Frequency Therapeutics — Hearing Loss Regeneration

[HootOwl]

Synapses, nerve or brain stem cannot be affected by damage (oxidation) due to stress?

I believe the synapses and hair cells can be damaged via stress due to the glutamate component. Glutamate storms can do a number on inner hair cell structures that are already inflamed or at risk for damage.

Not sure about brain stem.

 

[WickedCarnival]

Synapses, nerve or brain stem cannot be affected by damage (oxidation) due to stress?

I think the main cause of stress induced tinnitus or hearing loss is that stress suppresses the immune system which leaves you more vulnerable to infection and viruses. Both some known and many different unknown viruses can cause damage to the auditory system via nerve inflammation and damage, or possibly hair cell death.

Those are some of the suspicions of what contributes to "Sudden Sensorineural Hearing Loss" when the body reacts to a large viral load and affects the delicate auditory system. Sometimes the rest of your body may not react in the stereotypical way of fighting viruses such as respiratory symptoms, cough, ear fluids, etc. and that makes sense because a lot of case reports of SSHL often mention that the patient had it come on "suddenly" with only very mild symptoms of a cold, or none at all.

Over the course of one's life, a handful of viral infections can also slowly degrade the auditory system if a person lives a stressful life, eats an inflammatory diet, is exposed to environmental toxins that contribute to inflammation, and etc.

Again, this is all variable and each human being's system can react differently to a variety of circumstances. It can be a challenge, but trying to live your best life and reducing stress as much as possible seems to be a protective factor. But also again, we still need biomedical treatments and interventions to repair damage for the things we can't control.

 

[sssing]

I was looking through other trials for hearing issues (really cannot recall the trial anymore) and was surprised that tinnitus was tested too. My question is... could it be that Frequency tests tinnitus as it's a routine practice of ANY trial involving hearing issues? What I mean is tinnitus is tested not because of positive correlations from the safety trial but rather it is a safety net to see if it worsens a person's existing tinnitus etc... of course, I really hope it's not as what I guessed!

 

[Lucifer]

I was looking through other trials for hearing issues (really cannot recall the trial anymore) and was surprised that tinnitus was tested too. My question is... could it be that Frequency tests tinnitus as it's a routine practice of ANY trial involving hearing issues? What I mean is tinnitus is tested not because of positive correlations from the safety trial but rather it is a safety net to see if it worsens a person's existing tinnitus etc... of course, I really hope it's not as what I guessed!

When you are talking about the other trial, do you mean Audion Therapeutics?

 

[sssing]

No, it was just any other trial which involved the ears, not even sure if it was a drug or device trial. But the rationale behind why tinnitus was tested was to see if it was worsened...

 

[Lucifer]

No, it was just any other trial which involved the ears, not even sure if it was a drug or device trial. But the rationale behind why tinnitus was tested was to see if it was worsened...

I think with Frequency Therapeutics and Audion Therapeutics they both added tinnitus as an indication and I think none of the patients ended up worse as they stated there were no major side effects.

I would assume if tinnitus became worse because of these drugs it would be considered a major side effect.

 

[sssing]

Thanks, I really hope it's so. This question had been bugging me for a few weeks.

 

[Diesel]

No, it was just any other trial which involved the ears, not even sure if it was a drug or device trial. But the rationale behind why tinnitus was tested was to see if it was worsened...

I tend to agree with @Lucifer on this one, if tinnitus symptoms got worse in the safety phase of the trial, they probably would not have proceeded.

In an old presentation video just before the Phase 2a started, Carl LeBel specifically said that tinnitus is a secondary outcome because they want to measure if it improves as a result of receiving FX-322.

 

[patorjk]

I was browsing Frequency's website and found this presentation which is dated April 2020:

https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1

One bit of info that caught my eye was that it says: "Phase 2a study ongoing; ~50% enrolled*". That seems kind of low, especially considering that they expect to be done at the end of September [1]. With the study taking 210 days, and there being only ~180 days between March 26th and Sept 30th, I don't see how they can finish on time.

Based on the 50% number, they have 48 people enrolled. I'm not sure sure what number of people is needed for a phase II study, but maybe that's enough people?

[1] https://clinicaltrials.gov/ct2/show/NCT04120116

 

[FGG]

I was browsing Frequency's website and found this presentation which is dated April 2020:

https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1

One bit of info that caught my eye was that it says: "Phase 2a study ongoing; ~50% enrolled*". That seems kind of low, especially considering that they expect to be done at the end of September [1]. With the study taking 210 days, and there being only ~180 days between March 26th and Sept 30th, I don't see how they can finish on time.

Based on the 50% number, they have 48 people enrolled. I'm not sure sure what number of people is needed for a phase II study, but maybe that's enough people?

[1] https://clinicaltrials.gov/ct2/show/NCT04120116

I very highly doubt they can stick with the September date. Hopefully, it isn't delayed too much further though.

