Frequency Therapeutics — Hearing Loss Regeneration

[Zugzug]

As someone with hearing loss, I can spend all of my focus and energy trying to hear the TV better and it makes minimal difference.

No doubt.

I'm mostly wondering if it's possible, not that hidden hearing loss is a myth. There's no question that there are people in your (and @roy1159's) situation.

 

[Jurger]

Interesting. A few questions:

1) Did you notice the drastic improvements in clarity from the 0% to 64% or did it surprise you it went up quite that much?

2) I'm assuming this change was acute. OHCs/audiograms can dramatically recover acutely after inflammation is reduced so I imagine it could be the same with IHCs.

What was your cause?

1. I wasn't wearing a hearing aid at the time, so I didn't notice any improvement. I only got a hearing aid when the WR score stabilized. The thing with WR scores is that it doesn't mean anything without loudness. My 64% WR is at 90 dB I believe. At 70 dB it's much lower. My PTA is around 70-75 dB.

2. My cause was idiopathic SSHL. The name says it all; they don't know quite sure what causes it. Could be a virus, some inner ear vascular issue, automatic cell death etc. I lost my hearing in the right ear overnight (literally).

 

[Diesel]

For the life of me, I just don't understand why they didn't have word scores as a stability factor. As has been pointed out here, given the concept that someone is likely to have a loss of both OHC and IHC if they have hearing impairment (and actually, OHC are more easily lost), it's hard to recruit people that specifically have word problems. It's so unforgivable to not have a really high standard for getting in.

In all likelihood, the incremental success of this drug will simply be in IHC improvement. Forget about OHC, tinnitus, hyperacusis for now. Stay in the word score lane and do the trials right. High, high standards of repeat performance stability for getting in. If it takes longer to recruit, tough shit. We all have to swallow it and stop whining.

I honestly don't see how this would take any longer to recruit. All they need to do is find patients with a medical history of a consistent word score deficit over a certain period of time. Say, 5-years of records. It should be obvious what range to expect at screening and day-0.

 

[Philip83]

High, high standards of repeat performance stability for getting in. If it takes longer to recruit, tough shit.

Exactly. Test 300 people, once a month for five months straight — enroll the 100 with the most consistent scores.

 

[weab00]

If you really believe FX-322 doesn't work, stop posting. We don't need your negative energy.

So you literally want an echo chamber around FX-322 because you're too afraid to hear the opposing viewpoint?

 

[100Hz]

Interesting point.

I wonder if since there isn't any real good measure to specifically, only isolate IHC performance. If the distribution of missing/damaged IHC played a role in the success of the responders.

So, I am suggesting, much like tinnitus, that there may be a subset of hearing loss patients at every level that happen to have an imbalance of IHC damage that makes them better, there's just no objective test to identify them.

You're on the same page as me and that's why I wonder about the OAE test that I brought up yesterday. Bear with me - I'm going to try and do with graphics what @Zugzug does with math.

1. Healthy hearing (healthy IHCs, OHCs, afferents, synapses): Self explanatory, good OAE test, good audiogram.

2. Damaged OHCs. What state everything else is in is unknown. Apparently OAE tests are testing for OHC damage and this is how I interpret what we are lead to believe. In the case below it is picking up OHC damage before it shows on an audiogram (common with OAE tests apparently).

3. The above may well be true, but what if in certain circumstances (tinnitus, poor WR / WIN, maybe hyperacusis for example) where audiogram is good but OAE tests are bad, there is actually nothing wrong with OHCs and the reason for the lack of OA emissions is that they are being influenced by damage from another source (IHCs, afferents, synapses etc.).

This firstly could be a reason, as we are discussing, why FX-322 does not improve an audiogram but does improve WR.

Secondly, it's impossible IMO to say whether an OAE test is 100% detecting only OHC damage vs OHC response to damage elsewhere, but this test could be really useful for FX-322 trials because if FX-322 IS fixing something that doesn't show up on an audiogram BUT an improvement was noted between baseline and post drug treatment in an OAE test along with a WR score improvement, then that could indicate that FX-322 is fixing possibly IHCs plus IHC synaptopathy. Since I've been writing this, I've come to the conclusion that it's less likely that it would be fixing anything to do with type II afferents / extra ribbons because if it was it would first have to identify damaged OHCs for PCA, and if whole OHC bundles got replaced it would surely show up on an audiogram anyway.

What OAE tests actually test for plus what FX-322 actually fixes could possibly be established in both directions in one hit by using OAE tests in FX-322 trials. It could flop. But it's got to be a test worth trying with the worlds first hair cell regeneration drug I would think.

