Frequency Therapeutics — Hearing Loss Regeneration

#10,921
Carl LeBel said the phase 3 can take anywhere from 1-3 years. So worst case would be 2024.

Praying that isn't the case and the results are good enough to be granted Breakthrough Therapy drug designation. Or that they make it available through the Right to Try laws.

The next 6 months are so important. I can't stress that enough to anyone suffering from hearing loss and tinnitus. I will be nervously anticipating the results in April/May next year.
 
#10,922
Paulmanlike said:
These dates for 2022-23 appear very optimistic. I was under the impression it would be more like 2026-2027. The reason being is that it only went through phase 1 at the end of 2017 and on average it takes what 10 years to get through clinical trials.

Also for phase 3, it requires hundreds of patients and recruiting them won't be easy. How many people are available and willing to get an unknown drug injected to them this early on - even with good preliminary data?

Not to mention it will cost millions of pounds - how are they going to fund it? Or will Astellas be funding it, haven't Frequency Therapeutics got a deal for them to fund milestone payments?
Click to expand...
TIMELINE: Let's look at the Clinical Trial timeline for FX-322 and see what we can learn:

Phase 1 :
- Started: 2017.10
- Ended: 2018.04

Phase 1/2:
- Started: 2018.07
- Ended: 2019.04

Phase 2A:
- Started: 2019.09
- Ending: 2021.04 (Assumed)

ESTIMATED DURATION SO FAR: 3 years, 6 months.

First, the "average" of 10 years needs a little scrutiny. It assumes the start of the first Clinical Trial, and the Final Approval for release of the drug. Based on some of the googling I've done to understand this number, it generally references drugs relating to conditions like cancer, heart disease, etc, that take a long time to recruit and require a long time to reserve. It appears that the overall range driving that average is 5 years to 14 years.

Many of these trials have multi-year Phase 2s (3+ years) along with multi-year Phase 3s (3-7+ years).

Looking at the current duration of the FX-322 trials that we know about; and comparing them to what makes up the "10 Year" average in other trials, by breaking them down into their phases; it's hard to see the entire series of FX-322 clinical trials being above that average.

Carl LeBel also noted that FX-322 would likely undergo on "the shorter side" of Phase 3 trials; since the drug simply doesn't require a multi-year observation period. As we've seen from the Phase 1/2, improvements become significant after 90 days.

So I think it stands to reason, that FX-322 based on the data above is probably pacing towards 8 years in total duration, placing the final approval around 2025.

REASONS FOR OPTIMISM:

"WHAT ABOUT BREAKTHROUGH THERAPY DESIGNATION?" You all might be asking...

In my opinion, it's highly likely that FX-322 will be applicable for Breakthrough Therapy Designation if the Phase 2A can replicate what was seen in the Phase 1/2. Based on the FDA's website for the criteria that a drug must meet to receive Breakthrough Therapy Designation, it was already achieved in the Phase 1/2; and validated in the long-term study.

There are only a few articles/studies on how Breakthrough Therapy Designation reduce the "time to market" for drugs. Of those that I have found through googling (again, focusing on cancer):

What Does Breakthrough Therapy Designation Really Mean For My Company?

One "research" article that I found a while back that can't seem to find now showed that Fast Track and Breakthrough Therapy Designations typically reduced released time for any drug by 2 years.

So, based on my above assessment of 8 years above, Breakthrough Therapy Designation would shorten the release time to 6-years from the Phase 1 start; placing the release year at 2023.

THE PHASE 3 WILL BE WORLDWIDE, AND ASTELLAS IS FOOTING THE BILL:

Frequency Therapeutics and Astellas are going to partner on a multi-country Phase 3. This is written in their 10-K documentation on their website. This will enable greater access to patients and reduce recruiting time, it's also highly likely that Frequency Therapeutics will continue to partner with the same testing sites stateside.

I have reason to believe that Frequency Therapeutics may modify their acceptance criteria for the Phase 3 so that more patients can participate. At this point; they're looking for adverse reactions more than hitting high efficacy targets, like in the Phase 2A. Again, a bigger market.

