Frequency Therapeutics — Hearing Loss Regeneration

[Gb3]

The stock (FREQ) is at an all-time high! Is this due to the election or other factors, such as the announcement of the 90 day trial results release?

 

[FGG]

The stock (FREQ) is at an all-time high! Is this due to the election or other factors, such as the announcement of the 90 day trial results release?

Likely the election. Historically, the market always goes up after the outcome is known (no matter who wins an election). The market hates uncertainty.

COVID-19 vaccine news is a factor too. And it's also elevating biotech as a whole (IBB index is up).

 

[tommyd87]

Setting up contract drug manufacturing is COMPLEX. It won't be a single staffer, it will be a coordinated operation, even for compassionate use.

They'd still need setup contracts, supply chain, quality assurance, administrative, distribution, communication processes to essentially provide a short-run of the drug for a limited number of patients for a short period of time while they wait for the pivotal phase and FDA approval to go commercial. This is a HUGE investment. So, why not just invest all those same people, resources, processes in ensuring the unknown US drug maker and Astellas can pump out massive quantities of the drug worldwide as soon as the pivotal phase ends?

This doesn't even include dealing with the demand from millions of patients and doctors that will overwhelm Frequency Therapeutics with requests for compassionate use.

So, after all that; even if it does happen, the cost to the patient to finally get the drug might be substantially higher than getting the mass-produced product; let alone the wait time to get through the administrative process.

A lot of this stuff is seemingly being put in the works and will have to be, for the time that release comes around. As a result I don't see compassionate use as being something significant for Frequency Therapeutics, potentially for a short run if FX-322 is indeed successful and if indeed they are also fairly confident that it will get released. Furthermore from what Frequency Therapeutics has implied it is seemingly the case that a number of these processes have already been arranged in their deal and agreement with Astellas.

Stuff like supply chains, quality assurance and manufacturing are all actual elements that Frequency Therapeutics will have to deal with post release anyway so it wouldn't be at all unrealistic to deal with these now and set the processes and mechanisms in place.

Therefore if there was a fair amount of certainty that FX-322 was going to get FDA approval and also with what we know about the groundwork that Frequency Therapeutics has laid when it comes to FX-322, I don't necessarily see it as being as complex as having to come up with all these things like distribution and supply chains for a short run which inevitably will be really relevant again once FX-322 hopefully gets put into full scale production.

Oomph, that's one tough cookie, especially when it concerns Scotland's desire to stay in the EU (given SNP's + Scottish Greens' current polls). I really do hope that Astellas will also put a lot of effort in expanding their clinical trials to non-EU countries like the UK, although I understand that it seems like a lot of hassle for the company from a judicial & financial point of view.

I also wonder whether it is easier for Astellas to release FX-322 in the UK now off of the US trials because they no longer have to comply with EU rules relating to medicines. My take on it is that a part of the reason that Astellas required taking FX-322 through the EU trials was because the rules required medicines to be tested within the EU and given approval by the EU regulators before they could get released. Right now this has seemingly changed because the FDA and EU regulators have come to an agreement whereby they are willing to recognise each other's trials, though this didn't come into effect until after the trial process for FX-322 commenced.

 

[tommyd87]

The stock (FREQ) is at an all-time high! Is this due to the election or other factors, such as the announcement of the 90 day trial results release?

Likely the election. Historically, the market always goes up after the outcome is known (no matter who wins an election). The market hates uncertainty.

COVID-19 vaccine news is a factor too. And it's also elevating biotech as a whole (IBB index is up).

Otonomy is also up somewhat if it is of any interest.

 

[Philip83]

So if I understand this correctly, FX-322 does not deplete supporting cells? Does this technically mean that if, let's say, one gets an injection next year and gains 10-15 dB of hearing in some frequencies, they could potentially get another injection in, let's say, 5 years and get another boost? Maybe the delivery method and efficacy is even better by then as well.

