Frequency Therapeutics — Hearing Loss Regeneration

[tiredofit]

Do they know the cause? I think Decibel Therapeutics and Rinri Therapeutics are working on a couple of projects for those who are born deaf.

My cochlear and vestibular thingy are both slightly malformed, I don't know anything about my hair cells.

 

[wwtsai]

Since we're discussing genetic/hereditary hearing loss, I wanted to link a webinar conducted by Medicines Discovery Catapult on Tuesday regarding cell and gene therapy approaches to hearing loss. This webinar includes a presentation by the founder of Rinri Therapeutics and other experts regarding stem cell and AAV methods.

The Emerging Hearing Medicines Landscape Webinar Series - Webinar 4: The Challenges and Opportunities for Emerging Cell and Gene Therapy Approaches to Address Hearing Loss

 

[frpp]

Since we're discussing genetic/hereditary hearing loss, I wanted to link a webinar conducted by Medicines Discovery Catapult on Tuesday regarding cell and gene therapy approaches to hearing loss. This webinar includes a presentation by the founder of Rinri Therapeutics and other experts regarding stem cell and AAV methods.

The Emerging Hearing Medicines Landscape Webinar Series - Webinar 4: The Challenges and Opportunities for Emerging Cell and Gene Therapy Approaches to Address Hearing Loss

Can't view it. Is there anything in there on growing support cells, or transplanting hair cells/support cells?

 

[wwtsai]

Can't view it. Is there anything in there on growing support cells, or transplanting hair cells/support cells?

They grow pluripotent stem cells and convert them to either hair-like cells or auditory neurons.

 

[NateTwo]

Would being diagnosed with Outer Hair Cell Dysfunction increase one's chances of being selected for the FX-322 clinical trial?

 

[weab00]

Would being diagnosed with Outer Hair Cell Dysfunction increase one's chances of being selected for the FX-322 clinical trial?

I don't think we have the diagnostics to the determine cause of tinnitus yet, let alone which part of the cochlea is damaged. They select you based off how long you've had SNHL and an audiogram I think.

 

[serendipity1996]

They grow pluripotent stem cells and convert them to either hair-like cells or auditory neurons.

I watched the entire presentation live -- I wish I had taken notes though. The "hair-like cells" cells sort of gives me pause since they may not be as good as "natural" hair cells?

 

[Pre55ure]

Do you think FX-322 could also treat issues with balance?

Seems very unlikely. The part of your cochlea that FX-322 will help is is different and distinct from the part that regulates balance.

 

[wwtsai]

I watched the entire presentation live -- I wish I had taken notes though. The "hair-like cells" cells sort of gives me pause since they may not be as good as "natural" hair cells?

Yeah, that terminology made me pause too. I think they can replicate what seems to be hair cells, but aren't 100% at establishing function such as having them act as OHC or IHC.

 

[weab00]

I watched the entire presentation live -- I wish I had taken notes though. The "hair-like cells" cells sort of gives me pause since they may not be as good as "natural" hair cells?

Yeah, we don't want "hair-like cells," give me some damn new born stereocilia.

 

[Princebeyel]

Seems very unlikely. The part of your cochlea that FX-322 will help is is different and distinct from the part that regulates balance.

Damn. I had good balance before I lost my hearing!

 

[sensualmosquito]

Yeah, that terminology made me pause too. I think they can replicate what seems to be hair cells, but aren't 100% at establishing function such as having them act as OHC or IHC.

I believe this is a more scientific way of looking at it. They can observe these cells as exhibiting the characteristics of hair cells (as we understand) but in the end they cannot conclude with certainty that they are exactly the same.

 

[twa]

FX-322 regrows hair cells so it will help if you have hair cell loss. It's not a general tinnitus drug.

Hair cell loss isn't the mechanism of action for benzo induced tinnitus. However, if you had hair cell loss and the benzos worsened the tinnitus from the structural deficit, I could see it being helpful.

Yes, I could be wrong but I do think when a drug is ototoxic it causes some damage.

