approach, but even if we have setbacks, the long term trends are all working for us. Sequencing is getting better and cheaper, the synthetic biology ecosystem is developing rapidly, and the computational methods we’re using are improving almost monthly. We’re making progress quickly, but even if we did nothing for a year, we’d still end up with more data, lower costs, and better tools.

If successful, how might your company change the future of childbearing?

JEFF:

We’re very focused on the immediate goal, which is helping women who would otherwise rely on donor eggs to have genetic children for the first time. That is a super meaningful problem for us, and reason enough to pour everything into this company. That said, our long term goal is to ensure that every person and couple has the choice to have genetic children. There are hurdles along the way, or problems to solve, but this includes women and men of any age, including those with many conditions which currently complicate reproduction, as well as same-sex couples.

What lessons have you learned transitioning from scientist to entrepreneur during the IndieBio program?

JEFF:

One of the big attractions of becoming an entrepreneur is the freedom to work on problems and solutions you are passionate about. The valley is willing to take a risk on founders with plausible solutions to big problems whereas as a scientist you are often constrained to projects and funding that are often related to your previous work in very obvious and straightforward ways, whether that’s in academia or large corporate research organizations.

What Ivy Natal is trying to do would be life-altering for many prospective couples and families. That type of impact you can’t measure by publishing metrics or impact factors, and that’s in many ways shifted my own frame of thinking. Since we are developing a process that not only will work but scales to meet the demand of the market, I’ve learned that it doesn’t matter if we execute a protocol myself or work with partners and vendors. What matters is cost, reproducibility, quality of the results, and ability to scale.

Now, the biggest challenge for me has been transitioning from a fully resourced institution like the Cleveland Clinic to setting up a startup lab in the IndieBio basement. It’s just very different working without the existing physical and human infrastructure of a major research center. In some cases, we’re rebuilding that infrastructure for ourselves and in other cases we’re partnering with vendors to use their infrastructure, almost like cloud computing. For the human infrastructure, we’ve been tapping our existing networks for advice and insights that our team doesn’t have and also working to grow our networks.

We have the additional complication of relocating and starting up our lab work during the pandemic, but we’ve been able to make a huge amount of progress despite that!

What does the next year look like for Ivy Natal?

COLIN:

Right now, we’re completing a proof of concept for our approach. This involves producing a progenitor of egg cells called primordial germ cells, which will prove out a lot of our core hypotheses and de-risk our business. We want to complete this in Q4 of this year, and next year focus on egg cells. Our timeline for egg cells, how far we’ll get in 2021, depends on some of our ongoing work on our proof of concept. After we have data from those experiments and results from our scaling up partnerships, we’ll have a clearer picture of our progress in the next year.

New Age Meats: Leading a Cultural Shift in Protein Production

Posted on by Jun Axup

Cell-based meats, or clean meats, can alleviate pressures on the environment, end animal suffering, and produce sustainable protein for the growing world population. Yet, we are still far away from making cell-based meats a reality due to technological challenges. New Age Meats is tackling these challenges with automation and data to accelerate product development and bring pork sausages to market sooner. We chatted with Brian Spears, CEO of New Age Meats.

How did you become interested in the cell-based meat field?

I left my last company because — although it was extremely interesting, with great customers and cool technology — it wasn’t having a tremendous social impact. I’ve always believed in having a social impact mission. During my time at that company, I started other nonprofits, but they typically got the dregs of my time and energy. So, my conviction has been that your company should be a vehicle for how you see the world. I sold my ownership of that company, I’m still on great terms with my former co-founder, but I needed a technology or industry that was benefiting from this three-way collision of what I’m really good at, what I really care about, and what the world needs. I looked at industries that were making transformations to make the world a better place, and the more I learned about cell-based meat, the more it excited me.

Cell-based meat simultaneously solves big problems around the environment, human health, animal welfare, and food security. It’s also just really cool. It’s what we’re eating for the next century, what we’re eating in space stations, and on Mars. The more I researched it, the more I just thought it was amazing. I became involved with the Good Food Institute (GFI) and New Harvest in early 2017 and learned a lot about the space. GFI has an entrepreneur forum to meet potential co-founders. I started to look for co-founders, and that’s how I met Andra.

What are you building, what’s exciting about it, what’s your company focused on, and what’s special about it?

We make meat from animal cells instead of animal slaughter. We work on pork, which we chose because of the massive amount of research that’s been done on pork cell lines. There’s no animal that we consume in mass that has had more research done on it than pork.

Our big differentiator benefits from our team’s background: automation and data science. I have 12 years of industry experience automating deep research labs like NASA, US national labs, the Canadian Research Council, and the University of Texas. In those cases we put in hardware acquisition points to acquire more data and then assemble the data to make data-based decisions. Essentially that’s how you make research faster, and how you uncover connections that you didn’t know existed previously. So that’s on the deep research side. On the product side — with customers like Cisco, 3M, and GE — we ask, how do you then take that research and make products better and faster? How do you accelerate the pipeline from R&D to production?

