Frequency Therapeutics — Hearing Loss Regeneration
- Thread starter RB2014
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Yes. Watch the Q and A. Everyone should watch the JP Morgan presentation and the Q and A. In the Q and A, they were asked about tinnitus and saw positive trends.
They don't mention it but the likelihood of having tinnitus while having hearing loss is quite high so I expect a few patients would have tinnitus and hearing loss.
It will help your OHC loss from mild presbyacusis. If you have IHC it will help too if over 3500Hz. If you have synaptopathy also in areas without the hair cell loss this drug won't help that aspect. Unfortunately no diagnostic test can tell you if that's the case. You will just have to decide if you want to try the drug and see.
Edit: I should mention there are synaptopathy drugs that may help if FX-322 doesn't.
- May 29, 2015
- 664
- 30
- Tinnitus Since
- 2012
- Cause of Tinnitus
- I had tinnitus for as long as I can remember. Got bad later.
I didn't know support cells could deplete in the cochlea. That's concerning. Do you have a source I could read?
They were asked specifically about tinnitus in the Q and A and they said they saw "trends" in both the mild and moderate/severe groups. Trends implied positive to me or it would be listed as an adverse reaction and not included in the experimental arm of phase 2.
brokensoul
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- Dec 31, 2019
- 223
- Tinnitus Since
- 02/05/2019
- Cause of Tinnitus
- unknown:medication,cannabis,stress,sleep deprivation
In regards to epithelial scarring:
Cochlear pathology, sensory cell death and regeneration
https://academic.oup.com/bmb/article/63/1/25/377504
Contains a section on:
Cell elimination and scar formation
"... The term 'scar' is used to describe replacement of the original cell type (hair cell) by a 'filling' cell, a supporting cell. The use of the term scar in the organ of Corti is justified because the scar is permanent. The immediate role of the scarring process is to prevent fluid mixing. ..."
Scar tissue picture shown in a Stanford University presentation on hearing loss:
Cochlear pathology, sensory cell death and regeneration
https://academic.oup.com/bmb/article/63/1/25/377504
Contains a section on:
Cell elimination and scar formation
"... The term 'scar' is used to describe replacement of the original cell type (hair cell) by a 'filling' cell, a supporting cell. The use of the term scar in the organ of Corti is justified because the scar is permanent. The immediate role of the scarring process is to prevent fluid mixing. ..."
Scar tissue picture shown in a Stanford University presentation on hearing loss:
They can be, particularly with some ototoxins but with enough noise induced hearing damage they are lost too. Keep in mind that only LGR+ support cells (one specific type) are needed for regeneration and since FX-322 duplicates them before hair cell generation you shouldn't have further depletion.
I took a different conclusion than @mrbrightside614 from the data.
Let's look at this clinically. The people who had the biggest losses had great results in phase 1. It must mean there are enough support cells to work and in fact the greater the hearing loss, they got a more provable effect in word scores. Clearly the drug works even with presumably some support cell loss. Without any support cells in an area, I imagine you would be profoundly deaf at that frequency.
Also if some support cell loss were a catastrophic issue, Regain would never have passed phase 1 imo because it actually depletes those LGR+ cells.
- May 29, 2015
- 664
- 30
- Tinnitus Since
- 2012
- Cause of Tinnitus
- I had tinnitus for as long as I can remember. Got bad later.
There are several a few pages back here. It's more of a concern for people with significant hearing loss or damage from ototoxic substances. @HootOwl offered a really good response to my concerns like maybe 1 page back.
GOOD NEWS.
This says Frequency Therapeutics met with JP Morgan on the 13th:
https://thefly.com/landingPageNews....Therapeutics-management-to-meet-with-JPMorgan
Anyone want to speculate why?
https://thefly.com/landingPageNews....Therapeutics-management-to-meet-with-JPMorgan
Anyone want to speculate why?
Here I go again with my noob questions, sorry in advance.
So does this scarring prevent new hair cells from regrowing?
Yeah, is this epithelial scarring an issue? When you said "GOOD NEWS" @mrbrightside614, was that sarcasm, or did you actually mean it? Just wondering.
