Frequency Therapeutics — FX-345

I'll just leave it at this quote and relate it to funding.

“I wouldn't be surprised if in 10 or 15 years, because of the resources being put into this space and the incredible science being done, we can get to the point where [reversing hearing loss] would be similar to Lasik surgery, where you're in and out in an hour or two and you can completely restore your vision,” Karp says. “I think we'll see the same thing for hearing loss.”​

You are misunderstanding my point of view. I want this company to succeed, but FX-322 is a bomb until proven otherwise. It really is. Stock price down 90% shows that in hard evidence no matter what the company says. The market does not see it as a sure thing from a commercial perspective. Quite the contrary.

This is going to take time and lots of money. Frequency Therapeutics is capitalised until end of 2023. Funding is a legitimate concern and if you can't see that then you need LASIK too.

Sorry guys, but there is a long way to go in this story. Efficacy and funding are not certain. That is beyond question and I can't continue to point the blatantly bloody obvious out repeatedly.

To answer your question regarding having a dose of FX-322, I am in no position based on the existing facts to make a decision on that, but based on Phase 2 results I would 100% not pay big money for a shot... I need to see a lot more regarding efficacy.

BUT:

FX-345, which if it does regenerate deep into the cochlea below 4,000 Hz, I would take the shot in a heartbeat and pay big money for it too.

Only time and clinical trial success will tell.

 

There was that figure out once that a treatment for hearing loss would have the potential to create a company with one of the world's highest market cap.

A million treatments a year at $10,000 each is not unrealistic.

 

It is going to be a massive market for sure if and when a treatment exists, which as of yet, it doesn't unfortunately.

"33% of subjects achieved 10% or greater absolute improvement in word recognition in treated ear."

Would I pay big money for a 1 in 3 chance of gaining a 10% improvement in word recognition scores?

Absolutely not.

Would you get LASIK if there was a 1 in 3 chance of gaining 10% better eyesight?

Nothing commercial here with FX-322.

Here is the 1 out of 3 ten percent improvement for those that didn't see it:



And point of note that this greater than 10% results were not maintained.

Here is a chart showing WR scores for the 5 best responders:



This is the last post I put on here now until there is news on FX-345. My opinions on FX-322 are quite clear and they are only my opinion. It does not do enough to warrant commercialisation. PCA tech needs to mature.

I really really hope FX-345 is a game changer. It needs to be.

Come on FX-345!

 

Ironic that you tell people to think objectively when you are the one that can't look past your own solipsism and think critically about it. Simply because you may not benefit from FX-322, you think it's useless to the world yet it has the potential to help millions of people worldwide. Fortunately, FDA approval doesn't hinge upon whether or not it improves your hearing loss alone.

A multitude of studies have proven that extended high frequency hearing is key for speech perception, especially in noise.

• The Importance of High-Frequency Audibility in the Speech and Language Development of Children With Hearing Loss
• Extended high-frequency hearing enhances speech perception in noise
• Extended high frequency hearing and speech perception implications in adults and children

Hearing regeneration has never been done before in the history and now that we are seeing the first early evidence of it, you refuse to accept it since it's not to the level you want. If the year was 1903, you'd probably be saying that the Wright Brothers' first glider flight was trash too since it only lasted 12 seconds. I've provided links but seeing that you refuse to follow the science I'm afraid it won't do much good as you yourself admit that you are only interested in something that completely restores your hearing back to normal; and for that reason, I don't see much point in engaging with you further.

Not only do you refuse to understand the science but you straight up lie about it.

33% saw 10% improvement OR GREATER. 10% is the bar for clinical significance, it does not mean patients only improved 10%. Many patients DOUBLED or nearly doubled their word scores which was likely life changing for them.

You're going on my ignore list and I recommend everyone else do the same.

 

Crazy, they went to an empty restaurant during the pandemic and they could hear their kids.

jk jk

 

I really don't understand how those ultra high frequencies, 12-16 kHz, supposedly play such an important role in word recognition and speech perception. I mean those are useful for other reasons (for example, to anyone relating to music and sound, like me), but in real life, human voices do not have something that meaningful up there.

So, I went and recorded a random female news reporter from the internet and took some screenshots (couldn't post a video here) in a spectrum visualiser. The red vertical lines are the individual frequencies at some consonants and vowels from words. The brighter red, the louder the volume.

