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Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

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Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#41

Post by w1ntermute »

timr wrote: post #38
bbgm wrote: post #36

Earlier quoted context omitted.

The thing is this kind of idea is not new. Finding new targets is hard science that needs a ton of experiments to validate that your theoretical models even work. For now this is low risk and no cost to the pharma partner, but it's a not a new model and in my experience not one that works.

"The thing is this kind of idea is not new." ...most startup companies aren't doing anything new. How many different food-delivery services has YC funded? Photo-sharing services? Video startups? AirBnB wasn't anything new in 2007, either. Dropbox was criticized because everyone knew that file sharing had been done before. This goes back to what I was saying about biotech being stodgy: the one thing the software indus…

> ...most startup companies aren't doing anything new. How many different food-delivery services has YC funded? Photo-sharing services? Video startups? AirBnB wasn't anything new in 2007, either. Dropbox was criticized because everyone knew that file sharing had been done before.

There's a fundamental difference between trying something again where the customers weren't receptive and trying something again where the product couldn't be created. Customer reception can change over time, often quite rapidly and drastically, making previously failed business models successful (ex: Webvan -> Instacart). But nature doesn't just change (at least not over short timescales).

Moreover, as cge explains elsewhere in this thread, you cannot really iterate in biotech:

> Good ideas in software might not catch on, but good ideas in science more often than not turn out to be entirely wrong. Do a closed beta of your software, too, and while your users might not end up liking the software much, it's very unlikely that it's just going to fundamentally fail to work at all. Clinical trials can often end up that way.

Contrast this to business model-based innovation in tech, where a slight tweak can be the difference between a unicorn and a dud.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#42

Post by bbgm »

timr wrote: post #38
bbgm wrote: post #36

Earlier quoted context omitted.

The thing is this kind of idea is not new. Finding new targets is hard science that needs a ton of experiments to validate that your theoretical models even work. For now this is low risk and no cost to the pharma partner, but it's a not a new model and in my experience not one that works.

"The thing is this kind of idea is not new." ...most startup companies aren't doing anything new. How many different food-delivery services has YC funded? Photo-sharing services? Video startups? AirBnB wasn't anything new in 2007, either. Dropbox was criticized because everyone knew that file sharing had been done before. This goes back to what I was saying about biotech being stodgy: the one thing the software indus…

Biotech startups with a computational method of target discovery that is "different from the norm at Big Pharma" have been around at least since the late 90s. The problem is targets are cheap. Validating those targets is expensive and is the rate limiting step. I have no problems with these companies existing. They should and can tackle some hard problems and develop algorithms and methods that are difficult to pursue in Big Pharma. The problem is that too many are presented as silver bullets that will magically cure xyz, and that's just false.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#43

Post by chenja »

w1ntermute wrote: post #32
sethbannon wrote: post #29

Earlier quoted context omitted.

It's true that Moore's law doesn't apply everywhere. In fact, some costs (like the costs of sequencing a human genome) are falling much faster than Moore's law would predict: https://upload.wikimedia.org/wikipedia/commons/b/b7/DNA_Sequ...

1. That graph completely omits the quality of the sequence data being generated (hint: it's pretty terrible). 2. Hyping up cheaper sequencing the way you are is nothing more than what Sydney Brenner referred to as "low-input, high-throughput, no-output biology" (video source: http://thesciencenetwork.org/programs/reading-the-human-geno... ). Also see: http://wavefunction.fieldofscience.com/2015/03/cancer-genomi... 3.…

While cheaper sequencing hasn't really produced much in the way of new treatments (yet), I disagree that it hasn't been productive or that sequence data is of low accuracy. For example, it is striking to see how relatively little was known about Mendelian disease genes before 1990 (see https://www.genome.gov/Multimedia/Slides/GSPFuture2014/04_Mc..., slide 6, as an example for retinal diseases). I think one of the most frustrating things now is that the price of sequencing isn't continuing to decrease.

