Frequency Therapeutics — Hearing Loss Regeneration

[Diesel]

I believe they said there was no difference between placebo improvements and drug improvements.

Since no one knew if they got placebo or drug, both groups were equally impacted by bias, and both groups showed similar "improvement."

Unfortunately, that's not a meaningless result. It suggests the drug was not effective.

Otherwise, you would see bias "improvement" + actual improvement, i.e. more improvement, among the drug-receiving cohort.

Note that the only data they had at the interim readout was at a group-level.

I think it was @Zugzug that did an excellent assessment for the issue with trial design where participants artificially deflated their word scores to gain entrance into the trial.

If this bias is the case, and these participants were randomly distributed across all 4 cohorts, then it wouldn't necessarily be that the drug isn't effective, it would mean that they would have no way to prove at a group level whether it was or was not when compared to placebo.

 

[kiki]

I believe they said there was no difference between placebo improvements and drug improvements.

Since no one knew if they got placebo or drug, both groups were equally impacted by bias, and both groups showed similar "improvement."

Unfortunately, that's not a meaningless result. It suggests the drug was not effective.

Otherwise, you would see bias "improvement" + actual improvement, i.e. more improvement, among the drug-receiving cohort.

The statement could be the number of patients who have improved, both in WR and audiogram.
I think it may not be the magnitude of the improvement (increased number of words, improved dB).
Previously, the content I posted assumes that assumption.

View attachment 44643

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I thought about it by looking at the two slides of the latest presentation.

Slide 16 states "Incidence higher across all groups than in single dose studies".

And it has been described as "No discernible hearing improvement over placebo observed."

Let's make a Phase2a graph under the condition of "Exceeding Absolute 10%" like the graph of Slide 17. The graph would look like 40% (placebo), 55% (x1), 50% (x2), 45% (x4), for example.

In this case, for example, if you change "Exceeding Absolute 10%" to "Exceeding Absolute 20%", can you see a more accurate difference between the drug and the placebo?

Isn't 10% their standard as well as 10 dB in PTA?

Attention:
Are cheaters evenly distributed in each group?
Are each fraud about the same?(40 word→ 30 word? 40 word→ 20 word? etc)
What's the impact of the the ceiling effect?

In the "final report", I would like you to show me the corrected version of the "Interim report" .

 

[Ali.sy]

Hey, tinnitus community. FX-322 is dead. Let's start looking for other treatments, and moving the research forward. The COVID-19 vaccine took months, but eventually something will relieve the tinnitus. We must wait decades.

 

[MrCrybaby]

Hey, tinnitus community. FX-322 is dead. Let's start looking for other treatments, and moving the research forward. The COVID-19 vaccine took months, but eventually something will relieve the tinnitus. We must wait decades.

The COVID-19 vaccine was actually created using a technology that took decades of research to develop and had already been in clinical trial for vaccination against cancer for years.

 

[Street Novelist]

Hey, tinnitus community. FX-322 is dead. Let's start looking for other treatments, and moving the research forward. The COVID-19 vaccine took months, but eventually something will relieve the tinnitus. We must wait decades.

Hey look! GlennS just found a jerking off buddy.

 

[Tezcatlipoca]

Hey, tinnitus community. FX-322 is dead. Let's start looking for other treatments, and moving the research forward. The COVID-19 vaccine took months, but eventually something will relieve the tinnitus. We must wait decades.

You heard him guys, close the thread. We had a good run.

 

[Rajin]

The COVID-19 vaccine was actually created using a technology that took decades of research to develop and had already been in clinical trial for vaccination

Wow, I didn't know that. But tinnitus has been around 2000 years before Jesus.

Hopefully when he comes back, we get a cure, because scientists are not making any progress.

 

[Ali.sy]

Hey look! GlennS just found a jerking off buddy.

Your words are incomprehensible, my friend. Based on the news, FX-322 is a waste of time, and efforts should be directed to quick and fruitful research, no?

 

[Don Tinny]

I remember being in my car with my partner talking about FX-322. She was like "that's just an experiment". She was right. And the absence of good results explains why we didn't see news about this on mass media.

