Frequency Therapeutics — Hearing Loss Regeneration

[d'Wooluf]

And so it begins...

...again.

 

[Brian Newman]

Is FX-322 ever going to get to the market?

I read Frequency Therapeutics saying they're expecting results in June.

Should I be optimistic or pessimistic about FX-322?

And what about other companies? I keep telling myself at least one of these companies have to have something out in the next 10 years. I'm kinda losing hope though. Should I be optimistic? I'm only 22, no hearing loss, but my ears are still fucked.

 

[MadsWithT]

Why are you on here so much then?

It is both sad and comical to see how people get very excited over very little, especially now that this thread went from silent to silly mode after the trial results were released. Good to see someone pointing that out. Right now the FX-322 thread is dark comedy. Nothing of substance has been posted for months.

 

[RB2014]

Frequency Therapeutics just posted a pre-March infographic. Looks like they really are going for the clarity/WIN route. Thank God.

View attachment 45155

I guess this is what we end up with... An injection that helps with word scores. To be fair, if they go with this, it is a huge market.

Everyone of us will sign up for an injection no matter how small the benefits. If it makes tinnitus 5 percent more tolerable, then that is a benefit as well. I'm pretty sure this is the direction they are now headed.

If this helps bridge that gap to something better in the future and keeps the company viable for a longer period of time, then that is the positive that we can take from this.

 

[d'Wooluf]

It is both sad and comical to see how people get very excited over very little, especially now that this thread went from silent to silly mode after the trial results were released. Good to see someone pointing that out. Right now the FX-322 thread is dark comedy. Nothing of substance has been posted for months.

It's like a grieving process that's playing out. People are still trying to process the loss of something of great importance to them. While Frequency Therapeutics were doing a great job of raising money from investors they were also planting the seeds of future collateral damage to a group who also invested heavily, but not in money.

 

[rei]

It's like a grieving process that's playing out. People are still trying to process the loss of something of great importance to them. While Frequency Therapeutics were doing a great job of raising money from investors they were also planting the seeds of future collateral damage to a group who also invested heavily, but not in money.

Loss of what? Frequency Therapeutics still has money and the only thing that's been proven is that their FX-322 doesn't work well in its current form.

Maybe it doesn't work at all but until they reformulate the gel and get better penetration, how can we know.

 

[Jack V]

Is FX-322 ever going to get to the market?

I read Frequency Therapeutics saying they're expecting results in June.

Should I be optimistic or pessimistic about FX-322?

And what about other companies? I keep telling myself at least one of these companies have to have something out in the next 10 years. I'm kinda losing hope though. Should I be optimistic? I'm only 22, no hearing loss, but my ears are still fucked.

I think you should be neither optimistic or pessimistic, but rather realistic.

Realistically, right now, there's no compelling evidence that FX-322 works any better than a sprinkle of sugar.

However, the company continues to research it, and maybe they'll surprise and delight us with future developments.

 

[Jack V]

I guess this is what we end up with... An injection that helps with word scores. To be fair, if they go with this, it is a huge market.

Everyone of us will sign up for an injection no matter how small the benefits. If it makes tinnitus 5 percent more tolerable, then that is a benefit as well. I'm pretty sure this is the direction they are now headed.

If this helps bridge that gap to something better in the future and keeps the company viable for a longer period of time, then that is the positive that we can take from this.

That would be wonderful, agreed. But they have yet to credibly establish even that.

(To respond in advance: 3 people who showed word score improvements during an initial safety trial followed by a larger, more rigorous Phase II trial of almost 100 people that showed no FX-322 benefit whatsoever does not credibly establish that an injection can help word scores).

 

[Trevor_phillips]

If Frequency Therapeutics doesn't work on reformulation and deeper penetration, I don't see how it could be successful.

 

[GlennS]

To respond in advance: 3 people who showed word score improvements during an initial safety trial followed by a larger, more rigorous Phase II trial of almost 100 people in which participants who received FX-322 responded no differently from those who received placebo does not credibly establish that an injection can help word scores.

