Frequency Therapeutics — Hearing Loss Regeneration

[Zugzug]

I wonder if anyone knows the answer to this. It seems as though they have (even in phase 2a) participants with meaningful hearing loss. They are then given the drug or placebo. Isn't it of interest to see how the drug affects people with normal hearing?

Selfishly, I ask this because I may want to try the drug, but having severe hyperacusis, my audiograms are stupidly good. I would want to know if the drug could make hyperacusis worse if I were to take the drug without damaged hair cells. Maybe this is for later phases? Logically, I don't know why someone with normal hearing would want to be the first people experimented on. But maybe people with severe hyperacusis and normal audiograms would be interested...

 

[FGG]

Something that intrigues me is what the timeframe is for this drug to take effect and how long patients could expect to see improvements for.

They did say during the Fireside that the improvements remained a year later when they did a follow up. At this point, soon they could probably follow up two years later if they wanted.

 

[Diesel]

They did say during the Fireside that the improvements remained a year later when they did a follow up. At this point, soon they could probably follow up two years later if they wanted.

Yes! It's in the June 2020 presentation. Follow up was 12 - 21 months after exit from the Phase 1/2. I hope they continue to follow these folks.

 

[Lucifer]

Something that intrigues me is what the timeframe is for this drug to take effect and how long patients could expect to see improvements for.

Good question. I assume the best time for the drug to take into effect is when you are sleeping but it may end up regrowing hair cells and synapses throughout the day.

 

[FGG]

I wonder if anyone knows the answer to this. It seems as though they have (even in phase 2a) participants with meaningful hearing loss. They are then given the drug or placebo. Isn't it of interest to see how the drug affects people with normal hearing?

Selfishly, I ask this because I may want to try the drug, but having severe hyperacusis, my audiograms are stupidly good. I would want to know if the drug could make hyperacusis worse if I were to take the drug without damaged hair cells. Maybe this is for later phases? Logically, I don't know why someone with normal hearing would want to be the first people experimented on. But maybe people with severe hyperacusis and normal audiograms would be interested...

Have you had an extended audiogram?

I don't see how this drug would benefit people with truly normal hearing but I also don't see a reason it would be harmful to try considering how inadequate testing is and that the drug is given to people with normal patches of cochlea without adverse effects.

 

[Jurger]

Something that intrigues me is what the timeframe is for this drug to take effect and how long patients could expect to see improvements for.

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

Slide 21 and 22.

 

[Bobbette]

@Paulmanlike & other FREQ investors:

What do you consider the risk to be to buy $10k worth of shares? I suppose if phase 2 results are positive, it could be a nice windfall?

 

[Diesel]

@Paulmanlike & other FREQ investors:

What do you consider the risk to be to buy $10k worth of shares? I suppose if phase 2 results are positive, it could be a nice windfall?

Risk is what you're willing to accept losing in the market. Can you go without $10k for a few years until the return stabilizes?

 

[patorjk]

@Paulmanlike & other FREQ investors:

What do you consider the risk to be to buy $10k worth of shares? I suppose if phase 2 results are positive, it could be a nice windfall?

I own a decent amount of shares, but I've sort of rationalized it against the gains I've made in my other investments. So if things fall through, I'm still positive for what I've made in my account the past year. Only invest what you wouldn't be afraid to lose. At this point no one knows what will happen.

One problem about thinking about a windfall is that you won't think rationally, and it may cause you to buy more than you should because you'll be thinking about the big pay day.

Even though I think the Phase 2a results will be positive, I don't think they'll be blockbuster, and it's not clear how the market will react if the results are just decent or good.

 

[Lucifer]

I own a decent amount of shares, but I've sort of rationalized it against the gains I've made in my other investments. So if things fall through, I'm still positive for what I've made in my account the past year. Only invest what you wouldn't be afraid to lose. At this point no one knows what will happen.

One problem about thinking about a windfall is that you won't think rationally, and it may cause you to buy more than you should because you'll be thinking about the big pay day.

Even though I think the Phase 2a results will be positive, I don't think they'll be blockbuster, and it's not clear how the market will react if the results are just decent or good.

Imagine FX-322 ending up being as big as Tesla with their share prices. You guys who have bought Frequency Therapeutics' shares will be so rich.

 

[Diesel]

Imagine FX-322 ending up being as big as Tesla with their share prices. You guys who have bought Frequency Therapeutics' shares will be so rich.

Honestly, if FX-322 can show at least as good results in the Phase 2A as in the Phase 1/2, and can treat the range of hearing loss associated with hair cell loss that they think it can; a $50Billion market cap isn't out of the question after the product hits the market. That would put the stock price right around Tesla levels today. Provided they don't dilute the shares any further, or split the stocks.

 

[Lucifer]

Honestly, if FX-322 can show at least as good results in the Phase 2A as in the Phase 1/2, and can treat the range of hearing loss associated with hair cell loss that they think it can; a $50Billion market cap isn't out of the question after the product hits the market. That would put the stock price right around Tesla levels today. Provided they don't dilute the shares any further, or split the stocks.

