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

Khepra: Renewable fuels from waste

Khepra is building continuous flow reactors that deploy high-intensity ultrasound frequencies to take waste — everything from unrecyclable plastics to biomass to cardboard — and even mixed waste — and break the chemical bonds in the waste. The result is upcycled renewable chemicals and fuel components.

Today, I sat down with the founders to learn a bit more about the field and also about their personal motivations to run Khepra as they get ready for demo day. Below is a paraphrased and condensed version of a long discussion we had.

How did you guys get into this field?

Madeleine: Growing up in California, seeing solar panels all around, you start thinking solar panels are some be-all, end-all solution. Over time, I learned how without renewable energy storage the potential of solar cannot be realized. You know the infamous duck curve — the timing imbalance between peak demand and renewable energy production — leading to us literally throwing away solar energy. The sun shines the most when we don’t need it. I was working as a systems integration and testing engineer at Lockheed Martin, when Julie, who is my childhood friend, told me about this project, where she planned to put this excess solar energy to use, to breakdown waste into renewable fuels. I was in.

Julie: Yeah, I had been obsessed with renewable fuels for a long time. And obsessed with sustainability for even longer. My dad took me to see the movie, ‘Inconvenient truth’ when I was eight and that messed with my brain chemistry if I can put it that way. Sustainability was also a key theme for me throughout my education career. Reading a lot about space and going to school at the University of California San Diego, right in the neighborhood of pioneering companies such as Sapphire Energy, making algae-based biofuels by harnessing high energy, high pressure.

Fascinated by the idea I started reading a lot about these high-pressure, high-temperature methods in the field. I got very active in the cleantech community at UCSD when I got hooked to the concept of cavitation. There’s large amounts of energy stored in a cavitation bubble and a large amount is released when a bubble bursts. At its core, Khepra uses that energy to break long-chain organic polymers into shorter chain molecules, which are potentially higher value aromatic ingredients or precursors to fuels and/or fuel precursors. With the idea in mind, we started charting the concept more with waste as a feedstock.

Madeleine and I, staying true to our silicon valley origins, started tinkering in her garage. We played with cheap transducer units ordered from amazon and catalyst combinations, even accidentally burning stuff in Madeleine’s oven! The oven survived but we did have to brave some rank odours. Haha!

We were ultimately able to get access to a warehouse space in San Francisco, enabling us to prototype a bit more and hash out a solid blueprint of the tech-stack and file a provisional patent around the process. That’s around the time we spoke to you guys at IndieBio and started putting together a de-risking plan and budget against those blueprints. Going from theory to reactors in less than six months and that too during a pandemic!

Sustainability has become a buzz-word, rightly so in my opinion, yet this is not the first time cleantech startups are taking a shot at the problems the earth faces. As you must have seen with so many San Diego cleantech startups, they are no longer operational, unfortunately. What’s new; how is this time different?

Julie: There is an abundance of waste. Both waste in the traditional sense of the word — the mountains of trash out there — and that of renewables as Madeleine mentioned. Using renewable energy transforms our unit economics. Acting as a pontoon against the waves of commodity prices. Cost parity against commodities aside, failing to achieve margins was a big factor leading to the sad demise of the first wave of cleantech. By co-locating with refineries with installed CAPEX, collecting tipping fees on waste, monetizing offsets from progressive corporations, and finally selling the valorized waste gives us multiple revenue sources; We’ve created a two-sided marketplace. Which is what is new and exciting here.

Madeleine: I’ll also add that from a tech perspective, our use of high intensity focussed ultrasound for waste pyrolysis (breakdown) is completely new. This technology has a high energy efficiency from electrical to acoustic energy. Because our method is powered by renewable electricity, it has a positive EROI (ratio of energy returned on energy invested).

Now you may think there are many moving parts here, which there are. But the good news is that many of these parts have been de-risked by earlier cleantech or the refining industry. We specialize in orchestrating all of it together. That’s also where a good portion of our IP lies.

