Frequency Therapeutics — Hearing Loss Regeneration

[Street Novelist]

Details are in:

Local Drug Delivery to the Entire Cochlea without Breaching Its Boundaries

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

 

[Chinmoku]

I don't suspect straight insider trading, with the reputational risk the top guys face and with their record so far it is quite unlikely.

What I fear more is that someone inside FREQ and knowledgeable of the results informed some big investors of the bad results in advance. I have not analyzed the order flow or anything, but if there has been any irregular behaviour I'd go more with that.

Having said that, I care mostly about the research going on and the treatment becoming effective, so I really hope there have been no irregularities or, if there have been, I hope the perpetrators can be isolated without excessively damaging the company.

 

[MrCrybaby]

I'm surprised this thread is as busy as it is with the science being lackluster. I love the idea but I mean let it go guys. This one's not it. They have to go back to the drawing board.

There are others out there fighting for the cure too. Hough Ear Institute told me things are going really well with their proof of concept and are making progress on that front.

That's good to hear. I had been wondering how Hough Ear Institute was doing with their pill.

I have a number of non-tinnitus symptoms that I think will require multiple different approaches to resolve, so FX-322 will remain on my radar until either a) it works or b) they figure out why it doesn't.

 

[Zugzug]

I'm surprised this thread is as busy as it is with the science being lackluster. I love the idea but I mean let it go guys. This one's not it. They have to go back to the drawing board.

There are others out there fighting for the cure too. Hough Ear Institute told me things are going really well with their proof of concept and are making progress on that front.

Why isn't it possible to hold multiple beliefs?

I can always spot the people who don't do science because they think failure is always an indication that it's all a hoax. Here's an exercise: Go back and listen to the Tinnitus Talk Podcast with Professor Tzounopoulos -- read the transcript if you can't.

He is often dismayed and humbled by the sheer number of failures. He said that at least 90% of his experiments were failures (and honestly, it's probably a lot higher). He will also have many more failures in the future. This is what science is. It's 99% failures, and finally, a breakthrough.

But by saying this, people are going to think that I'm like some loon in denial, too emotionally weak to accept reality. Why can't I believe both? Why can't I say that Phase 2a failed, there's a ton of uncertainty as to why, but also the years of scientific discoveries are not all a hoax? Is that possible?

At least the optimistic people put themselves out there, on display, capable of looking embarrassed. The blind pessimists just give this ignorant, snobbish vibe that's pretty annoying.

If you're going to comment on something negative, say something of substance please.

 

[Rb86]

Why isn't it possible to hold multiple beliefs?

I can always spot the people who don't do science because they think failure is always an indication that it's all a hoax. Here's an exercise: Go back and listen to the Tinnitus Talk Podcast with Professor Tzounopoulos -- read the transcript if you can't.

He is often dismayed and humbled by the sheer number of failures. He said that at least 90% of his experiments were failures (and honestly, it's probably a lot higher). He will also have many more failures in the future. This is what science is. It's 99% failures, and finally, a breakthrough.

But by saying this, people are going to think that I'm like some loon in denial, too emotionally weak to accept reality. Why can't I believe both? Why can't I say that Phase 2a failed, there's a ton of uncertainty as to why, but also the years of scientific discoveries are not all a hoax? Is that possible?

At least the optimistic people put themselves out there, on display, capable of looking embarrassed. The blind pessimists just give this ignorant, snobbish vibe that's pretty annoying.

If you're going to comment on something negative, say something of substance please.

I never called it a hoax. I'm just wondering why, on multiple threads, people are still talking about FX-322 like it's still the one.

I suffer with this terribly and was really bummed when I got the news, but this thread keeps going and going and I come back like I've missed something. I haven't. It's back to the drawing board.

 

[Zugzug]

I never called it a hoax. I'm just wondering why, on multiple threads, people are still talking about FX-322 like it's still the one.

I suffer with this terribly and was really bummed when I got the news, but this thread keeps going and going and I come back like I've missed something. I haven't. It's back to the drawing board.

You're right, you never called it a hoax. I don't want to misrepresent your viewpoints.

I guess I saw your remarks about "giving it up" as kind of an overreaction. Like yeah, go to the drawing board and be prepared for all of the theories to be wrong. No question, FX-322 could fail outright, but my main point is that there are many aspects of it that are not speculative. It does cure mice, it does work on human cochlea ex vivo, it uses a highly novel PCA approach, it does make it's way into the perilymph (at least in the high frequencies).