 

[tommyd87]

So if I understand this correctly, FX-322 does not deplete supporting cells? Does this technically mean that if, let's say, one gets an injection next year and gains 10-15 dB of hearing in some frequencies, they could potentially get another injection in, let's say, 5 years and get another boost? Maybe the delivery method and efficacy is even better by then as well.

It does not deplete support cells. Currently we know that you can consequently have multiple treatments with progenitor cell activation, although how many times you can be treated we don't know.

The question is not necessarily about the boost from only one shot or a course of treatment; Frequency Therapeutics showed in the lab work that FX-322 can provide full hair cell regeneration. The only thing that we don't know is how good is the regeneration going to be in actual cochleas and how many injections are needed to provide a complete regrowth. Right now it is possible that the technique used to administer FX-322 is insufficient to get the medicine working with all frequencies and therefore this tends to mean that Frequency Therapeutics will potentially examine a redosing and/or reformulation if it is the case. In short the questions that are unanswered are how to get the medicine working with all frequencies and how much FX-322 is required to achieve full regrowth.

 

[Diesel]

I wanted to reply to a few comments with a visual to help clarify my position on why I think FX-322 is likely a few years away from commercial release; yet too close to have effort put into compassionate use.

Below is a quick sketch of what is essentially the Clinical Trial Pathway for FX-322. We see the original "series" in the top row, the new age-related hearing loss Phase 1b, and upcoming severe SNHL Phase 1b. I think, and a few others agree, that it is likely that Frequency Therapeutics' strategy is to establish a single pivotal "Phase 2b/3" that will encompass a wide range of SNHL/NIHL AND age-related hearing loss. This will enable the population of potential trial participants to be extremely large, thus keeping the trial on-time and of high-value data. This also makes FX-322 able to be approved for more types of hearing loss when it is commercially available.

Here's the rub with compassionate use. After the Phase 2a ends, and the Phase 1b trials are still in-progress; it doesn't seem timely to focus on compassionate use when they should be putting all energy into the second half of 2021 in getting drug ready for a worldwide Phase 2b/3. It seems right now that Frequency Therapeutics consistently has about a 1-Quarter gap between trials. So, I am assuming it will be no different for the pivotal phase. Also, there's the challenge of allowing compassionate use for those with Mild-Moderately-Severe hearing loss, but EXCLUDING those with Severe SNHL and age-related hearing loss... it wouldn't be approved for compassionate use since these diagnoses are still in Phase 1b.

I think they'll stick to a timeline close to the one above. FDA approval will likely take place sometime in 2023. I am speculating that in the pivotal trial, they won't see a need to measure patient outcomes for 7 months, but only for 3 months; since 90 days seems like the magic number to maximize the benefit of a single injection of FX-322.

 

[Street Novelist]

I hope not. That would mean 1.5 years of waiting. I hope they can push things faster.

 

[Lucifer]

I wanted to reply to a few comments with a visual to help clarify my position on why I think FX-322 is likely a few years away from commercial release; yet too close to have effort put into compassionate use.

Below is a quick sketch of what is essentially the Clinical Trial Pathway for FX-322. We see the original "series" in the top row, the new age-related hearing loss Phase 1b, and upcoming severe SNHL Phase 1b. I think, and a few others agree, that it is likely that Frequency Therapeutics' strategy is to establish a single pivotal "Phase 2b/3" that will encompass a wide range of SNHL/NIHL AND age-related hearing loss. This will enable the population of potential trial participants to be extremely large, thus keeping the trial on-time and of high-value data. This also makes FX-322 able to be approved for more types of hearing loss when it is commercially available.

View attachment 41592

Here's the rub with compassionate use. After the Phase 2a ends, and the Phase 1b trials are still in-progress; it doesn't seem timely to focus on compassionate use when they should be putting all energy into the second half of 2021 in getting drug ready for a worldwide Phase 2b/3. It seems right now that Frequency Therapeutics consistently has about a 1-Quarter gap between trials. So, I am assuming it will be no different for the pivotal phase. Also, there's the challenge of allowing compassionate use for those with Mild-Moderately-Severe hearing loss, but EXCLUDING those with Severe SNHL and age-related hearing loss... it wouldn't be approved for compassionate use since these diagnoses are still in Phase 1b.