That’s super exciting. I like how renewable energy-powered ultrasound is helping you connect the waste and commodity markets. Respectfully, I do have to ask, how do two undergrads catalyze change in such entrenched industries?

Julie: IndieBio opened doors to a lot of corporates, we have been made full use of the network and been actively reaching out to incumbents. To our surprise, we learned how corporates and oil and gas companies, juggernauts of emissions, understand the impact they have on the world, and they also understand the tipping points climate change will hit and how that will come back to hit their businesses. They are also incredibly practical and have already begun adapting their models. For example, for oil & gas, extraction drives a lot of the emissions. So many oil & gas companies are adapting by transferring a lot of their extraction budgets to venture capital arms. This has just started happening and shows you how they need something new, not just what they have, and had no incentive to change all these years. And these venture arms are very results-driven, you have to show them a product, not just projections. That’s been motivating us to prototype and scale rapidly. The impact multiplier with their distribution channels is manifold. With renewable chemicals and fuels that come out of our reactors, we see our company as a means of facilitating change for industries looking to add circularity in their processes.

Madeleine: In this process, a big learning has been to leverage the wealth of expertise out there. I am no longer afraid to reach out to and ask experts for help.

I learned how our process is so novel and exciting for many experts in the field, who know so much more than us and want to help because they love what they do, and now see a chance to make an impact.

One example is our chemical process design consultant, Kieth Gazda. With 30 years of experience, Kieth can design a reactor in his sleep. He’s been interested in our company even before we had a prototype. Skeptical at first, till he saw more data points and preliminary data from the small experiments we did where we were breaking down organic polymers with ultrasound. He is in a unique position in his career and can work on a lot of projects, but chose to work with Khepra as he sees the environmental impact we can create.

Julie: That’s a very good point Madeleine makes. Valuing experience beyond just effort and skills. I don’t fall for the mythology of the genius visionary founder. Getting top talent and mentors excited and on-board early is important to us. Creating value and therefore disrupting trillion-dollar industries can only be done if we aggregate experience and bring on people who know more than us. Kieth is an excellent example of the role experience plays in accelerating impact. I am excited, as CEO, to make Khepra into a platform for talent, from many disciplines to create impact through renewable fuels and circular products.

Team-building as a means of disruption. I love it! Let’s talk about where you are now. Recently you revealed your prototype to the world during an interview with our MD, Po Bronson. Where do you fo from here?

Julie: Khepra plans to scale up to a 500-liter reactor by the end of our Series Seed and add catalytic refinement capability to enable higher-value fuels. Looking very far out we want to get to 70 tons/day which is the waste output of a small city.

Madeleine: And scale is one dimension, as a pre-seed company we have had to tradeoff some complexity for budget and speed. We have been learning by breaking. With our Series Seed, we are also excited to optimize our process flow and demonstrate proof of concept of processing varying feedstocks. Going into demo day we are also looking forward to gathering insight around techno-economic analysis that shows the economic performance as a function of the inputs and economic value of our outputs. Really exciting times!

IndieBio’s Demo Day is October 27–28, with the New York batch on Tuesday the 27th at 10 am, and the San Francisco batch on October 28th at 10 am. Please follow this link to Eventbrite to RSVP. A single registration will grant you access to both days’ events.

Advanced Microbubbles: Drug delivery across tumor and brain barriers

Getting drugs through the tumor barrier and across the blood-brain barrier is a well-known, major challenge for medicine. Many clinical trials are underway using chemotherapy co-administered with diagnostic microbubbles, energized by ultrasound at the site of the tumor — but these are performing poorly, with inconsistent acoustics, because the bubbles are highly-varied in size.

Today, I sat down with Dr Jameel Feshitan, CEO and Connor Slagle, CTO of Advanced Microbubbles from our current class to learn more about not only the field but also how their product compares to the existing solutions out there. The conversation below is a paraphrased version of our interview.

How did you get into this field of microbubbles?

