[HN Gopher] How to Start a Biotech Company on a Budget
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How to Start a Biotech Company on a Budget
Author : flipchart
Score : 114 points
Date : 2021-01-21 13:26 UTC (9 hours ago)
(HTM) web link (blog.ycombinator.com)
(TXT) w3m dump (blog.ycombinator.com)
| nceqs3 wrote:
| Are there any guides on filing Patents as an individual for
| biotech inventions? Seems like that is the most obvious way to
| raise capital and protect IP.
|
| Patent fees for an individual/small entity are only a couple
| thousand dollars in the US.
| dvdt wrote:
| I'm the Co-founder and CTO of BillionToOne, one of the biotech
| companies profiled in the post.
|
| We're recently opened up a position for a Staff Software Engineer
| (https://apply.workable.com/billiontoone/j/2F0405817C/).
|
| If you're interested, please reach out to me directly at
| david+hn@billiontoone.com
| nceqs3 wrote:
| Did you guys use a law firm to file your patents? How difficult
| was the process?
| dvdt wrote:
| We used a law firm. The paperwork was quite straightforward
| because our attorney managed it.
| shrewdcomputer wrote:
| > Arpeggio used their own technology to do drug discovery, and
| sold it as "consulting" to build credibility with investors and
| trust with a few initial clients.
|
| This sounds like a great example of them focusing on one thing
| and doing it well. It must have been a tightrope walk not to give
| too much information away about their IP and get crushed by
| competitors.
| dnautics wrote:
| > Intensely focused on demonstrating technical feasibility, he
| and his co-founders found $75K in grant money and hired a postdoc
| at Cornell to do the first proof-of-principle study.
|
| That's _still_ quite a budget. Not the sort of thing accessible
| to many people. What if you 're a grad student that just finished
| their phd (coming off of making 40k a year for half a decade),
| and not, say, a professor that has connections? Where do you get
| this initial seed?
| JabavuAdams wrote:
| Well, hopefully you networked with your profs and their
| contacts during that time? They can probably help...
| dnautics wrote:
| Not all professors are good at that, or even practicioners.
| Ironically if you get away with doing good science as a grad
| student there may even be an inverse correlation. Less time
| networking = more time at the bench.
|
| While I appreciate that self-promotion is a valuable skill, I
| believed (possibly flawed) understanding? narrative? that
| part of the reason why YC / tech incubation / tech can be
| effective is that it provides a structure where folks who are
| highly technically minded and historically preferred to spend
| time leveling up on that can be given easy access to networks
| with a builtin trust biased to some relatively technical
| merit, and resources to help level up on networking at all
| stages (whether that's PG's imprimatur that gives you access
| to VC offices for late stage companies or resources to help
| you find networkers in early stage companies).
|
| If YC doesn't acknowledge the structural barriers that make
| identifying technically meritorious biotech founders (vs
| biotech founders that have focused on buzzwords and
| networking) difficult then it's going to have a rough time
| meeting the success expectation it has for software, on
| biotech. It's nice to say you want biotech portfolio, but the
| proof is in the pudding what are you _actually_ doing
| differently to get it done?
| JabavuAdams wrote:
| There's something to what you've written, but I wonder
| whether it's too black/white. Even successful paper
| submission involves some level of strategizing /
| networking, sadly. So if you're published at all, you
| probably have some networking skills. It doesn't mean that
| one has to take time away from the other.
|
| I have not yet worked in a lab setting or where my PI is
| strict about hours, but from my software background a lot
| of "butt in seat" time is not really productive. My
| instinct would be to automate as much as possible and spend
| less time at the bench. But again, this is theoretical at
| this point.
| dnautics wrote:
| Well usually your PI will do the initial stages of
| networking or carry enough weight that you don't have to
| do much networking on behalf of your publications. That
| is a separate question from if your PI will do networking
| FOR you. Some will, some won't, either by malice, by
| ignorance, or by temperament. I worked for a nobel
| laureate (who discovered restriction enzymes).
| Publication was not a problem. He was lovely and fun to
| work for, but in the end I had to leave academia because
| he couldn't be bothered to network for me (he was more
| interested in playing penny slots at the casino).