Also, if the Phase 2A doesn't produce any adverse events; participants in the Phase 3 will already be aware of the low-risk, and the potential benefit from participating. From what I have seen, when there are major adverse events in any phase of a trial, it is halted immediately. We haven't seen that at all with FX-322.

Bottom line: I don't see recruiting for Phase 3 being a huge concern.
 
#10,923
Diesel said:
TIMELINE: Let's look at the Clinical Trial timeline for FX-322 and see what we can learn:

Phase 1 :
- Started: 2017.10
- Ended: 2018.04

Phase 1/2:
- Started: 2018.07
- Ended: 2019.04

Phase 2A:
- Started: 2019.09
- Ending: 2021.04 (Assumed)

ESTIMATED DURATION SO FAR: 3 years, 6 months.

First, the "average" of 10 years needs a little scrutiny. It assumes the start of the first Clinical Trial, and the Final Approval for release of the drug. Based on some of the googling I've done to understand this number, it generally references drugs relating to conditions like cancer, heart disease, etc, that take a long time to recruit and require a long time to reserve. It appears that the overall range driving that average is 5 years to 14 years.

Many of these trials have multi-year Phase 2s (3+ years) along with multi-year Phase 3s (3-7+ years).

Looking at the current duration of the FX-322 trials that we know about; and comparing them to what makes up the "10 Year" average in other trials, by breaking them down into their phases; it's hard to see the entire series of FX-322 clinical trials being above that average.

Carl LeBel also noted that FX-322 would likely undergo on "the shorter side" of Phase 3 trials; since the drug simply doesn't require a multi-year observation period. As we've seen from the Phase 1/2, improvements become significant after 90 days.

So I think it stands to reason, that FX-322 based on the data above is probably pacing towards 8 years in total duration, placing the final approval around 2025.

REASONS FOR OPTIMISM:

"WHAT ABOUT BREAKTHROUGH THERAPY DESIGNATION?" You all might be asking...

In my opinion, it's highly likely that FX-322 will be applicable for Breakthrough Therapy Designation if the Phase 2A can replicate what was seen in the Phase 1/2. Based on the FDA's website for the criteria that a drug must meet to receive Breakthrough Therapy Designation, it was already achieved in the Phase 1/2; and validated in the long-term study.

There are only a few articles/studies on how Breakthrough Therapy Designation reduce the "time to market" for drugs. Of those that I have found through googling (again, focusing on cancer):

What Does Breakthrough Therapy Designation Really Mean For My Company?

One "research" article that I found a while back that can't seem to find now showed that Fast Track and Breakthrough Therapy Designations typically reduced released time for any drug by 2 years.

So, based on my above assessment of 8 years above, Breakthrough Therapy Designation would shorten the release time to 6-years from the Phase 1 start; placing the release year at 2023.

THE PHASE 3 WILL BE WORLDWIDE, AND ASTELLAS IS FOOTING THE BILL:

Frequency Therapeutics and Astellas are going to partner on a multi-country Phase 3. This is written in their 10-K documentation on their website. This will enable greater access to patients and reduce recruiting time, it's also highly likely that Frequency Therapeutics will continue to partner with the same testing sites stateside.

I have reason to believe that Frequency Therapeutics may modify their acceptance criteria for the Phase 3 so that more patients can participate. At this point; they're looking for adverse reactions more than hitting high efficacy targets, like in the Phase 2A. Again, a bigger market.

Also, if the Phase 2A doesn't produce any adverse events; participants in the Phase 3 will already be aware of the low-risk, and the potential benefit from participating. From what I have seen, when there are major adverse events in any phase of a trial, it is halted immediately. We haven't seen that at all with FX-322.

Bottom line: I don't see recruiting for Phase 3 being a huge concern.
Click to expand...
100% agree. Carl LeBel specifically contrasted their phase 3 timeline to, for example, cardiac drugs and pointed out that, since FX-322 is not subject to placebo hearing improvements (which are not possible), they don't need 1000's of patients and their timeline would be shorter. Also, as you mentioned, they don't have to be followed for as long.

In this context, it is not a good estimating metric to use the "average" across the pharmaceutical field.
 
