Unlocked Labs: Solutions for Chronic Illnesses with the Safety of Supplements, and the Efficacy of Drugs

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:

Unlocked Labs’ easy-to-take probiotic was designed after listening to the needs and wants of over 100 gout sufferers.

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.  

Founder, CEO, and test subject Christoph Geisler gets his blood uric acid levels low on his own supply.

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: Producing Foods Beneficial to Oceans, Terrestrial Ecosystems, and Future Generations

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:

Ireland has much to offer including mystical coastlines and delicious, yet healthful, native seaweeds – both shown here.

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. 

The latest prototype demonstrating the beloved flakiness of white cod.

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. \

Cellens: Bringing Clarity and Precision to Cancer Diagnostics

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:   

Professor Igor Sokolov (seated)

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. 

An epithelial cell undergoing the world’s tiniest and most information-dense caress.

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. 

Prothegen: Designing Next Generation Medicines Targeting Ferroptosis

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:

Prof. Derek Pratt being radical about free radical chemistry

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. 

There’s only one way to find out more about their confidential animal data: contact Davide today.

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.

Sóliome: Creating the World’s Best Sunscreen

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:

Sóliome’s product goes on almost invisible and definitively absorbs UV rays as demonstrated by CEO and sunscreen power-user, Micah Nelp.

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.  

Reapplication of commercial sunscreens isn’t a scam, it’s because they stop working in the sun. (Oh the irony.) Sóliome’s active ingredient withstands continued UV bombardment.

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. 

CellCrine: The World’s Cheapest Serum-Free Media

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:

Co-founder and inventor Rodolfo Faudoa’s favorite stance – as they say, a watched cell does not differentiate.

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.

Chicken cells grown in record-breaking media conditions

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: Making Vehicles All-Electric, Grid Optional

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.  

SolidOx brings solid oxide fuel cells onboard medium and heavy-duty battery electric trucks to trickle charge instead of plugging into a “fast” charger.

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.

Broadcasting live (over Zoom) from their garage in Pittsburgh, COO Brandon Balili demonstrates a hot-of-the-presses milestone proving SolidOx’s no-extra-energy condenser technology works.

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. 

Climate Crop: Small Edit, Big Impact

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. 

The proof is in the potatoes — yield results from early trials with potato crops.

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!  

Veloz Bio: We Make Complex Proteins Fast, and at Scale

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: 

Dr. Margarita López with her team evaluating the the latest complex proteins made in Veloz’s “biofactories”.

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. 

In three weeks, Veloz went from idea to gram-scale quantities (a whole bag!) of animal-free 𝝹-casein.

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.

Wayfinder: Engineering the Future of Smart Biotechnology

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.

Dr. Chuhern Hwang demonstrates flawless pipetting technique while building ultrafast, accurate, in vivo biosensors.

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.

Wayfinder’s biosensors turn off when the target molecule is removed – in about 30 minutes. (300x speed)

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.

ProtonIntel: The First Ever Continuous K+ Monitoring

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):

CEO and resident test subject, Sahan Ranamukha performing real-time testing of the ProtonIntel prototype during IndieBio’s Expo Day.

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! 

COO and resident test subject, Francis Steiner, demonstrates his potassium intake technique. Preliminary data reveals a discernible, transient, increase in potassium shortly after banana consumption as detected by the ProtonIntel prototype.

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.

Puna Bio: Using Extremophiles to Unf**k the Planet

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:

A Puna Bio scientist sciences in the eponymous La Puna region of Argentina.

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. 

Drs. Carolina Belfiore (l) and Elisa Violeta Bertini (c) inspect seedlings as CEO Franco Martinez Levis (r) looks on.

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.

Pyrone Systems: Making Petrochemicals Obsolete

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:

CEO and co-founder Alex Hutagalung, PhD working from the IndieBio lab.

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. 

The aftermath of early testing of the Pyrone biopesticide, pogostone, on resistant mosquitos at a University of Florida lab.

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.