|
| If you're in grad school, my strongest recommendation is
| to optimize first for a PI that will network for you.
| That is generally the most valuable form of networking,
| because 3rd party validation generally carries a strong
| amount of weight by human nature. Plus it potentially
| takes minimal effort on your part.
| hahla wrote:
| Grant money is definitely accessible at least here in the USA.
| I have seen grant funding available for various industries in
| my state alone, and it doesn't require any specialized
| expertise to apply for. Typically anything <$100k seems easier
| to come by.
| dnautics wrote:
| Real questions, I'd like to know from someone successful at
| it (is that you?): What was involved? How much of a proof of
| concept was necessary? How many connections did you have?
| [deleted]
| reasonattlm wrote:
| If you can get into an incubator lab space that isn't in a major
| market like SF or Boston, where the rents are insane, one can
| expect to set up a reasonable wet lab for most uses given $200k
| in equipment and reagent costs and a couple of months of time.
| Then expect $5-10k/month in operating costs outside of salaries.
| mc32 wrote:
| Without connections in the industry it would be hard.
|
| These things cost time and money. It's not something you can do
| in one year. You need five to seven years... if you're on the
| right track.
|
| Also you cannot know in advance if a clinical product can be
| repurposed because that's not evident till you begin studying
| your first target (where the data might show other unpredicted
| positive outcomes elsewhere.)
| koeng wrote:
| I've just started a bootstrapped biotech company in the last ~4
| months, and it's definitely possible, but does depend on your
| niche. I'm lucky because I can live with my parents and convert
| my room into a lab, but normally you have to rent a lab to even
| get things shipped to you. I also previously had intentionally
| developed the skills to do work on an actual "DIY" capex budget,
| which most folks coming out of academia don't have.
|
| Intense domain knowledge + knowledge of programming + affordable
| automation is really a fantastic combination to have with
| biotech. When the software isn't advanced enough, you can do
| tricks with hardware. When the hardware isn't advanced enough,
| you can do tricks with biology. When the biology isn't advanced
| enough, you can do tricks with software.
|
| It really does depend on connections, though. All of my early
| customers are folks I've known in the community for years, so I
| can get paid while working out all the kinks in the system.
| JabavuAdams wrote:
| I'm interested in lab automation, and ramping up on that. Do
| you have any automation needs?
| koeng wrote:
| Sure.
|
| Right now, Opentrons rules with their open source robots, so
| liquid handling robots are pretty well handled. Xarm makes
| good arms for interfacing with Opentrons, so then it comes to
| everything else necessary to get to full automation.
|
| 1. Automated plate hotels I need plate hotels to storage
| samples that interfaces with my robot arm and robot systems.
| This I'm basically using Theo Sanderson's designs for this
| https://www.thingiverse.com/thing:2668120 since buying them
| commercially is so darn expensive. I really need this for my
| system, so I am building em.
|
| 2. Plate sealer / unsealers My entire full automation
| pipeline is built around NOT needing a plate sealer or un
| sealer (something you can't do with the vast majority of
| screening systems). Automated versions of just the sealer
| itself cost more than 2 liquid handling robots and a robotic
| arm combined (and all it does is seal plates!) I think there
| is an opportunity for building simple but effective automated
| plate sealers and unsealers.
|
| 3. A train system I think Concentric (Ginkgo's COVID company)
| uses something similar, but basically a system that can use
| small trains to bring plates and reagents around a lab to
| different robotic stations. I'll probably just do that with
| lines of robotic arms, but I definitely spent quite a bit of
| time thinking of how to do this. (in my factorio megabase I
| really learned how to route trains, and I think it's exactly
| the same problem I face with my robotic work stations). I'm
| not sure how to scale the selling of that though.
| daemonk wrote:
| I completely agree with your point about being good at
| software/hardware/biology is the key to running a
| successful production biotech lab because you can try to
| supplement various weak points with the other domains. I've
| been 3d-printing devices that helps with DNA extraction in
| my lab.
|
| I am interested in automating the lab I am running now. We
| have an opentrons that we bought couple years ago that I
| never got around to using. But now that we are regularly
| getting a decent amount of samples in a week, I really want
| to get it going. Are you starting a lab automation service?
