morraa

This looks very similar to our Moonshot open-science initiative and we love the idea of using crowdsourcing when such diseases lack commercial funding. If you know the folks who are organising this we'd be very happy to discuss with them.

Thanks for this. Always keen to learn from older startups but I was unable to find the company you're referring to -- any idea as to the name?

This could be my misunderstanding of the definition of "designer drugs" but I interpreted this as substances which mimic controlled substances but don't trigger drug classification or testing. Assuming this definition then this is something we wouldn't feel comfortable supporting regardless of the cash or demand. My understanding is that these substances are not tested in animal and human trials or approved by governing bodies like the FDA which are critical for the safety and efficacy of use.

Though please do correct me if I'm missing the use case you are referring to.

Yes, certainly an interesting idea. For now our models are trained on large corpora of organic chemistry reactions so our tech has some way to go before extrapolating outside this space.

Ah yes, industrializing the Chemistry part of drug discovery is certainly a blue sky dream but a field nonetheless we try to stay updated on -- hardware to do automated synthesis continues to make incremental improvements.

As a company we certainly work hard to ensure our technology is used for approved drug development. We have internal alerts as a company as to the risk of compounds being entered into our system and certainly suppliers and chemical manufacturers have high regulatory oversight. But yes there is always such an unfortunate risk but something we do spend time thinking about.

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.

Very kind comment, thank you!

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.

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.

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.

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 through ML. As such we've found that the ability to search large chemical databases is a huge saving when many clients may often just default to use a single CRO provider who may not be the best provider for their synthesis request. We are aiming to build a good network of reliable CRO providers to address the shortcoming and work with them to improve algorithms to optimize for reaction conditions etc.

Regarding pricing model this is something we are still working on. And yes you've hit the nail on the head -- We could charge the drug hunter (SaaS or IP) or we could charge the CROs that we send the custom synthesis to. Love to hear your thoughts here.

That's a great description. For now we are focused on helping others discover novel drugs (rather than developing our own) and we think using ML to design 'recipes', while solving logistical challenges of shipping molecules around the globe, is a really key part of that process. And yes the manufacturers do use our ML generated recipes to make the compounds.

Outside of this we also engage clients on more in-depth partnerships where we help design, make and test new drug candidates but again our real value-add/USP here is the 'make' stage.