HootOwl
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- Jun 15, 2019
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- May 2019
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- Likely infection/ear stress after walking pneumonia
Total speculation but it could just be to update their knowledge after initiating coverage on Oct. 28 ("JPMorgan analyst Anupam Rama initiated coverage of Frequency Therapeutics with an Overweight rating and $25 price target. The analyst believes early data for FX-322 set the stage for potentially addressing a "large untapped" hearing loss market"). This doesn't necessarily mean JPMorgan will soon say anything new one way or other.
brokensoul
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- Dec 31, 2019
- 223
- Tinnitus Since
- 02/05/2019
- Cause of Tinnitus
- unknown:medication,cannabis,stress,sleep deprivation
Transcription:
https://www.tinnitustalk.com/thread...cs-—-hearing-loss-regeneration.18889/page-216
Audience:
Besides the word score in phase 1/2, did you look at any other secondary end-points that would give you any indication of <inaudible>?
Christopher Robert Loose (Chief Scientific Officer):
The question is, are there any other secondary end-points? So in addition to the word recognition score, which is a test in a quiet background. We also saw improvements in word-in-noise, which is basically repeating that test in a restaurant type of environment, where there are 6 people talking in the background, in a you know much more challenging environment. We saw similar improvers, improvements in that space. We also tested the loudness, test, the pure tone types of test there. We noticed that a number of patients with the biggest losses had improvements in the higher frequencies which is were the greatest amount of drug is present and people have the most loss. So moving forward we are going to be continuing with those three end-points, but we will also be adding ultra high frequencies going forward cause we know that's where the drug is concentrated, as well as quality-of-life, tinnitus and other end-points that we're thinking could give us a full picture of what this medication may potentially do.
Audience:
Just as a follow-up on that. Did you see any improvement in the secondary end-points in the mild hearing loss category?
Christopher Robert Loose (Chief Scientific Officer):
We saw trends across the population.
I wouldn't make any conclusions on this statement, but it's very good news that they added tinnitus as a secondary end point. We will see in September 2020 if it does anything in regards to tinnitus induced by hair cell loss. At the moment it's still speculation if it will help or not.
No matter the outcome in regards to tinnitus, this will still be a very important moment in the history of tinnitus. Even if it does nothing for tinnitus. All those years of speculating what the physiological cause is of tinnitus. There are so many theories even within the spectrum of hearing. We will finally get to know if regenerating hair cells (to some degree) impacts tinnitus or not. If we see serious audiogram improvements in the treated regions and we see tinnitus reduction we will finally know that hair cell loss is the main driver behind tinnitus (due to hearing loss). If tinnitus is not reduced at all, we will understand that it is more likely that it's loss of synapses or auditory nerve damage that causes tinnitus. This will be a significant improvement in the field of tinnitus research.
https://www.tinnitustalk.com/thread...cs-—-hearing-loss-regeneration.18889/page-216
Audience:
Besides the word score in phase 1/2, did you look at any other secondary end-points that would give you any indication of <inaudible>?
Christopher Robert Loose (Chief Scientific Officer):
The question is, are there any other secondary end-points? So in addition to the word recognition score, which is a test in a quiet background. We also saw improvements in word-in-noise, which is basically repeating that test in a restaurant type of environment, where there are 6 people talking in the background, in a you know much more challenging environment. We saw similar improvers, improvements in that space. We also tested the loudness, test, the pure tone types of test there. We noticed that a number of patients with the biggest losses had improvements in the higher frequencies which is were the greatest amount of drug is present and people have the most loss. So moving forward we are going to be continuing with those three end-points, but we will also be adding ultra high frequencies going forward cause we know that's where the drug is concentrated, as well as quality-of-life, tinnitus and other end-points that we're thinking could give us a full picture of what this medication may potentially do.
Audience:
Just as a follow-up on that. Did you see any improvement in the secondary end-points in the mild hearing loss category?
Christopher Robert Loose (Chief Scientific Officer):
We saw trends across the population.
I wouldn't make any conclusions on this statement, but it's very good news that they added tinnitus as a secondary end point. We will see in September 2020 if it does anything in regards to tinnitus induced by hair cell loss. At the moment it's still speculation if it will help or not.
No matter the outcome in regards to tinnitus, this will still be a very important moment in the history of tinnitus. Even if it does nothing for tinnitus. All those years of speculating what the physiological cause is of tinnitus. There are so many theories even within the spectrum of hearing. We will finally get to know if regenerating hair cells (to some degree) impacts tinnitus or not. If we see serious audiogram improvements in the treated regions and we see tinnitus reduction we will finally know that hair cell loss is the main driver behind tinnitus (due to hearing loss). If tinnitus is not reduced at all, we will understand that it is more likely that it's loss of synapses or auditory nerve damage that causes tinnitus. This will be a significant improvement in the field of tinnitus research.
Well in the cochlear implant studies, over time the people who improved did so whether the device was on or off so it seems to be related to actual improvement and not masking.
