Frequency Therapeutics — Hearing Loss Regeneration

[Diesel]

Can anyone comment on the above?

In the Phase 2A, up to 4 shots are being tested. However, it is one injection per week, over a 4-week period. As mentioned by Carl LeBel @ Frequency Therapeutics, they are hypothesizing one or more may happen with multiple dosing:

A. Continued improvements in the same region as the first injection. So, 8 kHz+ show greater improvement per injection.

B. Greater response across the patient population. More injections = more chances for some to meet the "average."

C. The drug gets pushed deeper into the cochlea. Each injection moves a little further, producing improvements below 8 kHz.

D. Any combination of A, B, and/or C.

EDIT:

I would like to add an "E" option as well. As, I presume Frequency Therapeutics may continue a second "long-term/durability" study on participants that received FX-322 in the Phase 2A.

E. The long-term word score remains higher due to increased dosage.

I would hypothesize that if multiple doses FX-322 can create any of the combinations of A,B, and or C. That word score and audiograms may continue to be stable for a longer period of time.

With the Phase 1/2, we know that the drug improved hearing above 8 kHz, and increase word score. For the most part, the benefit was retained up to two years. However, no hair cells were regenerated below 8 kHz, which are important for speech and word recognition, and as "original equipment" hair cells, likely continued to degrade, causing a slight reduction; as is seen in the charts.

It would be interesting to see at 2-years out, if the multiple injections reinforced greater durability as represented by increased word score or consistently improved audiogram.

I'm sure they've already thought of this...

 

[FGG]

The theory that if you have improvement at 16000 Hz, you will have improvement at 18000 Hz is also actually the same reasonable conclusion which can be drawn about why when we saw improvement at 8000 Hz in the inaugural trial, we could also assume an improvement was seen at those very high frequencies. Frequency Therapeutics cannot and will not declare that has happened however because it would be non-compliant with the FDA requirements.

Well they can't anyway. It wasn't part of phase 1 trial design so they didn't measure over 8000 Hz.

 

[tommyd87]

Well they can't anyway. It wasn't part of phase 1 trial design so they didn't measure over 8000 Hz.

Isn't that what I said lol? I know that and as a result it is exactly why Frequency Therapeutics said nothing about that and actually also is why they are looking at measuring it in the phase 2a trial.

 

[weab00]

Will they charge a base rate for one injection/ear and then up it by say $500 per additional shot needed?

 

[Diesel]

Will they charge a base rate for one injection/ear and then up it by say $500 per additional shot needed?

I would guess that it will be a flat rate per injection. The ENT will likely stock it and carry the cost onto the patient/insurer per injection. Frequency Therapeutics' manufacturer has no incentive to offer bulk rates or tiered payment.

 

[FGG]

Isn't that what I said lol? I know that and as a result it is exactly why Frequency Therapeutics said nothing about that and actually also is why they are looking at measuring it in the phase 2a trial.

Sorry. I misunderstood. I thought you meant they had tested it but couldn't divulge that info.

 

[tommyd87]

Will they charge a base rate for one injection/ear and then up it by say $500 per additional shot needed?

I would guess that it will be a flat rate per injection. The ENT will likely stock it and carry the cost onto the patient/insurer per injection. Frequency Therapeutics' manufacturer has no incentive to offer bulk rates or tiered payment.

I disagree with you Diesel. I think that they will go the airfare route where you pay a certain fixed price for the ticket and then when you want to add things like baggage or drinks you pay more accordingly, although at a cheaper rate to the price of the ticket.

I really would not be surprised if Frequency Therapeutics charged a fixed rate of just say $2000 for the initial dose to cover costs like overheads and also allow them to make a substantial profit off of all users. I would then expect them to charge a reduced rate like $500 for additional injections for the same purpose. This way they will be able to maximise their profit from all patients while simply not ending up ripping off any patients who require further dosing or treatments then while still being able to make good money off of them too.

 

[kiki]

Did Frequency Therapeutics measure 6000 Hz in the Pure tone test in Phase 1/2?

In my experience, otolaryngologists measure hearing at 125 Hz, 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz and 8000 Hz.