Very little happens after 10 kHz and, when there are frequencies up to around 12-13 kHz, those were mostly the higher part of letters "S" or "K". Most stuff happens (as expected) up to 10 kHz. Personally, even when I cut those ultra high frequencies, I couldn't hear any difference at all (note I have been tested for high frequency audiometry and had no losses). Maybe just a tiny tiny bit darker S's, K's etc.

But anyway, anything FX-322 can offer is good.

 

The science in the space is still evolving so I'm afraid there isn't a 100% locked down explanation for why it may be but the science is pointing us in the direction that EHF is important for speech in noise.

I'd postulate (and this is just my opinion) that it has to do with the ultra high frequencies helping when similar and identical middle & lower frequency sounds are stacked on top of each other and its the slight nuances in extended high frequency between the different sounds that help people pick it out. People with EHF hearing loss or "hidden hearing loss" often complain about noises getting jumbled together in a loud room. David Grohl from Foo Fighters said this in a recent article:

"That being said, like, if you were sitting next to me right here at dinner, I wouldn't understand a f***ing word you were saying to me, the whole f***ing time," Grohl said. "There's no way. In a crowded restaurant, that's worse."​

If you want to take your experiment further, I'd recommend stacking different women's voices on top of each other, add some background noise, and then play with pulling frequencies up and down and seeing if you can pick out voices.

Also, look at the comments from that article I linked to, very telling and interesting all the people that suffer from hearing loss. Multiple commenters saying they also suffer from having trouble understanding speech in loud environments. Here are a couple of them :

"I know exactly what his frustrations are as I have experienced that for decades too. I hate going to parties and large gatherings because I can't hear what anyone is saying and so I disengage."

"Hearing aids help me quite a bit but I agree that with everyone wearing masks, I find it terribly hard to understand speech."

"I am not a musician, but I do have hearing loss. I can empathize with everything he said about being unable to understand people in loud environments or when someone is wearing a mask. It's really difficult."

 

The only challenge here is the source. Audio streams from the internet are often cut off and use compression to eliminate high frequencies in audio. I did something similar by recording audio with my Zoom recorder at a somewhat busy restaurant that had concrete floors and walls (lots of reverb), and found a lot of high frequency information that was the peaks of voices, silverware and just general noise from the kitchen. My recorder picks up to 16 kHz pretty well (H6).

 

Here's a quote from the Frequency Therapeutics front page:

"Millions are impacted by hearing loss. We're seeking to restore the clarity they've lost."

12 kHz and up plays a somewhat small part in sound and speech clarity, but it is a great start nonetheless. FX-345 has a lot more potential as a treatment, and the efficacy will be a lot easier to measure than FX-322.

 

A few things to consider. It seems feasible that the current clinical tests they are utilizing aren't capturing the subtle quality of life improvements that patients are seeing, hence why they invented RADIAL, a patient reported outcome measure and the good news is that they are using RADIAL during the current Phase 2 in hopes of having it validated before they move to pivotal. The FDA will also consider the data from RADIAL as well when it comes time for approval.

As for if it's just one giant placebo effect, that is a valid question. I personally don't believe it is when you look at the totality of all the data.

The first Phase 1/2 trial was placebo controlled and there was no significant response in the placebo group.

The 111, open label study did not have a placebo group but it did use the contralateral ear as a control and they saw no significant response in the opposing ear.

The 112, age related study had only 1 statistically significant responder in the treated group and no responder in the placebo group. If it were one giant placebo response, one would expect to see up to 33% of subjects in either the treated group or placebo group respond but that wasn't the case for either group.

The 113 Severe hearing loss trial had 4 statistically significant responders in the treated group and one responder in the placebo group. They were randomized 4:1 so this is the only actual trial I would have concern about it being a true placebo response BUT it has been said that the Bamford-Kowal-Bench Sentence-in-Noise exam they used for this result is not the best or most reliable of hearing tests; it's just a test they had to use since Severe hearing loss is so much harder to test with more standard audiologic exams. Plus add the fact that it was a tiny placebo group.

