Sound Pharmaceuticals (SPI-5557 & SPI-1005)

[tommyd87]

I believe Rinri Therapeutics and a couple of other companies are working on remyelination and nerve regeneration.

This is correct, however what Rinri Therapeutics is working on probably won't help most people who have had hearing loss from synapse/hair cell damage and actually have functional nerve hearing currently.

Consequently their treatment will not be beneficial for most of us and thus there will only be benefit from FX-322 or synapse assisting medicines.

 

[frpp]

And actually Frequency Therapeutics as well (for MS at least).

If it works for MS by remyelination of the CNS it hopefully works for other nerves as well.

 

[Mathew Gould]

This is correct, however what Rinri Therapeutics is working on probably won't help most people who have had hearing loss from synapse/hair cell damage and actually have functional nerve hearing currently.

Consequently their treatment will not be beneficial for most of us and thus there will only be benefit from FX-322 or synapse assisting medicines.

@tommyd87 is there any drugs or treatments (not including University of Minnesota and University of Michigan) that help tinnitus from neck and TMJ issues that have a chance of working in the next few years??

 

[Dizzyhead888]

Can anyone who is following this thread kindly summarize it?

When are the phase 3 results due?

 

[FGG]

Can anyone who is following this thread kindly summarize it?

When are the phase 3 results due?

They haven't technically started phase 3 for Meniere's yet so no one knows when results are due.

They expect to be done with a phase 2 for COVID-19 by December though:

https://clinicaltrials.gov/ct2/show/NCT04484025

If that goes well, may be out very soon.

 

[Born To Slay]

They haven't technically started phase 3 for Meniere's yet so no one knows when results are due.

They expect to be done with a phase 2 for COVID-19 by December though:

https://clinicaltrials.gov/ct2/show/NCT04484025

If that goes well, may be out very soon.

Imagine getting so lucky that your drug helps COVID-19 and you get to release it quicker as a result? That's like a drug maker's lottery win.

 

[tommyd87]

They haven't technically started phase 3 for Meniere's yet so no one knows when results are due.

They expect to be done with a phase 2 for COVID-19 by December though:

https://clinicaltrials.gov/ct2/show/NCT04484025

If that goes well, may be out very soon.

See it wouldn't surprise me one bit if Sound Pharmaceuticals never actually completes the phase 3 for Meniere's, because they can use the COVID-19 component of this treatment to justify quicker release under the compassionate use allowance. At this stage, Sound Pharmaceuticals has had successful phase 2 clinical trials for Meniere's and the inflammation component too. There has recently also been positive research results from lab assignments for the inflammation aspect and also previously for Meniere's.

When you combine all these factors together, it is quite obvious that Sound Pharmaceuticals could have the necessary information and also the necessary trial outcomes to meet the FDA requirements for release. This could be as soon as early next year, as it is almost guaranteed that the FDA would allow this treatment to jump the queue and be reviewed for approval almost immediately due to its benefits on COVID-19.

Therefore doctors could commence prescribing this for non-COVID-19 indications off-label as Sound Pharmaceuticals could provide them with enough information and direction on what the medicine's benefit is, how it is to be prescribed and what it can be utilised for.

While COVID-19 is unfortunate and not what anybody wanted, it has been very fortunate for Sound Pharmaceuticals and their medicine SPI-1005 because it has resulted in it being able to achieve priority because of its apparent treatment outcomes.

 

[frpp]

See it wouldn't surprise me one bit if Sound Pharmaceuticals never actually completes the phase 3 for Meniere's, because they can use the COVID-19 component of this treatment to justify quicker release under the compassionate use allowance. At this stage, Sound Pharmaceuticals has had successful phase 2 clinical trials for Meniere's and the inflammation component too. There has recently also been positive research results from lab assignments for the inflammation aspect and also previously for Meniere's.

When you combine all these factors together, it is quite obvious that Sound Pharmaceuticals could have the necessary information and also the necessary trial outcomes to meet the FDA requirements for release. This could be as soon as early next year, as it is almost guaranteed that the FDA would allow this treatment to jump the queue and be reviewed for approval almost immediately due to its benefits on COVID-19.

