2020 STEX25 Accelerator Startups Day 2 - Startup Lightning Talks with Q&A, Session 2

MARCUS DAHLLOF: The next startup speaker is Michael Schrader, CEO of Vaxess.

MICHAEL SCHRADER: Well, thank you all for joining the discussion today. My name is Michael Schrader. I'm one of the co-founders and CEO of Vaxess. I'm going to talk to you today a little bit about our MIMIX platform, which, for the first time, enables self-application of vaccines and other biologics in a shelf-stable patch. I'm going to talk about it a little more in the context of our lead program, which is a single-dose, self-applied, shelf-stable COVID and influenza seasonal protection vaccine.

So quick introduction to COVID, I think it's something that's on a lot of people's minds right now. Our hypothesis from the start when we jumped into the COVID race back in March is that COVID is not going to go away anytime soon. And that, in fact, we're going to have a need for regular revaccinations in the future.

We've seen with coronaviruses historically is antibody protection tends to wane relatively quickly even after a pretty potent infection. So we have combined COVID and a seasonal flu vaccine into a patch that basically is designed to protect against this. And we do this with a platform I'm going to talk a little bit more about, which is the MIMIX patch platform.

So this is a platform that brought together a novel material technology from Tufts and a new delivery system from MIT into a system that you see here. In the center of the screen, you see a white device with a gray button in the middle. This is the applicator. For size perspective, it's a little larger than a quarter in diameter, so relatively small.

If you flip that applicator over on the underside, you'll see there's a patch contained within. And that patch, as you can see here, contains an array of very, very small needles, which I'll show in more detail in the next slide. Essentially, this platform is unique in enabling single dose protection.

And we do this with some pretty unique immunology of slowly releasing vaccines in the skin. It's unique in offering protection against strain drift. It's unique in offering shelf stability and simple administration. Ultimately, we see an opportunity after a $10 billion plus market here in looking at the flu and COVID markets combined.

So this is a closer image of our patch. What you'll see here is a needle that has a clear central portion and a blue tip. I'm going to go ahead and click Play, and you'll see what actually happens when these needles enter the patient's skin.

So what we've done here is basically load the vaccine into the blue tip in a sustained-release polymer. This clear central portion of the base does not contain the vaccine. It's simply a fast-dissolving polymer and sugar blend.

The patch is applied to the skin. Fluid in the skin very rapidly dissolves that central portion. The needle embeds those blue tips in the skin. Those slowly release over about a two week period of time, essentially fooling the body into thinking that there's an actual infection. So very different than a traditional vaccine injected into the muscle, which is not really an immunological active organ and cleared out of the body in a day or two. Ours sits in the skin for about two weeks, again, stimulating very, very potent immune responses.

The beauty of this system, as you can imagine, is now we can move vaccination out of the health care system and into patients' homes. So the idea here is having an app that basically allows a patient to directly order their vaccine. The other scenarios we're imagining are insurance providers shipping these vaccines directly to all of their insured patients.

The patient takes out the applicator, applies to the forearm, as you see here. That patch is left on the skin. The applicator can be thrown away immediately. The patch has to be left on the skin for only five minutes. So this is the magic of the system is that blue tip separates in a 5 minute window. After which, all of this can be thrown away in a traditional trashcan. You've got no sharps hazards remaining.

The beauty of this system, again, without going into too much detail, is that slowly releasing a vaccine in the skin for two weeks. Fooling a body into thinking there is an infection leads to dramatic enhancements in immune response. So you see here antibodies against HIV, not only an improvement in the quantity of antibodies, but we also see a shift from non-neutralizing to neutralizing antibodies.

We see dramatic enhancements in T-cell responses. And ultimately what this leads to for a product like a flu vaccine, which is not very effective, is better protection. What it leads to for a product like the COVID vaccine is that we can now enable protection with a single patch instead of two or three separate injections.

So as a company, our lead program is a pentavalent vaccine, again, combining four strains of flu with the COVID vaccine. And that will enter the clinic early next year. We're following that in-house with a melanoma therapeutic, so applied directly to a melanoma tumor, slowly releasing a couple of different compounds directly in the tumor.

From a partnership perspective, we actually do not have a ton of bandwidth, at the moment. We've had a lot of inbound interest. So you can imagine, due to COVID, a lot of emphasis around that program. But we are also looking for partners who see value in applying this platform to enable better vaccines or therapeutics or even creative applications, think of nutrition supplement delivery in this simple, convenient format. Happy to talk to partners who see opportunities in that space. So with that, happy to take questions.