 

[FGG]

Yes, I could be wrong but I do think when a drug is ototoxic it causes some damage.

Correct, which is why benzos aren't technically considered ototoxic.

 

[Greg Sacramento]

Correct, which is why benzos aren't technically considered ototoxic.

CT brain scans show a difference in ventricular cerebral spinal fluid space dimensions between benzodiazepine users and non-users, and also between high and low benzodiazepine users.

 

[FGG]

CT brain scans show a difference in ventricular cerebral spinal fluid space dimensions between benzodiazepine users and non-users, and also between high and low benzodiazepine users.

Oh it's definitely neurotoxic but not classically "ototoxic" in the strict sense.

 

[Greg Sacramento]

Oh it's definitely neurotoxic but not classically "ototoxic" in the strict sense.

Benzos can be very ototoxic on hearing with withdrawal from use as Frequency Therapeutics is well aware of.

I would need to post more than one-liners with data to explain about withdrawal from use, but not feeling well to do so.

I would like to give you a hug for all your outstanding contributions.

 

[FGG]

Benzos can be very ototoxic on hearing with withdrawal from use as Frequency Therapeutics is well aware of.

I would need to post more than one-liners with data to explain about withdrawal from use, but not feeling well to do so.

I would like to give you a hug for all your outstanding contributions.

I fully agree with you. They wreak havoc on the auditory system with tolerance or withdrawal.

I have seen benzos left off of lists of "ototoxins" because of its different mechanism of action though.

I think in general it is splitting hairs but probably in discussions about regenerative medicine it makes sense to point out the distinction because something like aminoglycosides destroy hair cells and FX-322 could help, where it is less straight forward with benzos and depends on whether hair cells are lost.

Can I give you a hug back? I have learned so much from you!

 

[HeavyMantra]

Can I ask that someone gives me a short version of what's going on with FX-322? I haven't read about this at all, do you think they really are on to something here?

 

[HeavyMantra]

It's just crazy how an audiologist can tell you that frequencies above 8 kHz are irrelevant to your hearing when it's information that can be readily accessed on Google.

My AuD legit told me it didn't matter; I think this is the case for many people here as well.

It's pretty crazy, I know. But I think that for these professionals who mostly deal with people struggling to communicate verbally with others at all, children developing language skills in spite of major hearing loss and so on, the frequency range of the human voice is what seems important. Hearing loss above that pretty much mostly becomes a major problem for us unfortunate enough to get tinnitus because of it or music lovers. Learning about what audiologists are trained to deal with makes my problems seem small in comparison. But it has still ruined my life so there's that, comparison doesn't change that or make it any less of a problem for me and my loved ones...

 

[Gb3]

Benzos can be very ototoxic on hearing with withdrawal from use as Frequency Therapeutics is well aware of.

I would need to post more than one-liners with data to explain about withdrawal from use, but not feeling well to do so.

I would like to give you a hug for all your outstanding contributions.

Could you explain more about how Frequency Therapeutics is aware of this?

 

[tommyd87]

It's pretty crazy, I know. But I think that for these professionals who mostly deal with people struggling to communicate verbally with others at all, children developing language skills in spite of major hearing loss and so on, the frequency range of the human voice is what seems important. Hearing loss above that pretty much mostly becomes a major problem for us unfortunate enough to get tinnitus because of it or music lovers. Learning about what audiologists are trained to deal with makes my problems seem small in comparison. But it has still ruined my life so there's that, comparison doesn't change that or make it any less of a problem for me and my loved ones...

The audiology profession is very interesting with what work they do. They totally tend to claim that sounds above 8000 Hz are irrelevant etc along with a whole load of other claims which don't stack up either. Essentially I have found that multiple audiologists are also very guarded and defensive when they are challenged on what they are claiming and presenting.

The thing that I notice is if the treatments like OTO-413 or FX-322 have a large influence on hearing then there will be a big shift in that industry, in particular relating to the way which they work which was why I believe we have seen some of them make the claims they have relating to such medicine.

