Category: Founder Stories

Probiotics on the market today promise all sorts of “good things” you need for a healthy gut, which we now know is important in many diseases and conditions. Unlocked Labs is taking the opposite approach – it is taking “bad things” out of the gut, with a small twist. 

Take hyperuricemia as an example, which occurs in over 20% of the adult population. This is a precursor condition to gout caused by a buildup of a waste product called uric acid in your blood. As the condition gets worse, uric acid crystals start to form and get deposited in tissues and joints – especially in the big toe, causing very severe pain and discomfort to tens of millions of sufferers. Increased serum uric acid above a specific threshold (over 7 mg/dL) is a requirement for the formation of uric acid crystals. Unlocked Labs is taking the interesting approach of sequestering and eliminating uric acid from the gut, thereby enabling the body to equilibrate and safely remove it from the vascular system, thus helping to prevent and alleviate severe joint pain. The same is true in hyperoxaluria (and a number of other conditions) where the build up of oxalic acid which, if left unchecked, leads to very painful kidney stones. 

One can certainly perform serious genetic engineering to turn microbes into super toxin scrubbers in your gut. But doing so might have unintended safety effects which would require a new drug application that goes through the live biotherapeutics (LBP) pathway to obtain FDA market approval.  We are yet to have a single approved drug from this pathway despite over a dozen companies with LBPs in clinical development, with cumulative clinical development investments now totaling several billion. What if certain selected probiotic bacteria already have dormant abilities to precisely sequester and biodegrade specific toxins? Further, what if unlocking this ability can be done in such a way as to allow the organism to still be classified as GRAS (Generally Recognized as Safe) and sold as a probiotic dietary supplement?  This would enable innovative and purposeful probiotics to come to market immediately to meet the unmet needs of those who spend hundreds of dollars each month trying to manage these and other similar painful conditions. 

Christoph Geisler, master microbiologist and CEO of Unlocked Labs, came upon this insight a few years ago and has been creating a library of dormant functionalities within probiotic bacteria as well as a method for safely unlocking this functionality without affecting anything else. He paired up with his business partner and co-founder, James Francis, who watched his rugged and tough dad suffer from gout pain and become determined to do something about it. The pair are also determined to answer the question: Can any good synbio innovations come from Laramie, Wyoming?

After searching to find a place in our basement where James (who is almost 7ft tall) could sit comfortably, we asked them a few questions:

What’s new and different about Unlocked Labs?

Well, first off, have you heard of any cool microbiome companies from Wyoming? Yeah, I thought so. Seriously though, probiotic bacteria have evolved for eons to function optimally. We have a platform that can identify which genes in which probiotic bacteria are precisely required to perform a specific toxin elimination function and then unlock these dormant genes to simply do what they were designed to do. Just like cool start-ups from Wyoming, this insight was hidden in plain sight. We have patents on our platform and will continue to file patents on our new class of probiotics as we reduce each of these to practice. During our time at IndieBio, we came to realize that there are a lot of different “toxins” that cause many chronic conditions, which we can reach through the gut to solve in this very safe manner. 

What did you accomplish during the IndieBio program?

We came into IndieBio with a single-product idea built around a research-grade probiotic strain showing preliminary in vitro efficacy. We are leaving IndieBio with a greatly expanded platform concept, two product candidates and several others in the making, two in vivo proof-of-concept experiments already in progress, hard thinking and iterating around our go-to-market, several market experiments underway to test true demand, a way to GMP manufacture commercial-grade products, and a carefully-designed plan for an alpha launch later this year. We have accelerated way beyond where we imagined we could be by now! Most importantly, we’ve also made great new friends, built an amazing network of contacts, and received a ton of exposure to investors who seem quite intrigued by our science, platform and purposeful approach to probiotics.  

What’s next for you guys?

After our funding round turns the corner, we will spend the next few months securing the needed inventory for our alpha launch and continuing various product-market-channel fit experiments. We also plan to run several omni-channel experiments including one with health practitioners who are high prescribers of science-based dietary supplements. We already have a community of gout and kidney stone sufferers who can’t wait for us to launch our product. So, that is our real focus – we are looking for investors who will fuel our obsession with getting our products to market so that people with painful conditions can feel empowered to take charge of their health, using science-driven, purposeful probiotics. 

Sea & Believe is developing a range of plant-based seafood using Irish native seaweed and microalgae innovation that doesn’t compromise on taste, nutrition or the health of the ocean. All over Europe, people know the best tasting seaweed comes from Ireland. Founder, Jennifer O’Brien, walked every beach in Ireland tasting the seaweed for her alternative seafood. She found one beach where the seaweed was remarkably tastier than all others. 

Their aim is to build a brand of sustainability with innovation by cutting out the middle – i.e., the fish – while still creating an awesome seafood experience that benefits the oceans, terrestrial ecosystems and future generations. Sea & Believe already has two products on the market in Ireland, the Irish Seaweed burger and Seaweed Goujons. Just a few weeks ago, they accomplished their desired milestone – we tasted what might well be the world’s first plant-based whole-cut filet of ‘cod’ that flakes like real fish. We wanted seconds! The seaweed is sourced from the west coast of Ireland with plans to scale up seaweed production by creating one of Ireland’s first seaweed farms later this year. Beyond saving our oceans from overfishing, their seaweed farms can absorb nutrients and carbon dioxide to grow, thereby improving water quality and buffering the effects of ocean acidification in surrounding areas. A true contribution to planetary health, as they scale.  

Jennifer, and her co-founder Piyali Chakraborty, had been cooking up impressively tasty flaky “fish” for investors at our Expo Day when we asked them to sit down a bit before washing all the dishes:

Jennifer, you are already known as a mover and shaker in the alternative protein space in Ireland with a product already on grocery store shelves there. But where did you get the inspiration to devote your life to this? 

Well, through most of my childhood growing up in Ireland, I had severe chronic asthma and spent a lot of my waking life managing my symptoms. I still remember when I took my first seaweed bath, started eating seaweed and getting much needed relief. I knew then that there was something special about Irish seaweed. I wanted to learn about its properties and figure out how to scale that into a business some day. My parents were entrepreneurs too and I knew how hard it was. I spent several years working in financial services, investment banking learning what it takes to run a business successfully. But that inspiration of Irish seaweed never left me. So when it was finally time to strike out on my own, I knew exactly what kind of business I wanted to start. 

What’s really cool about seaweed, and is there really something extra special about Irish seaweed?

Growing up in Ireland, I had the visceral experience of the goodness of seaweed, but had no clue about how exactly it exerted its health effects. But now, it’s been well studied and more of its many beneficial properties are being elucidated each day. It’s filled with essential nutrients, amino acids and proteins. Its antiviral and other health benefits are now widely known and we no longer have to educate people about that. 

Irish seaweed is all that and more. First off, you should know that seaweed isn’t the same even within Ireland. The seaweed harvested in the north is very different from that from the south. The texture and taste is quite different. After evaluating seaweed across Ireland, we chose County Sligo in the northwest as our source. The waters are pristine there and it is infused with the limestone mountains around it. To me, the unique seaweed there just has that distinctive spray of the ocean that I don’t find anywhere else. We are still scratching the surface of what makes this seaweed different and funding research around this. This will be a key part of our know-how as we scale. We are already building the first ever seaweed farm in Ireland there. 

Unlike many of your peers, you were already commercial in Ireland when you decided to join the IndieBio program. Share a bit about what you’ve learned and accomplished during the program?

I thought we had done a decent amount of pilot testing already prior to launching in Ireland. But the mindset here about incessant iteration and market testing takes us to another level. It taught us to move faster and not to wait for perfection. We are also in great company with the amazing alternative protein companies in the IndieBio network. The mentoring and networking here has been key to accelerating our business and planning our market entry into the US.  I’m also super proud of the accomplishment of actually achieving flaky “fish.” No one has been able to achieve this yet and it was truly an important program milestone for us. Of course, hiring Piyali and other key team members has been another key enabler to setting a strong foundation for growth. 

Piyali, let’s talk a bit about what made you believe in Sea & Believe?

I am a chemical engineer and food scientist and have been working on how to make food taste better in my program at Wageningen University, which is where I was first introduced to Jennifer. I also love eating fish, but I understand the destruction caused by overfishing. I’ve also dreamed of being an entrepreneur. So, when we met, I was totally inspired by Jennifer’s zeal around her mission. Not only am I now making better tasting food, I can also feel the impact we will have on the health of the planet, as we scale. I can’t think of a better job! 

What’s next ?

As the round comes together quickly, we are building the right team with the right skills to scale our version of plant-based fish. We will be scaling and commercializing into Europe shortly and hope to share the magic of Irish seaweed with the world, while making the huge positive impact we want on the planet. \

Recently, much of the focus in cancer diagnostics has been on advances in liquid biopsy-based tests, looking at molecular markers inside the cell. So, it takes a minute to truly appreciate what Cellens is trying to pull off.  It is going retro, in a way, with a major difference. For decades, pathologists have relied heavily on the morphological analysis of cells, i.e., looking at cells under a microscope trying to decipher something about their state from the way they look.  Cellens is bringing attention back to the morphology of cells but taking it to a whole new level – Cellens is introducing atomic force microscopy (AFM) into the clinical diagnostic lab to scan the surface of a 3D layer of cells at such high resolution that it can not only discriminate cancer cells from healthy cells, it can identify the stage and aggressiveness too. 

Mechanobiology is an emerging multidisciplinary field where physics and biology meet, compassing cell biology and biophysics, moving from analysis of visual to multidimensional properties of cells.. The time is ripe for AFM to become the workhorse method for mechano-markers of cancer. 

Jean Pham was a master’s student at Tufts, when she met Professor Igor Sokolov, who has spent over 30 years perfecting AFM. Igor’s passion met with Jean’s entrepreneurial spirit  to create Cellens. While AFM can have many potential applications over time, they quickly focused on applying it to monitoring for recurrence of bladder cancer using a simple urine sample. Jean understood that the real money in cancer diagnostics is not in screening or diagnostic tests, but rather in high value tests that monitor patients for potential recurrence, in repeated and frequent testing for years. Initial studies, already published, show that Cellens’ AFM test at 94% accuracy in detecting bladder cancer from urine. It can help avoid invasive cystoscopies, which is currently the standard practice for ruling-in bladder cancer recurrence. Cellens’ highly accurate test can help rule out cancer in most of the urine samples that are sent in for monitoring, thereby risk triaging patients for invasive workup only when truly warranted, saving costs to the system and avoiding pain for patients.  

The Cellens platform is an entirely new, proprietary, non-invasive method to detect many kinds of epithelial cancer, such as colorectal cancer and cervical  cancer. Jean and Igor have successfully rallied support from academic medical and scientific community on the potential of this new clinical diagnostics modality.  They have grant funding that covers a bulk of their costs of their clinical trials at top-tier academic medical institutions such as Dana Farber and Brigham and Women’s.

Jean is an entrepreneur who embraces the ABC motto, i.e., “Always Be Closing.” I had to wait 15 minutes while I watched her close yet another investor on her current financing round. Her next call after me was already scheduled with the ex-CEO of LabCorp, who is one of her strategic advisors. So, I had just a few minutes to squeeze in these few questions:   

There’s an explosion of methods and tools to truly interrogate molecular mechanisms of cancer. Can Cellens really add something special to this landscape?  

I think there are a lot of ways to look at clinical decisions where we need new information to change the practice of medicine for the better. Currently, there is a lot of hype around various DNA and RNA tests for cancer detection. We are taking an approach that no one else is taking – we are looking at the physical properties of cells because we know that cancer cells have very different stickiness, softness, and other physical properties compared with a normal cell.  No one else has leveraged until now to detect malignancy using the physics of cells at this level. The time is now to explore this and Cellens will be at the vanguard of bringing valuable life-changing “mechano-markers” to patients, using AFM as a new clinical diagnostics modality. 

Why is Cellens’ mission so personal for you?

I always wanted to be an entrepreneur even before I started my master’s program at Tufts. There are too many scientists with too many ideas that never get far from the lab. I knew that one of the rough places in our healthcare system today is when a person has a history of cancer and is anxiously undergoing testing to rule out a recurrence. The tests to rule out cancer are inhumane and I wanted to do my best to eliminate that. When I met Igor Sokolov, I experienced his passion and determination first hand. He has spent 30 years on this trying to get AFM out of the research lab and into the clinic where it can change people’s lives. Specifically, we both realized that this technology and modality could dramatically improve rule-outs for any cancer where we could touch and feel the cells using AFM.  Cellens was born right then and I am thrilled to be working closely with Igor to make this vision a reality. 

What milestones did you hit during the IndieBio program?

I am proud of many things we have achieved in the last few months. We completed the IP license from Tufts and have completed the technology transfer to our own labs. Our proprietary protocol cut down 50% of time required for preparing sample. We hired our first key employees. We managed to secure an A-list of clinical and business advisors who are all excited about our mission to bring AFM into the clinical lab and also to beneficially change the lives of patients who are worried about bladder cancer recurrence with our accurate and non-invasive test with just a urine sample. 

What’s next?

