Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

[Travis Henry]

So I got selected for the depression trial in Houston.

They pay you some money to do it. Not much but a couple hundred bucks.

Two MRIs by a Tesla model.

Tinnitus and hyperacusis are not an exclusion... although the lead psych was worried about anyone with hyperacusis, but not tinnitus.

2 months worth of the drug. 20 mg a day I believe.

 

[StoneInFocus]

So I got selected for the depression trial in Houston.

They pay you some money to do it. Not much but a couple hundred bucks.

Two MRIs by a Tesla model.

Tinnitus and hyperacusis are not an exclusion... although the lead psych was worried about anyone with hyperacusis, but not tinnitus.

2 months worth of the drug. 20 mg a day I believe.

Congratulations on making it through! Hopefully you don't get the placebo.

Considering the MRI scans, don't ever let the doctors or anyone else for that matter pressure you into sitting them through if you happen to feel uncomfortable.

Do you have any idea how and when Xenon is going to be distributed among the participants? Some may consider this unethical but if it's distributed all at once you could choose to skip the MRI's and still try out the stuff.

To be honest, I am bit worried about the "reasonably foreseeable risks and discomforts" of XEN1101.

I wish you the best of luck and hopefully little side effects.

Take care.

 

[Ela Stefan]

So I got selected for the depression trial in Houston.

They pay you some money to do it. Not much but a couple hundred bucks.

Two MRIs by a Tesla model.

Tinnitus and hyperacusis are not an exclusion... although the lead psych was worried about anyone with hyperacusis, but not tinnitus.

2 months worth of the drug. 20 mg a day I believe.

Can you get in the trial without doing the MRIs? Wouldn't the MRIs be dangerous?

 

[Travis Henry]

Can you get in the trial without doing the MRIs? Wouldn't the MRIs be dangerous?

Yes, I can't do it because of the MRIs. I am too far gone at the moment. My tinnitus is suicidal loud and reactive.

If I were to somehow able to do it, would 2 months of the medication give me a long term effect/relief since I've had intrusive tinnitus with mild hyperacusis since January 2022 and then in April 2022 worsening of both to a reactive level?

 

[InNeedOfHelp]

William Blair Biotech Focus Conference 2022

Here is a new Q&A on XEN1101 recorded yesterday. Didn't have a chance to listen yet. Maybe some info on timelines etc?

 

[Gb3]

I'm sure those MRIs are very quiet.

 

[InNeedOfHelp]

So I got selected for the depression trial in Houston.

They pay you some money to do it. Not much but a couple hundred bucks.

Two MRIs by a Tesla model.

Tinnitus and hyperacusis are not an exclusion... although the lead psych was worried about anyone with hyperacusis, but not tinnitus.

2 months worth of the drug. 20 mg a day I believe.

Great news for you. Keep in mind that the X-Tole XEN1101 studies allowed users to keep using the medicine even after the trial was over. Maybe something to discuss prior to signing. You might be the first one using it with tinnitus. I think the cohorts were 50/50% placebo with 2x 10 mg pills.

Did you apply for the Mt Sinai study or for the study led by Xenon Pharmaceuticals themselves?

 

[Travis Henry]

Great news for you. Keep in mind that the X-Tole XEN1101 studies allowed users to keep using the medicine even after the trial was over. Maybe something to discuss prior to signing. You might be the first one using it with tinnitus. I think the cohorts were 50/50% placebo with 2x 10 mg pills.

Did you apply for the Mt Sinai study or for the study led by Xenon Pharmaceuticals themselves?

It's a double blind trial so no drugs after the trial ends. Not going to be able to do it anyway. I would die trying to do the MRIs that are 130 dB for an hour in a head cage.

I applied by calling the number for the Houston one.

 

[InNeedOfHelp]

It's a double blind trial so no drugs after the trial ends. Not going to be able to do it anyway. I would die trying to do the MRIs that are 130 dB for an hour in a head cage.

I applied by calling the number for the Houston one.

Fully understand.

 

[Ela Stefan]

I would die trying to do the MRIs that are 130 dB for an hour in a head cage.

Did they give you any details as what they need the MRI for? Isn't depression a mental illness? Do they do a functional MRI? What parts of the brain would need to be affected? Maybe you just have mild depression which can't yet be seen on an MRI...

 

[Travis Henry]

Did they give you any details as what they need the MRI for? Isn't depression a mental illness? Do they do a functional MRI? What parts of the brain would need to be affected? Maybe you just have mild depression which can't yet be seen on an MRI...

They want to see the changes in the brain part that bring you joy.

 

[Ela Stefan]

Hi! I have sent an email to the company to ask, but does anyone here know if they conduct or are planning to conduct any Phase 3 clinical trials in Europe?

 

[grate_biff]

If I were to somehow able to do it, would 2 months of the medication give me a long term effect/relief since I've had intrusive tinnitus with mild hyperacusis since January 2022 and then in April 2022 worsening of both to a reactive level?

