Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

[jer]

I am not sure if this is already posted, but anyway.

http://epilepsy-london.org/clinical-trial-new-anti-epileptic-drug/

I hope someone on the board is in London and able to get in this trial.

Key Inclusion Criteria:

Healthy male or females aged between 18 and 55 years inclusive with a body mass index (BMI) between 18.50 and 30.00 kg/m2

Must agree to use effective methods of contraception, if applicable

Able to swallow capsules

Able to provide written, personally signed and dated ICF

Key Exclusion Criteria:

Any history of epileptic seizures

Any current and relevant history of significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk, affect clinical or laboratory results, or the subject's ability to participate in the study

Answering "yes" to any of the questions within the Columbia Suicide Severity Rating Scale

Mental incapacity or lingual barriers precluding adequate understanding, cooperation, and compliance with the study

No prescription or over-the-counter (OTC) medications (except hormonal contraception), herbal or dietary supplements OTC medications 14 days prior to dosing to study end

No smoking 60 days prior to dosing to study end

No soft drugs 3 months prior to Screening and hard drugs 2 years prior to Screening

 

[Danny Boy]

I am not sure if this is already posted, but anyway.

http://epilepsy-london.org/clinical-trial-new-anti-epileptic-drug/

I hope someone on the board is in London and able to get in this trial.

Key Inclusion Criteria:

Healthy male or females aged between 18 and 55 years inclusive with a body mass index (BMI) between 18.50 and 30.00 kg/m2

Must agree to use effective methods of contraception, if applicable

Able to swallow capsules

Able to provide written, personally signed and dated ICF

Key Exclusion Criteria:

Any history of epileptic seizures

Any current and relevant history of significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk, affect clinical or laboratory results, or the subject's ability to participate in the study

Answering "yes" to any of the questions within the Columbia Suicide Severity Rating Scale

Mental incapacity or lingual barriers precluding adequate understanding, cooperation, and compliance with the study

No prescription or over-the-counter (OTC) medications (except hormonal contraception), herbal or dietary supplements OTC medications 14 days prior to dosing to study end

No smoking 60 days prior to dosing to study end

No soft drugs 3 months prior to Screening and hard drugs 2 years prior to Screening

Interesting, so there's no exclusion criteria if you have tinnitus?

 

[Localboy]

Interesting, so there's no exclusion criteria if you have tinnitus?

It's epilepsy trial so no tinnitus as exclusion criteria. Phase 1 with healthy (no epilepsy or other major diseases the investigator can disqualify you at will) volunteers. You also get paid £1300 if you take part.

 

[jer]

I think it might be an excellent trial for people to partake in if they are in/near London, or are willing to travel there.

This is what it said on the link. I am not sure if it's not a criteria. But maybe check to see if it is or not.

 

[Danny Boy]

It's epilepsy trial so no tinnitus as exclusion criteria. Phase 1 with healthy (no epilepsy or other major diseases the investigator can disqualify you at will) volunteers. You also get paid £1300 if you take part.

Yes, I understand that... However, I would be willing to do the trial, but honestly, it'll be beneficial if they knew the medication has potential for tinnitus. But with how scattergun trobalt was, I guess it makes it harder to tell which channel worked better for tinnitus.

This medication it not working on (KCNQ) both KV7.2/3 , it might not work for tinnitus. I can't say for sure though. In research, the most important channels for epilepsy and tinnitus was KV7.2/3.

Knopp biosciences are making a medication on the same target for epilepsy, KCNQ2 and said this about tinnitus "In tinnitus, we are developing potent channel-subtype activators for proof-of-concept studies in animal models."

 

[Tezcatlipoca]

Great news from Xenon Pharmaceuticals!

Xenon Pharmaceuticals Reports First Quarter 2021 Financial Results and Provides Corporate Update

 

[Kleiner]

Great news from Xenon Pharmaceuticals!

Xenon Pharmaceuticals Reports First Quarter 2021 Financial Results and Provides Corporate Update

XEN496 is a reformulation of Retigabine? Do we know if there will be fewer side effects than from Trobalt?

 

[Matchbox]

Great news from Xenon Pharmaceuticals!

Xenon Pharmaceuticals Reports First Quarter 2021 Financial Results and Provides Corporate Update

Looks like we might have something for help sooner rather than later. It doesn't fix the root cause but I'm open to any Kv7 family drugs.

 

[Gb3]

Looks like we might have something for help sooner rather than later. It doesn't fix the root cause but I'm open to any Kv7 family drugs.

Which drug are we going to be interested in?

 

[Matchbox]

Which drug are we going to be interested in?

Take your pick, there are a few K channel modulators in the pipeline from Xenon.

There was only one (Trobalt/Retigabine), and it's a niche market which worked for a lot of tinnitus sufferers but it was super dangerous & too broad acting.

Xenon's act on a similar mechanism with stronger binding.

 

[Matchbox]

XEN496 is a reformulation of Retigabine? Do we know if there will be fewer side effects than from Trobalt?

Yes. Lower dosings and stronger bonds where they believe it is most likely to react means less side effects or deposition in other non target tissues.

If it's safe for developing babies, it's safe for you.

 

[Gb3]

Yes. Lower dosings and stronger bonds where they believe it is most likely to react means less side effects or deposition in other non target tissues.

If it's safe for developing babies, it's safe for you.

