7 ms·

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

52 points by katm 11y ago

alicexzhang 11y ago
Hi all! I'm one of the founders of Verge Genomics. We want to change the way drug discovery is done and are passionate about getting much-needed medicines into patients hands within their lifetimes. Happy to answer any questions!
- acalderaro 11y ago
  Hey! I'm a recent grad an have spent a lot of summers interning at some SF/Swiss Biotech companies and I'm particularly interested in how your software/algorithms work to directly impact the drug development process. Can you provide any insight or is everything still under wraps?
mswen 11y ago
I understand that journalists often create a simplified straw-man to contrast to a new and innovative upstart, however as someone who once served as an industry analyst at the intersection of life science discovery and technical computing this article's characterization of how big pharma approach drug discovery seems almost cartoon like in its stereotyping of the discovery and development process at big pharma. Can you point us to a link that has a more substantive discussion of the approach that you are taking?
- alicexzhang 11y ago
  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/nature08537.html http://www.nature.com/nature/journal/v461/n7266/full/nature0... http://www.nature.com/nrg/journal/v16/n8/pdf/nrg3934.pdf http://www.nature.com/nrg/journal/v16/n8/pdf/nrg3934.pdf
  - mswen 11y ago
    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 writing about their work. Admittedly, they were a small unit intended to drive innovation within discovery at that pharma. By 2007 it had been at least tried in most major pharma companies and John Russell was writing about the Awkward Adolescence of Systems Biology. http://www.bio-itworld.com/issues/2007/sept/cover-story/ http://www.bio-itworld.com/issues/2007/sept/cover-story/ Even if your characterization that large pharma prefer a different approach is mostly accurate it is a substantial disservice to the intelligence and hard work of hundreds of scientists who have worked on applying systems biology to the study of disease and treatments. Maybe I am over-reacting to this article and your video ...but from 2000 to 2004 I heard so many biotech and related software executives tell me that their company was going to solve these same discovery and development problems. Most faded into oblivion, others found a useful niche and a few got targets identified and development started and were acquired by a large pharma to bring them to market. I sincerely hope that you have discovered a new approach to system biology that will in fact provide breakthroughs. If you have something great let it stand on its own merits; there is no need to misrepresent the hard work and investments of other scientists or the companies they work for.
    - chuie 11y ago
      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.
      - DanBC 11y ago
        Does YC provide advice to tech companies about communicating complex ideas to not so technical writers and a non technical audience?
- dragonwriter 11y ago
  > I understand that journalists often create a simplified straw-man to contrast to a new and innovative upstart, however as someone who once served as an industry analyst at the intersection of life science discovery and technical computing this article's characterization of how big pharma approach drug discovery seems almost cartoon like in its stereotyping of the discovery and development process at big pharma. Journalists often don't create the simplified strawmen, the PR staff writing the press releases for the firm that they are covering do that for them.
w1ntermute 11y ago
The breathless tone of this TechCrunch article reminds me of this commentary on Atomwise (also a YC biotech): http://pipeline.corante.com/archives/2015/03/26/tone_it_down.php http://pipeline.corante.com/archives/2015/03/26/tone_it_down... In my opinion, YC has no idea what they're doing in biotech. Here's a much more credible neuro disease startup that was recently launched: http://www.forbes.com/sites/matthewherper/2015/05/14/former-genentech-researchers-raise-217-million-for-company-to-fight-alzheimers-and-parkinsons/ http://www.forbes.com/sites/matthewherper/2015/05/14/former-... I'm sure Alice and Jason are very intelligent and motivated, but the smart money's on Marc Tessier-Lavigne any day of the week. The industry dynamics of biotech are totally different - the small and nimble upstart with unconventional thinking rarely wins.
- deleted 11y ago
  [deleted]
- cge 11y ago
  This is what happens with media coverage of pharmaceutical development, and often science in general. Journalists want stories that people can relate to, that don't have the uncertainty that is inherent in science, and that will grab the public's attention. The ridiculous tone is often something that horrifies the people being reported on, but seems very difficult to escape. It doesn't help that here, I think, we're seeing a community and media largely centered around software development trying to deal with a field that is far, far riskier, and has far less certainty at every step. 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.
- eliben 11y ago