#10,924
FGG said:
100% agree. Carl LeBel specifically contrasted their phase 3 timeline to, for example, cardiac drugs and pointed out that, since FX-322 is not subject to placebo hearing improvements (which are not possible), they don't need 1000's of patients and their timeline would be shorter. Also, as you mentioned, they don't have to be followed for as long.

In this context, it is not a good estimating metric to use the "average" across the pharmaceutical field.
Click to expand...
Agreed. I didn't get into details in my post above, there are other time-factors to consider that positively affect the timeline.

First, over the past two decades, clinical trials have been getting shorter. It appears some point to better pre-clinical research leading to the reduction. FX-322 seems to apply here.

Breakthrough Therapy Designation is also relatively new, but it seems the FDA is increasing use of the designation each year.

It's possible that we may see the "Promising Pathways Act" reach the executive office. This bill would enable Frequency Therapeutics to begin producing FX-322 for end-patient use immediately after the Phase 2A. Obviously still a long-shot there, but as long as COVID-19 is at the forefront, the FDA will continue to get extra priority.
 
#10,925
Jurger said:
I'm not expecting any information on the trial results until they are fully released.

Maybe they'll announce the final dosage of the last patients. I do hope we'll see some more information on what they will do with the private placement funds. A couple of months ago they said something about further research into FX-322 and the severity of the hearing loss it can treat. Still hoping for that reformulation or partnership with Otomagnetics or something.
Click to expand...
I think that all of the above will inevitably happen. Frequency Therapeutics has stated that they are going to be looking at conducting side work to understand the benefits of dosing on other patient groups.

I have got a good feeling that they will also eventually do something with dosing, however this will not happen I think until after FX-322 is released and would be put on the back burner for now.
 
#10,926
Thanks for your well informed rationale @Diesel, this has given me great hope.

I'm hoping Otonomy's OTO-413 can get through at a similar rate too, and be successful.

My problem has always been tinnitus, my hearing loss, although it showed a loss on one audiogram and was fine on another, is not something that bothers me, but the tinnitus is insane at times. Really intrusive. Although thankfully I don't have a multitude of tones, hissing and electrical noises.

How realistic do you think it is that, FX-322 and OTO-413 will be able to fully recover a person's hearing and/or banish tinnitus?

I mean what if it helps 20% of tinnitus sufferers and it costs thousands, that'll be like facing another Lenire situation, pay for something with no guarantee it will work.

It's encouraging but I've followed tinnitus research for years and it always starts good and ends badly. Sadly it's just something I'm used to by now.
 
#10,927
Diesel said:
TIMELINE: Let's look at the Clinical Trial timeline for FX-322 and see what we can learn:

Phase 1 :
- Started: 2017.10
- Ended: 2018.04

Phase 1/2:
- Started: 2018.07
- Ended: 2019.04

Phase 2A:
- Started: 2019.09
- Ending: 2021.04 (Assumed)

ESTIMATED DURATION SO FAR: 3 years, 6 months.

First, the "average" of 10 years needs a little scrutiny. It assumes the start of the first Clinical Trial, and the Final Approval for release of the drug. Based on some of the googling I've done to understand this number, it generally references drugs relating to conditions like cancer, heart disease, etc, that take a long time to recruit and require a long time to reserve. It appears that the overall range driving that average is 5 years to 14 years.

Many of these trials have multi-year Phase 2s (3+ years) along with multi-year Phase 3s (3-7+ years).

Looking at the current duration of the FX-322 trials that we know about; and comparing them to what makes up the "10 Year" average in other trials, by breaking them down into their phases; it's hard to see the entire series of FX-322 clinical trials being above that average.

Carl LeBel also noted that FX-322 would likely undergo on "the shorter side" of Phase 3 trials; since the drug simply doesn't require a multi-year observation period. As we've seen from the Phase 1/2, improvements become significant after 90 days.

So I think it stands to reason, that FX-322 based on the data above is probably pacing towards 8 years in total duration, placing the final approval around 2025.

REASONS FOR OPTIMISM:

"WHAT ABOUT BREAKTHROUGH THERAPY DESIGNATION?" You all might be asking...