This is a LOOSE theory and probably has holes all over it, but I'm just chucking the general idea out there. Again, just looking for a shred of fact and this is something that could be tested.

 

[Aaron91]

I've had a reply from a second patient who took part in the trial.

As you'll recall, the first patient I found was quite positive about their experience. This one not so much. Here's what they had to say in their own words:

"Hello Aaron- I have not read the interim analysis. I should do that. But I am not surprised that it isn't encouraging. I have noticed no improvement at all since doing the trial. My word recognition went up a tiny bit but honestly, I think that's because I got better at taking that test. I did it so many times and it caused me a lot of anxiety at first. I got calmer about it after a while. And more willing to guess at the words I was hearing, so I think that gave me a better chance. But the improvement was incredibly minimal, and not clinically relevant. Or so I was told. I had a lot of hope when I was accepted into this trial and it was so disappointing to get nothing from it. But of course there is a chance that I got the placebo. As soon as I learn anything concrete about that I will definitely share.​

I went to ask some follow-up questions about the testing methods. Again, here's what they had to say in their own words:

"The word test was not exactly the same each time, although I think they had 2 or 3 versions and there was definitely repetition. So maybe I memorized some things. I was told to go ahead and guess. Sometimes it was only a vague vowel sound I could hear, so it was so much a guess as just making stuff up! I'm glad you heard from someone who saw improvement from the trial. I actually hope that I DID get the placebo since nothing changed. Gives me hope of getting the real thing down the road."​

As for the speculation surrounding the "burning" experienced by the other patient during 2/4 injections, again this is what the second patient had to say:

"For me, the injections were incredibly painful. All four of them. Yes, I would say it was a burning sensation. I was told that they would not be painful, but even with numbing medication first it was awful. The doctor was pretty surprised by that as he was sure I would not really feel it at all."
​

When I mentioned to them that some other patients may have purposely or subconsciously tanked their WR scores, here's what they had to say:

"Wow! It wouldn't have occurred to me to do that!"
​

The thing I was most curious about was whether Frequency Therapeutics had been in touch with the patient since the trial and asked for any further historical records. They haven't. The only record they gave Frequency Therapeutics was during screening:

"Sorry - what I said wasn't clear. To get into the trial in the first place I had to submit my most recent audiogram. I had one from an ENT that was incomplete and at first they rejected me. Then I sent them one from an otolaryngologist that showed more detail and they said I was perfect fit based on that one."
​

This was very interesting to me. Frequency Therapeutics seemed to imply in the conference call that there was a mismatch between the historical records and baselines (not screenings). That made me wonder: were the screening tests used as baseline? The first patient has come back to me and said that wasn't the case: there was a hearing test to screen the patient after submission of previous records, and then a new baseline was taken before the first injection. So that got me really confused, because if the whole incentive to tank a word score is to get into the trial, why would a patient keep a consistent score between their historical record and screening and then tank their score only once they're in the trial? Makes no sense at all. The only explanation I had was that word scores were not used as historical records, only audiograms. I've gone back to confirm this with both patients, but judging from what the patient said above, it would seem they only had to submit their audiogram. Can someone here who applied to get in confirm?

If this is the case, this is even more perplexing. How could Frequency Therapeutics claim there's a mismatch between historical records and baselines if no historical word recognition scores were provided in the first place and Frequency Therapeutics haven't since gone back to ask if they had any more records? The only assumption I can make is they're claiming there's a mismatch between the historical audiograms and the baseline audiograms and assuming the same of the WR scores, but that isn't possible because the incentive to tank is at screening, not once you're in the trial.

Something doesn't add up here. I must be missing something. Help?

Edit: the first patient has since come back and confirmed they had to submit both a WR score and audiogram.

Edit 2: this still isn't making sense. How could there be a mismatch between baseline and historical records if the whole point of screening is to prevent this in the first place? Is it possible that the very opposite happened to what we thought? Did patients go their doctors, fake their WR score and audiogram to apply to get in, did it again at screening, and then performed normally at baseline? Even this would seem a stretch.

 

[FGG]

I've had a reply from a second patient who took part in the trial.

