Frequency Therapeutics — Hearing Loss Regeneration

[Enclave]

Correct me if I'm wrong, but if you refer to the first graph on slide 79 you can see that the animals had a permanent threshold shift of approximately 90 decibels between 5khz - 20khz. This equates to profound hearing loss. Since this was the baseline prior to the drug administration, achieving a 10db increase in an animal model with profound hearing loss is a breakthrough in my opinion, especially since this treatment is predicated on the existence of supporting cells being present in order for the treatment to work. At a 90db threshold shift (profound) the epithelium is pretty much decimated at this point, which based on our current understanding of supporting cells would indicate that there are few to none supporting cells left at this point, so for them to restore 10db at the baseline represented in this graph is a big deal.

If the baseline was approximately 40 decibels between 5khz - 20khz in the animal models illustrated on slide 79, then we would see more substantial results in this experiment due to the fact that there are more supporting cells present at a these thresholds.

Also, based on their drug model here, if they can achieve 10db increase in one administration then applying multiple times should have more of an effect since the supporting cells that gave rise to the 10db increase in the first place are still present and don't disappear.

One last point, Slide 82 lists the sources that the data is pulled from, and the LGR5 paper from last February is the latest cited source in this dataset. Frequency isnt going to report any new information until they're published and protected.

I can't wait for the next paper to come out.

 

[ee9892]

God i hope theres a day where someone with tinnitus says "it worked".

What a joyous day on this forum that will be.

 

[threefirefour]

God i hope theres a day where someone with tinnitus says "it worked".

What a joyous day on this forum that will be.

I remember reading somewhere on the forum that there would be a massive party once there's a treatment.

[USERGROUP=4]@Moderators[/USERGROUP] hope you guys won't back away from that

 

[Bill Bauer]

I haven't read any posts in this thread. But I see this possible treatment being mentioned in multiple threads in the Support forum, so it finally got my attention. When will we know whether this treatment will work to alleviate T?

 

[Makrohn]

When will we know whether this treatment will work to alleviate T?

In general I think it is difficult to predict any timeframe bc of all the different variables in a project like this, however, phase II is scheduled to begin this year. Since this treatment is not developed to treat T alone but rather hearing loss, we need to wait for someone with hearing loss and some level of T to be included in the treatment/testing.

I have not seen the criteria for the phase II trials yet, so I'm guessing we just have to wait for the release of new and updated papers on this.

 

[Andrei90]

Correct me if I'm wrong, but if you refer to the first graph on slide 79 you can see that the animals had a permanent threshold shift of approximately 90 decibels between 5khz - 20khz. This equates to profound hearing loss. Since this was the baseline prior to the drug administration, achieving a 10db increase in an animal model with profound hearing loss is a breakthrough in my opinion, especially since this treatment is predicated on the existence of supporting cells being present in order for the treatment to work. At a 90db threshold shift (profound) the epithelium is pretty much decimated at this point, which based on our current understanding of supporting cells would indicate that there are few to none supporting cells left at this point, so for them to restore 10db at the baseline represented in this graph is a big deal.

If the baseline was approximately 40 decibels between 5khz - 20khz in the animal models illustrated on slide 79, then we would see more substantial results in this experiment due to the fact that there are more supporting cells present at a these thresholds.

Also, based on their drug model here, if they can achieve 10db increase in one administration then applying multiple times should have more of an effect since the supporting cells that gave rise to the 10db increase in the first place are still present and don't disappear.

One last point, Slide 82 lists the sources that the data is pulled from, and the LGR5 paper from last February is the latest cited source in this dataset. Frequency isnt going to report any new information until they're published and protected.

I can't wait for the next paper to come out.

I agree. It would be interesting to see if they applied the treatment more than once for cases of profound hearing loss. This way we could see if it was possible to take a few support cells and multiply them enough to restore functional hearing. I hope their next paper covers this.

 

[Bill Bauer]

phase II is scheduled to begin this year

Sounds like it will likely be at least another 10 years before one of us could benefit from it.