Lastly, we come to the 202, multi dose trial. Roughly 69 patients were dosed with FX-322 and 21 patients received placebo. Note that the placebo group was only 1/3 the size of the FX-322 group which compounded their problem. Of the 69 in the treated group, 30 patients saw a clinically significant response or 47% roughly. In the placebo group, 10 out of 21 saw an improvement or nearly 47%. They also used the untreated ear as a control. When the company reviewed all the data, they found a large response rate in the placebo group as well as a number of untreated ears in both groups. The fact that they have the untreated ear data tells them exactly who in both groups was "biased" and the company said that while they saw it in both groups, the bias was more prevalent in the placebo group. All it took was 10 people to ruin a nearly 90 person study.

So, say I'm wrong and we say that it is one giant placebo effect, it is a placebo effect that improves hearing to a degree that has never before been documented in history and that means the clinical historical literature collected over the last 75 years that states you should expect 2.5% of ears to improve to a level of clinical significance on their own is flat out wrong and needs to be re-written to account for approximately up to a 47% improvement rate. To me that seems much less likely than the explanation the company has given.

The company will have to issue shares to remain funded no matter what. The variable in it is a matter of when they decide to do it. If they get positive data back from FX-322 and FX-345, the share price should see some recovery and would then result in a much more acceptable amount of dilution.

 

Yea I'm lying when I post two charts with the precise information from Frequency Therapeutics' latest presentation for all to see. In both those charts it says exactly what you said. The information is in the two slides including the best responders from Phase 1B. It is all there for anyone here to digest. They also state that about 33/34% (one in three) had AT LEAST a clinically signifcant improvement of 10%. I posted that information so calling me a liar is downright insulting.

Get off your high horse and see how my argument is related to the funding concerns and lack of commercilisation prospects for any near term candidate from Frequency Therapeutics.

@Chad Lawton, people who ignore other opinions are practically acknowledging that they can't hande the truth.

Chad, the man who said a multi billion dollar takeover price is realistic for a company worth $75M. Zany stuff.

If you bothered to read any of my posts I have great faith in PCA tech and Bob Langer in particular.

BUT, even Karp says this will take 10-15 years to reach its potential in an article you posted.

You say I won't benefit from FX-322, when I posted my audiogram and anyone could see I am in the zone of what the company considers a target for FX-322.

We will see if FX-322 will make it to market. I bet you it won't. Canned after Phase 2 to concentrate resources on FX-345 is my bet, but a lot learned and progress made. FX-322 will not be a commercial product.

THAT DOES NOT MEAN THAT HEARING REGENERATION WILL NOT BE AND I HAVE REPEATEDLY SAID FX-345 HAS GREAT POTENTIAL.

Why continue with making a glider when you can make an aeroplane instead to use you analogy?

The likes of yourself and @Diesel need to see the wood from the trees.

We all want hearing regeneration, but it is going to take time and money. At present money is a concern for Frequency Therapeutics. That is a fact.

You both can make me eat my words in two years time if FX-322 is in the clinic being injected into ears.

BUT the thread needs balance.

There is a danger of hyping expectations again only to lead to disappointment.

Where are the mods when @Chad Lawton is calling someone a liar? Very insulting. There is zero lies in anything I posted. This is a discussion forum and I take great insult from being called a liar. Come on mods. Wakey wakey.

Some people can't handle balanced argument.

This post can be seen above with the highlighted part seen clearly in my original post. @Chad Lawton, I'm not putting you on ignore though because discussion is good and differing points of view are important for balance.

I'm done here until there is is news on the IND for FX-345 or any other significant news. I acknowledge I'm borderline spamming now.

 

I understand that FX-322's cochlea penetration is not as great as FX-345's, hitting only up to 8 kHz, but have any of you ever wondered what would happen if you at the time of the FX-322/FX-345 treatment stimulated the blood flow in the cochlea by multiple strategies, like exercise, massage of neck and tissues around it, some kind of heat stimulation, Niacin flush effect (this one works great with me), Betahistine, etc.

Betahistine taken alongside with Niacin literally floods my ears with blood (my personal experience).

Couldn't FX-322 (and FX-345) be much more effective and potent and penetrate deeper into cochlea with the above strategy?

