Industrial Bioreactors in Space with Ambrosia Space's Mario Maggio

Mario Maggio is founder and CEO of Ambrosia Space, which is building the hardware to make industrial biomanufacturing possible off Earth.

What does Ambrosia Space do?

Ambrosia is building the future of in-space manufacturing. Specifically, we're focused on biomanufacturing, which is all about using cells to produce products that are super valuable. This could be for astronauts, or eventual lunar or Martian settlers living on another planet; making all the other things we rely on Earth for either directly or indirectly, life support systems, water, food, as well as plastics, chemicals, and more. In the near term, though, it's going to be the critical capability necessary to scale the pharmaceutical industry off planet Earth.

What led you from lunar landers and spacesuits to building bioreactors?

My background has always been in aerospace. I did a master's at CU Boulder in bioastronautics, which is basically how you keep people alive and thriving in space. That opened my eyes to a lot of opportunities inside crewed spaceflight.

I didn't use too much of that when I first left grad school. I went to a company called Intuitive Machines, which was about a 30 to 40 person startup building lunar landers when I joined. Since then they've landed on the moon twice. Both landers promptly fell over after landing, but a third one is launching soon, and the company is now over a thousand people. I was there for three years, working on the propulsion systems and then the assembly, integration and test of their lunar lander. I got to work on the rocket engines, work on the test stands, drive the rocket truck, and build what I call the “IKEA manual” for the landers: the directions for actually assembling the vehicle, what torques, what bolts, what parts go on in what order.

After that I went to Paragon Space, working on a range of spacecraft life support systems  including the next-generation lunar spacesuit built by Axiom Space, where Paragon was a subcontractor. What that got me was seeing how we actually stay alive in space, and I got absolutely hooked on biomanufacturing. It's going to be a critical part of life support as we go further from Earth. Right now, the method is: you breathe out, something grabs the CO2, and you throw it out to space. You need to find a more circular way to do that in the long run. That led me down the rabbit hole of biomanufacturing for life support, which led to industrial biomanufacturing, which eventually led to biopharmaceutical manufacturing in space.

Why does it make sense to manufacture pharmaceuticals in space?

A lot of this is at the research stage right now, and there are two thrusts that are interesting. The first is stem cells, where you can build organoids and better understand how humans age, how organs age, how disease progresses. The other, where we see the most promise, is protein crystallization. When you're in space, you don't have gravity, so there's no convection, no buoyancy, no sedimentation. All of those things enable you to make a better crystal of just about anything, whether it's semiconductors or different types of drugs.

Proteins are uniquely challenged with crystallization on Earth because they're so big, and they're uniquely benefited by crystallization in space. For the vast majority of proteins the industry has tested, most show data pointing toward better stability and better injectability. A lot of these drugs are typically delivered through IV drip, and all of them have to be refrigerated. If you can make drugs that are currently IV-drip into shots, that opens up a huge market not just to compete against existing competitors, but to bring drugs to market that would otherwise fail on their way there. A good example — a little hyperbolic since it's a peptide that is about 100x smaller than the drugs we’re interested in, but illustrative — is GLP-1s. If GLP-1 was only an IV drip, would people be going every two weeks to a clinic and sitting there for an hour? Some would, yes. But not nearly as many. Now imagine that for other diseases.

The thing that really differentiates our approach is that we're not really interested in the crystals themselves. That's what makes space special, but it's not the what gets a product to market. Producing a large quantity of the protein that gets crystallized is the true bottleneck. We're trying to take research and get you toward that final product. Crystallization is something every pharmaceutical company knows how to do, and there are a number of players working in that space in orbit. The problem is that capability is good for research, but even if you have a good crystal from space, you still have to propagate those crystals into enough quantity for a single dose, let alone a clinical trial or monthly manufacturing quantities once a drug is on the market. So you can’t really scale that process on Earth, and if you fly up the already made proteins, it's really hard to make the unit economics work. As an example, if you're flying something to space that costs $1M per kilogram to manufacture, and the second it comes off the manufacturing line it's worth a lot more than that, are pharmaceutical companies going to fly it up and down every time, pay the insurance, take the risks? Probably not, because then their product gets more expensive. So we're looking at the alternative path: build the entire manufacturing process in space - which actually ends up being much more competitive.

If the microgravity benefits of manufacturing pharmaceuticals in space are known, why hasn't this scaled yet?

We've been doing protein crystallization in space since the 1980s. A lot of the value wasn't really there until large protein drugs came onto the market in the late 1990s and 2000s. Keytruda was one of the blockbusters of the monoclonal antibody space. As those drugs skyrocketed in use, that opened up the need for more indications to be targeted, and some of those drugs will need to be injectable from a market perspective. So you follow a path where there's now good timing and good rationale for the pharmaceutical industry as a whole to care about making protein crystals or protein injectable therapeutics. And at the same time, launch costs have come down dramatically, even with the current launch crunch. Those are the two market conditions that make it valuable for us to fly.

The challenge on the technical side is that nobody has really done this kind of cell growth in space before. It's mostly because we're always trying to cram as much research as we can into any experiment that goes to the ISS. The biggest bioreactor that has flown is about 150 milliliters, or 5 ounces, which is quite small. Most of the work happens at the 10 milliliter size or less. Small drops. Those give you data, but it's because you're trying to maximize sheer quantity, not necessarily replicate the processes used on Earth. Manufacturing on Earth can get as large as 10,000 liter batches.