* Cue gatekeepers to tell pessimists/realists they don't belong in this thread. *

 

[Diesel]

FDA Approval: What it means
FDA approval of a drug means that data on the drug's effects have been reviewed by CDER, and the drug is determined to provide benefits that outweigh its known and potential risks for the intended population. The drug approval process takes place within a structured framework that includes:

• Analysis of the target condition and available treatments—FDA reviewers analyze the condition or illness for which the drug is intended and evaluate the current treatment landscape, which provide the context for weighing the drug's risks and benefits.

• Assessment of benefits and risks from clinical data—FDA reviewers evaluate clinical benefit and risk information submitted by the drug maker, taking into account any uncertainties that may result from imperfect or incomplete data. Generally, the agency expects that the drug maker will submit results from two well-designed clinical trials, to be sure that the findings from the first trial are not the result of chance or bias. Evidence that the drug will benefit the target population should outweigh any risks and uncertainties.

• Strategies for managing risks—All drugs have risks. Risk management strategies include an FDA-approved drug label, which clearly describes the drug's benefits and risks, and how the risks can be detected and managed.

Population believed today to gain a benefit with a single dose:

• Moderate - Moderately Severe Sensorineural Hearing Loss
• Roughly 300-350 million people world wide
• (This does not include Mild or Severe)

Measurable Benefit:

• Clinical Endpoint: Word Score in Quiet
• Clinical Endpoint: Word in Noise

Safety Profile:

• Known to be well tolerated with no severe adverse events reported with a single dose

 

[Gb3]

@GlennS if you don't believe in it, move on. I get it you're frustrated and you're just releasing your negative energy. You really deep down want to be wrong. I get it.

 

[Tezcatlipoca]

@GlennS if you don't believe in it, move on. I get it you're frustrated and you're just releasing your negative energy. You really deep down want to be wrong. I get it.

Stop it! You are harassing him!

 

[Trevor_phillips]

FDA Approval: What it means
FDA approval of a drug means that data on the drug's effects have been reviewed by CDER, and the drug is determined to provide benefits that outweigh its known and potential risks for the intended population. The drug approval process takes place within a structured framework that includes:

• Analysis of the target condition and available treatments—FDA reviewers analyze the condition or illness for which the drug is intended and evaluate the current treatment landscape, which provide the context for weighing the drug's risks and benefits.

• Assessment of benefits and risks from clinical data—FDA reviewers evaluate clinical benefit and risk information submitted by the drug maker, taking into account any uncertainties that may result from imperfect or incomplete data. Generally, the agency expects that the drug maker will submit results from two well-designed clinical trials, to be sure that the findings from the first trial are not the result of chance or bias. Evidence that the drug will benefit the target population should outweigh any risks and uncertainties.

• Strategies for managing risks—All drugs have risks. Risk management strategies include an FDA-approved drug label, which clearly describes the drug's benefits and risks, and how the risks can be detected and managed.

Population believed today to gain a benefit with a single dose:

• Moderate - Moderately Severe Sensorineural Hearing Loss
• Roughly 300-350 million people world wide
• (This does not include Mild or Severe)

Measurable Benefit:

• Clinical Endpoint: Word Score in Quiet
• Clinical Endpoint: Word in Noise

Safety Profile:

• Known to be well tolerated with no severe adverse events reported with a single dose

Why wouldn't FX-322 work on people with mild hearing loss? I don't get it because we know that the hair cell architecture is more intact in this degree. Therefore there should be more support cells and FX-322 would work at its best.

 

[Diesel]

Why wouldn't FX-322 work on people with mild hearing loss? I don't get it because we know that the hair cell architecture is more intact in this degree. Therefore there should be more support cells and FX-322 would work at its best.

Because the benefit cannot be measured reliably on the tests used in the clinical trial (the standard clinical tests).

It frankly doesn't matter in the scope of the clinical trial if it works for mild hearing loss. If the FDA approves it for Moderate - Moderately Severe hearing loss, patients with mild hearing loss can still get the drug.

 

[Pete88]

Because the benefit cannot be measured reliably on the tests used in the clinical trial (the standard clinical tests).

It frankly doesn't matter in the scope of the clinical trial if it works for mild hearing loss. If the FDA approves it for Moderate - Moderately Severe hearing loss, patients with mild hearing loss can still get the drug.

Exactly. It should still benefit mild hearing loss and that is displayed in the detailed Phase 1/2 results. It's just that the ceiling doesn't allow for the definition of "clinically meaningful" etc to be achieved and that's nothing to be concerned about.