But this can probably be simulated with seeing if tinnitus is still reduced while wearing ear plugs.
I think they're due to release their 4th Quarter 2019 Financial Results soon. They released their 3rd quarter results on November 18th, last year. So I would imagine it's no coincidence that this meeting is occurred a week before the 4th quarter results. However, the only reason I can imagine that they'd want to talk to JPMorgan is because they want some money for something, but what? I know they have the Multiple Sclerosis program in the works, maybe they've found their drug and want to get started early? Or maybe they've come up with some additional areas they want to study but they don't have the financial strength to go after everything they want to, so they need an injection of cash.
My guess is we'll find out when they release the 4th quarter results (which I thought would happen today, but maybe it's delayed?). Though then again, if they didn't get what they wanted at the meeting, maybe we won't find out.
It's definitely peculiar though.
As a corollary to this. A few pages ago, I think @Diesel articulated it best:
It would a *terrible* idea on Frequency's part to add it to phase 2a if they didn't see improvement in phase 1.
No, this is actually great news. The verbiage is dumb as hell IMO (BS in exercise physiology). The fact that support cell formation directly proceeds hair cell loss is very encouraging that the support cell will be in place to appropriately differentiate into a hair cell, post-inoculation.
Scarring in any other physiological instance refers to the usually permanent formation of weaker, dysfunctional collagen fibers that can cause a host of issues (inhibit ROM, blood flow, etc.)
- Feb 14, 2020
- 1,630
- Tinnitus Since
- 1-2019
- Cause of Tinnitus
- 20+ Years of Live Music, Motorcycles, and Power Tools
It's not out of the ordinary for equity researchers from larger investment/financial firms to want to meet with execs of a firms to understand the business and product in greater detail; especially when they just had an IPO.
JPM had them at overweight for a while now, probably wants to include them in a SMID or biotech type fund.
Is management usually involved in those meetings? The notice specifically said management.
Auditory nerve damage? Aw ffs, isn't the Hough Pill only addressing that kind of damage? Jesus, so much can go wrong with the auditory system...
brokensoul
Member
- Dec 31, 2019
- 223
- Tinnitus Since
- 02/05/2019
- Cause of Tinnitus
- unknown:medication,cannabis,stress,sleep deprivation
I cannot tell with absolute certainty from that text if the epithelial scarring would affect hair cell regeneration, but the text confirms my earlier statement that supporting cells move in place where the hair cell is lost.
Looking at the images of noise induced damage for example does reveal malformations (scar tissue) in the epithelium.
I've also seen many images where the alignment (organisation and positioning) of remaining hair cells is no longer perfect after damage.
Even if hair cells are regenerated, they may not be perfectly organised as they were before any damage happened.
Further analysis should be done.
Looking at the images of noise induced damage for example does reveal malformations (scar tissue) in the epithelium.
I've also seen many images where the alignment (organisation and positioning) of remaining hair cells is no longer perfect after damage.
Even if hair cells are regenerated, they may not be perfectly organised as they were before any damage happened.
Further analysis should be done.
Could it be as simple as additional funding for the expanded trial? I believe they are estimating filing their MS IND 2H2021 which would make it quite early but i guess they could need pre-clinical funding. Very strange but, i agree, the Q4 conference call and financial release should clear some of that up.
It's possible they could be going to JP Morgan for capital but the fact that Astellas financed them for $80m upfront and $525m as they face "commercial milestones" should be everything they need, even considering their new hiring for a superior gel formulation. Astellas Pharma is flush with cash, $11B in straight revenue in 2013.
Dan from Pipeline told me that their regenerated OHCs go into normal alignment when I asked him. They have a gamma secretase inhibitor, which is more like Audion but not as potent or support cell depleting.
I imagine if their drug produces cells in the right alignment after injury, that bodes well for Frequency imo.
Edit: to add to this. somehow the neurites outgrow correctly to the precise right places with synaptopathy drugs too. There must be some really precise cellular and cell to cell signaling which makes sense considering it is a sensory organ that the body has to get right embrologically (which is similar to regenerative approaches).
brokensoul
Member
- Dec 31, 2019
- 223
- Tinnitus Since
- 02/05/2019
- Cause of Tinnitus
- unknown:medication,cannabis,stress,sleep deprivation
I hear what you're saying and both of you could be right, but at the moment I don't want to draw any speculative conclusions beyond the actual facts. This might create high expectations amongst some people here who don't look at the actual statement done by Chris Loose. Some people could be crushed if it turns out to be ineffective.
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