Auris Medical — Treatment of Tinnitus Through Modulation of Chloride Co-Transporter NKCC1

[ChrisBoyMonkey]

• Received "Intention to Grant" notice from European Patent Office
• Application covers invention of oral treatment for tinnitus

Hamilton, Bermuda, January 10, 2020 – Auris Medical Holding Ltd. (NASDAQ: EARS), a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in neurotology and central nervous system disorders, today announced that the European Patent Office (EPO) has issued a notice of "Intention to Grant" for its patent application entitled "Treatment of Tinnitus Through Modulation of Chloride Co-Transporter NKCC1 in the Auditory System" (European Patent Application 11 894 529.3).

The allowed claims cover compounds modulating the sodium potassium chloride co-transporter 1 (NKCC1) for use in the oral treatment or prevention of tinnitus. As demonstrated in an animal model of acute noise trauma, administration of an NKCC1 inhibitor resulted in a significant reduction of a biomarker for the presence of tinnitus (p<0.02). Inhibition of NKCC1 reduces trauma-induced excessive intracellular chloride ion levels in inner hair cells and the resulting neural hyperexcitability in the auditory system, which underlies the perception of tinnitus.

The communication from the EPO concludes substantive examination of the patent application, which is now expected to issue as a patent once the issue fees are paid and the patent office concludes its respective administrative procedures. A corresponding patent application is currently pending before the US Patent and Trademark Office (USPTO) and was already granted in Japan.

"We are very pleased with this new addition to our patent estate in tinnitus, which remains an area of great unmet medical need", commented Thomas Meyer, Auris Medical's founder, Chairman and CEO. "NKCC1 represents a new and promising target for tinnitus therapy, particularly because it may allow for oral treatment and thus complement Keyzilen®, our investigational tinnitus drug for intratympanic administration. We intend to develop a proprietary NKCC1 inhibitor through our new subsidiary, Zilentin Ltd., which we recently established in order to bundle our activities and assets within the therapeutic areas of tinnitus and hearing loss."

https://www.globenewswire.com/news-...llowance-for-European-Patent-Application.html

 

[TibuJenkins]

This is extremely interesting. Is this in the same vein as the KCNQ potassium channels investigated by Dr. Thanos?

 

[Benoves]

Is this only for acute tinnitus or also for chronic?

 

[El BUZZ]

But Keyzilen is nothing but AM-101 which just failed in its phase 3 clinical trial... Am I wrong?

 

[ChrisBoyMonkey]

But Keyzilen is nothing but AM-101 which just failed in its phase 3 clinical trial... Am I wrong?

It's not Keyzilen. It's more akin to what Dr. Tzounopoulos is working on, potassium ion channels.

 

[mrbrightside614]

As demonstrated in an animal model of acute noise trauma, administration of an NKCC1 inhibitor resulted in a significant reduction of a biomarker for the presence of tinnitus (p<0.02). Inhibition of NKCC1 reduces trauma-induced excessive intracellular chloride ion levels in inner hair cells and the resulting neural hyperexcitability in the auditory system, which underlies the perception of tinnitus.

Never seen a biomarker for tinnitus... this is definitely a completely unique approach, for which I am glad because there are at least 3 known companies working on Thanos's KV7 channel targets, with two of them indicating applications for tinnitus.

 

[Mentos]

Anyone have any idea when the clinical trials should start?

 

[Frédéric]

Is this "Treatment of Tinnitus Through Modulation of Chloride Co-Transporter NKCC1 in the Auditory System" AM-102?

https://aurismedical.com/product-candidates/pipeline

 

[FGG]

Is this "Treatment of Tinnitus Through Modulation of Chloride Co-Transporter NKCC1 in the Auditory System" AM-102?

View attachment 35466

https://aurismedical.com/product-candidates/pipeline

Apparently whatever it is, it has just been filed for a European patent:

https://www.hearingreview.com/hearing-loss/tinnitus/tinnitus-therapy/tinnitus

Will be easier to figure out once they put up a website for their otic spin off company, Zilentin.

 

[Frédéric]

Will be easier to figure out once they put up a website for their otic spin off company, Zilentin.

Yes I checked the Net, and it seems their website does not yet exist.

 

[Paulmanlike]

Auris Medical gained almost 20% on its stock price today. I have no idea why, nor researched it, but worth looking into.

 

[Greg Sacramento]

Auris Medical gained almost 20% on its stock price today. I have no idea why, nor researched it, but worth looking into.