Does your otolaryngologist measure hearing at 6000 Hz?

If Frequency Therapeutics was measuring hearing at 6000 Hz, is it possible that there was an improvement of about 5 dB?
And is it possible that they considered that degree of improvement to be insignificant?
And is it possible that "there was no improvement"?

In that case, is there a possibility that four injections will improve by 10 dB or more at 6000 Hz?

In addition, if there is an improvement of about 3 dB that is not detected in the measured value at 4000 Hz, is there a possibility that the improvement will be about 10 dB with 4 injections?

 

[FGG]

Did Frequency Therapeutics measure 6000 Hz in the Pure tone test in Phase 1/2?

In my experience, otolaryngologists measure hearing at 125 Hz, 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz and 8000 Hz.

Does your otolaryngologist measure hearing at 6000 Hz?

If Frequency Therapeutics was measuring hearing at 6000 Hz, is it possible that there was an improvement of about 5 dB?
And is it possible that they considered that degree of improvement to be insignificant?
And is it possible that "there was no improvement"?

In that case, is there a possibility that four injections will improve by 10 dB or more at 6000 Hz?

In addition, if there is an improvement of about 3 dB that is not detected in the measured value at 4000 Hz, is there a possibility that the improvement will be about 10 dB with 4 injections?

As far as I know, they haven't released any specific audiograms or detailed which frequencies they used.

I just took a look at my audiograms and see that 6000 Hz wasn't measured in mine either (US here as well). I also had only 125 Hz, 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz and 8000 Hz done on my standard audiograms.

If they use the same standard methodology, we will only be able to guess what happens between 4000 Hz and 8000 Hz.

Interesting question.

 

[Diesel]

As far as I know, they haven't released any specific audiograms or detailed which frequencies they used.

I just took a look at my audiograms and see that 6000 Hz wasn't measured in mine either (US here as well). I also had only 125 Hz, 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz and 8000 Hz done on my standard audiograms.

If they use the same standard methodology, we will only be able to guess what happens between 4000 Hz and 8000 Hz.

Interesting question.

My most recent audiogram in June included all of the frequencies mentioned above and included 6000 Hz.

 

[tommyd87]

Did Frequency Therapeutics measure 6000 Hz in the Pure tone test in Phase 1/2?

In my experience, otolaryngologists measure hearing at 125 Hz, 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz and 8000 Hz.

Does your otolaryngologist measure hearing at 6000 Hz?

If Frequency Therapeutics was measuring hearing at 6000 Hz, is it possible that there was an improvement of about 5 dB?
And is it possible that they considered that degree of improvement to be insignificant?
And is it possible that "there was no improvement"?

In that case, is there a possibility that four injections will improve by 10 dB or more at 6000 Hz?

In addition, if there is an improvement of about 3 dB that is not detected in the measured value at 4000 Hz, is there a possibility that the improvement will be about 10 dB with 4 injections?

If there was a 5 dB improvement, it is likely that this would have been reported unless they only test in 10 dB increments. I also think that it is too early to determine how many injections will lead to an improvement of how many dB at 4000 Hz, for example.

I still believe Frequency Therapeutics will be trying for full restoration if it is possible at some point.

 

[sensualmosquito]

My most recent audiogram in June included all of the frequencies mentioned above and included 6000 Hz.

My last audiogram in June also had 6000 Hz, which is also where I happen to have the most hearing loss.

 

[tommyd87]

In the Phase 2A, up to 4 shots are being tested. However, it is one injection per week, over a 4-week period. As mentioned by Carl LeBel @ Frequency Therapeutics, they are hypothesizing one or more may happen with multiple dosing:

A. Continued improvements in the same region as the first injection. So, 8 kHz+ show greater improvement per injection.

B. Greater response across the patient population. More injections = more chances for some to meet the "average."

C. The drug gets pushed deeper into the cochlea. Each injection moves a little further, producing improvements below 8 kHz.

D. Any combination of A, B, and/or C.

EDIT:

I would like to add an "E" option as well. As, I presume Frequency Therapeutics may continue a second "long-term/durability" study on participants that received FX-322 in the Phase 2A.