As you'll recall, the first patient I found was quite positive about their experience. This one not so much. Here's what they had to say in their own words:

"Hello Aaron- I have not read the interim analysis. I should do that. But I am not surprised that it isn't encouraging. I have noticed no improvement at all since doing the trial. My word recognition went up a tiny bit but honestly, I think that's because I got better at taking that test. I did it so many times and it caused me a lot of anxiety at first. I got calmer about it after a while. And more willing to guess at the words I was hearing, so I think that gave me a better chance. But the improvement was incredibly minimal, and not clinically relevant. Or so I was told. I had a lot of hope when I was accepted into this trial and it was so disappointing to get nothing from it. But of course there is a chance that I got the placebo. As soon as I learn anything concrete about that I will definitely share.​

I went to ask some follow-up questions about the testing methods. Again, here's what they had to say in their own words:

"The word test was not exactly the same each time, although I think they had 2 or 3 versions and there was definitely repetition. So maybe I memorized some things. I was told to go ahead and guess. Sometimes it was only a vague vowel sound I could hear, so it was so much a guess as just making stuff up! I'm glad you heard from someone who saw improvement from the trial. I actually hope that I DID get the placebo since nothing changed. Gives me hope of getting the real thing down the road."​

As for the speculation surrounding the "burning" experienced by the other patient during 2/4 injections, again this is what the second patient had to say:

"For me, the injections were incredibly painful. All four of them. Yes, I would say it was a burning sensation. I was told that they would not be painful, but even with numbing medication first it was awful. The doctor was pretty surprised by that as he was sure I would not really feel it at all."
​

When I mentioned to them that some other patients may have purposely or subconsciously tanked their WR scores, here's what they had to say:

"Wow! It wouldn't have occurred to me to do that!"
​

The thing I was most curious about was whether Frequency Therapeutics had been in touch with the patient since the trial and asked for any further historical records. They haven't. The only record they gave Frequency Therapeutics was during screening:

"Sorry - what I said wasn't clear. To get into the trial in the first place I had to submit my most recent audiogram. I had one from an ENT that was incomplete and at first they rejected me. Then I sent them one from an otolaryngologist that showed more detail and they said I was perfect fit based on that one."
​

This was very interesting to me. Frequency Therapeutics seemed to imply in the conference call that there was a mismatch between the historical records and baselines (not screenings). That made me wonder: were the screening tests used as baseline? The first patient has come back to me and said that wasn't the case: there was a hearing test to screen the patient after submission of previous records, and then a new baseline was taken before the first injection. So that got me really confused, because if the whole incentive to tank a word score is to get into the trial, why would a patient keep a consistent score between their historical record and screening and then tank their score only once they're in the trial? Makes no sense at all. The only explanation I had was that word scores were not used as historical records, only audiograms. I've gone back to confirm this with both patients, but judging from what the patient said above, it would seem they only had to submit their audiogram. Can someone here who applied to get in confirm?

If this is the case, this is even more perplexing. How could Frequency Therapeutics claim there's a mismatch between historical records and baselines if no historical word recognition scores were provided in the first place and Frequency Therapeutics haven't since gone back to ask if they had any more records? The only assumption I can make is they're claiming there's a mismatch between the historical audiograms and the baseline audiograms and assuming the same of the WR scores, but that isn't possible because the incentive to tank is at screening, not once you're in the trial.

Something doesn't add up here. I must be missing something. Help?

Edit: the first patient has since come back and confirmed they had to submit both a WR score and audiogram.

Edit 2: this still isn't making sense. How could there be a mismatch between baseline and historical records if the whole point of screening is to prevent this in the first place? Is it possible that the very opposite happened to what we thought? Did patients go their doctors, fake their WR score and audiogram to apply to get in, did it again at screening, and then performed normally at baseline? Even this would seem a stretch.

I applied. I happened to bring my two audiograms which happened to have one word score. Stability at least was determined by the audiogram only.

The word score I had for them was very recent before my interview.

They actually asked for my full records by the way, but i didn't get the impression they needed them that day. Had I qualified, I would have started my baseline measurements at screening so I believe the "records not matching" meant going further back.

I just remembered, when I called they told me to bring two recent audiograms. They said nothing about word scores. I just happened to have one. But I did sign something giving them permission to get my medical records.

Makes me wonder if the baseline that day was what they used if you passed the stability and history screen first?

Anyone else who interviewed have a similar experience?

 

[Lucifer]

During the teleconference call, when pressed by an investor on what mechanical or molecular effect could be causing the multi-dosing to dampen the effect, they had no answer. When subsequently asked whether there was any pre-clinical work to inform what might be happening, or why they pursued multi-dosing in the first place, again they had no answer. In their defence, they said it was impossible to try multi-dosing in vivo in animals as it would be too traumatic to the cochlea. I can only infer from that that any pre-clinical work in ex vivo human cochlea wouldn't serve to inform anything meaningful. Whatever way you look at it, Phase 2 was a giant experiment in multi-dosing that backfired spectacularly.