We actually started our life as a company together in November — as a horizontal company. We looked at the industry and evaluated where we could provide value. We talked to probably 150 people in existing cell-based meat companies, as well as academic researchers and nonprofit advocates. We found that people liked our vision of how to engineer biology using data science and automation, but as an incremental improvement, they didn’t see that it was pivotal to their success.

Andra’s degree from the University of Oxford is in interdisciplinary biosciences, so she took a lot of courses in engineering, statistics, math, and hardware acquisition in order to understand all the tools that she could use as a biologist to do better research.

Despite our backgrounds, when we approached companies, they just didn’t catch our vision. We were also looking at all the other companies that were providing technology and tools for human tissue engineering — like cell lines, the scaffolding, and the bioreactors. We were evaluating their capacity to re-engineer their technology to come into our market, because if they were well poised to do that, then that’s probably not a place we would provide unique value. We took a full view of the R&D to product pipeline. With this understanding and with our unique differentiators, we saw that we worked best as a vertically integrated company. So in April, we decided to deliver pork to people using our technology.

If you succeed, how do you think you will change the food industry landscape?

We can make tastier, healthier, and more sustainable meat. The way that meat is made now is kind of a race to the bottom. There is an appetite for really cheap meat. You have industrial animal agriculture that is creating more and more negative externalities for the world: climate change, deforestation, species lost, human health concerns like antibiotic-resistant infections, concentrated animal feedlots or feed sheds, which means poor animal welfare. We can change all that.

There’s only so much you can engineer an animal to give you different tastes, textures and food experiences. With cell-based meat, we control the entire environment in which we grow our cells. This means we can start with the perception of how humans enjoy meat, and then craft our meat to deliver new, interesting, better experiences. We can also take away a lot of the negative human health aspects I mentioned before. This world of cell-based meat is obviously much better for animals. They will be able to live their own natural lives.

What are the lessons learned coming from your old company to New Age Meats as CEO?

My last company was a bootstrapped company, and we took no outside investment. So from the very beginning, we had customers and we grew in accordance with their demands. If we had a big customer pulling us in a certain direction, it made sense for us as a business to go in that direction. We were constantly changing in order to adapt to our big customers, because we were so driven by these short-term returns on investment. This meant that sometimes we traded a clear vision for the future of our company with short term gains. And then when those customers suddenly canceled a contract because they had cutbacks, we were stuck with a product so tailored to their use case that we couldn’t use it with other customers without extensive rework.

I have a friend outside of Silicon Valley, in Chicago. We were recently chatting and he started to poke fun at Silicon Valley companies, saying that we don’t actually care about money or return on investment. We just care about these crazy ideas.

I’ve learned so much in the past two years moving into investor backed startups. In Silicon Valley, investors want me to come in and say, “Hey, the world currently looks a certain way, but it doesn’t have to. I see the way the world can be, and I see a pathway for my company to come in and be the catalyst to make it that way. So, after the existing ecosystem is disrupted, we’ll be the one standing there in the new future.” They want to give me the money so that I can follow that vision and not be pulled in different directions, and in so doing, make a product that changes the world.

In the short term, what are the important milestones and achievements you’re looking to hit as a company?

We’re raising 3 million dollars for a seed round. We have five scientific milestones that we’re going to hit, and we have seven business and product milestones. The science milestones include making progress on the cell lines and the infrastructure with the bioreactors. Then on the business/product side, we ask, What do our customers want? What is it that we’re delivering to them? And how do we make tastes and experiences that speak to them?

That leads to product definition. What is in the product that we’re going to make? When we make our bioreactors or cultivators, what will the production facility look like? And then, what is the experience the consumers are going to be having? We’ll design all of that, so that when we go to Series A, will be able to execute on that plan.

We are leading a cultural shift. People have been increasingly eating animals from factory farms. We’re going to change that. We’re going to shift consumption to meat that’s tastier, healthier, and more sustainable. To do that, we’re having that conversation with the public early and often.

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

Clinicai: Detecting Colorectal Cancer in Your Toilet

Posted on by Jun Axup

The successful treatment of cancer lies in early detection. If we can detect it as early as Phase 1 and 2, the outcomes for therapy are significantly better. Unfortunately, symptoms oftentimes will not present until Phase 3 and 4 which limits effectivity of therapeutic interventions. Clinicai is making a noninvasive monitor for colorectal cancer with a device that hooks on the side of your toilet. We asked Chun-Hao Huang, co-founder and CEO of Clinicai, about his journey as an entrepreneur.

How did you become interested in the early detection of colorectal cancer?

Chun-Hao: During my Ph.D. I built animal models mimicking human colon disease to find biomarkers and therapeutics. I was passionate about gastrointestinal biology and learned how to monitor mice’s poop every day, dissect the intestine and colon for pathology examination, and realized that, wow, the stool is actually very closely related to our gut system. I also realized that for colorectal cancer, if we can detect early, we can even use current treatments to cure this disease and every single patient would have the chance to survive.

I have now been working in cancer treatment for more than 10 years and have seen that the field puts a lot of effort into trying to develop new therapeutics. However, a lot of diseases, especially colorectal cancer, can be solved even right now if you detect it in time. But the early detection or preventative angles are not so appreciated by the field. So that’s why I started to focus on early detection because I believe the way to actually make cancer manageable today is by monitoring your body to capture the signals at the very outset so we can apply current therapies when they would be most effective.

