1st Order Pharmaceuticals Inc: 1OP-2198

No. The drug that Tzounopoulos developed is RL648_81 (no news about it since Q2 2016).

This one is aquired by Xenon pharma last April and is since rebranded as XEN1101. If everything goes as scheduled fase 1 trail will start in Q4 this year: http://investor.xenon-pharma.com/phoenix.zhtml?c=253202&p=irol-newsArticle_pf&ID=2265689

 

Why is there no news at all about RL648_81? Are they having problems or cannot find the funds to continue trials? What is going on?

 

No, and he didn't develop any medicine. He developed a chemical compound concept was my understanding; in practice and on humans it could be very different.

 

And as far as you know, is anything happening with that compound or is he just sitting on it?

 

Maury Raycroft

Got it. And then for 1101 you mentioned Tinnitus, Pain, and ALS, as other indications potentially and I was just wondering if one of the indications has a higher priority or maybe a better mechanistic perhaps [ph] now.

Simon Pimstone

Yes, no great question. I think if I had to order them I'd probably put sort of Tinnitus and ALS at the top and Pain following. There has been quite a bit of interesting reports of off label use of Ezogabine and patients with Tinnitus as far as I'm aware in a randomized control trial but quite a lot of interesting anecdotal data. We know that potassium channels are expressed in the hair cells and this is been an interesting target. So, we're thinking about this pretty significantly for the 1101 program. ALS as well, I think well I'm we should be offline can provide some of the mechanism based thinking that there is literature supports the role of this channel in neuronal cells and particularly in patients with ALS.

Some work that’s being done in pluripotent stem cells that may suggest that potassium channel modulators could be of benefit. So, again I think both in ALS and Tinnitus, the potassium channel mechanism I think is a very interesting one is data around the mechanism in both these indications and I think both obviously huge areas of opportunity in terms of current treatment gaps in areas of need. So while we're not yet ready for prime time to lay out development strategy for those indications and as we updated the focus initially is clearly to follow on what Ezogabine has done, the path has been very well laid out for us. There is going to be work that we will be adding both pre-clinically and hopefully clinically to test this drug based on the Phase 1 -- outcome of the Phase 1 safety PK to test this drug in other indications which we think could be very well suited.

 

What exactly is ezogabine?

 

Trobalt?

 

Correct. Many pharmaceutical compounds often have different trade names or product names.

 

Thank you for the explanation.

 

It's official ladies and gentlemen... phase 1 trial of XEN1101 (formerly known as 1OP-2198) will start in Q4 2017 with phase 2 following in second half of 2018. Initial for epilepsy targeting Kv7.2 channels, but who knows... maybe a miracle for tinnitus could also happen.

More information on the newly released product information page:

http://www.xenon-pharma.com/product-candidates/epilepsy/xen1101/

Fingers crossed!!

PS @Admin: Could the title of the thread be changed to: "Xenon pharma: XEN1101 (formerly known as 1OP-2198)". Thanks!

 

Brilliant work. Thanks for keeping the tinnitus community updated on the development of this.

 

It depends if tinnitus is listed as a secondary outcome in this trial, or if some participants (who had tinnitus) will spontanously indicate that their tinnitus have improved after the treatment.

 

I've been in touch with them a few days ago:

 

I personally think the most important thing is the Drug hits the market. Then is up to us to get our doctors to try it off label

 

Xenon Pharmaceuticals Announces Initiation of XEN1101 Phase 1 Clinical Trial
Pharmacodynamic read-out expected in Q1 2018 and XEN1101 Phase 2 proof-of-concept clinical trial anticipated to begin in Q3 2018

 

From their presentation at Stifel 2017 Healthcare Conference:

 

Hopefully it's succesful. Can't wait for this drug to hit the market.

 

@vermillion

 

Here is the clinicaltrials page for XEN1101 https://clinicaltrials.gov/ct2/show/NCT03340220?term=xen1101&recrs=ab&rank=1 They're looking for participants. Trial 1 is supposed to end next April. The trials are held in London.

They don't mention tinnitus as an exclusion criteria

 

Hope someone will join with T.

 

C'mon you Brits with tinnitus!