I was doing well with the ringing, it was less invasive, but I am now going through a relapse. I hope my tinnitus gets better again, now I don't have FX-322 on my mind to keep going forward.

Sorry about my poor English.

 

[Jazzer]

Another example of why it is fruitless and perhaps even damaging to take too much interest in, and get over excited about information and podcast interviews with researchers.

My only interest is in a treatment or preferably a cure, that actually proves 'itself in the field.'

I personally have no interest in the 'nitty-gritty,' which every single time (so far) has amounted to nothing.

Just my view folks.
Don't mind me.

Dave xx
Jazzer

 

[RingingBrother]

Your words are incomprehensible, my friend. Based on the news, FX-322 is a waste of time, and efforts should be directed to quick and fruitful research, no?

Frequency Therapeutics Expands its Clinical Development Team, Adding Expertise in Inner Ear Physiology and Translational Science

It doesn't seem like a waste of time if they are still hiring.

And the open label trial shows some hope.

"At day 90 following dosing, thirty-four percent (34%) of subjects achieved a ten percent (10%) or greater absolute improvement in WR scores in the treated ear, which was clinically meaningful and statistically significant compared to the untreated ear"

 

[Jazzer]

Frequency Therapeutics Expands its Clinical Development Team, Adding Expertise in Inner Ear Physiology and Translational Science

It doesn't seem like a waste of time if they are still hiring.

And the open label trial shows some hope.

"At day 90 following dosing, thirty-four percent (34%) of subjects achieved a ten percent (10%) or greater absolute improvement in WR scores in the treated ear, which was clinically meaningful and statistically significant compared to the untreated ear"

What are WR scores and how are they measured?

 

[tommyd87]

What are WR scores and how are they measured?

Word Recognition.

Reading out of random words which test the various elements of hearing (eg: words with sh like ship or words which can be misinterpreted like fin or even basic words like tin).

 

[RB2014]

Frequency Therapeutics Expands its Clinical Development Team, Adding Expertise in Inner Ear Physiology and Translational Science

It doesn't seem like a waste of time if they are still hiring.

And the open label trial shows some hope.

"At day 90 following dosing, thirty-four percent (34%) of subjects achieved a ten percent (10%) or greater absolute improvement in WR scores in the treated ear, which was clinically meaningful and statistically significant compared to the untreated ear"

The fact that they are hiring doesn't mean anything. They are a publicly traded company. They will keep going until FX-322 is proven successful, or they run out of money.

 

[Diesel]

The fact that they are hiring doesn't mean anything. They are a publicly traded company. They will keep going until FX-322 is proven successful, or they run out of money.

It depends on who they are hiring and why. For projects that are early in development like FX-322 / PCA, bringing on experience matters. Based on a quick google search, Lichtenhan and Franck are both well recognized and published in the hearing space. Hiring heavyweights like this is often an admission that the firm needs to strengthen an area of the business that was otherwise overlooked or lacking. It also reduces the time/expense needed for the firm to "learn" their way through problems with product/development. In Lichtenhan's case, he brings published experience in drug delivery into the cochlea and more precise diagnostic methods. These are two areas that even relatively uninformed posters here are a challenge for the current FX-322 formula. As an investor or patient, this experience may help expedite these challenges.

 

[Zugzug]

It depends on who they are hiring and why. For projects that are early in development like FX-322 / PCA, bringing on experience matters. Based on a quick google search, Lichtenhan and Franck are both well recognized and published in the hearing space. Hiring heavyweights like this is often an admission that the firm needs to strengthen an area of the business that was otherwise overlooked or lacking. It also reduces the time/expense needed for the firm to "learn" their way through problems with product/development. In Lichtenhan's case, he brings published experience in drug delivery into the cochlea and more precise diagnostic methods. These are two areas that even relatively uninformed posters here are a challenge for the current FX-322 formula. As an investor or patient, this experience may help expedite these challenges.

I genuinely don't understand the potential criticism of the Lichtenhan hire (not from you). Like what do we want them to do? Bang their heads against the wall until the absent audiogram results show up from divine intervention?