How did you decide to start the company and how did your team come together?

Chun-Hao: I almost was a scientist for life, and I really wanted to make a big science discovery creating a way to solve cancers. When I was at the Lindau Nobel Laureate Meeting, I heard a lot of top scientists and Nobel laureates talking about the future of medicine and how to manage diseases like cancer. The meeting inspired me but I realized it is actually a very long process from research to benefiting humanity, and I started to wonder if there is a way we can speed up this process and bring biotechnology into our daily lives.

So I asked what is the best way we can accelerate scientific discovery and also bring biotech to our daily life? It’s very interesting to me that the device we use daily is a cell phone when biotech should be the technology we are using every day. I found the answer is to start a company because you can put a lot of resources into building a product actually related to daily life. I met my co-founders Medina Baitemirova, Juan Carlos Guáqueta, and Mr. Toilet Jack Sim at Singularity in NASA Ames, and later on our CTO Dr. Ya-Ju Lin. We all have different expertise, but we share the same vision that we want to detect disease like cancer early. We wanted to make the most comfortable diagnostic platform, which in the end ended up being a toilet. We want to make people actually enjoy health monitoring.

How does your technology work? What is that key insight?

Chun-Hao: It’s pretty interesting, when we started developing this technology we hoped to achieve three things. First thing, if we want to do the most comfortable monitoring and diagnostic at home, then the technology needs to be non-invasive where the user puts in the minimum effort to maximize regular monitoring. Second is digital information; we need to have a technology which can digitalize the substance we detected. Third, it needs to continuously gather the data. The most current methodology, like biomarkers or chemical methods, are not able to do that, so we started testing a bunch of different sensors. We started with a narrow range optical sensor and in the end, we find out that there is a large wavelength hyperspectral imaging originated from space technology that can help us to gather all the information from the stool.

That’s how we started using that technology to check stool samples and that’s how our technology derived. This is not just technology we can use in the lab, or in the hospital, we actually integrated that into a prototype device that will snap on a toilet. Everyone can attach that device at home, I even tried it myself. Then it can turn on when you sit on the toilet and then gather the data. I think these will be pretty powerful in the future, not only for cancer detection but also can help detect other preventable diseases.

What lessons did you learn transitioning from scientist to entrepreneur at IndieBio?

Chun-Hao: As a scientist, every day you go to a lab, you have the experiment you want to do, but some experiments could take a couple weeks or even longer. But when you are designing your experimental plans in a startup environment, like IndieBio, you need to think about how we can leverage different resources to make this process faster. That’s actually what I really like about this environment because you’re still doing the very cool science, but you have a way to speed it up. The other thing which is quite important is that here we’re thinking of how we can actually turn our technology into a real product and then benefit people’s lives. As a scientist in the lab, you try to solve problems, but you don’t usually think that this can actually work in our daily life.Since we joined IndieBio, we have started to talk to the FDA, we talked to insurance companies, we talked to doctors, and especially to the users. We are building things they really want and also doing cool science. This is what makes being a scientist-entrepreneur great.

How do you think your success as a company will change the diagnostics industry?

Chun-Hao: I used a proteomics approach when I was in college to identify biomarkers and in the past 10 years I didn’t see that many biomarkers come into the diagnostic field. I think it’s time that we need something new to disrupt this field. Before we always relied on one or two biomarkers, but at Clinicai we believe the key is to detect signatures or patterns of the disease.

That’s why at Clinicai we are trying to get signatures and patterns from your stool or urine samples and then we use the machine learning to understand those features. I think that that will change the way we think about diagnosing. The other strong advantage we have is to actually bring the diagnostic into our home. Before it’s been pretty difficult and we find our best niche at home where our bathroom and toilet have a lot of information every day. We hope in the future everyone can really enjoy health monitoring and can live longer and healthier.

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

Chun-Hao: I want to thank IndieBio because we actually met our milestones here. We’ve built our first prototype, which we never thought about that before. The milestone for next year is to improve our prototype and then work with hospitals to install the device in hospital toilets or in patients’ toilets at home to monitor their stool signals for colorectal cancer detection. After that, we plan to go through the FDA path and we are pretty positive about that. After that, we hope our device will be in everyone’s home for future health monitoring and diagnosis.

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

Stämm: Reinventing the Bioreactor

Posted on by Jun Axup

Biology is the best platform for manufacturing cells. It can grow and produce all kinds of biomaterials very effectively. But for humans to be able to tap into this potential, we have to build bioreactors and figure out how to scale them in order to produce the massive amounts of biomaterials we need. Bioreactors technology is very different when you’re optimizing for one reaction at one liter versus 100,000 liters, but this is where Stämm comes in. They are reinventing the way bioreactors work by developing a modular microfluidic platform that controls all the physical parameters, such as nutrients and dissolved oxygen, in a controlled environment. Unlike traditional bioreactor systems, their microfluidic bioreactor scales by adding more modules to increase the size of the reactor.

We sat down with CEO Juan “Yuyo” Llamazares to learn more. (Fun fact: his name is pronounced like “shoe-show.”)

