Frequency Therapeutics — Hearing Loss Regeneration

[tommyd87]

Dosage details for FX-322's Phase 1: https://clinicaltrials.gov/ct2/show/NCT03616223

Excluding the placebo, they had a single dose for 16 patients: eight had low dose and eight had high dose.

For specific word scores, it's here: https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1

Excluding the placebo, they reported 15 patients even though clinical trials detailed a total of 16. Perhaps one patient discontinued for whatever reasons. The graph in the above frequencytx.com's link show word scores for all 6 patients with a dashed line demarcating the 4/6 patients that they think is significant. If someone says there's only 3/4 remaining significant, I wonder which patient became insignificant then...

@tommyd87 The above link does show word scores so you were right.

The interesting information from that graph is that two people both had the same score increase in word recognition, however only one of them was statistically significant. I actually get the logic as one of them improved by over 100% while the other one only improved by 37%.

Thus it is demonstrating that the treatment is working with all patients, however it is also demonstrating that someone doesn't need to improve by a statistically significant amount to show benefit.

Thus I wonder whether we learn over time that while some people do not show a statistically significant improvement in a trial situation, they do show a significant improvement in a treatment situation when they have been exposed to the required amount of treatment to gain the best results.

This is because as more is learnt about FX-322 we may find that some people hypothetically need five doses before they will show a statistically significant improvement while others actually only need one. Yet it is clear that the person from phase one with the clearly defined defined statistically insignificant improvement definitely benefitted from the medication.

Therefore, I strongly believe there are limitations in simply seeking to determine the validity of results from a statistically significant position in a trial. This is especially relevant when the dose is small.

What did you mean by "I got 6 right but I needed 8"? Are you referring to word scores count?

I'm so sorry you couldn't get in. To be honest, all these delays do not inspire confidence but it could just be me and many sufferers are already depressed and cynical about past companies being failures and even worst scams. Only thing we can do is just hope they're sincere in making money by delivering a legit product.

we know frequency is set up as a for profit firm. However we also know that Frequency has been very keen and very open in their aims to genuinely assist people and also has been very transparent throughout the process.

While these delays might be irritating to some and also may not make people feel confident for reasons like stringing you along, I think it is actually the opposite.

Frequency is trying to complete the trials properly and actually deliver the best information possible about the medications effectiveness to stakeholders. Some (including myself) might be more concerned if they shortcut the process to get something out which then turned out to inaccurately reflect the results of trials. Or furthermore if the treatment was substandard stuff when being used as a treatment.

This is exactly the concern currently had with Russia's coronavirus vaccine. Various bodies such as WHO and foreign regulators like PBS in Aus think that it has been rushed and not been proven to work well enough and more importantly to be safe as yet. Thus I think Frequency has made the right choice.

 

[serendipity1996]

What did you mean by "I got 6 right but I needed 8"? Are you referring to word scores count?

I'm so sorry you couldn't get in. To be honest, all these delays do not inspire confidence but it could just be me and many sufferers are already depressed and cynical about past companies being failures and even worst scams. Only thing we can do is just hope they're sincere in making money by delivering a legit product.

Yeah, I get you although I think it's useful to distinguish between failures and 'scams.' Failure is an inevitable risk when developing new drugs and it remains to be seen whether Frequency can pass all the remaining hurdles although I am encouraged by their progress so far. But I really don't think Frequency or any of these other hearing regeneration companies are pulling a Theranos on us and actively deceiving by creating a bunk product. Especially to have got this far and demonstrated evidence of hearing improvement for which there is no placebo or anything. That would be like Theranos 2.0.

 

[Piney]

I was told by the ENT directly because I missed two words. I am a Cochlear Candidate but not really, even though they are approved for single-sided deafness the doctors at UPenn said it would provide me no value since my other ear is good.

Has anyone here been in the FX-322 trial or attempted to enroll for it?

 

[Lucifer]

Yeah, I get you although I think it's useful to distinguish between failures and 'scams.' Failure is an inevitable risk when developing new drugs and it remains to be seen whether Frequency can pass all the remaining hurdles although I am encouraged by their progress so far. But I really don't think Frequency or any of these other hearing regeneration companies are pulling a Theranos on us and actively deceiving by creating a bunk product. Especially to have got this far and demonstrated evidence of hearing improvement for which there is no placebo or anything. That would be like Theranos 2.0.

