After some success in space, Varda raises $187M to expand ambitions

^^

I often see reporting about a company which has "plans" for a launch "in the next couple of years". Then ... nothing. (See: Kuiper on Vulcan; Sierra Nevada; Spinlaunch; Orbex)

It's possible that other company will do something in a couple of years, but not a given.
Maybe it's unrealistic expectations, based on business case by press release.

But Varda launched already. And has something to show for it.

From what I understand, the main use for crystalizing drugs is to analyze their structure using x-ray diffraction techniques. This might allow one to improve the structure or its mechanism of action. In case of the mechanism of action, this can be accomplished in some cases by crystalizing the drug along with some analogue of the drugs target bound to the drug. This only usually makes sense if either the drug or the target (or both) are fairly complex structures that computer modeling can't figure out.

Not sure if there is really a commercial therapeutic use for space crystalized drugs.

Oh! So it's for research when developing the drug, not full scale manufacturing? If that's so, then ~$20 million could be more reasonable.

And then there are the

entrepreneurs who want to go straight to rotating space stations or who base their business models on other companies’ long term roadmaps.

I looked back at Varda’s coverage when it emerged from stealth mode in 2021. Bootstrapping their way to a MVP microgravity research platform has been their goal all along. Seems like a more sustainable strategy.

That's literally how the human exploration has worked since before the concept of recorded history even began. It's always been driven by people with means or necessity deciding to leave in search of greener pastures, whether or not they're the ones responsible for wrecking their previous habitat.

If in some way you were trying to suggest that the people who are funding this endeavor actually expect to be able to leave the Earth because they've ruined it, then I think you've drunk too much of the Kool-Aid when it comes to the timelines for off-world habitation being anything besides short term novelty or extreme sport. It'll be a damned long time--many many decades if not a century--before anyone can retire comfortably to a destination that isn't here on Earth. Even then, if a critical mass of your fellow off-Earth inhabitants blame you for destroying Earth, there won't really be anything that stops them from just evicting you or killing you. There won't be disposable labor for body guards and maintenance of your private compound, nor will there be the social and governmental systems in place to ensure that whatever supplies you need would still be provided.

Ok assuming I'm remembering all this correctly from when they first launched and as I recall that was a mess.

But the short version of this is in space they can' control the Chirality of the drug meaning they can make the more stable longer lasting/more effective version in space for way cheaper then in gravity.

This is a drug that if the wrong chirality version is introduced requires scrubbing down the whole process top to bottom or it ruins the entire batch. It's like a prion where the misfolded protein in the drug makes it way less valuable/worthless.

So presuming they can do this at a volume and scale that makes sense, IE some kind of super high value drug made at a scale or launched cheaply enough (IE on a reusable ship and production platform) there might be value there.

Now for the part about why I said this was a mess as I recall.

If this is the one I'm thinking of they didn't acutally get permission to land their gear when they got their launch permit and were just going to randomly land it in the desert. Which is when the govt stepped in and said "No." They were as I recall getting close to it all burning up before they got the OK to land it.

So it's good to see things have successfully evolved since then. With three more launches that feels like they are making real progress.

So yay for science and hopefully someone can make all the math math and this works and makes awesome drugs people need to heal.

When the drug can be made at 200-500 times the production volume, for a launch cost of the $2 million that Spacex is targeting, and land with the same vehicle it launches on, at a US Spaceport. That will be quite a bit cheaper. The capsule return is a first step. When a 50-200 ton facility is doing the production, without landing out in the Mesquite lands for retrieval, it will be a cheaper product. As Caleth has noted, far more effective drugs may be coming back to Earth as well, because of better chirality.

I think a century is probably the minimum, considering we haven't put anyone on another celestial body for more than 50 years and that was just the moon. We're likely a decade away from the first boots on Mars, and it's very hard to imagine a scenario where anything more than a government-funded bare-bones research facility is operational there before 2100. My guess would be early 2100s for uber-wealthy to visit for short "adventure trips" and 2150 or later for retiring in a Mars villa. But maybe I'm just jaded from seeing almost nothing beyond LEO since I was old enough to actually watch it ...

They weren’t going to just randomly land in the desert. You are correct that they launched before they had a reentry licence. The mistake they made was they reckoned getting the reentry licence wouldn’t be too difficult. But they ran into all sorts of problems, not just from the FAA, but also from the military (they were planning to use a military range in Utah).