 

[patorjk]

Can I ask that someone gives me a short version of what's going on with FX-322? I haven't read about this at all, do you think they really are on to something here?

The best resource is Frequency Therapeutics' most recent overview presentation:

https://investors.frequencytx.com/static-files/4ac687f2-04b5-4d23-ab23-daa7826cd1b0

The short-short version is they have a drug that regrows hair cells. It improved several individuals' word recognition scores in Phase I/II (with statistical significance), and several other improvements were seen too (ex: some reports of improved tinnitus). Phase 2a is underway, they tried to recruit people like the "4 responders" from Phase I/II. Tinnitus is being explicitly looked at this time. Top-line results (from the first 90 days of Phase 2a) are due next March.

 

[tommyd87]

Can I ask that someone gives me a short version of what's going on with FX-322? I haven't read about this at all, do you think they really are on to something here?

> Phase 1/2 was only one dose/shot and it showed both non statistically significant and statistically significant improvement in word recognition and also statistically significant improvement in hearing volumes as well. We were also shown the medicine has been fairly safe thus far.

> Phase 2a is ongoing now and is a multi dose clinical trial with a readout of 90 day results due in March. This is 90 days from the time that the last patient got doses. The final Phase 2 results will be out in July next year.

> Frequency Therapeutics has expanded the scope of the clinical trials to test other categories too such as severe and age related hearing losses. These will be scheduled to be concluded around the same time as they will complete the noise phase 2a trial.

> The thought that Frequency Therapeutics has is that they will then proceed to Phase 3 according to Loose, their Chief Scientific Officer.

> The treatment has shown in the trials conducted in the lab that it is able to offer full regrowth across the board.

> Secondary measures such as speech in noise, tinnitus are being evaluated during this trial. There is no indication if it is going to be mentioned as part of the 90 day read out material or not, so this will mean that this then shall become part of the full trial outcomes.

> Frequency Therapeutics seems to be operating on a method of getting the treatment working now and showing it improves people's hearing to pass the FDA requirements and then look to improve the dosing later. This could be by basically doing more than four injections or looking at redosing after the clinical trial is done due to the fact that this means that they then do not need to revisit all aspects to pass the clinical trial.

> There is reasonable evidence that Frequency Therapeutics is onto something positive with FX-322 as so far they have demonstrated that the medicine can breach the blood barrier in the ear, that the medicine doesn't cause cancer like growth and that the medicine is effective at providing regrowth. These are all the factors that have alluded treatment in the past.

> Thus while we will need to wait for final results to come out, there is a lot of promise that this treatment will work and will provide benefit, and the evidence thus far demonstrates that it will.

 

[Diesel]

> Phase 1/2 was only one dose/shot and it showed both non statistically significant and statistically significant improvement in word recognition and also statistically significant improvement in hearing volumes as well. We were also shown the medicine has been fairly safe thus far.

> Phase 2a is ongoing now and is a multi dose clinical trial with a readout of 90 day results due in March. This is 90 days from the time that the last patient got doses. The final Phase 2 results will be out in July next year.

> Frequency Therapeutics has expanded the scope of the clinical trials to test other categories too such as severe and age related hearing losses. These will be scheduled to be concluded around the same time as they will complete the noise phase 2a trial.

> The thought that Frequency Therapeutics has is that they will then proceed to Phase 3 according to Loose, their Chief Scientific Officer.

> The treatment has shown in the trials conducted in the lab that it is able to offer full regrowth across the board.

> Secondary measures such as speech in noise, tinnitus are being evaluated during this trial. There is no indication if it is going to be mentioned as part of the 90 day read out material or not, so this will mean that this then shall become part of the full trial outcomes.

> Frequency Therapeutics seems to be operating on a method of getting the treatment working now and showing it improves people's hearing to pass the FDA requirements and then look to improve the dosing later. This could be by basically doing more than four injections or looking at redosing after the clinical trial is done due to the fact that this means that they then do not need to revisit all aspects to pass the clinical trial.