E. The long-term word score remains higher due to increased dosage.

I would hypothesize that if multiple doses FX-322 can create any of the combinations of A,B, and or C. That word score and audiograms may continue to be stable for a longer period of time.

With the Phase 1/2, we know that the drug improved hearing above 8 kHz, and increase word score. For the most part, the benefit was retained up to two years. However, no hair cells were regenerated below 8 kHz, which are important for speech and word recognition, and as "original equipment" hair cells, likely continued to degrade, causing a slight reduction; as is seen in the charts.

It would be interesting to see at 2-years out, if the multiple injections reinforced greater durability as represented by increased word score or consistently improved audiogram.

I'm sure they've already thought of this...

I reckon that this trial is an exploratory study on dosing outcomes as much as it is in regard to meeting FDA requirements. My view is that the trial is going to give Frequency Therapeutics as much information in regard to dosing as they can get and as a result it is eventually going to enable them to then move onto the planning probably about what to do next.

There will be two outcomes which will come out regarding dosing from the current trial. Firstly the current dosing method utilising up to four straight injections is effective and provides excellent performance outcomes which mean Frequency Therapeutics can stick with this in practice. Secondly Frequency Therapeutics will need to look at redosing and/or reformulation. This could include things such as an even slower release gel, looking at giving more injections (so just say 6 in a treatment course) or giving a bigger dose per injection than is currently offered.

I think that the reality is that there will be good information attained from the current trial in relation to dosing. As a result I think this will enable Frequency Therapeutics to hone their treatment to then enable best outcomes with FX-322 which has already been demonstrated to be effective and beneficial.

 

[Street Novelist]

I don't understand the only 10-20 dB improvement. If FX-322 completely regrow the hair cells, shouldn't full hearing be restored?

 

[patorjk]

I know this gets discussed to death, and most aren't too concerned, but I was looking at the insider trading activity of Frequency Therapeutics and noticed that Dr. Chris Loose (co-founder and Chief Scientific Officer) really ramped up his selling this past month. At the start of the year he had a little more than 200k shares, now he has a little less than 88k. 56k of the shares he's sold were sold this month.

However, I'm not too well versed in how these stock selling plans work. Could he have set this up before the company decided they needed to extend the study? And is it possible to stop these plans once they're set in motion?

One way to look at this is he thought the stock would pop in October and setup his plan to unload the most shares then.

However, if this was his intention and the plan could be stopped, I would assume he'd try and stop it.

If this isn't the case and he's just selling a lot this month it seems a bit strange there was such a boost in selling. Though it could be something as benign as trying to diversify his assets.

 

[FGG]

I don't understand the only 10-20 dB improvement. If FX-322 completely regrow the hair cells, shouldn't full hearing be restored?

It's likely those numbers were higher in the ultra high frequencies, which is what Frequency Therapeutics is trying to show in phase 2a.

In rodents, all frequencies were restored. Cochlear explant studies show hair cell regrowth and perilymph studies show at least some penetrance.

The issue seems to be penetrance but the multi dose strategy in phase 2a may alleviate some of this (we will know next spring). The ultra high frequency data from this phase should also be very illuminating.

 

[FGG]

I know this gets discussed to death, and most aren't too concerned, but I was looking at the insider trading activity of Frequency Therapeutics and noticed that Dr. Chris Loose (co-founder and Chief Scientific Officer) really ramped up his selling this past month. At the start of the year he had a little more than 200k shares, now he has a little less than 88k. 56k of the shares he's sold were sold this month.

However, I'm not too well versed in how these stock selling plans work. Could he have set this up before the company decided they needed to extend the study? And is it possible to stop these plans once they're set in motion?

One way to look at this is he thought the stock would pop in October and setup his plan to unload the most shares then.

However, if this was his intention and the plan could be stopped, I would assume he'd try and stop it.

If this isn't the case and he's just selling a lot this month it seems a bit strange there was such a boost in selling. Though it could be something as benign as trying to diversify his assets.

I suspect this is more of the same or perhaps concerns about the IBB biotech index (which, because it contains NASDAQ biotech shares, could affect Frequency Therapeutics in the short term without a catalyst until spring) dropping leading up to the uncertainty of the election which some analysts are predicting.