I also don't think it's a scam, or how did those patients have improved word scores after they got the FX-322 injection. The likelihood of the clinical trial centers increasing the volume of the hearing test is low.

Surely the OHCs, IHCs and synapses were regrown to allow the patients to hear better and to reduce their tinnitus. Even Carl LeBel stated some of the patients reported their tinnitus reducing therefore these hair cells and synapses must have been regrown to allow this to happen.

 

[jeff W]

It makes me wonder why evolution gave us the ability to hear all the way up to 18-20 kHz when we are young.

Why indeed!

 

[Billy_Shears]

I was told by the ENT directly because I missed two words. I am a Cochlear Candidate but not really, even though they are approved for single-sided deafness the doctors at UPenn said it would provide me no value since my other ear is good.

Has anyone here been in the FX-322 trial or attempted to enroll for it?

I attempted to enroll but my NIHL and audiogram is from only three months ago. They want six months that defines 'stable'. I was told all else was acceptable and that if they're still recruiting in November they would call me. Frequency should have Phase 2a wrapped up by mid October. I plan on going for Phase III in late 2021 - I hope, and if I do, I hope I do not get a placebo!

 

[tommyd87]

I also don't think it's a scam, or how did those patients have improved word scores after they got the FX-322 injection. The likelihood of the clinical trial centers increasing the volume of the hearing test is low.

Surely the OHCs, IHCs and synapses were regrown to allow the patients to hear better and to reduce their tinnitus. Even Carl LeBel stated some of the patients reported their tinnitus reducing therefore these hair cells and synapses must have been regrown to allow this to happen.

When it comes to hearing, you either hear or you don't.

The previous discussion was related to testing hearing, however there is no way Frequency Therapeutics could have amended the testing requirements without crushing the robustness of their results.

 

[serendipity1996]

Is a cochlear 'dead region' the same as flat epithelium?

 

[WillBeNimble]

I attempted to enroll but my NIHL and audiogram is from only three months ago. They want six months that defines 'stable'. I was told all else was acceptable and that if they're still recruiting in November they would call me. Frequency should have Phase 2a wrapped up by mid October. I plan on going for Phase III in late 2021 - I hope, and if I do, I hope I do not get a placebo!

They announced a delay till 2021 for data because of difficulty getting candidates due to COVID-19. You might still get a shot at being in the phase 2a.

 

[FGG]

Is a cochlear 'dead region' the same as flat epithelium?

From what i understand (correct me if I'm wrong), a "cochlear dead region" is defined as missing significant IHCs, thus hearing aids won't help (even if the audiogram isn't as bad). It doesn't necessarily mean flat epithelial.

 

[Diesel]

It's good to see Frequency is presenting how FX-322 will benefit ENT and Audiologist practices in the future. When FX-322 is commercialized, there will no doubt be a change to how ENT/Audiologist practices operate. I believe hearing care will transition to a routine-service model like we (in the US) see with Dentists and Optometrists.

Frequency has identified that they will need to lead this change in the ENT/Audiologist business model to support a more maintenance-driven business model. Also, to support considerable potential growth in the "Hearing Servicing" space (it may not be considered Hearing-loss anymore... who knows).

It's also good to see that they're transitioning some focus to commercialization of the drug mid-way through the Phase 2A. Promising news.

 

[Reinier]

I love these computer animations. (The one Jeff W posted). They can be so clarifying.

 

[tommyd87]

It's good to see Frequency is presenting how FX-322 will benefit ENT and Audiologist practices in the future. When FX-322 is commercialized, there will no doubt be a change to how ENT/Audiologist practices operate. I believe hearing care will transition to a routine-service model like we (in the US) see with Dentists and Optometrists.

Frequency has identified that they will need to lead this change in the ENT/Audiologist business model to support a more maintenance-driven business model. Also, to support considerable potential growth in the "Hearing Servicing" space (it may not be considered Hearing-loss anymore... who knows).

It's also good to see that they're transitioning some focus to commercialization of the drug mid-way through the Phase 2A. Promising news.

