Frequency Therapeutics — FX-345

[Joeseph Stope]

We believed in Frequency Therapeutics when, in reality, they were nothing but miserable scammers. What we are suffering now should have affected them instead.

Now that the dust is beginning to settle, we have to ask ourselves: "What was that all about?"

The main scientist—I can't recall his name, but it's mentioned somewhere in the FX-322 thread—seemed to have strong belief in his remedy involving small molecules.
Molecules of what, I wonder?

What made him think they could regrow inner or outer hair cells? Did he test it on lab animals? Did it alleviate or cure their tinnitus? Improve their hearing? Help with hyperacusis? Was any testing done using discarded cochleas from cochlear implant surgeries?

At one point, they appeared to have trouble with delivery, if I recall correctly. Something about the drug not reaching the frequencies at 8,000 Hz and below. One thing that sticks in my mind is that no mention was made of the synapse or stereocilia.

I'll need to check all this again to see if I misunderstood something.

After all the hullabaloo, it would be nice to think we've learned something new from it all, however simple that might be.

As it stands, though, the only thing we seem to have learned is about stock option payments and the finance market.

We need to let it go. Unfortunately, those who questioned the initial results and choice of outcome measures as "fishy" were shouted down. In the future, we need to ensure that people can freely challenge such claims and point out potential issues to those who may be overly trusting.

Any company that uses speech-in-noise tests or relies on mainstream media to hype their research is a big red flag.

I don't disagree with you—we do need to be more cautious.

Still, I can imagine that in a decade or so, a new wave of tinnitus sufferers might end up losing their money all over again. It's an ongoing question.

The principle itself—a private company collecting money from sufferers to fund research in hopes of finding a cure or alleviating tinnitus—isn't inherently bad or dishonest. After all, tinnitus and hearing damage seem to be the orphans of government research.

That said, it's crucial to keep a close eye on how much the company's staff are paid, whether they have clear and achievable goals, and what the research timeline looks like. However, funding might be better handled through straightforward cash grants rather than selling company shares.

There are some incredibly wealthy individuals who suffer from tinnitus. If they got organized, we might actually make significant progress.

 

[Nick47]

can imagine that in a decade or so, a new wave of tinnitus sufferers might end up losing their money all over again. It's an ongoing question.

@Joeseph Stope, I imagine that by then there will be several effective tinnitus treatments available. Additionally, we might finally see some semi-effective hearing solutions.

 

[KKGG]

@Joeseph Stope, I imagine that by then there will be several effective tinnitus treatments available. Additionally, we might finally see some semi-effective hearing solutions.

More and more research and the beginnings of clinical studies are emerging every week and month. Cilcare shows promise, as does Rinri Therapeutics. Mass Eye and Ear made impressive advancements this year. Here's to a hopeful 2025!

 

[DimLeb]

I imagine that by then there will be several effective tinnitus treatments available. Additionally, we might finally see some semi-effective hearing solutions.

Lol, I doubt it. More like a minimum of 50 years.

 

[Joeseph Stope]

Lol, I doubt it. More like a minimum of 50 years.

I don't think I'll be waiting around on Planet Earth that long, no matter how promising the research seems. But life goes on—people come and people go.

We need to stay vigilant about how and where the funding is allocated, should it come our way. I have no doubt that the management teams of these research groups genuinely believe they are onto something. A bit of belief can go a long way.

However, the failure of Frequency Therapeutics left many people disheartened and out of pocket. They have my sympathy.

 

[Luis Orozco]

Let's start fresh with a new class action. Given the medical impact, I believe we can build a strong case together. Many similar cases, even involving other securities scams, have been successful in progressing their class actions. For example, take a look at the Lightning eMotors class action case for reference.

 

[AnonymousMouse]

Something to consider: if companies fear being sued for any reason, they may have less incentive to continue research. At the same time, taking money based on false promises should be punished. It's definitely a catch-22.

 

[IYIiKe]

Yeah, that sucks for those of you who got duped. But spending thousands more just to find out—after possibly fighting a lengthy legal battle—that the LLC has no assets to secure a judgment from?