In my opinion, it's highly likely that FX-322 will be applicable for Breakthrough Therapy Designation if the Phase 2A can replicate what was seen in the Phase 1/2. Based on the FDA's website for the criteria that a drug must meet to receive Breakthrough Therapy Designation, it was already achieved in the Phase 1/2; and validated in the long-term study.

There are only a few articles/studies on how Breakthrough Therapy Designation reduce the "time to market" for drugs. Of those that I have found through googling (again, focusing on cancer):

What Does Breakthrough Therapy Designation Really Mean For My Company?

One "research" article that I found a while back that can't seem to find now showed that Fast Track and Breakthrough Therapy Designations typically reduced released time for any drug by 2 years.

So, based on my above assessment of 8 years above, Breakthrough Therapy Designation would shorten the release time to 6-years from the Phase 1 start; placing the release year at 2023.

THE PHASE 3 WILL BE WORLDWIDE, AND ASTELLAS IS FOOTING THE BILL:

Frequency Therapeutics and Astellas are going to partner on a multi-country Phase 3. This is written in their 10-K documentation on their website. This will enable greater access to patients and reduce recruiting time, it's also highly likely that Frequency Therapeutics will continue to partner with the same testing sites stateside.

I have reason to believe that Frequency Therapeutics may modify their acceptance criteria for the Phase 3 so that more patients can participate. At this point; they're looking for adverse reactions more than hitting high efficacy targets, like in the Phase 2A. Again, a bigger market.

Also, if the Phase 2A doesn't produce any adverse events; participants in the Phase 3 will already be aware of the low-risk, and the potential benefit from participating. From what I have seen, when there are major adverse events in any phase of a trial, it is halted immediately. We haven't seen that at all with FX-322.

Bottom line: I don't see recruiting for Phase 3 being a huge concern.
Click to expand...
I would note that phase 3 tends to be the quickest of all the phases because basically there is less scrutiny over what is happening because they don't need to prove dosing or the effectiveness of the medicine as stringently as in the previous phases.
 
#10,928
Paulmanlike said:
These dates for 2022-23 appear very optimistic. I was under the impression it would be more like 2026-2027. The reason being is that it only went through phase 1 at the end of 2017 and on average it takes what 10 years to get through clinical trials.

Also for phase 3, it requires hundreds of patients and recruiting them won't be easy. How many people are available and willing to get an unknown drug injected to them this early on - even with good preliminary data?

Not to mention it will cost millions of pounds - how are they going to fund it? Or will Astellas be funding it, haven't Frequency Therapeutics got a deal for them to fund milestone payments?
Click to expand...
The 10 to 15 year time frame is predominantly for medicines from the start of their development, through their research in a lab, through their IND filing and through the clinical trials.

This tends to get reduced somewhat if a pharmaceutical company gets it Fast Tracked by the FDA, approximately from 10-15 years to 7-10 years.

Obviously at this stage this rule isn't hard and fast and depending on what happens it can take more or less time too.
 
#10,931
tommyd87 said:
I would note that phase 3 tends to be the quickest of all the phases because basically there is less scrutiny over what is happening because they don't need to prove dosing or the effectiveness of the medicine as stringently as in the previous phases.
Click to expand...
I thought phase 3 was the longest.

Have you got evidence or sufficient knowledge for that comment?

I want to be well informed.

I thought phase 3 was the longest, being that it requires more candidates. Lots more.
 
#10,932
Joly said:
Will there be a phase 2B?
Click to expand...
I thought the phase 2a was sort of preliminary trial just to confirm there was more evidence before spending millions on a proper phase 2. But going on the comments it appears Frequency Therapeutics has little room for placebo effects. How can one have placebo hearing gains?

I'm also curious as to how they're going to measure tinnitus. Presumably TFI, which is highly susceptible to placebo. Unlike Hough Ear Institute who claim to have an objective way of measuring it, but don't state how.

How will Frequency Therapeutics be sure it lowers tinnitus?

Go to the Lenire results, and tinnitus trials in the past, the placebo effect is very high in a subjective condition like tinnitus. They're saying FX-322 is not a tinnitus drug, that is true, but it's obvious we are all counting on it to improve tinnitus.
 