I think they'll stick to a timeline close to the one above. FDA approval will likely take place sometime in 2023. I am speculating that in the pivotal trial, they won't see a need to measure patient outcomes for 7 months, but only for 3 months; since 90 days seems like the magic number to maximize the benefit of a single injection of FX-322.

2023 is a long way away. I do hope by March we get some positive news and an update on the timeline. I'm hoping 2022 if we are lucky.

 

[wwtsai]

I think they'll stick to a timeline close to the one above. FDA approval will likely take place sometime in 2023. I am speculating that in the pivotal trial, they won't see a need to measure patient outcomes for 7 months, but only for 3 months; since 90 days seems like the magic number to maximize the benefit of a single injection of FX-322.

Just wanted to clarify, the timeline you've posted is indicative of a 3 month phase 2b/3?

 

[tommyd87]

I wanted to reply to a few comments with a visual to help clarify my position on why I think FX-322 is likely a few years away from commercial release; yet too close to have effort put into compassionate use.

Below is a quick sketch of what is essentially the Clinical Trial Pathway for FX-322. We see the original "series" in the top row, the new age-related hearing loss Phase 1b, and upcoming severe SNHL Phase 1b. I think, and a few others agree, that it is likely that Frequency Therapeutics' strategy is to establish a single pivotal "Phase 2b/3" that will encompass a wide range of SNHL/NIHL AND age-related hearing loss. This will enable the population of potential trial participants to be extremely large, thus keeping the trial on-time and of high-value data. This also makes FX-322 able to be approved for more types of hearing loss when it is commercially available.

View attachment 41592

Here's the rub with compassionate use. After the Phase 2a ends, and the Phase 1b trials are still in-progress; it doesn't seem timely to focus on compassionate use when they should be putting all energy into the second half of 2021 in getting drug ready for a worldwide Phase 2b/3. It seems right now that Frequency Therapeutics consistently has about a 1-Quarter gap between trials. So, I am assuming it will be no different for the pivotal phase. Also, there's the challenge of allowing compassionate use for those with Mild-Moderately-Severe hearing loss, but EXCLUDING those with Severe SNHL and age-related hearing loss... it wouldn't be approved for compassionate use since these diagnoses are still in Phase 1b.

I think they'll stick to a timeline close to the one above. FDA approval will likely take place sometime in 2023. I am speculating that in the pivotal trial, they won't see a need to measure patient outcomes for 7 months, but only for 3 months; since 90 days seems like the magic number to maximize the benefit of a single injection of FX-322.

Here is the only question that I have with this. If Frequency Therapeutics gains positive benefits from the Phase 2A trial and also the Phase 1B trials, it is incredibly evident that they cannot consequently proceed to a phase 3 trial immediately because they have an agreement with Astellas to conduct a phase 2 and phase 3 trial in Europe.

Essentially my question is why wouldn't we see Frequency Therapeutics grant an allowance for compassionate use in the US if FX-322 is successful, when they will need to complete an additional European trial prior to being able to enter and complete the pivotal phase trial? Unless I am missing something, I have not read anything that actually states that Frequency Therapeutics will be able to run a Phase 2B in Europe simultaneously with their Phase 3/final/pivotal trial. Alternatively is it the case that Frequency Therapeutics will run a Phase 3 trial in the US and EU that are completely independent and disconnected from each other?

 

[Philip83]

I wanted to reply to a few comments with a visual to help clarify my position on why I think FX-322 is likely a few years away from commercial release; yet too close to have effort put into compassionate use.