 

Why would they? People with tinnitus can still be healthy enough to be enrolled in a phase 1's safety trial. I bet they won't mention tinnitus either in the exclusion criteria for phase 2, though only people with some kind of epilepsy will be able to participate. Perhaps I shall recall that XEN1101 isn't being trialed for tinnitus, but epilepsy.

 

Seems like getting people with tinnitus to join Phase 1 is the one shot we have to see if XEN1101 can help tinnitus.

 

It's a shame that they don't test tinnitus while also testing for Epilepsy, you know, could kill 2 birds with one stone

 

That's great, thanks for restoring my hope in this drug Benevos!

Aw man. I hope this work, tinnitus sucks.

Just a question regarding Trobalt to which this drug is based on/similar MoA. Just how successful was Trobalt? Was there any sort of sub group of sufferers that it benefited most (like noise induced/stress induced) any limitations to length of time of tinnitus onset to how it affected it? How much by and how long did it last?

I know all this is in the Trobalt comments but I'm trying to get an idea on how good it actually was and how this may have potential to suppress the t. Cheers

 

From what i've read 50/50. Don't forget this drug is like 10 till 15 times more potent in hitting the targets compared with Trobalt what i've heard. But it's only a phase 1 trial. Despite we've got many of them, no one did really a great thing. It's better then nothing. From every trial they learn something, so we will be closer. Maybe this drug is great for some with Tinnitus with lessen side effects, i pray for them.

I can't tell u anything about noise induced/stress induced. The theory i believe the most is from Josef Rauschecker, so it's a combination of both. If they can resolve Tinnitus with hair cell regeneration? I don't know, but it looks promising. Some good researchers also believe that regeneration will reverse Tinnitus. Maybe they can supress it with DBS (deep brain stimulation), but it's a long way to go. A researcher from our country (dr. De Ridder) tried with some DBS on a few patients, some others did too. The results where 50/50 for complete supressing, but not long term.What i've read they just used wrong stimulation, to much a rectangle impuls, electric impulses from the body are more fluently so our brain habituated to the strange impulses he said. There are some papers on the web which i read (in Dutch). From the theory of Rauschecker he also stimulated the wrong area's.

The theory of Rauschecker is the only one which can explain the differences (sounds, volume, intermittent, etc.) to me. I really believe there are lots of triggers to get Tinnitus, but i believe even more there is 1 solutions to supress the symptom (tinnitus). I think lots of people would be helped if they would be able to supress the symptom. The Pharma can make big money with a Drug to supress tinnitus. There are a lot of supress drugs on the market, even more then real solutions. I don't know why, but it's logic to me. Because of much different triggers i believe it's even better to focus onsupress the symptom instead of cure the cause, a lot more people would be helped i quess. The more i read the more i believe it's a brain thing.

Still praying for this drug to work. There are a LOT of other things going on. I hope in 10 years ENT's can say Tinnitus? Give it 4 weeks, doesn't it lessen get this drugs for a few days. Also hearing loss? If it affects your life a lot u should think about regeneration. Maybe the regeneration is a double edged sword and can cure both, we don't know thill they tried. It's a long wait, but i really believe it's worth waiting for. Look where we are now. I am 9 weeks into this. Did read a lot, especially research. If u are a stranger to this, it make me laugh a bit when you read threats from 2014. There were a lot of people and researchers who didn't believe there would be clinical trials till 2025. 3 Years further, look where we are now. Already a company in trial, lot's of other lining up.

It's a promising time right now. A lot of drugs where discoverd by accident, like viagra. Well dr., it didn't lessen my blood pressure but.... The same thing happened already with DBS by parkinson sufferers, who also had tinnitus. The DBS also lessened the tinnitus for some. They only don't know really why. Some people got car accidents and brain surgery, tinnitus gone. They only don't know really why. It's like shooting with a canon to kill a mosquito now. I really would love to be so wrong and some researchers are right at the moment.

 

I've gotten in touch with someone that has tinnitus who said they will be in the XEN1101 phase 1 trial. Looking forward to their experience.

 

Take it they have epilepsy? Or is phase 1 just for safety tests on healthy patients? Keep us posted and thanks for update

 

Very interesting. Keep us updated. When wil he/She start?