#10,933
Paulmanlike said:
I thought the phase 2a was sort of preliminary trial just to confirm there was more evidence before spending millions on a proper phase 2. But going on the comments it appears Frequency Therapeutics has little room for placebo effects. How can one have placebo hearing gains?

I'm also curious as to how they're going to measure tinnitus. Presumably TFI, which is highly susceptible to placebo. Unlike Hough Ear Institute who claim to have an objective way of measuring it, but don't state how.

How will Frequency Therapeutics be sure it lowers tinnitus?

Go to the Lenire results, and tinnitus trials in the past, the placebo effect is very high in a subjective condition like tinnitus. They're saying FX-322 is not a tinnitus drug, that is true, but it's obvious we are all counting on it to improve tinnitus.
Click to expand...
Phase 2a is simply a label. They can choose to do a 2b, or move to Phase 3. The design of the trial and outcomes are what matter. Right it's dosing and efficacy, which if proven significant, the next phase will likely be the last.

Frequency Therapeutics will have to continue using TFI as their measure for tinnitus. As far as I know, it's the only tinnitus measurement that is accepted by clinicians, researchers, and the FDA. Any other "new" test would have to go through years of rigorous validation; and Frequency Therapeutics doesn't want to wait.

The TFI is unfortunately the best we have. It may be subject to some placebo effect; but you can be sure that patients who have a real and consistently noticeable reduction in tinnitus are much more likely to produce a lower score when compared to placebo.

One way Frequency Therapeutics will be more sure is by observing the 4 dosage cohorts as it relates to TFI. When compared to the placebo group, they may see a more dramatic reduction in TFI score as the dosage increases.

I think they'll also be able to draw a positive relationship between a patient's HF Audiogram threshold and TFI. So, as the cohorts see their HF PTA improve (say, from 70 dB to 20 dB), they see the TFI score drop similarly, ex: 50 to 10.
 
#10,934
Paulmanlike said:
I thought phase 3 was the longest.

Have you got evidence or sufficient knowledge for that comment?

I want to be well informed.

I thought phase 3 was the longest, being that it requires more candidates. Lots more.
Click to expand...
Agree. I can't think of a single example where phase 3 was the shortest.
 
#10,935
Paulmanlike said:
I thought the phase 2a was sort of preliminary trial just to confirm there was more evidence before spending millions on a proper phase 2. But going on the comments it appears Frequency Therapeutics has little room for placebo effects. How can one have placebo hearing gains?

I'm also curious as to how they're going to measure tinnitus. Presumably TFI, which is highly susceptible to placebo. Unlike Hough Ear Institute who claim to have an objective way of measuring it, but don't state how.

How will Frequency Therapeutics be sure it lowers tinnitus?

Go to the Lenire results, and tinnitus trials in the past, the placebo effect is very high in a subjective condition like tinnitus. They're saying FX-322 is not a tinnitus drug, that is true, but it's obvious we are all counting on it to improve tinnitus.
Click to expand...
Phase 2a is part of a phase 2 trial. Sometimes they are split up.

Phase 2a is set up to assess dosing. It sounds like they might do a combined 2b/3 since they indicated they wish to go pivotal next trial.

Per their ClinicalTrials.gov page:

"Tinnitus Assessment [ Time Frame: Screening to Day 210 ]
Measured by the Tinnitus Functional Index (TFI), with a scale ranging from 0 to 100 that defines severity categories based on 25 self-reported answers."

Frequency Therapeutics have stated on the Tinnitus Talk Podcast that TFI is the preferred index of the FDA.
 
#10,936
FGG said:
Agree. I can't think of a single example where phase 3 was the shortest.
Click to expand...
Well if you count COVID-19 vaccines, they are already in Phase 3 right now and they only started Phase 1 in the beginning of this year. If only FX-322 was that quick though.
 
#10,937
Lucifer said:
Well if you count COVID-19 vaccines, they are already in Phase 3 right now and they only started Phase 1 in the beginning of this year. If only FX-322 was that quick though.
Click to expand...
Right, phase 1 and 2 were shorter, which is what I was arguing.
 