  Whether YC has an idea on biotech or not, I'm very happy to see more startups in this domain. I think we've had enough social networks and mobile app frameworks. Seriously cool that YC starts backing companies that want to bring real change to the world.
- 11y ago
lvs 11y ago
> 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.
- blacksmith_tb 11y ago
  Right, if they'd said "Verge hopes to be able to cure brain diseases 1000x more quickly" we might cut them some slack. Not to mention that many of these diseases haven't been cured by anyone before, 'big pharma' included, so I don't know how you'd estimate the improvement in time to market...
  - ams6110 11y ago
    Considering that the best ALS drugs cost about $1000/month and have results that statistically are barely distinguishable from placebos, there's a long way to go.
- bbgm 11y ago
  My biggest fear is that the folks at YC actually believe claims like that.
- chenja 11y ago
  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.
  - dekhn 11y ago
    So you've got one drug lead, and haven't gotten anything to market yet that I can tell- are you leads in Phase I, II, or III trials now? It is highly misleading to use the term cure in this case. You simply have no data to support that your costs are any lower than pharma until you actually show people being cured, and I think Phase II or III is the actual point where you can claim initial cure results, and it's not until the drug has been widely deployed for years without side effects that you can claim it's a treatment or a cure.
cge 11y ago
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 diseases with perhaps randomly misfolded proteins that recruit others and propagate through the brain is correct, for example, will targeting gene expression be able to do that much beyond treating symptoms? And if targeting genes that are not necessarily I'm divided on the usual search-of-preapproved-drug approach too. On the one hand, it vastly lowers costs, speeds up trials, and can actually make development somewhat feasible for startups, but on the other, it does really feel like searching through a bunch of drug candidates that have no reason why they'd be effective for your targets. It's unfortunate we don't have a better approach here. And of course, as I'm sure you know, success in mouse models often translates to nothing at all in humans. I'd be curious to know what sort of genomic data you're actually using for your analysis. Again, though, it's great to see a startup working in this area, and I'll look forward to seeing what you come up with.
- chenja 11y ago
  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!
searine 11y ago
Genomic vapor ware. When will people understand the problem with genomics isn't complexity, it is a lack of raw data. We simply have not collected enough annotation on what every gene does and how it interacts. Without that information, you have diddly-squat.
- toufka 11y ago
  "Garbage in, garbage out", or, "give me enough degrees of freedom and I can fit an elephant". It's a reasonable retort given what's on display here. On the other hand, if you do collect enough data in a particular domain to be able to call some interesting targets, it's straight-forward enough to validate the method. To presume generality (as the scientists probably do not, though as the article and every writeup I've seen here do) is surely foolhardy. As a side note, if the company wishes to pretty much sell to 'big pharma', why then do they publish these touchy-feely tech-crunch articles at all? Their website is designed for all those web-2.0 ideals of retaining customers and click-through and responsiveness, etc. But I doubt Roche cares about any of those things...
- bjwbell 11y ago
  The devil is in the details. Look at all the drug trials that work in mice or even monkeys but not humans.
- et2o 11y ago
  This isn't 100% wrong, but it's definitely close. To out it vaguely, there is enormous complexity and structure that we can't even model yet.
- gmarx 11y ago
  it might be fairer to say that before we even get to the complexity problem we have to solve the raw data problem.
chuie 11y ago
I have a hard time believing that large pharma research labs are limiting themselves to single loci for a given disease phenotype. But if they are, it makes sense why YC would see value in this.
- mswen 11y ago
  They aren't
  - chuie 11y ago
    I'm going to presume that I don't really understand the company then, because the founders and advisers should certainly know more than I do about drug discovery.
    - w1ntermute 11y ago
      > the founders and advisers should certainly know more than I do about drug discovery Unfortunately, the operative word here appears to be "should."
      - chenja 11y ago
        We are definitely not experts in regards to pharma (neither Alice or I have experience working in pharma) but our advisors include pharma consultants and senior scientists. We're constantly engaging them and meeting with pharma execs and scientists almost daily to learn what has and hasn't worked, and have received a lot of feedback about how to bring potential new drugs to patients. There's a line between being naive and being jaded and we are trying to stick to being as realistic as possible, and value any new information or feedback, if you know anything that's contrary to our experience.
- bbgm 11y ago
  They haven't for a while. Some of the claims, at least in this story, are way over the top.