 

@Padraigh Griffin, your words were uncalled for. You made a petty comment first. You’re turning into a real jerk when you could easily make more friends here. The reality is no one is against you or your drug of choice. It’s that you often totally disregard what others are saying. This has been coming for a long time due to your snide comments. Chad and Diesel have been doing their best to find ways to encourage others, to provide solid research, and to share their opinions. Somehow they've been respectful towards people like you and @Gb3 for who knows how long. Personalities like yours don’t usually stick around here. They insist others are wrong and they are right before they have no one left. I’ve known too many, and used to be friends with them too. I’m sick of it. Shame on you.

This isn’t to tear you apart because I’ve had my fair share of rants on here but you need to know that you’re only ostracizing yourself further from people you could be having constructive conversations with. Please don’t become like some of the previous members who used to believe in Frequency Therapeutics so much they tried preventing others from coping with their tinnitus. I’ve seen my fair share of breakdowns and suicide messages on Tinnitus Talk due to personalities similar to yours. Most of us aren’t scientist or doctors. A lot of us are just mentally unstable people right now who could benefit from stability instead of useless arguments.

Truthfully, no one knows your drug’s effect on tinnitus. If there are only a few testimonies of tinnitus improving after FX-322 or FX-345 that’s still a few more than yours.

 

Answer me this.

Please point out my 'petty comment' first?

Provide examples of 'snide comments'.

Would you take kindly to being called a liar?

Where am I providing lies?

Shame on me for what? For providing a contrarian opinion.

From my perspective it is I who have been the subject of derogatory comments. I will counter punch.

I've been suicidal many times with my condition, one of the most prevalent times was after March 2021, when my hopes for FX-322 were dashed. I had great hopes for the multi dose regimen and was telling everyone I knew about this amazing tech. However, I was crushed by the FX-322 Phase 2 results and have been cynical about the company since. Note that I am cynical about the company, not MIT, Langer or PCA in general.

I was suicidal for a period of time in early March this year with an escalation in my MEM. I will admit it. I am not superior in any way, and I am a weak person a lot of the time, and sometimes I just wish I was dead as my tinnitus is so bad. So I understand completely about hope. If you see all the other threads I am very optimistic about nearer term prospects for tinnitus treatments such as Ebselen, Auricle, Otonomy, Xenon, even Neuralink. I am one of the few posters keeping these threads updated.

BUT there is a lot of blind faith in this PCA tech. Diesel and Chad Lawton have complete blind faith in the tech. This is not balanced and any contrarian opinion it appears they can't handle. There is a long way to go before PCA is proven and commercialised as a treatment for hearing restoration at a level where we will see significant benefit. There is absolutely no solid EVIDENCE that it will improve tinnitus yet, but hopefully it will.

It is far more dangerous to build hype and then the subsequent meltdown can throw people over the edge.

I plan to stick around Tinnitus Talk, but I won't if it is going to be a 'la la land' only DISCUSSION forum.

Plus, I don't give a shit about being liked. I'm just stating the clear and obvious facts. FACTS only and yes I read everyone's opinion on the tech, but to honest we can talk until the cows come home (an Irish expression).

My father was from an Irish town called Killorglin and interestingly Astellas have a manufacturing plant there. It is about 1 hour drive from where I am. Next time I visit I might call in and see if they are ramping up for FX-322 production.

BTW, I was a teacher prior to this disability in a school of over 100 teachers. I never once fell out with any teacher or the 1000s of kids I taught for 20 years. Not once. I've moderated discussions for a living within my classroom for two decades and let it get heated, because that is how things are thrashed out, but never ever let it linger. My students enjoyed the heated debate and every time we discussed something we pointed out the different perspectives. Also, I was a teacher of business and have a degree in marketing. I've studied enough companies in my time to see there is a long long uncertain road to commercialisation here.

This time next year Frequency Therapeutics will have six months of cash left and needs two clinical trials to go their (and our) way between now and then. If still sitting at a market cap of c. $75M they and expenses of c. $90M per year they will have trouble raising funds as investors (existing and new) will only accept a private placing at a significant discount to the then share price.

Shame on you for slating me and calling me a jerk, but hey that is your opinion. I think you are a jerk too for judging someone else.

Anyway. I'm not posting here anymore until we have more solid information. I will post only to respond to existing posts. I've stated my opinion and have received nothing but abuse back.

Here is Astellas manufacturing facility near me. Hopefully in 3 or 4 years time FX-345 will be in production here or at a similar facility. Fingers crossed.

