Frequency Therapeutics — Hearing Loss Regeneration

[koffee_monster]

@Nobody19, @Diesel, @Padraigh Griffin (in no particular order),

It was not my intention to start a personal discussion here. I was inquiring if perhaps @Padraigh Griffin had certain information giving him a negative outlook on the FX-XYZ trials that I was unaware of.

I also pointed out some glaring issues with Potassium regulators and Trobalt in particular as a continuous treatment.

@Padraigh Griffin replied with the valid argument that my sources were pointing to Trobalt and not really Potassium regulators in general and that the FX-XYZ lineup has indeed been somewhat less performant than some of us would have expected at this point (I don't have an opinion on this, I try to look at research in the most objective way I can).

Some issues of Trobalt will most likely be part of the XEN side-effects too, but hopefully, it will indeed be to a lesser degree.

Both approaches still seem very valid to me and I do not at all have the feeling that one approach should cancel out the other. They can perfectly coexist and may even amplify each other's effect on tinnitus.

Tinnitus research is fragile as-is, let's not create in-fighting in the people that actively try to follow the research space.

Let us not break down other people's hopes and ideas about upcoming treatments as for many (including me) the built-up expectations for treatments is what makes having tinnitus a lot more bearable.

Even if those expectations aren't always correct or justified, they help people cope, push through and research the matter further. There's no point in attacking those expectations only for the sake of attacking them. If a person would be in danger because of misinformation that's another story.

I hope this conversation can continue in a polite fashion and that we can focus on the objective research part of this thread.

 

[SmallRonnie]

Long story short, to date FX-322 has shown consistent improvements in speech perception in early clinical trials but FREQ had a hang up in their last trial in that there was an unprecedented placebo response in the trial and they were unable to make an accurate assessment of improvements in the FX-322 group (there were improvements) because they didn't have an accurate baseline to compare to so they had to throw the baby out with the bathwater and say that FX-322 showed no benefit over placebo which is true BUT that's because nearly 50% of both groups saw improvement.

The company's explanation for the placebo response is that they made the mistake of telling patients entry criteria to get into the trial and they didn't anticipate subjects lying on their hearing exams to make it look like they had worse hearing than they actually did to get into the trial. They are currently running a new Phase 2 trial with results expected around the end of the year.

So either FX-322 works and it was a poorly designed trial that allowed placebo responders, or placebo injections consistently improve hearing to a degree never before documented in history.

This does sound really hopeful but again who knows what else may go wrong with it.

It will still take at least a couple more years before it's available too, if it even is at all.

I'm going to get stem cells in the mean time since it's so similar to this.

I really hope FX-322 it does work, it would bring so many people such great relief. Even if it just made things a little better.

FX-345 should be even better again.

Do you know the route of administration? Is it an injection through the ear drum or what?

 

[Chad Lawton]

Zilch, nothing, certainly nothing solid except anecdotal shite from a company prone to over hyping and unfortunately under delivering.

FREQ has gone above & beyond the vast majority of biotech companies in doing their due diligence with all of their preclinical and clinical research and sharing it all openly with the world but you consider it overhyping?

Here is all the "anecdotal shite" FREQ has done so far:

- They treated mouse cochlea ex vivo with aminoglycoside for 16 hours to kill off the cochlear hair cells, they then treated with FX-322 and returned cochlear hair cells back to healthy levels.

- They conducted a noise deafened study in 47 mice against a placebo group of 37 mice. They measured hearing via auditory brainstem response and saw 70% of the treated group recover after treatment with FX-322 while only 30% of the placebo group recovered. The placebo recovery was attributed to typical recovery of acute hearing loss and not attributed to hair cell death.

- They used in vitro rhesus macaque progenitor cells that showed FX-322 caused the progenitor cells to replicate and mature into hair cells just like it did in human cells.

- They've done perilymph sampling in guinea pigs of FX-322 distribution through the cochlea in order to assist their human modeling calculations.

- They conducted a cochlear implant study showing the FX-322 actually diffused through the round window membrane, proving that FX-322 reaches therapeutically active levels in the base of the cochlea.

- A Phase 1/2 placebo controlled safety study in humans with 23 participants which also measured hearing function and followed up 12 months later to asses durability of hearing improvements.

- A Phase 1, open label study of 33 participants testing different administration conditions across a wide range of severities and cohorts with an ongoing durability study follow up roughly a year later.

- A Phase 1, placebo controlled age related hearing loss study of 30 participants.

- A Phase 1, placebo controlled severe hearing loss study of 31 participants.

- A Phase 2a, placebo controlled study in approximately 95 participants.