 

[Reinier]

on slide 79 you can see that the animals had a permanent threshold shift of approximately 90 decibels between 5khz - 20khz.

If this is how the graph works than it shows more improvement in the relatively lower frequencies. (the 5 weeks line)
Was it not always the expectation that the higher frequencies are easier to reach? (base of cochlea).
Also this graph shows it takes longer than 24 hours for the regeneration to take effect.

But without the comments that go with these graphs we are almost in the dark.

 

[Enclave]

If this is how the graph works than it shows more improvement in the relatively lower frequencies. (the 5 weeks line)
Was it not always the expectation that the higher frequencies are easier to reach? (base of cochlea).
Also this graph shows it takes longer than 24 hours for the regeneration to take effect.

But without the comments that go with these graphs we are almost in the dark.

I was only pointing out the results in the 5khz - 20khz range because this was the range that was pertinent to our own hearing thresholds.

Either way, it doesn't negate the fact that on average at the baseline of this experiment the mice were deafened to the point of profound hearing loss. This is evident in the control group (grey line) that still had profound hearing loss after 5 weeks. Significant systemic structural damage occurs to the inner ear at this level of hearing loss, therefore, there is less present to regenerate in regards to supporting cells. Utilizing this as a baseline is an extreme case of hearing loss.

 

[Andrei90]

I was only pointing out the results in the 5khz - 20khz range because this was the range that was pertinent to our own hearing thresholds.

Either way, it doesn't negate the fact that on average at the baseline of this experiment the mice were deafened to the point of profound hearing loss. This is evident in the control group (grey line) that still had profound hearing loss after 5 weeks. Significant systemic structural damage occurs to the inner ear at this level of hearing loss, therefore, there is less present to regenerate in regards to supporting cells. Utilizing this as a baseline is an extreme case of hearing loss.

Didn't they mentioned significant growth of hait cells (over 10,000) in a previous statement? I find it hard to believe that what we got in this presentation is the equivalent of this. Perhaps they are withholding results on another study for the next paper? One where they tested on moderate loss as opposed to profound loss.

 

[Tempest]

I was only pointing out the results in the 5khz - 20khz range because this was the range that was pertinent to our own hearing thresholds.

Either way, it doesn't negate the fact that on average at the baseline of this experiment the mice were deafened to the point of profound hearing loss. This is evident in the control group (grey line) that still had profound hearing loss after 5 weeks. Significant systemic structural damage occurs to the inner ear at this level of hearing loss, therefore, there is less present to regenerate in regards to supporting cells. Utilizing this as a baseline is an extreme case of hearing loss.

We don't know yet what happens when humans get the treatment. I would assume mices have more hairs cells than humans do since they hear higher frequences and that also means there are more stuff to be healed. Of course this is just a stupid theory, but let say the healing would be identical to humans, I would assume results would be doubled since humans can only hear up to 20KHz, less stuff to healed. But then again, we don't know yet if the treatment causes people to start hearing stuff past 20KHz instead of healing the damaged frequences.

 

[Aaron123]

I would assume mices have more hairs cells than humans do since they hear higher frequences

The number of hair cells has nothing to do with frequency range. Mice have fewer hair cells: https://link.springer.com/article/10.1007/BF00611249

I would assume results would be doubled since humans can only hear up to 20KHz, less stuff to healed. But then again, we don't know yet if the treatment causes people to start hearing stuff past 20KHz instead of healing the damaged frequences.

I wouldn't assume that at all, and the treatment will not somehow cause humans to hear at higher frequencies. To the extent that the treatment works, it will mimic original development where hearing is limited to ~ 20 kHz.

 

[Gorbeh3]

Aaron123, you see to be the most knowledgeable about this stuff. So overall would you say this inspires further optimism? Or disappointment? Or really no change in outlook / we need to see more?