If you consistently score 46 out of 50 and then after a dosage of FX-322, consistently get 50 out of 50, even though you know it improved your hearing, it's not enough for the company to be allowed to market it as helping you.

 

[GlennS]

@GlennS if you don't believe in it, move on. I get it you're frustrated and you're just releasing your negative energy. You really deep down want to be wrong. I get it.

Strawman.

There are far more negative posters in this thread besides me.

I have a particular disdain for information silos. It seems wherever you go, people seek out groupthink and that's why the gatekeeping starts. A discussion group should allow free and open debate rather than just bobbleheading. Bobbleheading is just emotional junkfood.

 

[Brian Newman]

I think you should be neither optimistic or pessimistic, but rather realistic.

Realistically, right now, there's no compelling evidence that FX-322 works any better than a sprinkle of sugar.

However, the company continues to research it, and maybe they'll surprise and delight us with future developments.

Yeah, that's kind of what I was thinking. Maybe Otomony, Pipeline Therapeutics or Hough Ear Institute show results. Not anytime soon though.

 

[Pete88]

Strawman.

There are far more negative posters in this thread besides me.

I have a particular disdain for information silos. It seems wherever you go, people seek out groupthink and that's why the gatekeeping starts. A discussion group should allow free and open debate rather than just bobbleheading. Bobbleheading is just emotional junkfood.

I definitely understand your disdain for information silos, echo chamber etc and I can definitely see it happening in this thread from time to time.

At the same time, I do think there is good reason to be optimistic about a limited benefit that FX-322 may provide. No, it won't give everyone perfect hearing, but I think it can take the edge off a few ailments at least.

It's good to have dissenting voices to avoid echo chambers but it shouldn't come off as just sheer pessimism. One thing that does keep people going is hope, which there is reason these days to have.

 

[kiki]

Why wouldn't FX-322 work on people with mild hearing loss? I don't get it because we know that the hair cell architecture is more intact in this degree. Therefore there should be more support cells and FX-322 would work at its best.

The audiogram, 10 dB improvement, is 3 times improvement.

I think we need more hair cells regenerated to triple the improvement from milder deafness.

I'm obsessed with improving high frequencies because if it's not zero, there's hope.
Zero is zero, no matter what you do. If there is an improvement of 1 in 10 steps, it is possible to finally reach 10.

 

[WickedCarnival]

I would love to see FX-322 delivered as nanoparticles via Otomagnetics. It would be very interesting to see any contrast of results against passive diffusion through the round window.

I've been saying this countless of times and have sent several emails to Frequency Therapeutics asking if they are aware of this development. I haven't heard a single thing back. Someone has to print off a bunch of Otomagnetics business cards and physically dump them all over the desks of folks at Frequency Therapeutics for them to notice.

 

[Diesel]

I've been saying this countless of times and have sent several emails to Frequency Therapeutics asking if they are aware of this development. I haven't heard a single thing back. Someone has to print off a bunch of Otomagnetics business cards and physically dump them all over the desks of folks at Frequency Therapeutics for them to notice.

You're wasting your time.

1. Otomagnetics technology isn't anywhere close to being tested on humans or approved based on what's on their website. So, for FX-322 to be combined with that technology would mean starting completely over only AFTER Otomagnetics' compound + delivery method is approved.

2. There is no evidence/indication that FX-322 is even currently compatible with the Otomagnetics compound/delivery method. So, if #1 even happens above, there would need to be additional time/resources from both to get a specific "FX" formula through pre-clinical, trials, etc. We all know the drill... add a few more years.

3. Resource limitations. We know that Frequency Therapeutics has about 3 years of cash available to get a viable product on the market. The time and expenses related to making 1 and 2 happen right now is really not feasible for them. For Otomagnetics, it's not clear what resources they have, but based on the state of the website, they're obviously running on a shoestring budget as-is. If Frequency decided to move away from the single-dose strategy to partnering right now with Otomagnetics, they would certainly go bankrupt and there would be no FX and no Otomagnetics for any patient.