> There is reasonable evidence that Frequency Therapeutics is onto something positive with FX-322 as so far they have demonstrated that the medicine can breach the blood barrier in the ear, that the medicine doesn't cause cancer like growth and that the medicine is effective at providing regrowth. These are all the factors that have alluded treatment in the past.

> Thus while we will need to wait for final results to come out, there is a lot of promise that this treatment will work and will provide benefit, and the evidence thus far demonstrates that it will.

Excellent summary. However, it stands to reason that Frequency Therapeutics will, at the very least, report on the Primary Outcomes at the 90-day analysis of the Phase 2A in Q1 2021.

Primary Outcome Measures:

1. Speech Intelligibility [ Time Frame: Screening to Day 210 ]
   Assessment of speech intelligibility using the Word Recognition in Quiet test measured with Consonant-Nucleus-Consonant (CNC) word lists.
   
   
2. Speech Intelligibility [ Time Frame: Screening to Day 210 ]
   Speech intelligibility using the Words-in-Noise test measured with Consonant-Nucleus-Consonant (CNC) word lists
   
   
3. Standard Pure Tone Audiometry [ Time Frame: Screening to Day 210 ]
   Standard pure tone audiometry will be measured to determine a subject's threshold for hearing at standard frequencies (Hz)
   
   
4. Systemic Safety: Number of patients with treatment-related adverse events [ Time Frame: Screening to Day 210 ]
   Number of patients with treatment-related adverse events assessed by CTCAE v5.0
   
   
5. Local Safety: Number of patients with abnormal changes from baseline in otoscopic examinations [ Time Frame: Screening to Day 210 ]
   Microscopic otoscopy will be included to specifically record any abnormalities of the external ear canal, tympanic membrane and middle ear.
   
   
6. Local Safety: The number of patients with abnormal changes from baseline in tympanometry [ Time Frame: Screening to Day 210 ]
   Tympanometry tests the integrity of the tympanic membrane by varying air pressure in the ear canal. Middle ear compliance (mL), peak pressure (daPa), and ear canal volume (mL) will be recorded.

 

[frpp]

It's pretty crazy, I know. But I think that for these professionals who mostly deal with people struggling to communicate verbally with others at all, children developing language skills in spite of major hearing loss and so on, the frequency range of the human voice is what seems important. Hearing loss above that pretty much mostly becomes a major problem for us unfortunate enough to get tinnitus because of it or music lovers. Learning about what audiologists are trained to deal with makes my problems seem small in comparison. But it has still ruined my life so there's that, comparison doesn't change that or make it any less of a problem for me and my loved ones...

I agree that frequencies up to 8 kHz are important for speech but, everything above 8 kHz still heavily affects it as well.

It doesn't matter, in about 10 years with new surgeries and regenerative medicine most audiologists will be panhandlers or working at Burger King.

 

[Karl28]

I sometimes feel like my tinnitus comes from my brain, and not just my ears.

Would FX-322 help with that?

 

[HeavyMantra]

I agree that frequencies up to 8 kHz are important for speech but, everything above 8 kHz still heavily affects it as well.

It doesn't matter, in about 10 years with new surgeries and regenerative medicine most audiologists will be panhandlers or working at Burger King.

I think the main issue is that they mainly deal with hearing aids, and that they only work up to 8000 hz Hz far as I know. The audiologists working "on the floor" probably have a narrow view of things.

It certainly would make the need for audiologists lesser, but FX-322 wouldn't solve the need for CI implants, conductive hearing loss and more. Are there surgeries coming up for that?

 

[Philip83]

If I meet all the other criteria, would this audiogram qualify me for a Phase 2/3 trial?

If the criteria stays the same as they are now.

All I can find is that one should have hearing loss between 25-70 dB.

 

[sami23]

Hey, do you think that once Phase 2a clinical trials are completed, Frequency Therapeutics will do clinical trials in other locations (outside of the US)?