There are lots of unknowns as to what's going on in a live human. Does the body prioritize inner hair cells? Does it only work on inner hair cells? Does it hardly work at all in live humans and the 3 super responders from Phase 1/2 were Harvard educated savants that studied the test and aced it the second time?

There is so much to unpack. I understand that the wounds are fresh so people have their guards up. One of the reasons why I've made my timeline 10-20 years is to manage expectations. I do think, though, if I had to bet on one drug to succeed first, it would still be FX-322 just based on probabilities. It's the furthest along and at least has something of interest from Phase 1/2. Who knows though, maybe the delivery is so terrible that this formulation is just a flop? Definitely possible.

I can confidently say this. No offense to HEI, as I'm rooting for them too, but it's a little "grass is greener" to think they have a better chance of succeeding than Frequency Therapeutics. The operative word is "better," not "for sure."

 

[FGG]

I never called it a hoax. I'm just wondering why, on multiple threads, people are still talking about FX-322 like it's still the one.

I suffer with this terribly and was really bummed when I got the news, but this thread keeps going and going and I come back like I've missed something. I haven't. It's back to the drawing board.

I see your point a bit on this.

Even as someone who thinks the Phase 1 data was not a hoax and finds Frequency Therapeutics' explanation for why Phase 2a failed completely plausible (along with my own thoughts about IHCs vs OHCs, similar to Dr. Cliff's statements on the issue), this is a significant delay and we have to recognize that.

I don't see a repeat trial as being a "back to the drawing board" extreme but I don't think people should only have this on their radar because I think a two year delay is almost a given at this point even if the severe arm goes as well as the other Phase 1s.

I saw a comment on the Susan Shore thread basically saying "who cares what this device does as long as we have FX-322" or similar and I had a similar reaction to you.

I think the problem is people over simplify everything to do with this problem. Everything from the causes of tinnitus to the solutions. Then you have a situation where people proclaim the drug will even help non hair cell related problems, which clearly was never the case. But also on the other extreme people who say the drug is irrelevant if it can't fix every type.

Different drugs and devices may treat different people. This drug was never going to treat somatic causes, for instance (where the Shore device might).

I think there is a lot of evidence this drug will help tinnitus (and maybe loudness hyperacusis) related to IHC loss. I think there is also evidence that we don't yet know what it can do for OHCs because it's clear the drug is more dramatic for IHCs but that doesn't mean longer interval repeat dosing can't improve outcomes. (Also, @Diesel recently posted an interesting rat study on a selective loss of only one of the 3 OHC layers accounting for only 5-10 dB of hearing loss so that's pretty interesting as well).

All that to say, there is no harm in taking Frequency Therapeutics' claims and trying to see if they might have merit and analyzing if there are studies that could explain these results. Regardless, we of course still have to wait for the Phase 1b results. But if people want to dismiss every other avenue just because Frequency Therapeutics are continuing with their drug, I agree that's counterproductive too.

 

[RB2014]

You're right, you never called it a hoax. I don't want to misrepresent your viewpoints.

I guess I saw your remarks about "giving it up" as kind of an overreaction. Like yeah, go to the drawing board and be prepared for all of the theories to be wrong. No question, FX-322 could fail outright, but my main point is that there are many aspects of it that are not speculative. It does cure mice, it does work on human cochlea ex vivo, it uses a highly novel PCA approach, it does make it's way into the perilymph (at least in the high frequencies).

There are lots of unknowns as to what's going on in a live human. Does the body prioritize inner hair cells? Does it only work on inner hair cells? Does it hardly work at all in live humans and the 3 super responders from Phase 1/2 were Harvard educated savants that studied the test and aced it the second time?

There is so much to unpack. I understand that the wounds are fresh so people have their guards up. One of the reasons why I've made my timeline 10-20 years is to manage expectations. I do think, though, if I had to bet on one drug to succeed first, it would still be FX-322 just based on probabilities. It's the furthest along and at least has something of interest from Phase 1/2. Who knows though, maybe the delivery is so terrible that this formulation is just a flop? Definitely possible.

I can confidently say this. No offense to HEI, as I'm rooting for them too, but it's a little "grass is greener" to think they have a better chance of succeeding than Frequency Therapeutics. The operative word is "better," not "for sure."

You nailed it!!! The whole post!!!

 

[Zugzug]

You nailed it!!! The whole post!!!

I guess I'm just trying to help people to understand what scientists go through. I'm a research (some present, mostly in the past) mathematician, which is in just one type of science that's far different from lab experiments, but what's kind of funny is if you ever talk to someone who's knee deep in scientific research, they are often like weirdly unconfident. It's because of all of the failures. They fail so often that the humility is not an act to fit in or something. They genuinely feel stupid because their work provides so little short-term reward.