4. Market acceptance/adoption. Right now, every ENT office is equipped for intratympanic injections. Otomagnetics is an entirely new process that will require purchasing specialized equipment/training etc. So, even if somehow 1, 2 and 3 miraculously happen in our lifetime, 4 is even more difficult. I would put more emphasis on extended release intratympanic gels getting better since so many drug developers are using that method to get to the cochlea, and it's an established practice.

The best strategy for Frequency Therapeutics is the one they are on right now: Establish the patient population that benefits from a single injection of FX-322, and get it approved by the FDA. From there, in a relatively short period of time, by having a product that generates cashflow, they can invest in other partnerships for FX-322 "2.0"

Diesel's Opinion:

If it were me, I wouldn't bother risking any future development of FX-322 on Otomagnetics technology considering how little investment there is in developing Otomagnetics right now. I would seek out a developer/supplier of an extended-release gel that already has invested in it as a product and has the resources to integrate it with FX-322. This way, both firms have cashflow to invest and can share access to a market that already knows how to use the product. Maybe this is Otonomy, maybe it's another pharmaceutical provider that has a gel already on the market.

 

[Tezcatlipoca]

I've been saying this countless of times and have sent several emails to Frequency Therapeutics asking if they are aware of this development. I haven't heard a single thing back. Someone has to print off a bunch of Otomagnetics business cards and physically dump them all over the desks of folks at Frequency Therapeutics for them to notice.

Anything we could think of here they already did. They're testing methods.

 

[Pete88]

You're wasting your time.

1. Otomagnetics technology isn't anywhere close to being tested on humans or approved based on what's on their website. So, for FX-322 to be combined with that technology would mean starting completely over only AFTER Otomagnetics' compound + delivery method is approved.

2. There is no evidence/indication that FX-322 is even currently compatible with the Otomagnetics compound/delivery method. So, if #1 even happens above, there would need to be additional time/resources from both to get a specific "FX" formula through pre-clinical, trials, etc. We all know the drill... add a few more years.

3. Resource limitations. We know that Frequency Therapeutics has about 3 years of cash available to get a viable product on the market. The time and expenses related to making 1 and 2 happen right now is really not feasible for them. For Otomagnetics, it's not clear what resources they have, but based on the state of the website, they're obviously running on a shoestring budget as-is. If Frequency decided to move away from the single-dose strategy to partnering right now with Otomagnetics, they would certainly go bankrupt and there would be no FX and no Otomagnetics for any patient.

4. Market acceptance/adoption. Right now, every ENT office is equipped for intratympanic injections. Otomagnetics is an entirely new process that will require purchasing specialized equipment/training etc. So, even if somehow 1, 2 and 3 miraculously happen in our lifetime, 4 is even more difficult. I would put more emphasis on extended release intratympanic gels getting better since so many drug developers are using that method to get to the cochlea, and it's an established practice.

The best strategy for Frequency Therapeutics is the one they are on right now: Establish the patient population that benefits from a single injection of FX-322, and get it approved by the FDA. From there, in a relatively short period of time, by having a product that generates cashflow, they can invest in other partnerships for FX-322 "2.0"

Diesel's Opinion:

If it were me, I wouldn't bother risking any future development of FX-322 on Otomagnetics technology considering how little investment there is in developing Otomagnetics right now. I would seek out a developer/supplier of an extended-release gel that already has invested in it as a product and has the resources to integrate it with FX-322. This way, both firms have cashflow to invest and can share access to a market that already knows how to use the product. Maybe this is Otonomy, maybe it's another pharmaceutical provider that has a gel already on the market.

I agree. They already tried to fly too close to the sun with their gamble on multi-dosing for their Phase 2 and it cost them. Stick to what seems to work, get it to market and then start messing around with improvements after.

 

[Bill Arsenault]

Why are you on here so much then?

Haha. You would think that all the creeps would move on - but nobody else wants us either.
True Story.

 

[Jack V]

@GlennS if you don't believe in it, move on. I get it you're frustrated and you're just releasing your negative energy. You really deep down want to be wrong. I get it.

Suggesting that someone has to "believe in it" in order to weigh in sounds more like religion than science.

This thread is, in many ways, about hope as much as it's about anything else – the thread that people return to in the middle of the night when they can't get back to sleep.

But for it to work, it has to be real hope not false hope, and real hope is driven by a realistic assessment of the cutting-edge science, not just a faith-based embrace of a drug that has yet to prove itself.