 

[Tempest]

The number of hair cells has nothing to do with frequency range. Mice have fewer hair cells: https://link.springer.com/article/10.1007/BF00611249

I wouldn't assume that at all, and the treatment will not somehow cause humans to hear at higher frequencies. To the extent that the treatment works, it will mimic original development where hearing is limited to ~ 20 kHz.

Ah, thanks for correcting me then. It still will be interesting to see will we get back the frequencies that we have already lost for good, like if you can't hear anything after 16KHz or is it too late since our brains have been so long without them (or maybe in theory we can still hear them, but they are so silent that it's nothing basically).

 

[Bill Bauer]

@PetitGarsTimide Thank you for your kind "Genius" rating!

People were carrying on about this treatment in the Support section of the forum, and I thought it was indicative of something being available imminently. I made that post, hoping that if I was wrong, someone would correct me and explain why we were going to see a treatment a lot sooner.

 

[ee9892]

@PetitGarsTimide Thank you for your kind "Genius" rating!

People were carrying on about this treatment in the Support section of the forum, and I thought it was indicative of something being available imminently. I made that post, hoping that if I was wrong, someone would correct me and explain why we were going to see a treatment a lot sooner.

I think it will still take a couple years to get through phase II and III. From that point on they may be able to fast track the treatment through the FDA because there is no cure/treatment for tinnitus yet, and one is needed.

 

[Jim51042]

If this is how the graph works than it shows more improvement in the relatively lower frequencies. (the 5 weeks line)
Was it not always the expectation that the higher frequencies are easier to reach? (base of cochlea).

If this question was asked and answered during this presentation can someone who went fill us all in?

 

[derpytia]

Sounds like it will likely be at least another 10 years before one of us could benefit from it.

Unless it works so well that it gets fast tracked.

In order for the FDA to fast track a drug it has to meet one of these requirements:

• Showing superior effectiveness
• Avoiding serious side effects of an available treatment
• Improving the diagnosis of a serious disease where early diagnosis results in an improved outcome
• Decreasing a clinically significant toxicity of an available treatment
• Addressing an expected public health need

I'm pretty sure that if this is effective it will meet at least 2 of these.

 

[Yusher]

Why are they so slow in starting recruiting for phase 2 trial? What for are they waiting? 1st one passed successfully.

 

[derpytia]

Why are they so slow in starting recruiting for phase 2 trial? What for are they waiting? 1st one passed successfully.

They have to recruit people and file paperwork and get a whole host of things ready before they start.

But mostly likely there's a lot of paperwork

 

[Enclave]

In regards to Frequency, there are a few things we can expect to see here in the next 2-3 months:

1) Frequency announcing a very large Series B financing from their investors to help get them through Phase II and beyond. This number will be indicative of the level of confidence their private investors have in this drug/technology. Keep in mind, they have access to data and information we don't.

2) The elusive second paper.

3) Inclusion criteria for participants in Phase II.


All this will shed light on the many questions we have that are unanswered at this point. I strongly believe this is going to be our year this year. This is the closest the otology field has gotten to something meaningful.

 

[jeff W]

Also, based on their drug model here, if they can achieve 10db increase in one administration then applying multiple times should have more of an effect since the supporting cells that gave rise to the 10db increase in the first place are still present and don't disappear.

This is what makes Frequency a trial worth waiting for. Excluding surgical entry risks (the vestibular implant crowd are making huge progress with this) and tumoregenesis which is a risk factor in all cell based tech, undergoing this therapy is not crossing the Rubicon in that it will not disturb the supporting cells. I think there will be a lot of angry T sufferers about over the next few years that will regret not waiting for a "cleaner" tech trial to participate in, like a bad hair transplant that removed their donor hair with now nothing left to work with. I doubt frequency or any other newer biotechtech company will consider previous candidates from other failed first in humans for any of its trials, it will probably be in the exclusion criteria.