That's bordering on insanity, unless you've got monopoly money to spare.

 

[Luis Orozco]

We would be suing David Lucchino directly, not the LLC. Even then, since the LLC merged with Korro Bio, it is possible that Korro could also be held liable. However, in reality, Lucchino should be the one held responsible for his misleading statements, not the LLC.

So far, neither case has progressed because only two people have filed lawsuits against him. We need more participants, which is why it is called a Class Action.

 

[annV]

We would be suing David Lucchino directly, not the LLC. Even then, since the LLC merged with Korro Bio, it is possible that Korro could also be held liable. However, in reality, Lucchino should be the one held responsible for his misleading statements, not the LLC.

So far, neither case has progressed because only two people have filed lawsuits against him. We need more participants, which is why it is called a Class Action.

Honestly, nobody's interested in risking further losses or wasting their time. Good luck with your initiative to find people to take part...

Time to close the book on Frequency Therapeutics.

 

[dd314]

I lost a ton of money on FREQ as well. If I recall correctly, the placebo group showed unprecedented improvements, which likely means some participants were dishonest about their scores. However, there's no reason to suspect any deceit on the company's part—they genuinely believed their product would work.

 

[lymebite]

The product apparently worked amazingly well in vitro (cochleas that were removed). But it ended up not working in vivo (in alive people). Maybe there was an issue with delivery but unfortunately they ran out of funding before they could figure out how to get it to work in vivo.

 

[IvanRus]

I am not sure what their in vitro results were—if they even had any. In the end, they could not demonstrate anything in vivo. Honestly, I never believed it from the start. It seemed too sensational, something that would have turned the world upside down. Even billionaires today have to rely on hearing aids.

I do not believe that Numelicina will ever be able to regenerate hair cells in people. It seems absolutely impossible. The whole stem cell concept, in this case, feels like pure charlatanism. I am very sorry to say this.

 

[Joeseph Stope]

@lymebite, are you referring to FX-322, FX-345, or both? If what you say is true, then they should not discard the data. Someone in the future might discover the equation, delivery method, or "magic potion" needed to make it work in vivo.

But sinking another billion into this?
Jay, I am not sure.

At the very least, they should preserve the files and meeting minutes. Better yet, they should publish the findings. Who knows? Something valuable might come from it down the line.

Progress can be heartbreakingly full of near misses.

Perhaps the government should require, as a condition for receiving research grants, that companies publish their findings, methods, and results after an agreed-upon time span.

 

[lymebite]

@lymebite, are you referring to FX-322, FX-345, or both? If what you say is true, then they should not discard the data. Someone in the future might discover the equation, delivery method, or "magic potion" needed to make it work in vivo.

The scientific discovery of what worked in vitro forms the underlying foundation for both compounds. Researchers discovered molecules that could regenerate cells in the intestinal system and had the idea to apply these findings to other parts of the body. They explored several possibilities and decided to focus on hearing and cochlear regeneration first. This was all before the compounds were named FX-322 and FX-345.

Thomas Edison famously said, "I have not failed. I've just found 10,000 ways that won't work."

Unfortunately, breakthroughs in medicine often follow a similar path—it takes many failures to achieve success. The development process for medical interventions is also incredibly expensive, making it difficult to secure funding. In the case of Frequency Therapeutics, their original in vitro discovery showed such promising results that they were able to secure investor funding to conduct clinical trials. As we know, those trials were not successful, and the funding eventually ran out.

To my understanding, all of their discoveries have been published, so the science is accessible. In theory, anyone with access to a lab and the desire to do so could produce FX-322 and FX-345. However, patents, intellectual property rights, and other legal protections likely prevent another company from commercializing the compounds without obtaining proper permissions. Nonetheless, the scientific findings remain available.

 

[Joeseph Stope]

The scientific discovery of what worked in vitro forms the underlying foundation for both compounds. Researchers discovered molecules that could regenerate cells in the intestinal system and had the idea to apply these findings to other parts of the body. They explored several possibilities and decided to focus on hearing and cochlear regeneration first. This was all before the compounds were named FX-322 and FX-345.