How is Ambrosia's approach different from the other players doing crystallization in orbit?

Some other companies have made real inroads on small-batch R&D. What we're focused on is the latter half of R&D: process development. Drug development is, in a lot of ways, research: you're trying to find which drug to make. We're looking at how you make a given drug at scale. Once you've found that something works better in space, how do you make enough of it to run animal studies? How do you make enough to run a clinical trial? How do you meet GMP in these environments? Those are the questions we're solving.

In hardware, that means our bioreactor is starting at  two and a half liters, bigger than any ever flown, with all the capabilities a lab scientist is used to like mixing, gas control, feeding, and continuous monitoring of pH, temperature, dissolved oxygen, all the things that are standard in any benchtop-scale bioreactor test. As we scale, we also want to be able to expand our capabilities. To go down in size, so we can get better data and control for systems as small as 150 or 250 milliliters, because that's really where the science bleeds into the manufacturing world. And obviously we need to scale up for bigger systems too. We're the first company building hardware with that goal in mind.

Who is the ideal Ambrosia customer, and what does a flight actually involve?

There are two primary ICPs, and they all involve companies actively developing or already selling a drug in the antibody space. Monoclonal antibodies are specifically what we're trying to work on first, but we're interested in bispecifics and other antibodies as well. The first group is companies with an antibody struggling in formulation where they can't get it to the injectable status they need to make it to market, either because the indication requires injection for patients to be interested or because a competitor already has an injectable in their pipeline. The second group are companies with drugs that are facing the end of patent exclusivity. They will need to stand out in the market, and injectability is a fantastic way to compete. For either group, the first thing I'd tell them is: try to make a crystal. If they've tried on the ground and succeeded, that means it will likely crystallize in space, and the quality will be better. The second step for anyone interested in growing their monoclonal antibodies in space is to test their processes and see how it actually operates in space.

Mechanically, if a pharma customer comes to us, we start by understanding what they can do now and what their knowledge base is. Then we fly an experiment that mimics their benchtop-scale process: the same environmental conditions for their bioreactor and cell growth, following their manufacturing process as closely as we can for things like chromatography, ultrafiltration, and diafiltration. Then we either use their recipe or work with partners like Varda, BioOrbit, Exobiosphere, or Redwire to crystallize. All of this is only possible on the ISS today, because Dragon is the only vehicle with cold storage, and keeping a cold protein cold is incredibly important for these proteins to survive. We're also not interested in competing in launch or reentry capsules; there are something like 20 players in that space already, and as we grow we'll find the right partners.

Our go-to-market is really education-first. We're there to be the guiding hand, and even if our technology isn't the right first step for a customer, we want to help them do better science on Earth so they know they're answering the right questions to decide if it's worth doing in space. Because of the broadness of our hardware, and the traditional conservatism of biopharma manufacturing, we're also actively working with defense, universities, and NASA to build out core capabilities, as they  aren’t only useful for pharmaceutical work.

What's on the near-term roadmap?

We were recently awarded a Phase II STTR from the Department of Defense to build out biomanufacturing capability for space, in partnership with the University of Delaware. I can't go into too many details beyond that, but we're really stoked and are actively gearing up for that mission — it should lead to flight hardware.

The other thing is we're gearing up for the first flight of our 2.5 liter bioreactor. The hardware is through design, and we're going through the safety and manufacturing processes necessary to fly to the space station. The exact timing depends on funding. I thought it was going to be flying in October, so, you know, that's just the space industry. We anticipate having sufficient funding to fly sometime in the 2027 timeframe.

Longer term, as we scale we want to get outside the crewed environment, because the space station is kind of gross. You can't shower in orbit, isopropyl alcohol wipes aren't allowed, and there are a lot of constraints around maintaining a sterile environment on the ISS. So as we scale, we actively need to be outside that environment. Whether that means we're attached to the outside of a space station as part of a capsule, or have our own dedicated Starship…whatever it ends up being, our manufacturing is probably best done in vacuum. That's the most sterile environment known to mankind. We might as well take advantage of it.

What's the bigger vision beyond pharma?

It's easy to talk about drugs in space and about being a better pharma company. But part of the reason we're looking beyond just crystallization is the technology stack it builds. A bioreactor is really important for our bigger mission.

We want to be the industrial company for anything off Earth. When you think of a company like Bayer or DuPont, those are the kinds of companies we want to eventually be compared with.

Everything made off planet Earth needs to be built: your oxygen, your water, your waste reclamation, your food, your plastics, your chemicals. The list goes on and on. We want to be the hardware that makes every single one of those, and, if we can, be the company actually operating it as well.

The nice thing is we can actively make today's world better while building out the technology that makes the next world possible — to make Mars, the moon, actually possible to live on. Look at a place like Houston: it has the most solar and wind power, and a lot of interesting chemical companies — Solugen probably being the most notable — that are using biomanufacturing. It's already becoming a better way to do things we currently rely on oil and gas for. As it stands today, even if we were fully off fossil fuels for power forever, we'd still need to be drilling oil and gas for a long time, just for all the secondary products. Think about how many industries got thrown off kilter during the pandemic by supply chain disruptions — the hydrogen used for one thing, the helium used for another. All of those obscure secondary, tertiary, quaternary products made from the oil and gas pipeline eventually need to be replaced too. Biomanufacturing will make that possible, and like many other industries, space can help lead the way.