How did you become interested in building reactors?

Yuyo: My first interaction with microorganisms was to study the interaction between plants and soil bacteria called growth-promoting bacteria. I was amazed by the communication between these microorganisms, this ability to sense the environment and that the bacteria will provide to the plants. I wanted to make use of this knowledge to create a product. I quickly realized that I would have to use bioreactors, and it became clear that the whole industry is based on bioreactors. That’s when I decided that I wanted to learn more about how we create these environments to make the cells divide, or to induce synthesis of protein. That was the first time that I got to see a bioreactor. I was used to working with plants, so working with a bioreactor felt really unintuitive, given what I knew of how cells proliferate in nature. I saw a really big opportunity there to develop new approaches.

How did you come to start this company and how did your co founders come together?

Yuyo: Well, my cofounder is my cousin, so we grew up together. But also, my grandfather taught me how to brew beer when I was 12 years old, and Federico and I saw an opportunity to manufacture yeast for brewers. That was our first time making a product, and it showed us how difficult it is to build biotech facilities. Even people that have a lot of biotech experience have trouble translating their knowledge to the market because it’s hard to develop these facilities. We saw the need for a reinvention of bioreactors so they can be reproduced around the world. We actively started scouting researchers knowledgeable in microfluidics and robotics, and started seeing that we could make this a reality. Bringing the team together, for us, was key. When we communicated our vision for the company, we found that researchers were excited to join us.

It can be difficult to take the leap to make that transition and to advocate for impact and transformation in the real world, coming from an environment that gives you all the tools you need to be comfortable. In Argentina, where I am from, there’s a reason researchers choose to stay in the lab. You have a predictable career and life, and that’s reassuring. But I made a trip to Chile and I learned about spin-off companies. That was not a concept I had been exposed to in Argentina, and I decided I wanted to bring the knowledge at my university to the world through my own company.

How does your technology work and what is the key insight that you had?

Yuyo: The key insight was to try to think about how cells experience the process of biomanufacturing and identifying room for improvement in that process. We found that today, we look at biomanufacturing as a population of cells, so we try to control the cells inside our vessel as a whole. The problem is that each cell at some point is going to be going through different metabolic stages and we take the average of that complexity. With existing bioreactors, we don’t have the tools to control that complexity, so we try to create a different kind of bioreactor: if we can account for each cell’s microenvironment then we open up a way to address the cell complexity. From that insight, we turned to microfluidics because it gave us the ability to look at the individual cell, however, the problem is that it’s hard to scale microchannels. That’s what we’re addressing with a lattice that cells move through in a predictable manner, which provides consistent nutrients and oxygen.

So how do you think your success as a company it will change the bio manufacturing industry?

Yuyo: I think that more people will know what biomanufacturing is. People will recognize it as a tool to solve a problem. Right now, biomanufacturing is “hidden” in big facilities, but with our technology, it can be used by more people at a smaller scale and more people will see the power of biology to manufacture or to solve problems.

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

Yuyo: We want to manufacture the bioprocessor and sell it to companies so they can optimize their processes as they create their product. We want to prove that this novel approach is robust and that there’s a future there. So far, we have worked with CHO and HEK cells for the manufacture of monoclonal antibodies, and we have seen that in our system, individual cells perform better. This means our process is more efficient and has higher productivity per cell. One of the other companies currently at IndieBio used our system to significantly increase the productivity of their process over the course of 20 days.

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

BioROSA: Early Blood Test for Autism

Posted on by Jun Axup

BioROSA is building a blood-based test for diagnosing autism. Autism currently is diagnosed at age four, on average, with behavioral testing. Children are missing critical windows of opportunity where early diagnosis and access to treatment could improve prognosis. At BioROSA, we are mission-driven to enable earlier detection, potentially even before the child is born, in order to achieve better outcomes for children.

What got you into autism research?

John: It started way back in high school as one of my best friend’s brother has a severe form of autism. Seeing such an impaired person at an early point in my life made me wonder what could make the brain function that way, and this led me to do a lot of different neuroscience work in college. I was working on clinical studies in neurology and rehabilitation medicine for stroke and traumatic brain injury patients at UPenn for a while after college, doing some really cool brain imagining research. At Arkansas Children’s Hospital, where I worked from 2010 to 2017, I got involved in cutting-edge autism research and clinical operations while working on clinical studies involving biomarkers for detection and studies aimed at developing treatments to address core symptoms of autism. While at Arkansas Children’s, our team created one of the leading clinical and research operations in this country. It was an amazing group of scientists committed to improving patients’ lives, and the mission and values of that team live on in BioROSA. We highly value these collaborations and relationships with excellent clinicians and researchers.

What prompted you to start the company and how did you meet your co-founders?