Thomas Edison famously said, "I have not failed. I've just found 10,000 ways that won't work."

Unfortunately, breakthroughs in medicine often follow a similar path—it takes many failures to achieve success. The development process for medical interventions is also incredibly expensive, making it difficult to secure funding. In the case of Frequency Therapeutics, their original in vitro discovery showed such promising results that they were able to secure investor funding to conduct clinical trials. As we know, those trials were not successful, and the funding eventually ran out.

To my understanding, all of their discoveries have been published, so the science is accessible. In theory, anyone with access to a lab and the desire to do so could produce FX-322 and FX-345. However, patents, intellectual property rights, and other legal protections likely prevent another company from commercializing the compounds without obtaining proper permissions. Nonetheless, the scientific findings remain available.

It's great to have some clarity about the background of the Frequency Attempt. Scientists sometimes get excited, and that's completely understandable—it's probably one of the things that makes their profession so engaging.

Now that I think about it, earlier this year, I posted a link to New Scientist, a glossy magazine, where the main article focused on the excitement within the scientific and medical community about several potential breakthroughs in the tinnitus and hearing loss field.

Excitement can be infectious. It spreads from the scientific community to the business world and even to venture capitalists. So, there's more excitement to come—great! Just be cautious.

 

[RingingBrother]

Does anyone know anything about fibrosis scarring that can occur in the cochlea after hair cells are damaged? I was discussing this with Grok AI, and it suggested that this scarring could be one of the reasons why these drugs have failed. I think researchers would first need to figure out how to reverse the scarring in order to allow hair cells to regenerate.

 

[Jupiterman]

I thought this would have been obvious.

They should have considered it from the beginning.

No wonder the drug failed.

Incompetent knowledge would not have helped them succeed.

 

[Joeseph Stope]

I am bowled over by the depth of your scholarship.

My non-medical response would be: "Look and see!" An examination of a dissected cochlea should provide a quick answer, or perhaps someone has already done this at some point, somewhere.

There is also the recent innovation of the Optical Coherence Tomography scanner, which was introduced in this very research section:

Research on the Origins of Hyperacusis and Potential Future Cochlear Imaging

https://www.news-medical.net/news/20250224/New-imaging-tool-reveals-the-brains-role-in-cochlea-sensitivity.aspx TL;DR: The brain increasing gain in the cochlea after hearing loss appears to have been proven in mice. Researchers also developed a new imaging tool to observe the cochlea in real...

www.tinnitustalk.com

I hope this helps you move further along.

Oh, and yes, do not forget to post the results once you find out.

I really like your analogy of growing hair cells and choosing the right kind of subsoil

 

[RingerBell]

Does anyone know anything about fibrosis scarring that can occur in the cochlea after hair cells are damaged? I was discussing this with Grok AI, and it suggested that this scarring could be one of the reasons why these drugs have failed. I think researchers would first need to figure out how to reverse the scarring in order to allow hair cells to regenerate.

View attachment 60173

Reversing fibrosis is one of the holy grails in the entire field of medicine. Fibrosis can be life threatening when it affects internal organs, it can cause chronic pain, and it can end careers, especially for athletes, when it occurs in skeletal muscle. Yet even now, there is very little that can be done to reverse fibrosis or even muscle scarring after a severe tear.

If researchers need to figure out how to reverse fibrosis in addition to regenerating hair cells, then unfortunately that raises the complexity of the problem to an entirely new level.

 

[RingingBrother]

Reversing fibrosis is one of the holy grails in the entire field of medicine. Fibrosis can be life threatening when it affects internal organs, it can cause chronic pain, and it can end careers, especially for athletes, when it occurs in skeletal muscle. Yet even now, there is very little that can be done to reverse fibrosis or even muscle scarring after a severe tear.

If researchers need to figure out how to reverse fibrosis in addition to regenerating hair cells, then unfortunately that raises the complexity of the problem to an entirely new level.

I wonder if they ever did it in a mouse cochlea.