 

[AtlasFainted]

I was browsing Frequency's website and found this presentation which is dated April 2020:

https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1

One bit of info that caught my eye was that it says: "Phase 2a study ongoing; ~50% enrolled*". That seems kind of low, especially considering that they expect to be done at the end of September [1]. With the study taking 210 days, and there being only ~180 days between March 26th and Sept 30th, I don't see how they can finish on time.

Based on the 50% number, they have 48 people enrolled. I'm not sure sure what number of people is needed for a phase II study, but maybe that's enough people?

[1] https://clinicaltrials.gov/ct2/show/NCT04120116

I think it's enough people. They stated weeks ago that they have enough people enrolled to meet their key objectives.

I'd still say the more they enroll the better though. That should increase the odds of them either skipping phase 2b, or getting breakthrough therapy status. In either scenario, we get the drug on the market quicker.

 

[Lucifer]

I think it's enough people. They stated weeks ago that they have enough people enrolled to meet their key objectives.

I'd still say the more they enroll the better though. That should increase the odds of them either skipping phase 2b, or getting breakthrough therapy status. In either scenario, we get the drug on the market quicker.

I think it could be enough if those 48 participants have had exceptional improvements in their word scores.

But if they can get more participants even better.

 

[FGG]

I think it's enough people. They stated weeks ago that they have enough people enrolled to meet their key objectives.

I'd still say the more they enroll the better though. That should increase the odds of them either skipping phase 2b, or getting breakthrough therapy status. In either scenario, we get the drug on the market quicker.

Phase 2a is for figuring out effective dosing, phase 2b is for testing that dosing against placebo without the confounding variable of multiple dosing.

I don't see how skipping phase 2b is very likely because there would be only a handful of people at each dosing. I think skipping phase 3 is not that unrealistic though given there is no "standard treatment" to compare to.

 

[AtlasFainted]

Phase 2a is for figuring out effective dosing, phase 2b is for testing that dosing against placebo without the confounding variable of multiple dosing.

I don't see how skipping phase 2b is very likely because there would be only a handful of people at each dosing. I think skipping phase 3 is not that unrealistic though given there is no "standard treatment" to compare to.

Does it seem like dosing would vary depending on the amount of damage you have though?

Or maybe that's what they're trying to figure out; what a good baseline is to work off of...

Also if there are very clear and demonstrable results across the board with phase 2a, why do further testing against a placebo? I obviously don't understand the intricacies involved here, but it seems like that would prove it's efficacy at least enough to be considered for breakthrough therapy or some other form of early access.

Maybe they'll have production scaled up enough by then to open up compassionate use?

If we're looking at another year of trials minimum before we possibly get access, that is sad news. This drug has been in existence for over 3 years now...

 

[FGG]

Does it seem like dosing would vary depending on the amount of damage you have though?

Or maybe that's what they're trying to figure out; what a good baseline is to work off of...

Also if there are very clear and demonstrable results across the board with phase 2a, why do further testing against a placebo? I obviously don't understand the intricacies involved here, but it seems like that would prove it's efficacy at least enough to be considered for breakthrough therapy or some other form of early access.

Maybe they'll have production scaled up enough by then to open up compassionate use?

If we're looking at another year of trials minimum before we possibly get access, that is sad news. This drug has been in existence for over 3 years now...

The question about when they will scale up production enough for compassionate use will probably tell us when the soonest we will have access actually is.

 

[Lucifer]

Does it seem like dosing would vary depending on the amount of damage you have though?

Or maybe that's what they're trying to figure out; what a good baseline is to work off of...

Also if there are very clear and demonstrable results across the board with phase 2a, why do further testing against a placebo? I obviously don't understand the intricacies involved here, but it seems like that would prove it's efficacy at least enough to be considered for breakthrough therapy or some other form of early access.

Maybe they'll have production scaled up enough by then to open up compassionate use?

If we're looking at another year of trials minimum before we possibly get access, that is sad news. This drug has been in existence for over 3 years now...

I'm pretty sure they could easily find out the maximum dosage before any side effects or minimal side effects appear during Phase 2a clinical trials and then be able to use that as baseline to get the efficient dosage with less or no side effects. Hopefully they could release FX-322 ASAP.

 

[AtlasFainted]

The question about when they will scale up production enough for compassionate use will probably tell us when the soonest we will have access actually is.

Yeah, I'll keep an eye out for any news regarding this specifically. I check this forum daily but I also want to keep an eye out on other sources for new information (and possibly bring it here).

I guess Frequency's Twitter would be a good place to start. Any other suggestions as far as research goes?

 

[Danad]

If phase 2a gets top line results then hopefully that will trigger scaled up production which may allow for expanded access. It will be pricey more than likely (revenue stream) and could be a windfall as far as positive exposure for the drug even before FDA approval.
Well it's fun to dream of such things anyhow.