View attachment 40184

Frequency will have to instigate this themselves. This tends to be the time where the mainstays might attempt to cause disruption. I do think there might be some limitations in terms of where you can get this initially unfortunately.

 

[Jim51042]

Sorry if I missed this but did Frequency release a before and after test subject audiograms for the 8 kHz-20 kHz range? Personally, I'd love to see a large data set (say 800 patients) of before and after audiograms, particularly for the 13 kHz-20 kHz range.

 

[Rubenslash]

Frequency will have to instigate this themselves. This tends to be the time where the mainstays might attempt to cause disruption. I do think there might be some limitations in terms of where you can get this initially unfortunately.

Might be but I would travel to any place in the world if it could give me some relieve and improved hearing.

 

[Thuan]

Sorry if I missed this but did Frequency release a before and after test subject audiograms for the 8 kHz-20 kHz range? Personally, I'd love to see a large data set (say 800 patients) of before and after audiograms, particularly for the 13 kHz-20 kHz range.

Phase 1 involved 15 patients and they only did standard hearing tests up to 8 kHz with only 4/15 patients showing more than 10 dB improvements at 8 kHz. But no, they did not post full audiogram results for all patients.

https://investors.frequencytx.com/static-files/6d161090-16f5-49f4-9606-8caceb5a88a1

 

[FGG]

Sorry if I missed this but did Frequency release a before and after test subject audiograms for the 8 kHz-20 kHz range? Personally, I'd love to see a large data set (say 800 patients) of before and after audiograms, particularly for the 13 kHz-20 kHz range.

Will be released 2nd quarter of 2021 (delayed due to COVID-19).

 

[Thuan]

I really hope that FX-322 has at least some success and show investors the potential viability and the billion dollar market that will spur other companies and researchers to get seriously into figuring this problem out.

 

[FGG]

I really hope that FX-322 has at least some success and show investors the potential viability and the billion dollar market that will spur other companies and researchers to get seriously into figuring this problem out.

Something to consider along with this is that even if Frequency had been funded by Jeff Bezos, they couldn't have developed FX-322 until Jeff Karp discovered the potential of Lgr5+ cells in the small intestine (where they are plentiful and lead to very high mucosal cell turnover there naturally), which then prompted him to look elsewhere in the body for them and figure out when and where the signaling is turned off.

I bring this up because a lot of scientific advancement is due to chance discoveries that *then* researchers build on to get whole paradigm shifts (as in here). Penicillin is a famous historical example that preceded an explosion of antibiotics and other antimicrobials.

Anyway, this is why government funding of basic science is so important. After a eureka discovery that has market potential, getting investors is usually no problem but it's getting to that point that needs the most funding.

I realize both public and private funding is vitally important but throwing money at specific hearing research wouldn't have likely gotten anyone to look to the small intestine for help.

 

[GlennS]

Something to consider along with this is that even if Frequency had been funded by Jeff Bezos, they couldn't have developed FX-322 until Jeff Karp discovered the potential of Lgr5+ cells in the small intestine (where they are plentiful and lead to very high mucosal cell turnover there naturally), which then prompted him to look elsewhere in the body for them and figure out when and where the signaling is turned off.

I bring this up because a lot of scientific advancement is due to chance discoveries that *then* researchers build on to get whole paradigm shifts (as in here). Penicillin is a famous historical example that preceded an explosion of antibiotics and other antimicrobials.

Anyway, this is why government funding of basic science is so important. After a eureka discovery that has market potential, getting investors is usually no problem but it's getting to that point that needs the most funding.

I realize both public and private funding is vitally important but throwing money at specific hearing research wouldn't have likely gotten anyone to look to the small intestine for help.

This is what I've been saying in response to those here who can really get angry ranting about a lack of R&D money. Money does not directly translate into innovation. Look at how much money has been dumped into nuclear fusion, for instance, with nothing to show for it. Some things are damn hard.

 

[Billy_Shears]

Will be released 2nd quarter of 2021 (delayed due to COVID-19).

Actually, Frequency Therapeutics is nearly right on target with a said completion of Phase 2a early in the 4th Quarter - just a day or a few after September 30. The 2nd quarter of 2021 would be the normal length of time to gather the factual data and present its findings. It is both admirable and appreciated that they have accomplished this huge task with minimal interference from the coronavirus.

