Frequency Therapeutics — Hearing Loss Regeneration

[FGG]

This is what it says in the IPO document: "The drug diffuses into the cochlea and is expected to create the greatest concentration of drug in the high frequency region of the cochlea."

Frequency Therapeutics tested hearing up to 8000 Hz in the clinical trials. Some people on this site suggest there was no impact on audiogram because the drug did not reach inner cochlea where lower frequencies are located. If that is the case then there is a problem with drug delivery. Maybe you have to stand on your head for two days to make it work

I think if they can prove improvement in the ultra high frequency audiogram (though I suspect at the much higher doses the drug will very likely diffuse into the "standard" audiogram ranges) in phase 2a, then i think it's only a matter of time before they figure out how to get it deeper into the cochlea.

E.g..something like this?

https://www.ncbi.nlm.nih.gov/pubmed/12621336/

 

[JohnAdams]

I think if they can prove improvement in the ultra high frequency audiogram (though I suspect at the much higher doses the drug will very likely diffuse into the "standard" audiogram ranges) in phase 2a, then i think it's only a matter of time before they figure out how to get it deeper into the cochlea.

E.g..something like this?

https://www.ncbi.nlm.nih.gov/pubmed/12621336/

Minbo Shim told me that he believes that dexamethasone transiently makes the round window membrane more permeable. Perhaps they could start with an injection of something that does that, perhaps dexamethasone or even mannitol, then administer the FX-322.

 

[d'Wooluf]

E.g..something like this?

https://www.ncbi.nlm.nih.gov/pubmed/12621336/

There goes the 10 minute procedure in the doctor's office. Well, there's also magnetic nano-particles. I might have posted something before about a startup in that field signing an agreement with Decibel Therapeutics. And there's a silk-like substance that can release drugs over months. You'd think the drug delivery would be an easier problem to solve than mapping all of the signalling pathways. You'd think.

 

[JohnK]

Being totally selfish here, I'd be thrilled if FX-322 can fix high frequency hair cells, as that's precisely where my tinnitus and hearing loss (thanks Stanford for living up to your reputation and actually going all the way up to 16 kHz without being asked!) is.

 

[JohnK]

Minbo Shim told me that he believes that dexamethasone transiently makes the round window membrane more permeable

Why does Minbo Shim think that?

 

[JohnAdams]

Being totally selfish here, I'd be thrilled if FX-322 can fix high frequency hair cells, as that's precisely where my tinnitus and hearing loss (thanks Stanford for living up to your reputation and actually going all the way up to 16 kHz without being asked!) is.

High frequency waves carry the most energy.

 

[JohnAdams]

There goes the 10 minute procedure in the doctor's office. Well, there's also magnetic nano-particles. I might have posted something before about a startup in that field signing an agreement with Decibel Therapeutics. And there's a silk-like substance that can release drugs over months. You'd think the drug delivery would be an easier problem to solve than mapping all of the signalling pathways. You'd think.

That magneto nano particle thing is nonsense. Would ferrous (iron) nano particles be something we would even want in our cochleas? (Uh, hell no.) The procedure needs to take 1-2 hours because you need to lay with you head tilted in a certain angel for about an hour after each injection, so the gel can rest against the round window, also the patient needs to be given a box of tissues to spit into because swallowing will flush the drug down the eustachian tubes. Also, talking needs to be prohibited during this period. Things I learned from Dr. Minbo Shim.

 

[JohnAdams]

Why does Minbo Shim think that?

I guess from years of experience treating hearing loss and Meniere's disease. The man has probably done at least 100,000 IT injections of various medicines.

 

[Daniel Lion]

I guess from years of experience treating hearing loss and Meniere's disease. The man has probably done at least 100,000 IT injections of various medicines.

I'd go to Shim in a heartbeat if he can get his hands on these drugs. Super skilled surgeon without a doubt.

 

[JohnAdams]

When this is approved in Korea he will certainly offer it.

 

[JohnAdams]

I'd go to Shim in a heartbeat if he can get his hands on these drugs. Super skilled surgeon without a doubt.

Any of us can probably do it if we can fake lab credentials to approve the shipment.

 

[Daniel Lion]

When this is approved in Korea he will certainly offer it.

Any of us can probably do it if we can fake lab credentials to approve the shipment.

Perhaps down the road, Dr. Shim could get the license or access to use in Korea. It would be good for him and everybody in Asia. I'll consider fake lab credentials further down the road. Is he optimistic? What does he think of Regain?

I hope the nerds at Frequency can hammer down a good delivery system, and fast...

 

[d'Wooluf]

I got my silk and my magnetic nano-particles the wrong way around.

https://www.drugdeliverybusiness.co...le-drug-delivery-to-the-inner-ear-using-silk/

 

[John Queen]

Any news about their presentation at the AAO meeting?