 

[Daniel Lion]

Is Frequency actively involved with or collaborating with medtech companies to get a better delivery system? Perhaps a question to be asked if it isn't already on the Tinnitus Talk Podcast interview question list.

I read something by @AtlasFainted that really gave me some big optimism to the potentials of this drug if delivery is improved. My audiological needs are big.

 

[sssing]

https://masseyeandear.org/assets/MEE/pdfs/ent/tbregistry/2019-summer-vol-26-no2.pdf

Sorry if this is the wrong thread but I read something based on Harold Schuknecht's finding that was informative for me.. Something about extent of damages to the organ of Corti due to a blow on the head (temporal area). In the article, he likens the physical impact of a blow on temporal bones to that of an acoustic shock. Widespread damage to the organ of Corti and no more inner and outer hair cells... think someone here mentioned he would be excited to hear about regrowing hair cells if he were still alive.

 

[sssing]

Just went to cross reference the more current research done by Liberman... Can anyone help me square this finding on hair cell damage and the research by Liberman on no hair cell damage but synaptic loss? If what Schuknecht mentioned that a physical blow is akin to a noise trauma on the inner ear then it seems to me this two findings clash with one another... one stating that the damage noise does is hair cell loss and widespread damage to the organ of Corti is the problem but the other states that noise leads to neuronal degeneration in the absence of hair cell damage.

"Following this experiment, Schuknecht proposed that the mechanism of inner ear damage following head injury was very similar to intense noise and/or blast impulse trauma, in which a pressure wave or sound is transmitted through bone to the cochlea, resulting in a "shock pulse." This pressure pulse leads to violent displacement of the basilar membrane, causing injury of the organ of Corti. Schuknecht was also puzzled with high frequencies being the most commonly involved in his experiment, in particular the range from 3 to 8kHz. He considered some possible explanations for this finding, such as an inherent fragility in the upper region of the basal turn or physical properties of the impulse."

 

[Lucifer]

Is Frequency actively involved with or collaborating with medtech companies to get a better delivery system? Perhaps a question to be asked if it isn't already on the Tinnitus Talk Podcast interview question list.

I read something by @AtlasFainted that really gave me some big optimism to the potentials of this drug if delivery is improved. My audiological needs are big.

A while back @FGG found out that Frequency Therapeutics were hiring someone to improve their drug delivery method.

 

[FGG]

Yeah, I'll keep an eye out for any news regarding this specifically. I check this forum daily but I also want to keep an eye out on other sources for new information (and possibly bring it here).

I guess Frequency's Twitter would be a good place to start. Any other suggestions as far as research goes?

Their website lists their expanded use policy. I would check back there from time to time.

 

[aot]

Any idea on how FX-322 might affect Ménière's disease?

 

[sssing]

Like everyone here, I wish the results will be posted ASAP and hopefully there's good news for All of us

 

[sssing]

Any idea on how FX-322 might affect Ménière's disease?

Hi. I think FX-322 is supposed to regrow the hair cells that were lost on the organ of Corti.

Ménière's has to do with fluid imbalance in the bony labyrinth, especially the endolymph. I can't see how it might negatively affect Ménière's since it's fixing the structural damage... unless it's the chemistry of the drug in FX-322 that interferes further with the fluid imbalance.

I heard a case who contracted Ménière's after playing the flute since he was a boy... so I think maybe there's some connection between Ménière's and structural damage... this is just my own guess.

 

[FGG]

Any idea on how FX-322 might affect Ménière's disease?

It clearly won't affect hydrops or the abnormal Reissner's membrane in Meniere's but I suspect it will repair the hair cells damaged just as well if:

1) they can reduce the hydrops at the time of injection.

2) the round window isn't too impermeable in late stage Meniere's, though with even a little permeability I think some drug could get in.

With a lot of Meniere's patients, the hearing loss is very low frequency also so they may have to wait until FX-322 version 2.0 to reach that far into the cochlear, however.

 

[WickedCarnival]

Is Frequency actively involved with or collaborating with medtech companies to get a better delivery system? Perhaps a question to be asked if it isn't already on the Tinnitus Talk Podcast interview question list.

I read something by @AtlasFainted that really gave me some big optimism to the potentials of this drug if delivery is improved. My audiological needs are big.

A while back @FGG found out that Frequency Therapeutics were hiring someone to improve their drug delivery method.

This looks like a promising future technology for better drug delivery: https://otomagnetics.net/about

 

[Lucifer]

When Frequency Therapeutics showed what a healthy ear and a damaged ear looks like, how did they do the imaging for it?

 

[sssing]

I think the samples had to be cut out from the person or animal to be imaged. Most of the human cochlear samples we see if not all are from donated deceased from what I gather. Animals too, they'll euthanise it, remove and then image it.