Below is a quick sketch of what is essentially the Clinical Trial Pathway for FX-322. We see the original "series" in the top row, the new age-related hearing loss Phase 1b, and upcoming severe SNHL Phase 1b. I think, and a few others agree, that it is likely that Frequency Therapeutics' strategy is to establish a single pivotal "Phase 2b/3" that will encompass a wide range of SNHL/NIHL AND age-related hearing loss. This will enable the population of potential trial participants to be extremely large, thus keeping the trial on-time and of high-value data. This also makes FX-322 able to be approved for more types of hearing loss when it is commercially available.

View attachment 41592

Here's the rub with compassionate use. After the Phase 2a ends, and the Phase 1b trials are still in-progress; it doesn't seem timely to focus on compassionate use when they should be putting all energy into the second half of 2021 in getting drug ready for a worldwide Phase 2b/3. It seems right now that Frequency Therapeutics consistently has about a 1-Quarter gap between trials. So, I am assuming it will be no different for the pivotal phase. Also, there's the challenge of allowing compassionate use for those with Mild-Moderately-Severe hearing loss, but EXCLUDING those with Severe SNHL and age-related hearing loss... it wouldn't be approved for compassionate use since these diagnoses are still in Phase 1b.

I think they'll stick to a timeline close to the one above. FDA approval will likely take place sometime in 2023. I am speculating that in the pivotal trial, they won't see a need to measure patient outcomes for 7 months, but only for 3 months; since 90 days seems like the magic number to maximize the benefit of a single injection of FX-322.

Does Phase 2b/3 have any placebo controls?

 

[100Hz]

I wanted to reply to a few comments with a visual to help clarify my position on why I think FX-322 is likely a few years away from commercial release; yet too close to have effort put into compassionate use.

Below is a quick sketch of what is essentially the Clinical Trial Pathway for FX-322. We see the original "series" in the top row, the new age-related hearing loss Phase 1b, and upcoming severe SNHL Phase 1b. I think, and a few others agree, that it is likely that Frequency Therapeutics' strategy is to establish a single pivotal "Phase 2b/3" that will encompass a wide range of SNHL/NIHL AND age-related hearing loss. This will enable the population of potential trial participants to be extremely large, thus keeping the trial on-time and of high-value data. This also makes FX-322 able to be approved for more types of hearing loss when it is commercially available.

View attachment 41592

Here's the rub with compassionate use. After the Phase 2a ends, and the Phase 1b trials are still in-progress; it doesn't seem timely to focus on compassionate use when they should be putting all energy into the second half of 2021 in getting drug ready for a worldwide Phase 2b/3. It seems right now that Frequency Therapeutics consistently has about a 1-Quarter gap between trials. So, I am assuming it will be no different for the pivotal phase. Also, there's the challenge of allowing compassionate use for those with Mild-Moderately-Severe hearing loss, but EXCLUDING those with Severe SNHL and age-related hearing loss... it wouldn't be approved for compassionate use since these diagnoses are still in Phase 1b.

I think they'll stick to a timeline close to the one above. FDA approval will likely take place sometime in 2023. I am speculating that in the pivotal trial, they won't see a need to measure patient outcomes for 7 months, but only for 3 months; since 90 days seems like the magic number to maximize the benefit of a single injection of FX-322.

Would compassionate use be simply enrolling those compassionate use people into the existing trial conditions but giving them FX-322 and not placebo? Probably not but I am asking for a reason.

If FX-322 did get offered for compassionate use, which I also can't really see a benefit to for the above reasons, I'm assuming that they'd know it works by that time and the very fact it's now offered for compassionate use would tell us that, or am I missing something? They wouldn't let a load of, in effect, single person spin-off trials run in various locations would they?

There would presumably be NDAs involved as well because if word got around that it was working for various conditions I'd imagine people would be doing everything they could do to get it. If I found out it was genuinely curing noxacusis for example I'd rush anywhere in the world for it (and then probably invest heavily in FREQ stock). I'm sure there must be some kind of examples of what happens when this scenario of pivotal trial alongside compassionate use happens, I just wonder if something as significant as hearing regeneration might not fit the same mold as any existing precedents as if it really was working I can see it being explosive and unbalancing and skewing the remainder of the trial and approval process.