We will validate the test in our own hands with clinical studies already underway and then launch our 200-patient clinical validation with partner institutions like Tufts Medical Center, Dana-Farber and Brigham and Women’s who have committed to recruiting patients and sending the required samples to Cellens.  It’s all about data, data, and more data. We will amass compelling data to change the practice of medicine in this area so that the Cellens test becomes the new world standard for accurate and non-invasive clinical test for bladder cancer recurrence. 

We all need oxygen to survive. But we also need to manage the potential damage that can be caused by oxygen free radicals, which plays a key role in many disorders and diseases. In 2012, Stanford’s Dr. Scott Dixon, spearheaded the discovery of ferroptosis, an iron-mediated form of cell death that is characterized by oxygen free radical-mediated damage to membrane lipids. Davide Zanchi, ex-Roche and current Stanford GSB grad, partnered up with Scott Dixon, as well as chemist Derek Pratt – one of the world’s specialists in free radical chemistry – to form Prothegen. They are leading the way to developing a new class of drugs to regulate ferroptotic cell death with exquisite precision, opening up a new way to approach diseases previously considered untreatable such as stroke, neurodegeneration and cancer.

In a short few months, Davide has assembled a team with deep biology and expert chemistry knowledge necessary to create drugs for lipid oxidation that are way more potent than prior efforts and also able to act where needed most – within the phospholipid bilayer of affected cells. Their first molecule, PTG01, is demonstrated to be safe and efficacious in vitro and in vivo. Equipped with the right mechanism, right location of action, and the right biomarkers, Prothegen is poised to introduce the next generation of medicines targeting ferroptosis.

As I was checking out exhibits on Expo Day, I spotted all 3 founders in one place and got the rare opportunity to pose a few questions to all of them at the same time:

What’s really unique about ferroptosis?

Scott:  Ferroptosis is a new type of cell death. What’s unique about it is that it has a different biochemical mechanism compared to known pathways. Because it has a different biochemical mechanism, it presents new targets for drug development. Those new targets turn out to be very important for many diseases, including stroke and neurodegeneration. As you know there is currently a dearth of true disease-modifying therapies for such diseases. So, if we can inhibit those targets, then we can truly turn back the damage from these diseases for the first time.

How do you target ferroptosis?

Derek: Because ferroptosis is driven by oxidation of membrane phospholipids, we actually need to target radicals that propagate the oxidation of membrane phospholipids that are actually then within the lipid bilayer. Many drugs that purported to target lipid peroxidation were targeted to the cytosol and didn’t have activity on lipids in the membrane. Because this is now a chemical reaction, we use small molecules that can intercept the chain carrying radicals, or these propagating radicals to prevent the oxidation of membrane lipids. And that will enable us to save these damaged cells, for the first time.

What does this mean for humans?

Davide: It means that we can pursue indications like ALS, stroke, and other neurodegenerative diseases, wherever ferroptosis is now understood to be a major underlying driver of cell death. We started with CNS indications because 60% of the brain is made of lipids. We now also have the right animal data that predict what our drugs will mean in humans and help us sort through the optimal clinical development path for us. 

What did you accomplish during the IndieBio period?

Davide: When we joined, we had a plan on paper backed by decades of research pointing in the right direction. Within a few busy months after forming the company, we now have a series of first-in-class compounds that can inhibit ferroptosis. Some of these were made internally and some came via our exclusive option to license Derek’s molecules from his university, which we also negotiated during this time. We conducted our first animal models with great results, even without having all the resources and time I would have liked to fully optimize this. IndieBio greatly expanded our networks and we have been actively pitching to investors seeking bold biology approaches to intractable diseases. We are well on our way, having laid down a solid foundation. 

As you leave the program, what are your eyes on?

Davide: The next steps in small molecule drug development are pretty well mapped out – we will optimize the compound, run PK studies, run more animal models, and make sure that the molecule is safe. We are determined to secure a visionary lead investor for our Seed round who truly believes in what we are building. We are being selective with this because we want a solid anchor investor who will stay with us for the long term. We have the biology, the chemistry, the core team, and the right approach to be the world leader in inhibiting ferroptosis.

The world simply needs a better sunscreen – one that does the basic job of blocking UVA and UVB, to be sure. Consumer surveys scream for a sunscreen that goes on silky smooth, does not make you look like a ghost, and one that stays on and keeps doing the job without needing to reapply every few hours to maintain the same level of protection (Who actually does that, btw?!). It’s also high time that we have a sunscreen that doesn’t make you squint when trying to figure out whether it is safe for babies and coral (Yeah, I am sure you noticed that even those so-called “reef friendly” sunscreens come with fine print). 

The market is huge – $4B in the US alone – and we seem to be slathering more of it on ourselves each year. The regulatory tailwinds are favorable too. Congress is pressuring the FDA to streamline the approval process for new sunscreens. Tourist destinations with sensitive ecosystems such as Hawaii, Palau, and Thailand are banning chemical filters. Europe and Korea regulate sunscreens as cosmetics and are poised to approve safer, environmentally-friendly alternatives to existing sunscreens. 

So why haven’t we seen a rush of VC funded startups trying to fill this white space?  It might be because it’s really really difficult to make a sunscreen that actually meets these specifications, market requirements, customer wants and needs while being truly harmless to humans and totally safe for the environment. Enter Sóliome! We sat down with Micah Nelp, CEO of Sóliome, and asked him a few questions:

Why do you think now is the time to startup a company focused on bringing a new sunscreen to market?

First of all, we aren’t focused on bringing just another sunscreen to market.  We are single-minded and hell bent on creating the world’s best sunscreen! It’s abundantly clear to us that now is the perfect time to do this: Everyone, yeah you too, should be wearing sunscreen every single day. But let’s be honest: there is no sunscreen today that makes you LOVE doing that. And if you happen to be doing it every day, you’re probably harming your own health and the planet’s health. It’s time to give consumers a much better choice. 

There is dramatically rising awareness of not only the detrimental human health effects but also the environmental risk of current sunscreens. We are about to reach a tipping point on this and we will have our sunscreen products on the market, right when that happens. 

Let’s back up a second.  How did creating the world best sunscreen become your life mission? 

Anthony, my co-founder, and I were searching for a mission where we could apply our combined scientific creativity to solve a major world problem. We definitely wanted to work on something that would contribute to human health and take full ownership of the problem, which pharma jobs didn’t offer. We also wanted to do our part in making our planet a better place. And, frankly, we think that every single sunscreen available in the market today sucks. We can do way better. And we think we have figured out how.  

If I may be honest, you guys seem like two chemistry nerds. Why are you the best founders of a consumer-facing sunscreen company?  

Well, we think the real secret to making the world’s best sunscreen, one that is both biologically safe and environmentally friendly, is core expertise in protein chemistry. The human eye is naturally protected from the sun through highly evolved peptide chemistry. Our core technology is based on this biomimicry, bottling complex chemistry in a sunscreen bottle. Anthony and I are intensely curious chemists. Our idea of a great day is when we have iterated on synthetic chemistry approaches to create a new prototype using totally safe, protein-derived ingredients. 

The IndieBio program is drawing to a close. What is next and how do you plan to scale?

In these last couple of months of the program, we have exceeded the cost target (and therefore the expected margin target) we set for ourselves. We are already at COGS equivalent to that of fully scaled, on-market sunscreens. Anthony and I are so passionate about this specific change we want to see in this world that we will hire the right marketing and business rockstars to make our vision a reality. 

Cell cultured meat is finally coming into its moment. Broad adoption, however, will depend on dramatically reducing the cost of cell culture media and growth factors, which currently comprise over 50% of the total cost of cultured meat. 

CellCrine has discovered the role of certain proteins that improve cell growth. The cost of including these proteins in cell media is almost trivial, and in turn reduces the need for all other growth factors and recombinant proteins 90% or more. The impact on cost and growth is revolutionary. CellCrine’s media supplement can enable alternative meat manufacturers to reduce the cost of their most expensive process input.

It’s natural, and CellCrine believes it’s more natural than hammering cells with growth factors. CellCrine makes serum-free media supplements specifically formulated for each type of cell. Their pork and chicken cell media products are already being evaluated by potential customers. 

I followed Dr. Rodolfo Faudoa, CEO of CellCrine, as he went into the lab where he was showing me beautifully shaped myotubes forming in chicken muscle cells he was growing using his special media. I diverted his attention from his experiment for a few minutes to ask him these questions:

What is CellCrine’s defensible magic*? (*due creds to Omri Amirav-Drory who taught me this term and why it’s important for every founder to answer)

Our media is not really magic, although it works like it. It’s a result of decades of research culturing difficult to grow cells in an optimized, predictable, serum-free environment. We spent years studying what cells need to grow and distilled certain key insights that have eluded others. Specifically, we isolated, tested, and patented the use of certain proteins, which are not a component of any media sold today. A very small concentration of these proteins in our thoughtfully formulated proprietary media products is sufficient to activate and manage cell culture in a manner not possible previously. 

Cultivated meat companies spend a lot of money developing media with marginally improved results, but remain far away from producing cultivated meat at the cost equivalent to traditional meat. You can think of our proprietary proteins as a “cell culture activator” that coordinates the cell growth process and brings out the best performance from within cells. If you are growing cell cultured meat using today’s best practices, perhaps like a maestro conducting a symphony bringing out the best in each musician. If you are a cultivated meat company scientist today, you likely have an uncoordinated and uncharacterized cacophony going on in your cell culture which invariably results in erratic and modest yields. With our patented media, you can convert your process overnight into a magical symphony that yields beautiful results each time. 

What have you accomplished during the program here?

We have established 4 master cell lines – two for chicken and two for pork cells. We have made essential media supplements tailored for each. With access to IndieBio’s deep network, we have initiated discussions and pilots with several companies working on cell cultured meat.  Even the companies who thought their cell culture processes were sophisticated are impressed with the added boost our media gives their cells.

What’s next?  

While I am focused on expanding our product lines and continuing to perfect our media supplement, my business co-founder – Octavio Gonzalez – is hard at work forging win-win partnerships with selected cultured meat companies this year who are aligned with our vision. 

While we can purchase all our ingredients now, we will be scaling up production of our proteins to ensure the highest quality and lowest cost for our customers. Many companies are going through regulatory cycles right now; we need to become integrated into the workflow of those companies’ production quickly. 

We will continue to perfect our partnership business model as current pilot projects convert into valuable long-term strategic supply agreements. We will seek partners who respect our value-add while enjoying a dramatic reduction in their production cost of cell cultured meat. 

Solid Ox Motors is building an onboard trickle charger solution, initially for commercial fleets of electric trucks and buses. This unique range extending solution uses liquid fuel, where the CO2 is retained on board, right back into the fuel tank. Emissions-free. Commercial fleets that need long range are very price sensitive to fueling costs. They also run most of the day and night and thus have short windows to refuel and recharge. Solid Ox allows fleets to refuel in one-tenth of the time, at half the cost. 

CEO of Solid Ox Motors, Jared Moore, was a two-sport athlete in college who became an environmental activist and policy wonk.  After a decade in clean energy research and consulting (and watching “An Inconvenient Truth” multiple times), he decided the only way to drive change he wanted to see in the world was to become an entrepreneur. He was sealing a deal with a large EV fleet company, who had just decided to retrofit one of their trucks with SolidOx, when we caught up with him for this quick interview.  

Hey Jared, I know you are totally passionate about this.  But convince me and other VCs out there that solving charging issues for electric truck and bus fleets is a big enough problem to pursue?

There’s a lot of hype around the ease of transitioning to EV. With industrial fleets of trucks and buses, the problem is particularly acute. We know from speaking to companies that shareholders and top management want to transition as soon as possible to EV, but the pain points are quite severe. The CapEx and Opex costs, turnaround times, and logistics for charging of medium and heavy-duty fleets are heavily underestimated. Take USPS for instance: They recently published an analysis which estimated that electrifying their fleet would require one $20,000 charger per vehicle!   With those numbers, it’s obvious why they’re not going electric anytime soon. Regardless of this on-the-ground reality, there’s no question that there is tremendous optics and momentum around conversion to EV. This year alone, there will be over 20 million new medium-duty trucks sold in the US. Even if 10% of these adopt our liquid fuel retrofit, this will be a multi-billion monster market opportunity – hidden in plain view. 

What is your secret sauce exactly? 

Our patented technology enables the very efficient use of a liquid fuel such as ethanol or methanol. We are also able to efficiently retain the CO2 produced by our system in liquid form. Our solution is less than half the cost of competitive approaches, such as hydrogen, assuming the formidable infrastructure challenges for distributing hydrogen can even be solved. So, while the EV hype misleads investors to focus their investment dollars in other areas, we will steadily prove out a huge opportunity available for the Solid Ox liquid fuel EV retrofit. This is because we acknowledge key infrastructure realities as they truly are and enable large companies, under pressure to rapidly convert to EV, to actually meet their goals in the near term, before the grid and other infrastructure are up to the task. I should also mention our grid integration capabilities – as a portable power plant, as a temporary charger for other vehicles, and as a vehicle having the option to use excess grid capacity to top off its modest battery pack.

How did you move the ball forward during the IndieBio program? 