Jameel: In college, in my final year, I took an elective class on medicinal chemistry which proved to be among my favorite classes. I was fascinated by the design of drugs. The different ways we can engineer poisons into life-saving drugs and how entire drug classes such as, say,statens are found. That started a fire that stayed with me all the way till grad school, at Columbia University. There I had a chance encounter with Dr Mark Borden, he was the first person I met during orientation and he introduced me to the use of microbubbles in medicine. The rest is history.

I learned while there are many applications of bubbles in medical imaging, producing uniform sized bubbles in a reproducible manner was a big problem for the field. You cannot control bubbles of varied sizes. For bubbles to realize their potential for drug delivery they had to be uniform. Uniformity leads to consistency, an essential feature to control the dosage of the drugs our bubbles would enable. My first big project — to make bubbles uniform for their use to deliver drugs — turned into Advanced Microbubbles over time, the only company in the world currently offering uniform size-controlled microbubbles. It was also during my time at Columbia University, that I got to translate this work to that of other labs at Columbia University working on the use of microbubbles to deliver drugs across biological barriers and tumors.

Connor: Similar to Jameel, I had a chance encounter with bubbles. Got introduced to the company via a job-board posting for a chemical engineer to scale microbubble production. Dr Mark Borden, who at that time, was an Assistant Professor at my alma mater at Colorado University Boulder, where I studied Chemical and Environmental engineering, acted as the glue. He provided me with supplemental materials and some of the research on the field; that got me hooked. After going through the research and work done by the company thoroughly, uniform microbubbles emerged as a strangely commonsensical solution. Uniform bubbles and the use of ultrasound to trigger them was such an elegant solution not just for medical imaging but also for drug discovery, where controllable as well as localized response is key.

For you, it might seem commonsensical, but for the readers who are new to the product, injecting bubbles into the body is somewhat terrifying, no?

Jameel: When we talk about injecting bubbles people start thinking about embolisms and clots. It is, in reality, a very well characterized, commonly used and sophisticated engineered product similar to other prevalent delivery methods such as liposomes — which are spherical vesicles with lipid layers — used to deliver a range of drugs into the body. Our proprietary microbubbles are similar to liposomes, engineered on a microscale, except with a gas core. The gas core makes them reactive to ultrasound and they are precisely engineered to last for 30 minutes in the body.

Connor: And to give a bit more context, our bubbles can be easily co-administered with existing clinical protocols for the most part. They are injected systemically, using IV, which is already used in chemotherapy clinics and for most indications they can be triggered in a highly localized manner using conventional ultrasound machines. Our bubbles are designed with the clinic and the patient in mind. It is only for specialized indications of the brain that we look to R&D and partnerships with specialized ultrasound machines.

Now that we understand the concept, how will Advanced Microbubbles impact the space?

Connor: Delivering precise amounts of drugs in a precise space is the holy grail for oncology — really motivates me to work towards this goal. Our lofty goal is to pair our size-isolated microbubbles with promising drugs that can’t get to cancer or are injected at such high doses that cause debilitating side effects to the patient.

One example that comes to mind is glioblastoma, a notorious cancer of the brain that can’t be challenged well today, and a lot of it is due to the blood-brain barrier making it hard to deliver drugs with consistency and safety. With our technology, we have preliminary mice data showing that we can temporarily disrupt the blood-brain barrier. This data is published in a study Advanced Microbubbles did with NIH- NIDA, that showed dramatic improvement in delivery to the brain compared to non-uniform bubbles. And off that study, a dozen partners have interest in using AMB’s bubbles instead of conventional bubbles. Of course, the data is not in-human / clinical data, but offers promise to one day deliver the payload across the barrier and then the barrier heals for normal biological purposes.

Jameel: Couldn’t agree more. I see the potential of Advanced Microbubbles to enable a new standard of care in the field. The standard of care for chemotherapy hasn’t changed in hundreds of years.

With chemo, we have to poison the patient to hope to cure them. Advanced microbubbles can really impact the life of a lot of patients by making chemo less toxic and more efficacious.

Where are you currently in this process?