52 points by katm 11y ago

Hi all! I'm one of the founders of Verge Genomics. We want to change the way drug discovery is done and are passionate about getting much-needed medicines into patients hands within their lifetimes. Happy to answer any questions!

acalderaro 11y ago
Hey! I'm a recent grad an have spent a lot of summers interning at some SF/Swiss Biotech companies and I'm particularly interested in how your software/algorithms work to directly impact the drug development process. Can you provide any insight or is everything still under wraps?

mswen 11y ago

I understand that journalists often create a simplified straw-man to contrast to a new and innovative upstart, however as someone who once served as an industry analyst at the intersection of life science discovery and technical computing this article's characterization of how big pharma approach drug discovery seems almost cartoon like in its stereotyping of the discovery and development process at big pharma. Can you point us to a link that has a more substantive discussion of the approach that you are taking?

alicexzhang 11y ago
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/nature08537.html http://www.nature.com/nature/journal/v461/n7266/full/nature0... http://www.nature.com/nrg/journal/v16/n8/pdf/nrg3934.pdf http://www.nature.com/nrg/journal/v16/n8/pdf/nrg3934.pdf
- mswen 11y ago
  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 writing about their work. Admittedly, they were a small unit intended to drive innovation within discovery at that pharma. By 2007 it had been at least tried in most major pharma companies and John Russell was writing about the Awkward Adolescence of Systems Biology. http://www.bio-itworld.com/issues/2007/sept/cover-story/ http://www.bio-itworld.com/issues/2007/sept/cover-story/ Even if your characterization that large pharma prefer a different approach is mostly accurate it is a substantial disservice to the intelligence and hard work of hundreds of scientists who have worked on applying systems biology to the study of disease and treatments. Maybe I am over-reacting to this article and your video ...but from 2000 to 2004 I heard so many biotech and related software executives tell me that their company was going to solve these same discovery and development problems. Most faded into oblivion, others found a useful niche and a few got targets identified and development started and were acquired by a large pharma to bring them to market. I sincerely hope that you have discovered a new approach to system biology that will in fact provide breakthroughs. If you have something great let it stand on its own merits; there is no need to misrepresent the hard work and investments of other scientists or the companies they work for.
  - chuie 11y ago
    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.
    - DanBC 11y ago
      Does YC provide advice to tech companies about communicating complex ideas to not so technical writers and a non technical audience?
dragonwriter 11y ago
> I understand that journalists often create a simplified straw-man to contrast to a new and innovative upstart, however as someone who once served as an industry analyst at the intersection of life science discovery and technical computing this article's characterization of how big pharma approach drug discovery seems almost cartoon like in its stereotyping of the discovery and development process at big pharma. Journalists often don't create the simplified strawmen, the PR staff writing the press releases for the firm that they are covering do that for them.

w1ntermute 11y ago

The breathless tone of this TechCrunch article reminds me of this commentary on Atomwise (also a YC biotech): http://pipeline.corante.com/archives/2015/03/26/tone_it_down.php http://pipeline.corante.com/archives/2015/03/26/tone_it_down... In my opinion, YC has no idea what they're doing in biotech. Here's a much more credible neuro disease startup that was recently launched: http://www.forbes.com/sites/matthewherper/2015/05/14/former-genentech-researchers-raise-217-million-for-company-to-fight-alzheimers-and-parkinsons/ http://www.forbes.com/sites/matthewherper/2015/05/14/former-... I'm sure Alice and Jason are very intelligent and motivated, but the smart money's on Marc Tessier-Lavigne any day of the week. The industry dynamics of biotech are totally different - the small and nimble upstart with unconventional thinking rarely wins.

deleted 11y ago
[deleted]
cge 11y ago
This is what happens with media coverage of pharmaceutical development, and often science in general. Journalists want stories that people can relate to, that don't have the uncertainty that is inherent in science, and that will grab the public's attention. The ridiculous tone is often something that horrifies the people being reported on, but seems very difficult to escape. It doesn't help that here, I think, we're seeing a community and media largely centered around software development trying to deal with a field that is far, far riskier, and has far less certainty at every step. 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.
eliben 11y ago
Whether YC has an idea on biotech or not, I'm very happy to see more startups in this domain. I think we've had enough social networks and mobile app frameworks. Seriously cool that YC starts backing companies that want to bring real change to the world.
11y ago

lvs 11y ago

> 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.