We made great progress over the last few months from having a crazy looking solution on paper to a prototype that actually works!  Just last week, we condensed the CO2 produced by our system, and thus reduced to practice this key aspect of our technology. Probably the biggest moment for me during the program was when my co-founder, Brandon, decided to join me in this mission. Brandon is the only other engineer I have met more passionate about solid oxide fuel cells. When I first met him, we talked a little bit about football (both of us played), but hung out and talked the rest of the night about how to solve the problem no one was addressing. I suppose you could say that it was “co-founder at first sight” for me. So when he decided to hop aboard after intense pressure testing of the plan, it felt great and I knew we were on to something very real. Another key milestone we hit recently was working out the details of an attractive pilot project with a potential customer company which has one of the largest medium-duty EV fleets in operation.

What’s next for you? 

Brandon and I have a fun summer planned. Smith EV is giving us one of their medium-duty trucks to perform a Solid Ox retrofit. We plan to operationalize this and then drive across the country stopping at cool places along the way, posting on social media of course, and compiling a massive data set which will help improve our solution. We will prove to the world that our retrofit is a must-have for all medium-duty trucks. EV buses, which will require a slightly scaled up solution, will soon follow. Unless the grid infrastructure is dramatically accelerated, which I very much doubt, I think we will be retrofitting EV cars too with a scaled down solution in due course. 

Photosynthesis wastes sunlight. Many scientific efforts are underway to improve the efficiency of photosynthesis to increase yields. None of these efforts have translated from research/academia into the field. Others are too complicated for real world applications. Climate Crop – decades in the making at Weizmann Institute – will outgrow them all. They have found a side door to improve photosynthesis across thousands of plants, based on deep research on regulating leaf starch biosynthesis. During the day, plants increase their storage of transient starch; at night, they use this starch as building blocks for all cell matter. Climate Crop’s IP and technology relies on a small non-GM edit to increase starch synthesis in leaves resulting in crops with significantly increased yields, crops with resilience to survive extreme weather events, and a new route to more plant biomass for carbon sequestration. 

They have already observed dramatic yield jumps – 91% in potatoes, 40% Canola, 24% Sorghum. This appears to work in all vascular plants. It’s simple, yet powerful. Climate Crop’s potential is huge – it can power applications across both agriculture and industrial markets. Their current focus is on food crops, but it’s only a matter of time before they can be a powerful enabler of higher yielding cotton, carbon-sucking poplars, cheap aviation fuel from rapeseed, and beyond. The sky’s the limit.

Yehuda Borenstein, CEO of Climate Crop, is a no-nonsense experienced operator and entrepreneur from Israel. As with every conversation with him, we quickly cut the chase on a few questions we posed to him below:

I was just overhearing an investor talking to you just now. He was amazed by the yield improvements with such a small change to a single protein, and was asking, what’s the “catch?” Let’s start there, is there a catch? 

Yeah, this is often the first question we get. Our results look too good to be true. In fact, this is the question I asked myself when I first got into this. I asked so many experts in plant biology to verify this, including one friend who works at one of the large agricultural companies. He looked hard at all our data and came to the conclusion that we have actually landed on a way to increase the efficiency of photosynthesis. This was consistent with actual tests that my cofounders and original inventors, Vivek and Erez, performed while at Weizmann which showed a 15% increase in photosynthesis efficiency even in an unoptimized setting. When you are able to do this, seemingly magical things start to happen, which is why we have such great results. We have also been testing the nutrient content of our products, such as canola oil and it looks exactly the same as the reference standards, the results for potato will be available soon. There’s no reason for a catch; it is as real as our larger potatoes and higher yields we are observing across many crops and plants.  

What’s your business model?

We are going to be a seed company. We are going to take open varieties, upgrade them, and send them to end customers. Amazing technology, boring business model. Simple and proven. Since this mechanism exists in all vascular plants, we can partner with every ag company in the world, and still have thousands of plants to improve and take to market.

Yehuda, you are an experienced entrepreneur having started several companies. What did you get out of the IndieBio program? 

We joined IndieBio literally a few weeks after we established the company. We didn’t have clarity about our added value and the best way to capture that value. We also didn’t have a clear priority on the crops we wanted to work on. During the program, we gained an understanding of how to build the business, where our added value truly lay, and got a much better handle on the optimal business model. I think that clarity around who we are and how we can go forward is truly the solid foundation we needed for our company. 

What’s next for you?

First, I am going to be sad for a week after leaving this program. It was an amazing experience here where you gave us a framework and many many tools for how to build our business. Even more importantly, you shifted our mindset for the better in many ways, big and small. This is priceless and so hard to get anywhere else, especially in Israel. Even as an experienced entrepreneur, I learned many important things. We will move full speed ahead now – we will pick the right crops, the right investors to partner with us for the long term, move the company to the US since the markets are here, and go for it with great execution!  

Producing purified proteins is an expensive proposition, despite advances in expression systems, bioprocessing technologies and major strides in scale. The capital expense of bioreactors and bioprocessing equipment, combined with high variable costs for growth media, downstream processing, and quality control, continues to keep costs higher than desired. Proteins that are used as biotherapeutics are particularly expensive due to levels of purity and/or sterility required, even higher quality control costs, and the amortized overhead to meet FDA or other regulatory requirements. Besides being expensive, it is a risky and time-consuming undertaking to scale-up a protein production process. Many proteins are finicky to express even when DNA sequences and molecular structures are well known and characterized. Even today, bioprocessing scale-up experts deem it an art form to achieve industrial scale yields of many valuable proteins. 

Molecular farming came on the scene to address some of these problems. We have now successfully used plants to produce antibodies, vaccines, and medicinal proteins, as well as nutraceuticals and functional food. This growing field promises a future where farmers of the future could be growing crops to provide medicines as well as industrial proteins. However, molecular farming approaches usually require a transgenic plant to grow to full size before harvesting the leaves, where the target protein is usually expressed. So, while it can avoid the large capital expenditures of a modern bioprocessing plant, it is certainly not veloz (Spanish for “fast”), i.e., there are clear and inherent limitations to scaling molecular farming.

It is into this landscape that Veloz Bio came into being. Veloz Bio produces beautiful, high-grade proteins from ugly, discarded fruit. Veloz’s platform is built around harnessing the metabolism of post-harvest vegetables and fruits to transiently express target proteins at a speed, scale and cost previously thought impossible. Almost half of all bananas or tomatoes planted for human consumption never gets to the table. Veloz Bio, formed by two founders with learned competencies from working with post-harvest inputs to produce functional food extracts, is well poised to disrupt the economics of protein production using their fast, decentralized, and zero CapEx approach to protein production. They are perfecting molecular farming, without the farm.

We caught up with Enrique Gonzalez, CEO of Veloz Bio, as he was moving fast around our “ivory basement” and asked him a few questions: 

Why did you and Flavio start Veloz Bio?  

Flavio, my COO co-founder, and I have been committed to making high-quality food and food ingredients affordable for all. We worked together at a previous company where we deployed and perfected a reverse logistics supply chain, focused on taking discarded fruit to make processed food ingredients and flavorings much more affordable. While this made a dent in the economics of food ingredients, we were dissatisfied. When we came up with this breakthrough proprietary technology to use discarded fruit to make valuable proteins, we realized we had a fresh opportunity to expand our mission. We are now able to jump-start Veloz Bio by leveraging our expertise in the reverse logistics of large scale processing of second/third quality fruit inputs, sent directly to us from farmers.

What is your initial product focus and will you follow a B2B business model like your previous company? 

Proteins are the basis of life. Yes, we will become a B2B supplier of valuable proteins, but at speed and scale previously unimaginable. We are starting with an initial focus on specific high value proteins that are used in the production of meat and cheese alternatives. For example, 𝝹-casein is the holy grail of vegan cheese production. As we talk with potential customers, we are hearing loudly that no one has been able to make 𝝹-casein at reasonable yield or purity and are thus unable to provide a robust “casein solution” to vegan cheese producers. Despite the fact that the taste of vegan cheese is limited by the lack of key ingredients such as 𝝹-casein, that market is growing at a nice clip of 15-20% each year. Imagine how fast that market would grow if vegan cheese actually tasted anything like the original? We enable that. 

What milestones have you accomplished in the last few months?

During the IndieBio program, we validated that our “moon shot” protein production platform actually works. We were able to produce functional proteins using discarded fruits in a manner that is both technically and economically viable. We have already produced 𝝹-casein and other proof-of-concept proteins. And we did this at veloz speed and scale! We can take new proteins from nanogram to kilogram scale in just 2 weeks! Compare that to a precision fermentation company which would easily require 10 months or more to accomplish the same. And we do it at a cost trajectory that current producers cannot dream of achieving. 

Hear how they outcompeted their peers for the most progress in one week in our Killer of the Week podcast: #1219 – Vegan cheese just got a major boost.

Three Ph.D. students at the University of Washington started brainstorming about how they could help each other complete their research and graduate sooner. Jason Fontana was iterating on guide RNAs for CRISPR applications. David Sparkman-Yager was deciphering the rule book for how RNAs dynamically respond to binding. Chuhern Hwang was working on how to make new binding domains (or aptamers). They came together to form Wayfinder, which has a revolutionary way of building biosensors out of RNAs: nucleic acids that fold, like complex origami, into molecular machines. Wayfinder’s biosensors are not simply on-off switches, but are capable of analytically sensing specific molecules, in real time. The genius of their platform reflects their collective genius – it is a unique combination of deep RNA biology expertise, coupled to a powerful computation engine, to design smart, dynamic RNA aptamer biosensors. 

Jason Fontana, CEO, was politely trying to tell yet another VC that his round was already over-subscribed when I waved him down to chat with me for a few minutes.

I can never get enough of the origin story of Wayfinder. Jason, tell it to me one more time.

David, my co-founder, had been beavering away for years on the biophysics of RNA trying to figure out the ground rules of RNA functionality, e.g., the rules around RNA folding, binding, engineering, and shape-shifting. He came up with a way to computationally design RNA that combines these biophysical insights into a smart search of the design space. His algorithm, even at that time, could quickly narrow down from say 10³⁰ possible sequences of interest (which are impossible to screen through) to just about a million sequences, in a single day. Meanwhile, I was designing guide RNAs for CRISPR and experiencing very erratic results. Some of my designs would work while many would not. I asked David to collaborate with me on using his tool on guide RNAs and it worked beautifully every single time. We then tried it on aptamer-regulated mRNAs and other RNA applications and soon realized we had come up with a generalizable tool for designing reliable aptamer-based biosensors. Not only did we finish our Ph.D.s faster than planned, we also had jobs afterwards. And here we are!

So, you both came to the IndieBio program and made some amazing progress in the last few months. Tell us what you think you have achieved during the program. 

We have taken our tools and tried to apply it to real-world problems in new ways. On the first day in the basement labs, we made engineered RNAs that lit up, which had led us into fresh directions. We kept iterating on our technology platforms and RNA aptamer designs. We also iterated on the business side by speaking with small and large companies who wanted to measure something critical for their business. We suddenly find ourselves running at full capacity with these types of pilot projects. But we have learned from each one by adapting our technology for different needs. We have also met investors who get the potential of our evolving platform and we have raised the money we need for our next stage of growth.

What’s the next step on the way for Wayfinder?

We are focusing on improving and expanding our platform so we can address very large markets where our technology can help solve intractable problems. One of these is in drug discovery applications. We are working on biosensors that can target different RNAs in the cell. We think we can design drugs that can continuously sense their microenvironment, and turn modalities like CRISPR both on and off in response to what they are sensing.

Hear how they outcompeted their peers for the most progress in one week in our Killer of the Week podcast: #1218 – Seeing molecules with the naked eye.

The management guru, Peter Drucker, is said to have remarked, “You can’t improve what you don’t measure.” This certainly applies to continuous biological measures from wearable technologies. In recent years, these cool tools have helped us gain a fuller measure – and therefore improvement – of various aspects of our personal health and wellbeing. Continuous glucose monitors, for instance, are dramatically improving the quality of the lives of people with diabetes. While the obvious value proposition is to eliminate finger sticks and blood draws, studies are starting to validate the non-obvious and more subtle effects from empowering people to drive positive behavioral change. The feedback loop from continuous non-invasive sensors may indeed hold the key to sustainable behavior change, without which we may never be able to truly tame the rising toll and cost of many chronic diseases. 

Proton Intelligence is developing the first ever continuous wearable kidney health monitoring platform, starting with potassium. The kidneys control our potassium levels and potassium controls every single heartbeat. That’s why kidney patients die, not from failed kidneys per se, but from heart attacks. We’ve had no way to get continuous visibility to the dangers of potassium when kidneys start to fail. Nephrologists and kidney care teams around those undergoing dialysis are flying blind today when it comes to the potassium level in their vulnerable patients.

Sahan Ranamukha, biomedical engineer turned CEO of Proton Intelligence, is an entrepreneur in the true sense – he searches for change, responds to it, and exploits it as an opportunity. It is an understatement to say that kidney care, certainly in the US, is going through massive change. Large kidney care players are consolidating, trying to extend their footprint and purchasing power. Nephrology practices are also consolidating and adapting to risk-sharing contracts with payers. Can the continuous measurement of potassium become the key that unlocks and actualizes the promise of value-based kidney care?  Proton Intelligence’s sensor has the potential to underpin and provide actionable data to avoid hospitalizations, rationalize the use of potassium binding drugs, shift dialysis safely to the home, and become an integral part of other such critical changes required for extracting real cost savings from rationalized kidney care management. No wonder then that, in survey after survey with nephrologists, especially those already belaboring under the pressure of value-based contracts, there is clear demand for Proton Intelligence’s wearable. The challenge and the opportunity are huge.