Anyone listening in to that webcast could see a deer having been caught in the headlights. I think it's fair to say they know multi-dosing screwed things up, but not being able to explain it, let alone not being able to justify why they pursued multi-dosing without any pre-clinical work to inform making that decision the first place, makes for seriously bad optics. Chris Loose and David Lucchino strike me as very confident and the latter made it very clear they were not going to rest on their laurels and just wait for Phase 1b results to come out and see what happens. It sounded to me as if they're already drawing up some kind of contingency plan. The reality is that this is a new company testing a new platform in an area where there is an unmet need. The odds are stacked against them.

I hope the contingency plan is to cater to mild-moderately severe hearing loss sufferers and then work on a new delivery method for severe hearing loss sufferers after FX-322 is out in the market.

 

[Lucifer]

In hindsight, there were a few times in the past where Frequency Therapeutics was interviewed and they said they were unable to validate a multi-dose strategy with an animal model. Probably a bigger red flag than many of us realized.

However, multi-dosing being untested and ultimately needing more research doesn't mean the drug is a 100% flop. Showing those open-label trial results should be more revealing.

I'm curious if they could do a multi-dose open label trial? Just recruit groups into cohorts based on a 2x dose schedule length? Like a 2-week, 1-month, 2-month group?

It's kind of strange that they said that they couldn't do multi dosing with animals in the pre-clinical trials phase. Wouldn't that mean for humans, multi dosing won't work unless you space the dosing monthly to every 3 months?

 

[Greg Sacramento]

Place Types of Transport Biology into the forum search and look at images.

I posted links from my library with tags to @FGG and @Zugzug a few days ago. Some links are in post #16335 of this thread. They were liked with comments. I have had these articles for several years. This explains a lot on the subject matter.

With this, for a long time, I thought that they were over dosing, so I had limited conversation. I can't understand why Frequency Therapeutics said they don't not understand why, unless told by legal. I don't think that Frequency Therapeutics wanted to take out weak investors. Question some or much of the blame on fakers. Will one dose show great benefit per post #16335, images of transport biology and the link that I gave from MIT friend without cell therapy?

My MIT friend asked me not to quote him. It's hearsay, but Frequency Therapeutics is also a public company. Maybe some from the company were once students of his, as some had studied at MIT.

Also knowing all the different switches that cause tinnitus. Physical - often nerves - central nervous systems needs consideration as cause and nerves in middle and inner ear as receiver.

Short and other term stock charting is a mess. Delay the on quarter earnings probably due to full past year results and that of forward guidance. Price could move higher on news - and will that news just turn out to be more hype? Price could also continue to move lower. If I was thinking of investing, I wouldn't place price value of movement in either direction on anything but advanced charting filtering. I would use the live NASDAQ.com quote system for minute to minutes activity only to view any large sales. I won't buy on a spike unless there's real - non hype value news.

In the coming weeks or months security law firms may be all over Frequency Therapeutics. Frequency Therapeutics' legal may be working overtime telling management what to say and not to say. This may not matter much, unless a government agency gets mean.

It will be interesting if Frequency Therapeutics makes any employment replacements and type of backgrounds of any new hires including audiologists and hair cell therapy.

 

[Ed209]

If you really believe FX-322 doesn't work, stop posting. We don't need your negative energy.

I don't agree with people getting personal and insulting one another, but you can't just want to censor opposing views.

What you'll be left with is an echo chamber, and what good is that?

 

[Lucifer]

I've had a reply from a second patient who took part in the trial.

As you'll recall, the first patient I found was quite positive about their experience. This one not so much. Here's what they had to say in their own words:

"Hello Aaron- I have not read the interim analysis. I should do that. But I am not surprised that it isn't encouraging. I have noticed no improvement at all since doing the trial. My word recognition went up a tiny bit but honestly, I think that's because I got better at taking that test. I did it so many times and it caused me a lot of anxiety at first. I got calmer about it after a while. And more willing to guess at the words I was hearing, so I think that gave me a better chance. But the improvement was incredibly minimal, and not clinically relevant. Or so I was told. I had a lot of hope when I was accepted into this trial and it was so disappointing to get nothing from it. But of course there is a chance that I got the placebo. As soon as I learn anything concrete about that I will definitely share.​

I went to ask some follow-up questions about the testing methods. Again, here's what they had to say in their own words:

"The word test was not exactly the same each time, although I think they had 2 or 3 versions and there was definitely repetition. So maybe I memorized some things. I was told to go ahead and guess. Sometimes it was only a vague vowel sound I could hear, so it was so much a guess as just making stuff up! I'm glad you heard from someone who saw improvement from the trial. I actually hope that I DID get the placebo since nothing changed. Gives me hope of getting the real thing down the road."​

As for the speculation surrounding the "burning" experienced by the other patient during 2/4 injections, again this is what the second patient had to say:

"For me, the injections were incredibly painful. All four of them. Yes, I would say it was a burning sensation. I was told that they would not be painful, but even with numbing medication first it was awful. The doctor was pretty surprised by that as he was sure I would not really feel it at all."
​

When I mentioned to them that some other patients may have purposely or subconsciously tanked their WR scores, here's what they had to say:

"Wow! It wouldn't have occurred to me to do that!"
​

The thing I was most curious about was whether Frequency Therapeutics had been in touch with the patient since the trial and asked for any further historical records. They haven't. The only record they gave Frequency Therapeutics was during screening:

"Sorry - what I said wasn't clear. To get into the trial in the first place I had to submit my most recent audiogram. I had one from an ENT that was incomplete and at first they rejected me. Then I sent them one from an otolaryngologist that showed more detail and they said I was perfect fit based on that one."
​

This was very interesting to me. Frequency Therapeutics seemed to imply in the conference call that there was a mismatch between the historical records and baselines (not screenings). That made me wonder: were the screening tests used as baseline? The first patient has come back to me and said that wasn't the case: there was a hearing test to screen the patient after submission of previous records, and then a new baseline was taken before the first injection. So that got me really confused, because if the whole incentive to tank a word score is to get into the trial, why would a patient keep a consistent score between their historical record and screening and then tank their score only once they're in the trial? Makes no sense at all. The only explanation I had was that word scores were not used as historical records, only audiograms. I've gone back to confirm this with both patients, but judging from what the patient said above, it would seem they only had to submit their audiogram. Can someone here who applied to get in confirm?

If this is the case, this is even more perplexing. How could Frequency Therapeutics claim there's a mismatch between historical records and baselines if no historical word recognition scores were provided in the first place and Frequency Therapeutics haven't since gone back to ask if they had any more records? The only assumption I can make is they're claiming there's a mismatch between the historical audiograms and the baseline audiograms and assuming the same of the WR scores, but that isn't possible because the incentive to tank is at screening, not once you're in the trial.

Something doesn't add up here. I must be missing something. Help?

Edit: the first patient has since come back and confirmed they had to submit both a WR score and audiogram.

Edit 2: this still isn't making sense. How could there be a mismatch between baseline and historical records if the whole point of screening is to prevent this in the first place? Is it possible that the very opposite happened to what we thought? Did patients go their doctors, fake their WR score and audiogram to apply to get in, did it again at screening, and then performed normally at baseline? Even this would seem a stretch.

So either he got 4 injections of placebo or 4 injections of FX-322. We still do not know which one is causing the burning effect.

Either he experienced no improvement because he had 4 doses of FX-322 or 4 doses of placebo.

 

[Aaron91]

I've had a reply from a second patient who took part in the trial.

As you'll recall, the first patient I found was quite positive about their experience. This one not so much. Here's what they had to say in their own words:

"Hello Aaron- I have not read the interim analysis. I should do that. But I am not surprised that it isn't encouraging. I have noticed no improvement at all since doing the trial. My word recognition went up a tiny bit but honestly, I think that's because I got better at taking that test. I did it so many times and it caused me a lot of anxiety at first. I got calmer about it after a while. And more willing to guess at the words I was hearing, so I think that gave me a better chance. But the improvement was incredibly minimal, and not clinically relevant. Or so I was told. I had a lot of hope when I was accepted into this trial and it was so disappointing to get nothing from it. But of course there is a chance that I got the placebo. As soon as I learn anything concrete about that I will definitely share.​

I went to ask some follow-up questions about the testing methods. Again, here's what they had to say in their own words:

"The word test was not exactly the same each time, although I think they had 2 or 3 versions and there was definitely repetition. So maybe I memorized some things. I was told to go ahead and guess. Sometimes it was only a vague vowel sound I could hear, so it was so much a guess as just making stuff up! I'm glad you heard from someone who saw improvement from the trial. I actually hope that I DID get the placebo since nothing changed. Gives me hope of getting the real thing down the road."​

As for the speculation surrounding the "burning" experienced by the other patient during 2/4 injections, again this is what the second patient had to say:

"For me, the injections were incredibly painful. All four of them. Yes, I would say it was a burning sensation. I was told that they would not be painful, but even with numbing medication first it was awful. The doctor was pretty surprised by that as he was sure I would not really feel it at all."
​

When I mentioned to them that some other patients may have purposely or subconsciously tanked their WR scores, here's what they had to say:

"Wow! It wouldn't have occurred to me to do that!"
​

The thing I was most curious about was whether Frequency Therapeutics had been in touch with the patient since the trial and asked for any further historical records. They haven't. The only record they gave Frequency Therapeutics was during screening:

"Sorry - what I said wasn't clear. To get into the trial in the first place I had to submit my most recent audiogram. I had one from an ENT that was incomplete and at first they rejected me. Then I sent them one from an otolaryngologist that showed more detail and they said I was perfect fit based on that one."
​

This was very interesting to me. Frequency Therapeutics seemed to imply in the conference call that there was a mismatch between the historical records and baselines (not screenings). That made me wonder: were the screening tests used as baseline? The first patient has come back to me and said that wasn't the case: there was a hearing test to screen the patient after submission of previous records, and then a new baseline was taken before the first injection. So that got me really confused, because if the whole incentive to tank a word score is to get into the trial, why would a patient keep a consistent score between their historical record and screening and then tank their score only once they're in the trial? Makes no sense at all. The only explanation I had was that word scores were not used as historical records, only audiograms. I've gone back to confirm this with both patients, but judging from what the patient said above, it would seem they only had to submit their audiogram. Can someone here who applied to get in confirm?

If this is the case, this is even more perplexing. How could Frequency Therapeutics claim there's a mismatch between historical records and baselines if no historical word recognition scores were provided in the first place and Frequency Therapeutics haven't since gone back to ask if they had any more records? The only assumption I can make is they're claiming there's a mismatch between the historical audiograms and the baseline audiograms and assuming the same of the WR scores, but that isn't possible because the incentive to tank is at screening, not once you're in the trial.

Something doesn't add up here. I must be missing something. Help?

Edit: the first patient has since come back and confirmed they had to submit both a WR score and audiogram.

Edit 2: this still isn't making sense. How could there be a mismatch between baseline and historical records if the whole point of screening is to prevent this in the first place? Is it possible that the very opposite happened to what we thought? Did patients go their doctors, fake their WR score and audiogram to apply to get in, did it again at screening, and then performed normally at baseline? Even this would seem a stretch.

After more thought, the only answer I have to my question above is patients lied all the way through: they faked their tests to get to screening (because they already knew about the minimum entry criteria from social media), they then faked their screening test to match their application records, and then faked again at baseline to not raise suspicion, staying consistent all the way through. That would mean everyone improved regardless of whether they got placebo or FX-322.

I somehow find this possibility extremely unlikely, but even if true, I have to now agree with @Zugzug in that my instinct tells me that the number of people who would do this - let alone be successful at it - would be quite low. I don't even want to articulate what this means....

And again, even this isn't consistent with what Frequency Therapeutics have said. Frequency Therapeutics have said there is an inconsistency. At what point was there an inconsistency? I can't see any scenario anymore where this is a viable thesis but maybe I'm so tired and emotionally exhausted by all of this I'm not thinking straight.

 

[r34d1ng]

You are really coming off as ignorant.

Just don't feed the trolls. Use the Ignore function by clicking on his avatar.

 

[Diesel]

After more thought, the only answer I have to my question above is patients lied all the way through: they faked their tests to get to screening (because they already knew about the minimum entry criteria from social media), they then faked their screening test to match their application records, and then faked again at baseline to not raise suspicion, staying consistent all the way through. That would mean everyone improved regardless of whether they got placebo or FX-322.

I somehow find this possibility extremely unlikely, but even if true, I have to now agree with @Zugzug in that my instinct tells me that the number of people who would do this - let alone be successful at it - would be quite low. I don't even want to articulate what this means....

And again, even this isn't consistent with what Frequency Therapeutics have said. Frequency Therapeutics have said there is an inconsistency. At what point was there an inconsistency? I can't see any scenario anymore where this is a viable thesis but maybe I'm so tired and emotionally exhausted by all of this I'm not thinking straight.

So, help me understand the screening process? Does a central person at Frequency Therapeutics approve the applicants sitting in the screen queue to enter the trial? Or does a central independent screener review the applicants in the queue, and then approve those that meet Frequency Therapeutics' requirements?

I assume it is central because they're meeting a quota, so some type of centralization has to take place to report on the recruiting progress. Am I correct on this assumption?