It definitely might help your tinnitus and hyperacusis.

I have so much belief in this drug. I have tinnitus and severe noxacusis and I´m begging doctors to try and get me the drug through a "compassion use" program.

Just use earplugs and Peltors. All you will hear is the conductive noise. Your ears can take that.

I have done several lengthy MRIs with my damaged ears. With double protection it´s not that bad at all and I have not had any worsening. The nature of the noises can be scary, but they won´t hurt you. Are you even sure you will have to take the loud ones?

I would do anything to be in that trial.

 

[Brian Newman]

It definitely might help your tinnitus and hyperacusis.

I have so much belief in this drug. I have tinnitus and severe noxacusis and I´m begging doctors to try and get me the drug through a "compassion use" program.

Just use earplugs and Peltors. All you will hear is the conductive noise. Your ears can take that.

I have done several lengthy MRIs with my damaged ears. With double protection it´s not that bad at all and I have not had any worsening. The nature of the noises can be scary, but they won´t hurt you. Are you even sure you will have to take the loud ones?

I would do anything to be in that trial.

Wow man, you went through MRIs? I'm surprised your ears can take that. I hope you're doing ok these days.

 

[grate_biff]

Wow man, you went through MRIs? I'm surprised your ears can take that. I hope you're doing ok these days.

Custom made earplugs and Peltors. Sealed like a can of beans. Could hear my tinnitus very well though.

 

[grate_biff]

I hope you're doing ok these days.

Thanx but far from it. Still extreme noxacusis and benzos are killing me

ON and OFF all the time .

ON benzos = can live with tinnitus and noxacusis, but deeply depressed and have "brain zaps"

OFF benzos = pain and suffering, tremors and extreme anxiety, but no depression

I'm just so fucked. Catch 22. Trapped. Nowhere to hide. Fucked up two loooong drawn out attempts at getting off the benzos. Tapered slowly, only to crack when off because of noxacusis becoming unreal. Can't breathe. My own voice becomes poison in my brain. Even sound of bed sheets is like gun shots in my brain.

Regarding the MRI: Of course I had to medicate for it. 30 mg Remeron and 60 mg Codeine will calm you down. Worst part is you can't move for a long time. Then they will have to start over.

 

[Matchbox]

So I got selected for the depression trial in Houston.

They pay you some money to do it. Not much but a couple hundred bucks.

Two MRIs by a Tesla model.

Tinnitus and hyperacusis are not an exclusion... although the lead psych was worried about anyone with hyperacusis, but not tinnitus.

2 months worth of the drug. 20 mg a day I believe.

You lucky f/duck. Not sure if reporting here is a good idea for blinding though as much as we want to hear about it.

If the MRIs are 1.5T, it's worth the risk imo so long as you prepare with adequate ear protection and NAC.

3T would be bad. The new 5T ungodly.

 

[Geatly]

Thanx but far from it. Still extreme noxacusis and benzos are killing me

ON and OFF all the time .

ON benzos = can live with tinnitus and noxacusis, but deeply depressed and have "brain zaps"

OFF benzos = pain and suffering, tremors and extreme anxiety, but no depression

I'm just so fucked. Catch 22. Trapped. Nowhere to hide. Fucked up two loooong drawn out attempts at getting off the benzos. Tapered slowly, only to crack when off because of noxacusis becoming unreal. Can't breathe. My own voice becomes poison in my brain. Even sound of bed sheets is like gun shots in my brain.

Regarding the MRI: Of course I had to medicate for it. 30 mg Remeron and 60 mg Codeine will calm you down. Worst part is you can't move for a long time. Then they will have to start over.

I am sorry to hear this bro. This world sucks so much, person can damage their hearing within seconds, but repairing it takes months/years if ever.

I wish that you will overcome this, and that treatments become available as fast as possible. People need to understand that this is a serious injury even if it doesn't seems like that from the outside.

 

[Ela Stefan]

Thanx but far from it. Still extreme noxacusis and benzos are killing me

ON and OFF all the time .

ON benzos = can live with tinnitus and noxacusis, but deeply depressed and have "brain zaps"

OFF benzos = pain and suffering, tremors and extreme anxiety, but no depression

I'm just so fucked. Catch 22. Trapped. Nowhere to hide. Fucked up two loooong drawn out attempts at getting off the benzos. Tapered slowly, only to crack when off because of noxacusis becoming unreal. Can't breathe. My own voice becomes poison in my brain. Even sound of bed sheets is like gun shots in my brain.

Regarding the MRI: Of course I had to medicate for it. 30 mg Remeron and 60 mg Codeine will calm you down. Worst part is you can't move for a long time. Then they will have to start over.

How long have you taken benzos for? Was your noxacusis onset after you started taking benzos? Are those brain zaps sort of "fizzing" brain?

 

[grate_biff]

How long have you taken benzos for?

Benzos have been in my life for 30+ years. I was clear off them in spring of 2014. I was so happy and relieved.