All I can say is the study is blinded, so it wouldn't be based on drug performance or the trial (unless there was a supply issue for the trial--I am giving this as a for instance, there is no reason to think that). But I can't speculate on his reasons.

 

[Diesel]

I know this gets discussed to death, and most aren't too concerned, but I was looking at the insider trading activity of Frequency Therapeutics and noticed that Dr. Chris Loose (co-founder and Chief Scientific Officer) really ramped up his selling this past month. At the start of the year he had a little more than 200k shares, now he has a little less than 88k. 56k of the shares he's sold were sold this month.

However, I'm not too well versed in how these stock selling plans work. Could he have set this up before the company decided they needed to extend the study? And is it possible to stop these plans once they're set in motion?

One way to look at this is he thought the stock would pop in October and setup his plan to unload the most shares then.

However, if this was his intention and the plan could be stopped, I would assume he'd try and stop it.

If this isn't the case and he's just selling a lot this month it seems a bit strange there was such a boost in selling. Though it could be something as benign as trying to diversify his assets.

This is a nothingburger. The goal of the 10b5-1 is to protect the firm and executives from insider trading by setting up pre-defined trade activities over a given timeframe.

Rule 10b5-1 trading plans are set when submitted to the SEC. A financial advisor takes over the 10B5-1, and Loose or any other exec is hands-off until they reach period for the next 10b5-1 "amendment" to take effect. He probably believed the Phase 2A would end on-time; resulting in a substantial gain. Either way, it is still well up from its IPO price of $14/share.

There are exceptions where a 10b5-1 plan can be stopped; HOWEVER, it almost always ends in an SEC investigation of the firm and the individual. This would CRUSH Frequency Therapeutics' stock for longer than the duration of the investigation. So, the risks far outweigh outweigh the reaction.

NORMALLY, 10b5-1 plans are "amended" before their termination, and the amended plan carries on in sequence. I haven't looked if the Frequency Therapeutics 10b5-1s are on an annual, 3 year or longer cycle.

Frankly, it doesn't matter all that much.

Instead of going on about how Chris Loose's 10b5-1 plan is unloading shares... that make up a tiny tiny fraction of Frequency Therapeutics' ownership..

I'd like to know more about what triggered Wasatch to increase their position in FREQ by $42MM in the past week. If I recall correctly, they were in on the IPO, Private Placement, and now this... I wonder what they know that we don't?

Wasatch Advisors increased stake in Frequency Therapeutics, Inc.

 

[tommyd87]

I don't understand the only 10-20 dB improvement. If FX-322 completely regrow the hair cells, shouldn't full hearing be restored?

What 10-20 dB are you referring to?

If FX-322 did regrow hair cells completely - correct, then there would be full restoration.

 

[Danad]

I don't understand the only 10-20 dB improvement. If FX-322 completely regrow the hair cells, shouldn't full hearing be restored?

There are several limiting factors such as the drug's diffusion through the round window, whether the gel was positioned properly against the round window, whether there are viable progenitor cells within the cochlea, and whether the newly generated hair cells make the appropriate synaptic connections. In theory we should see better results than the previous phase due to multiple injections in the current phase 2a trial.

 

[FGG]

There are several limiting factors such as the drug's diffusion through the round window, whether the gel was positioned properly against the round window, whether there are viable progenitor cells within the cochlea, and whether the newly generated hair cells make the appropriate synaptic connections. In theory we should see better results than the previous phase due to multiple injections in the current phase 2a trial.

LeBel confirmed they make synaptic connections (which would have been easy to verify in humans in vivo in the explant studies).

LeBel also said very, very few people don't have viable support cells and one university researcher I corresponded with said that (complete loss of support cells) really only happens to anyone (regardless of etiology) when you have the "flat epithelia" in late stage hearing loss and shows up as profound SNHL in the audiogram (so if you have mixed you can subtract the conductive portion).

The question of drug diffusion though is hopefully what phase 2a will answer.

Can you clarify what you mean by "whether gel was positioned properly"?