If so, I am wondering if there isn't enough evidence to support the faker/liar theory, perhaps there was an ongoing error administering the screening process.

 

[FGG]

So, help me understand the screening process? Does a central person at Frequency Therapeutics approve the applicants sitting in the screen queue to enter the trial? Or does a central independent screener review the applicants in the queue, and then approve those that meet Frequency Therapeutics' requirements?

I assume it is central because they're meeting a quota, so some type of centralization has to take place to report on the recruiting progress. Am I correct on this assumption?

If so, I am wondering if there isn't enough evidence to support the faker/liar theory, perhaps there was an ongoing error administering the screening process.

I never had to speak to a central person. As far as I know only the local site was involved with at least my screening.

If it helps, she had a list that she appeared to refer to (that i couldn't see). I do know i was her very first fx-322 applicant because she told me.

 

[FGG]

After more thought, the only answer I have to my question above is patients lied all the way through: they faked their tests to get to screening (because they already knew about the minimum entry criteria from social media), they then faked their screening test to match their application records, and then faked again at baseline to not raise suspicion, staying consistent all the way through. That would mean everyone improved regardless of whether they got placebo or FX-322.

I somehow find this possibility extremely unlikely, but even if true, I have to now agree with @Zugzug in that my instinct tells me that the number of people who would do this - let alone be successful at it - would be quite low. I don't even want to articulate what this means....

And again, even this isn't consistent with what Frequency Therapeutics have said. Frequency Therapeutics have said there is an inconsistency. At what point was there an inconsistency? I can't see any scenario anymore where this is a viable thesis but maybe I'm so tired and emotionally exhausted by all of this I'm not thinking straight.

This is how I understand it, based on my own screening:

You go to appointment (I was told on phone to bring audiograms to appointment. I don't recall being asked to bring anything else that day). They looked at my two audiograms which happened to include 1 word score only (my recent one).

I signed the paperwork that gives them the right to request and receive my medical records and gave them the Otology name and numbers.

They gave me the trial info to review while she looked over my audiograms and looked over what I had given as my history to her with a sheet of paper that I gathered was metrics.

And then she said I didn't qualify. I asked why and she said my audiogram.

 

[GlennS]

If you really believe FX-322 doesn't work, stop posting. We don't need your negative energy.

I'm hardly the only pessimist here... gatekeeper.

more willing to guess at the words I was hearing,

Gee, that sounds awfully like what I said before about how and why word scores can be iffy. Imagine that.

 

[Lucifer]

Assuming Day 210 results aren't positive but they get positive results for both age-related and severe hearing loss trials, would that confirm that multi-dosing does not work?

I'm just thinking out loud the best chance to convince the FDA for a pivotal phase early next year. Multi-dosing does not work but if the single dosing of FX-322 does show improvements in all the Phase 1b trials, would the FDA be satisfied about FX-322 starting the pivotal phase early next year?

Safety has been proven as they have over 200 patients that have participated in the trials. Effectiveness of FX-322 has been proven from the word score improvements in Phase 1b.

I know many of you are saying they may need to repeat a Phase 2a again but I have hope that it is possible for them to go to the pivotal phase early next year if their age-related and severe hearing loss trials show word score improvements.

 

[Sunshine007]

After more thought, the only answer I have to my question above is patients lied all the way through: they faked their tests to get to screening (because they already knew about the minimum entry criteria from social media), they then faked their screening test to match their application records, and then faked again at baseline to not raise suspicion, staying consistent all the way through. That would mean everyone improved regardless of whether they got placebo or FX-322.

I somehow find this possibility extremely unlikely, but even if true, I have to now agree with @Zugzug in that my instinct tells me that the number of people who would do this - let alone be successful at it - would be quite low. I don't even want to articulate what this means....

And again, even this isn't consistent with what Frequency Therapeutics have said. Frequency Therapeutics have said there is an inconsistency. At what point was there an inconsistency? I can't see any scenario anymore where this is a viable thesis but maybe I'm so tired and emotionally exhausted by all of this I'm not thinking straight.

Essentially what has been stated by Frequency Therapeutics is an artificially low baseline was established. The faker intent being speculated here may not really apply to the entry but people might have faked their baseline thinking they are helping the trial outcome without really understanding the process.

There could be sufficient data for:

1) Frequency Therapeutics to say screening and baseline do not match
2) People dampened their baseline to show effect

I really am not sure how much this could be and why they called it out. I very much doubt this being anywhere close to 10 percentage point improvement in WRS except perhaps in a few people.