At one point in grad school, my work life was completely bipolar. I would do research and feel like the dumbest person in the world and then I would go teach to people who were actually average at math. It was always a reminder to me that my confidence was shaken from the high degree of difficulty -- both emotionally and intellectually -- which is failing daily for years. Many times, I pursued an idea for months only to abandon it. When this happens over and over again, it's incredibly humbling.

I will admit that I got too high on the 3 super responders in the sense that they would automatically predict huge groupwide results. But really, in hindsight, this is a standard scientific failure. I intend to have a much higher standard for "proof" in the future. Even if the remaining Phase 1b trials are successful, I will manage my expectations for the next one.

 

[GlennS]

this thread keeps going and going and I come back like I've missed something.

Long unbroken conversations between sufferers about hyped up treatments is part of the day to day coping mechanism.

 

[Lucifer]

[QUOTE="Zugzug, post: 590141, member: 37898" Even if the remaining Phase 1b trials are successful, I will manage my expectations for the next one.[/QUOTE]
Even if the severe hearing loss trial shows positive outcomes?

 

[Zugzug]

Even if the severe hearing loss trial shows positive outcomes?

Well, I think the scary part is that they burned their mulligan. What are the three main things we are talking about? Trial design (word score reliability), lawn/perilymph overflow theory, and IHC vs OHC preference. None of these three things were at the forefront of the discussion pre-results. There was definitely more of an interest in the obscene doubling of word scores than the subpar PTA improvements, but the PTA results didn't fall flat on their face like they did in Phase 2a.

Something will pop up that's unexpected, and by definition of unexpected, we don't know what it is. I would consider a strong result from the severe trial to be a victory for the future. Even if FX-322 fails, maybe their technology will be built upon. It's a win.

I believe people should be prepared to cope and lean on other things. This story isn't going to end with a miracle drug making our conditions go away. It will be one drug having a breakthrough and improving our lives by 10-20%. Then we are better rested for the next breakthrough that improves it by another 10-20%. Maybe there's a threshold where life is worth it. It never crosses my mind that my life will just go back to normal at some point. I will die with hearing problems, no question.

 

[Lucifer]

Well, I think the scary part is that they burned their mulligan. What are the three main things we are talking about? Trial design (word score reliability), lawn/perilymph overflow theory, and IHC vs OHC preference. None of these three things were at the forefront of the discussion pre-results. There was definitely more of an interest in the obscene doubling of word scores than the subpar PTA improvements, but the PTA results didn't fall flat on their face like they did in Phase 2a.

Something will pop up that's unexpected, and by definition of unexpected, we don't know what it is. I would consider a strong result from the severe trial to be a victory for the future. Even if FX-322 fails, maybe their technology will be built upon. It's a win.

I believe people should be prepared to cope and lean on other things. This story isn't going to end with a miracle drug making our conditions go away. It will be one drug having a breakthrough and improving our lives by 10-20%. Then we are better rested for the next breakthrough that improves it by another 10-20%. Maybe there's a threshold where life is worth it. It never crosses my mind that my life will just go back to normal at some point. I will die with hearing problems, no question.

I've just been thinking about the severe hearing loss sufferers, if they don't restore the low frequencies, but restore high-mid frequencies, would that make much difference to a severe hearing loss sufferer? Would that make them hear more high-mid frequencies e.g., birds?

 

[Zugzug]

I've just been thinking about the severe hearing loss sufferers, if they don't restore the low frequencies, but restore high-mid frequencies, would that make much difference to a severe hearing loss sufferer? Would that make them hear more high-mid frequencies e.g., birds?

I guess we'll have to see. The good thing is that strong results presumably mean almost undeniable word score improvements over placebo. I wouldn't know, but I have to imagine if you go from making out 50% of words at a comfortable level in conversation to 80%, that's probably a lot.

There's also an exponential improvement aspect to quality of life. For example, if you miss words here or there, the brain can fill them in. But if you miss 50% of words, it's a much more dramatic difference in understanding the gist of a movie, TV show, conversation, etc. At least, this is what I would think.

Really strong results would also be a good thing because it provides more data than just n=30 more people. It would help them design Phase 2 much better. That's my hope anyways, that a solid severe trial leads to a more straightforward recruiting process for the next Phase 2.