John: Working in academia, I was frustrated with how slowly research and development progressed, and I was introduced to entrepreneurship and startup culture at a time when I was losing my passion for academic research. While we were doing amazing, cutting-edge research and changing lives for patients in the clinic, the pace of the work and the inability to treat or see patients from around the world who couldn’t afford to come to see us clinically was really heartbreaking. Though we were seeing amazing outcomes and were publishing a lot, we were too boxed in from an administrative perspective and I started to feel that we weren’t doing enough for patients in need. I feared we would never be able to truly address the autism problem from inside the walls of academia, something needed to change in order for advancements to occur. Thus, BioROSA was born. We have licensed intellectual property to commercialize a novel diagnostic test that can transform autism clinical care and diagnosis. What’s amazing is that our technology is based on what I worked on in Arkansas with a scientist I truly admire and adore, Dr. Jill James.

In working to find a co-founder for BioROSA, I had researched companies who had previously tried to do something similar. One of the most noteworthy was a company called SynapDx, in which Dr. Marie Causey was a co-founder, and when I contacted her she luckily happened to be available. It was serendipitous that she was interested in becoming co-founder and CSO at BioROSA, Marie’s experience in the startup world, in establishing diagnostic labs, and in developing clinical tests is a great fit. We make probably an unorthodox but great co-founding team. We bring different perspectives and she holds me accountable and practical for my big picture dreams!

Let’s talk about your technology. What is the key insight and how did you come up with this diagnostic?

John: We have a body of research based on over 15 years of data in which metabolic systems have been consistently shown to be abnormal in patients either diagnosed with or at risk for autism. Dr. Jill James, another co-founder in BioROSA, made the key biomarker discoveries, but the breakthrough came when our SAB member and collaborator Dr. Juergen Hahn applied machine learning to come up with a robust classification algorithm. We have obtained a global exclusive licensed to Dr. Hahn’s IP from RPI. Juergen is our number one champion and a constant contributor that is extremely hands on.

During the IndieBio program, what are some lessons you’ve learned transitioning from scientists to entrepreneur?

John: First off, I don’t consider myself to actually be a scientist but more an entrepreneur with a passion for science and improving healthcare for patients. I’m fortunate to be surrounded by amazing scientists on our team. As far as lessons learned? You must really get out there, hustle, and be a constant driving force in order to ensure your company has a chance of success. As Arvind said from day one, “nobody cares”. It is your job as a founder to make them care and show why you will change the world and why your team is the capable group that can get things done. You must have extreme perseverance, resilience, structure, organization, meticulous thinking, and as much as I hate it, patience, in order to get things going and for you to position your company into the best chance to take flight. I think that really getting outside of the office, really trying to promote your business, knowing what your customers really want, and trying to promote your cause can go a long way in getting that initial traction. Once you start figuring these things out and getting those first bits of traction can be a pivotal inflection point for your ultimate ability to scale, grow, and succeed.

How do you think the success of your company will change the way autism is currently being diagnosed?

John: We will provide clinicians with a much-needed tool that is missing in the current process for determining who’s at risk for autism and to get at-risk children into services faster than is possible today. In a way, this allows the system to be more proactive instead of reactive in diagnosis and treatment. The ultimate goal is to create opportunities that can lead to prevention, or at least more optimal outcomes, for children.

What are the milestones you’re hitting in the near future?

John: Our first milestones is to conduct a prospective clinical trial of 800 patients in a multicenter study within the next 18 months to bring our first product, an ASD screening tool, to market. The success of this opens the way for the development of our flagship product, a pediatric ASD diagnostic test that will detect autism before children ever develop behavioral symptoms. We plan to secure contracts with pharmaceutical partners to conduct studies to demonstrate the clinical utility of our test as a companion diagnostic for ASD therapeutics as well and to create a new standard of care based on biology (instead of behavior) for this challenging disorder.

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

Serenity Bioworks: Unblocking Gene Therapy Delivery

Posted on by Jun Axup

Gene therapy recently has been extremely exciting in the news. However, the limitation of gene therapy is ineffective delivery. When injecting genes to be delivered, especially in adeno-associated virus (AAV), we are seeing an induced immune response where the body starts clearing out the virus. Serenity Bioworks is working to rid the immune response and instead induce a tolerance response, allowing the AAV to be dosed and redosed as necessary.

How did you become interested in immune tolerance?

Cody: The immune system is one of the most complex things in the universe, and that in itself is incredibly interesting. There is a lot yet to figure out. The more we understand about the immune system, the better the development of therapeutics will be able to unlock the next frontier of medicine for monogenic diseases. From a holistic viewpoint, our compounds have been detected in contexts where our own cells and microbiome communicate with the immune system to induce tolerance, as well as other instances where immune tolerance is present. Serenity’s key insight and my own interest in immune tolerance induction came from doing research in this area.

When did you decide to start the company and how did your team come together?

Cody: I decided to start the company after I developed my ideas in grad school, which involved applying certain concepts I learned. I decided to raise some money to look at these ideas a little bit more. At the time, I was living with Spencer Berg, my co-founder, and I would come home and talk about what I was up to, certain grants that I’d raised, pitch competitions I’d won. And then he developed an interest as well. Eventually, we got accepted into an incubator in Canada to further develop the technology behind our company.

So how does your technology work? What was that key insight?

Cody: The key insight is understanding how your immune system decides not to attack your microbiome or your own cells. There’s a set of compounds that kept on popping up in these contexts — this is what I was looking at in grad school, though in a different way. We thought that this would be a really good solution for developing tolerance for gene therapy products.