Sahan had just been crowned our “Killer of the Week*” by his very competitive peers when I called him to ask pesky questions about whether he is truly ready to embrace bold business models exploration necessary to maximize the value of his potassium sensor technology (*more at: IndieBio Killer of the Week Spotify Podcast):

I know that making the world’s first non-invasive potassium sensor is no easy feat. But what makes this a multi-billion dollar opportunity? 

When we initially looked broadly at where potassium levels – whether discrete, semi-continuous or continuous – can drive patient care decisions, we came up with 17 different use cases. That was surprising to us in itself because potassium, unlike glucose or other analytes, is mostly in the background in lab tests today. But when we zeroed in on people with later stage kidney disease, especially those on dialysis, it became rapidly clear that is where our beachhead market should be. 

Isn’t dialysis already a saturated market for innovations?

550,000 people are on dialysis each year costing the system $100,000 each – that’s $55B per year spent managing kidney care today. When we speak to nephrologists, kidney care companies, and payers, they worry that this burden will rise even further despite huge pressures to contain costs. Without question, they are desperately seeking innovative solutions, especially those that help them extract cost savings while also increasing the quality of care. 

So how does one little device upend this cost problem? 

Patients will change their behavior because they will love having visibility into what is going on with potassium (and over time, sodium and other key analytes) in their bodies at all times. That’s why we have the winning technology platform – we are the only ones who can cut this Gordian knot by providing a new stream of actionable data the care team needs to do their thing, while simultaneously empowering patients to take more control of their own health. Nephrology care teams will finally have a veil lifted so they can make smarter and safer decisions. This is what is needed to drive make value-based kidney care actually work and be sustainable in our healthcare system. When we deliver on our promised value, our share will be way more than $1B. And, this is just our beachhead! 

What did you achieve during the IndieBio program?

When we got here, we had a sensor that kinda sorta worked in a simulated interstitial fluid. It was not selective for K+, not biocompatible, and simply too large a form factor to be a viable product. In the last few months, we worked hard to hit our selectivity and biocompatibility specs and also miniaturized our sensor over a 1000-fold. On IndieBio Demo Day, we achieved a world first – we now have the world’s first K+ wearable. My co-founder, Francis Steiner, and I wore it for 8 hours and showed the continuous data stream to the delight of investors as we pitched to them.

What about the business side of things?
During the program, Francis led the way on the business side to engage with the entire kidney care ecosystem. We spoke with hundreds of nephrologists, the biggest dialysis companies, and a handful of chronic kidney disease management companies. We will be starting pilots with a selected few of these. All these discussions have validated and confirmed the criticality of our K+ sensor as a key enabling driver to achieve pareto superiority in the future of kidney care management. I am also happy that investors appreciated our progress and have already filled out our next round.

One thing we noticed you do amazingly well is to recruit and manage a trans-continental team during a pandemic. Tell us your secret to managing teams virtually. 

When we joined IndieBio, we had a small team, including Francis and me, who were based out of Vancouver. We added our third co-founder, Victor, who leads the sensor technical development team in Australia. We also managed to hire away a key hardware development engineer from a CGM company, and he happened to be based in Europe. We are rigorous about ensuring alignment across teams on key goals and resources required for successful execution. We are creating a company culture that thrives on virtual collaboration with flexibility across various time zones, while ensuring strong communications up, down and sideways. It’s still early and there are certainly challenges, but we are laying the foundation for a successful company that is able to tap talent across the globe and execute well under pressure, just as we demonstrated to the world on Demo Day. 

Hear how they outcompeted their peers for the most progress in one week in our Killer of the Week podcast: #1217 – Honey, I shrunk the electrode.

A third of the world’s agricultural soil is degraded by drought, high salinity and the increasing effects of climate change. Without bold innovation, we will soon run out of healthy arable soil sufficient to feed the planet. 

Puna Bio repairs and restores soil health using their proprietary extremophiles – organisms 3.5 billion years old, sourced from La Puna, Argentina, the highest and driest desert on Earth. These organisms grow where others can’t – and they sustain plant life, despite getting 1/5th the rainfall of Death Valley. When an athlete trains at altitude, she is even stronger at sea level. So it is with Puna’s extremophiles. They work wonders on degraded, acidic, UV-irradiated and salinated soil. In fertile soil, they boost yields 4x more than competitors, with far more consistent results.

Puna Bio is already at industrial scale, having treated +600 tonnes of seeds this season, and conducted over 20,000 acres of field trials. While they can easily secure high margins using a basic business model of directly supplying seed treatment to farmers, other innovative market value extraction models are available to them because of how their extremophile formulations are able to increase land value. The market value of farmland is driven by yield. For example, increasing soy yield by 10 bushels an acre can double the value of the farmland. Now, that’s a company that is matching their unique and defensible tech magic with an innovative disruptive business model. 

I interrupted Franco Martinez Levis, CEO of Puna Bio, as he was packing freshly formulated, ready-for-sale bottles of his company’s Extremia™ seed treatment to be shipped out to his very first US customer. He graciously tolerated my interruption to answer a few questions:

Soil and seed treatments promising amazing yield improvements aren’t new. What’s really cool and unique about Puna Bio’s seed treatment products? 

Yeah, you’re right. The Big Ag companies like Bayer, Corteva, and Syngenta use the same types of strains for specific crops. For example, for soybeans they tend to use Bradyrhizobium strains and Azospirillum for wheat. We do not use these typical strains at all. We use our unique extremophile strains that we isolated from the highest and driest desert on earth, which we can now produce at increasing scale. With climate change and erosion, most soils and ecosystems worldwide are subject to serious stresses such as high salinity, drought, and UV irradiation. The currently available seed treatments simply die and do not work as advertised under such conditions. Whereas, our strains consistently increase yields up to 25% even under these high stress conditions and they work better than comparable options in regular conditions. 

Ag markets are dominated by a few big companies and margins are tight. Can innovative companies like yours achieve decent margins and extract a fair proportion of your added value?

Since we currently only sell liquid soil treatment direct to farmers in LATAM, we can be fairly independent of Big Ag’s lock on distribution, for the time being. Even our current unoptimized startup margins are north of 80% and this will improve as we scale. We just had our first customer re-order for a second season and they easily accepted our revised premium pricing. Once farmers go through a single season of experiencing the magic of our extremophiles in increased yields, we won’t have to worry about margins. We will need to worry about scaling production dramatically to satisfy a practically insatiable demand in every country. 

What milestones did you accomplish during the IndieBio program?

Last season, before IndieBio, we did as few field trials on less than a thousand acres across Argentina. While at IndieBio, we scaled to over 20,000 acres of product coverage in the last few months. It was an amazing rush to get this done and we are on our way to the next step in scale. In terms of science, we continue to decipher most interesting functions that our extremophiles perform on seeds and soils.  We are still scratching the surface, but our scientists, who are world experts on these organisms, just uncovered a specific mechanism by which our organisms can reduce the need for nitrogen-fixing fertilizers by about 30%. Last but not least, we enjoyed our first revenue-generating partnership with a US customer last week. That was a great feeling!  

What’s next for you?

We are expanding our product line beyond soybeans to both wheat and corn. In parallel, we are also piloting with customers in other LatAm countries like Brazil and expanding our presence in the US. We will confirm and validate both yield improvements as well as the ability to decrease the use of nitrogen fertilizers, which will in turn reduce carbon emissions (1/3rd of total agricultural emissions come from nitrogen fertilizers) and shore up the large economic impact of our products on farmland yield and costs. With support from visionary investors, we want to seriously start exploring disruptive business models such as land value arbitraging to further capture the value of our innovations.

Hear how they outcompeted their peers for the most progress in one week in our Killer of the Week podcast: #1216 – A customer doubles down.

Four founders, each with deep experience in related areas, came together to form Pyrone Systems, an unusual company with an unusual platform and go-to-market plan. 

Alex Hutagalung, a biochemist, had patented a novel process of converting fatty acids to polyketides. He leveraged this patent into a proprietary bioprocess to make triacetic acid lactone, or TAL,which has a plethora of medicinal, agricultural, and industrial applications. Making TAL cost effectively has been a goal for green chemistry, given that it is a precursor molecule for many other valuable compounds and bio-based chemicals on par with the dominance of petrochemical building blocks. 

Brian Conn had worked with Alex at a prior company where they were using a yeast fermentation process to produce the active ingredients in cannabis and they decided to partner up again at Pyrone. Brent Shanks, the third founder, had been working extensively on using TAL to make products using very simple chemistry. Brent introduced them to Steve Bessette, the fourth co-founder, a 30-year veteran of the insecticide industry who introduced plant-based oils to the market and serendipitously found pogostone (made in one-step from TAL) as the most potent insecticide he’d ever seen.

I posed a few questions to Alex Hutagalung, CEO of Pyrone Systems to help me unravel how these various aspects of the founders manifested in the evolution of the company:

Alex, sort me out quickly: Are you an insecticide company or a green synthetic chemistry platform company? 

Ultimately, we are both. For the near-term, we will focus on introducing pogostone as a natural alternative to pyrethrin-based insecticides. Over time, as we scale, our mission is to evolve more fully into a unique green chemistry platform based on our singular ability to synthesize TAL and other biobased chemicals using a simple, cost-efficient process. We will make many other biobased chemicals like TAL, which will replace their respective petrochemical-derived versions in use today. But until we reach that point in our company’s scale and evolution, there is a clear and obvious answer for the best use of TAL today – it is the use as a precursor to make pogostone. The pricing potential and volumes required for a successful pogostone product are already within our reach. While TAL can be used to make many other downstream products with other industrial applications, these applications such as corrosion inhibitors or lubricants will require us to operate at volumes and scale that will take us a bit of time. In the meantime, using TAL to make pogostone and getting it approved by the EPA as a new insecticide will maximize the near-term opportunity, while also enabling us to move up the scale curve until the time is right to expand into our full potential as a chemistry platform company. 

What did you accomplish during the program?

Oh man, we got so much done! We literally had an idea on paper when we arrived. Now, we have a proprietary strain that uses fatty acids to make TAL in the unique way I had designed. We achieved proof of concept production of TAL. Further, we synthesized pogostone and have already begun testing it in 3 different locations in the US. We are also parallel tracking how to formulate pogostone into various kinds of final insecticidal products. Most importantly, we initiated talks with EPA and secured their blessing to apply for approval of pogostone as a bioinsecticide. So, we exceeded the main goals we had set for the program and more. Thinking beyond pogostone, we have also started building relationships with various ecosystem players on other uses of TAL (such as in lubricants) and already seeing keen interest in our approach. 

What’s your go-to-market for pogostone?

We plan to launch it as a bioinsecticide for public health pests such as mosquitos, ticks, cockroaches, and termites. We will partner with a professional household pest control market, which is surprisingly large at around $2B. We will market pogostone as an ingredient through the approximately dozen or so distributors that serve this marketplace, selling into end-users like Terminix and Rollins. We have already started discussions with several of these and they find our unique product profile and expected pricing quite attractive, filling a key gap they see for a natural yet effective biopesticide. 

What’s next for Pyrone?

After we conclude the financing round in progress, we will focus hard on getting pogostone approved by the EPA, which will raise a barrier for others. During this time, we will optimize our production process for TAL, mostly non-dilutive money from a DOE grant we have already. We will continue to build the necessary business relationships, both with potential pogostone distributors as well as those interested in creating other products from TAL. We will synthesize and synergize the complementary talents of the cofounders to build the leading green chemistry company in this space. 

Hear how they outcompeted their peers for the most progress in one week in our Killer of the Week podcast: #1215 – A yeast that eats fat.

Proteinea turns insect larvae into biofactories. Instead of cell-based biomanufacturing, their next-generation platform uses mass-reared insect larvae as fast growing, mini-biofactories to produce recombinant proteins of interest. From antibiotics to biosimilars to vaccines to aquaculture feed to growth factors and more, Proteinea makes valuable recombinant proteins affordable and accessible. And their Buggzy platform is just spinning up. We chatted with co-founder Mahmoud Eljendy and Abudulaziz Elgammal about the future of recombinant protein production. 

Proteins make every function you could imagine very fast and efficient. I dream of the day when we harness this power to make soft machinery.

CEO Mahmoud Eljendy

How did you two meet? 

Although we are originally from the same city 100 km away from Cairo, we only got to know each other from the entrepreneurial ecosystem in Cairo. Mahmoud had his previous startup, DeltaOil, where he built a success story that’s now Africa’s leading Used Cooking Oil (UCO) supplier for the Biodiesel industry in Europe. I (Abdulaziz, Aziz for short) was fascinated by the mission-driven and innovative approach he took to enable unprivileged communities to valorise an untapped source of income while making a good amount of money and saving the environment.

At that time, I was working with the leading accelerator in the Middle East North Africa region (Flat6Labs) and trying to build a community of science entrepreneurship enthusiasts. During one of our meetups for science entrepreneurs, I met with Mahmoud who was then raising insects in his own apartment and was looking for a technical cofounder. Funny enough, the place we first met years ago is now our own office and lab at Proteinea 🙂

What made you decide to start Proteinea? 

