7 ms·

Project Marilyn Part I: Non-Patented Cancer Pharmaceutical

95 points by ajaymehta 13y ago

pallandt 13y ago
For anyone else wondering on what types of cancer this might work on, from [1]: Q: Which cancers will 9DS work on? A: We don't have a definitive answer, but initial tests show that it's strongest against some forms of renal (kidney) cancer, melanoma(skin) cancer, and triple-negative breast cancer. We have reason to believe that variants of 9DS will target different cancer types, as well. [1]: http://www.indysci.org/details.html http://www.indysci.org/details.html "Details"
- ThomPete 13y ago
  Well given I already had one melanoma I would be interesting in anything that solves that area. But how do a layman determine whether they are on to something or not?
  - dnautics 13y ago
    (founder of indysci/main researcher on this project here). That's a great question. And I don't have a good answer for you. Any suggestions would be welcome.
    - ISL 13y ago
      This is the question you most need to answer. Why is this project, of all possible projects, a good scientific bet? Biology is complicated, which makes layman explanations a challenge. Perhaps the best you can do is lay out in clear terms what you know and what you don't. This compound has been shown to be XXX±XXX% effective against these three cancers. It has also been shown to kill 90% of test animals. These three respected theory papers [1,2,3] have highlighted the fact that, if only the animals hadn't died, this compound would be more promising than YYY,ZZZ, and QQQ. Furthermore, in these references [4-10], making the modification we propose to make (9DS) in other related substances has been shown to reduce lethality by 100x. Our goal is to explore this alteration to see if we can address the lethality of the compound while preserving its anti-cancer properties. Give people the references, and some laymen will dig all day long. Motivated people are really smart.
      - dnautics 13y ago
        like this? http://www.indysci.org/details.html http://www.indysci.org/details.html
        ISL 13y ago
        Yes, but with well-supported numbers (and uncertainties) and links to references? Not trying to be a hard-ass, just stating what I'd look for in either a paper up for funding review or for making my own crowdfunded investment. You guys are doing something awesome.
        dnautics 13y ago
        totally understood. It's really good that you're holding my feet to the fire. It's a little bit buried, but linked from the "details" page is the full proposal: https://drive.google.com/file/d/0By7AdX1eMEY2ZXZ5RzZ0Vl9QZG8/edit?usp=sharing https://drive.google.com/file/d/0By7AdX1eMEY2ZXZ5RzZ0Vl9QZG8... I apologize, I had accidentally put in a wrong link there previously, it's been fixed, but the file has been publically available and visible for a while. Some non-scientific aspects (like our launch date) have obviously been changed at the last minute, but the proposal stands.
  - JohnHaugeland 13y ago
    Generally speaking you don't. This is research funding. He's trying to raise money to see if it's something or not. If he can raise the money this way, then he can release it without patent encumbrance, and it's for everyone - including the world's poor. Most drugs fail. This one probably will too. I gave because I want to see intellectual property not be the only viable funding path anymore.
    - ThomPete 13y ago
      I appreciate that but I guess I am a little more biased perhaps because of my history.
    - dnautics 13y ago
      well we are trying to stack the deck in the drug's favor. A few things: 1) it's a "natural product derivative". These compounds do way way better than most other drug classes. 2) it has single-digit nanomolar activity in the dish. This is on-par and competitive with currently used chemotherapeutics, a prerequisite for any sort of chemotherapy. 3) there is another compound in the same family called SJG-136 which has passed phase II. 4) phase I trials for SJG-136 apparently showed extremely mild side effects. I still need to double-check clinicaltrials.gov on this, this was a personal communication from the developer of SJG-136. Because SJG-136 and 9DS broadly share the same mechanism it's very likely that 9DS will also have mild side effects. To answer ThomPete's question, I'm not sure how I can verify this besides "trust me" to the layperson (especially #4). However, there is literature on #1 and #2, although, again I'm not sure how useful this is to the lay person. #1: http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7915.2010.00221.x/abstract http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7915.2010.... #2: https://www.ncbi.nlm.nih.gov/pubmed/22390171 https://www.ncbi.nlm.nih.gov/pubmed/22390171
      - ThomPete 13y ago
        Thanks I will have a look and just to be clear, I trust your intend 100%. I have been lucky enough to be accepted at Sloan Memorial en New York given I have more than a thousand moles. I wonder if I could ask my dermatologist there.
tocomment 13y ago
This page isn't working? http://www.indysci.org/details.html http://www.indysci.org/details.html
- dnautics 13y ago
  sorry, it should work now. We redid the site and did a CNAME change; some people aren't getting the DNS-updated version yet =(
jdorw 13y ago
When you say "open notebook" does that mean outside people can see your results and contribute intellectually to the project? Is there a synthetic route to 9DS? I didn't see much on a quick google search but it doesn't look like a terribly difficult molecule to make.
- dnautics 13y ago
  see our results, definitely (I'll be working on some software to get this to work, but our fallback is to just use mediawiki). Contribute intellectually - we should have some sort of commenting system. 9DS is probably synthetically tractable, but attachment of the sugar typically uses chemistry that destroys the imine on the other side, and vice versa. So that kicks any industrial processes in the knees.
throwaway_yy2Di 13y ago
For perspective, the average R&D cost per successful drug is somewhere well into the billions: http://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-staggering-cost-of-inventing-new-drugs/ http://www.forbes.com/sites/matthewherper/2012/02/10/the-tru... Not sure what the idea is here. Going by cold statistics, this will cost orders of magnitude more than they are seeking from crowd funding. And even then, with overwhelming likelihood, it will fail in clinical trials.
- dnautics 13y ago
  that is total R&D cost divided by successful drugs. So think, a lot of failed candidates, dumb ideas, and since pharma is siloed and closed, duplicated effort between different companies' skunk works. Also, regulatory burden for things that are lifestyle drugs (think: viagra) is understandably higher than a chemotherapeutic. The actual cost of getting a chemotherapeutic developed is about 1-2 million in preclinical, and 12-20 million through clinical. Counting lots of inefficiencies, and, as I discuss downthread, we're stacking the deck in our favor. Indeed, though your broader point is correct, clinical is more expensive and I think ultimately that should be done by a for-profit entity. But crowdfunding can nudge things in that direction by completing the preclinical.
  - throwaway_yy2Di 13y ago
    Of course it's including the failures, we don't know whether your candidate will succeed. I'm reasoning in terms of the expectation value of the a success: the cost of one project such as yours, divided by the probability of it creating a useful drug. "The actual cost of getting a chemotherapeutic developed is about 1-2 million in preclinical, and 12-20 million through clinical. Counting lots of inefficiencies, and, as I discuss downthread, we're stacking the deck in our favor." That's only part of the equation. What's the probability that it fails preclinical or clinical trials? What are the historical success rates for chemotherapeutics? (Serious question) edit: I've Googled up what I think is a relevant statistic? According to this source, of cancer drug candidates which completed US clinical trials between 2004-2011, 6.7% of the ones which entered phase I ended up as approved drugs (the rest failing out). Apparently this is much worse than non-cancer drugs, which have a 12.1% rate. http://www.biotech-now.org/business-and-investments/2012/02/oncology-clinical-trials-secrets-of-success# http://www.biotech-now.org/business-and-investments/2012/02/...
shiven 13y ago
What about drug resistance? Any data available/planned in that regard? Curious about it, because I work on this stuff from a structural perspective as my profession.