 

[RingingBrother]

I used Grok AI's "Think" feature to generate possible solutions for how FX-322 and FX-345 could have succeeded instead of failed. Maybe AI can help accelerate the development of these types of cures and lead to future trials starting sooner, rather than taking over ten years.

"To imagine a scenario where FX-322 and FX-345, drugs developed to treat hearing loss, succeeded in clinical trials—fully restoring hearing, regenerating hair cells, and addressing cochlear fibrosis—we need to consider how their real-world limitations could have been overcome. In reality, these drugs, designed to regenerate hair cells in the cochlea (the inner ear structure responsible for hearing), failed to show significant improvements over placebo in speech perception, their primary endpoint. However, by optimizing several key factors, including drug delivery, dosing, combination therapies, patient selection, and trial design, a successful outcome could have been achieved. Below, I outline a plausible scenario where these drugs met their goals.

---

1. Enhanced Drug Delivery for Comprehensive Regeneration
In the actual trials, FX-322 primarily regenerated hair cells in the high-frequency region near the cochlea's base, with limited reach to the lower-frequency areas deeper in the cochlea, which are often more affected in sensorineural hearing loss. FX-345 was intended to penetrate further, but its development stalled after FX-322's failure.
How it could have succeeded: A more effective delivery system could have ensured the drugs reached all regions of the cochlea. For example, using a sustained-release gel or nanoparticle-based formulation, the drugs could have diffused deeper into the cochlea, regenerating hair cells across a full range of frequencies—from high-pitched sounds at the base to lower-pitched sounds at the apex. This broader regeneration would have restored hearing more completely, addressing the diverse patterns of damage seen in patients.

---

2. Optimized Dosing and Timing for Sustained Effects
The real trials administered FX-322 as a single injection, with outcomes assessed after 90 days. However, regenerating hair cells and restoring functional hearing might require more time or repeated exposure to the drug.
How it could have succeeded: Instead of a one-time dose, the drugs could have been administered in multiple injections or via a slow-release implant, maintaining therapeutic levels in the cochlea over weeks or months. Extending the follow-up period to 6 months or a year could have allowed newly regenerated hair cells to mature and integrate with the auditory system, leading to measurable hearing improvements. This approach would have mimicked natural regenerative processes seen in some animals, where recovery unfolds gradually.

---

3. Combination Therapy to Combat Cochlear Fibrosis
Cochlear fibrosis—scar tissue formation in the cochlea—poses a significant barrier to regeneration, potentially blocking hair cell growth or impairing cochlear function. The actual trials did not address this issue directly.
How it could have succeeded: Pairing FX-322 or FX-345 with an anti-fibrotic agent could have solved this problem. For instance, a drug that inhibits fibrosis (e.g., by targeting transforming growth factor-beta pathways) or breaks down existing scar tissue could have been co-administered. This combination would have maintained a healthier cochlear environment, allowing regenerated hair cells to thrive and function properly. By preventing or reversing fibrosis, the therapy could have ensured that structural restoration translated into functional hearing gains.

---

4. Targeted Patient Selection for Maximum Efficacy
Hearing loss varies widely in cause, severity, and progression, and the real trials included a broad patient population, which may have diluted the drugs' effects. Not all patients may have had the biological capacity to respond to regenerative therapy.
How it could have succeeded: Advanced diagnostic tools, such as genetic screening or cochlear imaging, could have identified patients most likely to benefit—those with active progenitor cells (the target of the drugs) or minimal fibrotic damage. For example, patients with recent-onset hearing loss or specific genetic profiles that enhance regenerative potential could have been prioritized. By focusing on this responsive subgroup, the trials could have demonstrated significant hearing restoration, even if the drugs weren't effective for everyone.

---

5. Enhanced Biological Activity for Human-Specific Challenges
FX-322 and FX-345 are small-molecule drugs that activate progenitor cells to regenerate hair cells, a process that works well in animal models. However, human cochlear biology may involve additional barriers, such as inhibitory signals or less responsive supporting cells, that weren't fully addressed.
How it could have succeeded: The drugs could have been reformulated to tackle these human-specific challenges. For instance, they might have included compounds to neutralize inhibitory factors (e.g., proteins that suppress regeneration) or to boost the activity of supporting cells, which play a key role in hair cell development. This dual-action approach—stimulating progenitor cells while optimizing the cochlear microenvironment—could have maximized hair cell regeneration and ensured the new cells connected properly to the auditory nerve, restoring hearing function.