 

If I may just throw out a suggestion for this thread and in life in general, try to be kind to yourself and to others. We are in a rough situation of having an incurable condition akin to endless pain. Give yourself a break, give others a break; they are in just as much impossible pain as you are none of us are our best selves, we all inflame sometimes when we should soothe. We are all imperfect broken beings. Be as kind as you are able.

 

To be honest, I believe that's what losses in between the tested in audiometry frequencies are causing. There is a huge field of hair cells between, for example, 4 kHz to 8 kHz that an audiogram never tests, and since voices jump all around all the time, it's easy to lose stuff at many places if a lot of environmental noise is happening. So, in that way, that is still "hidden hearing loss", but not necessarily that far up the spectrum, to 16 kHz.

As for the stacking up of multiple voices and sounds in general, it gets quite chaotic and too random to test. I mean that even a 100% healthy ear would have trouble picking up all words, if stuff gets on top of each other. One will surely lose words, let alone if you add a source of noise too. That's also why "mixing" in music and sound design, is probably the hardest one to master (even harder than composing itself).

There are a lot of variables at play and each voice, type of noise, type of situation is very individual and random. That's why I don't trust speech perception and such tests. There are also mechanisms that we don't understand yet, so as I always said, we need better screening and diagnostic tests of the inner ear.

 

Yeah true, the recording and playback devices play a huge role in all this. There is a lot of high frequency stuff, but usually not from voices. Ultra high frequencies are also very short-lived waves and don't travel that far out.

I recorded that sample from the BBC News site directly into FL Studio's recording plugin and then listened with JBL studio monitors. There is an obvious abrupt cut at like 15.820 Hz where compression happens. Before that frequency, stuff may or may not have a downwards volume slope, but there is movement, so I take it there are audible frequencies for me to hear at normal listening levels. Not willing to blast myself to find out more lol.

 

FREQ has a nice little simulator on their website somewhat demonstrating this:

https://www.frequencytx.com/speech-perception/

 

It could be a double edge sword. Does creating more blood flow in the cochlea help circulate the molecules better or would it clear the compounds out of the ear faster so they have less time to act? The theory behind NSAIDs causing hearing loss is due to vasoconstriction and the ear is unable to clear out oxidants as quickly and they have more time to cause damage so if you increase blood flow, you'd expect your ear to clear out the compounds quicker.

 

I just saw that! Yeah, an accurate animation, although very generalised and simplified as one would expect, so people masses can understand these meanings of course!

However, at the part where they simulated what impaired hearing sounds like, they cut all frequencies above 3-4 kHz though, which isn't just the ultra high frequencies, but a seriously impaired hearing.

It was a part of demonstration of course, but I don't believe FX-322 would regenerate that much, not even FX-345... However, I really hope they do great in these upcoming trials to finally combat hearing loss and other ear diseases, I really do, as hearing is my passion being a music producer.

It's just that they take so freaking long. It's easy for people to stop believing when the trials' results are not that great and they need to wait years before another trial ends.

 

Yeah, you are right about this, but I would definitely try it to see if it is a better or worse approach.

 

@Gb3, weren't you recently called out for bullying @Lucifer? You stopped posting on the Frequency Therapeutics thread for a minute because of it.

@Padraigh Griffin, I don’t think I got to finish editing my post from last night. The revised version wasn’t as harsh and I tried to see a bit more of your side. Honestly, I wasn’t in the right headspace at all and I apologize for that. In the moment I was really upset at the thought of more arguing. It was rude of me to call you a jerk. I’m sorry for calling you a name.

That being said, you do mirror certain personalities that have come and gone in ways I’m not sure you understand. That’s not necessarily a bad thing. You aren’t a bully but you sound hypocritical nearly every time you promote your drug (I don’t think you’re wrong but it’s weird). I’m not sure if Chad Lawton and Diesel have ever said Frequency Therapeutics will cure tinnitus. They’ve noted people’s experiences and other advancements but I doubt they’ve promoted FX-322/345 as some kind of perfect tinnitus treatment. They seem to be happy hearing about any advancement in the hearing community. Somehow sharing any information sends you on a long winded rant that usually ends with you promoting a drug that hasn’t been proven to help anyone here.