|
| I agree with your point about plate sealer/unsealer. It is
| a huge pain point in automation. However, I am not sure if
| you can convince regulatory bodies to approve it. Are you
| doing some kind of mineral oil top layer to prevent
| evaporation? We've actually tried that before and it kinda
| worked, but the problem is that the mineral layer messes
| with the SPRI bead purification step. I am sure it can be
| solved with more testing, but it just wasn't worth the
| inconsistency at the time.
| koeng wrote:
| I'm starting what could be thought of as a DNA cloning
| company. So sort of automation service, but for one
| specific application.
|
| > Are you doing some kind of mineral oil top layer to
| prevent evaporation
|
| The opposite: the process is pretty much based off of
| dessication (plus a little bit of tube opening by the
| bots for important chemicals). For thermocycling stuff,
| I'm planning on just using Opentrons module with the
| reusable seals. I really wanted to find a way to use
| reusable seals everywhere, but I just couldn't think of a
| way to do it well robotically. Thankfully, I don't need
| to convince the regulatory bodies of anything, since I'm
| just doing DNA cloning.
|
| > We have an opentrons that we bought couple years ago If
| you need to do multichannel stuff, do yourself a favor
| and go buy Gen2 multichannels and toss your old Gen1. The
| Gen1 multichannels are hilariously unreliable, but the
| Gen2 are pretty solid. Love those bots overall though - I
| got two of em so I can work in parallel!
| daemonk wrote:
| Desiccation is an interesting approach. I don't see it as
| being used for every step of a reaction though? It would
| take too long to wait for desiccation between every step?
| And depending on the buffers you are using, you might be
| increasing the salt concentrations after you re-
| constitute? I guess you can take that into account when
| you add the reconstitution buffer.
|
| Are you open to discussing some kind of consulting
| arrangement between you and my company? If so, how do I
| reach out?
| koeng wrote:
| > It would take too long to wait for desiccation between
| every step?
|
| Desiccation is just for the storage steps. Otherwise I
| just plan on passing liquids around, compensating for any
| evaporation.
|
| > Are you open to discussing some kind of consulting
| arrangement between you and my company?
|
| Sure! Contact me at koeng101 [@] gmail.com and we can
| talk
| JabavuAdams wrote:
| Could you elaborate on what you mean re: convincing
| regulatory bodies? I'm not used to working in a highly-
| regulated environment. Why are they involved? For
| certification of the lab?
|
| EDIT> I mean involved w.r.t plate sealers/unsealers, not
| more generally.
| daemonk wrote:
| If you want CLIA lab certification, there are a number of
| rules surrounding cross contamination, which not sealing
| a plate of samples properly might be a red flag.
| dekhn wrote:
| Are you really doing this at home, in a room converted to a
| lab, with actual live biology?
|
| I did that in my garage but after having to clean up a big
| contamination and debug experiments due to temperature
| fluctations, I realized there was a reason people use real
| labs.
| koeng wrote:
| Yes I am really doing this at home with actual living
| biology.
|
| Garages are terrible for biotech because of contamination
| problems. I have a bedroom that I've sealed quite well
| with 2 box fans constantly running filtering the air
| (tape a 20x20 filter to a box fan and it works great).
| When I work with media or anything I also use a flame. I
| still have some problems with contamination, but it is
| manageable.
|
| There are also biological ways to get around
| contamination problems. So long as your media is clean,
| if you use a strain like Vibrio natriegens, it just
| outgrows literally everything, so it's not that big of a
| worry.
|
| I have a few ruuvitags + a raspberry pi to monitor the
| temperature, and I live in Coastal California, so we
| don't have that much fluctuation. It hasn't mattered for
| my experiments, anyway, which are mainly just DNA
| cloning.
| throwaw4ybio wrote:
| How can I take this seriously when it doesn't mention ebay
| anywhere?
| JabavuAdams wrote:
| Explain?
| ChefboyOG wrote:
| I believe they're referring to buying lab equipment on eBay.