And about FX-322's effect on mid-low frequencies: my guess is that it will reach/affect the corresponding cochlear region if they increase the dose/concentration.

 

[FGG]

Short write up of the recent otological meeting talk on FX-322 Dr. King:

https://www.medpagetoday.com/meetingcoverage/aaohnsf/82242

 

[Lucifer]

Short write up of the recent otological meeting talk on FX-322 Dr. King:

https://www.medpagetoday.com/meetingcoverage/aaohnsf/82242

No mention of tinnitus though :'(

 

[FGG]

No mention of tinnitus though :'(

That's because it was not assessed in phase 1, will be assessed in phase 2a, however.

 

[FGG]

I think this answers the question if whether Frequency believes in their drug. These are actually pretty incredible changes in word scores especially after a single low dose.

 

[Lucifer]

That's because it was not assessed in phase 1, will be assessed in phase 2a, however.

Did Frequency actually quote on this?

I think this answers the question if whether Frequency believes in their drug. These are actually pretty incredible changes in word scores especially after a single low dose.

If they were only given one dose/injection and got 20% improvement on Day 15 and 30% Day 90 that's actually really good. Hopefully in Phase 2a multiple doses will be safe.

 

[JohnAdams]

Perhaps down the road, Dr. Shim could get the license or access to use in Korea. It would be good for him and everybody in Asia. I'll consider fake lab credentials further down the road. Is he optimistic? What does he think of Regain?

I hope the nerds at Frequency can hammer down a good delivery system, and fast...

When it is approved in Korea, Astella will be the ones marketing and selling it. He will undoubtedly offer it in his clinic, a few injections of FX-322 vs many many injections of PRP. It is a no-brainer. He even told me that when something better comes along that he will use it.

 

[FGG]

Did Frequency actually quote on this?

It's in their large IPO release doc. If you go back a bit on this thread, the relevant quote was cut and paste and bolded in read.

If they were only given one dose/injection and got 20% improvement on Day 15 and 30% Day 90 that's actually really good. Hopefully in Phase 2a multiple doses will be safe.

That's in aggregate. For some of the subjects, their words scores doubled. Someone with moderate to severe loss had near normal scores after the one low dose injection.

Promising af in my opinion.

 

[RB2014]

I know we have discussed the dosage possibly being low. I thought they had this figured out by now? Did they purposely give a low dosage to check for safety? Did they know it was a low dosage? Did they not realize it wouldn't diffuse into the cochlea?

If anyone has any additional insight it would be appreciated.

 

[Coleoptere]

Having four injection? I'm confident! I assume the Frequency team is getting their head around how to reach the <8K frequencies.

Any change it happens when a second dose is given because the first dealt with >8K frequencies leaving nothing there to be done then <8K?

 

[FGG]

I know we have discussed the dosage possibly being low. I thought they had this figured out by now? Did they purposely give a low dosage to check for safety? Did they know it was a low dosage? Did they not realize it wouldn't diffuse into the cochlea?

If anyone has any additional insight it would be appreciated.

Phase 1 doses are for safety only. Usually it is low. You check efficacy in phase 2 while monitoring for side effects at increased dose.

Phase 1 has a small number of participants and is low dose. Often it's on healthy volunteers since it's a safety study only.

Sorry for all my consistent typos y'all. Combo mobile phone and my mild dyslexia.

 

[Coleoptere]

@FGG: You are perfectly clear.

 

[JohnAdams]

@FGG: You are perfectly clear.

I agree, she is a valuable asset to this community.

 

[FGG]

Any change it happens when a second dose is given because the first dealt with >8K frequencies leaving nothing there to be done then <8K?

I was wondering the same thing. Did the people who had the positive changes at 8 kHz have less ultra high frequency damage (and therefore less damaged cells leading up to the 8 kHz cochlear zone)? If so, maybe the drug had less to bind to and "get stuck on" en route to the deeper areas of the cochlea--versus the people who had no standard audiogram changes but may have had more extensive extended audiogram changes, if they had measured that. Phase 2a should shed light on all of that.

 

[Mr Mister]

I think this answers the question if whether Frequency believes in their drug. These are actually pretty incredible changes in word scores especially after a single low dose.

Someone can check my math since I have not spent more than five minutes on this. 4 patients out of 15 treated with the drug got about 110% increase in word scores. Since the average increase for all 15 patients was 30% it means that the remaining 11 patients got no increase in word scores. The information they choose to publish is kind of selective. But they are not the first company to do it. So 27% got a material increase while 73% saw no change at all. If my math is right then the outcome is not normal distribution but rather a digital outcome that seems a bit odd.

 

[JohnAdams]

Phase 2a should shed light on all of that.

In a year

 

[JohnAdams]

Wait a second, that second hand story about the guy in Regain that said his tinnitus improved...... I thought having tinnitus was an exclusion criteria for Regain?