- They are currently enrolling a Phase 2b, double blind, placebo controlled trial with 124 participants.

And you think they're over here hyping when they are doing the exact opposite by proving that they have done their due diligence.

Source - https://investors.frequencytx.com/node/8296/html

 

[Chad Lawton]

Do you know the route of administration? Is it an injection through the ear drum or what?

Yes, it's administered via intratympanic injection. It then gels up at body temp in the middle ear space so that it can have time to diffuse through the round window membrane.

 

[Athens]

If tinnitus and/or hyperacusis is/are caused by damage to the auditory nerve, I assume that these drugs will likely not be helpful.

 

[Padraigh Griffin]

FREQ has gone above & beyond the vast majority of biotech companies in doing their due diligence with all of their preclinical and clinical research and sharing it all openly with the world but you consider it overhyping?

Here is all the "anecdotal shite" FREQ has done so far:

- They treated mouse cochlea ex vivo with aminoglycoside for 16 hours to kill off the cochlear hair cells, they then treated with FX-322 and returned cochlear hair cells back to healthy levels.

- They conducted a noise deafened study in 47 mice against a placebo group of 37 mice. They measured hearing via auditory brainstem response and saw 70% of the treated group recover after treatment with FX-322 while only 30% of the placebo group recovered. The placebo recovery was attributed to typical recovery of acute hearing loss and not attributed to hair cell death.

- They used in vitro rhesus macaque progenitor cells that showed FX-322 caused the progenitor cells to replicate and mature into hair cells just like it did in human cells.

- They've done perilymph sampling in guinea pigs of FX-322 distribution through the cochlea in order to assist their human modeling calculations.

- They conducted a cochlear implant study showing the FX-322 actually diffused through the round window membrane, proving that FX-322 reaches therapeutically active levels in the base of the cochlea.

- A Phase 1/2 placebo controlled safety study in humans with 23 participants which also measured hearing function and followed up 12 months later to asses durability of hearing improvements.

- A Phase 1, open label study of 33 participants testing different administration conditions across a wide range of severities and cohorts with an ongoing durability study follow up roughly a year later.

- A Phase 1, placebo controlled age related hearing loss study of 30 participants.

- A Phase 1, placebo controlled severe hearing loss study of 31 participants.

- A Phase 2a, placebo controlled study in approximately 95 participants.

- They are currently enrolling a Phase 2b, double blind, placebo controlled trial with 124 participants.

And you think they're over here hyping when they are doing the exact opposite by proving that they have done their due diligence.

Source - https://investors.frequencytx.com/node/8296/html

Nothing here for tinnitus YET.

I have repeatedly said that there is nothing but ANECDOTAL clutching at straws 3 participants, no TFI, no clinical significance, no placebo controlled evidence that FX-322 will help tinnitus.

I apologise if this is of offence to anyone but they are the FACTS as regards to tinnitus. Keep your eyes open. There were many depressed people on here after very poor Phase 2 results.

I will not post here on this thread anymore unless someone replies to my posts that are here already. I have stated counter arguments and if they are not factually correct then I hold my hands up, but I think you will find that they are.

I have also repeatedly said I believe in Frequency Therapeutics and have high hopes that FX-345 might help hearing loss and HOPEFULLY tinnitus.

The fact remains that none of us here know whether FX-322 or FX-345 help tinnitus.

I, like everyone here, hope they do.

 

[Chad Lawton]

An article that came out today from MIT about Frequency Therapeutics.

Reversing hearing loss with regenerative therapy

Some notable excerpts and quotes from the founders of the company:

"Some of these people [in the trials] couldn't hear for 30 years, and for the first time they said they could go into a crowded restaurant and hear what their children were saying," Langer says. "It's so meaningful to them. Obviously more needs to be done, but just the fact that you can help a small group of people is really impressive to me."

For now, Karp is already thrilled with Frequency's progress, which hit home the last time he was in Frequency's office and met a speaker who shared her experience with hearing loss.

"You always hope your work will have an impact, but it can take a long time for that to happen," Karp says. "It's been an incredible experience working with the team to bring this forward. There are already people in the trials whose hearing has been dramatically improved and their lives have been changed. That impacts interactions with family and friends. It's wonderful to be a part of."​

 

[GlennS]

I really don't know why the community has put so much hope into FX-322.

A lot of it seems to be driven by the anxieties of those with a vested stock position in the company.

 

[Diesel]

An article that came out today from MIT about Frequency Therapeutics.

Reversing hearing loss with regenerative therapy

Some notable excerpts and quotes from the founders of the company:

"Some of these people [in the trials] couldn't hear for 30 years, and for the first time they said they could go into a crowded restaurant and hear what their children were saying," Langer says. "It's so meaningful to them. Obviously more needs to be done, but just the fact that you can help a small group of people is really impressive to me."