|
| https://www.nature.com/articles/d41586-018-05655-3
| koeng wrote:
| You can buy a ton of very expensive biotech equipment off of
| ebay for very little, which is what a lot of bootstrapped
| biotech companies do (plus gov-deals and other pharma auction
| sites)
| throwaw4ybio wrote:
| Exactly this! (+1 to govdeals too, when the auction is in
| geographic range) While we've gotten nibbles from
| accelerators, up to the interview stage, they want to see
| an MVP before funding us. This is, of course, kind of a
| non-starter when you don't have 200k lying around for a
| minimal denovo lab, and there's not much in the way of
| rental lab space where we are. Thankfully, after four years
| of grinding on this as our side gig -- and a big slowdown
| due to the plague -- we've got enough preliminary data to
| apply for an NIH grant, which we're very optimistic about.
|
| My wife and I have a setup up in our house (it's all GRAS
| and Biosafety Level 1 stuff) and have mostly bought off
| ebay and govdeals. She's a neuroscientist and I'm a
| physics/engineering guy. My job is to handle the business
| end, acquire gear, and maintain it so that she can science
| as hard as possible.
|
| Most of our lab gear is 80s and 90s-vintage gear we've
| fixed up. You'd be amazed what a little analogue
| electronics knowledge can do here; people will throw out a
| device rather than replace the belts or motor brushes.
| We'll get used and broken gear at a fraction of of the cost
| of new and certified refurb machinery.
|
| I'm currently modding our venerable Labline orbital shaker
| incubator. Over the course to two months the tachometer and
| both of the remote bulb thermostats on it went out, so I'm
| installing a Johnson Controls A421 to manage the heater and
| adding a $20 Hall effect tachometer to replace the analog
| tach. The mechanicals are solid, though (got it for $300
| plus freight!) and getting another would be a slow
| expensive crap shoot.
|
| BTW, readers, do you think that there is an audience for a
| blog that talks about the details of rebuilding old
| equipment like this? I'm not big on video, so it would
| mostly be long form writing with lots of images.
| koeng wrote:
| I'd like that! If you want to get some readers for it,
| check out the DIYbio forums on google groups. They aren't
| as active as they were years ago, but there are still a
| bunch of knowledge people there.
| throwaw4ybio wrote:
| Thanks for the tip!
| daemonk wrote:
| I want to point out that it really depends a lot on what
| kind of lab it is. I think for R&D, buying cheap stuff
| off of ebay or labx is great.
|
| But if your goal is to eventually scale up and build a
| production lab, you will need to switch your mindset when
| you get some funding and buy some decent equipment. It
| can make a big difference from my experience. My company
| started out at a sub-par lab space with second hand
| equipment. When we moved to a very well equipped lab, we
| found ourselves exponentially more productive. Mainly
| because we no longer have to constantly second-guessing
| our results due to sub-optimal equipment/reagents. Re-
| running experiments because of potential equipment
| failure adds up in terms of resources and psychological
| stress.
| throwaw4ybio wrote:
| Oh absolutely agree. The amount of time we spend _washing
| dishes_ is absurd. We yearn for the end of the bootstrap
| phase.
| 1996 wrote:
| > Most of our lab gear is 80s and 90s-vintage gear we've
| fixed up. You'd be amazed what a little analogue
| electronics knowledge can do here; people will throw out
| a device rather than replace the belts or motor brushes.
| We'll get used and broken gear at a fraction of of the
| cost of new and certified refurb machinery.
|
| (...)
|
| > BTW, readers, do you think that there is an audience
| for a blog that talks about the details of rebuilding old
| equipment like this? I'm not big on video, so it would
| mostly be long form writing with lots of images
|
| I see a business spin: sell shovels for the upcoming
| biotech boom. Get equipment on the cheap, fix it,
| reseller it with a warranty.
| hsuduebc2 wrote:
| Absolutely! Blog about this is a wonderful idea. Sounds
| really interesting. Can I subscribe now?
| koeng wrote:
| Maybe they were all govdeals type of people
| ArtWomb wrote:
| >>> Finding an initial product that's reimbursable and then
| taking the shortest path to get there
|
| This is really inspiring. Contrast with the typical story like
| Sana Bio which burns tons of R&D cash. My question is: how do you
| systematically search the potential solution space which may not
| be your initial area of expertise? How did the solution to focus
| on easily billable pre-natal diagnostics present itself to a team
| with oncology expertise?
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