Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

Very true, the hype is a bit overblown imo. However, someone in the company said they are looking at tinnitus too:

Xenon Pharmaceuticals Inc (XENE) Q2 2020 Earnings Call Transcript | The Motley Fool

 

@Nobody19, one may wonder then, why didn't they test the drug on tinnitus, which is a far more common condition around the world? Epilepsy is like 1.2% of the total population or even less lol.

 

Can you cite the part with tinnitus? I tried to spot it in the whole text but I couldn’t find it.

 

Search for tinnitus in the transcript. Below is the only part that mentions tinnitus.

Simon Pimstone -- Chief Executive Officer

Sure. I'll take a stab at this, and Ian, please comment. It's Simon. Yes, I think in terms of the first question, no, we've been communicating for some time now. We're exploring indications outside of the focal epilepsy indication, which remains our primary indication for this drug, but there's a tremendous amount of literature that's building in the role of the KB72 and/or 3 channel in neuronal hyperexcitability that underlies a number of interesting neurological disorders where hyperexcitability appears to perhaps drive, for example, apoptosis in motor neuron disease in hyperexcitability through this channel, mediating Pain signaling. Hyperexcitability through this channel thought to have potentially a role in anhedonia and major depressive disorder. And we know these channels are also expressed in the ear and the hair cells, in particular, and the potential for treatment using a Kv7.2 modulator for tinnitus is also of interest.

So we're looking at a number of these types of disorders.​

 

Maybe because it’s easier to measure the improvement by counting number of seizures in a month. Current tinnitus indicators are vague, same for depression.

 

What is the timeline for this drug or the XEN-496?

 

Anyone knows how contact Xenon Pharmaceuticals? I tried to email to the address they have on their webpage and it says it is invalid. Thank you.

 

Official Title: A Phase 3 Study of Adjunctive XEN496 in Pediatric Subjects With KCNQ2 Developmental and Epileptic Encephalopathy

Actual Study Start Date: March 29, 2021

Estimated Primary Completion Date: November 2022

Estimated Study Completion Date: December 2022

 

I think if Phase 3 is successful it will be marketed at a high price point due to the niche area.

XEN1101 may be different particularly if it shows efficacy for depression.

 

Realistic concerns. A bunch of things could go wrong. It would be really disappointing if a bunch of other potassium channels need to be changed too.

I think the only real small evidence, other than it being called Trobalt 2.0, is I believe RL-81 which is called a revamped Trobalt prevented mice from getting chronic tinnitus.

Also even though I heard Danny Boy still had tinnitus, didn't he say he went from 10/10 to barely hearing it in 3 years?

 

Far more potency at a much much lower dose than Trobalt and more selective as regards the potassium channels, but yes there are adverse effects reported in the clinical trial.

 

Damn. Like what? Where can you see these results?

 

The most common TEAEs across all XEN1101 dose groups (n=211) were dizziness (n=52, 24.6%), somnolence (n=33, 15.6%), fatigue (n=23, 10.9%), and headache (n=21, 10.0%). Two TEAEs of urinary retention were reported in the active treatment groups, one of which required a dose reduction, and both subjects remained on drug with no other changes or intervention.

Xenon Pharmaceuticals Announces Positive Topline Results from Phase 2b ‘X-TOLE’ Clinical Trial of XEN1101 for the Treatment of Focal Epilepsy | Xenon Pharmaceuticals Inc. (xenon-pharma.com)

 

Interesting that the placebo group at 62% adverse effects were nearly as common as 10 mg and 20 mg groups at 67% and 68% respectively.

That gives me great hope of minimal ‘real’ side effects.

 

I would pop them like candy, severe tinnitus improving is much better than any side effect...

 

How good is that compared to other epilepsy drugs? Maybe this drug could find a good place because of its unique method and low risk of side effects.

 

There is no evidence that this works on tinnitus BUT, it could theoretically as it is a reformulation of Retigibaine, which is one of the few treatments that did work ever on this forum. It is more specific, potent, much lower dosing and most importantly when you look at that data objectively, the side effects are neglible, when compared to placebo.

The fact it targets potassium channels is also something that ties in with research out of Michigan, Oregon, and Pittsburgh.

Here's hoping!

 

Indeed. If Thanos Tzounopoulos gets his skates on we could potentially have two candidates for this type of therapy in a reasonable amount of time.

 

I don't know what he is waiting for... He has already had a $2M donation, and the molecule was designed years ago... Things are just too slow. We would need a good treatment within a year or two maximum.

 

Urinary retention still there which was also a side effect of Trobalt...

 

Tell me about it man. University research seems to take forever. But then the capitalised ventures get to market quicker yet leave us with a sense of shortfall and more questions than answers ala Neuromod.

I am actually quite optimistic at the moment. Susan Shore finally making steps to bringing her product to market after that press release in what, 2013??? And potentially an off-label pill to have a pop at. The next two years could be quite interesting for us.

 

Anyone knows how to contact Xenon Pharmaceuticals?

I tried to email to the address they have on their webpage and it says it is invalid. I will beg them XEN-496 and XEN-1101 for compassionate use, I don't mind being a guinea pig...

Thank you.

 

@DocTors_94, maybe you need to use the email address at the bottom of this page? I hope you find relief soon!

Xenon Pharmaceuticals - Expanded Access Program

 

I am to the point I don't care about the side effects, just long as it works.

 

Apologies, but how far away are the final test results?

 

Sorry for this stupid question, but how could this drug help us?

 

Phase 3 trial is planned for New Year 2023. Probably 2024/2025 before market.

 

By calming fusiform cells in the dorsal cochlear nucleus. It is a potassium channel modulator that in theory calms the over excitable cells by modifying the potassium levels. The DCN is thought to be the origin of tinnitus by a lot of researchers. It is the last point of entry for sound into the brain.

 

What is the difference between XEN-1101 and XEN-496? Is one more promising than the other?

 

One is for infant epilepsy and is a niche market. The other is for older people.