For now, Karp is already thrilled with Frequency's progress, which hit home the last time he was in Frequency's office and met a speaker who shared her experience with hearing loss.

"You always hope your work will have an impact, but it can take a long time for that to happen," Karp says. "It's been an incredible experience working with the team to bring this forward. There are already people in the trials whose hearing has been dramatically improved and their lives have been changed. That impacts interactions with family and friends. It's wonderful to be a part of."​

Good stuff. Interesting to see that participants with an injection in only 1 ear are seeing that type of improvement in daily life. Often in this forum, we overlook the QoL factors and get too fixated on the clinical measurements. However, the FDA will take into account QoL data as part of the evaluation process. It will be interesting to see how their "RADIAL" analysis works out in the Phase 2B.

 

[dbeats]

Frequency Therapeutics' approach to hair cell regeneration is to make use of progenitor cells which stem cell therapy destroys.

Do stem cells actually destroy progenitor cells, or did you make this up? Any sources?

 

[blamingeverything]

Do stem cells actually destroy progenitor cells, or did you make this up? Any sources?

They speak to this in the Tinnitus Talk Podcast with Frequency Therapeutics:

Episode 12: Hearing Lost and Found — Frequency Therapeutics

 

[dbeats]

They speak to this in the Tinnitus Talk Podcast with Frequency Therapeutics:

Episode 12: Hearing Lost and Found — Frequency Therapeutics

Thank you. Do you have a timestamp?

 

[blamingeverything]

Thank you. Do you have a timestamp?

It's in the latter half I believe.

 

[dbeats]

It's in the latter half I believe.

Around 52:00 is what I'm assuming he was referring to. Seems to me like they are talking about gene therapy and not stem cell therapy?

 

[Aaron91]

Do stem cells actually destroy progenitor cells, or did you make this up? Any sources?

I believe they are confusing the transdifferentiation approach trialed by some other biotechs (which depletes progenitor cells) with the asymmetrical approach used by FREQ (via Wnt and notch pathways), which doesn't deplete progenitor cells.

 

[Gorbeh3]

Does anyone have insight on the state of Frequency Therapeutics right now? I have been seeing a lot of new articles out there but no new information, possibly suggests they are on a media campaign to try to revive a company in decay. I also heard rumors they had to lay off a bunch of staff...

Doesn't look great tbh...

That being said, I'm really optimistic for FX-345.

 

[Nobody19]

Does anyone have insight on the state of Frequency Therapeutics right now? I have been seeing a lot of new articles out there but no new information, possibly suggests they are on a media campaign to try to revive a company in decay. I also heard rumors they had to lay off a bunch of staff...

Doesn't look great tbh...

That being said, I'm really optimistic for FX-345.

Their stock has been hammered over the past year. And yeah they had to lay off staff.

 

[Gb3]

Does anyone have insight on the state of Frequency Therapeutics right now? I have been seeing a lot of new articles out there but no new information, possibly suggests they are on a media campaign to try to revive a company in decay. I also heard rumors they had to lay off a bunch of staff...

Doesn't look great tbh...

That being said, I'm really optimistic for FX-345.

Ya, I've noticed the same article circulating about a patient that can hear better in a restaurant. I agree it seems like they are doing a rescue media campaign right now. We will just have to wait to see if the current trials will show any improvement.

 

[Chad Lawton]

Does anyone have insight on the state of Frequency Therapeutics right now? I have been seeing a lot of new articles out there but no new information, possibly suggests they are on a media campaign to try to revive a company in decay. I also heard rumors they had to lay off a bunch of staff...

Everything is still on track. They laid off 30% of their workforce in order to preserve capital. This move ensures that they will see data on FX-322, FX-345 and FREQ-162 before they run out of money. If these trials are successful, the stock should recover nicely and then they should have no issue doing a share offering. They may even be able to bring in a partner on FREQ-162 that could result in milestone payments much like they did with Astellas.

 

[Geatly]

Everything is still on track. They laid off 30% of their workforce in order to preserve capital. This move ensures that they will see data on FX-322, FX-345 and FREQ-162 before they run out of money. If these trials are successful, the stock should recover nicely and then they should have no issue doing a share offering. They may even be able to bring in a partner on FREQ-162 that could result in milestone payments much like they did with Astellas.

Amount of money going for war and armies, and we are unable to fund from public money such great opportunity to regain hearing for millions of people, shame.