It was a convergence of efforts to make an impact in people’s lives through know-how and innovation. We started Proteinea with the aim to solve a very local problem that’s at the core of our food value chain. The principle was to use insects as a protein source for animal and aquaculture feed as Egypt imports 90% of its feed components. During this process, we borrowed technologies from aerospace to machine learning to biotech and everything in between to scale up the production very efficiently and very cheaply.

We then realized that combining the process we built and our previous background, we have created the perfect solution to a more pressing problem the world is facing — recombinant protein production.

What does “recombinant” actually mean? 

Something recombinant means it is made by recombination. As scientists, when we want to engineer a living organism, we usually start with engineering it’s DNA. By assembling a DNA fragment from smaller pieces so that they contain specific instructions for the cell, we build what’s called a recombinant DNA. In some cases, these new instructions tell the cell to produce a specific protein. In this case the protein is called a recombinant protein.

Why is a fly larva an optimal protein factory? 

Compared to cell-based technologies, insect larvae can perform much better in the production of our complex proteins. Very low capex and opex – we do not have culture media, our culture media is wheat bran, fast time to market – it can take as little as two weeks to have our protein of interest, and the scalability – we can produce hundreds of kilos of larvae from very small area & what happens in one larvae can happens in millions of larvae – that’s minimal risk in the scale up.

Seems difficult to get proteins to fold the right way – how does it work in the insect larva if you’re trying to do humanized or otherwise proteins? 

Insect cells have long proven to make complex proteins. They have complex cellular machinery to produce virtually any protein you might need. In many cases, they are the go to platform for expressing proteins that don’t work well in other systems, Virus-Like Particles (VLP) vaccines make very good examples here. Even some of the most complex proteins like full humanized antibodies have been produced in insect cells before.

At Proteinea we work with a novel platform which requires some work from our side to identify the proteins and pathways to make proteins stable to express, purify, and  humanize and we have success with it. Our AI-based computational optimization goes hand in hand with experimental validation to build the next generation soft bioreactor.

How big is your team?  How did you find all the talent?  What industries do they come from?  How hard is it to build a company culture so quickly? 

We are 22 team members between the US and Egypt. From the beginning, we are very keen to build a robust culture that can proliferate. We have built our manifesto in which we have our values and principles. We provide 4 things in Proteinea for our team members. A cool technology and science; a product could have a huge impact on our biomanufacturing thus bioeconomy; a robust culture with stunning colleagues; and fair financial compensation of salary and stock options. 

What is the biggest difference between working in STEM in Egypt and the US? 

Between Egypt and the US, you face a completely different set of problems. There’s not much competition over the talent pool in Egypt, so you get to build a very strong team easily. But, the support system in Egypt is still nascent when compared to the US. You don’t have many options but to build your own path. I remember when we started doing experimentation in Egypt, we got help from big research institutions because they want to help on the personal level not because of the institutional direction of supporting entrepreneurs.

Logistical challenges in Egypt are also a bit harder than the US. Because there are no local manufacturers of biotech supplies, things might take longer to arrive in Egypt. We mitigate that by proper planning plus we do some of the more advanced research in the US to cut time.

What’s your favorite biomolecule in the central dogma?  Favorite amino acid?  

I’m a protein guy, look at this one. It’s beautiful. I remember my fascination with the protein myosin moving a molecular cargo across the cell over a protein railway (cytoskeleton). Proteins make every function you could imagine very fast and efficient. I dream of the day when we harness this power and make soft machinery. We started this at Proteinea and built the world’s fastest biomanufacturing platform based on our soft bioreactor. Cysteine, disulphide bridges also have a special place in my heart.

Canaery leverages the animal kingdom’s superior sense of smell to detect and digitize the world of scent.

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A dog’s nose is a smelling machine. From cancer to covid to cocaine to citrus greening, no other chemical sensor on the planet can smell and sort through the billions of environmental compounds like an animal’s olfactory bulb.  Today the only way to know what a dog or rodent is smelling is to interpret its trained behavior.  Canaery has brought us a way to read what the animal is detecting in the world without pre-training it on those compounds.  Deciphering the cacophony of scents we encounter daily is a daunting task, but done right you can unlock industries like agriculture, global shipping, and medical diagnostics.  Below are excerpts from our conversation with CEO and co-founder, Gabriel Lavella, Ph.D.

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Nobody has been close to reproducing an animal’s sense of smell in terms of range and sensitivity. Until now.

CEO, Gabriel Lavella

During IndieBio, Canaery designed and built a prototype neurotech device to digitize the sense of scent. What is so hard about digitizing olfaction and why you are different?

We have sensors that are spectacular at digitizing all human senses except scent. The reason for this is clear; it has been a daunting task to reproduce the animal sense of smell. In fact engineers and scientists have been working on it for decades.  It’s relatively easy to make a sensor that detects one type of molecule, for instance a CO2 detector.  However, scents are often complex mixtures. The nose detects billions of different scents and does this using a complex set of receptors and machinery for introducing and rapidly removing the scent molecules. Canaery didn’t recreate that feat of nature but instead we use it. That’s what makes us different, we use a sensor already perfected over millions of years of evolution. 

Canaery’s neural interface is smaller than a penny and thinner than tissue paper!

Tell us about your team and what led you to your major breakthrough? 

Back in 2019, I jumped on a plane and flew to Trieste, Italy from my home in Barcelona.  Dima [Rinberg, CSO and co-founder] was coming out from NYU to a conference on chemical senses, a couple years earlier he had made the first major breakthroughs on decoding scents using interfaces.  It didn’t take long for us to realize we were on the same page.  Those fascinating conversations centered on discussing how combining his theories with our efforts in high scale interfaces could produce the ultimate smell sensor. 

That combination was the key that unlocked Canaery’s capabilities today.  From there we knew the applications and impact were immense.

The world is awash in scents and smells. Can you describe how Canaery keeps us safe and open for business? 

Nearly all objects give off a unique scent profile that can be used to identify the underlying object or even the state of that object. Scents are essentially volatile compounds and there is a great diversity of them in air, trillions in fact. 

To humans these compounds are often invisible because our noses aren’t trained to smell them. It is unlike our eyes where we can easily recognize and categorize millions of objects. Nevertheless these scents are there and they identify things critical to human health and safety. We don’t want to shut down the economy again when the next pandemic hits, we want to be able to detect and contain it from day one, scent can do that.

Vertical Oceans is elevating shrimp through its advanced vertical aquaculture system integrating 83 different technologies to build a perfect ecosystem for the world’s cleanest, freshest, and most sustainably produced shrimp.  Below we caught up with John Diener and Enzo Acerbi, co-founders and CEO and CTO, respectively, of Vertical Oceans.  It was 3 AM in Singapore, but as usual, these two tech founders were game to talk seafood.  

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PW: Singapore is filled with fresh seafood, how has Vertical Oceans’ product garnered so much attention from foodies there? You’ve got chefs from some of the finest restaurants in Singapore clamoring for more product.  That’s impressive! 

JD: Even though we’re in the heartland of shrimp aquaculture in Southeast Asia, customers love our shrimp because it’s unlike anything available in the market.  Over and over again, our customers say, “I’ve never had anything this good and fresh before”. So even though we’re in the middle of so much shrimp farming and even fresh wild caught shrimp in Singapore, our product is on a different level and that really stands out. 

PW: Your shrimp are on a “different level” you say.   It sounds like you’re really . . . elevating shrimp.

JD: Yes!

PW: Sustainability and resilience in the food system has a lot to do with food miles.  Going from farm to fork with the least amount of process in between.  How long does it take to get the shrimp from the Vertical Oceans farms to your customers’ hands? 

JD: A few hours.  We start harvesting around 6AM and they’re in the customer’s hands before 2PM.  That’s less than 8 hours. 

PW: Not bad for an 8 hour day. 

JD: It’s hard, but worth it.  Here in Singapore we think a lot about food security and the COVID experience of 2020 only accelerated the urgency of that trend. It was a wake up call. Vertical Oceans sits at the cross section of two key themes: aquaculture and vertical farming. And as we mentioned before, if we can make the commercial side work in Singapore, where we are surrounded by shrimp aquaculture, imagine what we could do in a market much further away. 

PW: Let’s talk technology.  One metric that always catches the eye is your target feed conversion ratio of less than one.  First, what is FCR?  And second, how could you possibly get to less than one? That seems impossible.   

JD: Feed conversion ratio, or FCR, is a great metric in many ways, but also a bit misleading. 

Typically feed conversion ratio measures “as-is” meaning that you do not adjust for moisture content. So the feed moisture content of 10% is not adjusted to the shrimp moisture content of 70%. That’s why it is biologically possible to have a feed conversion ratio less than 1. But critically, shrimp and other aquaculture species are poikilothermic which means they do not produce metabolic heat to maintain a designated body temperature unlike farmed livestock. That, in addition to the fact they don’t need a large skeletal structure to fight gravity, makes aquaculture a potentially very efficient model of food production when done right because so much more of what they eat goes into their biomass.  

PW: You frequently say you came at the problem using first principles thinking – where do you think was the biggest leap you had to take to come up with a solution within your system? Or was it the whole system itself? 

JD: The first principles question is a good one. 

PW: Thank you. 

JD: The biggest leap happened when we flipped our perspective to thinking from the customer experience and working back from there. People want fresh seafood that looks and tastes like something that just came out of the ocean. Fresh seafood needs to be produced where it is consumed because it goes off very quickly if it’s not fresh and handled properly. 

So, that meant we had to go urban. Urban meant vertical. Vertical meant we had to re-think the entire system and that cascaded into the 83 technologies we have now. It was clear from thinking about it from a customer perspective that we needed a completely different approach. 

PW: Your tech stack is remarkable – from where do you draw inspiration and solutions? 

JD: We were laughing about this the other day. We have a database which contains 1,432 entries of various references, technical data sheets and other information. We’ve been collecting ideas since we first came up with the idea for Vertical Oceans in 2016.  A big part of it also comes from keeping your eyes open for technologies that could be applied. 

Like the time I was sitting on a plane watching them refuel it from under the wing and wondering “How do they do that without spilling jet fuel all over the place?”.  After researching airplane fuel handling, it inspired some new thinking about the water handling in our system. 

Some of the solutions were serendipitous like that, others were deliberate searches for new solutions to specific challenges. Probably 2/3rds was serendipitous.

PW: Speaking of the serendipitous tech solutions, what’s up with the disco lights? 

JD: Tony Manero (Saturday Night Fever) was Italian-American, the running hypothesis is that Enzo may have felt some inter-generational connection to that character.

EA: I confirm my love for disco lights. But who likes them even more is our seaweed. They literally cannot survive without disco lights, so we created this party environment for them to foster and live happily. 

PW: John you come from a long history in aquaculture, was Vertical Oceans a sudden fit of inspiration or a slow burn? 

JD: Vertical Oceans was a slow burn for several years. Then one last piece of the puzzle fell into place and the slow burn exploded into a full-on orbital burn.   

PW: Now I must ask, what was the last piece of the puzzle? 

JD: The last piece of the puzzle was how to really go vertical, not just the same tanks on multiple levels, but something automated, dense and vertical. And then I had the breakthrough – move the tanks, not the people. Making the tanks mobile and self-contained changed everything. It was an example of our first principles reasoning – there was no reason you couldn’t make the tanks mobile, just no one did it that way before. The idea was totally nuts, but the more we looked into it, the more we realized, “this works!”. 

PW: Enzo, how did John convince you to join him? 

EA: John fished me with the ability of an experienced fisherman. In fact, he’s pulled this trick on me twice — once before for an insect protein company. 

With no background in aquaculture, I was not quick in deciding to join Vertical Oceans. But John was patient and determined. During our chat John transmitted to me the vision and a lot of enthusiasm.  He explained to me the problem and the concept of Vertical Oceans in a very simple yet compelling way, highlighting the importance of digital technologies for the overall solution. His enthusiasm and drive was contagious. I decided to join him once I realized that what he wanted to do was revolutionary, and that my contribution could help achieve that vision. 

JD: There’s an additional anecdote to this story. In the interview, I was explaining what I had in mind on the white board and as we were talking through it we ran out of white board space. And at the end of the interview it was something like: “Ok, so can you do this? Is that interesting for you?”.

EA: The reality is that John and I get excited and motivated by the same kind of things.  Creating new solutions, that involve intersecting many technologies, to solve challenging problems, so it is easy for us to make plans together.

PW: What was your greatest accomplishment during IndieBio’s program? 

JD: These four-plus months were transformative. I think the biggest accomplishment was our ability to produce multiple batches of our shrimp that we sold direct-to-consumers and received so much positive feedback and interest. We progressed a lot on our technology and funding and other aspects, but proving out the product-market fit over and over again was huge. 

PW:  Most importantly, a wise man once said that shrimp is the fruit of the sea.  What’s your favorite way to prepare shrimp? Popcorn shrimp, pineapple shrimp, grilled shrimp. . . ? 

JD: The Vertical Oceans shrimp taste great as sashimi, but probably my favorite is just a quick pan sear with olive oil, sea salt and a touch of cooking sake.  