If what happened was honestly an actual measurement error, then why are you so upset? Why do you feel like you should be the person to keep some threads balanced? What if people dismissed every advancement you mentioned in XENON Pharmaceuticals by stating what happened to past members? Nearly every single time? Wouldn’t that disrupt your ability to have a constructive conversation about the research you’ve been conducting for months/years?

 

Katri... no hard feelings. I think if you honestly have a thorough read of my posts I am just concerned that FX-322 will not do enough to make it commercially. That is my opinion and it is not popular with some posters/believers on here who became aggressive to me first before I responded. I should learn to turn the other cheek sometimes but I have always had a character who punches back. I think I made a solid argument but got ridiculed by Chad Lawton and Diesel. Chad in particular called me a liar, which is a terrible insult and if you read my posts you will see zero lies. I can guarantee you that. What you see is what you get here. Just read where Chad referred to my apparent lie. You will see he was badly wrong. I posted two factual charts from Frequency Therapeutics' presentation where the information he specifically referred to that I apparently lied about is clear for everyone to see. In visual form no less.

Time will tell who is correct re: FX-322. I think a commercially available treatment for hearing loss from Frequency Therapeutics is at least 5 years away, but again that is only my opinion. It will be based on FX-345 imho too. That is $500M in cash away and I'd love to see where they will get it. Remember a lot of Biotechs fail (75-90% fail) despite having great intentions. If only we capitalised them instead of spending money on military expenditure and wars etc. the world would be a better place.

Again, I'm over and out from here, but tread carefully with your hopes. That is my last comment on Frequency Therapeutics until more solid news or unless someone replies to an existing post here.

Heated debate is good for balance. Pity it escalates.

In relation to Xenon Pharmaceuticals I just believe that it has a commercial product on its hands that will be available soon, but it might not work for tinnitus just like FX-345. The evidence is stronger that it will but again that is just in my opinion. I posted some detailed stuff on side effects today from Phase 2 if you want to have a look and hopefully it mitigates your concerns re: some of the past members' nightmare experiences. It really seems a mild drug, compared to placebo and certainly compared to its predecessor Trobalt. Xenon also has c. $500M in cash and funding is not a concern over there plus the share price is performing excellently. It contrasts massively with the unfortunate situation Frequency Therapeutics are in. Again in my opinion and from comprehensive research on the 'hyperexcitability' theory I believe Xenon Pharmaceuticals will treat a lot of tinnitus. Dr. Susan Shore's trial results will give us some information as she too is treating hyperexcitable fusiforms in the DCN. I believe in Xenon Pharmaceuticals getting XEN1101 to commercialisation and the stock market seems to agree.

Anyway, it's all just my two cents. You seem like a nice person and I apologise for counter punching you and calling you a jerk too. Actually in my part of Ireland we never use that word but replace it with the word 'langer'. Let us hope that Bob doesn't turn out to live up to his County Cork, Irish name.

Over and out. Keep the hopes alive. I'm a huge Rafa Nadal fan so I will end on the line 'Vamos FX-345!'

 

I never believed you were wrong for that. I didn’t have an issue with your response or most of the things you say actually. I was highly emotional when I typed my response so I’ll admit I didn’t properly read what you had to say. I’d like to stress how sorry I am for jumping to conclusions. It was a huge mistake on my part and I don’t mean that lightly. Thank you for contributing to these discussions.

 

Not a bother Katri. Hopefully all us tinnitus (and hearing loss) sufferers will have lots of good news soon. Most days I am sure of it, but like all of us it is hard to keep the faith all the time. I'm actually rooting for Frequency Therapeutics of course. My audiogram is there for all to see and with that of slope I know I'm missing lots in the ultra high frequencies. I can hear nothing at 12,000 Hz for example. Absolutely zilch. I'd love a treatment but there are lots and lots of hurdles to jump and a lot of time to wait yet. Some people don't like to be reminded of that and I know when I'm put on ignore list it's because they can't handle the critical view and like to insulate themselves and their hope from the opposing viewpoint. That is human nature. As you say yourself I have a bit of 'blind faith' in XEN1101 myself. FX-345 was a pleasant surprise after FX-322 disappointment but I'm not doing 'blind faith' again in Frequency Therapeutics after last year's crippling news. No harm pointing that out. We all get emotional on here sometimes. It comes with the condition. I sincerely hope your tinnitus experience is not that bad. Take care.