 

[Padraigh Griffin]

Yes it is confirmed that workforce reduction of 30% took place and also the CFO stood down on 31st March.

 

[JPGL]

FREQ rises 42% in the stock market. Is there any good news about FX-322 that justifies this rise?

 

[blamingeverything]

FREQ rises 42% in the stock market. Is there any good news about FX-322 that justifies this rise?

Wow. That's not nothing. CFO bowing out is not great either.

 

[Diesel]

Wow. That's not nothing. CFO bowing out is not great either.

He got fired.

 

[Chad Lawton]

Wow. That's not nothing. CFO bowing out is not great either.

CFO was part of the layoffs based on the fact that they are paying him an entire year salary, $189k bonus and $20k in relocation expenses after he is gone. He was given the option to "step down". They then promoted the Vice Financial Officer up to CFO who has been with the company longer so they essentially trimmed the fat.

https://investors.frequencytx.com/node/8316/html

 

[LAnative]

I have two theories for today's stock spike:

1. Things are looking good in the trial. Perhaps some insiders are leaking info to their friends/relatives. Some might say this is not likely, but do you guys remember the sketchy sell offs in the days before the bad Phase 2 came out? I personally believe there was something sketchy going on back then, because there were big sell offs RIGHT before the news came out. It could be happening again, but at least this time it could mean the drug is working.

2. We all saw the random news articles about Frequency Therapeutics' drug making the rounds in the last few weeks. If I'm not mistaken, the first one came from MIT, which a lot of the top brass in this company graduated from. The same article was repackaged from maybe half a dozen different science sites. My own friends were sending me the articles, even though this was quite old news. A classic pump. There were large Easter family gatherings just yesterday where word of mouth could have spread, and now everyone's uncles and aunties buy into the hearing restoration stock.

Just some random guy's two cents.

 

[Geatly]

I have two theories for today's stock spike:

1. Things are looking good in the trial. Perhaps some insiders are leaking info to their friends/relatives. Some might say this is not likely, but do you guys remember the sketchy sell offs in the days before the bad Phase 2 came out? I personally believe there was something sketchy going on back then, because there were big sell offs RIGHT before the news came out. It could be happening again, but at least this time it could mean the drug is working.

2. We all saw the random news articles about Frequency Therapeutics' drug making the rounds in the last few weeks. If I'm not mistaken, the first one came from MIT, which a lot of the top brass in this company graduated from. The same article was repackaged from maybe half a dozen different science sites. My own friends were sending me the articles, even though this was quite old news. A classic pump. There were large Easter family gatherings just yesterday where word of mouth could have spread, and now everyone's uncles and aunties buy into the hearing restoration stock.

Just some random guy's two cents.

I really would love to buy their stock, but since I am from Slovakia, I can't find a webpage or broker, or anything where can I buy. I am not doing it for money, to be honest, I just want to put my trust in them.

 

[blamingeverything]

I'm guessing they might have secured additional funding. Though positive trial results could be it. If the price sticks, we will know it's more than a good news pump.

 

[Chad Lawton]

1. Things are looking good in the trial. Perhaps some insiders are leaking info to their friends/relatives. Some might say this is not likely, but do you guys remember the sketchy sell offs in the days before the bad Phase 2 came out? I personally believe there was something sketchy going on back then, because there were big sell offs RIGHT before the news came out. It could be happening again, but at least this time it could mean the drug is working.

As much as I'd love to believe it is this first one, it seems highly unlikely it would be either of the 2 suggestions. Volume of shares traded was 20x what it normally is so this would indicate that it's likely either hedge funds or a group of retail investors/day traders like wallstreetbets having their fun with it. There was little reason for it to fall from $5 to $1.25 over the last couple months so it doesn't need much reason to go back up as well.

Granted, maybe I'm completely wrong and they release some good news in the coming days but I personally don't think that will be the case.

 

[Padraigh Griffin]

I really would love to buy their stock, but since I am from Slovakia, I can't find a webpage or broker, or anything where can I buy. I am not doing it for money, to be honest, I just want to put my trust in them.

It's pity projects like this are unavailable to the common investor. If this was a DeFi project I'm sure many of us would gladly contribute our hard earned cash. Buying stock now is not supportive. If we could give them new funding it would be far more beneficial. Hopefully in the future the ordinary person can participate in fundraisers. In fact in crypto it is easy now, but not for a company that needs this kind of cash. If everyone who suffers from hearing loss could contribute €1,000 if they can afford it, we would have a treatment far faster.

As I pointed out to much abuse, Wall St. doesn't give a damn about the moral benefits.

It unfortunately is all about the $.

Frequency Therapeutics looks goosed from a funding perspective unfortunately.