#33

It seems that Peter Diamandis would be a good fit as a funder for Ora Biomedical. Can anyone bring this to his attention?

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#34

I’m watching a talk from ARDD 2023 John Speakman at ARDD2023: Stepping stones towards anti-ageing drug discovery

He talks about the worm bot & says that while things that work in mice (& humans) generally work in worms, the converse isn’t true. Things that work in worms have a low chance of working in mice. I still hope there is enough cross over to make the faster results from worms worth the effort.

His talk is about testing faster in mice by finding biomarkers that show up early in the mouse lifespan, which would also be useful if possible.

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#35

I think the idea with wormbot is to create a first pass filter. If it’s true that things that work in humans also work in worms, but the reverse is only sometimes true… then testing 1,000,000 molecules in worms will reveal some number of molecules that work in worms and very likely some smaller percentage of those will work in humans.

But the advantage of the worms is the speed at which you can test massive numbers of molecules. It gives you have a pipeline. Test 1 million in worms → test the 1000 that pass in mice → then test the 100 that pass in humans. (I’m making up the exact numbers)

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#36

I’m passing for now. They aren’t able to do deuterated PUFAs, heavy isotopes, or any of the “interesting molecules”

#37

I had a go with citrate, but it serms to have got stuck.

#38

I wanted to sponsor oral semaglutide (rybelsus), selegiline (deprenyl) and sotagliflozin (alone or in combination with other compounds like rapa or taurine) but they’re all absent from their list. I told them weeks ago, to no avail…

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#39

I’m passing for now as well.

As much as I applaud their efforts. I just don’t their lack of transparency as concerns the publishing of data. Maybe that will change.

“just from a small pilot screen of a few mTOR inhibitors, Ora has already identified one that works better than rapamycin.”

But they haven’t said what it is !

We will probably never know, just like we never found out which compounds were synergistic with metformin.

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#40

To be fair to them, however, if they are testing even thousands of combinations then that will take quite a bit of organising.

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#41

I’m not trying to knock them, we need more people and organisations like them. It’s just that I would think that publishing of results was at least as important as organising studies, else what’s the point in doing the studies.

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#42

It takes time & energy to publish which could be spent instead on getting more results. I’m not seeing this as a problem.

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#43

I finished Speakman’s lecture – I think he would agree.

FWIW, I’m still planning to donate to them. I don’t plan to pick out any particular chemical, I don’t have any reason to think I would be able to make a good choice.

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#44

Ah, I think I know why Ora aren’t naming the FDA drugs that are showing interesting results…it’s all about the money :moneybag: and patents.

Below is an excerpt from a conversation with Dr. Matt Kaeberlein of Ora Biomedical (link shown above)

Blockquote

So, I could continue banging my head against the wall writing grant after grant, but we decided that there’s an opportunity to spin this out as a company. It’s not an easy sell as a company because it doesn’t fit into the culture of traditional biotech either.

Right, because what’s the product?

That’s a good question. I am certain that we can come up with interventions, combinations with FDA-approved drugs or new drugs, that are at least twice or even an order of magnitude more effective than the interventions we have today that target the biology of aging. I think that’s a pretty goddamn good product.

I certainly will. But there’s a major problem with repurposing drugs, isn’t it? Little commercial incentive here.

I’d say this is an open question. There’s certainly a perception that there’s no path to profitability with repurposing drugs. I’m not sure it’s true. It’s an unusual path, but at least in some cases, you can get some kind of unique IP around it. Anyway, you don’t have to start with FDA-approved drugs. Or you start with them and then, if you know what the target is, in theory, you could develop or identify new drugs that work on the same target.

For example, I mentioned this one drug that interacts with metformin. We know what the biochemistry is, what the target is, and we have this synergistic effect. Our prediction is that other drugs that hit that biochemical target will show the same synergy with metformin. If that’s true, there are other drugs out there that have IP around them.

Yes, the company has absolutely gotten that question, “what’s the product,” and that’s a challenge. You have to convince the investor that the idea is solid enough and that it’s important, that identifying interventions that are significantly better than what we have today is important. We’ll see how successful we are.

Blockquote

It would explain why @RapAdmin has had no luck (AFAIK) in reaching out to Ora to get a list of the drug combinations.

I suppose if they are to make a success of their company, then that’s what they need to do. It’s just so frustrating, knowing there’s data out there that you can’t access.

I think I’d have better luck trying to find out who shot Kennedy :smiley:

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#45

Oh - I’ve only really asked Mitch at Ora Biomedical about the drugs and supplements that are negative in terms of their combinations. I wouldn’t expect him to share the positive ones (unless for some reason they are not at all interested in them). yes - their entire business model is based on patenting the combinations for future drug production/sales.

and, as an example, here is another company that is taking a similar approach on the IP (intellectual property) issue, with success:

Amylyx - Went public this year, current market cap is $2.4 Billion. It is based on the unique combination of two generic / supplement compounds being combined and packaged together for treatment of ALS.

AMX0035 is a combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO) significantly slowed the loss of physical function in people living with ALS in a randomized, placebo-controlled clinical trial. AMX0035 is designed to slow disease progression by slowing or preventing motor neuron cell death.

AMX0035 comes in sachet packets of a powder that is dissolved in room temperature water. It can be administered by mouth or by feeding tube. In the phase 2 trial, the dose regimen was to take the drug once daily for first three weeks and then twice daily if tolerating. The most common adverse events occurring with RELYVRIO (at least 15% and at least 5% greater than placebo) were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first three weeks of treatment.

More info: AMX0035 (RELYVRIO) | The ALS Association

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#46

Not being a biologist, I did likewise; said “select an intervention for me”; then I heard nothing. Later, I followed up to ask which was selected for me. I got no answer. Lack of transparency! I would have given/selected more, but now probably not.
@RapAdmin said: " yes - their entire business model is based on patenting the combinations for future drug production/sales."
Why then are/were they soliciting $$$ from the interested public instead of the venture capitalists?

#47

For the publicly funded compound selections, their policy may be different. I’ve not followed up on that. It would make sense that it would be different…

I think they are doing both; the funding approaches are not mutually exclusive.

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#48

Isn’t one of the best outcomes knowing which had negative results? If something is bad for C. Elegans it’s probably bad for mice and humans. Toxins are toxins after all.

But if something is good for C. Elegans it may not be so for mice and humans. So they need additional testing on mice. This theory is mostly correct?

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#49

Not necessarily. A good example for a toxic substance that kills dogs and cats but not humans is minoxidil. While millions of men use it topically to grow their hair, getting even a bit of it on a cat/dog will kill them because they lack the specific enzymes to break down minoxidil.

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#50

But if something is good for C. Elegans it may not be so for mice and humans. So they need additional testing on mice. This theory is mostly correct?

That’s what John Speakman said, yes.

FWIW, he did mention Ora & I got the impression that he has access to their result because he said something about testing compounds that passed their screen. OTOH, I watch these while exercising, so my understanding might be (cough) not perfect, due to not paying complete attention.

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#51

102 posts were split to a new topic: Ora Biomedical Million Molecule Challenge Results

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