Frequency Therapeutics — Hearing Loss Regeneration

[Jrblovsky]

The reason why it failed is because weekly doses were not effective. If you take a look at previous trials, they have stated single dosing of FX-322 was more effective.

There will be people here still saying FX-322 won't work when the positive outcomes for age-related and severe hearing loss trials come out in June and Q3.

I would like FX-322 to work as much as the next guy but it doesn't. The Phase 1 results were debatable as well. I doubt the next trial will result in any useful information beyond what is already known.

 

[Lucifer]

I would like FX-322 to work as much as the next guy but it doesn't. The Phase 1 results were debatable as well. I doubt the next trial will result in any useful information beyond what is already known.

I see your point and maybe you're right that FX-322 may not work like you said.

We just need to wait and see what the outcomes are for the next set of trials. I just hope Frequency Therapeutics have substantial proof that FX-322 works.

 

[Lucifer]

I can't wait to see all you bears turn into bulls when the positive results come out for age-related and severe hearing loss trials.

 

[Zugzug]

The company still has trials that are active; so select few don't yet see the dead-end for FX-322. It's not exactly normal to see a single drug applied this many parallels at once, let alone a hearing drug, especially two Phase 1s for a similar underlying condition (SNHL) after a Phase 2 flopped for basically, SNHL.

The two remaining Phase 1bs are all that's left. Let people pontificate; if the two remaining trials flop, you'll be happy to see this thread die a slow death and move on to the second page of the Research News section.

I have a somewhat granular question that you may know the answer to.

I wonder, when they compared the 4 cohorts across time periods, I would imagine (and I think you've mentioned this before) that the time was after their last dose. So "30 days" is really Day 37, 44, 58 for the dosing cohorts 1x, 2x, and 4x, respectively. In this way, one is comparing apples to apples, or so they thought.

However, now there's this overdosing business. I wonder what actual day the placebo data was compared to. It seems like "30 days" for the placebo group should correspond with Day 30, but it could also be day 58 if we count time as after the last placebo injection.

Anyways, here's my thought. There's a boatload of post hoc analysis they can do on this lawn effect and overdosing stuff. I don't really understand why the 4x group did the worst. If time measurements started for them after the last dose, wouldn't they have the advantage of no lawn effect (only treatment group, since the last shot was the drug)?

Is their hypothesis basically that the drug shots caused the lawn effect, but not the placebo shots? So 1x performed the best because the drug settled and then was never disrupted by the placebo shots? Doesn't that damage the theory that it was from the injections themselves (i.e. trauma or perilymph overflow)? I would think if it was the injections themselves, the 4x group would perform the best.

BTW, I'm not sold on any of it, I'm just trying to understand.

 

[FGG]

Everyone's very defensive. I understand why.

Honestly I'm not trying to belittle the science, the achievement, etc. Of course, as one of "us" I was rooting big time for them. But my opinion is, if the mechanism worked, we'd see more positive results, or statistically significant changes. You have to understand what this company had riding on these results. Tons of money. If there was a twinkle in the eye it would've been reported. They had to swallow their pride and admit nothing was gained right now.

And for the record - gains made in mice doesn't mean much. They're good for testing mechanisms and hypotheses, and indications of whether or not to move forward - but we are different. Curing mice doesn't guarantee anything at all for us. Unfortunately.

On the bright side, progress. Failure is progress. And, Frequency Therapeutics are not the only players in the game.

COVID-19 causing tinnitus is a small silver lining.

Genuine question, but why is it automatically considered "defensive" or a "coping mechanism" to even entertain the idea that Frequency Therapeutics might be right about what happened with their Phase 2a and to discuss things like what Dr. Cliff did about the results showing an IHC preference?

Are we just supposed to just say "Frequency Therapeutics is most definitely wasting their time with the single dose studies", assume they are just incompetent fools and/or frauds we should never bring their (cursed) name up again?

I truly don't understand the hostility towards even talking about the analysis of what the company said went wrong and what that might mean for a future direction.

 

[Matchbox]

The stock price is a bargain right now. If they can get positive outcomes for both age-related and severe hearing loss sufferers I expect the share price to go back up to $20-$30 and any announcement of the pivotal phase will make it go back up to $60 or more. This is a good time to get back in.

The stock price is just in line with the market as a whole, it's probably bots buying ETFs with FREQ.

Just hold on for the big ride when a bunch more hedge funds fail to deliver and we get a minicrash... Well more like flatline with all the money being pulled from the Fed's ass.