Therefore doctors could commence prescribing this for non-COVID-19 indications off-label as Sound Pharmaceuticals could provide them with enough information and direction on what the medicine's benefit is, how it is to be prescribed and what it can be utilised for.

While COVID-19 is unfortunate and not what anybody wanted, it has been very fortunate for Sound Pharmaceuticals and their medicine SPI-1005 because it has resulted in it being able to achieve priority because of its apparent treatment outcomes.

If only the government would show the same level of concern and effort towards fixing people's hearing and other major health issues as they do with COVID-19 vaccines/treatments, the world would be a much better place.

 

[tommyd87]

If only the government would show the same level of concern and effort towards fixing people's hearing and other major health issues as they do with COVID-19 vaccines/treatments, the world would be a much better place.

I don't disagree with your comment at all. Although I would say that the government is making allowances for these hearing treatments and also some of these other health treatments to get released as quickly as possible with their fast tracking and compassionate use provisions.

I actually am of the opinion that SPI-1005 is no different to any of the other medicines in terms of how it is proceeding through the clinical trial processes. It was just very fortunate that this treatment could be used for respiratory issues like those associated with COVID-19 and that the medicine already had been through the safety trial element. This therefore allowed Sound Pharmaceuticals to commence a phase 2 COVID-19 trial virtually immediately.

I think that the only benefit that Sound Pharmaceuticals will probably obtain from the approval process thanks to COVID-19 is the fact that they can probably get approval almost immediately after reporting the results from the phase 2 trial. This is a fairly small gain and in the scheme of things this expedited meeting with the FDA probably wouldn't be happening that much faster than any other FDA approved fast track treatment.

 

[Born To Slay]

I don't disagree with your comment at all. Although I would say that the government is making allowances for these hearing treatments and also some of these other health treatments to get released as quickly as possible with their fast tracking and compassionate use provisions.

I actually am of the opinion that SPI-1005 is no different to any of the other medicines in terms of how it is proceeding through the clinical trial processes. It was just very fortunate that this treatment could be used for respiratory issues like those associated with COVID-19 and that the medicine already had been through the safety trial element. This therefore allowed Sound Pharmaceuticals to commence a phase 2 COVID-19 trial virtually immediately.

I think that the only benefit that Sound Pharmaceuticals will probably obtain from the approval process thanks to COVID-19 is the fact that they can probably get approval almost immediately after reporting the results from the phase 2 trial. This is a fairly small gain and in the scheme of things this expedited meeting with the FDA probably wouldn't be happening that much faster than any other FDA approved fast track treatment.

Plus, I read articles in the Wall Street Journal that the trend is now to fast track drugs and they're fast tracking more than ever. So it seems drugs are coming faster these days.

 

[paul mclean]

So SPI-1005 is just an otoprotective drug after noise exposure?

 

[tommyd87]

So SPI-1005 is just an otoprotective drug after noise exposure?

No, not entirely. Essentially it can work to reduce other troubles like inflammation if you take a course of it. It can be used for multiple issues.

 

[tommyd87]

I found this thing through a search.

It seems Sound Pharmaceuticals are actually at the point of being able to lodge this, although I am not sure if it is delayed further due to the issues around COVID-19, or due to the fact that there have been big changes and developments in what happens with SPI-1005, especially since Sound Pharmaceuticals ended up adding the COVID-19 indication because it was seemingly successful at treating it.

This treatment tends to look promising and I hope that it is successful.

 

[GBB]

View attachment 41059

I found this thing through a search.

It seems Sound Pharmaceuticals are actually at the point of being able to lodge this, although I am not sure if it is delayed further due to the issues around COVID-19, or due to the fact that there have been big changes and developments in what happens with SPI-1005, especially since Sound Pharmaceuticals ended up adding the COVID-19 indication because it was seemingly successful at treating it.

This treatment tends to look promising and I hope that it is successful.

What is an IND?

 

[FGG]

What is an IND?

"Investigational New Drug"

In a nutshell, an application to the FDA start clinical trials. This is for Sound Pharmaceuticals' regenerative drug that was in pre-clinical, not SPI-1005 (which is already in trials).

