
Project Marilyn Part I: Non-Patented Cancer Pharmaceutical - ajaymehta
https://www.crowdtilt.com/campaigns/project-marilyn-part-i?utm_source=HackerNews&utm_medium=HNPost&utm_campaign=ProjectMarilyn
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throwaway_yy2Di
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-
tru...](http://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-
staggering-cost-of-inventing-new-drugs/)

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
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
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/...](http://www.biotech-now.org/business-and-
investments/2012/02/oncology-clinical-trials-secrets-of-success#)

~~~
JohnHaugeland
Research should not be avoided merely because it isn't likely to succeed.

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pallandt
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
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?

~~~
JohnHaugeland
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.

~~~
dnautics
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....](http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7915.2010.00221.x/abstract)

#2:
[https://www.ncbi.nlm.nih.gov/pubmed/22390171](https://www.ncbi.nlm.nih.gov/pubmed/22390171)

~~~
throwaway_yy2Di
Yes, but don't _all_ pharma researchers "stack their decks" in similar ways,
to maximize their chance of success? And still fail with the dismal statistics
I linked to?

~~~
dnautics
yes and no.

For example, the trend now is toward maintenance drugs and biologicals,
because that's what the execs want. Whether or not this has anything to do
with efficacy is questionable. During my biophysics days, I saw so many drugs
enter the clinical pipeline even purporting to treat alzheimers, that were
basically following up on "popular memes in the field" that from first
principles I would look at and say, there's no way this will work.

I've spoken to one pharma consultant (to get the chat, I didn't tell him I was
making an unpatented drug) who basically lamented what had happened to the
cancer field as the big companies lost their R&D and turned to acquiring
biotechs for their blue sky stuff - and he characterized biotechs as being on
to "fad-dey" stuff. Now, it's alos possible that he's wrong too, and that I'm
on the wrong track. So you are correct to worry about the likelihood of
success.

~~~
throwaway_yy2Di
I don't know how bad pharma politics are, but I have hard time imagining
they're worse than crowdfunding! I think no one on this site really
understands what you're doing. We know you're more credible than a homeopathic
scam artist, which is _to our credit_ because the broader crowdfunding
demographic is unlikely to figure out the difference. (See fig. 1, sales of
homeopathic remedies in billion USD). But would you trust us to figure out
that your compound is more promising than some other one, with similar-looking
technical jargon, proposed by similarly credentialed researchers?

I think the concept is incredibly radical. If this were a business idea, it
would be functionally illegal: you could only solicit funding from wealthy,
accredited investors under highly regulated procedures. Because people are
easily mislead. And that's for stupid things like selling sporks. But here we
are, pretending to scrutinize a million-dollar medical research grant, as if
we were PhDs at the NIH office or something. Where do you want to go with
this?

~~~
dnautics
Is your presupposition that the TLAs are better at this than you are? There's
a huge project right now at DARPA
([https://www.fbo.gov/index?s=opportunity&mode=form&id=0d71fc7...](https://www.fbo.gov/index?s=opportunity&mode=form&id=0d71fc7acd93ac77427181635651ed28&tab=core&_cview=1))
that is being led by program manager whose graduate work is increasingly
suspected of being completely artefactual.
[http://raphazlab.wordpress.com/2012/12/11/seven-years-of-
ima...](http://raphazlab.wordpress.com/2012/12/11/seven-years-of-imaging-
artifacts/)

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jdorw
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
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.

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shiven
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.

------
tocomment
This page isn't working?
[http://www.indysci.org/details.html](http://www.indysci.org/details.html)

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