 

[Lucifer]

The stock price is just in line with the market as a whole, it's probably bots buying ETFs with FREQ.

Just hold on for the big ride when a bunch more hedge funds fail to deliver and we get a minicrash... Well more like flatline with all the money being pulled from the Fed's ass.

What do you mean by bots buying ETFs with FREQ? How do they do this?

 

[Diesel]

I have a somewhat granular question that you may know the answer to.

I wonder, when they compared the 4 cohorts across time periods, I would imagine (and I think you've mentioned this before) that the time was after their last dose. So "30 days" is really Day 37, 44, 58 for the dosing cohorts 1x, 2x, and 4x, respectively. In this way, one is comparing apples to apples, or so they thought.

However, now there's this overdosing business. I wonder what actual day the placebo data was compared to. It seems like "30 days" for the placebo group should correspond with Day 30, but it could also be day 58 if we count time as after the last placebo injection.

Anyways, here's my thought. There's a boatload of post hoc analysis they can do on this lawn effect and overdosing stuff. I don't really understand why the 4x group did the worst. If time measurements started for them after the last dose, wouldn't they have the advantage of no lawn effect (only treatment group, since the last shot was the drug)?

Is their hypothesis basically that the drug shots caused the lawn effect, but not the placebo shots? So 1x performed the best because the drug settled and then was never disrupted by the placebo shots? Doesn't that damage the theory that it was from the injections themselves (i.e. trauma or perilymph overflow)? I would think if it was the injections themselves, the 4x group would perform the best.

BTW, I'm not sold on any of it, I'm just trying to understand.

Interesting thoughts. The only thing I have understood is that they sampled at the "Day 90" follow-up visit. Which would vary depending on dose group. And is a bit of a flaw in trial design as well. What they probably should have done was front-loaded the placebo shots for the 1x and 2x groups, and then followed with FX-322; so the Day-90 was an actual Day-90 following the end of the.

Their hypothesis seems to be the lawn effect is from FX-322 overdosing the cochlea. There has been no post-mortem, so your guess is as good as mine.

I also can't quite understand how they looked at the averages for each cohort and established that they had both cheating and this dosage problem. The data would be too vague; unless they were able to unmask screening data from the accepted patients, and "back into" it.

 

[Tezcatlipoca]

Genuine question, but why is it automatically considered "defensive" or a "coping mechanism" to even entertain the idea that Frequency Therapeutics might be right about what happened with their Phase 2a and to discuss things like what Dr. Cliff did about the results showing an IHC preference?

Are we just supposed to just say "Frequency Therapeutics is most definitely wasting their time with the single dose studies", assume they are just incompetent fools and/or frauds we should never bring their (cursed) name up again?

I truly don't understand the hostility towards even talking about the analysis of what the company said went wrong and what that might mean for a future direction.

Don't you know? We're supposed to be all negativity here, we can't even entertain the idea of talking about science. Nothing works, nothing will ever work. Long live audiograms!

 

[MrCrybaby]

This forum has been a hotspot of speculation every day for the past year. I think Frequency Therapeutics may have given like 3 solid press releases in that time? Of course now that Frequency Therapeutics has announced results from Phase 2a and their plan for moving forward this thread is going to explode...

 

[Diesel]

Genuine question, but why is it automatically considered "defensive" or a "coping mechanism" to even entertain the idea that Frequency Therapeutics might be right about what happened with their Phase 2a and to discuss things like what Dr. Cliff did about the results showing an IHC preference?

Are we just supposed to just say "Frequency Therapeutics is most definitely wasting their time with the single dose studies", assume they are just incompetent fools and/or frauds we should never bring their (cursed) name up again?

I truly don't understand the hostility towards even talking about the analysis of what the company said went wrong and what that might mean for a future direction.

Is it ironic that Tinnitus Talk members use hostile dialog against each other on this particular thread that looks grossly similar to the same dialog they've received from ENTs and Audiologists when seeking help for their hearing problems?

Maybe it's a form of schadenfreude?

 

[Street Novelist]

Also have to take into account that the placebo may have washed FX-322 away as well. Not sure how long FX-322 stays in your ear after injection.

I hope in the next trial they do just that. Give us 1 dose of FX-322 and see what happens; no following it with a placebo.

 

[GlennS]

I truly don't understand the hostility towards even talking about the analysis of what the company said went wrong and what that might mean for a future direction.

Well, companies make excuses all the time. The whole idea behind these trials is that it's a process that goes beyond company spin.

 

[RingingBrother]

I would like FX-322 to work as much as the next guy but it doesn't. The Phase 1 results were debatable as well. I doubt the next trial will result in any useful information beyond what is already known.