You bring up another good point about "Eroom's Law" in which pharma productivity is actually decreasing, and that article was actually one of the things that got us interested in trying to do something new. What we are trying to do is to help reverse that trend by doing something different than what large pharma companies are already working on - if we keep doing the same thing despite ever-decreasing productivity, then I don't see how we can expect the trend to change.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#44

Post by chenja »

mswen wrote: post #16
alicexzhang wrote: post #4

Earlier quoted context omitted.

Hi there - thanks for the interest! For a more technical dissection of some of the genomics approaches we employ to identify neurodegenerative disease targets, check out these reviews: http://www.nature.com/nature/journal/v461/n7266/full/nature0... http://www.nature.com/nrg/journal/v16/n8/pdf/nrg3934.pdf

I don't currently have access to those publications and not willing to pay just to read these articles but from the titles, abstracts and citations it sounds like basically you are taking a systems biology and GWAS approach? The Institute for Systems Biology has been around since 2000. I remember interviewing people in an internal systems biology group at one of the largest pharma companies in the world in 2004 and w…

I really appreciate your feedback and of course we have studied a lot of what worked (and mostly, didn't work) in systems biology over the past decade, but the field has shifted dramatically since 2004. A lot more data is available, and experiments are designed much more carefully nowadays. In fact, the thing we worry about most is that the field still isn't rigorous enough and the quality of the data still isn't good enough to translate into druggable targets. And we don't intend to belittle the work of scientists who really laid the foundation for what we are trying to do today, but surprisingly few of the big pharma companies we talked to have active systems biology programs for neurological diseases (we have also learned about others, like at Janssen, that are just getting started). I think it's not a question of if systems biology will lead to new therapies, but rather when the methods and field are mature enough.

Also regarding articles, please email me at jason@vergegenomics.com and I will send you PDF versions to read.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#45

Post by timr »

bbgm wrote: post #42
timr wrote: post #38

Earlier quoted context omitted.

"The thing is this kind of idea is not new." ...most startup companies aren't doing anything new. How many different food-delivery services has YC funded? Photo-sharing services? Video startups? AirBnB wasn't anything new in 2007, either. Dropbox was criticized because everyone knew that file sharing had been done before. This goes back to what I was saying about biotech being stodgy: the one thing the software indus…

Biotech startups with a computational method of target discovery that is "different from the norm at Big Pharma" have been around at least since the late 90s. The problem is targets are cheap. Validating those targets is expensive and is the rate limiting step. I have no problems with these companies existing. They should and can tackle some hard problems and develop algorithms and methods that are difficult to pursu…

Yeah, I know what you're saying here, and I don't disagree. I only disagree with the comment that they aren't "doing something new". It's sufficient to do some old thing better in some way that matters to existing customers -- and that's an implementation detail that will never come out of a TechCrunch press release.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#46

Post by timr »

w1ntermute wrote: post #41
timr wrote: post #38

Earlier quoted context omitted.

"The thing is this kind of idea is not new." ...most startup companies aren't doing anything new. How many different food-delivery services has YC funded? Photo-sharing services? Video startups? AirBnB wasn't anything new in 2007, either. Dropbox was criticized because everyone knew that file sharing had been done before. This goes back to what I was saying about biotech being stodgy: the one thing the software indus…

> ...most startup companies aren't doing anything new. How many different food-delivery services has YC funded? Photo-sharing services? Video startups? AirBnB wasn't anything new in 2007, either. Dropbox was criticized because everyone knew that file sharing had been done before. There's a fundamental difference between trying something again where the customers weren't receptive and trying something again where the…

The difference between success and failure in biotech lead generation is finding a good lead.

That's something that is strongly influenced by luck. I can point to famous researchers who have made entire careers out of this sort of momentary serendipity, actually.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#47

Post by chenja »

bbgm wrote: post #42
timr wrote: post #38

Earlier quoted context omitted.

