[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 "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?

[dnautics]

(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]

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]

like this? http://www.indysci.org/details.html

[ISL]

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]

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...

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]

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....

#2: https://www.ncbi.nlm.nih.gov/pubmed/22390171

[ThomPete]

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.

[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?

[suchire]

Just FYI, I wouldn't put too much faith in safety profiles of related family drugs. The classic med chem example of really unpredictable toxicology is mevastatin vs lovastatin, which have exactly the same structure but for one lowly methyl group. The former molecule was basically an unusably toxic drug candidate that never would have been approved by the FDA, whereas the latter was the first safe and effective statin to go to market.

[dnautics]

it's a known mechanistic issue. the pyrrolobenzodiazepine molecules are pretty selective DNA alkylators. Cardiotox is caused probably by transport chain involvement when the 9-position is oxygenated (makes it look like Co-Q). Without that oxygen, the PBDs zip on over to the DNA. PBDs have a slight twist to the molecule which allows them to nestle in the minor groove with exactly the right pitch so that the lesion evades base excision repair response, which is what is thought to cause the more serious side effects in DNA-alkylating chemotherapies.

However, you are right, there could be unforseen toxicity issues.

[ThomPete]

I appreciate that but I guess I am a little more biased perhaps because of my history.