 

[tommyd87]

What is an IND?

Basically it is the license from the FDA to confirm clinical trials can commence for a particular medicine. It is where the FDA basically scrutinises and assesses the trial process and gives it the go ahead accordingly if it is something they are happy with.

 

[tommyd87]

Found this when I was looking into SPI-5557 and its benefits and mechanism of action.

Sound Pharmaceuticals also aims to regenerate cochlear cells, but taking a small interfering RNA approach. The therapeutic agent is SPI-5557, which inhibits p27Kip1, an inhibitor of cyclin-dependent kinase whose deletion in mice leads to proliferation of supporting cells and the regeneration of hair cells.

If it is the case that this can be replicated in people like it has been done in rats, and to date we are actually well aware that there are a lot of similarities between rats and people as has been shown in the lab for example with FX-322, SPI-1005 and OTO-413, then I think that this treatment could be really promising if it is effective. Essentially this treatment then might help much more widely than the other hair cell medicines, although I could be wrong.

 

[weab00]

Found this when I was looking into SPI-5557 and its benefits and mechanism of action.

If it is the case that this can be replicated in people like it has been done in rats, and to date we are actually well aware that there are a lot of similarities between rats and people as has been shown in the lab for example with FX-322, SPI-1005 and OTO-413, then I think that this treatment could be really promising if it is effective. Essentially this treatment then might help much more widely than the other hair cell medicines, although I could be wrong.

Wait, so this will have the ability to regenerate hair cells as well?

 

[FGG]

Found this when I was looking into SPI-5557 and its benefits and mechanism of action.

If it is the case that this can be replicated in people like it has been done in rats, and to date we are actually well aware that there are a lot of similarities between rats and people as has been shown in the lab for example with FX-322, SPI-1005 and OTO-413, then I think that this treatment could be really promising if it is effective. Essentially this treatment then might help much more widely than the other hair cell medicines, although I could be wrong.

Seems similar to the drug Hough Ear Institute has in pre clinical for hair cell regeneration (which is also an interfering RNA treatment for the p27Kip1 gene).

The main question I have about this approach is whether the support cells are preserved or not.

 

[tommyd87]

Seems similar to the drug Hough Ear Institute has in pre clinical for hair cell regeneration (which is also an interfering RNA treatment for the p27Kip1 gene).

The main question I have about this approach is whether the support cells are preserved or not.

Is it possible to preserve the support cells utilising this method or is it not? At this stage if it is going to remove those support cells and the method is effective I would consider using it. Otherwise I would happily take FX-322 or similar any day over this.

Also looks like Hough Ear Institute could potentially be beaten to the punch.

 

[FGG]

Is it possible to preserve the support cells utilising this method or is it not?

From the Hough Ear Institute page, it seems to convert support cells to hair cells:

"Treating cochleae with siRNA to Hes1 associated with a transfection
reagent or siRNA to Hes1 delivered by PLGA nanoparticles decreased Hes1 mRNA and up-regulated Atoh1 mRNA expression allowing supporting cells (SCs) to acquire a HC fate"

Regeneration of mammalian cochlear and vestibular hair cells through Hes1/Hes5 modulation with siRNA

 

[Croaker]

From the Hough Ear Institute page, it seems to convert support cells to hair cells:

"Treating cochleae with siRNA to Hes1 associated with a transfection
reagent or siRNA to Hes1 delivered by PLGA nanoparticles decreased Hes1 mRNA and up-regulated Atoh1 mRNA expression allowing supporting cells (SCs) to acquire a HC fate"

Regeneration of mammalian cochlear and vestibular hair cells through Hes1/Hes5 modulation with siRNA

The earlier quote states that the treatment "leads to proliferation of supporting cells and the regeneration of hair cells."

To me that implies the converted support cells are replaced rather than depleted.

Perhaps they just think differently from Hough Ear Institute or maybe the method is not quite the same.

 

[FGG]

The earlier quote states that the treatment "leads to proliferation of supporting cells and the regeneration of hair cells."

To me that implies the converted support cells are replaced rather than depleted.

Perhaps they just think differently from Hough Ear Institute or maybe the method is not quite the same.