The company is not pulling the veil over my eyes. I know what they are doing. Their product failed and they are now trying to turn failure into a non-binary event. This is called logic and how most successful people run their lives.

 

[tommyd87]

The fact that they are hiring doesn't mean anything. They are a publicly traded company. They will keep going until FX-322 is proven successful, or they run out of money.

I probably have to disagree with this. The key is who a particular company is hiring, not merely the fact that they are either hiring or not hiring. The fact that Frequency Therapeutics has gone out of their way to hire someone relevant to the drug delivery process shows that they are interested and keen to resolve what has been their biggest problem to date overall. Obviously this demonstrates that Frequency Therapeutics is aiming to conquer the issue present of being able to gain regeneration in cochleas in the lab but struggling to gain sufficient regeneration presently in cochleas in humans.

Hence this demonstrates that there tends to be a focus on making the medicine attain the greatest and best outcomes possible overall. Obviously if Frequency Therapeutics was just hiring someone to work in their office administration then this would be a completely different story too.

The other thing that should be noted is that Frequency Therapeutics had success in their initial single injection trial and hence they theoretically could have proceeded with this to try to gain approval. All issues with the second trial appeared to be with the dosing methods and nothing else, so their latest hiring is both relevant and appropriate.

 

[RB2014]

I probably have to disagree with this. The key is who a particular company is hiring, not merely the fact that they are either hiring or not hiring. The fact that Frequency Therapeutics has gone out of their way to hire someone relevant to the drug delivery process shows that they are interested and keen to resolve what has been their biggest problem to date overall. Obviously this demonstrates that Frequency Therapeutics is aiming to conquer the issue present of being able to gain regeneration in cochleas in the lab but struggling to gain sufficient regeneration presently in cochleas in humans.

Hence this demonstrates that there tends to be a focus on making the medicine attain the greatest and best outcomes possible overall. Obviously if Frequency Therapeutics was just hiring someone to work in their office administration then this would be a completely different story too.

The other thing that should be noted is that Frequency Therapeutics had success in their initial single injection trial and hence they theoretically could have proceeded with this to try to gain approval. All issues with the second trial appeared to be with the dosing methods and nothing else, so their latest hiring is both relevant and appropriate.

Frequency Therapeutics' issues aren't just limited to dosing methods. They have many issues that they need to address before this can go to market. They have already done several single dose studies and the results are still not what they expected.

I know we have all speculated on this thread, but have Frequency Therapeutics provided any reasoning behind the increased word scores?

 

[Zugzug]

I know we have all speculated on this thread, but have Frequency Therapeutics provided any reasoning behind the increased word scores?

Unfortunately, this is a classic "damned if you do, damned if you don't" situation. Speculate incorrectly and it comes off like they are misleading shareholders without evidence. Don't speculate at all and it seems like there could be nothing to it.

As it is, their multi-dose "don't step on the lawn" speculation went down the hatch like battery acid...

 

[Diesel]

Frequency Therapeutics' issues aren't just limited to dosing methods. They have many issues that they need to address before this can go to market. They have already done several single dose studies and the results are still not what they expected.

I know we have all speculated on this thread, but have Frequency Therapeutics provided any reasoning behind the increased word scores?

It seems like they're satisfied with the two single dose studies on their investor presentation. Have you listened to the Goldman webinar? They seem confident that they can build multiple Phase 2 trials off of those two trials, and potentially the severe trial outcomes.

They definitely missed the mark trying to hit all SNHL cases. However, it's not out of the ordinary to establish a viable product that has a known beachhead (in this case moderate or worse SNHL). Still ends up being a lucrative market of 10-15m Americans.

Frequency Therapeutics believes that progenitor cell activation leading to hair cell regrowth is the reason for hearing improvement.

 

[RingingBrother]

Frequency Therapeutics' issues aren't just limited to dosing methods. They have many issues that they need to address before this can go to market. They have already done several single dose studies and the results are still not what they expected.

I know we have all speculated on this thread, but have Frequency Therapeutics provided any reasoning behind the increased word scores?

Since FX-322 will be focused on regrowing inner hair cells instead of outer hair cells, it will mostly benefit clarity over volume/loudness.