"The thing is this kind of idea is not new." ...most startup companies aren't doing anything new. How many different food-delivery services has YC funded? Photo-sharing services? Video startups? AirBnB wasn't anything new in 2007, either. Dropbox was criticized because everyone knew that file sharing had been done before. This goes back to what I was saying about biotech being stodgy: the one thing the software indus…

Biotech startups with a computational method of target discovery that is "different from the norm at Big Pharma" have been around at least since the late 90s. The problem is targets are cheap. Validating those targets is expensive and is the rate limiting step. I have no problems with these companies existing. They should and can tackle some hard problems and develop algorithms and methods that are difficult to pursu…

We have been actively validating targets, and in fact Alice's PhD work was centered on performing the in vitro and in vivo validation experiments for computational drug leads. We aren't asking for people to believe in magic, and ultimately we hope that our preclinical experiments will reveal whether or not we have something.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#48

Post by chenja »

DanBC wrote: post #27
chuie wrote: post #25

Earlier quoted context omitted.

Keep in mind that this article was not written by the founders of Verge Genomics, but by a journalist who "writes about internet culture, social networks, and consumer-facing technology." So they are probably going to use speech that will make the more science/biotech literate person bristle.

Does YC provide advice to tech companies about communicating complex ideas to not so technical writers and a non technical audience?

YC doesn't provide advice about this in a systematic way, but we have been trying to learn how to engage the lay public mostly from talking to other YC founders. It's hard to communicate the exact details that we want to share, but I hope that the spirit of our ideas comes across clearly.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#49

Post by chenja »

lvs wrote: post #6

> But Verge Genomics is able to cure brain diseases 1000x more quickly than big pharma by using algorithms Guffaw. Tech journalism at its finest. The company sounds great, but I'm not sure Techcrunch is really doing them a lot of favors by just making stuff up.

The 1000X number should only be attached to "cheaper", and comes from in vivo and in vitro validation experiments we have done; our drug hit rate was almost 1000X higher than high-throughput screens from the literature, and our total spend to get to our one drug lead was almost that many times cheaper than what we learned that pharma spends. We think we are faster as well (our first proof-of-concept study took about 9 months, which is faster but definitely not 1000X as fast), but I think the most important thing is to find something that actually works to treat patients. That's what we want to prove out with backing from YC.

Re: Verge Genomics (YC S15) Wants to Cure Neurodegenerative Diseases with Algorithms

#50

Post by chenja »

cge wrote: post #7

It's always great to see new approaches to pharmaceutical development. It's a field that's desperately in need of a better approach. I do have to wonder, however, when having a focus on neurodegenerative diseases that are largely seen as proteopathies, how useful a method that is presumably targeting only gene expression can be, which is what I assume you're targeting. If the view of diseases like PD as prion-like di…

I am a big believer in the prion-like spread hypothesis which seems to be a common thread for neurodegenerative disease, and led a study (in press) that supports this idea in Alzheimer's disease and frontotemporal dementia. Once there is a critical mass, I think it would be challenging to slow the progression of the disease, which may speak to the importance of early treatment. However, given the proven genetic risk factors for these diseases (Mendelian forms, GWAS hits) - which are related to things like UPR, microglia activation, etc - I think that there is a possibility to slow the progression of disease. We also feel the same way you do about the repositioning angle, but it is a nice way to try to get something safe to patients that can potentially be proven quickly and cheaply in a small Phase 2 trial.

In terms of the expression data for diseases, we are doing a systemic review and re-analysis of publically available raw micoarray data from GEO, as well as RNA-sequencing and microarray data that we will publish soon and make publically available. That part is what I mentioned in the video; rather than just looking for differentially expressed genes (which is what most of the associated studies have done), we use network methods we developed to identify what we think are the key drivers of disease. Also, by combining data we get more power to find signal. To match these with drugs, we use a combination of proprietary gene expression data as well as data from large public projects.

Thanks for your comments and wishes!

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