 

@katri, I’ve been distant from Frequency Therapeutics threads because it does not show any benefit for tinnitus. Prior to the failed Phase 2b FX-322 trial they stated there was anecdotal evidence of tinnitus improvement which they have not mentioned since. Which they did collect data for in Phase 2b.

 

Well, since I'm being told about Padraigh's responses to my posts through other social media, it's too hard for me to stay silent. I did actually click the ignore button on him and now see no way to undo it so in order to read his posts I have to view this thread not logged into Tinnitus Talk (which is probably for the best lol).

So I will address you directly Padraigh and I stand by what I said.

Firstly, you said, and I quote "Nothing commercial here with FX-322." You are not attempting to make that as a statement of opinion, you're stating that as if it is a statement of fact which makes it a lie. You are more than free to say "I don't think there is anything commercial here with FX-322" but that is not what you said.

Here are a couple of direct quotes from David Lucchino, CEO, in regards to FX-322 that have been made in the last 3 months:

"We believe that we have a drug candidate for hearing restoration in FX 322 with clear patient response."

"These factors support our belief that we have a very promising candidate to be the first approved therapeutic for hearing restoration."

"We believe these data inform a clear path to developing the first therapeutics to restore hearing."​

Carl LeBel, Chief Development Officer, also recently said:

"I think that, we've got a high likelihood of success here as we keep advancing the program through development."​

Kevin Franck, Senior Vice President and former had of Audiology at Mass Eye and Ear/Harvard Medical School said:

"To me, these early data from small exploratory trials are very encouraging. Each of our responders would have experienced a life-altering improvement and we’re beginning to recognize characteristics about them. We’ve pushed these subjects up on the graph, something no one’s been able to do before. As a clinician, I wouldn’t hesitate to recommend a drug like this."​

All of these statements from upper management combined with the clinical trial data we've seen so far that show clinically and statistically significant improvements in speech perception indicate that there is still a chance for commercial potential for FX-322 so for you to make the statement "Nothing commercial here with FX-322.", that is a lie.

Secondly, you made the statement "And point of note that this greater than 10% results were not maintained." All you have to do is look at the Phase 1/2 data bar chart you provided to prove that is a lie. On the bar chart, subjects 1 through 4 all maintained at a minimum a 10% improvement when they were tested 1 to 2 years later. Subject 5 is the only one that lost their improvement. The 10% clinically significant bar they use is based on an absolute score on a 50 word Maryland CNC Word Recognition test so if the subjects remain 5 words above their original score at the 1 to 2 year mark, they maintained their 10% clinically significant improvement. What I assume you meant to say was that some responders across the studies have lost their statistically significant improvements at a confidence interval of 95% which is calculated using the Thornton and Raffin statistical model and is an additional statistical rigor that the company uses on top of the clinically significant improvements they see. It is possible for patients to retain their clinically significant improvements while losing their statistically significant improvements and many have.

So if you willingly made the statement "And point of note that this greater than 10% results were not maintained." and you didn't know the difference between clinical significance and statistical significance, it shows you're ignorant about the company's trials and their methods for data analysis & presentation. If you did know the difference and still made that statement, then you are lying.

I haven't ignored you because I want to insulate myself from contrarian view points, I'm more than happy to engage with those who disagree with me. But it seems like a giant waste of time to try and engage with you when you refuse to accept the basic facts. I can link to you all the data, all the charts, all the studies, but it won't do any good. You ever see the movie Don't Look Up? Arguing with you feels like I'm talking to the Don't Look Uppers in that movie that refused to accept that a meteor is hurdling toward earth.

 

Do you think FX-345 can help with hypercacusis? Could it be just the brain on high drive from hearing loss in higher frequencies...

 

Maybe. While the outer hair cells of the cochlea are typically known for amplifying sound, I've read before that they also could be responsible for suppressing sound so if you can restore healthy outer hair cells, it could help.

As an anecdotal experience, this seems true for me. The super loud percussion fireworks on the 4th of July use to never bother me when they went off at random throughout the day but after I acquired my hearing loss, I now have a jump/startle reflex to them if one goes off near by and I don't know about it in advance.

 

If the theory that Type II nerve fibers send out pain signals because the outer hair cells they're connected to are damaged, then restoring those hair cells might help. But for now we can only speculate.