It was a 10% improvement over 90 days with one dose in Phase 1. Who would say no to that?

 

[Auricle]

How do they deliver the drug using this method? Is it still a needle through the eardrum?

The figure at the front of the publication shows two purple arrows, one trans-tympanic and one from the direction of the Eustachian tube.

It's gotta come from somewhere...

 

[Billy_Shears]

This forum has been a hotspot of speculation every day for the past year. I think Frequency Therapeutics may have given like 3 solid press releases in that time? Of course now that Frequency Therapeutics has announced results from Phase 2a and their plan for moving forward this thread is going to explode...

Frequency Therapeutics is a good, sound company with strong management and expertise in the field of progenitor cellular science that happens to have credence in restoring sensorineural hearing loss one day. Restoring hearing loss is like the final frontier of potential medical breakthroughs and most all of us can feel that it is near.

Frequency Therapeutics provides us with the greatest hope of ending our long struggle of despair with newfound clarity of sweet sound. The company is quite aware of the formidable task at hand with millions of onlookers seeking help and a return to life and living. On the contrary, canned lawyers salivate at the notion of less than adequate clinical trial results from biopharma companies causing great financial losses to those who bet it all on, for instance, FX-322. They'll only get what they deserve - nothing.

We had a setback. We, as in Frequency Therapeutics and the community on this board who share a common bond for the most part. Progenitor Cellular science will one day find perfection in the cochlea, thereby, restoring clarity and eventually ending tinnitus as we know it.

 

[ajc]

It was a 10% improvement over 90 days with one dose in Phase 1. Who would say no to that?

10% improvement for 30% of participants, was it not? It was very likely either placebo, chance, or fraud. Day 210 results should tell more...

 

[Greg Sacramento]

I posted that there was a sell of 477,629 shares, plus 4 other sells of 1 million or over on Friday 19th March. This is why I sold my 75 shares as I said.

I also said some big boys did know something and that price weakness other than NASDAQ had little to do with volatile downwards trading.

I mentioned all this 2 trading days before the big drop.

However, I was watching live trading from time to time on the NASDAQ official site since price was at $54 and noticed then many large sales.

I said after the big drop that I expected security litigation, but may not affect stock price with investigation news.

Legal will be looking at large sales from all time high to day before drop.

Regardless on what caused failure results, I would be watching the option chain and checking trading for at least a few minutes a day if I had a large position.

https://www.nasdaq.com/market-activity/stocks/freq

I wish to give no opinion on future.

 

[Lucifer]

I hope in the next trial they do just that. Give us 1 dose of FX-322 and see what happens; no following it with a placebo.

It was dumb in the first place to inject FX-322 first followed by placebo. I do hope positive results for Day 210 but I don't think it will be happening unless a miracle happens and all of a sudden they get word score improvements.

 

[Tezcatlipoca]

It was a 10% improvement over 90 days with one dose in Phase 1. Who would say no to that?

"What, only 10%??? I'd rather continue to have hearing loss than inject a subpar drug" - The people on this forum.

 

[Lucifer]

"What, only 10%??? I'd rather continue to have hearing loss than inject a subpar drug" - The people on this forum.

10% could mean a lot for even mild hearing loss sufferers. I do believe that multi-dosing works but it needs to be at least monthly for it to work.

I really wish they had just continued with the single dosing and then do another trial separately with multiple doses.

 

[Philip83]

"What, only 10%??? I'd rather continue to have hearing loss than inject a subpar drug" - The people on this forum.

Especially since it won't give me any juicy side effects either...

 

[Jurger]

"What, only 10%??? I'd rather continue to have hearing loss than inject a subpar drug" - The people on this forum.

10% improvement in WR scores only in 34% of patients. Nothing for the audiogram. It's true current treatments for hearing loss don't treat the condition at all, but FX-322 is not the game changer it was made out to be.

 

[r34d1ng]

"What, only 10%??? I'd rather continue to have hearing loss than inject a subpar drug" - The people on this forum.

Not only that, but who knows what other inner ear regeneration may FX-322 trigger. I will gladly take only a 10% hearing improvement if it improves a 100% my tinnitus.

 

[Zugzug]

Their hypothesis seems to be the lawn effect is from FX-322 overdosing the cochlea. There has been no post-mortem, so your guess is as good as mine.

I also can't quite understand how they looked at the averages for each cohort and established that they had both cheating and this dosage problem. The data would be too vague; unless they were able to unmask screening data from the accepted patients, and "back into" it.

