I've been reading the last bit of this thread. It's remarkable how much is based on wishful thinking. You would think FX-322 is about to be approved.
For background, I've been following Frequency since July 2016: (Inner Ear Hair Cell Regeneration — Maybe We Can Know More) I believe that is the first mention of Frequency on this site.
I've been quite disappointed at the lack of a follow-up paper to McLean et al (2017) - published over two years ago. For those who haven't read the paper, I summarize what they did in this post: Frequency Therapeutics — Hearing Loss Regeneration
In that post I also talk about things to look for in the "next" paper and things that I would expect would be in place before human trials. Since there hasn't been a "next" paper, we don't yet know what other pre-clinical data they have. I am still looking forward to see what is in the next paper.
I am still cautiously optimistic, though the balance has shifted from optimistic to cautiously. Below are some of my thoughts on where we are now.
1) The departure of Weber last year was a bigger deal than his going to Decibel this year. His going to Decibel makes sense though because Decibel is a hearing loss company while Frequency is a company built around a tool - it's just that the first thing they are using that tool on is hearing (It is notable that Weber is a Neurotologist (or at least did a fellowship in Neurotology) while Chin is an endocrinologist. Thus, I think Weber's departure said more about Frequency's expansion beyond hearing. (See below for more.)
2) Based on the paper from 2017, it seemed very unlikely that one injection would work so I am not concerned about multiple injections. I wouldn't read anything into the fact that they said it would be one injection in the past. I'm sure that is what they were hoping for, but they probably knew at the time that it was unlikely. (This is also why you should downplay anything said by anyone associated with a company - e.g., time lines, results, etc - unless it is in published paper or has already happened. Even if it is in a published paper, you need to read very carefully and pay attention to the quality of the journal. And a single paper doesn't prove anything by itself. Pay even less attention to press releases.)
3) The most important thing to keep in mind is that this is incredibly hard and more likely to fail than to be successful. The inner ear is singularly difficult to reach clinically, and the PCA technology itself is unproven even in much simpler settings. It's also the case that regenerating hair cells in adults is much harder than doing so in a petri dish or newborns - this is a constant theme across many studies. The idea that this is figured out and we somehow *know* that Frequency will be successful is wishful thinking not grounded in any publicly available knowledge - or at this point likely any privately available knowledge.
I've responded to a few things people have said or asked in the last few pages of the thread below.
It wasn't "just" a phase 1 study. The two dose levels was the phase 2 component of the trial. While they may have done hearing tests to look for TEAEs. The study is too small to provide useful information about efficacy.
It is a negative, but it is not surprising.The patent applications talked about the possibility of multiple treatments (though patent applications are written to be as broad as possible: they typically seem something like "in one embodiment, this invention uses one or more of 5 million different compounds that may be applied between 0 and an infinite number of times.....") It's also the case that the treatment times were so long in the paper that a single dose was unlikely to be effective. So no big surprise. I'd be interested to know how closely spaced the multiple injections will be. For example, are they spaced closely to try to get sustained exposure or are they more widely spaced.
I assume that larger won't work because there is a limit to how long the fluid/gel will remain in the middle ear, how quickly it diffuses to the inner ear, and how much can be put in the inner ear.
I will talk about fast tracking below, but one comment on believing what people say. There is no cost to talk about fast tracking. What they are attempting to treat has a large unmet need so they are eligible. As far as I know, there is no cost to the company of asking for fast track status (though I am a bit surprised at that and could be wrong), so at this stage it is something they can talk about and it doesn't really cost them anything. Moreover it does speed things up, but not by years.
My guess is that this comes more from pre-clinical studies in animals than the Phase 1/2.
Even if they have measurements - and they may well from there focus on TEAEs, the sample was too small to learn much. It is possible they will say something, but it really won't be meaningful given the sample size. Keep in mind that many trials that appear to be successful in Phase 2 (with much larger samples than in the Phase 1/2 here) subsequently fail in Phase 3. So even seeing something "promising" in these small samples isn't really much information.
And depending on how much tinkering they do, they will have to do new pre-clinical work, go through safety trials, etc.
Journalist.
Could you point me to the paper that shows this?
Have you read McLean et al (2017)? In some experiments, tissue was treated 20 days or so - the human tissue was 22 days. They did shorter treatment (3 days) but that was on newborn (2 day old) mice. Thus, it seems exposure time matters.
It doesn't have as much effect as you would think from reading things here
Here's what it entails:
"A drug that receives Fast Track designation is eligible for some or all of the following:
All of this is useful and will, if all goes well, reduce the time, but it will be a matter of months not years.