 

[FGG]

Assuming Day 210 results aren't positive but they get positive results for both age-related and severe hearing loss trials, would that confirm that multi-dosing does not work?

I'm just thinking out loud the best chance to convince the FDA for a pivotal phase early next year. Multi-dosing does not work but if the single dosing of FX-322 does show improvements in all the Phase 1b trials, would the FDA be satisfied about FX-322 starting the pivotal phase early next year?

Safety has been proven as they have over 200 patients that have participated in the trials. Effectiveness of FX-322 has been proven from the word score improvements in Phase 1b.

I know many of you are saying they may need to repeat a Phase 2a again but I have hope that it is possible for them to go to the pivotal phase early next year if their age-related and severe hearing loss trials show word score improvements.

Assuming everything Frequency Therapeutics reported is correct and the remaining trials have good results, I still strongly believe they will end up repeating Phase 2a.

 

[FGG]

Essentially what has been stated by Frequency Therapeutics is an artificially low baseline was established. The faker intent being speculated here may not really apply to the entry but people might have faked their baseline thinking they are helping the trial outcome without really understanding the process.

There could be sufficient data for:

1) Frequency Therapeutics to say screening and baseline do not match
2) People dampened their baseline to show effect

I really am not sure how much this could be and why they called it out. I very much doubt this being anywhere close to 10 percentage point improvement in WRS except perhaps in a few people.

I can't speculate on percentage but that's how I understand it (not the motive but where the fake happened) too based on what they said and my own interview experience.

 

[Lucifer]

Assuming everything Frequency Therapeutics reported is correct and the remaining trials have good results, I still strongly believe they will end up repeating Phase 2a.

Damn, that sucks if they have to repeat Phase 2a trials. Just thinking how with the COVID-19 vaccines they could complete all phases of the trial within a year and FX-322 has been in trials since 2017. Just hoping that with the FDA being lenient with the COVID-19 trials, it would make them lenient with FX-322 if it shows that it is safe and effective.

 

[Lucifer]

I can't speculate on percentage but that's how I understand it (not the motive but where the fake happened) too based on what they said and my own interview experience.

Since the fakers may have screwed the trial up, would there be penalties for them to confess that they lied about their hearing results? Hoping this may change the outcome of the Phase 2a trials.

 

[Tezcatlipoca]

Assuming everything Frequency Therapeutics reported is correct and the remaining trials have good results, I still strongly believe they will end up repeating Phase 2a.

What about them implying that they would advance to a pivotal phase in the press release?

 

[Diesel]

What about them implying that they would advance to a pivotal phase in the press release?

Do you mean this?

"The results clearly demonstrated that a treatment regimen using four weekly injections is unfavorable and we will continue to move ahead with single-dose administrations in future studies. We believe in the potential of FX-322 given the demonstrated hearing signal and favorable safety profile observed with a single dose and in the future, we may evaluate re-treatment at longer intervals," said David L. Lucchino, Frequency's President and Chief Executive Officer."​

This is letting everyone know that Phase 2A/multi-dosing going south isn't taking FX-322 down in their opinion.

 

[Tezcatlipoca]

Do you mean this?

"The results clearly demonstrated that a treatment regimen using four weekly injections is unfavorable and we will continue to move ahead with single-dose administrations in future studies. We believe in the potential of FX-322 given the demonstrated hearing signal and favorable safety profile observed with a single dose and in the future, we may evaluate re-treatment at longer intervals," said David L. Lucchino, Frequency's President and Chief Executive Officer."​

This is letting everyone know that Phase 2A/multi-dosing going south isn't taking FX-322 down in their opinion.

This one was very encouraging but there was another paragraph, implying heavily that a Pivotal Phase was happening.

 

[FGG]

This one was very encouraging but there was another paragraph, implying heavily that a Pivotal Phase was happening.

I don't believe they ever said "straight to pivotal" but yes if they are continuing, the eventual goal is a pivotal trial.

 

[Joe72]

Damn, that sucks if they have to repeat Phase 2a trials. Just thinking how with the COVID-19 vaccines they could complete all phases of the trial within a year and FX-322 has been in trials since 2017. Just hoping that with the FDA being lenient with the COVID-19 trials, it would make them lenient with FX-322 if it shows that it is safe and effective.

Allow me to take a stab at the reason - billions of dollars on a recurring global annual basis for "vaccines" vs a tiny % of the population that suffers from tinnitus that is difficult to measure and can manifest itself from a hundred different causes.

Hmmm... sounds like Big Money wins again. And again. And again. Sucks, but it's true.