Could it also have various kinds of impacts on the trials? I.e. If it blatantly worked but you could get compassionate use, it's been questioned that the rush of people desperate for it compassionately could deplete the potential trial candidate pool (even if the trials were full, people could drop out and go for compassionate instead of risk placebo), delaying the final approval as no doubt it would have to be finished to satisfy the FDA protocols. On a bad note though what if someone appeared to have a bad adverse reaction from compassionate use? Could that affect the trials?

Also if it obviously worked for tinnitus and hyperacusis of any kind I assume it would still only ever be prescribed off-label unless it went through proper trials for these conditions.

If it looked like it was working in compassionate usage, it could send the share price through the roof prior to FDA approval, I'm guessing.

I can't see it being released for compassionate use unless they knew it worked.

 

[Christiaan]

I actually forgot to mention this, but I've asked an agency back in July (My Tomorrows, specialised in arranging compassionate use) if Astellas is open for considering compassionate use for us peeps. The answer to my mail might be of interest to some of you in Europe:

--------------------------------------------------------------------------------------------------------------------------------------------
Dear Christiaan,

I understood from (....) that you were also interested in FX322. Some time ago I inquired for someone else here at Astellas about the EAP [Early Access Program] and trial options. The person had eventually managed to get contact details from a Medical Director at Astellas who told him that those options [EAP] are not yet available for Europe, but that they plan to do so in the future. How long you should wait for this is unknown.

Unfortunately, there is currently nothing available to you with FX322. If you are interested in one of the options of the report, I can of course help you to make contact.

If you have any questions, do not hesitate to email me.

Nice weekend!

 

[Diesel]

Here is the only question that I have with this. If Frequency Therapeutics gains positive benefits from the Phase 2A trial and also the Phase 1B trials, it is incredibly evident that they cannot consequently proceed to a phase 3 trial immediately because they have an agreement with Astellas to conduct a phase 2 and phase 3 trial in Europe.

Essentially my question is why wouldn't we see Frequency Therapeutics grant an allowance for compassionate use in the US if FX-322 is successful, when they will need to complete an additional European trial prior to being able to enter and complete the pivotal phase trial? Unless I am missing something, I have not read anything that actually states that Frequency Therapeutics will be able to run a Phase 2B in Europe simultaneously with their Phase 3/final/pivotal trial. Alternatively is it the case that Frequency Therapeutics will run a Phase 3 trial in the US and EU that are completely independent and disconnected from each other?

I think we'll see the Pivotal Phase 2b/3 be in clinical sites the US, Europe, and Asia simultaneously. This would satisfy Frequency Therapeutics' contract and cash payment agreement with Astellas, and wrap up the trial for review with all respective governing bodies enabling commercial release worldwide.

The finished product is what both companies are incentivized to complete. So, the faster they can get through the trials, the faster both can make real money from FX-322.

 

[FGG]

Does Phase 2b/3 have any placebo controls?

I'm sure it does and if nothing else, the untreated ear is still a control.

 

[Philip83]

I'm sure it does and if nothing else, the untreated ear is still a control.

After doing some more googling, yes, that seems to be the case. A usual ratio for placebo in phase 3 trials is apparently 1/3.

 

[Diesel]

I'm sure it does and if nothing else, the untreated ear is still a control.

It would be interesting though to see the Phase 2b/3 be placebo controlled with BOTH ears treated. The benefits there are still unknown.

 

[tommyd87]

I think we'll see the Pivotal Phase 2b/3 be in clinical sites the US, Europe, and Asia simultaneously. This would satisfy Frequency Therapeutics' contract and cash payment agreement with Astellas, and wrap up the trial for review with all respective governing bodies enabling commercial release worldwide.

The finished product is what both companies are incentivized to complete. So, the faster they can get through the trials, the faster both can make real money from FX-322.