 

[ee9892]

This is what makes Frequency a trial worth waiting for. Excluding surgical entry risks (the vestibular implant crowd are making huge progress with this) and tumoregenesis which is a risk factor in all cell based tech, undergoing this therapy is not crossing the Rubicon in that it will not disturb the supporting cells. I think there will be a lot of angry T sufferers about over the next few years that will regret not waiting for a "cleaner" tech trial to participate in, like a bad hair transplant that removed their donor hair with now nothing left to work with. I doubt frequency or any other newer biotechtech company will consider previous candidates from other failed first in humans for any of its trials, it will probably be in the exclusion criteria.

Do other hair cell regen treatments ruin the supporting cells?

 

[Contrast]

Do other hair cell regen treatments ruin the supporting cells?

As far as I am concerned, yes. Other bio tech firms working on cochlear hair cell regeneration convert supporting cells into hair cells where Frequency-tx does something along the line of duplicating supporting cells before converting them. This way they are getting the maximum amount of hair cells regenerated and possibly this will allow multiple reapplications of the drug but we don't know for sure about the multiple reapplications part until we get more updates from Frequency-tx.

 

[Flamingo1]

I don't remember having seen this posted yet. I may be wrong but I interpret this as Frequency's confidence that they have something that WORKS.

https://www.businesswire.com/news/h...ntinues-Expansion-Leadership-Team-Appointment

 

[Aaron123]

I don't remember having seen this posted yet. I may be wrong but I interpret this as Frequency's confidence that they have something that WORKS.

Already posted: https://www.tinnitustalk.com/threads/frequency-therapeutics-—-hearing-loss-regeneration.18889/page-40#post-326265

Since his title is "Chief Medical Officer, Platform" as opposed to Peter Weber whose title is "Chief Medical Officer, Hearing Program", I interpret this as continued expansion by Frequency into areas beyond hearing.

 

[Flamingo1]

Already posted: https://www.tinnitustalk.com/threads/frequency-therapeutics-—-hearing-loss-regeneration.18889/page-40#post-326265

Since his title is "Chief Medical Officer, Platform" as opposed to Peter Weber whose title is "Chief Medical Officer, Hearing Program", I interpret this as continued expansion by Frequency into areas beyond hearing.

Thanks for the clarification. I still maintain that they wouldn't be venturing into other areas if they didn't have some sort of confidence that their approach will provide an effective treatment one day.

 

[Margus]

Thanks for the clarification. I still maintain that they wouldn't be venturing into other areas if they didn't have some sort of confidence that their approach will provide an effective treatment one day.

Why not? It's just like any other business, they exist only to make a profit. I think it's actually not a good sign they try to expand the program before results from phase1 trial are in. Looks more like diversification and preparation for failure from phase 1, perhaps blaming delivery method hence maybe instead will focus on other diseases, where the same molecule can be used, but no hassle with delivering. And if this is a case then in makes perfect sense, they obviously know more then we do from phase 1.

 

[grate_biff]

Why not? It's just like any other business, they exist only to make a profit. I think it's actually not a good sign they try to expand the program before results from phase1 trial are in. Looks more like diversification and preparation for failure from phase 1, perhaps blaming delivery method hence maybe instead will focus on other diseases, where the same molecule can be used, but no hassle with delivering. And if this is a case then in makes perfect sense, they obviously know more then we do from phase 1.

LOL. Nice try Margus!

 

[lymebite]

Just a short summary blurb and nothing new, but the just-published Harvard Stem Cell Institute Annual Report for 2017 mentions Frequency Tx.

REPLACING HAIR CELLS IN THE EAR TO TREAT HEARING LOSS

Sounds are picked up by hair cells in the inner ear, which translate them into signals for the brain to interpret. Because these hair cells do not regenerate, any damage to them results in hearing loss.

To tackle this problem, Jeffrey Karp, PhD and Albert Edge, PhD collaborated on a method to replace hair cells in both mouse and human ear tissue. First, they identified a drug combination that increased a certain population of stem cells in the ear. Then, they converted the stem cells into hair cells.

This therapeutic approach is under further development by Frequency Therapeutics, a biotechnology company co-founded by Karp.

http://www.report.hsci.harvard.edu/research-highlights