During IndieBio, what lessons have you learned transitioning from scientist to entrepreneur?

Cody: There are so many lessons! For one, you pick up a lot of jargon as a scientist, and you’re used to communicating with scientists. An entrepreneur has to communicate to a broad range of audiences. You might be talking to an accountant, a lawyer, an investor… You will find yourself talking to people who have never heard of your field before. As an entrepreneur, it’s incumbent upon you to properly communicate to a broad range of audiences. You have to lose all of the jargon you pick up in academia and adapt.

And how do you think your success as a company will change the gene therapy industry?

Cody: We are developing an immune-compatible gene therapy. For the last 30 years, gene therapies have been combatting against the immune system. We want to work with the immune system to unlock these therapeutics. If we’re successful we will make these therapeutics safer and more effective.

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

Cody: In the near future? We’re going to wrap up our first set of studies in vivo, raise our next round of financing and conduct IND-enabling studies next year. We’re also looking to develop partnerships with pharmaceutical and gene therapy companies that are running into issues with the immune system.

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

Convalesce: Curing Parkinson’s Disease with Stem Cell Therapy

Posted on by Jun Axup

Neurodegeneration is one of the most devastating diseases of aging, and today there is no cure. Stem cells are a very promising way of regenerating the faulty neurons, which would potentially create a cure. Convalesce is working on injecting stem cells into the brain using a special matrix that mimics the brain’s architecture, allowing the stem cells to survive, differentiate. and reconnect those neurons for Parkinson’s patients. We chatted with Subhadeep Das, co-founder and CEO of Convalesce.

How did you become interested in stem cell research?

Subhadeep: When I was a grad student I read a lot about the potential of stem cells in regenerative medicine and I was fascinated by the things stem cell therapies could unlock. Especially so for diseases that cannot be treated using traditional medicine, or are facing certain limitations within current treatment options. Stem cell-based treatment could overcome these drawbacks and limitations, which is how I got interested in the field. It was fascinating for me to work in an interdisciplinary area and not exclusively in hardcore biology or hardcore material science. I started working at the intersections of material science, especially with nanomaterials and stem cells, and when we came up with extracellular matrices which mimic the natural tissue it was a great thing for us from a science perspective. When we found that it could potentially solve some of the very key problems of stem cell therapy for neurodegenerative diseases like Parkinson’s, we eventually came up with a therapy for Parkinson’s disease using our discovery.

How did you decide to start the company and how does your team come together?

Subhadeep: I honestly didn’t have any plan of starting a company when I began my Ph.D. At that time I was just interested in doing cutting-edge science, but eventually, when I saw the potential of the technology that we developed, I was saddened to see that academia is happy with just publishing some papers. I wanted to push it further to bring the technology to the clinic where real people would get help out of the technology. During the final years of my Ph.D., I decided to take the leap to become an entrepreneur and try to commercialize this technology. Eventually, I started participating in startup boot camps, business competitions to at least have an idea of how a startups work and what are the non-science aspects that I should think of to start with.

After I got interested in entrepreneurship, I was talking to my friends and acquaintances regarding my ideas. My benchmate from IIT Bombay, Amrutraj, got interested and he had the type of cell biology background that was complementary to the skills that I have. We decided, okay, let’s give it a shot — let’s form a company and see if we can bring this thing together to solve the pending science problems and then bring the technology to the market.

How does your technology work? What was the key insight?

Subhadeep: The fundamental insight for us was to understand how stem cells would react to their microenvironment. Subsequently, we engineered that microenvironment specifically for neurons. It was such an amazing technical insight to learn during the process, now we believe that we have a platform where we can engineer multiple tissue matrices for multiple applications. The key for us was the realization of how crucial a matrix is for regenerative medicine for any organ. Most of the biology research has been focused on cells which, while crucial, as they are will actually do the job, if you consider any organ there are a lot of support systems that play a critical role. These were sort of neglected by biologists and we tried to bridge the gap between material science and biology by engineering specific niches for organs or stem cells. This was the insight for developing what we are currently doing.

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

Subhadeep: We learned a lot of things during IndieBio, especially how to run a business. We always think about science and focus on the next scientific milestones, but after coming to IndieBio, we realized that there are a lot of things we need to have an understanding of if we are to bring this therapy to the market. When we started this was just a science project, not a business. Here we benefitted by getting insights on running a business and developing a business model, an idea of manufacturing, and the regulatory hurdles that are coming for us. I’d say these are critical to running a business.

How do you think your success as a company will change the therapeutics industry?

Subhadeep: The traditional therapeutic industry works by generating drugs from small molecules, but there is a whole emerging industry focusing on regenerative medicine which encompasses both stem cell therapy and gene therapy. Even in the cell therapy space most of the companies are still focused on cell type because that’s what comes to a biologist’s mind first: how to engineer the cells and get them to work more efficiently. We are radically changing that approach by engineering not only cells but also their microenvironment. If cells get a much better environment to survive and differentiate in, then they can finally do the job they are sent in to do. I think the holistic approach that we are creating will change the way therapies are done today, the microenvironment is critical for cell-based therapies to be successful.

What milestones are in the near future?