I agree. I see the lawn effect as mostly unproven spin. If it does work in the severe hearing loss trial, my guess is that it only works on IHC. The idea of IHC first pass, OHC later passes is nice, but in all likelihood, the delivery is so bad that it never really advances beyond helping the most prioritized signaling pathways first (i.e. some IHC improvement).

If the severe trial fails, I won't have much faith at all in the drug before the next Phase 2. Maybe the technology will be bought and improved upon.

 

[Diesel]

@Zugzug, I was rethinking your comment yesterday where you were questioning why the 4x dose group still didn't look better, since that last dose should have been able to cause some growth. I think this is probably where, as usual, an analogy like "walking on the grass" falls short.

I suspect that by the 4th dose, the concentration of FX-322, or whatever byproducts may exist from the drug/body's reaction was so high in perilymph that the body may have limited the ability for PCA to take place. Total speculation, but perhaps since the chemical signaling from PCA has only been studied to be really effective in vitro, that living tissue has a "circuit breaker" type signal? I believe that McLean mentioned that in living mice they had observed that PCA was "self-limiting." Perhaps that "self-limiting" signal ramps up dramatically as the concentration of FX-322 flows through those progenitor cells.

Just theorizing here.

 

[FGG]

Well, companies make excuses all the time. The whole idea behind these trials is that it's a process that goes beyond company spin.

I think you and I have some sort of communication failure. You misread my points every single time (or I am not doing a good enough job articulating them).

Anyway, my point was that I really didn't understand why people on this thread were trying to shut down any analysis of the company's claims to try to assess if they have merit or not. I.e. is this an excuse or does the company have a point? That's what we are trying to figure out.

That's why I said the binary was do we believe the company and the Phase 1 responders or do we not?

 

[just1morething]

Not too proud to admit I have no clue if this is a reference to Breaking Bad or if you're serious...

I was joking about wannabe scientists from this forum. Nothing personal.

 

[FGG]

@Zugzug, I was rethinking your comment yesterday where you were questioning why the 4x dose group still didn't look better, since that last dose should have been able to cause some growth. I think this is probably where, as usual, an analogy like "walking on the grass" falls short.

I suspect that by the 4th dose, the concentration of FX-322, or whatever byproducts may exist from the drug/body's reaction was so high in perilymph that the body may have limited the ability for PCA to take place. Total speculation, but perhaps since the chemical signaling from PCA has only been studied to be really effective in vitro, that living tissue has a "circuit breaker" type signal? I believe that McLean mentioned that in living mice they had observed that PCA was "self-limiting." Perhaps that "self-limiting" signal ramps up dramatically as the concentration of FX-322 flows through those progenitor cells.

Just theorizing here.

I took it a different way. If, for instance, the problem was fluid overload then the problem is closer to a mild iatrogenic hydrops in which there would be residual inflammation in the "disturbed" area.

 

[Zugzug]

@Zugzug, I was rethinking your comment yesterday where you were questioning why the 4x dose group still didn't look better, since that last dose should have been able to cause some growth. I think this is probably where, as usual, an analogy like "walking on the grass" falls short.

I suspect that by the 4th dose, the concentration of FX-322, or whatever byproducts may exist from the drug/body's reaction was so high in perilymph that the body may have limited the ability for PCA to take place. Total speculation, but perhaps since the chemical signaling from PCA has only been studied to be really effective in vitro, that living tissue has a "circuit breaker" type signal? I believe that McLean mentioned that in living mice they had observed that PCA was "self-limiting." Perhaps that "self-limiting" signal ramps up dramatically as the concentration of FX-322 flows through those progenitor cells.

Just theorizing here.

My belief about this stuff is that the big picture is that there could be super responders that are super responders for reasons we don't totally understand. But most of the story is just a bad delivery mess.

Something I am extremely interested in, aside from group dominance, is if the severe arm again shows no super responders from the placebo group. All it takes is one placebo star to negatively change all of the theories.

I recall computing the probabilities from Phase 1/2 that all of the super responders happened to land in the treatment group by chance (i.e. assumed null hypothesis). It was actually pretty high. But if 2-3 studies have super responders in the treatment groups, but none in the placebo groups, I will at least believe in the future outlook of the drug. It still may not be good enough or pervasive enough to justify clearing Phase 2 repeat, but it's at least encouraging.

But if there's a placebo patient that goes from 50% to 80% or something, we have to look at these super responders very critically. Group dominance will be especially important, both for getting the drug through Phase 2 repeat and for a belief in the drug.