Jameel: We have been hard at work to get preliminary in-vivo data during IndieBio. Despite the pandemic and limitations of being a pre-seed startup, we were able to work with an excellent partner lab at the University of Texas. Led by company co-founder Dr Shashank Sirisi. Dr Sirsi has been with the company since it’s origins at Columbia University. There he was the key liaison between laboratories for the execution of microbubble development and therapy experiments.

Thanks to his support the team was able to get preliminary results in animal data. In “n of three”, small cohorts of neuroblastoma mice models — a tumor and rare disease that develops in adrenal glands. We are excited to showcase the data this demo day where we demonstrate not only proof of delivery, relative to control, with a commonly used chemo-drug. But more importantly, we show efficacy, a 1mg/Kg effect at significantly lower doses. Sending a strong signal in support of our thesis of low-dose efficacy without chemo-like side effects.

Excited to see this data this demo day. Looking beyond demo day, what does the next phase look like for Advanced Microbubbles?

Jameel: Work in mice models can always go wrong. Demonstrating reproducible and consistent results in-vivo, and in outcompeting non-uniform bubbles is where we are going next. This would mean running larger cohorts. We plan to show the efficacy of the platform in Neuroblastoma and pancreatic cancer animal models by the end of next year.

Looking beyond next year we want to show the versatility of this platform in more than one indication. Extending in-vivo proof of concept in a wide range of chemo toxic drugs expanding the market to other cancers such as breast cancer, prostate, and lung cancer. Showing we can take existing chemo toxic drugs and achieve higher efficacy at hopefully lower doses also plays into our business model to partner with Pharma to enable the efficacy and safety of their old and new drug classes.

With clinical trials coming next, should we be preparing for a long wait to see your product commercialized? Curious to learn more about your regulatory strategy and some learnings in this process?

Connor: At a very high level this data helps us gather more safety data points, setting us on a trajectory to get to IND and therefore, into the clinic in two year’s time. We do realize that there are many indications and potential drugs we can partner with.

Bubbles can go so many places, but at IndieBio, we learned that focus will set you free.

Jameel: Totally. To piggyback off that comment, focus is key. Bubbles have been used in ultrasound imaging, tumor ablation and other medical uses as an approved product for many years. IndieBio emphasized the value of tying key scientific milestones and data to a good go to market strategy. Starting with hard and rare diseases to drug tumors and then opening up to broader markets as we gather more performance and safety data.

Delving into regulatory strategy, early-on, was also a big learning that came out of the program. We didn’t wait instead the regulatory strategy helped us focus on our experiments. We learned how we can leverage the existing safety profile of bubbles and use an accelerated FDA pathway, the 505 (b) 2 to speed up going to market. An eye-opening experience to learn the role of the regulatory process in go-to-market decisions. Furthermore, based on advice from industry experts, we plan on combining this pathway with the orphan drug pathway can cut our time to market to 3 to 4 years.

Connor: When I come to think of it went from the mode of optimizing the best bubble and researching methods to do so in the lab to operationalizing the company to scale and sell the best bubble coming out of that research. In doing so we learned there is a new set of skills one has to code-switch to. Acknowledging this mindset shift is important as there is a stigma of moving too slowly in the lab. It is also exciting as we face a new set of challenges.

Jameel: In all this, I must say, IndieBio network really helped get a sense of the bigger picture and conveying that to a different set of audiences. We are gaining a sense of pitching the company to a rare disease investor versus a platform investor. How to engage different stakeholders and get people excited about what we are doing. We will continue to advance our relationship with regulatory experts and mentors we gained through the program. Look forward to keeping the momentum going around demo day and recruiting post-doc scientists to help speed up our preclinical data package.

IndieBio’s Demo Day is October 27–28, with the New York batch on Tuesday the 27th at 10 am, and the San Francisco batch on October 28th at 10 am. Please follow this link to Eventbrite to RSVP. A single registration will grant you access to both days’ events.

Introducing IndieBio Class Six

Today we’re extremely excited to announce the fourteen startups joining IndieBio Class Six in downtown San Francisco.