EA: One funny aspect of this is that I am not a big lover of shrimps or seafood in general. I used to have one or two shrimps, then get bothered by their chewiness and stop eating. But the first time I tried our shrimps, I could not stop eating them. Their snappiness and freshness is addictive.  

I have this feeling, but limited means to confirm it, that deep in the archives of Russian scientific literature lies a treasure trove of valuable new technologies, just waiting to spring forth and solve big problems.

It turns out that secret treasure trove landed on our doorsteps a stone’s throw away in Nova Scotia, Canada.  Khorcheska Bhatyrova and Anna Khusnutdinova are two biochemistry Ph.D.s who are taking on greenhouse gas emissions and the petrochemical industry with their invention, the zombie cell.

OzoneBio is producing an emissions-free, low-cost adipic acid produced from waste feedstocks to make the world’s only bio-nylon 6, 6 that can compete in the open market. No green premiums needed here. The zombie cell technique invented by co-founders Khorcheska Batyrova and Anna Khusnutdinova eliminates the need for costly metal catalysts. This adipic acid is scalable, cost competitive with petroleum-derived products, and can be made from wood-derived aromatics.

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How did you come up with the idea for the zombie cells?

Everyone knows that all living organisms consist of enzymes, biological molecules that perform all kinds of chemical reactions inside living cells.  We thought, what if we can make this enzyme work robustly in our target reactions. We were lucky to have great profs in Russia who passed to us their knowledge and skills. Back in Russia we discussed with our profs the idea of what will happen if we make enzymes so stable and active so they would perform like chemical catalysts in the reactions, that is how we invented zombie cells.

Why is it you’re taking on nylon 6, 6? What’s so special about it?

Nylon 6, 6 is used everywhere from car parts to running shoes, it is used also to make your favorite yoga pants.  

Our first product is adipic acid (one of two key building blocks of Nylon 6, 6).  Currently, adipic acid is made only from oil, and it is one of the most toxic production processes in the world.  It leads to at least 60 million tons per year of greenhouse gases.  Especially nitrous oxide, which should scare us all, a gas that is 300 times more toxic than CO2 and stays in the atmosphere for 115 years destroying our only protection from UV radiation — the ozone layer.  That is why we named our company Ozonebio.

Seems limited to only make nylon 6, 6.

Alone, the fact that we already can make the powder of emission-free adipic acid on the bench is super exciting.  Adding in the fact that at scale we can make it cost competitive with the petroleum-derived adipic acid is revolutionary. 

We have made a complex family of enzymes work in our zombie cells.  This makes us a platform company.  That family of enzymes can be used to produce plastic precursors, fragrances or drugs. 

Why is your process so much less expensive than other bio-processes for adipic acid?

Using our zombie cells there is no need to use expensive manipulations to purify enzymes and there is no enzyme degradation.  No need to express helper proteins to ensure your product comes out the cells, [and] we discover[ed] the way to make cells porous just enough.  In addition, zombie cells together with our cheap helper chemical allow us to replace the expensive protein cofactors and Pt/Pd catalysts with hydrogenation facilities. 

And we have no need to keep cells happy and in a comfortable environment to make them produce your product. 

Keeping cells happy, this is where the capex and opex in biofermentation drives up cost and energy requirements in traditional biomanufacturing?

Yes, exactly.  Plus, we can use challenging / toxic feed stocks that [would otherwise] simply kill alive cells. And our feedstocks are waste products.

Circular and emissions-free and cost-competitive!

Yes.

It seems like you want to save the world one yoga pant at a time.  Why the urgency?

For over a decade, industry was looking for the replacement of expensive NAD(P)H cofactors and Pt/Pd catalysts using a cheap, robust approach. We could stabilize enzymes inside the cells without degradation and found a replacement for expensive cofactors, that is when I realized it is the time for the fast actions.  Thankfully, IndieBio is the place where things get done super-fast and efficiently.  That awesome team took our company to the completely different level in just 4.5 month! [Editor’s note: your check’s in the mail.]

This is a very difficult problem that many before you have failed to solve in a way that can compete on cost.  What possessed you to go after such a hard problem?

Throughout our careers in academia we used to work on complex enzymes trying to make them work, either adjusting reaction conditions or engineering enzymes. Same happened in this case, it was one of the complex enzymes we were working on, and in that case an uncommon technique worked to solve the problem of this enzyme stability and function.  That’s how we invented the zombie cells approach.  We made one of the most complicated and sensitive families of enzymes in the world to work without any extra manipulations.

How did you meet?

We met in 2007 in the Institute of Basic Biological Problems, in Russia, where we both got our PhD. There we worked on another group of complex enzymes that are responsible for hydrogen production. 

How did you two decide to start this company?

We started our company because I realized that it is time for us to be independent and start our own journey.  Anna and I had become experienced enough to identify the direction of our research and decide how to proceed.

Nova Scotia isn’t the first place that comes to mind for building a start-up, tell us a little bit about your journey there.

In Canada, the pandemic made many [start-up spaces] disappear.  Nova Scotia responded quickly to our request and they had the facility we needed to succeed through the IndieBio program.  We moved here 2 months ago, and during these two months we were able to make our first batch of the first in the world emissions-free adipic acid.  We only regret we did not move here earlier, right away after we were accepted to IndieBio, I think now we would already have Nylon 6, 6 chips made. But we are working on it now!

How did you feel the first time you produced adipic acid using your process?

We felt immediately that there is so much more work we need to do, and we kept going!

Quick word association exercise, what is your first reaction to the following phrase: You can’t do that.

Anna: Why?

Khorcheska: I prefer to decide it on my own, whether I can or can’t do it 😊

The AltProtein space is abuzz, but lacking in products that engender the same finger-licking scrumptiousness of devouring a plate of tasty wings. Sundial Foods developed a novel processing technology for creating plant-based whole cuts of meat — complete with skin, meat and bone. The beauty is in how it ends up on your plate from only eight clean-label ingredients. Dr. Jun Axup, CSO of SOSV’s IndeBio sat down with co-founders Jessica Schwabach and Siwen Deng to reflect on Sundial’s journey of discovery.

The crazy thing about our wings is that all the texture and complexity – the skin, meat, muscle, and bone – comes from just eight clean ingredients.

Jessica Schwabach, CEO of Sundial Foods

Can you tell us a little bit about what the product you’ve created is?

At Sundial we’re making plant-based whole cuts, and the first thing we’re launching is chicken wings. So the basic premise is that for plant-based meats, there’s a single processing method, called high moisture extrusion, that’s used to create most of what you see on the market. It’s a really cool and versatile process, and can give you a nice protein base to work with, but then you are going to need more processing and some less pleasant ingredients — binders like methylcellulose for instance — to make a cohesive and meatlike product. Creating something like the complex cuts of meat that we are doing would require even more processing and assembly work.

So the process that we’ve developed allows us to have more of a one-and-done approach.  Like extrusion, we combine plant ingredients under thermal processing to generate a fibrous bite texture, but there are two key differences. First, we don’t have that shear, so we’re able to create a cohesive three dimensional product in one shot – no assembly required later. Second, we don’t just use the functionality of protein isolates to create these fibers — we use intrinsically present starches, fiber, and so on to our advantage when we’re trying to create this texture. Not only is the structure of our fibers and skin built differently, but once we’re done with this one thermal process, we’ve got a whole, cohesive, already delicious cut of plant-based meat. It’s much simpler.

And the reason we’re starting with chicken wings is just because people love them. It’s just a really nice experience — part of a chicken that’s genuinely fun to eat. Like seriously — Americans eat something like 1.4 billion wings over Super Bowl Weekend. But animal free versions are sorely lacking, and we know how to make them, so here we are.

And you’ve actually been able to make some and prototype them in stores and Europe. Can you tell us a little bit about the customer feedback and what you’ve learned?

Yes. So we did test them for two months in about 40 grocery stores in Switzerland last year, late 2020. And we got some super interesting feedback.  We asked a lot of questions. Probably the leading question is, is the concept of a whole cut with skin meat and bone made from plants something that’s just currently too weird for consumers, which we were worried about because when you look at the product, it’s a bit jarring or uncanny how much it looks like chicken.

What we found is that people are actually attracted to it by appearance.

People also liked that it was clean label and high protein, which comes from our process, so we were quite happy about that. Interestingly, the product was chickpea based and we thought this would be important because it’s a differentiator from soy or pea-based proteins, but consumers didn’t seem to care so much about that as long as it was healthy.

But the most interesting thing we learned about the product was that people really liked the plant-based skin. I know it sounds sort of weird because it seems like something that is just a strange concept, but it really takes things to the next level in terms of not only the initial appearance, but also the cooking experience and similarity to chicken. Or to put it more simply it just tastes good.

Looking at the cell based meat industry, with the first cell based chicken for sale being approved in Singapore, what do you see as the near future  — the convergence — between cell-based and plant-based meats? Where do you position Sundial?

Interesting question. 

The raison d’être for Sundial is that we need to provide center of plate protein options that are not derived from concentrated animal feeding operations because these operations cannot sustainably meet protein demand. If making protein taste like meat is what will make people buy it then we can do that, as long as we’re making sure it stays nutritious and is truly on par with or even better than meat in that regard. Also of course it’s gotta taste really good.

And cell-based meat has a similar purpose. And I think that both of them will take chunks out of the animal agriculture industry, but not necessarily out of each other. I guess it remains to be seen and everybody’s wondering, but I do feel that the consumer segments won’t overlap that much.

OncoPrecision can predict a patient’s response to cancer therapies by replicating the tumor microenvironment ex vivo. Their unique, triple co-culture method increases patient-derived cancer cell viability 60x in a 2.5D format that has been validated using real patient data.  For patients in dire need of the right cancer treatment the first time, OncoPrecision offers doctors the assurance that decisions made today will make the difference tomorrow.  When time is of the essence, being able to screen potential therapies with your personalized cancer avatar in under 10 days is fast.  Doing so with more accuracy than today’s sequencing or organoid approaches is huge. Through their growing list of strategic partnerships, OncoPrecision is screening, selecting, and speeding up the delivery of precision oncology.

What inspired you to start OncoPrecision?

Fighting cancer is the life purpose of OncoPrecision’s founders. As an academic spin-off, OncoPrecision follows the scientific journey of its CSO. Gaston Soria started working in cancer genetics during his MSc, which continued during his PhD training. After realizing that genetics was not sufficient to explain the complex behavior of cancer cells, he decided  to focus his postdoctoral training in the epigenetic field. Disappointed, and with the increasing conviction that every -omic only explains a single dimension of cancer, he founded a drug-discovery lab asking questions directly to the cancer cells.

He figured that cancer cells are the minimal unit that will provide us with reliable outputs for multidimensional phenoma, such as the response to anticancer agents. OncoPrecision originated as the evolution of cell-based screening technologies developed at Gaston’s Lab, but with its own fingerprint: working with cancer cells that directly derive from patients before therapy prescription. 

Why AML/ALL and how does your approach differ?

OncoPrecision’s MVP focuses on acute leukemias, with particular focus on AML. AML is a devastating disease, with about 50% of patients not responding to standard of therapies and with very common multi-resistant phenotypes. OncoPrecision’s technology can work with minimal biopsies, even utilizing the remaining pathological cells that are leftover from leukemia diagnosis samples. 

In other words, we work with the patients’ cells and combine them with two cell lines we’ve selected that enable us to replicate what’s going on in the tumor, so we can then analyze the response to different therapies. We decided to initially focus on AML because of its extremely high relapse rates and the challenge of patients responding favorably to the first line of treatment. AML also has the advantage of enabling us to use the patients’ blood for our analysis, rather than requiring invasive biopsies as other types of cancers might.

In other words, we take patient-derived cancer cells, culture them to mimic the body’s environment, screen for the best treatment. AML is a difficult cancer to cure, with higher than average relapse rates, but easier for us to approach as our first target. 

What made you realize you could accelerate the screening and selection process for cancer therapeutics? 

There are ex-vivo functional tests, such as patient-derived xenograft in mice (growing a tumor in a lab mouse) and organoids, which have had remarkable success in pre-clinical settings. However, due to their high costs and extended length (up to several months), the translation of these technologies into clinical settings failed thus far.

Our approach uses patient-derived cancer cells that are immediately set for screening in a triple co-culture setup that we call 2.5D Micro Cancer Avatars. Our platform allows us to obtain actionable results within 7 to 10 days, which is remarkably faster than current approaches. This is possible due to our extreme miniaturization procedure, which does not require the amplification of cancer cells, yet retains the clonal heterogeneity found in all cancers.

You already have a 15-person team coming from Argentina, can you tell us more about the cast of characters at OncoPrecision?

One of our Team’s pillars is Candelaria (Cande pronounced “Candy”) who is our master of organization and perfectionism at the lab. She’s been recognized by the Ministry of Science and Technology as one of the emerging female leaders in science (she’s also a leader within our team). We also have Gerardo who has a network of clinicians in Argentina like no other. He’s been elemental in rapidly building our network of clinics that are participating in our studies. Gaston is another pillar of our Team who we like to call “The Professor” (he’s actually Tarek’s Oncology tutor) for his incredible mentorship to our senior and junior talent. We would be lost without his guidance. Finally, Tarek is our youngest founder and the CEO.  After selling his first company, this second-time founder has learned OncoPrecision’s science quickly and is great at communicating that science and the vision. 