When are these expected on the market?

 

[Tezcatlipoca]

When are these expected on the market?

2023 at the latest. Could be sooner if the FDA takes interest.

If it's safe for developing babies, it's safe for you.

It's also going to be tested for MDD, which I think means it is safe to take long term. Let's hope it doesn't give visual snow like Trobalt used to.

 

[Matchbox]

Let's hope it doesn't give visual snow like Trobalt used to.

Well, that might have to be a tradeoff, depends how much visual snow. Babies don't know if they get visual snow.

 

[Kleiner]

Well, that might have to be a tradeoff, depends how much visual snow. Babies don't know if they get visual snow.

XEN1101 seems to be an even better reformulation than XEN496. It targets KV7.2/3 channels and is much more selective.

In addition, it's tested on 300 adults, it will provide more information on side effects.

In the Phase 2 trial, subjects take one dose per day for 8 weeks. I don't know if this treatment is designed to be used for a long time.

The drug has not yet shown its effectiveness, but it's interesting.

 

[Tezcatlipoca]

XEN1101 seems to be an even better reformulation than XEN496. It targets KV7.2/3 channels and is much more selective.

In addition, it's tested on 300 adults, it will provide more information on side effects.

In the Phase 2 trial, subjects take one dose per day for 8 weeks. I don't know if this treatment is designed to be used for a long time.

The drug has not yet shown its effectiveness, but it's interesting.

And Quralis's QRA-244 is even more specific and potent than XEN1101, but they're only in pre-clinical stage.

 

[Lucifer]

Xenon Pharmaceuticals Announces Completion of Patient Randomization in XEN1101 Phase 2b "X-TOLE" Clinical Trial and Announces Upcoming Investor Webinar with Leading Epilepsy Key Opinion Leaders

XEN1101 Phase 2b "X-TOLE" clinical trial, announcing that randomization of 326 patients was completed in late June. Based on completion of patient randomization, Xenon anticipates topline results from the Phase 2b X-TOLE clinical trial in late September to mid-October 2021.

 

[Paulmanlike]

There won't be any tinnitus data though?

 

[Lucifer]

Xenon Pharmaceuticals Announces Conference Call and Webcast to Discuss Topline Results from Phase 2b 'X-TOLE' Clinical Trial of XEN1101

 

[Alan P]

Can someone help break the significance down a little for a dullard over here... Trying to follow along. Seems like this is good news but can't tell.

 

[Padraigh Griffin]

The big one. Best potential in short to medium term for relief along with Dr. Shore's device. Both focus on calming over excitable potassium channel cells, which cause tinnitus in a particular area of the auditory network.

 

[AfroSnowman]

So Phase 2b results, if they are magically awesome, can they move to market or do we need to wait 1-2 years for a Phase 3 to complete?

 

[r34d1ng]

Xenon Pharmaceuticals Announces Positive Topline Results from Phase 2b 'X-TOLE' Clinical Trial of XEN1101 for the Treatment of Focal Epilepsy

Stock +80% as of now.

 

[Stacken77]

I'm kinda hopeful, this could be big. But it'll most likely take some time before we know if it can benefit tinnitus for sure.

 

[Padraigh Griffin]

This will be big for tinnitus. Very big. Excellent results from the initial readout and the stock price tells the story.

 

[Joeseph Stope]

We'll all have a big party to celebrate at Pádraigh's house. I'll be taking my tent and pitching it in your front garden. Uncork the wine glasses and the Champagne.

Oh then there was FX-322. Hey! Wait a minute...

 

[Padraigh Griffin]

You are more than welcome. Loving the fada in the spelling too.

Honestly though. Trobalt showed efficacy for tinnitus for many. This is more potent, without the significant side effects. Dosage for focal epilepsy is 20-25 mg, but I'd say 10 mg off label might give a tinnitus effect. All speculation, but is it really when Retigibaine was efficacious. This only focuses on the Potassium channels that are needed.

Dr. Shore and many other reckon if we can put the brakes on these overactive cells, then tinnitus will improve. This drug will do that.

Let's wait and see but I have great hope for this.

FX-322 is incomparable as it was never proven for tinnitus in any shape or form. Anecdotal isn't solid proof as we were shown.

 

[Matchbox]

You are more than welcome. Loving the fada in the spelling too.

Honestly though. Trobalt showed efficacy for tinnitus for many. This is more potent, without the significant side effects. Dosage for focal epilepsy is 20-25 mg, but I'd say 10 mg off label might give a tinnitus effect. All speculation, but is it really when Retigibaine was efficacious. This only focuses on the Potassium channels that are needed.

Dr. Shore and many other reckon if we can put the brakes on these overactive cells, then tinnitus will improve. This drug will do that.

Let's wait and see but I have great hope for this.

FX-322 is incomparable as it was never proven for tinnitus in any shape or form. Anecdotal isn't solid proof as we were shown.

To be fair these forums would be considered case studies which is arguably not much better.

I think the stock is being overly optimistic. Phase 3 is the big hurdle to clear.

 

[Gb3]

Don't they have fast track status from the FDA? Do they have to have a Phase 3?

 

[r34d1ng]

Don't they have fast track status from the FDA? Do they have to have a Phase 3?

I believe they said during the call that this trial was not enough for the FDA to go straight to market and that they would need to do another one.