 

[tommyd87]

This is a nothingburger. The goal of the 10b5-1 is to protect the firm and executives from insider trading by setting up pre-defined trade activities over a given timeframe.

Rule 10b5-1 trading plans are set when submitted to the SEC. A financial advisor takes over the 10B5-1, and Loose or any other exec is hands-off until they reach period for the next 10b5-1 "amendment" to take effect. He probably believed the Phase 2A would end on-time; resulting in a substantial gain. Either way, it is still well up from its IPO price of $14/share.

There are exceptions where a 10b5-1 plan can be stopped; HOWEVER, it almost always ends in an SEC investigation of the firm and the individual. This would CRUSH Frequency Therapeutics' stock for longer than the duration of the investigation. So, the risks far outweigh outweigh the reaction.

NORMALLY, 10b5-1 plans are "amended" before their termination, and the amended plan carries on in sequence. I haven't looked if the Frequency Therapeutics 10b5-1s are on an annual, 3 year or longer cycle.

Frankly, it doesn't matter all that much.

Instead of going on about how Chris Loose's 10b5-1 plan is unloading shares... that make up a tiny tiny fraction of Frequency Therapeutics' ownership..

I'd like to know more about what triggered Wasatch to increase their position in FREQ by $42MM in the past week. If I recall correctly, they were in on the IPO, Private Placement, and now this... I wonder what they know that we don't?

Wasatch Advisors increased stake in Frequency Therapeutics, Inc.

I also actually am thinking Christopher loose likely wouldn't be the type of person who wants to get fines for dodgy trading or get gaol for this too.

Think that the investment is very interesting.

LeBel confirmed they make synaptic connections (which would have been easy to verify in humans in vivo in the explant studies).

LeBel also said very, very few people don't have viable support cells and one university researcher I corresponded with said that (complete loss of support cells) really only happens to anyone (regardless of etiology) when you have the "flat epithelia" in late stage hearing loss and shows up as profound SNHL in the audiogram (so if you have mixed you can subtract the conductive portion).

The question of drug diffusion though is hopefully what phase 2a will answer.

Can you clarify what you mean by "whether gel was positioned properly"?

That's a relief re: support cells lol.

I think that there has been other research from organisations like Pipeline Therapeutics where you cannot connect and grow synapses without a functioning hair cell.

 

[patorjk]

This is a nothingburger. The goal of the 10b5-1 is to protect the firm and executives from insider trading by setting up pre-defined trade activities over a given timeframe.

Rule 10b5-1 trading plans are set when submitted to the SEC. A financial advisor takes over the 10B5-1, and Loose or any other exec is hands-off until they reach period for the next 10b5-1 "amendment" to take effect. He probably believed the Phase 2A would end on-time; resulting in a substantial gain. Either way, it is still well up from its IPO price of $14/share.

There are exceptions where a 10b5-1 plan can be stopped; HOWEVER, it almost always ends in an SEC investigation of the firm and the individual. This would CRUSH Frequency Therapeutics' stock for longer than the duration of the investigation. So, the risks far outweigh outweigh the reaction.

NORMALLY, 10b5-1 plans are "amended" before their termination, and the amended plan carries on in sequence. I haven't looked if the Frequency Therapeutics 10b5-1s are on an annual, 3 year or longer cycle.

Frankly, it doesn't matter all that much.

Instead of going on about how Chris Loose's 10b5-1 plan is unloading shares... that make up a tiny tiny fraction of Frequency Therapeutics' ownership..

I'd like to know more about what triggered Wasatch to increase their position in FREQ by $42MM in the past week. If I recall correctly, they were in on the IPO, Private Placement, and now this... I wonder what they know that we don't?

Wasatch Advisors increased stake in Frequency Therapeutics, Inc.

If changing the plan would lead to as bad as an income as you described, then I would take his large October stock selling as a positive sign. It means he thought Phase 2a would deliver the goods.

I don't see any rise in stock volume for September 30th. I don't doubt that they increased their position but it seems odd that there's no volume spike on the charts I'm looking at.