#10,939
kiki said:
If the clinical trial in the next article is successful, will it affect Frequency Therapeutics?

Otonomy, Kyorin.

Frequency Therapeutic, Astellas.

Will Astellas work with us?

Otonomy Announces Exclusive License Agreement with Kyorin for Novel Compound in OTO-6XX Hearing Loss Program
Click to expand...
Will the above four companies work together?
Is it possible to collaborate to take advantage of each other?

Advantages of gel, advantages of progenitor cell activation, advantages of nerve treatment...
 
#10,940
Joly said:
Will there be a phase 2B?
Click to expand...
We don't know yet. They said the next Phase will be "pivotal", probably meaning the last Phase before application for approval. We do know they've agreed with Astellas to receive payments for a Phase 2b and Phase 3 in Europa/Asia.

If they change the delivery method/formulation I could see a Phase 2b. If not, there's a good chance they'll go straight to Phase 3.
 
#10,943
Lucifer said:
But isn't Phase 3 for COVID-19 vaccines going to be the same length of time as Phase 1 and 2? I thought results were coming out by the end of this month or so?
Click to expand...
Combined phase 1/2 for most vaccine candidates went from mid March to mid to July (4 months). Just Phase 3 will take that long or longer as thousands of patients are needed. It's still moving really fast though!
 
#10,944
Jurger said:
We don't know yet. They said the next Phase will be "pivotal", probably meaning the last Phase before application for approval. We do know they've agreed with Astellas to receive payments for a Phase 2b and Phase 3 in Europa/Asia.

If they change the delivery method/formulation I could see a Phase 2b. If not, there's a good chance they'll go straight to Phase 3.
Click to expand...
I still don't think that the delivery method would be changed prior to FDA's approval of FX-322 and its subsequent release. Provided that Frequency Therapeutics is obtaining the results using intratympanic injections which would be sufficient enough to get FX-322 to receive FDA approval, there is no reason to change the delivery/dosing mid trial. This would ultimately delay things further because there would be another 7-9 month delay until FX-322 is released.

Thus I really reckon that Frequency Therapeutics would focus on redosing/reformulating after the release of FX-322 because they can treat people who would benefit from the intratympanic injection method while they work out to fruther improve the effectiveness.
 
#10,945
tommyd87 said:
I still don't think that the delivery method would be changed prior to FDA's approval of FX-322 and its subsequent release. Provided that Frequency Therapeutics is obtaining the results using intratympanic injections which would be sufficient enough to get FX-322 to receive FDA approval, there is no reason to change the delivery/dosing mid trial. This would ultimately delay things further because there would be another 7-9 month delay until FX-322 is released.

Thus I really reckon that Frequency Therapeutics would focus on redosing/reformulating after the release of FX-322 because they can treat people who would benefit from the intratympanic injection method while they work out to fruther improve the effectiveness.
Click to expand...
Correct. The drug+delivery agent that's in the trials now is going to be what we get at the end of Phase 3. Even though it may not be what we all want, it's a HUGE step forward in terms of hearing restoration. And, there's a quantifiable market for the drug in its current site.

There would need to be a separate set of trials for a "2.0" with a revised goop to get it deeper in the ear; if that is even what the problem is (we really don't know, as they have never specifically said IIRC).

Bottom line: It's not going to be financially feasible to "restart" FX-322 mid-trials to change the delivery gel, and delay the release of a drug that already shows significant improvement in clinically meaningful ways that already has a ready market.
 
#10,946
kiki said:
Will the above four companies work together?
Is it possible to collaborate to take advantage of each other?

Advantages of gel, advantages of progenitor cell activation, advantages of nerve treatment...
Click to expand...
That would be in the best interest of patients, but there are various stakeholders where it wouldn't be in their best interests. Frequency Therapeutics are a business, they believe their approach is superior so why would they want to merge with their competitors if they want to capture the most market share?
 
#10,950
Christopher Loose disposes of almost half a million dollars worth of stock.

NOTE - these are automated sells and shouldnt be much concern, if any at all...
 

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