I mean no other clinical trials have got as much of an improved hearing than FX-322. That 1 patient went from 27/50 to a 47/50 word score, which is unbelievable that it made such a difference.

 

[WillBeNimble]

Imagine FX-322 ending up being as big as Tesla with their share prices. You guys who have bought Frequency Therapeutics' shares will be so rich.

I want to buy more but I'm waiting for it to drop a bit. I expect that there's going to be more of a slow down from COVID-19.

 

[all to gain]

This thread has become very disheartening what with that talk of only 10% of new drugs getting to the market.
I know I'm pessimistic, but figures like that are a body blow for sure.

What are the chances that we will have anything on the market for hearing loss/tinnitus within the next 20 years?

 

[FGG]

This thread has become very disheartening what with that talk of only 10% of new drugs getting to the market.
I know I'm pessimistic, but figures like that are a body blow for sure.

What are the chances that we will have anything on the market for hearing loss/tinnitus within the next 20 years?

A few things to note about that 10% figure. One is that only 10% of drugs *that have filed an IND (phase 0)* make it:

https://www.sciencedirect.com/science/article/pii/S2452302X1600036X

The only drug actively discussed on this forum in that category is PIPE-505. Everything else has at least passed phase 1 already.

Past phase 1, the approval rate is about 1 in 7 for lead indications:

Source:

https://archive.bio.org/media/press...rate-drug-approvals-lower-previously-reported

• Overall success rates from Phase I to FDA approval is nearly 9%. This number is comprised of lead and secondary indications. When separated, lead indications have close to a one in seven rate of approval and secondary indications have a rate of one in 30.

These figures are usually brought up in the context of biotech investing (like the organization from the link above) because it is useful to them to track the average across all classes and types of drugs. So for instance, if you are investing in the field, you need to be well diversified or invest in the IBB to mitigate your risk. It's not really that useful of a figure otherwise in looking at individual drugs imo because it varies hugely by type of drug and indication. To use another example: investors don't use overall market rate to predict the trajectory of individual stocks (which would be very inaccurate most of the time) but rather to argue for investing in index funds. You can't use the equivalent of the "overall stock market performance" here either.

Many indications (e.g. Alzheimer's drugs) have a close to zero approval rate and bring the average down. So if you thought an individual Alzheimer's drug had a 1 in 10 chance, based on the broad market figures, you'd be really disappointed to find less than a handful in a few hundred were approved. Other classes have a much higher percentage of approval.

The two reasons drugs fail are:

1) They aren't safe and have unforeseen side effects. This is much more likely with a systemic drug vs intratympanic because you can't predict "off target" side effects pre-clinically as easily with a systemic drug. The pharmacologic testing in phase 1 for FX-322 showed that it doesn't have appreciable systemic absorption so its effects would be well predicted with pre-clinical studies on the target tissue.

2) Efficacy. The drug has to be proven effective over placebo.

As was pointed out in the recent Tinnitus Talk Podcast, you can't just "squint your ears" to double your word score. A notable aspect about hearing regeneration is it unambiguously works or it doesn't. The placebo effect for hearing better doesn't really exist.

We don't know the approval rate for hearing regeneration drugs as a class because it's never been done before.

You can say "based on all drugs for all indications, the figure is around 10% so I chose to think hearing regeneration drugs will fall in line with the mean" but that's a huge assumption based on zero evidence at this point (because again, this tech is brand new) and honestly extraordinarily pessimistic based on the data that is known at this point.

 

[Jurger]

I mean no other clinical trials have got as much of an improved hearing than FX-322. That 1 patient went from 27/50 to a 47/50 word score, which is unbelievable that it made such a difference.

That's promising, but keep in mind they're not saying how loud they had to set the sound to get to a 47/50 score. There's obviously a difference between setting the sound to 40 dB to get 47/50 instead of 70 dB.

 

[GlennS]

Today I read about the Oxford´s vaccine to treat COVID-19 and it just irritates me (sorry for being miserable). They did it so fast! And here we are always projecting our life in 5 or 10 years.

I´m not reading Tinnitus Talk so frequently but it´s always depressing when I come back and there is no exciting news.

Apples and oranges. Creating flu vaccines is a well-known process. Curing tinnitus is moonshot territory.

 

[FGG]

That's promising, but keep in mind they're not saying how loud they had to set the sound to get to a 47/50 score. There's obviously a difference between setting the sound to 40 dB to get 47/50 instead of 70 dB.

There is a standard loudness for this test, I imagine they didn't do anything unorthodox. And if someone needed 70 dB to hear 27/50 words, it would be even more impressive if that kind of hearing loss improved that much.

 

[PauloZ]

Apples and oranges. Creating flu vaccines is a well-known process. Curing tinnitus is moonshot territory.

True, but it is also true that almost every research lab dropped everything to search for a vaccine.

I'm also a bit frustrated to see that if the world economy and a lot of money is at stake, all of a sudden a lot is possible. But if it's 'only' people suffering, projects even struggle to find enough funds to research.