Not so much drugs (unless they are proteins), but they did try to grow protein crystals in microgravity because they couldn't crystallize them otherwise, and you need crystals to determine protein structure with X-rays. However, it seems that AlphaFold made it much less of a problem.

Ritonavir mentioned in the article can crystallize in two forms, and one form IIRC is insoluble and thus not bioavailable, so how do you crystallize it matters.

Chirality is extremely important for drugs, but you can't control it in space...

I could be misremembering, or maybe conflating more than one incident. But IIRC, the FAA was legally required (under the new "streamlined" regulations at the time) to give them a yes/no on their reentry license within 90(?) days. Varda applied for a reentry license well in advance, but FAA took a very excessive amount of time to actually respond in any way.
And with no response from the FAA and their scheduled launch looming, Varda decided to just roll the dice.
Which eventually worked out for them, but I recall a lot of nasty sneering "techbro" comments here on Ars after Varda's first attempt ended up stranded in orbit with no reentry license.

Plus, since when is growing pharmaceutical crystals in space considered "maunfacturing"? I scoured the article to find one thing "manufactured" in space and got crystals. So, the ground based actual manufacturing sector seems to be in absolutely no threat.

At the current SpaceX ride share prices, 300kg W-4 capsule is more like $2 million, not $20 millions.

Whether it is enough to make this a business is still an open question.

https://www.spacex.com/rideshare/

I’m interested in why it would be the case that you could produce 200-500 the volume successfully in space. Not doubting it, I just don’t know enough about chemistry. Which kinds of drugs or molecules would this apply to? Things that already exist or hypothetical future ones we want to make but haven’t been able to yet?

That was like literally the point of this test. They grow the type I version that crystalizes the entire batch as Type I and because it's done in space the risk of a alternate nucleation site causing a Type II contamination is reduced or minimized.

(Note I'm not a chemist of any note I took a few classes in college, but the articles on this subject said this was the approximate point of it.)

You can't literally control the Chirality of the chemicals in a like hand of God sense, but the point was that the lack of gravity caused better homogeneity while also allowing for better/larger crystals with far fewer to no impurities. So you get a better, purer product with a massively reduced risk of the batch going bad due to chirality because the crystallization works differently and more uniformly.

The excerpt of the papers talks about the lack of amorphous phases and the fact there didn't seem to be spontaneous conversions to type II in the type I products.

So maybe I'm misunderstanding something, but I thought that was like the point.

Interesting, I was probably still thinking of the protein crystallization experiments that I remembered from the ISS.

I mean I understand that the specific structure of a compound can make something soluble or not (tons of protein examples, like egg whites). Guess not quite seeing why being in space would make a difference or not, but then again I am no chemical engineer.

Fantastic video thank you. Really takes you on the journey looking out of your own little “window.”

Ok, a chemist here: chirality usually refers to the structure of the molecule: the chiral forms of a molecule are otherwise totally identical but cannot be superimposed just like the right and the left hands.

When you synthesize chiral molecules you usually get 50/50 mixture of both forms.

For drugs, often one chiral form is an active one, another is inactive and sometimes even harmful (like the infamous Thalidomide), so chirality could be super-important.

Synthesizing only one chiral form—stereoselective synthesis—is possible but difficult (unless you’re using enzymes), microgravity wouldn’t help here at all.

How molecules crystallize can be affected by weightlessness but it cannot change the chirality of the molecules, only the way they pack into a crystal.

To me the biggest challenge is getting the reagents to LEO. For reactions that have low yields this would mean 5-10x the weight. The same for crystallization: methods like thermal evaporation may be 1:1 but in reality there is a lot of mass loss due to geometric factors. In solution-based methods most of your mass is solvent.

A pseudo use if I ever saw one. One can imagine trying to go co-crystals of drugs and their target proteins/oligos in space, which might occasionally prove to be a not wildly expensive Hail Mary. But drug product crystals themselves? Why? The purpose of recrystallizing a drug is to purify it chemically. The more crystalline the drug is, the more likely it is to have very poor solubility in biological fluids without a complex and costly formulation. Generally speaking, the commercial guys tend to get very nervous if the total cost of goods rise above about 8% of the selling price, so if you add a megabuck/kilo to shoot the finished drug off into space for one processing step, you will have either unhappy beancounters, or even unhappier customers.