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Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

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Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#11

Post by morraa »

101008 wrote: post #8

Wow, this seems very interesting. As someone who did his CS Master thesis with vaccines, medicinal chemistry is something that I always enjoy, so I chcked your open positions. Sadly, I saw that even for Remote positions you are asking for a VISA. Can I ask why? Thank you!

Ah thanks for pointing this out; it is slightly misleading. Visa is only required if applicants want to work with us in our in-person office in the Bay Area, CA. If they are a non-US citizen we sadly can't sponsor a visa. Though certainly for remote work we wouldn't require it.

Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#12

Post by morraa »

JunkDNA wrote: post #5

A few random thoughts I'm curious about (full disclosure: I worked in anti-infectives R&D as a bioinformatician early in my career for a major pharma) 1) One big challenge in synthesis is ensuring compound purity. Even when I was working in pharma, it was often the case that some of the compounds in the screening library could be contaminated with intermediates. This is murder for any kind of anti-infectives research…

1. We ensure that the compound is pure using analytical methods like NMR and LC/MS. In our Moonshot project, the assay cascade comprises biochemical assays against the main protease (2 different assay methodologies, run in Oxford and Weizmann Institute) and live virus assays, thus we should be able to infer whether the activity is caused by impurities killing the virus. In addition, we also perform high-throughput x-ray crystallography to determine the structures of all the protein-ligand complexes, which serves an an orthogonal assay.

2. Yes, our algorithm does factor in the yield when it decides which reaction to use.

3. You're absolutely right. It is very ambitious but we've realized that even if we don't get our compounds into human trials (currently aiming for in-vivo testing in next few weeks) that we will still have generated a lot of useful data that is there in the open for when the next pandemic comes around. This has been a real weakness from prior pandemic where research wasn't continued and certainly wasn't stored in clean accessible ways. As I'm sure you know SARS has super high genetic similarity to current COV-2 so having prior data accessible and cleaned would have given researchers a real head start.

4. Yes Derek is aware of COVID Moonshot and is also of the opinion that is it both ambitious but sadly necessary. We continue to follow his posts as healthy skepticism particularly in the area of AI for drug discovery is always helpful.

Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#13

Post by kayhi »

morraa wrote: post #10
kayhi wrote: post #7

Great idea! If I have a list of drug candidates and your software can apply a confidence level on the best route to synthesize a product that is better than chemists you're company is very valuable. Inital thoughts - defining easy of synthetic pathway seems hard. If I'm an organic chemist and the recommended molecule involves a cost, technique or equipment that's inaccessible then I'd be stuck. However, if your netwo…

Yes absolutely, the variance of pricing across different custom synthesis providers can be surprising. This we think though is actually an opportunity to serve our end users (drug hunters) better. Generally the cost of synthesis is a function of raw material costs and the labor time (translates to number of synthetic steps and risk of each step). All these parameters are datapoints we have access to or can model thro…

In my experience, cost is not related to materials and labor. For example, CROs know if they're likely the only company that can make a product and will charge accordingly. Often and to me sadly, a bidding processes is needed to determine market value of production. I've seen CROs instantly cut pricing in half if you present another option.

I would be cautious with chemical database (unsure which you are using) as there are companies that post chemicals as lead generation and cannot make them.

If you solve the selection of the best route, helping with sourcing the product may not be worth your resources. In other words, just that piece alone, if done well, is very valuable and hope the market sees it.

Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#14

Post by morraa »

kayhi wrote: post #13
morraa wrote: post #10

Earlier quoted context omitted.

Yes absolutely, the variance of pricing across different custom synthesis providers can be surprising. This we think though is actually an opportunity to serve our end users (drug hunters) better. Generally the cost of synthesis is a function of raw material costs and the labor time (translates to number of synthetic steps and risk of each step). All these parameters are datapoints we have access to or can model thro…

In my experience, cost is not related to materials and labor. For example, CROs know if they're likely the only company that can make a product and will charge accordingly. Often and to me sadly, a bidding processes is needed to determine market value of production. I've seen CROs instantly cut pricing in half if you present another option. I would be cautious with chemical database (unsure which you are using) as th…

Yes I guess I was referring to more robust, standard chemistry for which we would expect the pricing to be a little more formulaic.