Subhadeep: We aspire to apply our first therapy, which is a stem cell therapy for Parkinson’s, in a human brain. We want to treat Parkinson’s patients as soon as possible. Our key milestone is to do our first human trials so that we know we have a cure for Parkinson’s.

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

Call for Applications

Posted on by Jun Axup

Biology is the next big technology and we are looking for scientists that will usher the new wave of iconic life science companies.

“Nothing is normal in the new biotech; it’s inherently cross-disciplinary and purposefully attacks preconceptions of what can’t be done.”- Po Bronson

Why Scientists?

Scientists make amazing entrepreneurs due to their technical expertise, problem solving skills, resourcefulness and persistence. Over the years, the number of life science PhDs has been rising exponentially and at the same time running biological experiments is becoming faster and cheaper. Our ability to read, write, cut, copy and paste DNA more efficiently is significantly decreasing costs and increasing speed and accessibility of experiments. Tying these trends together, IndieBio enables scientists to build radically transformative companies through our unique program.

Our Program

We take a design-driven approach to integrate product and business development in continuous feedback loops. Startups can rapidly prototype and get early customer traction at a pace that is closer to an IT startup rather than traditional biotech.

During our 4-month program in downtown San Francisco, scientists leverage $250,000 in funding with our fully-equipped labs, 300+ mentors and a galvanized ecosystem of industry, academia and investors that enables life science businesses to thrive. Our interdisciplinary team works with the companies every day to enable scientists to de-risk their science and business. Together we build the foundations of a viable and scalable business that can impact billions of people.

 

What types of companies do we look for?

We are here to fund scientists that can translate scientific insights into commercializable products that solve large scale human and planetary problems.

The biggest advantage a startup has is the precise focus on solving a problem from first principles. Our most successful founders build on deep technical knowledge with market insights that come from approaching the problem from all angles. As a result, startups create new business models, reimagine antiquated systems, or build industries from the ground up.

We welcome applications of biology for any industry. Thus far, our companies have represented the eight categories below, but we are most excited about companies that bridge multiple categories or invent new categories.

 

Therapeutics

Despite the billions spent in R&D, we continue to treat symptoms and not the causes of disease. New modalities such as immunomodulation and functional metabolomics are setting a new paradigm in drug discovery and delivery. With gene therapy we will have the ability to directly edit our own genomes to fix inherited diseases and transcend our parents’ genetic material. Across all these modalities there has been a rise in platform technologies enabling repeated target and therapeutic discovery.

Regenerative Medicine

Regenerative medicine and tissue engineering will give us control of how we treat damage to our bodies, from losing limbs to restoring loss of function from paralysis to growing whole replacement organs. Furthermore, we can intervene and reverse the processes of aging.

Neurotechnology

We are only beginning to understand the brain. New biological and digital tools are needed to understand and treat neurodegeneration and mental health. Brain computer interfaces open up new possibilities for human consciousness.

Medical Devices, Tools & Diagnostics

Early detection of diseases that can seamlessly integrate in to healthcare workflows not only enhances decision making through precise real-time biomarkers, but also, eliminates centralized labs and administrative bottlenecks that are burdening the healthcare system. The advancement of research tools is critical for unlocking new knowledge that can lead to life-saving solutions.

Future of Food & Agriculture

Food supply cannot catch up with food demand at the same time supply remains inefficient and unethical. New biotechnologies are changing the unit economics of how we produce protein. Vertical integration of food and agtech can enable us to unbundle the food supply system and increase efficiencies of production.

Consumer Biology

Driven by faster and cheaper science, companies will bring biology direct to consumers in an increasingly personalized manner. The first human genome cost $2.7B. Today people can order an at-home sequencing kit for $100. Products are increasingly putting the power in the hands of the consumer to manage their own health.

Computational Biology, BioData, & AI

Biology is rich with data and complexity and companies are increasingly leveraging bio-processes with machine learning and automation, creating bio-feedback-loops to optimize each stage of a life science company: from discovery to manufacturing.

Industrial Biology, Biomaterials, & Clean Biotech

Not only is our demand for commodities unsustainable, the industrial processes for converting commodities into everyday products remains inefficient. Biology is inherently versatile and scalable. Cells, the building blocks of life, live to divide, and under the right conditions they can be engineered to create bio-materials and novel commodities that can then be scaled exponentially using fermentation without harming the planet.

 

Our Application Process

Online Application. Our application process begins with an online submission at http://indiebio.co/apply.

Technical due diligence. Selected companies are invited to a 30-minute video interview that focuses on technical due diligence. We encourage applicants to ask questions about the IndieBio program throughout the process.

De-risking milestones. If the first call is favorable, our team will set up additional calls to discuss the product, the business plan, and discuss the derisking milestones that the company aims to achieve by the end of the 4-month program. Often, homework is assigned to address certain questions. Once discussions are mutually favorable, an offer is made.

Deeper look into how do we evaluate companies. We evaluate companies based on five key questions.