 

[Lucifer]

I guess we'll have to see. The good thing is that strong results presumably mean almost undeniable word score improvements over placebo. I wouldn't know, but I have to imagine if you go from making out 50% of words at a comfortable level in conversation to 80%, that's probably a lot.

There's also an exponential improvement aspect to quality of life. For example, if you miss words here or there, the brain can fill them in. But if you miss 50% of words, it's a much more dramatic difference in understanding the gist of a movie, TV show, conversation, etc. At least, this is what I would think.

Really strong results would also be a good thing because it provides more data than just n=30 more people. It would help them design Phase 2 much better. That's my hope anyways, that a solid severe trial leads to a more straightforward recruiting process for the next Phase 2.

That's what I'm hoping for. At least if they get good results for the severe hearing loss trial, then we know that FX-322 is the real deal and the other Phase 1b trials weren't a fluke.

 

[kiki]

I agree. It's still too early to know how everything works with these new regeneration drugs but I think Frequency Therapeutics are honest people though. I don't think they will lie about a drug that can help with hearing loss and tinnitus. Some of the anecdotes got tinnitus improvements from FX-322.

I'm not expecting the Day 210 to be positive unless somehow many of the patients had experienced more improvements after Day 90 due to weekly dosing of FX-322 killing the process and needing to wait even longer for the regrowing process.

I also don't expect positive Day 210 results.

But for the Day 210 results, I really want to see the individual details.

In addition, if possible, first of all, I would like to see a validation comparing only the single injection group of FX-322 with placebo, except for patients who appear to have cheated.

Then, I would like to see a comparative verification between the single injection group and the multiple injection group.

 

[Lucifer]

I also don't expect positive Day 210 results.

But for the Day 210 results, I really want to see the individual details.

In addition, if possible, first of all, I would like to see a validation comparing only the single injection group of FX-322 with placebo, except for patients who appear to have cheated.

Then, I would like to see a comparative verification between the single injection group and the multiple injection group.

I would be very interested in that information as well. I would have preferred they inject placebo first, then FX-322 as the placebo may be washing out the FX-322.

I'm hoping that those who only got one or two doses of FX-322 to show more improvement than those who got 3 or 4 doses of FX-322.

It will be a long shot that there will be positive results for Day 210 but if there is some proof that lesser doses show more improvement then they could potentially move on to the pivotal phase.

 

[Jrblovsky]

I've just been thinking about the severe hearing loss sufferers, if they don't restore the low frequencies, but restore high-mid frequencies, would that make much difference to a severe hearing loss sufferer? Would that make them hear more high-mid frequencies e.g., birds?

I have both and men are much easier to hear than women and children. I would much rather have my high frequencies repaired. Too bad FX-322 didn't work.

 

[RingingBrother]

I'm surprised this thread is as busy as it is with the science being lackluster. I love the idea but I mean let it go guys. This one's not it. They have to go back to the drawing board.

There are others out there fighting for the cure too. Hough Ear Institute told me things are going really well with their proof of concept and are making progress on that front.

The problem was multiple doses. A single dose would show improvement. FX-322 still works.

 

[Lucifer]

I have both and men are much easier to hear than women and children. I would much rather have my high frequencies repaired. Too bad FX-322 didn't work.

Thanks for that information, maybe FX-322 will make a difference for severe hearing loss sufferers.

 

[RingingBrother]

I noticed FREQ gained 10% just now. This all feels like just a temporary setback to me.

 

[chinup]

Our best bet might be an infamous group of scientists developing an IT tinnitus formula. They are rumored to be operating out of a RV someplace in the Nevada desert. Also, buy some FREQ stock as it is very cheap right now.

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

 

[Lucifer]

The problem was multiple doses. A single dose would show improvement. FX-322 still works.

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.

 

[Jrblovsky]

Thanks for that information, maybe FX-322 will make a difference for severe hearing loss sufferers.

I think that is a pipe dream. The compound doesn't work, the trial just confirmed that. Back to formula.

 

[Lucifer]

I noticed FREQ gained 10% just now. This all feels like just a temporary setback to me.

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.

 

[Rb86]

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.

 

[Lucifer]

I think that is a pipe dream. The compound doesn't work, the trial just confirmed that. Back to formula.

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.

 

[Tezcatlipoca]

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.

To be fair, we don't know if the next results will be positive. I believe in FX-322 but I think we need to lower our expectations.

 

[Lucifer]

To be fair, we don't know if the next results will be positive. I believe in FX-322 but I think we need to lower our expectations.

Good point, but if I see positive outcomes for the severe hearing loss trial, I'll be back on team bull.

 

[Diesel]

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.

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.