95 points by ajaymehta 13y ago

For anyone else wondering on what types of cancer this might work on, from [1]: Q: Which cancers will 9DS work on? A: We don't have a definitive answer, but initial tests show that it's strongest against some forms of renal (kidney) cancer, melanoma(skin) cancer, and triple-negative breast cancer. We have reason to believe that variants of 9DS will target different cancer types, as well. [1]: http://www.indysci.org/details.html http://www.indysci.org/details.html "Details"

ThomPete 13y ago
Well given I already had one melanoma I would be interesting in anything that solves that area. But how do a layman determine whether they are on to something or not?
- dnautics 13y ago
  (founder of indysci/main researcher on this project here). That's a great question. And I don't have a good answer for you. Any suggestions would be welcome.
  - ISL 13y ago
    This is the question you most need to answer. Why is this project, of all possible projects, a good scientific bet? Biology is complicated, which makes layman explanations a challenge. Perhaps the best you can do is lay out in clear terms what you know and what you don't. This compound has been shown to be XXX±XXX% effective against these three cancers. It has also been shown to kill 90% of test animals. These three respected theory papers [1,2,3] have highlighted the fact that, if only the animals hadn't died, this compound would be more promising than YYY,ZZZ, and QQQ. Furthermore, in these references [4-10], making the modification we propose to make (9DS) in other related substances has been shown to reduce lethality by 100x. Our goal is to explore this alteration to see if we can address the lethality of the compound while preserving its anti-cancer properties. Give people the references, and some laymen will dig all day long. Motivated people are really smart.
    - dnautics 13y ago
      like this? http://www.indysci.org/details.html http://www.indysci.org/details.html
      - ISL 13y ago
        Yes, but with well-supported numbers (and uncertainties) and links to references? Not trying to be a hard-ass, just stating what I'd look for in either a paper up for funding review or for making my own crowdfunded investment. You guys are doing something awesome.
        dnautics 13y ago
        totally understood. It's really good that you're holding my feet to the fire. It's a little bit buried, but linked from the "details" page is the full proposal: https://drive.google.com/file/d/0By7AdX1eMEY2ZXZ5RzZ0Vl9QZG8/edit?usp=sharing https://drive.google.com/file/d/0By7AdX1eMEY2ZXZ5RzZ0Vl9QZG8... I apologize, I had accidentally put in a wrong link there previously, it's been fixed, but the file has been publically available and visible for a while. Some non-scientific aspects (like our launch date) have obviously been changed at the last minute, but the proposal stands.
- JohnHaugeland 13y ago
  Generally speaking you don't. This is research funding. He's trying to raise money to see if it's something or not. If he can raise the money this way, then he can release it without patent encumbrance, and it's for everyone - including the world's poor. Most drugs fail. This one probably will too. I gave because I want to see intellectual property not be the only viable funding path anymore.
  - ThomPete 13y ago
    I appreciate that but I guess I am a little more biased perhaps because of my history.
  - dnautics 13y ago
    well we are trying to stack the deck in the drug's favor. A few things: 1) it's a "natural product derivative". These compounds do way way better than most other drug classes. 2) it has single-digit nanomolar activity in the dish. This is on-par and competitive with currently used chemotherapeutics, a prerequisite for any sort of chemotherapy. 3) there is another compound in the same family called SJG-136 which has passed phase II. 4) phase I trials for SJG-136 apparently showed extremely mild side effects. I still need to double-check clinicaltrials.gov on this, this was a personal communication from the developer of SJG-136. Because SJG-136 and 9DS broadly share the same mechanism it's very likely that 9DS will also have mild side effects. To answer ThomPete's question, I'm not sure how I can verify this besides "trust me" to the layperson (especially #4). However, there is literature on #1 and #2, although, again I'm not sure how useful this is to the lay person. #1: http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7915.2010.00221.x/abstract http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7915.2010.... #2: https://www.ncbi.nlm.nih.gov/pubmed/22390171 https://www.ncbi.nlm.nih.gov/pubmed/22390171
    - ThomPete 13y ago
      Thanks I will have a look and just to be clear, I trust your intend 100%. I have been lucky enough to be accepted at Sloan Memorial en New York given I have more than a thousand moles. I wonder if I could ask my dermatologist there.