Where is that quote from? Frequency Therapeutics? Because their method does not deplete support cells or is that a quote from Sound Pharmaceuticals?

 

[Croaker]

Where is that quote from? Frequency Therapeutics? Because their method does not deplete support cells or is that a quote from Sound Pharmaceuticals?

"Sound Pharmaceuticals also aims to regenerate cochlear cells, but taking a small interfering RNA approach. The therapeutic agent is SPI-5557, which inhibits p27Kip1, an inhibitor of cyclin-dependent kinase whose deletion in mice leads to proliferation of supporting cells and the regeneration of hair cells."

Source: from @tommyd87's post.

 

[weab00]

"Sound Pharmaceuticals also aims to regenerate cochlear cells, but taking a small interfering RNA approach. The therapeutic agent is SPI-5557, which inhibits p27Kip1, an inhibitor of cyclin-dependent kinase whose deletion in mice leads to proliferation of supporting cells and the regeneration of hair cells."

Source: from @tommyd87's post.

Is that bad?

 

[FGG]

"Sound Pharmaceuticals also aims to regenerate cochlear cells, but taking a small interfering RNA approach. The therapeutic agent is SPI-5557, which inhibits p27Kip1, an inhibitor of cyclin-dependent kinase whose deletion in mice leads to proliferation of supporting cells and the regeneration of hair cells."

Source: from @tommyd87's post.

I missed that. Thanks. This may mean it has more potential than the Hough Ear Institute injection.

 

[Croaker]

I hope we have more information soon about how "inflammation" (such a broad term!) relates to tinnitus spikes/hyperacusis. Clearly, many spikes/setbacks are not the result of additional hair cell death. But then why do they happen? Temporary hyperactivity, maybe in the cochlear nerve bushy cells Dr. Shore has referred to? Something going on in the type II fibers? Brain activity? Why does hyperacusis spread equally to both ears (the way tinnitus usually does) if it is supposedly more peripheral than tinnitus?

I tried researching the role of glutamate but it's difficult for a layman because apparently it's the most common neurotransmitter!

 

[100Hz]

I hope we have more information soon about how "inflammation" (such a broad term!) relates to tinnitus spikes/hyperacusis. Clearly, many spikes/setbacks are not the result of additional hair cell death. But then why do they happen? Temporary hyperactivity, maybe in the cochlear nerve bushy cells Dr. Shore has referred to? Something going on in the type II fibers? Brain activity? Why does hyperacusis spread equally to both ears (the way tinnitus usually does) if it is supposedly more peripheral than tinnitus?

I tried researching the role of glutamate but it's difficult for a layman because apparently it's the most common neurotransmitter!

Exactly, I don't see how setbacks can necessarily be the result of fresh hair cell death every time either as I doubt the noise that typically triggers setbacks is anywhere near noxious. Enough to cause a fresh spark of ATP release though, yes definitely, and I believe that's where the short sharp noise shock and sensitivity comes into play.

I don't think noxacusis or tinnitus spreads equally to both ears though, not typically. Mine has always has been almost exclusively my left ear. My right ear gets maybe 5% of the severity of symptoms of my left ear. Both ears have very different tinnitus symptoms as well. Its the main reason that I don't like the central brain gain theory. Independent left / right temporary heightened neural response to noise I do think happens though.

 

[weab00]

I missed that. Thanks. This may mean it has more potential than the Hough Ear Institute injection.

So from what I've come to understand SPI-1005 proliferates the number of support cells. Is this good or bad for stuff like FX-322? And what is a support cell's function?

 

[Croaker]

Enough to cause a fresh spark of ATP release though, yes definitely, and I believe that's where the short sharp noise shock and sensitivity comes into play.

Where do you think this ATP is coming from? I thought it only happened upon initial cell death. Unless damaged yet still living cells are doing it. In which case no upcoming medication would solve the problem unless SPI-1005 can clean ATP up as part of its antioxidant effects?

So from what I've come to understand SPI-1005 proliferates the number of support cells. Is this good or bad for stuff like FX-322? And what is a support cell's function?

No, this is about SPI-5557. Different drug at the preclinical stage.