---

6. Refined Trial Design and Sensitive Outcome Measures
In the actual trials, success hinged on speech perception, a complex measure that depends not just on cochlear hair cells but also on auditory nerve and brain processing. This may have masked subtle improvements in hair cell regeneration. Patient variability and short follow-up times further complicated the results.
How it could have succeeded: The trials could have used more sensitive and specific outcome measures, such as extended high-frequency audiometry (to detect changes across all cochlear regions) or electrophysiological tests (e.g., auditory brainstem response) to confirm hair cell activity. Stricter inclusion criteria—excluding patients with severe nerve damage or inconsistent baseline hearing—would have reduced noise in the data. A longer follow-up period would have captured delayed improvements, proving the drugs' efficacy in restoring hearing over time.

---

A Successful Scenario in Action
Imagine a clinical trial where:

• Patients with recent noise-induced hearing loss and minimal fibrosis are selected using genetic and imaging biomarkers.
• FX-322 and FX-345 are delivered via a nanoparticle gel that releases the drugs steadily over weeks, penetrating the entire cochlea.
• An anti-fibrotic drug is co-administered, keeping the cochlear tissue flexible and receptive to regeneration.
• Over 6 months, patients undergo detailed audiometric and electrophysiological testing, revealing significant improvements in hearing across all frequencies.

In this scenario, the drugs regenerate hair cells throughout the cochlea, fibrosis is prevented or reversed, and the new hair cells integrate with the auditory system, fully restoring natural hearing. Patients report clearer speech understanding and a return to normal sound perception, validated by objective tests.

---

Conclusion
For FX-322 and FX-345 to have succeeded in clinical trials, they could have overcome their real-world shortcomings through:

• Deeper cochlear penetration via advanced delivery systems.
• Sustained dosing and longer follow-up to allow full regeneration.
• Anti-fibrotic combination therapy to address cochlear fibrosis.
• Targeted patient selection to focus on likely responders.
• Enhanced drug design to tackle human-specific barriers.
• Better trial methods to detect subtle but meaningful improvements.

By integrating these changes, the drugs could have regenerated hair cells effectively, restored hearing comprehensively, and solved the problem of cochlear fibrosis, transforming them into groundbreaking treatments for hearing loss. While this didn't happen in reality, this scenario highlights the potential adjustments that could pave the way for future successes in regenerative ear therapies."

 

[Joeseph Stope]

I used Grok AI's "Think" feature to generate possible solutions for how FX-322 and FX-345 could have succeeded instead of failed. Maybe AI can help accelerate the development of these types of cures and lead to future trials starting sooner, rather than taking over ten years.

Careful there! You might be causing a lot of people in supervisory positions to go red in the face, or worse.

All those research hours, all that time, effort, and sweat.

Just kidding. It's about time the discussion of "What went wrong, what went right?" made its way down to our level.

I'm sure the scientists at Frequency Therapeutics worked through the scenarios a long time ago. As far as I remember, their explanation was that although they had the right mixture to do the job, when they injected it into the cochlea, it did not reach the areas responsible for frequencies below 8,000 kHz. Is that correct? Most tinnitus seems to occur around 6,000 or so. Please correct me if I'm wrong.

Taking a layperson's perspective, if your AI-generated explanation is accurate, meaning the mixture failed due to fibrosis (scarring) of the Organ of Corti, then surely, as you suggested, this could be tested by delivering FX-322 to acute or early onset patients to see if it works.

What went wrong, what went right, and how can things be improved? Those are the real questions. We're getting there.

 

[fletchermunson]

Stem cell study uncovers shared genes for hearing and vision repair

If discoveries like this are made and could make FX-322 or FX-345 functional, is there anyone out there who could bring it back and try again? Or is it legally buried forever?