We have a multidisciplinary team that includes biotechnologists, geneticists, immunologists, bioengineers, biochemists and medical scientific liaisons. Moreover, it is remarkable that a big part of our team had a shared scientific history. Our team leaders and medical scientific liaison manager have worked together in academia for more than 5 years, developing strong professional and personal bonds that set the ground of OncoPrecision’s culture. 

We’re thrilled by the scientific progress we’ve made in such a short time since we founded the company in September 2020. The truth is that we couldn’t have come this far without the deep scientific talent that’s available in Argentina, combined with the unbeatable cost advantages (the ratio of scientists we could hire with the same seniority there vs. the US is about 7:1).

What are your plans for clinical studies? 

We’re now raising our Seed Round to move rapidly towards proving out the predictive power of our platform in clinical studies for AML patients, as well as beginning proof-of-concept for adapting our technology to be able to work with solid tumors. We’re also in the process of taking our first steps towards building our New York Hub, which will be the core of our US operations.

Precision oncology is a tough space to break into, tell us a bit about your advisors. 

We’re very excited about the advisors who have joined our journey over the past few months, both on the Business and Clinical sides. As our Business Advisor, we have Darrin Crisitello who has a wealth of experience building and scaling precision medicine businesses. He’s currently the Chief Commercial Officer of Mission Bio, a leading Single-Cell Sequencing startup and previously held leadership roles building the businesses of Color Genomics as well as Natera. As our Medical Advisor, we have Jorge Solimano, MD who leads Hematology at CEMIC, one of Latin America’s top cancer centers. Dr. Solimano has been elemental in designing our clinical validation milestones, as well as bringing his collaboration expertise with pharmaceutical companies to some key conversations. We actually are in the process of adding our third advisor who we’re thrilled about. We can’t say too much about her yet, but she’s a world-leading expert in heme malignancies and has done a tremendous amount of work to advance research in the field, as well as practiced as a leading clinician. 

What’s your vision for OncoPrecision in the future? 

Our mission is to dramatically improve cancer patient outcomes and ensure that each patient receives the best possible therapy. We envision a world where NO patient is prescribed therapy before understanding how the patient will respond to therapy.

Innate Biology produces supplements to mimic the same cellular benefits you would get from fasting, without having to fast. Their formulation uses a unique combination of natural human molecules and has been clinically shown to produce the same anti-inflammatory, antioxidant, and cardioprotective benefits of fasting — so you can live life and thrive. Sibling founders Dr. Chris Rhodes and Caitlin Beatty share their journey to unleashing a healthier life below.

Using fasting as a roadmap to optimal human functionality we’re decoding and recreating our body’s innate “bio-programs” for cellular health and regeneration with the world’s first fasting mimetic supplement.

Dr. Chris Rhodes, CEO of Innate Biology

We’ve all explored ways to enhance our own health, whether diet, exercise, food, or drug — can you tell us what you are working on and how that led you to found Innate Biology? 

I’ve spent the majority of my scientific career studying human fasting at the University of California at Davis and can say first hand that fasting is one of the most powerful nutritional interventions out there for increasing human health. I can also say as someone who spent two years practicing alternate-day-fasting, that it can be a pain in the butt (if not impossible) to actually put into long-term practice and it’s definitely not for everyone.

While I felt the physical benefits of fasting, I also experienced a lot of social isolation and missed out on a lot of experiences that actually make life worth living. Until one day my sister (and now COO) asked me, “What’s the point of living longer if it means you have to live less?” and that was the big inspiration for me that there had to be a better way to get these amazing health benefits without sacrificing life in the process. And thus Innate Biology was born. Using fasting as a roadmap to optimal human functionality we’re decoding and recreating our body’s innate “bio-programs” for cellular health and regeneration with the world’s first fasting mimetic supplement. 

What breakthrough did you achieve during SOSV’s IndieBio program?

Our biggest accomplishment was pulling off a clinical study at UC Davis during the tail end of the pandemic. We were able to show that supplementing with our fasting mimetic was able to mimic the anti-inflammatory, antioxidant, and cardioprotective effects of fasting in human subjects even when they were eating. Best of all, supplementing with the fasting mimetic was able to increase plasma cholesterol efflux ability, which is the golden standard clinical marker of cardiovascular disease and directly related to the prevention of arterial plaque formation. Having clinical data showing that the fasting mimetic works to fight against the negative effects of eating and move a validated clinical disease marker was a huge win for us.

How does Innateness support human health over the long term?

Innate is a really unique company that takes a widely overlooked and undervalued approach to solving human health:  actually studying humans! Our fasting mimetics are designed exclusively from human research and are made of the same natural human molecules that the body produces during a prolonged fast. 

By recreating the regenerative and protective state of fasting through supplementation we are providing people with a whole host of beneficial effects from autophagy to cognitive boosts to reductions in cellular inflammation. Even better, we’ve shown that our fasting mimetic combination can provide holistic long-term benefits and extend the lifespan of model organisms by a whopping 96%.

Tell us about your team

We have a really robust team of scientists, serial entrepreneurs, academic professors, and business advisors in the supplement space. I’m a PhD in Nutritional Biochemistry and a nutrition influencer on TikTok with over 150K followers (@thatnutritiondr; like, follow, subscribe!). Our COO (and my sister), Caitlin Beatty, has years of startup experience in biotech and athletics (she’s a national champion in both field hockey AND tennis; nbd). Our third co-founder, Dr. Angela Zivkovic, is a PhD in Clinical Nutrition and a tenured professor in UC Davis’ nutrition department providing both academic expertise and clinical research capabilities to Innate.

Can you share how you are taking Innate to market?

We’re going to market as a direct-to-consumer e-commerce brand and leveraging my TikTok following as our early adopter customer base to drive enthusiasm and awareness around the brand. Our fasting mimetic is just our first product, with more supplement formulations on the way based on data from our clinical trials. We’re also teaming up with Hatch San Francisco which has done some legendary brands (SmartWater, Smashmallow, and Krave Jerky) to develop our visual identity and unique market positioning. 

What does the future Chris say to the current Chris? 

I would hope that I say something useful like, “Buy more Dogecoin!”, but in all honesty it would probably be something more cryptic and Yoda-esque like, “How is a raven like a writing desk?” just so I could laugh at my past self scrambling around trying to find the answer to life in a Lewis Carol quote. 

Making plant-based foods without compromise. Lypid’s secret sauce: a sustainable, healthy and tastier fat alternative.

We’ve had an on again, off again relationship with fats.  One crucial challenge for plant-based foods is that they’re missing the fat.  Most of the time, they incorporate coconut oil as an ersatz lard or butter, and it’s simply not hitting the spot. As a B2B company, Lypid is putting a new spin on fats to bring lip-smacking goodness to the exploding plant-based meat category.  

Who is Lypid and what was its genesis?

I’m Jen-Yu, the co-founder and CEO of Lypid. I did my PhD in chemical engineering at Cornell where I actually did a lot of research on carbon capture. And I interviewed more than a hundred companies in 3 months to figure out whether there’s a way to commercialize the technology I was building in the lab. And what I figured out is that why not just eat less animal meat, then we don’t need to worry about capturing those carbon dioxide. Then that’s how I started my journey in the food space. And that I did try a lot of  alternative protein and plant-based meat on the market. But as a meat eater myself, I have to be honest, that current product is not there yet to totally change my diet and I happen to be a scientist. So I decided to do more research and study in this space and to figure out why plant-based meat doesn’t taste like real meat.

I’m also pretty lucky to have met my co-founder and Michelle at Cornell. We found out that fat is the key missing part to elevate the taste, texture and appearance of plant-based products. So that’s how we started our journey.

What is the fat you are making? 

We enable a tech that allows vegan oils to perform like animal fat. We take liquid vegan oils, and with our special processing technology and formulation strategy, it can perform like animal fat which stands above cooking temperature. The new vegan fat can cook above 165 degrees Celsius and it will still stay on the pan. No matter how you cook our new vegan fat, it behaves like real bacon fat.

How is Lypid’s technology going to deploy into the market? 

Currently, almost all of the alternative protein products on the market need improvements, especially in terms of tastes and textures. We think fat is the key missing part for such improvements. That’s why we decided that we would go with a B2B business model to elevate the entire alternative protein industry. We position ourselves as an upstream technology provider for other companies. Not only do we want to sell fat, but in the long term we also want to provide a high-tech full solution to the industry.

What has been the biggest thing you’ve learned during the IndieBio program?

I will say it’s getting connected to partners and talking to a lot of customers. Since Michelle and I are both scientists, both of us spent most of our time in the lab. So talking to people is very challenging in the beginning. At IndieBio, we learn to discover customers’ needs by utilizing our entrepreneurship and scientist mindset. In the past four months, we have talked with more than fifteen customers and are designing solutions for them.

If you haven’t been following the trends in synthetic biology, just know that bio-based chemicals are the future. Capra Biosciences reimagined biosynthesis by developing a low-cost, continuous flow method that scales OUT without having to scale up. Pairing a proprietary continuous flow bioreactor with a novel biofilm forming organism, they are producing hyrdophobic products like retinol and performance lubricants, but without the petroleum.They do this using a fraction of the water required compared to traditional batch fermentation methods. Less water means less volume means less stainless steel. We sat down with CEO Liz Onderko and CSO Andrew Magyar to understand how Capra is upending the conventional wisdom that biomanufacturing is capex intensive. 

When we co-invented this technology… this was really something that I could see taking my love and belief in the power of biology and being able to turn it into something that could really impact the world.

Liz Onderko, CEO Capra Biosciences

The latest trends in synthetic biology point to a future of bio-based chemicals and materials that exceed performance specs. You’ve mentioned lubricants with improved performance specs, but during SOSV’s IndieBio program, you set out to make bio-retinol for the clean cosmetics market – what prompted this path? 

The decision to start with retinol – a small volume, high value cosmetics ingredient –  was influenced by the challenges the early biofuels companies faced. By starting out with retinol, we can fold our learnings back into our platform as we gradually scale up to larger volume products. 

The IndieBio team has helped us to learn a lot more about the cosmetics industry through both directly and through the program mentors they’ve connected us with. Through these interactions, we’ve been able to recognize some of the unique requirements for cosmetics products but also the tremendous market opportunity that clean retinol presents.

The novel organism you use naturally forms biofilms, and why is that so important?
Biofilms are really what enables our technology. A lot of people might not even have heard of biofilms before – I definitely hadn’t given them much thought before my postdoc! Biofilms are formed when microbes stick to each other and to surfaces. In a biofilm, microbes are more robust than if they are floating around alone in solution – this can make biofilms like dental plaque hard to remove, but this robustness is a great feature for our bioreactor. We’ve designed our bioreactor to work with biofilms – this combination is what allows us to operate in continuous flow as well as efficiently extract our product. 

As a bio-based chemicals company, how does Capra scale out?
The way our bioreactors scale is really different from how it’s done with conventional fermentation. By multiplexing our production scale bioreactors which are about 10 Liters, instead of making larger and larger bioreactors, we can avoid the productivity drop that is often seen when scaling up in the fermentation systems used today. You might think that multiplexing our bioreactors would increase our infrastructure costs, but the most exciting thing we learned from our technoeconomic analysis is that because our technology uses up to 100x less water, our capex costs actually go way down. 

Tell us about your team. What made you take the leap into entrepreneurship?
Andrew and I met when I was doing a postdoctoral fellowship at the Naval Research Lab and he was a principal scientist at Draper Labs. I was working on engineering biofilm-forming organisms and Andrew was focused on developing bioinstrumentation for synthetic biology – it was this combination of biology and instrumentation that led us to the idea for our bioreactor technology and the vision for our company.  

We both see a need for technologies that will drive down the cost of biological chemical manufacturing so it can become accessible for a much wider range of products and believe our bioreactor technology can play an important role in the future of chemical manufacturing.

What do you envision for the future of Capra? 

We envision a future where our proprietary biofilm bioreactor platform is the standard way to produce non-water soluble chemicals. In this future, Capra Biosciences has grown to become a large B2B chemical manufacturer selling retinol, specialty high-performance lubricants, and other hydrophobic chemicals, contributing to the replacement of petrochemicals with sustainable biologically-produced chemicals.

“This is bone black” she said as she handed me a sample of jet black hair.  Silky smooth, shiny, and knottable — the bundle of plant-based hair extensions was, unmistakably, hair.

Aja Labs’ biodegradable, plant-based hair samples on display at IndieBio Batch 11’s Expo on 12 July 2021

Co-founded by Osahon Ojeaga and Suna Lumeh, Aja Labs is a direct-to-consumer company premiering at IndieBio San Francisco’s Demo Day on July 15th.  Their mission is to make superhuman hair, from plants, for healthier hair, healthier people, and a healthier planet.

Ojeaga’s vision sprang from her experiences using and selling hair extensions and braids.  During her travels through Asia, she grew disillusioned with the hair industry’s toll on the environment, users’ health, and the human exploitation powering human hair products.

After recruiting Chief Scientific Officer Dr. Mary Moore, a polymer engineer who had pivoted from R&D in the Department of Defense and Raytheon to starting her own natural products line to solve her daughter’s hair product allergies – the Aja Labs team developed two product-line prototypes for plant-based hairs.  They boast a growing following of users, stylists, and distributors alike. 