 

[RingingBrother]

Frequency Therapeutics believes that progenitor cell activation leading to hair cell regrowth is the reason for hearing improvement.

I still wonder if the new hair cells will easily reattach to the nerve.

 

[ThomasRobert]

I still wonder if the new hair cells will easily reattach to the nerve.

No issue. OTO-413 is just starting recruiting.

OTO-413 in Subjects With Speech-in-Noise Hearing Impairment

 

[Diesel]

No issue. OTO-413 is just starting recruiting.

OTO-413 in Subjects With Speech-in-Noise Hearing Impairment

Good point. Still specific to inner hair cells. Which may reinforce the *hypothesis* circulating here that FX-322 may be regenerating and synapsing IHC. OHC still remain in question.

 

[kiki]

Since FX-322 will be focused on regrowing inner hair cells instead of outer hair cells, it will mostly benefit clarity over volume/loudness.

Inner hair cell priority is speculation in this thread.

Frequency Therapeutics have not made such a statement.

 

[Chad Lawton]

I know we have all speculated on this thread, but have Frequency Therapeutics provided any reasoning behind the increased word scores?

It's due to where the drug reaches in the cochlea. It saturates the area of the cochlea where the higher frequencies are. The high frequencies allow for better clarity in hearing. FX-322 doesn't reach the lower frequencies with the current drug administration method. The shaded blue area on this cochlea diagram is where the drug reaches.

 

[Chad Lawton]

Inner hair cell priority is speculation in this thread.

Frequency Therapeutics have not made such a statement.

Yeah, I have no idea where people came up with this idea from.

 

[Zugzug]

It's due to where the drug reaches in the cochlea. It saturates the area of the cochlea where the higher frequencies are. The high frequencies allow for better clarity in hearing. FX-322 doesn't reach the lower frequencies with the current drug administration method. The shaded blue area on this cochlea diagram is where the drug reaches.

Yeah, I have no idea where people came up with this idea from.

The story here is definitely not as simple as the drug fully absorbing in higher frequencies and the results are all explained by the drug just not going deep enough.

Although, clearly, the drug is also not going very deep. However, if the issue was just frequencies hit, we would see stratified (<8 kHz and >8 kHz) audiogram results too -- I know, unbelievable that I would bring audiograms into the discussion since I'm a weak-minded loon who can't accept reality.

If we are willing to believe that the super WR responders are legit, then it's logical to believe that they are seeing IHC improvements and negligible OHC improvements. This is speculative, of course, but for sure, the drug is not translating the pharmacology study (attached) into one-to-one OHC and IHC hearing improvements in those ranges.

 

[Diesel]

Yeah, I have no idea where people came up with this idea from.

It's a running hypothesis that has come up on occasion:

- In humans inner hair cell health is responsible for WR & WIN score performance explaining the 10% + improvements in these measures, but not on the audiogram, which tends to indicate OHC performance.

- Inner hair cells are observed to start developing in utero in higher order mammals before OHC start to develop.

- Since PCA is believed to activate a biological program that only runs in utero once, one member theorized that the inner ear biology only activated IHC progenitors with the first pass of FX-322, and subsequent passes would cause adjacent OHC to develop

- Frequency Therapeutics' graphics have shown more support cells per IHC than per OHC, so perhaps the odds of creating an IHC are higher.

- Carl LeBel noted on the Tinnitus Talk Podcast that in human cochlea, no supernumerary cells were created, indicating the ability for the organ to "throttle" cell regeneration.

 

[Pete88]

Yeah, I have no idea where people came up with this idea from.

Same. I also noticed that the popular understanding of IHC and OHC changed. Until the Phase 2 results were released, everyone was saying that the OHC were for higher frequencies while the IHC were for lower frequencies and found deeper in the cochlea. The theory was the OHC were reached while the IHC were not, which was why the word scores and higher frequencies improved. Like "inner" and "outer" referred to their physical location in the cochlea as it spiraled. Suddenly overnight, the uses of these terms flipped and IHC is what apparently is fixed by FX-322 and that's why the word scores get better without audiograms.

Maybe I missed something but it seemed like overnight someone redefined these terms and everyone just jumped on board.