The uncertain part though is how can Frequency Therapeutics run a Phase 2b in Europe while running a Phase 3 at the same time? I thought that they would need to run both.

 

[Princebeyel]

I just don't understand if FX-322 continues to show it's safe and in fact works why they wouldn't release it ASAP or allow expanded access when there are so many of us on the verge of suicide and have socially isolated our selves from the world because of our hearing loss?

 

[Diesel]

The uncertain part though is how can Frequency Therapeutics run a Phase 2b in Europe while running a Phase 3 at the same time? I thought that they would need to run both.

A Phase 2b/3 fits the definition. It's a combined trial.

 

[tommyd87]

A Phase 2b/3 fits the definition. It's a combined trial.

I've seen that. This is what I hope is meant by the agreement between Frequency Therapeutics and Astellas. All good. Thanks for clarifying.

 

[Diesel]

I just don't understand if FX-322 continues to show it's safe and in fact works why they wouldn't release it ASAP or allow expanded access when there are so many of us on the verge of suicide and have socially isolated our selves from the world because of our hearing loss?

Safety isn't always binary. Right now the safety is "favorable" amongst a group of about 120 patients to have received FX-322. But what is unknown, and unmeasured, are the side effects that start to exist in a larger population. 120 patients aren't enough to measure significant side effects/negative interactions. These need to be understood so both the physician and patient are making an informed decision before taking the treatment.

 

[TrevorSanders]

Safety isn't always binary. Right now the safety is "favorable" amongst a group of about 120 patients to have received FX-322. But what is unknown, and unmeasured, are the side effects that start to exist in a larger population. 120 patients aren't enough to measure significant side effects/negative interactions. These need to be understood so both the physician and patient are making an informed decision before taking the treatment.

Many of us wouldn't care what the side effects are as long as it fixes our hearing.

 

[frpp]

Safety isn't always binary. Right now the safety is "favorable" amongst a group of about 120 patients to have received FX-322. But what is unknown, and unmeasured, are the side effects that start to exist in a larger population. 120 patients aren't enough to measure significant side effects/negative interactions. These need to be understood so both the physician and patient are making an informed decision before taking the treatment.

Personally I think there should just be a waiver if you're willing to risk side effects. I agree It's great that the FDA likes to make sure things are "safe" and regulated to a degree in order to keep snake oil off the market but a sane consenting adult should be allowed to make the decision to take the risk.

 

[frpp]

Many of us wouldn't care what the side effects are as long as it fixes our hearing.

10000%.

 

[TrevorSanders]

Personally I think there should just be a waiver if you're willing to risk side effects. I agree It's great that the FDA likes to make sure things are "safe" and regulated to a degree in order to keep snake oil off the market but a sane consenting adult should be allowed to make the decision to take the risk.

With Oregon decriminalizing all drugs, I should be allowed to take a drug that could give me my life back.

 

[Gb3]

Has anyone here ever decided to take some action and write the local state reps about possible freedom of use?

 

[Lucifer]

Personally I think there should just be a waiver if you're willing to risk side effects. I agree It's great that the FDA likes to make sure things are "safe" and regulated to a degree in order to keep snake oil off the market but a sane consenting adult should be allowed to make the decision to take the risk.

Yes I agree. This drug has been tested since 2017 so likely if there were any side effects we would know by now. It was only this current Phase 2a clinical trial where we would know if additional doses benefit more and if there are more side effects with additional doses. If this phase does pass and shows there are no side effects then bring in compassionate use or early release.

 

[Street Novelist]

I just don't understand if FX-322 continues to show it's safe and in fact works why they wouldn't release it ASAP or allow expanded access when there are so many of us on the verge of suicide and have socially isolated our selves from the world because of our hearing loss?

You would think so, now wouldn't you? Why release early results in March if you don't plan on doing anything? Why not just release everything in May? Can you imagine if we have to wait several years for this drug? How many of us will have committed suicide?