So I understand him being irritated.

 

[tommyd87]

I have just read that paper.

@FGG, I'd like to thank you for all information you bring to this community.

Just 4 out of 15 patients with 10 dB Improvement at 8000 Hz among those who received FX-322 is something (considering that there is nothing so far), but it is not an impressive result (considering this is an optimistic headline from the company).

Maybe, I'm pessimistic by nature.

It was one dose done in only one ear and its primary purpose was safety. Note that the scores for the words also actually improved. It is looking very positive when you consider it.

The guy who bought had previously been selling.

Interesting and am hoping is a positive sign.

 

[Jurger]

There is a standard loudness for this test, I imagine they didn't do anything unorthodox. And if someone needed 70 dB to hear 27/50 words, it would be even more impressive if that kind of hearing loss improved that much.

Word recognition on hearing tests is measured by different levels of loudness. A patient that has 47/50 score on 90 dB might have 20/50 on 50 dB or whatever. 47/50 in itself doesn't paint the entire picture. Take me for example. I score 33/50 in my right ear. Not that bad right? Except my ear has to blast the sound in on 90 dB to get there. Not that swell walking around with a hearing aid that's on jet fighter sound level.

 

[sssing]

That's promising, but keep in mind they're not saying how loud they had to set the sound to get to a 47/50 score. There's obviously a difference between setting the sound to 40 dB to get 47/50 instead of 70 dB.

The machines will be calibrated for this kind of testing, if not, there's no point in doing the test at all.

 

[FGG]

Word recognition on hearing tests is measured by different levels of loudness. A patient that has 47/50 score on 90 dB might have 20/50 on 50 dB or whatever. 47/50 in itself doesn't paint the entire picture. Take me for example. I score 33/50 in my right ear. Not that bad right? Except my ear has to blast the sound in on 90 dB to get there. Not that swell walking around with a hearing aid that's on jet fighter sound level.

So you are saying, you think they increased the loudness for the follow up?

 

[Diesel]

So you are saying, you think they increased the loudness for the follow up?

My understanding is the words are presented at a decibel level that is equivalent to everyday conversation level. Based on this document, looks like 50 dB - 55 dB. In my last two word score tests, I was presented words at 50 dB.

https://www.hearingloss.org/wp-cont...sky_Audiogram2.pdf?pdf=2014-hlm-so-lmedwetsky

 

[Jurger]

So you are saying, you think they increased the loudness for the follow up?

I'm saying that we don't know at what loudness they measured those promising word scores.

 

[Jurger]

The machines will be calibrated for this kind of testing, if not, there's no point in doing the test at all.

What do you mean? I'm not saying anything was wrong with the test, I'm saying that hearing 47/50 at 35 dB is not the same as hearing it at 70 dB, even though the scores are the same.

 

[tommyd87]

So you are saying, you think they increased the loudness for the follow up?

There's no way where they would have altered volumes at the follow up unless they were crazy. It would completely corrupt their data. They definitely want to show it was the same at both points for efficacy.

 

[FGG]

I'm saying that we don't know at what loudness they measured those promising word scores.

Let's say they did it louder than typical (70 dB), that would mean the people who had a result of 27/50 had pretty substantial hearing loss (more than someone who had the same score at 50 dB) and if those people doubled their word score at the same volume it's even more impressive.

If they did it at less than conversational loudness, i'm not sure the test would even have been useful at all so I doubt the independent audiologists/ENTs at the testing site would have administered it.

Per the Tinnitus Talk Podcast, the testing was carried out by 3 different San Antonio area independent ENTs. I would think they'd have a set standard for word score loudness and it would be the "typical" standard.

 

[Jurger]

Let's say they did it louder than typical (70 dB), that would mean the people who had a result of 27/50 had pretty substantial hearing loss (more than someone who had the same score at 50 dB) and if those people doubled their word score at the same volume it's even more impressive.

If they did it at less than conversational loudness, i'm not sure the test would even have been useful at all so I doubt the independent audiologists/ENTs at the testing site would have administered it.

Per the Tinnitus Talk Podcast, the testing was carried out by 3 different San Antonio area independent ENTs. I would think they'd have a set standard for word score loudness and it would be the "typical" standard.

Again, I'm not saying there was anything unorthodox or wrong about the test or that they changed the loudness. All I'm saying that in daily life for a person with hearing loss, "47/50" doesn't say everything. Nor to an audiologist. In a standard hearing test, they register multiple word scores at different volumes. That's why the words you have to repeat keep getting less loud as the test progresses. If you have to set your hearing aid to 70 dB or whatever to get to your best word score, it has all kinds of other drawbacks. Trust me, living with a loud ass hearing aid is no fun. That's one of the reasons why you want to have a situation where both your word scores and your PTA improve. It's better to get the loudness from the cochlea itself than from an aid.

 

[Hazel]

Aaaaand it's out!

Tinnitus Talk Podcast: Hearing Lost and Found — Frequency Therapeutics

Listen here