 

[sssing]

I'm worried about the delay... Is there some bad news from the trial results? Maybe I'm thinking too much into it? Frankly, the the Audion and Susan Shore delays have made me wary and a bit scared, I am worried it's going to be like that, some vague excuse...

 

[FGG]

This is what I've been saying in response to those here who can really get angry ranting about a lack of R&D money. Money does not directly translate into innovation. Look at how much money has been dumped into nuclear fusion, for instance, with nothing to show for it. Some things are damn hard.

Thankfully, biological problems are in general a lot more solvable than nuclear fusion but people clamor for funding for step 4 without realizing funding for basic science (step 1) is just as important.

 

[FGG]

Actually, Frequency Therapeutics is nearly right on target with a said completion of Phase 2a early in the 4th Quarter - just a day or a few after September 30. The 2nd quarter of 2021 would be the normal length of time to gather the factual data and present its findings. It is both admirable and appreciated that they have accomplished this huge task with minimal interference from the coronavirus.

They are still recruiting. The extra time isn't just for data compiling.

 

[serendipity1996]

I'm worried about the delay... Is there some bad news from the trial results? Maybe I'm thinking too much into it? Frankly, the the Audion and Susan Shore delays have made me wary and a bit scared, I am worried it's going to be like that, some vague excuse...

In light of COVID-19, it is not surprising that they have had to delay their initial timeframe and as FGG has said, they are still recruiting. I can imagine that it's the same with other ongoing clinicial trials. I very very much doubt that they are doing this to somehow cover up bad news.

 

[BBakkers]

So Frequency Therapeutics is stating the following:

• "Later this year the Company plans to commence a safety study of FX-322 in patients with age-related hearing loss, and also is evaluating other potential studies."

• "Planning for near-term studies in additional patient populations."

What could these studies be? Any idea? Besides the age-related thingy of course.

 

[Jurger]

So Frequency Therapeutics is stating the following:

• "Later this year the Company plans to commence a safety study of FX-322 in patients with age-related hearing loss, and also is evaluating other potential studies."

• "Planning for near-term studies in additional patient populations."

What could these studies be? Any idea? Besides the age-related thingy of course.

Perhaps ototoxicity and patients with severe and profound hearing loss, regardless of the cause of the hearing loss. Lucchino once stated he hoped the drug could help cochlear implant candidates (meaning severe and profound hearing loss).

 

[Diesel]

So Frequency Therapeutics is stating the following:

• "Later this year the Company plans to commence a safety study of FX-322 in patients with age-related hearing loss, and also is evaluating other potential studies."

• "Planning for near-term studies in additional patient populations."

What could these studies be? Any idea? Besides the age-related thingy of course.

I suspect specific groups that are outside of the Phase 2A acceptance criteria. Ie: profound hearing loss, normal audiogram but have speech-in-noise difficulty, tinnitus with normal audiogram, who knows... hyperacusis...

Frequency Therapeutics has noted how selective they've been to get a consistent patient group in the Phase 2A. This leads me to believe that they also have a lot of data on patients that were not accepted. This makeup of "rejected" participants represents one or more cross-sections of the real-world population. The more data that the firm can collect on the benefit that FX-322 may provide these other groups, the better they can inform/prepare ENTs.

I find the ability for FX-322 to address age-related hearing loss (which is now really just SNHL according to the recent study) really interesting. This is probably the easiest way to help most understand how FX-322 treat a well known problem.

 

[BBakkers]

Nevermind my former post, at 1:00:45 during the Tinnitus Talk Podcast interview you can hear Carl LeBel stating the possible two additional patient testing groups. Mystery solved.

• Age-related hearing loss, younger than 65 with no evidence of extensive noise exposure
• Ototoxicity group, common cancer chemo therapy & hearing loss because off aminoglycosides

Perhaps they will add more, who knows. Can't think of any though.

 

[Emgee]

Anyone think FX-322 or regenerative medicine may help with Tonic Tensor Tympani Syndrome (TTTS)?

I know it's primarily a middle-ear issue, but could it have any relationship with inner-ear damage?