Then in the fall of 2014, BOOM, a few seconds with loud noise, while at work using HF.

I went back on benzos because they totally muted the tinnitus for me. I tried to be careful. Not over use, but BOOM, in spring of 2019 I realized I was totally hooked again

Was your noxacusis onset after you started taking benzos?

Noxacusis was there, but very mild. I could live without protection. Benzo withdrawal probably made it much worse with a CNS out of control. It's a good question, but I can't answer it. In 2020 I went 10 months off benzos, but crashed because of noxacusis.

In hindsight it was probably a little better. The reactiveness was gone.

Then I tapered all of 2021. Went through hell, then cracked again. This year has been ON/OFF benzos as I said.

Noxacusis and benzos have total control of my life. I tried to get committed to a ward three times. I could not handle the noise. I went home in my father's ultra quiet basement. I feel safe here. But I'm soon out, because he is moving

Are those brain zaps sort of "fizzing" brain?

They are like those you get when tapering SSRI/SNRIs. I'm on two ADs and I believe benzos are inhibiting the serotonergic transmission in the brain. Hence the depression and brain zaps. Benzos affect GABA. And GABA slows everything down.

I'm in need of a somewhat more specific inhibitor, like XEN1101.

 

[Travis Henry]

You lucky f/duck. Not sure if reporting here is a good idea for blinding though as much as we want to hear about it.

If the MRIs are 1.5T, it's worth the risk imo so long as you prepare with adequate ear protection and NAC.

3T would be bad. The new 5T ungodly.

The side effects are huge and the MRI is like 130dB.

Would this be a drug that would make me feel better forever? Or just while taking it?

I would do anything to be in that trial.

Long lasting relief?!

 

[Brian Newman]

I'm in need of a somewhat more specific inhibitor, like XEN1101.

You think XEN1101 will help a lot? I hope it does. No guarantee. I think it could but we won't know till people take it.

 

[Ela Stefan]

I'm in need of a somewhat more specific inhibitor, like XEN1101.

Will XEN1101 help up on the auditory network? That's the question! Seems like it is more made for DCN hyperecxitability. Mine is a sort of fizz thing, lateral, but can go all over brain. More or less intense. From a clogged ear, less auditory input and an irritated trigeminal nerve. Unbelivable.

I have taken 0.5 mg Rivotril (Clonazepam) for almost 3 years now. But my tinnitus has lately been more and more reactive to surrounding noise, of any kind. Like you, Clonazepam used to calm the brain tinnitus in the first months. I really don't know, maybe it is from tolerance...

the MRI is like 130dB.

Can you ask for a silent MRI for anxiety, for example? There are MRIs that go up to like 70 dB...

 

[grate_biff]

The side effects are huge

Just like any other drug. They are there just there for legal purposes. So they can't get sued. Does not mean you will get the side effects.

The retina thing is of course of concern, but I bet they have looked at that closely. It's been through two phases already.

 

[grate_biff]

Like you, Clonazepam used to calm the brain tinnitus in the first months. I really don't know, maybe it is from tolerance...

It is. Benzo is not a sustainable treatment.

 

[Ela Stefan]

Just like any other drug. They are there just for legal purposes. So they can't get sued. Does not mean you will get the side effects.

The retina thing is of course of concern, but I bet they have looked at that closely. It's been through two phases already.

Does XEN1101 act on the whole CNS or just the DCN?

 

[grate_biff]

Does XEN1101 act on the whole CNS or just the DCN?

What do potassium channels do in neurons?

Voltage-gated potassium channels (VGKC) are transmembrane channels responsible for returning the depolarized cell to a resting state after each nerve impulse. They are, therefore, important in modulating neuronal excitability in the CNS and peripheral nervous system.

 

[Ela Stefan]

What do potassium channels do in neurons?

View attachment 50983

Voltage-gated potassium channels (VGKC) are transmembrane channels responsible for returning the depolarized cell to a resting state after each nerve impulse. They are, therefore, important in modulating neuronal excitability in the CNS and peripheral nervous system.

Someone posted the below picture. Looks like for each level you will need a different drug? And up to MGN it is just maladaptive brain response all over. I wonder how much XEN1101 will help in the whole picture?

 

[AxEars]

Opening New Doors: First Synthetic Mechanosensitive Potassium Channel

The above sounds like it'll help in the future. If Xenon is the beginning, I'm sure synthetic potassium ions will be able to help cochlear cells in the future. Mechanosensitive Potassium Ion Channels are a big part of the cochlea and hair cells.

Small steps forward, month by month.

 

[StoneInFocus]

It definitely might help your tinnitus and hyperacusis.

I would do anything to be in that trial.

QurAlis is planning on starting clinical trials with QRL-101, another Kv7.2/.3 opener, "end of this year or early next year", so maybe you could keep an eye on that one. I'm almost 100% certain these types of drugs will help with noxacusis.