There would be little point if they had to wait that long in the process. All the information is online so you can read about the process.
"Peter is the Chief Medical Officer, Hearing Program for Frequency Therapeutics. Prior to Frequency, Peter was the Director of the Ear Institute at the New York Eye and Ear Infirmary of Mount Sinai (NYEE), where he was also a Professor of Otolaryngology-Head and Neck Surgery at the Icahn School of Medicine at Mount Sinai. Before joining NYEE, Peter served as Chief Medical Officer at Cochlear Americas and was a Professor and Director of Otology-Neurotology at the University of Massachusetts Medical School. He was also formerly the head of the Otology-Neurotology Department and Co-Director of the Hearing Implant Program at the Cleveland Clinic, and was previously named Acting Chairman in the Department of Otolaryngology-Head and Neck Surgery at the Medical University of South Carolina. Peter has served on the Board of Directors of the American Academy of Otolaryngology-Head and Neck Surgery and is a former President of the Board of Governors for Otolaryngology. Peter received his B.S. and M.S. in Engineering from Washington University and his M.D. from Albany Medical College. He completed his residency at the University of Pittsburgh Medical Center, a fellowship in Neurotology at the University of Iowa, and received an M.B.A. from Duke University's Fuqua School of Business." (http://www.frequencytx.com/our-company/bio-cab-peter-weber.php)
Weber left in the summer 2018 - July or thereabouts. So, while he didn't leave recently, Chin is an endocrinologist who replaced an someone whose specialty Neurotology. To me this reflected a change in emphasis at the company as they expanded into juvenile diabetes, muscle injury, and other areas.
I don't think there is any evidence that there is a collaboration.
This has been posted multiple times already.
This strikes me as too optimistic. At this point, it has been 7 months since the Phase 1/2 started, and the Phase 2 trial hasn't started. The Phase 1/2 was small compared to what the Phase 2 and 3 trials will be so setting up trials will take longer. More data will take longer to analyze so I would expect time between trials to increase. We also don't know how long those trials will take. FDA may require some proof of durability of any benefits. Finally, if successful, it will take time to set up manufacturing.
I am certainly hopeful that they will be successful. We will know more with any new publications and when they announce the structure of the trial.
For background, I've been following Frequency since July 2016: (Inner Ear Hair Cell Regeneration — Maybe We Can Know More) I believe that is the first mention of Frequency on this site.
I've been quite disappointed at the lack of a follow-up paper to McLean et al (2017) - published over two years ago. For those who haven't read the paper, I summarize what they did in this post: Frequency Therapeutics — Hearing Loss Regeneration
In that post I also talk about things to look for in the "next" paper and things that I would expect would be in place before human trials. Since there hasn't been a "next" paper, we don't yet know what other pre-clinical data they have. I am still looking forward to see what is in the next paper.
I am still cautiously optimistic, though the balance has shifted from optimistic to cautiously. Below are some of my thoughts on where we are now.
1) The departure of Weber last year was a bigger deal than his going to Decibel this year. His going to Decibel makes sense though because Decibel is a hearing loss company while Frequency is a company built around a tool - it's just that the first thing they are using that tool on is hearing (It is notable that Weber is a Neurotologist (or at least did a fellowship in Neurotology) while Chin is an endocrinologist. Thus, I think Weber's departure said more about Frequency's expansion beyond hearing. (See below for more.)
2) Based on the paper from 2017, it seemed very unlikely that one injection would work so I am not concerned about multiple injections. I wouldn't read anything into the fact that they said it would be one injection in the past. I'm sure that is what they were hoping for, but they probably knew at the time that it was unlikely. (This is also why you should downplay anything said by anyone associated with a company - e.g., time lines, results, etc - unless it is in published paper or has already happened. Even if it is in a published paper, you need to read very carefully and pay attention to the quality of the journal. And a single paper doesn't prove anything by itself. Pay even less attention to press releases.)
3) The most important thing to keep in mind is that this is incredibly hard and more likely to fail than to be successful. The inner ear is singularly difficult to reach clinically, and the PCA technology itself is unproven even in much simpler settings. It's also the case that regenerating hair cells in adults is much harder than doing so in a petri dish or newborns - this is a constant theme across many studies. The idea that this is figured out and we somehow *know* that Frequency will be successful is wishful thinking not grounded in any publicly available knowledge - or at this point likely any privately available knowledge.
I've responded to a few things people have said or asked in the last few pages of the thread below.
They are claiming phase 1/2 was just a "phase 1" study... nothing about efficacy.