  1. What is the technical insight that gives you an unfair advantage? This is often the core technology that can be patent-protected, whether it is licensed from an academic institution or developed in-house. What advantages does your technology have over competing technologies? How does your technology address the core problems you are trying to solve?
  2. How is the insight made into a product? Science itself is not a product. Product development starts with understanding the end user. What problem are you solving for the end user? What is the form factor? What is the workflow? What are the parameters for a successful drug? What product do you focus on first when you have a platform technology?
  3. How does the product form a sustainable business? What is the go-to-market strategy for roll-out when the startup is cash limited? How to gain adoption? How to navigate regulatory pathways?
  4. Can this business make $1 billion or touch the lives of 1 billion people? Venture capital investment seeks the potential for big returns and big impact.
  5. Is this the team to make it all happen? Arguably, the most important aspect of selecting teams at an early stage is the founders themselves. Do they have the experience and expertise to turn their technical insight into a viable business and propel the company into a flourishing venture? We look for founders who are coachable, able to make decisions rapidly, take responsibility, are resilient, and are passionate about their work. We look for founders who are self-aware and possess a growth mindset.

The interview style is informal conversations and we often instill a mini preview of the IndieBio program during the interviews. Our application timeline is rolling, with set deadlines that batch the interviews. We encourage applying early and sending periodic updates of progress even if you don’t hear back immediately. Updates are also encourage between interviews as it could take time for both sides to come up with good strategies. We also encourage re-applications if you were not selected for one class. Some of our most successful companies reapplied 6 months later with significant momentum. Most ideas and teams will take a while to mature. (Read “I have an idea. What’s next?” for the starter checklist.)

Lastly, we encourage you to due diligence on us. Learn more about our story and our program featured in Neo.Life. Attend or livestream our next Demo Day on Nov. 6th at the Herbst Theatre or watch the previous ones on Youtube. Talk to founders of any of our alumni companies or attend an event at our space.

 

Apply Now!

We look forward to hearing your world-changing idea! Apply now at http://indiebio.co/apply!

I have an idea. What next?

Posted on by Jun Axup

At IndieBio, we often get bright scientists and aspiring entrepreneurs asking us what they should do to transform their idea into a company. We’ve all heard that “ideas are a dime a dozen” and “it’s all about the execution”. So, what are the best ways to execute?

Here are the steps we suggest to take:

1) Do Your Homework

It is very unlikely that no one has thought of your idea before. Do a thorough search of the web, scientific literature, and intellectual property landscape to see what has already been done and what similar technologies, products, or services are available. If your idea is truly original, be suspicious of why that might be. It could be that the technology is impossible, the business model is unsustainable, or the market is too small.

If there are competitors in the space already, it does not mean you should give up. Instead, understand the competitors’ businesses and assess your potential advantages and disadvantages. You will need to step up your game in speed and execution.

Check the intellectual property landscape to see whether you have freedom to operate. If not, are there ways to get around existing patents? There may be the possibility to license from the patent holder. If you have novel IP, submit a provisional patent as soon as possible. This will greatly help your chances with securing funding.

2) Build an A+++ Team

When asking investors what they look for when investing in a company, the overwhelming top answer is confidence in the team. The best teams can turn even mediocre ideas into gold, whereas the best ideas won’t even see the light of day with a dysfunctional team. The best teams recognize what skillsets are missing and bring in those who have complementary skills. The best teams are clearly aligned in mission and communicate effectively and frequently. The best teams care about building company culture with a unified vision and put aside individual egos. Founding teams are very much like a marriage, so chose very wisely.

Do not underestimate the need for sales, marketing, and communication. In fact, all the co-founders are responsible for pitching the company. Effective communication and presentation skills are just as important as technical skills.

3) Building a Product Prototype

A technology itself is not a product, and without a product, there can be no business. From an initial technological insight, a single product must be identified and prototyped as much as possible. To determine what product to pursue, interview potential customers and talk to experts in the field. Most people would not be critical to your face, so find ways to get honest answers. An initial strategy is to distribute anonymous surveys to your target demographic. However, ultimately, the biggest validation is when you receive purchase commitments. Even if you can’t deliver the product yet, signed letters of intent are very valuable for fundraising.

4) Soul-Searching

The path of an entrepreneur is full of dark forests and windy roads. Your passion and devotion to the mission of your company is the only thing that will keep you going when times get tough. Make sure you and your co-founders are in it for the right reasons and dedicated to solving your particular problem over the next 5, 10, or 20 years.

Start the Journey

Once you have carefully considered the four steps above, it is time to begin your entrepreneurship journey. The best strategy is to start selling your product to customers as soon as possible. It is only when direct sales is not possible that you seek funding, such as needing initial capital for research and development. Common funding sources are government grants, friends and family investments, angel investments, or applying to an accelerator program like IndieBio.

About IndieBio

IndieBio is the world’s largest life sciences accelerator. Companies from all over the world apply to be part of a 4 month acceleration program which includes $250,000 funding, dedicated mentorship, and 24/7 access to a co-working space and bio-safety level 1 & 2 labs. During the program, teams are focused on turning science into product, closing customers, and raising follow-on investment.

With a focus on biology as a technology, IndieBio companies solve problems in a huge range of industries such as the future of food, biopharma and healthcare, agtech, regenerative medicine, neurotech, biomaterials, and more.

Apply today and begin your journey!