At IndieBio, we are on a mission to solve the world’s biggest and toughest problems by using biology as a technology. We are giving scientists the resources they need to drive innovations across food, biopharma and healthcare, agtech, regenerative medicine, neurotech, biomaterials and beyond.

When we first introduced the first class in 2015, we made a bet that scientists are more creative, driven and entrepreneurial than most VCs give them credit for. IndieBio was built on the belief that with the right environment and structure, scientists can make the shift to entrepreneur and build transformational companies. Three years later, we are amazed at the results: we’ve had the privilege of working with 81 of of the most exciting founders in the world and playing a role in their growth – including Memphis Meats (cultured meat), Koniku (biological neurochips), SyntheX Therapeutics (targeted therapeutics), Catalog (biological data archiving), Ava Winery (engineered wine) and Qidni Labs (implantable artificial kidneys). We are proud to have created a repeatable design-driven process to enable scientists productize their discovery.

Class Six is comprised of therapeutics, cell therapies, food & agriculture and diagnostics for cancer and neurological disease hailing from all over the world. More than ever, the IndieBio teams are on the cutting edge of science and solving massive problems in the world today.

Check out our events and make sure to RSVP for Demo Day, which is happening on April 17th at the Herbst Theatre.

 

Antibiotic Adjuvant

Delivering AI-powered decision support software designed to monitor and reduce antibiotic resistance.

 

BeeFlow

Developing smart and strong bees for crop pollination. With their technologies, farmers can increase crop yields up to 90%, target specific crops for pollination, and substantially reduce bee population decline.

 

Dahlia Biosciences

Leading the next generation of multiplexed in situ single-cell RNA analysis tools for research and diagnostic applications.

 

Jointech Labs

Pioneering access to high quality fat grafts, fat-derived stem cells and cell therapies. Their device enables doctors, clinics and hospitals to provide safe and cost-effective non-surgical treatments for patients.

 

Lingrove

Creating ‘wood’ without the tree. Their formable, natural fiber and resin replicates the performance, look, feel and re-usability of premium wood from scalable, carbon negative materials.

 

MezoMax

MezoMax enables faster bone fracture healing, improved osteoporosis treatment, and stronger bones in elderly patients with their novel calcium gluconate stereoisomer, which regulates calcium and mineral metabolism.

 

Neurocarrus

Developing long acting non-opioid chronic pain medications. Its novel delivery system eliminates addiction potential and side effects that are seen across all opioids.

 

Nivien Therapeutics

Nivien Therapeutics is developing the first small molecule drugs to enhance both chemo and immunotherapies. Their compounds overcome multiple resistance mechanisms across 15 cancers to increase efficacy and decrease toxicity of treatments.

 

Nuro

Nuro enables instant communication and computing for millions of incapacitated patients in ​post-surgeries and ICUs, ​nursing homes and rehabilitation​​ by using brain signals.

 

Onconetics Pharmaceuticals

Onconetics Pharmaceuticals develops gene therapies which target tumor cells with specific gene expression profiles. The effector arm of the therapy involves a genetic switch which activates an apoptotic inducer to kill the cancer cell and spares healthy tissue.

 

sRNAlytics

sRNAlytics has developed a novel bioinformatics platform to identify error-free, small RNA biomarkers. Their Proof-of-Concept work in Huntington’s Disease validated eight biomarkers that are 100% accurate for classifying early vs. late stage disease, and disease progression.

 

Sun Genomics

Sun Genomics is a microbiome health company focused on curing dysbiosis through personalized probiotics. Their platform enables the highest resolution profiling of customer gut makeup, empowering them to make and track changes over time.

 

Terramino Foods

Terramino Foods is reimagining seafood, using fungi and algae to make healthy, affordable, and toxin-free products.

 

Vetherapy

Vetherapy creates novel stem cell therapies for cats, dogs, and horses.  Their most innovative product speeds up wound healing and treats autoimmune and inflammatory diseases.