It wasn't "just" a phase 1 study. The two dose levels was the phase 2 component of the trial. While they may have done hearing tests to look for TEAEs. The study is too small to provide useful information about efficacy.
It is a negative, but it is not surprising.The patent applications talked about the possibility of multiple treatments (though patent applications are written to be as broad as possible: they typically seem something like "in one embodiment, this invention uses one or more of 5 million different compounds that may be applied between 0 and an infinite number of times.....") It's also the case that the treatment times were so long in the paper that a single dose was unlikely to be effective. So no big surprise. I'd be interested to know how closely spaced the multiple injections will be. For example, are they spaced closely to try to get sustained exposure or are they more widely spaced.
I assume that larger won't work because there is a limit to how long the fluid/gel will remain in the middle ear, how quickly it diffuses to the inner ear, and how much can be put in the inner ear.
I will talk about fast tracking below, but one comment on believing what people say. There is no cost to talk about fast tracking. What they are attempting to treat has a large unmet need so they are eligible. As far as I know, there is no cost to the company of asking for fast track status (though I am a bit surprised at that and could be wrong), so at this stage it is something they can talk about and it doesn't really cost them anything. Moreover it does speed things up, but not by years.
My guess is that this comes more from pre-clinical studies in animals than the Phase 1/2.
Even if they have measurements - and they may well from there focus on TEAEs, the sample was too small to learn much. It is possible they will say something, but it really won't be meaningful given the sample size. Keep in mind that many trials that appear to be successful in Phase 2 (with much larger samples than in the Phase 1/2 here) subsequently fail in Phase 3. So even seeing something "promising" in these small samples isn't really much information.
And depending on how much tinkering they do, they will have to do new pre-clinical work, go through safety trials, etc.
Journalist.
Could you point me to the paper that shows this?
Have you read McLean et al (2017)? In some experiments, tissue was treated 20 days or so - the human tissue was 22 days. They did shorter treatment (3 days) but that was on newborn (2 day old) mice. Thus, it seems exposure time matters.
It doesn't have as much effect as you would think from reading things here
Here's what it entails:
"A drug that receives Fast Track designation is eligible for some or all of the following:
- More frequent meetings with FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
- More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
- Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
- Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA"
All of this is useful and will, if all goes well, reduce the time, but it will be a matter of months not years.
There would be little point if they had to wait that long in the process. All the information is online so you can read about the process.
Chin was hired in April 2018. When he was hired Weber became "Chief Medical Officer, Hearing Program":
"Peter is the Chief Medical Officer, Hearing Program for Frequency Therapeutics. Prior to Frequency, Peter was the Director of the Ear Institute at the New York Eye and Ear Infirmary of Mount Sinai (NYEE), where he was also a Professor of Otolaryngology-Head and Neck Surgery at the Icahn School of Medicine at Mount Sinai. Before joining NYEE, Peter served as Chief Medical Officer at Cochlear Americas and was a Professor and Director of Otology-Neurotology at the University of Massachusetts Medical School. He was also formerly the head of the Otology-Neurotology Department and Co-Director of the Hearing Implant Program at the Cleveland Clinic, and was previously named Acting Chairman in the Department of Otolaryngology-Head and Neck Surgery at the Medical University of South Carolina. Peter has served on the Board of Directors of the American Academy of Otolaryngology-Head and Neck Surgery and is a former President of the Board of Governors for Otolaryngology. Peter received his B.S. and M.S. in Engineering from Washington University and his M.D. from Albany Medical College. He completed his residency at the University of Pittsburgh Medical Center, a fellowship in Neurotology at the University of Iowa, and received an M.B.A. from Duke University's Fuqua School of Business." (http://www.frequencytx.com/our-company/bio-cab-peter-weber.php)
Weber left in the summer 2018 - July or thereabouts. So, while he didn't leave recently, Chin is an endocrinologist who replaced an someone whose specialty Neurotology. To me this reflected a change in emphasis at the company as they expanded into juvenile diabetes, muscle injury, and other areas.
I don't think there is any evidence that there is a collaboration.
This has been posted multiple times already.
This strikes me as too optimistic. At this point, it has been 7 months since the Phase 1/2 started, and the Phase 2 trial hasn't started. The Phase 1/2 was small compared to what the Phase 2 and 3 trials will be so setting up trials will take longer. More data will take longer to analyze so I would expect time between trials to increase. We also don't know how long those trials will take. FDA may require some proof of durability of any benefits. Finally, if successful, it will take time to set up manufacturing.
I am certainly hopeful that they will be successful. We will know more with any new publications and when they announce the structure of the trial.
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