ARIANNA: Great. Thanks, Michael. So maybe you can expand a little on the partnerships, what current ones might look like. And you can touch on some global ones as well.

MICHAEL SCHRADER: Yeah. So the two partnerships we have in place right now have a very similar structure. We actually approached partners to see if they would be willing to provide us with their vaccines and let Vaxess own the development of the product. So we are a full-blown vaccine developer.

So in the case of these products, we've got molecules coming from partners. They're providing regulatory support on assay protocols. We are driving the clinical development activities. And then on the back end, we own the products.

And as you can imagine, there's a couple different structures to this. Some of these partners are global partners who have asked [AUDIO OUT] Others are looking for licensing royalties everywhere we choose to sell the product. So that's one model we are operating under currently that we really like.

The other model we operate under is the more traditional approach, where a partner has a molecule. They want to launch a product under their brand that uses our platform. We have shied away from those up until now, quite frankly. We think the development pace in many of these partners just doesn't align with the rate that we can move internally. So we've shied away from those. But we do have, I'll say, two discussions ongoing right now that look like they may result in partnerships in that space, again, where we're providing the platform. We're supporting those partners. We move the manufacturing of our patch into their facilities. And ultimately, on the back end, we draw royalties from that product.

ARIANNA: Great. What is the regulatory timeline?

MICHAEL SCHRADER: Yeah. So this is actually the beauty of COVID is the path into the market is much, much quicker with COVID. Essentially, you're looking at a traditional vaccine approval process for a product on our patch. So it's a full phase one, phase two, phase three. It's a drug device combination product, which certainly has some complexity to it. It will not be treated as a standalone delivery system using [INAUDIBLE] 501 pathway. So it's going to require a full phase one, phase two, phase three, and eventual approval as a new vaccine.

ARIANNA: OK. And a final question, could you talk a little more about any side effects or how safe it is for the skin and the level of risk?

MICHAEL SCHRADER: Yeah. So that's really the beauty of this is we've done now work in probably eight different animal models, everything from mice, Guinea pigs, pigs, primates, you name it along the way, a few others in there that I've skipped over. So we've got a tremendous amount of data showing that this is very safe, very well-tolerated.

Certainly, until we do that first appointment in humans next year, this will be an open question. That's the primary focus of our phase one clinical trial next year. But everything that we're using in this in terms of materials are well-validated. There are a number of other microneedle companies that have come before that have really validated the concept of skin delivery. So there's a lot of precedent we're building on here. Certainly, that phase one will be the key validator.

ARIANNA: Thanks, Michael. Back to you, Marcus.

MARCUS DAHLLOF: Thank you, Arianna. Thank you, Michael. The next presenter is Paolo Garcia, co-founder and CEO of Kytopen.

PAULO GARCIA: Thank you, Marcus. And we are Kytopen. And we're shaping the future of engineered cell therapies with our non-viral delivery Flowfect technology. We spun out of MIT in 2017. And currently, our team has four members that are connected to MIT, including our co-founder Cullen Buie, who is a tenured professor in mechanical engineering.

Imagine a world in which your own cells become living medicines to fight cancer, genetic diseases, and infectious diseases, such as COVID. These personalized therapies are a reality today. And the main step in being able to engineer those cells is to introduce genetic material for coding the desired therapeutic effect.

The process generally uses [INAUDIBLE] And this takes on the order of three to four weeks. It doesn't reach all of the patient population. And really, it has resulted in medicines that are effective but that have a high cost of manufacturing. Our goal is really to shorten that manufacturing time period and reduce the cost by implementing our non-viral delivery technology.

The secret sauce of our non-viral delivery solution is combining fluid flow with electric fields in order to open up cells and introduce genetic material into them without compromising cell health. We have adapted a commercially available liquid [INAUDIBLE] system to drive samples through our flow cell. And this gives us high throughput capabilities. Later this summer, we will be beta testing our scale up device that has the potential to process on the order of a billion cells per minute, which is more than enough for a therapeutically relevant dose of CAR T-cells, for example.

The important thing is that, between the two platforms, we use the same flow cell, same electric fields, same material, same geometry, same buffer, same flow rates in order to process the cells. And this gives us seamless scalability for therapeutic applications. Here, I am showing a video that demonstrates the simplicity and elegance of our Flowfect approach to deliver genetic material into cells.