And you make a great point. We've been constantly reminded that virtual spaces created by CROs are not always executable. As such we can actually constrain our algorithms to require very high probability of reaction success to remove false positives. We then tell the CRO what building blocks they need and the route design. We're still figuring how much of the lifecycle of making molecules is worth going after or, if indeed as you say, the route itself is the key solution.

Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#15

Post by JunkDNA »

morraa wrote: post #12
JunkDNA wrote: post #5

A few random thoughts I'm curious about (full disclosure: I worked in anti-infectives R&D as a bioinformatician early in my career for a major pharma) 1) One big challenge in synthesis is ensuring compound purity. Even when I was working in pharma, it was often the case that some of the compounds in the screening library could be contaminated with intermediates. This is murder for any kind of anti-infectives research…

1. We ensure that the compound is pure using analytical methods like NMR and LC/MS. In our Moonshot project, the assay cascade comprises biochemical assays against the main protease (2 different assay methodologies, run in Oxford and Weizmann Institute) and live virus assays, thus we should be able to infer whether the activity is caused by impurities killing the virus. In addition, we also perform high-throughput x-…

It didn't come across in my post in retrospect, but just want to say clearly I love this idea and the ambitious nature of it. I think when someone works in drug discovery, it's hard to escape this feeling that there has to be a better, faster, cheaper way. But at the same time, the reality of seeing how little we actually understand about biological systems on display each and every day tends to be quite a downer! The world sorely needs more of this kind of thinking.

Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#16

Post by coding123 »

nlh wrote: post #3

This is an EXCELLENT write-up. Thank you for both doing what you’re doing and for explaining it so well. I’m a software guy and have always found biosciences to be a mysterious black box, and you’ve cracked it open it in a wonderfully enlightening way. Best of luck to your team and the project!

Definitely an excellent write up if not one of the best Launch HN write ups I have seen.

Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#17

Post by morraa »

coding123 wrote: post #16
nlh wrote: post #3

This is an EXCELLENT write-up. Thank you for both doing what you’re doing and for explaining it so well. I’m a software guy and have always found biosciences to be a mysterious black box, and you’ve cracked it open it in a wonderfully enlightening way. Best of luck to your team and the project!

Definitely an excellent write up if not one of the best Launch HN write ups I have seen.

Very kind comment, thank you!

Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#18

Post by lukevp »

coding123 wrote: post #16
nlh wrote: post #3

This is an EXCELLENT write-up. Thank you for both doing what you’re doing and for explaining it so well. I’m a software guy and have always found biosciences to be a mysterious black box, and you’ve cracked it open it in a wonderfully enlightening way. Best of luck to your team and the project!

Definitely an excellent write up if not one of the best Launch HN write ups I have seen.

Agreed. I don’t think I can really help with this but I know exactly what they’re doing and wish them luck. The copy was very clear and immediately lends confidence to the team.

Re: Launch HN: PostEra (YC W20) Medicinal Chemistry-as-a-Service and Covid Moonshot

#20

Post by morraa »

drc007 wrote: post #19

Sounds interesting and I'll be following you with interest. That said in my experience deciding how to make a compound is not really the challenge, the real challenge is deciding what to make.

Certainly we can appreciate that better designs are important though we chose to focus on synthesis as there is an oversupply of algorithms in literature/industry that can suggest designs ideas (we published a few of our own) while the synthesis space was less explored and we think provides the biggest leverage point to speed up cycle times.

Ultimately when partnering with drug hunters, outside of our cloud-based platform, we offer the integration of molecular design with chemical synthesis as we believe computational approaches are at their most useful when these two aspects are coupled.

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