Which is to say, I don't find @GlennS's energy negative at all, and I appreciate his input, just as I appreciate all the other thoughtful people adding their input as well.

 

[Zugzug]

I hope to ask this question every once in a while until it's answered:

Should Frequency Therapeutics ditch the project because No AuDiOgRaMs? Should all investors leave and we take the FX-322 project, burn all remnants of it, and start over from scratch in Zugzug's parents' basement?

Yes, blind optimism can be a religion, but so can directionless doubt. If I'm supposed to ditch this drug, why should I?

Is Robert Langer a similar character to Joseph Smith? If you want the hope -- of all forms -- of this drug to die, be careful what you wish for. You may just slow down hearing research instead of doing that actual logical thing which is diagnostics.

 

[GlennS]

blind optimism can be a religion, but so can directionless doubt.

I see this as an emerging behavioral pattern on Tinnitus Talk, one that can be best described as a 'fool me once, fool me twice' phenomenon.

The reason why Neuromod had so many believers (including me at one time) is that it looked like the only source of hope on the horizon. People don't let go easily when they feel like they're grasping at their last straw. Had Dr. Susan Shore looked like she'd release something in this century and had Minnesota not folded then people would not have put all their eggs into the Lenire basket. When it finally became clear that Lenire was a bust, most clambered out of Neuromod's lifeboat and over here to FREQ (including me).

The distinction between the two is that while FX-322 may be the farthest along, it isn't the only game in town for hearing/synapse restoration. There's less of a rationalization to be made for clutching at FX-322 as a last hope, shifting goalposts, creating qualifications, fudging statistics the way that became all too common with the Lenire die-hards. Other than those with a vested interest in a stock position, well, spread your hope around. For instance, has everyone listened to the interview between Tinnitus Talk and Otonomy?

It might be an OK coping mechanism now but it's not a good feeling when die-hards are finally forced to capitulate that a treatment is a failure. You pay for it in the end one way or another. I can't imagine people would subject themselves to this again and again before realizing it ain't worth it and adopting a more dispassionate approach to discussion and analysis.

 

[Zugzug]

I see this as an emerging behavioral pattern on Tinnitus Talk, one that can be best described as a 'fool me once, fool me twice' phenomenon.

The reason why Neuromod had so many believers (including me at one time) is that it looked like the only source of hope on the horizon. People don't let go easily when they feel like they're grasping at their last straw. Had Dr. Susan Shore looked like she'd release something in this century and had Minnesota not folded then people would not have put all their eggs into the Lenire basket. When it finally became clear that Lenire was a bust, most clambered out of Neuromod's lifeboat and over here to FREQ (including me).

The distinction between the two is that while FX-322 may be the farthest along, it isn't the only game in town for hearing/synapse restoration. There's less of a rationalization to be made for clutching at FX-322 as a last hope, shifting goalposts, creating qualifications, fudging statistics the way that became all too common with the Lenire die-hards. Other than those with a vested interest in a stock position, well, spread your hope around. For instance, has everyone listened to the interview between Tinnitus Talk and Otonomy?

It might be an OK coping mechanism now but it's not a good feeling when die-hards are finally forced to capitulate that a treatment is a failure. You pay for it in the end one way or another. I can't imagine people would subject themselves to this again and again before realizing it ain't worth it and adopting a more dispassionate approach to discussion and analysis.

You didn't answer my question, literally at all. I never said FX-322 is the only game in town or that hope shouldn't be diversified. I asked a simple question. Would it be a positive thing for everyone to totally give up on FX-322? Would it be beneficial to hearing research? That's all I'm wondering. If the answer is yes, why, beyond purely emotional reasons? Is there something about the FX-322 biotech that contaminates the other drugs? Does it need to get burned to the ground in order for us to proceed with our lives? Is that really better than continuing to work at diagnosing the reasons why it works in vitro (proven), but less so in vivo?

 

[GlennS]

Does it need to get burned to the ground

I'm not the one calling for FX-322 to be "burned to the ground". It will play out however it plays out. Heck, even if Neuromod magically versions up Lenire to the point where it actually works unequivocally and eliminates risk of "disimprovement" I'll reconsider them as well.