We process these cells by aspirating the cells that are in combination with the payload of interest. That payload can be mRNA, DNA, or CRISPR. And it is resuspended in our proprietary buffer that maintains high cell viability. When the samples are flowing out of the devices, that's when we energize the tips with low-energy electric fields in order to introduce the genetic material into them. And they go directly into growth media.

Our goal is really to improve patients' lives through automated cell engineering. And as a case study here, we are showing some preliminary results that we have achieved in engineering B-cells with our technology. These results are just the first step in this journey. And this demonstrates the ability for us to deliver with high cell viability and high tranfection efficiency with mRNA.

What we did is we leveraged the power of our high throughput platform. And our scientist James took a cell type that we have never worked with-- these are the B-cells-- performed four experiments in less than two months. And now we have defined a starting protocol that we can use with potential partners.

And what we are seeking is industry collaborations with ILP members that are interested in accelerating discovery of future engineered cell therapies, being able to accelerate into the clinic with a manufacturing platform that scales and expanding beyond the traditional primary T-cells. We return the most advanced therapies with applications in stem cells, natural killer cells, B-cells, and macrophages. And what we want to do is also identify complementary technologies that can help automate the process even further and reduce the cost associated with these promising therapies, so that many more patients can benefit from this revolution in medicine. I would love to connect with you. I'll take any questions. Thank you.

ARIANNA: Great, Paolo. Thank you. First question, how does your non-viral delivery tech scale up to be able to handle the 1 billion cells?

PAULO GARCIA: Great question. And our technology is based on continuous fluid flow. And this is using very high flow rates. And so just to give you an example, these flow rates can be on the order of 20 milliliter per minute. And if you have a volume of 10 milliliters containing your 1 billion cells, you can process those billion cells in 30 seconds. If you're interested in processing 5 billion cells, then we just flow forward a little bit longer for 2 and 1/2 minutes. And we can process because our systems can scale with time and not with larger vessels.

ARIANNA: OK. And how does your gentle delivery process impact cell viability?

PAULO GARCIA: When we tune the flow rate and the electric fields appropriately, we actually do not have any deleterious impact in viability. So our technology can achieve high cell recovery, high cell viability, and high gene editing efficiency, so that you result in high yields from that input number of cells. And that's something that we don't have to compromise on.

ARIANNA: OK. And turning to COVID-19, what are some of the things that you're thinking about how to pivot to try other tests or other things that you're working on or thinking about?

PAULO GARCIA: So really, what we have is a technology that can deliver genetic material into the cells. And what we're looking for is for partners that perhaps have some payloads in order to code for the production of neutralizing antibodies. And so we would facilitate the delivery of those payloads, so that the cells can produce neutralizing antibodies as a potential treatment.

ARIANNA: Great. And a final question, is the flow required for enabling intracellular delivery of genetic payloads?

PAULO GARCIA: If we just use the flow rates that we are employing, we do not get delivery. If we just use the electric fields that we are using, we don't get delivery either. It is the synergistic combination of both types of energy, mechanical energy and electrical energy from both processes, that allows us to actually deliver all the way into the nucleus and attest stable gene editing.

ARIANNA: Great. Thanks, Paolo.

MARCUS DAHLLOF: Our next speaker is Jack Baron, co-founder and president of Sweetwater Energy.

JACK BARON: Hello, everyone. As Marcus said, thank you. My name is Jack Baron. Sweetwater Energy has developed a platform technology that is truly a breakthrough in efficiently breaking down over 90% of a given sustainable biomass into high-value building blocks that economically replace petroleum-based ingredients in products that we all use every day at lower cost. Our goal is that green no longer comes at a premium.

The global problem that we address is current biomass processing is inefficient. It's high waste and high cost and carries a substantial negative environmental impact. Because of the inefficiency, sustainable products made from wood and crop residues simply can't compete economically with low-cost oil in markets for fuels, chemicals, paints, and all the markets that we've come to know oil participates in. As a result, green solutions often carry a premium [AUDIO OUT] enough to address global climate change, but they must. Green solutions must, in fact, be cost-effective with petroleum to get to scale.

Our solution is that we've developed a platform technology that produces sustainable products at scale with lower cost. We're using patented modified twin-screw extrusion to break down biomass in less than 20 seconds. We have a team right now in Estonia that is actually proving our technology at commercial scale today for a plant that will, in fact, prove the technology by the end of this August.