I saw a large block share buy backed by a spread option at the open of regular hours. It dipped a little from a 20% rise and then smaller block shares that were also supported by option spreads were made. Only 6% of holdings is that of institutions and none appear to have spread options - eagle spreads, so probably an investor group wanted to close the money gap on open interest.

The only news that I could find at the open was that analysis of top-line data - their Phase 1b trial -
that is evaluating AM-201 in healthy volunteers will be released soon.

I think that the gap was closed too tight - no room for investment error, unless the analysis of news is quite outstanding.

 

[Croaker]

This is interesting. If this works along the same lines as Thanos' Trobalt reformulation, it means that we may see phase 1 results within a year or so! I think this strategy looks very promising (are they saying they found tinnitus biomarkers?!) but I thought it would be years before we saw any quality data one way or another. (Data about any drug trying this potassium ion channel blocking to clarify.)

That being said, they haven't updated their pipeline so AM 102 still says they're searching for a compound... hopefully that changes soon.

 

[Matchbox]

There is already a loop diuretic used in Meniere's which antagonizes this receptor. It's also present in your kidneys. It's also a minor GABA antagonist as well.

In the acoustic model of blast damage in mice, hydrops do form. However, they are temporary... but do cause neuron losses. They can be reversed as well as the neuron damage by preventing the initial hydrops with that drug and guess this... hypertonic saline on the round window as well in mice models. It might explain why even placebo tests show drugs to be ineffective when in fact the placebo turns out to have a real effect.

There's a YouTube video outlining the paper by the head researcher.

 

[BB23]

Apparently Auris Medical had their name change to Altamira Theraputics, and I don't see the NKCC1 drug in their pipeline anymore. I can't find the reason why they dropped it from their pipeline.

I was doing some research on NKCC1 drugs online. It has some promise. Some people also expect it to work for visual snow syndrome as well.

Treatment of tinnitus through modulation of chloride co-transporter NKCC1 in the auditory system

Other companies came to the rescue though, these drugs are still being developed:

Iama Therapeutics' IAMA-6 shows promise in preclinical mesial temporal lobe epilepsy

Preclinical Development of the Na-K-2Cl Co-transporter-1 (NKCC1) Inhibitor ARN23746 for the Treatment of Neurodevelopmental Disorders

 

[Nick47]

@BB23, nothing anywhere near human clinical trials and not even a throwaway comment to the tinnitus community. As good as dead and/or decades away!

 

[BB23]

@BB23, nothing anywhere near human clinical trials and not even a throwaway comment to the tinnitus community. As good as dead and/or decades away!

"We expect to begin a first-in-human, Phase 1 clinical study evaluating the safety, tolerability, and pharmacokinetic characterization of single and multiple doses of IAMA-6 in late 2023."

(Source)

 

[StoneInFocus]

The allowed claims cover compounds modulating the sodium potassium chloride co-transporter 1 (NKCC1) for use in the oral treatment or prevention of tinnitus. As demonstrated in an animal model of acute noise trauma, administration of an NKCC1 inhibitor resulted in a significant reduction of a biomarker for the presence of tinnitus (p<0.02). Inhibition of NKCC1 reduces trauma-induced excessive intracellular chloride ion levels in inner hair cells and the resulting neural hyperexcitability in the auditory system, which underlies the perception of tinnitus.

From this excerpt alone alone it is not clear to what extent increased NKCC1 activity specifically, instead of excessive intracellular chloride ion levels in inner hair cells in general, is the cause of tinnitus.

IAMA mentions that "the activity of NKCC1 increases in several pathological conditions; this is why NKCC1 inhibition shows great potential in treating idiopathic and secondary forms of autism (autism spectrum disorder, or ASD), refractory epilepsy, and other neurological conditions."

Does tinnitus also belong to that group of pathological conditions in which NKCC1 activity is increased?

 

[BB23]

IAMA Therapeutics Announces Approval of Clinical Trial Application (CTA) by the Italian Medicines Agency (AIFA) to Initiate a Phase 1 Study of IAMA-6 for the Treatment of Autism and Epilepsy

IAMA-6 has shown encouraging in vitro and in vivo proof of concept results in autism spectrum disorders and drug-resistant epilepsies. The compound is designed to directly target and inhibit NKCC1 and neuronal hyperexcitability.

The Company expects to begin dosing healthy adults in the Phase 1 study in January 2024.

Should we email them and ask whether they want to test the drug on tinnitus and/or visual snow syndrome patients? Letting them know we are interested in possible treatments with this drug?