Aja Labs’ co-founder, Suna Lumeh, models their caramel-colored, plant-based hair at IndieBio Batch 11’s Expo

By some estimates, hair extension and braid users spend between $2000 and $5000 per year on hair extensions alone and no products exist that address the comfort and safety of the users while simultaneously creating minimal environmental or human cost in the production process.  Combining their vision, biotech and chemistry backgrounds, and extensive experience in the market the Aja team executed a two-pronged development plan — first a nourishing, biodegradable, biopolymer to improve the user experience and second a low energy, green chemistry approach directly transforming agricultural waste into supple, beautiful hair that rivals the natural products “donated” from India.  Seeing their technical development paths unfold, there is no question the team is committed to the overall vision for Aja Labs to give the consumer what she wants, ethically, sustainably, and healthfully.  

If you’re interested in learning more about Aja Labs, come to IndieBio SF’s Batch 11 Demo Day on July 15th and book your time with Osahon and Suna!

California Cultured produces sustainable chocolate from plant stem cells cultured to highlight the vast array of flavinols and functional compounds. Led by CEO and repeat founder Alan Perlstein, the team at California Cultured created the world’s first cell-cultured chocolate bar grown in a low-cost, high performance, food-grade cacao cell media. Or as Alan prefers — Chocolate that is simply better for the consumer and the planet. Dr. Jun Axup, CSO of SOSV’s IndieBio, sat down with California Cultured CEO and Founder Alan Perlstein to discuss his journey on bringing cell-based chocolate to market. 

Watch California Cultured unveil their first cell-based chocolate bar during SOSV’s IndieBio Demo Day on July 15th 2021 here

“The global chocolate industry is ripe for disruption. We can now make full bodied chocolate that reflects all of the global terroir — but without the deforestation and questionable supply chain.” – Alan Perlstein, CEO of California Cultured

Q: As a previous IndieBio founder, tell us a little bit about your journey of how you got into the food industry or what you’re really driven by and what you’re working on. 

About 15 years ago was when I first started to hear about cell cultured anything. I worked in one of the first labs in the US to work on cell cultured fish. And the more I learned about the reasoning of why making things cell cultured can be better, the more I fell in love with the field. I saw the challenges that the science has to go through as well as I think almost the writing on the wall when it came with both climate change, deforestation, overfishing, ethical issues for animals and people, and you combine all these different separate elements. Developing newer, better, healthier food systems started to make more and more sense.

And that sort of put me on my journey, working in different companies, working for different universities until today. But one of the major detours was one of my previous company. When we were looking to trade a product made with protein sweeteners, and I saw chocolate as a very serious product, but in itself, by looking through the supply chain of chocolate, looking through the health concerns or even the future of chocolate, I saw, wow.  It’s a giant industry. It’s I think right now $130 billion, it’s growing lightning quick over the past even year, there was a giant growth in chocolate because not only do people see it as healthy, but chocolate was one of the things that honestly got people through another day of a lockdown pandemic.

So I saw demand, a bunch of ethical environmental issues. I saw that I had the basic technical and business background. I looked deeper and I saw that all the talent to build the company, to do the science, and to scale up was literally right around me in Davis, California.

And, it just clicked. It made so much sense to work in cell culture chocolate. That we can make it healthier. We can make it tastier. We could make it a lot more cleaner,  and as the chocolate industry is going to go through severe disruptions over the next decade, we can provide a more, sustainable and ethical product for both the large corporations and the consumers who are looking for these things in the foods they are eating today.

Q: For those who aren’t familiar, can you tell us some of the problems with sourcing chocolate and the ethical problems as you mentioned?

So, the way how chocolate is made is close to stone age processes. It’s pretty similar to how it was done thousands of years ago where the seeds get planted, it takes half a decade or more before the cocoa plants may actually produce good quality pods and beans. And then the pods get picked by hand, they get split. They get put into fermentation pits, then they get dried and then ground up with other ingredients. And that is how most of the chocolate of the world is made. 

And this happens across thousands of tiny little farms all over the world from South America, Africa and Asia. Even the process to grow them, for many places, need to spray pesticides, antifungal agents, fertilizers that get them to grow. They need different light conditions whereas when they’re young, they need to grow in the understory, but when they mature, they need full light. 

Unfortunately that incentivizes many farmers to go clear cuts a lot of the surrounding forest areas, specifically the incredibly vital rainforests. Since it’s incredibly labor intensive, many farmers and other groups basically look for very, very inexpensive labor. And that usually either falls down to kids or the more unscrupulous farmer that would result in slave labor. Whereas in many countries in West Africa, there are cumulatively over a million child slaves all involved in the chocolate growing industry. And that’s besides for the amount of just regular kids helping their families grow chocolate. And even with all the claims by the giants corporates chocolate companies around the world, deforestation has increased, child labor has increased, the spraying of all these damaging and toxic chemicals are still continuing even more now at a frenzy pace than ever before, because there are more viruses and insects that are attacking the cocoa crops.

And these are just some of the problems I’m not even talking about mycotoxins in the chocolate or the chocolate itself. The reason why you get all these unique flavor profiles, it’s a bio accumulator. That means that it sucks up the heavy metals, many times lead, cadmium, and chromium in the surrounding soils. They accumulate in both the seed and the shell of where it goes into the chocolate making process.

So everything from the beginning to the end is incredibly problematic. And on top of that, all the chocolate companies that we’ve basically talked to have said, there’s just not enough room. There’s not enough farmers, not enough even region to grow the growing customer base, which is right now, very heavily, not only in the US and Europe, but increasingly in China and India who are just starting to really get a hankering for chocolate. And over the next five, 10 years, that demand is only going to increase massively.

Q: Let’s talk a little bit about plant cell culture. People have heard of people doing bacterial cell culture, people do cell culture with mammalian cells. Where does plant cell culture as a technique lie in that spectrum and what are some of the challenges for making this commercially viable?

Plant cell culture was originally developed the same time as animal cell culture around a hundred years ago. But it was still very primitively done for a very long time. And only in the past, maybe 20 or 30 years was there seriously some scientific advancements trying to figure out how to turn plant cells into production factories for food flavorings, for pharmaceuticals, or anti-cancer agents for dozens of different products and ingredients, but it’s not that widely known outside of a couple of core industries. 

One of the main reasons why was how these cells were grown. They were usually grown using undesirable synthetic chemicals that are also found in many other herbicides, for instance, one of the most powerful synthetic plant hormones is something called 24D. It sounds pretty innocuous, but it’s one of the main ingredients of Roundup weed killer. And the reason why it’s so effective, it makes weeds start accumulating nutrients fast. It basically overloads their internal circuitry and kills them. 

So, traditionally this was done in a very small amount of plant cell culture, but many different countries started putting very, very tight restrictions on the use of these chemicals in food and ingredients. And the entire field went static. 

And it really took, uh, some interesting companies and scientists and academics to really gently push it forward. And it sort of quietly chugged it along while the, the traditional fermentation such as yeast or microorganisms, or even the newer cell culture, food and ingredient products from meat are becoming well-known.

So what we’re able to do is take advantage of the many different metabolomic processes, as well as internal processes that are happening in plant cells. And we can make them not necessarily just produce one specific compound, but we can make them produce thousands of natural compounds all at the same time without changing the DNA of appliance cell or without putting in any undesirable ingredient and our thought was: imagine you could replace these synthetic ingredients with actual food grade ingredients, because there are many plants that we love and eat that have tons of natural plant hormones in them. But no one has actually looked at how useful they can be for plant cell agriculture.

So in essence, what we’re doing is a cross between clean meat and vertical agriculture. That’s how we tend to look at it. We basically have to give the cells food, we grow them in large tanks and you need to give them the right environment to grow and the right way that are flavors to develop as well. So for us, it’s sort of a learning process. And at the same time, we are going to be publishing some very cool scientific advances. So the world can understand a little bit better about the field of plant cell culture for food.

Q: What has been your biggest learning over the last four months at IndieBio and challenges that you faced?

Our biggest challenge was figuring out the best go to market. We came in to IndieBio with some specific assumptions of launching a product as quick as possible while at the same time developing the core technology. And by speaking with many different segments and investors, we saw that we needed to put some of our product launch on hold and just focus on derisking the initial technology as fast as possible. 

And by talking with many different customers, we saw that there was actually a very big need to make some ultra premium chocolate flavinols and high value compounds that are very, very difficult and expensive to retain in the industry. Usually they run for about a million dollars per kilogram. So that was our interesting discovery process. 

Eliminating excessive false positives is the holy grail in gene discovery – it saves money and time. Its Gene Discovery by Informationless Perturbation (GDIP) method has reduced false positive rates by 10-100x (depending on the trait and the organism) and they are bringing the power of GDIP to breeding climate-resilience traits into crops ranging from rice to rubber-producing plants. Avalo.ai is the seed company where sustainability and crop science are converging.

With a pinkish glow, the silvery door opened to reveal trays of dirt and seedlings.  Held at a cool 54°F, Avalo CEO Brendan Collins gingerly removes the trays and proceeds to count with surgical concentration. Two new seedlings had popped and, notably, one their algorithm predicted would be the highest performing knock-out.  

Based off a computational platform CSO Mariano Alvarez developed during his postdoctoral fellowship at Duke, Avalo’s ultra-fast, high sensitivity, and high accuracy gene discovery platform is being used to generate cold tolerant rice strains that can stave off the harvest shattering effects of weedy rice and late frosts. 

Gene discovery itself isn’t new, but the gold standard, Genome Wide Association Studies or GWAS, is fraught with a major problem: too many false positives.  A plant breeder who wants to target a specific trait is left with hundreds of gene targets to address, the vast majority of which are a waste of time (read: $20M dollars worth of time and effort wasted for each wrong gene target). 

We’ve seen how this type of baked-in R&D cost is passed down to the payers in pharmaceuticals. Outside of major row crops, the agriculture industry simply cannot bear these types of excessive development costs.  Enter Avalo’s Gene Discovery by Informationless Perturbation approach (GDIP, for short).  Powered by Prof. Cynthia Rudin’s pioneering work in interpretable artificial intelligence, Avalo is using GDIP to solve the urgent problem of developing climate-resilient crops to feed the next billion people.

The excitement around Avalo’s early data is palatable.  The 5 month old company has initiated four new academic and industry partnerships during IndieBio and last month it raised its Seed round.  Brendan and Mariano are building their team and churning out new performance data every week.

We are creating the genetic blueprints for the fastest sustainable transformation in agricultural history. 

Brendan Collins, CEO of Avalo

Yeah, totally!

Mariano Alvarez, CSO of Avalo

During SOSV’s IndieBio program we asked you prove your next generation gene discovery for the future of plants works. What did you discover? 

We needed to show one major thing: that GDIP–Gene Discovery via Informationless Perturbation–finds usable gene targets the first time. We decided to take some publicly-available data on cold tolerance in rice (a major problem for California growers) and try to find a target that we could break quickly and inexpensively. At the Phytotron in Duke University, we were able to validate four genes for cold tolerance over a three month experiment for about $15,000. Pretty good compared to the alternative!

Can you explain a little bit about how your predictive algorithm actually works relative to current approaches?

We know that biology is inherently complex. However, to interpret biology, we have to simplify the model and that is what we are doing every time we run a genome wide association study. This allows scientists to bring some interpretability to biology, but the downside is that it lets in hundreds of false positives. By employing interpretable machine learning we can create a much more realistic model of biology that doesn’t compromise on complexity and using our informationless perturbations (our proprietary technique to explain black box models) we can probe that model and make discoveries.

Why does predicting crop or plant phenotype matter?

Plant products are all around us – not just as food, but as cosmetics, perfumes, and industrial feedstocks. The phenotypes of the plants – from the color of an aesthetically pleasing flower to the ability of a crop to shrug off infection – usually have some genetic component that we can amplify to make the plant more useful.

The problem is that most traits are the result of complex architectures, many genes interacting with each other and the environment to produce the observable outcome. This makes both gene discovery and trait prediction… well, hard! Current genetic tools cannot accommodate this complexity. We make it easy.

Who is Avalo?

When we started this whole thing, we were just two scientists from North Carolina with a good idea. Mariano was a postdoctoral researcher at Duke University with a background in plant evolutionary and computational biology. Brendan has a background in cell and clinical biology and has spent the last seven years doing software development for startups around Durham. 

IndieBio really believed in us from a very early stage. Now, we’re growing to a team of 7 by the end of the year, with a team of superstar scientific advisors including Cynthia Rudin (head of the Prediction Analysis Lab at Duke) and Daniel Pomp (Professor Emeritus of Genetics at UNC Chapel Hill and co-founder of GeneSeek) as well as an amazing group of investors and supporters behind us. We feel pretty lucky.

We often joke that Avalo will develop partnerships on all 7 continents — from rice to wheat to dandelion to corals — do you think you will develop something for Antarctica?

That’s funny — our first in planta trial was cold tolerance in rice, so maybe we’ll just ratchet that up a bit. There are some cold tolerant varieties in Japan, so… maybe? In all seriousness, I think there are some really interesting opportunities to work on marine organisms in Antarctica – reefs, microbes, and even fish. We’d love to find a partner for those projects in the future!