tocomment 13y ago

This page isn't working? http://www.indysci.org/details.html http://www.indysci.org/details.html

dnautics 13y ago
sorry, it should work now. We redid the site and did a CNAME change; some people aren't getting the DNS-updated version yet =(

jdorw 13y ago

When you say "open notebook" does that mean outside people can see your results and contribute intellectually to the project? Is there a synthetic route to 9DS? I didn't see much on a quick google search but it doesn't look like a terribly difficult molecule to make.

dnautics 13y ago
see our results, definitely (I'll be working on some software to get this to work, but our fallback is to just use mediawiki). Contribute intellectually - we should have some sort of commenting system. 9DS is probably synthetically tractable, but attachment of the sugar typically uses chemistry that destroys the imine on the other side, and vice versa. So that kicks any industrial processes in the knees.

throwaway_yy2Di 13y ago

For perspective, the average R&D cost per successful drug is somewhere well into the billions: http://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-staggering-cost-of-inventing-new-drugs/ http://www.forbes.com/sites/matthewherper/2012/02/10/the-tru... Not sure what the idea is here. Going by cold statistics, this will cost orders of magnitude more than they are seeking from crowd funding. And even then, with overwhelming likelihood, it will fail in clinical trials.

dnautics 13y ago
that is total R&D cost divided by successful drugs. So think, a lot of failed candidates, dumb ideas, and since pharma is siloed and closed, duplicated effort between different companies' skunk works. Also, regulatory burden for things that are lifestyle drugs (think: viagra) is understandably higher than a chemotherapeutic. The actual cost of getting a chemotherapeutic developed is about 1-2 million in preclinical, and 12-20 million through clinical. Counting lots of inefficiencies, and, as I discuss downthread, we're stacking the deck in our favor. Indeed, though your broader point is correct, clinical is more expensive and I think ultimately that should be done by a for-profit entity. But crowdfunding can nudge things in that direction by completing the preclinical.
- throwaway_yy2Di 13y ago
  Of course it's including the failures, we don't know whether your candidate will succeed. I'm reasoning in terms of the expectation value of the a success: the cost of one project such as yours, divided by the probability of it creating a useful drug. "The actual cost of getting a chemotherapeutic developed is about 1-2 million in preclinical, and 12-20 million through clinical. Counting lots of inefficiencies, and, as I discuss downthread, we're stacking the deck in our favor." That's only part of the equation. What's the probability that it fails preclinical or clinical trials? What are the historical success rates for chemotherapeutics? (Serious question) edit: I've Googled up what I think is a relevant statistic? According to this source, of cancer drug candidates which completed US clinical trials between 2004-2011, 6.7% of the ones which entered phase I ended up as approved drugs (the rest failing out). Apparently this is much worse than non-cancer drugs, which have a 12.1% rate. http://www.biotech-now.org/business-and-investments/2012/02/oncology-clinical-trials-secrets-of-success# http://www.biotech-now.org/business-and-investments/2012/02/...

shiven 13y ago

What about drug resistance? Any data available/planned in that regard? Curious about it, because I work on this stuff from a structural perspective as my profession.