 

[Michael01]

I really would not be surprised if Frequency Therapeutics charged a fixed rate of just say $2000 for the initial dose to cover costs like overheads and also allow them to make a substantial profit off of all users

I'm really hoping that Frequency Therapeutics decide on a lower price than that.

$2000 initially plus $500 for each additional shot is still a substantial amount. Unless they have payment plans for such things, for those of us that don't have medical health insurance.

 

[Paulmanlike]

I know this gets discussed to death, and most aren't too concerned, but I was looking at the insider trading activity of Frequency Therapeutics and noticed that Dr. Chris Loose (co-founder and Chief Scientific Officer) really ramped up his selling this past month. At the start of the year he had a little more than 200k shares, now he has a little less than 88k. 56k of the shares he's sold were sold this month.

However, I'm not too well versed in how these stock selling plans work. Could he have set this up before the company decided they needed to extend the study? And is it possible to stop these plans once they're set in motion?

One way to look at this is he thought the stock would pop in October and setup his plan to unload the most shares then.

However, if this was his intention and the plan could be stopped, I would assume he'd try and stop it.

If this isn't the case and he's just selling a lot this month it seems a bit strange there was such a boost in selling. Though it could be something as benign as trying to diversify his assets.

Automatic sales. This shouldn't concern you at all.

@Diesel has explained it thoroughly.

 

[kiki]

@FGG, and @tommyd87, thank you for your replies.

I was wondering about the following, so I asked about 5 dB at 6000 Hz and 3 dB at 4000 Hz.

In Phase 1/2, 4 of the 13 subjects reported an improvement of 10 dB on a hearing test at 8000 Hz.

However, no one was reported to have improved by 5 dB.
Even though 5 dB is less improvement.

This made me feel very strange.

The result is zero or one, none or yes, and I don't know the gradation.

I wonder if they were in the no-improvement group, even if there were subjects with a 5 dB improvement.

Excuse me, but am I thinking too much?

 

[Pete88]

@FGG, and @tommyd87, thank you for your replies.

I was wondering about the following, so I asked about 5 dB at 6000 Hz and 3 dB at 4000 Hz.

In Phase 1/2, 4 of the 13 subjects reported an improvement of 10 dB on a hearing test at 8000 Hz.

However, no one was reported to have improved by 5 dB.
Even though 5 dB is less improvement.

This made me feel very strange.

The result is zero or one, none or yes, and I don't know the gradation.

I wonder if they were in the no-improvement group, even if there were subjects with a 5 dB improvement.

Excuse me, but am I thinking too much?

Well, for one, apparently anything less than 10 dB is considered insignificant and can be blamed on other factors. Even if 6,000 Hz went up by 5 dB legitimately by FX-322, it's not enough to classify as anything they can actually report on.

As others have stated, this is likely due to the single safety dose simply being used up in the first 9,000 or so Hz and running out prior to being able to raise 6,000 Hz by at least 10 dB. Multiple injections is theorized to overcome this problem.

 

[Danad]

LeBel confirmed they make synaptic connections (which would have been easy to verify in humans in vivo in the explant studies).

Can you clarify what you mean by "whether gel was positioned properly"?

As the gel solidifies it must be positioned against the cochlea, if the patient swallows during this time period or the IT injection is misplaced I believe that could impact the treatment.

I was merely listing the possible impediments to full hearing restoration with FX-322.

 

[all to gain]

As the gel solidifies it must be positioned against the cochlea, if the patient swallows during this time period or the IT injection is misplaced I believe that could impact the treatment.

I was merely listing the possible impediments to full hearing restoration with FX-322.

How long would a person have to avoid swallowing?

 

[tommyd87]

I'm really hoping that Frequency Therapeutics decide on a lower price than that.

$2000 initially plus $500 for each additional shot is still a substantial amount. Unless they have payment plans for such things, for those of us that don't have medical health insurance.

I think that they can take advantage of the hearing aid pricing which is exactly around that. I cannot see FX-322 being cheap at all as it is going to need to be profitable and also recoup the cost of the drug development.

I definitely think that some countries may arrange a lower pricing for FX-322 if it is successful and if it does replace hearing aids by potentially negotiating a deal with Frequency Therapeutics.