In less than 20 seconds, our technology breaks down biomass into cellulosic sugars for transportation fuels and for biochemicals. We produce a lignin that is unlike the lignin produced in pulp and paper facilities. Ours is suitable for resins, paints, coatings, polyurethane foams.

Perhaps most exciting, we make a microcrystalline and nanofibrillated cellulose. Our partners globally are beginning to use that technology to create low-weight and low-cost packaging, processed wood products, furniture, and cabinetry. You can even find specialty cellulose like ours in food products. And the Japanese government recently produced an electric vehicle, whose body was made from nanofibrillated cellulose like ours, at five times the strength of steel and 1/2 the weight.

We're working with multiple industries. Packaging and paper is one area we've focused. We have multiple corporate partners now globally, in the US, Europe, Southeast Asia, and South America. Our partners are working with us to collaborate using this platform technology to create new products of their own and [AUDIO OUT] saving, sustainability, performance, and profitability.

Specifically, in the paper industry, one partner is lightweighting their product to enhance strength and reduce cost. They have over 150 paper companies around the world that they're working with. They estimate that our technology can help each of their customers save up to $5 million per year. Another partner is using our nanofibrillated cellulose to act as a coating to reduce or eliminate petroleum-based ingredients, saving cost and improving oxygen barrier performance in packaging.

We're seeking additional collaboration opportunities, companies that are willing to use our building blocks to create their own new proprietary products and lower their costs, companies that are focused on improving existing product performance, cost, and sustainability. We're working in industries and applications such as packaging and paper, processed wood for construction, furniture and auto parts, and cement, where one recent partner has had a breakthrough. Using just 1/2 of 1% of our microcrystalline cellulose in a concrete mixture, they increased the tensile strength of that concrete by 100%, doubled the tensile strength. We're working with partners in fuels, chemicals, polyurethane foams, paints, and coatings. I'm Jack Baron, Sweetwater Energy. Thank you.

ARIANNA: Super, Jack. Thank you. The first question for you, I know that climate change is a priority for Sweetwater and also for many or most of our IoT members. How does Sweetwater's technology can successfully address that?

JACK BARON: Thanks, Arianna. First, we're replacing petroleum products, which, of course, allows our technology to reduce the amount of petroleum required. We're using sustainable wood [AUDIO OUT] plants as they grew. The value of our co-products is so high, with microcrystalline and nanofibrillated cellulose and even this unique lignin, that, effectively, the cost of our sugars is extremely low. So creating transportation fuels that can compete effectively with petroleum-based fuels without incentives is one thing this technology, as it's adopted globally, will allow.

ARIANNA: Great. Another question. Why has it taken so long for a platform tech to be developed that effectively competes with fossil fuels and products?

JACK BARON: The problem is challenging. Mother Earth takes over 100 million years to break down oil into a usable product and to down plants and animals. And we're using this platform technology in just 20 seconds. But it's a competing problem that we had to fix.

And that is you have a thorough process to get to products that allow you to compete economically. And it had to be gentle enough. So you have to be able to create products that, in fact, can separate wood and crops into component parts to compete economically with oil.

ARIANNA: OK. Next question, can you produce biofuel competing with the current oil prices?

JACK BARON: Yes. Short answer is absolutely. The technology is true biorefining. So based on producing multiple products at a given facility, we're creating these specialty cellulose products, the lignin, which are saleable. And we're working with partners and contracts around the globe for that. And we have contracts now for ethanol, which, obviously, is a drop in fuel. And we're working with other partners for drop in hydrocarbons well beyond ethanol.

ARIANNA: Great. And a final question, can you talk a little more about plastics and the polymer industry?

JACK BARON: Sure. Our lignin is a natural biopolymer. And it has highly reactive hydroxyl groups. So it already is working in polyurethane foams and as a polymer replacement from the petroleum industry. That's today.

Many of you are probably aware of PLA, Polylactic Acid, and products that are made from fermentable sugars. Ours are some of the most formentable sugars, our partners tell us, that they've ever encountered from cellulosic sustainable sources.

ARIANNA: OK. Thanks, jack.

JACK BARON: Thank you.

ARIANNA: Back to you, Marcus.

MARCUS DAHLLOF: Great. Thank you, Arianna. Thank you, Jack. We're going to go to our last startup presenter. This is Adam Behrens, co-founder and CEO of Mori, formerly known as Cambridge Crops.