blacksmith_tb 11y ago
Right, if they'd said "Verge hopes to be able to cure brain diseases 1000x more quickly" we might cut them some slack. Not to mention that many of these diseases haven't been cured by anyone before, 'big pharma' included, so I don't know how you'd estimate the improvement in time to market...
- ams6110 11y ago
  Considering that the best ALS drugs cost about $1000/month and have results that statistically are barely distinguishable from placebos, there's a long way to go.
bbgm 11y ago
My biggest fear is that the folks at YC actually believe claims like that.
chenja 11y ago
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.
- dekhn 11y ago
  So you've got one drug lead, and haven't gotten anything to market yet that I can tell- are you leads in Phase I, II, or III trials now? It is highly misleading to use the term cure in this case. You simply have no data to support that your costs are any lower than pharma until you actually show people being cured, and I think Phase II or III is the actual point where you can claim initial cure results, and it's not until the drug has been widely deployed for years without side effects that you can claim it's a treatment or a cure.

cge 11y ago

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 diseases with perhaps randomly misfolded proteins that recruit others and propagate through the brain is correct, for example, will targeting gene expression be able to do that much beyond treating symptoms? And if targeting genes that are not necessarily I'm divided on the usual search-of-preapproved-drug approach too. On the one hand, it vastly lowers costs, speeds up trials, and can actually make development somewhat feasible for startups, but on the other, it does really feel like searching through a bunch of drug candidates that have no reason why they'd be effective for your targets. It's unfortunate we don't have a better approach here. And of course, as I'm sure you know, success in mouse models often translates to nothing at all in humans. I'd be curious to know what sort of genomic data you're actually using for your analysis. Again, though, it's great to see a startup working in this area, and I'll look forward to seeing what you come up with.

chenja 11y ago
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!

searine 11y ago

Genomic vapor ware. When will people understand the problem with genomics isn't complexity, it is a lack of raw data. We simply have not collected enough annotation on what every gene does and how it interacts. Without that information, you have diddly-squat.

toufka 11y ago
"Garbage in, garbage out", or, "give me enough degrees of freedom and I can fit an elephant". It's a reasonable retort given what's on display here. On the other hand, if you do collect enough data in a particular domain to be able to call some interesting targets, it's straight-forward enough to validate the method. To presume generality (as the scientists probably do not, though as the article and every writeup I've seen here do) is surely foolhardy. As a side note, if the company wishes to pretty much sell to 'big pharma', why then do they publish these touchy-feely tech-crunch articles at all? Their website is designed for all those web-2.0 ideals of retaining customers and click-through and responsiveness, etc. But I doubt Roche cares about any of those things...
bjwbell 11y ago
The devil is in the details. Look at all the drug trials that work in mice or even monkeys but not humans.
et2o 11y ago
This isn't 100% wrong, but it's definitely close. To out it vaguely, there is enormous complexity and structure that we can't even model yet.
gmarx 11y ago
it might be fairer to say that before we even get to the complexity problem we have to solve the raw data problem.

chuie 11y ago

I have a hard time believing that large pharma research labs are limiting themselves to single loci for a given disease phenotype. But if they are, it makes sense why YC would see value in this.

mswen 11y ago
They aren't
- chuie 11y ago
  I'm going to presume that I don't really understand the company then, because the founders and advisers should certainly know more than I do about drug discovery.
  - w1ntermute 11y ago
    > the founders and advisers should certainly know more than I do about drug discovery Unfortunately, the operative word here appears to be "should."
    - chenja 11y ago
      We are definitely not experts in regards to pharma (neither Alice or I have experience working in pharma) but our advisors include pharma consultants and senior scientists. We're constantly engaging them and meeting with pharma execs and scientists almost daily to learn what has and hasn't worked, and have received a lot of feedback about how to bring potential new drugs to patients. There's a line between being naive and being jaded and we are trying to stick to being as realistic as possible, and value any new information or feedback, if you know anything that's contrary to our experience.
bbgm 11y ago
They haven't for a while. Some of the claims, at least in this story, are way over the top.