ADAM BEHRENS: Thanks, Marcus. I'm really happy to be talking today. As Marcus mentioned, we recently rebranded to Mori. I'm Adam Behrens, co-founder and CEO, formerly was an MIT Langer Lab post-doc . I co-founded this company with Benedetto Marelli a couple of years ago out of MIT civil engineering.

Mori exists because of food waste. Today, about 1/3 of the food produced globally is wasted. That represents about $1 trillion in economic losses. As a company, we're looking to recapture a lot of that lost economic value as well as create more through extending shelf life.

To extend shelf life, we have to directly address why food goes bad. The three mechanisms that we care about are dehydration, gas exchange in the form of both oxygen and ethylene transport, and microbial growth. And we directly attack all three of those mechanisms by forming a natural barrier on the surface of the food item directly.

It has barrier properties as well as some chemical properties that allow us to directly address all those mechanisms. The basis of that barrier is a protein that we extract from silk. Why it works so well as it's able to self-assemble on the surface of a food item and form great barrier properties.

A big differentiator is it's film-forming ability. It's amphiphilic, and it has relatively high molecular weight, which allows us to form barriers across a wide variety of substrates-- hydrophobic, hydrophilic, old produce, cut produce, and even protein. The last feature of the protein that's important to our application is that it deters microbial growth. The silk films that we're forming on the surface of these food items do not allow for easy cellular adhesion, having a great antimicrobial effect.

At the end of the day, what we're doing is making a water soluble powder that we're shipping to our partners. At our partners, either packaging or manufacturing sites, they're simply redissolving that powder into existing unit operations where food items are being sprayed or washed today. Again, we work across category. Generally, we like to form really deep partnerships around single food items, as well as more platform plays.

Right now, we're working really hard on leafy greens, both improving supply chain efficiency, quality, and shelf life, allowing for the decommoditization of fruit and vegetables, and putting them in a value added form like taking a cut vegetable and making it a cut vegetable while still having the parent shelf life of the parent ingredient. In whole produce, we're able to maintain quality, allow high-quality produce to be shipped to further terminal markets, and also are deeply exploring the protein space. We're extending shelf life and reducing shrink for a variety of our partners.

At Mori, we deeply care about food waste. Food waste, from a bottom line perspective, most directly affects retailers, food service, and consumers. And so it's really important to us that we also affect the supply chain in a positive way.

And then so we end up looking for other very important value propositions that affect the stakeholders. The first of which is packaging. Through creating barrier on the surface of a food item directly, we're actually able to take some of the barrier of performance away from the packaging, allowing for transitions to be made without a reduction in performance and at a decreased cost.

From a logistics perspective, we're allowing things to be shipped more densely, shipped hotter, or even provide insurance against when the cold chain does break down. I'm sorry. That should go forward. And lastly, we're providing access to new markets and enabling new product combinations altogether by making ingredients that weren't shippable shippable now.

We're currently converting from pre-commercial pilots into commercial deployments next year, alongside ramping up our production. And we're still looking for deep partnerships in fruit, vegetable, protein, and processed food categories. In the more medium term, we're looking for manufacturing and distribution partnerships, especially internationally, and are generally interested in a more medium to long-term joint development arrangement as we push some aspects of our technology into the pre-harvest and direct packaging space. Thank you for your time.

ARIANNA: Adam, thanks. A first question for you, can you talk a little about any added cost to cover the foods?

ADAM BEHRENS: Yeah, so we end up charging on a per pound food item basis. And generally, we're adding single digit cents per pound of food.

ARIANNA: Next question. How much shelf life extension are you seeing?

ADAM BEHRENS: Sure. So it really depends on the context of which it is applied. But generally, we're seeing 50% to 100% shelf life extension. And that could be not the top of the supply chain where we're adding weeks or at the very end of the supply chain where we're adding days.

ARIANNA: How about any side effects or safety concerns that you've addressed?

ADAM BEHRENS: Sure. Yeah, so we actually self-designated generally recognized as safe in early April after expert panel review. Really important that this can be broadly applicable for all food categories. So very deep investigation into anything like allerginicity, toxicity, or otherwise. And we have extremely high safety margins that make this really a complete go ahead for the full public.

ARIANNA: Great. Thanks, Adam. Sure. And now we will have a final poll for the audience.